bluuebunny/crossref_metadata_2025 huggingface dataset:
Luminescence Change from Orange to Blue for Zero‐Dimensional Cs2InCl5(H2O) Metal Halides in Water and a New Post‐doping Method
Authors: Yang Chuang , Guo Fengwan , Zhang Yu , Zhong Xinxin , Feng Jing , Wang Nan , Wang Juan
Published: May 2021

Zero‐dimensional metal halides have attracted much attention due to their attractive photoelectric properties. Here, we propose a new strategy of synthesizing metal halides crystals by recrystallization in water. The as‐synthesized Cs2InCl5(H2O)‐orange crystals are dissolved and recrystallized in water (Cs2InCl5(H2O)‐blue), with its photoluminescence (PL) changing from orange to blue, both of which are derived from self‐trapping excitons (STEs). The time‐resolved photoluminescence (TRPL) spectrum of Cs2InCl5(H2O)‐blue shows that it has an ultralong lifetime up to milliseconds (τ=52.98 ms), which is expected to be applied in biological sensors. The photoluminescence quantum yield (PLQY) increases from 2.25% to 11.61% in the self‐assembly process. By using a post‐doping method, the PL of crystals turns into red when we introduce Mn2+ as dopant while there is no obvious change upon using a traditional solvent‐thermal method. Recrystallization in water and post‐doping provide a new perspective for the synthesis and doping of metal halides.
Hyaluronic acid–graphene quantum dot nanocomposite: Potential target drug delivery and cancer cell imaging
Authors: Vahedi Nasrin , Tabandeh Fatemeh , Mahmoudifard Matin
Published: May 2021

Nowadays, the use of nanoparticle‐based drug delivery systems has received much more attention. In this regard, here, graphene quantum dots (GQD) were used as drug carriers as well as imaging agents for cancer cells. In order to optimize the dose of the drug and reduce its side effects for healthy cells, hyaluronic acid was decorated on the surface of GQD to target cancer cells. The morphology and size of the synthesized nanoparticles alone and conjugated with hyaluronic acid were investigated using scanning electron microscopy (SEM) and transmission electron microscopy (TEM); TEM images revealed a particles size of ∼5.67 and ∼8.69 nm, respectively. In the presence of 1‐ethyl‐3‐[3(dimethylamino)propyl]carbodiimide hydrochloride/N‐hydroxysuccinimide (EDC/NHS), hyaluronic acid was bounded to dopamine hydrochloride and was prepared to react with GQD. After synthesis of graphene quantum dot‐hyaluronic acid nanocomposite, curcumin (CUR) as a drug model was loaded on the synthesized nanocarriers, and its loading percentage was measured. The results showed that 98.02% of the drug was loaded on the nanocarriers. Also, the conjugation of each agent on the nanocarrier was approved by photoluminescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), and UV–visible absorption techniques, and the results showed that the reactions were performed correctly. The effect of GQD, graphene quantum dot–hyaluronic acid, CUR, graphene quantum dot‐hyaluronic acid–CUR on the viability of HeLa and L929 cells was evaluated by the MTT test. The results showed that the synthesized nanocarrier is completely biocompatible, and the drug nanocarriers reduce HeLa cell viability significantly due to the mediation of hyaluronic acid–CD44 for drug cell uptake. Simultaneously with drug delivery, the other goal of these nanocarriers is to image cancer cells by emitting fluorescent light. Fluorescent microscopy showed that these nanocarriers were adsorbed on HeLa cells, unlike L929 cells.
Natural History as a Family Enterprise: Kinship and Inheritance in Eighteenth‐Century Science**
Authors: Cooper Alix
Published: May 2021

As recent research has shown, many of the activities of early modern (including eighteenth‐century) naturalists were carried out in the household. This article investigates the ways in which family members in particular, both male and female, ended up engaging in kinds of labor which furthered the pursuit of natural history in the eighteenth century. Examining evidence from various different parts of Europe and its colonies, the article argues that natural history can be seen to have often been what might be termed a family enterprise, one to which many different family members might contribute in ways shaped by concerns of kinship and inheritance.
Improvement of quantum efficiency through Gd3+ to Eu3+ energy transfer in YF3 phosphor
Authors: Jaiswal Shailesh R. , Nagpure Pankaj A. , Omanwar Shreeniwas K.
Published: May 2021

This paper reports the energy transfer from Gd3+ to Eu3+ in YF3 and the consequent downconversion luminescence for the YF3:Gd3+, Eu3+ fluoride phosphor. The phosphor was synthesized using a soft chemical route, followed by a reactive atmosphere process. Because of the wide band gap in YF3 and the correct energy site for 8S7/2–6GJ transitions of Gd3+ ions, fluoride YF3 doped with Gd3+−Eu3+ were studied in their vacuum–ultraviolet (VUV) spectral regions. Powder X‐ray diffraction (XRD) analysis showed the structural purity of YF3. VUV excitation and emission properties were explored using a VUV synchrotron radiation beam line. Downconversion of energy from VUV (157 nm) to visible light with quantum efficiency c. 189% was seen. This YF3:Gd3+, Eu3+ phosphor would be an option for mercury‐free fluorescence lamps.
Analysis of alpha‐alumina by variable dose and Tm–TSTOP methods and simulations of the whole process
Authors: Uzun Erdem
Published: May 2021

The Tm–TSTOP and the variable dose methods were applied to alumina experimentally, and then all the steps of the methods were simulated numerically. The Tm–TSTOP experiments were performed between 70 and 300°C, and results showed that the glow curve of the used alumina had six distinct peaks between 40 and 400°C. The glow curves were analyzed using computerized glow curve fitting programs, the analytical equations were also fitted to the experimental data, and the trapping parameters of the peaks were measured. The samples were irradiated above the saturation level to ensure the complete filling of the electron traps and, therefore, the concentrations of traps were measured experimentally. Short‐term anomalous fading behaviours of the peaks were investigated, and a new equation was proposed to compute the anomalous fading rate. In addition, the variable dose and Tm–TSTOP methods were simulated using the six trap‐one recombination centre (6T1C) model and the experimental trapping parameters. Results showed that there was good harmony between numerical and experimental glow curves. After all the simulations were performed with acceptable accuracy, an estimate was made for the trapping coefficients (Ai = 1–6) that could not be measured directly from thermoluminescence experiments. Results showed that the trapping coefficients were affected by the applied dose.
A simple and rapid HPLC method for determination of parabens and their degradation products in pharmaceutical dosage forms
Authors: Katakam Lakshmi Narasimha Rao , Ettaboina Santhosh Kumar , Dongala Thirupathi
Published: May 2021

A stability‐indicating HPLC method was developed for the simultaneous determination of paraben mixture and its degradation products in effervescent potassium chloride tablets. The chromatographic separation was achieved on a Waters Cortecs C18 column (2.7 μm, 4.6 × 150 mm) using gradient elution. The optimized mobile phase consisted of 0.1% orthophosphoric acid in purified water as solvent A and purified water, acetonitrile, and orthophosphoric acid (100:900:1, v/v) as solvent B. The flow rate was 0.8 mL/min, and column temperature was maintained at 35°C. The injection volume was 10 μL, and UV detection was carried out at 254 nm. The selectively developed method has optimal separation among p‐hydroxybenzoic acid, methylparaben, ethylparaben, propylparaben, and butylparaben peaks in the presence of specified and unspecified degradation products in the determination of drug product. The mass balance obtained from forced degradation studies was ≥95% and thus proves the stability‐indicating property of the developed method. The developed reversed‐phase HPLC method has been validated according to the International Conference on Harmonization guidelines. The correlation coefficients for all the peaks were >0.9999. The results of the other validation parameters were found within the limits. Finally, the optimized method was used in the quality control lab for stability analysis.
Psychiatric risk and resilience: Plasticity genes and positive mental health
Authors: Nestor Paul G. , Choate Hasler Victoria , O'Donovan Keira , Lapp Hannah E. , Boodai Sara B. , Hunter Richard
Published: May 2021

Objective

The at‐risk mental state (ARMS) for psychosis has long played a key role in diathesis‐stress models of schizophrenia. More recent studies, however, have called for extending the boundaries of the ARMS construct beyond attenuated psychosis in nonhelp‐seeking samples to include not only other vulnerability indicators but also protective factors related to genotype, mental health, personality, and cognition.

Method

Accordingly, we assessed in a sample of 100 college students, the ARMS construct with the Brief Prodromal Questionnaire (PQ‐B) for psychosis, in conjunction with measures of positive mental health, childhood adversity, psychiatric symptoms, personality traits, social cognition, and genetic variables derived from assays of the serotonin transporter (5‐HTTLPR) and the brain‐derived neurotrophic factor (BDNF).

Results

Higher PQ‐B scores correlated positively with vulnerability indicators of childhood adversity and heightened levels of a wide variety of psychiatric symptoms but correlated negatively with protective factors of better overall mental health, social cognition as well as with a distinct NEO profile marked by reduced neuroticism and elevated agreeableness and conscientiousness. Multivariate analyses indicated that a composite ARMS measure comprised of PQ‐B scores plus anxiety and depression symptoms revealed significant genotype differences, with lowest risk and highest resilience for allelic carriers of 5‐HTTLPR‐short and BDNF Met polymorphisms.

Conclusions

Results provided support for extending the ARMS construct, pointing to important contributions of personality, social cognition, and genes that support neural plasticity in mitigating vulnerability and enhancing resilience and well‐being.
Decreased survival in patients treated by chemotherapy after targeted therapy compared to immunotherapy in metastatic melanoma
Authors: Mangin Marie‐Alix , Boespflug Amélie , Maucort Boulch Delphine , Vacheron Charles‐Hervé , Carpentier Isabelle , Thomas Luc , Dalle Stéphane
Published: May 2021

Background

Cytotoxic chemotherapy (CC) is currently used in metastatic melanoma after patients have developed resistance to immune checkpoint inhibitors (ICI) and/or Mitogen‐Activated Protein Kinase inhibitors (MAPKi). We sought to evaluate if a previous treatment by ICI or MAPKi influences clinical outcomes in patients treated by CC in metastatic melanoma.

Methods

Eighty‐eight patients with a metastatic melanoma, treated by CC after a previous treatment by ICI or MAPKi between January 2009 and October 2019, were retrospectively analyzed. Progression‐Free‐Survival (PFS), Overall Survival (OS), Overall Response Rate (ORR), and Disease Control Rate (DCR) were evaluated in patients treated by CC according to their prior treatment by ICI or MAPKi.

Results

Patients treated by CC after ICI tended to have a better median PFS (2.81 months (2.39–5.30) versus 2.40 months (0.91–2.75), p = 0.023), median OS (6.03 months (3.54–11.54) versus 4.44 months (1.54–8.59), p = 0.27), DCR (26.0% vs. 10.5%, p = 0.121) and ORR (22.0% vs. 7.9% p = 0.134) than those previously treated by MAPKi.

Conclusions

A prior treatment by an MAPKi may be associated with a worse response to CC than ICI, and further investigations should be performed to confirm if there is a clinical benefit to propose CC in this setting.
Haematologic malignancies with unfavourable gene mutations benefit from donor lymphocyte infusion with/without decitabine for prophylaxis of relapse after allogeneic HSCT: A pilot study
Authors: Zhang Rui , Wang Lili , Chen Peng , Gao Xiaoning , Wang Shuhong , Li Fei , Dou Liping , Gao Chunji , Li Yan , Liu Daihong
Published: May 2021

Relapse is the main cause of treatment failure for leukaemia patients with unfavourable gene mutations who receive allogeneic haematopoietic stem cell transplantation (allo‐HSCT). There is no consensus on the indication of donor lymphocyte infusion (DLI) for prophylaxis of relapse after allo‐HSCT. To evaluate the tolerance and efficacy of prophylactic DLI in patients with unfavourable gene mutations such as FLT3‐ITD, TP53, ASXL1, DNMT3A or TET2, we performed a prospective, single‐arm study. Prophylactic use of decitabine followed by DLI was planned in patients with TP53 or epigenetic modifier gene mutations. The prophylaxis was planned in 46 recipients: it was administered in 28 patients and it was not administered in 18 patients due to contraindications. No DLI‐associated pancytopenia was observed. The cumulative incidences of grade II–IV and III–IV acute graft‐versus‐host disease (GVHD) at 100 days post‐DLI were 25.8% and 11.0%, respectively. The rates of chronic GVHD, non‐relapse mortality and relapse at 3 years post‐DLI were 21.6%, 25.0% and 26.1%, respectively. The 3‐year relapse‐free survival and overall survival (OS) rates were 48.9% and 48.2%, respectively. Acute GVHD (HR: 2.30, p = 0.016) and relapse (HR: 2.46, p = 0.003) after DLI were independently associated with inferior OS. Data in the current study showed the feasibility of prophylactic DLI with/without decitabine in the early stage after allo‐HSCT in patients with unfavourable gene mutations.
Sputum cell‐free DNA: Valued surrogate sample for the detection of EGFR exon 20 p.T790M mutation in patients with advanced lung adenocarcinoma and acquired resistance to EGFR‐TKIs
Authors: Wang Zheng , Li Xiaoguang , Zhang Lin , Xu Yan , Wang Mengzhao , Liang Li , Jiao Peng , Li Yuanming , He Shurong , Du Jun , He Lei , Tang Min , Sun Mingjun , Yang Li , Di Jing , Zhu Guanshan , Li Lin , Liu Dongge
Published: May 2021

Background

Sputum cell‐free DNA (cfDNA) is a valuable surrogate sample for assessing EGFR‐sensitizing mutations in patients with advanced lung adenocarcinoma. Detecting EGFR exon 20 p.T790 M (p.T790 M) is much more challenging due to its limited availability in tumor tissues. Exploring sputum cfDNA as an alternative for liquid‐based sample type in detecting p.T790 M requires potential improvement in clinical practice.

Methods

A total of 34 patients with EGFR‐sensitive mutation‐positive lung adenocarcinoma and acquired resistance to the first generation of epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) were enrolled. The sputum samples, and paired tumors and/or plasma samples were tested for p.T790 M mutation and concordance of p.T790 M status among the three sample types was analyzed.

Results

The overall concordance rate of p.T790 M mutation between sputum cfDNA and tumor tissue samples was 85.7%, with a sensitivity of 66.7% and a specificity of 100%. The sensitivity for detecting p.T790 M in sputum cfDNA was 100%, 66.7%, and 0% in the three sputum groups of malignant, satisfactory but no malignant cells, and unsatisfactory, respectively. The combined results of plasma cfDNA testing and sputum cfDNA testing further increased the sensitivity to 100% for p.T790 M detection in satisfactory but no malignant cells sputum group.

Conclusion

These findings revealed that cfDNA from malignant or satisfied but no malignant cells sputum is considered suitable for detecting p.T790 M mutation in patients with acquired resistance to first or second‐generation EGFR‐TKIs. The sputum cytological pathological evaluation‐guided sputum cfDNA testing assists in significantly improving the sensitivity of p.T790 M detection, bringing significant value for the maximal application of third‐generation EGFR‐TKIs in second‐line treatment.
TNF‐α/NF‐κB signaling epigenetically represses PSD4 transcription to promote alcohol‐related hepatocellular carcinoma progression
Authors: Shi Jia’ning , Song Shupeng , Li Shuangxing , Zhang Kaili , Lan Yinghua , Li Yongguo
Published: May 2021

Background

Chronic alcohol consumption is more frequently associated with advanced, aggressive hepatocellular carcinoma (HCC) tumors. Alcohol adversely impacts ER/Golgi membrane trafficking and Golgi protein N‐glycosylation in hepatocytes; these effects have been attributed (in part) to dysregulated adenosine diphosphate‐ribosylation factor (ARF) GTPase signaling. Here, we investigated the role of the ARF GTPase guanine exchange factor PSD4 in HCC progression.

Methods

R‐based bioinformatics analysis was performed on publicly available array data. Modulating gene expression was accomplished via lentiviral vectors. Gene expression was analyzed using quantitative real‐time PCR and immunoblotting. PSD4 promoter methylation was assessed using quantitative methylation‐specific PCR. Phospho‐p65(S276)/DNMT1 binding to the PSD4 promoter was analyzed via chromatin immunoprecipitation. We constructed ethanol/DEN‐induced and DEN only‐induced transgenic murine models of HCC.

Results

We identified PSD4 as a hypermethylated, suppressed gene in alcohol‐related HCC tumors; however, PSD4 was not dysregulated in all‐cause HCC tumors. Certain HCC cell lines also displayed varying degrees of PSD4 downregulation. PSD4 overexpression or knockdown decreased and increased cell migration and invasiveness, respectively. Mechanistically, PSD4 transcription was repressed by TNF‐α‐induced phospho‐p65(S276)’s recruitment of DNA methyltransferase 1 (DNMT1), resulting in PSD4 promoter methylation. PSD4 inhibited pro‐EMT CDC42 activity, resulting in downregulation of E‐cadherin and upregulation of N‐cadherin and vimentin. Hepatocyte‐specific PSD4 overexpression reduced ethanol/DEN‐induced HCC tumor progression and EMT marker expression in vivo.

Conclusions

PSD4 is a hypermethylated, suppressed gene in alcohol‐related HCC tumors that negatively modulated pro‐EMT CDC42 activity. Furthermore, we present a novel phospho‐NF‐κB p65(S276)/DNMT1‐mediated promoter methylation mechanism by which TNF‐α/NF‐κB signaling represses PSD4 transcription in HCC cells.
ONC201 induces the unfolded protein response (UPR) in high‐ and low‐grade ovarian carcinoma cell lines and leads to cell death regardless of platinum sensitivity
Authors: Rumman Marufa , Buck Steven , Polin Lisa , Dzinic Sijana , Boerner Julie , Winer Ira S.
Published: May 2021

Objectives

Treatment of both platinum resistant high grade (HG) and low‐grade (LG) ovarian cancer (OVCA) poses significant challenges as neither respond well to conventional chemotherapy leading to morbidity and mortality. Identification of novel agents that can overcome chemoresistance is therefore critical. Previously, we have demonstrated that OVCA has basal upregulated unfolded protein response (UPR) and that targeting cellular processes leading to further and persistent upregulation of UPR leads to cell death. ONC201 is an orally bioavailable Dopamine Receptor D2 inhibitor demonstrating anticancer activity and was found to induce UPR. Given its unique properties, we hypothesized that ONC201 would overcome platinum resistance in OVCA.

Methods

Cisplatin sensitive and resistant HG OVCA and two primary LG OVCA cell lines were studied. Cell viability was determined using MTT assay. Cell migration was studied using wound healing assay. Apoptosis and mitochondrial membrane potential were investigated using flow cytometry. Analysis of pathway inhibition was performed by Western Blot. mRNA expression of UPR related genes were measured by qPCR. In vivo studies were completed utilizing axillary xenograft models. Co‐testing with conventional chemotherapy was performed to study synergy.

Results

ONC201 significantly inhibited cell viability and migration in a dose dependent manner with IC50’s from 1‐20 µM for both cisplatin sensitive and resistant HG and LG‐OVCA cell lines. ONC201 lead to upregulation of the pro‐apoptotic arm of the UPR, specifically ATF‐4/CHOP/ATF3 and increased the intrinsic apoptosispathway. The compensatory, pro‐survival PI3K/AKT/mTOR pathway was downregulated. In vivo, weekly dosing of single agent ONC201 decreased xenograft tumor size by ~50% compared to vehicle. ONC201 also demonstrated significant synergy with paclitaxel in a highly platinum resistant OVCA cell‐line (OV433).

Conclusions

Our findings demonstrate that ONC201 can effectively overcome chemoresistance in OVCA cells by blocking pro‐survival pathways and inducing the apoptotic arm of the UPR. This is a promising, orallybioavailable therapeutic agent to consider in clinical trials for patients with both HG and LG OVCA.
Real‐world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B‐cell lymphoma
Authors: Iacoboni Gloria , Villacampa Guillermo , Martinez‐Cibrian Nuria , Bailén Rebeca , Lopez Corral Lucia , Sanchez Jose M. , Guerreiro Manuel , Caballero Ana Carolina , Mussetti Alberto , Sancho Juan‐Manuel , Hernani Rafael , Abrisqueta Pau , Solano Carlos , Sureda Anna , Briones Javier , Martin Garcia‐Sancho Alejandro , Kwon Mi , Reguera‐Ortega Juan Luis , Barba Pere ,   GETH, GELTAMO Spanish Groups
Published: May 2021

Tisagenlecleucel (tisa‐cel) is a second‐generation autologous CD19‐targeted chimeric antigen receptor (CAR) T‐cell therapy approved for relapsed/refractory (R/R) large B‐cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa‐cel in the standard‐of‐care (SOC) setting for R/R LBCL. Data from all patients with R/R LBCL who underwent leukapheresis from December 2018 until June 2020 with the intent to receive SOC tisa‐cel were retrospectively collected at 10 Spanish institutions. Toxicities were graded according to ASTCT criteria and responses were assessed as per Lugano 2014 classification. Of 91 patients who underwent leukapheresis, 75 (82%) received tisa‐cel therapy. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 5% and 1%, respectively; non‐relapse mortality was 4%. Among the infused patients, best ORR and CR were 60% and 32%, respectively, with a median duration of response of 8.9 months. With a median follow‐up of 14.1 months from CAR T‐cell infusion, median progression‐free survival and overall survival were 3 months and 10.7 months, respectively. At 12 months, patients in CR at first disease evaluation had a PFS of 87% and OS of 93%. Patients with an elevated lactate dehydrogenase showed a shorter PFS and OS on multivariate analysis. Treatment with tisa‐cel for patients with relapsed/refractory LBCL in a European SOC setting showed a manageable safety profile and durable complete responses.
Surgery shows survival benefit in patients with primary intestinal diffuse large B‐cell lymphoma: A population‐based study
Authors: Wang Moran , Ma Shengling , Shi Wei , Zhang Yuanyuan , Luo Shanshan , Hu Yu
Published: May 2021

Background

The clinical characteristics and prognosis of primary intestinal diffuse large B‐cell lymphoma (PI‐DLBCL) are rarely reported. We aimed to explore the role of surgery in patients with PI‐DLBCL.

Methods

Adult PI‐DLBCL patients were included from the Surveillance, Epidemiology, and End Results database. The effect of surgery was evaluated by Kaplan–Meier and Cox proportional regression analyses. Propensity score matching (PSM) was used to reinforce our results. Lasso regression was utilized to determine independent risk factors of overall survival (OS) for a nomogram and a novel web‐based calculator. The performance of the model was measured via concordance index, receiver operating characteristic curve, and calibration plots in both cohorts.

Results

Overall, 1602 patients with PI‐DLBCL were analyzed. Surgery significantly improved survival in both univariate and multivariate analyses (p = 0.007, p < 0.001, respectively). Before PSM, local tumor destruction (LTD) displayed a survival advantage over resection in patients without chemotherapy (p = 0.034). After PSM, surgery was still identified as a beneficial factor for OS (p = 0.0015). However, there was no statistical difference between LTD and resection (p = 0.32). The nomogram for 3‐, 5‐, and 10‐year OS predictions exhibited dependable consistency between internal and external validation.

Conclusion

This study approves the beneficial effect of surgery on clinical endpoints in PI‐DLBCL patients. For those who are not suitable for resection, LTD may also be a practical option. The predictive nomogram and the web‐based calculator could help clinicians individually evaluate the prognosis and optimize personalized treatment decisions for these patients.
BACH1 promotes the progression of esophageal squamous cell carcinoma by inducing the epithelial–mesenchymal transition and angiogenesis
Authors: Zhao Yan , Gao Jiajia , Xie Xiufeng , Nan Peng , Liu Fang , Sun Yulin , Zhao Xiaohang
Published: May 2021

Metastasis to regional lymph nodes or distal organs predicts the progression of the disease and poor prognosis in esophageal squamous cell carcinoma (ESCC). Previous studies demonstrated that BTB and CNC homology 1 (BACH1) participates in various types of tumor metastasis. However, the function of BACH1 in ESCC was rarely reported. The present study demonstrated that BACH1 protein was overexpressed in ESCC tissues compared with paired esophageal epithelial tissues according to immunohistochemical staining (IHC). Higher levels of BACH1 mRNA were associated with decreased overall survival (OS) and shorter disease‐free survival (DFS) of ESCC patients based on an analysis of The Cancer Genome Atlas (TCGA) datasets. BACH1 significantly enhanced the migration and invasion of ESCC in vitro. Mechanistically, BACH1 promoted the epithelial–mesenchymal transition (EMT) by directly activating the transcription of CDH2, SNAI2, and VIM, as determined by chromatin immunoprecipitation‐quantitative polymerase chain reaction (ChIP‐qPCR). BACH1 overexpression significantly enhanced CDH2 promoter activity according to the results of a luciferase assay. The results of subsequent experiments indicated that BACH1 enhanced the growth of tumor xenografts. The density of CD31+ blood vessels and the expression of vascular endothelial growth factor C (VEGFC) in tumor xenografts were significantly associated with BACH1 levels according to the results of IHC and immunofluorescence (IF) analyses performed in vivo. Moreover, ChIP‐qPCR analysis demonstrated that the transcriptional activity of VEGFC was also upregulated by BACH1. Thus, BACH1 contributes to ESCC metastasis and tumorigenesis by partially facilitating the EMT and angiogenesis, and BACH1 may be a promising therapeutic target or molecular marker in ESCC.
Retroperitoneal or transperitoneal approach in robot‐assisted partial nephrectomy, which one is better?
Authors: Zhou Jing , Liu Zheng‐Huan , Cao De‐Hong , Peng Zhu‐Feng , Song Pan , Yang Luchen , Liu Liang‐Ren , Wei Qiang , Dong Qiang
Published: May 2021

Purpose

To systematically assess the perioperative outcomes of retroperitoneal (RP) and transperitoneal (TP) approaches in robot‐assisted partial nephrectomy (RAPN), we conducted an updated meta‐analysis.

Methods

A literature retrieval of multi‐database including PubMed, Web of Science, Embase, Cochrane Library, and CNKI was performed to identify eligible comparative studies from the inception dates to January 2021. Perioperative outcomes included operative time (OT), estimated blood loss (EBL), warm ischemia time (WIT), postoperative length of stay (PLOS), positive surgical margin (PSM), and complications (major complications and overall complications). Outcomes of data were pooled and analyzed with Review Manager 5.4.1.

Results

Twenty‐one studies involving a total of 2482 RP and 3423 TP approach RAPN patients met the inclusion criteria. Operating time (OT) (weighted mean difference [WMD] −16.60; 95% confidence interval [CI] −23.08, −10.12; p < 0.01) and PLOS (WMD −0.46 days; 95% CI −0.69, −0.23; p < 0.01) were shorter in RP‐RAPN. Besides, lower EBL (WMD −21.67; 95% CI −29.74, −13.60; p < 0.05) was also found in RP‐RAPN. Meanwhile, no significant differences were found in other outcomes.

Conclusions

RP‐RARN was superior to TP‐RAPN in patients undergoing RAPN in terms of OT, PLOS, and estimated blood loss. Besides these two approaches have no significant differences in PSMs or perioperative complications.
Patient perspectives on chemotherapy de‐escalation in breast cancer
Authors: Rocque Gabrielle B. , Williams Courtney P. , Andrews Courtney , Childers Timothy C. , Wiseman Kimberly D. , Gallagher Kathleen , Tung Nadine , Balch Alan , Lawhon Valerie M , Ingram Stacey A , Brown Thelma , Kaufmann Tara , Smith Mary L. , DeMichele Angela , Wolff Antonio C. , Wagner Lynne
Published: May 2021

Background

Given excellent survival outcomes in breast cancer, there is interest in de‐escalating the amount of chemotherapy delivered to patients. This approach may be of even greater importance in the setting of the COVID‐19 pandemic.

Methods

This concurrent mixed methods study included (1) interviews with patients and patient advocates and (2) a cross‐sectional survey of women with breast cancer served by a charitable nonprofit organization. Questions evaluated interest in de‐escalation trial participation, perceived barriers/facilitators to participation, and language describing de‐escalation.

Results

Sixteen patient advocates and 24 patients were interviewed. Key barriers to de‐escalation included fear of recurrence, worry about decision regret, lack of clinical trial interest, and dislike for focus on less treatment. Facilitators included trust in physician recommendation, toxicity avoidance, monitoring for progression, perception of good prognosis, and impact on daily life. Participants reported that the COVID‐19 pandemic made them more likely to avoid chemotherapy if possible. Of 91 survey respondents, many (43%) patients would have been unwilling to participation in a de‐escalation clinical trial. The most commonly reported barrier to participation was fear of recurrence (85%). Few patients (19%) considered clinical trials themselves as a barrier to de‐escalation trial participation. The most popular terminology describing chemotherapy de‐escalation was “lowest effective chemotherapy dose” (53%); no patients preferred the term “de‐escalation.”

Conclusions

Fear of recurrence is a common concern among breast cancer survivors and patient advocates, contributing to resistance to de‐escalation clinical trial participation. Additional research is needed to understand how to engage patients in de‐escalation trials.
Expression and ERG regulation of PIM kinases in prostate cancer
Authors: Eerola Sini K. , Kohvakka Annika , Tammela Teuvo L. J. , Koskinen Päivi J. , Latonen Leena , Visakorpi Tapio
Published: May 2021

The three oncogenic PIM family kinases have been implicated in the development of prostate cancer (PCa). The aim of this study was to examine the mRNA and protein expression levels of PIM1, PIM2, and PIM3 in PCa and their associations with the MYC and ERG oncogenes. We utilized prostate tissue specimens of normal, benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), untreated PCa, and castration‐resistant prostate cancer (CRPC) for immunohistochemical (IHC) analysis. In addition, we analyzed data from publicly available mRNA expression and chromatin immunoprecipitation sequencing (ChIP‐Seq) datasets. Our data demonstrated that PIM expression levels are significantly elevated in PCa compared to benign samples. Strikingly, the expression of both PIM1 and PIM2 was further increased in CRPC compared to PCa. We also demonstrated a significant association between upregulated PIM family members and both the ERG and MYC oncoproteins. Interestingly, ERG directly binds to the regulatory regions of all PIM genes and upregulates their expression. Furthermore, ERG suppression with siRNA reduced the expression of PIM in PCa cells. These results provide evidence for cooperation of PIM and the MYC and ERG oncoproteins in PCa development and progression and may help to stratify suitable patients for PIM‐targeted therapies.
Surgical strategies for hepatocellular carcinoma located in the left lateral lobe: A propensity score‐matched and prognostic nomogram study
Authors: Zou Jingwen , Li Shaohua , Wang Qiaoxuan , Mei Jie , Lu Lianghe , Lin Wenping , Wen Yuhua , Li Yuechao , Wei Wei , Guo Rongping
Published: May 2021

Purpose

For hepatocellular carcinoma (HCC) located in the left lateral lobe, the optimal surgical procedure is still controversial. This study aimed to optimize surgical strategies and to construct a nomogram to predict the postoperative survival of patients with HCC.

Methods

Between 1 January 2005 and 30 September 2018, a total of 493 patients were enrolled. Propensity score matching (PSM) was performed between the left lateral lobectomy (LLL) and left hepatectomy (LH) groups (1:1). The study endpoints were overall survival (OS), recurrence‐free survival (RFS), and safety. A nomogram was generated using a multivariate Cox proportional hazards model. The discriminative ability and calibration of the nomogram were evaluated using C‐statistics and calibration plots.

Results

After matching, 87 pairs were included. The LH group had better 1‐, 3‐, and 5‐year OS rates than the LLL group (88%, 73%, and 69% vs. 73%, 57%, and 49%, respectively; p = 0.017). The 1‐, 3‐, and 5‐year RFS rates of the LH group were similar to those of the LLL group (64%, 49%, and 46% vs. 63%, 51%, and 42%, respectively; p = 0.652). There were no significant differences in postoperative complications. Eight factors were integrated into the nomogram and it had good discriminative ability and calibration.

Conclusion

Our data revealed that compared to LLL, LH may result in better OS and have similar postoperative complications for HCC. The nomogram may serve as a practical tool for the individual prognostic evaluation of patients with HCC.
Patient‐reported outcomes following neoadjuvant endocrine therapy, external beam radiation, and adjuvant continuous/intermittent endocrine therapy for locally advanced prostate cancer: A randomized phase III trial
Authors: Yokomizo Akira , Koga Hirofumi , Ito Kazuto , Takezawa Yutaka , Komiyama Motokiyo , Nishimura Kazuo , Yonese Junji , Hashine Katsuyoshi , Masumori Naoya , Arai Gaku , Saito Shiro , Shinohara Mitsuru , Shimizu Nobuaki , Yamauchi Atsushi , Satoh Takefumi , Tochigi Tatsuo , Kobayashi Mikio , Fujimoto Hiroyuki , Kakimoto Ken‐ichi , Fukui Iwao , Tsukamoto Taiji , Nozaki Miwako , Karasawa Katsuyuki , Hasumi Masaru , Ohtani Mikinobu , Ishiyama Hiromichi , Kuwahara Masaaki , Harada Masaoki , Ohashi Yasuo , Kotake Toshihiko , Kakizoe Tadao , Suzuki Kazuhiro , Naito Seiji , Yamanaka Hidetoshi ,   National Research Project on Endocrine‐Radiation Combination Therapy for Locally Advanced Prostate Cancer investigators
Published: May 2021

Background

We evaluated patient‐reported outcomes (PRO) during neoadjuvant androgen deprivation therapy (ADT) plus external beam radiation therapy (EBRT) followed by either adjuvant continuous ADT (CADT) or intermittent ADT (IADT) for patients with locally advanced prostate cancer (Pca).

Methods

A multicenter, randomized phase III trial enrolled 303 patients with locally advanced Pca. The patients were treated with 6 months (M) of ADT followed by 72 Gy of EBRT, and were randomly assigned to CADT or IADT after 14 M. The PROs were evaluated at sic points: baseline, 6 M, 8 M, 14 M, 20 M, and 38 M using FACT‐P questionnaires and EPIC urinary, bowel, and sexual bother subscales.

Results

The FACT‐P total scores were significantly better (p < 0.05) in IADT versus CADT at 20 M (121.6 vs.115.4) and at 38 M (119.9 vs. 115.2). The physical well‐being scores (PWB) were significantly better (p < 0.05) in IADT versus CADT at 38 M (25.4 vs. 24.0). The functional scores were significantly better in IADT than those in CADT at 14 M (20.2 vs18.7, p < 0.05) and at 20 M (21.0 vs.18.9, p < 0.05).

Conclusion

The PRO was significantly favorable in IADT on FACT‐P total score at 20 M and 38 M, PWB and functional scores at 38 M.
A systematic review of recommendations on screening strategies for breast cancer due to hereditary predisposition: Who, When, and How?
Authors: Cai Yitong , Li Jiang , Gao Ya , Yang Kelu , He Jie , Li Ni , Tian Jinhui
Published: May 2021

Background

Breast cancer is a global health problem that cannot be underestimated. Many studies have shown that breast cancer is related to pathogenic mutations in hereditary predisposition genes. Clinical practice guidelines play a vital role in guiding the selection of breast cancer screening. Little is known about the quality and consistency of guidelines’ recommendations and their changes over these years.

Methods

We reviewed the existing screening guidelines for genetic susceptibility to breast cancer and assessed the methodological quality, and summarized the recommendations to aid clinicians to make decisions. We conducted a systematic search in PubMed, Embase, Web of Science, and guideline‐specific databases, aiming to find the guidelines of breast cancer due to hereditary predisposition. The necessary information was exacted by Excel. We also summarized different evidence grading systems. The qualities of the guidelines were assessed by the Appraisal of Guidelines Research and Evaluation II (AGREE II) instrument.

Results

A total of 54 recommendations from 13 guidelines were extracted. Generally speaking, the recommendations were consistent, mainly focusing on mammography and MRI.

Conclusions

The recommendations differ in details. Moreover, different guidelines are based on different grading systems, and some guidelines are not divided for age limits, which may limit the promotion and implementation of the guidelines. It is suggested that improvement can be made in this regard in the future.
Detection of asymptomatic recurrence improves survival of gastric cancer patients
Authors: Park Ji Soo , Choe Eun‐Ah , Park Sejung , Nam Chung Mo , Hyung Woo Jin , Noh Sung Hoon , Lee Seoyoung , Kim Hyo Song , Jung Minkyu , Chung Hyun Cheol , Rha Sun Young
Published: May 2021

Background

The effect of long‐term surveillance for asymptomatic patients after curative resection of gastric cancer is being debated. We compared the prognosis of Korean patients with recurrent gastric cancer according to the presence or absence of cancer‐related symptoms at the time of recurrence detection.

Methods

We retrospectively reviewed the medical records of 305 Korean patients who experienced recurrence after curative resection of primary gastric cancer between March 2002 and February 2017 at Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.

Results

The median follow‐up duration was 169.8 months (1–267.2), and the median age at first recurrence was 58.1 years (23.4–81.9). Among 305 patients with recurrence, 97 of 231 (42.0%) patients with early recurrence (≤5 years after curative surgical resection) and 47 of 74 (63.5%) patients with late recurrence (>5 years after curative surgical resection) had cancer‐related symptoms at recurrence (p = 0.001). For survival after recurrence, detection of asymptomatic recurrence was an independent favorable factor (hazard ratio, 0.527; 95% confidence interval, 0.409–0.681; p < 0.001) accompanied with the possibility of subsequent treatment, targeted‐, or immunotherapy for recurrent disease, and locoregional recurrence only. In the late‐recurrence group, the patients with asymptomatic detection of recurrence showed favorable post‐recurrence survival (median, 33.3 months vs. 14.7 months; p = 0.002), overall survival (median, 136.3 months vs. 106.1 months; p = 0.010), and cancer‐specific survival (median, 177.5 months vs. 106.1 months; p = 0.005) than the patients with symptomatic detection.

Conclusion

The detection of gastric cancer recurrence in patients without cancer‐related symptoms may be related to improved survival, suggesting the potential benefit of long‐term surveillance.
Identification of inhibitory immune checkpoints and relevant regulatory pathways in breast cancer stem cells
Authors: Shi Haojun , Yang Yisi
Published: May 2021

Immune checkpoint blockade (ICB) has become one of the most promising approaches to activating antitumor immunity. However, only a small subset of patients with breast cancer benefit from ICB treatment. To improve the therapeutic effect in the clinic, precision immunotherapy is proposed to accurately eliminate cancer stem cells that contribute to local recurrence or metastasis, but currently little is known about their immunological properties. In this study, breast cancer–specific datasets in The Cancer Genome Atlas were collected and analyzed by using multiple open‐access web servers. We found that the immunophenotype of breast cancer was characterized by a hypoactive immune microenvironment and a low response to immune checkpoint blockade. The innate immune checkpoint CD200 and the adaptive immune checkpoint CD276, respectively, exhibited a strong correlation with basal/stem gene signature and invasiveness gene signature, both of which represent breast cancer stem cells. Wnt, TGF‐β, and Hedgehog signaling, which are recognized as stemness‐related pathways, showed a significant association with the expression of CD200 and CD276, suggesting cancer stem cell–specific immune checkpoints could be downregulated by inhibiting these pathways. Of note, levels of CD200 and CD276 expression were higher in TGF‐β dominant breast cancer than in other immune types of breast cancer. We also identified gene signatures that represent Wnt, TGF‐β, and Hedgehog signaling‐related CD200 and CD276 expression in breast cancer stem cells. For the luminal A subtype, the patient group with a high level of these gene signatures plus a low infiltration of CD8+ T cells, or dendritic cells, or M1 macrophages had poor overall survival. Our study suggested that CD200 and CD276 are candidate inhibitory immune checkpoints in breast cancer stem cells, which are potentially regulated by Wnt, TGF‐β, and Hedgehog signaling. Synergistic inhibition of these stemness‐related pathways may improve the efficacy of ICB treatment targeting breast cancer stem cells in precision immunotherapy.
Patient‐reported distress and age‐related stress biomarkers among colorectal cancer patients
Authors: Eddington Hyrum S. , McLeod Megan , Trickey Amber W. , Barreto Nicolas , Maturen Katherine , Morris Arden M.
Published: May 2021

Objective

Distress among cancer patients has been broadly accepted as an important indicator of well‐being but has not been well studied. We investigated patient characteristics associated with high distress levels as well as correlations among measures of patient‐reported distress and “objective” stress‐related biomarkers among colorectal cancer patients.

Methods

In total, 238 patients with colon or rectal cancer completed surveys including the Distress Thermometer, Problem List, and the Hospital Anxiety and Depression Scale. We abstracted demographic and clinical information from patient charts and determined salivary cortisol level and imaging‐based sarcopenia. We evaluated associations between patient characteristics (demographics, clinical factors, and psychosocial and physical measures) and three outcomes (patient‐reported distress, cortisol, and sarcopenia) with Spearman's rank correlations and multivariable linear regression. The potential moderating effect of age was separately investigated by including an interaction term in the regression models.

Results

Patient‐reported distress was associated with gender (median: women 5.0, men 3.0, p < 0.001), partnered status (single 5.0, partnered 4.0, p = 0.018), and cancer type (rectal 5.0, colon 4.0, p = 0.026); these effects varied with patient age. Cortisol level was associated with “emotional problems” (ρ = 0.34, p = 0.030), anxiety (ρ = 0.46, p = 0.006), and depression (ρ = 0.54, p = 0.001) among younger patients. We found no significant associations between patient‐reported distress, salivary cortisol, and sarcopenia.

Conclusions

We found that young, single patients reported high levels of distress compared to other patient groups. Salivary cortisol may have limited value as a cancer‐related stress biomarker among younger patients, based on association with some psychosocial measures. Stress biomarkers may not be more clinically useful than patient‐reported measures in assessing distress among colorectal cancer patients.
Working with British Army Families: A Qualitative Study of Child Protection Practitioners' Views and Experiences
Authors: Taylor Julie , Bradbury‐Jones Caroline , Held Jane , Isham Louise , McConnell Nicola
Published: May 2021

Key Practitioner Messages

Closed, often tight‐knit army communities can potentially provide protective factors for children; however, this environment can make it difficult to seek help or to speak out when there are concerns about children's safety or wellbeing.

The needs and experiences of non‐serving parents (often female partners) can be overlooked unless, or until, child protection concerns are serious.

Army‐connected children benefit from accessing army and civilian health, education and welfare services; however, transitions and communication between these services need to be improved.
Analytical Profiling of Phenolic Compounds in Extracts of Three Cistus Species from Sardinia and Their Potential Antimicrobial and Antioxidant Activity
Authors: Mastino Patrizia Monica , Marchetti Mauro , Costa Jean , Juliano Claudia , Usai Marianna
Published: May 2021

The Cistaceae family is well represented in Sardinia, and the Cistus genus is widely used in traditional medicine. Nowadays only few studies have been performed on this genus vegetating in Sardinia in spite of its ethnobotanical importance. Moreover, in the past there have been conflicting opinions among botanists for the exact assignment of the species growing in Sardinia. We started several years ago to carried out studies on this genus and in the present study was to evaluate the in vitro activity of several samples of Cistus salvifolius L., Cistus monspeliensis L., and Cistus albidus L. collected in Sardinia as antimicrobial agents against Escherichia coli, Staphylococcus aureus, and four Candida species and their antioxidant activity using DPPH, ABTS, and FRAP assays. Furthermore, the phenolic content and composition of the extracts were first evaluated. Using statistical multivariate analysis on the complete metabolomics profile of all Cistus species growing wild in Sardinia, we confirmed the botanical classification, and we observed an interesting correlation between metabolomics profile and antioxidant activity.