bluuebunny/crossref_metadata_2025 huggingface dataset:
Ichthyological ethnoknowledge of the “piabeiros” from the Amazon region, Brazil
Authors: da Silva Ladislau Daniel , Ribeiro Maiko Willas Soares , da Silva Castro Philip Dalbert , Pantoja-Lima Jackson , Aride Paulo Henrique Rocha , de Oliveira Adriano Teixeira
Published: June 2021

Background

The capture of ornamental fish is one of the main economic activities of riverine families in the Amazon. However, studies regarding the local ecological knowledge of workers in this activity are still incipient. In view of this, we have studied and explored the local ecological knowledge of artisanal fishers who specialize in the capture of fish for the aquarium trade in the middle part of the Negro River basin and investigated issues related to the ecological aspects of the fish species that are targeted by this trade in the region.

Methods

Therefore, we conducted semi-structured interviews and applied questionnaires to artisanal fishers of ornamental fish (N = 89), from the municipality of Barcelos, from January to April 2016.

Results

In total, 41 popular names were cited, which correspond to four ethnocategories and 10 families. The main species were Paracheirodon axelrodi (12.5%), Hemigrammus bleheri (8.3%), Ancistrus dolichopterus (6.4%), Symphysodon discus (5.3%), and Potamotrygon motoro (3.8%). According to the fishers, the species of fish known in the region as “piabas” have a preference for living in clusters (28.9%) and carry out migratory movements (26.1%). The diet of local fish species reported by fisheries is diverse, though mainly based on periphyton (42.2%), and the reproductive cycle directly influenced by the period of flooding of rivers in the region (37.6%)

Conclusion

Our study revealed that the fishers possess information on the ecological aspects of local ornamental fish species, many of which are consistent with scientific literature. The information presented may assist in the decision-making process for the management of local fishery resources and contribute to the resumption of growth and sustainability in the capture of ornamental fish.
Dose escalation in advanced floor of the mouth cancer: a pilot study using a combination of IMRT and stereotactic boost
Authors: Blažek Tomáš , Zděblová Čermáková Zuzana , Knybel Lukáš , Hurník Pavel , Štembírek Jan , Resová Kamila , Paračková Tereza , Formánek Martin , Cvek Jakub , Soumarová Renata
Published: June 2021

Purpose

We evaluated the efficiency and toxicity of stereotactic hypofractionated boost in combination with conventionally fractionated radiotherapy in the treatment of advanced floor of the mouth cancer.

Methods

Thirty-seven patients with advanced stage of the floor of the mouth cancer, histologically confirmed squamous cell carcinoma (p16 negative) ineligible for surgical treatment, were indicated for radiochemotherapy or hyperfractionated accelerated radiotherapy (HART). The radiotherapy protocol combined external beam radiotherapy (EBRT) and a stereotactic hypofractionated boost to the primary tumor. The dose delivered from EBRT was 70–72.5 Gy in 35/50 fractions. The hypofractionated boost followed with 10 Gy in two fractions. For the variables—tumor volume, stage and grade a multivariate analysis was performed to find the relationship between overall survival, local progression and metastasis. Toxicity was evaluated according to CTCAE scale version 4.

Results

After a median follow-up of 16 months, 23 patients (62%) achieved complete remission. The median time to local progression and metastasis was 7 months. Local control (LC) at 2 and 5-years was 70% and 62%, respectively. Progression-free survival (PFS) and overall survival (OS) were 57% and 49% at 2 years and 41% and 27% at 5 years, respectively. Statistical analysis revealed that larger tumors had worse overall survival and a greater chance of metastasis. Log-Rank GTV > 44 ccm (HR = 1.96; [95% CI (0.87; 4.38)]; p = 0.11). No boost-related severe acute toxicity was observed. Late osteonecrosis was observed in 3 patients (8%).

Conclusion

The combination of EBRT and stereotactic hypofractionated boost is safe and seems to be an effective option for dose escalation in patients with advanced floor of the mouth tumors who are ineligible for surgical treatment and require a non-invasive approach.
DeepBeam: a machine learning framework for tuning the primary electron beam of the PRIMO Monte Carlo software
Authors: Tabor Zbisław , Kabat Damian , Waligórski Michael P. R.
Published: June 2021

Background

Any Monte Carlo simulation of dose delivery using medical accelerator-generated megavolt photon beams begins by simulating electrons of the primary electron beam interacting with a target. Because the electron beam characteristics of any single accelerator are unique and generally unknown, an appropriate model of an electron beam must be assumed before MC simulations can be run. The purpose of the present study is to develop a flexible framework with suitable regression models for estimating parameters of the model of primary electron beam in simulators of medical linear accelerators using real reference dose profiles measured in a water phantom.

Methods

All simulations were run using PRIMO MC simulator. Two regression models for estimating the parameters of the simulated primary electron beam, both based on machine learning, were developed. The first model applies Principal Component Analysis to measured dose profiles in order to extract principal features of the shapes of the these profiles. The PCA-obtained features are then used by Support Vector Regressors to estimate the parameters of the model of the electron beam. The second model, based on deep learning, consists of a set of encoders processing measured dose profiles, followed by a sequence of fully connected layers acting together, which solve the regression problem of estimating values of the electron beam parameters directly from the measured dose profiles. Results of the regression are then used to reconstruct the dose profiles based on the PCA model. Agreement between the measured and reconstructed profiles can be further improved by an optimization procedure resulting in the final estimates of the parameters of the model of the primary electron beam. These final estimates are then used to determine dose profiles in MC simulations.

Results

Analysed were a set of actually measured (real) dose profiles of 6 MV beams from a real Varian 2300 C/D accelerator, a set of simulated training profiles, and a separate set of simulated testing profiles, both generated for a range of parameters of the primary electron beam of the Varian 2300 C/D PRIMO simulator. Application of the two-stage procedure based on regression followed by reconstruction-based minimization of the difference between measured (real) and reconstructed profiles resulted in achieving consistent estimates of electron beam parameters and in a very good agreement between the measured and simulated photon beam profiles.

Conclusions

The proposed framework is a readily applicable and customizable tool which may be applied in tuning virtual primary electron beams of Monte Carlo simulators of linear accelerators. The codes, training and test data, together with readout procedures, are freely available at the site: https://github.com/taborzbislaw/DeepBeam.
Honeysuckle-derived microRNA2911 inhibits tumor growth by targeting TGF-β1
Authors: Liu Chunyan , Xu Mengzhen , Yan Luocheng , Wang Yulian , Zhou Zhen , Wang Shaocong , Sun Yajie , Zhang Junfeng , Dong Lei
Published: June 2021

Background

Honeysuckle is a time‐honored herb with anticancer activity in traditional Chinese medicine. Recently, accumulating reports are suggesting that the microRNAs in this medicinal plant not only play a physiological role in their original system, but also can be transmitted to another species as potential therapeutic components. In the numerous bioactive investigations, the anti-tumor effects of these microRNAs in the magical herb are rarely studied, especially the special miR2911, a honeysuckle-encoded atypical microRNA, with high stability during the boiling process and unique biological activity to target TGF-β1 mRNA.

Methods

Luciferase assay was conducted to test the ability of miR2911 to target TGF-β1 mRNA. ELISA was performed to determine the expression level of TGF-β1 of mouse colorectal adenocarcinoma CT26 cells when treated with miR2911 and tumor tissue in Sidt1+/+ and Sidt1−/− mice. qRT-PCR was performed to examine the level of expression of miR2911. Tumor-bearing wild and nude mice were employed to evaluate the anti-tumor effect of honeysuckle and miR2911 in vivo. Tumor tissue necrosis was observed by H&E staining. Besides, the infiltration of T lymphocytes across solid tumors was tested by immunostaining staining.

Results

Our results showed that honeysuckle slowed the development of colon cancer down. Further research showed that miR2911 could bind strongly to TGF-β1 mRNA and down-regulate the expression of TGF-β1 and had a high stability under boiling and acid condition. Moreover, SIDT1 mediated dietary miR2911 inter-species absorption. And we found that miR2911 had a similar anticancer effect as honeysuckle. Mechanistically, miR2911 reversed the tumor-promoting effect of TGF-β1 by an increase of T lymphocytes infiltration, resulting in slowing the colon cancer process in immunocompetent mice. Consistent with this inference, the anti-tumor effect of miR2911 was revealed to be abolished in T cell immune deficiency mice.

Conclusion

Taken together, honeysuckle-derived miR2911 showed an anti-tumor effect in colon cancer through targeting TGF-β1 mRNA. The down-regulation of TGF-β1 promoted T lymphocytes infiltration, and accordingly impeded the colon tumor development.
Structural design of tetravalent T-cell engaging bispecific antibodies: improve developability by engineering disulfide bonds
Authors: Yu Lin , Huang Nan , Ge Liangpeng , Sun Heng , Fu Yuna , Liu Chundong , Wang Jianhua
Published: June 2021

Since the advances in protein engineering and manufacture, over the last 30 years, antibody-based immunotherapeutic has become a powerful strategy to treat diseases. The T-cell engaging bispecific antibody (BsAb) by combining the Fab binding domain of tumor antigens and Fab or single-chain variable fragments (scFvs) binding domain of CD3 molecules, could redirect cytotoxic T cells to kill tumor cells. The IgG-scFv format of BsAb is a dual bivalent and asymmetrical design, which adds the benefit of potent cytotoxicity and less complicated for manufacture but limits the stability and production. Here, we engineered a series of interchain disulfide bonds in the Fab region of IgG-svFv BsAbs and evaluated its biophysical and biological properties. We found that simultaneously replaced the position of VH44-VL100 and CH1126-CL121 residues with cysteine, to form two additional disulfide bonds, could markedly increase monomeric BsAb formation and yield. The thermostability and stability against aggregation and degradation also performed better than BsAbs without extra disulfide bonds introduction. Besides, the affinity of engineered BsAbs was maintained, and the h8B-BsAb antibody had a slight enhancement in an inhibitory effect on target cells.
Improving analysis practice of continuous adverse event outcomes in randomised controlled trials - a distributional approach
Authors: Chis Ster Anca , Phillips Rachel , Sauzet Odile , Cornelius Victoria
Published: June 2021

Background

Randomised controlled trials (RCTs) provide valuable information for developing harm profiles but current analysis practices to detect between-group differences are suboptimal. Drug trials routinely screen continuous clinical and biological data to monitor participant harm. These outcomes are regularly dichotomised into abnormal/normal values for analysis. Despite the simplicity gained for clinical interpretation, it is well established that dichotomising outcomes results in a considerable reduction in information and thus statistical power. We propose an automated procedure for the routine implementation of the distributional method for the dichotomisation of continuous outcomes proposed by Peacock and Sauzet, which retains the precision of the comparison of means.

Methods

We explored the use of a distributional approach to compare differences in proportions based on the comparison of means which retains the power of the latter. We applied this approach to the screening of clinical and biological data as a means to detect ‘signals’ for potential adverse drug reactions (ADRs). Signals can then be followed-up in further confirmatory studies. Three distributional methods suitable for different types of distributions are described. We propose the use of an automated approach using the observed data to select the most appropriate distribution as an analysis strategy in a RCT setting for multiple continuous outcomes. We illustrate this approach using data from three RCTs assessing the efficacy of mepolizumab in asthma or COPD. Published reference ranges were used to define the proportions of participants with abnormal values for a subset of 10 blood tests. The between-group distributional and empirical differences in proportions were estimated for each blood test and compared.

Results

Within trials, the distributions varied across the 10 outcomes demonstrating value in a practical approach to selecting the distributional method in the context of multiple adverse event outcomes. Across trials, there were three outcomes where the method chosen by the automated procedure varied for the same outcome. The distributional approach identified three signals (eosinophils, haematocrit, and haemoglobin) compared to only one when using the Fisher’s exact test (eosinophils) and two identified by use of the 95% confidence interval for the difference in proportions (eosinophils and potassium).

Conclusion

When dichotomisation of continuous adverse event outcomes aids clinical interpretation, we advocate use of a distributional approach to retain statistical power. Methods are now easy to implement. Retaining information is especially valuable in the context of the analysis of adverse events in RCTs. The routine implementation of this automated approach requires further evaluation.
Survival analysis for AdVerse events with VarYing follow-up times (SAVVY)—estimation of adverse event risks
Authors: Stegherr Regina , Schmoor Claudia , Beyersmann Jan , Rufibach Kaspar , Jehl Valentine , Brückner Andreas , Eisele Lewin , Künzel Thomas , Kupas Katrin , Langer Frank , Leverkus Friedhelm , Loos Anja , Norenberg Christiane , Voss Florian , Friede Tim
Published: June 2021

Background

The SAVVY project aims to improve the analyses of adverse events (AEs), whether prespecified or emerging, in clinical trials through the use of survival techniques appropriately dealing with varying follow-up times and competing events (CEs). Although statistical methodologies have advanced, in AE analyses, often the incidence proportion, the incidence density, or a non-parametric Kaplan-Meier estimator are used, which ignore either censoring or CEs. In an empirical study including randomized clinical trials from several sponsor organizations, these potential sources of bias are investigated. The main purpose is to compare the estimators that are typically used to quantify AE risk within trial arms to the non-parametric Aalen-Johansen estimator as the gold-standard for estimating cumulative AE probabilities. A follow-up paper will consider consequences when comparing safety between treatment groups.

Methods

Estimators are compared with descriptive statistics, graphical displays, and a more formal assessment using a random effects meta-analysis. The influence of different factors on the size of deviations from the gold-standard is investigated in a meta-regression. Comparisons are conducted at the maximum follow-up time and at earlier evaluation times. CEs definition does not only include death before AE but also end of follow-up for AEs due to events related to the disease course or safety of the treatment.

Results

Ten sponsor organizations provided 17 clinical trials including 186 types of investigated AEs. The one minus Kaplan-Meier estimator was on average about 1.2-fold larger than the Aalen-Johansen estimator and the probability transform of the incidence density ignoring CEs was even 2-fold larger. The average bias using the incidence proportion was less than 5%. Assuming constant hazards using incidence densities was hardly an issue provided that CEs were accounted for. The meta-regression showed that the bias depended mainly on the amount of censoring and on the amount of CEs.

Conclusions

The choice of the estimator of the cumulative AE probability and the definition of CEs are crucial. We recommend using the Aalen-Johansen estimator with an appropriate definition of CEs whenever the risk for AEs is to be quantified and to change the guidelines accordingly.
Prospective Randomized Evaluation of Decompressive Ipsilateral Craniectomy for Traumatic Acute Epidural Hematoma (PREDICT-AEDH): study protocol for a randomized controlled trial
Authors: Yang Chun , Huang Xianjian , Feng Junfeng , Xie Li , Hui Jiyuan , Li Weiping , Jiang Jiyao
Published: June 2021

Background

The expeditious surgical evacuation of acute epidural hematoma (AEDH) is an attainable gold standard and is often expected to have a good clinical outcome for patients with surgical indications. However, controversy exists on the optimal surgical options for AEDH, especially for patients with brain herniation. Neurosurgeons are confronted with the decision to evacuate the hematoma with decompressive craniectomy (DC) or craniotomy.

Methods/design

Patients of both sexes, age between 18 and 65 years, who presented to the emergency room with a clinical and radiological diagnosis of AEDH with herniation, were assessed against the inclusion and exclusion criteria to be enrolled in the study. Clinical and radiological information, including diagnosis of AEDH, treatment procedures, and follow-up data at 1, 3, and 6 months after injury, was collected from 120 eligible patients in 51 centers. The patients were randomized into groups of DC versus craniotomy in a 1:1 ratio. The primary outcome was the Glasgow Outcome Score-Extended (GOSE) at 6 months post-injury. Secondary outcomes included incidence of postoperative cerebral infarction, incidence of additional craniocerebral surgery, and other evaluation indicators within 6 months post-injury.

Discussion

This study is expected to support neurosurgeons in their decision to evacuate the epidural hematoma with or without a DC, especially in patients with brain herniation, and provide additional evidence to improve the knowledge in clinical practice.

Trial registration

ClinicalTrials.govNCT 04261673. Registered on 04 February 2020
Cost talk: protocol for a stepped-wedge cluster randomized trial of an intervention helping patients and urologic surgeons discuss costs of care for slow-growing prostate cancer during shared decision-making
Authors: Politi Mary C. , Forcino Rachel C. , Parrish Katelyn , Durand Marie-Anne , O’Malley A. James , Elwyn Glyn
Published: June 2021

Background

Costs of care are important to patients making cancer treatment decisions, but clinicians often do not feel prepared to discuss treatment costs. We aim to (1) assess the impact of a conversation-based decision aid (Option Grid) containing cost information about slow-growing prostate cancer management options, combined with urologic surgeon training, on the frequency and quality of patient-urologic surgeon cost conversations, and (2) examine the impact of the decision aid and surgeon training on decision quality.

Methods

We will conduct a stepped-wedge cluster randomized trial in outpatient urology practices affiliated with a large academic medical center in the USA. We will randomize five urologic surgeons to four intervention sequences and enroll their patients with a first-time diagnosis of slow-growing prostate cancer independently at each period. Primary outcomes include frequency of cost conversations, initiator of cost conversations, and whether or not a referral is made to address costs. These outcomes will be collected by patient report (post-visit survey) and by observation (audio-recorded clinic visits) with consent. Other outcomes include the following: patient-reported decisional conflict post-visit and at 3-month follow-up, decision regret at 3-month follow-up, shared decision-making post-visit, communication post-visit, and financial toxicity post-visit and at 3-month follow-up; clinician-reported attitudes about shared decision-making before and after the study, and feasibility of sustained intervention use. We will use hierarchical regression analysis to assess patient-level outcomes, including urologic surgeon as a random effect to account for clustering of patient participants.

Discussion

This study evaluates a two-part intervention to improve cost discussions between urologic surgeons and patients when deciding how to manage slow-growing prostate cancer. Establishing the effectiveness of the strategy under study will allow for its replication in other clinical decision contexts.

Trial registration

ClinicalTrials.govNCT04397016. Registered on 21 May 2020
Stereotactic EEG-guided radiofrequency thermocoagulation versus anterior temporal lobectomy for mesial temporal lobe epilepsy with hippocampal sclerosis: study protocol for a randomised controlled trial
Authors: Wang Yi-He , Chen Si-Chang , Wei Peng-Hu , Yang Kun , Fan Xiao-Tong , Meng Fei , Du Jia-Lin , Ren Lian-Kun , Shan Yong-Zhi , Zhao Guo-Guang
Published: June 2021

Introduction

In this report, we aim to describe the design for the randomised controlled trial of Stereotactic electroencephalogram (EEG)-guided Radiofrequency Thermocoagulation versus Anterior Temporal Lobectomy for Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (STARTS). Mesial temporal lobe epilepsy (mTLE) is a classical subtype of temporal lobe epilepsy that often requires surgical intervention. Although anterior temporal lobectomy (ATL) remains the most popular treatment for mTLE, accumulating evidence has indicated that ATL can cause tetartanopia and memory impairments. Stereotactic EEG (SEEG)-guided radiofrequency thermocoagulation (RF-TC) is a non-invasive alternative associated with lower seizure freedom but greater preservation of neurological function. In the present study, we aim to compare the safety and efficacy of SEEG-guided RF-TC and classical ATL in the treatment of mTLE.

Methods and analysis

STARTS is a single-centre, two-arm, randomised controlled, parallel-group clinical trial. The study includes patients with typical mTLE over the age of 14 who have drug-resistant seizures for at least 2 years and have been determined via detailed evaluation to be surgical candidates prior to randomisation. The primary outcome measure is the cognitive function at the 1-year follow-up after treatment. Seizure outcomes, visual field abnormalities after surgery, quality of life, ancillary outcomes, and adverse events will also be evaluated at 1-year follow-up as secondary outcomes.

Discussion

SEEG-guided RF-TC for mTLE remains a controversial seizure outcome but has the advantage for cognitive and visual field protection. This is the first RCT studying cognitive outcomes and treatment results between SEEG-guided RF-TC and standard ATL for mTLE with hippocampal sclerosis. This study may provide higher levels of clinical evidence for the treatment of mTLE.

Trial registration

ClinicalTrials.gov NCT03941613. Registered on May 8, 2019. The STARTS protocol has been registered on the US National Institutes of Health. The status of the STARTS was recruiting and the estimated study completion date was December 31, 2021.
Data-driven and interpretable machine-learning modeling to explore the fine-scale environmental determinants of malaria vectors biting rates in rural Burkina Faso
Authors: Taconet Paul , Porciani Angélique , Soma Dieudonné Diloma , Mouline Karine , Simard Frédéric , Koffi Alphonsine Amanan , Pennetier Cedric , Dabiré Roch Kounbobr , Mangeas Morgan , Moiroux Nicolas
Published: June 2021

Background

Improving the knowledge and understanding of the environmental determinants of malaria vector abundance at fine spatiotemporal scales is essential to design locally tailored vector control intervention. This work is aimed at exploring the environmental tenets of human-biting activity in the main malaria vectors (Anopheles gambiae s.s.,Anopheles coluzziiandAnopheles funestus) in the health district of Diébougou, rural Burkina Faso.

Methods

Anopheleshuman-biting activity was monitored in 27 villages during 15 months (in 2017–2018), and environmental variables (meteorological and landscape) were extracted from high-resolution satellite imagery. A two-step data-driven modeling study was then carried out. Correlation coefficients between the biting rates of each vector species and the environmental variables taken at various temporal lags and spatial distances from the biting events were first calculated. Then, multivariate machine-learning models were generated and interpreted to (i) pinpoint primary and secondary environmental drivers of variation in the biting rates of each species and (ii) identify complex associations between the environmental conditions and the biting rates.

Results

Meteorological and landscape variables were often significantly correlated with the vectors’ biting rates. Many nonlinear associations and thresholds were unveiled by the multivariate models, for both meteorological and landscape variables. From these results, several aspects of the bio-ecology of the main malaria vectors were identified or hypothesized for the Diébougou area, including breeding site typologies, development and survival rates in relation to weather, flight ranges from breeding sites and dispersal related to landscape openness.

Conclusions

Using high-resolution data in an interpretable machine-learning modeling framework proved to be an efficient way to enhance the knowledge of the complex links between the environment and the malaria vectors at a local scale. More broadly, the emerging field of interpretable machine learning has significant potential to help improve our understanding of the complex processes leading to malaria transmission, and to aid in developing operational tools to support the fight against the disease (e.g. vector control intervention plans, seasonal maps of predicted biting rates, early warning systems).

Graphical abstract
Benign meningioma manifesting with acute subdural hematoma and cerebral edema: a case report and review of the literature
Authors: Nam Ji Won , Park Eun Suk , Park Jun Bum , Seo Jae Hee , Kim Minsoo , Jung Na Young
Published: June 2021

Background

Spontaneous subdural hematoma rarely presents with a hypervascular or malignant tumor but even less frequently in a benign tumor like meningioma. We encountered a patient with acute subdural hematoma associated with benign meningioma. Here, we report this case along with a review of previous reports, especially focusing on their clinical features and possible bleeding mechanisms.

Case presentation

A 53-year-old Asian woman presented with severe headache and progressive neurologic deterioration due to cerebral edema. The patient was submitted to open surgery for evacuation of the subdural hematoma and concurrent tumor removal on the ipsilateral parietal convexity. A hypervascular, encapsulated mass was identified during surgery and completely removed including the adjacent dura mater (Simpson grade 0). The tumor was histologically confirmed as an angiomatous meningioma (World Health Organization grade I). Her clinical course was uneventful after surgery.

Conclusions

Although meningiomas are commonly benign according to their histological traits, they can lead to spontaneous bleeding and cause neurologically unstable condition. Therefore, meningiomas need to be considered as a cause of spontaneous subdural hematoma if radiologically suspicious, which should be reflected by proper management for a positive outcome.
Integrin αvβ6-targeted MR molecular imaging of breast cancer in a xenograft mouse model
Authors: Li Dengfeng , Dong Chengyan , Ma Xiaohong , Zhao Xinming
Published: June 2021

Background

The motif RXDLXXL-based nanoprobes allow specific imaging of integrin αvβ6, a protein overexpressed during tumorigenesis and tumor progression of various tumors. We applied a novel RXDLXXL-coupled cyclic arginine-glycine-aspartate (RGD) nonapeptide conjugated with ultrasmall superparamagnetic iron oxide nanoparticles (referred to as cFK-9-USPIO) for the application of integrin αvβ6-targeted magnetic resonance (MR) molecular imaging for breast cancer.

Methods

A novel MR-targeted nanoprobe, cFK-9-USPIO, was synthesized by conjugating integrin αvβ6-targeted peptide cFK-9 to N-amino (−NH2)-modified USPIO nanoparticles via a dehydration esterification reaction. Integrin αvβ6-positive mouse breast cancer (4 T1) and integrin αvβ6 negative human embryonic kidney 293 (HEK293) cell lines were incubated with cFK-9-AbFlour 647 (blocking group) or cFK-9-USPIO (experimental group), and subsequently imaged using laser scanning confocal microscopy (LSCM) and 3.0 Tesla magnetic resonance imaging (MRI) system. The affinity of cFK-9 targeting αvβ6 was analyzed by calculating the mean fluorescent intensity in cells, and the nanoparticle targeting effect was measured by the reduction of T2 values in an in vitro MRI. The in vivo MRI capability of cFK-9-USPIO was investigated in 4 T1 xenograft mouse models. Binding of the targeted nanoparticles to αvβ6-positive 4 T1 tumors was determined by ex vivo histopathology.

Results

In vitro laser scanning confocal microscopy (LSCM) imaging showed that the difference in fluorescence intensity between the targeting and blocking groups of 4 T1 cells was significantly greater than that in HEK293 cells (P < 0.05). The in vitro MRI demonstrated a more remarkable T2 reduction in 4 T1 cells than in HEK293 cells (P < 0.001). The in vivo MRI of 4 T1 xenograft tumor-bearing nude mice showed significant T2 reduction in tumors compared to controls. Prussian blue staining further confirmed that αvβ6 integrin-targeted nanoparticles were specifically accumulated in 4 T1 tumors and notably fewer nanoparticles were detected in 4 T1 tumors of mice injected with control USPIO and HEK293 tumors of mice administered cFK-9-USPIO.

Conclusions

Integrin αvβ6-targeted nanoparticles have great potential for use in the detection of αvβ6-overexpressed breast cancer with MR molecular imaging.
Colorectal cancer screening in Uruguay: current assessment and roadmap for the future
Authors: Reich Micaela , Buki Lydia P.
Published: June 2021

Cancer is a leading cause of death worldwide and is expected to remain a public health concern for years to come. Within Latin America, Uruguay has the highest colorectal cancer rates. Heeding past calls to action, in this article we provide a critical assessment of colorectal cancer needs and opportunities in Uruguay with a focus on developing a roadmap for future action. First, we provide an overview of risk factors, screening procedures and guidelines, and screening rates. Next, we provide an overview of psychosocial factors that influence colorectal cancer screening, with the goal of providing guidance for future behavioral health promotion initiatives in Uruguay. In this effort, we present four conceptual models that may be used for interventions: the ecological systems theory, informed decision-making, the health beliefs model, and the health literacy model. Subsequently, we propose using an integrated model based on the ecological systems theory and health literacy model to develop national, local, and community-based interventions to increase screening rates and lower the colorectal cancer burden in Uruguay. We close the paper with a summary and implications section, including recommendations for future research programs focused on the assessment of factors that influence screening.
Protocol for a pharmacogenomic study on individualised antipsychotic drug treatment for patients with schizophrenia
Authors: Su Yi , Yu Hao , Wang Zhiren , Liu Sha , Zhao Liansheng , Fu Yingmei , Yang Yongfeng , Du Bo , Zhang Fuquan , Zhang Xiangrong , Huang Manli , Hou Cailan , Huang Guoping , Su Zhonghua , Peng Mao , Yan Ran , Zhang Yuyanan , Yan Hao , Wang Lifang , Lu Tianlan , Jia Fujun , Li Keqing , Lv Luxian , Wang Hongxing , Yu Shunying , Wang Qiang , Tan Yunlong , Xu Yong , Zhang Dai , Yue Weihua
Published: June 2021

Background

Schizophrenia is a severe and complex psychiatric disorder that needs treatment based on extensive experience. Antipsychotic drugs have already become the cornerstone of the treatment for schizophrenia; however, the therapeutic effect is of significant variability among patients, and only around a third of patients with schizophrenia show good efficacy. Meanwhile, drug-induced metabolic syndrome and other side-effects significantly affect treatment adherence and prognosis. Therefore, strategies for drug selection are desperately needed. In this study, we will perform pharmacogenomics research and set up an individualised preferred treatment prediction model.

Aims

We aim to create a standard clinical cohort, with multidimensional index assessment of antipsychotic treatment for patients with schizophrenia.

Method

This trial is designed as a randomised clinical trial comparing treatment with different kinds of antipsychotics. A total sample of 2000 patients with schizophrenia will be recruited from in-patient units from five clinical research centres. Using a computer-generated program, the participants will be randomly assigned to four treatment groups: aripiprazole, olanzapine, quetiapine and risperidone. The primary outcomes will be measured as changes in the Positive and Negative Syndrome Scale of schizophrenia, which reflects the efficacy. Secondary outcomes include the measure of side-effects, such as metabolic syndromes. The efficacy evaluation and side-effects assessment will be performed at baseline, 2 weeks, 6 weeks and 3 months.

Results

This trial will assess the efficacy and side effects of antipsychotics and create a standard clinical cohort with a multi-dimensional index assessment of antipsychotic treatment for schizophrenia patients.

Conclusion

This study aims to set up an individualized preferred treatment prediction model through the genetic analysis of patients using different kinds of antipsychotics.
NGS in Lung, Breast, and Unknown Primary Cancer in Colombia: A Multidisciplinary Consensus on Challenges and Opportunities
Authors: Mantilla William Armando , Sanabria-Salas María Carolina , Baldion Ana Margarita , Sua Luz F. , Gonzalez Diego Mauricio , Lema Mauricio
Published: June 2021

Given the benefits and likely future applications, there is an urgent need to expand the use of next-generation sequencing (NGS) in breast, lung, and unknown primary cancers in Colombia. The objective of this review is to address the barriers limiting access to the use of NGS in Colombia, specifically for patients with breast, lung, and unknown primary cancers in the public health care system. A selected Panel of Colombian experts in NGS were provided with a series of relevant questions to address in a multiday conference. Each narrative was discussed and edited by the Panel through numerous drafts and rounds of discussion until consensus was achieved. There are limitations to the widespread adoption of innovative technology inherent to the Colombian health care system. Barriers identified to implementing NGS in Colombia include availability, accessibility, and affordability; limited infrastructure; training and awareness of health personnel; quality-control procedures; and collection of local data. Stakeholders must align to adapt the implementation of NGS to the constraints of resource-limited environments. Diagnostic algorithms were developed to guide molecular testing for lung, breast, and unknown primary cancers. Recommendations on overcoming the barriers to the widespread adoption of NGS include country-specific molecular testing guidelines, creating a national genetic registry, improving infrastructure, and creating health policy that favors the adoption of innovative technology.
Tobacco Use and Tobacco Treatment Referral Response of Patients With Cancer: Implementation Outcomes at a National Cancer Institute–Designated Cancer Center
Authors: Burris Jessica L. , Borger Tia N. , Shelton Brent J. , Darville Audrey K. , Studts Jamie L. , Valentino Joseph , Blair Courtney , Davis D. Bront , Scales Joan
Published: June 2021

PURPOSE:

Smoking after a cancer diagnosis is linked to cancer-specific and all-cause mortality, among other adverse outcomes. Yet, 10%-20% of US cancer survivors are current smokers. Implementation of evidence-based tobacco treatment in cancer care facilities is widely recommended, yet rarely accomplished. This study focuses on the early outcomes of a population-based tobacco treatment program integrated within an National Cancer Institute–designated cancer center.

METHODS AND MATERIALS:

The sample consists of 26,365 patients seen at the cancer center during the first 18 months of program implementation. The study is a retrospective chart review of patients' tobacco use and, among current users, patients' treatment referral response.

RESULTS:

More than 99% of patients were screened for tobacco use. Current (past month) use was observed in 21.05% of patients; cigarettes were the most popular product. Only 17.22% of current users accepted a referral for tobacco treatment; among current users who declined, the majority were not ready to quit (65.84%) or wanted to quit on their own (27.01%). Multiple demographic variables were associated with tobacco use and treatment referral response outcomes.

CONCLUSION:

Despite cancer diagnosis presenting a teachable moment for tobacco cessation, patients with cancer may not be ready to quit or engage with treatment. Clinically proven strategies to increase motivation, prompt quit attempts, and encourage treatment use should be key components of tobacco treatment delivery to patients with cancer.
Cardiometabolic Outcomes and Mortality in Patients with Adrenal Adenomas in a Population-based Setting
Authors: Zhang Catherine D , Li Dingfeng , Kaur Ravinder Jeet , Ebbehoj Andreas , Singh Sumitabh , Atkinson Elizabeth J , Achenbach Sara J , Young William F , Arlt Wiebke , Rocca Walter A , Bancos Irina
Published: June 2021

Context

While adrenal adenomas have been linked with cardiovascular morbidity in convenience samples of patients from specialized referral centers, large-scale population-based data are lacking.

Objective

To determine the prevalence and incidence of cardiometabolic disease and assess mortality in a population-based cohort of patients with adrenal adenomas.

Design

Population-based cohort study.

Setting

Olmsted County, Minnesota, USA.

Patients

Patients diagnosed with adrenal adenomas without overt hormone excess and age- and sex-matched referent subjects without adrenal adenomas.

Main outcome measure

Prevalence, incidence of cardiometabolic outcomes, mortality.

Results

(Adrenal adenomas were diagnosed in 1004 patients (58% women, median age 63 years) from 1/01/1995 to 12/31/2017. At baseline, patients with adrenal adenomas were more likely to have hypertension [adjusted odds ratio (aOR) 1.96, 95% CI 1.58-2.44], dysglycemia (aOR 1.63, 95% CI 1.33-2.00), peripheral vascular disease (aOR 1.59, 95% CI 1.32-2.06), heart failure (aOR 1.64, 95% CI 1.15-2.33), and myocardial infarction (aOR 1.50, 95% CI 1.02-2.22) compared to referent subjects. During median follow-up of 6.8 years, patients with adrenal adenomas were more likely than referent subjects to develop de novo chronic kidney disease [adjusted hazard ratio (aHR) 1.46, 95% CI 1.14-1.86], cardiac arrhythmia (aHR 1.31, 95% CI 1.08-1.58), peripheral vascular disease (aHR 1.28, 95% CI 1.05-1.55), cardiovascular events (aHR 1.33, 95% CI 1.01-1.73), and venous thromboembolic events (aHR 2.15, 95% CI 1.48-3.13). Adjusted mortality was similar between the 2 groups.

Conclusion

Adrenal adenomas are associated with an increased prevalence and incidence of adverse cardiometabolic outcomes in a population-based cohort.
Secondary Breast Cancer Sociodemographic Characteristics and Survival by Age Group
Authors: Sauder Candice A. M. , Li Qian , Bold Richard J. , Ruddy Kathryn J. , Keegan Theresa H. M.
Published: June 2021

Background

Secondary cancers account for 16% of all new cancer diagnoses, with breast cancer (BC) the most common secondary cancer. We have shown that secondary BC has unique characteristics and decreased survival compared with primary BC in adolescent and young adults (AYA; 15–39 years old). However, older BC populations are less well studied.

Methods

Females (age ≥ 15 years) diagnosed with primary BC during 1991–2015 (n = 377,167) and enrolled in the California Cancer Registry were compared with those with secondary BC (n = 37,625) by age (15–39, 40–64, ≥ 65 years). We examined BC-specific survival (BCSS) accounting for other causes of death as a competing risk using multivariable Cox proportional hazards regression.

Results

Most secondary BC patients were of older age (15–39, n = 777; 40–64, n = 15,848; ≥ 65, n = 21,000). Compared with primary BC treatment, secondary BCs were more often treated with mastectomy and less often with chemotherapy and/or radiation. BCSS was shorter in secondary BC patients than primary BC patients, but the survival difference between secondary and primary BC diminished with age [15–39 hazard ratio (HR): 2.09, 95% confidence interval (CI) 1.83–2.39; 40–64 HR: 1.51; 95% CI 1.44–1.58; ≥ 65 HR: 1.14; 95% CI 1.10–1.19]. Survival differences were most pronounced in women with hormone receptor positive disease and Hispanic and Asian/Pacific Islanders 40–64 years of age.

Conclusions

When BC is diagnosed following a prior cancer of any organ site, BCSS is worse than when compared with patients for whom BC is the primary diagnosis, suggesting that we may need to tailor our treatments for women with secondary BC.
Tight Money-Tight Credit: Coordination Failure in the Conduct of Monetary and Financial Policies
Authors: Carrillo Julio A. , Mendoza Enrique G. , Nuguer Victoria , Roldán-Peña Jessica
Published: June 2021

Violations of Tinbergen’s rule and strategic interaction undermine stabilization policies in a New Keynesian model with the Bernanke-Gertler accelerator. Welfare costs of risk shocks are large because of efficiency losses and income effects of costly monitoring, but they are much larger under a simple Taylor rule (STR) or a Taylor rule augmented with credit spreads (ATR) than with a Taylor rule and a separate financial rule targeting spreads. ATR and STR are tight money-tight credit regimes responding too much (little) to inflation (spreads). The Nash equilibrium of monetary and financial policies is also tight money-tight credit but it dominates ATR and STR. (JEL E12, E31, E44, E43, E52, E63)
Features of the Personal Adaptability of Medical Students in Different Courses of Study
Authors: Timofeeva Yuliya
Published: June 2021

The article is devoted to the study of personal adaptability of medical students enrolled in different courses. Various approaches to the concept of personal adaptability are analyzed, methods of its diagnostics are considered, the structure of personal adaptability of medical students of all courses is revealed. As a result of empirical research, it is possible to state that the greatest deficiency in the structure of personal adaptability characterized by a socio-oriented type prevails in the first, second and fourth years of study at a medical school. Personal adaptability of third-year students has an average level. The most harmoniously developed adaptability with the predominant characteristics of an autonomously oriented personality is possessed by students of the fifth and sixth years of a medical school.
The Personality of the Serviceman and His Leadership Qualities
Authors: Yunel' S.
Published: June 2021

The article presents a study conducted to study the relationship between personality traits and leadership qualities of military personnel in the Armed Forces of the Russian Federation. Approaches to the study of leadership as a socio-psychological phenomenon are described. Scientific approaches to the concepts of "personal qualities" and "leadership qualities" are analyzed. The features of the personality of military personnel are considered. The aim is to identify the relationship between personality traits and leadership qualities of military personnel. The objectives of the study are: description of approaches to the definition of personality and personal properties in the works of foreign and domestic psychologists; empirical identification of personality traits in military personnel; identification of the severity of leadership qualities in military personnel; establishing the relationship between personality traits and leadership qualities of military personnel. The research uses theoretical, empirical, and statistical research methods. The obtained data suggest that the relationship between personal characteristics and leadership qualities is reliable. The results of the study can be useful for improving the effectiveness of working with military personnel, the formation of professionally important leadership qualities.
Between Hopelessness and Despair: Afropessimism and Black Nihilism in Ta-Nehisi Coates's Works
Authors: Puyuelo Ureña Eva
Published: June 2021

Most of the criticism that Ta-Nehisi Coates received in the aftermath of the publication of his work Between the World and Me orbits around its lack of hopefulness. Indeed, it is several times in the text that Coates tempers his son’s expectations about foreseeing an end to racial conflicts as he tells him that “I do not believe that we can stop [racists], Samori, because they must ultimately stop themselves” (Between the World 151). Certainly, the previous contention has drawn critics into reading Coates’s work as an attack against black agency (Chatterton Williams n.p.). It is our contention that, far from being read as a manifestation of cynicism, Coates’s negativity also has a galvanizing dimension. In fact, by emphasizing the futility of hope, which for Coates traps black individuals in an “unending pursuit” of progress (Warren “Black Nihilism” 221), he provides readers with many alternatives to confront the rampant racism that still pervades U.S. society nowadays.
The Hybridization Of The Noir Genre As Expression Of Ethnic Heritage: Rafael Navarro’s Sonambulo
Authors: Marta Marini Anna
Published: June 2021

In his ongoing comic book series Sonambulo, versatile artist Rafael Navarro has been able to channel his Mexican American cultural heritage by creating a unique blend of narrative genres. In his work, Navarro exploits classic American film noir as a fundamental reference and hybridizes it with elements distinctive to a shared Chicanx heritage, such as lucha libre cinema, horror folktales, and border-crossing metaphors; the construction of an oneiric dimension helps bring the narrative together, marking it with a peculiar ambiance. Drawing heavily on a diverse range of film genres, as well as ethnocultural pivots, this comic book series carves out a definite space in the panorama of the Mexican American production of popular culture, adding a powerful voice to the expression of US ethnic minorities.