bluuebunny/crossref_metadata_2025_split huggingface dataset:
Au-siRNA@ aptamer nanocages as a high-efficiency drug and gene delivery system for targeted lung cancer therapy
Authors: Yang Yuming , Han Yu , Sun Qiuyang , Cheng Jin , Yue Caixia , Liu Yanlei , Song Jie , Jin Weilin , Ding Xianting , de la Fuente Jesús M. , Ni Jian , Wang Xiaoqiang , Cui Daxiang 
Published: February 2021

Abstract
Background
Gene and chemical therapy has become one of the rising stars in the field of molecular medicine during the last two decades. However, there are still numerous challenges in the development of efficient, targeted, and safe delivery systems that can avoid siRNA degradation and reduce the toxicity and adverse effects of chemotherapy medicine.

Results
In this paper, a highly efficient AS1411 aptamer modified, dsDNA and MMP-2 cleavable peptide-fabricated gold nanocage vehicle, which could load doxorubicin hydrochloride (DOX) and siRNAs to achieve a combination of tumor responsive genetic therapy, chemotherapy, and photothermal treatment is presented. Our results show that this combined treatment achieved targeted gene silencing and tumor inhibition. After nearly one month of treatment with DOX-loaded Au-siRNA-PAA-AS1411 nanoparticles with one dose every three days in mice, a synergistic effect promoting the eradication of long-lived tumors was observed along with an increased survival rate of mice. The combined genetic, chemotherapeutic, and photothermal treatment group exhibited more than 90% tumor inhibition ratio (tumor signal) and a ~ 67% survival rate compared with a 30% tumor inhibition ratio and a 0% survival rate in the passive genetic treatment group.

Conclusions
The development of nanocarriers with double-stranded DNA and MMP-2 cleavable peptides provides a new strategy for the combined delivery of gene and chemotherapy medicine. Au-siRNA-PAA-AS1411 exerts high anticancer activities on lung cancer, indicating immense potentials for clinical application.
Inflammasome activation controlled by the interplay between post-translational modifications: emerging drug target opportunities
Authors: Liang Zhu , Damianou Andreas , Di Daniel Elena , Kessler Benedikt M. 
Published: February 2021

AbstractControlling the activation of the NLRP3 inflammasome by post-translational modifications (PTMs) of critical protein subunits has emerged as a key determinant in inflammatory processes as well as in pathophysiology. In this review, we put into context the kinases, ubiquitin processing and other PTM enzymes that modify NLRP3, ASC/PYCARD and caspase-1, leading to inflammasome regulation, activation and signal termination. Potential target therapeutic entry points for a number of inflammatory diseases focussed on PTM enzyme readers, writers and erasers, leading to the regulation of inflammasome function, are discussed.
Regulating cell fate of human amnion epithelial cells using natural compounds: an example of enhanced neural and pigment differentiation by 3,4,5-tri-O-caffeoylquinic acid
Authors: Bejaoui Meriem , Ferdousi Farhana , Zheng Yun-Wen , Oda Tatsuya , Isoda Hiroko 
Published: February 2021

AbstractOver the past years, Human Amnion Epithelial Cells (hAECs), a placental stem cell, are gaining higher attention from the scientific community as they showed several advantages over other types of stem cells, including availability, easy accessibility, reduced rejection rate, non-tumorigenicity, and minimal legal constraint. Recently, natural compounds are used to stimulate stem cell differentiation and proliferation and to enhance their disease-treating potential. A polyphenolic compound 3,4,5-Tri-O-Caffeoylquinic Acid (TCQA) has been previously reported to induce human neural stem cell differentiation and may affect melanocyte stem cell differentiation as well. In this study, TCQA was tested on 3D cultured hAECs after seven days of treatment, and then, microarray gene expression profiling was conducted of TCQA-treated and untreated control cells on day 0 and day 7. Analyses revealed that TCQA treatment significantly enriched pigment and neural cells sets; besides, genes linked with neurogenesis, oxidation–reduction process, epidermal development, and metabolism were positively regulated. Interestingly, TCQA stimulated cell cycle arrest-related pathways and differentiation signaling. On the other hand, TCQA decreased interleukins and cytokines expression and this due to its anti-inflammatory properties as a polyphenolic compound. Results were validated to highlight the main activities of TCQA on hAECs, including differentiation, cell cycle arrest, and anti-inflammatory. This study highlights the important role of hAECs in regenerative medicine and the use of natural compounds to regulate their fate.
Plant diseases and pests detection based on deep learning: a review
Authors: Liu Jun , Wang Xuewei 
Published: February 2021

AbstractPlant diseases and pests are important factors determining the yield and quality of plants. Plant diseases and pests identification can be carried out by means of digital image processing. In recent years, deep learning has made breakthroughs in the field of digital image processing, far superior to traditional methods. How to use deep learning technology to study plant diseases and pests identification has become a research issue of great concern to researchers. This review provides a definition of plant diseases and pests detection problem, puts forward a comparison with traditional plant diseases and pests detection methods. According to the difference of network structure, this study outlines the research on plant diseases and pests detection based on deep learning in recent years from three aspects of classification network, detection network and segmentation network, and the advantages and disadvantages of each method are summarized. Common datasets are introduced, and the performance of existing studies is compared. On this basis, this study discusses possible challenges in practical applications of plant diseases and pests detection based on deep learning. In addition, possible solutions and research ideas are proposed for the challenges, and several suggestions are given. Finally, this study gives the analysis and prospect of the future trend of plant diseases and pests detection based on deep learning.
Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice
Authors: Guo Yujun , Zou Guichang , Qi Keke , Jin Jin , Yao Lei , Pan Yang , Xiong Wei 
Published: February 2021

AbstractLipophilic statins which are blood brain barrier (BBB) permeable are speculated to affect the cholesterol synthesis and neural functions in the central nervous system. However, whether these statins can affect cholesterol levels and synaptic plasticity in hippocampus and the in vivo consequence remain unclear. Here, we report that long-term subcutaneous treatments of simvastatin significantly impair mouse hippocampal synaptic plasticity, reflected by the attenuated long-term potentiation of field excitatory postsynaptic potentials. The simvastatin administration causes a deficiency in recognition and spatial memory but fails to affect motor ability and anxiety behaviors in the mice. Mass spectrometry imaging indicates a significant decrease in cholesterol intensity in hippocampus of the mice receiving chronic simvastatin treatments. Such effects of simvastatin are transient because drug discontinuation can restore the hippocampal cholesterol level and synaptic plasticity and the memory function. These findings may provide further clues to elucidate the mechanisms of neurological side effects, especially the brain cognitive function impairment, caused by long-term usage of BBB-permeable statins.
Helmet CPAP to treat hypoxic pneumonia outside the ICU: an observational study during the COVID-19 outbreak
Authors: Coppadoro Andrea , Benini Annalisa , Fruscio Robert , Verga Luisa , Mazzola Paolo , Bellelli Giuseppe , Carbone Marco , Mulinacci Giacomo , Soria Alessandro , Noè Beatrice , Beck Eduardo , Di Sciacca Riccardo , Ippolito Davide , Citerio Giuseppe , Valsecchi Maria Grazia , Biondi Andrea , Pesci Alberto , Bonfanti Paolo , Gaudesi Davide , Bellani Giacomo , Foti Giuseppe 
Published: February 2021

Abstract
Background
Respiratory failure due to COVID-19 pneumonia is associated with high mortality and may overwhelm health care systems, due to the surge of patients requiring advanced respiratory support. Shortage of intensive care unit (ICU) beds required many patients to be treated outside the ICU despite severe gas exchange impairment. Helmet is an effective interface to provide continuous positive airway pressure (CPAP) noninvasively. We report data about the usefulness of helmet CPAP during pandemic, either as treatment, a bridge to intubation or a rescue therapy for patients with care limitations (DNI).

Methods
In this observational study we collected data regarding patients failing standard oxygen therapy (i.e., non-rebreathing mask) due to COVID-19 pneumonia treated with a free flow helmet CPAP system. Patients’ data were recorded before, at initiation of CPAP treatment and once a day, thereafter. CPAP failure was defined as a composite outcome of intubation or death.

Results
A total of 306 patients were included; 42% were deemed as DNI. Helmet CPAP treatment was successful in 69% of the full treatment and 28% of the DNI patients (P < 0.001). With helmet CPAP, PaO2/FiO2 ratio doubled from about 100 to 200 mmHg (P < 0.001); respiratory rate decreased from 28 [22–32] to 24 [20–29] breaths per minute, P < 0.001). C-reactive protein, time to oxygen mask failure, age, PaO2/FiO2 during CPAP, number of comorbidities were independently associated with CPAP failure. Helmet CPAP was maintained for 6 [3–9] days, almost continuously during the first two days. None of the full treatment patients died before intubation in the wards.

Conclusions
Helmet CPAP treatment is feasible for several days outside the ICU, despite persistent impairment in gas exchange. It was used, without escalating to intubation, in the majority of full treatment patients after standard oxygen therapy failed. DNI patients could benefit from helmet CPAP as rescue therapy to improve survival.
Trial Registration: NCT04424992
Patients in intensive care unit for COVID-19 pneumonia: the lung ultrasound patterns at admission and discharge. An observational pilot study
Authors: Persona Paolo , Valeri Ilaria , Zarantonello Francesco , Forin Edoardo , Sella Nicolò , Andreatta Giulio , Correale Christelle , Serra Eugenio , Boscolo Annalisa , Volpicelli Giovanni , Navalesi Paolo 
Published: February 2021

Abstract
Background
During COVID-19 pandemic, optimization of the diagnostic resources is essential. Lung Ultrasound (LUS) is a rapid, easy-to-perform, low cost tool which allows bedside investigation of patients with COVID-19 pneumonia. We aimed to investigate the typical ultrasound patterns of COVID-19 pneumonia and their evolution at different stages of the disease.

Methods
We performed LUS in twenty-eight consecutive COVID-19 patients at both admission to and discharge from one of the Padua University Hospital Intensive Care Units (ICU). LUS was performed using a low frequency probe on six different areas per each hemithorax. A specific pattern for each area was assigned, depending on the prevalence of A-lines (A), non-coalescent B-lines (B1), coalescent B-lines (B2), consolidations (C). A LUS score (LUSS) was calculated after assigning to each area a defined pattern.

Results
Out of 28 patients, 18 survived, were stabilized and then referred to other units. The prevalence of C pattern was 58.9% on admission and 61.3% at discharge. Type B2 (19.3%) and B1 (6.5%) patterns were found in 25.8% of the videos recorded on admission and 27.1% (17.3% B2; 9.8% B1) on discharge. The A pattern was prevalent in the anterosuperior regions and was present in 15.2% of videos on admission and 11.6% at discharge. The median LUSS on admission was 27.5 [21–32.25], while on discharge was 31 [17.5–32.75] and 30.5 [27–32.75] in respectively survived and non-survived patients. On admission the median LUSS was equally distributed on the right hemithorax (13; 10.75–16) and the left hemithorax (15; 10.75–17).

Conclusions
LUS collected in COVID-19 patients with acute respiratory failure at ICU admission and discharge appears to be characterized by predominantly lateral and posterior non-translobar C pattern and B2 pattern. The calculated LUSS remained elevated at discharge without significant difference from admission in both groups of survived and non-survived patients.
Perceived barriers and facilitators to uptake of non-traditional roles by pharmacists in Saudi Arabia and implications for COVID-19 pandemic and beyond: a qualitative study using Theoretical Domain Framework
Authors: Mohammed Eeman , Khanal Saval , Jalal Zahraa , Cheema Ejaz , Abutaleb Mohammed H. , Paudyal Vibhu 
Published: February 2021

AbstractBackgroundThe COVID-19 pandemic has further strengthened the need for pharmacists to uptake non-traditional roles. Pharmacy practice in Saudi Arabia is emerging in recent years with greater policy emphasis on pharmacists taking new clinical roles. This study aimed to explore the experiences, perceptions and barriers of Saudi pharmacists about their uptake of non-traditional roles using Theoretical Domains Framework (TDF).MethodsA qualitative semi-structured study using face-to-face or telephone interviews were conducted. Eligible participants included qualified pharmacists from Saudi Arabia. Interviews focused on pharmacist’s perceptions, current opportunities and key challenges towards the uptake of non-traditional roles. Interviews were audiotaped and transcribed verbatim. Results were analysed through the framework analysis method and were later mapped with respective domains of TDF.ResultsA total of 14 pharmacists completed the interview (9 females and 5 males). Participants showed an overall positive attitude towards the uptake of non-traditional roles. Participants felt that there was wider support available for pharmacists at the policy level to uptake non-traditional roles. However, a need for greater recognition of roles by other healthcare professionals and patients were identified. Participants alluded to reluctance of some physicians to take on board the suggestions from a pharmacist. Key barriers to uptake of non-traditional roles were related to environmental context and resources domain of TDF. For example, participants discussed the need for even further practical experiences during their undergraduate degree to become ready to adopt non-traditional roles in clinical practice.ConclusionsParticipants of this theoretically informed qualitative study showed an overall positive attitude towards the way pharmacy practice is progressing in Saudi Arabia and their uptake of non-traditional roles. However, there is a need to improve interdisciplinary working, patient awareness of pharmacist competencies and their educational preparedness in furthering their uptake of non-traditional roles. Addressing such barriers and promoting uptake of novel roles by pharmacists is imperative in the context of emerging COVID-19 and future pandemics.
Continuous erector spinae plane block versus intercostal nerve block in patients undergoing video-assisted thoracoscopic surgery: a pilot randomized controlled trial
Authors: Horth Dillon , Sanh William , Moisiuk Peter , O’Hare Turlough , Shargall Yaron , Finley Christian , Hanna Waël , Agzarian John , Forero Mauricio , Davis Kim , Vanniyasingam Thuva , Thabane Lehana , Shanthanna Harsha 
Published: February 2021

Abstract
Background
The optimal analgesia method in video-assisted thoracoscopic surgery (VATS) remains controversial. Intercostal nerve blockade (ICNB) is limited by its duration of action. The erector spinae plane (ESP) block has the potential to provide satisfactory analgesia for VATS; however, the effectiveness of continuous ESP versus surgeon-performed ICNB has not been investigated. The objectives of this study were to establish feasibility of patient recruitment and follow-up before undertaking a fully powered randomized controlled trial (RCT); and, secondarily, to compare opioid usage, pain control, and sensory blockade.

Methods
This feasibility RCT was undertaken at St Joseph’s Hospital, Hamilton, Ontario, Canada, and included 24 patients (>18 years) having elective VATS with at least one overnight stay. Exclusion criteria were patient refusal, body mass index >40 kg/m2, contraindications to neuraxial analgesia techniques as per the American Society of Regional Anesthesia and Pain guidelines, known allergy to local anesthetics, language or comprehension barriers, procedures with a higher chance of open surgery, and regular opioid use for ≥3 months preoperatively. Patients underwent either continuous ESP (n=12) or surgeon-performed ICNB (n=12). All patients received routine intraoperative anesthesia care and multimodal analgesia. Feasibility criteria were recruitment rate of two patients/week and full follow-up in all patients in-hospital. We compared opioid consumption, postoperative pain scores (0–10 numerical rating scale), adverse events, patient satisfaction, and distribution of sensory blockade as clinical outcomes (secondary).

Results
Feasibility of primary outcomes was successfully demonstrated. Five patients had an epidural in anticipation of open surgery. Mean opioid consumption as equivalent morphine units was less in the ESP group over the first 24 h (mean difference, 1.63 [95% CI –1.20 to 4.45]) and 48 h (mean difference, 2.34 [95% CI –1.93 to 6.61]). There were no differences in adverse effects.

Conclusions
A fully powered RCT is feasible with modifications. Our results also suggest that continuous ESP is safe and can decrease opioid needs. However, it is important to consider procedures to improve compliance to protocol and adherence to assigned interventions.

Trial registration
Clinicaltrials.gov identifier: NCT03176667. Registered June 5, 2017.
Risk of malignancy long after acute coronary syndrome in selected urban and rural areas and comparison with smoking risk: the ABC-7* study on Heart Disease
Authors: Berton Giuseppe , Mahmoud Heba T. , Palmieri Rosa , Cavuto Fiorella , Cordiano Rocco , Lorenzon Elisabetta , Bagato Francesco 
Published: February 2021

Abstract
Background
Increased cancer risk has been reported in patients with acute coronary syndrome (ACS).

Objectives
To investigate geographic differences in risk malignancy long after ACS.

Methods
We enrolled 586 ACS patients admitted to hospitals in three provinces in the Veneto region of Italy in this prospective study. Patient’s residency was classified into three urban and three nearby rural areas.

Results
All (except for 3) patients completed the follow-up (22 years or death) and 54 % were living in rural areas. Sixteen patients had pre-existing malignancy, and 106 developed the disease during follow-up. Cancer prevalence was 17 % and 24 % (p = 0.05) and incidence of malignancy was 16 and 21/1000 person-years for urban and rural areas, respectively. In unadjusted logistic regression analysis, cancer risk increased from urban to rural areas (odds ratio [OR] 3.4;95 % confidence interval [CI] 1.7–7.1; p = 0.001), with little change from north to south provinces (OR 1.5;95 % CI 1.0-2.2; p = 0.06). Yet, we found a strong positive interaction between urban-rural areas and provinces (OR 2.1;95 % CI 1.2–3.5; p = 0.003). These results kept true in the fully adjusted model. Unadjusted Cox regression analysis revealed increasing hazards ratios (HRs) for malignancy onset from urban to rural areas (HR 3.0;95 % CI 1.5–6.2; p = 0.02), but not among provinces (HR 1.3;95 % CI 1.0–2.0; p = 0.14). Also, we found a strong positive interaction between geographic areas (HR 2.1;95 % CI 1.3–3.5; p = 0.002), even with a fully adjusted model.

Conclusions
The results in unselected real-world patients demonstrate a significant geographic difference in malignancy risk in ACS patients, with the highest risk in the north-rural area.
Remimazolam for a patient with myotonic dystrophy type 1 who underwent endoscopic retrograde cholangiopancreatography under general anesthesia: a case report
Authors: Fukuda Masakazu , Tachibana Shunsuke , Nishihara Noriaki , Yamakage Michiaki 
Published: February 2021

Abstract
Background
Remimazolam is a benzodiazepine receptor agonist with an ultra-short-acting anesthetic effect. We used remimazolam for anesthesia in a patient with myotonic dystrophy type 1 who underwent endoscopic retrograde cholangiopancreatography (ERCP).

Case presentation
A 58-year-old woman received ERCP under general anesthesia. She had impaired respiratory function due to myotonic dystrophy type I and was at a risk of respiratory complications after anesthesia. General anesthesia was induced with remimazolam 12 mg/kg/h, remifentanil 0.1 μg/kg/min and rocuronium 15 mg, followed by tracheal intubation and maintained with remimazolam 0.8−1.0 mg/kg/h. At the end of anesthesia, we injected sugammadex 150 mg and flumazenil 0.2 mg, allowing smooth and clear emergence from anesthesia. She was discharged from the hospital without any respiratory problems on postoperative day 5.

Conclusions
Remimazolam was safe to use for general anesthesia in a patient with myotonic dystrophy type 1 undergoing ERCP.
Translation and psychometric evaluation of the Swedish versions of the Nuss Questionnaire modified for Adults and the Single Step Questionnaire
Authors: Norlander Louise , Karlsson Jan , Anderzén-Carlsson Agneta , Vidlund Mårten , Dreifaldt Mats , Andreasson Jesper , Sundqvist Ann-Sofie 
Published: February 2021

Abstract
Background
Pectus excavatum (PE) is the most common congenital chest wall deformity. Most individuals with PE suffer from psychosocial problems, with low self-esteem and poor body image. Correctional surgery for PE is available, the most widely used is the Nuss procedure. The Nuss procedure has previously been reported to improve self-esteem, body image and health-related quality of life (HRQoL). To assess HRQoL among individuals with PE, the Nuss Questionnaire modified for Adults (NQ-mA) and Single Step Questionnaire (SSQ) has been developed. The aim of the current study was to translate and culturally adapt NQ-mA and SSQ to fit a Swedish context, and to evaluate the psychometric properties, and validate the culturally adapted versions.

Methods
Individuals who had undergone the Nuss procedure for pectus excavatum were invited to participate in a multicentre study with cross-sectional design. HRQoL was assessed by NQ-mA, SSQ and RAND-36. Psychometric properties for NQ-mA and SSQ were evaluated by content validity index and construct validity (exploratory factor analysis, confirmatory factor analysis, and inter-scale correlations). Known-groups validity, as well as floor and ceiling effects, were evaluated. Internal consistency reliability was examined using Cronbach’s alpha.

Results
In total 236 individuals participated in the study. Content validity index for NQ-mA showed satisfactory results, except for two items. Factor analysis for NQ-mA suggested a two-factor model, with exclusion of two items. Subscales correlated adequately with RAND-36’s domains. Known-groups validity for NQ-mA demonstrated high sensitivity for between-group differences. Ceiling effects were present in several items. Cronbach’s alpha for NQ-mA was .89. Confirmatory factor analysis for SSQ resulted in a three-factor model, with exclusion of five items. However, this model was shown to be unstable through further exploratory factor analysis testing, and no further psychometric tests were conducted for SSQ.

Conclusion
The 10-item Swedish version of NQ-mA was shown to be valid for research and clinical assessment of HRQoL in individuals with pectus excavatum. The Swedish version of SSQ requires revision of items before further validation can be performed.