bluuebunny/crossref_metadata_2025 huggingface dataset:
Making Sense of the World: Infant Learning From a Predictive Processing Perspective
Authors: Köster Moritz , Kayhan Ezgi , Langeloh Miriam , Hoehl Stefanie
Published: March 2020

For human infants, the first years after birth are a period of intense exploration—getting to understand their own competencies in interaction with a complex physical and social environment. In contemporary neuroscience, the predictive-processing framework has been proposed as a general working principle of the human brain, the optimization of predictions about the consequences of one’s own actions, and sensory inputs from the environment. However, the predictive-processing framework has rarely been applied to infancy research. We argue that a predictive-processing framework may provide a unifying perspective on several phenomena of infant development and learning that may seem unrelated at first sight. These phenomena include statistical learning principles, infants’ motor and proprioceptive learning, and infants’ basic understanding of their physical and social environment. We discuss how a predictive-processing perspective can advance the understanding of infants’ early learning processes in theory, research, and application.
Health promotion strategy as part of Vision 2050 in Oman: the way forward
Authors: Al Hinai Halima , Al Mufarji Khuloud , Al Siyabi Huda , Al Anqoudi Zahir , Al Saadi Rashid , Al Awaidy Salah
Published: March 2020

Introduction:

Non-communicable diseases (NCDs) have become a significant cause of morbidity and mortality in Oman. The adoption of unhealthy and sedentary lifestyles associated with rising income is trending with a large number of individuals and is contributing to the emergence of substantial health issues. Ultimately, the incidence of NCDs has increased considerably. This review aims to define strategies that can help in attaining Oman’s national health promotion goals.

Results:

The current health promotion strategies have not been adequate or sufficient to meet the national Health Vision 2050 of Oman.

Conclusion:

Unsafe behaviors and unhealthy lifestyles that led to a significant increase in NCDs have emerged in Oman. Careful re-planning and continuous monitoring and evaluation of health promotion activities are necessary for effective implementation of health policies, with the ultimate goal of reducing the NCD burden in Oman.
One-step nitrogen plasma process for bimetallic impregnation to obtain N-TiO2−X/Au/Ag composite
Authors: Trejo-Tzab R , Aguilar-Jiménez JA , Quintana-Owen P , Ávila-Ortega Alejandro , Alvarez-Lemus MA , Medina-Esquivel RA
Published: March 2020

The main motivation of this work is to deposit two different metals (gold and silver) on titanium oxide nanoparticles surface in a one-step simple and fast physical process by applying a nitrogen plasma as the main source of nitrogen atoms to obtain nanostructured N-TiO2 − X/Au/Ag materials. The obtained nanomaterials were characterized by X-ray photoelectron spectroscopy, X-ray diffraction, diffuse reflectance spectroscopy, scanning electron microscopy–energy dispersive X-ray spectroscopy, and high-resolution transmission electron microscopy. Based on the characterization results, we found that gold and silver nanoparticles were uniformly loaded on the titanium oxide nanocomposite surface, showing a surface plasmon absorption band due to the loading of the metal nanoparticles over titania samples. The results of this work have shown that nitrogen plasma technique is a more feasible and simple alternative to obtain the N-TiO2 − X/Au/Ag nanocomposite. Moreover, this plasma technique could be used to impregnate with other kind of metals over the surface of diverse nanomaterials.
A novel PillCam Crohn’s capsule score (Eliakim score) for quantification of mucosal inflammation in Crohn’s disease
Authors: Eliakim Rami , Yablecovitch Doron , Lahat Adi , Ungar Bella , Shachar Eyal , Carter Dan , Selinger Limor , Neuman Sandra , Ben‐Horin Shomron , Kopylov Uri
Published: March 2020

Introduction

Capsule endoscopy is an important modality for monitoring of Crohn’s disease. Recently, a novel panenteric capsule, PillCam Crohn’s (Medtronic, USA), was approved for use. No quantitative index of inflammation for this method is currently available. This sub‐study of a prospective randomized controlled Comprehensive individUalized pRoactive ThErapy of Crohn’s Disease trial (CURE‐CD) which aimed to compare the correlation and reliability of the novel PillCam Crohn’s score with the existing small bowel capsule Lewis inflammatory score.

Methods

The study cohort included Crohn’s disease patients in remission who were evaluated with PillCam Crohn’s. Each result was independently reviewed by two experienced readers. Inflammation was scored in all studies using Lewis inflammatory score and PillCam Crohn’s score (comprised of a sum of scores for most common and most severe lesions multiplied by percentage of segmental involvement + stricture score).

Results

Fifty‐four PillCam Crohn’s studies from 41 patients were included. The median Lewis inflammatory score was 225 for both readers. The median PillCam Crohn’s score was six (0–14) and four (3–15) for readers 1 and 2, respectively. There was a high inter‐rater reliability coefficient between the two readers for Lewis inflammatory and PillCam Crohn’s score (0.9, p  < 0.0001 for both). The correlation between PillCam Crohn’s score and fecal calprotectin was stronger than for Lewis inflammatory score (r  = 0.32 and 0.54 respectively, p  = 0.001 for both).

Conclusions

The novel panenteric capsule score correlates well with the Lewis inflammatory score, has excellent reliability, and may be potentially more accurate in estimation of the panenteric inflammatory burden.
Comparison between semitendinosus transfer to distal femur and medial hamstrings surgical lengthening for treatment of flexed knee gait in cerebral palsy
Authors: de Morais Filho Mauro César , Fujino Marcelo Hideki , Blumetti Francesco Camara , dos Santos Carlos Alberto , Kawamura Cátia Miyuki , Ramos Bruna Caroline Alexandrino , Lopes José Augusto Fernandes
Published: March 2020

Purpose:

Hamstrings surgical lengthening (HSL) has been frequently used for the treatment of flexed knee gait in cerebral palsy; however, recurrence of knee flexion deformity (KFD) and increase of anterior pelvic tilt (APT) were reported in a long-term follow-up.

Research question:

The aim of this study was to compare semitendinosus transfer to distal femur (STTX) and semitendinosus surgical lengthening (STL) regarding the reduction of KFD and the increase of APT after flexed knee gait treatment.

Methods:

One hundred and eleven patients were evaluated and they were divided into two groups according to surgical procedures at knees: group A (65 patients/130 knees), including patients who received medial HSL as part of multilevel approach; group B (46 patients/92 knees), represented by patients who underwent orthopedic surgery including an STTX instead of STL.

Results:

Fixed knee flexion deformity (FKFD) decreased only in group B (from 6.79° to 2.96°, p < 0.001) after intervention. In kinematics, APT increased from 16.38° to 19.03° in group A ( p = 0.003), while group B also increased from 15.26° to 20.59° ( p < 0.001). The minimum knee flexion in stance phase (MKFS) reduced from 25.34° to 21.65° ( p = 0.016) in group A and from 31° to 19.57° ( p < 0.001) in group B. In the comparison between groups A and B, the increase of APT ( p = 0.028) and reduction of FKFD ( p < 0.001), popliteal angle ( p = 0.001), bilateral popliteal angle ( p = 0.003) and MKFS ( p = 0.006) were higher after STTX than STL.

Conclusion:

In the present study, patients who received STTX exhibited more improvement of knee extension at clinical examination and during gait than those who underwent to STL; however, STTX was not effective to prevent the increase of APT after flexed knee gait treatment.
Freelancers as Part-time Employees: Dimensions of FVP and FJS in E-Lancing Platforms
Authors: Nawaz Zubair , Zhang Jing , Mansoor Rafiq , Hafeez Saba , Ilmudeen Aboobucker
Published: March 2020

The purpose of this study is to explore the dimensions of Freelancer Value Proposition (FVP) and Freelancer Job Stress (FJS). This study provides insights about the factors which create value for freelancers and also sheds light on the factors which cause stress to freelancers while freelancing with the help of an online platform. Semi-structured interviews were conducted for data collection from freelancers. The grounded theory approach was used and data analysis follows the process of open coding, axial coding and themes formulation. Findings indicate that work-life balance value, developmental value, economic value, autonomy value, hedonistic value and social value are dimensions of FVP. Lack of role clarity, payment issues, time management issue, work availability issue, lack of perks and benefits and work rejections are dimensions of FJS. This study is the first effort to find out the dimensions of FVP and FJS, which will help to construct long-term relationship between freelancers and platform.
Regional differences in airway susceptibility to cigarette smoke: An investigational case study of epithelial function and gene alterations in in vitro airway epithelial three-dimensional cultures
Authors: Matsumura Kazushi , Kurachi Takeshi , Ishikawa Shinkichi , Kitamura Nobumasa , Ito Shigeaki
Published: March 2020

Cigarette smoke (CS) is a risk factor contributing to lung remodeling in chronic obstructive pulmonary disease (COPD). COPD is a heterogeneous disease because many factors contribute in varying degrees to the resulting airflow limitations in different regions of the respiratory tract. This heterogeneity makes it difficult to understand mechanisms behind COPD development. In the current study, we investigate the regional heterogeneity of the acute response to CS exposure between large and small airways using in vitro three-dimensional (3D) cultures. We used two in vitro 3D human airway epithelial tissues from large and small airway epithelial cells, namely, MucilAir™ and SmallAir™, respectively, which were derived from the same single healthy donor to eliminate donor differences. Impaired epithelial functions and altered gene expression were observed in SmallAir™ exposed to CS at the lower dose and earlier period following the last exposure compared with MucilAir™. In addition, severe damage in SmallAir™ was retained for a longer duration than MucilAir™. Transcriptomic analysis showed that although well-known CS-inducible biological processes (i.e. inflammation, cell fate, and metabolism) were disturbed with consistent activity in both tissues exposed to CS, we elucidated distinctively regulated genes in only MucilAir™ and SmallAir™, which were mostly related to catalytic and transporter activities. Our findings suggest that CS exposure elicited epithelial dysfunction through almost the same perturbed pathways in both airways; however, they expressed different genes related to metabolic and transporter activities in response to CS exposure which may contribute to cytotoxic heterogeneity to the response to CS in the respiratory tract.
Evaluation of the Safety and Efficacy of Metformin Use in Hospitalized, Non–Critically Ill Patients
Authors: Alauddin Tahnia , Petite Sarah E.
Published: March 2020

Background: Contraindications and precautions to metformin have limited inpatient use, and limited evidence exists evaluating metformin in hospitalized patients. Objective: This study aimed to determine the safety and efficacy of inpatient metformin use. Methods: This study was an observational, retrospective, cohort study at an academic medical center between June 1, 2016, and May 31, 2018. Hospitalized adults with type 2 diabetes mellitus receiving at least 1 metformin dose were included. The primary endpoint was to identify hospitalized patients using metformin with at least 1 contraindication or precautionary warning against use. Secondary endpoints included assessing metformin efficacy with glycemic control, characterizing adverse outcomes of inpatient metformin, and comparing the efficacy of metformin-containing regimens. Results: Two hundred patients were included. There were 126 incidences of potentially unsafe use identified in 111 patients (55.5%). The most common reasons were age ≥65 years (47%), heart failure diagnosis (7.5%), and metformin within 48 hours of contrast (6%). Metformin was contraindicated in 2 patients (1%) with an estimated glomerular filtration rate ≤30 mL/min/1.73 m2. The overall median daily blood glucose was 146 mg/dL (interquartile range [IQR] = 122-181). Patients were divided into 3 groups: metformin monotherapy, metformin plus oral antihyperglycemic therapy, and metformin plus insulin. The median daily blood glucoses were 129 mg/dL (IQR = 110-152), 154 mg/dL (IQR = 133-178), and 174 mg/dL (IQR = 142-203; P < .001), respectively. Two patients (1%) developed acute kidney injury, and no patients developed lactic acidosis. Conclusions: Metformin was associated with goal glycemic levels in hospitalized patients with no adverse outcomes. These results suggest the potential for metformin use in hospitalized, non–critically ill patients.
A European proposal for quality control and quality assurance of tandem mass spectral libraries
Authors: Oberacher Herbert , Sasse Michael , Antignac Jean-Philippe , Guitton Yann , Debrauwer Laurent , Jamin Emilien L. , Schulze Tobias , Krauss Martin , Covaci Adrian , Caballero-Casero Noelia , Rousseau Kathleen , Damont Annelaure , Fenaille François , Lamoree Marja , Schymanski Emma L.
Published: March 2020

Background

High resolution mass spectrometry (HRMS) is being used increasingly in the context of suspect and non-targeted screening for the identification of bioorganic molecules. There is correspondingly increasing awareness that higher confidence identification will require a systematic, group effort to increase the fraction of compounds with tandem mass spectra available in central, publicly available resources. While typical suspect screening efforts will only result in tentative annotations with a moderate level of confidence, library spectral matches will yield higher confidence or even full confirmation of the identity if the reference standards are available.

Results

This article first explores representative percent coverage of measured tandem mass spectra in selected major environmental suspect databases of interest in the context of human biomonitoring, demonstrating the current extensive gap between the number of potential substances of interest (up to hundreds of thousands) and measured spectra (0.57–3.6% of the total chemicals have spectral information available). Furthermore, certain datasets are benchmarked, based on previous efforts, to show the extent to which acquired experimental data were comparable between laboratories, even with HRMS instruments based on different technologies (i.e., quadrupole–quadrupole-time of flight versus ion trap/quadrupole-Orbitrap). Instruments and settings that are less comparable are also revealed, primarily linear ion trap instruments, which show distinctly lower comparability.

Conclusions

Based on these efforts, harmonization guidelines for the acquisition and processing of tandem mass spectrometry data are proposed to enable European (and ideally worldwide) laboratories to contribute to common resources, without requiring extensive changes to their current in house methods.
Prediction of tumor location in prostate cancer tissue using a machine learning system on gene expression data
Authors: Hamzeh Osama , Alkhateeb Abedalrhman , Zheng Julia , Kandalam Srinath , Rueda Luis
Published: March 2020

Background

Finding the tumor location in the prostate is an essential pathological step for prostate cancer diagnosis and treatment. The location of the tumor – the laterality – can be unilateral (the tumor is affecting one side of the prostate), or bilateral on both sides. Nevertheless, the tumor can be overestimated or underestimated by standard screening methods. In this work, a combination of efficient machine learning methods for feature selection and classification are proposed to analyze gene activity and select them as relevant biomarkers for different laterality samples.

Results

A data set that consists of 450 samples was used in this study. The samples were divided into three laterality classes (left, right, bilateral). The aim of this work is to understand the genomic activity in each class and find relevant genes as indicators for each class with nearly 99% accuracy. The system identified groups of differentially expressed genes (RTN1, HLA-DMB, MRI1) that are able to differentiate samples among the three classes.

Conclusion

The proposed method was able to detect sets of genes that can identify different laterality classes. The resulting genes are found to be strongly correlated with disease progression. HLA-DMB and EIF4G2, which are detected in the set of genes can detect the left laterality, were reported earlier to be in the same pathway called Allograft rejection SuperPath.
visGReMLIN: graph mining-based detection and visualization of conserved motifs at 3D protein-ligand interface at the atomic level
Authors: Ribeiro Vagner S. , Santana Charles A. , Fassio Alexandre V. , Cerqueira Fabio R. , da Silveira Carlos H. , Romanelli João P. R. , Patarroyo-Vargas Adriana , Oliveira Maria G. A. , Gonçalves-Almeida Valdete , Izidoro Sandro C. , de Melo-Minardi Raquel C. , Silveira Sabrina de A.
Published: March 2020

Background

Interactions between proteins and non-proteic small molecule ligands play important roles in the biological processes of living systems. Thus, the development of computational methods to support our understanding of the ligand-receptor recognition process is of fundamental importance since these methods are a major step towards ligand prediction, target identification, lead discovery, and more. This article presents visGReMLIN, a web server that couples a graph mining-based strategy to detect motifs at the protein-ligand interface with an interactive platform to visually explore and interpret these motifs in the context of protein-ligand interfaces.

Results

To illustrate the potential of visGReMLIN, we conducted two cases in which our strategy was compared with previous experimentally and computationally determined results. visGReMLIN allowed us to detect patterns previously documented in the literature in a totally visual manner. In addition, we found some motifs that we believe are relevant to protein-ligand interactions in the analyzed datasets.

Conclusions

We aimed to build a visual analytics-oriented web server to detect and visualize common motifs at the protein-ligand interface. visGReMLIN motifs can support users in gaining insights on the key atoms/residues responsible for protein-ligand interactions in a dataset of complexes.
BLAMM: BLAS-based algorithm for finding position weight matrix occurrences in DNA sequences on CPUs and GPUs
Authors: Fostier Jan
Published: March 2020

Background

The identification of all matches of a large set of position weight matrices (PWMs) in long DNA sequences requires significant computational resources for which a number of efficient yet complex algorithms have been proposed.

Results

We propose BLAMM, a simple and efficient tool inspired by high performance computing techniques. The workload is expressed in terms of matrix-matrix products that are evaluated with high efficiency using optimized BLAS library implementations. The algorithm is easy to parallelize and implement on CPUs and GPUs and has a runtime that is independent of the selected p-value. In terms of single-core performance, it is competitive with state-of-the-art software for PWM matching while being much more efficient when using multithreading. Additionally, BLAMM requires negligible memory. For example, both strands of the entire human genome can be scanned for 1404 PWMs in the JASPAR database in 13 min with a p-value of 10−4 using a 36-core machine. On a dual GPU system, the same task can be performed in under 5 min.

Conclusions

BLAMM is an efficient tool for identifying PWM matches in large DNA sequences. Its C++ source code is available under the GNU General Public License Version 3 at https://github.com/biointec/blamm.
Mortality prediction by SOFA score in ICU-patients after cardiac surgery; comparison with traditional prognostic–models
Authors: Schoe Abraham , Bakhshi-Raiez Ferishta , de Keizer Nicolette , van Dissel Jaap T. , de Jonge Evert
Published: March 2020

Background

There are many prognostic models and scoring systems in use to predict mortality in ICU patients. The only general ICU scoring system developed and validated for patients after cardiac surgery is the APACHE-IV model. This is, however, a labor-intensive scoring system requiring a lot of data and could therefore be prone to error. The SOFA score on the other hand is a simpler system, has been widely used in ICUs and could be a good alternative.

The goal of the study was to compare the SOFA score with the APACHE-IV and other ICU prediction models.

Methods

We investigated, in a large cohort of cardiac surgery patients admitted to Dutch ICUs, how well the SOFA score from the first 24 h after admission, predict hospital and ICU mortality in comparison with other recalibrated general ICU scoring systems. Measures of discrimination, accuracy, and calibration (area under the receiver operating characteristic curve (AUC), Brier score, R2, and Ĉ-statistic) were calculated using bootstrapping. The cohort consisted of 36,632 Patients from the Dutch National Intensive Care Evaluation (NICE) registry having had a cardiac surgery procedure for which ICU admission was necessary between January 1st, 2006 and June 31st, 2018.

Results

Discrimination of the SOFA-, APACHE-IV-, APACHE-II-, SAPS-II-, MPM24-II - models to predict hospital mortality was good with an AUC of respectively: 0.809, 0.851, 0.830, 0.850, 0.801. Discrimination of the SOFA-, APACHE-IV-, APACHE-II-, SAPS-II-, MPM24-II - models to predict ICU mortality was slightly better with AUCs of respectively: 0.809, 0.906, 0.892, 0.919, 0.862. Calibration of the models was generally poor.

Conclusion

Although the SOFA score had a good discriminatory power for hospital- and ICU mortality the discriminatory power of the APACHE-IV and SAPS-II was better. The SOFA score should not be preferred as mortality prediction model above traditional prognostic ICU-models.
Correction to: Kallistatin inhibits tumour progression and platinum resistance in high-grade serous ovarian cancer
Authors: Wu Huan , Li Rongrong , Zhang Zhiwei , Jiang Huiyang , Ma Hanlin , Yuan Cunzhong , Sun Chenggong , Li Yingwei , Kong Beihua
Published: March 2020

The original article [1] contains errors in Fig. 3C, Results and Discussion.
Effects of Pidotimod on recurrent respiratory infections in children with Down syndrome: a retrospective Italian study
Authors: Valentini Diletta , Di Camillo Chiara , Mirante Nadia , Marcellini Valentina , Carsetti Rita , Villani Alberto
Published: March 2020

Background

Children with Down syndrome (DS) show a high susceptibility to recurrent infections (RI), caused by immune defects and abnormalities of the airways. Our goal was to investigate the effects of Pidotimod on RI prevention in children with DS, comparing immune and clinical parameters before (T0) and after (T1) the treatment with Pidotimod.

Methods

The study was conducted at the Down syndrome outpatient Center of Bambino Gesù Children’s Hospital, in Rome. We reviewed the medical records of all children with a positive history for RI and who received oral prophylaxis of Pidotimod from September 2016 to February 2017.

Results

Thirty-three children met the inclusion criteria (males: 51.5%; average age: 6 years ±SD: 3). We found a significant decrease in the number of children with upper respiratory infections (82% at T0 vs 24% at T1; p = 0,0001) and with lower respiratory infections (36% at T0 vs 9% at T1; p = 0.003) after treatment with Pidotimod. We also demonstrated a significant decrease in the number of children hospitalized for respiratory infections (18% at T0 vs 3% at T1; p = 0.03). We measured T and B cells in the peripheral blood and B cell function in vitro at T0 and T1. We found that the response to CpG improved at T1. A significant increase of B cell frequency (p = 0.0009), B cell proliferation (p = 0.0278) and IgM secretion (p = 0.0478) were observed in children with DS after treatment.

Conclusions

Our results provided evidence that Pidotimod may be able to prevent RI in children with Down syndrome.
Diffuse optical spectroscopic imaging reveals distinct early breast tumor hemodynamic responses to metronomic and maximum tolerated dose regimens
Authors: Tank Anup , Peterson Hannah M. , Pera Vivian , Tabassum Syeda , Leproux Anais , O’Sullivan Thomas , Jones Eric , Cabral Howard , Ko Naomi , Mehta Rita S. , Tromberg Bruce J. , Roblyer Darren
Published: March 2020

Background

Breast cancer patients with early-stage disease are increasingly administered neoadjuvant chemotherapy (NAC) to downstage their tumors prior to surgery. In this setting, approximately 31% of patients fail to respond to therapy. This demonstrates the need for techniques capable of providing personalized feedback about treatment response at the earliest stages of therapy to identify patients likely to benefit from changing treatment. Diffuse optical spectroscopic imaging (DOSI) has emerged as a promising functional imaging technique for NAC monitoring. DOSI uses non-ionizing near-infrared light to provide non-invasive measures of absolute concentrations of tissue chromophores such as oxyhemoglobin. In 2011, we reported a new DOSI prognostic marker, oxyhemoglobin flare: a transient increase in oxyhemoglobin capable of discriminating NAC responders within the first day of treatment. In this follow-up study, DOSI was used to confirm the presence of the flare as well as to investigate whether DOSI markers of NAC response are regimen dependent.

Methods

This dual-center study examined 54 breast tumors receiving NAC measured with DOSI before therapy and the first week following chemotherapy administration. Patients were treated with either a standard of care maximum tolerated dose (MTD) regimen or an investigational metronomic (MET) regimen. Changes in tumor chromophores were tracked throughout the first week and compared to pathologic response and treatment regimen at specific days utilizing generalized estimating equations (GEE).

Results

Within patients receiving MTD therapy, the oxyhemoglobin flare was confirmed as a prognostic DOSI marker for response appearing as soon as day 1 with post hoc GEE analysis demonstrating a difference of 48.77% between responders and non-responders (p < 0.0001). Flare was not observed in patients receiving MET therapy. Within all responding patients, the specific treatment was a significant predictor of day 1 changes in oxyhemoglobin, showing a difference of 39.45% (p = 0.0010) between patients receiving MTD and MET regimens.

Conclusions

DOSI optical biomarkers are differentially sensitive to MTD and MET regimens at early timepoints suggesting the specific treatment regimen should be considered in future DOSI studies. Additionally, DOSI may help to identify regimen-specific responses in a more personalized manner, potentially providing critical feedback necessary to implement adaptive changes to the treatment strategy.
Enzymatic production of 4-O-methyl d-glucaric acid from hardwood xylan
Authors: Vuong Thu V. , Master Emma R.
Published: March 2020

Background

Dicarboxylic acids offer several applications in detergent builder and biopolymer fields. One of these acids, 4-O-methyl d-glucaric acid, could potentially be produced from glucuronoxylans, which are a comparatively underused fraction of wood and agricultural biorefineries.

Results

Accordingly, an enzymatic pathway was developed that combines AxyAgu115A, a GH115 α-glucuronidase from Amphibacillus xylanus, and GOOX, an AA7 gluco-oligosaccharide oxidase from Sarocladium strictum, to produce this bio-based chemical from glucuronoxylan. AxyAgu115A was able to release almost all 4-O-methyl d-glucuronic acid from glucuronoxylan while a GOOX variant, GOOX-Y300A, could convert 4-O-methyl d-glucuronic acid to the corresponding glucaric acid at a yield of 62%. Both enzymes worked effectively at alkaline conditions that increase xylan solubility. Given the sensitivity of AxyAgu115A to hydrogen peroxide and optimal performance of GOOX-Y300A at substrate concentrations above 20 mM, the two-step enzyme pathway was demonstrated as a sequential, one-pot reaction. Additionally, the resulting xylan was easily recovered from the one-pot reaction, and it was enzymatically hydrolysable.

Conclusions

The pathway in this study requires only two enzymes while avoiding a supplementation of costly cofactors. This cell-free approach provides a new strategy to make use of the underutilized hemicellulose stream from wood and agricultural biorefineries.
Murine hepatoblast-derived liver tumors resembling human combined hepatocellular-cholangiocarcinoma with stem cell features
Authors: Cai Xiong , Li Heli , Kaplan David E.
Published: March 2020

Background

Combined hepatocellular-cholangiocarcinoma (CHC) is a primary hepatic malignancy with heterogeneously combined histological features of putative hepatic progenitor cells (HPC) origin. We describe a mouse model that exhibits the heterogenous histological and phenotypic finding similar to human CHC.

Methods

We injected hepatoblasts isolated from p53−/− C57BL/6 mice into syngeneic wild-type pre-conditioned C57BL/6 mice. We confirmed that p53−/− murine hepatoblasts act as tumor-initiating cells (TICs) that generate CHC both in situ and within metastases. For comparative pathological study, 8 human cases of CHC with stem cell features were recruited by immunohistochemistry and multicolor fluorescence immunostaining.

Results

We identified corresponding areas in murine tumors matching each WHO criteria-described subtype of human CHC. In both murine and human tumors, HPC-like cells in tumor nests and associated stem cell features/traits are suggested histologically to be the progenitor origin of the cancer

Conclusions

The pathological characteristics of murine tumors recapitulate human CHC with stem cell features. These data provide additional comparative pathological evidence that CHC with stem cell features originate from HPCs and validate a model to study this cancer type in vivo.
Colorimetric detection of Cr3+ based on gold nanoparticles functionalized with 4-mercaptobenzoic acid
Authors: Zhang Zhikun , Ye Xiaojie , Liu Qingqing , Liu Yumin , Liu Runjing
Published: March 2020

Herein, we report the construction of a colorimetric probe used to detecting Cr3+ ions in aqueous solution based on functionalized gold nanoparticles. We investigated 4-mercaptobenzoic acid, 4-nitrobenzenethiol, and a mixture of 4-mercaptobenzoic acid and 4-nitrobenzenethiol as ligands for Cr3+ ions to functionalize the gold nanoparticles, respectively. The results showed that the three probes were all aggregated in the presence of Cr3+ ions, which induces a color change from ruby to violet. Moreover, gold nanoparticles modified with 4-mercaptobenzoic acid exhibit a higher response toward Cr3+ than the two other probes, which can be detected by the naked eye and UV-vis absorption spectroscopy. The detection time was rapid (within 25 min). A linear relationship was obtained from 20 to 25 μM between the ratio of the absorbance observed at 635 nm and 520 nm (A635 nm/A520 nm) with the limit of detection was 5 × 10−6 M. This method exhibited excellent selectivity for Cr3+ ions over other tested heavy metal ions, anions, and organic molecules in the absence of another shielding reagent of metal ion. The system was successfully utilized to detect Cr3+ ions in simulated samples.
Nonprostatic diseases on PSMA PET imaging: a spectrum of benign and malignant findings
Authors: de Galiza Barbosa Felipe , Queiroz Marcelo Araujo , Nunes Rafael Fernandes , Costa Larissa Bastos , Zaniboni Elaine Caroline , Marin José Flavio Gomes , Cerri Giovanni Guido , Buchpiguel Carlos Alberto
Published: March 2020

PSMA PET imaging was originally used to assess biochemical recurrence of prostate cancer (PCa), but its clinical use was promptly extended to detection, staging and therapy response assessment. The expanding use of PSMA PET worldwide has also revealed PSMA ligand uptake in diverse nonprostatic diseases, which raised questions about the specificity of this imaging modality. Although not very common initially, a growing number of pathologies presenting PSMA uptake on PET have been reported in the last few years, and a proper interpretation of PSMA PET imaging findings suddenly became challenging and, to some extent, confusing. Compared to cytoplasmic PSMA expression in nonprostatic cells, the molecular features of apical PSMA expression in PCa cells can help to distinguish these various conditions. Correlations of imaging findings to patient history, to the expected pattern of disease spread and mainly to computed tomography (CT) and/or magnetic resonance imaging (MRI) characteristics will reinforce the distinction of lesions that are more likely related to PCa from those that could lead to an incorrect diagnosis. The overall benefits of endothelial PSMA expression, which is associated with the neovasculature of malignant neoplasms, will be highlighted, stating the potential use of PSMA ligand uptake as a theranostic tool. This review aims to cover the collection of nonprostatic diseases, including benign and malignant tumors, in a didactic approach according to disease etiology, with discussion of bone-related conditions and inflammatory and infectious processes.
In vitro assessment of the cytotoxic effects of secondary metabolites from Spirulina platensis on hepatocellular carcinoma
Authors: Akbarizare Mahboobeh , Ofoghi Hamideh , Hadizadeh Mahnaz , Moazami Nasrin
Published: March 2020

Background

Spirulina platensis, an edible cyanobacterium, is considered as a valuable and natural resource of novel anticancer agents. This study aimed to investigate the anticancer potential of major bioactive metabolites from Spirulina platensis on hepatocellular carcinoma cells. The total phenolic and alkaloid content of S. platensis were determined using spectrophotometric procedures and thin-layer chromatography. ‍‍Cellular viability of HepG2 cancer cells and normal fibroblasts was evaluated using MTT assay after 24 h treatment with 0.02–2 mg/ml of alkaloids, phenolic compounds, aqueous, and methanol extracts from Spirulina platensis.

Results

Total phenolic and total alkaloid compounds were 150.5 ± 1.18 mg gallic acid equivalents/mg extract and 11.4 ± 0.05 mg atropine equivalents/mg extract, respectively. All tested extracts and compounds demonstrated the inhibitory effect on the viability of HepG2 cells in a dose-dependent manner without cytotoxicity on normal cells. The most potent anticancer activity was induced by alkaloids (2 ± 0.001 mg/ml) with 80% reduction in cell viability and an IC50 of 0.53 ± 0.08 mg/ml. IC50 values of the aqueous extract, the methanolic extract, and phenolic compounds were 1.7 ± 0.14, 1.28 ± 0.22, and 0.86 ± 0.14 mg/ml, respectively.

Conclusions

This is the first report to demonstrate anticancer effects of alkaloids and phenolic compounds of Spirulina platensis in relation to liver cancer.
Sex differences in cognitive functioning of patients at-risk for psychosis and healthy controls: Results from the European Gene–Environment Interactions study
Authors: Menghini-Müller Stephanie , Studerus Erich , Ittig Sarah , Valmaggia Lucia R. , Kempton Matthew J. , van der Gaag Mark , de Haan Lieuwe , Nelson Barnaby , Bressan Rodrigo A. , Barrantes-Vidal Neus , Jantac Célia , Nordentoft Merete , Ruhrmann Stephan , Sachs Garbiele , Rutten Bart P. , van Os Jim , Riecher-Rössler Anita ,   the EU-GEI High Risk Study Group
Published: March 2020

Background.

Sex differences in cognitive functioning have long been recognized in schizophrenia patients and healthy controls (HC). However, few studies have focused on patients with an at-risk mental state (ARMS) for psychosis. Thus, the aim of the present study was to investigate sex differences in neurocognitive performance in ARMS patients compared with HC.

Methods.

The data analyzed in this study were collected within the multicenter European Gene–Environment Interactions study (11 centers). A total of 343 ARMS patients (158 women) and 67 HC subjects (33 women) were included. All participants completed a comprehensive neurocognitive battery. Linear mixed effects models were used to explore whether sex differences in cognitive functioning were present in the total group (main effect of sex) and whether sex differences were different for HC and ARMS (interaction between sex and group).

Results.

Women performed better in social cognition, speed of processing, and verbal learning than men regardless of whether they were ARMS or HC. However, only differences in speed of processing and verbal learning remained significant after correction for multiple testing. Additionally, ARMS patients displayed alterations in attention, current IQ, speed of processing, verbal learning, and working memory compared with HC.

Conclusions.

Findings indicate that sex differences in cognitive functioning in ARMS are similar to those seen between healthy men and women. Thus, it appears that sex differences in cognitive performance may not be specific for ARMS, a finding resembling that in patients with schizophrenic psychoses.
Schizophrenia and “unmet needs”: From diagnosis to care in Italy
Authors: Galderisi Silvana , Riva Marco A. , Girardi Paolo , Amore Mario , Carpiniello Bernardo , Aguglia Eugenio , Fagiolini Andrea , Mucci Armida , Vita Antonio
Published: March 2020

Background.

Schizophrenia is a leading cause of disability. People living with schizophrenia (PLWS) present unemployment, social isolation, excess mortality and morbidity, and poor quality of life. Early recognition and appropriate treatment reduce the risk of chronicity and comorbidity. Personalization and integration of pharmacological and psychosocial interventions, as well as accurate identification and management of psychiatric and somatic comorbidities, can significantly improve mental and physical health of PLWS, promoting recovery.

Methods.

A three-step Delphi approach was used to explore consensus on the essential components of early recognition and intervention, personalization, and integration of care to improve schizophrenia outcome, and on barriers and challenges to close treatment gaps. The consensus involved 8 Italian experts of schizophrenia, 100 psychiatrists from academic and nonacademic settings, including representatives of Italian Society of Psychiatry, and 65 trainees in psychiatry.

Results.

A strong consensus (from mostly agree to totally agree) emerged on the importance of early diagnosis (97%), standardized assessments (91%), correct management of somatic and psychiatric comorbidities (99%), and personalization and integration of care (94%). Lack of time, human resources, and training were identified as the main barriers and challenges to the translation of knowledge into clinical practice.

Conclusions.

The results of this Delphi study demonstrated a strong consensus on main components of schizophrenia care, as well as on unmet needs to promote best practice and gaps between knowledge and clinical practice. The involvement of a large group of professionals and trainees in this in-depth consensus process might contribute to raise awareness and stimulate innovative strategies to improve the outcome of PLWS.
Factors Affecting Sentinel Node Metastasis in Thin (T1) Cutaneous Melanomas: Development and External Validation of a Predictive Nomogram
Authors: Maurichi Andrea , Miceli Rosalba , Eriksson Hanna , Newton-Bishop Julia , Nsengimana Jérémie , Chan May , Hayes Andrew J. , Heelan Kara , Adams David , Patuzzo Roberto , Barretta Francesco , Gallino Gianfranco , Harwood Catherine , Bergamaschi Daniele , Bennett Dorothy , Lasithiotakis Konstantinos , Ghiorzo Paola , Dalmasso Bruna , Manganoni Ausilia , Consoli Francesca , Mattavelli Ilaria , Barbieri Consuelo , Leva Andrea , Cortinovis Umberto , Espeli Vittoria , Mangas Cristina , Quaglino Pietro , Ribero Simone , Broganelli Paolo , Pellacani Giovanni , Longo Caterina , Del Forno Corrado , Borgognoni Lorenzo , Sestini Serena , Pimpinelli Nicola , Fortunato Sara , Chiarugi Alessandra , Nardini Paolo , Morittu Elena , Florita Antonio , Cossa Mara , Valeri Barbara , Milione Massimo , Pruneri Giancarlo , Zoras Odysseas , Anichini Andrea , Mortarini Roberta , Santinami Mario
Published: March 2020

PURPOSE

Thin melanomas (T1; ≤ 1 mm) constitute 70% of newly diagnosed cutaneous melanomas. Regional node metastasis determined by sentinel node biopsy (SNB) is an important prognostic factor for T1 melanoma. However, current melanoma guidelines do not provide clear indications on when to perform SNB in T1 disease and stress an individualized approach to SNB that considers all clinicopathologic risk factors. We aimed to identify determinants of sentinel node (SN) status for incorporation into an externally validated nomogram to better select patients with T1 disease for SNB.

PATIENTS AND METHODS

The development cohort comprised 3,666 patients with T1 disease consecutively treated at the Istituto Nazionale Tumori (Milan, Italy) between 2001 and 2018; 4,227 patients with T1 disease treated at 13 other European centers over the same period formed the validation cohort. A random forest procedure was applied to the development data set to select characteristics associated with SN status for inclusion in a multiple binary logistic model from which a nomogram was elaborated. Decision curve analyses assessed the clinical utility of the nomogram.

RESULTS

Of patients in the development cohort, 1,635 underwent SNB; 108 patients (6.6%) were SN positive. By univariable analysis, age, growth phase, Breslow thickness, ulceration, mitotic rate, regression, and lymphovascular invasion were significantly associated with SN status. The random forest procedure selected 6 variables (not growth phase) for inclusion in the logistic model and nomogram. The nomogram proved well calibrated and had good discriminative ability in both cohorts. Decision curve analyses revealed the superior net benefit of the nomogram compared with each individual variable included in it as well as with variables suggested by current guidelines.

CONCLUSION

We propose the nomogram as a decision aid in all patients with T1 melanoma being considered for SNB.
Addressing the Challenge of Pain Education in Low-Resource Countries: Essential Pain Management in Papua New Guinea
Authors: Marun Gertrude N. , Morriss Wayne W. , Lim Jessica S. , Morriss Jacqueline L. , Goucke C. Roger
Published: March 2020

Papua New Guinea (PNG) is a low-resource country in the South-West Pacific with considerable health care challenges, including a high burden of painful disease. The Essential Pain Management (EPM) educational program was developed to address the challenge of inadequate pain education in PNG and the first workshop was held in 2010. The aims of EPM are to improve pain knowledge, teach a simple system for managing pain, and address local pain management barriers. It is usually delivered as an interactive, multidisciplinary 1-day workshop with an emphasis on developing local solutions to local problems. The program includes an instructor workshop to encourage early handover to local health care workers. Between 2010 and 2018, a total of 42 one-day workshops and 6 instructor workshops were held throughout PNG, and 783 health care workers were trained, as well as 60 instructors. Over two-thirds of the 1-day workshops were taught entirely by local instructors. A shorter version of the workshop, called EPM Lite, was used to train 109 medical and nursing students. Program evaluation has included participant feedback (reaction) and preworkshop and postworkshop tests (knowledge) since inception. Evaluation of behavioral and organizational change has proved more challenging; however, a survey of past participants suggests some important behavioral changes and points to areas for formal research. The uptake of the EPM program in PNG is encouraging and suggests that there is a need for a pain management education program that is simple and easily adopted by local health care workers. There are still significant challenges, including a lack of funding, limited uptake at undergraduate level, the need for more formal evaluation of clinical impact, and the requirement for an all-of-system approach to improve pain management in PNG. Worldwide, EPM has now been taught in more than 60 countries. Our priorities for coming years include support for embedding EPM into health care systems and teaching programs, increased mentorship for instructors, assistance with overcoming local pain management barriers, and development of specific projects that will assess the impact of EPM education on patient outcomes.
McGrath Video Laryngoscope Versus Macintosh Direct Laryngoscopy for Intubation of Morbidly Obese Patients: A Randomized Trial
Authors: Ruetzler Kurt , Rivas Eva , Cohen Barak , Mosteller Lauretta , Martin Adriana , Keebler Allen , Maheshwari Kamal , Steckner Karen , Wang Mi , Praveen Chahar , Khanna Sandeep , Makarova Natalya , Sessler Daniel I. , Turan Alparslan
Published: March 2020

BACKGROUND:

Two-thirds of the US population is considered obese and about 8% morbidly obese. Obese patients may present a unique challenge to anesthesia clinicians in airway management. Videolaryngoscopes may provide better airway visualization, which theoretically improves intubation success. However, previous work in morbidly obese patients was limited. We therefore tested the primary hypothesis that the use of McGrath video laryngoscope improves visualization of the vocal cords versus Macintosh direct laryngoscopy (Teleflex, Morrisville, NC) in morbidly obese patients.

METHODS:

We enrolled 130 surgical patients, aged 18–99 years, with a body mass index ≥40 kg/m2 and American Society of Anaesthesiologists (ASA) physical status I–III. Patients were randomly allocated 1:1—stratified for patient’s body mass index ≥50 kg/m2—to McGrath video laryngoscope versus direct laryngoscopy with a Macintosh blade. The study groups were compared on glottis visualization, defined as improved Cormack and Lehane classification, with proportional odds logistic regression model.

RESULTS:

McGrath video laryngoscope provided significantly better glottis visualization than Macintosh direct laryngoscopy with an estimated odds ratio of 4.6 (95% confidence interval [CI], 2.2–9.8; P < .01). We did not observe any evidence that number of intubation attempts and failed intubations increased or decreased.

CONCLUSIONS:

McGrath video laryngoscope improves glottis visualization versus Macintosh direct laryngoscopy in morbidly obese patients. Large clinical trials are needed to determine whether improved airway visualization with videolaryngoscopy reduces intubation attempts and failures.