bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the effect of high protein supply on diaphragm atrophy in critically ill patients receiving prolonged mechanical ventilation
Authors: Zhang Qian , Zhou Jing , Zhu Dongmei , Zhou Suming
Published: June 2021

Background

Our aim was to evaluate the effect of high protein to the target of 2.0 g/kg/d on diaphragm atrophy and clinical prognosis of patients receiving prolonged mechanical ventilation (MV).

Methods

This prospective, randomized, controlled, single‐center study included 41 patients who were treated with ≥7 days’ MV. The patients were randomly divided into a standard nutrition treatment (SNT) group and intensive nutrition treatment (INT) group, followed by evaluation of computer tomography–analyzed diaphragm volume, the level of butyrylcholinesterase (BChE) as a muscle mass indicator, and respiratory mechanics indices weekly to observe and compare the differences between the groups.

Results

In the INT group, the actual protein (1.70 ± 0.21 vs 1.06 ± 0.21 g/kg/d, P < .001) and calorie intake (33.46 ± 2.78 vs 25.75 ± 4.81 kcal/kg/d, P < .001) were significantly different from those of the SNT group. Compared with the SNT group, the INT group's diaphragm atrophy improved in the fourth and fifth weeks (all P < .05). The BChE after the third week was higher (all P < .05). No significant differences in respiratory mechanical indices and clinical outcomes were found in the surviving patients between the groups.

Conclusion

INT improved the diaphragm atrophy and muscle mass of critically ill patients receiving prolonged MV. There was no evidence that increasing protein to the target amount of 2.0 g/kg/d is related to improvement in clinical prognosis for patients receiving prolonged MV.
Performing nutrition assessment remotely via telehealth
Authors: Mauldin Kasuen , Gieng John , Saarony Dania , Hu Catherine
Published: June 2021

Performing nutrition assessment remotely via telehealth is a topic of significant interest given the global pandemic in 2020 that has necessitated physical distancing and virtual communications. This review presents an evidence‐based approach to conducting nutrition assessments remotely. The authors present suggestions for adaptations that can be used to perform a remote nutrition‐focused physical exam. Direct‐to‐consumer technologies that can be used in remote nutrition assessment are discussed and compared. Practice tips for conducting a telehealth visit are also presented. The aim of this publication is to provide interdisciplinary clinicians a set of guidelines and best practices for performing nutrition assessments in the era of telehealth.
Clinicopathologic and Genomic Landscape of Breast Carcinoma Brain Metastases
Authors: Huang Richard S.P. , Haberberger James , McGregor Kimberly , Mata Douglas A. , Decker Brennan , Hiemenz Matthew C. , Lechpammer Mirna , Danziger Natalie , Schiavone Kelsie , Creeden James , Graf Ryon P. , Strowd Roy , Lesser Glenn J. , Razis Evangelia D. , Bartsch Rupert , Giannoudis Athina , Bhogal Talvinder , Lin Nancy U. , Pusztai Lajos , Ross Jeffrey S. , Palmieri Carlo , Ramkissoon Shakti H.
Published: June 2021

Background

Among patients with breast carcinoma who have metastatic disease, 15%–30% will eventually develop brain metastases. We examined the genomic landscape of a large cohort of patients with breast carcinoma brain metastases (BCBMs) and compared it with a cohort of patients with primary breast carcinomas (BCs).

Material and Methods

We retrospectively analyzed 733 BCBMs tested with comprehensive genomic profiling (CGP) and compared them with 10,772 primary breast carcinomas (not-paired) specimens. For a subset of 16 triple-negative breast carcinoma (TNBC)–brain metastasis samples, programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) was performed concurrently.

Results

A total of 733 consecutive BCBMs were analyzed. Compared with primary BCs, BCBMs were enriched for genomic alterations in TP53 (72.0%, 528/733), ERBB2 (25.6%, 188/733), RAD21 (14.1%, 103/733), NF1 (9.0%, 66/733), BRCA1 (7.8%, 57/733), and ESR1 (6.3%,46/733) (p < .05 for all comparisons). Immune checkpoint inhibitor biomarkers such as high tumor mutational burden (TMB-high; 16.2%, 119/733); high microsatellite instability (1.9%, 14/733); CD274 amplification (3.6%, 27/733); and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like mutational signature (5.9%, 43/733) were significantly higher in the BCBM cohort compared with the primary BC cohort (p < .05 for all comparisons). When using both CGP and PD-L1 IHC, 37.5% (6/16) of patients with TNBC brain metastasis were eligible for atezolizumab based on PD-L1 IHC, and 18.8% (3/16) were eligible for pembrolizumab based on TMB-high status.

Conclusion

We found a high prevalence of clinically relevant genomic alterations in patients with BCBM, suggesting that tissue acquisition (surgery) and/or cerebrospinal fluid for CGP in addition to CGP of the primary tumor may be clinically warranted.

Implications for Practice

This study found a high prevalence of clinically relevant genomic alterations in patients with breast carcinoma brain metastasis (BCBM), suggesting that tissue acquisition (surgery) and/or cerebrospinal fluid for comprehensive genomic profiling (CGP) in addition to CGP of the primary tumor may be clinically warranted. In addition, this study identified higher positive rates for FDA-approved immunotherapy biomarkers detected by CGP in patients with BCBM, opening a possibility of new on-label treatments. Last, this study noted limited correlation between tumor mutational burden and PD-L1 immunohistochemistry (IHC), which shows the importance of testing patients with triple-negative BCBM for immune checkpoint inhibitor eligibility with both PD-L1 IHC and CGP.
Liquid Biopsy in Glioblastoma Management: From Current Research to Future Perspectives
Authors: Gatto Lidia , Franceschi Enrico , Di Nunno Vincenzo , Tosoni Alicia , Lodi Raffaele , Brandes Alba Ariela
Published: June 2021

Glioblastoma (GBM) is the most common primary tumor of the central nervous system. Arising from neuroepithelial glial cells, GBM is characterized by invasive behavior, extensive angiogenesis, and genetic heterogeneity that contributes to poor prognosis and treatment failure. Currently, there are several molecular biomarkers available to aid in diagnosis, prognosis, and predicting treatment outcomes; however, all require the biopsy of tumor tissue. Nevertheless, a tissue sample from a single location has its own limitations, including the risk related to the procedure and the difficulty of obtaining longitudinal samples to monitor treatment response and to fully capture the intratumoral heterogeneity of GBM. To date, there are no biomarkers in blood or cerebrospinal fluid for detection, follow-up, or prognostication of GBM. Liquid biopsy offers an attractive and minimally invasive solution to support different stages of GBM management, assess the molecular biology of the tumor, identify early recurrence and longitudinal genomic evolution, predict both prognosis and potential resistance to chemotherapy or radiotherapy, and allow patient selection for targeted therapies. The aim of this review is to describe the current knowledge regarding the application of liquid biopsy in glioblastoma, highlighting both benefits and obstacles to translation into clinical care.

Implications for Practice

To translate liquid biopsy into clinical practice, further prospective studies are required with larger cohorts to increase specificity and sensitivity. With the ever-growing interest in RNA nanotechnology, microRNAs may have a therapeutic role in brain tumors.
Regional air transportation of ovarian tissue for cryopreservation in a prepubertal female with cancer
Authors: Schermerhorn Sophia M. V. , Rosen Mitchell P. , Blevins Erin M. , Byrd Kevin A. , Rabban Joseph T. , Marsh Philip , Lucas Donald J.
Published: June 2021

Ovarian tissue cryopreservation is the only fertility preservation (FP) option available to prepubescent females receiving gonadotoxic therapy, but it has limited availability. A 6‐year‐old female was diagnosed with high‐risk rhabdomyosarcoma, and the planned treatment carried an 80% risk of ovarian failure. Her parents desired FP, but the nearest center was 500 miles away. The patient underwent oophorectomy at the cancer center with air transport of the tissue to the oncofertility center, where it was successfully cryopreserved. Formation of networks between full‐service and limited oncofertility centers in a hub‐and‐spoke model would increase access to FP services, particularly in children.
A green approach for the development of functionalized graphene and cardanol‐based polybenzoxazine nanocomposite
Authors: Sambandam Sahila , Nallamuthu Prabhu , Lakshmanan Saraswathi Jayakumari
Published: June 2021

A new facile synthesis of functionalized graphene (fg‐p) reinforced bio‐based polybenzoxazine nanocomposite (pbf2%–pbf10%) was developed in this work. Cardanol, formaldehyde, and furfuryl amine were used to make a bio‐based benzoxazine monomer (bf). bf and benzoxazine polymer (pbf) were characterized by Fourier transform infrared (FT‐IR) and nuclear magnetic resonance spectroscopies, and fg‐p was characterized by FT‐IR spectroscopy, X‐ray diffraction, and scanning electron microscopy. The electrochemical properties of the fg‐p sheets and their nanocomposites (pbf2%–pbf10%) were examined using cyclic voltammetry and electrochemical impedance spectroscopy. The results of electrochemical measurements showed that pbf4% has the largest specific capacitance of 78.2 F/g when compared to pbf (36.98 F/g), which shows that fg‐p reinforced pbf nanocomposites have potential application as the high‐performance capacitor electrode material.
Preparation of poly(acrylamide‐co‐2‐acrylamido‐2‐methylpropan sulfonic acid)‐g‐Carboxymethyl cellulose/Titanium dioxide hydrogels and modeling of their swelling capacity and mechanic strength behaviors by response surface method technique
Authors: Boztepe Cihangir , Daskin Mahmut , Erdogan Ahmet , Sarici Talha
Published: June 2021

It is very important that new generation, unique, high mechanical strength, and biocompatible hydrogel composites are developed due to their potential to be used as biomaterials in the biomedical field. Modeling of the swelling capacity and mechanical strength behavior of hydrogels is a domain of steadily increasing academic and industrial importance. These behaviors are difficult to model accurately due to hydrogels show very complex behavior depending on the content. In this study, a series of poly(acrylamide‐co‐2‐acrylamido‐2‐methylpropan sulfonic acid)‐g‐carboxymethyl cellulose/TiO2 (poly(AAm‐co‐AMPS)‐g‐CMC/TiO2) superabsorbent hydrogel composites were prepared by free‐radical graft copolymerization in aqueous solution. Structural and surface morphology characterizations were conducted by using Fourier‐transform infrared spectroscopy and scanning electron microscope analysis techniques. For modeling the equilibrium swelling capacity and fracture strength behaviors of hydrogels, the composition parameters (such as mole ratio of AMPS/AAm, wt% of CMC, and wt% of TiO2) was proposed by response surface method (RSM) Design Expert‐10 software. Statistical parameters showed that the RSM model has good performance in modeling the swelling capacity and mechanic fracture strength behaviors of poly(AAm‐co‐AMPS)‐g‐CMC/TiO2 hydrogel composites. According to the RSM model results, the maximum swelling capacity and fracture strength values were calculated as 270.39 g water/g polymer and 159.23 kPa, respectively.
Fabrication and applications of stimuli‐responsive micro/nanopillar arrays
Authors: Park Jeong Eun , Won Sukyoung , Cho Woongbi , Kim Jae Gwang , Jhang Saebohm , Lee Jae Gyeong , Wie Jeong Jae
Published: June 2021

The functional surface features of living creatures are driven by the complex morphology of periodically arranged micro/nanoscale structures. Various fabrication processes have been devised mimic the performance of natural features; these methods morph hierarchical and multi‐leveled pillar arrays, such as top‐down, bottom‐up, and a hybrid of top‐down and bottom‐up processes. Different methodologies are employed depending on the materials, such as polymeric composites, metal oxides, metals, and carbon nanotubes. In this review, we discuss the shape‐reconfiguration of stimuli‐responsive micro/nanopillar arrays achieved by capillary force, light, magnetic field, and heat. In particular, photo‐ and magnetic actuation of pillar arrays revealed programmability according to the arrangement of the liquid crystal molecules or magnetic particles by remote control. Furthermore, applications of micro/nanopillar arrays, such as adhesives, omniphobicity, optics, and biomedical technologies, are also discussed.
Role of montelukast in multitrigger wheezers attending chest clinic in Punjab, India
Authors: Kahlon Gursavreen K. , Pooni Puneet A. , Bhat Deepak , Dhooria Gurdeep S. , Bhargava Siddharth , Arora Kamal , Gill Karambir S.
Published: June 2021

Background

Wheeze is seen in 40% of preschool children, one‐third of these may develop recurrent wheeze. Montelukast is an oral, once a day, easy to give therapy but there is no definite evidence to support its use in a recent meta‐analysis. Present study was done to evaluate role of daily montelukast and various factors affecting the outcome after therapy in multitrigger wheeze (MTW).

Methods

A prospective study conducted in Pediatric chest clinic over 18 months at DMCH, Ludhiana. Children from 6 months to 5 years, diagnosed cases of MTW were started on montelukast. Diagnosis based on symptoms of recurrent wheeze triggered by various allergens/precipitants was made by pediatrician in charge of chest clinic. Children were followed up at 1 and 3 months. They were labeled as controlled, partially controlled, or uncontrolled as per global initiative for asthma guidelines. Data were used to compare the outcome related to various factors.

Results

Total 139 out of 150 children came for regular follow‐up. At the end of 3 months, 94 (67.7%) were controlled, 8 (5.7%) partially controlled, and 37 (26.6%) children remained uncontrolled on montelukast. Factors associated with poor control were onset of symptoms at younger age (<6 months of age), family history of allergies, prior multiple visits or hospitalizations due to MTW, use of MDI in the past. No significant side effects were reported by parents.

Conclusion

Symptomatically two‐third of children became better after starting montelukast. There were few factors which resulted in poorer control in subset of patients.
Proteomic analysis of a murine model of lung hypoplasia induced by oligohydramnios
Authors: Najrana Tanbir , Ahsan Nagib , Abu‐Eid Rasha , Uzun Alper , Noble Lelia , Tollefson George , Sanchez‐Esteban Juan
Published: June 2021

Severe oligohydramnios (OH) due to prolonged loss of amniotic fluid can cause pulmonary hypoplasia. Animal model of pulmonary hypoplasia induced by amniotic fluid drainage is partly attributed to changes in mechanical compression of the lung. Although numerous studies on OH‐model have demonstrated changes in several individual proteins, however, the underlying mechanisms for interrupting normal lung development in response to a decrease of amniotic fluid volume are not fully understood. In this study, we used a proteomic approach to explore differences in the expression of a wide range of proteins after induction of OH in a mouse model of pulmonary hypoplasia to find out the signaling/molecular pathways involved in fetal lung development. Liquid chromatography‐massspectromery/mass spectrometry analysis found 474 proteins that were differentially expressed in OH‐induced hypoplastic lungs in comparison to untouched (UnT) control. Among these proteins, we confirmed the downregulation of AKT1, SP‐D, and CD200, and provided proof‐of‐concept for the first time about the potential role that these proteins could play in fetal lung development.
Catalytically impaired TrpA subunit of tryptophan synthase from Chlamydia trachomatis is an allosteric regulator of TrpB
Authors: Michalska Karolina , Wellington Samantha , Maltseva Natalia , Jedrzejczak Robert , Selem‐Mojica Nelly , Rosas‐Becerra L. Rodrigo , Barona‐Gómez Francisco , Hung Deborah T. , Joachimiak Andrzej
Published: June 2021

Intracellular growth and pathogenesis of Chlamydia species is controlled by the availability of tryptophan, yet the complete biosynthetic pathway for l‐Trp is absent among members of the genus. Some representatives, however, preserve genes encoding tryptophan synthase, TrpAB – a bifunctional enzyme catalyzing the last two steps in l‐Trp synthesis. TrpA (subunit α) converts indole‐3‐glycerol phosphate into indole and glyceraldehyde‐3‐phosphate (α reaction). The former compound is subsequently used by TrpB (subunit β) to produce l‐Trp in the presence of l‐Ser and a pyridoxal 5′‐phosphate cofactor (β reaction). Previous studies have indicated that in Chlamydia, TrpA has lost its catalytic activity yet remains associated with TrpB to support the β reaction. Here, we provide detailed analysis of the TrpAB from C. trachomatis D/UW‐3/CX, confirming that accumulation of mutations in the active site of TrpA renders it enzymatically inactive, despite the conservation of the catalytic residues. We also show that TrpA remains a functional component of the TrpAB complex, increasing the activity of TrpB by four‐fold. The side chain of non‐conserved βArg267 functions as cation effector, potentially rendering the enzyme less susceptible to the solvent ion composition. The observed structural and functional changes detected herein were placed in a broader evolutionary and genomic context, allowing identification of these mutations in relation to their trp gene contexts in which they occur. Moreover, in agreement with the in vitro data, partial relaxation of purifying selection for TrpA, but not for TrpB, was detected, reinforcing a partial loss of TrpA functions during the course of evolution.
Excipient knowledgebase: Development of a comprehensive tool for understanding the disposition and interaction potential of common excipients
Authors: McFeely Savannah J. , Yu Jingjing , Wang Yan , Wu Cheryl , Ragueneau‐Majlessi Isabelle
Published: June 2021

Although the use of excipients is widespread, a thorough understanding of the drug interaction potential of these compounds remains a frequent topic of current research. Not only can excipients alter the disposition of coformulated drugs, but it is likely that these effects on co‐administered drugs can reach to clinical significance leading to potential adverse effects or loss of efficacy. These risks can be evaluated through use of in silico methods of mechanistic modeling, including approaches, such as population pharmacokinetic (PK) and physiologically‐based PK modeling, which require a comprehensive understanding of the compounds to ensure accurate predictions. We established a knowledgebase of the available compound (or substance) and interaction‐specific parameters with the goal of providing a single source of physiochemical, in vitro, and clinical PK and interaction data of commonly used excipients. To illustrate the utility of this knowledgebase, a model for cremophor EL was developed and used to hypothesize the potential for CYP3A‐ and P‐gp‐based interactions as a proof of concept.
Preparation and characterization of whey protein isolate/chitosan/microcrystalline cellulose composite films
Authors: Zhai Xinyu , Zhang Xia , Ao Huanping , Yin Yuxi , Li Xue , Ren Difeng
Published: June 2021

A bio‐based composite film was prepared using whey protein isolate (WPI), chitosan (CS) and microcrystalline cellulose (MCC). The effects of film‐forming material concentration ratio, pH value and glycerin addition on the mechanical properties, water vapour permeability and transmittance of the composite film were investigated using response surface methodology. Optimum film‐forming process conditions were obtained, including a CS/MCC concentration ratio of 1.5:1, pH 3.6 and 30% glycerin addition. Scanning electron microscopy and atomic force microscopy images showed that the surface of the WPI/CS/MCC composite films was flat, uniform and smooth. Fourier‐transform infrared spectroscopy analysis indicated that hydrogen bonds occurred between the film‐forming materials. The film‐forming materials were concluded to have good compatibility, while the WPI/CS/MCC composite film showed better mechanical properties and moisture barrier properties, which will provide a good application prospect and foundation for the food packaging industry.
First‐principles study on the plutonium ions interaction with diamide molecules in acid solutions
Authors: Ryzhkov Mikhail V. , Enyashin Andrei N. , Delley Bernard
Published: June 2021

Theoretical study of the formation of PuZ+ (Z = 3, 4, 5, 6) complexes with the two types of diamide molecules C8N2H10O2(CH3)2 (dimethylbicyclicdiamide—DMDA) with bicyclic structure and C3N2H2O2(CH3)4 (tetramethylmalonamide—TMMA) with acyclic structure was carried out using ab initio DFT based DMol3 and relativistic discrete variational methods. The results of gas phase modeling showed that the appropriate positions of the oxygen atoms in DMDA in comparison with TMMA cannot explain the considerable difference in sorption affinity of these molecules. For the modeling of solutions, the implicit (COSMO) and explicit methods were used. In the latter approach, we included 40 water molecules, 16NO3− or 16Cl− and 16H+ ions into the systems under investigation. The obtained results showed the principle role of solution in the weakening of actinide bonding with TMMA and DMDA molecules due to interaction with H2O and NO3− or Cl− ions.
Voltage‐Tunable Ultra‐Steep Slope Atomic Switch with Selectivity over 1010
Authors: Kim Kwang‐Hyun , Park Youngjun , Kim Min‐Kyu , Lee Jang‐Sik
Published: June 2021

Atomic switch‐based selectors, which utilize the formation of conductive filaments by the migration of ions, are researched for cross‐point array architecture due to their simple structure and high selectivity. However, the difficulty in controlling the formation of filaments causes uniformity and reliability issues. Here, a multilayer selector with Pt/Ag‐doped ZnO/ZnO/Ag‐doped ZnO/Pt structure by the sputtering process is presented. A multilayer structure enables control of the filament formation by preventing excessive influx of Ag ions. The multilayer selector device exhibits a high on‐current density of 2 MA cm−2, which can provide sufficient current for the operation with the memory device. Also, the device exhibits high selectivity of 1010 and a low off‐current of 10−13 A. The threshold voltage of selector devices can be controlled by modulating the thickness of the ZnO layer. By connecting a multilayer selector device to a resistive switching memory, the leakage current of the memory device can be reduced. These results demonstrate that a multilayer structure can be used in a selector device to improve selectivity and reliability for use in high‐density memory devices.
Supramolecular Nanosubstrate‐Mediated Delivery for CRISPR/Cas9 Gene Disruption and Deletion
Authors: Ban Qian , Yang Peng , Chou Shih‐Jie , Qiao Li , Xia Haidong , Xue Jingjing , Wang Fang , Xu Xiaobin , Sun Na , Zhang Ryan Y. , Zhang Ceng , Lee Athena , Liu Wenfei , Lin Ting‐Yi , Ko Yu‐Ling , Antovski Petar , Zhang Xinyue , Chiou Shih‐Hwa , Lee Chin‐Fa , Hui Wenqiao , Liu Dahai , Jonas Steven J. , Weiss Paul S. , Tseng Hsian‐Rong
Published: June 2021

The clustered regularly interspaced short palindromic repeats (CRISPR)‐associated protein 9 (CRISPR/Cas9) is an efficient and precise gene‐editing technology that offers a versatile solution for establishing treatments directed at genetic diseases. Currently, CRISPR/Cas9 delivery into cells relies primarily on viral vectors, which suffer from limitations in packaging capacity and safety concerns. These issues with a nonviral delivery strategy are addressed, where Cas9•sgRNA ribonucleoprotein (RNP) complexes can be encapsulated into supramolecular nanoparticles (SMNP) to form RNP⊂SMNPs, which can then be delivered into targeted cells via supramolecular nanosubstrate‐mediated delivery. Utilizing the U87 glioblastoma cell line as a model system, a variety of parameters for cellular‐uptake of the RNP‐laden nanoparticles are examined. Dose‐ and time‐dependent CRISPR/Cas9‐mediated gene disruption is further examined in a green fluorescent protein (GFP)‐expressing U87 cell line (GFP‐U87). The utility of an optimized SMNP formulation in co‐delivering Cas9 protein and two sgRNAs that target deletion of exons 45–55 (708 kb) of the dystrophin gene is demonstrated. Mutations in this region lead to Duchenne muscular dystrophy, a severe genetic muscle wasting disease. Efficient delivery of these gene deletion cargoes is observed in a human cardiomyocyte cell line (AC16), induced pluripotent stem cells, and mesenchymal stem cells.
Bond strength degradation in concrete cracked by expansion agent filled pipes
Authors: Syll Amadou Sakhir , Aburano Togo , Kanakubo Toshiyuki
Published: June 2021

In this study, the bond behavior of corroded reinforced concrete was investigated by conducting pull‐out tests on concrete specimens with variable induced crack widths and different splitting modes. To simulate cracks due to corrosion and focus on their effect on bond strength degradation, a novel method using expansion agent filled pipes is proposed. With the increase of the crack width over elapsed time from filling the aluminum pipe with an expansion agent, a target crack width was obtained. The results confirm that the type of splitting greatly influences the reduction in bond strength with deterioration of bond strength more severe in “Side‐split” than in “Single‐split.” Furthermore, using the surface crack width as a variable, empirical formulas to predict bond strength degradation due to corrosion of rebar are proposed. These prediction models give a good correlation when compared to the available literature.
The incidence and outcome of postoperative hepatic encephalopathy in patients with cirrhosis
Authors: Saleh Zachary M. , Solano Quintin P. , Louissaint Jeremy , Jepsen Peter , Tapper Elliot B.
Published: June 2021

Background

Cirrhosis is associated with increased perioperative risks related to hepatic decompensation. However, data are lacking regarding the incidence and outcomes of postoperative hepatic encephalopathy (HE).

Objective

To determine the incidence of HE postoperatively, factors associated with its development, and its association with in‐hospital mortality.

Methods

Retrospective cohort study of 583 patients with cirrhosis undergoing non‐hepatic surgery over a 10‐year period. Outcomes included postoperative HE and in‐hospital mortality and were, respectively, evaluated using multi‐state modeling and Fine‐Gray competing risk regression (with postoperative HE as a time‐varying covariate).

Results

Overall, the median Model for End‐Stage Liver Disease Sodium was 10, 61.7% had a history of ascites, 49.9% esophageal varices, and 34.6% HE. The most common surgeries including abdominal/non‐bowel (33.3%), orthopedic (18.0%), and bowel (12.2%). A total of 42 (7.2%) patients developed HE postoperatively during admission. The cumulative risk of HE was 7.2%, which was most associated with a history of HE, ASA class, postoperative AKI, and postoperative infection. In‐hospital mortality occurred in 34 (5.8%) individuals. Only ASA class was independently associated (HR 2.46, 95%CI 1.21–5.02), but there was a trend for postoperative HE (HR 1.71, 95%CI 0.73–3.98).

Discussion

HE is an uncommon but not rare postoperative complication that increases the risk of patient harm. This study implies its development is predictable. Consequently, at‐risk patients should have consultation with a hepatologist before undergoing elective surgery.
Semi-supervised Text Mining for Monitoring the News About the ESG Performance of Companies
Authors: Borms Samuel , Boudt Kris , Holle Frederiek Van , Willems Joeri
Published: June 2021

We present a general monitoring methodology to summarize news about predefined entities and topics into tractable time-varying indices. The approach embeds text mining techniques to transform news data into numerical data, which entails the querying and selection of relevant news articles and the construction of frequency- and sentiment-based indicators. Word embeddings are used to achieve maximally informative news selection and scoring. We apply the methodology from the viewpoint of a sustainable asset manager wanting to actively follow news covering environmental, social, and governance (ESG) aspects. In an empirical analysis, using a Dutch-written news corpus, we create news-based ESG signals for a large list of companies and compare these to scores from an external data provider. We find preliminary evidence of abnormal news dynamics leading up to downward score adjustments and of efficient portfolio screening.
Extraction and Representation of Financial Entities from Text
Authors: Repke Tim , Krestel Ralf
Published: June 2021

In our modern society, almost all events, processes, and decisions in a corporation are documented by internal written communication, legal filings, or business and financial news. The valuable knowledge in such collections is not directly accessible by computers as they mostly consist of unstructured text. This chapter provides an overview of corpora commonly used in research and highlights related work and state-of-the-art approaches to extract and represent financial entities and relations.The second part of this chapter considers applications based on knowledge graphs of automatically extracted facts. Traditional information retrieval systems typically require the user to have prior knowledge of the data. Suitable visualization techniques can overcome this requirement and enable users to explore large sets of documents. Furthermore, data mining techniques can be used to enrich or filter knowledge graphs. This information can augment source documents and guide exploration processes. Systems for document exploration are tailored to specific tasks, such as investigative work in audits or legal discovery, monitoring compliance, or providing information in a retrieval system to support decisions.
Supervised Learning for the Prediction of Firm Dynamics
Authors: Bargagli-Stoffi Falco J. , Niederreiter Jan , Riccaboni Massimo
Published: June 2021

Thanks to the increasing availability of granular, yet high-dimensional, firm level data, machine learning (ML) algorithms have been successfully applied to address multiple research questions related to firm dynamics. Especially supervised learning (SL), the branch of ML dealing with the prediction of labelled outcomes, has been used to better predict firms’ performance. In this chapter, we will illustrate a series of SL approaches to be used for prediction tasks, relevant at different stages of the company life cycle. The stages we will focus on are (1) startup and innovation, (2) growth and performance of companies, and (3) firms’ exit from the market. First, we review SL implementations to predict successful startups and R&D projects. Next, we describe how SL tools can be used to analyze company growth and performance. Finally, we review SL applications to better forecast financial distress and company failure. In the concluding section, we extend the discussion of SL methods in the light of targeted policies, result interpretability, and causality.
Inquiry Systems: How Do We Know What We Need to Know?
Authors: Mitroff Ian I. , Kilmann Ralph H.
Published: June 2021

No less problematic than the various elements we’ve been discussing are the kinds of knowledge that are needed to navigate a complex world of Wicked Messes. As we shall see, it’s not just a matter of Epistemology, i.e., formal theories of knowledge, but how they are affected by and interact with different Psychological states of mind, especially the Parent, Adult, Child, and Secure versus Insecure Adults.
Towards a Standardized Questionnaire for Measuring Agility at Team Level
Authors: Looks Hanna , Fangmann Jannik , Thomaschewski Jörg , Escalona María-José , Schön Eva-Maria
Published: June 2021

Context: Twenty years after the publication of the agile manifesto, agility is becoming more and more popular in different contexts. Agile values are changing the way people work together and influence people’s mindset as well as the culture of organizations. Many organizations have understood that continuous improvement is based on measurement.

Objective: The objective of this paper is to present how agility can be measured at the team level. For this reason, we will introduce our questionnaire for measuring agility, which is based on the agile values of the manifesto.

Method: We developed a questionnaire comprising 36 items that measure the current state of a team’s agility in six dimensions (communicative, change-affine, iterative, self-organized, product-driven and improvement-oriented). This questionnaire has been evaluated with respect to several expert reviews and in a case study.

Results: The questionnaire provides a method for measuring the current state of agility, which takes the individual context of the team into account. Furthermore, our research shows, that this technique enables the user to uncover dysfunctionalities in a team.

Conclusion: Practitioners and organizations can use our questionnaire to optimize collaboration within their teams in terms of agility. In particular, the value delivery of an organization can be increased by optimizing collaboration at the team level. The development of this questionnaire is a continuous learning process with the aim to develop a standardized questionnaire for measuring agility.
Black holes and the swampland: the deep throat revelations
Authors: Li Yixuan
Published: June 2021

Abstract

Multi-centered bubbling solutions are black hole microstate geometries that arise as smooth solutions of 5-dimensional $$ \mathcal{N} $$
N
= 2 Supergravity. When these solutions reach the scaling limit, their resulting geometries develop an infinitely deep throat and look arbitrarily close to a black hole geometry. We depict a connection between the scaling limit in the moduli space of Microstate Geometries and the Swampland Distance Conjecture. The naive extension of the Distance Conjecture implies that the distance in moduli space between a reference point and a point approaching the scaling limit is set by the proper length of the throat as it approaches the scaling limit. Independently, we also compute a distance in the moduli space of 3-centre solutions, from the Kähler structure of its phase space using quiver quantum mechanics. We show that the two computations of the distance in moduli space do not agree and comment on the physical implications of this mismatch.
Status and advances in mining for blackleg (Leptosphaeria maculans) quantitative resistance (QR) in oilseed rape (Brassica napus)
Authors: Amas Junrey , Anderson Robyn , Edwards David , Cowling Wallace , Batley Jacqueline
Published: June 2021

Key message

Quantitative resistance (QR) loci discovered through genetic and genomic analyses are abundant in theBrassica napusgenome, providing an opportunity for their utilization in enhancing blackleg resistance.

Quantitative resistance (QR) has long been utilized to manage blackleg inBrassica napus(canola, oilseed rape), even before major resistance genes (R-genes) were extensively explored in breeding programmes. In contrast to R-gene-mediated qualitative resistance, QR reduces blackleg symptoms rather than completely eliminating the disease. As a polygenic trait, QR is controlled by numerous genes with modest effects, which exerts less pressure on the pathogen to evolve; hence, its effectiveness is more durable compared to R-gene-mediated resistance. Furthermore, combining QR with major R-genes has been shown to enhance resistance against diseases in important crops, including oilseed rape. For these reasons, there has been a renewed interest among breeders in utilizing QR in crop improvement. However, the mechanisms governing QR are largely unknown, limiting its deployment. Advances in genomics are facilitating the dissection of the genetic and molecular underpinnings of QR, resulting in the discovery of several loci and genes that can be potentially deployed to enhance blackleg resistance. Here, we summarize the efforts undertaken to identify blackleg QR loci in oilseed rape using linkage and association analysis. We update the knowledge on the possible mechanisms governing QR and the advances in searching for the underlying genes. Lastly, we lay out strategies to accelerate the genetic improvement of blackleg QR in oilseed rape using improved phenotyping approaches and genomic prediction tools.
Ordinary varieties with trivial canonical bundle are not uniruled
Authors: Patakfalvi Zsolt , Zdanowicz Maciej
Published: June 2021

We prove that smooth, projective,K-trivial, weakly ordinary varieties over a perfect field of characteristic$$p>0$$p>0are not geometrically uniruled. We also show a singular version of our theorem, which is sharp in multiple aspects. Our work, together with Langer’s results, implies that varieties of the above type have strongly semistable tangent bundles with respect to every polarization.
Playing your pain away: designing a virtual reality physical therapy for children with upper limb motor impairment
Authors: Phelan Ivan , Furness Penny Jayne , Matsangidou Maria , Carrion-Plaza Alicia , Dunn Heather , Dimitri Paul , Lindley Shirley A.
Published: June 2021

Children with upper limb motor impairment often undergo repetitive therapeutic physiotherapy sessions to minimize functional disabilities of the affected area. Even though therapeutic processes can improve functional outcomes and minimize persistent disabilities, patients often neglect to participate fully in physical therapies due to the associated procedural pain. Over recent decades, there has been a growing interest in designing non-pharmacological interventions which aim to minimize pain during physical therapies and improve functional outcomes. Via two interrelated studies, we explored the use of virtual reality (VR) as a tool to provide therapeutic physiotherapy for child patients in an out-patient hospital department. We found that VR is an effective solution for children with upper limb motor impairment undergoing painful therapeutic process within a hospital environment. VR can improve functional disabilities, alleviate perceived pain, reduce the perceived difficulty of rehabilitation exercises, increase exercise duration and produce positive emotions towards the therapy.

Trial registration number and date of registration Protocol ID NCT03998995. Release Date: June 25, 2019.
Diagnostic performance of four SARS-CoV-2 antibody assays in patients with COVID-19 or with bacterial and non-SARS-CoV-2 viral respiratory infections
Authors: Huber Timo , Steininger Philipp , Irrgang Pascal , Korn Klaus , Tenbusch Matthias , Diesch Katharina , Achenbach Susanne , Kremer Andreas E. , Werblow Marissa , Vetter Marcel , Bogdan Christian , Held Jürgen
Published: June 2021

SARS-CoV-2 antibody assays are used for epidemiological studies and for the assessment of vaccine responses in highly vulnerable patients. So far, data on cross-reactivity of SARS-CoV-2 antibody assays is limited. Here, we compared four enzyme-linked immunosorbent assays (ELISAs; Vircell SARS-CoV-2 IgM/IgA and IgG, Euroimmun SARS-CoV-2 IgA and IgG) for detection of anti-SARS-CoV-2 antibodies in 207 patients with COVID-19, 178 patients with serological evidence of different bacterial infections, 107 patients with confirmed viral respiratory disease, and 80 controls from the pre-COVID-19 era. In COVID-19 patients, the assays showed highest sensitivity in week 3 (Vircell-IgM/A and Euroimmun-IgA: 78.9% each) and after week 7 (Vircell-IgG: 97.9%; Euroimmun-IgG: 92.1%). The antibody indices were higher in patients with fatal disease. In general, IgM/IgA assays had only limited or no benefit over IgG assays. In patients with non-SARS-CoV-2 respiratory infections, IgG assays were more specific than IgM/IgA assays, and bacterial infections were associated with more false-positive results than viral infections. The specificities in bacterial and viral infections were 68.0 and 81.3% (Vircell-IgM/IgA), 84.8 and 96.3% (Euroimmun-IgA), 97.8 and 86.0% (Vircell-IgG), and 97.8 and 99.1% (Euroimmun-IgG), respectively. Sera from patients positive for antibodies against Mycoplasma pneumoniae, Chlamydia psittaci, and Legionella pneumophila yielded particularly high rates of unspecific false-positive results in the IgM/IgA assays, which was revealed by applying a highly specific flow-cytometric assay using HEK 293 T cells expressing the SARS-CoV-2 spike protein. Positive results obtained with anti-SARS-CoV-2 IgM/IgA ELISAs require careful interpretation, especially if there is evidence for prior bacterial respiratory infections.
Maturing Autophagosomes are Transported Towards the Cell Periphery
Authors: Hilverling Anna , Szegö Eva M. , Dinter Elisabeth , Cozma Diana , Saridaki Theodora , Falkenburger Björn H.
Published: June 2021

Autophagosome maturation comprises fusion with lysosomes and acidification. It is a critical step in the degradation of cytosolic protein aggregates that characterize many neurodegenerative diseases. In order to better understand this process, we studied intracellular trafficking of autophagosomes and aggregates of α-synuclein, which characterize Parkinson’s disease and other synucleinopathies. The autophagosomal marker LC3 and the aggregation prone A53T mutant of α-synuclein were tagged by fluorescent proteins and expressed in HEK293T cells and primary astrocytes. The subcellular distribution and movement of these vesicle populations were analyzed by (time-lapse) microscopy. Fusion with lysosomes was assayed using the lysosomal marker LAMP1; vesicles with neutral and acidic luminal pH were discriminated using the RFP-GFP “tandem-fluorescence” tag. With respect to vesicle pH, we observed that neutral autophagosomes, marked by LC3 or synuclein, were located more frequently in the cell center, and acidic autophagosomes were observed more frequently in the cell periphery. Acidic autophagosomes were transported towards the cell periphery more often, indicating that acidification occurs in the cell center before transport to the periphery. With respect to autolysosomal fusion, we found that lysosomes preferentially moved towards the cell center, whereas autolysosomes moved towards the cell periphery, suggesting a cycle where lysosomes are generated in the periphery and fuse to autophagosomes in the cell center. Unexpectedly, many acidic autophagosomes were negative for LAMP1, indicating that acidification does not require fusion to lysosomes. Moreover, we found both neutral and acidic vesicles positive for LAMP1, consistent with delayed acidification of the autolysosome lumen. Individual steps of aggregate clearance thus occur in dedicated cellular regions. During aggregate clearance, autophagosomes and autolysosomes form in the center and are transported towards the periphery during maturation. In this process, luminal pH could regulate the direction of vesicle transport.

Graphic Abstract

(1) Transport and location of autophagosomes depend on luminal pH: Acidic autophagosomes are preferentially transported to the cell periphery, causing more acidic autophagosomes in the cell periphery and more neutral autophagosomes at the microtubule organizing center (MTOC). (2) Autolysosomes are transported to the cell periphery and lysosomes to the MTOC, suggesting spatial segregation of lysosome reformation and autolysosome fusion. (3) Synuclein aggregates are preferentially located at the MTOC and synuclein-containing vesicles in the cell periphery, consistent with transport of aggregates to the MTOC for autophagy.
Phase 1a study of the CDK4/6 inhibitor, FCN-437c, in Chinese patients with HR + /HER2- advanced breast cancer
Authors: Zhang Jian , Wang Xiaojia , Wang Xian , Hui Aimin , Wu Zhuli , Tian Ling , Xu Changjiang , Yang Yuchen , Zhang Wenjing , Hu Xichun
Published: June 2021

Summary Purpose This phase 1a, first-in-human study assessed the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), and antitumor activity of FCN-437c, a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Methods The study enrolled female patients with HR + /HER2- advanced breast cancer (BC) who failed standard of care therapy. A 3 + 3 dose-escalation design was utilized with a starting dose of 50 mg daily for 3 weeks on and 1 week off treatment in 28-day cycles. Patients received escalating doses of FCN-437c monotherapy (50, 100, 200, 300, and 450 mg). Results Seventeen patients received FCN-437c 50 mg (n = 3), 100 mg (n = 3), 200 mg (n = 3), 300 mg (n = 6), and 450 mg (n = 2). Two patients who received the 450-mg dose experienced dose-limiting toxicities (DLTs; grade 4 thrombocytopenia and neutropenia); no DLT was observed at any other dose level. Frequently reported treatment-emergent adverse events (TEAEs) of any grade were hematological: leukopenia (94.1%), neutropenia (88.2%), anemia (64.7%), and thrombocytopenia (47.1%). Grade 3–4 TEAEs included neutropenia (64.7%) and leukopenia (47.1%). Exposure of FCN-437c increased almost proportionally to doses ranging from 50 to 200 mg. At doses from 200 to 450 mg, there appeared to be a trend of saturation. The MTD was determined to be 300 mg. Of 15 patients with measurable disease, nine (60.0%) patients experienced stable disease; no complete or partial responses were observed. Conclusions These results established an acceptable safety profile for FCN-437c in patients with advanced BC, and there were no unexpected signals relative to other CDK4/6 inhibitors. (NCT04488107; July 13, 2020)
Experiences and Perceived Effects of Rosary Praying: A Qualitative Study
Authors: Stöckigt Barbara , Jeserich F. , Walach H. , Elies M. , Brinkhaus B. , Teut M.
Published: June 2021

The aim of this study is to explore experiences and perceived effects of the Rosary on issues around health and well-being, as well as on spirituality and religiosity. A qualitative study was conducted interviewing ten Roman Catholic German adults who regularly practiced the Rosary prayer. As a result of using a tangible prayer cord and from the rhythmic repetition of prayers, the participants described experiencing stability, peace and a contemplative connection with the Divine, with Mary as a guide and mediator before God. Praying the Rosary was described as helpful in coping with critical life events and in fostering an attitude of acceptance, humbleness and devotion.
Effect of mānuka (Leptospermum scoparium) on nitrogen and Escherichia coli reductions in soils: a field experiment
Authors: Halford Sky , Gutiérrez-Ginés María J. , Rees Andrew , Alderton Izzie , Schaller Kolja , Smith Rawiri , Horswell Jacqui
Published: June 2021

Purpose

Planting strategies can be effective mechanisms to reduce diffuse pollution from agricultural catchments reaching water bodies. Plants with antimicrobial properties such as mānuka (Leptospermum scoparium) demonstrated in controlled conditions the ability to inhibit nitrification and growth of pathogens in soils. This potential in a real on-farm setting was still to be investigated.

Methods

In a stock-excluded riparian area, planted with mānuka on a dry stock farm, synthetic excrement patches high in urea (950 kg N ha−1 equiv.) and Escherichia coli (7.9 × 109 cfu plant-1) underneath mānuka saplings and pasture were applied. Soil was sampled at three depths over 21 days after the excrement application and analysed for total C and N, inorganic N, pH, soil moisture and E. coli.

Results

There was no significant difference between the pasture and mānuka for total C and N, C:N ratio, and soil moisture. E. coli was only different between both at 20–30 cm deep. NO3− - N and NH4+ - N concentrations were significantly lower under mānuka compared to pasture for the upper two soil depths (NO3− - N: 109 mg kg−1 vs 205 mg kg−1 in the topsoil).

Conclusions

The results of this study indicate that mānuka may inhibit urease activity and nitrification and could reduce on-farm nitrate leaching, while also highlighting that field conditions make quantifying such phenomenon more complex.