bluuebunny/crossref_metadata_2025 huggingface dataset:
Across‐species meta‐analysis of dexamethasone pharmacokinetics utilizing allometric and scaling modeling approaches
Authors: Song Dawei , Jusko William J
Published: February 2021

The pharmacokinetic (PK) parameters of dexamethasone (DEX) in 11 species were collected from the literature and clearances (CL) assessed by basic allometric methods, and concentration–time course profiles were fitted using two PK models incorporating physiological or allometric scaling. Plots of log CL vs. log body weights (BW) correlated reasonably withR2 = 0.91, with a maximum ratio of actual to fitted CL of 6 (for pig). A minimal physiologically‐based pharmacokinetic (mPBPK) model containing blood and two lumped tissue compartments and integrated utilization of physiological parameters was compared to an allometric two‐compartment model (a2CM). The plasma PK profiles of DEX from 11 species were analyzed jointly, with the mPBPK model having conserved partition coefficients (Kp), physiologic blood and tissue volumes, and species‐specific CL values. The DEX PK profiles were reasonably captured by the mPBPK model for 9 of 11 species in the joint analysis with three fitted parameters (besides CL) including an overall tissue‐to‐plasma partition coefficient of 1.07. The a2CM with distribution CL and central and peripheral volumes scaled allometrically fitted the plasma concentration profiles similarly but required a total of six parameters (besides CL). Overall, the literature reported that DEX CL values exhibit moderate variability (mean = 0.64 L/h/kg; coefficient of variation = 105%), but distribution parameters were largely conserved across most species.
Enhancing protein A productivity and resin utilization within integrated or intensified processes
Authors: Brinkmann Alex , Elouafiq Sanaa
Published: February 2021

Recent interest in continuous manufacturing of biologics has driven the development and evaluation of multicolumn chromatography systems to drive down resin costs by increasing productivity and maximizing resin utilization, especially for the expensive protein A capture step. Single‐pass tangential flow filtration can be used to reduce the volume of perfusion harvest, enabling a further increase in the productivity of the capture step by up to fivefold. However, there are expected to be practical limits for the productivity of the capture step, which must be determined based on the manufacturing batch size, duration, and frequency, especially as it relates to efficient utilization of the column lifetime. For short fed‐batch manufacturing campaigns, intensified capture processes may result in up to 82% lower resin consumption, while avoiding the long‐term storage of used resin. For perfusion processes and longer fed‐batch campaigns, it may be more efficient to operate at a lower productivity that enables the column lifetime to be routinely achieved and achieves the desired resin and buffer savings without introducing unnecessary process risk or complexity. An intensified batch capture process, “super‐batch,” will be compared as an alternative to multicolumn chromatography processes to achieve high productivity and resin utilization with a potentially simpler process.
Microbial fatty acid transport proteins and their biotechnological potential
Authors: Salvador López José M. , Van Bogaert Inge N. A.
Published: February 2021

Fatty acid metabolism has been widely studied in various organisms. However, fatty acid transport has received less attention, even though it plays vital physiological roles, such as export of toxic free fatty acids or uptake of exogenous fatty acids. Hence, there are important knowledge gaps in how fatty acids cross biological membranes, and many mechanisms and proteins involved in these processes still need to be determined. The lack of information is more predominant in microorganisms, even though the identification of fatty acids transporters in these cells could lead to establishing new drug targets or improvements in microbial cell factories. This review provides a thorough analysis of the current information on fatty acid transporters in microorganisms, including bacteria, yeasts and microalgae species. Most available information relates to the model organisms Escherichia coli and Saccharomyces cerevisiae, but transport systems of other species are also discussed. Intracellular trafficking of fatty acids and their transport through organelle membranes in eukaryotic organisms is described as well. Finally, applied studies and engineering efforts using fatty acids transporters are presented to show the applied potential of these transporters and to stress the need for further identification of new transporters and their engineering.
Spectrum–effect relationship between GC‐QTOF‐MS fingerprint and antioxidant, anti‐inflammatory activities of Schizonepeta tenuifolia essential oil
Authors: Bai Xi , Liu Liu , Zhang Junping , Chen Li , Wu Tao , Aisa Haji Akber , Maiwulanjiang Maitinuer
Published: February 2021

Schizonepeta tenuifolia (Benth.) Briq, a traditional Chinese medicine, is an annual herbaceous plant that is widely distributed in China, Japan, and Korea. The essential oil (EO) of S. tenuifolia has antioxidant and anti‐inflammatory properties. However, the components contributing to its antioxidant and anti‐inflammatory activities remain unclear. This study was aimed at investigating the spectrum–effect relationship between GC–MS fingerprint and the antioxidant and anti‐inflammatory effects of S. tenuifolia EO. Here, the fingerprints of EO from 10 batches of S. tenuifolia from various sources were established using GC–MS, and the antioxidant and anti‐inflammatory bioactivities were evaluated using 2,2‐diphenyl‐1‐picrylhydrazyl and nitric oxide inhibitory assays, respectively. Finally, 13 common peaks were identified from 10 batches of S. tenuifolia by searching against the standard mass spectra in NIST 14 and comparing the literature retention index. The different sources of S. tenuifolia EO exhibit mild antioxidant activities and significant anti‐inflammatory effects. In particular, menthone (peak 3), isomenthone (peak 4), pulegone (peak 7), piperitone (peak 8), and β‐caryophyllene (peak 11) might be the dominant constituents responsible for the antioxidant and anti‐inflammatory activities of S. tenuifolia EO. This method may provide a time‐saving, convenient way to screen the potential effective components of S. tenuifolia EO.
Incidence of venous thromboembolism after standard treatment in patients with epithelial ovarian cancer in Korea
Authors: Shin Wonkyo , Lee Sanghee , Lim Myong Cheol , Jung Jipmin , Kim Hak Jin , Cho Hyunsoon
Published: February 2021

Background

Venous thromboembolism (VTE) is a hospital‐associated severe complication that may adversely affect patient prognosis. In this study, we evaluated the incidence of VTE and its risk factors in patients with epithelial ovarian cancer (EOC).

Methods

We retrospectively analyzed the electronic health record data of 1268 patients with EOC who received primary treatment at the National Cancer Center, Korea between January 2007 and December 2017 to identify patients who developed VTE. Demographic, clinical, and surgical characteristics of these patients were ascertained. Competing risks analyses were performed to estimate the cumulative incidence of VTE according to the treatment type. The associations between putative risk factors and the incidence of VTE were evaluated using the Fine–Gray regression models accounting for competing risks of death.

Results

VTE was the most prevalent cardiovascular event, found in 9.6% (n = 122) of all patients. Of these VTE events, 115 (94.3%) occurred within 2 years of EOC diagnosis. Advanced cancer stage at diagnosis (distant vs. localized, hazards ratio [HR])= 14.49, p = 0.015) and extended hospital stay (≥15 days, HR =3.87, p = 0.004) were associated with the incidence of VTE. There was no significant difference in the cumulative incidence of VTE between primary cytoreductive surgery followed by adjuvant chemotherapy and neoadjuvant chemotherapy followed by interval cytoreductive surgery (HR =0.81, p = 0.390).

Conclusions

Approximately 10% of patients with EOC were diagnosed with VTE, which was the most common cardiovascular disease found in this study. The assessment of VTE risks in patients with advanced‐stage EOC with an extended hospital stay is needed to facilitate adequate prophylactic treatment.
Psychogenic polydipsia in a female adolescent without a psychiatric background: A case report
Authors: Nauwynck Elise , Van De Maele Karolien , Vanbesien Jesse , Staels Willem , De Schepper Jean , Gies Inge
Published: February 2021

Psychological stress is a risk factor for primary polydipsia in adolescents without psychiatric comorbidity. Taking a detailed family and social history can help to distinguish primary polydipsia from diabetes insipidus in adolescents with challenging presentations of polydipsia and polyuria.
High‐performance IO for seismic processing on the cloud
Authors: Guimarães Antonio , Lacalle Luis , Rodamilans Charles B. , Borin Edson
Published: February 2021

Most of the applications in the seismology field rely on the processing of up to hundreds of terabytes of data and their performance is strongly affected by IO operations. In this article, we analyze the main file structures currently used to store seismic data and propose a new intermediate data structure to improve IO performance while still complying with established standards. We show that, throughout a common workflow in seismic data analysis, our IO performance gain greatly surpasses the overhead of translating data to the intermediate structure. This approach enables a speedup of up to 208 times in reading time when using classical standards (e.g., SEG‐Y) and our intermediate structure is up to 1.8 times more efficient than modern formats (e.g., ASDF). Considering cache‐friendly applications, our speedups over the direct use of SEG‐Y reach 8000 times. We also performed a cost analysis on the AWS cloud showing that, in our approach, HDDs can be 1.25 times more cost‐effective than SSDs.
Delineating the roles of Grhl2 in craniofacial development through tissue‐specific conditional deletion and epistasis approaches in mouse
Authors: de Vries Michael , Owens Harley G. , Carpinelli Marina R. , Partridge Darren , Kersbergen Ariena , Sutherland Kate D. , Auden Alana , Anderson Peter J. , Jane Stephen M. , Dworkin Sebastian
Published: February 2021

Background

The highly conserved Grainyhead‐like (Grhl) family of transcription factors play critical roles in the development of the neural tube and craniofacial skeleton. In particular, deletion of family member Grainyhead‐like 2 (Grhl2) leads to mid‐gestational embryonic lethality, maxillary clefting, abdominoschisis, and both cranial and caudal neural tube closure defects. These highly pleiotropic and systemic defects suggest that Grhl2 plays numerous critical developmental roles to ensure correct morphogenesis and patterning.

Results

Here, using four separate Cre‐lox conditional deletion models, as well as one genetic epistasis approach (Grhl2+/−;Edn1+/− double heterozygous mice) we have investigated tissue‐specific roles of Grhl2 in embryonic development, with a particular focus on the craniofacial skeleton. We find that loss of Grhl2 in the pharyngeal epithelium (using the ShhCre driver) leads to low‐penetrance micrognathia, whereas deletion of Grhl2 within the ectoderm of the pharynx (NestinCre) leads to small, albeit significant, differences in the proximal‐distal elongation of both the maxilla and mandible. Loss of Grhl2 in endoderm (Sox17‐2aiCre) resulted in noticeable lung defects and a single instance of secondary palatal clefting, although formation of other endoderm‐derived organs such as the stomach, bladder and intestines was not affected. Lastly, deletion of Grhl2 in cells of the neural crest (Wnt1Cre) did not lead to any discernible defects in craniofacial development, and similarly, our epistasis approach did not detect any phenotypic consequences of loss of a single allele of both Grhl2 and Edn1.

Conclusion

Taken together, our study identifies a pharyngeal‐epithelium intrinsic, non‐cell‐autonomous role for Grhl2 in the patterning and formation of the craniofacial skeleton, as well as an endoderm‐specific role for Grhl2 in the formation and establishment of the mammalian lung.
2D/2D Heterostructures: Rational Design for Advanced Batteries and Electrocatalysis
Authors: Mei Jun , Liao Ting , Sun Ziqi
Published: February 2021

Two‐dimensional/two‐dimensional (2D/2D) heterostructures consisting of two or more 2D building blocks possess intriguing electronic features at the nanosized interfacial regions, endowing the possibility for effectively modulating the confinement, and transport of charge carriers, excitons, photons, phonons, etc. to bring about a wide range of extraordinary physical, chemical, thermal, and/or mechanical properties. By rational design and synthesis of 2D/2D heterostructures, electrochemical properties for advanced batteries and electrocatalysis can be well regulated to meet some practical requirements. In this review, a summary on the commonly employed synthetic strategies for 2D/2D heterostructures is first given, followed by a comprehensive review on recent progress for their applications in batteries and various electrocatalysis reactions. Finally, a critical outlook on the current challenges and promising solutions is presented, which is expected to offer some insightful ideas on the design principles of advanced 2D‐based nanomaterials to address the current challenges in sustainable energy storages and green fuel generations.
Low‐fat hypocaloric diet reduces neprilysin in overweight and obese human subjects
Authors: Henke Christine , Haufe Sven , Ziehl Doreen , Bornstein Stefan R. , Schulz‐Menger Jeanette , Heni Martin , Engeli Stefan , Jordan Jens , Birkenfeld Andreas L.
Published: February 2021

Aims

Neprilysin (NEP), a zinc metallopeptidase, degrades a variety of bioactive peptides including natriuretic peptides terminating their biological action on arterial blood pressure and natriuresis. Pharmacological inhibition of NEP reduces mortality in patients with heart failure with reduced ejection fraction. Physiological interventions reducing NEP levels are unknown in humans. Because obesity leads to increased NEP levels and increases the risk for heart failure, we hypothesized that weight loss reduces NEP concentrations in plasma and tissue.

Methods and results

We randomized overweight to obese human subjects to a low‐fat or low‐carbohydrate hypocaloric 6 month weight loss intervention. Soluble NEP was determined in plasma, and NEP mRNA was analysed from subcutaneous adipose tissue before and after diet. Low‐fat diet‐induced weight loss reduced soluble NEP levels from 0.83 ± 0.18 to 0.72 ± 0.18 μg/L (P = 0.038), while subcutaneous adipose tissue NEP mRNA expression was reduced by both dietary interventions [21% (P = 0.0057) by low‐fat diet and 16% (P = 0.048) by low‐carbohydrate diet]. We also analysed the polymorphisms of the gene coding for NEP, rs9827586 and rs701109, known to be associated with plasma NEP levels. For both single‐nucleotide polymorphisms, minor allele carriers (A/A) had higher baseline plasma NEP levels (rs9827586: β = 0.53 ± 0.23, P < 0.0001; rs701109: β = 0.43 ± 0.22, P = 0.0016), and minor allele carriers of rs9827586 responded to weight loss with a larger NEP reduction (rs9827586: P = 0.0048).

Conclusions

Our study identifies weight loss via a hypocaloric low‐fat diet as the first physiological intervention in humans to reduce NEP in plasma and adipose tissue. Specific single‐nucleotide polymorphisms further contribute to the decrease. Our findings may help to explain the beneficial effect of weight loss on cardiac function in patients with heart failure.
Anticancer Activity and Mode of Action of Copper(II)‐Bis(thiosemicarbazonato) Complexes with Pendant Nitrogen Heterocycles
Authors: Palma Elisa , Raposinho Paula , Campello Maria Paula Cabral , Belo Dulce , Guerreiro Joana F. , Alves Vítor , Fonseca Alexandra , Abrunhosa Antero J. , Paulo António , Mendes Filipa
Published: February 2021

Exploring the potential of bis(thiosemicarbazones) (BTSC), a new family of BTSC ligands derived from GTSM (glyoxal‐bis(N4‐methylthiosemicarbazonato) and respective CuIIBTSC complexes were synthesized. These complexes, having pendant nitrogen heterocycles, exhibited increased water‐solubility, lower lipophilicity at physiological pH and more negative Cu(II)/Cu(I) redox potential, when compared with the parental complex. The cytotoxic evaluation performed in a panel of cancer cells lines showed an important effect of the metal complexation, and furthermore correlated well with the cellular uptake of the compounds, which was determined using their 64Cu congeners. The radiolabelling of the complexes also allowed more detailed uptake studies, with the results suggesting an active transport or facilitated diffusion mechanism for the cellular uptake of 64CuGTSMpip and 64CuGTSMmor, with pendant piperidine and morpholine rings, respectively. Additionally, a comparative study with the corresponding Cu(II) complexes derived from ATSM (diacetyl‐bis(N4‐methylthiosemicarbazonato) that we have previously described, demonstrated a clear difference in their lysosomotropic properties in particular for the piperidine derivatives. From this study, CuGTSMpip emerged as the most promising compound to be further evaluated as an anticancer metallodrug.
Anthropogenic relief changes in a long‐lasting lignite mining area (‘Ville’, Germany) derived from historic maps and digital elevation models
Authors: Henselowsky Felix , Rölkens Julian , Kelterbaum Daniel , Bubenzer Olaf
Published: February 2021

Humans constitute one of the main geomorphological agents in modern times. As an example, post‐mining regions represent a typical landscape of the Anthropocene. Strong relief modifications are particularly obvious with open pit mining. However, many existing mining areas are lacking detailed pre‐mining information for the quantification of anthropogenic relief changes, which is a considerable challenge in regions with historic mining activities.

Here, the Ville (Rhenish lignite district, Germany) is used to quantify surface mining induced relief changes in one of the oldest and currently largest lignite districts in Europe. Historical maps from first geodetic mapping in 1893 enabled construction of a historic digital elevation model to quantify the relief changes in comparison to elevation data from 2000 and 2015. The vertical accuracy of the historic data is remarkably high, with relief differences < 2 m in areas not affected by mining. In total, 49.2% of the investigated area (184 km2) shows a relief deficit and 14.5% has positive relief differences. Absolute changes account for more than 80 m heightening (dumpsites of overburden) and lowering of the natural relief (pits). Besides these altitudinal changes, overall steeper slopes are significant for the new topography, but levelling exists likewise. The spatial variabilities are discussed in the context of the regional geology and the mining techniques.

Undoubtedly, such large‐scale anthropogenic relief changes persist for a very long time and will last as a human legacy far into the future. Only the detailed reconstruction of the pre‐mining relief offers the ability to clarify the dimension of humans as geomorphological agents and to understand landscape perception. Due to the fact that the impact of open pit mining has such a large vertical and horizontal extension, their consideration as part of anthropogeomorphology can significantly contribute to support future Critical Zone research in the Anthropocene.
Replicating extensive brain structural heterogeneity in individuals with schizophrenia and bipolar disorder
Authors: Wolfers Thomas , Rokicki Jaroslav , Alnæs Dag , Berthet Pierre , Agartz Ingrid , Kia Seyed Mostafa , Kaufmann Tobias , Zabihi Mariam , Moberget Torgeir , Melle Ingrid , Beckmann Christian F. , Andreassen Ole A. , Marquand Andre F. , Westlye Lars T.
Published: February 2021

Identifying brain processes involved in the risk and development of mental disorders is a major aim. We recently reported substantial interindividual heterogeneity in brain structural aberrations among patients with schizophrenia and bipolar disorder. Estimating the normative range of voxel‐based morphometry (VBM) data among healthy individuals using a Gaussian process regression (GPR) enables us to map individual deviations from the healthy range in unseen datasets. Here, we aim to replicate our previous results in two independent samples of patients with schizophrenia (n1 = 94; n2 = 105), bipolar disorder (n1 = 116; n2 = 61), and healthy individuals (n1 = 400; n2 = 312). In line with previous findings with exception of the cerebellum our results revealed robust group level differences between patients and healthy individuals, yet only a small proportion of patients with schizophrenia or bipolar disorder exhibited extreme negative deviations from normality in the same brain regions. These direct replications support that group level‐differences in brain structure disguise considerable individual differences in brain aberrations, with important implications for the interpretation and generalization of group‐level brain imaging findings to the individual with a mental disorder.
Hepatobiliary Organoids and Their Applications for Studies of Liver Health and Disease: Are We There Yet?
Authors: Shiota Junya , Samuelson Linda C. , Razumilava Nataliya
Published: February 2021

Organoid culture systems have emerged as a frontier technology in liver and biliary research. These three‐dimensional (3D) cell cultures derived from pluripotent and adult hepatobiliary cells model organ structure and function. Building on gastrointestinal organoid establishment, hepatobiliary organoid cultures were generated from mouse leucine‐rich repeat–containing G‐protein–coupled receptor 5–positive liver progenitor cells. Subsequently, 3D hepatobiliary organoid cultures were developed from hepatocytes and cholangiocytes to model human and animal hepatobiliary health and disease. Hepatocyte organoids have been used to study Alagille syndrome, fatty liver disease, Wilson disease, hepatitis B viral infection, and cystic fibrosis. Cholangiocyte organoids have been established to study normal cholangiocyte biology and primary sclerosing cholangitis and to test organoid potential to form bile ducts and gallbladder tissue in vitro. Hepatobiliary cancer organoids, termed tumoroids, have been established from frozen and fresh human tissues and used as a drug‐testing platform and for biobanking of cancer samples. CRISPR‐based gene modifications and organoid exposure to infectious agents have permitted the generation of organoid models of carcinogenesis. This review summarizes currently available adult cell–derived hepatobiliary organoid models and their applications. Challenges faced by this young technology will be discussed, including the cellular immaturity of organoid‐derived hepatocytes, co‐culture development to better model complex tissue structure, the imperfection of extracellular matrices, and the absence of standardized protocols and model validation.
Collagen based electrospun materials for skin wounds treatment
Authors: Hernández‐Rangel A. , Martin‐Martinez E. San
Published: February 2021

Materials used for wound care have evolved from simple covers to functional wound dressings with bioactive properties. Electrospun nanofibers show great similarity to the natural fibrillar structure of skin extracellular matrix (ECM); therefore, by mimic, the morphology of ECM, nanofibers show high potential for facilitating the healing of skin injuries. Besides morphology, scaffold composition is another important parameter in the production of bioactive wound dressings. Collagen type I is the main structural protein of skin ECM is biocompatible, biodegradable, and its extraction from animal sources is relatively simple. The fabrication of electrospun wound dressings based on collagen and its blends have been studied for skin tissue engineering applications. This review focus on the new advances of collagen electrospun materials for skin wound treatment. It summarizes the recent research on pristine collagen, collagen blends, and collagen surface modifications on nanofibers mats. Finally, the strategies for three‐dimensional nanofibers production will also be discussed.
Predicting improvement of work ability in modalities of short‐ and long‐term psychotherapy: The differential impact of reflective ability and other aspects of patient suitability
Authors: Alanne Carita , Heinonen Erkki , Knekt Paul , Rissanen Julius , Virtala Esa , Lindfors Olavi
Published: February 2021

Objectives

We investigated how patients' psychological capacities to engage in psychotherapy predict changes in work ability in short‐ and long‐term psychotherapy.

Methods

A cohort study of 326 patients, aged 20–46 years and suffering from mood and anxiety disorders, treated by short‐term solution‐focused, short‐term psychodynamic, or long‐term psychodynamic psychotherapy, followed‐up for 5 years. The Suitability for Psychotherapy Scale, assessed at baseline, was the predictor. Outcomes were assessed at baseline and at six follow‐up occasions using the Work Ability Index as the primary indicator.

Results

Patients with good pretreatment psychological suitability for psychotherapy, good reflective ability in particular, improved more than patients with poor suitability in short‐term psychodynamic psychotherapy. Comparisons between therapy groups showed poorer suitability to predict more improvement in solution‐focused and in long‐term psychodynamic psychotherapy than in short‐term psychodynamic psychotherapy.

Conclusion

Patients' psychological suitability for psychotherapy has a different impact on work ability in different therapy modalities and durations.
Feasibility and usability study of a pilot immersive virtual reality‐based empathy training for dental providers
Authors: Amini Homa , Gregory Megan E. , Abrams Mary Ann , Luna John , Roland Maxwell , Sova Lindsey N. , Bean Canise , Huang Yungui , Pfeil Sheryl A. , Townsend Janice , Lin En‐Ju D
Published: February 2021

Purpose

Social determinants of health (SDOH) significantly impact individuals’ engagement with the healthcare system. To address SDOH‐related oral health disparities, providers must be equipped with knowledge, skills, and attitudes (KSAs) to understand how SDOH affect patients and how to mitigate these effects. Traditional dental school curricula provide limited training on recognizing SDOH or developing empathy for those with SDOH‐related access barriers. This study describes the design and evaluation of such a virtual reality (VR)‐based simulation in dental training. We hypothesize the simulation will increase post‐training KSAs.

Methods

We developed “MPATHI” (Making Professionals Able THrough Immersion), a scripted VR simulation where participants take the role of an English‐speaking caregiver with limited socioeconomic resources seeking dental care for a child in a Spanish‐speaking country. The simulation is a combination of 360° video recording and virtual scenes delivered via VR headsets. A pilot was conducted with 29 dental
residents/faculty, utilizing a pre‐post design to evaluate effectiveness in improving immediate and retention of KSAs toward care delivery for families facing barriers.

Results

MPATHI led to increased mean scores for cognitive (pre = 3.48 ± 0.80, post = 4.56 ± 0.51, p < 0.001), affective (pre = 4.20 ± 0.4, post = 4.47 ± 0.44, p < 0.001), and skill‐based learning (pre = 4.00 ± 0.47, post = 4.52 ± 0.37, p < 0.001) immediately post‐training. There was not a significant difference between skills measured immediately post‐training and in the 1‐month post‐training survey (p = 0.41). Participants reported high satisfaction with the content and methods used in this training.

Conclusions

This pilot study supports using VR SDOH training in dental education. VR technology provides new opportunities for innovative content design.
Evaluation of accuracy of laparoscopic liver mono‐segmentectomy using the Glissonian approach with indocyanine green fluorescence negative staining by comparing estimated and actual resection volumes: A single‐center retrospective cohort study
Authors: Funamizu Naotake , Ozaki Takahiro , Mishima Kohei , Igarashi Kazuharu , Omura Kenji , Takada Yasutsugu , Wakabayashi Go
Published: February 2021

Background/Purpose

Laparoscopic liver mono‐segmentectomy (LLMS) may improve patient outcomes, but it is difficult and its accuracy and safety are unknown. We evaluated the accuracy of LLMS using Glissonian approach with indocyanine green fluorescence (ICG) negative staining.

Methods

Seventy‐four patients eligible for LLMS except for segment 1 were enrolled. Preoperative three‐dimensional CT‐based surgical simulation was used to determine estimated liver resection volume (ELRV), which was compared with modified actual liver resection volume (ALRV) obtained from actual liver resection mass. The LLMS accuracy was also evaluated based on operator's experience (attending surgeon [AS] or trainee surgeon [TS]).

Results

Estimated liver resection volumes significantly correlated with ALRVs (r = .82) in all cases. Moreover, TS‐conducted LLMS also showed acceptable difference between ELRV and ALRV compared with AS‐conducted LLMS. There were no intergroup differences in estimated blood loss, operation time, time of Pringle maneuver, postoperative complications, and length of postoperative hospitalization (P < .05). Moreover, R0 resection was comparable between the AS and TS groups.

Conclusions

Laparoscopic liver mono‐segmentectomy with Glissonian approach using ICG negative imaging ensured safe and accurate procedure owing to facilitated visualization of the resection line. Our approach was effective in avoiding postoperative liver dysfunction and securing radical resection. In addition, it might be helpful in TS education of LLMS.
Synthesis and biological evaluation of benzimidazolone bridged triheterocyclic compounds
Authors: Menteşe Emre , Güven Okan , Çalışkan Nedime , Baltaş Nimet
Published: February 2021

A new series of benzimidazolone bridged triheterocyclic compounds bearing thiosemicarbazide, thiadiazole, triazole, moieties was synthesized and then screened for their in vitro urease, α‐glucosidase, and acetylcholinesterase inhibition properties for the first time. All the synthesized compounds showed an outstanding urease inhibitory effect when compared with standards. Compounds 1, 4, 5b, 5d, 6b, 6d, 7b, and 7d showed significant acetylcholinesterase inhibitory activity with IC50 values between 7.32 ± 0.58 and 12.52 ± 0.13 μg/ml comparable to donepezil (15.12 ± 0.20 μg/ml). Compound 5c, having thiosemicarbazide moiety at the positions N‐1 and N‐3 of benzimidazolone nucleus, showed the highest α‐glucosidase inhibitory activity (IC50 = 11.42 ± 0.11 μg/ml).
LI‐RADS Major Features on MRI for Diagnosing Hepatocellular Carcinoma: A Systematic Review and Meta‐Analysis
Authors: Shin Jaeseung , Lee Sunyoung , Yoon Ja Kyung , Chung Yong Eun , Choi Jin‐Young , Park Mi‐Suk
Published: February 2021

Background

The reported diagnostic performance for hepatocellular carcinoma (HCC) of each major imaging feature on MRI using standardized definitions of the Liver Imaging Reporting and Data System (LI‐RADS) is variable. It is important to know the actual performance of each LI‐RADS major imaging feature for imaging diagnosis of HCC and determine the sources of heterogeneity between the reported results.

Purpose

To systematically determine the performance of each major imaging feature of LI‐RADS for diagnosing HCC using either extracellular contrast agent‐enhanced MRI (ECA‐MRI) or gadoxetate disodium‐enhanced MRI (EOB‐MRI).

Study Type

Systematic review and meta‐analysis.

Subjects

Sixteen original articles with 3542 lesions.

Field Strength

A 1.5 T and 3.0 T.

Assessment

Data extraction was independently performed by two reviewers who identified and reviewed original articles reporting the diagnostic performance of each LI‐RADS major imaging feature—arterial phase hyperenhancement (APHE), observation size, washout appearance, enhancing “capsule,” and threshold growth—using MRI. Study characteristics, study population characteristics, MRI characteristics, contrast agent, LI‐RADS version, reference standards, and study outcomes were extracted from included studies. Risk of bias and concerns regarding applicability were evaluated using the Quality Assessment of Diagnostic Accuracy Studies‐2 tool.

Statistical Tests

Bivariate random‐effects models were used to obtain summary estimates of the diagnostic performance of each LI‐RADS major imaging feature. Hierarchical summary receiver operating characteristic curves were plotted. Meta‐regression analyses were performed to explore potential sources of heterogeneity.

Results

The pooled per‐observation sensitivities and specificities for diagnosing HCC were 85% (95% confidence interval [CI] = 78%–89%) and 57% (95% CI = 44%–70%) for arterial phase hyperenhancement (APHE), 77% (95% CI = 72%–82%), and 74% (95% CI = 63%–83%) for washout appearance, and 52% (95% CI = 41%–64%) and 90% (95% CI = 85%–94%) for enhancing “capsule,” respectively.

Data Conclusions

Among the LI‐RADS major features, the sensitivity was the highest for APHE and the specificity was the highest for enhancing “capsule” in the diagnosis of HCC.

Evidence Level

3

Technical Efficacy

Stage 2
Spiking dependence of SARS‐CoV‐2 pathogenicity on TMPRSS2
Authors: Abbasi Asim Z. , Kiyani Dania A. , Hamid Syeda M. , Saalim Muhammad , Fahim Ammad , Jalal Nasir
Published: February 2021

Epidemiological data shows a discrepancy in COVID‐19 susceptibility and outcomes with some regions being more heavily affected than others. However, the factors that determine host susceptibility and pathogenicity remain elusive. An increasing number of publications highlight the role of Transmembrane Serine Protease 2 (TMPRSS2) in the susceptibility of the host cell to SARS‐CoV‐2. Cleavage of viral spike protein via the host cell's TMPRSS2 enzyme activity mediates viral entry into the host cell. The enzyme synthesis is regulated by the TMPRSS2 gene, which has also been implicated in the entry mechanisms of previously reported Coronavirus infections. In this review, we have investigated the pathogenicity of SARS‐CoV‐2 and disease susceptibility dependence on the TMPRSS2 gene as expressed in various population groups. We further discuss how the differential expression of this gene in various ethnic groups can affect the SARS‐CoV‐2 infection and Coronavirus disease (COVID)‐19 outcomes. Moreover, promising new TMPRSS2 protease blockers and inhibitors are discussed for COVID‐19 treatment.
Regional frequency analysis of annual daily rainfall maxima in Skåne, Sweden
Authors: Ul Hassan Mahmood , Noreen Zahra , Ahmed Rashid
Published: February 2021

Extreme daily rainfall events are critical for the urban drainage system, human life, agriculture and small catchments. The information about extreme rainfall magnitudes and frequencies is immensely important for civil engineers, city planners, scientists related to water management, rescue operations and flood control works. This study illustrates the results of regional frequency analysis (RFA) of annual maximum daily rainfall (AMDR) of Skåne County, Sweden. L‐moments based heterogeneity measure (H) reveals that the Skåne County is a homogeneous region. Based on the L‐moment ratio diagram andZDiststatistic results, the generalized normal (GNO) distribution is selected as the most suitable regional distribution. The accuracy measures used in K‐fold cross validation indicate that support vector machine (SVM) model is an appropriate model to find the index rainfall at ungauged sites in the region. The sites characteristics, elevation and latitude are identified as the most important variables to explain the variation in mean annual maximum daily rainfall (MAMDR). Finally, spatial maps of predicted MAMDR for different return periods are constructed by using index rainfall combined with regional quantiles. Spatial maps offer an overall view of the expected MAMDR in the region that is helpful for multiple decision makers including infrastructure planners, city planners, emergency managers, engineers and many others.
The effects of board games on creative potential
Authors: Mercier Maxence , Lubart Todd
Published: February 2021

The current study aimed to investigate whether board games could be used to improve creative potential. Games have proven to be effective learning tools, and some studies have indicated positive links between creativity and other types of games, namely video games and role‐playing games. However, less is known regarding board games’ potential benefits on creativity. This exploratory study compared two types of board games: creative and non‐creative board games. We used a within‐subject repeated‐measurement design, in which participants played to both types of games, across two sessions separated by one week. We assessed creative potential with a divergent thinking task, using fluency and originality as indicators. We controlled for openness, mood states, and enjoyment. Results suggest an improvement of originality after playing both types of games, whereas no differences were observed for fluency. Considering the base level of participants, we found improvement for low‐performing participants specifically, in both fluency and originality, although analyses’ limited statistical power may have impacted the findings. These findings provide a first step in the study of creativity and board games and suggest they could help temporarily improve one’s divergent thinking capacity.
Assessing the use of mangrove pollen as a quantitative sea‐level indicator on Mahé, Seychelles
Authors: Sefton Juliet P. , Woodroffe Sarah A.
Published: February 2021

We investigated the potential of mangrove pollen from Mahé, Seychelles, to improve existing metre‐scale Late Holocene sediment‐based sea‐level reconstructions. Mangrove species at two mangrove sites are broadly zoned according to elevation within the tidal frame. Modern pollen rain from traps deployed for 1 year generally have a poor relationship with modern vegetation, and relatively low pollen production rates. Pollen from mangrove species that live in narrow elevation zones (e.g. Avicennia marina) are poorly represented in modern pollen rain, while pollen from mangrove species that live across a larger elevational range (e.g. Rhizophora mucronata) are relatively well represented. Pollen was found in extremely low concentrations in mangrove surface and core sediments, which inhibited further study into pollen transport and preservation. The results from this modern study demonstrate that utilizing mangrove pollen would not decrease existing metre‐scale vertical uncertainties in Late Holocene sea‐level reconstructions in the Seychelles. We suggest that this approach may still be successful in other locations if mangrove vegetation is (i) zoned at a more extensive lateral scale and (ii) is closely associated with modern pollen rain and surface sediments, and (iii) sedimentological conditions promote the preservation of pollen in fossil sequences.
Enhanced radiation gain and efficiency of a metamaterial‐inspired wideband microstrip antenna using substrate integrated waveguide technology for sub‐6 GHz wireless communication systems
Authors: Althuwayb Ayman A.
Published: February 2021

This paper shows a technique to enhance the radiation gain and efficiency of metamaterial (MTM) inspired planar antenna using substrate integrated waveguide (SIW) technology for sub‐6 GHz wireless communication systems. The antenna consists of MTM unit‐cells comprising series interdigital‐capacitor and short‐circuited spiral stub. The proposed antenna behaves like a leaky wave antenna. In the transmission mode the input signal propagating along the antenna structure and leaks energy. The performance of the antenna is shown to enhance by embedding a column of metallic vias between the MTM unit‐cells. This technique has no impact on the size of the antenna. The antenna was constructed on a standard FR4 dielectric substate. It had dimensions of 23.2×6.4×0.8 mm3 and had a wide operational frequency range 1.8 GHz from 3.0–4.8 GHz. After applying SIW the average gain and efficiency of the antenna were 5.8 dBi and 78%, respectively, which is an improvement of 2 dBi and 21% across 3–4.8 GHz.
Characterisation of prostate cancer using texture analysis for diagnostic and prognostic monitoring
Authors: Singh Dharmesh , Kumar Virendra , Das Chandan J. , Singh Anup , Mehndiratta Amit
Published: February 2021

Automated classification of significant prostate cancer (PCa) using MRI plays a potential role in assisting in clinical decision‐making. Multiparametric MRI using a machine‐aided approach is a better step to improve the overall accuracy of diagnosis of PCa. The objective of this study was to develop and validate a framework for differentiating Prostate Imaging‐Reporting and Data System version 2 (PI‐RADS v2) grades (grade 2 to grade 5) of PCa using texture features and machine learning (ML) methods with diffusion‐weighted imaging (DWI) and apparent diffusion coefficient (ADC). The study cohort included an MRI dataset of 59 patients with clinically proven PCa. Regions of interest (ROIs) for a total of 435 lesions were delineated from the segmented peripheral zones of DWI and ADC. Six texture methods comprising 98 texture features in total (49 each of DWI and ADC) were extracted from lesion ROIs. Random forest (RF) and correlation‐based feature selection methods were applied on feature vectors to select the best features for classification. Two ML classifiers, support vector machine (SVM) and K‐nearest neighbour, were used and validated by 10‐fold cross‐validation. The proposed framework achieved high diagnostic performance with a sensitivity of 85.25% ± 3.84%, specificity of 95.71% ± 1.96%, accuracy of 84.90% ± 3.37% and area under the receiver‐operating characteristic curve of 0.98 for PI‐RADS v2 grades (2 to 5) classification using the RF feature selection method and Gaussian SVM classifier with combined features of DWI + ADC. The proposed computer‐assisted framework can distinguish between PCa lesions with different aggressiveness based on PI‐RADS v2 standards using texture analysis to improve the efficiency of PCa diagnostic performance.
A solution approach for multi‐trip vehicle routing problems with time windows, fleet sizing, and depot location
Authors: Fermín Cueto Paula , Gjeroska Ivona , Solà Vilalta Albert , Anjos Miguel F.
Published: February 2021

We present a solution approach for a multi‐trip vehicle routing problem with time windows in which the locations of a prescribed number of depots and the fleet sizes must also be optimized. Given the complexity of the task, we divide the problem into subproblems that are solved sequentially. First, we address strategic decisions, which are solved once and remain constant thereafter. Depots are allocated by solving a p‐median problem and fleet sizes are determined by identifying the vehicle requirements of several worst‐case demand instances. Then, we address the operational planning aspect: optimizing the vehicle routes on a daily basis to satisfy the fluctuating customer demand. We assign customers to depots based on distance and “routing effort,” and for the routing problem we combine a tailor‐made branch‐and‐cut algorithm with a heuristic consisting of a route construction phase and packing of routes into vehicle trips. Our strategic decision models are robust in the sense that when applied to unseen data, all customers could be visited with the allocated fleet sizes and depot locations. Our operational routing methods are both time and cost‐effective. The exact method yields acceptable optimality gaps in 20 min and the heuristic runs in less than 2 min, finding optimal or near‐optimal solutions for small instances. Finally, we explore the trade‐off between depot and fleet costs, and routing costs to make recommendations on the optimal number of depots. Our solution approach was entered into the 12th AIMMS‐MOPTA Optimization Modeling Competition and was awarded the first prize.
Health outcomes coding trends in the US Food and Drug Administration's Sentinel System during transition to International Classification of Diseases‐10 coding system: A brief review
Authors: Nam Young Hee , Mendelsohn Aaron B. , Panozzo Catherine A. , Maro Judith C. , Brown Jeffrey S.
Published: February 2021

Background and purpose

The transition from International Classification of Diseases, 9th revision, clinical modification (ICD‐9‐CM) to ICD‐10‐CM poses a challenge to epidemiologic studies that use diagnostic codes to identify health outcomes and covariates. We evaluated coding trends in health outcomes in the US Food and Drug Administration's Sentinel System during the transition.

Methods

We reviewed all health outcomes coding trends reports on the Sentinel website through November 30, 2019 and analyzed trends in incidence and prevalence across the ICD‐9‐CM and ICD‐10‐CM eras by visual inspection.

Results

We identified 78 unique health outcomes (22 acute, 32 chronic, and 24 acute or chronic) and 140 time‐series graphs of incidence and prevalence. The reports also included code lists and code mapping methods used. Of the 140 graphs reviewed, 81 (57.9%) showed consistent trends across the ICD‐9‐CM and ICD‐10‐CM eras, while 51 (36.4%) and 8 (5.7%) graphs showed inconsistent and uncertain trends, respectively. Chronic HOIs and acute/chronic HOIs had higher proportions of consistent trends in prevalence definitions (83.9% and 78.3%, respectively) than acute HOIs (28.6%). For incidence, 55.6% of acute HOIs showed consistent trends, while 41.2% of chronic HOIs and 39.3% of acute/chronic HOIs showed consistency.

Conclusions

Researchers using ICD‐10‐CM algorithms obtained by standardized mappings from ICD‐9‐CM algorithms should assess the mapping performance before use. The Sentinel reports provide a valuable resource for researchers who need to develop and assess mapping strategies. The reports could benefit from additional information about the algorithm selection process and additional details on monthly incidence and prevalence rates.

Key points

We reviewed health outcomes coding trends reports on the US FDA Sentinel website through November 30, 2019 and analyzed trends in incidence and prevalence across the International Classification of Diseases, 9th revision, Clinical Modification (ICD‐9‐CM) and ICD‐10‐CM eras by code mapping method and the type of health outcomes of interest (acute, chronic, acute or chronic).

More than a third of the 140 time‐series graphs of incidence and prevalence of health outcomes showed inconsistent or uncertain trends. Consistency in trends varied by code mapping method, type of health outcomes of interest, and whether the measurement was incidence or prevalence.

Studies using ICD‐9‐CM‐based algorithms mapped to ICD‐10‐CM codes need to assess the performance of the mappings and conduct manual refinement of the algorithms as needed before using them.