bluuebunny/crossref_metadata_2025 huggingface dataset:
Biophysical Approaches for Applying and Measuring Biological Forces
Authors: Sun Wenxu , Gao Xiang , Lei Hai , Wang Wei , Cao Yi
Published: December 2021

Over the past decades, increasing evidence has indicated that mechanical loads can regulate the morphogenesis, proliferation, migration, and apoptosis of living cells. Investigations of how cells sense mechanical stimuli or the mechanotransduction mechanism is an active field of biomaterials and biophysics. Gaining a further understanding of mechanical regulation and depicting the mechanotransduction network inside cells require advanced experimental techniques and new theories. In this review, the fundamental principles of various experimental approaches that have been developed to characterize various types and magnitudes of forces experienced at the cellular and subcellular levels are summarized. The broad applications of these techniques are introduced with an emphasis on the difficulties in implementing these techniques in special biological systems. The advantages and disadvantages of each technique are discussed, which can guide readers to choose the most suitable technique for their questions. A perspective on future directions in this field is also provided. It is anticipated that technical advancement can be a driving force for the development of mechanobiology.
Recent Advances in New Materials for 6G Communications
Authors: Li Zechen , Pan Jialiang , Hu Haowen , Zhu Hongwei
Published: December 2021

5G communication has begun commercial deployment. To maintain the sustainability and competitiveness of wireless communication systems, various industries and academic institutions around the globe are designing the framework for 6G communications. Compared with the previous generations of communication systems, 6G will be revolutionary, with unprecedented requirements in data transmission rates, delays, and global coverage. Many promising technologies in 6G systems, including terahertz communication, ultra‐large‐scale antenna arrays, large‐scale intelligent surfaces, quantum communication, and computing, have differing material requirements compared with previous systems. With the development of materials science, an increasing number of new materials will play important roles in 6G communications. Herein, the high demand of 6G systems is introduced first in this review, and recent advances of new materials having a broad variety of applications with great potential in 6G systems are systematically summarized. Perspectives on the research areas that require special attention are also presented.
Defect State Modulation of TiO2 Nanostructures for Photocatalytic Abatement of Emerging Pharmaceutical Pollutant in Wastewater Effluent
Authors: Kar Prasenjit , Aggarwal Deepanshu , Shukla Komal , Gupta Raju Kumar
Published: December 2021

Rapid industrialization has resulted in a significant presence of pharmaceutical compounds in aqueous effluents, and therefore, effluents must be effectively treated before discharging them to water bodies. The removal of emerging pharmaceutical pollutants in wastewater using TiO2 via photocatalysis technique is limited because of its wide bandgap (≈3.2 eV). Herein, defect state modulation of TiO2 for degradation of pharmaceutical pollutant “antipyrine” under visible light irradiation is investigated. A simple hydrothermal technique for synthesis of TiO2 microspheres (average diameter ≈2.94 μm), followed by chemical reduction method for formation of defective‐TiO2 microspheres using NaBH4 under an inert atmosphere for different durations (3, 5, and 8 h) is used. Defective‐TiO2 microspheres are utilized for photocatalytic degradation of antipyrine under visible light illumination. Improved photocatalytic activity for the defective‐TiO2 samples is observed due to a reduction in bandgap as well as incorporation of Ti3+, acting as a trap site and resulting in reduced electron‐hole recombination. For practical application, a continuous prototype reactor comprising defective‐TiO2 particles immobilized over glass beads is developed and efficient photocatalytic degradation of antipyrine under continuous operation is observed. Excellent recyclability and efficient photocatalytic degradation indicate a promising future for the developed defective‐TiO2 particles toward real‐world wastewater treatment applications.
Creation and evaluation of a novel, interdisciplinary debriefing program using a design‐based research approach
Authors: Lech Christie A. , Betancourt Erika , Shapiro Jo , Dolmans Diana H. J. M. , Pusic Martin
Published: December 2021

Background

The emergency department (ED) witnesses the close functioning of an interdisciplinary team in an unpredictable environment. High‐stress situations can impact well‐being and clinical practice both individually and as a team. Debriefing provides an opportunity for learning, validation, and conversation among individuals who may not typically discuss clinical experiences together. The current study examined how a debriefing program could be designed and implemented in the ED so as to help teams and individuals learn from unique, stressful incidents.

Methods

Based on the theory of workplace‐based learning and a design‐based research approach, the evolved nature of a debriefing program implemented in the real‐life context of the ED was examined. Focus groups were used to collect data. We report the design of the debriefing intervention as well as the program outcomes in terms of provider's self‐perceived roles in the program and program impact on provider's self‐reported clinical practice as well as the redesign of the program based on said feedback.

Results

The themes of barriers to debriefing, provision of perspectives, psychological trauma, and nurturing of staff emerged from focus group sessions. Respondents identified barriers and concerns regarding debriefing, and based on this information, changes were made to the program, including offering of refresher sessions for debriefing, inclusion of additional staff members in the training, and remessaging the purpose of the program.

Conclusions

Data from the study reinforced the need to increase the frequency and availability of debriefing didactics along with clarifying staff roles in the program. Future work will examine continued impact on provider practice and influence on departmental culture.
Tendon‐Driven Auxetic Tubular Springs for Resilient Hopping Robots
Authors: Lee Young-Joo , Misra Shivangi , Chen Wei-Hsi , Koditschek Daniel E. , Sung Cynthia , Yang Shu
Published: December 2021

Compliance in jumping robots improves gait stability and enables energy‐efficient locomotion. Here, 3D printable auxetic tubular springs from thermoplastic polyurethane (TPU) for rapid and sustainable hopping are developed. Because the springs have negative Poisson's ratios, they become stiffer as compression proceeds and theoretically stores 35.2% more energy than a linear spring with the same stiffness. As the stress concentrates on the hinges, it is revealed through experimental, numerical, and analytical investigations that hinge geometries, for example, the lattice angle and hinge radius, governs the global stiffness and robustness of the springs. The hopping robot leg composed of three auxetic tubular springs in parallel sustains more than 1,000 cycles of repeated, one‐degree‐of‐freedom (1‐DOF) vertical hopping and two‐degree‐of‐freedom (2‐DOF) forward hopping. The 2.5 kg‐robot system requires minimum 420 mJ of elastic energy for repeated hopping. The springs are pre‐compressed by tendon‐driven actuators and stores 1.08 J during jumping and release the springs when touching the ground. The power stroke is calculated as 15–18 W. The average velocity of the hopping robot reaches 0.06 m s−1with the increase of touchdown angle to 0.125 rad. The cost of transport is calculated as 6.7, similar to those of the living organisms.
Highly Concentrated Nitrogen‐Doped Carbon Nanotubes in Alginate–Gelatin 3D Hydrogels Enable in Vitro Breast Cancer Spheroid Formation
Authors: Munguia-Lopez Jose G. , Jiang Tao , Ferlatte Audrey , Fajardo-Diaz Juan L. , Munoz-Sandoval Emilio , Tran Simon D. , Kinsella Joseph M.
Published: December 2021

Carbon nanotubes’ (CNTs) physicochemical and mechanical properties make them ideal reinforcement materials for hydrogels, but distributing CNTs homogeneously in hydrogels remains a challenge. Chemical modifications to CNTs are used to facilitate nanomaterial dispersion, thus improving hydrogels’ physicochemical properties. Among CNTs, nitrogen‐doped CNTs (CNx) possess both great dispersibility in solution and biocompatibility properties. By formulating a method to incorporate CNxwithin alginate (i.e., covalently grafting alginate to the CNxsurface versus noncovalently adsorbing alginate to the CNxsurface) creates extrudable materials with tunable physical, chemical, and thermal properties. Herein, three new composites of alginate‐CNxare created. The results indicate that all composites present different physicochemical and thermal properties, suggesting that alginate is reorganized according to their degree of oxidation. These composites show cytocompatibility with MDA‐MB‐231 and regulation over the size of spheroids formed within the matrix. CNxwithin the matrix negatively affects MCF‐7 cells viability, spheroid formation rate, and the quantity of spheroids developed during culture. These materials provide a useful 3D hydrogel that can be used to develop in vitro models to understand the role of microenvironmental factors such as stiffness or surface roughness on the development of spheroids and their subsequent phenotypic behavior.
Modular Hydrogel−Mesoporous Silica Nanoparticle Constructs for Therapy and Diagnostics
Authors: Gerstenberg Melanie , Stürzel Christina M. , Weil Tanja , Kirchhoff Frank , Lindén Mika
Published: December 2021

Self‐assembled peptide fibrils are abundant in in vivo systems and have been associated both with normal physiological functions and with different diseases. Herein, a proof‐of‐concept study is presented, where aggregates of synthetic, fibril‐forming peptides are studied as carriers for mesoporous silica nanoparticles (MSNs), giving a hydrogel@MSN hybrid structure. It is shown that when the peptide carries a cellular‐targeting motif, in this case arg‐gly‐asp (RGD), the fibrillar aggregates efficiently attach to cancer cells, and the attached MSNs can then be locally taken up by the cells and intracellularly release their cargo or release their cargo close to the outer membrane of the cells. If the targeting motif is not present on the fibrils, hardly any attachment of the fibrillar aggregates to the target cells occurs. The higher drug carrying capacity of the MSNs together with the efficient cellular attachment of the fibrillar aggregates represents a synergistic approach toward reaching a modular drug release system, bringing together the strengths of each component of the system. Finally, it is noted that although the experimental design is such that the fibrillar aggregates would not be capable of entering cells due to their large size, the approach would also be applicable to smaller fibrillar aggregates.
Evaluation of sex differences in the pharmacokinetics of oral sumatriptan in healthy Korean subjects using population pharmacokinetic modeling
Authors: Ohk Boram , Seong Sookjin , Lee Joomi , Gwon Miri , Kang Wooyoul , Lee Haewon , Yoon Youngran , Yoo Heedoo
Published: December 2021

Sumatriptan was introduced in 1983, as the first of the triptans, selective 5‐hydroxytryptamine (5‐HT1B/1D) receptor agonists, to treat moderate to severe migraine. Migraine predominates in females. Although there have been reports of sex differences in migraine‐associated features and pharmacokinetics (PKs) of some triptans, sex differences in the PKs of oral sumatriptan have never been evaluated in Korean. We conducted this study of oral sumatriptan to assess the sex differences in Korean population. Thirty‐eight healthy Korean subjects who participated in two separate clinical studies receiving a single oral dose of 50 mg sumatriptan with the same protocols were included in this analysis. A total of 532 sumatriptan concentration observations were used for a population PK modeling. Validation of final population PK model of sumatriptan was performed using bootstrap and visual predictive check. The PK profile of oral sumatriptan was adequately described by a one‐compartmental model with combined transit compartment model and a first‐order absorption. The covariate analysis showed that the clearance of oral sumatriptan was significantly higher in males than in females (male: 444 L/h, female: 281 L/h). Our results showed that there were sex differences in the clearance of oral sumatriptan. These results encourage further studies to establish the sumatriptan pharmacokinetic–pharmacodynamic model considering sex‐related PK differences, which may help to determine optimal dosing regimens for effective treatment of migraine in males and females. Clinical trial registration: CRIS Registration No. KCT0001784.
Forty years of directed evolution and its continuously evolving technology toolbox: A review of the patent landscape
Authors: Iqbal Zarina , Sadaf Saima
Published: December 2021

Generating functional protein variants with novel or improved characteristics has been a goal of the biotechnology industry and life sciences, for decades. Rational design and directed evolution are two major pathways to achieve the desired ends. While rational protein design approach has made substantial progress, the idea of using a method based on cycles of mutagenesis and natural selection to develop novel binding proteins, enzymes and structures has attracted great attention. Laboratory evolution of proteins/enzymes requires new tools and analytical approaches to create genetic diversity and identifying variants with desired traits. In this pursuit, construction of sufficiently large libraries of target molecules to search for improved variants and the need for new protocols to alter the properties of target molecules has been a continuing challenge in the directed evolution experiments. This review will discuss the in vivo and in vitro gene diversification tools, library screening or selection approaches, and artificial intelligence/machine‐learning‐based strategies to mutagenesis developed in the last 40 years to accelerate the natural process of evolution in creating new functional protein variants, optimization of microbial strains, and transformation of enzymes into industrial machines. Analyzing patent position over these techniques and mechanisms also constitutes an integral and distinctive part of this review. The aim is to provide an up‐to‐date resource/technology toolbox for research‐based and pharmaceutical companies to discover the boundaries of competitor's intellectual property (IP) portfolio, their freedom‐to‐operate in the relevant IP landscape, and the need for patent due diligence analysis to rule out whether use of a particular patented mutagenesis method, library screening/selection technique falls outside the safe harbor of experimental use exemption. While so doing, we have referred to some recent cases that emphasize the significance of selecting a suitable gene diversification strategy in directed evolution experiments.
Development of a stem cell spheroid‐laden patch with high retention at skin wound site
Authors: Jeong Gun‐Jae , Im Gwang‐Bum , Lee Tae‐Jin , Kim Sung‐Won , Jeon Hye Ran , Lee Dong‐Hyun , Baik Sangyul , Pang Changhyun , Kim Tae‐Hyung , Kim Dong‐Ik , Jang Young Charles , Bhang Suk Ho
Published: December 2021

Mesenchymal stem cells such as human adipose tissue‐derived stem cells (hADSCs) have been used as a representative therapeutic agent for tissue regeneration because of their high proliferation and paracrine factor‐secreting abilities. However, certain points regarding conventional ADSC delivery systems, such as low cell density, secreted cytokine levels, and cell viability, still need to be addressed for treating severe wounds. In this study, we developed a three‐dimensional (3D) cavity‐structured stem cell‐laden system for overdense delivery of cells into severe wound sites. Our system includes a hydrophobic surface and cavities that can enhance the efficiency of cell delivery to the wound site. In particular, the cavities in the system facilitate hADSC spheroid formation, increasing therapeutic growth factor expression compared with 2D cultured cells. Our hADSC spheroid‐loaded patch exhibited remarkably improved cell localization at the wound site and dramatic therapeutic efficacy compared to the conventional cell injection method. Taken together, the hADSC spheroid delivery system focused on cell delivery, and stem cell homing effect at the wound site showed a significantly enhanced wound healing effect. By overcoming the limitations of conventional cell delivery methods, our overdense cell delivery system can contribute to biomedical and clinical applications.
Synergistic strategy with hyperthermia therapy based immunotherapy and engineered exosomes−liposomes targeted chemotherapy prevents tumor recurrence and metastasis in advanced breast cancer
Authors: Huang Haiqin , Shao Lanlan , Chen Yan , Tang Lan , Liu Tianqing , Li Junxu , Zhu Hongyan
Published: December 2021

Advanced breast cancer with recurrent and distal organ metastasis is aggressive and incurable. The current existing treatment strategies for advanced breast cancer are difficult to achieve synergistic treatment of recurrent tumors and distant metastasis, resulting in poor clinical outcomes. Herein, a synergistic therapy strategy composed of biomimetic tumor‐derived exosomes (TEX)‐Liposome‐paclitaxel (PTX) with lung homing properties and gold nanorods (GNR)‐PEG, was designed, respectively. GNR‐PEG, with well biocompatibility, cured recurrent tumors effectively by thermal ablation under the in situ NIR irradiation. Meanwhile, GNR‐mediated thermal ablation activated the adaptive antitumor immune response, significantly increased the level of CD8+ T cells in lungs and the concentration of serum cytokines (tumor necrosis factor‐α, interlekin‐6, and interferon‐γ). Subsequently, TEX‐Liposome‐PTX preferentially accumulated in lung tissues due to autologous tumor‐derived TEX with inherent specific affinity to lung, resulting in a better therapeutic effect on lung metastasis tumors with the assistance of adaptive immunotherapy triggered by GNR in vivo. The enhanced therapeutic efficacy in advanced breast cancer was a combination of thermal ablation, adaptive antitumor immunotherapy, and targeted PTX chemotherapy. Hence, the synergistic strategy based on GNR and TEX‐Liposome provides selectivity to clinical treatment of advanced breast cancer with recurrent and metastasis.
Monocytes engineered with iSNAP inhibit human B‐lymphoma progression
Authors: Wu Haohsiang , Amirfakhri Siamak , Lin Hsin‐Hung , Hollandsworth Hannah , Filemoni Filemoni , Liu Yahan , Wu Yiqian , Li Julie Y. S. , Xu Hongquan , Chien Shu , Bouvet Michael , Wang Yingxiao
Published: December 2021

Monocytes are important regulators for the maintenance of homeostasis in innate and adaptive immune system and have been reported to play important role in cancer progression. CD47‐SIRPα recognition is a coinhibitory immune signal to inhibit phagocytosis in monocytes and macrophages and has been well‐known as the “Don't eat me” signal. By using an approach of integrated sensing and activating proteins (iSNAPs), we have rewired the CD47‐SIRPα axis to create iSNAP‐M which activates pathways in engineered human monocytes (iSNAP‐MC). The mRNA expression levels of the monocyte/macrophage markers CD11b, CD14, and CD31 are upregulated in iSNAP‐monocytes (iSNAP‐MC). With PMA induction, the iSNAP‐MC‐derived macrophages (iSNAP‐MΦ) showed upregelation in CD86 and CD80, but not CD206. TNFα expression and secretion were also increased in iSNAP‐MΦ. Furthermore, the injection of iSNAP‐MC into mice bearing human B‐lymphoma tumors led to the suppression of tumor progression. Therefore, the engineered monocytes, via blockage of coinhibitory immune signals by rewiring CD47‐SIRPα axis, can be applied to suppress target tumors for cancer immunotherapy.
Avoiding invasive surgical procedures for a slow‐growing asymptomatic huge anterior mediastinal lipoma under watchful waiting
Authors: Motomura So , Yamashita Shun , Tago Masaki , Yamashita Shu‐ichi
Published: December 2021

A mass shadow in the right lower lung field was detected by chest X‐ray in a 79‐year‐old woman, which was eventually diagnosed as anterior mediastinal lipoma. She remained under watchful waiting without surgery for 9 years without developing symptoms, even though the lipoma had grown to an extremely large size.
Transverse myelitis after SARS‐CoV‐2 infection: Report of two cases with COVID‐19
Authors: Advani Soroor , Hosseini Seyyed Mohammad‐Mahdi , Zali Alireza , Ommi Davood , Fatemi Alireza , Jalili Khoshnoud Reza , Ashrafi Farzad
Published: December 2021

Transverse myelitis has been reported as a complication of COVID‐19 in recent studies. Here, we report two cases of transverse myelitis related to COVID‐19. Both patients underwent plasma exchange after being treated with antibiotics and corticosteroids which lead to the recovery of one of them.
Lipoma arborescens in a 16‐year‐old male: A case report
Authors: Baidoo Paa Kwesi , Nketiah‐Boakye Frank , Tano Emile Kouakou , Al‐Hassan Majeedallahi , Yorke Gaddiel Obo Mensa , Awoonor‐Williams Ronald , Boakye Ernest
Published: December 2021

Lipoma arborescens is a benign intra‐articular tumor characterized by joint effusions, pain, and reduced range of motion. It is rare in adults and children. We present a case of lipoma arborescens in a 16‐year‐old male. The work up involved plain radiographs, MRI, incisional biopsy, and laboratory analysis.
Theoretical analyses of NH3‐SCR reaction‐mass transfer over Cu‐ZSM‐5
Authors: Zhong Chao , Wu Chenxi , Zuo Hongyan , Gu Zhong
Published: December 2021

NH3‐selective catalytic reduction (NH3‐SCR) is a very effective technical means to control NOx emissions from diesel engines, and Zeolite Selony Mobil No. 5 (SiO2/Al2O3 ratio 53:1) ion exchanged with Cu (Cu‐ZSM‐5) provides support for the high performance of NH3‐SCR within a wide temperature window under diesel engine operating conditions. The mechanism of the NH3‐SCR reaction based on Cu‐ZSM‐5 is established. Resistance analysis, effective factor analysis, and characteristic time analysis are used to analyze the influence of external mass transfer limitation and washcoat diffusion limitation on NH3‐SCR reaction and the transition between the washcoat diffusion control regime, the external mass transfer control regime, and the kinetic control regime of the NH3‐SCR over Cu‐ZSM‐5. It provides the basis for the optimization of the catalyst structure and the support for the improvement of NH3‐SCR performance.
Photocatalytic and Optoelectronic Properties of Polycrystalline Diamond
Authors: Hao Jianxin , Cheng Lin , Zhao Hongyang , Fu Qiuming , Tao Hong , Wang Huan , Man Weidong , Weng Jun , Xiong Liwei , Li Tianwei , Ma Zhibin , Ding Jianxu
Published: December 2021

Polycrystalline diamonds are grown by microwave plasma chemical vapor deposition techniques. The structures and morphologies are investigated by X‐ray diffraction, Raman, and atomic force microscope. The photocatalytic characterizations show that diamond has a certain degradation ability for rhodamine B, and the degradation rate of nanocrystalline diamond is faster than that of microcrystalline diamond. Diamond based photoconductor‐type photodetector with Au electrode is prepared and it shows high photoresponsivity. This research has opened up new opportunities for diamond in various fields including photocatalysis and photodetectors.
Nitrogen enrichment buffers phosphorus limitation by mobilizing mineral‐bound soil phosphorus in grasslands
Authors: Wang Ruzhen , Yang Junjie , Liu Heyong , Sardans Jordi , Zhang Yunhai , Wang Xiaobo , Wei Cunzheng , Lü Xiaotao , Dijkstra Feike A. , Jiang Yong , Han Xingguo , Peñuelas Josep
Published: December 2021

Phosphorus (P) limitation is expected to increase due to nitrogen (N)‐induced terrestrial eutrophication, although most soils contain large P pools immobilized in minerals (Pi) and organic matter (Po). Here we assessed whether transformations of these P pools could increase plant available pools alleviating P limitation under enhanced N availability. The mechanisms underlying these possible transformations were explored by combining results from a 10‐year field N addition experiment and a 3700‐km transect covering wide ranges in soil pH, soil N, aridity, leaching, and weathering that could affect soil P status in grasslands. Nitrogen addition promoted the dissolution of immobile Pi (mainly Ca‐bound recalcitrant P) to more available forms of Pi (including Al‐ and Fe‐bound P fractions and Olsen P) by decreasing soil pH from 7.6 to 4.7, but did not affect Po. Soil total P declined by 10% from 385 ± 6.8 to 346 ± 9.5 mg kg−1, whereas available P increased by 546% from 3.5 ± 0.3 to 22.6 ± 2.4 mg kg−1 after the 10‐year N addition, associated with an increase in Pi mobilization, plant uptake, and leaching. Similar to the N addition experiment, the drop in soil pH from 7.5 to 5.6 and increase in soil N concentration along the grassland transect were associated with an increased ratio between relatively mobile Pi and immobile Pi. Our results provide a new mechanistic understanding of the important role of soil Pi mobilization in maintaining plant P supply and accelerating biogeochemical P cycles under anthropogenic N enrichment. This mobilization process temporarily buffers ecosystem P limitation or even causes P eutrophication, but will extensively deplete soil P pools in the long run.
Niche dynamics suggest ecological factors influencing migration in an insectivorous owl
Authors: Yanco Scott W. , Linkhart Brian D. , Marra Peter P. , Mika Markus , Ciaglo Max , Carver Amber , Wunder Michael B.
Published: December 2021

Seasonal migration is a widespread phenomenon undertaken by myriad organisms, including birds. Competing hypotheses about ultimate drivers of seasonal migration in birds contrast relative resource abundances at high latitudes (“southern home hypothesis”) against avoidance of winter resource scarcity (“dispersal‐migration hypothesis”). However, direct tests of these competing hypotheses have been rare and to date limited to historical biogeographic reconstructions. Here we derive novel predictions about the dynamics of individual niches from each hypothesis and provide a framework for evaluating support for these competing hypotheses using contemporary environmental and behavioral data. Using flammulated owls (Psiloscops flammeolus) as a model, we characterized year‐round occupied niche dynamics using high‐resolution global positioning system tracking and remote‐sensed environmental data. We also compared occupied niche dynamics to counterfactual niches using simulated alternative nonmigratory strategies. Owl occupied mean niche was conserved among seasons, whereas niche variance was generally higher during migratory periods. Simulated year‐round residents in Mexico would have experienced putatively more productive niches than migrants. These findings provide ecological support for the “dispersal‐migration” hypothesis in which winter resource scarcity is the primary driver of migration rather than summer resource abundances.
Overdiagnosis of hepatocellular carcinoma: Prevented by guidelines?
Authors: Rich Nicole E. , Singal Amit G.
Published: December 2021

Overdiagnosis refers to detection of disease that would not otherwise become clinically apparent during a patient’s lifetime. Overdiagnosis is common and has been reported for several cancer types, although there are few studies describing its prevalence in HCC surveillance programs. Overdiagnosis can have serious negative consequences including overtreatment and associated complications, financial toxicity, and psychological harms related to being labeled with a cancer diagnosis. Overdiagnosis can occur for several different reasons including inaccurate diagnostic criteria, detection of premalignant or very early malignant lesions, detection of indolent tumors, and competing risks of mortality. The risk of overdiagnosis is partly mitigated, albeit not eliminated, by several guideline recommendations, including definitions for the at‐risk population in whom surveillance should be performed, surveillance modalities, surveillance interval, recall procedures, and HCC diagnostic criteria. Continued research is needed to further characterize the burden and trends of overdiagnosis as well as identify strategies to reduce overdiagnosis in the future.
Hepatic fibrosis 2022: Unmet needs and a blueprint for the future
Authors: Friedman Scott L. , Pinzani Massimo
Published: December 2021

Steady progress over four decades toward understanding the pathogenesis and clinical consequences of hepatic fibrosis has led to the expectation of effective antifibrotic drugs, yet none has been approved. Thus, an assessment of the field is timely, to clarify priorities and accelerate progress. Here, we highlight the successes to date but, more importantly, identify gaps and unmet needs, both experimentally and clinically. These include the need to better define cell–cell interactions and etiology‐specific elements of fibrogenesis and their link to disease‐specific drivers of portal hypertension. Success in treating viral hepatitis has revealed the remarkable capacity of the liver to degrade scar in reversing fibrosis, yet we know little of the mechanisms underlying this response. Thus, there is an exigent need to clarify the cellular and molecular mechanisms of fibrosis regression in order for therapeutics to mimic the liver’s endogenous capacity. Better refined and more predictive in vitro and animal models will hasten drug development. From a clinical perspective, current diagnostics are improving but not always biologically plausible or sufficiently accurate to supplant biopsy. More urgently, digital pathology methods that leverage machine learning and artificial intelligence must be validated in order to capture more prognostic information from liver biopsies and better quantify the response to therapies. For more refined treatment of NASH, orthogonal approaches that integrate genetic, clinical, and pathological data sets may yield treatments for specific subphenotypes of the disease. Collectively, these and other advances will strengthen and streamline clinical trials and better link histologic responses to clinical outcomes.
Digital storytelling to facilitate consumer engagement in healthcare research
Authors: Pu Dai , Bonnici Rachel , Shorr Ronald , Haines Terry
Published: December 2021

Issues addressed

Consumer engagement in healthcare research presents with challenges, one of which is ensuring that the consumers have comprehended the often complex concepts in scientific research. This study aimed to compare how well older adult consumers understood video‐based versus written and verbal description approaches to provision of information.

Methods

Twenty adults in the community aged 60 years and older were recruited for this study; half were randomised to receive the information via a digital story, and the other half received the same information from a written brief. Both mediums were presented via video teleconferencing. An interviewer was present to ask questions and address queries.

Results

Participants who viewed the digital story requested for clarifications less frequently compared to those who received the written brief. Difficulty in understanding the information rose with complexity, but providing concrete examples aided comprehension of the information.

Conclusions

Complex concepts benefit from the provision of concrete examples to facilitate understanding. Video‐based approaches to provision of information are acceptable forms of participant engagement in research and require less human resources to successfully convey key information and facilitate understanding of the information. Research procedures that employ large amounts of data collection and/or asynchronous methods should consider the use of video‐based approaches, such as digital stories, to increase cost‐effectiveness.
An open‐source automated workflow to delineate storm events and evaluate concentration‐discharge relationships
Authors: Millar David , Buda Anthony , Duncan Jonathan , Kennedy Casey
Published: December 2021

The advent of in situ optical sensors that can collect sub‐daily measurements of nutrients and turbidity in flowing water bodies has yielded comparatively much larger water quality data sets than were previously available. With these newly available data sets, there has been increased interest in studying event‐based concentration‐discharge (c‐Q) relationships to infer the sources and pathways of various watershed constituents during storms. With water quality data sets increasingly growing in size and scope, the need to automate the processing and analyses of such data has become apparent. However, consensus on storm event delineation methods as they pertain to c‐Q analysis is currently lacking, and methodological details, including parameter values, are sometimes unreported in the literature. Here, we present an open‐source workflow using the programming language R that automates the processing of sub‐daily c‐Q data to analyze event‐based hysteresis patterns. Briefly, the workflow accepts a time series of concentration and discharge data, extracts stormflow from streamflow, delineates storm events and then evaluates c‐Q relationships using widely applied metrics like the hysteresis index (HI) and the flushing index (FI). We applied the workflow to three watersheds in the mid‐Atlantic United States, including a 0.4‐km2 agricultural watershed, a 150‐km2 urbanizing watershed and a 29 940‐km2 mixed land use river basin. Sub‐daily sensor‐based nutrient concentrations and discharge data were collected in each watershed. Using the small agricultural watershed as an example, we demonstrate the step‐by‐step application of the workflow. We then present results from the larger watersheds as a means for comparison and to illustrate the flexibility of the code. We believe that this rapid approach to event‐based c‐Q analysis will allow scientists and practitioners more time to focus on interpreting results, and promote greater scientific reproducibility. Likewise, we conclude this Scientific Briefing with suggested future improvements to the workflow to increase the automation of data analyses and reproducibility.
Magnitude, consequences and correction oftemperature‐derivederrors for absolute pressure transducers under common monitoring scenarios
Authors: Shannon Joseph , Liu Fengjing , Van Grinsven Matthew , Kolka Randall , Pypker Thomas
Published: December 2021

Continuous water level monitoring using absolute pressure transducers with onboard data logging is common practice in hydrologic studies. While there has been some discussion and study of temperature‐derived error (TDE), there has not been a systematic evaluation of the problem. We sought to answer three questions: (1) are current best practices enough to avoid these errors, (2) can laboratory correction be used to correct field data from varying conditions, and (3) what is the scale of the additional uncertainty of the correction procedure? We evaluated the magnitude of such errors under laboratory conditions that mimicked common monitoring scenarios. Using field data, we also demonstrated the impact of TDEs on calculated daily mean water level and diurnal signal decomposition to estimate evapotranspiration (ET). To address instrument and model uncertainty, we fit 1000 possible correction models using a double‐bootstrap approach. Correction models fit expected error as a function of water and air temperature and rate of change of air temperature. TDEs were a significant source of error, resulting in recorded data outside of manufacturer‐stated instrument uncertainty, with 45% of bootstrap models showing significant but small TDEs under best‐practice deployment. Correction equations did introduce additional error, often on a much smaller scale than instrument uncertainty. When tested against a validation data set, correction equations effectively reduced total measurement uncertainty below instrument uncertainty by up to 65%. The effects of TDEs on case‐study field data resulted in 56% of daily mean values outside of instrument error bounds (errors: −1.5 to 4.2 cm). Our results suggest that a single laboratory correction equation can be used across monitoring scenarios, though we suggest matching deployment conditions as closely as practical. Identification and correction of TDEs is essential to avoid erroneous conclusions, downstream analyses and water resources management.
Strontium isotope dynamics reveal streamflow contributions from shallow flow paths during snowmelt in a montane watershed, Provo River, Utah, USA
Authors: Hale Colin A. , Carling Gregory T. , Nelson Stephen T. , Fernandez Diego P. , Brooks Paul D. , Rey Kevin A. , Tingey David G. , Packer Brian N. , Aanderud Zachary T.
Published: December 2021

Quantifying the routing of snowmelt to surface water is critical for predicting the impacts of atmospheric deposition and changing land use on water quality in montane catchments. To investigate solute sources and streamflow in the montane Provo River watershed (Utah, USA), we used time‐series 87Sr/86Sr ratios sampled at three sites (Soapstone, Woodland and Hailstone) across a gradient of bedrock types. Soils are influenced by aeolian dust contributions, with distinct 87Sr/86Sr ratios relative to siliciclastic bedrock, providing an opportunity to investigate shallow versus deeper flow paths for controlling water chemistry. At the most upstream site (Soapstone), Sr concentrations averaged ~17 μg/L with minimal dilution during snowmelt suggesting subsurface flow paths dominated streamflow. However, a decrease in 87Sr/86Sr ratios from ~0.717 during baseflow to as low as ~0.713 during snowmelt indicated the activation of shallow flow paths through dust‐derived soils. In contrast, downstream sites receiving water inputs from Sr‐rich carbonate bedrock (Woodland and Hailstone) exhibited strong dilution of Sr from ~120 to 20 μg/L and an increase in 87Sr/86Sr ratios from ~0.7095 to ~0.712 during snowmelt. A three‐component mixing model using 87Sr/86Sr ratios and Sr concentrations at Soapstone showed water inputs were dominated by direct snowmelt and flushed soil water during runoff and groundwater during baseflow. At Woodland and Hailstone, a two‐component mixing model showed that the river was a mixture of groundwater and up to 75% upstream channel water during snowmelt. Our findings highlight the importance of flushed soil water for controlling stream water discharge and chemistry during snowmelt, with the signal from the upstream site propagating downstream in a nested catchment. Further, aeolian dust contributes to the solute chemistry of montane streams with potential impacts on water quality along shallow flow paths. Potential contaminants in these surface soils (e.g., Pb deposition in dust) may have significant impacts on water quality during snowmelt runoff.
Changes in postoperative inpatient and outpatient opioid utilization after pharmacist‐led order set standardization and education for total knee and hip replacement at an academic medical center
Authors: Patel Kenil , Stranges Paul M. , Bobko Aimee , Yan Connie H. , Thambi Mathew
Published: December 2021

Introduction

Opioid analgesics are often overprescribed after orthopedic procedures. Several strategies have been implemented nationally to curb opioid overprescription with modest success. At an institutional level, one novel idea is to implement surgery‐specific guidelines limiting opioid quantities prescribed postoperatively.

Objectives

The primary objective of this study was to evaluate the effect of our institution's new standardized postoperative multimodal pain regimen guidance on cumulative opioid prescribed postoperatively at discharge, as measured in morphine equivalent dose (MED).

Methods

Adults (≥18 years old) who underwent total knee or total hip replacement from August 2019 through March 2020 were eligible. Patients not prescribed opioids at discharge, incarcerated, or had postoperative stays 7 or more days were excluded. A pharmacist‐led standardized protocol was implemented on 21 November 2020, and provider education was completed on 18 December 2021. Patients were assigned to historical (August 2019 to November2019) or standardized (December 2019 to March 2020) cohorts based on discharge date. Secondary outcomes are cumulative and per‐prescription opioid pills, morphine equivalent daily dose (MEDD) prescribed at discharge, inpatient opioid, diazepam, and gabapentin utilization, and outpatient post‐op opioid and pain outcomes.

Results

Forty patients preintervention and 52 patients postintervention were included. For postoperative discharge opioids prescribed, median cumulative MED decreased 46% (560.0 vs 300.0, P < .001), quantity of pills decreased 14.3% (70 vs 60, P = .03), and MEDD decreased 16.7% (60.0 vs 50.0, P < .001). Inpatient opioid exposure decreased 49% (38.1 vs 19.4, P < .001), concurrent diazepam (20.0% vs 1.9%, P = .009), and gabapentin (85.0% vs 13.5%, P < .001) use with opioids also decreased. Postoperative pain scores did not significantly differ (4.0 vs 5.0, P = .63).

Conclusion

Pharmacist‐led standardized protocol implementation resulted in reduced postoperative opioid prescription and exposure, and decreased concurrent use of high‐risk drugs without affecting pain control. Opportunities exist to further decrease opioid prescribing by matching inpatient requirements.
Production of vitamin B2 (riboflavin) by Bacillus subtilis
Authors: Chu Ronghao , Li Rui , Wang Chen , Ban Rui
Published: December 2021

Riboflavin is one of the main micronutrients required for the human body for cellular respiration. It is the precursor of flavin mononucleotide and flavin adenine dinucleotide coenzymes crucial for the production of energy. The development of biotechnology has given rise to microbial procedures that strongly compete with the chemical synthesis approach and hence the fermentation process of riboflavin by microorganisms was initiated. Therefore, the main aim of this review is to investigate the production of riboflavin by Bacillus subtilis fermentation. The introduction of the microbial synthesis method has found that regulatory and structural genes involved in the synthesis of vitamin B2 are overexpressed, which has eventually enhanced the strain productivity and production of the vitamin via industrial fermentation. Using B. subtilis to synthesize riboflavin can reduce the production cost and increase the yield of riboflavin. The emergence of microbial synthesis methods has effectively increased the yield of riboflavin, and the study of the process of riboflavin synthesis by B. subtilis is of great significance for improving production, reducing costs and using renewable raw materials. © 2021 Society of Chemical Industry (SCI).
Geosmin synthase ges1 knock‐down by siRNA in the dikaryotic fungus Tricholoma vaccinum
Authors: Abdulsalam Oluwatosin , Ueberschaar Nico , Krause Katrin , Kothe Erika
Published: December 2021

Genetic manipulation for generating knock‐out experiments is essential in deciphering the precise function of a gene. However, dikaryotic fungi pose the inherent challenge of having two allelic versions of each gene, one in each nucleus. In addition, they often are slow‐growing and do not withstand protoplasting, which is why Agrobacterium tumefaciens‐mediated transformation has been adapted. To obtain knock‐out strains, however, is not feasible with a mere deletion construct transformation and screening for deletions in both nuclear copies. Hence, a convenient method using chemically synthesized dicer substrate interfering RNA (DsiRNA) for posttranscriptional interference of targeted mRNA was developed, based on the fungal dicer/argonaute system inherent in fungi for sequence recognition and degradation. A proof‐of‐principle using this newly established method for knock‐down of the volatile geosmin is presented in the dikaryotic fungus Tricholoma vaccinum that is forming ectomycorrhizal symbiosis with spruce trees. The gene ges1, a terpene synthase, was transcribed with a 50‐fold reduction in transcript levels in the knockdown strain. The volatile geosmin was slightly reduced, but not absent in the fungus carrying the knockdown construct pointing at low specificity in other terpene synthases known for that class of enzymes.
Antioxidant and anti‐tyrosinase activity of a novel stilbene analogue as an anti‐browning agent
Authors: Xia Wei , Chen Kai , Zhu Yu‐Zhu , Zhang Chang‐Jun , Chen Yu‐Lin , Wang Fan , Xie Yuan‐Yuan , Hider Robert C , Zhou Tao
Published: December 2021

BACKGROUND

Tyrosinase inhibitors find potential application in food, cosmetic and medicinal products, but most of the identified tyrosinase inhibitors are not suitable for practical use because of safety regulations or other problems. For the purpose of development of novel tyrosinase inhibitors that meet the requirement for practical application, a novel stilbene analogue (SA) was designed.

RESULTS

SA was found to possess a potent inhibitory effect against both mono‐ and diphenolase activities of mushroom tyrosinase, with IC50 values of 1.56 and 7.15 μmol L–1, respectively. Compared with a natural tyrosinase inhibitor – kojic acid – the anti‐tyrosinase effect of SA was significantly improved. Analysis of inhibition kinetics indicated that SA was a reversible and competitive–noncompetitive mixed‐type inhibitor. SA was also found to possess more potent antioxidant activities (DPPH, superoxide anion radical and hydroxyl radical scavenging ability) than those of kojic acid. Cell viability studies revealed that SA was non‐toxic to two cell lines. Furthermore, an anti‐browning test demonstrated that SA effectively delayed the blackening of shrimp.

CONCLUSION

SA has potential as an anti‐browning agent in foods. © 2021 Society of Chemical Industry.
One‐step preparation of hydrogel based on different molecular weights of chitosan with citric acid
Authors: Wei Benxi , Zou Jin , Pu Qianqian , Shi Ke , Xu Baoguo , Ma Yongkun
Published: December 2021

BACKGROUND

Chitosan‐based hydrogels have been prepared previously by a two‐step protocol in which chitosan was first dissolved in dilute acetic acid and then crosslinked by glutaraldehyde or genipin. This was a time‐consuming method, which had the disadvantages of high costs and biological safety problems.

RESULTS

Scanning electron microscopy (SEM) results verified the successful preparation of hydrogels based on high, medium, and low molecular‐weight chitosan (HCS, MCS, and LCS), respectively. The hydrogels prepared with HCS, MCS, and LCS were formed through the accumulation of different‐sized crystals. The framework density of the hydrogel was enhanced by an increase in the chitosan molecular weight and exhibited a crack pore pattern composed of flake particles. Medium molecular‐weight chitosan‐based hydrogel exhibited the highest specific surface area and total pore volume, with values of 3.81 m2 g–1 and 0.0109 cm3 g–1, respectively. The water absorption rate of the chitosan based hydrogels was influenced by its molecular weights at the sequence of LCS > HCS > MCS, while the maximum compression stress was affected at the sequence of HCS > MCS > LCS. The network structure was enhanced with an increase in the chitosan molecular weight and reached maximum stress levels of 4.50, 1.50 and 0.75 MPa for HCS‐, MCS‐, and LCS‐based hydrogels, respectively.

CONCLUSION

Citric acid was shown to be an effective dissolving and crosslinking agent in the preparation of MCS‐ and HCS‐based hydrogels. The physiochemical properties of the hydrogels were enhanced as the molecular weight of the chitosan increased. © 2021 Society of Chemical Industry.