bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractGenerating 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

AbstractMesenchymal 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

AbstractAdvanced 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

AbstractMonocytes 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

AbstractA 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

AbstractTransverse 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

AbstractLipoma 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

AbstractNH3‐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

AbstractPolycrystalline 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

AbstractPhosphorus (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

AbstractSeasonal 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

Abstract
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

Abstract
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

AbstractIssues addressedConsumer 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.MethodsTwenty 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.ResultsParticipants 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.ConclusionsComplex 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

AbstractThe 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

AbstractContinuous 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.