bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly synergistic combinations of nanobodies that target SARS-CoV-2 and are resistant to escape
Authors: Mast Fred D , Fridy Peter C , Ketaren Natalia E , Wang Junjie , Jacobs Erica Y , Olivier Jean Paul , Sanyal Tanmoy , Molloy Kelly R , Schmidt Fabian , Rutkowska Magdalena , Weisblum Yiska , Rich Lucille M , Vanderwall Elizabeth R , Dambrauskas Nicholas , Vigdorovich Vladimir , Keegan Sarah , Jiler Jacob B , Stein Milana E , Olinares Paul Dominic B , Herlands Louis , Hatziioannou Theodora , Sather D Noah , Debley Jason S , Fenyö David , Sali Andrej , Bieniasz Paul D , Aitchison John D , Chait Brian T , Rout Michael P
Published: December 2021

The emergence of SARS-CoV-2 variants threatens current vaccines and therapeutic antibodies and urgently demands powerful new therapeutics that can resist viral escape. We therefore generated a large nanobody repertoire to saturate the distinct and highly conserved available epitope space of SARS-CoV-2 spike, including the S1 receptor binding domain, N-terminal domain, and the S2 subunit, to identify new nanobody binding sites that may reflect novel mechanisms of viral neutralization. Structural mapping and functional assays show that indeed these highly stable monovalent nanobodies potently inhibit SARS-CoV-2 infection, display numerous neutralization mechanisms, are effective against emerging variants of concern, and are resistant to mutational escape. Rational combinations of these nanobodies that bind to distinct sites within and between spike subunits exhibit extraordinary synergy and suggest multiple tailored therapeutic and prophylactic strategies.
Characterization of the endogenous DAF-12 ligand and its use as an anthelmintic agent in Strongyloides stercoralis
Authors: Wang Zhu , Cheong Mi Cheong , Tsien Jet , Deng Heping , Qin Tian , Stoltzfus Jonathan DC , Jaleta Tegegn G , Li Xinshe , Lok James B , Kliewer Steven A , Mangelsdorf David J
Published: December 2021

A prevalent feature of Strongyloides stercoralis is a life-long and potentially lethal infection that is due to the nematode parasite’s ability to autoinfect and, thereby, self-replicate within its host. Here, we investigated the role of the parasite’s nuclear receptor, Ss-DAF-12, in governing infection. We identified Δ7-DA as the endogenous Ss-DAF-12 ligand and elucidated the hormone’s biosynthetic pathway. Genetic loss of function of the ligand’s rate-limiting enzyme demonstrated that Δ7-DA synthesis is necessary for parasite reproduction, whereas its absence is required for the development of infectious larvae. Availability of the ligand permits Ss-DAF-12 to function as an on/off switch governing autoinfection, making it vulnerable to therapeutic intervention. In a preclinical model of hyperinfection, pharmacologic activation of DAF-12 suppressed autoinfection and markedly reduced lethality. Moreover, when Δ7-DA was administered with ivermectin, the current but limited drug of choice for treating strongyloidiasis, the combinatorial effects of the two drugs resulted in a near cure of the disease.
Munchausen Syndrome by Proxy as a Cause of Child Abuse
Authors: Kim Youn Shin , Yu Jin , Jeong Ha Ri , Ryu Kyoung-Won
Published: December 2021

Munchausen syndrome by proxy (MSBP) is a rare form of mental disorder and is known as a particular type of child abuse. MSBP has been described since 1977 as a severe form of abuse with illness falsification or the intentional harming by guardians, mostly mothers. The perpetrator of MSBP may inflict damage to the child directly or indirectly through medical procedures. The perpetrator’s alleged motive is to satisfy her psychological needs, and she has a history of mental illness, mostly, factitious disorder, personality disorder, and somatic disorder. The pathology is not well known; as such, it is difficult for medical personnel to detect it early. In addition, it is hard to be handled effectively by the police and child welfare agencies because of the scarcity of evidence. Therefore, the authors attempt to examine the essential information from early detection and child abuse prevention by analyzing its clinical characteristics and the perpetrator’s characteristics, including alerting signs of MSBP. For this purpose, we focus on the role of nursing staff to detect this unusual cause of child abuse.
A Statistical Analysis of Forensic Autopsies Performed in the Jungbu Province of Korea in 2020
Authors: Kim Jeong Hwan , Kim Dayoung , Kim Taegong , Na Jongin , Park Min Jee , Park Ji Hye , Lee Nak-won , Yi Hyelim , Hyun Jinyoung , Kim Minjung
Published: December 2021

We analyzed the manner and cause of death in 945 forensic autopsies from the Jungbu province (Central part of South Korea) conducted by the National Forensic Service Daejeon institute in 2020. Analysis of the manner of death revealed that 43.6% (412/945 cases) were natural deaths, 41.6% (393/945 cases) were unnatural deaths, and 14.8% (140/945 cases) deaths were unknown. Among the unnatural deaths, the major manner of death (40.7%, 160/393 cases) were by accidents, 29.5% (116/393 cases) were by suicide, 21.6% (85/393 cases) were undetermined, and 8.1% (32/393 cases) were by homicide. Among the unnatural deaths, the major cause of death (42.7%, 168/393 cases) were by trauma, 19.3% (76/393 cases) were by poisoning, and 16.5% (65/393 cases) were by asphyxia. Falling was the major cause of death by trauma (42.9%, 72/168 cases) and strangulation was the major cause of death by asphyxia (72.3%, 47/65 cases). Among natural deaths, heart disease was the major cause (43.7%, 180/412 cases), followed by vascular disease (18.9%, 78/412 cases). This study is the first statistical analysis of the manner and cause of deaths in the Jungbu province. A time-series statistical analysis of the manner and cause of deaths in this province might allow more advanced interpretations about both public safety and healthcare in the future.
Acute Myocardial Infarction with Microthrombi in Cardiac Small Vessels after COVID-19 Vaccination (ChAdOx1 nCov-19): A Case Report
Authors: Park Sohyung , Choi Byung-Ha
Published: December 2021

We present the postmortem findings of an unexpected death due to acute myocardial infarction (AMI) with microthrombi and thrombosis in other vessels after the first dose of coronavirus disease 2019 (COVID-19) vaccination (ChAdOx1 nCov-19). The deceased was a 69-year-old woman who complained of nonspecific symptoms shortly after vaccination and was found dead on the sixth day. Postmortem examination revealed AMI and complications (left ventricular rupture, hemopericardium) with microthrombi in small cardiac vessels, which are similar to the characteristic findings of myocardial injury caused by microthrombi in patients with COVID-19. Nonobstructive thromboembolism in the pulmonary arteries and inferior vena cava, and fibrin microthrombi in some small vessels in the brain were also observed. It is unclear whether these findings are associated with COVID-19 vaccination, and further comprehensive studies are needed.
Therapy-Related Acute Myeloid Leukemia Diagnosed at Postmortem in a Long-term Survivor of Advanced Hepatocellular Carcinoma
Authors: Lee Ki Rim , Paik Jin Ho , Lee Soong Deok , Kim Moon-Young
Published: December 2021

Acute myeloid leukemia (AML) is a common hematologic malignancy with high mortality and a short survival period in adults. About 10% of these cases, called therapy-related AML, are reported to be the consequence of chemotherapy or radiotherapy of previous malignancy. In a clinical setting, this is usually diagnosed by peripheral blood smear or bone marrow biopsy by assessing the proportion of blasts. However, postmortem blood samples are not suitable for smear analysis because of hemolysis. Therefore, ancillary tests for identifying leukemic infiltration or related molecular change can provide an alternative diagnostic clue for AML. The deceased had been treated for 3 years for a combined type of hepatocellular carcinoma with multiple pulmonary metastases. Treatments included the resections of primary and metastatic tumors, chemotherapy, and radiotherapy, which prevented further progression of his cancer. One year after the last treatment, he suddenly collapsed without any specific symptoms and shortly died. The microscopic examination of the autopsy samples revealed extensive extramedullary infiltration of leukemia, which was confirmed as an AML by a series of ancillary immunohistochemical staining. This case illustrates both the importance of careful hematologic observation in cancer survivors and the necessity of a detailed medical diagnosis in a medicolegal autopsy.
Pathological Features of COVID-19 Pneumonia Diagnosed Following an Autopsy
Authors: Koo Hyun Lyoung , Kwon Hee Joo , Lee Won Tae
Published: December 2021

After initial emergence at the end of 2019, coronavirus disease 19 (COVID-19) rapidly spread to become a pandemic. The causative agent is recognized as a novel coronavirus, named as severe acute respiratory syndrome coronavirus 2, which is known to primarily affect the respiratory system. We present the case of a 60-year-old man who was diagnosed to have COVID-19 pneumonia following an autopsy. Microscopic examination of the lung tissue showed acute (exudative) phase of diffuse alveolar damage, inflammatory infiltrates in alveolar spaces and interstitium, atypical pneumocytes with prominent nucleoli and expanded cytoplasm, and thrombi in small arterioles. Some megakaryocytes were observed, which were positive for immunohistochemical stain for CD61. The pathological findings observed in this case were consistent with those of previously published reports of COVID-19 pneumonia. This is the first case of COVID-19 pneumonia diagnosed with an autopsy in Korea.
Investigation of Mosaicism Detected in STR Typing
Authors: You Haeun , Lee Sang Won , Lee Soong Deok , Cho Sohee
Published: December 2021

Short tandem repeats (STRs) are the most popular markers for human identification in forensics. These markers can be easily analyzed through a multiplex polymerase chain reaction and electrophoresis and provide high discrimination power. However, in STR analysis, several atypical phenomena can be observed such as allelic dropouts, drop-ins, or imbalance, which may be due to DNA polymerase slippage or DNA degradation effects. The observed atypical STR profiles can also provide information for mixed DNA samples or chromosomal abnormalities. In this study, we report a case of mosaicism detected in routine casework of paternity testing. Hair samples from a phenotypically normal male were tested, and the result presented a typical STR profile of a female for the amelogenin gene (XX). Through chromosome analysis using peripheral blood, it was found that 45,X/46,XY mosaicism resulted in the discrepancy between the genotype and the phenotype. In addition, the amount of Y chromosome detected was particularly low in hair compared to that in blood. This study shows that mosaicism can make interpretation difficult during STR analysis and suggests that sample types and repeated analysis should be considered even for routine STR testing.
An Autopsy Report of Hypoplastic Coronary Artery Disease Incidentally Identified in a Young Man
Authors: Park Ji Hyun , Jeon Yo Han , Choi Sangjoon , Lee Jong Kyu , Yeo Nam Seok , Lee SangHan
Published: December 2021

Hypoplastic coronary artery disease (HCAD) is a rare congenital abnormality characterized by underdevelopment of one or more major branches of the coronary arteries, which may lead to myocardial infarction and sudden death. We report a case of HCAD that was incidentally detected during autopsy in a 25-year-old male soldier who died during underwater escape training. On macroscopic examination, the right coronary artery measured 1 mm in diameter, which was significantly smaller than that of other coronary arteries. We observed no anomalies in addition to HCAD. Death was attributed to drowning, which was consistent with autopsy findings and the circumstances of death. Although extremely rare, if sudden cardiac death is suspected in children and young adults, it must be confirmed through careful evaluation.
Narratiiv ja topos Heino Elleri “Sümfoonilises legendis”
Authors:   Institute of Philosophy and Semiotics, University of Tartu, Estonia, Pihel Karl Joosep
Published: December 2021

This article focuses on the narrative analysis of late-romantic instrumental music. Having adopted the structuralist-semiotic conception of musical narrative as proposed by Byron Almén (2008) as the transvaluation of an opposing hierarchy, and the concept of the musical topic as musical elements with specific stylistic-cultural associations, I analyse the expressive form of Heino Eller’s early symphonic poem “Symphonic Legend” (1923). Narrative logic was found to permeate the musical work despite its collage or suite-like form, as the composer introduces characteristic musical actors that re-appear in different musical contexts. These actors are largely distinguished by musical topics, the conventional stylistic associations related with their musical characteristics as Eller’s piece presents a wide synthesis of styles – from musical impressionism and expressionism to lyrical or chromatic late-romantic; and various topics, such as fantastic, ombra, apassionata, pianto, heroic, and pastoral. Further, I propose a layered narrative structure for the “Symphonic Legend”, as the jarring and abrupt changes in musical material, affect and topic between different movements of the piece suggest shifts in the level of musical discourse and a framed narrative, as proposed by Hatten (1994). The primary order-imposing hierarchy is identified as the pastoral-impressionist topic that acts as the introduction and coda to the entire piece while the transgressive hierarchy is carried by antagonistic musical material associated with fantastical and dysphoric topics (whole-tone scale, chromaticism, fanfare-like brass and ombra) and with the main theme-actor of the piece (a theme strongly resembling the main theme of the first part of Rimsky-Korsakov’s “Scheherezade”). While the pastoral beginning and end of the piece (1st and 11th sections) suggest a narrative trajectory of a romance or “the victory of the order-imposing hierarchy over the transgression”, the abrupt shifts that occur between those sections and the middle-sections of the piece suggest that these take place at a different level of discourse, placing the narrative weight in sections 2–10, where the primary conflict seems to be between the antagonistic material and the theme-actor. In the middle sections Eller seems to problematize the typical narrative trajectory of dysphoric to euphoric in 19th-century symphonic poems, as the theme-actor’s heroic apotheosis in the 9th section is undermined by its reprise in section 10 and ultimate inability to be united with the order-imposing hierarchy in the coda, suggesting an ironic narrative. This reading is hopefully the first of many narrative analyses of Eller’s and other Estonian composers’ unique late-romantic and early modern symphonic poems.
The external and data loose coupling for the integration of software units: a systematic mapping study
Authors: Ruiz Ceniceros Juan Antonio , Aguilar-Calderón José Alfonso , Espinosa Roberto , Tripp-Barba Carolina
Published: December 2021

Integration of legacy and third-party software systems is almost mandatory for enterprises. This fact is based mainly on exchanging information with other entities (banks, suppliers, customers, partners, etc.). That is why it is necessary to guarantee the integrity of the data and keep these integration’s up-to-date due to the different global business changes is facing today to reduce the risk in transactions and avoid losing information. This article presents a Systematic Mapping Study (SMS) about integrating software units at the component level. Systematic mapping is a methodology that has been widely used in medical research and has recently begun to be used in Software Engineering to classify and structure the research results that have been published to know the advances in a topic and identify research gaps. This work aims to organize the existing evidence in the current scientific literature on integrating software units for external and data loose coupling. This information can establish lines of research and work that must be addressed to improve the integration of low-level systems.
A cross-sectional study for the mental health status and sleep quality among college students in Macao during the COVID-19 pandemic
Authors: Tao Xiaoyu , Chen Dong , Fan Yawen , Zhang Lanxin , Shan Houqian , Wei Yi , Yu Xi , Zhong Tian , Wang Ling , Chung Sookja Kim , Yu Yaqin , Xiao Ying
Published: December 2021

Objectives

The main focus of this study was to investigate the effect of the coronavirus disease (COVID-19) pandemic on the mental health condition and sleep quality of college students in Macao. In addition, the students’ behaviours during the pandemic, such as drinking alcohol, taking sleeping pills, and seeking psychological counselling were analyzed.

Method

A cross-sectional survey of mental health and sleep quality status, as well as the possible behavioral risk factors, was conducted among the college students of Macao in August, 2020 during the COVID-19 pandemic. An online self-report questionnaire survey method was applied to assess the general demographics and related lifestyle behaviors of students. The general mental health condition and sleep quality were evaluated through the General Health Questionnaire (GHQ-12) and Pittsburgh Sleep Quality Index (PSQI) questionnaires, respectively. The main statistical methods included the Chi-square test, Bonferroni correction, and Pearson correlation. Data analysis was performed using SPSS Version 24.0.

Results

A total of 980 students were investigated in the study, of which 977 completed the survey. During the COVID-19 pandemic period, overall college students in Macao were psychologically well adjusted and reported good quality of sleep. However, female students were in poorer psychological condition than males (P < 0.05). Moreover, the students over 20 years of age had poorer sleep quality than students aged less than or equal to 20 (P < 0.05). The significant differences were found among the students in different study majors for the mental health status and sleep quality (both P < 0.05), which were associated with certain behaviors, such as drinking alcohol, taking sleeping pills, and seeking for help in psychological counselling during the COVID-19 pandemic period.

Conclusions

Poor mental health status could be either the consequence or cause of sleep disturbance, which might further affected physical health. Therefore, regular assessment of mental health condition and sleep quality of college students is particularly necessary during public health emergencies, such as the COVID-19 pandemic, and appropriate intervention should be provided to the students.
First report of the genus Bicorniphontodes (Copepoda, Harpacticoida, Ancorabolidae) in South Korea, with descriptions of three new species
Authors: Kim Jong Guk , Lee Jimin , Cho Kyuhee
Published: December 2021

We report the occurrence of the genus Bicorniphontodes George, Glatzel & Schröder, 2019 in Korean waters, with descriptions of three new species: Bicorniphontodes lacuna sp. nov., B. comptus sp. nov., and B. huysi sp. nov. Morphology analysis was carried out to reconstruct the phylogenetic relationships of Bicorniphontodes species, including the three new species. Parsimony analysis based on 41 characters revealed that the three new species are clustered together as a monophyletic clade, of which B. horstgeorgei (George & Gheerardyn, 2015) is a sister species. The monophyletic status of three new species was supported by five synapomorphies, such as the micro-morphological conditions of the exopodal segments of the first leg, coxae of the second to fourth legs, exopod of the fifth leg in the female and baseoendopod of the fifth leg in the male, and the maxillular endopod represented by two setae. These three species can be easily distinguished based on the morphology of the rostrum, cephalothoracic processes, female genital double-somite, caudal rami, and second endopodal segment of the third leg in the male. The taxonomic position of B. bicornis sensu Kim, 2013 in Korean fauna was reevaluated based on the newly collected material from Udo Islet near Jeju Island; this resulted in a synonym of B. huysi sp. nov.
Rapid detection ofEnterococcusand vancomycin resistance using recombinase polymerase amplification
Authors: Panpru Pimchanok , Srisrattakarn Arpasiri , Panthasri Nuttanun , Tippayawat Patcharaporn , Chanawong Aroonwadee , Tavichakorntrakool Ratree , Daduang Jureerut , Wonglakorn Lumyai , Lulitanond Aroonlug
Published: December 2021

Vancomycin-resistant enterococci (VRE), especiallyEnterococcus faecium, have been a global concern, often causing serious healthcare-associated infections. We established a rapid approach for detectingE. faeciumand vancomycin-resistance genes (vanAandvanB) in clinical samples using isothermal recombinase polymerase amplification (RPA) combined with a lateral-flow (LF) strip. Specific RPA primer sets and probes forddl(to identify the presence ofE. faecium)vanAandvanBgenes were designed. The RPA reaction was performed under isothermal condition at 37 °C within 20 min and read using the LF strip within a further 5 min. A total of 141 positive blood-cultures and 136 stool/rectal swab samples were tested using RPA-LF method compared to the conventional PCR method. The RPA-LF method exhibited 100% sensitivity in both blood-culture (60E. faecium; 35vanAtype and twovanBtype) and stool/rectal-swab samples (63E. faeciumand 36vanAtype) without cross-reaction (100% specificity). The lower detection limit of the RPA-LF was approximately 10 times better than that of the conventional PCR method. The RPA-LF method is an alternative rapid method with excellent sensitivity and specificity for detectingE. faecium,vanA, andvanB, and it has the potential to be used as a point-of-care device for VRE therapy and prevention.
Functional analysis of a Phytophthora host-translocated effector using the yeast model system
Authors: Wilson Avery C. , Morgan William R.
Published: December 2021

Background

Phytophthora plant pathogens secrete effector proteins that are translocated into host plant cells during infection and collectively contribute to pathogenicity. A subset of these host-translocated effectors can be identified by the amino acid motif RXLR (arginine, any amino acid, leucine, arginine). Bioinformatics analysis has identified hundreds of putative RXLR effector genes in Phytophthora genomes, but the specific molecular function of most remains unknown.

Methods

Here we describe initial studies to investigate the use of Saccharomyces cerevisiae as a eukaryotic model to explore the function of Phytophthora RXLR effector proteins.

Results and Conclusions

Expression of individual RXLR effectors in yeast inhibited growth, consistent with perturbation of a highly conserved cellular process. Transcriptome analysis of yeast cells expressing the poorly characterized P. sojae RXLR effector Avh110 identified nearly a dozen yeast genes whose expression levels were altered greater than two-fold compared to control cells. All five of the most down-regulated yeast genes are normally induced under low phosphate conditions via the PHO4 transcription factor, indicating that PsAvh110 perturbs the yeast regulatory network essential for phosphate homeostasis and suggesting likely PsAvh110 targets during P. sojae infection of its soybean host.
In vivo Evaluation of Nanostructured Lipid Carrier System in Rats Bearing Breast Tumor
Authors: Tagde Priti , Nagpal Kalpana , Kulkarni Giriraj T.
Published: December 2021

The aim of this work is to study the anti-proliferative potential of two anticancer drugs loaded in nanostructured lipid carriers (NLCs).The maximal inhibition of cell growth by Raloxifene (RLX) & Curcumin (CUM) nanostructured lipid carriers (RLX-CUM-NLCs) was determined by assessing the viability of MDA-MB 231 cells. As far as we know, this is the first research to look at the effects of RLX-CUM-NLCs on DMBA-induced breast carcinogenesis in a rat model. RLX-CUM-NLCs reduced the number of tumors in an in-vivo investigation. After 14 weeks of induction, we discovered a tumor with a 100% incidence rate. The incidence of experimental breast cancer was decreased to 83.33% in the RLX-treated group. In contrast, RLX-CUM-NLCs demonstrated a significant anticancer effect with a 50% incidence in the RLX-CUM-NLCs group. Compared to controls, the RLX-CUM-NLCs therapy did not cause any toxicity in the animals in terms of food intake, body weight, or activity levels until 300 mg/kg BW. The current research shows that the RLX-CUM-NLCs has a chemopreventive impact on DMBA-induced breast cancer in rats by decreasing tumor burden and restoring marker enzymes activity.
Consensus for Statements Regarding a Definition for Spinal Osteoarthritis for Use in Research and Clinical Practice: A Delphi Study
Authors: de Luca Katie , Chiarotto Alessandro , Cicuttini Flavia , Creemers Laura , de Schepper Evelien , Ferreira Paulo H. , Foster Nadine E. , Hartvigsen Jan , Kawchuk Gregory , Little Christopher B. , Oei Edwin H. , Suri Pradeep , Vleggeert‐Lankamp Carmen , Bierma‐Zeinstra Sita M. A. , Ferreira Manuela L.
Published: December 2021

Objective

To determine consensus among an international, multidisciplinary group of experts regarding definitions of spinal osteoarthritis for research and for clinical practice.

Methods

A 15‐member, multidisciplinary steering committee generated 117 statements for a 3‐round Delphi study. Experts in back pain and/or osteoarthritis were identified and invited to participate. In round 1, participants could propose additional statements for voting. All statements were rated on a 1–9 Likert scale, and consensus was set at ≥70% of respondents agreeing or disagreeing with the statement and <15% of respondents providing the opposite response.

Results

In total, 255 experts from 11 different professional backgrounds were invited. From 173 available experts, 116 consented to participate. In round 1, 103 participants completed the survey, followed by 85 of 111 participants in round 2 (77%) and 87 of 101 participants in round 3 (86%). One‐third of participants were from Europe (30%), most were male (58%), one‐fifth were physical therapists (21%), and over one‐third had been in their profession for 11–20 years (35%). Of 131 statements, consensus was achieved for 71 statements (54%): 53 in agreement (75%) and 18 in disagreement (25%).

Conclusion

Although there was consensus for statements for definitions of spinal osteoarthritis that were analogous to definitions of osteoarthritis in appendicular joints, a future definition still needs refinement. Importantly, this Delphi highlighted that a future definition should be considered across a spectrum of structural changes and patient symptoms and expressed on a progressive scale.
Canakinumab's Effect Against Subsequent Gout Flares and High‐Sensitivity C‐Reactive Protein Levels: A Causal Mediation Analysis
Authors: Yoshida Kazuki , Glynn Robert J. , Choi Hyon K. , Everett Brendan M. , Li Yi , MacFadyen Jean G. , Ridker Paul M. , Solomon Daniel H.
Published: December 2021

Objective

The objective of this study was to quantify the value of early suppression of high‐sensitivity C‐reactive protein (hsCRP) levels as a biomarker of the protective role of canakinumab against future gout flares.

Methods

We conducted a post hoc causal mediation analysis of the Canakinumab Anti‐Inflammatory Thrombosis Outcome Study for gout flares. The 3‐month change in the log hsCRP level was the mediator of interest. We used linear regression for the hsCRP level mediator and Cox or Weibull regression for gout‐flare outcomes, combining them in causal mediation analysis. We examined the cohort overall, as well as stratified by prevalent gout at baseline.

Results

We analyzed 9,221 patients without prevalent gout and 747 with prevalent gout. The Cox regression hazard ratio (HR) for a gout flare was 0.50 (95% confidence interval [95% CI] 0.37–0.68) comparing canakinumab with placebo, of which 6% was explained by the mediated effect through hsCRP level reduction in the first 3 months. In the prevalent‐gout subgroup, the HR was 0.58 (95% CI 0.36–0.95), of which 31% was explained by the mediated effect through hsCRP level reduction. The Weibull analysis gave a proportion‐mediated estimate of 47%. The indirect effect via hsCRP level reductions was unclear in the subgroup without prevalent gout.

Conclusion

The first 3‐month reduction in hsCRP level was not a good biomarker for canakinumab's protective effect on future gout flares in the overall cohort. Among patients with prevalent gout, there may be a potential role for early hsCRP level reduction as a biomarker for interleukin‐1β inhibitors' future gout‐flare benefit.
Tackling Humidity with Designer Ionic Liquid‐Based Gas Sensing Soft Materials
Authors: Esteves Carina , Palma Susana I. C. J. , Costa Henrique M. A. , Alves Cláudia , Santos Gonçalo M. C. , Ramou Efthymia , Carvalho Ana Luísa , Alves Vitor , Roque Ana C. A.
Published: December 2021

Relative humidity is simultaneously a sensing target and a contaminant in gas and volatile organic compound (VOC) sensing systems, where strategies to control humidity interference are required. An unmet challenge is the creation of gas‐sensitive materials where the response to humidity is controlled by the material itself. Here, humidity effects are controlled through the design of gelatin formulations in ionic liquids without and with liquid crystals as electrical and optical sensors, respectively. In this design, the anions [DCA]− and [Cl]− of room temperature ionic liquids from the 1‐butyl‐3‐methylimidazolium family tailor the response to humidity and, subsequently, sensing of VOCs in dry and humid conditions. Due to the combined effect of the materials formulations and sensing mechanisms, changing the anion from [DCA]− to the much more hygroscopic [Cl]−, leads to stronger electrical responses and much weaker optical responses to humidity. Thus, either humidity sensors or humidity‐tolerant VOC sensors that do not require sample preconditioning or signal processing to correct humidity impact are obtained. With the wide spread of 3D‐ and 4D‐printing and intelligent devices, the monitoring and tuning of humidity in sustainable biobased materials offers excellent opportunities in e‐nose sensing arrays and wearable devices compatible with operation at room conditions.
Functional Magnetic Microdroplets for Antibody Extraction
Authors: Al‐Terke Hedar H. , Latikka Mika , Timonen Jaakko V. I. , Vékás Ladislau , Paananen Arja , Joensuu Jussi , Ras Robin H. A.
Published: December 2021

Antibodies play an essential role in modern medicine for diagnostic and therapeutic applications. Even though the production of antibodies is the fastest growing pharmaceutical industry area, the cost of antibodies remains high, which limits access to antibody‐based medicine both in developing and developed countries. The bottleneck and major cost factor in the production is purification of the antibody. Here, a proof‐of‐concept is presented for antibody extraction using ferrofluid microdroplets. An external magnetic field splits oil‐based ferrofluid droplets into an array of daughter microdroplets, which serve as a magnetically tunable, hydrophobic, liquid substrate with a relatively large surface area. A fusion protein (HFBI‐Protein A), added to the solution surrounding the magnetic droplets, adsorbs strongly at the liquid‐liquid interface by the hydrophobin HFBI moiety, creating a bifunctional monolayer that can catch antibody molecules. After adsorption at the liquid‐liquid interface, these antibody molecules can be released by decreasing the pH of the solution. The antibody extraction process is investigated using confocal microscopy and gel electrophoresis. In addition, the effect of HFBI on the field‐induced ferrofluid droplet splitting is examined. This study provides a proof of concept for utilizing liquid‐liquid instead of a solid‐liquid system in antibody handling.
Control of Surface Wrinkling through Compliant Nanostructured Interfaces
Authors: Hung Kuo‐Kang , Chasiotis Ioannis
Published: December 2021

Surface wrinkling occurs due to the mechanical instability induced by the stiffness mismatch between a soft substrate and a stiff film. In a two‐layer system comprised of a thick compliant substrate and a thin stiff film, the wrinkle pattern, as described by the wrinkle wavelength, amplitude, and orientation, is limited by the material properties and thickness of the two layers. In this work, an interface layer of nanostructures fabricated by glancing angle deposition (GLAD) is introduced to modify the surface wrinkling of polydimethylsiloxane due to a Cu film, thus enabling improved control of wrinkling in an otherwise constrained material system. Isotropic (nanospring) and orthotropic (nanochevron) Cu interfaces are GLAD‐deposited with different geometric parameters to control the in‐plane stiffness of the interface. The isotropic nanospring films provide a novel means to control the physical length scale of wrinkle patterns, namely, both the wavelength and the amplitude of surface wrinkles, while maintaining the amplitude‐to‐wavelength aspect ratio. The anisotropic nanochevron films result in anisotropy ratio of ≈10 which provides a unique means to modify the wrinkle direction independently of the direction of the applied load. The prediction by the experimentally calibrated analytical model is shown to be in good agreement with the experiment.
Disordered Nano‐Hemisphere Molybdenum Trioxide for Enhanced Light Out‐Coupling in Organic Light‐Emitting Diodes
Authors: Ren ZhanPeng , Cheng Jiang , Liao XiaoQing , Song Zhihao , Xu Da , Li Lu , Yu Junsheng
Published: December 2021

A 2D‐array scattering layer composed of disordered, wavelength‐sized molybdenum trioxide (MoO3) nano‐hemispheres that are introduced into existing organic light‐emitting diodes (OLEDs) can maximize light out‐coupling. This MoO3 nano‐hemisphere scattering layer (M‐NSL) obtained by in situ annealing‐spraying is investigated in depth based on considerations of larger refractive index, higher transparency, and internal light scattering. With the simulation of finite‐difference time‐domain, M‐NSL can effectively reduce the optical loss among the structural layers caused by the mismatch of refractive indexes is observed and induce strong diffuse transmission, which reduces the total internal reflection in the substrate, thus improving light out‐coupling. The power efficiency and external quantum efficiency of the device with M‐NSL demonstrated performance metrics of 139.5 lm W−1 power efficiency and 47.5% external quantum efficiency at 1000 cd m−2, which increased by 82.4% and 64.5%, respectively, compared with the control device without M‐NSL. Potentially, the scheme will be easy to implement and incorporate into existing semiconductor device technologies, and it can be used separately or in conjunction with other methods to mitigate the critical angle loss in OLEDs.
Characterize and Retard the Impact of the Bias‐Induced Mobile Ions in CH3NH3PbBr3 Perovskite Light‐Emitting Diodes
Authors: Shen Teng Lam , Loganathan Aswaghosh , Do Thi Hoai , Wu Chang‐Min , Chen Yu‐Ting , Chen Zheng‐Jun , Chiu Nan‐Chieh , Shih Chun‐Hua , Wang Hsin‐Chih , Chou Jia‐Hsian , Hsu Yao‐Yuan , Liu Chi‐Ching , Chang Yun‐Chorng , Fu Yaw‐Shyan , Lai Wei‐Chi , Chen Peter , Wen Ten‐Chin , Guo Tzung‐Fang
Published: December 2021

Herein, the aspects of ion migration in polycrystalline CH3NH3PbBr3 thin film and their phenomenal influences on the output performance of perovskite light‐emitting diodes (PeLEDs) are reported. The physical insight of bias‐induced migration of mobile ions in the perovskite active layer effectuating the observed non‐linearity in the increased magnitude of electroluminescence (EL) and luminous efficiency (LE) as a function of current density for PeLEDs is directly evidenced using the capacitance spectroscopy. Adding the zwitterion molecule, Choline chloride (Ch.Cl), in CH3NH3PbBr3 precursor solution for preparing polycrystalline perovskite film effectively passivates the charged defects, either positively or negatively, in organic‐inorganic halide perovskite and most importantly interferes the migration of ions crossing the grains in PeLEDs as verified by the higher calculated magnitude of the activation energy for the migration of mobile ions. As a result, the Ch.Cl‐additive devices exhibit the rather stable EL and LE magnitude under the electric bias. EL magnitude increases linearly as a function of current density, revealing the epitome of output characteristics for decent light‐emitting diodes. To suppress the influence of the migrating ions on operating PeLEDs is a key issue before it is stepped further to advance the efficiencies and the operational stabilities of perovskite devices.
Wafer‐Scale Two‐Dimensional Molybdenum Diselenide Phototransistor Array via Liquid‐Precursor‐Assisted Chemical Vapor Deposition
Authors: Jeon Youngseo , Seo Jihyung , Kim Jihyun , Rhee Dongjoon , Jung Myeongjin , Park Hyesung , Kang Joohoon
Published: December 2021

Monolayer transition metal dichalcogenides (TMDs) have received considerable interest as a candidate material for ultrathin photodetectors, but their practical applications are hindered by difficulties in synthesizing high‐quality films over centimeter‐scale areas. Although chemical vapor deposition (CVD) based on liquid‐phase precursors has shown promise for large‐area synthesis of TMDs, the resulting films typically exhibit much lower optoelectronic performance due to the lack of wafer‐scale uniformity with monolayer thickness and inferior electrical properties induced by defects. In this article, the authors present a wafer‐scale, gate‐tunable photodetector array from high‐quality monolayer molybdenum diselenide (MoSe2) films synthesized with the liquid‐phase CVD process assisted by a growth promoter. Continuous monolayer MoSe2 can form by introducing potassium iodide as a growth promoter for selenizing the metal‐precursor film. Side‐by‐side comparison between MoSe2 formed with and without the potassium iodide reveal that the promoter‐assisted growth strategy significantly improves the crystallinity, which results in enhanced optoelectronic properties. The resulting photodetector array is highly photosensitive over the visible wavelengths with photoresponsivities higher than those of the previously reported devices based on CVD‐synthesized monolayer TMDs and even comparable to the devices fabricated from mechanical exfoliation approach.
Quantifying Exciton Annihilation Effects in Thermally Activated Delayed Fluorescence Materials
Authors: Thakur Kalyani , van der Zee Bas , Wetzelaer Gert‐Jan A. H. , Ramanan Charusheela , Blom Paul W. M
Published: December 2021

Important parameters for the design and performance of thermally activated delayed fluorescence (TADF) emitters are the forward and reverse intersystem crossing rates between singlet and triplet states. The magnitude of these rates is determined from the prompt and delayed transient photoluminescence decay. It is demonstrated that this photoluminescence decay strongly depends on the initial photoexcited population density due to exciton–exciton annihilation processes. By kinetic modeling of the power‐dependent time‐resolved photoluminescence of the TADF emitter 9,10‐bis(4‐(9H‐carbazol‐9‐yl)‐2,6‐dimethylphenyl)‐9,10‐diboraanthracene (CzDBA), singlet–triplet annihilation and triplet–triplet annihilation are identified as the main loss processes with rate constants in the order of 10−17 m3 s−1. Neglecting these quenching processes leads to erroneous estimates of the (reverse) intersystem crossing rates.
Tailoring Circular Dichroism in an Isomeric Manner: Complete Control of Amplitude and Phase for High‐Quality Hologram and Beam Forming
Authors: Li Yongfeng , Pang Yongqiang , Wang Jiafu , Zheng Qiqi , Zhang Jieqiu , Zhang Jingjing , Jing Yao , Zheng Lin , Feng Maochang , Wang He , Qu Shaobo , Cui Tiejun
Published: December 2021

Nowadays, the research of metasurfaces has been developed from single‐dimensional toward multi‐dimensional manipulation of electromagnetic (EM) waves, which greatly boosts the practical application of metasurfaces in both microwave and optics regimes. Currently, the demand for new methods to implement effective manipulation of EM waves in multiple dimensions is ever being increased yet it is still a challenging task. Here, a metasurface‐based paradigm is proposed for tailoring both amplitude and phase by isomeric manner in a dichroism level, which reveals a flexible capability of manipulating EM waves within all isotropic, anisotropic and chiral characteristics. Circular dichroism (CD) meta‐atoms are implemented via loading lumped resistors into planar chiral resonators. The cross‐polarization reflection amplitude of the circularly polarized wave is tailored precisely and continuously from 0 to 1 using the diastereomers of CD meta‐atoms, while the phase is independently manipulated by the rotamer counterparts based on Pancharatnam‐Berry (PB) phase. By controlling both amplitude and phase profiles of the metasurfaces with subwavelength spatial resolution, high‐quality complex amplitude hologram and far‐field beam forming are demonstrated. Encouragingly, this approach for achieving simultaneous control of amplitude and phase makes a milestone on multi‐dimensional metasurfaces which may find applications in integrated planar EM functional systems.
Innovation Quinary and n‐Value toward Fuzzy Logic QCA Cell Design
Authors: Akbari‐Hasanjani Reza , Sabbaghi‐Nadooshan Reza
Published: December 2021

Quantum Cellular automata (QCA) is a technology developed to replace complementary metal‐oxide‐semiconductor (CMOS) technology that faces increasing challenges due to the miniaturization of CMOS dimensions. The use of multi‐valued QCA is of interest because of its proximity to fuzzy logic, and lower power consumption. A two‐layer quinary system is proposed and the basic logic gates are examined and simulated to confirm the correct performance of the proposed cell. The proposed cell employs two layers because the presence of more than two particles per layer destabilizes the design of logic gates. The proposed Quinary QCA(QuQCA) cell can be implemented in one layer using input and output derives. Simple relationships are proposed to calculate the polarization values and the number and type of layers, so complex quantum computations can be avoided. The quantum power consumption and the proposed cell power consumption of the quinary system are calculated and compared. Finally, we present n‐valued cells without using quantum computation, and these cells are examined in terms of the number of particles, polarization value, and cell structure. The n‐level cell can be investigated more easily than other technologies due to its proximity to fuzzy logic and the design of the input, output, and fuzzy membership function.
Enhanced Terahertz Spectral‐Fingerprint Detection of α‐Lactose Using Sub‐Micrometer‐Gap On‐Chip Waveguides
Authors: Park Sae June , Parker‐Jervis Rowan S. , Cunningham John E.
Published: December 2021

We investigate using finite element methods how sub‐micrometer to micrometer‐scale coplanar waveguide (CPW) can be used for the detection of fingerprint spectra of very small (of order 10−14 mL) volumes of analytes in the terahertz (THz) frequency range. The electric field distribution is investigated near the waveguide for various gap widths between the center conductor and ground plane using a finite element simulation (ANSYS High Frequency Structure Simulator, HFSS). Taking lactose monohydrate as an exemplar material, a Drude–Lorentz model is combined for its real and imaginary permittivities with this numerical simulation, finding a significant enhancement in fingerprint detection as the gap width is reduced; the electric field in the CPW is found to increase by a factor ≈14 times moving from a 20 to 0.5‐µm‐wide gap between center conductor and ground plane, while the on‐resonance THz absorption increases ≈14 times. The effective absorption coefficient of the lactose at 530 GHz is investigated as a function of the slot width for various lactose block thicknesses to understand how change in the field confinement and in the effective overlap between the lactose block and incident THz waves affect the effective absorption coefficient.
Compact SchCas9 Recognizes the Simple NNGR PAM
Authors: Wang Shuai , Mao Huilin , Hou Linghui , Hu Ziying , Wang Yao , Qi Tao , Tao Chen , Yang Yuan , Zhang Chengdong , Li Miaomiao , Liu Huihui , Hu Shijun , Chai Renjie , Wang Yongming
Published: December 2021

Clustered regularly interspaced short palindromic repeat (CRISPR)/SaCas9 is the most popular tool for in vivo genome editing due to its high efficiency and small genome. The authors previously developed four SaCas9 orthologs as genome‐editing tools. Here, to expand the targeting scope, they investigate the diversity of protospacer adjacent motifs (PAMs) by screening a list of 16 SaCas9 orthologs, twelve of which display editing activity in mammalian cells. They recognize five types of PAMs: NNGRRT, NNGRRR, NNGRC, NNGA, and NNGR. Importantly, SchCas9 recognizes the simple NNGR PAM, representing the most relaxed PAM preference of compact Cas9s to date. It is further demonstrated that SchCas9 enables efficient genome editing in multiple human cell lines. Altogether, these compact Cas9 tools offer a new option for both basic research and clinical applications.
Identification of root bacteria associated with different stripe rust resistance in wheat cultivars
Authors: Yang Zhengting , Huang Yufeng , Shi Tianlong , Liu Jie , Yi Yin , Tang Xiaoxin , Li Fei
Published: December 2021

The plant rhizosphere bacterial community influences plant stress resistance. Stripe rust causes severe damage to wheat (Triticum aestivum L.) production. To reveal the composition and function of root bacterial communities in wheat cultivars with different stripe rust resistance, rhizosphere soil samples were collected from four wheat cultivars. High‐throughput 16S rRNA gene sequencing was used to study the rhizobacterial community structure and function in stripe rust‐resistant (Guinong 19 and Huamai 1223) and ‐susceptible (Mingxian 169 and Taichung 29) wheat cultivars. A total of 6,392 operational taxonomic units (OTUs) were detected, belonging to 29 bacterial phyla. Analysis showed the susceptible and resistant wheat cultivars had different microbial communities. Principal coordinate analysis showed that all wheat rhizosphere bacterial samples could be divided into two groups, according to different disease resistance. Linear discriminant analysis effect size analysis showed that different bacterial taxa were enriched in the rhizosphere soil between resistant and susceptible wheat cultivars. Functional analysis showed that the bacterial community in stripe rust‐resistant wheat had greater amino acid transport and metabolic functions. Our research not only provides basic knowledge of the composition of wheat‐related microbiota but also reveals the microbial taxa that could be integrated into the management strategy of wheat stripe rust.