bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Ultratough Topological Tissue Adhesives
Authors: Cintron‐Cruz Juan A. , Freedman Benjamin R. , Lee Matthew , Johnson Christopher , Ijaz Hamza , Mooney David J.
Published: July 2022

Tissue adhesives capable of achieving strong and tough adhesion in permeable wet environments are useful in many biomedical applications. However, adhesion generated through covalent bond formation directly with the functional groups of tissues (i.e., COOH and NH2 groups in collagen), or using non‐covalent interactions can both be limited by weak, unstable, or slow adhesion. Here, it is shown that by combining pH‐responsive bridging chitosan polymer chains and a tough hydrogel dissipative matrix one can achieve unprecedented ultratough adhesion to tissues (>2000 J m−2) in 5–10 min without covalent bond formation. The strong non‐covalent adhesion is shown to be stable under physiologically relevant conditions and strongly influenced by chitosan molecular weight, molecular weight of polymers in the matrix, and pH. The adhesion mechanism relies primarily on the topological entanglement between the chitosan chains and the permeable adherends. To further expand the applicability of the adhesives, adhesion time can be decreased by dehydrating the hydrogel matrix to facilitate rapid chitosan interpenetration and entanglement (>1000 J m−2 in ≤1 min). The unprecedented adhesive properties presented in this study open opportunities for new strategies in the development of non‐covalent tissue adhesives and numerous bioapplications.
Self‐Powered Multifunctional Human–Machine Interfaces for Respiratory Monitoring and Smart System Control
Authors: Pang Yaokun , Chen Shoue , Cao Yunteng , Huang Zhida , Xu Xianchen , Fang Yuhui , (Chase) Cao Changyong
Published: July 2022

Innovative human–machine interfaces (HMIs) have attracted increasing attention in the field of system control and assistive devices for disabled people. Conventional HMIs that are designed based on the interaction of physical movements or language communication are not effective or appliable to severely disabled users. Here, a breath‐driven triboelectric sensor is reported consisting of a soft fixator and two circular‐shaped triboelectric nanogenerators (TENGs) for self‐powered respiratory monitoring and smart system control. The sensor device is capable of effectively detecting the breath variation and generates responsive electrical signals based on different breath patterns without affecting the normal respiration. A breathing‐driven HMI system is demonstrated for severely disabled people to control electrical household appliances and shows an intelligent respiration monitoring system for emergence alarm. The new system provides the advantages of high sensitivity, good stability, low cost, and ease of use. This work will not only expand the development of the TENGs in self‐powered sensors, but also opens a new avenue to develop assistive devices for disabled people through innovation of advanced HMIs.
High‐Performance Inverted Tandem OLEDs with the Charge Generation Layer based on MoOx and Ag Doped Planar Heterojunction
Authors: Xu Yachen , Niu Yixiao , Gong Chunliu , Shi Wei , Yang Xuyong , Wei Bin , Wong Wai‐Yeung
Published: July 2022

The morphological and electrical characteristics of a planar‐heterojunction structured charge generation layer (CGL) consisting of MoO3 doped N,N′‐bis‐(1‐naphthalenyl)‐N, N′‐bis‐phenyl‐(1,1′‐biphenyl)‐4,4′‐diamine (NPB) as the p‐type material and Ag‐doped 4,7‐diphenyl‐1,10‐phenanthroline (Bphen) as the n‐type counterpart (NPB:MoO3/Bphen:Ag). A significant charge generation effect of CGL is observed and its mechanism is analyzed. The introduction of CGL can enhance the concentration of the charge carrier and balance the injection of carriers. Inverted tandem organic light‐emitting diodes (OLEDs) with the CGL are fabricated. The inverted tandem OLEDs exhibit excellent optoelectronic performance due to the charge generation effect and the suppression of the high concentration quenching. The maximum current efficiency and external quantum efficiency of the inverted tandem OLED reached 27.91 cd A−1 and 11.18%, respectively, which are 110.95% and 95.79% higher than that of the inverted OLED.
Ultralow Current Switching of Synthetic‐Antiferromagnetic Magnetic Tunnel Junctions Via Electric‐Field Assisted by Spin–Orbit Torque
Authors: Zink Brandon R. , Zhang Delin , Li Hongshi , Benally Onri J. , Lv Yang , Lyu Deyuan , Wang Jian‐Ping
Published: July 2022

Spintronic devices, especially electric‐field and spin–orbit torque driven magnetic tunnel junctions (MTJs), are promising candidates to replace the current memory and logic components for satisfying future computing demands. Current spin–orbit torque based MTJ devices with a single free layer and spin Hall channel still face high current density for switching. Here, 150‐nm perpendicular MTJs are designed and fabricated with a synthetic‐antiferromagnetic free layer and a bilayered spin Hall channel. The switching behavior is investigated via combination of forces from electric‐field and spin–orbit torque, where the electric field can modulate the exchange coupling of the synthetic‐antiferromagnetic free layer. Through an assistance of spin–orbit torque, bidirectional switching is obtained with switching current density as low as 3 × 103 A cm−2, which is two orders of magnitude lower than that of the current best reported values. These results suggest that electric‐field switching of synthetic‐antiferromagnetic MTJs could be a promising approach for reducing write current density of spintronic devices.
Sputtered Electrolyte‐Gated Transistor with Modulated Metaplasticity Behaviors
Authors: Fu Yang Ming , Li Hu , Huang Long , Wei Tianye , Hidayati Faricha , Song Aimin
Published: July 2022

Electrolyte‐gated transistors have been proposed as promising candidates for neuromorphic applications. Synaptic plasticity behaviors and most recently synaptic metaplasticity or plasticity of plasticity behaviors have been mimicked on electrolyte‐gated transistors. In this work, indium‐gallium‐zinc‐oxide thin‐film transistors gated with sputtered SiO2 electrolytes are fabricated. Both spiking‐width‐dependent and spiking‐height‐dependent metaplasticity behaviors are successfully mimicked. The effects are modulated by the drain voltage bias. A physical model based on the electric‐double‐layer coupling, the RC circuit theory, and the stretched‐exponential diffusion is proposed for the metaplasticity behaviors. The experiment data have been well fitted by the proposed model. Meanwhile, the Bienenstock, Cooper, and Munro learning rule, which describes the threshold‐tunable, spiking‐rate‐dependent plasticity behaviors, is also successfully emulated, providing insight into the synaptic metaplasticity behaviors in electrolyte‐gated synaptic transistors.
Innovative strategies to improve hematopoietic stem cell transplant outcomes in myelofibrosis
Authors: Perram Jacinta , Ross David M. , McLornan Donal , Gowin Krisstina , Kröger Nicolas , Gupta Vikas , Lewis Clinton , Gagelmann Nico , Hamad Nada
Published: July 2022

Myelofibrosis (MF) is a clonal myeloproliferative neoplasm characterized by inflammation, marrow fibrosis, and an inherent risk of blastic transformation. Hematopoietic allogeneic stem cell transplant is the only potentially curative therapy for this disease, however, survival gains observed for other transplant indications over the past two decades have not been realized for MF. The role of transplantation may also evolve with the use of novel targeted agents. The chronic inflammatory state associated with MF necessitates pretransplantation assessment of end‐organ function. Applying the transplant methodology employed for other myeloid disorders to patients with MF fails to acknowledge differences in the underlying disease pathophysiology. Limited understanding of the causes of poor transplant outcomes in this cohort has prevented refinement of transplant eligibility criteria in MF. There is increasing evidence of heterogeneity in molecular disease grade, beyond the clinical manifestations which have traditionally guided transplant timing. Exploring the physiological consequences of disease chronicity unique to MF, acknowledging the heterogeneity in disease grade, and using advanced prognostic models, molecular diagnostics and other organ function diagnostic tools, we present an innovative review of strategies with the potential to improve transplant outcomes in this disease. Larger, prospective studies which consider the impact of molecular‐based disease grade are needed for MF transplantation.
Genomic and biochemical analysis of repeatedly observed variants in DBT in individuals with maple syrup urine disease of Central American ancestry
Authors: Billington Charles J. , Chapman Kimberly A. , Leon Eyby , Meltzer Beatrix W. , Berger Seth I. , Olson Matthew , Figler Robert A. , Hoang Steve A. , Wanxing Cui , Wamhoff Brian R. , Collado M. Sol , Cusmano‐Ozog Kristina
Published: July 2022

Maple syrup urine disease (MSUD) is an intoxication‐type inherited metabolic disorder in which hyperleucinemia leads to brain swelling and death without treatment. MSUD is caused by branched‐chain alpha‐ketoacid dehydrogenase deficiency due to biallelic loss of the protein products from the genes BCKDHA, BCKDHB, or DBT, while a distinct but related condition is caused by loss of DLD. In this case series, eleven individuals with MSUD caused by two pathogenic variants in DBT are presented. All eleven individuals have a deletion of exon 2 (delEx2, NM_001918.3:c.48_171del); six individuals are homozygous and five individuals are compound heterozygous with a novel missense variant (NM_001918.5:c.916 T > C [p.Ser306Pro]) confirmed to be in trans. Western Blot indicates decreased amount of protein product in delEx2;c.916 T > C liver cells and absence of protein product in delEx2 homozygous hepatocytes. Ultrahigh performance liquid chromatography–tandem mass spectrometry demonstrates an accumulation of branched‐chain amino acids and alpha‐ketoacids in explanted hepatocytes. Individuals with these variants have a neonatal‐onset, non‐thiamine‐responsive, classical form of MSUD. Strikingly, the entire cohort is derived from families who immigrated to the Washington, DC, metro area from Honduras or El Salvador suggesting the possibility of a founder effect.
Tuning the Interlayer Interactions of 2D Covalent Organic Frameworks Enables an Ultrastable Platform for Anhydrous Proton Transport
Authors: Jiang Guoxing , Zou Wenwu , Ou Zhaoyuan , Zhang Longhai , Zhang Weifeng , Wang Xiujun , Song Huiyu , Cui Zhiming , Liang Zhenxing , Du Li
Published: July 2022

The development of effective, stable anhydrous proton‐conductive materials is vital but challenging. Covalent organic frameworks (COFs) are promising platforms for ion and molecule conduction owing to their pre‐designable structures and tailor‐made functionalities. However, their poor chemical stability is due to weak interlayer interactions and intrinsic reversibility of linkages. Herein, we present a strategy for enhancing the interlayer interactions of two‐dimensional COFs via importing planar, rigid triazine units into the center of C3‐symmetric monomers. The developed triazine‐core‐based COF (denoted as TPT‐COF) possesses a well‐defined crystalline structure, ordered nanochannels, and prominent porosity. The proton conductivity was ≈10 times those of non‐triazinyl COFs, even reaching up to 1.27×10−2 S cm−1 at 160 °C. Furthermore, the TPT‐COF exhibited structural ultrastability, making it an effective proton transport platform with remarkable conductivity and long‐term durability.
Suppression of SARS‐CoV‐2 Replication with Stabilized and Click‐Chemistry Modified siRNAs
Authors: Traube Franziska R. , Stern Marcel , Tölke Annika J. , Rudelius Martina , Mejías‐Pérez Ernesto , Raddaoui Nada , Kümmerer Beate M. , Douat Céline , Streshnev Filipp , Albanese Manuel , Wratil Paul R. , Gärtner Yasmin V. , Nainytė Milda , Giorgio Grazia , Michalakis Stylianos , Schneider Sabine , Streeck Hendrik , Müller Markus , Keppler Oliver T. , Carell Thomas
Published: July 2022

The emergence of more transmissible or aggressive variants of SARS‐CoV‐2 requires the development of antiviral medication that is quickly adjustable to evolving viral escape mutations. Here we report the synthesis of chemically stabilized small interfering RNA (siRNA) against SARS‐CoV‐2. The siRNA can be further modified with receptor ligands such as peptides using CuI‐catalysed click‐chemistry. We demonstrate that optimized siRNAs can reduce viral loads and virus‐induced cytotoxicity by up to five orders of magnitude in cell lines challenged with SARS‐CoV‐2. Furthermore, we show that an ACE2‐binding peptide‐conjugated siRNA is able to reduce virus replication and virus‐induced apoptosis in 3D mucociliary lung microtissues. The adjustment of the siRNA sequence allows a rapid adaptation of their antiviral activity against different variants of concern. The ability to conjugate the siRNA via click‐chemistry to receptor ligands facilitates the construction of targeted siRNAs for a flexible antiviral defence strategy.
Die Kernresonanzspektren von Pyridin‐Derivaten
Authors: Brügel W.
Published: July 2022

Die Kernresonanzspektren von 154 Pyridinderivaten werden bei 40 und teilweise bei 60 MHz in reiner Form ‐ soweit es sich um Flüssigkeiten handelt ‐ und in Lösung in Dimethylsulfoxyd untersucht. Die Spektren werden dem Spektraltyp gemäß auf chemische Verschiebungswerte und Kopplungskonstanten ausgewertet.

Die Kopplungskonstanten erweisen sich als nur wenig von den Substituenten beeinflußt, mit Ausnahme von starken Elektronendonatoren in 3‐Stellung. In den Werten der chemischen Verschiebung spiegeln sich die Elektronendonator‐ bzw. ‐akzeptoreigenschaften der Substituenten wider, wobei allerdings auch noch Anisotropieeffekte berücksichtigt werden müssen. Eine Sonderstellung nehmen 2‐ bzw. 6‐Hydroxypyridine ein, was auf ihre Pyridon‐Konstitution zurückzuführen ist.
On‐line untargeted metabolomics monitoring of an Escherichia coli succinate fermentation process
Authors: Cortada‐Garcia Joan , Haggarty Jennifer , Moses Tessa , Daly Rónán , Arnold Susan Alison , Burgess Karl
Published: July 2022

The real‐time monitoring of metabolites (RTMet) is instrumental for the industrial production of biobased fermentation products. This study shows the first application of untargeted on‐line metabolomics for the monitoring of undiluted fermentation broth samples taken automatically from a 5 L bioreactor every 5 min via flow injection mass spectrometry. The travel time from the bioreactor to the mass spectrometer was 30 s. Using mass spectrometry allows, on the one hand, the direct monitoring of targeted key process compounds of interest and, on the other hand, provides information on hundreds of additional untargeted compounds without requiring previous calibration data. In this study, this technology was applied in an Escherichia coli succinate fermentation process and 886 different m/z signals were monitored, including key process compounds (glucose, succinate, and pyruvate), potential biomarkers of biomass formation such as (R)‐2,3‐dihydroxy‐isovalerate and (R)‐2,3‐dihydroxy‐3‐methylpentanoate and compounds from the pentose phosphate pathway and nucleotide metabolism, among others. The main advantage of the RTMet technology is that it allows the monitoring of hundreds of signals without the requirement of developing partial least squares regression models, making it a perfect tool for bioprocess monitoring and for testing many different strains and process conditions for bioprocess development.
“I wasn’t feeling like I belonged in my skin”: How self‐identified gay men in theUKexperience unhelpful incidents in talking therapy1
Authors: Televantos Mike , Strauss Susan Maise
Published: July 2022

Background

Contemporary psychological research and practice in Western Societies oppose pathologising perspectives about same‐sex attraction. Nonetheless, recent research indicates gay men may still experience unhelpful incidents in talking therapy in relation to their sexual/affectional orientation. Research focusing on how self‐identified gay men (SIGM) experience these unhelpful incidents, however, remains sparse.

Aim

The objective of the present study is to offer insight into the phenomenon of unhelpful experiences of SIGM clients in relation to their sexual/affectional orientation.

Method

The data were collected through individual, semi‐structured interviews of six SIGM (aged 25–57), describing how they currently experience these unhelpful incidents. This study employed Interpretative Phenomenological Analysis (IPA) to capture the lived experiences and sense‐making of the participants.

Findings

The following three Master Themes were identified: (1) Making Sense of Disconnection, (2) A Rejecting Therapy for a Gay Individual, and (3) Understanding the Impact of Unhelpful Incidents Outside Therapy. The unhelpful experiences of SIGM clients appeared to be largely coloured by the sense of disconnection they felt from their therapists. These followed an experience of therapy that they felt did not acknowledge or embrace their individual gay identity. Participants relayed how these experiences impacted their lives outside therapy. Despite the significant and lasting negative impact, however, all imparted a sense of managing to move on to some extent.

Conclusions

The present research could encourage therapists and researchers to continue pursuing and embracing helpful ways of working therapeutically with SIGM and other sexual, gender and intersecting identities.
Research on occlusion block face recognition based on feature point location
Authors: Shi Jianguo , Xiu Yu , Tang Ganyi
Published: July 2022

Aiming at improving the poor face recognition accuracy under occlusion, a multipose block occlusion face recognition method based on feature point location is proposed. Face segmentation is carried out according to the location results of face feature points and occlusion areas. The local features of each face block are extracted by deep convolution neural network. The dynamic adaptive weighting method is used to give different weights to the face block information, and the occluded face recognition is completed according to the results of face segmentation, which effectively reduces the impact of pose change and occlusion on face recognition. The experiment is analyzed from two aspects: frontal occlusion and multipose face occlusion. The results show that fewer blocks in the frontal occlusion experiment are conducive to maintaining good local integrity and relatively good recognition performance; When the proportion of frontal occlusion reaches 50%, the recognition rate of our algorithm can still be up to 92.68%, which is significantly better than other algorithms.
OVS‐Net: An effective feature extraction network for optical coherence tomography angiography vessel segmentation
Authors: Zhu Chengzhang , Wang Han , Xiao Yalong , Dai Yulan , Liu Zixi , Zou Beiji
Published: July 2022

Optical coherence tomography angiography (OCTA), as a noninvasive imaging modality, has been widely used in clinical ophthalmology. However, the segmentation of retinal vessels in OCTA is under‐studied due to OCTA is a relatively new technology. In this article, an effective feature extraction network, OVS‐Net, is proposed for OCTA vessel segmentation. The OVS‐Net is divided into coarse stage and refine stage which structures are basically the same. In each stage, we utilize OctaveResBlock as the basic block to better extract the hierarchical multifrequency features of OCTA and capture the multiscale semantic features of the vessels. In order to improve the feature characterization, feature enhanced attention block is introduced into the network, which is proved to be more conducive for microvessel segmentation in our experiments. Multiscale feature blocks are introduced into the network to promote the deep integration of semantic features at different scales. Experiments on OCTA‐SS and OCTA‐500 datasets show that our proposed OVS‐Net achieves more competitive segmentation results than the existing methods, especially for microvessel segmentation.
Low‐grade serous carcinoma detected from intraoperative peritoneal washings: Cytological findings and detection of KRAS mutation
Authors: Yamamoto Eriko , Warigaya Kenji , Kinoshita Yuichi , Yamamoto Ayana , Murata Shin‐ichi
Published: July 2022

Background

Low‐grade serous carcinoma (LGSC) of the ovary, which is extremely rare tumor, has better prognosis than high‐grade serous carcinoma (HGSC). Genetic backgrounds of those are different, so that LGSC usually shows KRAS or BRAF mutation, whereas HGSC does not show such mutations. Since treatment strategies of those are different, differential pathological diagnosis between LGSC and HGSC is very important.

Case

We report a case of LGSC that was diagnosed by both cytological findings and genetic analysis using small amount cells from cytological specimen. The 30‐year‐old Japanese woman with bilateral ovarian tumors underwent salpingo‐oopherectomy. The peritoneal washing cytologic specimen and touched cytologic specimen from the tumor included non‐complex clusters with psammoma bodies composed of tumor cells with mild to moderate atypia and without bizarre nuclei. The ovarian tumor was histologically diagnosed as LGSC. The genetic analysis that was done using exfoliated cells from peritoneal washings specimen by idensy™, detected KRAS mutation at codon 12/13.

Conclusion

The genetic investigation using cytological specimen as well as characteristic cytological findings were useful to make differential diagnosis between LGSC and HGSC.
Sowing date affects soybean biological nitrogen fixation
Authors: Barat‐Carnino Mercedes , Santachiara Gabriel A. , Borras Lucas , Rotundo Jose L.
Published: July 2022

In many temperate soybean [Glycine max (L.) Merr.] production systems sowing date expands for several months. Early sowing dates commonly show maximum yields, but their consequences for crop N uptake and biological nitrogen fixation (BNF) are unknown. Our objective was to evaluate the role of sowing date, a major management variable defining soybean yield, on BNF. We hypothesized BNF is maximum at intermediate sowings because BNF is limited by low soil temperatures at early sowing dates and by high soil nitrate concentrations at later sowings. Four genotypes (maturity groups [MGs] IV and V) were tested over a 16‐wk sowing date period, and a N fertilizer treatment at sowing was added in all sowing date by genotype combinations (0 and 100 kg N ha–1). The N fertilization treatment helped to test sowing date effects independently of soil N availability. Seed yield and total N uptake were affected by sowing date and genotype, but not by the N treatment. Both seed yield and total N uptake followed similar quadratic responses, but MG V genotypes maximized yield and N uptake at the earliest sowing while MG IV cultivars maximized both traits at intermediate sowings. However, delaying sowing date always decreased the proportion of total aboveground N that came from BNF (average decline 0.22% d–1). Nitrogen fertilization reduced BNF by 15% across sowing dates and genotypes, with no yield effect. The linear decline in BNF with delayed sowing dates, instead of an optimum response, supports the concept that soil nitrates are the main driver of soybean BNF in this production system.
Inflammasome activation: from molecular mechanisms to autoinflammation
Authors: Lara‐Reyna Samuel , Caseley Emily A , Topping Joanne , Rodrigues François , Jimenez Macias Jorge , Lawler Sean E , McDermott Michael F
Published: July 2022

Inflammasomes are assembled by innate immune sensors that cells employ to detect a range of danger signals and respond with pro‐inflammatory signalling. Inflammasomes activate inflammatory caspases, which trigger a cascade of molecular events with the potential to compromise cellular integrity and release the IL‐1β and IL‐18 pro‐inflammatory cytokines. Several molecular mechanisms, working in concert, ensure that inflammasome activation is tightly regulated; these include NLRP3 post‐translational modifications, ubiquitination and phosphorylation, as well as single‐domain proteins that competitively bind to key inflammasome components, such as the CARD‐only proteins (COPs) and PYD‐only proteins (POPs). These diverse regulatory systems ensure that a suitable level of inflammation is initiated to counteract any cellular insult, while simultaneously preserving tissue architecture. When inflammasomes are aberrantly activated can drive excessive production of pro‐inflammatory cytokines and cell death, leading to tissue damage. In several autoinflammatory conditions, inflammasomes are aberrantly activated with subsequent development of clinical features that reflect the degree of underlying tissue and organ damage. Several of the resulting disease complications may be successfully controlled by anti‐inflammatory drugs and/or specific cytokine inhibitors, in addition to more recently developed small‐molecule inhibitors. In this review, we will explore the molecular processes underlying the activation of several inflammasomes and highlight their role during health and disease. We also describe the detrimental effects of these inflammasome complexes, in some pathological conditions, and review current therapeutic approaches as well as future prospective treatments.
Monocyte biomarkers define sargramostim treatment outcomes for Parkinson's disease
Authors: Abdelmoaty Mai M. , Machhi Jatin , Yeapuri Pravin , Shahjin Farah , Kumar Vikas , Olson Katherine E. , Mosley R. Lee , Gendelman Howard E.
Published: July 2022

Background

Dysregulation of innate and adaptive immunity heralds both the development and progression of Parkinson's disease (PD). Deficits in innate immunity in PD are defined by impairments in monocyte activation, function, and pro‐inflammatory secretory factors. Each influences disease pathobiology.

Methods and Results

To define monocyte biomarkers associated with immune transformative therapy for PD, changes in gene and protein expression were evaluated before and during treatment with recombinant human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF, sargramostim, Leukine®). Monocytes were recovered after leukapheresis and isolation by centrifugal elutriation, before and 2 and 6 months after initiation of treatment. Transcriptome and proteome biomarkers were scored against clinical motor functions. Pathway enrichments from single cell‐RNA sequencing and proteomic analyses from sargramostim‐treated PD patients demonstrate a neuroprotective signature, including, but not limited to, antioxidant, anti‐inflammatory, and autophagy genes and proteins (LRRK2, HMOX1, TLR2, TLR8, RELA, ATG7, and GABARAPL2).

Conclusions

This monocyte profile provides an “early” and unique biomarker strategy to track clinical immune‐based interventions, but requiring validation in larger case studies.
Patient‐derived renal cell carcinoma organoids for personalized cancer therapy
Authors: Li Zhichao , Xu Haibo , Yu Lei , Wang Jia , Meng Qian , Mei Hongbing , Cai Zhiming , Chen Wei , Huang Weiren
Published: July 2022

Background

Kidney cancer is one of the most common solid tumors. The advancement of human kidney cancer research and treatment has been hindered by a lack of research models that faithfully recapitulate the diversity of the disease.

Methods

We established an effective three‐dimensional culture system for generating kidney cancer organoids from clinical renal cell carcinoma samples. Renal cell carcinoma (RCC) organoids were characterized by H&E staining, immunofluorescence, whole‐exome sequencing, RNA sequencing and single‐cell RNA sequencing. The use of RCC organoids in personalized cancer therapy was assessed by testing their responses to treatment drugs and chimeric antigen receptor T cells.

Results

Using this organoid culture system, 33 kidney cancer organoid lines from common kidney cancer subtypes, including clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), and chromophobe renal cell carcinoma (chRCC), were generated. RCC organoids preserved the histological architectures, mutational landscapes, and transcriptional profile of the parental tumor tissues. Single‐cell RNA‐sequencing revealed inter‐ and intra‐tumoral heterogeneity in RCC organoids. RCC organoids allowed for in vitro drug screening and provided a tool for assessing the efficacy of chimeric antigen receptor T cells.

Conclusions

Patient‐derived RCC organoids are valuable pre‐clinical models for academic research and personalized medicine.
Privacy Risks in Microbiome Research: Public Perspectives before and during a Global Pandemic
Authors: Shin Andrea , Xu Huiping
Published: July 2022

We assessed public perspectives of microbiome research privacy risks before and after a nationwide emergency was declared in the United States regarding the Covid‐19 pandemic. From January to July of 2020, we conducted an online survey of perceived privacy risks of microbiome research among U.S. adults. Among 3,106 participants (the preemergency group), most expressed that the microbiome posed privacy risks similar to those associated with DNA (60.3%) or medical records (50.6%) and that they would prefer detailed explanations (70.2%) of risk in consent materials. Only 8.9% reported moderate to high familiarity with microbiome privacy risks. In adjusted analyses, individuals who participated in the study after the Covid‐19 emergency was declared (the Covid‐19 emergency group) were less likely to express that microbiome privacy risks were similar to those of DNA or medical records and more likely to report familiarity with the privacy risks of microbiomes. There was a trend toward increased concern after the Covid‐19 emergency was declared (p = 0.053). Overall, the study revealed that many U.S. adults believe that microbiome privacy risks are similar to those associated with DNA or medical records, and they prefer detailed explanations in consent documents. Individuals who participated after the Covid‐19 emergency was declared reported greater knowledge of microbiome privacy risks but had more concern.
Urban biotic homogenization: Approaches and knowledge gaps
Authors: Lokatis Sophie , Jeschke Jonathan M.
Published: July 2022

Urbanization is restructuring ecosystems at an unprecedented pace, with complex and profound consequences for life on Earth. One of the hypothesized trajectories of urban ecosystems and species communities is biotic homogenization, possibly leading to very similar species assemblages in cities across the globe. Urbanization can, however, also have the opposite effect: biotic diversification, with cities, at least at the local scale, becoming biologically more diverse, mainly as a consequence of high species introduction rates and habitat diversification. Applying the hierarchy‐of‐hypotheses approach, we systematically map and structure the comprehensive body of literature on the urban biotic homogenization (UBH) hypothesis, comprising 225 individual studies (i.e., tests of the hypothesis) retrieved from 145 publications. The UBH hypothesis is studied at multiple levels with a multitude of approaches and underlying assumptions. We show that UBH is generally used with two very different connotations: about half of the studies investigated a potential increase in community similarity across cities, whereas the other half investigated biotic homogenization within cities, the latter being supported more frequently. We also found strong research biases: (1) a taxonomic bias towards birds and plants, (2) a bias towards small and medium distances (<5000 km) in comparisons across cities, (3) a dominance of studies substituting space for time versus true temporal studies, (4) a strong focus on terrestrial versus aquatic systems, (5) more extraurban (including periurban) areas than natural or rural ecosystems for comparison to urban systems, (6) a bias towards taxonomic versus functional, phylogenetic, and temporal homogenization, and (7) more studies undertaken in Europe and North America than in other continents. The overall level of empirical support for the UBH hypothesis was mixed, with 55% of the studies reporting supporting evidence. Results significantly differed when a natural/nature reserve, an extraurban, or rural/agricultural area served as reference to infer biotic homogenization, with homogenization being detected least frequently when urban systems were compared to agricultural, i.e., other anthropogenically influenced, study sites. We provide an evidence map and a bibliographic network and identify key references on UBH with the goal to enhance accessibility and orientation for future research on this topic.
Defining, estimating, and understanding the fundamental niches of complex animals in heterogeneous environments
Authors: Matthiopoulos Jason
Published: July 2022

During the past century, the fundamental niche, the complete set of environments that allow an individual, population, or species to persist, has shaped ecological thinking. It is a crucial concept connecting population dynamics, spatial ecology, and evolutionary theory, and a prerequisite for predictive ecological models at a time of rapid environmental change. Yet, its properties have eluded quantification, particularly for mobile, cognitively complex organisms. These difficulties are mainly a result of the separation between niche theory and field data, and the dichotomy between environmental and geographical spaces. Here, I combine recent mathematical and statistical results linking habitats to population growth, to achieve a quantitative and intuitive understanding of the fundamental niches of animals. I trace the development of niche ideas from the early steps of ecology to their use in modern statistical and conservation practice. I examine how animal mobility and behavior may blur the division between geographical and environmental space. I discuss how the central models of population and spatial ecology lead to a concise mathematical equation for the fundamental niche of animals and demonstrate how fitness parameters can be understood and directly estimated by fitting this model simultaneously to data on population growth and spatial distributions. I first illustrate these concepts theoretically for territorial species. I then fit the fundamental niche model to a data set of house sparrow colonies to quantify how a species of selective animals can increase their fitness in heterogeneous environments. This work confirms ideas that had been anticipated in the historical niche literature. Specifically, within traditionally defined environmental spaces, habitat heterogeneity and behavioral plasticity make the fundamental niche more complex and malleable than was historically envisaged. However, once examined in higher‐dimensional environmental spaces, accounting for spatial heterogeneity, the niche is more predictable than recently suspected. This re‐evaluation quantifies how organisms might buffer themselves from change by bending the boundaries of viable environmental space and offers a framework for designing optimal habitat interventions to protect biodiversity or obstruct invasive species. It therefore promotes the fundamental niche as a key concept for understanding animal responses to changing environments and a central tool for environmental management.
A Person‐Centred Prehabilitation Program based on Cognitive Behavioural Physical Therapy for patients scheduled for Lumbar Fusion surgery: A mediation analysis to assess fear of movement (kinesiophobia), self‐efficacy and catastrophizing as mediators of health outcomes
Authors: Mansell Gemma , den Hollander Marlies , Lotzke Hanna , Smeets Rob J. E. M. , Lundberg Mari
Published: July 2022

Objective

To investigate whether early changes in fear of movement (kinesiophobia), self‐efficacy and catastrophizing were mediators of the relationship between allocation to the pre‐habilitation intervention and later changes in health outcomes.

Methods

The original pre‐habilitation trial (PREPARE, ISRCTN17115599) recruited 118 participants awaiting lumbar fusion surgery, half of whom received a prehabilitation intervention designed based on the modified fear‐avoidance model and half of whom received usual care. Mediation analysis was performed to test each mediator separately. Analysis was performed on each outcome of interest separately (Oswestry disability index, patient‐specific function, EQ general health and moderate/vigorous physical activity). Mediation analysis was carried out using PROCESS. Beta coefficients and bootstrapped 95% CIs were used to interpret the results.

Results

None of the potential mediators was found to mediate the relationship between allocation to the intervention and 3‐month scores on any of the health outcomes tested.

Conclusions

Screening patients for higher levels of catastrophizing and fear avoidance and lower levels of self‐efficacy could help ensure only the patients who are most likely to benefit from the intervention are included.

Significance

Prehabilitation interventions for spinal fusion surgery have been found to improve health outcomes for patients. Theory‐based interventions that target key mechanisms are more effective at improving outcomes than non‐theory‐based interventions. While no mediating effects were found for this particular intervention, the analysis suggests that the underlying theoretical model and treatment targets are appropriate and could drive improvement if more strongly targeted.
Body composition does not influence conditioned pain modulation and exercise‐induced hyperalgesia in healthy males and females
Authors: Peterson Jessica A. , Lohman Cameron , Larson Rebecca D. , Bemben Michael G. , Black Christopher D.
Published: July 2022

Background

Obese individuals report a higher susceptibility to chronic pain. Females are more likely to have chronic pain and excess adipose tissue. Chronic pain is associated with dysfunctional pain‐modulatory mechanisms. Body composition differences may be associated with pain modulation differences in males and females. The purpose of this study was to investigate body composition (lean vs fat mass) differences and pain‐modulatory functioning in healthy males and females.

Methods

Pressure pain thresholds (PPT) of 96 participants (47 M; 49F) were assessed in both arms and legs before and after a double‐footed ice bath (2°C) for 1 min and an isometric knee extension, time to failure task. The difference between post‐ and pre‐measures was defined as conditioned pain‐modulatory (CPM) response (ice bath) and exercise‐induced hypoalgesia (EIH) response. Whole‐body and site‐specific fat and lean tissue were assessed via the DXA scan.

Results

Sex differences were found in whole‐body lean mass (61.5 ± 6.7 kg vs 41.2 ± 5.4 kg; p < 0.001) but not fat mass amount (17.2 ± 10.5 kg vs 21.0 ± 9.7 kg; p = 0.068). No effect of sex was found between limb CPM (p = 0.237) and limb EIH (p = 0.512). When controlling for lean mass, there was no significant effect of sex on CPM (p = 0.732) or EIH (p = 0.474) response. Similar findings were found for fat mass.

Conclusion

The lack of difference suggests that males and females have similar modulatory functioning. It appears that in healthy adults free from chronic pain, neither fat mass nor lean mass has an influence on endogenous pain‐modulatory function.

Significance

Men and women exhibited similar CPM and EIH despite marked differences in body composition. Our findings suggest whole‐body and limb‐specific lean tissue mass and fat mass do not influence CPM and EIH in adults without chronic pain.
Deciphering the pharmacological mechanisms of Chaenomeles Fructus against rheumatoid arthritis by integrating network pharmacology and experimental validation
Authors: Sun Mengjia , Zhao Haijun , Liu Yuecheng , Ma Yanni , Tian Zhenhua , Wang Huanjun , Wei Sheng , Guo Qingmei , Gu Zhengwei , Jiang Haiqiang
Published: July 2022

Chaenomeles Fructus is a plant that can be used for both food and medicine. Modern studies have shown that Chaenomeles Fructus has anti‐inflammatory and immunosuppressive effects on arthritis. However, the mechanism of action of Chaenomeles Fructus on rheumatoid arthritis (RA) and its main active ingredients are still unclear. This study was aimed at devising an integrated strategy for investigating the bioactivity constituents and possible pharmacological mechanisms of Chaenomeles Fructus against RA. The components of Chaenomeles Fructus were analyzed using UPLC‐Q‐Exactive orbitrap MS techniques and applied to screen the active components of Chaenomeles Fructus according to their oral bioavailability and drug‐likeness index. Then, we speculated on the potential molecular mechanisms of Chaenomeles Fructus against RA through a network pharmacology analysis. Finally, the potential molecular mechanisms of Chaenomeles Fructus against RA were validated in a complete Freund's adjuvant (CFA)‐induced RA rat model. We identified 48 components in Chaenomeles Fructus and screened seven bioactive ingredients. The results of the network pharmacology prediction and the experimental verification results were analyzed by Venn analysis, and the experimental results concluded that Chaenomeles Fructus mainly interferes with the inflammation of RA by inhibiting arachidonic acid metabolism and the MAPK signaling pathway. This study identified the ingredients of Chaenomeles Fructus by UPLC‐Q‐Exactive orbitrap MS and explained the possible mechanisms of Chaenomeles Fructus against RA by integrating network pharmacology and experimental validation.
Performance of the Neck Imaging Reporting and Data System as applied by general neuroradiologists to predict recurrence of head and neck cancers
Authors: Lee Jonathan , Kaht Dagan , Ali Syed , Johnson Scott , Bullen Jennifer , Karakasis Christopher , Lamarre Eric , Geiger Jessica , Koyfman Shlomo , Stock Sarah
Published: July 2022

Background

The Neck Imaging Reporting and Data System (NI‐RADS) is used to assess imaging after head and neck cancer treatment. We evaluated NI‐RADS with general neuroradiologists rather than with head and neck subspecialists.

Methods

Computed tomography and magnetic resonance imaging examinations with/without positron emission tomography from May 2018 to September 2020 were retrospectively identified. NI‐RADS scores at the primary site and lymph nodes were provided by 21 neuroradiologists. Recurrence status was based on clinical and imaging findings. Area under the curve (AUC) was used to assess accuracy.

Results

We assessed 608 scans from 464 patients. For NI‐RADS categories 1, 2, and 3, primary site recurrence rates were 5%, 29%, and 65% with AUC of 0.765, while lymph node recurrence rates were 3%, 10%, and 80% with AUC of 0.820.

Conclusions

NI‐RADS as used by general neuroradiologists is effective in separating head and neck cancers into discrete categories for predicting recurrent disease.
Association of post‐treatment longitudinal symptom severity clusters with subsequent survival in oropharyngeal cancer
Authors: Haddad Ghazal , Hueniken Katrina , Xu Maria Christine , Bratman Scott , de Almeida John , Goldstein David , Huang Shao Hui , Hansen Aaron , Hope Andrew , Spreafico Anna , Xu Wei , Liu Geoffrey
Published: July 2022

Background

Patients with cancer often experience multiple symptoms concurrently. We identified patient clusters based on longitudinal symptom severity trajectories in oropharyngeal cancer (OPC) and evaluated the potential clinical utility of this approach.

Methods

A retrospective OPC patient cluster analysis using 6 months of symptom severity data from radiotherapy initiation. The clinico‐demographic characteristics and overall survival of patients were compared between clusters.

Results

We identified four clusters of patients differing in longitudinal symptom severity. Cluster A (n = 168) included patients with the mildest longitudinal symptoms, cluster B (n = 59) and cluster C (n = 63) were intermediate, and cluster D (n = 30) included patients with the worst symptoms. The clusters differed in their HPV status, ECOG performance status, smoking history, drinking history, treatment modality, and 5‐year survival. These clusters separated symptom severity trajectories more distinctly than individual clinico‐demographic characteristics.

Conclusions

Early symptom severity trajectory clustering revealed distinct patient clusters that were prognostic of overall survival.
A competing risk analysis of adherence to the American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and obesity‐related cancer risk in Hispanic/Latino adults in the NIH‐AARP Diet and Health Study
Authors: Pichardo Margaret S. , Irwin Melinda L. , Esserman Denise , Molina Yamile , Ferrucci Leah M.
Published: July 2022

Incidence of obesity‐related cancers (ORCs) is rising among US Hispanic/Latino adults, which may be partly due to inadequate engagement in healthy lifestyle behaviors. Prior research on cancer prevention guideline adherence and cancer risk has not considered competing events that may lead to misinterpreting the magnitude of risk between guideline adherence and cancer incidence. Among Hispanic/Latino adults (N = 9204) in the NIH‐AARP Diet and Health Study, we examined the association between adherence to the 2012 American Cancer Society (ACS) guidelines (high, moderate, low) on nutrition and physical activity for cancer prevention and risk of any first observed ORC using Fine and Gray methods for competing risk analysis. Over a median of 10.5 years of follow‐up, there were 619 first ORCs. The cumulative risk of ORC over a 15‐year period was not significantly different across ACS guideline adherence categories (high cumulative incidence function [CIF]: 2.2%‐5.8%; moderate CIF: 2.2%‐6.6%; low CIF: 2.3%‐6.7%, PGray's log rank = .690). In competing risk analysis, high (compared to low) adherence to the ACS guidelines was associated with reduced probability of ORC (subdistribution hazard [SHR]: 0.76, 95% CI: 0.58‐0.996, P = .047), with evidence of a linear trend for increasing adherence (Ptrend = .039). Our findings were consistent with hypothesized inverse associations between ACS guideline adherence and ORC incidence accounting for competing risks. These findings suggest a need for continued public health efforts focused on promoting engagement in healthy lifestyle behaviors to reduce ORC incidence among US Hispanic/Latino adults.