bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrient Composition of Phosphorus Enriched Compost from Seafood Processing Unit Waste
Authors: Shenbagavalli S. , Prabu T. , Dhanushkodi V.
Published: June 2023

Seafood is gaining in popularity because of its health benefits. At the same time, large amounts of fish waste are being generated, mostly from the industrial processing of fish. These large quantities of fish waste have not been utilized efficiently, and the disposal of fish waste can have large negative impacts on local environments.  Unutilized fish waste is often disposed of by land fill or incineration, or by dumping into the sea. Therefore, there is an urgent need to find ecologically acceptable means for reutilization of fish waste. In this study, fish waste samples are collected and characterised. The fish waste was acidic in pH (6.1) with EC of 3.8 dSm-1. The total N, P, K of the fish waste was 10.17, 0.20 and 0.74 % respectively. It also had an appreciable amount of organic carbon content 46.22%. Fish waste was mixed with saw dust (2:1) and Rock Phosphate - Phosphorus (RP-P) at the rate of 0, 2.5, 5, 7.5 and 10 % for enrichment of compost The results showed that the application of different levels of (RP-P) reduce the pH, slightly increased the EC, N,P,K and Organic carbon content.  Thus, rock phosphate enriched fish waste compost could be an alternative and viable technology to manage the solid waste generated from the seafood industries as well as crop production.
Diagnosis and Management of Tropomyosin Receptor Kinase Fusion-Positive Thyroid Carcinomas
Authors: Haddad Robert , Elisei Rossella , Hoff Ana O. , Liu Zhiyan , Pitoia Fabian , Pruneri Giancarlo , Sadow Peter M. , Soares Fernando , Turk Andrew , Williams Michelle D. , Wirth Lori J. , Cabanillas Maria E.
Published: June 2023

Importance

Thyroid epithelial malignant neoplasms include differentiated thyroid carcinomas (papillary, follicular, and oncocytic), follicular-derived high-grade thyroid carcinomas, and anaplastic and medullary thyroid carcinomas, with additional rarer subtypes. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions has fostered developments in precision oncology, with the approval of tropomyosin receptor kinase inhibitors (larotrectinib and entrectinib) for patients with solid tumors, including advanced thyroid carcinomas, harboring NTRK gene fusions.

Observations

The relative rarity and diagnostic complexity of NTRK gene fusion events in thyroid carcinoma present several challenges for clinicians, including variable access to robust methodologies for comprehensive NTRK fusion testing and poorly defined algorithms of when to test for such molecular alterations. To address these issues in thyroid carcinoma, 3 consensus meetings of expert oncologists and pathologists were convened to discuss diagnostic challenges and propose a rational diagnostic algorithm. Per the proposed diagnostic algorithm, NTRK gene fusion testing should be considered as part of the initial workup for patients with unresectable, advanced, or high-risk disease as well as following the development of radioiodine-refractory or metastatic disease; testing by DNA or RNA next-generation sequencing is recommended. Detecting the presence of NTRK gene fusions is important to identify patients eligible to receive tropomyosin receptor kinase inhibitor therapy.

Conclusions and Relevance

This review provides practical guidance for optimal integration of gene fusion testing, including NTRK gene fusion testing, to inform the clinical management in patients with thyroid carcinoma.
Socio‐ecological interactions promote outbreaks of a harmful invasive plant in an urban landscape
Authors: Caughlin T. Trevor , Clark Matthew , Jochems Louis W. , Kolarik Nick , Zaiats Andrii , Hall Cody , Winiarski Jason M. , Powers Breanna F. , Brabec Martha M. , Hopping Kelly
Published: June 2023

Urban landscapes often harbour organisms that harm people and threaten native biodiversity. These landscapes are characterized by differences in socioeconomic context, habitat suitability and patch connectedness. Identifying which spatial differences enable outbreaks of pests, pathogens and invasive species will improve targeted control efforts.

We tested hypotheses to explain the distribution and demography of puncturevine Tribulus terrestris, a human‐dispersed invasive plant in Boise, a city in the western United States. We hypothesized an increase in puncturevine infestations near low‐valued properties with a high proportion of bare ground, the species' preferred microhabitat, that are well connected on the urban road network. To test these hypotheses, we collected data on the abundance, emergence and persistence of reproductive plants in transects spanning >100 km of our study city. We then used hierarchical Bayesian models to evaluate the impacts of spatial covariates on puncturevine distribution and demography.

Bare ground cover consistently increased abundance, emergence and persistence of puncturevine, indicating the overarching importance of suitable establishment sites for this invasive species.

Property value had the strongest impact on puncturevine abundance and was the most important main effect in the model for puncturevine emergence. In both models, lower‐valued properties had a higher risk of puncturevine occurrence.

The effects of road network connectivity depended on bare ground cover, with the highest predicted abundance and emergence of puncturevine in patches with low connectivity on the road network and high bare ground cover. Understanding these relationships will require data that can disentangle seed dispersal from establishment limitations.

Identifying characteristics of urban patches that promote outbreaks of harmful species will improve the effectiveness and equity of control efforts. The prevalence of puncturevine in lower‐valued properties is cause for concern as the plant impedes bicycle transportation, with the potential for disproportionate impacts on marginalized groups that lack resources to repair punctured tires. Our results add to a growing recognition that low‐connectivity street networks have undesirable outcomes for environmental sustainability. As urban land cover continues to grow worldwide, accounting for interactions between human, natural and built systems will play a crucial role in managing invasive species.
Same‐Sex Marriage
Authors: Corvino John
Published: June 2023

This entry reviews deontological and consequentialist arguments for and against the social and legal recognition of same‐sex marriage.
Pedophilia
Authors: Benatar David
Published: June 2023

Pedophilia may seem like an odd entry for an encyclopedia on ethics. It is a practice that is seen as clearly wrong, at least in those parts of the world where such an encyclopedia is most likely to be read. However, pedophilia has been widely practiced, both in the past and in some places today. Moreover, while it is taboo in societies that have otherwise liberalized their views of sex, the very view that underlies that liberalization brings the taboo into question. This view and its main rival are presented and considered, after some definitional issues are clarified, and after other objections to pedophilia are discussed.
Consent
Authors: Kleinig John
Published: June 2023

Consent is a communicative act that is generally morally transformative by signifying moral permission or self‐binding. As such, it requires signification and uptake. To be valid, it is presumed that the consenter is competent, knowledgeable, and acts voluntarily and intentionally. In some cases, consent is not sufficient to overcome normative deficits associated with what is consented to.
Multiple Electronic Phase Transitions of NiO via Manipulating the NiO6 Octahedron and Valence Control
Authors: Zhou Xuanchi , Mao Wei , Cui Yuchen , Zhang Hao , Liu Qi , Nie Kaiqi , Xu Xiaoguang , Jiang Yong , Chen Nuofu , Chen Jikun
Published: June 2023

While the multiple Mottronic and electronic phase transitions as recently discovered in nickelates (e.g., ReNiO3) open up a new paradigm in correlated electronic applications, these applications are largely impeded by the intrinsic material metastability of the perovskite nickelates. Herein, the study demonstrates the analogous multiple electronic phase transition properties in the thermodynamically stable NiO, compared to ReNiO3, from both perspectives of band gap regulation and orbital filling regulation. The adjustment in band gap of NiO with t2g6eg2 orbital configuration is achieved via establishing biaxial tensile or compressive interfacial strains that increase or reduce the material resistivity, respectively. The relaxor ferroelectricity of 0.7Pb(Mg2/3Nb1/3)O3‐0.3PbTiO3 (PMNPT) further enables an electric field adjustable resistance switch (ΔR/R) within NiO/PMNPT heterostructure with higher performances (e.g., ΔR/R of 82% upon a bias voltage of 20 V) than the reported oxides/PMNPT heterostructure. Furthermore, the magnitude in resistance switch of the tensile strained NiO via hydrogenation associated Mottronic process reaches ≈1011 that exceeds the previously reported ones. This study highlights the higher material stability and easier growth of NiO, compared to ReNiO3, with analogous multiple Mottronic and electronic phase transition properties that pave the way to its practical applications in correlated electronics.
Acceptor‐Donor‐Acceptor‐Configured Delayed Fluorescence Emitters for Efficient Orange‐Red and White Devices with Low Roll‐off
Authors: He Yi‐Hui , Xie Feng‐Ming , Zhang Kai , Yang Dezhi , Shen Yang , Li Hao‐Ze , Ma Dongge , Li Yan‐Qing , Tang Jian‐Xin
Published: June 2023

Organic light‐emitting diodes (OLEDs) based on thermally activated delayed fluorescence (TADF) materials are promising for the realization of highly efficient emitters. However, severe efficiency roll‐off at high brightness still remains as a huge challenge for TADF‐based OLEDs. Herein, rod‐like orange‐red TADF emitters of 2BNCz‐PZ and 2BNtCz‐PZ with acceptor‐donor‐acceptor (A‐D‐A) configuration are developed by bearing dihydrophenazine donor and discoidal rigid boron, nitrogen‐contained polycyclic aromatic hydrocarbons acceptors. Both emitters exhibit hybrid long‐range/short‐range charge‐transfer excitation for small singlet‐triplet energy splitting, short delayed lifetime, and high photoluminescence quantum yield, leading to fast singlet radiation rate over 107 s−1 and fast reverse intersystem crossing rate over 106 s−1. Furthermore, a horizontal emitting dipole orientation factor over 90% is realized. The optimized orange‐red OLED based on 2BNtCz‐PZ presents a maximum external quantum efficiency (EQE) of 31.0% and a slight EQE roll‐off to 22.2% at 1 000 cd m−2 with emission peak over 600 nm. In addition, the single‐emitting layer white OLEDs achieve a maximum EQE of 30.6% due to the use of these orange‐red dopants with intense charge‐transfer absorption band. This work reveals the potential of the rod‐like A‐D‐A configuration for constructing highly efficient orange‐red TADF emitters with low‐efficiency roll‐off.
Lifelike Transformative Materials for Biohybrid Implants: Inspired by Nature, Driven by Technology
Authors: Fernández‐Colino Alicia , Kiessling Fabian , Slabu Ioana , De Laporte Laura , Akhyari Payam , Nagel Saskia K. , Stingl Julia , Reese Stefanie , Jockenhoevel Stefan
Published: June 2023

Today's living world is enriched with a myriad of natural biological designs, shaped by billions of years of evolution. Unraveling the construction rules of living organisms offers the potential to create new materials and systems for biomedicine. From the close examination of living organisms, several concepts emerge: hierarchy, pattern repetition, adaptation, and irreducible complexity. All these aspects must be tackled to develop transformative materials with lifelike behavior. This perspective article highlights recent progress in the development of transformative biohybrid systems for applications in the fields of tissue regeneration and biomedicine. Advances in computational simulations and data‐driven predictions are also discussed. These tools enable the virtual high‐throughput screening of implant design and performance before committing to fabrication, thus reducing the development time and cost of biomimetic and biohybrid constructs. The ongoing progress of imaging methods also constitutes an essential part of this matter in order to validate the computation models and enable longitudinal monitoring. Finally, the current challenges of lifelike biohybrid materials, including reproducibility, ethical considerations, and translation, are discussed. Advances in the development of lifelike materials will open new biomedical horizons, where perhaps what is currently envisioned as science fiction will become a science‐driven reality in the future.
Dry‐Transferable Photoresist Enabled Reliable Conformal Patterning for Ultrathin Flexible Electronics
Authors: Chen Lei , Liu Peng , Feng Bo , Shu Zhiwen , Liang Huikang , Chen Yiqin , Dong Xiaoqian , Xie Jianfei , Duan Huigao
Published: June 2023

Photolithographic techniques, which are widely used in the silicon‐based semiconductor industry, enable the manufacture of high‐yield and high‐resolution features at the micrometer and nanometer scales. However, conventional photolithographic processes cannot accommodate the micro/nanofabrication of flexible and stretchable electronics. In this study, a microfabrication approach that uses a synthesized, environmentally friendly, and dry‐transferable photoresist to enable the reliable conformal manufacturing of thin‐film electronics is reported, which is also compatible with the existing cleanroom processes. Photoresists with high‐resolution, high‐density, and multiscale patterns can be transferred onto various substrates in a defect‐free and conformal‐contact manner, thus enabling multiple wafer reuses. Theoretical studies are conducted to investigate the damage‐free peel‐off mechanism of the proposed approach. The in situ fabrication of various electrical components, including ultralight and ultrathin biopotential electrodes, has been demonstrated, which offer lower interfacial impedance, durability, and stability, and the components are applied to collect electromyography signals with superior signal‐to‐noise ratio (SNR) and quality. Additionally, an exemplary demonstration of a human‐machine interface indicates the potential of these electrodes in many emerging applications, including healthcare, sensing, and artificial intelligence.
Rational Design of Highly Efficient Orange‐Red/Red Thermally Activated Delayed Fluorescence Emitters with Submicrosecond Emission Lifetimes
Authors: Hu Jia‐Xuan , Jiang Shanshan , Zhang Dong‐Hai , Zhao Tianxiang , Lin Fu‐Lin , Meng Lingyi , Chen Xu‐Lin , Lu Can‐Zhong
Published: June 2023

The development of orange‐red/red thermally activated delayed fluorescence (TADF) materials with both high emission efficiencies and short lifetimes is highly desirable for electroluminescence (EL) applications, but remains a formidable challenge owing to the strict molecular design principles. Herein, two new orange‐red/red TADF emitters, namely AC‐PCNCF3 and TAC‐PCNCF3, composed of pyridine‐3,5‐dicarbonitrile‐derived electron‐acceptor (PCNCF3) and acridine electron‐donors (AC/TAC) are developed. These emitters in doped films exhibit excellent photophysical properties, including high photoluminescence quantum yields of up to 0.91, tiny singlet‐triplet energy gaps of 0.01 eV, and ultrashort TADF lifetimes of less than 1 µs. The TADF‐organic light‐emitting diodes employing the AC‐PCNCF3 as emitter achieve orange‐red and red EL with high external quantum efficiencies of up to 25.0% and nearly 20% at doping concentrations of 5 and 40 wt%, respectively, both accompanied by well‐suppressed efficiency roll‐offs. This work provides an efficient molecular design strategy for developing high‐performance red TADF materials.
MSL1 Promotes Liver Regeneration by Driving Phase Separation of STAT3 and Histone H4 and Enhancing Their Acetylation
Authors: He Yucheng , Wang Shichao , Liu Shenghui , Qin Dan , Liu Zhangmei , Wang Liqiang , Chen Xiangmei , Zhang Lisheng
Published: June 2023

Male‐specific lethal 1 (MSL1) is critical for the formation of MSL histone acetyltransferase complex which acetylates histone H4 Lys16 (H4K16ac) to activate gene expression. However, the role of MSL1 in liver regeneration is poorly understood. Here, this work identifies MSL1 as a key regulator of STAT3 and histone H4 (H4) in hepatocytes. MSL1 forms condensates with STAT3 or H4 through liquid–liquid phase separation to enrich acetyl‐coenzyme A (Ac‐CoA), and Ac‐CoA in turn enhances MSL1 condensate formation, synergetically promoting the acetylation of STAT3 K685 and H4K16, thus stimulating liver regeneration after partial hepatectomy (PH). Additionally, increasing Ac‐CoA level can enhance STAT3 and H4 acetylation, thus promoting liver regeneration in aged mice. The results demonstrate that MSL1 condensate‐mediated STAT3 and H4 acetylation play an important role in liver regeneration. Thus, promoting the phase separation of MSL1 and increasing Ac‐CoA level may be a novel therapeutic strategy for acute liver diseases and transplantation.
Single Atom Iron‐Doped Graphic‐Phase C3N4 Semiconductor Nanosheets for Augmented Sonodynamic Melanoma Therapy Synergy with Endowed Chemodynamic Effect
Authors: Feng Guiying , Huang Hui , Zhang Min , Wu Zhuole , Sun Dandan , Chen Qiqing , Yang Dayan , Zheng Yuanyi , Chen Yu , Jing Xiangxiang
Published: June 2023

Sonodynamic therapy (SDT) is a non‐invasive therapeutic modality with high tissue‐penetration depth to induce reactive oxygen species (ROS) generation for tumor treatment. However, the clinical translation of SDT is restricted seriously by the lack of high‐performance sonosensitizers. Herein, the distinct single atom iron (Fe)‐doped graphitic‐phase carbon nitride (C3N4) semiconductor nanosheets (Fe‐C3N4 NSs) are designed and engineered as chemoreactive sonosensitizers to effectively separate the electrons (e−) and holes (h+) pairs, achieving high yields of ROS generation against melanoma upon ultrasound (US) activation. Especially, the single atom Fe doping not only substantially elevates the separation efficiency of the e−‐h+ pairs involved in SDT, but also can serve as high‐performance peroxidase mimetic enzyme to catalyze the Fenton reaction for generating abundant hydroxyl radicals, therefore synergistically augmenting the curative effect mediated by SDT. As verified by density functional theory simulation, the doping of Fe atom significantly promotes the charge redistribution in the C3N4‐based NSs, which improves their synergistic SDT/chemodynamic activities. Both the in vitro and in vivo assays demonstrate that Fe‐C3N4 NSs feature an outstanding antitumor effect by aggrandizing the sono‐chemodynamic effect. This work illustrates a unique single‐atom doping strategy for ameliorating the sonosensitizers, and also effectively expands the innovative anticancer‐therapeutic applications of semiconductor‐based inorganic sonosensitizers.
Spotlighting racism in schools: Teacher mentors and the mediating effect of school safety
Authors: Flitner Anna , McQuillin Samuel , Kornbluh Mariah , Thompson Daria
Published: June 2023

Youth are more likely to succeed when they feel safe at school and have access to caring relationships with adults. Systemic racism interrupts access to these assets. Within schools, racially/ethnically minoritized youth encounter policies rooted in racism, leading to decreased perceptions of school safety. Having a teacher mentor may mitigate some of the harmful effects of systemic racism and discriminatory practices. Yet, teacher mentors may not be accessible to all students. In this study, the authors tested a putative explanatory hypothesis for differences between Black and white children's access to teacher mentors. Data from the National Longitudinal Study of Adolescent Health were used. Linear regression models were used to predict access to teacher mentors, and a mediational analysis was conducted to determine the effect of school safety on the relationship between race and teacher mentor access. Results indicate that students from higher SES backgrounds and those with parents who have greater educational attainment are more likely to have a teacher mentor. Furthermore, Black students are less likely than white students to have a teacher mentor, and school safety mediates that relationship. The implications of this study suggest that challenging institutional racism and structures may improve perceptions of school safety and teacher mentor accessibility.
Myelodysplastic syndromes: 2023 update on diagnosis, risk‐stratification, and management
Authors: Garcia‐Manero Guillermo
Published: June 2023

Disease overview

The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy.

Diagnosis

Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry, and molecular genetics is usually complementary and may help refine diagnosis. A new WHO classification of MDS was proposed in 2022. Under this classification, MDS is now termed myelodysplastic neoplasms.

Risk‐stratification

Prognosis of patients with MDS can be calculated using a number of scoring systems. All these scoring systems include analysis of peripheral cytopenias, percentage of blasts in the bone marrow, and cytogenetic characteristics. The most commonly accepted system is the Revised International Prognostic Scoring System (IPSS‐R). Recently, genomic data has been incorporated resulting in the new IPSS‐M classification.

Risk‐adapted therapy

Therapy is selected based on risk, transfusion needs, percent of bone marrow blasts, cytogenetic and mutational profiles, comorbidities, potential for allogeneic stem cell transplantation (alloSCT), and prior exposure to hypomethylating agents (HMA). Goals of therapy are different in lower risk patients than in higher risk and in those with HMA failure. In lower risk, the goal is to decrease transfusion needs and transformation to higher risk disease or AML, as well as to improve survival. In higher risk, the goal is to prolong survival. In 2020, two agents were approved in the US for patients with MDS: luspatercept and oral decitabine/cedazuridine. In addition, currently other available therapies include growth factors, lenalidomide, HMAs, intensive chemotherapy, and alloSCT. A number of phase 3 combinations studies have been completed or are ongoing at the time of this report. At the present time there are no approved interventions for patients with progressive or refractory disease particularly after HMA based therapy. In 2021, several reports indicated improved outcomes with alloSCT in MDS as well as early results from clinical trials using targeted intervention.
Oculoauriculofrontonasal syndrome: Refining the phenotype through a new case series and literature review
Authors: Serigatto Henrique Regonaschi , Kokitsu‐Nakata Nancy Mizue , Vendramini‐Pittoli Siulan , Tonello Cristiano , Moura Priscila Padilha , Peixoto Adriano Porto , Gomes Luiz Paulo , Zechi‐Ceide Roseli Maria
Published: June 2023

The oculoauriculofrontonasal syndrome (OAFNS) is a rare condition, with unknown etiology, characterized by the association of frontonasal dysplasia (FND) and oculoauriculovertebral spectrum (OAVS). Main clinical findings include widely spaced eyes, epibulbar dermoid, broad nose, mandibular hypoplasia, and preauricular tags. Here, we describe a case series of 32 Brazilian individuals with OAFNS and review the literature ascertaining individuals presenting phenotypes compatible with the diagnosis of OAFNS, aiming to refine the phenotype. This series emphasizes the phenotypic variability of the OAFNS and highlights the occurrence of rare craniofacial clefts as a part of the phenotype. The ectopic nasal bone, a hallmark of OAFNS, was frequent in our series, reinforcing the clinical diagnosis. The absence of recurrence, consanguinity, chromosomal, and genetic abnormalities reinforces the hypothesis of a nontraditional inheritance model. The phenotypic refinement provided by this series contributes to an investigation regarding the etiology of OAFNS.
Childhood adversity during the post‐apartheid transition and COVID‐19 stress independently predict adult PTSD risk in urban South Africa: A biocultural analysis of the stress sensitization hypothesis
Authors: Kim Andrew Wooyoung , Said Mohamed Rihlat , Norris Shane A. , Naicker Sara , Richter Linda M. , Kuzawa Christopher W.
Published: June 2023

Objectives

The COVID‐19 pandemic in South Africa introduced new societal adversities and mental health threats in a country where one in three individuals are expected to develop a psychiatric condition sometime in their life. Scientists have suggested that psychosocial stress and trauma during childhood may increase one's vulnerability to the mental health consequences of future stressors—a process known as stress sensitization. This prospective analysis assessed whether childhood adversity experienced among South African children across the first 18 years of life, coinciding with the post‐apartheid transition, exacerbates the mental health impacts of psychosocial stress experienced during the 2019 coronavirus (COVID‐19) pandemic (ca. 2020–2021).

Materials and Methods

Data came from 88 adults who participated in a follow‐up study of a longitudinal birth cohort study in Soweto, South Africa. Childhood adversity and COVID‐19 psychosocial stress were assessed as primary predictors of adult PTSD risk, and an interaction term between childhood adversity and COVID‐19 stress was calculated to evaluate the potential effect of stress sensitization.

Results

Fifty‐six percent of adults exhibited moderate‐to‐severe PTSD symptoms. Greater childhood adversity and higher COVID‐19 psychosocial stress independently predicted worse post‐traumatic stress disorder symptoms in adults. Adults who reported greater childhood adversity exhibited non‐significantly worse PTSD symptoms from COVID‐19 psychosocial stress.

Discussion

These results highlight the deleterious mental health effects of both childhood trauma and COVID‐19 psychosocial stress in our sample and emphasize the need for greater and more accessible mental health support as the pandemic progresses in South Africa.
Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer's disease
Authors: Lathe Richard , Schultek Nikki M. , Balin Brian J. , Ehrlich Garth D. , Auber Lavinia Alberi , Perry George , Breitschwerdt Edward B. , Corry David B. , Doty Richard L. , Rissman Robert A. , Nara Peter L. , Itzhaki Ruth , Eimer William A. , Tanzi Rudolph E. ,   the Intracell Research Group Consortium Collaborators
Published: June 2023

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes inpost mortembrains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will be evaluated, in addition to direct microbial culture and metabolomic techniques. The goal is to provide a roadmap for detecting infectious agents in patients with mild cognitive impairment or AD. Positive findings would then prompt tailoring of antimicrobial treatments that might attenuate or remit mounting clinical deficits in a subset of patients.
Network Localization of Awareness in Visual and Motor Anosognosia
Authors: Kletenik Isaiah , Gaudet Kyla , Prasad Sashank , Cohen Alexander L. , Fox Michael D.
Published: June 2023

Objective

Unawareness of a deficit, anosognosia, can occur for visual or motor deficits and lends insight into awareness itself; however, lesions associated with anosognosia occur in many different brain locations.

Methods

We analyzed 267 lesion locations associated with either vision loss (with and without awareness) or weakness (with and without awareness). The network of brain regions connected to each lesion location was computed using resting‐state functional connectivity from 1,000 healthy subjects. Both domain specific and cross‐modal associations with awareness were identified.

Results

The domain‐specific network for visual anosognosia demonstrated connectivity to visual association cortex and posterior cingulate while motor anosognosia was defined by insula, supplementary motor area, and anterior cingulate connectivity. A cross‐modal anosognosia network was defined by connectivity to the hippocampus and precuneus (false discovery rate p < 0.05).

Interpretation

Our results identify distinct network connections associated with visual and motor anosognosia and a shared, cross‐modal network for awareness of deficits centered on memory‐related brain structures. ANN NEUROL 2023;94:434–441
Highly Twisted Thermally Activated Delayed Fluorescence (TADF) Molecules and Their Applications in Organic Light‐Emitting Diodes (OLEDs)
Authors: Zhang Tiantian , Xiao Yuxin , Wang Hailan , Kong Shuting , Huang Rongjuan , Ka‐Man Au Vonika , Yu Tao , Huang Wei
Published: June 2023

Thermally activated delayed fluorescence (TADF) materials have attracted great potential in the field of organic light‐emitting diodes (OLEDs). Among thousands of TADF materials, highly twisted TADF emitters have become a hotspot in recent years. Compared with traditional TADF materials, highly twisted TADF emitters tend to show multi‐channel charge‐transfer characters and form rigid molecular structures. This is advantageous for TADF materials, as non‐radiative decay processes can be suppressed to facilitate efficient exciton utilization. Accordingly, OLEDs with excellent device performances have also been reported. In this Review, we have summarized recent progress in highly twisted TADF materials and related devices, and give an overview of the molecular design strategies, photophysical studies, and the performances of OLED devices. In addition, the challenges and perspectives of highly twisted TADF molecules and the related OLEDs are also discussed.
Association of Interosseous Tendon Inflammation in the Hand With Different Early Arthritides in a 10‐Year Magnetic Resonance Imaging Study
Authors: van Dijk Bastiaan T. , Reijnierse Monique , van der Helm‐van Mil Annette H. M.
Published: June 2023

Objective

Inflammation around the tendons of the hand interosseous muscles (interosseous tendon inflammation [ITI]) was recently identified on magnetic resonance imaging (MRI) in a set of patients with rheumatoid arthritis (RA) and arthralgia. We conducted a large MRI study to assess the prevalence of ITI at diagnosis of RA and of other arthritides, as well as its relationship with clinical signs.

Methods

A total of 1,205 patients presenting with various types of early arthritis between 2010 and 2020 underwent contrast‐enhanced hand MRI as part of the prospective Leiden Early Arthritis Cohort. MRI was evaluated with blinding for clinical data, for ITI lateral of metacarpophalangeal (MCP) joints 2–5, and for synovitis/tenosynovitis/osteitis. We assessed ITI presence at baseline per diagnosis and its relationship with clinical characteristics (ie, presence of hand arthritis, increased acute phase reactants, and local joint swelling and tenderness). Logistic regression and generalized estimating equations were used with adjustment for age and established local inflammation features (synovitis/tenosynovitis/osteitis).

Results

A total of 36% of patients with early RA (n = 532) had ITI; this was similar in patients with anti–citrullinated protein antibody (ACPA)‐negative RA (37%) and those with ACPA‐positive RA (34%; P = 0.53). ITI occurred regularly in remitting seronegative symmetrical synovitis with pitting edema (60%) and connective tissue diseases (44%) and less frequently in undifferentiated arthritis (14%), psoriatic arthritis (14%), inflammatory osteoarthritis (8%), reactive arthritis (7%), crystal arthritis (7%), and peripheral spondylarthritis (4%). ITI occurred more often in diagnoses with frequent arthritis of the hands (P < 0.001) and increased acute‐phase reactants (P < 0.001). Within RA, ITI occurred together with local MCP joint synovitis (odds ratio [OR] 2.4, 95% confidence interval [95% CI] 1.7–3.4), tenosynovitis (OR 2.4, 95% CI 1.8–3.3), and osteitis (OR 2.2, 95% CI 1.6–3.1) on MRI. Moreover, ITI presence was associated with local MCP joint tenderness (OR 1.6, 95% CI 1.2–2.1) and swelling (OR 1.8, 95% CI 1.3–2.6), independent of age and MRI‐detected synovitis/tenosynovitis/osteitis.

Conclusion

ITI occurs regularly in RA and other arthritides with preferential involvement of hand joints and increased acute‐phase reactants. At the MCP joint level, ITI associates independently with joint tenderness and swelling. Hence, ITI is a newly identified inflamed tissue mainly found in arthritides with particularly extensive and symptomatic inflammation.
Cyanobacteria mitigation using low power ultrasound for gas vesicle collapse
Authors: Bohrerova Zuzana , Yousuf Yousuf , Crafton‐Nelson Elizabeth , Cheng Chin‐Min , Weaver Christopher R. , Weavers Linda K.
Published: June 2023

The ability of a low‐power ultrasound system to alter the physiology of cyanobacteria cells in controlled field applications was evaluated. Serratia sp., a model bacteria, and cyanobacteria collected from a bloom containing Microcystis sp. and Aphanizomenon sp., were placed in sound transparent containers and exposed to ultrasound in field studies. No observed changes in Serratia sp. and cyanobacteria gas vesicles between unexposed controls and ultrasound exposed samples were found. Cell viability and phycocyanin concentration for both model bacteria and environmental samples were not significantly affected. At the highest acoustic pressure measured (3.5 kPa), 1 m from the transducer, the acoustic pressures were over 100× lower than gas vesicle critical collapse pressures. Moreover, the ultrasound frequencies emitted are significantly lower than gas vesicle resonance frequencies. Therefore, consistent with pressure and frequency measurements, we found no evidence that gas vesicle collapse is the mechanism of ultrasound as a cyanobacteria mitigation strategy.
Construction and application of a new CRISPR/Cas12a system in Stenotrophomonas AGS‐1 from aerobic granular sludge
Authors: Meng Wei , Qiao Kai , Liu Fan , Gao Xu , Hu Xuan , Liu Jia , Gao Yiyun , Zhu Jianrong
Published: June 2023

Aerobic granular sludge (AGS) is a microbial aggregate with a biofilm structure. Thus, investigating AGS in the aspect of biofilm and microbial attachment at the genetic level would help to reveal the mechanism of granule biofilm formation. In this work, a two‐plasmid clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated proteins (Cas)12a genome editing system was constructed to identify attachment genes for the first time in Stenotrophomonas AGS‐1 from AGS. One plasmid contained a Cas12a cassette driven by an arabinose‐inducible promoter, and another contained the specific crRNA and homologous arms (HAs). Acidaminococcus sp. Cas12a (AsCas12a) was adopted and proven to have mild toxicity (compared to Cas9) and strong cleavage activity for AGS‐1. CRISPR/Cas12a‐mediated rmlA knockout decreased attachment ability by 38.26%. Overexpression of rmlA in AGS‐1 resulted in an increase of 30.33% in attachment ability. These results showed that the modulation of rmlA was an important factor for the biofilm formation of AGS‐1. Moreover, two other genes (xanB and rpfF) were knocked out by CRISPR/Cas12a and identified as attachment‐related genes in AGS‐1. Also, this system could achieve point mutations. These data indicated that the CRISPR/Cas12a system could be an effective molecular platform for attachment gene function identification, which would be useful for the development of AGS in wastewater treatment.
Increased yield of 2‐O‐α‐d‐glucopyranosyl‐l‐ascorbic acid synthesis by α‐glucosidase using rational design that regulating the ground state of enzyme and substrate complex
Authors: Zheng Shao‐Yan , Zhou Wei‐Jie , Lin Xiang‐Na , Li Fei‐Fei , Xie Chun‐Fang , Liu Da‐Ling , Yao Dong‐Sheng
Published: June 2023

Background

α‐Glucosidase (AG) is a bifunctional enzyme, it has a capacity to synthesize 2‐O‐α‐d‐glucopyranosyl‐l‐ascorbic acid (AA‐2G) from l‐ascorbic acid (L‐AA) and low‐cost maltose under mild conditions, but it can also hydrolyze AA‐2G, which leads to low synthesis efficiency of AA‐2G.

Main Methods and Major Results

This study introduces a rational molecular design strategy to regulate enzymatic reactions based on inhibiting the formation of ground state of enzyme‐substrate complex. Y215 was analyzed as the key amino acid site affecting the affinity of AG to AA‐2G and L‐AA. For the purpose of reducing the hydrolysis efficiency of AA‐2G, the mutant Y215W was obtained by analyzing the molecular docking binding energy and hydrogen bond formation between AG and the substrates. Compared with the wild‐type, isothermal titration calorimetry (ITC) results showed that the equilibrium dissociation constant (KD) of the mutant for AA‐2G was doubled; the Michaelis constant (Km) for AA‐2G was reduced by 1.15 times; and the yield of synthetic AA‐2G was increased by 39%.

Conclusions and Implications

Our work also provides a new reference strategy for the molecular modification of multifunctional enzymes and other enzymes in cascade reactions system.
Circadian rhythm of daytime sleepiness in pediatric narcolepsy: A pilot study
Authors: Ouyang Hui , Zhou Zechen , Dai Xiaotong , Zhang Jun
Published: June 2023

Background and objective

Excessive daytime sleepiness (EDS) has been far back reported as the most disabling symptom in the pediatric narcoleptic patients. However, there is a lack of studies to examine the circadian rhythms of EDS in pediatric narcoleptic population. Therefore, we aim to investigate the circadian rhythm of EDS in pediatric narcolepsy patients.

Methods

We identified 50 pediatric narcoleptic patients (36 males and 14 females, mean age 13.68 ± 2.75 years). Data were collected through interviews and the relevant questionnaires (children depression inventory [CDI] and the pediatric quality of life inventory [PedsQL]).

Result

The frequencies of sleep attacks during different intervals of the day differed significantly, with higher frequency in the morning (p < .001). The times of sleep attacks in the morning and in the afternoon were significantly associated with the degree of impairment on class and the severity of worry about sleepiness, with spearman correlation coefficient ranging from .289 to .496 (p < .05). The total scores of PedsQL and CDI differed significantly among morning sleepiness dominant, afternoon sleepiness dominant, and evening sleepiness dominant groups (p = .042, p = .040). The severity scores of the narcoleptic patients’ sleepiness had two peaks, one of which occurred at 16:00, and the other peaks occurred at about 11:00.

Conclusion

These results suggest that changes based on the circadian rhythm of sleepiness of the pediatric narcoleptic patients should be made in the treatment strategy. In addition, regulating the secretion of melatonin could serve as a promising treatment to relieve sleepiness in the future.
The impact of stimulus configuration on visual short‐term memory decline in normal aging and mild cognitive impairment
Authors: Sapkota Raju P. , van der Linde Ian , Grunwald Iris Q. , Upadhyaya Tirthalal , Lamichhane Nirmal , Pardhan Shahina
Published: June 2023

Introduction

When we memorize simultaneous items, we not only store information about specific items and/or their locations but also how items are related to each other. Such relational information can be parsed into spatial (spatial configuration) and identity (object configuration) components. Both these configurations are found to support performance during a visual short‐term memory (VSTM) task in young adults. How the VSTM performance of older adults is influenced by object/spatial configuration is less understood, which this study investigated.

Methods

Twenty‐nine young adults, 29 normally aging older adults, and 20 older adults with mild cognitive impairment (MCI) completed two yes–no memory‐recognition experiments for four simultaneously presented items (2.5 s). Test display items were presented either at the same locations as the memory items (Experiment 1) or were globally shifted (Experiment 2). One of the test display items (target) was highlighted with a square box; participants indicated whether this item was shown in the preceding memory display. Both experiments comprised four conditions where nontarget items changed as follows: (i) nontarget items remained the same; (ii) nontarget items were replaced by new items; (iii) nontarget items switched locations; (iv) nontarget items were replaced by square boxes.

Results

Performance (% correct) in both older groups was significantly reduced than young adults in both experiments and each condition. For the MCI adults, significantly reduced performance (vs. normal older adults) was found only for Experiment 1.

Conclusion

VSTM for simultaneous items declines significantly in normal aging; the decline is not influenced differently by spatial/object configuration change. The ability of VSTM to differentiate MCI from normal cognitive aging is apparent only where the spatial configuration of stimuli is retained at original locations. Findings are discussed in terms of the reduced ability to inhibit irrelevant items and location priming (by repetition) deficits.
Inhibition of FGFR3 upregulates MHC‐I and PD‐L1 via TLR3/NF‐kB pathway in muscle‐invasive bladder cancer
Authors: Wu WenBo , Chen Lei , Jia GaoZhen , Tang QiLin , Han BangMin , Xia ShuJie , Jiang Qi , Liu HaiTao
Published: June 2023

Background

Improving the potency of immune response is paramount among issues concerning immunotherapy of muscle‐invasive bladder cancer (MIBC).

Methods

On the basis of immune subtypes, we investigated possible molecular mechanisms involved in tumor immune escape in MIBC. According to the 312 immune‐related genes, three MIBC immune subtypes were clustered.

Results

Cluster 2 subtype is characterized by FGFR3 mutations and has a better clinical prognosis. However, the expression levels of MHC‐I and immune checkpoints genes were the lowest, indicating that this subtype is subject to immune escape and has a low response rate to immunotherapy. Bioinformatics analysis and immunofluorescence staining of clinical samples revealed that the FGFR3 is involved in the immune escape in MIBC. Besides, after FGFR3 knockout with siRNA in RT112 and UMUC14 cells, the TLR3/NF‐kB pathway was significantly activated and was accompanied by upregulation of MHC‐I and PD‐L1 gene expression. Furthermore, the use of TLR3 agonists poly(I:C) can further improve the effect.

Conclusion

Together, our results suggest that FGFR3 might involve in immunosuppression by inhibition of NF‐kB pathway in BC. Considering that TLR3 agonists are currently approved for clinical treatment as immunoadjuvants, our study might provide more insights for improving the efficacy of immunotherapy in MIBC.
A rare case of dentinogenic ghost cell tumor with concomitant odontoma
Authors: Okui Tatsuo , Morioka Reon , Iwahashi Teruaki , Matsuda Yuhei , Ishizuka Shinji , Okuma Satoe , Tatsumi Hiroto , Kanno Takahiro
Published: June 2023

Key Clinical Message

A case of dentinogenic ghost cell tumor occurring simultaneously with a clinically diagnosed odontoma. The occurrence of epithelial and mesenchymal tumors at the same site is very rare, but should be kept in mind during pathological diagnosis.

Dentinogenic ghost cell tumor (DGCT) is a rare and benign odontogenic tumor composed of ghost cells, calcified tissue, and dentin. We present an extremely rare case of a 32‐year‐old female who was clinically diagnosed with an odontoma presenting with a painless swelling in her maxilla. Radiographic examination showed a well‐defined radiolucent lesion with tooth‐like calcified areas. The tumor was resected under general anesthesia. No recurrence was noted at the 12‐month follow‐up. Histopathological examination of the surgically resected tumor yielded a diagnosis of DGCT with odontoma.
Pathologic complete response to neoadjuvant imatinib of a gastric stromal tumor with concomitant mutations in KIT: A case report and literature review
Authors: Rekaya Mariem Ben , Ksontini Feryel , Kacem Linda Bel Haj , Sassi Farah , Harigua‐Souiai Emna , Boujneh Ryma , H'mayada Ahmed , Zaimi Yosra , Ayadi Mouna , Trabelsi Mediha , Mrad Ridha , Rammeh Soumaya
Published: June 2023

Key clinical message

We report the first case of pathologic complete response (pCR) to neoadjuvant imatinib in a gastric stromal tumor harboring KIT mutations in both exons 11 and 9. The significance of this co‐occurrence is unknown and might increase the responsiveness of gastrointestinal stromal tumors (GISTs) to imatinib.

pCR of GIST to neoadjuvant imatinib is rare. We report a case of pCR to neoadjuvant imatinib in a gastric stromal tumor that harbored co‐occurrence of multiple KIT mutations in exons 11 and 9. This co‐occurrence in exons 9 and 11 is the first to be reported in the English literature.
Peri‐implant proximal femur fracture in a poliomyelitis survivor: A surgical and medical challenge
Authors: Sakellariou Evangelos , Galanis Athanasios , Vavourakis Michail , Papagrigorakis Eftychios , Vlachos Christos , Zachariou Dimitrios , Vasiliadis Elias , Pneumaticos Spiros
Published: June 2023

Key Clinical Message

The treatment of long bone fractures in post‐polio survivors is indubitably an exacting task. Out of this complicated case presented in this paper, it can be deduced that it is attainable to repair a peri‐implant subtrochanteric refracture or a complex non‐union of the proximal femur with plate and screws with grafting.

Post‐polio survivors are prone to low‐energy bone fractures. The management of such cases is exigent, as no literature data indicate the best surgical approach. This paper presents an intricate peri‐implant proximal femoral fracture in a polio survivor treated in our institution and accentuates the various challenges we encountered.
Steroid‐induced inflammatory papillary hyperplasia?—A new entity in a non‐denture wearing patient
Authors: Gupta Abhishek , Lamichhane Ram Sudan , Redhu Anju
Published: June 2023

Key Clinical Message

Inflammatory papillary hyperplasia can be seen in a non‐denture‐wearing patient also therfore other etiologies need to be explored as well.

Inflammatory papillary hyperplasia (IPH) is a benign lesion of the palatal mucosa, usually found in denture wearers. This case history report describes an example of the dentate patients with no history of wearing maxillary prostheses and highlights the importance of professional awareness to diagnose IPH among non‐denture‐wearing patients.