bluuebunny/crossref_metadata_2025 huggingface dataset:
Structured Exposure in an Unstructured Setting: Case Study of Parental Exposure Intervention to Increase Parental Mastery of Medical Care During Inpatient Hospitalization
Authors: Albright Dana K. , Kullgren Kristin A. , Andersen Melissa N.
Published: June 2022

Objective:

Parental stress can have an impact on health outcomes of chronically ill children ( Cousino & Hazen, 2013 ). Pediatric psychologists are well suited to address these issues with understanding of empirically supported treatments, impact of mental health on medical care behaviors, and parent–child interactions ( Ernst et al., 2015 ). Use of empirically supported treatments, such as graduated exposure therapy (ET), within an uncontrolled environment such as an inpatient setting can be challenging. This case study illustrates adaptation of ET in an inpatient setting to address parental mastery of medical care.

Method:

ET was implemented with a mother of an infant with a newly placed tracheostomy to reduce her severe anxiety that was preventing her from interacting with her infant or engaging in medical care necessary for hospital discharge.

Results:

Through 31 exposure sessions, the patient’s mother met all four treatment targets: daily tracheostomy care, stoma desensitization, tracheostomy tube changes, and suctioning. Self-reported distress data were presented for each exposure.

Conclusions:

Use of ET with a clear treatment plan and coordinated multidisciplinary inpatient team efforts can successfully reduce severe parental anxiety that is impeding medical care, hindering parent–child interaction, and interfering with parental ability to care for a child with complex medical needs. This article discusses multiple factors that are unique to the inpatient setting and the target behaviors for consideration.

Implications for Impact Statement

This case highlights the use of empirically supported treatments to target complex parent behaviors in a pediatric inpatient setting. Reducing barriers to discharge, such as inability to demonstrate adequate medical care, promotes better patient and family outcomes.
Meta-analysis of mucosal microbiota reveals universal microbial signatures and dysbiosis in gastric carcinogenesis
Authors: Liu Changan , Ng Siu-Kin , Ding Yanqiang , Lin Yufeng , Liu Weixin , Wong Sunny Hei , Sung Joseph Jao-Yiu , Yu Jun
Published: June 2022

The consistency of the associations between gastric mucosal microbiome and gastric cancer across studies remained unexamined. We aimed to identify universal microbial signatures in gastric carcinogenesis through a meta-analysis of gastric microbiome from multiple studies. Compositional and ecological profiles of gastric microbes across stages of gastric carcinogenesis were significantly altered. Meta-analysis revealed that opportunistic pathobionts Fusobacterium, Parvimonas, Veillonella, Prevotella and Peptostreptococcus were enriched in GC, while commensals Bifidobacterium, Bacillus and Blautia were depleted in comparison to SG. The co-occurring correlation strengths of GC-enriched bacteria were increased along disease progression while those of GC-depleted bacteria were decreased. Eight bacterial taxa, including Veillonella, Dialister, Granulicatella, Herbaspirillum, Comamonas, Chryseobacterium, Shewanella and Helicobacter, were newly identified by this study as universal biomarkers for robustly discriminating GC from SG, with an area under the curve (AUC) of 0.85. Moreover, H. pylori-positive samples exhibited reduced microbial diversity, altered microbiota community and weaker interactions among gastric microbes. Our meta-analysis demonstrated comprehensive and generalizable gastric mucosa microbial features associated with histological stages of gastric carcinogenesis, including GC associated bacteria, diagnostic biomarkers, bacterial network alteration and H. pylori influence.
Big data, machine learning, and population health: predicting cognitive outcomes in childhood
Authors: Bowe Andrea K. , Lightbody Gordon , Staines Anthony , Murray Deirdre M.
Published: June 2022

The application of machine learning (ML) to address population health challenges has received much less attention than its application in the clinical setting. One such challenge is addressing disparities in early childhood cognitive development—a complex public health issue rooted in the social determinants of health, exacerbated by inequity, characterised by intergenerational transmission, and which will continue unabated without novel approaches to address it. Early life, the period of optimal neuroplasticity, presents a window of opportunity for early intervention to improve cognitive development. Unfortunately for many, this window will be missed, and intervention may never occur or occur only when overt signs of cognitive delay manifest. In this review, we explore the potential value of ML and big data analysis in the early identification of children at risk for poor cognitive outcome, an area where there is an apparent dearth of research. We compare and contrast traditional statistical methods with ML approaches, provide examples of how ML has been used to date in the field of neurodevelopmental disorders, and present a discussion of the opportunities and risks associated with its use at a population level. The review concludes by highlighting potential directions for future research in this area.

Impact

To date, the application of machine learning to address population health challenges in paediatrics lags behind other clinical applications. This review provides an overview of the public health challenge we face in addressing disparities in childhood cognitive development and focuses on the cornerstone of early intervention.

Recent advances in our ability to collect large volumes of data, and in analytic capabilities, provide a potential opportunity to improve current practices in this field.

This review explores the potential role of machine learning and big data analysis in the early identification of children at risk for poor cognitive outcomes.
Post-transplant cyclophosphamide and sirolimus based graft-versus-host disease prophylaxis after allogeneic stem cell transplantation for acute myeloid leukemia
Authors: Lazzari Lorenzo , Balaguer-Roselló Aitana , Montoro Juan , Greco Raffaella , Hernani Rafael , Lupo-Stanghellini Maria Teresa , Villalba Marta , Giglio Fabio , Facal Ana , Lorentino Francesca , Guerreiro Manuel , Bruno Alessandro , Pérez Ariadna , Xue Elisabetta , Clerici Daniela , Piemontese Simona , Piñana José Luis , Sanz Miguel Ángel , Solano Carlos , de la Rubia Javier , Ciceri Fabio , Peccatori Jacopo , Sanz Jaime
Published: June 2022

Post-transplant cyclophosphamide (PTCy) has emerged as a promising graft-versus-host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, no studies have reported the efficacy of a GvHD prophylaxis based on PTCy with sirolimus (Sir-PTCy) in patients with acute myeloid leukemia (AML). In this retrospective study, we analyze the use of sirolimus in combination with PTCy, with or without mycophenolate mofetil (MMF), on 242 consecutive adult patients with AML undergoing a myeloablative first allo-HSCT from different donor types, in three European centers between January 2017 and December 2020. Seventy-seven (32%) patients received allo-HSCT from HLA-matched sibling donor, 101 (42%) from HLA-matched and mismatched unrelated donor, and 64 (26%) from haploidentical donor. Except for neutrophil and platelet engraftment, which was slower in the haploidentical cohort, no significant differences were observed in major transplant outcomes according to donor type in univariate and multivariate analysis. GvHD prophylaxis with Sir-PTCy, with or without MMF, is safe and effective in patients with AML undergoing myeloablative allo-HSCT, resulting in low rates of transplant-related mortality, relapse/progression, and acute and chronic GvHD in all donor settings.
Splicing analyses for variants in MMR genes: best practice recommendations from the European Mismatch Repair Working Group
Authors: Morak Monika , Pineda Marta , Martins Alexandra , Gaildrat Pascaline , Tubeuf Hélène , Drouet Aurélie , Gómez Carolina , Dámaso Estela , Schaefer Kerstin , Steinke-Lange Verena , Koehler Udo , Laner Andreas , Hauchard Julie , Chauris Karine , Holinski-Feder Elke , Capellá Gabriel
Published: June 2022

Over 20% of the DNA mismatch repair (MMR) germline variants in suspected Lynch syndrome patients are classified as variants of uncertain significance (VUS). Well-established functional assays are pivotal for assessing the biological impact of these variants and provide relevant evidence for clinical classification. In our collaborative European Mismatch Repair Working Group (EMMR-WG) we compared three different experimental approaches for evaluating the effect of seven variants on mRNA splicing in MMR genes: (i) RT-PCR of full-length transcripts (FLT), (ii) RT-PCR of targeted transcript sections (TTS), both from patient biological samples and (iii) minigene splicing assays. An overall good concordance was observed between splicing patterns in TTS, FLT and minigene analyses for all variants. The FLT analysis depicted a higher number of different isoforms and mitigated PCR-bias towards shorter isoforms. TTS analyses may miss aberrant isoforms and minigene assays may under/overestimate the severity of certain splicing defects. The interpretation of the experimental findings must be cautious to adequately discriminate abnormal events from physiological complex alternative splicing patterns. A consensus strategy for investigating the impact of MMR variants on splicing was defined. First, RNA should be obtained from patient’s cell cultures (such as fresh lymphocyte cultures) incubated with/without a nonsense-mediated decay inhibitor. Second, FLT RT-PCR analysis is recommended to oversee all generated isoforms. Third, TTS analysis and minigene assays are useful independent approaches for verifying and clarifying FLT results. The use of several methodologies is likely to increase the strength of the experimental evidence which contributes to improve variant interpretation.
Precocious puberty in a case of Simpson–Golabi–Behmel syndrome with a de novo 240-kb deletion including GPC3
Authors: Watanabe Keisuke , Noguchi Atsuko , Takahashi Ikuko , Yamada Mamiko , Suzuki Hisato , Takenouchi Toshiki , Kosaki Kenjiro , Takahashi Tsutomu
Published: June 2022

Here, we report a Japanese patient with Simpson–Golabi–Behmel syndrome involving a de novo 240-kb deletion including a part of GPC3. The patient showed pre- and postnatal macrosomia associated with coarse face, macrocephaly, supernumerary nipples, and cryptorchidism and characteristically presented with precocious puberty, mostly evaluated as advanced pubertal age of 15 years at the chronological age of 11.5 years.
Learning emergent partial differential equations in a learned emergent space
Authors: Kemeth Felix P. , Bertalan Tom , Thiem Thomas , Dietrich Felix , Moon Sung Joon , Laing Carlo R. , Kevrekidis Ioannis G.
Published: June 2022

We propose an approach to learn effective evolution equations for large systems of interacting agents. This is demonstrated on two examples, a well-studied system of coupled normal form oscillators and a biologically motivated example of coupled Hodgkin-Huxley-like neurons. For such types of systems there is no obvious space coordinate in which to learn effective evolution laws in the form of partial differential equations. In our approach, we accomplish this by learning embedding coordinates from the time series data of the system using manifold learning as a first step. In these emergent coordinates, we then show how one can learn effective partial differential equations, using neural networks, that do not only reproduce the dynamics of the oscillator ensemble, but also capture the collective bifurcations when system parameters vary. The proposed approach thus integrates the automatic, data-driven extraction of emergent space coordinates parametrizing the agent dynamics, with machine-learning assisted identification of an emergent PDE description of the dynamics in this parametrization.
Effectiveness of BBIBP-CorV vaccine against severe outcomes of COVID-19 in Abu Dhabi, United Arab Emirates
Authors: Al Kaabi Nawal , Oulhaj Abderrahim , Ganesan Subhashini , Al Hosani Farida Ismail , Najim Omer , Ibrahim Halah , Acuna Juan , Alsuwaidi Ahmed R. , Kamour Ashraf M. , Alzaabi Ashraf , Al Shehhi Badreyya Ahmed , Al Safar Habiba , Hussein Salah Eldin , Abdalla Jehad Saleh , Al Mansoori Dalal Saeed Naser , Al Hammadi Ahmed Abdul Kareem , Amari Mohammed A. , Al Romaithi Ahmed Khamis , Weber Stefan , Elavalli Santosh , Eltantawy Islam , Alghaithi Noura Khamis , Al Azazi Jumana Nafiz , Holt Stephen Geoffrey , Mostafa Mohamed , Halwani Rabih , Khalak Hanif , Elamin Wael , Beiram Rami , Zaher Walid
Published: June 2022

The effectiveness of the inactivated BBIBP-CorV vaccine against severe COVID-19 outcomes (hospitalization, critical care admission and death due to COVID-19) and its long-term effectiveness have not been well characterized among the general population. We conducted a retrospective cohort study using electronic health records of 3,147,869 adults, of which 1,099,886 vaccinated individuals were matched, in a 1:1 ratio to 1,099,886 unvaccinated persons. A Cox-proportional hazard model with time varying coefficients was used to assess the vaccine effectiveness adjusting for age, sex, comorbidity, ethnicity, and the calendar month of entry into the study. Our analysis showed that the effectiveness was 79.6% (95% CI, 77.7 to 81.3) against hospitalization, 86% (95% CI, 82.2 to 89.0) against critical care admission, and 84.1% (95% CI, 70.8 to 91.3) against death due to COVID-19. The effectiveness against these severe outcomes declined over time indicating the need for booster doses to increase protection against severe COVID-19 outcomes.
Teaming up main group metals with metallic iron to boost hydrogenation catalysis
Authors: Färber Christian , Stegner Philipp , Zenneck Ulrich , Knüpfer Christian , Bendt Georg , Schulz Stephan , Harder Sjoerd
Published: June 2022

Hydrogenation of unsaturated bonds is a key step in both the fine and petrochemical industries. Homogeneous and heterogeneous catalysts are historically based on noble group 9 and 10 metals. Increasing awareness of sustainability drives the replacement of costly, and often harmful, precious metals by abundant 3d-metals or even main group metals. Although not as efficient as noble transition metals, metallic barium was recently found to be a versatile hydrogenation catalyst. Here we show that addition of finely divided Fe0, which itself is a poor hydrogenation catalyst, boosts activities of Ba0 by several orders of magnitude, enabling rapid hydrogenation of alkynes, imines, challenging multi-substituted alkenes and non-activated arenes. Metallic Fe0 also boosts the activity of soluble early main group metal hydride catalysts, or precursors thereto. This synergy originates from cooperativity between a homogeneous, highly reactive, polar main group metal hydride complex and a heterogeneous Fe0 surface that is responsible for substrate activation.
Physiological adaptive traits are a potential allele reservoir for maize genetic progress under challenging conditions
Authors: Welcker Claude , Spencer Nadir Abusamra , Turc Olivier , Granato Italo , Chapuis Romain , Madur Delphine , Beauchene Katia , Gouesnard Brigitte , Draye Xavier , Palaffre Carine , Lorgeou Josiane , Melkior Stephane , Guillaume Colin , Presterl Thomas , Murigneux Alain , Wisser Randall J. , Millet Emilie J. , van Eeuwijk Fred , Charcosset Alain , Tardieu François
Published: June 2022

Combined phenomic and genomic approaches are required to evaluate the margin of progress of breeding strategies. Here, we analyze 65 years of genetic progress in maize yield, which was similar (101 kg ha−1 year−1) across most frequent environmental scenarios in the European growing area. Yield gains were linked to physiologically simple traits (plant phenology and architecture) which indirectly affected reproductive development and light interception in all studied environments, marked by significant genomic signatures of selection. Conversely, studied physiological processes involved in stress adaptation remained phenotypically unchanged (e.g. stomatal conductance and growth sensitivity to drought) and showed no signatures of selection. By selecting for yield, breeders indirectly selected traits with stable effects on yield, but not physiological traits whose effects on yield can be positive or negative depending on environmental conditions. Because yield stability under climate change is desirable, novel breeding strategies may be needed for exploiting alleles governing physiological adaptive traits.
Evolutionary action of mutations reveals antimicrobial resistance genes in Escherichia coli
Authors: Marciano David C. , Wang Chen , Hsu Teng-Kuei , Bourquard Thomas , Atri Benu , Nehring Ralf B. , Abel Nicholas S. , Bowling Elizabeth A. , Chen Taylor J. , Lurie Pamela D. , Katsonis Panagiotis , Rosenberg Susan M. , Herman Christophe , Lichtarge Olivier
Published: June 2022

Since antibiotic development lags, we search for potential drug targets through directed evolution experiments. A challenge is that many resistance genes hide in a noisy mutational background as mutator clones emerge in the adaptive population. Here, to overcome this noise, we quantify the impact of mutations through evolutionary action (EA). After sequencing ciprofloxacin or colistin resistance strains grown under different mutational regimes, we find that an elevated sum of the evolutionary action of mutations in a gene identifies known resistance drivers. This EA integration approach also suggests new antibiotic resistance genes which are then shown to provide a fitness advantage in competition experiments. Moreover, EA integration analysis of clinical and environmental isolates of antibiotic resistant of E. coli identifies gene drivers of resistance where a standard approach fails. Together these results inform the genetic basis of de novo colistin resistance and support the robust discovery of phenotype-driving genes via the evolutionary action of genetic perturbations in fitness landscapes.
Dual phase patterning during a congruent grain boundary phase transition in elemental copper
Authors: Langenohl Lena , Brink Tobias , Freitas Rodrigo , Frolov Timofey , Dehm Gerhard , Liebscher Christian H.
Published: June 2022

The phase behavior of grain boundaries can have a strong influence on interfacial properties. Little is known about the emergence of grain boundary phases in elemental metal systems and how they transform. Here, we observe the nanoscale patterning of a grain boundary by two alternating grain boundary phases with distinct atomic structures in elemental copper by atomic resolution imaging. The same grain boundary phases are found by computational grain boundary structure search indicating a first-order transformation. Finite temperature atomistic simulations reveal a congruent, diffusionless transition between these phases under ambient pressure. The patterning of the grain boundary at room temperature is dominated by the grain boundary phase junctions separating the phase segments. Our analysis suggests that the reduced mobility of the phase junctions at low temperatures kinetically limits the transformation, but repulsive elastic interactions between them and disconnections could additionally stabilize the pattern formation.
Dynamic mRNA degradome analyses indicate a role of histone H3K4 trimethylation in association with meiosis-coupled mRNA decay in oocyte aging
Authors: Wu Yun-Wen , Li Sen , Zheng Wei , Li Yan-Chu , Chen Lu , Zhou Yong , Deng Zuo-Qi , Lin Ge , Fan Heng-Yu , Sha Qian-Qian
Published: June 2022

A decrease in oocyte developmental potential is a major obstacle for successful pregnancy in women of advanced age. However, the age-related epigenetic modifications associated with dynamic transcriptome changes, particularly meiotic maturation-coupled mRNA clearance, have not been adequately characterized in human oocytes. This study demonstrates a decreased storage of transcripts encoding key factors regulating the maternal mRNA degradome in fully grown oocytes of women of advanced age. A similar defect in meiotic maturation-triggered mRNA clearance is also detected in aged mouse oocytes. Mechanistically, the epigenetic and cytoplasmic aspects of oocyte maturation are synchronized in both the normal development and aging processes. The level of histone H3K4 trimethylation (H3K4me3) is high in fully grown mouse and human oocytes derived from young females but decreased during aging due to the decreased expression of epigenetic factors responsible for H3K4me3 accumulation. Oocyte-specific knockout of the gene encoding CxxC-finger protein 1 (CXXC1), a DNA-binding subunit of SETD1 methyltransferase, causes ooplasm changes associated with accelerated aging and impaired maternal mRNA translation and degradation. These results suggest that a network of CXXC1-maintained H3K4me3, in association with mRNA decay competence, sets a timer for oocyte deterioration and plays a role in oocyte aging in both mouse and human oocytes.
Observation of non-Hermitian topological Anderson insulator in quantum dynamics
Authors: Lin Quan , Li Tianyu , Xiao Lei , Wang Kunkun , Yi Wei , Xue Peng
Published: June 2022

Disorder and non-Hermiticity dramatically impact the topological and localization properties of a quantum system, giving rise to intriguing quantum states of matter. The rich interplay of disorder, non-Hermiticity, and topology is epitomized by the recently proposed non-Hermitian topological Anderson insulator that hosts a plethora of exotic phenomena. Here we experimentally simulate the non-Hermitian topological Anderson insulator using disordered photonic quantum walks, and characterize its localization and topological properties. In particular, we focus on the competition between Anderson localization induced by random disorder, and the non-Hermitian skin effect under which all eigenstates are squeezed toward the boundary. The two distinct localization mechanisms prompt a non-monotonous change in profile of the Lyapunov exponent, which we experimentally reveal through dynamic observables. We then probe the disorder-induced topological phase transitions, and demonstrate their biorthogonal criticality. Our experiment further advances the frontier of synthetic topology in open systems.
Profiling Fusobacterium infection at high taxonomic resolution reveals lineage-specific correlations in colorectal cancer
Authors: Bi Dexi , Zhu Yin , Gao Yaohui , Li Hao , Zhu Xingchen , Wei Rong , Xie Ruting , Cai Chunmiao , Wei Qing , Qin Huanlong
Published: June 2022

The bacterial genus Fusobacterium promotes colorectal cancer (CRC) development, but an understanding of its precise composition at the species level in the human gut and the relevant association with CRC is lacking. Herein, we devise a Fusobacterium rpoB amplicon sequencing (FrpoB-seq) method that enables the differentiation of Fusobacterium species and certain subspecies in the microbiota. By applying this method to clinical tissue and faecal samples from CRC patients, we detect 62 Fusobacterium species, including 45 that were previously undescribed. We additionally reveal that Fusobacterium species may display different lineage-dependent functions in CRC. Specifically, a lineage (designated L1) including F. nucleatum, F. hwasookii, F. periodonticum and their relatives (rather than any particular species alone) is overabundant in tumour samples and faeces from CRC patients, whereas a non-enriched lineage (designated L5) represented by F. varium and F. ulcerans in tumours has a positive association with lymphovascular invasion.
Light-activated photodeformable supramolecular dissipative self-assemblies
Authors: Chen Xu-Man , Feng Wei-Jie , Bisoyi Hari Krishna , Zhang Shu , Chen Xiao , Yang Hong , Li Quan
Published: June 2022

Dissipative self-assembly, one of fundamentally important out-of-equilibrium self-assembly systems, can serve as a controllable platform to exhibit temporal processes for various non-stimulus responsive properties. However, construction of light-fueled dissipative self-assembly structures with transformable morphology to modulate non-photoresponsive properties remains a great challenge. Here, we report a light-activated photodeformable dissipative self-assembly system in aqueous solution as metastable fluorescent palette. Zwitterionic sulfonato-merocyanine is employed as a light-induced amphiphile to co-assemble with polyethyleneimine after light irradiation. The formed spherical nanoparticles spontaneously transform into cuboid ones in the dark with simultaneous variation of the particle sizes. Then the two kinds of nanoparticles can reversibly interconvert to each other by periodical light irradiation and thermal relaxation. Furthermore, after loading different fluorophores exhibiting red, green, blue emissions and their mixtures, all these fluorescent dissipative deformable nanoparticles display time-dependent fluorescence variation with wide range of colors. Owing to the excellent performance of photodeformable dissipative assembly platform, the light-controlled fluorescence has achieved a 358-fold enhancement. Therefore, exposing the nanoparticles loaded with fluorophores to light in a spatially controlled manner allows us to draw multicolored fluorescent images that spontaneously disappeared after a specific period of time.
Direct investigation of the atomic structure and decreased magnetism of antiphase boundaries in garnet
Authors: Xu Kun , Lin Ting , Rao Yiheng , Wang Ziqiang , Yang Qinghui , Zhang Huaiwu , Zhu Jing
Published: June 2022

The ferrimagnetic insulator iron garnets, tailored artificially with specific compositions, have been widely utilized in magneto-optical (MO) devices. The adjustment on synthesis always induces structural variation, which is underestimated due to the limited knowledge of the local structures. Here, by analyzing the structure and magnetic properties, two different antiphase boundaries (APBs) with individual interfacial structure are investigated in substituted iron garnet film. We reveal that magnetic signals decrease in the regions close to APBs, which implies degraded MO performance. In particular, the segregation of oxygen deficiencies across the APBs directly leads to reduced magnetic elements, further decreases the magnetic moment of Fe and results in a higher absorption coefficient close to the APBs. Furthermore, the formation of APBs can be eliminated by optimizing the growth rate, thus contributing to the enhanced MO performance. These analyses at the atomic scale provide important guidance for optimizing MO functional materials.
Climate and hydraulic traits interact to set thresholds for liana viability
Authors: Willson Alyssa M. , Trugman Anna T. , Powers Jennifer S. , Smith-Martin Chris M. , Medvigy David
Published: June 2022

Lianas, or woody vines, and trees dominate the canopy of tropical forests and comprise the majority of tropical aboveground carbon storage. These growth forms respond differently to contemporary variation in climate and resource availability, but their responses to future climate change are poorly understood because there are very few predictive ecosystem models representing lianas. We compile a database of liana functional traits (846 species) and use it to parameterize a mechanistic model of liana-tree competition. The substantial difference between liana and tree hydraulic conductivity represents a critical source of inter-growth form variation. Here, we show that lianas are many times more sensitive to drying atmospheric conditions than trees as a result of this trait difference. Further, we use our competition model and projections of tropical hydroclimate based on Representative Concentration Pathway 4.5 to show that lianas are more susceptible to reaching a hydraulic threshold for viability by 2100.
Diamagnetically levitated nanopositioners with large-range and multiple degrees of freedom
Authors: Vikrant K. S. , Jayanth G. R.
Published: June 2022

Precision positioning stages are often central to science and technology at the micrometer and nanometer length scales. Compact, multi-degree-of-freedom stages with large dynamic range are especially desirable, since they help to improve the throughput and versatility in manipulation without introducing spatial constraints. Here, we report compact diamagnetically levitated stages, which employ dual-sided actuation to achieve large-range, six degrees-of-freedom positioning. Dual-sided actuation is demonstrated to enable trapping a magnet array in 3D, with independent control of the trap stiffness about two axes, independent control of forces in 3D and torque about 2 axes. A simplified model is proposed to directly relate these physical quantities to the necessary actuation currents. Experimentally, we demonstrate six degrees-of-freedom positioning with low cross-axis motion, large range and nanometer-scale resolution. In particular, here we show linear motion range of 5 mm with positioning precision better than 1.88 nm, and angular motion range of 1.1 radian with a resolution of 50 micro-radian. With the volume of the stage being between 10-20 cm3, its utility as a compact nano-positioner is showcased by using it to automatically replace the tip of an atomic force microscope probe.
Rapid syntheses of N-fused heterocycles via acyl-transfer in heteroaryl ketones
Authors: Ye Dan , Lu Hong , He Yi , Zheng Zhaojing , Wu Jinghao , Wei Hao
Published: June 2022

The wide-ranging potencies of bioactive N-fused heterocycles inspire the development of synthetic transformations that simplify preparation of their complex, diverse structural motifs. Heteroaryl ketones are ubiquitous, readily available, and inexpensive molecular scaffolds, and are thus synthetically appealing as precursors in preparing N-fused heterocycles via intramolecular acyl-transfer. To best of our knowledge, acyl-transfer of unstrained heteroaryl ketones remains to be demonstrated. Here, we show an acyl transfer-annulation to convert heteroaryl ketones to N-fused heterocycles. Driven via aromatisation, the acyl of a heteroaryl ketone can be transferred from the carbon to the nitrogen of the corresponding heterocycle. The reaction commences with the spiroannulation of a heteroaryl ketone and an alkyl bromide, with the resulting spirocyclic intermediate undergoing aromatisation-driven intramolecular acyl transfer. The reaction conditions are optimised, with the reaction exhibiting a broad substrate scope in terms of the ketone and alkyl bromide. The utility of this protocol is further demonstrated via application to complex natural products and drug derivatives to yield heavily functionalised N-fused heterocycles.
Donor-dependent fecal microbiota transplantation efficacy against necrotizing enterocolitis in preterm pigs
Authors: Hui Yan , Vestergaard Gisle , Deng Ling , Kot Witold Piotr , Thymann Thomas , Brunse Anders , Nielsen Dennis Sandris
Published: June 2022

The development of necrotizing enterocolitis (NEC), a life-threatening inflammatory bowel disease affecting preterm infants, is connected with gut microbiota dysbiosis. Using preterm piglets as a model for preterm infants we recently showed that fecal microbiota transplantation (FMT) from healthy suckling piglet donors to newborn preterm piglets decreased the NEC risk. However, in a follow-up study using donor stool from piglets recruited from another farm, this finding could not be replicated. This allowed us to study donor-recipient microbiota dynamics in a controlled model system with a clear difference in NEC phenotype. Preterm piglets (n = 38) were randomly allocated to receive control saline (CON), or rectal FMT using either the ineffective (FMT1) or the effective donor stool (FMT2). All animals were followed for four days before necropsy and gut pathological evaluation. Donor and recipient colonic gut microbiota (GM) were analyzed by 16 S rRNA gene amplicon sequencing and shotgun metagenomics. As expected, only FMT2 recipients were protected against NEC. Both FMT groups had shifted GM composition relative to CON, but FMT2 recipients had a higher lactobacilli relative abundance compared to FMT1. Limosilactobacillus reuteri and Lactobacillus crispatus strains of FMT recipients showed high phylogenetic similarity with their respective donors, indicating engraftment. Moreover, the FMT2 group had a higher lactobacilli replication rate and harbored specific glycosaminoglycan-degrading Bacteroides. In conclusion, subtle species-level donor differences translate to major changes in engraftment dynamics and the ability to prevent NEC. This could have implications for proper donor selection in future FMT trials for NEC prevention.
Lysosome lipid signalling from the periphery to neurons regulates longevity
Authors: Savini Marzia , Folick Andrew , Lee Yi-Tang , Jin Feng , Cuevas André , Tillman Matthew C. , Duffy Jonathon D. , Zhao Qian , Neve Isaiah A. , Hu Pei-Wen , Yu Yong , Zhang Qinghao , Ye Youqiong , Mair William B. , Wang Jin , Han Leng , Ortlund Eric A. , Wang Meng C.
Published: June 2022

Lysosomes are key cellular organelles that metabolize extra- and intracellular substrates. Alterations in lysosomal metabolism are implicated in ageing-associated metabolic and neurodegenerative diseases. However, how lysosomal metabolism actively coordinates the metabolic and nervous systems to regulate ageing remains unclear. Here we report a fat-to-neuron lipid signalling pathway induced by lysosomal metabolism and its longevity-promoting role in Caenorhabditis elegans. We discovered that induced lysosomal lipolysis in peripheral fat storage tissue upregulates the neuropeptide signalling pathway in the nervous system to promote longevity. This cell-non-autonomous regulation is mediated by a specific polyunsaturated fatty acid, dihomo-γ-linolenic acid, and LBP-3 lipid chaperone protein transported from the fat storage tissue to neurons. LBP-3 binds to dihomo-γ-linolenic acid, and acts through NHR-49 nuclear receptor and NLP-11 neuropeptide in neurons to extend lifespan. These results reveal lysosomes as a signalling hub to coordinate metabolism and ageing, and lysosomal signalling mediated inter-tissue communication in promoting longevity.
Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer
Authors: Lips Esther H. , Kumar Tapsi , Megalios Anargyros , Visser Lindy L. , Sheinman Michael , Fortunato Angelo , Shah Vandna , Hoogstraat Marlous , Sei Emi , Mallo Diego , Roman-Escorza Maria , Ahmed Ahmed A. , Xu Mingchu , van den Belt-Dusebout Alexandra W. , Brugman Wim , Casasent Anna K. , Clements Karen , Davies Helen R. , Fu Liping , Grigoriadis Anita , Hardman Timothy M. , King Lorraine M. , Krete Marielle , Kristel Petra , de Maaker Michiel , Maley Carlo C. , Marks Jeffrey R. , Menegaz Brian A. , Mulder Lennart , Nieboer Frank , Nowinski Salpie , Pinder Sarah , Quist Jelmar , Salinas-Souza Carolina , Schaapveld Michael , Schmidt Marjanka K. , Shaaban Abeer M. , Shami Rana , Sridharan Mathini , Zhang John , Stobart Hilary , Collyar Deborah , Nik-Zainal Serena , Wessels Lodewyk F. A. , Hwang E. Shelley , Navin Nicholas E. , Futreal P. Andrew ,   Grand Challenge PRECISION consortium, Futreal P. Andrew , Hwang E. Shelley , Jonkers Jos , Jacco  , Behbod Fariba , Rea Daniel , Bhattacharjee Proteeti , Pinto Donna , Verschuur Ellen , van Oirsouw Marja , Thompson Alastair M. , Wesseling Jelle , Sawyer Elinor J.
Published: June 2022

Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer and, despite treatment, a small fraction (5–10%) of DCIS patients develop subsequent invasive disease. A fundamental biologic question is whether the invasive disease arises from tumor cells in the initial DCIS or represents new unrelated disease. To address this question, we performed genomic analyses on the initial DCIS lesion and paired invasive recurrent tumors in 95 patients together with single-cell DNA sequencing in a subset of cases. Our data show that in 75% of cases the invasive recurrence was clonally related to the initial DCIS, suggesting that tumor cells were not eliminated during the initial treatment. Surprisingly, however, 18% were clonally unrelated to the DCIS, representing new independent lineages and 7% of cases were ambiguous. This knowledge is essential for accurate risk evaluation of DCIS, treatment de-escalation strategies and the identification of predictive biomarkers.
Mendelian imputation of parental genotypes improves estimates of direct genetic effects
Authors: Young Alexander I. , Nehzati Seyed Moeen , Benonisdottir Stefania , Okbay Aysu , Jayashankar Hariharan , Lee Chanwook , Cesarini David , Benjamin Daniel J. , Turley Patrick , Kong Augustine
Published: June 2022

Effects estimated by genome-wide association studies (GWASs) include effects of alleles in an individual on that individual (direct genetic effects), indirect genetic effects (for example, effects of alleles in parents on offspring through the environment) and bias from confounding. Within-family genetic variation is random, enabling unbiased estimation of direct genetic effects when parents are genotyped. However, parental genotypes are often missing. We introduce a method that imputes missing parental genotypes and estimates direct genetic effects. Our method, implemented in the software package snipar (single-nucleotide imputation of parents), gives more precise estimates of direct genetic effects than existing approaches. Using 39,614 individuals from the UK Biobank with at least one genotyped sibling/parent, we estimate the correlation between direct genetic effects and effects from standard GWASs for nine phenotypes, including educational attainment (r = 0.739, standard error (s.e.) = 0.086) and cognitive ability (r = 0.490, s.e. = 0.086). Our results demonstrate substantial confounding bias in standard GWASs for some phenotypes.
Dynamic World, Near real-time global 10 m land use land cover mapping
Authors: Brown Christopher F. , Brumby Steven P. , Guzder-Williams Brookie , Birch Tanya , Hyde Samantha Brooks , Mazzariello Joseph , Czerwinski Wanda , Pasquarella Valerie J. , Haertel Robert , Ilyushchenko Simon , Schwehr Kurt , Weisse Mikaela , Stolle Fred , Hanson Craig , Guinan Oliver , Moore Rebecca , Tait Alexander M.
Published: June 2022

Unlike satellite images, which are typically acquired and processed in near-real-time, global land cover products have historically been produced on an annual basis, often with substantial lag times between image processing and dataset release. We developed a new automated approach for globally consistent, high resolution, near real-time (NRT) land use land cover (LULC) classification leveraging deep learning on 10 m Sentinel-2 imagery. We utilize a highly scalable cloud-based system to apply this approach and provide an open, continuous feed of LULC predictions in parallel with Sentinel-2 acquisitions. This first-of-its-kind NRT product, which we collectively refer to as Dynamic World, accommodates a variety of user needs ranging from extremely up-to-date LULC data to custom global composites representing user-specified date ranges. Furthermore, the continuous nature of the product’s outputs enables refinement, extension, and even redefinition of the LULC classification. In combination, these unique attributes enable unprecedented flexibility for a diverse community of users across a variety of disciplines.
PAPILA: Dataset with fundus images and clinical data of both eyes of the same patient for glaucoma assessment
Authors: Kovalyk Oleksandr , Morales-Sánchez Juan , Verdú-Monedero Rafael , Sellés-Navarro Inmaculada , Palazón-Cabanes Ana , Sancho-Gómez José-Luis
Published: June 2022

Glaucoma is one of the ophthalmological diseases that frequently causes loss of vision in today’s society. Previous studies assess which anatomical parameters of the optic nerve can be predictive of glaucomatous damage, but to date there is no test that by itself has sufficient sensitivity and specificity to diagnose this disease. This work provides a public dataset with medical data and fundus images of both eyes of the same patient. Segmentations of the cup and optic disc, as well as the labeling of the patients based on the evaluation of clinical data are also provided. The dataset has been tested with a neural network to classify healthy and glaucoma patients. Specifically, the ResNet-50 has been used as the basis to classify patients using information from each eye independently as well as using the joint information from both eyes of each patient. Results provide the baseline metrics, with the aim of promoting research in the early detection of glaucoma based on the joint analysis of both eyes of the same patient.
The DeepFish computer vision dataset for fish instance segmentation, classification, and size estimation
Authors: Garcia-d’Urso Nahuel , Galan-Cuenca Alejandro , Pérez-Sánchez Paula , Climent-Pérez Pau , Fuster-Guillo Andres , Azorin-Lopez Jorge , Saval-Calvo Marcelo , Guillén-Nieto Juan Eduardo , Soler-Capdepón Gabriel
Published: June 2022

Preserving maritime ecosystems is a major concern for governments and administrations. Additionally, improving fishing industry processes, as well as that of fish markets, to have a more precise evaluation of the captures, will lead to a better control on the fish stocks. Many automated fish species classification and size estimation proposals have appeared in recent years, however, they require data to train and evaluate their performance. Furthermore, this data needs to be organized and labelled. This paper presents a dataset of images of fish trays from a local wholesale fish market. It includes pixel-wise (mask) labelled specimens, along with species information, and different size measurements. A total of 1,291 labelled images were collected, including 7,339 specimens of 59 different species (in 60 different class labels). This dataset can be of interest to evaluate the performance of novel fish instance segmentation and/or size estimation methods, which are key for systems aimed at the automated control of stocks exploitation, and therefore have a beneficial impact on fish populations in the long run.
AAV2-mediated gene therapy for Bietti crystalline dystrophy provides functional CYP4V2 in multiple relevant cell models
Authors: Wang Jiang-Hui , Lidgerwood Grace E. , Daniszewski Maciej , Hu Monica L. , Roberts Georgina E. , Wong Raymond C. B. , Hung Sandy S. C. , McClements Michelle E. , Hewitt Alex W. , Pébay Alice , Hickey Doron G. , Edwards Thomas L.
Published: June 2022

Bietti crystalline dystrophy (BCD) is an inherited retinal disease (IRD) caused by mutations in the CYP4V2 gene. It is a relatively common cause of IRD in east Asia. A number of features of this disease make it highly amenable to gene supplementation therapy. This study aims to validate a series of essential precursor in vitro experiments prior to developing a clinical gene therapy for BCD. We demonstrated that HEK293, ARPE19, and patient induced pluripotent stem cell (iPSC)-derived RPE cells transduced with AAV2 vectors encoding codon optimization of CYP4V2 (AAV2.coCYP4V2) resulted in elevated protein expression levels of CYP4V2 compared to those transduced with AAV2 vectors encoding wild type CYP4V2 (AAV2.wtCYP4V2), as assessed by immunocytochemistry and western blot. Similarly, we observed significantly increased CYP4V2 enzyme activity in cells transduced with AAV2.coCYP4V2 compared to those transduced with AAV2.wtCYP4V2. We also showed CYP4V2 expression in human RPE/choroid explants transduced with AAV2.coCYP4V2 compared to those transduced with AAV2.wtCYP4V2. These preclinical data support the further development of a gene supplementation therapy for a currently untreatable blinding condition—BCD. Codon-optimized CYP4V2 transgene was superior to wild type in terms of protein expression and enzyme activity. Ex vivo culture of human RPE cells provided an effective approach to test AAV-mediated transgene delivery.
Dietary restriction ameliorates TBI-induced phenotypes in Drosophila melanogaster
Authors: Delventhal Rebecca , Wooder Emily R. , Basturk Maylis , Sattar Mohima , Lai Jonathan , Bolton Danielle , Muthukumar Gayathri , Ulgherait Matthew , Shirasu-Hiza Mimi M.
Published: June 2022

Traumatic brain injury (TBI) affects millions annually and is associated with long-term health decline. TBI also shares molecular and cellular hallmarks with neurodegenerative diseases (NDs), typically increasing in prevalence with age, and is a major risk factor for developing neurodegeneration later in life. While our understanding of genes and pathways that underlie neurotoxicity in specific NDs has advanced, we still lack a complete understanding of early molecular and physiological changes that drive neurodegeneration, particularly as an individual ages following a TBI. Recently Drosophila has been introduced as a model organism for studying closed-head TBI. In this paper, we deliver a TBI to flies early in adult life, and then measure molecular and physiological phenotypes at short-, mid-, and long-term timepoints following the injury. We aim to identify the timing of changes that contribute to neurodegeneration. Here we confirm prior work demonstrating a TBI-induced decline in lifespan, and present evidence of a progressive decline in locomotor function, robust acute and modest chronic neuroinflammation, and a late-onset increase in protein aggregation. We also present evidence of metabolic dysfunction, in the form of starvation sensitivity and decreased lipids, that persists beyond the immediate injury response, but does not differ long-term. An intervention of dietary restriction (DR) partially ameliorates some TBI-induced phenotypes, including lifespan and locomotor function, though it does not alter the pattern of starvation sensitivity of injured flies. In the future, molecular pathways identified as altered following TBI—particularly in the short-, or mid-term—could present potential therapeutic targets.
Novel electromagnetic induction heat curing process of fly ash geopolymer using waste iron powder as a conductive material
Authors: Nongnuang Toon , Jitsangiam Peerapong , Rattanasak Ubolluk , Chindaprasirt Prinya
Published: June 2022

Geopolymer (GP) was invented to replace concrete, but its heat curing requirement hinders extensive use in real-world construction. Past studies have tested several methods of heat curing. However, the conventional heat curing process (using an oven) is still required for GP to develop good strength on the laboratory scale. This study introduces a new heat curing method for GP based on an electromagnetic field (EMF)generator and a ferromagnetic material. Waste iron powder (WIP) was used as the ferromagnetic material mixed with the fly ash-based GP to generate heat through induction. The sample was cured at 1.18 kW with 150–200 kHz of EMF generator for 15 min. The results showed that 5% of the WIP mixed sample gained compressive and flexural strength at 28 days more than the control (oven-cured). Compressive and flexural strengths of 76.8 MPa and 11.3 MPa were obtained, respectively. In addition, heat induction enhanced the densification and geopolymerization in the GP matrix following SEM and XRD results. This alternative method of heat curing accelerated the formation of the GP matrix, reduced curing time, and increased strength. Moreover, this EMF curing method can save 99.70% of the energy consumed compared to the conventional heat curing method.