bluuebunny/crossref_metadata_2025_split huggingface dataset:
Technical Report: A New Device Attached to a Smartphone for Objective Vision Screening
Authors: Wang Guang-Ji , Wang John Y. , Scott Clifford , Qu Jia , Lu Fan , Rio David , Purcell Howard , Chen Jie 
Published: December 2020

SIGNIFICANCE
A new device attached to a smartphone was created for objective vision screening of young children including infants and newborns. The device is compact, lightweight, portable, cost-effective, and easy to operate. Therefore, it is suitable for screening large numbers of children in clinical settings, schools, and communities.

PURPOSE
This article introduces a new device attached to a smartphone for objective vision screening. It can detect and categorize significant refractive errors, anisometropia, strabismus, cloudy ocular media, and ptosis that may cause amblyopia.

METHODS
The new device applies the same principles as conventional streak retinoscopy but examines both eyes simultaneously and records the results electronically. The device comprises optical elements that produce a precise streak light beam and move it across a child's both eyes. The smartphone's video camera catches and records the motion of retinal reflex inside the child's pupils. By observing the direction of motion of the retinal reflex relative to the light beam motion, as well as its speed, width, and brightness, the examiner is able to assess the individual and comparative refractive status, ocular alignment, and other conditions.

RESULTS
Vision screening with this device does not require any subjective response from children. The examination can be performed and analyzed by nonprofessionals after a short learning period of time. Because the examination results are electronically recorded by the smartphone, they can be stored in the child's files and sent out for professional consultations.

CONCLUSIONS
The new device will provide the same functions as conventional streak retinoscopy but examines a child's both eyes simultaneously, so that, in addition to categorizing refractive errors and assessing clarity of refractive media of the eyes, it can also detect anisometropia, strabismus, and anisocoria. In addition to showing the examination results on the smartphone's screen, the device can also store the results electronically.
In Vivo Human Corneal Shear-wave Optical Coherence Elastography
Authors: Lan Gongpu , Aglyamov Salavat R. , Larin Kirill V. , Twa Michael D. 
Published: December 2020

SIGNIFICANCE
A novel imaging technology, dynamic optical coherence elastography (OCE), was adapted for clinical noninvasive measurements of corneal biomechanics.

PURPOSE
Determining corneal biomechanical properties is a long-standing challenge. Elasticity imaging methods have recently been developed and applied for clinical evaluation of soft tissues in cancer detection, atherosclerotic plaque evaluation, surgical guidance, and more. Here, we describe the use of dynamic OCE to characterize mechanical wave propagation in the human cornea in vivo, thus providing a method for clinical determination of corneal biomechanical properties.

METHODS
High-resolution phase-sensitive optical coherence tomography imaging was combined with microliter air-pulse tissue stimulation to perform dynamic elasticity measurements in 18 eyes of nine participants. Low-pressure (0.1 mmHg), spatiotemporally discreet (150 μm, 800 μs) tissue stimulation produced submicron-scale tissue deformations that were measured at multiple positions over a 1-mm2 area. Surface wave velocity was measured and used to determine tissue stiffness. Elastic wave propagation velocity was measured and evaluated as a function of IOP and central corneal thickness.

RESULTS
Submicron corneal surface displacement amplitude (range, 0.005 to 0.5 μm) responses were measured with high sensitivity (0.24 nm). Corneal elastic wave velocity ranged from 2.4 to 4.2 m/s (mean, 3.5; 95% confidence interval, 3.2 to 3.8 m/s) and was correlated with central corneal thickness (r = 0.64, P < .001) and IOP (r = 0.52, P = .02).

CONCLUSIONS
Phase-sensitive optical coherence tomography imaging combined with microliter air-pulse mechanical tissue stimulation has sufficient detection sensitivity to observe submicron elastic wave propagation in corneal tissue. These measurements enable in vivo corneal stiffness determinations that will be further studied for use with disease detection and for monitoring clinical interventions.
Speckle tracking echocardiographic assessment of left ventricular longitudinal strain in female patients with subclinical hyperthyroidism
Authors: Abdelrazk Randa R. , El-Sehrawy Amr A. , Ghoniem Mohamed G. M. , Amer Maged Z. 
Published: December 2020

Background
Patients with subclinical hypothyroidism (SCH) are subjected to many cardiac changes. However, these changes are of gradual onset and cannot be usually detected using conventional diagnostic methods. Speckle tracking echocardiography (STE) is capable to detect cardiac function alterations usually unidentified by conventional echocardiography. The present study aimed to evaluate the role of STE in the detection of early cardiac changes in female patients with SCH.

Methods
The study included 33 female patients with SCH and 30 matched healthy volunteer women with normal thyroid functions who served as controls. Upon recruitment, all participants were subjected to careful history taking, thorough clinical examination and routine laboratory investigations, including thyroid-stimulating hormone and Free T4. The echocardiographic examination included conventional, color Doppler and two-dimensional STE.

Results
Analysis of conventional echocardiographic data revealed that patients had significantly higher end-systolic volume when compared with controls. In addition, it was noted that SCH patients had significantly lower mitral E/A ratio, isovolumetric relaxation time and significantly higher left atrium volume index in comparison to controls. In respect to STE data, we noted that patients had significantly lower values of mid-anteroseptal, apical lateral, apical septal, apical apex, AP4L strain and global strain % when compared with controls.

Conclusions
Patients with SCH have deteriorated global strain in comparison to healthy controls.
CKS1-dependent proteostatic regulation has dual roles combating acute myeloid leukemia whilst protecting normal hematopoiesis
Authors: Grey W. , Rio-Machin A. , Casado-Izquierdo P. , Miettinen J.J. , Copley F. , Parsons A. , Heckman C.A. , Cutillas P. , Gribben J. , Fitzgibbon J. , Bonnet D. 
Published: December 2020

AbstractAcute myeloid leukemia (AML) is an aggressive hematological disorder comprising a hierarchy of quiescent leukemic stem cells (LSCs) and proliferating blasts with limited self-renewal ability. AML has a dismal prognosis, with extremely low two-year survival rates in the poorest cytogenetic risk patients, primarily due to the failure of intensive chemotherapy protocols unable to deplete LSCs, which reconstitute the diseasein vivo, and the significant toxicity towards healthy hematopoietic cells. Whilst much work has been done to identify genetic and epigenetic vulnerabilities in AML LSCs, little is known about protein dynamics and the role of protein degradation in drug resistance and relapse. Here, using a highly specific inhibitor of the SCFSKP2-CKS1complex, we report a dual role for CKS1-dependent protein degradation in reducing AML blastsin vivo, and importantly depleting LSCs. Whilst many AML LSC targeted therapies show significant toxicity to healthy hematopoiesis, inhibition of CKS1-dependent protein degradation has the opposite effect, protecting normal hematopoietic cells from chemotherapeutic toxicity. Together these findings demonstrate CKS1-dependent proteostasis is key for normal and malignant hematopoiesis.SignificanceCKS1-dependent protein degradation is a specific vulnerability in AML LSCs. Specific inhibition of SCFSKP2-CKS1is lethal toCKS1BhighAML blasts and all AML LSCs. Normal hematopoiesis is protected from chemotherapeutic toxicity by inhibition of CKS1-dependent protein degradation, substantiating a dual role for CKS1-dependent protein degradation in clinical treatment of AML.
Novel insights into the mode of action of 1,4-dioxane using a systems screening approach
Authors: Charkoftaki Georgia , Golla Jaya Prakash , Santos-Neto Alvaro , Orlicky David J. , Garcia-Milian Rolando , Chen Ying , Rattray Nicholas J.W. , Cai Yuping , Wang Yewei , Shern Colin T , Mironova Varvara , Wang Yensheng , Johnson Caroline H. , Thompson David C. , Vasiliou Vasilis 
Published: December 2020

Abstract1,4-Dioxane (1,4-DX) is an environmental contaminant found in drinking water throughout the United States (US). While it is a suspected liver carcinogen, there is no federal or state maximum contaminant level for 1,4-DX in drinking water. Very little is known about the mechanisms by which this chemical elicits liver carcinogenicity. In the present study, female BDF-1 mice were exposed to 1,4-DX (0, 50, 500 and 5,000 mg/L) in their drinking water for one or four weeks, to explore the toxic effects. Histopathological studies and a multi-omics approach (transcriptomics and metabolomics) were performed to investigate potential mechanisms of toxicity. Immunohistochemical analysis of the liver revealed increased H2AXγ-positive hepatocytes (a marker of DNA double strand breaks), and an expansion of precholangiocytes (reflecting both DNA damage and repair mechanisms) after exposure. Liver transcriptomics revealed 1,4-DX-induced perturbations in signaling pathways predicted to impact the oxidative stress response, detoxification, and DNA damage. Liver, kidney, feces and urine metabolomic profiling revealed no effect of 1,4-DX exposure, and bile acid quantification in liver and feces similarly showed no effect of exposure. We speculate that the results may be reflective of DNA damage being counterbalanced by the repair response, with the net result being a null overall effect on the systemic biochemistry of the exposed mice. Our results show a novel approach for the investigation of environmental chemicals that do not elicit cell death but have activated the repair systems in response to 1,4-DX exposure.
Feeding intervention potentiates the effect of mechanical loading to induce new bone formation in mice
Authors: Samvelyan Hasmik Jasmine , Mathers John Cummings , Skerry Timothy Michael 
Published: December 2020

AbstractThe benefits of increased human lifespan depend upon duration of healthy, independent living; the healthspan. Bone-wasting disorders contribute significantly to loss of independence, frailty and morbidity in older people. Therefore, there is an unmet need globally for lifestyle interventions to reduce the likelihood of bone fractures with age. Although many mechanisms are involved in disorders of bone loss, there is no single regulatory pathway and, therefore, there is no single treatment available to prevent their occurrence. Our aim in these studies was to determine whether fasting/feeding interventions alter the effect of mechanical loading on bone anabolic activities and increase bone mass. In young 17-week-old mice, 16-hour fasting period followed by reintroduction of food for 2 hours increased markedly the potency of mechanical loading, that mimics the effect of exercise, to induce new cortical bone formation. Consistent with this finding, fasting and re-feeding increased the response of bone to a loading stimulus that, alone, does not stimulate new bone formation in ad-lib fed mice. Older mice (20-months) experienced no potentiation of loading-induced bone formation with the same timing of feeding interventions. Interestingly, the pre-, prandial and postprandial endocrine responses in older mice were different from those in young animals. The hormones that change in response to timing of feeding have osteogenic effects that interact with loading-mediated effects. Our findings indicate associations between timing of food ingestion and bone adaptation to loading. If translated to humans, such non-pharmacological lifestyle interventions may benefit skeletal health of humans throughout life-course and in older age.
Attentionally modulated subjective images reconstructed from brain activity
Authors: Horikawa Tomoyasu , Kamitani Yukiyasu 
Published: December 2020

SummaryVisual image reconstruction from brain activity produces images whose features are consistent with the neural representations in the visual cortex given arbitrary visual instances [1–3], presumably reflecting the person’s visual experience. Previous reconstruction studies have been concerned either with how stimulus images are faithfully reconstructed or with whether mentally imagined contents can be reconstructed in the absence of external stimuli. However, many lines of vision research have demonstrated that even stimulus perception is shaped both by stimulus-induced processes and top-down processes. In particular, attention (or the lack of it) is known to profoundly affect visual experience [4–8] and brain activity [9–21]. Here, to investigate how top-down attention impacts the neural representation of visual images and the reconstructions, we use a state-of-the-art method (deep image reconstruction [3]) to reconstruct visual images from fMRI activity measured while subjects attend to one of two images superimposed with equally weighted contrasts. Deep image reconstruction exploits the hierarchical correspondence between the brain and a deep neural network (DNN) to translate (decode) brain activity into DNN features of multiple layers, and then create images that are consistent with the decoded DNN features [3, 22, 23]. Using the deep image reconstruction model trained on fMRI responses to single natural images, we decode brain activity during the attention trials. Behavioral evaluations show that the reconstructions resemble the attended rather than the unattended images. The reconstructions can be modeled by superimposed images with contrasts biased to the attended one, which are comparable to the appearance of the stimuli under attention measured in a separate session. Attentional modulations are found in a broad range of hierarchical visual representations and mirror the brain–DNN correspondence. Our results demonstrate that top-down attention counters stimulus-induced responses and modulate neural representations to render reconstructions in accordance with subjective appearance. The reconstructions appear to reflect the content of visual experience and volitional control, opening a new possibility of brain-based communication and creation.
Conflict-mediated tasks for studying the act of facing threats in pursuit of rewards
Authors: Illescas-Huerta Elizabeth , Ramirez-Lugo Leticia , Sierra Rodrigo Ordonez , Quillfeldt Jorge A. , Sotres-Bayon Francisco 
Published: December 2020

AbstractSurvival depends on the ability of animals to avoid threats and approach rewards. Traditionally, these two opposing motivational systems have been studied separately. In nature, however, they regularly occur simultaneously. When threat- and reward-eliciting stimuli (learned or unlearned) co-occur, a motivational conflict emerges that challenges individuals to weigh available options and execute a single behavioral response (avoid or approach). Previous animal models using approach-avoidance conflicts have often focused on the ability to avoid threats by forgoing the opportunity to obtain rewards. In contrast, behavioral tasks designed to capitalize on the ability to actively choose to execute approach behaviors despite threats are lacking. Thus, we developed three conflict-mediated tasks to directly study rats confronting threats to obtain rewards guided by innate and conditioned cues. One conflict task involves crossing a potentially electrified grid to obtain food on the opposite end of a straight alley, the second task is based on the step-down threat avoidance paradigm, and the third one is a modified version of the open field test. We used diazepam to pharmacologically validate conflict-mediated behaviors in our tasks. We found that, regardless of whether competing stimuli were conditioned or innate, a low diazepam dose facilitated taking action to obtain rewards in the face of threats during conflict, without affecting choice behavior when there was no conflict involved. Using this validated set of innate/learned conflict-mediated tasks could help understand the underlying brain mechanisms that allow animals to confront threats, by actively suppressing defensive responses, to achieve goals.
SPINT2 controls SARS-CoV-2 viral infection and is associated to disease severity
Authors: Alvarez Carlos Ramirez , Sharma Ashwini Kumar , Kee Carmon , Thomas Leonie , Boulant Steeve , Herrmann Carl 
Published: December 2020

AbstractCOVID-19 outbreak is the biggest threat to human health in recent history. Currently, there are over 1.5 million related deaths and 75 million people infected around the world (as of 22/12/2020). The identification of virulence factors which determine disease susceptibility and severity in different cell types remains an essential challenge. The serine proteaseTMPRSS2has been shown to be important for S protein priming and viral entry, however, little is known about its regulation.SPINT2is a member of the family of Kunitz type serine protease inhibitors and has been shown to inhibitTMPRSS2. Here, we explored the existence of a co-regulation betweenSPINT2/TMPRSS2and found a tightly regulated protease/inhibitor expression balance across tissues. We found thatSPINT2negatively correlates with SARS-CoV-2 expression in Calu-3 and Caco-2 cell lines and was down-regulated in secretory cells from COVID-19 patients. We validated our findings using Calu-3 cell lines and observed a strong increase in viral load afterSPINT2knockdown. Additionally, we evaluated the expression ofSPINT2in datasets from comorbid diseases using bulk and scRNA-seq data. We observed its down-regulation in colon, kidney and liver tumors as well as in alpha pancreatic islets cells from diabetes Type 2 patients, which could have implications for the observed comorbidities in COVID-19 patients suffering from chronic diseases.
Presynaptic autophagy is coupled to the synaptic vesicle cycle via ATG-9
Authors: Yang Sisi , Park Daehun , Manning Laura , Hill Sarah E. , Cao Mian , Xuan Zhao , Gonzalez Ian , Shao Lin , Okeke Ifechukwu , De Camilli Pietro , Colón-Ramos Daniel A. 
Published: December 2020

SummaryAutophagy is a cellular degradation pathway essential for neuronal health and function. Autophagosome biogenesis occurs at synapses, is locally regulated and increases in response to neuronal activity. The mechanisms that couple autophagosome biogenesis to synaptic activity remain unknown. In this study we determine that trafficking of ATG-9, the only transmembrane protein in the core autophagy pathway, links the synaptic vesicle cycle with autophagy. ATG-9 positive vesicles inC. elegansare generated from the trans-Golgi network via AP3-dependent budding, and delivered to presynaptic sites. At presynaptic sites, ATG-9 undergoes exo-endocytosis in an activity-dependent manner. Mutations that disrupt endocytosis, including one associated with Parkinson’s disease, result in abnormal ATG-9 accumulation at clathrin-rich synaptic foci and defects in activity-dependent presynaptic autophagy. Our findings uncover regulated key steps of ATG-9 trafficking at presynaptic sites, and provide evidence that ATG-9 exo-endocytosis couples autophagosome biogenesis at presynaptic sites with the activity-dependent synaptic vesicle cycle.HighlightsInC. elegans, ATG-9 is delivered to presynaptic sites in vesicles generated from the trans-Golgi network via AP-3-dependent buddingATG-9 vesicles undergo activity-dependent exo-endocytosis at presynaptic sitesMutations in endocytic proteins, including a mutation associated with Parkinson’s disease, result in abnormal ATG-9 accumulation at clathrin-rich fociAbnormal accumulation of ATG-9 at clathrin-rich foci is associated with defects in activity-dependent presynaptic autophagy
Functional evolution of a bark beetle odorant receptor clade detecting monoterpenoids of different ecological origins
Authors: Hou Xiao-Qing , Yuvaraj Jothi Kumar , Roberts Rebecca E. , Zhang Dan-Dan , Unelius C. Rikard , Löfstedt Christer , Andersson Martin N. 
Published: December 2020

AbstractInsects detect odors using an array of odorant receptors (ORs), which may expand through gene duplication. How specificities evolve and new functions arise in related ORs within a species remain poorly investigated. We addressed this question by functionally characterizing ORs from the Eurasian spruce bark beetleIps typographus, in which antennal detection and behavioral responses to pheromones, volatiles from host and non-host trees, and fungal symbionts are well described. In contrast, knowledge of OR function is restricted to two receptors detecting the pheromone compounds (S)-(–)-ipsenol (ItypOR46) and (R)-(–)-ipsdienol (ItypOR49). These receptors belong to a species-specific OR-lineage comprising seven ItypORs. To gain insight into the functional evolution of related ORs, we characterized the five remaining ORs in this clade, usingXenopusoocytes. Two receptors responded primarily to the host tree monoterpenes (+)-3-carene (ItypOR25) andp-cymene (ItypOR27). Two receptors responded to oxygenated monoterpenoids produced in relatively large amounts by the beetle-associated fungi, with ItypOR23 specific for (+)-trans-(1R,4S)-4-thujanol, and ItypOR29 responding to (+)-isopinocamphone and similar ketones. ItypOR28 responded to the pheromoneE-myrcenol from the competitorIps duplicatus. Overall, the OR responses match well with those of previously characterized olfactory sensory neuron classes except that neurons detectingE-myrcenol have not been identified. The characterized ORs are under strong purifying selection and demonstrate a shared functional property in that they all primarily respond to monoterpenoids. The variation in functional groups among OR ligands and their diverse ecological origins suggest that neofunctionalization has occurred early in the evolution of this OR-lineage following gene duplication.
Identification of proximal SUMO-dependent interactors using SUMO-ID
Authors: Barroso-Gomila Orhi , Trulsson Fredrik , Muratore Veronica , Canosa Iñigo , Merino-Cacho Laura , Cortazar Ana Rosa , Perez Coralia , Azkargorta Mikel , Iloro Ibon , Carracedo Arkaitz , Aransay Ana M , Elortza Felix , Mayor Ugo , Vertegaal Alfred C. O. , Barrio Rosa , Sutherland James D. 
Published: December 2020

ABSTRACTThe fast dynamics and reversibility of posttranslational modifications by the ubiquitin family pose significant challenges for research. Here we present SUMO-ID, a technology that merges proximity biotinylation by TurboID and protein-fragment complementation to find SUMO-dependent interactors of proteins of interest. We developed an optimized split-TurboID version and show SUMO interaction-dependent labelling of proteins proximal to PML and RANGAP1. SUMO-dependent interactors of PML are involved in transcription, DNA damage, stress response and SUMO modification and are highly enriched in SUMO Interacting Motifs, but may only represent a subset of the total PML proximal proteome. Likewise, SUMO-ID also allowed us to identify novel interactors of SUMOylated SALL1, a less characterized SUMO substrate. Thus, SUMO-ID is a powerful tool that allows to study the consequences of SUMO-dependent interactions, and may further unravel the complexity of the ubiquitin code.