Miracle-dz/UniFAR-FTUs huggingface dataset:
Mapping allele with resolved carrier status of Robertsonian and reciprocal translocation in human preimplantation embryos

Significance In in vitro fertilization, it is difficult, if not impossible, with current methods to determine whether an embryo carries a chromosomal translocation. We have established a method for diagnosing chromosome abnormality named “Mapping Allele with Resolved Carrier Status” (MaReCs), which enables simultaneous screening of chromosomal ploidy and translocation in an embryo by next-generation sequencing. We demonstrate and validate that MaReCs allows accurate selection of translocation-free embryos, preventing the transmission of chromosomal translocations to future generations. Reciprocal translocations (RecT) and Robertsonian translocations (RobT) are among the most common chromosomal abnormalities that cause infertility and birth defects. Preimplantation genetic testing for aneuploidy using comprehensive chromosome screening for in vitro fertilization enables embryo selection with balanced chromosomal ploidy; however, it is normally unable to determine whether an embryo is a translocation carrier. Here we report a method named “Mapping Allele with Resolved Carrier Status” (MaReCs), which enables chromosomal ploidy screening and resolution of the translocation carrier status of the same embryo. We performed MaReCs on 108 embryos, of which 96 were from 13 RecT carriers and 12 were from three RobT carriers. Thirteen of the sixteen patients had at least one diploid embryo. We have confirmed the accuracy of our carrier status determination in amniotic fluid karyotyping of seven cases as well as in the live birth we have thus far. Therefore, MaReCs accurately enables the selection of translocation-free embryos from patients carrying chromosomal translocations. We expect MaReCs will help reduce the propagation of RecT/RobT in the human population.
Right-Sizing Geo-distributed Data Centers for Availability and Latency

We show cloud developers how to right size data center (DC) capacity for geo-distributed applications deployed on several multi-megawatt DCs, possibly also using many smaller edge DCs. Note that capacity considerations for a geo-distributed infrastructure do not decompose into individual DC capacity planning. When edge DCs are used, heterogeneous availability and costs affect the capacity split between the edge and core DCs. Non-uniform spatial distribution of clients and interdependence between latency and availability constraints make it non-trivial to provision the right capacity at each DC. We develop a geo-distributed capacity planning framework to capture the key factors that influence capacity, ranging from application demand patterns, latency and availability requirements, DC cost-availability trade-offs, and data replication overheads. We apply our framework to a realistic application and DC infrastructure setting to gather insights into how capacity should be provisioned and allocated across DCs for a representative set of requirements and costs.
Electron–hole asymmetry of the topological surface states in strained HgTe

Significance Topological insulators possess metallic surfaces states that are generally perceived as electrons and holes with a linear symmetric dispersion around the Dirac point. In this work, we show that this symmetry is significantly distorted in the 3D topological insulator-strained HgTe. In thermopower experiments, we show a distinctively different behavior of surface electrons and holes that originates from a strongly asymmetric dispersion of surface states. Nonetheless, the surface states themselves remain topologically protected as evidenced by the observation of an ambipolar surface quantum Hall effect and quantum oscillations in the thermoelectric response. This observation shows that the physics of topological surface states in 3D topological insulators is far richer than previously envisaged. Topological insulators are a new class of materials with an insulating bulk and topologically protected metallic surface states. Although it is widely assumed that these surface states display a Dirac-type dispersion that is symmetric above and below the Dirac point, this exact equivalence across the Fermi level has yet to be established experimentally. Here, we present a detailed transport study of the 3D topological insulator-strained HgTe that strongly challenges this prevailing viewpoint. First, we establish the existence of exclusively surface-dominated transport via the observation of an ambipolar surface quantum Hall effect and quantum oscillations in the Seebeck and Nernst effect. Second, we show that, whereas the thermopower is diffusion driven for surface electrons, both diffusion and phonon drag contributions are essential for the hole surface carriers. This distinct behavior in the thermoelectric response is explained by a strong deviation from the linear dispersion relation for the surface states, with a much flatter dispersion for holes compared with electrons. These findings show that the metallic surface states in topological insulators can exhibit both strong electron–hole asymmetry and a strong deviation from a linear dispersion but remain topologically protected.
The sclerostin story: From human genetics to the development of novel anabolic treatment for osteoporosis

Sclerosteosis and Van Buchem disease are two rare bone sclerosing disorders characterized by increased bone mineral density, tall stature and entrapment of cranial nerves due to overgrowth of a highly dense bone. Recent advances in human genetics have revealed the genetic background of these disorders by cloning the SOST gene, which is localized on chromosome region 17q12-q21 and codes for sclerostin. Sclerostin is a protein produced almost exclusively from osteocytes inhibiting bone formation by both osteoblasts and osteocytes. At the molecular level, sclerostin inhibits the Wnt signaling pathway, which plays a critical role in osteoblast development and function. Induced sclerostin deficiency in mice reproduces the bone sclerosing human diseases, while sclerostin excess leads to bone loss and reduced bone strength. The extracellular nature of sclerostin has rendered it a promising target for the development of novel anti-osteoporotic treatment. Otherwise healthy carriers of the SOST mutation present with increased bone mass and low levels of sclerostin in serum in contrast to patients with sclerosteosis, who exhibit undetectable levels, thus pointing to the possibility of titration of sclerostin levels in the circulation. Based on these unique characteristics, human anti-sclerostin antibodies have been developed and tested in ovariectomized rats and monkeys, demonstrating very promising results in bone formation. Clinical phase II and III trials are currently underway thereby translating human genetics to drug development.
An Official American Thoracic Society/European Respiratory Society Policy Statement: Enhancing Implementation, Use, and Delivery of Pulmonary Rehabilitation.

RATIONALE Pulmonary rehabilitation (PR) has demonstrated physiological, symptom-reducing, psychosocial, and health economic benefits for patients with chronic respiratory diseases, yet it is underutilized worldwide. Insufficient funding, resources, and reimbursement; lack of healthcare professional, payer, and patient awareness and knowledge; and additional patient-related barriers all contribute to the gap between the knowledge of the science and benefits of PR and the actual delivery of PR services to suitable patients. OBJECTIVES The objectives of this document are to enhance implementation, use, and delivery of pulmonary rehabilitation to suitable individuals worldwide. METHODS Members of the American Thoracic Society (ATS) Pulmonary Rehabilitation Assembly and the European Respiratory Society (ERS) Rehabilitation and Chronic Care Group established a Task Force and writing committee to develop a policy statement on PR. The document was modified based on feedback from expert peer reviewers. After cycles of review and revisions, the statement was reviewed and formally approved by the Board of Directors of the ATS and the Science Council and Executive Committee of the ERS. MAIN RESULTS This document articulates policy recommendations for advancing healthcare professional, payer, and patient awareness and knowledge of PR, increasing patient access to PR, and ensuring quality of PR programs. It also recommends areas of future research to establish evidence to support the development of an updated funding and reimbursement policy regarding PR. CONCLUSIONS The ATS and ERS commit to undertake actions that will improve access to and delivery of PR services for suitable patients. They call on their members and other health professional societies, payers, patients, and patient advocacy groups to join in this commitment.
Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact

A common strategy by which developing neurons locate their synaptic partners is through projections to circuit-specific neuropil sublayers. Once established, sublayers serve as a substrate for selective synapse formation, but how sublayers arise during neurodevelopment remains unknown. Here we identify the earliest events that initiate formation of the direction-selective circuit in the inner plexiform layer of mouse retina. We demonstrate that radially-migrating newborn starburst amacrine cells establish homotypic contacts on arrival at the inner retina. These contacts, mediated by the cell-surface protein MEGF10, trigger neuropil innervation resulting in generation of two sublayers comprising starburst-cell dendrites. This dendritic scaffold then recruits projections from circuit partners. Abolishing MEGF10-mediated contacts profoundly delays and ultimately disrupts sublayer formation, leading to broader direction tuning and weaker direction-selectivity in retinal ganglion cells. Our findings reveal a mechanism by which differentiating neurons transition from migratory to mature morphology, and highlight this mechanism’s importance in forming circuit-specific sublayers. Impact statement Selective synapse formation in a retinal motion-sensitive circuit is orchestrated by starburst amacrine cells, which use homotypic interactions to initiate formation of a dendritic scaffold that recruits projections from circuit partners.
Inhibition of miRNA-210 reverses nicotine-induced brain hypoxic-ischemic injury in neonatal rats

Maternal tobacco use in pregnancy increases the risk of neurodevelopmental disorders and neurobehavioral deficits in postnatal life. The present study tested the hypothesis that perinatal nicotine exposure exacerbated brain vulnerability to hypoxic-ischemic (HI) injury in neonatal rats through up-regulation of miR-210 expression in the developing brain. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps. Experiments of HI brain injury were performed in 10-day-old pups. Perinatal nicotine treatment significantly decreased neonatal body and brain weights, but increased the brain to body weight ratio. Perinatal nicotine exposure caused a significant increase in HI brain infarct size in the neonates. In addition, nicotine enhanced miR-210 expression and significantly attenuated brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase isoform B (TrkB) protein abundance in the brain. Of importance, intracerebroventricular administration of a miR-210 inhibitor (miR-210-LNA) significantly decreased HI-induced brain infarct size and reversed the nicotine-increased vulnerability to brain HI injury in the neonate. Furthermore, miR-210-LNA treatment also reversed nicotine-mediated down-regulation of BDNF and TrkB protein expression in the neonatal brains. These findings provide novel evidence that the increased miR-210 plays a causal role in perinatal nicotine-induced developmental programming of ischemic sensitive phenotype in the brain. It represents a potential novel therapeutic approach for treatment of brain hypoxic-ischemic encephalopathy in the neonate-induced by fetal stress.
Jiangsu Four Cancers Study: a large case–control study of lung, liver, stomach, and esophageal cancers in Jiangsu Province, China

Cancer is a major public health burden both globally and in China. The most common cancer-related deaths in China are attributable to cancers of the lung, liver, stomach, and esophagus. Previous epidemiologic studies on cancer in China have often been limited by small sample sizes, inconsistent measurements, and lack of precise and accurate data. The Jiangsu Four Cancers (JFC) Study is a population-based case–control study carried out in an effort to obtain consistent and high-quality data to investigate the life style, behavioral, environmental, and genetic factors associated with the four major cancers in China. The aim of this paper is to describe the overall design of the JFC Study and report selected findings on the major risk factors for cancers. Epidemiologic data were collected from 2003 to 2010 through in-person interviews using a structured questionnaire and blood samples were drawn. Unconditional logistic regression was used to estimate the associations of putative risk factors with risks of cancers of the lung, liver, stomach, and esophagus. The study included 2871 lung cancer cases, 2018 liver cancer cases, 2969 esophageal cancer cases, 2216 stomach cancer cases, and 8019 community controls. Low educational level, low income level, tobacco smoking, alcohol drinking, and family history of cancer were confirmed as risk factors for these major cancers. The JFC Study is one of the largest case–control studies of cancers in the Chinese population and will serve as a rich resource for future research on the four major cancers in China.
Neurocognitive Function after Cardiac Surgery: From Phenotypes to Mechanisms

For half a century, it has been known that some patients experience neurocognitive dysfunction after cardiac surgery; however, defining its incidence, course, and causes remains challenging and controversial. Various terms have been used to describe neurocognitive dysfunction at different times after cardiac surgery, ranging from “postoperative delirium” to “postoperative cognitive dysfunction or decline. ” Delirium is a clinical diagnosis included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Postoperative cognitive dysfunction is not included in the DSM-5 and has been heterogeneously defined, though a recent international nomenclature effort has proposed standardized definitions for it. Here, the authors discuss pathophysiologic mechanisms that may underlie these complications, review the literature on methods to prevent them, and discuss novel approaches to understand their etiology that may lead to novel treatment strategies. Future studies should measure both delirium and postoperative cognitive dysfunction to help clarify the relationship between these important postoperative complications.
Beneficial effects of oleuropein on glucose uptake and on parameters relevant to the normal homeostatic mechanisms of glucose regulation in rat skeletal muscle

Oleuropein, the main constituents of leaves and fruits of the olive tree, has been demonstrated to exert various therapeutic and pharmacological properties including antidiabetic effect. However, the effectiveness of oleuropein on glucose homeostasis in intact rat skeletal muscle ex vivo has never been explored. Therefore, our current study was carried out to investigate and confirm the beneficial effect of oleuropein (1.5 mM) on glucose uptake and on parameters relevant to the normal homeostatic mechanisms of glucose regulation in rat skeletal muscle. For this purpose, soleus muscles were incubated for 12 hr without (control) or with oleuropein, in the presence or absence of AMP‐activated protein kinase (AMPK) inhibitor, compound C, or wortmannin, an inhibitor of phosphatidylinositol kinase. Oleuropein‐stimulated glucose transport, plasmalemmal glucose transporter 4 (GLUT4), and phosphorylation of phosphatidylinositol kinase and AMPK were examined. We observed that oleuropein treatment enhanced glucose transport, GLUT4 translocation, and AMPK phosphorylation. The oleuropein‐stimulated glucose uptake and GLUT4 translocation were inhibited by compound C and were not affected by wortmannin. These results suggest that increased glucose uptake induced by oleuropein might be mediated through activation of AMPK and the subsequent increase in GLUT4 translocation in skeletal muscles.
Development of the Malocclusion Impact Questionnaire (MIQ) to measure the oral health-related quality of life of young people with malocclusion: part 1 – qualitative inquiry

Objectives To seek the views of adolescents with malocclusion about how the appearance and arrangement of their teeth affects their everyday life and to incorporate these views into a new Malocclusion Impact Questionnaire (MIQ). Methods Semi-structured interviews were undertaken with a purposive sample of 30 young people (10–16 years) referred for orthodontic treatment to two dental teaching hospitals. The interviews were recorded, transcribed and analysed using framework analysis. Several themes and sub themes were identified and these were used to identify items to include in the new measure. Result Three themes emerged which were: concerns about the appearance of their teeth, effect on social interactions and oral health/function. Participants expressed the view that their teeth did not look normal, causing them embarrassment and a lack of confidence, particularly when they were with their peers or having their photograph taken. Concerns regarding the potential effect of a malocclusion on oral health, in terms of food becoming stuck between crooked teeth, interferences when chewing and increased risk of damaging the teeth were also identified. The themes were used to generate individual items for inclusion in the questionnaire. Conclusions Common themes relating to the impact of malocclusion on the lives of young people were identified and generated items for the new MIQ to measure the oral health-related quality of life of young people with malocclusion. Part 2 outlines the further development and testing of the MIQ.
Analysis of Partial Axial Symmetry on 3D Surfaces and Its Application in the Restoration of Cultural Heritage Objects

Symmetry is a ubiquitous concept that can help to understand the structure of real objects. One of the main challenging problems in the analysis of symmetry is the robustness against high partiality, i.e., when the support of the symmetry in the input geometry is small. In this paper, we address the problem of finding the partial axial symmetry of 3D objects through the analysis of surface descriptors with invariance to partiality. These descriptors are used to reduce the search space of axial symmetric correspondences, and allows us to design an effective and efficient algorithm to detect the generator axis of the symmetry. Our algorithm collects enough evidence of the presence of the axial symmetry in a consensus-based approach. Our algorithm can also identify the support of the axial symmetry. Our experiments show the robustness of our method in challenging scenarios. We show that our method is good to generate plausible restorations of damaged cultural heritage objects.
Shape Adaptation Exaggerates Shape Differences

Adaptation to different visual properties can produce distinct patterns of perceptual aftereffect. Some, such as those following adaptation to color, seem to arise from recalibrative processes. These are associated with a reappraisal of which physical input constitutes a normative value in the environment—in this case, what appears “colorless,” and what “colorful. ” Recalibrative aftereffects can arise from coding schemes in which inputs are referenced against malleable norm values. Other aftereffects seem to arise from contrastive processes. These exaggerate differences between the adaptor and other inputs without changing the adaptor’s appearance. There has been conjecture over which process best describes adaptation-induced distortions of spatial vision, such as of apparent shape or facial identity. In 3 experiments, we determined whether recalibrative or contrastive processes underlie the shape aspect ratio aftereffect. We found that adapting to a moderately elongated shape compressed the appearance of narrower shapes and further elongated the appearance of more-elongated shapes (Experiment 1). Adaptation did not change the perceived aspect ratio of the adaptor itself (Experiment 2), and adapting to a circle induced similar bidirectional aftereffects on shapes narrower or wider than circular (Experiment 3). Results could not be explained by adaptation to retinotopically local edge orientation or single linear dimensions of shapes. We conclude that aspect ratio aftereffects are determined by contrastive processes that can exaggerate differences between successive inputs, inconsistent with a norm-referenced representation of aspect ratio. Adaptation might enhance the salience of novel stimuli rather than recalibrate one’s sense of what constitutes a “normal” shape.
Neuroserpin restores autophagy and promotes functional recovery after acute spinal cord injury in rats

This study is to reveal the characteristics of autophagy and the effect of neuroserpin (NSP) treatment on autophagy during the process of functional recovery following spinal cord injury (SCI). After the clip compress rat model of SCI had been made, autophagy-associated proteins, including LC3-II, beclin-1 and p62, were evaluated at 2, 4, 24, 72 h, and 168 h in the experimental group, and the sham group as control. Transmission electron microscopy (TEM) was further used for autophagy detection at 4 and 72 h. All the male rats were randomly divided into three groups: Sham, vehicle and NSP group. NSP or an equal volume of saline vehicle was administered via intrathecal injection immediately after SCI. Each group was further divided into subgroups for the following experiments: i)Western blot (LC3-II and p62); ii) Immunofluorescent double staining (LC3/MAP-2/DAPI); iii) Nissl staining and Basso Beattie Bresnahan (BBB score) for NSP neuroprotection evaluation. Our results revealed both LC3-II and p62 expression trended upward at 24, 72 and 168 h after SCI. The LC3-II peaked at 72 h, while p62 peaked at 24 h. Beclin-1 dropped significantly at 72 and 168 h. TEM results showed that autophagosomes largely accumulated at 72 h after SCI when compared with the sham group. Western blot analysis showed that LC3-II and p62 were markedly decreased with NSP treatment at 72 h after injury compared with that of the vehicle-group. Immunofluorescent double labeling indicated that accumulation of autophagosomes was reduced in the NSP group. Further, post-SCI treatment with NSP improved the BBB scale and increased the number of anterior horn motor neurons. Together, this study demonstrates that autophagic flux is impaired, meanwhile NSP restores autophagic flux and promotes functional recovery after SCI in rats.