bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle
Authors: Halsall John A. , Andrews Simon , Krueger Felix , Rutledge Charlotte E. , Ficz Gabriella , Reik Wolf , Turner Bryan M. 
Published: February 2021

AbstractChromatin configuration influences gene expression in eukaryotes at multiple levels, from individual nucleosomes to chromatin domains several Mb long. Post-translational modifications (PTM) of core histones seem to be involved in chromatin structural transitions, but how remains unclear. To explore this, we used ChIP-seq and two cell types, HeLa and lymphoblastoid (LCL), to define how changes in chromatin packaging through the cell cycle influence the distributions of three transcription-associated histone modifications, H3K9ac, H3K4me3 and H3K27me3. We show that chromosome regions (bands) of 10–50 Mb, detectable by immunofluorescence microscopy of metaphase (M) chromosomes, are also present in G1 and G2. They comprise 1–5 Mb sub-bands that differ between HeLa and LCL but remain consistent through the cell cycle. The same sub-bands are defined by H3K9ac and H3K4me3, while H3K27me3 spreads more widely. We found little change between cell cycle phases, whether compared by 5 Kb rolling windows or when analysis was restricted to functional elements such as transcription start sites and topologically associating domains. Only a small number of genes showed cell-cycle related changes: at genes encoding proteins involved in mitosis, H3K9 became highly acetylated in G2M, possibly because of ongoing transcription. In conclusion, modified histone isoforms H3K9ac, H3K4me3 and H3K27me3 exhibit a characteristic genomic distribution at resolutions of 1 Mb and below that differs between HeLa and lymphoblastoid cells but remains remarkably consistent through the cell cycle. We suggest that this cell-type-specific chromosomal bar-code is part of a homeostatic mechanism by which cells retain their characteristic gene expression patterns, and hence their identity, through multiple mitoses.
Freely scalable and reconfigurable optical hardware for deep learning
Authors: Bernstein Liane , Sludds Alexander , Hamerly Ryan , Sze Vivienne , Emer Joel , Englund Dirk 
Published: February 2021

AbstractAs deep neural network (DNN) models grow ever-larger, they can achieve higher accuracy and solve more complex problems. This trend has been enabled by an increase in available compute power; however, efforts to continue to scale electronic processors are impeded by the costs of communication, thermal management, power delivery and clocking. To improve scalability, we propose a digital optical neural network (DONN) with intralayer optical interconnects and reconfigurable input values. The path-length-independence of optical energy consumption enables information locality between a transmitter and a large number of arbitrarily arranged receivers, which allows greater flexibility in architecture design to circumvent scaling limitations. In a proof-of-concept experiment, we demonstrate optical multicast in the classification of 500 MNIST images with a 3-layer, fully-connected network. We also analyze the energy consumption of the DONN and find that digital optical data transfer is beneficial over electronics when the spacing of computational units is on the order of $$>10\,\upmu $$

>
10

μ

m.
Deformation of the Fermi surface of a spinless two-dimensional electron gas in presence of an anisotropic Coulomb interaction potential
Authors: Ciftja Orion 
Published: February 2021

AbstractWe consider the stability of the circular Fermi surface of a two-dimensional electron gas system against an elliptical deformation induced by an anisotropic Coulomb interaction potential. We use the jellium approximation for the neutralizing background and treat the electrons as fully spin-polarized (spinless) particles with a constant isotropic (effective) mass. The anisotropic Coulomb interaction potential considered in this work is inspired from studies of two-dimensional electron gas systems in the quantum Hall regime. We use a Hartree–Fock procedure to obtain analytical results for two special Fermi liquid quantum electronic phases. The first one corresponds to a system with circular Fermi surface while the second one corresponds to a liquid anisotropic phase with a specific elliptical deformation of the Fermi surface that gives rise to the lowest possible potential energy of the system. The results obtained suggest that, for the most general situations, neither of these two Fermi liquid phases represent the lowest energy state of the system within the framework of the family of states considered in this work. The lowest energy phase is one with an optimal elliptical deformation whose specific value is determined by a complex interplay of many factors including the density of the system.
Pruritus is common in patients with chronic liver disease and is improved by nalfurafine hydrochloride
Authors: Yoshikawa Shuhei , Asano Takeharu , Morino Mina , Matsumoto Keita , Kashima Hitomi , Koito Yudai , Miura Takaya , Takahashi Yuko , Tsuboi Rumiko , Ishii Takehiro , Otake Haruka , Fujiwara Junichi , Sekine Masanari , Uehara Takeshi , Yuhashi Kazuhito , Matsumoto Satohiro , Asabe Shinichi , Miyatani Hiroyuki , Mashima Hirosato 
Published: February 2021

AbstractPruritus is known to be a common complication in hepatitis patients, but the exact frequency and degree are not fully elucidated. Thus, we evaluated pruritus of 450 patients with chronic liver disease at our hospital. Pruritus was observed in 240 (53%) of the patients. Pruritus was significantly associated with males (OR = 1.51, P = 0.038) and patients with alkaline phosphatase (ALP) ≥ 200 U/L (OR = 1.56, P = 0.0495) and was significantly less in HBsAg-positive patients (OR = 0.449, P = 0.004). Seasonally, there was no difference in the frequency of pruritus between summer and winter. Of the 24 refractory pruritus patients treated with nalfurafine, 17 (71%) indicated improvement of itch, which is defined as a decrease in the visual analog scale score ≥ 30 mm. Pruritus was improved by nalfurafine both during daytime and nighttime in the Kawashima’s scores evaluation. All patients who received nalfurafine exhibited improved Kawashima’s scores ≥ 1 point during the daytime or nighttime. In conclusion, pruritus occurred in > 50% of patients with chronic liver disease, and predictors of pruritus were males and ALP ≥ 200 U/L. Nalfurafine may be useful for pruritus, regardless of whether daytime or nighttime.
Risk compensation and face mask mandates during the COVID-19 pandemic
Authors: Yan Youpei , Bayham Jude , Richter Aaron , Fenichel Eli P. 
Published: February 2021

AbstractFace masks are an important component in controlling COVID-19, and policy orders to wear masks are common. However, behavioral responses are seldom additive, and exchanging one protective behavior for another could undermine the COVID-19 policy response. We use SafeGraph smart device location data and variation in the date that US states and counties issued face mask mandates as a set of natural experiments to investigate risk compensation behavior. We compare time at home and the number of visits to public locations before and after face mask orders conditional on multiple statistical controls. We find that face mask orders lead to risk compensation behavior. Americans subject to the mask orders spend 11–24 fewer minutes at home on average and increase visits to some commercial locations—most notably restaurants, which are a high-risk location. It is unclear if this would lead to a net increase or decrease in transmission. However, it is clear that mask orders would be an important part of an economic recovery if people otherwise overestimate the risk of visiting public places.
Theta-modulated oscillatory transcranial direct current stimulation over posterior parietal cortex improves associative memory
Authors: Vulić Katarina , Bjekić Jovana , Paunović Dunja , Jovanović Miloš , Milanović Slađan , Filipović Saša R. 
Published: February 2021

AbstractAssociative memory (AM) reflects the ability to remember and retrieve multiple pieces of information bound together thus enabling complex episodic experiences. Despite growing interest in the use of transcranial direct current stimulation (tDCS) for the modulation of AM, there are inconsistent evidence regarding its benefits. An alternative to standard constant tDCS could be the application of frequency-modulated tDCS protocols, that mimic natural function-relevant brain rhythms. Here, we show the effects of anodal tDCS oscillating in theta rhythm (5 Hz; 1.5 ± 0.1 mA)versusconstant anodal tDCS and sham over left posterior parietal cortex on cued recall of face-word associations. In a crossover design, each participant completed AM assessment immediately following 20-min theta-oscillatory, constant, and sham tDCS, as well as 1 and 5 days after. Theta oscillatory tDCS increased initial AM performance in comparison to sham, and so did constant tDCS. On the group level, no differences between oscillatory and constant tDCS were observed, but individual-level analysis revealed that some participants responded to theta-oscillatory but not to constant tDCS, and vice versa,which could be attributed to their different physiological modes of action. This study shows the potential of oscillatory tDCS protocols for memory enhancement to produce strong and reliable memory-modulating effects which deserve to be investigated further.
Visual outcomes of lens subluxation surgery with Cionni modified capsular tension rings in Marfan syndrome
Authors: Chen Tianhui , Deng Michael , Zhang Min , Chen Jiahui , Chen Zexu , Jiang Yongxiang 
Published: February 2021

AbstractMarfan syndrome (MFS) is a hereditary disease with an incidence of 0.3% in the general population. Approximately 60% of MFS patients with FBN1 gene mutation will suffer ectopia lentis (EL) from the age of 3. With the development of EL, severe loss of vision will accrue because of lens tilt and glaucoma. Cionni modified capsular tension rings (MCTR) has been applied in the surgery for EL in MFS patients. To evaluate visual acuity and safety of using MCTR during lens subluxation surgery in MFS patients, 66 MFS patients (110 eyes) were included in our study, with the mean duration of follow-up of 4.7 months (SD 1.76 months). The capsular bags were preserved in 101 eyes (91.81%) with MCTR implantation. There was an overall significant improvement in BCVA at 1-month follow-up which was maintained at 3 months. Multivariable linear regression revealed that older age at first visit was associated with greater postoperative BCVA at the 1-month follow-up (P = 0.007). A significant difference was found between different degrees of lens subluxation and the length of surgical time and complications. At follow-up, only two eyes (1.98%) were identified to have developed retinal detachments. In conclusion, better visual outcomes can be achieved when patients received an early operation with MCTR implantation.
White matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling
Authors: Sarma Manoj K. , Pal Amrita , Keller Margaret A. , Welikson Tamara , Ventura Joseph , Michalik David E. , Nielsen-Saines Karin , Deville Jaime , Kovacs Andrea , Operskalski Eva , Church Joseph A. , Macey Paul M. , Biswal Bharat , Thomas M. Albert 
Published: February 2021

AbstractIn perinatally HIV-infected (PHIV) children, neurodevelopment occurs in the presence of HIV-infection, and even with combination antiretroviral therapy (cART) the brain can be a reservoir for latent HIV. Consequently, patients often demonstrate long-term cognitive deficits and developmental delay, which may be reflected in altered functional brain activity. Our objective was to examine brain function in PHIV on cART by quantifying the amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo). Further, we studied ALFF and ReHo changes with neuropsychological performance and measures of immune health including CD4 count and viral loads in the HIV-infected youths. We found higher ALFF and ReHo in cerebral white matter in the medial orbital lobe for PHIV (N = 11, age mean ± sd = 22.5 ± 2.9 years) compared to controls (N = 16, age = 22.5 ± 3.0 years), with age and gender as co-variates. Bilateral cerebral white matter showed increased spontaneous regional activity in PHIV compared to healthy controls. No brain regions showed lower ALFF or ReHo in PHIV compared to controls. Higher log10 viral load was associated with higher ALFF and ReHo in PHIV in bilateral cerebral white matter and right cerebral white matter respectively after masking the outcomes intrinsic to the brain regions that showed significantly higher ALFF and ReHo in the PHIV compared to the control. Reductions in social cognition and abstract thinking in PHIV were correlated with higher ALFF at the left cerebral white matter in the left medial orbital gyrus and higher ReHo at the right cerebral white matter in the PHIV patients. Although neuroinflammation and associated neuro repair were not directly measured, the findings support their potential role in PHIV impacting neurodevelopment and cognition.
Body mass index trajectories and the risk for Alzheimer’s disease among older adults
Authors: Kang Seo Young , Kim Ye-Jee , Jang Wooyoung , Son Ki Young , Park Hye Soon , Kim Young Sik 
Published: February 2021

AbstractThe effect of body mass index (BMI) changes and variability on the risk for Alzheimer’s disease (AD) remains unclear. We analyzed 45,076 participants, whose BMI were measured on phase 1 (2002–2003), phase 2 (2004–2005), and phase 3 (2006–2007), of the Korean National Health Insurance Service-Health Screening Cohort. We evaluated the effect of 2- and 4-year BMI changes and BMI variability on the risk of AD using Cox regression models. In men, association between 2-year BMI changes, BMI variability, and the risk of AD was not significant. Risk of AD was higher in men whose BMI had decreased 10.1–15.0% over 4 years. In women, aHRs and 95% CIs for AD were 1.14 (1.02–1.29), 1.44 (1.17–1.79), and 1.51 (1.09–2.09) when 2-year BMI loss was 5.1–10.0%, 10.1–15.0%, and > 15.0%. The HRs for AD in women significantly increased when 4-year BMI loss was > 5.0%. The aHR and 95% CI for AD was 1.31 (1.17–1.46) in the 4th quartile of average successive variability (ASV) compared with the 1st quartile of ASV in women. BMI loss over 2- and 4-year period was associated with increased risk for AD, and risk increased in women with higher BMI variability. Appropriate body weight management is recommended to prevent AD.
Comprehensive characterization and quantification of adeno associated vectors by size exclusion chromatography and multi angle light scattering
Authors: McIntosh Nicole L. , Berguig Geoffrey Y. , Karim Omair A. , Cortesio Christa L. , De Angelis Rolando , Khan Ayesha A. , Gold Daniel , Maga John A. , Bhat Vikas S. 
Published: February 2021

AbstractAdeno associated virus (AAV) capsids are a leading modality for in vivo gene delivery. Complete and precise characterization of capsid particles, including capsid and vector genome concentration, is necessary to safely and efficaciously dose patients. Size exclusion chromatography (SEC) coupled to multiangle light scattering (MALS) offers a straightforward approach to comprehensively characterize AAV capsids. The current study demonstrates that this method provides detailed AAV characterization information, including but not limited to aggregation profile, size-distribution, capsid content, capsid molar mass, encapsidated DNA molar mass, and total capsid and vector genome titer. Currently, multiple techniques are required to generate this information, with varying accuracy and precision. In the current study, a new series of equations for SEC-MALS are used in tandem with intrinsic properties of the capsids and encapsidated DNA to quantify multiple physical AAV attributes in one 20-min run with minimal sample manipulation, high accuracy, and high precision. These novel applications designate this well-established method as a powerful tool for product development and process analytics in future gene therapy programs.
The role of inflammatory cytokines in anemia and gastrointestinal mucosal injury induced by foot electric stimulation
Authors: Fan Fangcheng , Ai Yangwen , Sun Ting , Li Shuran , Liu Hua , Shi Xiaojie , Zhang Ziqian , Liu Qingshan , Cheng Yong 
Published: February 2021

AbstractFoot electrical stimulation (FES) has been considered as a classic stressor that can disturb homeostasis. Acute anemia was observed in the model induced by FES. The aim of this study was to explore the role of inflammatory cytokines underlying the acute anemia and gastrointestinal (GI) mucosal injury in the FES. Twenty-four male Kunming mice (20 ± 2 g) were randomly divided into control group and experimental group. The mice were placed in a footshock chamber that can generate 0.5 mA electrical impulse periodically for 0.5 h. After the process, red blood cell count, hemoglobin concentration and hematocrit, the levels of corticotropin releasing hormone (CRH) in serum and hypothalamus, and adrenocorticotropic hormone (ACTH) in serum and pituitary were detected separately. In addition, we investigated the expressions of inflammatory cytokines (IL-1, IL-6, TNF-α, iNOS, and IL-10) in the hypothalamus and duodenum by Polymerase Chain Reaction (PCR). Results showed that this FES model induced anemia, increased CRH and ACTH activity in the serum after the FES. Moreover, the expressions of IL-1β, IL-6, TNF-α, and iNOS were significantly increased following the process, while IL-10 was not activated. These findings suggest that anemia, the inflammatory cytokines in the hypothalamus and duodenum of the mice in the model induced by FES is closely related to GI mucosal injury/bleeding. Taken together, these results underscore the importance of anemia, GI mucosal injury/bleeding and stress, future studies would be needed to translate these findings into the benefit of affected patients.
Obstructive sleep apnoea syndrome (OSAS) as a risk factor for secondary osteoporosis in children
Authors: Sies Nur Syazwin , Zaini Azriyanti Anuar , de Bruyne Jessie Anne , Jalaludin Muhammad Yazid , Nathan Anna Marie , Han Ng Yit , Thavagnanam Surendran 
Published: February 2021

AbstractRepetitive hypoxia seen in obstructive sleep apnoea syndrome (OSAS) may affect bone metabolism increasing the risk for secondary osteoporosis. This study investigates the association between OSAS in children and secondary osteoporosis. This cross-sectional study included 150 children aged 10–17 years: 86 with OSAS and 64 with no OSAS. OSAS was confirmed by polysomnography. Quantitative ultrasound (QUS) of calcaneum measuring speed of sound (SoS) and broadband ultrasound attenuation (BUA) were collected. Other parameters collected including bone profile, vitamin D levels, physical activity scoring and dietary calcium intake. Majority were male and Malay ethnicity. OSAS children were mostly obese (84%) and 57% had moderate to severe OSAS. Most had lower physical activities scores. Mean (SD) phosphate and Alkaline phosphatase were lower in OSA children compared to controls: PO4, p = 0.039 and ALP, p < 0.001. Using both single and multivariate analysis, children with OSAS had a lower mean SoS value, p < 0.001 and p = 0.004 respectively after adjusting for age, BMI and bone profile. Children with OSAS had lower SoS suggesting risk for secondary osteoporosis. QUS calcaneus is a non-invasive, feasible tool and can be used to screen risk of osteoporosis in children. Further bone mineral density assessment is needed in these groups of children to confirm diagnosis of osteoporosis.
The safety and efficacy of BCG encapsulated alginate particle (BEAP) against M.tb H37Rv infection in Macaca mulatta : A pilot study
Authors: Kesarwani Ashwani , Sahu Parul , Jain Kshama , Sinha Prakriti , Mohan K. Varsha , Nagpal Puja S. , Singh Surender , Zaidi Rana , Nagarajan Perumal , Upadhyay Pramod 
Published: February 2021

AbstractDue to the limited utility of Bacillus Calmette–Guérin (BCG), the only approved vaccine available for tuberculosis, there is a need to develop a more effective and safe vaccine. We evaluated the safety and efficacy of a dry powder aerosol (DPA) formulation of BCG encapsulated alginate particle (BEAP) and the conventional intradermal BCG immunization in infant rhesus macaques (Macaca mulatta). The infant macaques were immunized intratracheally with DPA of BEAP into the lungs. Animals were monitored for their growth, behaviour, any adverse and allergic response. The protective efficacy of BEAP was estimated by the ex-vivo H37Rv infection method. Post-immunization with BEAP, granulocytes count, weight gain, chest radiography, levels of liver secreted enzymes, cytokines associated with inflammation like TNF and IL-6 established that BEAP is non-toxic and it does not elicit an allergic response. The T cells isolated from BEAP immunized animals’ blood, upon stimulation with M.tb antigen, secreted high levels of IFN-γ, TNF, IL-6 and IL-2. The activated T cells from BEAP group, when co-cultured with M.tb infected macrophages, eliminated largest number of infected macrophages compared to the BCG and control group. This study suggests the safety and efficacy of BEAP in Non-human primate model.
In vivo measurement of pH and CO2 levels in the uterus of sows through the estrous cycle and after insemination
Authors: López-Albors Octavio , Llamas-López Pedro José , Ortuño Joaquín Ángel , Latorre Rafael , García-Vázquez Francisco Alberto 
Published: February 2021

AbstractThe pH–CO2–HCO3− system is a ubiquitous biological regulator with important functional implications for reproduction. Knowledge of the physiological values of its components is relevant for reproductive biology and the optimization of Assisted Reproductive Technologies (ARTs). However, in situ measurements of these parameters in the uterus are scarce or null. This study describes a non-invasive method for in situ time-lapse recording of pH and CO2 within the uterus of non-anesthetized sows. Animals were at three different reproductive conditions, estrous with no insemination and two hours after insemination, and diestrous. From pH and CO2 data, HCO3− concentration was estimated. The non-invasive approach to the porcine uterus with novel optical probes allowed the obtaining of in situ physiological values of pH, CO2, and HCO3−. Variable oscillatory patterns of pH, CO2 and HCO3− were found independently of the estrous condition. Insemination did not immediately change the levels of uterine pH, CO2 (%) and HCO3− concentration, but all the values were affected by the estrous cycle decreasing significantly at diestrous condition. This study contributes to a better understanding of the in vivo regulation of the pH-CO2-HCO3− system in the uterus and may help to optimize the protocols of sperm treatment for in vitro fertilization.