bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sperm DNA methylation altered by THC and nicotine: Vulnerability of neurodevelopmental genes with bivalent chromatin
Authors: Schrott Rose , Rajavel Maya , Acharya Kelly , Huang Zhiqing , Acharya Chaitanya , Hawkey Andrew , Pippen Erica , Lyerly H. Kim , Levin Edward D. , Murphy Susan K. 
Published: September 2020

AbstractMen consume the most nicotine and cannabis products but impacts on sperm epigenetics are poorly characterized. Evidence suggests that preconception exposure to these drugs alters offspring neurodevelopment. Epigenetics may in part facilitate heritability. We therefore compared effects of exposure to tetrahydrocannabinol (THC) and nicotine on DNA methylation in rat sperm at genes involved in neurodevelopment. Reduced representation bisulfite sequencing data from sperm of rats exposed to THC via oral gavage showed that seven neurodevelopmentally active genes were significantly differentially methylated versus controls. Pyrosequencing data revealed majority overlap in differential methylation in sperm from rats exposed to THC via injection as well as those exposed to nicotine. Neurodevelopmental genes including autism candidates are vulnerable to environmental exposures and common features may mediate this vulnerability. We discovered that autism candidate genes are significantly enriched for bivalent chromatin structure, suggesting this configuration may increase vulnerability of genes in sperm to disrupted methylation.
Preclinical dosimetry models and the prediction of clinical doses of novel positron emission tomography radiotracers
Authors: Garrow Adam A. , Andrews Jack P. M. , Gonzalez Zaniah N. , Corral Carlos A. , Portal Christophe , Morgan Timaeus E. F. , Walton Tashfeen , Wilson Ian , Newby David E. , Lucatelli Christophe , Tavares Adriana A. S. 
Published: September 2020

AbstractDosimetry models using preclinical positron emission tomography (PET) data are commonly employed to predict the clinical radiological safety of novel radiotracers. However, unbiased clinical safety profiling remains difficult during the translational exercise from preclinical research to first-in-human studies for novel PET radiotracers. In this study, we assessed PET dosimetry data of six 18F-labelled radiotracers using preclinical dosimetry models, different reconstruction methods and quantified the biases of these predictions relative to measured clinical doses to ease translation of new PET radiotracers to first-in-human studies. Whole-body PET images were taken from rats over 240 min after intravenous radiotracer bolus injection. Four existing and two novel PET radiotracers were investigated: [18F]FDG, [18F]AlF-NOTA-RGDfK, [18F]AlF-NOTA-octreotide ([18F]AlF-NOTA-OC), [18F]AlF-NOTA-NOC, [18F]ENC2015 and [18F]ENC2018. Filtered-back projection (FBP) and iterative methods were used for reconstruction of PET data. Predicted and true clinical absorbed doses for [18F]FDG and [18F]AlF-NOTA-OC were then used to quantify bias of preclinical model predictions versus clinical measurements. Our results show that most dosimetry models were biased in their predicted clinical dosimetry compared to empirical values. Therefore, normalization of rat:human organ sizes and correction for reconstruction method biases are required to achieve higher precision of dosimetry estimates.
Hardware implementation of Bayesian network building blocks with stochastic spintronic devices
Authors: Debashis Punyashloka , Ostwal Vaibhav , Faria Rafatul , Datta Supriyo , Appenzeller Joerg , Chen Zhihong 
Published: September 2020

AbstractBayesian networks are powerful statistical models to understand causal relationships in real-world probabilistic problems such as diagnosis, forecasting, computer vision, etc. For systems that involve complex causal dependencies among many variables, the complexity of the associated Bayesian networks become computationally intractable. As a result, direct hardware implementation of these networks is one promising approach to reducing power consumption and execution time. However, the few hardware implementations of Bayesian networks presented in literature rely on deterministic CMOS devices that are not efficient in representing the stochastic variables in a Bayesian network that encode the probability of occurrence of the associated event. This work presents an experimental demonstration of a Bayesian network building block implemented with inherently stochastic spintronic devices based on the natural physics of nanomagnets. These devices are based on nanomagnets with perpendicular magnetic anisotropy, initialized to their hard axes by the spin orbit torque from a heavy metal under-layer utilizing the giant spin Hall effect, enabling stochastic behavior. We construct an electrically interconnected network of two stochastic devices and manipulate the correlations between their states by changing connection weights and biases. By mapping given conditional probability tables to the circuit hardware, we demonstrate that any two node Bayesian networks can be implemented by our stochastic network. We then present the stochastic simulation of an example case of a four node Bayesian network using our proposed device, with parameters taken from the experiment. We view this work as a first step towards the large scale hardware implementation of Bayesian networks.
Nephronophthisis gene products display RNA-binding properties and are recruited to stress granules
Authors: Estrada Mallarino Luisa , Engel Christina , Ilık İbrahim Avşar , Maticzka Daniel , Heyl Florian , Müller Barbara , Yakulov Toma A. , Dengjel Jörn , Backofen Rolf , Akhtar Asifa , Walz Gerd 
Published: September 2020

AbstractMutations of cilia-associated molecules cause multiple developmental defects that are collectively termed ciliopathies. However, several ciliary proteins, involved in gating access to the cilium, also assume localizations at other cellular sites including the nucleus, where they participate in DNA damage responses to maintain tissue integrity. Molecular insight into how these molecules execute such diverse functions remains limited. A mass spectrometry screen for ANKS6-interacting proteins suggested an involvement of ANKS6 in RNA processing and/or binding. Comparing the RNA-binding properties of the known RNA-binding protein BICC1 with the three ankyrin-repeat proteins ANKS3, ANKS6 (NPHP16) and INVERSIN (NPHP2) confirmed that certain nephronophthisis (NPH) family members can interact with RNA molecules. We also observed that BICC1 and INVERSIN associate with stress granules in response to translational inhibition. Furthermore, BICC1 recruits ANKS3 and ANKS6 into TIA-1-positive stress granules after exposure to hippuristanol. Our findings uncover a novel function of NPH family members, and provide further evidence that NPH family members together with BICC1 are involved in stress responses to maintain tissue and organ integrity.
Underwater sound to probe sea ice melting in the Arctic during winter
Authors: Mahanty Madan M. , Latha G. , Venkatesan R. , Ravichandran M. , Atmanand M. A. , Thirunavukarasu A. , Raguraman G. 
Published: September 2020

AbstractOver a 4-year period between 2015 and 2019, in-situ time series measurements of ocean ambient noise over the frequency range 100 Hz to 10 kHz, by an autonomous passive acoustic monitoring system have been made in the Kongsfjorden, Svalbard, Arctic. We characterize the noise due to sea ice melting during winter (December–January). This unique observation reveals loud noise signatures, of the order of 8 dB higher than the background noise, showing the signature of sea ice melting. Such observations are crucial for monitoring sea ice melting, especially during winter, to understand the recent warming of Arctic waters. The anomalous air temperature due to local atmospheric forcing and warming of ocean temperature in the fjord through ocean tunneling, individually or combinedly, is responsible for such sea ice melting. The cyclonic events in the Arctic are responsible for the anomalous atmospheric and ocean conditions, causing sea ice melting in winter.
Uptake and predictors of colonoscopy use in family members not participating in cascade genetic testing for Lynch syndrome
Authors: Hadley Donald W. , Eliezer Dina , Addissie Yonit , Goergen Andrea , Ashida Sato , Koehly Laura 
Published: September 2020

AbstractCascade genetic testing provides a method to appropriately focus colonoscopy use in families with Lynch syndrome (LS). However, research suggests that up to two-thirds at risk to inherit LS don’t participate. Within the United States, no studies have assessed colonoscopy use within this elusive and high-risk subset. We set forth to (1) document colonoscopy use within those not undergoing genetic testing (NGT) and (2) identify factors associated with completing colonoscopy. Data came from a cross sectional survey of families with molecularly confirmed LS. One hundred seventy-six (176) adults participated; 47 of unknown variant status and 129 with variant status known (59 carriers/70 non-carriers). Despite a high level of awareness of LS (85%) and identical recommendations for colonoscopy, NGT reported significantly lower use of colonoscopy than carriers (47% vs. 73%; p = 0.003). Our results show that perceived risk to develop colon cancer (AOR = 1.99, p < 0.05) and physician recommendations (AOR = 7.64, p < 0.01) are significant predictors of colonoscopy use across all family members controlling for carrier status. Given these findings, health care providers, should assess patients’ perceived risk to develop cancer, assist them in adjusting risk perceptions and discuss recommendations for colonoscopy with all members in families with LS.Trial Registration Clinical Trials.gov Identifier: NCT00004210.
Asymmetric dimethylarginine (ADMA) accelerates renal cell fibrosis under high glucose condition through NOX4/ROS/ERK signaling pathway
Authors: Jayachandran Isaivani , Sundararajan Saravanakumar , Venkatesan Saravanakumar , Paadukaana Sairaj , Balasubramanyam Muthuswamy , Mohan Viswanathan , Manickam Nagaraj 
Published: September 2020

AbstractWe previously reported that the circulatory level of Asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase, was increased in diabetic kidney disease patients. However, the mechanism and the role of ADMA in diabetic kidney injury remain unclear. Hence, our principal aim is to investigate the causal role of ADMA in the progression of renal cell fibrosis under high glucose (HG) treatment and to delineate its signaling alterations in kidney cell injury. High Glucose/ADMA significantly increased fibrotic events including cell migration, invasion and proliferation along with fibrotic markers in the renal cells; whereas ADMA inhibition reversed the renal cell fibrosis. To delineate the central role of ADMA induced fibrotic signaling pathway and its downstream signaling, we analysed the expression levels of fibrotic markers, NOX4, ROS and ERK activity by using specific inhibitors and genetic manipulation techniques. ADMA stimulated the ROS generation along with a significant increase in NOX4 and ERK activity. Further, we observed that ADMA activated NOX-4 and ERK are involved in the extracellular matrix proteins accumulation. Also, we observed that ADMA induced ERK1/2 phosphorylation was decreased after NOX4 silencing. Our study mechanistically demonstrates that ADMA is involved in the progression of kidney cell injury under high glucose condition by targeting coordinated complex mechanisms involving the NOX4- ROS-ERK pathway.
GPS-telemetry unveils the regular high-elevation crossing of the Himalayas by a migratory raptor: implications for definition of a “Central Asian Flyway”
Authors: Kumar Nishant , Gupta Urvi , Jhala Yadvendradev V. , Qureshi Qamar , Gosler Andrew G. , Sergio Fabrizio 
Published: September 2020

AbstractRemote technologies are producing leapfrog advances in identifying the routes and connectivity of migratory species, which are still unknown for hundreds of taxa, especially Asian ones. Here, we used GPS-telemetry to uncover the migration routes and breeding areas of the massive population of migratory Black-eared kites wintering around the megacity of Delhi-India, which hosts the largest raptor concentration of the world. Kites migrated for 3300–4800 km along a narrow corridor, crossing the Himalayas at extremely high elevations (up to > 6500 m a.s.l.) by the K2 of the Karakoram Range and travelled long periods at elevations above 3500 m. They then crossed/circumvented the Taklamakan Desert and Tian Shan Range to reach their unknown breeding quarters at the intersection between Kazakhstan, Russia, China and Mongolia. Route configuration seemed to be shaped by dominant wind support and barrier avoidance. Wintering ranges were smaller than breeding ranges and concentrated around Delhi, likely in response to massive human food-subsidies. Our results illustrate that high-elevation crossings by soaring migrants may be more common than previously appreciated and suggest the delineation of a hitherto poorly-appreciated “Central Asian Flyway”, which must funnel hundreds of thousands of migrants from central Asia into the Indian subcontinent via multiple modes of the Himalayan crossing.
Microtiter plate-based antibody-competition assay to determine binding affinities and plasma/blood stability of CXCR4 ligands
Authors: Harms Mirja , Gilg Andrea , Ständker Ludger , Beer Ambros J. , Mayer Benjamin , Rasche Volker , Gruber Christian W. , Münch Jan 
Published: September 2020

AbstractC-X-C chemokine receptor type 4 (CXCR4) is involved in several intractable disease processes, including HIV infection, cancer cell metastasis, leukemia cell progression, rheumatoid arthritis, asthma and pulmonary fibrosis. Thus, CXCR4 represents a promising drug target and several CXCR4 antagonizing agents are in preclinical or clinical development. Important parameters in drug lead evaluation are determination of binding affinities to the receptor and assessment of their stability and activity in plasma or blood of animals and humans. Here, we designed a microtiter plate-based CXCR4 antibody competition assay that enables to measure inhibitory concentrations (IC50 values) and affinity constants (Ki values) of CXCR4 targeting drugs. The assay is based on the observation that most if not all CXCR4 antagonists compete with binding of the fluorescence-tagged CXCR4 antibody 12G5 to the receptor. We demonstrate that this antibody-competition assay allows a convenient and cheap determination of binding affinities of various CXCR4 antagonists in living cells within just 3 h. Moreover, the assay can be performed in the presence of high concentrations of physiologically relevant body fluids, and thus is a useful readout to evaluate stability (i.e. half-life) of CXCR4 ligands in serum/plasma, and even whole human and mouse blood ex vivo. Thus, this optimized 12G5 antibody-competition assay allows a robust and convenient determination and calculation of various important pharmacological parameters of CXCR4 receptor-drug interaction and may not only foster future drug development but also animal welfare by reducing the number of experimental animals.
An efficient microinjection method to generate human anaplasmosis agent Anaplasma phagocytophilum-infected ticks
Authors: Taank Vikas , Ramasamy Ellango , Sultana Hameeda , Neelakanta Girish 
Published: September 2020

AbstractTicks are important vectors that transmit several pathogens including human anaplasmosis agent, Anaplasma phagocytophilum. This bacterium is an obligate intracellular rickettsial pathogen. An infected reservoir animal host is often required for maintenance of this bacterial colony and as a source for blood to perform needle inoculations in naïve animals for tick feeding studies. In this study, we report an efficient microinjection method to generate A. phagocytophilum-infected ticks in laboratory conditions. The dense-core (DC) form of A. phagocytophilum was isolated from in vitro cultures and injected into the anal pore of unfed uninfected Ixodes scapularis nymphal ticks. These ticks successfully transmitted A. phagocytophilum to the murine host. The bacterial loads were detected in murine blood, spleen, and liver tissues. In addition, larval ticks successfully acquired A. phagocytophilum from mice that were previously infected by feeding with DC-microinjected nymphal ticks. Transstadial transmission of A. phagocytophilum from larvae to nymphal stage was also evident in these ticks. Taken together, our study provides a timely, rapid, and an efficient method not only to generate A. phagocytophilum-infected ticks but also provides a tool to understand acquisition and transmission dynamics of this bacterium and perhaps other rickettsial pathogens from medically important vectors.
Neo-antigens for the serological diagnosis of IgE-mediated drug allergic reactions to antibiotics cephalosporin, carbapenem and monobactam
Authors: Peña-Mendizabal Edurne , Morais Sergi , Maquieira Ángel 
Published: September 2020

AbstractNew antigens deriving from -lloyl and -llanyl, major and minor determinants, respectively, were produced for β-lactam antibiotics cefuroxime, cefotaxime, ceftriaxone, meropenem and aztreonam. Twenty β-lactam antigens were produced using human serum albumin and histone H1 as carrier proteins. Antigens were tested by multiplex in vitro immunoassays and evaluated based on the detection of specific IgG and IgE in the serum samples. Both major and minor determinants were appropriate antigens for detecting specific anti-β-lactam IgG in immunised rabbit sera. In a cohort of 37 allergic patients, we observed that only the minor determinants (-llanyl antigens) were suitable for determining specific anti-β-lactam IgE antibodies with high sensitivity (< 0.01 IU/mL; 24 ng/L) and specificity (100%). These findings reveal that not only the haptenisation of β-lactam antibiotics renders improved molecular recognition events when the 4-member β-lactam ring remains unmodified, but also may contribute to develop promising minor antigens suitable for detecting specific IgE-mediated allergic reactions. This will facilitate the development of sensitive and selective multiplexed in vitro tests for drug-allergy diagnoses to antibiotics cephalosporin, carbapenem and monobactam.
Genopo: a nanopore sequencing analysis toolkit for portable Android devices
Authors: Samarakoon Hiruna , Punchihewa Sanoj , Senanayake Anjana , Hammond Jillian M. , Stevanovski Igor , Ferguson James M. , Ragel Roshan , Gamaarachchi Hasindu , Deveson Ira W. 
Published: September 2020

AbstractThe advent of portable nanopore sequencing devices has enabled DNA and RNA sequencing to be performed in the field or the clinic. However, advances in in situ genomics require parallel development of portable, offline solutions for the computational analysis of sequencing data. Here we introduce Genopo, a mobile toolkit for nanopore sequencing analysis. Genopo compacts popular bioinformatics tools to an Android application, enabling fully portable computation. To demonstrate its utility for in situ genome analysis, we use Genopo to determine the complete genome sequence of the human coronavirus SARS-CoV-2 in nine patient isolates sequenced on a nanopore device, with Genopo executing this workflow in less than 30 min per sample on a range of popular smartphones. We further show how Genopo can be used to profile DNA methylation in a human genome sample, illustrating a flexible, efficient architecture that is suitable to run many popular bioinformatics tools and accommodate small or large genomes. As the first ever smartphone application for nanopore sequencing analysis, Genopo enables the genomics community to harness this cheap, ubiquitous computational resource.
Arthroscopic treatment for nonunion of the scaphoid
Authors: Haugstvedt Jan Ragnar , Wong Clara Wing-yee 
Published: September 2020

AbstractScaphoid nonunion has traditionally been treated by open surgery where the pseudarthrosis has been cleaned while either a structural wedged bone graft, or chips of cancellous bone has been used to fill the defect. K-wires or a screw has been used to stabilize the bone. Using the arthroscopic technique for treatment of nonunion of the scaphoid gives us small exposure to the joint, however with an excellent view of the bones, the articular surfaces and the intraarticular ligaments. The results from arthroscopic treatment for scaphoid nonunion with bone grafting using chips of cancellous bone are as good as from the open technique. The arthroscopic treatment, though, helps us to diagnose and treat concomitant lesions. There is less damage of blood supply, nerves and capsule, which might lead to a faster recovery and rehabilitation. The technique will be described and discussed.
Klinische und bildgebende Diagnostik der Kahnbeinfraktur und -pseudarthrose
Authors: Fodor Stefan Georg , Christopoulos Georgios , Lehmkuhl Lukas , Prommersberger Karl-Josef , Mühldorfer-Fodor Marion 
Published: September 2020

ZusammenfassungKlinische und radiologische Diagnostik sind die Grundlage jeder differenzierten Therapieplanung karpaler Pathologien. Gerade bei der Kahnbeindiagnostik sind nicht nur die Auswahl und korrekte Durchführung der bildgebenden Verfahren entscheidend, sondern es müssen auch deren methodische Limitationen berücksichtig werden. Kaum eine andere Fraktur wird so häufig nicht erkannt, da nicht abgeklärt oder übersehen. Gleichzeitig führen die Folgen einer verspätet und/oder nicht behandelten Kahnbeinfraktur zu aufwändigen, nicht immer erfolgreichen Folgetherapien und langfristig zu funktionellen Einschränkungen. Diese Arbeit gibt einen Überblick über die klinische und bildgebende Diagnostik bei Kahnbeinfrakturen und -pseudarthrosen.
Timing of Emergency Postpartum Hospital Visits in the Fourth Trimester
Authors: Rodriguez Aldeboran N. , Patel Shivani , Macias Devin , Morgan Jamie , Kraus Alexandria , Spong Catherine Y. 
Published: September 2020

Objective The concept of the “fourth trimester” emphasizes the importance of individualized postpartum follow-up. Women seek care for urgent issues during this critical time period. Our objective was to evaluate trends in presenting complaints and admissions in an emergency setting over the first 42 days following delivery.
Study Design Postpartum hospital encounters within 42 days of delivery at our institution from 2015 to 2019 were studied. Demographic information, delivery route, and emergent hospital encounter details were obtained from the electronic medical record. The postpartum encounters were analyzed by week of presentation. Statistical analysis included Student's t-test and Mantel–Haenszel test with p <0.05 considered significant.
Results Of the 8,589 deliveries, 491 (5.7%) were complicated by an emergent hospital presentation within 42 days of delivery resulting in 576 hospital encounters. 35.9% of these visits occurred in the first week and 75.5% occurred within the first 3 weeks. Women presenting to the hospital were more commonly African American, higher body mass index, and delivered via cesarean. The most common chief complaints were fever, headache, abdominal pain, vaginal bleeding, hypertension, and wound concerns with temporal trends noted. 72% of admissions occur within 14 days of delivery and drop dramatically thereafter (p = 0.001). The most common diagnoses were hypertension/preeclampsia with severe features, vaginal bleeding/delayed postpartum hemorrhage, and wound infection.
Conclusion We observed important trends in presenting complaints and admission diagnoses of emergency postpartum visits in the first 42 days. The majority of hospital visits and admissions occur within the first 2 weeks postpartum. Understanding maternal conditions and reasons for accessing care through an emergency setting allows for tailoring of routine postpartum follow-up.
Key Points