bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triphasic Waves Are Generated by Widespread Bilateral Cortical Networks
Authors: Kural Mustafa Aykut , Fabricius Martin , Christensen Jakob , Kaplan Peter W. , Beniczky Sándor 
Published: August 2020

Purpose:
Triphasic waves (TWs) have been observed in the EEG recorded in patients with various types of encephalopathy, yet their genesis and significance is still debated. The aim of this study was to elucidate the localization of the cortical generators of TWs using EEG source imaging.

Methods:
In 20 consecutive patients who had encephalopathy with TWs, EEG source imaging of the first negative and the positive phases of the TW was performed. Three different approaches were used: equivalent current dipoles, a distributed source model, and a recently described spatial filtration method for visualizing EEG in source space.

Results:
Equivalent current dipole models failed to provide valid solutions. The distributed source model and the spatial filtration method suggested that TWs were generated by large, bilateral cortical networks, invariably involving the anterior frontal and the temporo-polar areas.

Conclusions:
Source imaging localized TWs to anterior frontal and temporo-frontal structures. Involvement of these regions is consistent with the typical pathophysiological changes of altered consciousness and cognitive changes observed in patients with TW encephalopathy.
Clinical and Electrophysiological Features of Chronic Motor Axonal Neuropathy
Authors: Zhang Dong , Geng Hongzhi , Cao Lili , Li Wei 
Published: August 2020

Purpose:To determine the clinical and electrophysiological characteristics of chronic motor axonal neuropathy (CMAN) and identify the associated similarities and differences between CMAN, acute motor axonal neuropathy (AMAN), and motor neuropathy secondary to amyotrophic lateral sclerosis.Methods:The study described clinical and electrophysiological features of five patients with CMAN and compared with 20 AMAN patients, 42 amyotrophic lateral sclerosis patients and 41 healthy controls. To compare the distribution of different nerve involvement in the same limb, split ratio was introduced. Split ratio of upper limb = amplitude of compound muscle action potential abductor pollicis brevis (APB)/amplitude of compound muscle action potential abductor digiti minimi, and split ratio of lower limb = amplitude of compound muscle action potential extensor digitorum brevis/amplitude of compound muscle action potential abductor hallucis.Results:Chronic motor axonal neuropathy patients manifested lower motor neuron syndrome with positive IgG anti-monosialoganglioside antibodies and good outcome. The CMAN patients shared similar clinical manifestation with AMAN patients except for disease course and higher Medical Research Council scores. Compared with healthy controls, the split ratio of lower limb was higher in both CMAN and AMAN, despite comparable split ratio of upper limb. There was significant difference between CMAN group and amyotrophic lateral sclerosis group in nerve involvement presented as split hand and split leg signs in amyotrophic lateral sclerosis and reverse split leg sign in CMAN.Conclusions:Chronic motor axonal neuropathy associated with monosialoganglioside might be a “mild” AMAN with chronic onset by similar clinical and electrophysiological features. There was a unique pattern of nerve involvement presenting as reverse split leg sign in both CMAN and AMAN.
Can Public Libraries Be Leveraged to Expand Access to Telehealth? Exploration of a Strategy to Mitigate Rural Health Disparities
Authors: DeGuzman Pamela B. , Jain Neha 
Published: August 2020

AbstractIn the U.S., those who lack broadband internet have limited ability to connect to care providers over a telemedicine video visit (VV). During the coronavirus disease pandemic, VVs have become increasingly common, but are not equitably accessible, which may exacerbate existing health disparities. Widening health disparities are of particular concern in the rural U.S. where broadband is lacking. We term this inequity in healthcare access due to limited internet access the “digital health divide.” Because public libraries typically offer free use of broadband internet to patrons, they can help bridge the digital health divide and assist patrons with VVs. However, no guidelines currently exist for care providers and libraries to implement this needed, but potentially complex undertaking. Individual programs in which community members have used public libraries as a place from which to connect to a VV may offer insight into guidance needed. Thus, we conducted a scoping review to explore interventions reporting use of public libraries for community members to connect to a healthcare provider via telemedicine. One article was found describing the use of a public library for community members to connect to a telemedicine VV. The use of public libraries as spaces from which patrons can participate in VVs with providers is promising, but research is urgently needed to guide implementation.
Patient-specific hemodynamics of new coronary artery bypass configurations
Authors: Rezaeimoghaddam Mohammad , Oguz Gokce Nur , Ates Sanser , Bozkaya Tijen Alkan , Piskin Senol , Lashkarinia S. Samaneh , Tenekecioglu Erhan , Karagoz Haldun , Pekkan Kerem 
Published: August 2020

AbstractPurposeThis study aims to quantify the patient-specific hemodynamics of complex conduit routing configurations of coronary artery bypass grafting (CABG) operation which are specifically suitable for off-pump surgeries. Coronary perfusion efficacy and local hemodynamics of multiple left internal mammary artery (LIMA) with sequential and end-to-side anastomosis are investigated. Using a full anatomical model comprised of aortic arch and coronary artery branches the optimum perfusion configuration in multi-vessel coronary artery stenosis is desired.MethodologyTwo clinically relevant CABG configurations are created using a virtual surgical planning tool where for each configuration set, the stenosis level, anastomosis distance and angle were varied. A non-Newtonian computational fluid dynamics solver in OpenFOAM incorporated with resistance boundary conditions representing the coronary perfusion physiology was developed. The numerical accuracy is verified and results agreed well with a validated commercial cardiovascular flow solver and experiments. For segmental performance analysis, new coronary perfusion indices to quantify deviation from the healthy scenario were introduced.ResultsThe first simulation configuration set; - a CABG targeting two stenos sites on the left anterior descending artery (LAD), the LIMA graft was capable of 31 mL/min blood supply for all the parametric cases and uphold the healthy LAD perfusion in agreement with the clinical experience. In the second end-to-side anastomosed graft configuration set; -the radial artery graft anastomosed to LIMA, a maximum of 64 ml/min flow rate in LIMA was observed. However, except LAD, the obtuse marginal (OM) and second marginal artery (m2) suffered poor perfusion. In the first set, average wall shear stress (WSS) were in the range of 4 to 35 dyns/cm2 for in LAD. Nevertheless, for second configuration sets the WSS values were higher as the LIMA could not supply enough blood to OM and m2.ConclusionThe virtual surgical configurations have the potential to improve the quality of operation by providing quantitative surgical insight. The degree of stenosis is a critical factor in terms of coronary perfusion and WSS. The sequential anastomosis can be done safely if the anastomosis angle is less than 90 degrees regardless of degree of stenosis. The smaller proposed perfusion index value, O(0.04-0)×102, enable us to quantify the post-op hemodynamic performance by comparing with the ideal healthy physiological flow.
In-house assembled protective devices in laboratory safety against SARS-nCoV-2 in clinical biochemistry laboratory of a COVID dedicated hospital
Authors: Dubey Abhishek , Bansal Aastha , Sonkar Subash Chandra , Goswami Binita , Makwane Naina , Manchanda Vikas , Koner Bidhan Chandra 
Published: August 2020

AbstractHealth Care Workers (HCWs) of diagnostic laboratory handling COVID positive samples are at risk and need to take protective measures. Many protective materials were not available when the pandemic reached India forcing laboratory managers to take innovative measures to protect the laboratory staffs. We made face shields from OHP sheets and substitute of biosafety cabinets from cardboard boxes fitted with hypochlorite spraying devices. Here we present if these two in-house developed safety devices when incorporated in standard operating procedure (SOP) of laboratory safety were effective in clinical biochemistry laboratory of dedicated COVID hospitals. We assessed contamination of laboratory surfaces (n=6) and rate of SARS-nCov-2 positivity from their nasal and throat swab by RT-PCR among laboratory personnel (n=18) after 14 days of their use along with other routine safety devices like use of gloves, surgical masks, OT gowns etc. These HCWs were checked regularly for signs and symptoms of COVID-19 and none had any signs and symptoms during these 14days. The SARS-nCov-2 test report was negative for the staff members and no surface contamination was detected. We conclude that innovative and cost effective protective devices can be built in-house with locally available resources and are effective in preventing the spread of COVID 19 among the staff working in clinical biochemistry laboratories. Laboratory managers in resource scarce areas need to be innovative to face such sudden safety challenges like COVID-19 pandemic.The highlight of the manuscript areStrengthening the Basics Approaches to protect the lab personnel in dedicated COVID hospital of Low-Resource Settings.Designed and developed in-house standard operating procedure (SOP) to fill the gap and evaluate the effect in dedicated COVID-19 hospitals.Innovative protective devices made from OHP sheets and cardboard boxes fitted with hypochlorite spraying devices as alternatives to biosafety cabinets on contamination of laboratory surfaces.Performance of the devices were clinically validated and it can be used as alternative in low resources settings.
Remote digital measurement of visual and auditory markers of Major Depressive Disorder severity and treatment response
Authors: Galatzer-Levy Isaac R. , Abbas Anzar , Yadav Vijay , Koesmahargyo Vidya , Aghjayan Allison , Marecki Serena , Evans Miriam , Sauder Colin 
Published: August 2020

AbstractObjectivesMultiple machine learning-based visual and auditory digital markers have demonstrated associations between Major Depressive Disorder (MDD) status and severity. The current study examines if such measurements can quantify response to antidepressant treatment (ADT) with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine uptake inhibitors (SNRIs).MethodsVisual and auditory markers were acquired through an automated smartphone task that measures facial, vocal, and head movement characteristics across four weeks of treatment (with timepoints at baseline, 2 weeks, and 4 weeks) on ADT (n = 12). The Montgomery-Asberg Depression Rating Scale (MADRS) was collected concordantly through clinical interviews to confirm diagnosis and assess changes in MDD severity.ResultsPatient responses to ADT demonstrated clinically and statistically significant changes in the MADRS F(2,34) = 51.62, p <.0001. Additionally, patients demonstrated significant increases in multiple digital markers including facial expressivity, head movement, and amount of speech. Finally, patients demonstrated significant decreased frequency of fear and anger facial expressions.ConclusionDigital markers associated with MDD demonstrate validity as measures of treatment response.
Tracheal aspirate with closed suction device: a modified technique developed during COVID-19 outbreak
Authors: Schverdfinger Sofia , Bisso Indalecio Carboni , Famiglietti Romina , Grazia Marcelo Di , Stefano Sabrina Di , Heras Marcos Las 
Published: August 2020

ABSTRACTBackgroundBacterial superinfection as well as ventilation associated pneumonia (VAP) are both frequent events in critical care. During COVID-19 pandemic, usual diagnostic practices such as bronchoalveolar lavage and tracheal aspirate are limited due to their associated high risk of exposure for the operator. In order to set primary focus on the protection of health care personnel, a modified tracheal aspiration (M-TA) technique is developed and used for acquiring a lower respiratory tract of microbiological samples with a closed suction device.MethodsRetrospective observational study to evaluate effectiveness of M-TA is conducted.ResultsA total of 33 M-TA samples were analyzed. In 66,6% of the cases, results led to a change in medical decision making. A 100% accuracy was achieved regarding COVID-19 diagnosis and a 56% bacterial growth-rate in cultives where VAP was suspected. No health care personnel have developed symptoms nor tested positive for COVID-19 during or after sample collection.ConclusionM-TA technique presented could be considered as a safe and effective procedure with low percentage of complications.
Systematic bias in studies of consumer functional responses
Authors: Novak Mark , Stouffer Daniel B. 
Published: August 2020

AbstractFunctional responses are a cornerstone to our understanding of consumer-resource interactions, so how to best describe them using models has been actively debated. Here we focus on the consumer dependence of functional responses to evidence systematic bias in the statistical comparison of functional-response models and the estimation of their parameters. Both forms of bias are universal to nonlinear models (irrespective of consumer dependence) and are rooted in a lack of sufficient replication. Using a large compilation of published datasets, we show that – due to the prevalence of low sample size studies – neither the overall frequency by which alternative models achieve top rank nor the frequency distribution of parameter point estimates should be treated as providing insight into the general form or central tendency of consumer interference. We call for renewed clarity in the varied purposes that motivate the study of functional responses, purposes that can compete with each other in dictating the design, analysis, and interpretation of functional-response experiments.
Stimulation of the human mitochondrial transporter ABCB10 by zinc-mesoporphrin
Authors: Martinez Melissa , Fendley Gregory A. , Saxberg Alexandra D. , Zoghbi Maria E. 
Published: August 2020

AbstractHeme biosynthesis occurs through a series of reactions that take place within the cytoplasm and mitochondria, thus intermediates need to move across these cellular compartments. However, the specific membrane transport mechanisms involved in the process are not yet identified. The ATP-binding cassette protein ABCB10 is essential for normal heme production, as knocking down this transporter in mice is embryonically lethal and accompanied by severe anemia plus oxidative damage. The role of ABCB10 is unknown, but given its location in the inner mitochondrial membrane, it has been proposed as a candidate to export either an early heme precursor or heme. Alternatively, ABCB10 might transport a molecule important for protection against oxidative damage. To help discern between these possibilities, we decided to study the effect of heme analogs, precursors and antioxidant peptides on purified human ABCB10. Since substrate binding increases the ATP hydrolysis rate of ABC transporters, we have determined the ability of these molecules to activate purified ABCB10 reconstituted in lipid nanodiscs using ATPase measurements. Under our experimental conditions, we found that the only heme analog increasing ABCB10 ATPase activity was Zinc-mesoporphyrin. This activation of almost seventy percent was specific for ABCB10, as the ATPase activity of a negative control bacterial ABC transporter was not affected. The activation was also observed in cysteine-less ABCB10, suggesting that Zinc-mesoporphyrin’s effect did not require binding to typical heme regulatory motifs. Furthermore, our data indicate that ABCB10 was not directly activated by neither the early heme precursor delta-aminolevulinic acid nor glutathione, downsizing their relevance as putative substrates for this transporter. Although additional studies are needed to determine the physiological substrate of ABCB10, our findings reveal Zinc-mesoporphyrin as the first tool compound to directly modulate ABCB10 activity and raise the possibility that some actions of Zinc-mesoporphyrin in cellular and animal studies could be mediated by ABCB10.
Group I p21-activated kinases in leukemia cell adhesion to fibronectin
Authors: Kuželová Kateřina , Obr Adam , Röselová Pavla , Grebeňová Dana , Otevřelová Petra , Brodská Barbora , Holoubek Aleš 
Published: August 2020

AbstractP21-activated kinases (PAK) regulate many processes associated with cytoskeleton dynamics, including cell adhesion, migration, and apoptosis. PAK function is frequently altered in cancer, and PAK were proposed as therapy targets both in solid tumors and in hematological malignancies. However, current knowledge about PAK function in cell adhesion is mainly based on adherent cell models. Moreover, existing functional differences among the individual PAK family members are unsufficiently characterized.We measured expression of PAK group I members in leukemia cell lines and in primary leukemia cells, both on protein and mRNA levels. In functional assays, we analyzed the effect of two PAK inhibitors with different mechanisms of action, IPA-3 and FRAX597. Changes in cell interaction with fibronectin were monitored through impedance measurement and by interference reflection microscopy. Cytotoxic effects of inhibitors were assessed by Annexin V/propidium iodide test. PAK intracellular localization was analyzed by confocal microscopy.PAK2 transcript was dominant in cell lines, whereas primary leukemia cells also expressed comparable amount of PAK1, which was detected as two transcription isoforms: PAK1-full and PAK1Δ15. PAK1Δ15 and PAK2 transcript levels correlated with surface density of integrins β1 and αVβ3. PAK1-full, but not PAK2, was present in membrane protrusions. The inhibitors had partly opposed effects: IPA-3, which prevents PAK activation, induced cell contraction in semi-adherent HEL cells only. FRAX597, which inhibits PAK kinase activity, increased cell-surface contact area in all leukemia cells. Both inhibitors reduced the stability of cell attachment and induced cell death. Although many cells accumulated high FRAX597 amounts, low doses were sufficient to kill sensitive cells. FRAX597-induced cell death was fast in the MV4-11 cell line and in primary AML cells.Although PAK group I seem to be essential for leukemia cell adhesion and survival, and might thus serve as therapy targets, many PAK functions still remain to be attributed to individual isoforms and to their functional domains.
Tumor-educated monocyte-dendritic progenitors promote a metastatic switch
Authors: Magidey-Klein Ksenia , Kveler Ksenya , Cooper Tim J. , Normand Rachelly , Zhang Tongwu , Timaner Michael , Raviv Ziv , James Brian , Gazit Roi , Ronai Ze’ev A. , Shen-Orr Shai S. , Shaked Yuval 
Published: August 2020

AbstractMyeloid skewing of hematopoietic cells is a prominent promoter of metastasis. However, little is known about their education and differentiation pattern from hematopoietic stem and progenitor cells (HSPCs) during tumor progression and metastasis. Here we show that metastatic tumors dictate a unique differentiation pattern of HSPCs towards a specific myeloid progeny. Using single cell RNA-sequencing analysis integrated with proteomic screen of tumor secretome, we demonstrate that highly metastatic tumors dictate a long-lived differentiation of HSPCs towards monocyte-dendritic progenitors (MDPs) while low-metastatic tumors promote their differentiation into granulocyte-monocyte progenitors (GMPs). This effect is driven by IL-6 axis that is highly active in metastatic tumors. Consequently, loss and gain of function of IL-6 in tumor cells resulted in decreased and increased metastasis and corresponding MDP levels, respectively. Consistently, IL-6-educated MDPs but not GMPs obtained from highly metastatic tumors, adoptively transferred into mice bearing low metastatic tumors resulted in increased metastasis due to their further differentiation into immunosuppressive (M2) macrophages. Overall, our study reveals a new role for tumor-derived IL-6 that hijacks HSPC differentiation program towards myeloid cells that contribute to metastasis.
Precision digital mapping of endogenous and induced genomic DNA breaks by INDUCE-seq
Authors: Dobbs Felix M , van Eijk Patrick , Fellows Mick D , Loiacono Luisa , Nitsch Roberto , Reed Simon H. 
Published: August 2020

AbstractUnderstanding how breaks form and are repaired in the genome depends on the accurate measurement of the frequency and position of DNA double strand breaks (DSBs). This is crucial for identification of a chemical’s DNA damage potential and for safe development of therapies, including genome editing technologies. Current DSB sequencing methods suffer from high background levels, the inability to accurately measure low frequency endogenous breaks and high sequencing costs. Here we describe INDUCE-seq, which overcomes these problems, detecting simultaneously the presence of low-level endogenous DSBs caused by physiological processes, and higher-level recurrent breaks induced by restriction enzymes or CRISPR-Cas nucleases. INDUCE-seq exploits an innovative NGS flow cell enrichment method, permitting the digital detection of breaks. It can therefore be used to determine the mechanism of DSB repair and to facilitate safe development of therapeutic genome editing. We discuss how the method can be adapted to detect other genomic features.
Discovery of 5,5’-methylenedi-2,3-cresotic acid as a potent inhibitor of chemotactic activity of the HMGB1•CXCL12 heterocomplex using Virtual Screening and NMR validation
Authors: De Leo F. , Quilici G. , De Marchis F. , Mantonico M. V. , Bianchi M. E. , Musco G. 
Published: August 2020

AbstractHMGB1 is a key molecule that both triggers and sustains inflammation following infection or injury, and is involved in a large number of pathologies, including cancer. HMGB1 participates to the recruitment of inflammatory cells forming a heterocomplex with the chemokine CXCL12 (HMGB1•CXCL12), herewith activating the G-protein coupled receptor CXCR4. Thus, identification of molecules that disrupt this heterocomplex can offer novel pharmacological opportunities to treat inflammation related diseases. To identify new HMGB1•CXCL12 inhibitors we have performed a study on the ligandability of the single HMG boxes of HMGB1 followed by a virtual screening campaign on both HMG boxes using Zbc Drugs and three different docking programs (Glide, AutoDock Vina, AutoDock 4.2.6). The best poses in terms of scoring functions, visual inspection and predicted ADME properties were further filtered according to a pharmacophore model based on known HMGB1 binders and clustered according to their structures. Eight compounds representative of the clusters were tested for HMGB1 binding by NMR. We identified 5,5’-methylenedi-2,3-cresotic acid (2a) as binder of both HMGB1 and CXCL12; 2a also targets the HMGB1•CXCL12 heterocomplex. In cell migration assays 2a inhibited the chemotactic activity of HMGB1•CXCL12 with IC50 in the subnanomolar range, the best documented up to now. These results pave the way for future structure activity relationship studies to optimize the pharmacological targeting of HMGB1•CXCL12 for anti-inflammatory purposes.