bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inclusion of Albumin in the Initial Resuscitation of Adult Patients with Medical Sepsis or Septic Shock: a Propensity Score-Matched Analysis
Authors: Liu Chang , Li Heyi , Peng Zhiyong , Hu Bo , Dong Yue , Gao Xiaolan , Frank Ryan D. , Kashyap Rahul , Gajic Ognjen , Kashani Kianoush B. 
Published: May 2021

ABSTRACT

Introduction:
The impact of albumin resuscitation on sepsis outcomes is debated, particularly in the initial phase of resuscitation. We aimed to investigate the association between albumin use in the initial 6 h of resuscitation and subsequent outcomes in adult septic patients.

Methods:
This single-center, retrospective, propensity score-matched cohort study included adult patients admitted to intensive care units (ICUs) with sepsis or septic shock from January 1, 2006, to May 4, 2018, at a tertiary referral hospital. We compared two groups based on albumin receipt within the initial six resuscitation hours (albumin group vs. non-albumin group). We performed a 1:2 propensity score matching to assess shock-free time in ICU as the primary outcome.

Results:
Of 2,732 patients with medical sepsis, 286 cases in the albumin group were matched with 549 individuals in the non-albumin group. Compared to the non-albumin group, the albumin group required more intravenous fluids and had higher net fluid balance, lower mean arterial pressure, and lower serum base excess level in the initial 6 and 24 h of resuscitation. Shock-free time, ICU and hospital length of stay, and 28-day mortality were not different between albumin and non-albumin groups (56 vs. 66 h, P = 0.18; 3.5 days vs. 3.7 days, P = 0.61; 9.1 days vs. 9.5 days, P = 0.27; 36% vs. 32%, P = 0.25, respectively).

Conclusions:
Using albumin during the initial 6 h of resuscitation was not associated with benefits in clinical outcomes of patients with medical sepsis.
Cost savings from managing hypertension in primary health care clinics in Kuwait
Authors: Odeh Ayah , Aljunid Syed Mohamed , Al-Wotayan Rihab , Annaka Mahmoud , Mari Mohammad Al 
Published: May 2021

AbstractBackgroundGeneric medications are one of the most common solutions for bringing down pharmaceutical costs for both patients and health care providers. Efforts to increase uptake of generics include policies to support generic substitution and prescription. The aim of this study is to estimate the total cost of drugs prescribed by physicians in selected primary health care centers for managing hypertension and the potential cost savings from substituting generic drugs for branded onesMethods and FindingsOne thousand patients with hypertension were randomly selected from the Primary Care Information System database from among patients who sought treatment at three primary health care centers from Al-Jahra governorate in Kuwait from January to December 2018. Generic antihypertensive drugs were substituted for branded ones, and cost savings were calculated by referring to the International Drug Price Indicator Guide. The mean age of 1,000 patients was 57.01 (SD = 11.82) years. Most (57.4%) of the patients were females, and 50.2% were Kuwaitis. The mean number of drugs per prescription was 1.78 (SD = 1.25; range: 1 to 9 drugs). The total number of drugs prescribed was 1,781, with a total cost of KD 10,093 and with a mean of KD 10.09 (SD = 7.34). Only 71 generic drugs had been prescribed, making the generic prescription rate 4.0%. The total number of antihypertensive drugs prescribed was 1,206 (mean: 1.21; SD = 0.46), with a cost of KD 7,678.5 (mean = KD 7.68; SD = 4.06) and with ACE inhibitors as the most prescribed class at 32.19%. Eight hundred ninety antihypertensive drugs were substituted for 774 patients at estimated cost savings of KD 5,675; that is, substituting generic drugs reduced antihypertensive drug cost by 74%.ConclusionGeneric drug prescription appears to be low among primary care physicians in health care centers in Kuwait, but these centers could see substantial cost savings from substituting generic antihypertensive drugs for branded ones. Active interventions are needed to encourage generic prescription among health practitioners to reduce the overall pharmaceutical expenditures.
Thalamic white matter macrostructure and subnuclei volumes in Parkinson’s disease depression
Authors: Bhome R , Zarkali A , Cole JH , Weil RS 
Published: May 2021

AbstractObjectiveDepression is a common non-motor feature of Parkinson’s disease (PD) which confers significant morbidity and is often challenging to treat. The thalamus is a key component in the basal ganglia - thalamocortical network critical to pathogenesis of PD and depression but the precise thalamic subnuclei involved in PD depression have not yet been identified and may even represent potential therapeutic targets.MethodsWe performed structural and diffusion weighted imaging on 76 participants with PD to evaluate the relationship between PD depression and grey and white matter thalamic subnuclear changes. We used a thalamic segmentation method to divide the thalamus into its 50 constituent subnuclei (25 each hemisphere). We used fixel based analysis of diffusion weighted imaging data to calculate mean fibre cross section (FC) for white matter tracts connected to each subnucleus and assessed volume and FC at baseline and 14-20 months follow-up. A generalised linear mixed model was used to evaluate the relationship between depression, subnuclei volume and mean FC for each of the 50 thalamic subnuclei, adjusting for age, gender, intracranial volume and time.ResultsWe found that depression scores in PD were associated with lower right pulvinar anterior (PuA) subnucleus volume. Antidepressant use was associated with higher right PuA volume suggesting a possible protective effect of treatment. After follow-up, depression scores were associated with decreases in white matter tract macrostructure across almost all tracts connected to thalamic subnuclei.ConclusionWe demonstrate that depression is associated with right thalamic PuA subnucleus volume loss and widespread thalamic white matter macrostructural changes, but that antidepressants may protect against volume loss in PD depression. Our work provides mechanistic insights for depression in PD, suggests possible benefits of actively treating depression, and a potential target for therapeutic intervention to the PuA subnucleus for PD depression.
7-Tesla Functional Cardiovascular MR Using Vectorcardiographic Triggering – overcoming the magnetohydrodynamic effect
Authors: Hamilton-Craig Christian , Stäeb Daniel , Najjar Aiman Al , O’Brien Kieran , Crawford William , Fletcher Sabine , Barth Markus , Galloway Graham 
Published: May 2021

ABSTRACTObjectiveUltra-high-field (B0 ≥ 7 Tesla) cardiovascular magnetic resonance (CMR) offers increased resolution. However, ECG gating is impacted by the magneto-hydrodynamic (MHD) effect distorting the ECG trace. We explored the technical feasibility of a 7T MR scanner using ECG trigger learning algorithm to quantitatively assess cardiac volumes and vascular flow.Methods7T scans performed on 10 healthy volunteers on a whole-body research MRI (Siemens Healthcare, Erlangen, Germany) with 8 channel Tx/32 channel Rx cardiac coil (MRI Tools GmbH, Berlin, Germany). Vectorcardiogram ECG was performed using a learning phase outside of the magnetic field, with a trigger algorithm overcoming severe ECG signal distortions.Vectorcardiograms were quantitatively analyzed for false negative and false positive events. Cine CMR was performed after 3rd-order B0 shimming using a high-resolution breath-held ECG-retro-gated segmented spoiled gradient echo, and 2D phase contrast flow imaging. Artefacts were assessed using a semi-quantitative scale.Results7T CMR scans were acquired in all patients (100%) using the VCG learning method. 3,142 R-waves were quantitatively analyzed, yielding sensitivity 97.6%, specificity 98.7%. Mean image quality score was 0.9, sufficient to quantitate both cardiac volumes, ejection fraction (EF), aortic and pulmonary blood flow. Mean LVEF was 56.4%, RVEF 51.4%.ConclusionReliable cardiac ECG triggering is feasible in healthy volunteers at 7T utilizing a state-of-the-art 3-lead trigger device despite signal distortion from the MHD effect. This provides sufficient image quality for quantitative analysis. Other ultra-high-field imaging applications such as human brain functional MRI with physiologic noise correction may benefit from this method of ECG triggering.Key pointsUltra-high field 7 Tesla cardiac MRI is challenging due to the impact of the magneto-hydrodynamic (MHD) effect causing severe distortions in the ECG trace.Using VCG with a learning phase outside the ultra-high field magnet, the R waves can be adequately detected to perform high quality Cardiac MRI scans, overcoming signal distortion from the MHD effect.
COVID-19 case definitions, diagnostic testing criteria, and surveillance across the pandemic’s 25 highest burden countries
Authors: Suthar Amitabh B. , Schubert Sara , Garon Julie , Couture Alexia , Brown Amy M. , Charania Sana 
Published: May 2021

AbstractObjectiveWe compared suspect, probable, and confirmed case definitions, as well as diagnostic testing criteria, used in the COVID-19 pandemic’s 25 highest burden countries to aid interpretation of global and national surveillance data.MethodsWe identified the COVID-19 pandemic’s 25 countries with the highest disease burden based on the number of cumulative reported cases to the World Health Organization (WHO) as of 1 October 2020. We searched official websites of these countries for suspect, probable, and confirmed case definitions. Given that confirmation of COVID-19 usually requires diagnostic testing, we also searched for diagnostic testing eligibility criteria in these countries. Extracted case definitions and testing criteria were managed in a database and analyzed in Microsoft Excel.FindingsWe identified suspect, probable, and confirmed case definitions in 96%, 64%, and 100% of countries, respectively. Testing criteria were identified in 100% of countries. 56% of identified countries followed WHO recommendations for using a combination of clinical and epidemiological criteria as part of the suspect case definition. 75% of identified countries followed WHO recommendations on using clinical, epidemiological, and diagnostic criteria for probable cases. 72% of countries followed WHO recommendations on using PCR testing for confirming a case of COVID-19. Finally, 64% of countries used testing eligibility criteria at least as permissive as WHO.ConclusionThere is marked heterogeneity in who is eligible for testing in countries and how countries define a case of COVID-19. This affects the ability to compare burden, transmission, and response impact estimates derived from case surveillance data across countries.
A protein microarray-based in vitro transglutaminase assay platform for epitope mapping and immunogen design: implication for transglutaminase-mediated immunodominant determination
Authors: Liu Chen 
Published: May 2021

AbstractTransglutaminases (TGs) are a family of crosslinking enzymes catalyzing the formation of intra- and inter-molecular glutamine-lysine isopeptide bonds in a calcium dependent manner. Activation of transglutaminases is pathogenically associated with severe human diseases including neurodegenerations, cardiovascular diseases, and autoimmune diseases. Although continuous efforts determining the enzymes’ substrate preference have been witnessed, a high-throughput assay platform with the “omic” efficiency is still missing for the global identification of substrate-specific TG modification sites. In this study we report a protein microarray-based in vitro TG assay platform for rapid and large-scale (up to 30000 reactions per chip) determination of the glutamine (Q)-bearing TG modification motifs. With this platform we identified the Q16 in superoxide dismutase 1 and Q109 in alpha-synuclein as the primary modification sites for tissue transglutaminase (TG2), the most ubiquitous member of the enzyme family. Of particular interest, we found a close match between the modification motifs and published vaccine epitope sequences in alpha-synuclein, implying an essential and intrinsic role transglutaminase might play in the determination of immunodominant epitopes. Our data collectively suggest the glutamine and its follow-up five residues on the C terminal of a protein compose a minimal determinant motif for TG2 modification and, more importantly, the TG2 modification motifs determined by our platform could finally correspond to the substrate’s immunodominant epitope sequences in antigen processing. To establish an efficient approach to optimize the enzyme modification motifs and screen for site-specific interfering peptides, we scanned the known TG2 modification motifs with onchip amino-acid swapping and glutamine repeat addition, and obtained multiple variants with significantly upregulated TG2 reactivity. This approach could also be employed to improve the target peptide’s immunogenicity. Taken together, our synthetic transglutaminase assay platform might be able to deliver a precise epitope blueprint for immunotherapeutic targeting and provide pilot and directional studies for TG-based peptide discovery and immunogen design.
The Origin of Bladder Cancer from Mucosal Field Effects
Authors: Bondaruk Jolanta , Jaksik Roman , Wang Ziqiao , Cogdell David , Lee Sangkyou , Chen Yujie , Dinh Khanh Ngoc , Majewski Tadeusz , Zhang Li , Cao Shaolong , Yao Hui , Weinstein John N. , Navai Neema , Dinney Colin , Gao Jianjun , Theodorescu Dan , Logothetis Christopher , Guo Charles C. , Wang Wenyi , McConkey David , Wei Peng , Kimmel Marek , Czerniak Bogdan 
Published: May 2021

ABSTRACTWe used whole-organ mapping to study loco-geographic molecular changes in evolution of human bladder cancer from mucosal field effects. The integrative multi-platform analyses based on genome-wide RNA sequencing, methylation, copy number variations, and whole exome sequencing identified over 100 dysregulated canonical pathways involving immunity, tissue differentiation and transformation as initiators of bladder carcinogenesis. Widespread dysregulation of interleukin signaling was the dominant change signifying the important role of inflammation and immunity in the incipient phases of urothelial carcinogenesis. The analyses of mutational patterns identified three types of mutations based on their geographic distribution and variant allele frequencies. The most common were low frequency subclonal mutations restricted to individual mucosal samples which were the progeny of their respective uroprogenitor cells. The two additional types of mutations were associated with clonal expansion and involved large areas of bladder mucosa. The first group referred to as α mutations, showed a low mutational frequency across the mucosa. The second group referred to as β mutations increased in their frequencies with disease progression and a large proportion of them represented mutated transcriptional regulators controlling proliferation. Time modeling revealed that bladder carcinogenesis is spanning 10-15 years and can be divided into dormant and progressive phases. The progressive phase lasted 1-2 years and was primarily driven by β mutations with high proliferative advantage. This is the first detailed molecular characterization of mucosal field effects initiating bladder carcinogenesis on the whole-organ scale. It provides novel insights into incipient phases of bladder carcinogenesis and biomarkers for early detection of bladder cancer as well as targets for preventive therapies.
Neural cell injury pathology due to high-rate mechanical loading
Authors: Estrada Jonathan B. , Cramer Harry C. , Scimone Mark T. , Buyukozturk Selda , Franck Christian 
Published: May 2021

AbstractSuccessful detection and prevention of brain injuries relies on the quantitative identification of cellular injury thresholds associated with the underlying pathology. Here, by combining a recently developed inertial microcavitation rheology technique with a 3D in vitro neural tissue model, we quantify and resolve the structural pathology and critical injury strain thresholds of neural cells occurring at high loading rates such as encountered in blast, cavitation or directed energy exposures. We find that neuronal dendritic spines characterized by MAP2 displayed the lowest physical failure strain at 7.3%, whereas microtubules and filamentous actin were able to tolerate appreciably higher strains (14%) prior to injury. Interestingly, while these critical injury thresholds were similar to previous literature values reported for moderate and lower strain rates (< 100 1/s), the pathology of primary injury reported here was distinctly different by being purely physical in nature as compared to biochemical activation during apoptosis or necrosis.TeaserControlled microcavitation enables quantitative identification of injury thresholds in neural cells.
Variable brain wiring through scalable and relative synapse formation inDrosophila
Authors: Kiral F. Ridvan , Dutta Suchetana B. , Linneweber Gerit Arne , Poppa Caroline , von Kleist Max , Hassan Bassem A. , Hiesinger Peter Robin 
Published: May 2021

AbstractVariability of synapse numbers and partners despite identical genes reveals limits of genetic determinism. Non-genetic perturbation of brain wiring can therefore reveal to what extent synapse formation is precise and absolute, or promiscuous and relative. Here, we show the role of relative partner availability for synapse formation in the fly brain through perturbation of developmental temperature. Unexpectedly, slower development at lower temperatures substantially increases axo-dendritic branching, synapse numbers and non-canonical synaptic partnerships of various neurons, while maintaining robust ratios of canonical synapses. Using R7 photoreceptors as a model, we further show that scalability of synapse numbers and ratios is preserved when relative availability of synaptic partners is changed in a DIPγ mutant that ablates R7’s preferred synaptic partner. Behaviorally, movement activity scales inversely with synapse numbers, while movement precision and relative connectivity are congruently robust. Hence, the fly genome encodes scalable relative connectivity to develop functional, but not identical, brains.One-Sentence SummaryNon-identical connectivity and behavior result from temperature-dependent synaptic partner availability inDrosophila.
Complex introgression among three diverged largemouth bass lineages
Authors: Silliman Katherine , Zhao Honggang , Justice Megan , Thongda Wilawan , Bowen Bryant , Peatman Eric 
Published: May 2021

AbstractHybrid zones between diverged lineages offer an unique opportunity to study evolutionary processes related to speciation. Natural and anthropogenic hybridization in the black basses (Micropterus spp.) is well documented, including an extensive intergrade zone between the widespread northern Largemouth Bass (M. salmoides) and the Florida Bass (M. floridanus). Phenotypic surveys have identified an estuarine population of Largemouth Bass (M. salmoides) in the Mobile-Tensaw Delta, with larger relative weight and smaller adult size compared to inland populations, suggesting a potential third lineage of largemouth bass. To determine the evolutionary relationships between these Mobile Delta bass populations, M. salmoides, and M. floridanus, putative pure and intergrade populations of all three groups were sampled across the eastern United States. Phylogenetic analyses of 8,582 nuclear SNPs derived from genotype-by-sequencing and the ND2 mitochondrial gene determined that Delta bass populations stem from a recently diverged lineage of Largemouth Bass. Using a novel quantitative pipeline, a panel of 73 diagnostic SNPs was developed for the three lineages, evaluated for accuracy, and then used to screen 881 samples from 52 sites for genetic integrity and hybridization on the Agena MassARRAY platform. These results strongly support a redrawing of native ranges for both the intergrade zone and M. floridanus, which has significant implications for current fisheries management. Furthermore, Delta bass ancestry was shown to contribute significantly to the previously described intergrade zone between northern Largemouth Bass and Florida Bass, suggesting a more complex pattern of secondary contact and introgression among these diverged Micropterus lineages.
Developmental single-cell transcriptomics of hypothalamic POMC progenitors reveal the genetic trajectories of multiple neuropeptidergic phenotypes
Authors: Yu Hui , Rubinstein Marcelo , Low Malcolm J 
Published: May 2021

AbstractProopiomelanocortin (POMC) neurons of the hypothalamic arcuate nucleus are essential to regulate food intake and energy balance. However, the ontogenetic transcriptional programs that specify the identity and functioning of these neurons are poorly understood. Here, we use scRNAseq to define the transcriptomes characterizing POMC progenitors in the developing hypothalamus and TRAP-seq to analyze the subsequent translatomes of mature POMC neurons. Our data show that Pomc-expressing neurons originate from multiple developmental pathways expressing distinct combinations of transcription factors. The predominant cluster, featured by high levels of Pomc and Prdm12 transcripts represents the precursor of canonical arcuate POMC neurons. Additional clusters of progenitors expressing lower levels of Pomc mature into different neuronal phenotypes characterized by distinct combinations of transcription factors, neuropeptides, processing enzymes, cell surface and nuclear receptors. We conclude that the genetic programs specifying the identity and differentiation of arcuate POMC neurons are diverse and generate a heterogeneous repertoire of neuronal phenotypes early in development that continue to evolve postnatally.
Mice lacking the cAMP effector protein POPDC1 show enhanced hippocampal synaptic plasticity
Authors: Shetty Mahesh Shivarama , Ris Laurence , Schindler Roland F. R. , Mizuno Keiko , Fedele Laura , Giese Karl Peter , Brand Thomas , Abel Ted 
Published: May 2021

AbstractExtensive research has uncovered diverse forms of synaptic plasticity and a wide array of molecular signaling mechanisms that act as positive or negative regulators. Specifically, cAMP-dependent signaling pathways have been crucially implicated in long-lasting synaptic plasticity. In this study, we examine the role of POPDC1 (or BVES), a cAMP effector protein expressed in brain, in modulating hippocampal synaptic plasticity. Unlike other cAMP effectors, such as PKA and EPAC, POPDC1 is membrane-bound and the sequence of the cAMP-binding cassette differs from canonical cAMP-binding domains. These properties suggest that POPDC1 may have a unique role in cAMP-mediated signaling underlying synaptic plasticity. Our results show that POPDC1 is enriched in hippocampal synaptoneurosomes. Acute hippocampal slices from Popdc1 knockout (KO) mice exhibit enhanced long-term potentiation (LTP) induced by a variety of stimulation paradigms, particularly in response to weak stimulation paradigms that in slices from wildtype mice induce only transient LTP. Furthermore, Popdc1 KO mice did not display any further enhancement in forskolin-induced LTP observed following inhibition of phosphodiesterases (PDEs), suggesting a possible modulation of cAMP-PDE signaling by POPDC1. Taken together, these data reveal POPDC1 as a novel player in the regulation of hippocampal synaptic plasticity and as a potential target for cognitive enhancement strategies.