bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of efficacy, efficiency, and durability in novel tourniquet designs
Authors: Treager Christopher , Lopachin Tyler , Mandichak Sally , Kinney Bradley , Bohan Megan , Boboc Michael , Go Christian , Friedrich Emily , Stuart Sean 
Published: April 2021

BACKGROUND
Exsanguination due to extremity hemorrhage is a major cause of preventable traumatic deaths. Extremity tourniquet use has been shown to be safe and improve survival. The purpose of this study was to compare the efficacy, efficiency, and durability of the Generation 7 Combat Application Tourniquet (CAT; North American Rescue, Greer, SC), the Tactical Mechanical Tourniquet (TMT; Combat Medical Systems, Harrisburg, NC), and the SOF Tactical Tourniquet—Wide (SOFTT-W; Tactical Medical Solutions, Anderson, SC).

METHODS
This study was a three-phase randomized, cross-over trial. In successive trials, subjects were timed during the application of each tourniquet to the upper and lower extremity. Following successful lower extremity application, subjects low crawled 25 ft and then were dragged 25 ft, after which effectiveness was reassessed, as defined by the cessation of distal pulses by Doppler ultrasound.

RESULTS
In arm application, both the CAT and TMT had significantly less failure rates than the SOFTT-W (5.56%, 19.44%, 58.33%), with the CAT being the fastest tourniquet when compared with TMT and SOFTT-W (37.8 seconds, 65.01 seconds, 63.07 seconds). In leg application, the CAT had significantly less rates of failure when compared with the SOFTT-W, but there was no other significant difference between the tourniquets (27.78%, 44.44%, 61.11%). In addition, the CAT was significantly faster than both the TMT and SOFTT-W when applied to the leg (8.33 seconds, 40.96 seconds, 34.5 seconds). There was no significant difference in tourniquet failure rates between the three tourniquets after subject maneuvers in phase 3 (34.29%, 42.86%, 45.45%).

DISCUSSION
The CAT is as effective as the TMT and significantly more effective than the SOFTT-W. In addition, the CAT demonstrated shorter application times than either the TMT or SOFTT-W. However, there was no significant difference between the three tourniquets in their ability to maintain pulselessness after subject maneuvers.

LEVEL OF EVIDENCE
Care management, level II.
Kidney Transplantation in Small Children: Association Between Body Weight and Outcome—A Report From the ESPN/ERA-EDTA Registry
Authors: Boehm Michael , Bonthuis Marjolein , Aufricht Christoph , Battelino Nina , Bjerre Anna , Edvardsson Vidar O. , Herthelius Maria , Hubmann Holger , Jahnukainen Timo , de Jong Huib , Laube Guido F. , Mattozzi Francesca , Molchanova Elena A. , Muñoz Marina , Noyan Aytul , Pape Lars , Printza Nikoleta , Reusz George , Roussey Gwenaelle , Rubik Jacek , Spasojevic'-Dimitrijeva Brankica , Seeman Tomas , Ware Nicholas , Vidal Enrico , Harambat Jérôme , Jager Kitty J. , Groothoff Jaap 
Published: April 2021

Background.
Many centers accept a minimum body weight of 10 kg as threshold for kidney transplantation (Tx) in children. As solid evidence for clinical outcomes in multinational studies is lacking, we evaluated practices and outcomes in European children weighing below 10 kg at Tx.

Methods.
Data were obtained from the European Society of Paediatric Nephrology/European Renal Association and European Dialysis and Transplant Association Registry on all children who started kidney replacement therapy at <2.5 y of age and received a Tx between 2000 and 2016. Weight at Tx was categorized (<10 versus ≥10 kg) and Cox regression analysis was used to evaluate its association with graft survival.

Results.
One hundred of the 601 children received a Tx below a weight of 10 kg during the study period. Primary renal disease groups were equal, but Tx <10 kg patients had lower pre-Tx weight gain per year (0.2 versus 2.1 kg; P < 0.001) and had a higher preemptive Tx rate (23% versus 7%; P < 0.001). No differences were found for posttransplant estimated glomerular filtration rates trajectories (P = 0.23). The graft failure risk was higher in Tx <10 kg patients at 1 y (graft survival: 90% versus 95%; hazard ratio, 3.84; 95% confidence interval, 1.24-11.84), but not at 5 y (hazard ratio, 1.71; 95% confidence interval, 0.68-4.30).

Conclusions.
Despite a lower 1-y graft survival rate, graft function, and survival at 5 y were identical in Tx <10 kg patients when compared with Tx ≥10 kg patients. Our results suggest that early transplantation should be offered to a carefully selected group of patients weighing <10 kg.
Quetiapine for Bipolar Depressive Episode in Obsessive-Compulsive Disorder Patients Maintained on Selective Serotonin Reuptake Inhibitor Treatment
Authors: Poyurovsky Michael , Weizman Abraham 
Published: April 2021

Objectives
A meaningful proportion of patients with obsessive-compulsive disorder (OCD) develop symptoms of bipolar depression (BP-D). In the present investigation, we aimed to determine whether quetiapine is efficacious in OCD patients who despite continuous treatment with a selective serotonin reuptake inhibitor developed an acute episode of BP-D.

Methods
We analyzed 68 charts of Diagnostic and Statistical Manual of Mental Disorders Fifth Edition OCD patients from our outpatient clinic and identified 15 patients who in addition met Diagnostic and Statistical Manual of Mental Disorders Fifth Edition criteria for bipolar II disorder, depressive episode. Eleven (7 men and 4 women, aged 24–54 years) patients for whom quetiapine was added to treat the index episode of BP-D were included. Treatment response was assessed retrospectively and defined as a score of “much improved” or “very much improved” on the Clinical Global Impression—Improvement scale.

Results
Quetiapine was added for treatment of BP-D in a dose range of 150 to 400 mg (mean, 273 mg). Eight (73%) of the 11 study patients fulfilled the criterion of response, that is a score of “much improve” (4 patients) and “very much improved” (4 patients) on the Clinical Global Impression—Improvement scale. Notably, quetiapine was associated with additional improvement of OCD symptoms in 6 of 8 study responders. Quetiapine was well tolerated. The most frequently detected side effects were drowsiness (5 patients), constipation (4 patients), and orthostatic hypotension (2 patients).

Conclusions
The revealed beneficial effect of quetiapine addition for acute episode of BP-D in OCD patients maintained on selective serotonin reuptake inhibitor treatment merits further controlled investigation.
Electroconvulsive Therapy Applications on Children in the 1940s
Authors: Sirgiovanni Elisabetta 
Published: April 2021

Abstract
The existence of pediatric applications of electroconvulsive therapy (ECT) in the 1940s in Italy has been neglected by international literature. However, 2 case reports by Ferdinando Accornero and Mario Anderson, both assistants of Ugo Cerletti at the Sapienza Clinic for Nervous and Mental Diseases, should be brought to the attention of historians of ECT. The work presented therein began in Rome in September 1940, approximately at the same time of the first reported ECT administration on a child in Bristol, United Kingdom. The 2 reports described applications on 19 children and adolescents during 3 different sessions (1940–1941, 1944–1947, and 1947–1949), with a 3-year-long interruption due to the circumstances of World War II. Unfortunately, this research appeared belatedly in 2 articles from 1948 and 1950, respectively, in an Italian journal with limited distribution, when more extensive research contributions on pediatric ECT had already received international exposure. The Italian reports may cast light on the progress made by the early generation of ECT researchers in the 1940s toward the refinement of ECT techniques and the subsequent identification of diagnostic indicators for ECT among children.
Repeated stimulation of the HPA axis alters white blood cell counts without increasing oxidative stress or inflammatory cytokines in fasting elephant seal pups
Authors: Ensminger David C. , Crocker Daniel E. , Lam Emily K. , Kaitlin N. Allen , Vázquez-Medina José Pablo 
Published: April 2021

AbstractThe hypothalamic-pituitary-adrenal (HPA) axis controls the release of glucocorticoids, which regulate immune and inflammatory function by modulating cytokines, white blood cells (WBCs), and oxidative stress via glucocorticoid receptor (GR) signaling. Although the response to HPA activation is well characterized in many species, little is known about the impacts of HPA activation during extreme physiological conditions in marine mammals. Hence, we challenged 18 simultaneously fasting and developing elephant seal pups with daily intramuscular injections of adrenocorticotropin (ACTH), a GR antagonist (RU486), or a combination (ACTH+RU486) for four days (4d). We collected blood at baseline, two hours (2h), and 4d after the beginning of treatment. ACTH and ACTH+RU486 elevated serum aldosterone and cortisol at 2h, with effects diminishing at 4d. RU486 alone induced a compensatory increase in aldosterone, but not cortisol, at 4d. ACTH decreased neutrophils at 2h while decreasing lymphocytes and increasing neutrophil:lymphocyte ratio at 4d. These effects were abolished by RU486. Despite alterations in WBCs, there was no effect of ACTH or RU486 on transforming growth factor-β or interleukin-6 levels; however, both cytokines decreased with the 4-d fasting progression. Similarly, ACTH did not impact protein oxidation, lipid peroxidation, or antioxidant enzymes, but plasma isoprostanes and catalase activity decreased while glutathione peroxidase increased with fasting progression. These data demonstrate differential acute (2h) and chronic (4d) modulatory effects of HPA activation on WBCs and that the chronic effect is mediated, at least in part, by GR. These results also underscore elephant seals’ resistance to potential oxidative stress derived from repeated HPA activation.Summary statementMany species experience oxidative stress and inflammation after repeated activation of the hypothalamic-pituitary-adrenal axis. We show that simultaneously fasting and developing elephant seals are resistant to repeated hypothalamic-pituitary-adrenal axis activation.
Region-specific effects of early-life status epilepticus on the adult hippocampal CA3 – medial entorhinal cortex circuitryin vitro: focus on interictal spikes and concurrent high-frequency oscillations
Authors: Lisgaras Christos Panagiotis , Mikroulis Apostolos , Psarropoulou Caterina 
Published: April 2021

ABSTRACTConvulsive status epilepticus (SE) in immature life is often associated with lasting neurobiological changes. We provoked SE by pentylenetetrazole in postnatal day 20 rat pups and examined communication modalities between the temporal hippocampus and medial entorhinal cortex (mEC)in vitro. After a minimum of 40 days post-SE, we prepared combined temporal hippocampal - medial entorhinal cortex (mEC) slices from conditioned (SE) and naïve (N) adult rats and recorded 4-aminopyridine-induced spontaneous epileptiform interictal-like discharges (IED) simultaneously from CA3 and mEC layer V-VI. We analyzed IED frequency and high frequency oscillations (HFOs) in intact slices and after surgical separation of hippocampus from mEC, by two successive incisions (Schaffer collateral cut, Parasubiculum cut). In all slices, IED frequency was higher in CA3 vs mEC and Raster plots indicated no temporal coincidence between them either in intact or in CA1-cut slices. IED frequency was significantly higher in SE mEC, but similar in SE and N CA3, independently of connectivity state. Ripples (R) and Fast Ripples (FR) coincided with IEDs and their power differed between SE and N intact slices, both in CA3 and mEC. CA3 FR/R ratios were higher in the absence of mEC. Moreover, SE (vs N) slices showed significantly higher FR/R ratios independently of the presence of mEC. Taken together, these findings suggest lasting effects of immature SE in network dynamics governing hippocampal-entorhinal communication which may impact adult cognitive, behavioral and/or seizure threshold sequalae.HIGHLIGHTSEarly-life Status Epilepticus (SE) impacts on the adult hippocampal – entorhinal communication in thein vitro4-AP modelPost-SE CA3 output decreases in HFO power with no change in interictal discharge frequencyPost-SE mEC output increases both in HFO power and interictal discharge frequencyInterictal HFO dynamics in CA3-mEC change upon the connectivity state of the two areas and priorhistory of early-life SE
Fungicide resistance characterised across seven modes of action inBotrytis cinereaisolated from Australian vineyards
Authors: Harper Lincoln A. , Paton Scott , Hall Barbara , McKay Suzanne , Oliver Richard P. , Lopez-Ruiz Francisco J. 
Published: April 2021

AbstractBACKGROUNDBotrytis bunch rot, caused byBotrytis cinerea, is an economically important disease of grapes in Australia and across grape growing regions worldwide. Control of this disease relies on canopy management and the application of fungicides. Fungicide application can lead to the selection of resistantB. cinereapopulations, which has an adverse effect on management of the disease. Characterising the distribution and severity of resistantB. cinereapopulations is needed to inform resistance management strategies.RESULTSIn this study, 725 isolates were sampled from 75 Australian vineyards during 2013 – 2016 and were screened against seven fungicides with different modes of action (MOAs). The resistance frequencies for azoxystrobin, boscalid, fenhexamid, fludioxonil, iprodione, pyrimethanil and tebuconazole were 5, 2.8, 2.1, 6.2, 11.6, 7.7 and 2.9% respectively. Nearly half of the resistant isolates (43.8%) were resistant to more than one of the fungicides tested. The frequency of vineyards with at least one isolate simultaneously resistant to 1, 2, 3, 4 or 5 fungicides was 19.5, 7.8, 6.5, 10.4 and 2.6%. Resistance was associated with previously published genotypes inCytB(G143A),SdhB(H272R/Y),Erg27(F412S),Mrr1(D354Y),Bos1(I365S, N373S + Q369P, I365S + D757N) andPos5(V273I, P319A, L412F/V). Novel genotypes were also described inMrr1(S611N, D616G)Pos5(V273L) andCyp51(P347S). Expression analysis was used to characterise fludioxonil resistant isolates exhibiting overexpression (6.3-9.6-fold) of the ABC transporter geneAtrB(MDR1 phenotype).CONCLUSIONResistance frequencies were lower when compared to most previously published surveys ofB. cinerearesistance in grape and other crops. Nevertheless, continued monitoring of critical MOAs used in Australian vineyards is recommended.
A simple assay for quantification of plant-associative bacterial nitrogen fixation
Authors: Haskett Timothy L , Poole Philip S 
Published: April 2021

AbstractAccurate quantification of plant-associative bacterial nitrogen (N) fixation is crucial for selection and development of elite diazotrophic inoculants that could be used to supply cereal crops with nitrogen in a sustainable manner. Because a low oxygen environment that may not be conducive to plant growth is essential for optimal stability and function of the N-fixing catalyst nitrogenase, quantification of N fixation is routinely carried out on “free-living” bacteria grown in the absence of a host plant. Such experiments may not divulge the true extent of N fixation occurring in the rhizosphere where the availability and forms of nutrients such as carbon and N, which are key regulators of N fixation, may vary widely. Here, we present a modifiedin plantaacetylene reduction assay, utilising the model cereal barley as a host, to quantify associative N fixation by diazotrophic bacteria. The assay is rapid, highly reproducible, applicable to a broad range of diazotrophs, and can be performed with simple equipment commonly found in most laboratories that investigate plant-microbe interactions.ImportanceExploiting “nitrogen-fixing” bacteria that reduce atmospheric dinitrogen into ammonia as inoculants of cereal crops has great potential to alleviate current inputs of environmentally deleterious fertiliser nitrogen and drive more sustainable crop production. Accurately quantifying plant-associative bacterial nitrogen fixation is central to the development of such inoculant bacteria, but most assays fail to adequately reproduce the conditions of plant root systems. In this work, we have validated and optimised a simplein plantaassay to accurately quantify N fixation in bacteria occupying the root and surrounding soil of the model cereal barley. This assay represents a benchmark for quantification of plant-associative bacterial N fixation.
RNA-controlled nucleocytoplasmic shuttling of mRNA decay factors regulates mRNA synthesis and initiates a novel mRNA decay pathway
Authors: Chattopadhyay Shiladitya , Garcia-Martinez Jose , Haimovich Gal , Khwaja Aya , Barkai Oren , Ghosh Ambarnil , Chuarzman Silvia Gabriela , Schuldiner Maya , Elran Ron , Rosenberg Miriam , Bohnsack Katherine , Bohnsack Markus , Perez-Ortin Jose E , Choder Mordechai 
Published: April 2021

AbstractmRNA level is controlled by factors that mediate both mRNA synthesis and decay, including the exonuclease Xrn1 - a major mRNA synthesis and decay factor. Here we show that nucleocytoplasmic shuttling of Xrn1 and of some of its associated mRNA decay factors plays a key role in determining both mRNA synthesis and decay. Shuttling is regulated by RNA-controlled binding of the karyopherin Kap120 to two nuclear localization sequences (NLSs) in Xrn1. The decaying RNA binds and masks NLS1, establishing a link between mRNA decay and Xrn1 shuttling. Mutations in the two NLSs, which prevent Xrn1 import, compromise transcription and, unexpectedly, also the cytoplasmic decay of ∼50% of the cellular mRNAs - comparably to Xrn1 deletion. These findings uncover a cytoplasmic mRNA decay pathway that begins in the nucleus. Interestingly, Xrn1 shuttling is required for proper adaptation to environmental changes, in particular to ever changing environmental fluctuations.
Novel zebrafish mutants reveal new roles for Apolipoprotein B during embryonic development and pathological conditions
Authors: Templehof Hanoch , Moshe Noga , Avraham-Davidi Inbal , Yaniv Karina 
Published: April 2021

ABSTRACTApolipoprotein B (ApoB) is the primary protein of chylomicrons, VLDLs and LDLs and is essential for their assembly. Defects in ApoB synthesis and secretion result in several human diseases, including abetalipoproteinemia and familial hypobetalipoproteinemia. Conversely, high levels of APOB in plasma are associated with increased risk for coronary heart disease and atherosclerosis.The involvement of APOB in lipid metabolism and atherogenesis prompted the generation of several mutant mice. However, as APOB is required for supplying nutrients to the developing embryo,ApoBnull mice are embryonic lethal, thereby precluding the study of the roles of this protein during development.Here, we established novel zebrafish mutants for twoapoBgenes:apoBaandapoBb.1. Double-mutant embryos display clear hallmarks of human hypolipidemia-related diseases, including intestinal defects and fatty liver, as well as profound vascular defects. We further use these models to identify the domains within ApoB responsible for its functions. By assessing the ability of different truncated forms of human APOB to rescue the mutant phenotypes, we demonstrate the benefits of this model for prospective therapeutic screens. Overall, our novel zebrafish models uncover new functions of ApoB in organ development and morphogenesis and shed new light on the mechanisms underlying hypolipidemia-related diseases.
Single-Cell Multiomics Reveals Distinct Cell States at the Top of the Human Hematopoietic Hierarchy
Authors: Sommarin Mikael N.E. , Dhapola Parashar , Safi Fatemeh , Warfvinge Rebecca , Ulfsson Linda Geironson , Erlandsson Eva , Konturek-Ciesla Anna , Thakur Ram Krishna , Böiers Charlotta , Bryder David , Karlsson Göran 
Published: April 2021

AbstractThe advent of single cell (Sc) genomics has challenged the dogma of haematopoiesis as a tree-like structure of stepwise lineage commitment through distinct and increasingly restricted progenitor populations. Instead, analysis of ScRNA-seq has proposed that the earliest events in human hematopoietic stem cell (HSC) differentiation are characterized by only subtle molecular changes, with hematopoietic stem and progenitor cells (HSPCs) existing as a continuum of low-primed cell-states that gradually transition into a specific lineage (CLOUD-HSPCs). Here, we combine ScRNA-seq, ScATAC-seq and cell surface proteomics to dissect the heterogeneity of CLOUD-HSPCs at different stages of human life. Within CLOUD-HSPCs, pseudotime ordering of both mRNA and chromatin data revealed a bifurcation of megakaryocyte/erythroid and lympho/myeloid trajectories immediately downstream a subpopulation with an HSC-specific enhancer signature. Importantly, both HSCs and lineage-restricted progenitor populations could be prospectively isolated based on correlation of their molecular signatures with CD35 and CD11A expression, respectively. Moreover, we describe the changes that occur in this heterogeneity as hematopoiesis develops from neonatal to aged bone marrow, including an increase of HSCs and depletion of lympho-myeloid biased MPPs. Thus, this study dissects the heterogeneity of human CLOUD-HSPCs revealing distinct HSPC-states of relevance in homeostatic settings such as ageing.
IRC3regulates mitochondrial translation in response to metabolic cues inSaccharomyces cerevisiae
Authors: Kaur Jaswinder , Datta Kaustuv 
Published: April 2021

AbstractMitochondrial oxidative phosphorylation (OXPHOS) enzymes are made up of dual genetic origin. Mechanism regulating expression of nuclear encoded OXPHOS subunits in response to metabolic cues (glucose vs. glycerol), is significantly understood while regulation of mitochondrially encoded OXPHOS subunits is poorly defined. Here, we show thatIRC3a DEAD/H box helicase, previously implicated in mitochondrial DNA maintenance, is central to integrating metabolic cues with mitochondrial translation. Irc3 associates with mitochondrial small ribosomal subunit in cells consistent with its role in regulating translation elongation based on Arg8mreporter system. Glucose grownΔirc3ρ+andirc3temperature sensitive cells at 37⁰C have reduced translation rates from majority of mRNAs. In contrast, when galactose was the carbon source, reduction in mitochondrial translation was observed predominantly from Cox1 mRNA inΔirc3ρ+but no defect was observed inirc3temperature sensitive cells, at 37⁰C. In support, of a model wherebyIRC3responds to metabolic cues, suppressors of Δirc3isolated for restoration of growth on glycerol media restore mitochondrial translation differentially in presence of glucose vs. glycerol.