bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence-based intrapartum care practice and its associated factors among obstetric care providers working in hospitals of the four Wollega Zones, Oromia Region, West Ethiopia, 2022
Authors: Wodajo Seid , Olani Adugna , Mosisa Alemnesh , Misganaw Dawit , Minayehu Ambaye , Teklay Berhane , Desalew Yaregal , Gashaw Yegoraw , Dagnaw Yilkal 
Published: September 2022

AbstractBackgroundEven though Evidence-Based Practice (EBP) is a key component of quality of Intrapartum care and links to improved health care outcomes, consistent application of EBP in patient care remains a challenge for health care providers. In the study area, there are no previous studies conducted on evidence-based Intrapartum care practice among obstetric care providers. Therefore, this study was aimed to assess the magnitude of evidence based intra-partum care practice and its associated factors among obstetric care providers working in hospitals of Wollega zones, Oromia, Western Ethiopia, 2022.MethodAn institution-based cross-sectional study design using quantitative method was conducted from January to April/2022 in 11 hospitals of the four Wollega zones. All obstetric care providers (278) who were practicing Intrapartum care in the selected hospitals were included. The data was collected using structured self-administered questionnaire and paper-based observational checklist. Data was entered via Epi-Data version 3.1 and analyzed by SPSS version 25 statistical software. To see the association between the independent variables and evidence based Intrapartum care practice, multivariable logistic regression analysis was done. Adjusted odds ratios (OR) with their 95% Confidence interval were reported. The statistical significance of association was declared at p-value ≤ 0.05. Tables, figures and charts were also used in descriptive statistics.ResultThe overall magnitude of evidence-based Intrapartum care practice was found to be 63.7% [95% CI (59.7, 67.7)]. There was a statistically significant association between evidence-based Intrapartum care practice and having good knowledge about Intrapartum care practice [AOR=2.95; 95% CI (1.52,5.73)], positive attitude towards Intrapartum care practice [AOR=3.13; 95% CI (1.59,6.16)], availability of updated Intrapartum care guideline [AOR=2.88; 95% CI (1.46,5.70)], number of obstetric care providers per a shift (≥5 care providers) [AOR=2.31; 95% CI (1.01,5.29)], number of deliveries within a day (<10 deliveries) [AOR=4.61; 95% CI (2.28,9.31)], educational level (MSc and above) [AOR=5.75; 95% CI (2.23,14.84)] at p-value ≤ 0.05.Conclusion and recommendationsOur study revealed that, magnitude of evidence-based Intrapartum care practice was found to be low according to the WHO recommendation. These findings indicate that additional attention and monitoring is required to implement current Intrapartum care practices with the WHO guidelines.
Inactivation of DRG1, encoding a translation factor GTPase, causes a Recessive Neurodevelopmental Disorder
Authors: Westrip Christian A. E. , Paul Franziska , Al-Murshedi Fathiya , Qaitoon Hashim , Cham Breana , Fletcher Sally C. , Hendrix Eline , Boora Uncaar , Ng Alvin Yu Jin , Bonnard Carine , Najafi Maryam , Alawbathani Salem , Lambert Imelda , Fox Gabriel , Venkatesh Byrappa , Bertoli-Avella Aida , Tan Ee Shien , Al-Maawali Almundher , Reversade Bruno , Coleman Mathew L. 
Published: September 2022

ABSTRACTDRG1 is a highly conserved member of a class of GTPases implicated in ribosome biogenesis and translation. The expression of mammalian DRG1 is elevated in the central nervous system during development, and its function has been implicated in fundamental cellular processes including protein synthesis and cellular proliferation. Using exome sequencing, we identified rare and likely pathogenic germlineDRG1variants including three stop-gained p.Gly54*, p.Arg140*, p.Lys263* and a p.Asn248Phe missense variant. These alleles segregate recessively in four affected individuals from three unrelated families and cause a neurodevelopmental disorder with global developmental delay, microcephaly, short stature and craniofacial anomalies. Using functional assays, we show that these loss-of-function variants: 1) severely disrupt DRG1 mRNA/protein stability in patient-derived fibroblasts, 2) impair it’s GTPase activityin vitroand 3) compromise it’s binding to partner protein ZC3H15. Consistent with the importance of DRG1 in humans, targeted inactivation ofDrg1in mice resulted in pre-weaning lethality. Our work highlights the importance of DRG1 GTPase activity for normal development and underscores the significance of translation factor GTPases in human physiology and homeostasis.
Predictive Biomarkers for the Responsiveness of Recurrent Glioblastomas to Activated Killer Cell Immunotherapy
Authors: Hwang Sohyun , Lim Jaejoon , Kang Haeyoun , Jeong Ju-Yeon , Joung Je-Gun , Heo Jinhyung , Jung Daun , Cho Kyunggi , An Hee Jung 
Published: September 2022

AbstractBackgroundRecurrent glioblastoma multiforme (GBM) is a highly aggressive primary malignant brain tumor that is resistant to existing treatments. Recently, we reported that activated autologous natural killer (NK) cell therapeutics induced a marked increase in survival of some patients with recurrent GBM.MethodsTo identify biomarkers that predict responsiveness to NK therapeutics, we examined immune profiles in tumor tissues using NanoString nCounter analysis and compared the profiles between 5 responders and 7 non-responders. Through a three-step data analysis, we identified three candidate biomarkers (TNFRSF18, TNFSF4, and IL12RB2) and performed validation with qRT-PCR. We also performed immunohistochemistry and an NK cell migration assay to assess the function of these genes.ResultsResponders had higher expression of many immune-signaling genes compared with non-responders, which suggests an immune-active tumor microenvironment in responders. The random forest model that identified TNFRSF18, TNFSF4, and IL12RB2 showed a 100% accuracy (95% CI: 73.5%–100%) for predicting the response to NK therapeutics. The expression levels of these three genes by qRT-PCR were highly correlated with the NanoString levels, with high Pearson’s correlation coefficients (0.419 (TNFRSF18), 0.700 (TNFSF4), and 0.502 (IL12RB2)); their prediction performance also showed 100% accuracy (95% CI: 73.54%–100%) by logistic regression modeling. We also demonstrated that these genes were related to cytotoxic T cell infiltration and NK cell migration in the tumor microenvironment.ConclusionsWe identified TNFRSF18, TNFSF4, and IL12RB2 as biomarkers that predict response to NK cell therapeutics in recurrent GBM, which might provide a new treatment strategy for this highly aggressive tumor.
Screening and Development of Constitutively Synergistic Combination Drug Formulations for T Cell Acute Lymphoblastic Leukemia
Authors: Kelvin James M , Zhang Dan Y , Williams Evelyn K , Moore Samuel G , Birnbaum Lacey A , Zecca Henry , Wang Xiaodong , Jain Juhi , Qui Min , Jui Nathan T , Fu Haian , Du Yuhong , Kemp Melissa L , Lam Wilbur A , DeRyckere Deborah , Graham Douglas K , Dreaden Erik C 
Published: September 2022

ABSTRACTAdvances in multiagent chemotherapy have led to recent improvements in overall survival for patients with acute lymphoblastic leukemia (ALL); however, a significant fraction do not respond to frontline chemotherapy or later relapse with recurrent disease, after which long-term survival rates remain low. To address the challenge of developing new, effective treatment options for these patients, we conducted a series of high-throughput combination drug screens to identify chemotherapies that synergize in a lineage-specific manner with MRX-2843, a small molecule dual MERTK and FLT3 kinase inhibitor currently in clinical testing for treatment of relapsed/refractory leukemias and solid tumors. Using experimental and computational approaches, we found that MRX-2843 synergized strongly – and in a ratio-dependent manner – with vincristine chemotherapy to inhibit T-ALL cell expansion and, based on these findings, we developed multiagent lipid nanoparticle formulations of these drugs that not only constitutively maintained ratiometric drug synergy following T-ALL cell delivery, but also improved anti-leukemic activity following drug encapsulation. To determine the clinical relevance of these combination drug formulations and the therapeutic impact of ratiometric drug synergy, we compared the efficacy of lipid nanoparticles comprising synergistic, additive, and antagonistic ratios of MRX-2843 and vincristine, and observed that trends in in vitro synergy were directly recapitulated in primary T-ALL patient samples. Together, these findings present a systematic approach to high-throughput combination drug screening and multiagent drug delivery that maximizes the therapeutic potential of combined MRX-2843 and vincristine in T-ALL. This broadly generalizable approach could lead to the development of constitutively synergistic combination products for the treatment of cancer and other diseases.
MalariaSED: a deep learning framework to decipher the regulatory contributions of noncoding variants in malaria parasites
Authors: Wang Chengqi , Dong Yibo , Li Chang , Oberstaller Jenna , Zhang Min , Gibbons Justin , Pires Camilla Valente , Xiao Mianli , Zhu Lei , Jiang Rays H.Y. , Kim Kami , Miao Jun , Otto Thomas D. , Cui Liwang , Adams John H. , Liu Xiaoming 
Published: September 2022

AbstractMalaria remains one of the deadliest infectious diseases. Transcriptional regulation effects of noncoding variants in this unusual genome of malaria parasites remain elusive. We developed a sequence-based,ab initiodeep learning framework, MalariaSED, for predicting chromatin profiles in malaria parasites. The MalariaSED performance was validated by published ChIP-qPCR and TF motifs results. Applying MalariaSED to ∼1.3 million variants shows that geographically differentiated noncoding variants are associated with parasite invasion and drug resistance. Further analysis reveals chromatin accessibility changes atPlasmodium falciparumrings are partly associated with artemisinin resistance. MalariaSED illuminates the potential functional roles of noncoding variants in malaria parasites.
Deep proteomics identifies shared molecular pathway alterations in synapses of schizophrenia and bipolar disorder patients and mouse model
Authors: Aryal Sameer , Bonanno Kevin , Song Bryan , Mani D.R. , Keshishian Hasmik , Carr Steven A. , Sheng Morgan , Dejanovic Borislav 
Published: September 2022

AbstractSynaptic dysfunction is implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BP). We used quantitative mass-spectrometry to carry out deep and unbiased profiling of the proteome of synapses purified from the dorsolateral prefrontal cortex of 35 cases of SCZ, 35 cases of BP, and 35 controls. Compared to controls, SCZ and BP synapses showed substantial and similar proteomic alterations. Network and gene set enrichment analyses revealed upregulation of proteins associated with autophagy and certain vesicle transport pathways, and downregulation of proteins related to synaptic, mitochondrial, and ribosomal function in the synapses of individuals with SCZ or BP. Some of the same pathways (e.g., upregulation of vesicle transport, downregulation of mitochondrial and ribosomal proteins) were similarly dysregulated in the synaptic proteome of mutant mice deficient in Akap11, a recently discovered shared risk gene for SCZ and BP. Our work provides novel biological insights into molecular dysfunction at the synapse in SCZ and BP and serves as a resource for understanding the pathophysiology of these debilitating neuropsychiatric disorders.
Contribution of private game ranching and captive bred operations in South Africa to White rhinoCeratotherium simumspecies survival conservation
Authors: Furstenburg Deon , Otto Michelle , Van Niekerk Pieter , Lewitton Derek 
Published: September 2022

AbstractThe southern white rhinoceros (SWR)Ceratotherium simum simum,like all extant rhinoceros’ species, is under global threat of extinction, due to their dwindling wild population numbers in protected areas and state-owned parks as a result of poaching. The Kruger National Park (KNP), the renowned state-owned stronghold for SWR, has suffered an estimated decline of over 75.0% of its population since 2011, with the highest annual poaching rates over the past decade and a remaining population estimated at only 2,607 animals by the end of 2020, which is an average annual population decline of −10.2% from 2008 to 2020, and 2,458 animals left by the end of June 2022. On the contrary, SWR under private custodianship and management on rewilded agro-sustainable biodiversity game ranches in South Africa (estimated currently at >8,000 animals, some of which are registered Captive Breeding Operations [CBO]; assessed CBOs contained 2,882 rhinos at the time of this study (Sep 2021), have increased in population numbers and survival rates, sustaining average annual population growth performances of 9.0%. This increase has been attributed to effective security, provision of additional habitat, dispersal, and frequent genetic exchange of rhinos between breeding subpopulations by the private sector. The conservation success of the private sector has largely been overlooked and disregarded by world conservation bodies and organizations, mostly due to misguided and prejudiced media publicity and the lack of scientific analytical assessment. Private rhino custodians and their biological/ conservation breeding practices, with private agro-sustainable biodiversity wildlife management and/ or captive breeding, generally being perceived and branded as either “canned” or equated to “captive zoological-gardens”. Since the commencement of the International Convention on Biodiversity, global controversy exists whereby most of mankind today perceive bio-conservation of a species to be assigned in principle solely to protected areas and state-owned parks. The unique and advantageous roles of rewilded bio-conservation and sustainable-use conservation CBOs, being a key to green-economy and natural capital in a post-Covid-19 struggle, are mostly ignored. This study serves to assess and quantify the impact of private wildlife ranching in South Africa with specific focus on its potential contribution to rhino conservation specifically for that of the SWRC.s. simum.Data Availability StatementThe data belong to third parties, six different private owners respectively, and cannot be shared publicly. Interested, qualified researchers can request the data by contacting the author, subject to owner’s permission. The authors confirm that they did not have any special access privileges to the data and data will be made available to other researchers in the same manner that the authors accessed it.
New estimates of genome size in Orthoptera and their evolutionary implications
Authors: Hawlitschek Oliver , Sadílek David , Dey Lara-Sophie , Buchholz Katharina , Noori Sajad , Baez Inci Livia , Wehrt Timo , Brozio Jason , Trávníček Pavel , Seidel Matthias , Husemann Martin 
Published: September 2022

AbstractAnimal genomes vary widely in size, and much of their architecture and content remains poorly understood. Even among related groups, such as orders of insects, genomes may vary in size by orders of magnitude – for reasons unknown. The largest known insect genomes were repeatedly found in Orthoptera, e.g.,Podisma pedestris(1C = 16.93 pg),Stethophyma grossum(1C = 18.48 pg) andBryodemella holdereri(1C = 18.64 pg). While all these species belong to the suborder of Caelifera, the ensiferanDeracantha onos(1C = 19.60 pg) was recently found to have the largest genome. Here, we present new genome size estimates of 50 further species of Ensifera (superfamilies Gryllidea, Tettigoniidea) and Caelifera (Acrididae, Tetrigidae) based on flow cytometric measurements. We found thatBryodemella tuberculata(Caelifera: Acrididae) has the so far largest measured genome of all insects with 1C = 21.96 pg (21.48 gBp). Species with 2n = 16 and 2n = 22 chromosomes have significantly larger genomes than species with other chromosome counts. Gryllidea genomes vary between 1C = 0.95 and 2.88 pg, and Tetrigidae between 1C = 2.18 and 2.41, while the genomes of all other studied Orthoptera range in size from 1C = 1.37 to 21.96 pg. Reconstructing ancestral genome sizes based on a phylogenetic tree of mitochondrial genomic data, we found genome size values of >15.84 pg only for the nodes ofBryodemella holdereri/B. tuberculataandChrysochraon dispar/Euthystira brachyptera. The predicted values of ancestral genome sizes are 6.19 pg for Orthoptera, 5.37 pg for Ensifera, and 7.28 pg for Caelifera. The reasons for the large genomes in Orthoptera remain largely unknown, but a duplication seems unlikely as chromosome numbers do not differ. Sequence-based genomic studies may shed light on the underlying evolutionary mechanisms.
Using occipital ⍺-bursts to modulate behaviour in real-time
Authors: Vigué-Guix Irene , Soto-Faraco Salvador 
Published: September 2022

ABSTRACTSpontaneous oscillatory neural activity can influence the processing of incoming sensory input and subsequent behavioural reactions. Spontaneous oscillatory activity mostly appears in stochastic bursts, but typical trial-averaged approaches fail to capture this. We aimed at relating oscillatory bursts in the alpha band (8-13 Hz) to behaviour directly, via an EEG-based brain-computer interface (BCI) that allowed for burst-triggered stimulus presentation in real-time in a visual detection task. According to alpha theories, we hypothesised that targets presented during alpha-bursts should lead to slower responses and higher miss rates, whereas targets presented in the absence of bursts should lead to faster responses and higher false alarm rates. Our findings support the role of bursts in alpha-oscillations in visual perception and exemplify how real-time BCI systems can be used as a test bench for brain-behavioural theories.
Syndecan-4 Proteoliposomes Enhance Revascularization in a Rabbit Hind Limb Ischemia Model of Peripheral Ischemia
Authors: Sligar Andrew D , Howe Gretchen , Goldman Julia , Felli Patricia , Gómez-Hernández Almudena , Takematsu Eri , Veith Austin , Desai Shubh , Riley William J. , Singeetham Rohan , Mei Lei , Callahan Gregory , Ashirov David , Smalling Richard , Baker Aaron B. 
Published: September 2022

AbstractRegenerative therapeutics for treating peripheral arterial disease are an appealing strategy for creating more durable solutions for limb ischemia. In this work, we performed preclinical testing of an injectable formulation of syndecan-4 proteoliposomes combined with growth factors as treatment for peripheral ischemia delivered in an alginate hydrogel. We tested this therapy in an advanced model of hindlimb ischemia in rabbits with diabetes and hyperlipidemia. Our studies demonstrate enhancement in vascularity and new blood vessel growth with treatment with syndecan-4 proteoliposomes in combination with FGF-2 or FGF-2/PDGF-BB. The effects of the treatments were particularly effective in enhancing vascularity in the lower limb with a 2-4 increase in blood vessels in the treatment group in comparison to the control group. In addition, we demonstrate that the syndecan-4 proteoliposomes have stability for at least 28 days when stored at 4°C to allow transport and use in the hospital environment. In addition, we performed toxicity studies in the mice and found no toxic effects even when injected at high concentration. Overall, our studies support that syndecan-4 proteoliposomes markedly enhance the therapeutic potential of growth factors in the context of disease and may be promising therapeutics for inducing vascular regeneration in peripheral ischemia.
Magnitude and kinetics of the human immune cell response associated with severe dengue progression by single-cell proteomics
Authors: Robinson Makeda L. , Glass David R. , Duran Veronica , Rojas Olga Lucia Agudelo , Sanz Ana Maria , Consuegra Monika , Sahoo Malaya Kumar , Hartmann Felix J. , Bosse Marc , Gelvez Rosa Margarita , Bueno Nathalia , Pinsky Benjamin A. , Montoya Jose G. , Maecker Holden , Cardenas Maria Isabel Estupiñan , Villar Centeno Luis Angel , Garrido Elsa Marina Rojas , Rosso Fernando , Bendall Sean C. , Einav Shirit 
Published: September 2022

SummaryApproximately five million dengue virus-infected patients, particularly children, progress to a potentially life-threatening severe dengue (SD) infection annually. To identify the immune features and temporal dynamics underlying SD progression, we performed deep immune profiling by mass cytometry of PBMCs collected longitudinally from SD progressors (SDp) and uncomplicated dengue (D) patients. While D is characterized by early activation of innate immune responses, in SDp there is rapid expansion and activation of IgG-secreting plasma cells and memory and regulatory T cells. Concurrently, SDp, particularly children, demonstrate increased proinflammatory NK cells, inadequate expansion of CD16+ monocytes, and high expression of the FcγR, CD64 on myeloid cells, yet diminished antigen presentation. Syndrome-specific determinants include suppressed dendritic cell abundance in shock/hemorrhage vs. enriched plasma cell expansion in organ impairment. This study reveals uncoordinated immune responses in SDp and provides insights into SD pathogenesis in humans with potential implications for prediction and treatment.
Development of muti-agent-simulation models for intercellular communication via cytokines and extracellular matrices
Authors: Inoue Ken-ichi , Kishimoto Satoko , Mogami Tomoki , Toyoda Shigeru , Hariyama Masanori 
Published: September 2022

AbstractBackgroundIntercellular communication is a critical innovation during multicellular organismal evolution. Cells release / receive cytokines and utilize them as intercellular signal entities. How a well-orchestrated communication emerges from individual cell behavior remains largely unknown. Here we abstracted the biological phenomenon and developed multi-agent-simulation to investigate the intracellular communication.MethodsTwo dimensional MAS platform was developed using Artisoc 4.2.1 standard software. We focused on intercellular communication via cytokines and extracellular matrices. Three agents, “cells”, “cytokines” and “extracellular matrices” were defined and the interaction rules among the agents were designed. Two different mathematical models of cytokine-gradient determination were tested: spatial derivative and temporal derivative models. As a case study, neutrophil swarming was modeled and the cell swarming was defined as an evaluation criterion. Moreover, a surgically injured mouse model and a fluorescent time-lapse imaging were used to observe neutrophil swarming.ResultsWe performed multiple simulations with six different virtual conditions, changing multiple parameters simultaneously and randomly. After 400 simulations for each condition, we counted the number of successful trials (i.e. neutrophil swarming within 10000 steps). Spatial derivative model showed more successes compared to temporal derivative model. Among eight parameters randomly assigned, cell’s exploration speed by random walk most remarkably influenced on success rate of neutrophil swarming. In in vivo model, bone marrow derived neutrophils gather towards the clumps with various migration speed. The mode of approaching resembles to spatial derivative model, rather than temporal derivative model.ConclusionsMAS could be a useful approach to investigate the emergence of intercellular communication during multicellular evolution. Neutrophil could adopt the spatial derivative model as a sensing mechanism of cytokine gradient.