bluuebunny/crossref_metadata_2025_split huggingface dataset:
Marching with ants to a new nest
Authors: Annagiri Sumana , Halder Eshika 
Published: January 2023

AbstractIn this review, we journey withDiacamma indicuma Ponerine ant over the last decade as they relocate to new nests and discover the challenges they face along the way and how they solve them. Colony relocation is a goal oriented dynamic task that involves all the colony members and impacts the colonies’ fitness. After explaining how I initiated this journey, we examine colony composition of this species by analysing data from 1200 colonies collected over the last 13 years. On average colonies are constituted with 89.35 adult females, 0.29 males and 56.6 brood items of different development stages and these were significantly impacted by seasonality with Pre monsoon having the highest numbers. After explaining how colonies are collected and maintained in the lab, we explore the architectural components of the subterrain nests built by this species in the natural habitat. Colonies live in relatively simple single chambered nest that does not change significantly across seasons and consists of an entrance tunnel and a secondary runoff tunnel. All members of the colony are recruited to the new nest through tandem running and this species shows the highest documented tandem running speeds at 4.35 body lengths per second and a path efficiency of 83.95% with only 2.4% of tandem runs being unsuccessful in the natural habitat. Even in lab conditions, when colonies are given defined paths of different lengths, colonies showed significant preference to travel through short paths, highlighting their ability to optimizes their path even in the absence of chemical trails. A combination of experiments in the natural habitat and controlled experiments in the lab which are anchored in theumweltof the organism has enabled us to understand howD. indicumfunctions and reveals the selection forces that are operating on the organization and performances of relocation. Our journey has brought to light several answers but has opened several more avenues for exploration branching out in different directions. With time and dedicated minds, we hope to continue on this route to marvel at the achievements of these superorganisms.
A Public Health Hackathon for Medical Students in Africa: Process, Outcome and Recommendations
Authors: Babatunde Abdulhammed Opeyemi , Brimmo Farida Oluwabukola , Arama Umulkhairah Onyioiza , Onyinyechi Madu Gloria , Josephat Kasule Aiden , Osiene Austine Oluwatobi 
Published: January 2023

ABSTRACTAfrica has a dual burden of disease, which causes preventable morbidities and fatalities. This is a result of our healthcare system’s deficiencies, which has suffered a serious decline since the COVID-19 pandemic. However, this opened up the possibilities for digital health interventions, which innovators could utilize to provide solutions to these public health issues. Health hackathons, which offer an environment for innovators to brainstorm and collaborate, are rare in Africa. This paper outlines the planning and execution of a virtual hackathon and explores its implications for the promotion of public health in Africa.Over the course of a month, we collaborated with innovation hubs in Africa to hold an open call, a training session, a design sprint, as well as a 48-hour virtual hackathon. We received 68 submissions from 13 African nations. Following the selection of 10 teams, design thinking was employed to develop solutions to a public health problem in Africa. The theme for the hackathon was ‘Promoting Health Equity with Digital Technology in Africa’ and areas of focus were non-communicable diseases; infectious disease epidemiology and surveillance; and health information and data management. All ten teams developed prototypes, the top three teams were offered the opportunity to continue on to the start-up accelerator program, while the winning team also received a cash prize.In conclusion, the public health hackathon challenged African medical students to develop innovations for healthcare problems. There is a need for further study to evaluate the solutions developed.
SURGICALLY IMPORTANT ANATOMIC VARIATIONS OF EXTRAHEPATIC BILIARY SYSTEM AMONG BLACK KENYAN CADAVERS AT MOI UNIVERSITY HUMAN ANATOMY LABORATORY
Authors: Ndiwa Dan , Wandera Andrew , Njoroge Anthony , Lwande Gerald , El-Badawi Mohamed 
Published: January 2023

SummaryBackgroundAnatomical variations of the human body including the extra hepatic biliary system exist across various individuals. Understanding the variant anatomy of the extrahepatic biliary system aids surgeons in avoiding iatrogenic injuries. This is important in resource limited settings where it is not possible to perform adequate radiological investigations of the hepatobiliary system prior to surgery. This study described the anatomic variation of the extrahepatic biliary system among Kenyans.MethodsThis was a cross-sectional study conducted at Moi University’s Anatomy Laboratories among 42 adult cadaveric specimens. Specimen dissections were conducted as per the fifteenth edition of Cunningham’s manual of Practical Anatomy. The variant anatomy data collected were filled in a structured data collection form, analysed and presented using descriptive statistics.Study FindingsOf the 42 cadavers sampled, 62% (n=26) were male while 38% (n=16) were female. All had a gall bladder being drained by the cystic duct. The length of the cystic duct ranged between 7-35 mm joining the common hepatic duct to form the common bile duct in 98% (n=41) of all the cadavers sampled. This confluence was to the left in 7.1% (n=3), right 42.9% (n=18), anteriorly in 14.3% (n=6) and posteriorly 35.7% (n=14). A single cadaver (2%) had the cystic duct drain into the right hepatic duct. Two thirds (66.7%; n=28) of the cadavers sampled had the confluence of the right and the left hepatic duct outside the liver. There were no cholecystohepatic ducts in this study.ConclusionThe study determined the existence of surgically important variant anatomy of the extrahepatic biliary system. There is need for greater appreciation of the extrahepatic biliary system variant anatomy by both surgeons and radiologists so as to decrease morbidity and improve on surgical outcomes.
Inter-step Variations of Stairways and Associations of High-Contrast Striping and Fall-related Event Observations
Authors: Brown Chayston B. , Poulsen Shandon L. , Barrett Tyson S. , Dakin Christopher J. , Harper Sara A. 
Published: January 2023

AbstractBackgroundVariability in the riser and depth of each step in a stairway can decrease step predictability, and increase users’ fall risk. Unfortunately, inconsistencies in inter-step riser height and depth are common, but their impact may be lessened by adding high-contrast tread edges and vertical, monochrome striping applied to the bottom and top steps’ faces. Such contrast enhancement may draw greater attention to the steps’ edges or enhance the precision of the edge’s estimated location.PurposeTo determine if greater inconsistency in inter-step riser height and depth are associated with more frequent slips, trips, and falls, and if these events are reduced in flights of stairs with contrast-enhanced step edges.MethodsStair users were videotaped on two public stairways. One stairway had black vinyl strips applied to the steps’ edges and black-and-white vertical stripes on the first and last steps’ faces. The intervention stairway was switched halfway through data collection. Stair users were coded for whether they experienced a fall-related event. A Monte Carlo simulation was used to determine the probability of observing a range of plausible distributions of fall-related events.ResultsFlights of stairs with riser height variability of 14 mm and tread depth variability of 38 mm were associated with 80% of the observed fall-related events. 13 of 16 (81%) fall-related events occurred on the control stairway compared to 3 of 16 (19%) on the intervention stairway. The distribution of fall-related events observed between conditions had a probability of occurring by random chance of less than 0.04.ConclusionThese data suggest a vision-based strategy (i.e., striping) may counteract fall risk associated with inter-step riser height and depth inconsistencies. While the mechanisms of its action remain unclear, the high-contrast striping appears to reduce the incidence of fall-related events in the presence of inter-step riser height and depth inconsistencies.
The parasubthalamic nucleus refeeding ensemble delays feeding initiation
Authors: Dunning Jeffery L , Lopez Catherine , Krull Colton , Kreifeldt Max , Angelo Maggie , Ramakrishnan Charu , Deisseroth Karl , Contet Candice 
Published: January 2023

AbstractThe parasubthalamic nucleus (PSTN) is responsive to refeeding after food deprivation and PSTN subpopulations can suppress feeding. However, no study directly addressed the role of PSTN neurons activated upon food access resumption. Here we show that the ensemble of refeeding-activated PSTN neurons drastically increases the latency to initiate refeeding with both familiar and novel food but exerts limited control over the amount of food consumed by hungry mice. This ensemble also delays sucrose consumption but accelerates water consumption in thirsty mice. We next sought to identify which subpopulations of PSTN neurons might be driving these effects. We discovered that PSTNTac1neurons projecting to the CeA selectively suppress feeding initiation while PSTNCrhneurons surprisingly promote the consumption of novel, palatable substances. Our results demonstrate the key role of endogenous PSTN activity in the control of feeding initiation and identify PSTN subpopulations counteracting each other’s influence on consummatory behaviors.
Myeloperoxidase promotes a tumorigenic microenvironment in non-small cell lung cancer
Authors: Valadez-Cosmes Paulina , Maitz Kathrin , Kindler Oliver , Mujkanovic Nejra Cosic , Lueger Anna , Raftopoulou Sofia , Kienzl Melanie , Mihalic Zala Nikita , Santiso Ana , Sarsembayeva Arailym , Brcic Luka , Lindenmann Jörg , Sattler Wolfgang , Heinemann Akos , Schicho Rudolf , Marsche Gunther , Houghton A. McGarry , Kargl Julia 
Published: January 2023

AbstractMyeloperoxidase (MPO) is a heme peroxidase that is mainly expressed and secreted by neutrophils. MPO’s role in inflammatory diseases has been highlighted in recent years, but its role in tumor development remains unclear. Therefore, we investigated the role of MPO in non-small cell lung cancer (NSCLC).In silicoanalysis revealed a survival benefit in patients with NSCLC and low MPO expression. Furthermore, a syngeneic tumor model using MPO knockout (KO) mice revealed that mice lacking MPO had lower tumor growth than controls. The reduction in tumor size was accompanied by an increase in lymphoid populations, including natural killer cells and CD8+T cells, suggesting a shift to a more anti-tumorigenic immune environment in MPO-KO mouse tumors. The T cell induced interferon-gamma (IFN-γ) expression was increased in MPO-KO tumors, indicating increased tumoricidal activity. CD8 depletion abolished the previously observed reduction in tumor size in MPO-KO mice, indicating that CD8+T cells play an important role.In vitro, T cells treated with MPO showed reduced proliferation and IFN-γ expression. Furthermore, MPO could be internalized into T cells. Heparin pretreatment of T cells blocked MPO binding and internalization into T cells and reversed MPO-induced proliferation reduction. Interestingly, MPO+lymphocytes were found in tumor samples from patients with NSCLC. Our findings suggest that MPO plays an immunosuppressive role in NSCLC.One Sentence SummaryHigh myeloperoxidase (MPO) expression in non-small cell lung cancer patients is a predictor for adverse outcome and mice lacking MPO showed enhanced anti-tumorigenic leukocyte infiltration, suggesting a pro-tumorigenic role of MPO.
HTLV-1 Splice Sites in Prevalent Gene Vectors Cause Splicing Perturbations in Transgenic Human Cells
Authors: Miskey Csaba , Prommersberger Sabrina , Mestermann Katrin , Hudecek Michael , Ivics Zoltán 
Published: January 2023

ABSTRACTThe use of any semi-randomly integrating gene vector in a therapeutic setting is associated with genotoxic risks. The two major mechanisms of genotoxicity are disruption of a coding sequence (loss-of-function) or transcriptional upregulation of genes (gain-of-function) in the cellular genome where the genetic modifications are executed. A third, less widely recognized genotoxic risk stems from splice sites and polyadenylation sites within the vector sequences. These transcriptional elements may drive aberrant splicing and/or polyadenylation between transgene-contained and genomic sequences. A widely used promoter/enhance element present in gene vectors to ensure high transgene expression levels in mammalian cells is composed of a hybrid EF1α/HTLV-1 LTR, in which the retroviral LTR contains an intron. We assessed aberrant splicing initiated from the splice donor (SD) element present in the HTLV-1 LTR in CAR-T cells that had been engineered by either lentiviral vector (LV) orSleeping Beauty(SB) transposon-mediated gene transfer. We establish that the vector-contained canonical SD site gives rise to aberrantly spliced RNA species and thereby can cause misexpression of host gene segments that are involved in various host cell functions. This, potentially genotoxic, effect could be abrogated by mutating or completely eliminating the SD (or the entire intron) from the HTLV-1 LTR segment. CAR-T cells generated by the modified vectors are equally potent in efficiency of CAR-T cell manufacturing and in functionality. The simple genetic modifications that we describe here affecting vector design therefore enhance genomic safety while maintaining efficacy of gene-modified therapeutic cells.
PPAD: A deep learning architecture to predict progression of Alzheimer’s disease
Authors: Al Olaimat Mohammad , Martinez Jared , Saeed Fahad , Bozdag Serdar ,   Alzheimer's Disease Neuroimaging Initiative
Published: January 2023

AbstractAlzheimer’s disease (AD) is a neurodegenerative disease that affects millions of people worldwide. Mild cognitive impairment (MCI) is an intermediary stage between cognitively normal (CN) state and AD. Not all people who have MCI convert to AD. The diagnosis of AD is made after significant symptoms of dementia such as short-term memory loss are already present. Since AD is currently an irreversible disease, diagnosis at the onset of disease brings a huge burden on patients, their caregivers, and the healthcare sector. Thus, there is a crucial need to develop methods for the early prediction AD for patients who have MCI. Recurrent Neural Networks (RNN) have been successfully used to handle Electronic Health Records (EHR) for predicting conversion from MCI to AD. However, RNN ignores irregular time intervals between successive events which occurs common in EHR data. In this study, we propose two deep learning architectures based on RNN, namely Predicting Progression of Alzheimer’s Disease (PPAD) and PPAD-Autoencoder (PPAD-AE). PPAD and PPAD-AE are designed for early predicting conversion from MCI to AD at the next visit and multiple visits ahead for patients, respectively. To minimize the effect of the irregular time intervals between visits, we propose using age in each visit as an indicator of time change between successive visits. Our experimental results conducted on Alzheimer’s Disease Neuroimaging Initiative (ADNI) and National Alzheimer’s Coordinating Center (NACC) datasets showed that our proposed models outperformed all baseline models for most prediction scenarios in terms of F2 and sensitivity. We also observed that the age feature was one of top features and was able to address irregular time interval problem.
Biosimilarity of GBPD002 compared with Eprex®through clinical evaluation in human
Authors: Nag Kakon , Mohiuddin Mohammad , Mahtab Mamun Al , Bachar Sitesh Chandra , Rahim Abdur , Uddin Helal , Kumar Samir , Khan Maksudur Rahman , Sarker Enamul Haq , Chowdhury Mashfiqur Rahman , Roy Rony , Chakraborty Sourav , Biswas Bipul Kumar , Bappi Emrul Hasan , Roy Ratan , Barman Uttam , Sultana Naznin 
Published: January 2023

AbstractBackgroundThe biosimilarity for erythropoietin (EPO) functionality of GBPD002 (test candidate) and Eprex®(comparator) has been evaluated by comparing the pharmacokinetic (PK) and pharmacodynamic (PD) properties following subcutaneous injection.MethodsThis was a randomized, double-blinded, two-sequence, crossover clinical trial. Subjects were randomly assigned and received a dose (4,000 IU) of either the test or comparator EPO, and received the alternative formulations after 4-weeks of washout period.ResultsThe PK parameters,viz., maximum observed concentration (Cmax) and area under the curve extrapolated to infinity (AUC0-inf), were calculated with the serum EPO concentrations from blood samples and were found comparable for both formulations. The geometric mean ratios (at 90% CI) of the Cmaxand AUCinfwere 0.89 and 1.16, respectively, which were within the regulatory range of 0.80 – 1.25. The time-matched serum EPO concentrations and PD markers (reticulocyte, hematocrit, hemoglobin, and red blood cell) denoted a counterclockwise hysteresis, suggesting a time delay between the observed concentration and the response. ANOVA-derivedP-values (>0.05) for the effectors clearly revealed the similarity between effects on PD markers for the test and comparator drugs. Both formulations were found tolerated well, and anti-drug antibodies were not observed.ConclusionsThus, the two formulations are projected to be used interchangeably in clinical settings.
The artemisinin-induced dormant stages ofPlasmodium falciparumexhibit hallmarks of cellular senescence and drug resilience
Authors: Tripathi Jaishree , Stoklasa Michal , Nayak Sourav , Low Kay En , Lee Erica Qian Hui , Rénia Laurent , Malleret Benoit , Bozdech Zbynek 
Published: January 2023

AbstractRecrudescent infections with human malaria parasite,Plasmodium falciparum, presented traditionally the major setback of artemisinin-based monotherapies. Although introduction of artemisinin combination therapies (ACT) largely solved the problem, the ability of artemisinin to induce dormant parasites still poses major obstacle for current as well as future malaria chemotherapeutics. Here, we developed a robust laboratory model for induction of dormantP. falciparumparasites and characterized their transcriptome, drug sensitivity profile and cellular ultrastructure. We show thatP. falciparumdormancy requires a ~5-days maturation process during which the genome-wide gene expression pattern gradually transitions from the ring-like state to a highly unique form. The transcriptome of the mature dormant stage carries hallmarks of cellular senescence with downregulation of most cellular functions associated with growth and development, but upregulation of selected metabolic functions and DNA repair. Moreover, theP. falciparumdormant stage is considerably more resistant to essentially all antimalaria drugs compared to the fast-growing asexual stages. Finally, the unique cellular ultrastructure further suggests unique properties of this new developmental stage of theP. falciparumlife cycle that should be taken into consideration by new malaria control strategies.
An orally bioavailable 4-phenoxy-quinoline compound as a potent AURKB relocation blocker for cancer treatment
Authors: Li Jinhua , Zhang Ting , Shi Qiong , Lv Gang , Zhou Xiaohu , Choudhry Namrta , Kalashova Julia , Yang Chenglu , Li Hongmei , Long Yan , Sakthivel Balasubramaniyan , Nimishetti Naganna , Liu Hong , Allen Thaddeus D. , Zhang Jing , Yang Dun 
Published: January 2023

AbstractWe investigated a novel 4-phenoxy-quinoline-based scaffold that mislocalizes the essential mitotic kinase, AURKB. Here, we evaluated the impact of halogen substitutions (F, Cl, Br, I) on this scaffold with respect to various drug parameters. Br-substitutedLXY18was found to be a potent and orally bioavailable disruptor of cell division, at sub-nanomolar concentrations.LXY18prevents cytokinesis by blocking AURKB relocalization in mitosis and exhibits broad-spectrum antimitotic activityin vitro. With a favorable PK profile, it shows widespread tissue distribution including the blood-brain barrier penetrance and effective accumulation in tumor tissues. More importantly, it markedly suppresses tumor growth. The novel mode of action ofLXY18may eliminate some drawbacks of direct catalytic inhibition of AURKs. Successful development ofLXY18as a clinical candidate for cancer treatment could enable a new, less toxic means of antimitotic attack that avoids drug resistance mechanisms.
Phosphorylation of the inner core oligosaccharide of lipopolysaccharide mediates recognition and phagocytosis of Gram-negative bacteria by Brain Angiogenesis Inhibitor 1 (BAI1)
Authors: Billings Emily A. , Columbus Linda , Casanova James E. 
Published: January 2023

AbstractRecognition of lipopolysaccharide (LPS) is critical for host defense against Gram-negative bacteria and the regulation of local inflammatory responses at the host-microbial interface. We have previously shown that the adhesion G-protein-coupled receptor (aGPCR) BAI1 acts as a phagocytic pattern recognition receptor (PRR) that selectively recognizes Gram-negative bacteria through a series of five Type I thrombospondin repeats (TSRs) in its extracellular domain. Unlike Toll-like receptor 4 (TLR4), which recognizes the hydrophobic lipid A region of LPS, the BAI1 TSRs bind the core oligosaccharide of canonical LPS structures (1). In this study, we report that BAI1 requires the phosphorylated inner core L-glycero-d-manno-heptose moiety of LPS for recognition, in the context of intact, live bacteria. Mutant strains ofSalmonella entericaserovar Typhimurium orE. coliBW25113 K-12 that fail to phosphorylate the inner core oligosaccharide, specifically heptose I, are not recognized by BAI1. Phosphorylation of inner core oligosaccharides is critical for membrane stability and function and is conserved across most Gram-negative species, thus allowing BAI1 to recognize a broad range of organisms.
Deletion of genes linked to the C1-fixing gene cluster affects growth, by-products, and proteome ofClostridium autoethanogenum
Authors: Nwaokorie Ugochi Jennifer , Reinmets Kristina , de Lima Lorena Azevedo , Pawar Pratik Rajendra , Shaikh Kurshedaktar Majibullah , Harris Audrey , Köpke Michael , Valgepea Kaspar 
Published: January 2023

ABSTRACTGas fermentation has emerged as a sustainable route to produce fuels and chemicals by recycling inexpensive one-carbon (C1) feedstocks from gaseous and solid waste using gas-fermenting microbes. Currently, acetogens that utilise the Wood-Ljungdahl pathway to convert carbon oxides (CO and CO2) into valuable products are the most advanced biocatalysts for gas fermentation. However, our understanding of the functionalities of the genes involved in the C1-fixing gene cluster and its closely-linked genes is incomplete. Here, we investigate the role of two genes with unclear functions – hypothetical protein (hp;LABRINI_07945) and CooT nickel binding protein (nbp;LABRINI_07950) – directly adjacent and expressed at similar levels to the C1-fixing gene cluster in the gas-fermenting model-acetogenClostridium autoethanogenum. Targeted deletion of either thehpornbpgene using CRISPR/nCas9, and phenotypic characterisation in heterotrophic and autotrophic batch and autotrophic bioreactor continuous cultures revealed significant growth defects and altered by-product profiles for both Δhpand Δnbpstrains. Variable effects of gene deletion on autotrophic batch growth on rich or minimal media suggest that both genes affect the utilisation of complex nutrients. Autotrophic chemostat cultures showed lower acetate and ethanol production rates and higher carbon flux to CO2and biomass for both deletion strains. Additionally, proteome analysis revealed that disruption of either gene affects the expression of proteins of the C1-fixing gene cluster and ethanol synthesis pathways. Our work contributes to a better understanding of genotype-phenotype relationships in acetogens and offers engineering targets to improve carbon fixation efficiency in gas fermentation.