bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scoping Review of Ethical Discourse in Global Cleft Surgery Literature
Authors: Shamim Abrar , Ming Neil , Choi Ju Yeon , Seo Ga Young , Khalili Tali , Brady Noah , Wu Anette 
Published: December 2024

Background:
The ethical discourse regarding the delivery of global surgical care has increased in the 21st century. The aims of this manuscript are to explore the differences in ethical domains in the global cleft surgical literature discussed by authors from high-income countries versus lower-middle-income countries and to elucidate changes in ethical discussions over the last decade.

Methods:
A thematic coding analysis was completed using NVivo 12 qualitative data analysis software. Articles were analyzed and coded for discussion of 24 distinct subdomains in the global cleft surgical literature from 1992 to 2022.

Findings:
The domains with the most significant discourse in the global cleft surgery literature found were (1) clinical care and delivery and (2) engagement in collaborations and partnerships. Furthermore, when manuscripts are first authored by low- and middle-income country (LMIC) authors, the subdomains of (1) level of visiting trainee supervision, (2) relevance of educational activities, and (3) patient/procedure/location selection increase in relative discourse. The impact of visiting trainees on local educational programs is the ethical subdomain that has the largest increase in the last decade. There are barriers to publication as evidenced by the exclusion of abstracts which included LMIC authors but did not result in publications in peer-reviewed journals.

Conclusions:
A critical finding of this study is that the distribution of discussed ethical domains differs when LMIC authors are included as authors, in particular when primary authorship is from an LMIC author. To the authors' knowledge, there is no other study to date which has attempted this form of analysis.
Impact of obesity on low density lipoprotein plasmatic levels 6 weeks after an acute coronary syndrome
Authors: Bourgeois Elise , Benchalkha Daylale , Brobst Morgane , Herman Fanchon , Molinari Nicolas , Breuker Cyril , Chapet Nicolas , Roubille François , Sultan Ariane 
Published: December 2024

Introduction
Cardiovascular disease is the leading cause of death. One of the main factors is obesity, which is on the rise. LDL levels below 0.55 g/L are recommended after ACS. To date, there are no specific recommendations for obese subjects.

Objective
The primary objective was to assess the impact of obesity on LDL-c target attainment 6 weeks after initiation of statin therapy in subjects admitted for ACS. The secondary objectives were to assess the evolution of cholesterol levels and to characterize lipid-lowering treatments.

Methods
The single-center observational study took place at Montpellier University Hospital and included patients admitted to the ICU for ACS not treated with statins (T0). Biological tests were performed at 6 weeks. At 3 months, a telephone call was made by two pharmacists to collect the results of their biological work-up and any therapeutic modifications.

Results
The results were analyzed on 286 patients. A total of 39.5% were overweight and 22.7% obese. After hospitalization, 95.4% were prescribed statins. At 6 weeks, LDL cholesterol averaged 1.58 mmol/L, lower in subjects with a BMI greater than 30 kg/m2 (1.32 mmol/L). On average, 49.46% of subjects reached the LDL cholesterol target, with obese subjects achieving a higher rate of 64.9%. There was no significant difference in the prescription of lipid-lowering treatments between the two groups.

Conclusion
Despite high-intensity statin prescription, the target was achieved by 67.6% of obese subjects and 44.8% of subjects with a BMI of less than 30 kg/m2. This shows that post-SCA management needs to be reinforced for the general population.
Unveiling the Ecology ofLegionellain a Stratified Freshwater Lake: Seasonal Dynamics, Host Interactions, and Persistence Under Oxygen Limited Conditions
Authors: Berman O. , Be’eri-Shlevin Y. , Ninio S. 
Published: December 2024

AbstractBackgroundLegionellaare predominantly recognized as aerobic pathogens in man-made water systems. However, their potential persistence in natural freshwater environments, particularly under oxygen limited conditions, remains poorly explored. In this study we investigated the spatio-temporal dynamics ofLegionellaoccurrence in a seasonally stratified sub-tropical freshwater lake, with a focus on anaerobic conditions of the anoxic hypolimnion.ResultsOur study reveals significant seasonal variations inLegionellaabsolute abundance, with the highest concentrations occurring during and immediately following lake mixing events. Unexpectedly, high levels ofLegionellawere measured in the anaerobic hypolimnion layer of the lake. Utilizing genus specific amplicon-based sequencing, we found significant shifts inLegionellacommunity composition, that are related to the sampling month. Several environmental factors were associated with the observed changes, including temperature, DO, chlorophyll and dinoflagellate biomass. Moreover, we identifiedLegionellagenotypes unique to samples presenting hypoxic conditions - that were not closely related to knownLegionellaspecies. In addition, we noted genotypes present in anoxic samples, that were absent from the oxic layers of the corresponding sampling dates. These results were accompanied by changes in the interaction patterns betweenLegionellaand their potential hosts, in oxic and anoxic conditions.ConclusionsThis study challenges the conventional view ofLegionellaas a strictly aerobic pathogen by demonstrating its persistence in anoxic freshwater environments. Our findings suggest that certainLegionellaspecies may have adapted to low- oxygen conditions, potentially through alternate metabolic pathways or by residing within protozoan hosts. The identification of uniqueLegionellagenotypes in the hypolimnion, along with shifts in occurrence, diversity, and host interactions, underscores the complexity ofLegionellaecology. These results highlight the need for further research onLegionellain natural freshwater systems, which serve as reservoirs for the bacteria and potential sources for human infection. Further investigation into the mechanisms underlyingLegionellapersistence in anaerobic conditions and its interactions with environmental hosts is essential for a better understanding of the evolutionary forces shaping this family of human pathogens.
RpiBeh: a multi-purpose open-source solution for real-time tracking and behavior-driven closed-loop interventions in rodent neuroethology
Authors: Sun Yiqi , Zhang Jie , Wang Qianyun , Ni Jianguang 
Published: December 2024

AbstractHigh-precision behavior tracking and closed-loop intervention are essential for studying the neural basis of cognition and behavior. Existing commercial systems are costly and inflexible for customization, while current open-source tools are often lack of real-time functionality and suffer from steep learning curve. To address these issues, we developed RpiBeh, an open-source, cost-effective, and versatile software tailored for rodent neuroethological research. The software features an intuitive interface with extensive customization options. RpiBeh leverages a Raspberry Pi and camera for video streaming, enabling behavior-driven closed-loop control. Additionally, it provides frame-by-frame video timestamp output for precise synchronization with external devices. For real-time tracking and locomotion pattern analysis, RpiBeh utilizes several novel algorithms and integrated newly developed deep-learning method. Specifically, we introduced two algorithms: a Background Subtraction Method (BSM) for real-time position tracking and a Frame Difference (FD) algorithm for freezing behavior detection. RpiBeh was validated in single animal real-time tracking and locomotion pattern detection, demonstrating flexibility and effectiveness in configurating behavior-triggered closed-loop reinforcement experiments including passive place avoidance task and social fear conditioning tasks. It achieved the same level of performance in tracking and locomotion pattern detection comparing to benchmark software including ANY-maze and DeepLabCut, with superior customization and expandability. Consequently, RpiBeh offers an efficient, affordable, and open-source solution for video tracking and behavior-driven closed-loop experiments.
From Pigments to Precision: Exploring Genetic Transformation and Genome Editing in Wheat and Barley
Authors: Prusty Manas Ranjan , Shatil-Cohen Arava , Kumar Rakesh , Sharma Davinder , Minz-Dub Anna , Ezrati Smadar , Hihinashvili Avigail , Sharon Amir 
Published: December 2024

SummaryGenetic engineering of wheat is complex due to its large genome size, the presence of numerous genes with high sequence similarities, and a multitude of repetitive elements. In addition, genetic transformation of wheat has been difficult, mainly due to poor regeneration in tissue cultures. Recent advances in plant biotechnology, particularly the use of the regenerative genes GROWTH-REGULATING FACTOR (GRF) and GRF-INTERACTING FACTOR (GIF), have provided new tools for wheat transformation and regeneration. Another transformative tool is the RUBY system, that involves genetic engineering of three betalain biosynthesis genes, providing a noninvasive, visually detectable red pigment. In this study, we used theGRF4-GIF1chimera along with the RUBY system to advance transformation and gene editing in wheat and barley. The GRF4-GIF1 chimera significantly aided wheat regeneration; however, it had an opposite effect in barley, where it inhibited the regeneration process. Therefore, we primarily generated RUBY transgenic barley lines using constructs that did not include the GRF4-GIF1 chimera. Additionally, we used the RUBY cassette for fast assessment of gene editing by knockingout the first betalain biosynthetic gene in RUBY-positive transgenic wheat plants, resulting in a change of leaf color from red to green. The edited RUBY wheat lines lost more than just the red color. They also lost betalain-related traits, such as being less likely to get leaf rust (Puccinia triticina) and salt stress. Importantly, the loss of RUBY did not affect plant viability, making it a useful tool for genome editing and a viable alternative to destructive methods.
Hybridogenetic reproduction ofPelophylaxwater frogs from different R-E hemiclonal population systems from Eastern Ukraine: selective mortality, clonal and ploidy diversity
Authors: Fedorova Anna , Pustovalova Eleonora , Drohvalenko Mykola , Biriuk Olha , Doležálková-Kaštánková Marie , Kravchenko Maryna , Korshunov Olexii , Mikulíček Peter , Choleva Lukáš , Holovnia Dmytro , Dedukh Dmitrij , Shabanov Dmytro 
Published: December 2024

AbstractEuropean water frogs from thePelophylax esculentuscomplex include two sexual species,P. ridibundusandP. lessonae,and their hybrids, which usually clonally transmit one of the parental species’ genomes. This unique reproductive strategy allows hybrids to reproduce with one or both parental species, creating diverse population systems. Unlike most well-studied population systems in Europe, the Siverskyi Donets River basin in Eastern Ukraine features diploid and polyploid hybrids coexisting withP. ridibundus, whileP. lessonaeis absent (R-E systems). To reveal diverse system compositions, genetic divergence, and tadpole selective mortality, we combined novel data from over a decade of observations with previous research on population systems in the Siverskyi Donets River. Two main types of R-E systems were identified: those with diploid hybrids in northern localities and those with both diploid and triploid hybrids, extending from the mainstream of the Siverskyi Donets River to its tributaries. Additionally, we found higher genetic diversity in R-genomes compared to L-genomes, likely due to the absence ofP. lessonaeand the ongoing input of recombined R-genomes fromP. ridibundusand triploid hybrids. This study highlights the importance of continuous monitoring and research to unravel the dynamics and complexity of water frog population systems.
PRX-3140, a 5-HT4 Partial Agonist and Sigma-1 Agonist/Antagonist, Modulates Glucocorticoid Insulin Suppression and Cortisol Levels
Authors: Hood B.L. , McLaughlin J.P. , Alleyne A.R. , Thinschmidt J.S. , Harden S.W. , Frazier C.J. , Talton J.D. 
Published: December 2024

AbstractPRX-3140 is a partial agonist to the 5-hydroxytryptamine receptor 4 (5-HT4) and a ligand for the sigma-1 (S1R) and sigma-2 (S2R) receptors. Although few publications have inferred S1R agonists/antagonists modulate blood glucose, Di et.al (2017) reported S1R deficiency in knockout mice impacted regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis, with a dexamethasone-induced reduction in level of corticosterone markedly attenuated in S1R −/− knockout mice, implicating S1R in feedback response to the HPA axis. The hypothesis that S1R deficiency causes down-regulation of the glucocorticoid receptor (GR) and attenuates GR-mediated feedback inhibition of HPA axis, as well as stress response of HPA axis, suggest that the inverse, the activation of S1R under normal conditions, may modulate glucocorticoid insulin suppression (as a direct S1R-GR effect) as well as cortisol levels (producing HPA axis feedback inhibition). In the present study, coadministration of 10 µM PRX-3140 with 100 nM cortisol significantly increased insulin release (to 74.8 ng/ml, P-value <0.0001). Similar effects were observed when cells were exposed to dexamethasone (Dex), with 10 µM PRX-3140 and 10 nM Dex producing 1.87-fold significantly more insulin than 10 nM Dex alone. Daily glucose concentrations in the 14-day clinical study (NCT00384423) of PRX-3140 demonstrate a reduction for 10 mg once-daily at days 1, 7, 10, and 15. Urine free cortisol levels at 10, 30, 100 and 200 mg dose levels of PRX-3140 demonstrated a larger reduction at 7 and 14 days compared to placebo. As an agonist of S1R that acts as a chaperone of GR, PRX-3140 has demonstrated GR modulating effects in INS-1 cells and in 14-day clinical studies in healthy adults with low incidence of side effects. The results of the present study suggest that S1R activation, with PRX-3140 and NP-18-2 S1R agonists, modulates glucocorticoid insulin suppression and cortisol levels.
Development and validation of a real-time PCR assay for the diagnosis of rabies virus Philippine strain in non-brain samples
Authors: Manalo Daria L. , Bolivar Jude Karlo G. , Bondoc Jeromir G. , Nagataki Blanca J. , Nacion Leilanie B. , Espino Mark Joseph M. , Park Chun-Ho , Inoue Satoshi 
Published: December 2024

ABSTRACTRabies is a fatal neurotropic and zoonotic disease responsible for thousands of deaths yearly. Direct fluorescent antibody test (dFAT), the gold standard in routine rabies diagnosis, requires dog brain samples, and takes 5-7 hours to obtain results. Brain specimen degradation due to inappropriate transport and storage conditions most of the time leads to false negative results, hence the need for an alternative diagnostic method that can also utilize non-brain specimens. In this study, an RT-qPCR assay was developed to specifically target the N gene of the Philippine rabies isolate. The assay was optimized using RNA from dFAT-positive dog brain tissues as templates. In-silico and in vitro evaluations both showed 100% specificity to rabies RNA, with a detection limit of 1 copy per microliter. Validation of the assay was done using dFAT-tested brain samples and potential brain specimen-alternates, specifically the dog nasal planum (NP) and follicle sinus complex (FSC). One hundred percent of the NP and FSC samples showed concordance with the respective dFAT-positive brain samples. Only 97% concordance was observed with the dFAT-negative brain samples. These results collectively validate the efficiency, sensitivity and specificity of the assay developed, indicating its potential utilization for in rabies diagnosis using clinical samples besides the brain tissues.
Significance of the CTP-binding motif for the interactions ofS. coelicolorParB with DNA, chromosome segregation, and sporogenic hyphal growth
Authors: Szymczak J. , Strzałka A. , Jakimowicz D. , Szafran MJ. 
Published: December 2024

ABSTRACTThe segregation of bacterial chromosomes is widely mediated by partitioning proteins (ParAB). While ParB binds DNA specifically by recognising short, palindromic sequences known asparSsites, ParA utilises its ATPase activity to generate the force to translocate ParB-DNA nucleoprotein complexes (segrosomes). The assembly of the segrosome requires the association of ParB withparS,followed by nonspecific spread of the protein along the DNA. To spread on DNA, the ParB dimer must entrap theparSsite within the complex, a process triggered by CTP binding to the conserved GERR amino acid motif. InStreptomyces, a genus of soil-dwelling, multigenomic bacteria that have a complex life cycle, ParB-dependent chromosome partitioning is initiated during the growth of sporogenic hyphae. However, the molecular mechanisms underlying segrosome formation inStreptomycesand their ability to coordinate with sporogenic development remain incompletely understood.In this study, we advance the understanding of chromosome segregation in bacteria by exploring the effects of CTP binding and hydrolysis on the formation of the partitioning complex inS. coelicolor. Here, viain vitroapproaches, we demonstrate that a conserved GERR motif is essential for CTP binding and hydrolysis byS. coelicolorParB. Moreover, the motif is crucial for CTP-dependent ParB accumulation on DNA. Using mutant strains, we show the significance of the GERR motif for segrosome complex assembly. Additionally, we provide data showing that the CTP-binding motif contributes to the regulation of the growth of sporogenic cells. Overall, we show that CTP-dependent segrosome assembly impacts the development ofS. coelicolorsporogenic cells.
Optimizing a Human Monoclonal Antibody for Better Neutralization of SARS-CoV-2
Authors: Wang Qian , Guo Yicheng , Casner Ryan G. , Yu Jian , Nair Manoj S. , Ho Jerren , Reddem Eswar R. , Tzang Chih Chen , Huang Yaoxing , Shapiro Lawrence , Liu Lihong , Ho David D. 
Published: December 2024

SUMMARYSARS-CoV-2 has largely evolved to resist antibody pressure, with each successive viral variant becoming more and more resistant to serum antibodies in the population. This evolution has rendered inactive all therapeutic monoclonal antibodies previously authorized, and it is now threatening the remaining clinical product for immunoprophylaxis against COVID-19. We report herein the isolation of a human monoclonal antibody with a broad but incomplete SARS-CoV-2 neutralization profile, but structural analyses and mutational scanning led to the engineering of variants that resulted in greater antibody flexibility while binding to the viral spike. Three such optimized monoclonal antibodies neutralized all SARS-CoV-2 strains tested with much improved potency and breadth, including against subvariants KP.3.1.1 and XEC that are dominant today. The findings of this study not only present new antibody candidates for clinical development against COVID-19, but also introduce a unique engineering approach to improve antibody activity via increasing conformational flexibility.
DynaMAP: Dynamic Microbiome Abundance Profiling through high density optical mapping
Authors: Abakumov Sergey , Ruppeka-Rupeika Elizabete , Chen Xiong , Engelbrecht Mattias , Mestdagh Inge , D’huys Thomas , Mlodzinska Agata , Leen Volker , Szymanek Agata , Badola Aditya , Lukes Tomas , Demuyser Thomas , Hofkens Johan , Dedecker Peter , Bouwens Arno 
Published: December 2024

AbstractMicrobial abundance profiling is rapidly becoming an essential method in biomedical research, though it is often costly and time intensive. We present DynaMAP, a rapid approach for microbiome profiling that uses single-molecule imaging to develop an optical map of metagenomic DNA. DynaMAP achieves strain-level taxonomic profiling without requiring base-by-base sequencing and with a one-day turnaround time. In doing so, it delivers microbiome profiling that is comparable to shotgun sequencing but operates more efficiently, strongly expanding the possibility for microbiome analysis.
Divergence in poxvirus-encoded E3-like proteins can dictate poxvirus activation of cellular necroptosis
Authors: Enow Junior A. , Munig Saige , Sample Mathew L. , Speyer Gil , Chandrakanth Raghavi , Williams Jacqueline , Bonner James , McFadden Grant , Jacobs Bertram , Rahman Masmudur M. 
Published: December 2024

AbstractPoxviruses encode a plethora of proteins to modulate diverse cellular responses against viruses. Poxvirus-encoded E3-like proteins are multifunctional, regulating diverse cellular antiviral responses. The canonical Vaccinia E3-like proteins have two domains: an N-terminal Z-form nucleic acid binding domain (Zα-BD) and a C-terminal double-stranded RNA binding domain (dsRNA-BD)-.Using protein sequence and structural homology modeling, we identified the presence of dsRNA- BD-containing proteins in all the poxviruses except Avipoxviruses, Salmon poxvirus and Entemopoxviruses. However, the acquisition of these proteins likely happened under three distinct events. Using structural homology modeling and FATCAT score, we can classify E3-like proteins in three distinct categories: i) the E3-like proteins with highly conserved dsRNA-BD but with or without the N-terminal domain, present in most poxviruses; ii) unconventional E3-like proteins with highly diverged dsRNA-BD, present in Macropoxvirus and Molluscipoxvirus and iii) E3-like protein with dsRNA-BD that may have different origin present in Crocodilepoxvirus.12–52–6Members of Leporipoxvirus, Waddenpoxvirus, Cetaceanpoxvirus, and selected members of Orthopoxvirus contain E3-like proteins missing the N-terminal Zα-BD required for necroptosis inhibition. Additionally, using Alphafold, we show that the Zα-BD of Chordopoxviruses E3-like proteins is structurally more variable than the ds-RNA binding domain. Compared to members of Orthopoxviruses–Vaccinia virus (VACV) and Cowpox virus (CPXV) that have been shown to inhibit necroptosis and contain an N-terminus Zα-BD of the canonical E3 protein, our results show that members of leporipoxviruses induce necroptosis in human and mouse necroptosis competent cell lines. Furthermore, myxoma virus (MYXV) infection activates RIP1 and RIP3-mediated necroptosis in both human and mouse necroptosis-competent cells. These data suggest that Leporipoxviruses lack countermeasures to necroptosis compared to Orthopoxviruses that encode multiple key regulators of necroptosis, possibly due to a lack of selective pressure within the viral host species (Lagomorphs).Graphical Abstract