bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of mechanisms modulating chlorhexidine and octenidine susceptibility inProteus mirabilis
Authors: Pelling Harriet , Bennett Vicky , Bock Lucy J , Wand Matthew E , Denham Emma L , MacFarlane Wendy M , Sutton J Mark , Jones Brian V 
Published: July 2024

AbstractAimsWe aimed to identify mechanisms underlying the tolerance of Proteus mirabilis—a common cause of catheter associated urinary tract infection—to the clinically used biocides chlorhexidine (CHD) and octenidine (OCT).Methods and resultsWe adapted three clinical isolates to grow at concentrations of 512 µg ml−1 CHD and 128 µg ml−1 OCT. Genetic characterization and complementation studies revealed mutations inactivating the smvR repressor and increasing smvA efflux expression were associated with adaptation to both biocides. Mutations in mipA (encoding the MltA interacting protein) were less prevalent than smvR mutations and only identified in CHD adapted populations. Mutations in the rppA response regulator were exclusive to one adapted isolate and were linked with reduced polymyxin B susceptibility and a predicted gain of function after biocide adaptation. Biocide adaptation had no impact on crystalline biofilm formation.ConclusionsSmvR inactivation is a key mechanism in both CHD and OCT tolerance. MipA inactivation alone confers moderate protection against CHD, and rppA showed no direct role in either CHD or OCT susceptibility.
Evaluation of the capacity and effective angle of thalamic damage for 2 commercially available captive bolt tool types on cadaver heads from sows &gt;200 kg body weight
Authors: Anderson Karly N , Woiwode Ruth , Kirk Ashlynn A , Berger Jennifer , Reyes Arquimides A , Zhitnitskiy Perle E , Vogel Kurt D 
Published: July 2024

Abstract
This study evaluated the ability of 2 penetrating captive bolt (PCB) types (PISTOL, INLINE) to reach and disrupt the thalamus when applied in 2 placements (FRONTAL, BEHIND EAR) to chilled cadaver heads (N = 60) from sows &gt;200 kg. Heads were randomly distributed across 6 treatments (n = 10): FRONTAL-INLINE, FRONTAL-PISTOL, FRONTAL-NO SHOT, BEHIND EAR-INLINE, BEHIND EAR-PISTOL, and BEHIND EAR-NO SHOT. The FRONTAL shot was placed 3.5 cm superior to the optic orbits at the midline; the BEHIND EAR shot was placed directly caudal to the pinna of the ear on the same plane as the eyes and targeting the middle of the opposite eye. For INLINE treatments, a Jarvis PAS—Type C 0.25R Super Heavy Duty PCB with a Long Bolt and 6.0 GR power loads was used. For PISTOL treatments, a Jarvis PAS—Type P 0.25R Pistol PCB with a Long Stunning Rod Nosepiece Assembly and 3.5 GR power loads was used. Heads were split along the bolt with a band saw. Tissue depth measurements are reported as Mean ± SE followed by 97.5% one-sided upper reference limit (URL). Total tissue thickness was less (P &lt; 0.0001) at the FRONTAL (56.31 ± 1.76 mm; URL: 73.17 mm) than the BEHIND EAR placement (95.52 ± 3.30 mm; URL: 126.53 mm). Thalamic depth was less (P &lt; 0.0001) at the FRONTAL (78.31 ± 1.32 mm; URL: 88.19 mm) than the BEHIND EAR placement (111.86 ± 3.22 mm; URL: 135.99 mm). The effective angle was greater (P &lt; 0.0001) at the FRONTAL (4.72 ± 0.20°) than the BEHIND EAR placement (3.22 ± 0.17°). Potential for bolt-brain contact was not different (P = 1.0000) between FRONTAL-INLINE (10/10, 100% ± 0.01%), FRONTAL-PISTOL (10/10, 100% ± 0.01%), BEHIND EAR-INLINE (9/10, 90% ± 9.49%), and BEHIND EAR-PISTOL (10/10, 100% ± 0.01%); brain damage (P = 0.5577) between FRONTAL-INLINE (9/9, 100% ± 0.02%), FRONTAL-PISTOL (10/10, 100% ± 0.02%), BEHIND EAR-INLINE (4/10, 40% ± 15.49%), and BEHIND EAR-PISTOL (1/10, 10% ± 9.49%); potential for bolt-thalamus contact (P = 0.0683) for FRONTAL-INLINE (2/10, 20% ± 12.65%), FRONTAL-PISTOL (8/10, 80% ± 12.65%), BEHIND EAR-INLINE (7/9, 77.78% ± 13.86%), and BEHIND EAR-PISTOL (9/9, 100% ± 0.02%); or thalamic damage (P = 0.8041) for FRONTAL-INLINE (1/10, 10% ± 9.49%), FRONTAL-PISTOL (1/10, 10% ± 9.49%), BEHIND EAR-INLINE (2/8, 25% ± 15.31%), and BEHIND EAR-PISTOL (0/9, 0% ± 0.00%). The FRONTAL placement with an INLINE PCB may present the least risk of failure for the PCB euthanasia of mature sows &gt;200 kg body weight due to less total tissue thickness and thalamic depth, greater effective angle, and prevalent brain damage.
In Search of the Prototype of Forced Marriage
Authors: Quackelbeen Ligeia 
Published: July 2024

Abstract
This article discusses the categorization of the phenomenon of bush wives as forced marriage under the residual category of other inhumane acts in the Ongwen case. It reveals how judges at the International Criminal Court have used an Aristotelian Approach to characterization which entailed them to examine, on the basis of a jurisprudentially established checklist, whether the bush wives phenomenon shares the properties of the crime category of other inhumane acts. By discussing the forced marriage practices through an ‘other inhumane acts’ categorization, this article reveals the limits and pitfalls of the Aristotelian Approach. The main problem is that the Aristotelian Approach fails to grasp that categorization does not merely work on the basis of a checklist logic but also is a culturally determined process in which cultural prototypes need to be examined. This article’s main proposition is to consider an alternative way of categorization drawing from the philosophy of language and social sciences and suggests judges adopt a Prototype Approach. This approach enables judges to move away from a generic way of labelling different fact patterns through a checklist of properties and take on a more tailor-made and culturally sensitive approach that involves categorization through the discussion of the similarity and distinctiveness of a certain fact pattern to a prototype. In this way, judges can diversify interpretation of the other inhumane acts category in light of local practices as it requires a fresh decision of the facts by engaging with cultural practices in a more sensitive way and examining whether this phenomenon entails prototypical marriage practices. In this way, prototype theory opens new pathways in terms of how we label cultural practices and how we use the residual category of other inhumane acts.
Diversity and relative abundance of immature mosquitoes (Diptera: Culicidae) in Hohenbergia catingae Ule bromeliads and larvitraps in the Nísia Floresta National Forest, northeast Brazil
Authors: da Silva José Hilário Tavares , Silva-Inacio Cássio Lázaro , Gama Renata Antonaci , Ximenes Maria de Fátima Freire de Melo 
Published: July 2024

Abstract
The Nísia Floresta National Forest, located in Rio Grande do Norte (RN), is an important remnant of the Atlantic Forest biome in Brazil. Bromeliad tanks in this forest offer suitable breeding sites for mosquito species that may act as viral vectors, thus posing an epidemiological concern. However, studies investigating the presence of immature Culicidae in natural breeding sites in RN have thus far been restricted to Caatinga vegetation. This study investigated mosquitoes and their natural breeding sites in bromeliads growing in the Nísia Floresta National Forest. From March 2013 to February 2014, monthly samples were collected from the tanks of five randomly selected bromeliads and larvitraps placed in each of the three forest management areas. Hohenbergia catingae Ule (Hohenbergia bromeliad) is an important shelter for immature mosquitoes. Culex (Microculex) was the predominant species, representing 86% of the immature mosquitoes collected. A rare occurrence of Aedes (Stegomyia) aegypti (Linnaeus, 1762) (generally associated with urban areas under high anthropogenic influence) was observed, highlighting the importance of investigating the presence of mosquitoes in different natural habitats. An analysis of species diversity revealed that species such as Culex imitator Theobald, 1903 and Culex davisi Kumm, 1933, have a strong association with bromeliads. In tire traps (larvitraps) Aedes (Stegomyia) albopictus Skuse, 1894 was predominant. Environmental changes, such as deforestation, removal of bromeliads, and climate change in the area, can influence the migration of species and adaptation to new habitats in a peridomiciliary environment around the forest, consequently the possibility of transmission of virus and other pathogens.
ERBB2 amplification in gastric cancer: a genomic insight into ethnic disparities
Authors: Mirza Muhammad Bilal , Choi Jungyoon , Marincola Smith Paula , Baechle Jordan J , Padmanabhan Chandrasekhar , Holowatyj Andreana N , Shah Shailja C , Guo Xingyi , Idrees Kamran 
Published: July 2024

Abstract
Overall, gastric adenocarcinoma (GC) incidence rates have declined in recent years, but racial and ethnic disparities persist. Individuals who identify as Hispanic/Spanish/Latino are diagnosed with GC at younger ages and have poorer outcomes than non-Hispanic individuals. However, our understanding of GC biology across racial/ethnic groups remains limited. We assessed tumor genomic patterns by race/ethnicity among 1019 patients with primary GC in the American Association for Cancer Research (AACR) Project GENIE Consortium. Hispanic individuals presented with significantly higher rates of ERBB2/HER2 amplification vs other racial/ethnic groups (Hispanic: 13.9% vs 9.8% non-Hispanic White, 8.1% non-Hispanic Asian, and 11.0% non-Hispanic Black; P &lt; .001, FDR adjusted q &lt; 0.001). Hispanic patients also had higher odds of an ERBB2 amplification vs non-Hispanic Whites in adjusted models (OR = 2.52, 95%CI = 1.20 to 5.33, P = .015). These findings underscore the important role of genomic factors in GC disparities. Ensuring equitable access to genomic profiling and targeted therapies, such as trastuzumab for HER2-overexpressing GC, is a promising avenue to mitigate GC disparities and improve outcomes.
Prevalence of monoclonal gammopathy of undetermined significance in Eswatini: a population-based study in Africa
Authors: Cicero Kara I , Dlamini Xolisile , Mavengere Yvonne , Justman Jessica , Nuwagaba-Biribonwoha Harriet , Dlamini Sindisiwe , Dlamini Mxolisi , Ngwenyama Simphiwe , Ngcamphalala Cebisile , Low Andrea , Philip Neena M , El-Sadr Wafaa M , Sahabo Ruben , Abreha Tesfay , Temesgen Sintayehu , Mahlalela Nokuthula , Chiuzan Codruta , Chen Yuxuan , Pan Samuel S , Lentzsch Suzanne , Neugut Alfred I 
Published: July 2024

Abstract

Background
Although monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma disproportionately affect Black individuals, few epidemiological studies have been conducted on these plasma cell disorders in Africa. Here we describe the prevalence of MGUS in Eswatini and compare our results to the landmark Olmsted County, Minnesota study.

Methods
Between 2016 and 2017, 13 339 residents of Eswatini participated in the Swaziland HIV Incidence Measurement Survey, from which a nationally representative biorepository was created. Plasma samples were then randomly selected and analyzed for MGUS. MGUS prevalence in Eswatini was compared with that of Olmsted County. In addition, demographic and HIV-related associations with MGUS were assessed.

Results
Of the 515 samples randomly selected, the median age was 50 years (range = 35-80 years); 60% were female; and 38.6% were HIV positive, of whom 82.4% were on antiretroviral therapy. We found that 68 participants had evidence of MGUS, for a prevalence of 13.2%. HIV status was not significantly associated with MGUS (odds ratio = 1.05, 95% confidence interval = 0.62 to 1.77), but among HIV-positive individuals, MGUS was less frequent for patients on antiretroviral therapy (adjusted odds ratio = 0.31, 95% confidence interval = 0.11 to 0.82). The prevalence of conventional MGUS was similar between Eswatini and Olmsted County (3.4% vs 3.2%-3.4%), whereas the incidence of light-chain MGUS was significantly greater in Eswatini (12.3% vs 0.8%).

Conclusion
Our study suggests that the incidence of MGUS is similar between ethnicities and raises the question of whether the current definition of light-chain MGUS reliably reflects a true monoclonal protein precursor state. Perhaps the current definition of light-chain MGUS may be capturing alternate etiologies, such as untreated HIV infection.
Analysis of cancer drugs receiving FDA’s Accelerated Approval between 1992 and 2021
Authors: Lim Heeyeon , Kim Minji , Kang Geeyoon , Ko Minji , Kim Eunyoung 
Published: July 2024

Abstract

Objectives
This cross-sectional study examines the Food and Drug Administration (FDA)’s Accelerated Approval (AA) pathway for cancer drugs from 1992 to 2021, which expedites the development and approval of new drugs, including biologics, for severe or life-threatening conditions such as cancers.

Methods
Based on the ‘CDER Drug and Biologic AAs Based on a Surrogate Endpoint’ report, the number of indications where anticancer agents received AA and the conversion rates to Full Approval (FA) were analysed. Outcome measures used in phase II and phase III trials for these drugs were obtained from US National Library of Medicine for comparison.

Key findings
Of the 278 AA-granted indications, 67% were for anticancer agents. Lymphoma, leukemia, and lung cancer had the highest number of AA indications among all cancer types. The conversion rates to FA varied among periods: Early (1995–2003), Middle (2004–2012), and Late (2013–2021). The conversion rates for drugs were 82%, 79%, and 31%, while biologics exhibited rates of 100%, 78%, and 27%, respectively. The overall response rate was often the primary outcome measure in phase II trials, whereas overall survival and progression-free survival were the common outcome measures in phase III trials. Secondary outcome measures included disease control rate and duration of response.

Conclusions
This study provides valuable insights for stakeholders seeking to understand the approval criteria and processes for cancer drugs via the AA pathway. However, limitations in data availability, phase-specific variations in drug doses and combinations, and the inability to manage uncertain data should be acknowledged. Research on the AA program to non-cancer drugs is also required.
Understanding the Regulatory Pathways Used to Develop, Evaluate, Authorize, and Approve New Drugs and Vaccines in the United States
Authors: Domachowske Joseph B 
Published: July 2024

Abstract
The United States (U.S.) Food and Drug Administration (FDA) oversees the safety and quality of drugs and vaccines that are used in the U.S. Administration of the FDA falls under the jurisdiction of the U.S. Department of Health and Human Services (HHS). The regulatory oversight of the FDA is complex and comprehensive, requiring the various roles and responsibilities to be divided across six main centers. The activities of two of these centers, the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) are the primary focus of this review.
Roles of plastoglobules and lipid droplets in leaf neutral lipid accumulation during senescence and nitrogen deprivation
Authors: Coulon Denis , Nacir Houda , Bahammou Delphine , Jouhet Juliette , Bessoule Jean-Jacques , Fouillen Laëtitia , Bréhélin Claire 
Published: July 2024

Abstract
Upon abiotic stress or senescence, the size and/or abundance of plastid-localized plastoglobules and cytosolic lipid droplets, both compartments devoted to neutral lipid storage, increase in leaves. Meanwhile, plant lipid metabolism is also perturbed, notably with the degradation of thylakoidal monogalactosyldiacylglycerol (MGDG) and the accumulation of neutral lipids. Although these mechanisms are probably linked, they have never been jointly studied, and the respective roles of plastoglobules and lipid droplets in the plant response to stress are totally unknown. To address this question, we determined and compared the glycerolipid composition of both lipid droplets and plastoglobules, followed their formation in response to nitrogen starvation, and studied the kinetics of lipid metabolism in Arabidopsis leaves. Our results demonstrated that plastoglobules preferentially store phytyl-esters, while triacylglycerols (TAGs) and steryl-esters accumulated within lipid droplets. Thanks to a pulse–chase labeling approach and lipid analyses of the fatty acid desaturase 2 (fad2) mutant, we showed that MGDG-derived C18:3 fatty acids were exported to lipid droplets, while MGDG-derived C16:3 fatty acids were stored within plastoglobules. The export of lipids from plastids to lipid droplets was probably facilitated by the physical contact occurring between both organelles, as demonstrated by our electron tomography study. The accumulation of lipid droplets and neutral lipids was transient, suggesting that stress-induced TAGs were remobilized during the plant recovery phase by a mechanism that remains to be explored.
The baryon cycle in modern cosmological hydrodynamical simulations
Authors: Wright Ruby J , Somerville Rachel S , Lagos Claudia del P , Schaller Matthieu , Davé Romeel , Anglés-Alcázar Daniel , Genel Shy 
Published: July 2024

ABSTRACT
In recent years, cosmological hydrodynamical simulations have proven their utility as key interpretative tools in the study of galaxy formation and evolution. In this work, we present a comparative analysis of the baryon cycle in three publicly available, leading cosmological simulation suites: EAGLE, IllustrisTNG, and SIMBA. While these simulations broadly agree in terms of their predictions for the stellar mass content and star formation rates of galaxies at $z\approx 0$, they achieve this result for markedly different reasons. In EAGLE and SIMBA, we demonstrate that at low halo masses ($M_{\rm 200c}\lesssim 10^{11.5}\, \mathrm{M}_{\odot }$), stellar feedback (SF)-driven outflows can reach far beyond the scale of the halo, extending up to $2\!-\!3\times R_{\rm 200c}$. In contrast, in TNG, SF-driven outflows, while stronger at the scale of the interstellar medium, recycle within the circumgalactic medium (within $R_{\rm 200c}$). We find that active galactic nucleus (AGN)-driven outflows in SIMBA are notably potent, reaching several times $R_{\rm 200c}$ even at halo masses up to $M_{\rm 200c}\approx 10^{13.5}\, \mathrm{M}_{\odot }$. In both TNG and EAGLE, AGN feedback can eject gas beyond $R_{\rm 200c}$ at this mass scale, but seldom beyond $2\!-\!3\times R_{\rm 200c}$. We find that the scale of feedback-driven outflows can be directly linked with the prevention of cosmological inflow, as well as the total baryon fraction of haloes within $R_{\rm 200c}$. This work lays the foundation to develop targeted observational tests that can discriminate between feedback scenarios, and inform subgrid feedback models in the next generation of simulations.
Comparison of models for the warm-hot circumgalactic medium around Milky Way-like galaxies
Authors: Singh Priyanka , Lau Erwin T , Faerman Yakov , Stern Jonathan , Nagai Daisuke 
Published: July 2024

ABSTRACT
A systematic comparison of the models of the circumgalactic medium (CGM) and their observables is crucial to understanding the predictive power of the models and constraining physical processes that affect the thermodynamics of CGM. This paper compares four analytic CGM models: precipitation, isentropic, cooling flow, and baryon pasting models for the hot, volume-filling CGM phase, all assuming hydrostatic or quasi-hydrostatic equilibrium. We show that for fiducial parameters of the CGM of a Milky Way (MW)-like galaxy ($M_{\rm vir} \sim 10^{12}~{\rm M}_{\odot }$ at $z\sim 0$), the thermodynamic profiles – entropy, density, temperature, and pressure – show most significant differences between different models at small ($r\lesssim 30$ kpc) and large scales ($r\gtrsim 100$ kpc) while converging at intermediate scales. The slope of the entropy profile, which is one of the most important differentiators between models, is $\approx 0.8$ for the precipitation and cooling flow models, while it is $\approx 0.6$ and 0 for the baryon pasting and isentropic models, respectively. We make predictions for various observational quantities for an MW mass halo for the different models, including the projected Sunyaev–Zeldovich effect, soft X-ray emission (0.5–2 keV), dispersion measure, and column densities of oxygen ions (O vi, O vii, and O viii) observable in absorption. We provide Python packages to compute the thermodynamic and observable quantities for the different CGM models.
The timing of pronuclear transfer critically affects the developmental competence and quality of embryos
Authors: Znachorova Tereza , Dudko Nataliia , Ming Hao , Jiang Zongliang , Fulka Helena 
Published: July 2024

Abstract
Pronuclear transfer has been successfully used in human-assisted reproduction to suppress the adverse effects of a defective oocyte cytoplasm or to bypass an idiopathic developmental arrest. However, the effects of the initial parental genome remodelling in a defective cytoplasm on the subsequent development after pronucleus transfer have not been systematically studied. By performing pronuclear transfer in pre-replication and post-replication mouse embryos, we show that the timing of the procedure plays a critical role. Although apparently morphologically normal blastocysts were obtained in both pre- and post-replication pronuclear transfer groups, post-replication pronuclear transfer led to a decrease in developmental competence and profound changes in embryonic gene expression. By inhibiting the replication in the abnormal cytoplasm before pronuclear transfer into a healthy cytoplasm, the developmental potential of embryos could be largely restored. This shows that the conditions under which the first embryonic replication occurs strongly influence developmental potential. Although pronuclear transfer is the method of choice for mitigating the impact of a faulty oocyte cytoplasm on early development, our results show that the timing of this intervention should be restricted to the pre-replication phase.
SMCHD1 activates the expression of genes required for the expansion of human myoblasts
Authors: Wong Matthew Man-Kin , Hachmer Sarah , Gardner Ed , Runfola Valeria , Arezza Eric , Megeney Lynn A , Emerson Charles P , Gabellini Davide , Dilworth F Jeffrey 
Published: July 2024

Abstract
SMCHD1 is an epigenetic regulatory protein known to modulate the targeted repression of large chromatin domains. Diminished SMCHD1 function in muscle fibers causes Facioscapulohumeral Muscular Dystrophy (FSHD2) through derepression of the D4Z4 chromatin domain, an event which permits the aberrant expression of the disease-causing gene DUX4. Given that SMCHD1 plays a broader role in establishing the cellular epigenome, we examined whether loss of SMCHD1 function might affect muscle homeostasis through additional mechanisms. Here we show that acute depletion of SMCHD1 results in a DUX4-independent defect in myoblast proliferation. Genomic and transcriptomic experiments determined that SMCHD1 associates with enhancers of genes controlling cell cycle to activate their expression. Amongst these cell cycle regulatory genes, we identified LAP2 as a key target of SMCHD1 required for the expansion of myoblasts, where the ectopic expression of LAP2 rescues the proliferation defect of SMCHD1-depleted cells. Thus, the epigenetic regulator SMCHD1 can play the role of a transcriptional co-activator for maintaining the expression of genes required for muscle progenitor expansion. This DUX4-independent role for SMCHD1 in myoblasts suggests that the pathology of FSHD2 may be a consequence of defective muscle regeneration in addition to the muscle wasting caused by spurious DUX4 expression.