bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterotrimeric Gα-subunit regulates flower and fruit development in CLAVATA signaling pathway in cucumber
Authors: Han Lijie , Huang Yafei , Li Chuang , Tian Di , She Daixi , Li Min , Wang Zhongyi , Chen Jiacai , Liu Liu , Wang Shaoyun , Song Weiyuan , Wang Liming , Gu Chaoheng , Wu Tao , Zhao Jianyu , Zhou Zhaoyang , Zhang Xiaolan
Published: April 2024

Flowers and fruits are the reproductive organs in plants and play essential roles in natural beauty and the human diet. CLAVATA (CLV) signaling has been well characterized as regulating floral organ development by modulating shoot apical meristem (SAM) size; however, the signaling molecules downstream of the CLV pathway remain largely unknown in crops. Here, we found that functional disruption of CsCLV3 peptide and its receptor CsCLV1 both resulted in flowers with extra organs and stumpy fruits in cucumber. A heterotrimeric G protein α-subunit (CsGPA1) was shown to interact with CsCLV1. Csgpa1 mutant plants derived from gene editing displayed significantly increased floral organ numbers and shorter and wider fruits, a phenotype resembling that of Csclv mutants in cucumber. Moreover, the SAM size was enlarged and the longitudinal cell size of fruit was decreased in Csgpa1 mutants. The expression of the classical stem cell regulator WUSCHEL (WUS) was elevated in the SAM, while the expression of the fruit length stimulator CRABS CLAW (CRC) was reduced in the fruit of Csgpa1 mutants. Therefore, the Gα-subunit CsGPA1 protein interacts with CsCLV1 to inhibit floral organ numbers but promote fruit elongation, via repressing CsWUS expression and activating CsCRC transcription in cucumber. Our findings identified a new player in the CLV signaling pathway during flower and fruit development in dicots, increasing the number of target genes for precise manipulation of fruit shape during crop breeding.
Circulating HBV RNA and Hepatitis B Core–Related Antigen Trajectories in Persons With HIV/HBV Coinfection and Hepatitis B Surface Antigen Loss During Tenofovir Therapy
Authors: Begré Lorin , Boyd Anders , Plissonnier Marie-Laure , Testoni Barbara , Salazar-Vizcaya Luisa , Suter-Riniker Franziska , Scholtès Caroline , Béguelin Charles , Rockstroh Jürgen K , Günthard Huldrych F , Calmy Alexandra , Cavassini Matthias , Hirsch Hans H , Schmid Patrick , Bernasconi Enos , Levrero Massimo , Wandeler Gilles , Zoulim Fabien , Rauch Andri ,   the Swiss HIV Cohort Study, Abela I , Aebi-Popp K , Anagnostopoulos A , Battegay M , Bernasconi E , Braun D L , Bucher H C , Calmy A , Cavassini M , Ciuffi A , Dollenmaier G , Egger M , Elzi L , Fehr J , Fellay J , Furrer H , Fux C A , Günthard H F , Hachfeld A , Haerry D , Hasse B , Hirsch H H , Hoffmann M , Hösli I , Huber M , Jackson-Perry D , Kahlert C R , Keiser O , Klimkait T , Kouyos R D , Kovari H , Kusejko K , Labhardt N , Leuzinger K , Martinez de Tejada B , Marzolini C , Metzner K J , Müller N , Nemeth J , Nicca D , Notter J , Paioni P , Pantaleo G , Perreau M , Rauch A , Salazar-Vizcaya L , Schmid P , Speck R , Stöckle M , Tarr P , Trkola A , Wandeler G , Weisser M , Yerly S
Published: April 2024

Background

We evaluated long-term trajectories of circulating hepatitis B virus (HBV) RNA and hepatitis B core–related antigen (HBcrAg) in persons with and without hepatitis B surface antigen (HBsAg) loss during tenofovir therapy in the Swiss HIV Cohort Study.

Methods

We included 29 persons with HIV with HBsAg loss and 29 matched persons with HIV without HBsAg loss. We compared HBV RNA and HBcrAg decline and assessed the cumulative proportions with undetectable HBV RNA and HBcrAg levels during tenofovir therapy using Kaplan-Meier estimates.

Results

HBsAg loss occurred after a median of 4 years (IQR, 1–8). All participants with HBsAg loss achieved suppressed HBV DNA and undetectable HBV RNA preceding undetectable quantitative HBsAg levels, whereas 79% achieved negative HBcrAg. In comparison, 79% of participants without HBsAg loss achieved undetectable HBV-RNA and 48% negative HBcrAg. After 2 years of tenofovir therapy, an HBV RNA decline ≥1 log10 copies/mL had 100% sensitivity and 36.4% specificity for HBsAg loss, whereas an HBcrAg decline ≥1 log10 U/mL had 91.0% sensitivity and 64.5% specificity.

Conclusions

HBV RNA suppression preceded undetectable quantitative HBsAg levels and had high sensitivity but low specificity for HBsAg loss during tenofovir therapy in persons with HIV. HBcrAg remained detectable in approximately 20% of persons with HBsAg loss and 50% of persons without HBsAg loss.
Babesia duncani, a Model Organism for Investigating Intraerythrocytic Parasitism and Novel Antiparasitic Therapeutic Strategies
Authors: Fang Tiffany , Ben Mamoun Choukri
Published: April 2024

Pathogens such as Plasmodium, Babesia, and Theileria invade and multiply within host red blood cells, leading to the pathological consequences of malaria, babesiosis, and theileriosis. Establishing continuous in vitro culture systems and suitable animal models is crucial for studying these pathogens. This review spotlights the Babesia duncani in culture-in mouse (ICIM) model as a promising resource for advancing research on the biology, pathogenicity, and virulence of intraerythrocytic parasites. The model offers practical benefits, encompassing well-defined culture conditions, ease of manipulation, and a well-annotated genome. Moreover, B. duncani serves as a surrogate system for drug discovery, facilitating the evaluation of new antiparasitic drugs in vitro and in animals, elucidating their modes of action, and uncovering potential resistance mechanisms. The B. duncani ICIM model thus emerges as a multifaceted tool with profound implications, promising advancements in our understanding of parasitic biology and shaping the development of future therapies.
Morphological Diversity and Evolution of Jaw Morphologies in Zeiform Fishes (Teleostei, Paracanthopterygii)
Authors: Peters J W , Duclos K K , Wilson M V H , Grande T C
Published: April 2024

Synopsis

Zeiformes (dories, tinselfishes, and oreos) are primarily benthopelagic acanthomorph fishes, distributed between 50 and 1000 m depth on continental slopes and on flanks of oceanic islands and seamounts. Among the interesting morphological adaptations of zeiform fishes are their unique and highly protrusible jaws involving premaxillae with long ascending processes and a four-bar linkage, including mobile palatines that pivot on their posterior articulation. This adaptation for increased jaw protrusion has enabled zeiform fishes to capture elusive prey more efficiently and is arguably a major factor in their morphological diversity and evolutionary success. This study examines the evolution of zeiform jaw morphologies using 3D landmark-based multivariate morphometrics as well as phylomorphospace analysis. Results show that the descendants of the zeiform ancestor branched rapidly early in their history, retaining conservative jaw morphologies during this early branching, but subsequently strongly diverged in many of the resulting lineages. Results from this study are compared with earlier research based on overall body form, demonstrating that morphological variation within Zeiformes arose along at least two distinct trajectories: body form and jaw morphology. Variation among genera in body form is not associated with variation among the same genera in jaw morphology, and vice versa. Hypotheses to explain the apparent decoupling of body shape and jaw morphology are addressed along with avenues for further study to better understand the morphological evolution of these iconic fishes.
Iron limitation of heterotrophic bacteria in the California Current System tracks relative availability of organic carbon and iron
Authors: Manck Lauren E , Coale Tyler H , Stephens Brandon M , Forsch Kiefer O , Aluwihare Lihini I , Dupont Christopher L , Allen Andrew E , Barbeau Katherine A
Published: April 2024

Iron is an essential nutrient for all microorganisms of the marine environment. Iron limitation of primary production has been well documented across a significant portion of the global surface ocean, but much less is known regarding the potential for iron limitation of the marine heterotrophic microbial community. In this work, we characterize the transcriptomic response of the heterotrophic bacterial community to iron additions in the California Current System, an eastern boundary upwelling system, to detect in situ iron stress of heterotrophic bacteria. Changes in gene expression in response to iron availability by heterotrophic bacteria were detected under conditions of high productivity when carbon limitation was relieved but when iron availability remained low. The ratio of particulate organic carbon to dissolved iron emerged as a biogeochemical proxy for iron limitation of heterotrophic bacteria in this system. Iron stress was characterized by high expression levels of iron transport pathways and decreased expression of iron-containing enzymes involved in carbon metabolism, where a majority of the heterotrophic bacterial iron requirement resides. Expression of iron stress biomarkers, as identified in the iron-addition experiments, was also detected in  situ. These results suggest iron availability will impact the processing of organic matter by heterotrophic bacteria with potential consequences for the marine biological carbon pump.
Transnational Legal Spillover? A Re-Appraisal of the OECD Anti-Bribery Convention
Authors: Acorn Elizabeth , Allen Michael O
Published: April 2024

Can prosecutions by US authorities help spread enforcement of foreign bribery laws to other countries? In this article, we explore this question by re-examining earlier scholarship that found that US prosecutions of foreign corporations under the Foreign Corrupt Practices Act (FCPA) increase the likelihood that the corporation's home state will enforce its own foreign bribery laws. Using a conditional-frailty Cox model that allows us to model foreign bribery enforcement actions as repeat-events, we do not find evidence that FCPA prosecutions lead to sustained increases of foreign bribery enforcement by target countries. We also find that prior results are not robust to the inclusion of an important confounding variable: a country's level of exposure to corruption in their trading partners. Still, while our findings indicate a more limited role of US law enforcement in this area, we nonetheless see many promising avenues for future research on transnational law enforcement and its consequences.
Illuminating the landscape of high-level clinical trial opportunities in the All of Us Research Program
Authors: Shyr Cathy , Sulieman Lina , Harris Paul A
Published: April 2024

Objective

With its size and diversity, the All of Us Research Program has the potential to power and improve representation in clinical trials through ancillary studies like Nutrition for Precision Health. We sought to characterize high-level trial opportunities for the diverse participants and sponsors of future trial investment.

Materials and Methods

We matched All of Us participants with available trials on ClinicalTrials.gov based on medical conditions, age, sex, and geographic location. Based on the number of matched trials, we (1) developed the Trial Opportunities Compass (TOC) to help sponsors assess trial investment portfolios, (2) characterized the landscape of trial opportunities in a phenome-wide association study (PheWAS), and (3) assessed the relationship between trial opportunities and social determinants of health (SDoH) to identify potential barriers to trial participation.

Results

Our study included 181 529 All of Us participants and 18 634 trials. The TOC identified opportunities for portfolio investment and gaps in currently available trials across federal, industrial, and academic sponsors. PheWAS results revealed an emphasis on mental disorder-related trials, with anxiety disorder having the highest adjusted increase in the number of matched trials (59% [95% CI, 57-62]; P < 1e-300). Participants from certain communities underrepresented in biomedical research, including self-reported racial and ethnic minorities, had more matched trials after adjusting for other factors. Living in a nonmetropolitan area was associated with up to 13.1 times fewer matched trials.

Discussion and Conclusion

All of Us data are a valuable resource for identifying trial opportunities to inform trial portfolio planning. Characterizing these opportunities with consideration for SDoH can provide guidance on prioritizing the most pressing barriers to trial participation.
Transparent deep learning to identify autism spectrum disorders (ASD) in EHR using clinical notes
Authors: Leroy Gondy , Andrews Jennifer G , KeAlohi-Preece Madison , Jaswani Ajay , Song Hyunju , Galindo Maureen Kelly , Rice Sydney A
Published: April 2024

Objective

Machine learning (ML) is increasingly employed to diagnose medical conditions, with algorithms trained to assign a single label using a black-box approach. We created an ML approach using deep learning that generates outcomes that are transparent and in line with clinical, diagnostic rules. We demonstrate our approach for autism spectrum disorders (ASD), a neurodevelopmental condition with increasing prevalence.

Methods

We use unstructured data from the Centers for Disease Control and Prevention (CDC) surveillance records labeled by a CDC-trained clinician with ASD A1-3 and B1-4 criterion labels per sentence and with ASD cases labels per record using Diagnostic and Statistical Manual of Mental Disorders (DSM5) rules. One rule-based and three deep ML algorithms and six ensembles were compared and evaluated using a test set with 6773 sentences (N = 35 cases) set aside in advance. Criterion and case labeling were evaluated for each ML algorithm and ensemble. Case labeling outcomes were compared also with seven traditional tests.

Results

Performance for criterion labeling was highest for the hybrid BiLSTM ML model. The best case labeling was achieved by an ensemble of two BiLSTM ML models using a majority vote. It achieved 100% precision (or PPV), 83% recall (or sensitivity), 100% specificity, 91% accuracy, and 0.91 F-measure. A comparison with existing diagnostic tests shows that our best ensemble was more accurate overall.

Conclusions

Transparent ML is achievable even with small datasets. By focusing on intermediate steps, deep ML can provide transparent decisions. By leveraging data redundancies, ML errors at the intermediate level have a low impact on final outcomes.
Assessment of causal association between the socio-economic status and osteoporosis and fractures: a bidirectional Mendelian randomization study in European population
Authors: Duan Jia-Yue , You Rui-Xuan , Zhou Yong , Xu Feng , Lin Xiao , Shan Su-Kang , Zheng Ming-Hui , Lei Li-Min , Li Fu-Xing-Zi , Guo Bei , Wu Yun-Yun , Chen Xi , Tang Ke-Xin , Cao Ye-Chi , Wu Yan-Lin , He Si-Yang , Xiao Rong , Yuan Ling-Qing
Published: April 2024

The correlation between socio-economic status (SES) and bone-related diseases garners increasing attention, prompting a bidirectional Mendelian randomization (MR) analysis in this study. Genetic data on SES indicators (average total household income before tax, years of schooling completed, and Townsend Deprivation Index at recruitment), femoral neck bone mineral density (FN-BMD), heel bone mineral density (eBMD), osteoporosis, and five different sites of fractures (spine, femur, lower leg-ankle, foot, and wrist-hand fractures) were derived from genome-wide association summary statistics of European ancestry. The inverse variance weighted method was employed to obtain the causal estimates, complemented by alternative MR techniques, including MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO). Furthermore, sensitivity analyses and multivariable MR were performed to enhance the robustness of our findings. Higher educational attainment exhibited associations with increased eBMD (β: .06, 95% confidence interval [CI]: 0.01–0.10, P = 7.24 × 10−3), and reduced risks of osteoporosis (OR: 0.78, 95% CI: 0.65–0.94, P = 8.49 × 10−3), spine fracture (OR: 0.76, 95% CI: 0.66–0.88, P = 2.94 × 10−4), femur fracture (OR: 0.78, 95% CI: 0.67–0.91, P = 1.33 × 10−3), lower leg-ankle fracture (OR: 0.79, 95% CI: 0.70–0.88, P = 2.05 × 10−5), foot fracture (OR: 0.78, 95% CI: 0.66–0.93, P = 5.92 × 10−3), and wrist-hand fracture (OR: 0.83, 95% CI: 0.73–0.95, P = 7.15 × 10−3). Material deprivation appeared to increase the risk of spine fracture (OR: 2.63, 95% CI: 1.43–4.85, P = 1.91 × 10−3). A higher FN-BMD level positively affected increased household income (β: .03, 95% CI: 0.01–0.04, P = 6.78 × 10−3). All these estimates were adjusted for body mass index, type 2 diabetes, smoking initiation, and frequency of alcohol intake. The MR analyses show that higher educational levels is associated with higher eBMD, reduced risk of osteoporosis and fractures, while material deprivation is positively related to spine fracture. Enhanced FN-BMD correlates with increased household income. These findings provide valuable insights for health guideline formulation and policy development.
The effect of environmental variation on the relationship between survival and risk-taking behaviour in a migratory songbird
Authors: Krenhardt Katalin , Martínez-Padilla Jesús , Canal David , Jablonszky Mónika , Hegyi Gergely , Herényi Márton , Laczi Miklós , Markó Gábor , Nagy Gergely , Rosivall Balázs , Szász Eszter , Szöllősi Eszter , Török János , Vaskuti Éva , Zsebők Sándor , Garamszegi László Zsolt
Published: April 2024

Temporal changes in environmental conditions may play a major role in the year-to-year variation in fitness consequences of behaviours. Identifying environmental drivers of such variation is crucial to understand the evolutionary trajectories of behaviours in natural contexts. However, our understanding of how environmental variation influences behaviours in the wild remains limited. Using data collected over 14 breeding seasons from a collared flycatcher (Ficedula albicollis) population, we examined the effect of environmental variation on the relationship between survival and risk-taking behaviour, a highly variable behavioural trait with great evolutionary and ecological significance. Specifically, using annual recapture probability as a proxy of survival, we evaluated the specific effect of predation pressure, food availability, and mean temperature on the relationship between annual recapture probability and risk-taking behaviour (measured as flight initiation distance [FID]). We found a negative trend, as the relationship between annual recapture probability and FID decreased over the study years and changed from positive to negative. Specifically, in the early years of the study, risk-avoiding individuals exhibited a higher annual recapture probability, whereas in the later years, risk-avoiders had a lower annual recapture probability. However, we did not find evidence that any of the considered environmental factors mediated the variation in the relationship between survival and risk-taking behaviour.
Missing history of a modern domesticate: Historical demographics and genetic diversity in farm-bred red fox populations
Authors: Rando Halie M , Alexander Emmarie P , Preckler-Quisquater Sophie , Quinn Cate B , Stutchman Jeremy T , Johnson Jennifer L , Bastounes Estelle R , Horecka Beata , Black Kristina L , Robson Michael P , Shepeleva Darya V , Herbeck Yury E , Kharlamova Anastasiya V , Trut Lyudmila N , Pauli Jonathan N , Sacks Benjamin N , Kukekova Anna V
Published: April 2024

The first record of captive-bred red foxes (Vulpes vulpes) dates to 1896 when a breeding enterprise emerged in the provinces of Atlantic Canada. Because its domestication happened during recent history, the red fox offers a unique opportunity to examine the genetic diversity of an emerging domesticated species in the context of documented historical and economic influences. In particular, the historical record suggests that North American and Eurasian farm-bred populations likely experienced different demographic trajectories. Here, we focus on the likely impacts of founder effects and genetic drift given historical trends in fox farming on North American and Eurasian farms. A total of 15 mitochondrial haplotypes were identified in 369 foxes from 10 farm populations that we genotyped (n = 161) or that were previously published. All haplotypes are endemic to North America. Although most haplotypes were consistent with eastern Canadian ancestry, a small number of foxes carried haplotypes typically found in Alaska and other regions of western North America. The presence of these haplotypes supports historical reports of wild foxes outside of Atlantic Canada being introduced into the breeding stock. These putative Alaskan and Western haplotypes were more frequently identified in Eurasian farms compared to North American farms, consistent with historical documentation suggesting that Eurasian economic and breeding practices were likely to maintain low-frequency haplotypes more effectively than in North America. Contextualizing inter- vs. intra-farm genetic diversity alongside the historical record is critical to understanding the origins of this emerging domesticate and the relationships between wild and farm-bred fox populations.
Empirically derived profiles of neurocognitive functioning in youth and young adults with sickle cell disease
Authors: Ellison Vinkrya , Berlin Kristoffer S , Longoria Jennifer , Potter Brian , Raches Darcy , Hankins Jane S , Takemoto Clifford , Heitzer Andrew M
Published: April 2024

Objective

Sickle cell disease (SCD) is an inherited blood disorder associated with neurocognitive deficits. In contrast to variable-centered approaches, no known research has utilized person-centered strategies to identify multidimensional patterns of neurocognitive functioning of an individual with SCD. The purpose of the present study was to create empirically derived profiles and identify predictors of neurocognitive functioning subgroups among youth and young adults with SCD.

Methods

Individuals with SCD (N = 393, mean age 14.05 years, age range 8–24, 50.4% female/49.6% male) completed neurocognitive assessments. Latent profile analysis derived subgroups/classes of neurocognitive functioning and determined relations with demographic and medical variables.

Results

Three latent classes emerged: average functioning (n = 102, 27%), low average functioning (n = 225, 60%), and exceptionally low functioning (n = 46, 12%). Older age was associated with membership in the low average and exceptionally low functioning groups (relative to the average group). Being prescribed hydroxyurea was associated with membership in the average functioning group (relative to the low average group) and absence of hydroxyurea use was associated with membership in the exceptionally low group (relative to the low average group). Lower social vulnerability was associated with membership in the average functioning group compared to the low average and exceptionally low groups.

Conclusions

Clinicians can help reduce disparities in cognitive development for individuals with SCD by promoting early treatment with hydroxyurea and implementing methods to reduce social vulnerabilities that can interfere with access to evidence-based care.
The genus Ranunculus L. (Ranunculus) in Asia: a review of its botany, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations
Authors: Dai Yun-Lei , Liu Qing-Zhi , Wang Jian , Sun Meng , Niu Feng-Jv , Wei Hao-Cheng , Zhou Chang-Zheng , Zhang Li
Published: April 2024

Objectives

Ranunculus L. genus contains 413 species, and it is the biggest genus in the family Ranunculaceae Juss. This review is to provide botanical characteristics, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations of the genus Ranunculus.

Key findings

The genus Ranunculus contains flavonoids, organic acids, coumarins, lactones, glycosides, sterols, polysaccharides, and trace elements. These chemical constituents complement the pharmacological actions and work together to exert anti-inflammatory, anticancer, antitubercular, antibacterial, antimalarial, etc. Those traditional Chinese medicine characteristics, like clearing away heat and detoxification, make this genus significant in ethnic medicine. The progress in research and the development of various pharmaceutical preparations made it appear in epidemiological and clinical studies.

The genus Ranunculus has attracted the attention of experts and scholars in many fields due to its unique advantages. However, there are many species that are not scientifically investigated. The toxicity issues are also a huge concern. Fortunately, the toxicity can be overcome via special processes like drying or heating and by choosing a safe extraction solvent, such as water thus ensuring the safety of medication. Pharmaceutical preparations containing the plants from Ranunculus have gratifying clinical value, but they are not promoted sufficiently. Therefore, further research should be carried out to promote the genus for its health benefits to humans.
Dexmedetomidine affects the NOX4/Nrf2 pathway to improve renal antioxidant capacity
Authors: Yang Haotian , Chen Yongping , Wang Zhiqiang , Huang Yuxiang , Ma Zhigang , Zou Yue , Dong Jiaqiang , Zhang Hong , Huo Mingdong , Lv Mingzhe , Liu Xuesong , Zhang Guohua , Wang Shuang , Yang Kun , Zhong Peng , Jiang Botao , Kou Yuhong , Chen Zhifeng
Published: April 2024

Objectives

The study aimed to investigate the protective effects of dexmedetomidine (DEX) on renal injury caused by acute stress in rats and explore the protective pathways of DEX on rat kidneys in terms of oxidative stress.

Methods

An acute restraint stress model was utilized, where rats were restrained for 3 hours after a 15-minute swim. Biochemical tests and histopathological sections were conducted to evaluate renal function, along with the measurement of oxidative stress and related pathway proteins.

Key findings

The open-field experiments validated the successful establishment of the acute stress model. Acute stress-induced renal injury led to increased NADPH oxidase 4 (NOX4) protein expression and decreased expression levels of nuclear transcription factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1). Following DEX treatment, there was a significant reduction in renal NOX4 expression. The DEX-treated group exhibited normalized renal biochemical results and less damage observed in pathological sections compared to the acute stress group.

Conclusions

The findings suggest that DEX treatment during acute stress can impact the NOX4/Nrf2/HO-1/NQO1 signaling pathway and inhibit oxidative stress, thereby preventing acute stress-induced kidney injury. Additionally, DEX shows promise for clinical applications in stress syndromes.
Severe traumatic atlantoaxial dislocation and type III odontoid fracture treated with occipitocervical fixation: a case report
Authors: Mahadewa Tjokorda Gde Bagus , Junus Eufrata Silvestris , Awyono Steven , Japardi Denny , Lauren Christopher
Published: April 2024

The combination of atlantoaxial joint dislocation accompanied by an odontoid process fracture is exceptionally rare, with only a few cases reported. The estimated frequency of these cases is < 2% of all upper cervical spine injuries. In this report, the authors describe an unusual case of traumatic atlantoaxial dislocation with a type III odontoid fracture in a 44-year-old male patient. Before the diagnosis, the patient had a history of seeking a masseur for a neck massage. Subsequently, the patient underwent occipitocervical stabilization to address the underlying condition. This procedure aims to treat the instability between the skull and cervical spine and should be considered in the treatment planning if the patient’s anatomy suits it.
Hooks & Bends in the radial acceleration relation: discriminatory tests for dark matter and MOND
Authors: Mercado Francisco J , Bullock James S , Moreno Jorge , Boylan-Kolchin Michael , Hopkins Philip F , Wetzel Andrew , Faucher-Giguère Claude-André , Samuel Jenna
Published: April 2024

The radial acceleration relation (RAR) connects the total gravitational acceleration of a galaxy at a given radius, atot(r), with that accounted for by baryons at the same radius, abar(r). The shape and tightness of the RAR for rotationally-supported galaxies have characteristics in line with MOdified Newtonian Dynamics (MOND) and can also arise within the cosmological constant + cold dark matter (ΛCDM) paradigm. We use zoom simulations of 20 galaxies with stellar masses of M⋆ ≃ 107–11 M⊙ to study the RAR in the FIRE-2 simulations. We highlight the existence of simulated galaxies with non-monotonic RAR tracks that ‘hook’ down from the average relation. These hooks are challenging to explain in Modified Inertia theories of MOND, but naturally arise in all of our ΛCDM-simulated galaxies that are dark-matter dominated at small radii and have feedback-induced cores in their dark matter haloes. We show, analytically and numerically, that downward hooks are expected in such cored haloes because they have non-monotonic acceleration profiles. We also extend the relation to accelerations below those traced by disc galaxy rotation curves. In this regime, our simulations exhibit ‘bends’ off of the MOND-inspired extrapolation of the RAR, which, at large radii, approach atot ≈ abar/fb, where fb is the cosmic baryon fraction. Future efforts to search for these hooks and bends in real galaxies will provide interesting tests for MOND and ΛCDM.
A novel transient receptor potential C3/C6 selective activator induces the cellular uptake of antisense oligonucleotides
Authors: Kohashi Hiroto , Nagata Ryu , Tamenori Yusuke , Amatani Tomorrow , Ueda Yoshifumi , Mori Yasuo , Kasahara Yuuya , Obika Satoshi , Shimojo Masahito
Published: April 2024

Antisense oligonucleotide (ASO) therapy is a novel therapeutic approach in which ASO specifically binds target mRNA, resulting in mRNA degradation; however, cellular uptake of ASOs remains critically low, warranting improvement. Transient receptor potential canonical (TRPC) channels regulate Ca2+ influx and are activated upon stimulation by phospholipase C-generated diacylglycerol. Herein, we report that a novel TRPC3/C6/C7 activator, L687, can induce cellular ASO uptake. L687-induced ASO uptake was enhanced in a dose- and incubation-time-dependent manner. L687 enhanced the knockdown activity of various ASOs both in vitro and in vivo. Notably, suppression of TRPC3/C6 by specific siRNAs reduced ASO uptake in A549 cells. Application of BAPTA-AM, a Ca2+ chelator, and SKF96365, a TRPC3/C6 inhibitor, suppressed Ca2+ influx via TRPC3/C6, resulting in reduced ASO uptake, thereby suggesting that Ca2+ influx via TRPC3/C6 is critical for L687-mediated increased ASO uptake. L687 also induced dextran uptake, indicating that L687 increased endocytosis. Adding ASO to L687 resulted in endosome accumulation; however, the endosomal membrane disruptor UNC7938 facilitated endosomal escape and enhanced knockdown activity. We discovered a new function for TRPC activators regarding ASO trafficking in target cells. Our findings provide an opportunity to formulate an innovative drug delivery system for the therapeutic development of ASO.
Nutritional strategies to reduce intestinal cell apoptosis by alleviating oxidative stress
Authors: Li Baofeng , Zhang Xiaoli , Zhang Qianzi , Zheng Tenghui , Li Qihui , Yang Siwang , Shao Jiayuan , Guan Wutai , Zhang Shihai
Published: April 2024

The gut barrier is the first line of defense against harmful substances and pathogens in the intestinal tract. The balance of proliferation and apoptosis of intestinal epithelial cells (IECs) is crucial for maintaining the integrity of the intestinal mucosa and its function. However, oxidative stress and inflammation can cause DNA damage and abnormal apoptosis of the IECs, leading to the disruption of the intestinal epithelial barrier. This, in turn, can directly or indirectly cause various acute and chronic intestinal diseases. In recent years, there has been a growing understanding of the vital role of dietary ingredients in gut health. Studies have shown that certain amino acids, fibers, vitamins, and polyphenols in the diet can protect IECs from excessive apoptosis caused by oxidative stress, and limit intestinal inflammation. This review aims to describe the molecular mechanism of apoptosis and its relationship with intestinal function, and to discuss the modulation of IECs' physiological function, the intestinal epithelial barrier, and gut health by various nutrients. The findings of this review may provide a theoretical basis for the use of nutritional interventions in clinical intestinal disease research and animal production, ultimately leading to improved human and animal intestinal health.
Case Series of People With HIV on the Long-Acting Combination of Lenacapavir and Cabotegravir: Call for a Trial
Authors: Gandhi Monica , Hill Lucas , Grochowski Janet , Nelson Alexander , Koss Catherine A , Mayorga-Munoz Francis , Oskarsson Jon , Shiels Mary , Avery Ann , Bamford Laura , Baron Jillian , Short William R , Hileman Corrilynn O
Published: April 2024

Background

Injectable cabotegravir (CAB)/rilpivirine (RPV) is the only combination long-acting (LA) antiretroviral regimen approved for HIV. RPV may not be effective among individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, which has >10% prevalence in many countries. Lenacapavir (LEN) is an LA capsid inhibitor given every 6 months, but has not been studied in combination with other LA agents.

Methods

We assembled a case series from 4 US academic medical centers where patients with adherence challenges were prescribed LEN subcutaneously every 26 weeks/CAB (+/− RPV) intramuscularly every 4 or 8 weeks. Descriptive statistics, including viral load (VL) outcomes, were summarized.

Results

All patients (n = 34: 76% male; 24% cis/trans female; 41% Black; 38% Latino/a; median age [range], 47 [28–75] years; 29% and 71% on CAB every 4 or 8 weeks) reported challenges adhering to oral ART. The reasons for using LEN/CAB with or without RPV were documented or suspected NNRTI mutations (n = 21, 59%), integrase mutations (n = 5, 15%), high VL (n = 6, 18%), or continued viremia on CAB/RPV alone (n = 4, 12%). Injection site reactions on LA LEN were reported in 44% (32% grade I, 12% grade 2). All patients but 2 (32/34; 94%) were suppressed (VL <75 copies/mL) after starting LEN at a median (range) of 8 (4–16) weeks, with 16/34 (47%) suppressed at baseline.

Conclusions

In this case series of 34 patients on LEN/CAB, high rates of virologic suppression (94%) were observed. Reasons for using LEN/CAB included adherence challenges and underlying resistance, mostly to NNRTIs. These data support a clinical trial of LEN/CAB among persons with NNRTI resistance.
Characterizing Ertapenem Neurotoxicity: A Systematic Review and Experience at a Tertiary Medical Center
Authors: Mitaka Hayato , Hasegawa Shinya , Lan Kristine F , Jain Rupali , Rakita Robert M , Pottinger Paul S
Published: April 2024

Ertapenem-induced neurotoxicity has not been well characterized and is potentially underreported. We conducted a systematic review of the literature and included 11 additional cases from the University of Washington Medicine health system. A total of 125 individual patient cases were included in the data analysis. The mean age was 72 years, and 62% and 42% of patients had renal dysfunction and preexisting central nervous system (CNS) conditions, respectively. Only 15% of patients received inappropriately high ertapenem dosing based on kidney function. Patients developed neurological signs and symptoms after a median of 4 days (interquartile range, 3–9 days). The most common clinical features were seizures (70%), altered level of consciousness or delirium (27%), and hallucinations (17%). An estimated incidence in our health system was 1 in 102 courses of ertapenem. Ertapenem neurotoxicity should be suspected when a patient with renal dysfunction or predisposing CNS conditions develops neurological signs and symptoms, especially within several days after initiating the antibiotic. This study underscores the need for a large prospective study to assess the true incidence and outcomes of ertapenem neurotoxicity.
Entomopathogenic nematodes as an effective and sustainable alternative to control the fall armyworm in Africa
Authors: Fallet Patrick , Bazagwira Didace , Ruzzante Livio , Ingabire Geraldine , Levivier Sacha , Bustos-Segura Carlos , Kajuga Joelle , Toepfer Stefan , Turlings Ted C J
Published: April 2024

The recent invasion of the fall armyworm (FAW), a voracious pest, into Africa and Asia has resulted in unprecedented increases in insecticide applications, especially in maize cultivation. The health and environmental hazards posed by these chemicals have prompted a call for alternative control practices. Entomopathogenic nematodes are highly lethal to the FAWs, but their application aboveground has been challenging. In this study, we report on season-long field trials with an innocuous biodegradable gel made from carboxymethyl cellulose containing local nematodes that we specifically developed to target the FAW. In several Rwandan maize fields with distinct climatic conditions and natural infestation rates, we compared armyworm presence and damage in control plots and plots that were treated with either our nematode gel formulation, a commercial liquid nematode formulation, or the commonly used contact insecticide cypermethrin. The treatments were applied to the whorl of each plant, which was repeated three to four times, at 2-week intervals, starting when the plants were still seedlings. Although all three treatments reduced leaf damage, only the gel formulation decreased caterpillar infestation by about 50% and yielded an additional ton of maize per hectare compared with untreated plots. Importantly, we believe that the use of nematodes can be cost-effective, since we used nematode doses across the whole season that were at least 3-fold lower than their normal application against belowground pests. The overall results imply that precisely formulated and easy-to-apply nematodes can be a highly effective, affordable, and sustainable alternative to insecticides for FAW control.
A primal–dual data-driven method for computational optical imaging with a photonic lantern
Authors: Santos Garcia Carlos , Larchevêque Mathilde , O’Sullivan Solal , Van Waerebeke Martin , Thomson Robert R , Repetti Audrey , Pesquet Jean-Christophe
Published: April 2024

Optical fibers aim to image in vivo biological processes. In this context, high spatial resolution and stability to fiber movements are key to enable decision-making processes (e.g. for microendoscopy). Recently, a single-pixel imaging technique based on a multicore fiber photonic lantern has been designed, named computational optical imaging using a lantern (COIL). A proximal algorithm based on a sparsity prior, dubbed SARA-COIL, has been further proposed to solve the associated inverse problem, to enable image reconstructions for high resolution COIL microendoscopy. In this work, we develop a data-driven approach for COIL. We replace the sparsity prior in the proximal algorithm by a learned denoiser, leading to a plug-and-play (PnP) algorithm. The resulting PnP method, based on a proximal primal–dual algorithm, enables to solve the Morozov formulation of the inverse problem. We use recent results in learning theory to train a network with desirable Lipschitz properties, and we show that the resulting primal–dual PnP algorithm converges to a solution to a monotone inclusion problem. Our simulations highlight that the proposed data-driven approach improves the reconstruction quality over variational SARA-COIL method on both simulated and real data.
Arrangers and orchestrators: the diverging role of the state in Danish and German vocational education and training
Authors: Ibsen Christian Lyhne , Thelen Kathleen
Published: April 2024

This article compares the changing role of the state in initial vocational education and training (VET) in Germany and Denmark. Scholars have argued that collectivist VET systems face a stark choice between erosion through dualization or state take-over that crowds out decentralized cooperation by firms. Yet, recent work suggests that the state can revitalize the traditional firm-based system of VET through so-called state ‘orchestration’ and soft measures promoting inclusive training. Comparing Germany to Denmark, we argue that there is a second path to revitalization when the state acts as an ‘arranger’, more heavily involved in the provision and governance of VET, and using it for second-chance education. Unlike orchestration, arrangement is only possible where the state itself has achieved some independent capacity in training. We trace this divergence to small policy choices in the 1970s that have had large downstream effects on state capacity and power relations with business.
Better Regulation and the Secretariat General for Legal and Parliamentary Affairs of the Presidency of the Hellenic Government: A Considerable Work Already in Progress
Authors: Koromilas Ilias
Published: April 2024

This paper article scrutinizes the initiatives for Better Regulation implemented in Greece, set against the backdrop of a globalized world that is persistently grappling with sporadic, and occasionally dramatic and chaotic, challenges. A significant proportion of these initiatives are designed to mitigate the enduring adverse effects on Greece economy, environment, and society, which are the consequences of a flawed legislative process. This process has been criticized in numerous studies and reports for its bureaucratic red tape, inefficiency, fragmentation, and lack of a culture promoting better regulation. The handbooks and methodologies examined in this article originate from the law on the Executive State and were executed under the auspices of the European Commission (DG REFORM) Technical Support Action, which was implemented by Expertise France and is titled: “Support Public Administration Reform and its Digital Transformation.” Most of these initiatives have been successfully completed and implemented, while the completion of others is imminent. In conclusion, the author suggests several additional measures for implementation, which are intended to enhance the reforms that are already in place.
Interleaving Foundational Nursing Concepts for Accelerated Nursing Students Through Gamification
Authors: Traister Tyler
Published: April 2024

As nursing education adapts to post-COVID learning and an ever-increasing data-connected world, interactive gaming experiences may help students retain information and encourage teamwork and critical thinking skills. This article explores the innovative use of an escape room as a means to interleave essential nursing concepts for first-semester students pursuing an accelerated bachelor's degree in nursing. The unique approach proved to be an effective and engaging way to introduce and reinforce key principles.
Discovering the Intriguing Properties of Extrasynaptic γ-Aminobutyric Acid Type A Receptors
Authors: Orser Beverley A.
Published: April 2024

Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by α5 subunit-containing γ-aminobutyric acid type A receptors. By Caraiscos VB, Elliott EM, You-Ten KE, Cheng VY, Belelli D, Newell JG, Jackson MF, Lambert JJ, Rosahl TW, Wafford KA, MacDonald JF, Orser BA. Proc Natl Acad Sci U S A 2004; 101:3662–7. Reprinted with permission.

In this Classic Paper Revisited, the author recounts the scientific journey leading to a report published in the Proceedings of the National Academy of Sciences (PNAS) and shares several personal stories from her formative years and “research truths” that she has learned along the way. Briefly, the principal inhibitory neurotransmitter in the brain, γ-aminobutyric acid (GABA), was conventionally thought to regulate cognitive processes by activating synaptic GABA type A (GABAA) receptors and generating transient inhibitory synaptic currents. However, the author’s laboratory team discovered a novel nonsynaptic form of tonic inhibition in hippocampal pyramidal neurons, mediated by extrasynaptic GABAA receptors that are pharmacologically distinct from synaptic GABAA receptors. This tonic current is highly sensitive to most general anesthetics, including sevoflurane and propofol, and likely contributes to the memory-blocking properties of these drugs. Before the publication in PNAS, the subunit composition of GABAA receptors that generate the tonic current was unknown. The team’s research showed that GABAA receptors containing the α5 subunit (α5GABAARs) generated the tonic inhibitory current in hippocampal neurons. α5GABAARs are highly sensitive to GABA, desensitize slowly, and are thus well suited for detecting low, persistent, ambient concentrations of GABA in the extracellular space. Interest in α5GABAARs has surged since the PNAS report, driven by their pivotal roles in cognitive processes and their potential as therapeutic targets for treating various neurologic disorders.
Effects of Positive End-expiratory Pressure on Pulmonary Perfusion Distribution and Intrapulmonary Shunt during One-lung Ventilation in Pigs: A Randomized Crossover Study
Authors: Wittenstein Jakob , Scharffenberg Martin , Fröhlich Jonathan , Rothmann Carolin , Ran Xi , Zhang Yingying , Chai Yusen , Yang Xiuli , Müller Sabine , Koch Thea , Huhle Robert , Gama de Abreu Marcelo
Published: April 2024

Background

During one-lung ventilation (OLV), positive end-expiratory pressure (PEEP) can improve lung aeration but might overdistend lung units and increase intrapulmonary shunt. The authors hypothesized that higher PEEP shifts pulmonary perfusion from the ventilated to the nonventilated lung, resulting in a U-shaped relationship with intrapulmonary shunt during OLV.

Methods

In nine anesthetized female pigs, a thoracotomy was performed and intravenous lipopolysaccharide infused to mimic the inflammatory response of thoracic surgery. Animals underwent OLV in supine position with PEEP of 0 cm H2O, 5 cm H2O, titrated to best respiratory system compliance, and 15 cm H2O (PEEP0, PEEP5, PEEPtitr, and PEEP15, respectively, 45 min each, Latin square sequence). Respiratory, hemodynamic, and gas exchange variables were measured. The distributions of perfusion and ventilation were determined by IV fluorescent microspheres and computed tomography, respectively.

Results

Compared to two-lung ventilation, the driving pressure increased with OLV, irrespective of the PEEP level. During OLV, cardiac output was lower at PEEP15 (5.5 ± 1.5 l/min) than PEEP0 (7.6 ± 3 l/min) and PEEP5 (7.4 ± 2.9 l/min; P = 0.004), while the intrapulmonary shunt was highest at PEEP0 (PEEP0: 48.1% ± 14.4%; PEEP5: 42.4% ± 14.8%; PEEPtitr: 37.8% ± 11.0%; PEEP15: 39.0% ± 10.7%; P = 0.027). The relative perfusion of the ventilated lung did not differ among PEEP levels (PEEP0: 65.0% ± 10.6%; PEEP5: 68.7% ± 8.7%; PEEPtitr: 68.2% ± 10.5%; PEEP15: 58.4% ± 12.8%; P = 0.096), but the centers of relative perfusion and ventilation in the ventilated lung shifted from ventral to dorsal and from cranial to caudal zones with increasing PEEP.

Conclusions

In this experimental model of thoracic surgery, higher PEEP during OLV did not shift the perfusion from the ventilated to the nonventilated lung, thus not increasing intrapulmonary shunt.

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“We Come From Different Worlds”
Authors: Jenkins Danisha , Burton Candace , Holmes Dave
Published: April 2024

The purpose of this study was to give voice to the lived experiences of nurses and law enforcement officers whose professional responsibilities converge in the acute care setting, while gaining insight into the perspectives and interpretations of their experiences. Using interpretative phenomenological analysis, this quality study contributes to a growing body of literature exploring the influence of law enforcement in the hospital. Overwhelmingly, participants in this study expressed a contentious dynamic, fueled by arguments, struggles for power, and a feeling of coming from “different worlds.” The influence of socially and spatially constructed territories was critical points of contention.