bluuebunny/crossref_metadata_2025 huggingface dataset:
Meso-cortical pathway damage in cognition, apathy and gait in cerebral small vessel disease
Authors: Li Hao , Jacob Mina A , Cai Mengfei , Kessels Roy P C , Norris David G , Duering Marco , de Leeuw Frank-Erik , Tuladhar Anil M
Published: May 2024

Cerebral small vessel disease (SVD) is known to contribute to cognitive impairment, apathy and gait dysfunction. Although associations between cognitive impairment and either apathy or gait dysfunction have been shown in SVD, the inter-relations among these three clinical features and their potential common neural basis remain unexplored. The dopaminergic meso-cortical and meso-limbic pathways have been known as the important brain circuits for both cognitive control, emotion regulation and motor function. Here, we investigated the potential inter-relations between cognitive impairment, apathy and gait dysfunction, with a specific focus on determining whether these clinical features are associated with damage to the meso-cortical and meso-limbic pathways in SVD.

In this cross-sectional study, we included 213 participants with SVD for whom MRI and comprehensive neurobehavioural assessments were performed. These assessments comprised six clinical measures: processing speed, executive function, memory, apathy (based on the Apathy Evaluation Scale) and gait function (based on the time and steps in the Timed Up and Go Test). We reconstructed five tracts connecting the ventral tegmental area (VTA) and dorsolateral prefrontal cortex (PFC), ventral lateral PFC, medial orbitofrontal cortex, anterior cingulate cortex (ACC) and nucleus accumbens within meso-cortical and meso-limbic pathways using diffusion weighted imaging. The damage along the five tracts was quantified using the free water (FW) and FW-corrected mean diffusivity indices. Furthermore, we explored the inter-correlations among the six clinical measures and identified their common components using principal component analysis (PCA).

Linear regression analyses showed that higher FW values of tracts within meso-cortical pathways were related to these clinical measures in cognition, apathy, and gait (all P-corrected values < 0.05). The PCA showed strong inter-associations among these clinical measures and identified a common component wherein all six clinical measures loaded on. Higher FW values of tracts within meso-cortical pathways were related to the PCA-derived common component (all P-corrected values < 0.05). Moreover, FW values of the VTA-ACC tract showed the strongest contribution to the PCA-derived common component over all other neuroimaging features.

In conclusion, our study showed that the three clinical features (cognitive impairment, apathy, and gait dysfunction) of SVD are strongly inter-related and that the damage in meso-cortical pathway could be the common neural basis underlying the three features in SVD. These findings advance our understanding of the mechanisms behind these clinical features of SVD and have the potential to inform novel management and intervention strategies for SVD.
Special Issue: International Conference on Sustainable Energy Sources, Technologies and Systems 2023 (ICSESTS-2023)
Authors: Kumar Ravinder , Ahmadi Mohammad Hossein
Published: May 2024

Guest editorial introducing the special issue on the International Conference on Sustainable Energy Sources, Technologies and Systems 2023.
Prevention of Vascular Access Device–Associated Hospital-Onset Bacteremia and Fungemia: A Review of Emerging Perspectives and Synthesis of Technical Aspects
Authors: Garcia Robert , Septimus Edward J , LeDonne Jack , Sturm Lisa K , Moureau Nancy , DeVries Michelle , DeBaun Barbara
Published: May 2024

Significant events that have impacted healthcare over the last several years have been associated with escalating rates of healthcare-associated infections. This has resulted in increased efforts to reinstitute well-established and evidence-based infection prevention (IP) practices, particularly for central line–associated bloodstream infections. However, implementation of prevention initiatives beyond central lines has not received the same level of acknowledgment and response as being a considerable risk to patients. This article, authored by IP, infectious disease, and vascular access professionals, provides emerging perspectives and technical aspects associated with the complete “life cycle” of a vascular access device. The intent is to provide insight and perspective on enhancing current IP practices in the acute care hospital setting. This will also help prepare hospitals for upcoming broader surveillance and intervention activities aimed at reducing hospital-onset bacteremia and fungemia associated with all types of vascular access devices.
Usefulness of the Clinical Frailty Scale in patients with end-stage kidney disease
Authors: Lamberink Kyra , Vermeeren Yolande M , Moes Arthur D , Mulderij Jeanette , Rootjes Paul A , Zomer Tizza P
Published: May 2024

Background

The frailty index (FI) is commonly used to estimate frailty in end-stage kidney disease (ESKD) patients. The Clinical Frailty Scale (CFS) is a less time-consuming alternative. We aimed to determine the test performance of the CFS for pre-dialysis and dialysis patients and patients receiving conservative therapy from the Dialysis Centre Apeldoorn.

Methods

In this cross-sectional study, haemodialysis, peritoneal dialysis, pre-dialysis patients and patients receiving conservative therapy from the Dialysis Centre Apeldoorn were included and subjected to frailty assessment. Nephrologists not familiar with the CFS completed the frailty score after medical consultation. The sensitivity, specificity and area under the curve (AUC) of the CFS were determined. The FI was used as the gold standard.

Results

Included were 144 patients, of whom 60 (41.7%) were considered frail according to the FI. The mean age was 67.4 ± 13.5 years and 56 (38.9%) were female. The cut-off point of the CFS for ‘vulnerable’ (CFS ≥4) had a sensitivity of 63.3%, a specificity of 81.0% and an AUC of 0.72. The cut-off point of the CFS for ‘frail’ (CFS ≥5) had a sensitivity of 50.0%, a specificity of 91.7% and an AUC of 0.71.

Conclusions

The CFS is a quick and easy-to-use tool for the determination of frailty in ESKD patients with a high prevalence of frailty. Nevertheless, the sensitivity of the CFS in the present study was considered too low to implement into daily clinical practice. The sensitivity might be increased by training nephrologists in the use of the CFS.
Prediction of Student Performance Using Random Forest Combined With Naïve Bayes
Authors: Manzali Youness , Akhiat Yassine , Abdoulaye Barry Khalidou , Akachar Elyazid , El Far Mohamed
Published: May 2024

Random forest is a powerful ensemble learning technique celebrated for its heightened predictive performance and robustness in handling complex datasets; nevertheless, it is criticized for its computational expense, particularly with a large number of trees in the ensemble. Moreover, the model’s interpretability diminishes as the ensemble’s complexity increases, presenting challenges in understanding the decision-making process. Although various pruning techniques have been proposed by researchers to tackle these issues, achieving a consensus on the optimal strategy across diverse datasets remains elusive. In response to these challenges, this paper introduces an innovative machine learning algorithm that integrates random forest with Naïve Bayes to predict student performance. The proposed method employs the Naïve Bayes formula to evaluate random forest branches, classifying data by prioritizing branches based on importance and assigning each example to a single branch for classification. The algorithm is utilized on two sets of student data and is evaluated against seven alternative machine-learning algorithms. The results confirm its strong performance, characterized by a minimal number of branches.
Clinical significance of residual ischaemia in acute myocardial infarction complicated by cardiogenic shock undergoing venoarterial–extracorporeal membrane oxygenation
Authors: Hong David , Choi Ki Hong , Ahn Chul-Min , Yu Cheol Woong , Park Ik Hyun , Jang Woo Jin , Kim Hyun-Joong , Bae Jang-Whan , Kwon Sung Uk , Lee Hyun-Jong , Lee Wang Soo , Jeong Jin-Ok , Park Sang-Don , Park Taek Kyu , Lee Joo Myung , Song Young Bin , Hahn Joo-Yong , Choi Seung-Hyuk , Gwon Hyeon-Cheol , Yang Jeong Hoon
Published: May 2024

Aims

Although culprit-only revascularization during the index procedure has been recommended in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS), the reduction in residual ischaemia is also emphasized to improve clinical outcomes. However, few data are available about the significance of residual ischaemia in patients undergoing mechanical circulatory supports. This study aimed to evaluate the effects of residual ischaemia on clinical outcomes in patients with AMI undergoing venoarterial–extracorporeal membrane oxygenation (VA-ECMO).

Methods and results

Patients with AMI with multivessel disease who underwent VA-ECMO due to refractory CS were pooled from the RESCUE and SMC-ECMO registries. The included patients were classified into three groups according to residual ischaemia evaluated using the residual Synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery (SYNTAX) score (rSS): rSS = 0, 0 < rSS ≤ 8, and rSS > 8. The primary outcome was 1-year all-cause death. A total of 408 patients were classified into the rSS = 0 (n = 100, 24.5%), 0 < rSS ≤ 8 (n = 136, 33.3%), and rSS > 8 (n = 172, 42.2%) groups. The cumulative incidence of the primary outcome differed significantly according to rSS (33.9 vs. 55.4 vs. 66.1% for rSS = 0, 0 < rSS ≤ 8, and rSS > 8, respectively, overall P < 0.001). In a multivariable model, rSS was independently associated with the risk of 1-year all-cause death (adjusted hazard ratio 1.03, 95% confidence interval 1.01–1.05, P = 0.003). Conversely, the baseline SYNTAX score was not associated with the risk of the primary outcome. Furthermore, when patients were stratified by rSS, the primary outcome did not differ significantly between the high and low delta SYNTAX score groups.

Conclusion

In patients with AMI with refractory CS who underwent VA-ECMO, residual ischaemia was associated with an increased risk of 1-year mortality. Future studies are needed to evaluate the efficacy and safety of revascularization strategies to minimize residual ischaemia in patients with CS supported with VA-ECMO.

Clinical trial registration

REtrospective and Prospective Observational Study to Investigate Clinical oUtcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With Cardiogenic Shock (RESCUE), NCT02985008.
Use of cangrelor for complex percutaneous coronary intervention in the context of concomitant severe aortic stenosis: a case series
Authors: Soriano Francesco , Munafò Andrea R , Baydaroglu Nurcan , Nava Stefano , Bruschi Giuseppe , Esposito Giuseppe , Oreglia Jacopo A , Montalto Claudio
Published: May 2024

Background

There is a growing need for percutaneous coronary intervention (PCI) to be performed within the same transcatheter aortic valve implantation (TAVI) procedure. In such cases, cangrelor, a fast-acting intravenous P2Y12-inhibitor with a short offset, is potential clinical utility to minimize bleeding and vascular complications during large-bore arterial access (LBAA) as well as the thrombotic risk associated with concomitant PCI.

Case summary

We report two cases of TAVI with an indication to concomitant, high-risk PCI. In the first one, cangrelor was started only after LBAA was secured and TAVI completed, just before the initiation of complex PCI. In the second case, due to predicted complex coronary cannulation after TAVI, complex PCI was performed before TAVI and cangrelor started just after LBAA. In both cases, use of cangrelor (vs. pre-treatment with oral P2Y12-i) allowed for a tailored minimization of the risk of bleeding and vascular complications during LBAA while offering full platelet inhibition during a complex/high-risk PCI.

Discussion

In this case series, we illustrate a possible approach to the use of cangrelor for patients undergoing TAVI and complex/high-risk PCI. In such complex cases, thorough pre-procedural planning might include a cangrelor to minimize vascular, bleeding, and ischaemic complications.
Right ventricular outflow tract diameter change with exercise: a prospective exercise echocardiography and invasive CPET study
Authors: El Shaer Ahmed , Garcia-Arango Mariana , Korcarz Claudia , Broman Aimee Teo , Lechuga Christopher G , Chesler Naomi C , Raza Farhan
Published: May 2024

While cardiac output reserve with exercise predicts outcomes in cardiac and pulmonary vascular disease, precise quantification of exercise cardiac output requires invasive cardiopulmonary testing (iCPET). To improve the accuracy of cardiac output reserve estimation with transthoracic echocardiography (TTE), this prospective study aims to define changes in right ventricular outflow tract diameter (RVOTd) with exercise and its relationship with invasively measured haemodynamics. Twenty subjects underwent simultaneous TTE and iCPET, with data collected at rest, leg-raise, 25 W, 50 W (n = 16), 75 W (n = 14), and 100 W (n = 6). This was followed by a second exercise study with real-time RV pressure–volume loops at similar stages (except leg-raise). The overall cohort included heart failure with preserved ejection fraction (n = 12), pulmonary arterial hypertension (n = 5), and non-cardiac dyspnoea (n = 3). RVOTd was reverse engineered from the TTE-derived RVOT velocity time integral (VTI) and iCPET-derived stroke volume, using the formula: Fick stroke volume = RVOT VTI × RVOT area (wherein RVOT area = π × [RVOTd/2]2). RVOTd increased by nearly 3–4% at every 25 W increment. Using linear regression models, where each subject is treated as a categorical variable and adjusting for subject intercept, RVOTd was correlated with haemodynamic variables (cardiac output, heart rate, pulmonary artery and RV pressures). Of all the predictor haemodynamic variables, cardiac output had the highest r2 model fit (adjusted r2 = 0.68), with a unit increase in cardiac output associated with a 0.0678 increase in RVOTd (P < 0.001). Our findings indicate that RVOTd increases by 3–4% with every 25 W increment, predominantly correlated with cardiac output augmentation. These results can improve the accuracy of cardiac output reserve estimation by adjusting for RVOTd with graded exercise during non-invasive CPET and echocardiogram. However, future studies are needed to define these relationships for left ventricular outflow tract diameter.
Paravalvular regurgitation after transcatheter aortic valve replacement: incidence, quantification, and prognostic impact
Authors: van Wely Marleen , Rooijakkers Maxim , Stens Niels , El Messaoudi Saloua , Somers Tim , van Garsse Leen , Thijssen Dick , Nijveldt Robin , van Royen Niels
Published: May 2024

Transcatheter aortic valve replacement (TAVR) is the standard of care in aortic stenosis with results comparable to surgical aortic valve replacement. However, paravalvular regurgitation (PVR) is more common after TAVR. With the alteration of devices and implantation techniques, the incidence of moderate or more PVR has declined. Mild PVR is still common in around 30% of TAVR patients in low-risk trials. Progression of AS causes myocardial hypertrophy and varying degrees of diastolic dysfunction which may cause heart failure even in combination with small volumes of PVR. Any degree of PVR is associated with an increased risk of overall and cardiovascular mortality. Predictors of PVR are annular eccentricity, severe calcification of the aortic valve, bicuspid aortic valves, and type of prosthesis where balloon-expandable devices are associated with less PVR. PVR is diagnosed using echocardiography, aortic angiogram with or without videodensitometry, haemodynamic parameters, or cardiac magnetic resonance. PVR can be treated using post-dilation, interventional treatment using a vascular plug, or implantation of a second device. Successful post-dilation depends on balloon size which should at least be equal to or >95% of the mean annulus diameter. Implantation of a second device to reduce PVR is successful in ∼90% of cases, either through lengthening of the sealing skirt in case of inadequate position or through further expansion of the index device. Implantation of a vascular plug can successfully reduce PVR and reduce mortality.
Senolytics and cell senescence: historical and evolutionary perspectives
Authors: Finch Caleb E
Published: May 2024

Senolytics are a new class of anti-aging drugs developed to selectively kill ‘senescent’ cells that are considered harmful in normal aging. More than 20 drug trials are ongoing with diverse ‘senolytic cocktails’. This commentary on recent reviews of senolytics gives a historical context of mammalian cell senescence that enabled these new drugs. While cell senescence is considered harmful to aging tissues, many studies show its essential role in some regenerative and developmental processes for which senolytic drugs may interfere. Longer-term studies of side effects are needed before senolytics are considered for general clinical practice. The wide occurrence of cell senescence in eukaryotes, yeast to fish to humans, and suggests an ancient eukaryotic process that evolved multiple phenotypes.
Juvenile mortality and sibling replacement: a kin selection approach
Authors: Giaimo Stefano , Traulsen Arne
Published: May 2024

Mortality generally is higher around birth and then progressively declines through the juvenile stage. In species where offspring depend upon their parents during maturation, a factor behind this mortality decline could be sibling replacement: offspring sacrifice their survival to benefit future or present siblings as early as possible in order to minimize losses in parental investment. Here, we propose a kin-selection model of sibling replacement. Theoretical analysis of the model and its application to demographic data of mammals suggest that sibling replacement consistently generates a selective incentive for increasing juvenile mortality at early ages when this mortality increment is the result of positive selection for juvenile altruism within the nuclear family. The model highlights how sibling replacement goes beyond optimal allocation of parental resources into dependents and can provoke greater mortality closer to birth also in response to a more favorable ratio of actors to recipients of altruism among siblings.
Exploring ethnic differences in the distribution of blood test results in healthy adult populations to inform earlier cancer detection: a systematic review
Authors: Chen Ge , Barlow Melissa , Down Liz , Mounce Luke Timothy Allan , Merriel Samuel William David , Watson Jessica , Martins Tanimola , Bailey Sarah Elizabeth Rose
Published: May 2024

Background

In primary care, health professionals use blood tests to investigate nonspecific presentations to inform referral decisions. Reference ranges for the commonly used blood tests in western countries were developed in predominately White populations, and so may perform differently when applied to non-White populations. Knowledge of ethnic variation in blood test results in healthy/general populations could help address ethnic inequalities in cancer referral for diagnosis and outcomes.

Objective

This systematic review explored evidence of ethnic differences in the distribution of selected blood test results among healthy/general populations to inform future research aimed at addressing inequalities in cancer diagnosis.

Methods

We searched PubMed and EMBASE to identify studies reporting measures of haemoglobin, MCV, calcium, albumin, platelet count, and CRP in nondiseased adults from at least 2 different ethnic groups. Two reviewers independently screened studies, completed data extraction and quality assessment using an adapted Newcastle-Ottawa scale. Participants were stratified into White, Black, Asian, Mixed, and Other groups. Data were synthesised narratively and meta-analyses were conducted where possible.

Results

A total of 47 papers were included. Black men and women have lower average values of haemoglobin, MCV, and albumin, and higher average values of CRP relative to their White counterparts. Additionally, Black men have lower average haemoglobin than Asian men, whereas Asian women have lower average CRP values when compared with White women.

Conclusions

There is evidence of ethnic differences in average values of haemoglobin, MCV, CRP, and albumin in healthy/general populations. Further research is needed to explore the reasons for these differences. Systematic review registration: CRD42021274580
Changes in nutrient availability substantially alter bacteria and extracellular enzymatic activities in Antarctic soils
Authors: Nair Girish R , Kooverjee Bhaveni B , de Scally Storme , Cowan Don A , Makhalanyane Thulani P
Published: May 2024

In polar regions, global warming has accelerated the melting of glacial and buried ice, resulting in meltwater run-off and the mobilization of surface nutrients. Yet, the short-term effects of altered nutrient regimes on the diversity and function of soil microbiota in polyextreme environments such as Antarctica, remains poorly understood. We studied these effects by constructing soil microcosms simulating augmented carbon, nitrogen, and moisture. Addition of nitrogen significantly decreased the diversity of Antarctic soil microbial assemblages, compared with other treatments. Other treatments led to a shift in the relative abundances of these microbial assemblages although the distributional patterns were random. Only nitrogen treatment appeared to lead to distinct community structural patterns, with increases in abundance of Proteobacteria (Gammaproteobateria) and a decrease in Verrucomicrobiota (Chlamydiae and Verrucomicrobiae).The effects of extracellular enzyme activities and soil parameters on changes in microbial taxa were also significant following nitrogen addition. Structural equation modeling revealed that nutrient source and extracellular enzyme activities were positive predictors of microbial diversity. Our study highlights the effect of nitrogen addition on Antarctic soil microorganisms, supporting evidence of microbial resilience to nutrient increases. In contrast with studies suggesting that these communities may be resistant to change, Antarctic soil microbiota responded rapidly to augmented nutrient regimes.
Gene Function is a Driver of Activin Signaling Pathway Evolution Following Whole-Genome Duplication in Rainbow Trout (Oncorhynchus mykiss)
Authors: Richman Jasmine A , Davis Leah R , Phelps Michael P
Published: May 2024

The genomes of plant and animal species are influenced by ancestral whole-genome duplication (WGD) events, which have profound impacts on the regulation and function of gene networks. To gain insight into the consequences of WGD events, we characterized the sequence conservation and expression patterns of ohnologs in the highly duplicated activin receptor signaling pathway in rainbow trout (RBT). The RBT activin receptor signaling pathway is defined by tissue-specific expression of inhibitors and ligands and broad expression of receptors and Co-Smad signaling molecules. Signaling pathway ligands exhibited shared expression, while inhibitors and Smad signaling molecules primarily express a single dominant ohnolog. Our findings suggest that gene function influences ohnolog evolution following duplication of the activin signaling pathway in RBT.
Loss of FMRP affects ovarian development and behaviour through multiple pathways in a zebrafish model of fragile X syndrome
Authors: Rani Rita , Sri N Sushma , Medishetti Raghavender , Chatti Kiranam , Sevilimedu Aarti
Published: May 2024

Fragile X syndrome (FXS) is an inherited neurodevelopmental disorder and the leading genetic cause of autism spectrum disorders. FXS is caused by loss of function mutations in Fragile X mental retardation protein (FMRP), an RNA binding protein that is known to regulate translation of its target mRNAs, predominantly in the brain and gonads. The molecular mechanisms connecting FMRP function to neurodevelopmental phenotypes are well understood. However, neither the full extent of reproductive phenotypes, nor the underlying molecular mechanisms have been as yet determined. Here, we developed new fmr1 knockout zebrafish lines and show that they mimic key aspects of FXS neuronal phenotypes across both larval and adult stages. Results from the fmr1 knockout females also showed that altered gene expression in the brain, via the neuroendocrine pathway contribute to distinct abnormal phenotypes during ovarian development and oocyte maturation. We identified at least three mechanisms underpinning these defects, including altered neuroendocrine signaling in sexually mature females resulting in accelerated ovarian development, altered expression of germ cell and meiosis promoting genes at various stages during oocyte maturation, and finally a strong mitochondrial impairment in late stage oocytes from knockout females. Our findings have implications beyond FXS in the study of reproductive function and female infertility. Dissection of the translation control pathways during ovarian development using models like the knockout lines reported here may reveal novel approaches and targets for fertility treatments.
Evolutionary conservation of receptor compensation for stem cell homeostasis in Solanaceae plants
Authors: Seo Myeong-Gyun , Lim Yoonseo , Hendelman Anat , Robitaille Gina , Beak Hong Kwan , Hong Woo-Jong , Park Soon Ju , Lippman Zachary B , Park Young-Joon , Kwon Choon-Tak
Published: May 2024

Stem cell homeostasis is pivotal for continuous and programmed formation of organs in plants. The precise control of meristem proliferation is mediated by the evolutionarily conserved signaling that encompasses complex interactions among multiple peptide ligands and their receptor-like kinases. Here, we identified compensation mechanisms involving the CLAVATA1 (CLV1) receptor and its paralogs, BARELY ANY MERISTEMs (BAMs), for stem cell proliferation in two Solanaceae species, tomato and groundcherry. Genetic analyses of higher-order mutants deficient in multiple receptor genes, generated via CRISPR-Cas9 genome editing, reveal that tomato SlBAM1 and SlBAM2 compensate for slclv1 mutations. Unlike the compensatory responses between orthologous receptors observed in Arabidopsis, tomato slclv1 mutations do not trigger transcriptional upregulation of four SlBAM genes. The compensation mechanisms within receptors are also conserved in groundcherry, and critical amino acid residues of the receptors associated with the physical interaction with peptide ligands are highly conserved in Solanaceae plants. Our findings demonstrate that the evolutionary conservation of both compensation mechanisms and critical coding sequences between receptor-like kinases provides a strong buffering capacity during stem cell homeostasis in tomato and groundcherry.
Scrutinizing the current management units of the greater argentine in the light of genetic structure
Authors: Quintela María , Seljestad Gaute W , Dahle Geir , Hallfredsson Elvar H , Enberg Katja , Langbehn Tom J , Jansson Eeva , Glover Kevin A , Westgaard Jon-Ivar
Published: May 2024

The greater argentine is a benthopelagic fish with a northern amphi-Atlantic and southern Arctic distribution. Landings of this species have been steadily increasing since the early 2000s, mainly for ultra-processed fish food. The rising economic importance of this species begs for an accurate delineation of the management units needed to ensure the sustainability of the fishery. The alignment between management and biological units was investigated on three of the ICES stocks in the NE Atlantic (123a4, 5a14, and 5b6a) by genotyping 88 ad hoc-developed SNPs on 1299 individuals sampled along the Norwegian coast, north of Shetland, around the Faroe Islands, and in the Denmark Strait within Icelandic waters. Candidate loci to positive selection were particularly crucial for units’ delineation and supported the current ICES 5b6a and 5a14 stocks around the Faroe Islands and Iceland, respectively. However, within the third stock investigated, 123a4, which corresponded mainly to the Norwegian coast, the sample from area 3a (Skagerrak) was significantly different from all the remaining in the same stock. This differentiation advocates for reconsideration of the present policy and suggests considering ICES Area 3a (Skagerrak) as an independent management unit. The environmental conditions in the Skagerrak area have left a genetic print on other marine taxa, which could putatively be the case in the greater argentine.
Ground Reaction Forces and Energy Exchange During Underwater Walking
Authors: Gamel K M , Pinti S , Astley H C
Published: May 2024

Synopsis

Underwater walking was a crucial step in the evolutionary transition from water to land. Underwater walkers use fins and/or limbs to interact with the benthic substrate and produce propulsive forces. The dynamics of underwater walking remain poorly understood due to the lack of a sufficiently sensitive and waterproof system to measure substrate reaction forces (SRFs). Using an underwater force plate (described in our companion paper), we quantify SRFs during underwater walking in axolotls (Ambystoma mexicanum) and Spot prawn (Pandalus platyceros), synchronized with videography. The horizontal propulsive forces were greater than the braking forces in both species to overcome hydrodynamic drag. In axolotls, potential energy (PE) fluctuations were far smaller than kinetic energy (KE) fluctuations due to high buoyant support (97%), whereas the magnitudes were similar in the prawn due to lower buoyant support (93%). However, both species show minimal evidence of exchange between KE and PE, which, along with the effects of hydrodynamic drag, is incompatible with inverted pendulum dynamics. Our results show that, despite their evolutionary links, underwater walking has fundamentally different dynamics compared with terrestrial walking and emphasize the substantial consequences of differences in body plan in underwater walking.
Vascular function and skeletal fragility: a study of tonometry, brachial hemodynamics, and bone microarchitecture
Authors: Usiskin Ilana M , Mitchell Gary F , Bouxsein Mary L , Liu Ching-Ti , Kiel Douglas P , Samelson Elizabeth J
Published: May 2024

Osteoporosis and cardiovascular disease frequently occur together in older adults; however, a causal relationship between these 2 common conditions has not been established. By the time clinical cardiovascular disease develops, it is often too late to test whether vascular dysfunction developed before or after the onset of osteoporosis. Therefore, we assessed the association of vascular function, measured by tonometry and brachial hemodynamic testing, with bone density, microarchitecture, and strength, measured by HR-pQCT, in 1391 individuals in the Framingham Heart Study. We hypothesized that decreased vascular function (pulse wave velocity, primary pressure wave, brachial pulse pressure, baseline flow amplitude, and brachial flow velocity) contributes to deficits in bone density, microarchitecture and strength, particularly in cortical bone, which is less protected from excessive blood flow pulsatility than the trabecular compartment. We found that individuals with increased carotid-femoral pulse wave velocity had lower cortical volumetric bone mineral density (tibia: −0.21 [−0.26, −0.15] standardized beta [95% CI], radius: −0.20 [−0.26, −0.15]), lower cortical thickness (tibia: −0.09 [−0.15, −0.04], radius: −0.07 [−0.12, −0.01]) and increased cortical porosity (tibia: 0.20 [0.15, 0.25], radius: 0.21 [0.15, 0.27]). However, these associations did not persist after adjustment for age, sex, height, and weight. These results suggest that vascular dysfunction with aging may not be an etiologic mechanism that contributes to the co-occurrence of osteoporosis and cardiovascular disease in older adults. Further study employing longitudinal measures of HR-pQCT parameters is needed to fully elucidate the link between vascular function and bone health.
Cross-sectional associations between accelerometer-measured physical activity and hip bone mineral density: the Tromsø Study 2015-2016
Authors: Mikkilä Saija , Handegård Bjørn Helge , Johansson Jonas , Hopstock Laila A , Van den Tillaar Roland , Emaus Nina , Morseth Bente , Welde Boye
Published: May 2024

Positive associations between physical activity and bone health have been found in population-based studies, however, mostly based on self-reported physical activity. Therefore, we investigated the association between accelerometer-measured physical activity, measured in steps per day and minutes of moderate to vigorous physical activity (MVPA) per day, and total hip areal BMD (aBMD) measured by DXA in a general population, utilizing multiple regression models. The study participants, 1560 women and 1177 men aged 40–84 yr, were part of the seventh survey of the Tromsø Study (2015-2016). In both genders, we found a positive association between the number of daily steps and aBMD adjusted for age, BMI, and smoking status (P < .001). In women, an increase of 1000 steps per day was associated with 0.005 g/cm2 higher aBMD. For men, a polynomial curve indicated a positive association with aBMD up to 5000 steps per day, plateauing between 5000 and 14 000 steps, and then increasing again. Additionally, MVPA duration was positively associated with aBMD in both women (P < .001) and men (P = .004) when adjusted for age, BMI, and smoking status. Specifically, each 60-min increase in daily MVPA was associated with 0.028 and 0.023 g/cm2 higher aBMD in women and men, respectively. Despite positive associations, the clinical impact of physical activity on aBMD in this general population of adults and older adults was relatively small, and a large increase in daily MVPA might not be achievable for most individuals. Therefore, further longitudinal population-based studies incorporating device-based measures of physical activity could add more clarity to these relationships.
A stochastic gradient relational event additive model for modelling US patent citations from 1976 to 2022
Authors: Filippi-Mazzola Edoardo , Wit Ernst C
Published: May 2024

Until 2022, the US patent citation network contained almost 10 million patents and over 100 million citations, presenting a challenge in analysing such expansive, intricate networks. To overcome limitations in analysing this complex citation network, we propose a stochastic gradient relational event additive model (STREAM) that models the citation relationships between patents as time events. While the structure of this model relies on the relational event model, STREAM offers a more comprehensive interpretation by modelling the effect of each predictor non-linearly. Overall, our model identifies key factors driving patent citations and reveals insights in the citation process.
Semi-simultaneous hand-assisted laparoscopic (HAL) bilateral nephrectomy and kidney transplantation from the same incision in ADPKD, first case report in Saudi Arabia
Authors: Shaheen Mohammed F , Aljehaiman Fahad , Altheaby Abdulrahman
Published: May 2024

This case report discusses the management of a 46-year-old male patient with autosomal dominant polycystic kidney disease and a high body mass index, who underwent a semi-simultaneous procedure involving hand-assisted laparoscopic bilateral nephrectomy to alleviate severe abdominal symptoms and prepare for a kidney transplantation, all using the same incision. This is the first reported occurrence of such a procedure in Saudi Arabia. Post-operatively, the patient made a successful recovery with excellent kidney function and no complications.
Hypoxia makes EZH2 inhibitor not easy—advances of crosstalk between HIF and EZH2
Authors: Huang Zhanya , Tang Yuanjun , Zhang Jianlin , Huang Jiaqi , Cheng Rui , Guo Yunyun , Kleer Celina G , Wang Yuqing , Xue Lixiang
Published: May 2024

Histone methylation plays a crucial role in tumorigenesis. Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that regulates chromatin structure and gene expression. EZH2 inhibitors (EZH2is) have been shown to be effective in treating hematologic malignancies, while their effectiveness in solid tumors remains limited. One of the major challenges in the treatment of solid tumors is their hypoxic tumor microenvironment. Hypoxia-inducible factor 1-alpha (HIF-1α) is a key hypoxia responder that interacts with EZH2 to promote tumor progression. Here we discuss the implications of the relationship between EZH2 and hypoxia for expanding the application of EZH2is in solid tumors.
Structural snapshots of phenuivirus cap-snatching and transcription
Authors: Williams Harry M , Thorkelsson Sigurdur R , Vogel Dominik , Busch Carola , Milewski Morlin , Cusack Stephen , Grünewald Kay , Quemin Emmanuelle R J , Rosenthal Maria
Published: May 2024

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a human pathogen that is now endemic to several East Asian countries. The viral large (L) protein catalyzes viral transcription by stealing host mRNA caps via a process known as cap-snatching. Here, we establish an in vitro cap-snatching assay and present three high-quality electron cryo-microscopy (cryo-EM) structures of the SFTSV L protein in biologically relevant, transcription-specific states. In a priming-state structure, we show capped RNA bound to the L protein cap-binding domain (CBD). The L protein conformation in this priming structure is significantly different from published replication-state structures, in particular the N- and C-terminal domains. The capped-RNA is positioned in a way that it can feed directly into the RNA-dependent RNA polymerase (RdRp) ready for elongation. We also captured the L protein in an early-elongation state following primer-incorporation demonstrating that this priming conformation is retained at least in the very early stages of primer extension. This structural data is complemented by in vitro biochemical and cell-based assays. Together, these insights further our mechanistic understanding of how SFTSV and other bunyaviruses incorporate stolen host mRNA fragments into their viral transcripts thereby allowing the virus to hijack host cell translation machinery.
DeepMicroClass sorts metagenomic contigs into prokaryotes, eukaryotes and viruses
Authors: Hou Shengwei , Tang Tianqi , Cheng Siliangyu , Liu Yuanhao , Xia Tian , Chen Ting , Fuhrman Jed A , Sun Fengzhu
Published: May 2024

Sequence classification facilitates a fundamental understanding of the structure of microbial communities. Binary metagenomic sequence classifiers are insufficient because environmental metagenomes are typically derived from multiple sequence sources. Here we introduce a deep-learning based sequence classifier, DeepMicroClass, that classifies metagenomic contigs into five sequence classes, i.e. viruses infecting prokaryotic or eukaryotic hosts, eukaryotic or prokaryotic chromosomes, and prokaryotic plasmids. DeepMicroClass achieved high performance for all sequence classes at various tested sequence lengths ranging from 500 bp to 100 kbps. By benchmarking on a synthetic dataset with variable sequence class composition, we showed that DeepMicroClass obtained better performance for eukaryotic, plasmid and viral contig classification than other state-of-the-art predictors. DeepMicroClass achieved comparable performance on viral sequence classification with geNomad and VirSorter2 when benchmarked on the CAMI II marine dataset. Using a coastal daily time-series metagenomic dataset as a case study, we showed that microbial eukaryotes and prokaryotic viruses are integral to microbial communities. By analyzing monthly metagenomes collected at HOT and BATS, we found relatively higher viral read proportions in the subsurface layer in late summer, consistent with the seasonal viral infection patterns prevalent in these areas. We expect DeepMicroClass will promote metagenomic studies of under-appreciated sequence types.
Koori Quit Pack: A Feasibility Study of a Multi-Component Mailout Smoking Cessation Support for Aboriginal and Torres Strait Islander People: “I Would Recommend it to Anybody. It’s Just so Much Easier.”
Authors: Kennedy Michelle , Maddox Raglan , Mersha Amanual Getnet , Chamberlain Catherine , Segan Catherine , Clarke Kerindy , Donaldson Belinda , Roberts-Barker Kayden , Forster Joley , Booth Kade , Bonevski Billie
Published: May 2024

Introduction

Smoking is the leading cause of preventable death among Aboriginal and Torres Strait Islander people.

Aims and Methods

The Koori Quit Pack study aimed to assess the feasibility of a multi-component mailout smoking cessation intervention to reduce smoking among Aboriginal and Torres Strait Islander people. A non-randomized, single-group feasibility study was conducted among Aboriginal and Torres Strait Islander people who reported current smoking. The intervention package included information pamphlets and resources on quitting, referral offer to Aboriginal Quitline and optional free Nicotine Replacement Therapies (NRT). Follow-up was conducted at 2-week, 6-week, 10-week, and 6-month post-recruitment. Feasibility outcomes were recruitment and retention rates, uptake of intervention components, and smoking abstinence at 6-week follow-up (primary endpoint). Cessation outcomes were analyzed using both a complete case analysis and intention-to-treat approach.

Results

165 participants were recruited, 111 (67.3%), 79 (47.9%), 59 (35.8%), and 94 (57%) participants completed the 2-week, 6-week, 10-week, and 6-month follow-up. At 10-week follow-up, 40.7% of participants used pamphlets and booklets, 13.6% used Quitline and > 90% used NRT. At 6-week follow-up, 87.3% reported a quit attempt and 46.8% sustained quitting. 46.8% were continuously smoke-free at the 6-week timepoint. The complete case analysis and the intention-to-treat analysis at 6 months show a 7-day self-reported point prevalence abstinence of 34% and 19.4% respectively.

Conclusions

The Koori Quit Pack mailout smoking cessation program was feasible to support Aboriginal and Torres Strait Islander people. The intervention resulted in a high smoking cessation rate and should be upscaled, implemented, and evaluated nationally.

Implications

Aboriginal and Torres Strait Islander people are disproportionately impacted by tobacco-related harms; however, the majority want to quit or wish they never took up smoking. Mailout cessation support is feasible, overcomes access barriers to evidence-based support and increases quitting success. We recommend a national mailout smoking cessation program is implemented for, and by Aboriginal and Torres Strait Islander people to accelerate declines in smoking prevalence to eliminate tobacco-related death and disease.
Magic speed under radiation drag for the optically thick outflows and SS 433 jets
Authors: Fukue Jun
Published: May 2024

One of the promising mechanisms to explain the stable jet speed of SS 433 is the magic speed, which is established by the balance between radiation pressure and radiation drag (and gravity). We examine the magic speed in the optically thick sub-relativistic flows for several typical situations, such as plane-parallel and spherical cases, and show that it is difficult to establish the magic speed in the simple optically thick flows in contrast to the optically thin ones. Instead, we propose the funnel jets as an improved model. That is, we consider the optically thick flows in the funnel, which is formed by the supercritical accretion disk, and mass and radiation energy are injected from the funnel wall. In this model the mass-accretion rate determines the configuration of the funnel, the increasing mass-loss rate of jets, the radiative environments, and then the sub-relativistic magic speed is naturally established.
A maize semi-dwarf mutant reveals a GRAS transcription factor involved in brassinosteroid signaling
Authors: Kaur Amanpreet , Best Norman B , Hartwig Thomas , Budka Josh , Khangura Rajdeep S , McKenzie Steven , Aragón-Raygoza Alejandro , Strable Josh , Schulz Burkhard , Dilkes Brian P
Published: May 2024

Brassinosteroids (BR) and gibberellins (GA) regulate plant height and leaf angle in maize (Zea mays). Mutants with defects in BR or GA biosynthesis or signaling identify components of these pathways and enhance our knowledge about plant growth and development. In this study, we characterized three recessive mutant alleles of GRAS transcription factor 42 (gras42) in maize, a GRAS transcription factor gene orthologous to the DWARF AND LOW TILLERING (DLT) gene of rice (Oryza sativa). These maize mutants exhibited semi-dwarf stature, shorter and wider leaves, and more upright leaf angle. Transcriptome analysis revealed a role for GRAS42 as a determinant of BR signaling. Analysis of the expression consequences from loss of GRAS42 in the gras42-mu1021149 mutant indicated a weak loss of BR signaling in the mutant, consistent with its previously demonstrated role in BR signaling in rice. Loss of BR signaling was also evident by the enhancement of weak BR biosynthetic mutant alleles in double mutants of nana plant1-1 and gras42-mu1021149. The gras42-mu1021149 mutant had little effect on GA-regulated gene expression, suggesting that GRAS42 is not a regulator of core GA signaling genes in maize. Single-cell expression data identified gras42 expressed among cells in the G2/M phase of the cell cycle consistent with its previously demonstrated role in cell cycle gene expression in Arabidopsis (Arabidopsis thaliana). Cis-acting natural variation controlling GRAS42 transcript accumulation was identified by expression genome-wide association study (eGWAS) in maize. Our results demonstrate a conserved role for GRAS42/SCARECROW-LIKE 28 (SCL28)/DLT in BR signaling, clarify the role of this gene in GA signaling, and suggest mechanisms of tillering and leaf angle control by BR.
CO2 response screen in grass Brachypodium reveals the key role of a MAP kinase in CO2-triggered stomatal closure
Authors: Lopez Bryn N K , Ceciliato Paulo H O , Takahashi Yohei , Rangel Felipe J , Salem Evana A , Kernig Klara , Chow Kelly , Zhang Li , Sidhom Morgana A , Seitz Christian G , Zheng Tingwen , Sibout Richard , Laudencia-Chingcuanco Debbie L , Woods Daniel P , McCammon James Andrew , Vogel John P , Schroeder Julian I
Published: May 2024

Plants respond to increased CO2 concentrations through stomatal closure, which can contribute to increased water use efficiency. Grasses display faster stomatal responses than eudicots due to dumbbell-shaped guard cells flanked by subsidiary cells working in opposition. However, forward genetic screening for stomatal CO2 signal transduction mutants in grasses has yet to be reported. The grass model Brachypodium distachyon is closely related to agronomically important cereal crops, sharing largely collinear genomes. To gain insights into CO2 control mechanisms of stomatal movements in grasses, we developed an unbiased forward genetic screen with an EMS-mutagenized B. distachyon M5 generation population using infrared imaging to identify plants with altered leaf temperatures at elevated CO2. Among isolated mutants, a “chill1” mutant exhibited cooler leaf temperatures than wild-type Bd21-3 parent control plants after exposure to increased CO2. chill1 plants showed strongly impaired high CO2-induced stomatal closure despite retaining a robust abscisic acid-induced stomatal closing response. Through bulked segregant whole-genome sequencing analyses followed by analyses of further backcrossed F4 generation plants and generation and characterization of sodium azide and CRISPR-cas9 mutants, chill1 was mapped to a protein kinase, Mitogen-Activated Protein Kinase 5 (BdMPK5). The chill1 mutation impaired BdMPK5 protein-mediated CO2/HCO3− sensing together with the High Temperature 1 (HT1) Raf-like kinase in vitro. Furthermore, AlphaFold2-directed structural modeling predicted that the identified BdMPK5-D90N chill1 mutant residue is located at the interface of BdMPK5 with the BdHT1 Raf-like kinase. BdMPK5 is a key signaling component that mediates CO2-induced stomatal movements and is proposed to function as a component of the primary CO2 sensor in grasses.