bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Role of Digital Literacy in Accessing and Utilising Virtual Healthcare Services: A Systematic Review Protocol
Authors: Hung Caitlin , Katapally Tarun Reddy
Published: November 2024

Rationale

Emerging digital technologies are accelerating the transition of healthcare services from traditional in‐person settings to virtual platforms. As a result, digital literacy is becoming essential for individuals to effectively engage with these services. However, inadequate digital literacy poses a significant barrier to both accessing and utilising virtual healthcare, potentially widening existing health disparities.

Aims and Objectives

This protocol outlines the approach for systematically reviewing and synthesising the existing literature on the influence of digital literacy on accessing and utilising virtual healthcare services.

Methods

A comprehensive literature search will be conducted across five databases: Web of Science, Medline, Scopus, CINAHL and IEEE Xplore, covering publications from 2014 to 2024. The review will include all age cohorts and demographics, focusing on studies that examine digital literacy and measures of access to and utilisation of virtual healthcare services. Two independent reviewers will screen studies using pre‐determined search strategies for inclusion.

Conclusion

Findings from this study will provide valuable insights into the challenges and facilitators of digital literacy in engaging with virtual healthcare services. This review will also offer evidence‐based recommendations to optimise digital health interventions and promote inclusive, equitable healthcare delivery.
Swimming kinematics of deep‐sea fishes
Authors: Woodworth Brett , Palmeri Jessica , Flannery Patrick , Fregosi Lydia , Donatelli Cassandra , Gerringer Mackenzie E.
Published: November 2024

Although the deep oceans represent Earth's largest habitat, the challenges of studying deep‐sea organisms in situ have limited our understanding of adaptation, ecology, and behaviour in these important ecosystems. One fundamental trait of fishes that remains largely unexplored in the deep ocean is swimming, a vital process for movement, migration, and dispersal in marine habitats. Deep‐sea conditions such as temperature, pressure, and food availability could each impact the speed and efficiency of swimming in fishes. To investigate swimming kinematics of fishes with increasing depth, we analysed in situ video of bony fishes across a 6000‐m depth gradient. We compared open‐source videos of fishes from National Oceanic and Atmospheric Administration (NOAA) Ocean Exploration with tank‐based recordings of shallow‐water relatives from Puget Sound, Washington, USA to understand how both habitat depth and phylogeny influence swimming in fishes. We analysed kinematics in four dominant demersal fish groups, the orders Anguilliformes, Gadiformes, Ophidiiformes, and Perciformes. Deep‐sea fishes swam consistently slowly. Swimming kinematics varied across temperature, oxygen, body elongation, and depth. These results suggest that swimming kinematics do not change linearly with increasing habitat depth in fishes and that the impacts of deep‐sea conditions such as low temperatures, high pressures, and low nutrient availability on swimming behaviour need to be considered independently of one another. These findings provide insight into the evolution of fish form and function in the deep ocean.
PLK2 inhibited oxidative stress and ameliorated hepatic ischemia–reperfusion injury through phosphorylating GSK3β
Authors: Ge Wenwen , Wang Zhoucheng , Zhong Xinyang , Chen Yutong , Tang Xiao , Zheng Shusen , Xu Xiao , Wang Kai
Published: November 2024

Background and Aim

Hepatic ischemia–reperfusion (I/R) injury is the primary cause of liver dysfunction and liver failure, commonly occurring in liver transplantation, hepatectomy, and hemorrhagic shock. Polo‐like kinase 2 (PLK2), a pivotal regulator of centriole duplication, plays a crucial role in cell proliferation and injury repair. However, the function of PLK2 in hepatic I/R remains unclear.

Methods

The effect of PLK2 was investigated in the mouse hepatic I/R model and the hepatocyte hypoxia‐reoxygenation (H/R) model. Liver injury was assessed by serum transaminase and hematoxylin and eosin staining. Cell apoptosis was analyzed using TUNEL analysis and immunoblotting. Inflammatory factors were evaluated by reverse transcription‐quantitative polymerase chain reaction. Mice or cultured cells during the I/R or H/R were treated by overexpressing PLK2. ROS fluorescence staining was used to assess oxidative stress injury.

Results

PLK2 was upregulated after hepatic I/R injury. Overexpressed PLK2 significantly improved liver enzyme levels and alleviated liver histological injury. Moreover, PLK2 decreased hepatocyte apoptosis and inhibited the expression of inflammatory factors in liver. Mechanistically, PLK2 increased the phosphorylation of GSK3β and enhanced expression of the antioxidant enzyme HO‐1, leading to less ROS production. Inhibition of the HO‐1 aggravated ROS generation and abolished the protective effect of PLK2.

Conclusion

Overall, these findings revealed that PLK2 enhanced HO‐1 expression and reduced oxidative stress damage in hepatic I/R injury, and this protective effect related to GSK3β activity.
Quantifying whole human hair scalp fibres of varying curl: A micro‐computed tomographic study
Authors: Berg Claire van den , Khumalo Nonhlanhla P. , Ngoepe Malebogo N.
Published: November 2024

Scalp hair is a key feature of humans and its variability has been the subject of a broad range of studies. A small subset of these studies has focused on geometric quantification of human scalp hair fibres, however the use of race‐ and ethnicity‐based classification systems makes it challenging to draw objective conclusions about fibre variability. Furthermore, sample preparation techniques for micro‐imaging studies often alter the original form of hair fibres. This study sought to determine which of the commonly reported descriptors could be resolved using micro‐computed tomography (micro‐CT) for fibres of varying curl. Images obtained from micro‐CT were used to reconstruct three‐dimensional images that were then analysed. The study also explored the capabilities and limitations of micro‐CT as an imaging modality by comparing and cross‐validating findings with those obtained from scanning electron microscopy (SEM) and laser micrometry. The former deals with surface imaging while the latter deals with cross‐sectional measurements. Micro‐CT was found to be highly effective at resolving cross‐sectional ellipsoidal parameters, but performed more poorly than SEM in reconstructing surface level details at a 2 resolution. The technique was, however, able to reveal the presence of the medulla in type VI (high curl) hair fibres. When compared with high curl fibres, greater intra‐fibre variability was observed for the low and medium curl fibres, highlighting the importance more objective classification systems.
Current status of peptide receptor radionuclide therapy in grade 1 and 2 gastroenteropancreatic neuroendocrine tumours
Authors: Kuiper Jelka , Zoetelief Eline , Brabander Tessa , de Herder Wouter W. , Hofland Johannes
Published: November 2024

Peptide receptor radionuclide therapy (PRRT) using [177Lu‐DOTA0,Tyr3]octreotate (177Lu‐DOTATATE) represents an established treatment modality for somatostatin receptor‐positive, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NET) of grade 1 or 2. The studies have demonstrated that four cycles of PRRT with 177Lu‐DOTATATE prolongs progression‐free survival and preserves quality of life, in patients with grade 1 and 2 advanced GEP NET. Notably, first‐line PRRT using 177Lu‐DOTATATE in grade 2 and 3 GEP NET patients has also shown efficacy and safety. Furthermore, PRRT can ameliorate symptoms in patients with NET‐associated functioning syndromes. Although various studies have explored alternative radionuclides for PRRT, none currently meet the criteria for routine clinical implementation. Ongoing research aims to further enhance PRRT, and the results from large clinical trials comparing PRRT with other NET treatments are anticipated, potentially leading to significant modifications in NET treatment strategies and PRRT protocols. The results of these studies are likely to help address existing knowledge gaps in the coming years. This review describes the clinical practice, recent developments and future treatment options of PRRT in patients with grade 1 and 2 GEP NET.
Treatment of Cognitive Behavior Therapy for the Locus of Control with Internet Gaming Addiction Problem
Authors: Sugara Gian Sugiana , Nurfadila Ninda Amety , Arumsari Cucu , Rahimsyah Anandha Putri , Muhajirin Muhammad
Published: November 2024

Research has identified Internet gaming addiction as a new and often unrecognized clinical disorder that impacts users' ability to control Internet gaming use, which can lead to relational, work, and social problems. The locus of control is a factor in controlling the use of Internet games. Researchers have suggested using cognitive behavior therapy (CBT) as the treatment of choice for Internet addiction. This paper presents the findings of a study that utilized an A‐B‐A single‐case research design to explore the impact of CBT on enhancing internal locus of control and reducing Internet gaming addiction. The participants in this study were three high school students (N = 3) who exhibited a high level of Internet gaming addiction and a predominantly external locus of control. CBT intervention was provided in six sessions. Treatment focused on modified cognitive distortion and developing positive behavior using the down arrow technique, acting as if, shaping, problem‐solving, and behavior reinforcement. Participants completed the Game Addiction Scale for Adolescents and the Locus of Control Scale for Game Addiction. Data were obtained at three distinct phases: before, during, and after the CBT intervention. Results show that CBT reduced Internet gaming addiction and enhanced internal locus of control both during and after the intervention, indicating its potential as an effective treatment for students with gaming addiction issues.
Warfarin and Aspirin Versus Warfarin Alone in Patients With HeartMate 3 Left Ventricular Assist Device: A Systematic Review and Meta‐Analysis
Authors: Viana Patricia , Lopes Lucca Moreira , Cabral Thamiris Dias Delfino , Persson Jorge , Tapioca Vanessa de Oliveira , Freire Camila Veronica S. , Relvas Jessica Hoffmann , Mesquita Yasmin , Marques Isabela Reis , Gomes Wilton Francisco
Published: November 2024

Background and Aims

HeartMate 3 (HM3), a fully magnetically levitated ventricular assist device (LVAD), has been associated with reduced thromboembolic events compared to HeartMate II. However, bleeding events remained significant. Among patients undergoing HM3 implantation, the standard antithrombotic regimen comprises both warfarin and aspirin (ASA), but there is a lack of evidence on the optimum antithrombotic therapy. We performed a systematic review and meta‐analysis assessing the impact of combined ASA and warfarin therapy compared to warfarin alone on the incidence of non‐surgical bleeding events in patients with HM3 LVAD.

Methods

MEDLINE, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) and observational studies comparing warfarin alone with warfarin combined with ASA in patients with HM3 LVAD. Binary endpoints were analyzed using computed risk ratios (RRs) with 95% confidence intervals (CIs). A random‐effect model was applied for all endpoints.

Results

Five studies (one RCT and four observational) encompassing 869 patients were included, with 424 (48.8%) prescribed warfarin alone, and 662 (76.2%) being male. Compared with the combined anticoagulation regimen, warfarin alone significantly reduced non‐surgical bleeding (RR 0.30; 95% CI 0.09–0.95; p = 0.04) and gastrointestinal bleeding (RR 0.26; 95% CI 0.12–0.58; p < 0.001). There was no statistically significant difference between the groups for all‐cause mortality (RR 1.02; 95% CI 0.45–2.32; p = 0.963).

Conclusions

Our findings indicate that the use of warfarin alone for anticoagulation in HM3 patients is associated with a reduced risk of bleeding events when compared to the combined therapy with ASA.
Plant‐produced SARS‐CoV‐2 antibody engineered towards enhanced potency and in vivo efficacy
Authors: de Taeye Steven W. , Faye Loïc , Morel Bertrand , Schriek Angela I. , Umotoy Jeffrey C. , Yuan Meng , Kuzmina Natalia A. , Turner Hannah L. , Zhu Xueyong , Grünwald‐Gruber Clemens , Poniman Meliawati , Burger Judith A. , Caniels Tom G. , Fitchette Anne‐Catherine , Desgagnés Réjean , Stordeur Virginie , Mirande Lucie , Beauverger Guillaume , de Bree Godelieve , Ozorowski Gabriel , Ward Andrew B. , Wilson Ian A. , Bukreyev Alexander , Sanders Rogier W. , Vezina Louis‐Philippe , Beaumont Tim , van Gils Marit J. , Gomord Véronique
Published: November 2024

Prevention of severe COVID‐19 disease by SARS‐CoV‐2 in high‐risk patients, such as immuno‐compromised individuals, can be achieved by administration of antibody prophylaxis, but producing antibodies can be costly. Plant expression platforms allow substantial lower production costs compared to traditional bio‐manufacturing platforms depending on mammalian cells in bioreactors. In this study, we describe the expression, production and purification of the originally human COVA2‐15 antibody in plants. Our plant‐produced mAbs demonstrated comparable neutralizing activity with COVA2‐15 produced in mammalian cells. Furthermore, they exhibited similar capacity to prevent SARS‐CoV‐2 infection in a hamster model. To further enhance these biosimilars, we performed three glyco‐ and protein engineering techniques. First, to increase antibody half‐life, we introduced YTE‐mutation in the Fc tail; second, optimization of N‐linked glycosylation by the addition of a C‐terminal ER‐retention motif (HDEL), and finally; production of mAb in plant production lines lacking β‐1,2‐xylosyltransferase and α‐1,3‐fucosyltransferase activities (FX‐KO). These engineered biosimilars exhibited optimized glycosylation, enhanced phagocytosis and NK cell activation capacity compared to conventional plant‐produced S15 and M15 biosimilars, in some cases outperforming mammalian cell produced COVA2‐15. These engineered antibodies hold great potential for enhancing in vivo efficacy of mAb treatment against COVID‐19 and provide a platform for the development of antibodies against other emerging viruses in a cost‐effective manner.
Accelerometer‐based heart rate adjustment for ambulatory stress research
Authors: van de Ven Sjors R. B. , Gevonden Martin J. , Noordzij Matthijs L. , de Geus Eco J. C.
Published: November 2024

Using heart rate (HR) measurements to detect mental stress in naturalistic settings is hampered by the physiological impact of hemodynamic and metabolic demands. Correcting HR for these demands can help isolate fluctuations in HR associated with psychosocial stress responses, a concept termed additional heart rate (aHR). This study examined whether adding predictors for posture, activity type, and lagged movement intensity for the prolonged impact of physical activity (PA) improved aHR estimation across various manipulations of mental stress, posture, and PA in a controlled laboratory environment (n = 197). Accelerometer signals were used to obtain the movement intensity and to classify posture and activity type. Posture, activity type, and lagged movement intensity each led to a significant improvement in HR estimation, as measured by adjusted R2 and root mean squared error. However, HR was overestimated during quiet sitting. The aHR, computed as the difference between observed and predicted HR, generally underestimated observed task‐baseline reactivity but was sensitive to individual differences in reactivity to mental stressors. Between‐subject correlations of aHR with task‐baseline reactivity ranged from 0.62 to 0.93 across conditions. On a within‐subject level, the ability of aHR to differentiate between exposure to physical stress and mental stress was limited (recall = 0.32, precision = 0.31), but better than that of observed HR (recall = 0.02, precision = 0.02). Future research should explore the potential of this novel aHR estimation method in differentiating physical and mental demands on HR in daily life, and its predictive value for health outcomes.
Impact of stockpiling on soil fungal communities and their functions
Authors: Cabrera‐Hernandez Julian A. , Davidson Hanna , MacKenzie Michael D. , Lanoil Brian D.
Published: November 2024

Fungal communities are important components of soil biology and play crucial roles in multiple ecosystem functions and services; therefore, they can be used as effective indicators of soil function in stockpiled reclamation soils. We profiled the fungal communities of seven stockpiles of different ages (0.5, 1.5, 2, 5, 7, 11, and 28 years old) at various soil depths (0–300 cm) in two oil sand extraction locations in northern Alberta. Fungal communities of the stockpiles differed from the communities in the nearby undisturbed reference soils. The differences with the reference soils were more pronounced for the oldest and some of the younger stockpiled soils. Similar to previous studies, there was a decrease in fungal richness and overall diversity with increasing stockpile depth. Furthermore, soil stockpiling generated a shift in the functional composition based on inferred fungal guilds and trophic modes. Ectomycorrhizal fungi decreased and saprotrophic fungi increased in the stockpiles relative to the reference soils. Such a shift may have important implications for ecosystem functions and services associated with fungal communities, such as litter decomposition and plant growth promotion, when these stockpiles are used to reclaim ecosystems. Our results align with previous research identifying the negative effects of stockpiling on soil microbial communities, shed light on the soil functions that may be affected by this disturbance and their consequences for ecosystem functioning, and reflect the high sensitivity of fungal communities to soil disturbances like stockpiling.
The TIPping point: Inflammation and Ionocyte loss
Authors: Shah Viral S. , Rajagopal Jayaraj
Published: November 2024

See related article
Automatically Prepared? How Frontline Workers Cope in the Face of Automation
Authors: Jørring Louise
Published: November 2024

Public sector digitalisation is often described as a help to frontline workers, who must deal with a high workload, too few resources, and complex professional dilemmas. Digitalisation nevertheless, also creates new challenges that become intertwined with the already existing challenges in street‐level bureaucracies. Based on 25 interviews and more than 80 h of observations conducted in the Danish employment services, this study examines how frontline workers make using automatically generated representations of the clients manageable and meaningful. Drawing on coping theory and abductive analysis three distinct digital coping strategies are identified: automatic (simplification); extended (complication); and in situ (flexibility) preparation. The contribution of the study is twofold. First, it expands the current understanding of coping strategies as simplifying or complicating the work of frontline workers with a third flexibility strategy. This strategy shows how frontline workers cope by minimizing time spent on preparation and instead flexibly search out information during meetings with clients, relying on their skills to lithely manoeuvre in both digital and bureaucratic systems. Second, it provides insight into understanding how digital efficiency initiatives in the public sector often end up playing a different role than intended. Finally, I compare and discuss the consequences of these ambiguous digital coping strategies and point to future avenues of research.
Direct Alcoholysis of Glucose into Alkyl Levulinates Catalysed by Metal-Doped Sulfonated Activated Carbon
Authors: Krishnasamy Kirrthana , Chee Shu Yi , Mohammed Yussuf Mohd Asmadi , Zakaria Zaki Yamani , Zainol Muzakkir Mohammad , Abdullah Sureena
Published: November 2024

Lignocellulosic biomass is widely studied to produce alkyl levulinate through alcoholysis catalysed by acid catalyst, which potentially used as a biofuel additive. However, the poor properties of homogeneous catalyst have prompted this study to focus on enhancing the yield of alkyl levulinate by using sulfonated activated carbon (AC-S) doped with different metals as a heterogeneous catalyst with co-existence of Brønsted and Lewis acidic sites. The activated carbon (AC) precursor was modified via sulfonation and impregnated with iron (Fe), copper (Cu) and cobalt (Co) metals, which were further characterised to evaluate their physicochemical properties as a catalyst. Their catalytic activity was evaluated for glucose alcoholysis in a stainless-steel batch reactor at 180 ˚C for 4 h, by charging 0.6 g of glucose, 40 mL of alcohol (methanol and ethanol) and 0.3 g of catalyst. From the result, the catalyst properties were improved after sulfonation and metal doping. Among the employed heterogeneous catalysts, AC-S-Cu exhibited the highest catalytic activity, which was contributed mainly by its co-existence of Brønsted and Lewis acidic sites with significant Brønsted acidity, higher thermal stability with minimum weight loss up to 200 ˚C (<2 wt%), better morphology, and larger surface area (928 m2/g). The maximum alkyl levulinate yield (15.04 wt%) was obtained for ethyl levulinate production under conditions of 180 ˚C, 4 hr, 0.6 g of glucose, 0.3 g of AC-S-Cu and 40mL of ethanol. The outcome of this study provides an insight on the potential of AC-S-Cu in facilitating the direct alcoholysis of glucose to alkyl levulinate
Double covers of smooth quadric threefolds with Artin–Mumford obstructions to rationality
Authors: Kuznetsova Alexandra
Published: November 2024

We study obstructions to rationality on a nodal Fano threefold that is a double cover of a smooth quadric threefold ramified over an intersection with a quartic threefold in . We prove that if admits an Artin–Mumford obstruction to rationality then it lies in one of three explicitly described families. Conversely, a general element of any of these families admits an Artin–Mumford obstruction to rationality. Only one of these three families was known before; other two families of nodal Fano threefolds with obstructions to rationality are new.
Graphs with nonnegative curvature outside a finite subset, harmonic functions, and number of ends
Authors: Hua Bobo , Münch Florentin
Published: November 2024

We study graphs with nonnegative Bakry–Émery curvature or Ollivier curvature outside a finite subset. For such a graph, via introducing the discrete Gromov–Hausdorff convergence, we prove that the space of bounded harmonic functions is finite dimensional and, as a corollary, the number of nonparabolic ends is finite.
Study of a Cavitation Treatment in Kaplan Hydro-Turbine
Authors: ElGammal Tarek , Amano Ryoichi S. , Abousabae Mohamed
Published: November 2024

This research proposes an air-injection treatment for the cavitation phenomena in the Kaplan turbine. An unsteady numerical model is created to predict the cavitating flow through a 3-in. axial hydroturbine before and after the air injection. Pressurized air (jet-in-crossflow) injection is set to be through the turbine housing, and the configuration was altered between 1, 2, 4, and 12 circumferential jets to test the effects of air mass flowrate and injection distribution. Interactions between three fluids (liquid water, water vapor, and air) were considered by utilizing the physics models of volume of fluid (VOF) multiphase, cavitation, and large eddy simulation (LES) turbulence. Surface and time-average results are to be compared with a baseline case of pure cavitation. With the vapor volume fraction created on the rotor components during the cavitation, the absolute pressure scenes clarified the connection between the air treatment and cavitation reduction. While rotation causes negative pressure in the system, the injected air is sucked to such low-pressure zones, and consequently, increasing the absolute pressure above the vapor limit reduces the vapor formation. Preliminary outcomes at 1000 rpm show a 55% reduction in the formed vapor on the blades after air injection by a time corresponding to six cycles of the turbine. A corresponding mechanical power of 12% increase was observed. Moreover, the curve fitting of the data shows that the vapor reduction and power regain are in second order correlation with the increased air volume.
Acoustic scattering and “failure” of the optical theorem
Authors: Martin P. A.
Published: November 2024

For plane wave scattering by an obstacle, the optical theorem relates the scattering cross section to the far-field scattered field in the forward direction. This simple and useful result fails to hold when the incident field is not a plane wave. “Failures” of this kind are explored. For scattering by a sphere, an explicit formula for the scattering cross section is obtained, applicable to arbitrary incident fields.
Robots and animals teaming up in the wild to tackle ecosystem challenges
Authors: Schmickl Thomas , Romano Donato
Published: November 2024

Interactively teaming up animals and robots could facilitate basic scientific research and address environmental and ecological crises.
Monoclonal antibodies that block Roundabout 1 and 2 signaling target pathological ocular neovascularization through myeloid cells
Authors: Geraldo Luiz Henrique , Xu Yunling , Mouthon Gaspard , Furtado Jessica , Leser Felipe Saceanu , Blazer Levi L. , Adams Jarrett J. , Zhang Sophia , Zheng Lana , Song Eric , Robinson Mark E. , Thomas Jean-Leon , Sidhu Sachdev S. , Eichmann Anne
Published: November 2024

Roundabout (ROBO) 1 and 2 are transmembrane receptors that bind secreted SLIT ligands through their extracellular domains (ECDs) and signal through their cytoplasmic domains to modulate the cytoskeleton and regulate cell migration, adhesion, and proliferation. SLIT-ROBO signaling regulates pathological ocular neovascularization, which is a major cause of vision loss worldwide, but pharmacological tools to prevent SLIT-ROBO signaling are lacking. Here, we developed human monoclonal antibodies (mAbs) against the ROBO1 and ROBO2 ECDs. One antibody that inhibited in vitro SLIT2 signaling through ROBO1 and ROBO2 (anti-ROBO1/2) also reduced ocular neovascularization in oxygen-induced retinopathy (OIR) and laser-induced corneal neovascularization (CNV) mouse models in vivo. Single-cell RNA sequencing of OIR retinas revealed that antibody treatment affected several cell types relevant to physiological and pathological angiogenesis, including endothelial cells, pericytes, and a heterogeneous population of myeloid cells. mAb treatment improved blood-retina barrier integrity and prevented pathological pericyte activation in OIR. SLIT-ROBO signaling inhibition prevented pathological activation of myeloid cells and increased neuroprotective myeloid populations normally seen in the developing retina. Microglia/infiltrating macrophage–specific ablation of
Robo1
and
Robo2
or knockout of the downstream effector phosphatidylinositol 3-kinase (
Pik3cg
) encoding PI3Kγ in both OIR and CNV models phenocopied anti-ROBO1/2 treatment, further demonstrating the key role of myeloid cells as drivers of ocular neovascular diseases. ROBO1/2 blocking antibodies may thus provide a promising strategy to combat inflammation in blinding eye diseases.
Genipin rescues developmental and degenerative defects in familial dysautonomia models and accelerates axon regeneration
Authors: Saito-Diaz Kenyi , Dietrich Paula , Saini Tripti , Rashid Md Mamunur , Wu Hsueh-Fu , Ishan Mohamed , Sun Xin , Bedillion Sydney , Patel Archie Jayesh , Prudden Anthony Robert , Wzientek Camryn Gale , Knight Trinity Nora , Chen Ya-Wen , Boons Geert-Jan , Chen Shuibing , Studer Lorenz , Tiemeyer Michael , Xu Bingqian , Dragatsis Ioannis , Liu Hong-Xiang , Zeltner Nadja
Published: November 2024

The peripheral nervous system (PNS) is essential for proper body function. A high percentage of the world’s population suffers from nerve degeneration or peripheral nerve damage. Despite this, there are major gaps in the knowledge of human PNS development and degeneration; therefore, there are no available treatments. Familial dysautonomia (FD) is a devastating disorder caused by a homozygous point mutation in the gene
ELP1
. FD specifically affects the development and causes degeneration of the PNS. We previously used patient-derived induced pluripotent stem cells (iPSCs) to show that peripheral sensory neurons (SNs) recapitulate the developmental and neurodegenerative defects observed in FD. Here, we conducted a chemical screen to identify compounds that rescue the SN differentiation inefficiency in FD. We identified that genipin restores neural crest and SN development in patient-derived iPSCs and in two mouse models of FD. Additionally, genipin prevented FD degeneration in SNs derived from patients with FD, suggesting that it could be used to ameliorate neurodegeneration. Moreover, genipin cross-linked the extracellular matrix (ECM), increased the stiffness of the ECM, reorganized the actin cytoskeleton, and promoted transcription of yes-associated protein–dependent genes. Last, genipin enhanced axon regeneration in healthy sensory and sympathetic neurons (part of the PNS) and in prefrontal cortical neurons (part of the central nervous system) in in vitro axotomy models. Our results suggest that genipin has the potential to treat FD-related neurodevelopmental and neurodegenerative phenotypes and to enhance neuronal regeneration of healthy neurons after injury. Moreover, this suggests that the ECM can be targeted to treat FD.
Durlobactam to boost the clinical utility of standard of care β-lactams against
Mycobacterium abscessus
lung disease
Authors: Negatu Dereje A. , Aragaw Wassihun Wedajo , Gebresilase Tewodros T. , Paruchuri Sindhuja , Kaya Firat , Shin Sung Jae , Sander Peter , Dartois Véronique , Dick Thomas
Published: November 2024

β-Lactams present several desirable pharmacodynamic features leading to the rapid eradication of many bacterial pathogens. Imipenem (IPM) and cefoxitin (FOX) are injectable β-lactams recommended during the intensive treatment phase of pulmonary infections caused by
Mycobacterium abscessus
(Mab). However, their potency against Mab is many-fold lower than against Gram-positive and Gram-negative pathogens for which they were optimized, putting into question their clinical utility. Here, we show that adding the recently approved durlobactam-sulbactam (DUR-SUL) pair to either IPM or FOX achieves growth inhibition, bactericidal, and cytolytic activity at concentrations that are within those achieved in patients and below the clinical breakpoints established for each agent. Synergies between DUR-SUL and IPM or FOX were confirmed across a large panel of clinical isolates. Through
in vitro
resistant mutant selection, we also show that adding DUR-SUL abrogates acquired resistance to IPM and FOX. Since the use of β-lactam injectables is firmly grounded in clinical practice during the intensive treatment phase of Mab pulmonary disease, their potentiation by FDA-approved DUR-SUL to bring minimum inhibitory concentration distributions within achievable concentration ranges could offer significant short-term benefits to patients, while novel β-lactam combinations are optimized specifically against Mab pulmonary infections, for which no reliable cure exists.
Debris flows and sediment transport at Yucaipa Ridge and impacts to Oak Glen and Forest Falls area, southern California, following the 2020 El Dorado and Apple Fires
Authors: Swanson Brian J. , Lindsay Donald N. , Cato Kerry , DiBiase Roman A. , Neely Alexander B.
Published: November 2024

The 2020 El Dorado and Apple Fires burned a combined area of ~225 km2 in the San Bernardino Mountains, California, USA, including much of the steep terrain of Yucaipa Ridge. Wildfire increases the potential for debris flows, flooding, and rockfall hazards. A California Watershed Emergency Response Team assessed these hazards to assist affected portions of San Bernardino and Riverside counties with their emergency preparedness efforts. These assessments identified high hazard sites in the Forest Falls and Oak Glen areas on the north and south flanks of Yucaipa Ridge, respectively. Subsequent monitoring by the California Geological Survey documented 16 flow events from nine study area basins and their impacts to downstream communities generated by six storms between fall 2020 and August 2023. Tropical Storms Kay (2022) and Hilary (2023) and monsoonal thunderstorms on August 13, 2022, produced the most widespread and severe impacts. Observations of flow characteristics were then used to determine flow type behavior and estimate flow velocities and discharge for 11 flow events, and the total volume of mobilized debris was estimated for three flow events. Debris flow velocities were found to range from 2.1 to 11.2 m/s (4.7–25 mph) and associated discharge values were estimated to range from 12 to 311 m3/s (~425–11,000 cfs). Observed discharges were then used to assess and calibrate previous flow bulking multipliers for post-fire emergency planning. Volumes of debris mobilized during three events were estimated based on hydraulic methods, field observations, and lidar differencing, respectively, with resulting volumes ranging from ~19,000 m3 to more than 100,000 m3. Rainfall data were also acquired and reviewed to assess rainfall intensity thresholds for the generation of post-fire debris flows. Concurrently, studies were conducted to assess sediment transport and yields based on the distribution of fractured rock outcrops, colluvial debris, and dry ravel generated by fire impacts, as documented by repeat surveys of selected source basin areas. The surveys showed a mixture of fractured rock outcrops, and steep soil mantled slopes provided both coarse (>3 m) boulders and fine sediment. The latter was preferentially delivered to debris flow prone channels as post-fire dry ravel. Debris flows generated by Tropical Storms Kay and Hilary mobilized all of these grain size fractions downstream to alluvial fans and developed areas.
Stress and mental health symptoms in early pregnancy are associated with the oral microbiome
Authors: Alex Ann M , Levendosky Alytia A , Bogat G Anne , Muzik Maria , Nuttall Amy K , Knickmeyer Rebecca C , Lonstein Joseph S
Published: November 2024

Background

Research has revealed associations between microbes of the gastrointestinal tract and stress, anxiety and depression in pregnant or postpartum women. While these studies suggest a gut-brain-behaviour axis, no studies have examined microbes of the oral cavity in relation to maternal mental health.

Objective

To explore a potential oral-brain-behaviour axis related to maternal mental health.

Methods

Microbes were measured in saliva obtained from 224 second-trimester (mean±SD = 17±2 weeks) women oversampled for stress. Oralome data were associated with women’s recent or cumulative pregnancy stress, trait and state anxiety, depression symptoms and post-traumatic stress disorder (PTSD) symptoms. Covariates explored included age, income, alcohol and tobacco use, dental issues and physical health problems.

Results

Pregnant women in the high trait anxiety or depression symptom groups had higher oral alpha diversity, indicating higher richness of species within samples. Groups with high and low PTSD symptoms differed in beta diversity, reflecting differences in community composition. Linear discriminant analysis showed differently abundant microbes in women with high stress versus low life stress, anxiety, depression, and PTSD, with the affected microbes mostly differing by symptom. Notably, members of phylumProteobacteriawere more abundant in women with high recent life stress andSpirochaeteswas more abundant in women with high depression symptoms. Members of phylumFirmicuteswere more abundant in the high trait anxiety and high depression groups. GenusDialister(previously found to be lower in the gut of depressed non-pregnant people) was higher in women experiencing either high trait or state anxiety, or experiencing high depression symptoms, while genusEikenellawas elevated with high trait anxiety, depression or PTSD.

Conclusions

The oral microbiome is associated with stress and mental health in pregnant women, in ways different from the gut microbiome or what has been found in non-pregnant people.

Clinical implications

Understanding oral microbiome–mental health relations may reveal future microbial targets to improve maternal psychological well-being.
Evaluating the effects of recreational drug use on ruptured cerebral arteriovenous malformation presentation and in-hospital outcomes: a national inpatient sample analysis
Authors: Gajjar Avi A , Goyal Aditya , Gill Karmen , Behal Aditya , Custozzo Amanda , Boulos Alan S , Dalfino John C , Field Nicholas C , Paul Alexandra R
Published: November 2024

Background

Recent literature highlights the adverse effects of recreational marijuana on cerebrovascular pathologies and outcomes. However, its impact on arteriovenous malformation (AVM) outcomes is unknown.

Objective

To investigate the differences in AVM outcomes between marijuana users and non-users, focusing primarily on the likelihood of presenting with rupture and secondly, on the effects of other drugs on in-hospital mortality and complications.

Methods

Adult patients diagnosed with cerebral AVMs from the National Inpatient Sample were included. Use of recreational drugs, including marijuana, alcohol, opioids, hallucinogens, stimulants, and tobacco, was documented. Univariate and multivariate logistic regression analyses identified associations between drug use and AVM outcomes.

Results

A total of 46 480 patients were analyzed, with 11 580 (24.9%) presenting with rupture. Smoking was the most prevalent substance used (18 010, 38.7%), followed by alcohol (3 065, 6.6%), and cannabis (745, 1.6%). Smoking tobacco (OR=0.801; P=0.0002) and cannabis use (OR=0.613; P=0.0523) showed trends towards a protective effect against presentation with AVM rupture. Tobacco use was associated with reduced likelihood of extended length of stay (OR=0.837; P=0.0013), any complications (OR=0.860; P=0.0082), and in-hospital mortality (OR=0.590; P=0.0003). Alcohol use was linked to increased extended length of stay (OR=1.363; P=0.0033) and complications (OR=1.442; P=0.0007).

Conclusions

Stimulant use increases the likelihood of presenting with ruptured AVMs and is associated with higher mortality. Tobacco and cannabis use appear to reduce the possibility of extended hospital stays and complications.
Comprehensive evaluation of management strategies and rupture status in partially thrombosed aneurysms: a systematic review and meta-analysis
Authors: Elek Alperen , Allahverdiyev Irshad , Ozcinar Kenan Kerem , Yazici Adem C , Cinar Celal , Kusbeci Mahmut , Ozturk Egemen , Oran Ismail
Published: November 2024

Background

This meta-analysis aims to evaluate and compare the clinical and angiographic outcomes of different management strategies for partially thrombosed intracranial aneurysms (PTIAs).

Methods

A systematic review was conducted using MEDLINE, Scopus, and Web of Science databases up to September 2024. Studies providing clinical and angiographic outcomes of PTIAs were included. Favorable outcomes were defined as those reported directly in the studies or, when the modified Rankin Scale (mRS) was available, as an mRS score of 0–2. Statistical analysis was conducted using R, with pooled estimates under a random-effects model.

Results

Eighteen studies involving 362 patients with 363 PTIAs were analyzed. Favorable neurological outcomes were observed in 76% of patients, while 20% experienced procedure-related complications. Recurrence occurred in 36% of cases, and retreatment was required in 23%. Mortality was low at 0.8%. Subgroup analysis revealed that reconstructive approaches were associated with higher rates of favorable outcomes (72%) and lower complication rates (21%) compared with deconstructive methods (60% and 28%, respectively). Among the reconstructive techniques, flow diverter stenting showed the highest rate of favorable outcomes (82%), while simple coiling had the lowest (71%). Additionally, unruptured PTIAs had a significantly better prognosis, with 69% achieving favorable outcomes, fewer complications (22% vs 51% for ruptured), and lower mortality (0.8% vs 27%) compared with ruptured aneurysms. Among the reconstructive techniques, flow diverter stenting showed the best outcomes.

Conclusion

PTIAs treated with reconstructive approaches that are unruptured, non-giant, and located in the anterior circulation show higher rates of favorable neurological outcomes with acceptable complications. However, outcomes, complications, and occlusion rates are slightly worse compared with typical non-thrombotic saccular aneurysms, indicating that these aneurysms pose a greater challenge.
The potential role of AhR/NR4A1 in androgen-dependent prostate cancer: focus on TCDD-induced ferroptosis
Authors: Chen Xiang , Yao Yuan , Gong Guotong , He Tianji , Ma Chenjun , Yu Jingsong
Published: November 2024

Prostate cancer (PCa) is a complex disease with diverse molecular alterations. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that exhibits pleiotropic roles in PCa, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent ligand for AhR. While targeting ferroptosis is an innovative PCa therapeutic strategy, the impact of AhR on this process remains unclear. This study aimed to investigate the influence of AhR on lipid peroxidation and ferroptosis. Results showed that TCDD activated AhR, as evidenced by increased CYP1A1 expression, leading to reduced cell viability. TCDD caused mitochondria shrinkage, decreased the GSH/GSSG ratio, and elevated the MDA levels and lipid peroxidation. Interestingly, AhR knockdown reversed these effects, similar to the action of ferroptosis inhibitors. Mechanistically, TCDD suppressed nuclear receptor subfamily 4 group A member 1 (NR4A1) expression, in part due to AhR activation. This suppression subsequently led to a reduction in the expression of the NR4A1 downstream target stearoyl-CoA desaturase 1 (SCD1). NR4A1 overexpression counteracted the effects of TCDD. In vivo, TCDD activated AhR, downregulated NR4A1 and SCD1 expression, induced mitochondria shrinkage, and increased the MDA and 4-hydroxynonenal (4-HNE) levels. In summary, TCDD promotes ferroptosis in androgen-dependent PCa via inhibiting the NR4A1/SCD1 axis, in part dependent on AhR activation.
A rapid segmentation and occlusion completion method for packed granular particles considering uncertainty
Authors: Zhang Haoran , Yin Zhen-Yu , Zhang Ning , Wang Xiang
Published: November 2024

Occlusions of granular particles in images significantly affect the accuracy of evaluating particle morphology for granular materials. In this study, a novel framework of SOLO-PCNet is proposed, which can automatically segment all the particles and predict the complete contours of the occluded particles in densely packed materials. Firstly, the instance segmentation model SOLOv2 is trained for the prediction of all the detectable particles. Then a self-supervised learning algorithm PCNet-M is introduced for the inference of the complete contours of the occluded particles so that the prediction of SOLOv2 can be directly input to PCNet-M for the subsequent completion. Thereafter, the particle morphology characteristics including elongation, equivalent mean size, convexity, and circularity are automatically calculated. Then, the evaluation metrics of the segmentation model and morphology characteristics are validated, and the results exhibit the strong generalization ability of the segmentation and completion tasks. Finally, the uncertainty of the completed contours with morphology properties is explored for reliable analysis. This study successfully acquires the complete contours for each particle and provides the foundation for evaluating the mechanical properties of the packed granular materials from individual particles.
Evaluation of a Wisconsin-type bioenergetics model to estimate brook charr (Salvelinus fontinalis) growth and food consumption under two salinity conditions
Authors: Chalifoux Virginie , Audet Céline , Deslauriers David
Published: November 2024

In Québec, Canada, brook charr ( Salvelinus fontinalis) is the most sought-after species for recreational fisheries, which makes it economically important. To improve population monitoring and better anticipate climate change impacts on brook charr, bioenergetics models can be useful. The objective of this research was to evaluate the performance of a resident brook charr Wisconsin Energy Budget (WEB) model applied to an anadromous strain under two salinity treatments. Growth and food consumption were predicted by the model and compared to the observed values obtained after a 60 day experiment in the laboratory on fish reared in fresh or brackish water. Predictions for fish reared in fresh water better estimated growth rate and consumption than for fish reared in brackish water, for which growth was overestimated and consumption was underestimated. Overall, these results suggest that there is a difference for the WEB model’s predictions depending on the salinity and that observed food consumption is predicted more accurately than growth.
Carvacrol, a monoterpenoid, binds quorum sensing proteins (LasI and LasR) and swarming motility protein BswR of Pseudomonas aeruginosa, resulting in loss of pathogenicity: an in silico approach
Authors: Datta Susmita , Singh Vishal , Nag Soma , Roy Dijendra Nath
Published: November 2024

The pathogenic Pseudomonas aeruginosa utilizes a quorum-sensing pathway for biofilm formation. The quorum-sensing proteins LasI and LasR of the Las system, alongside the swarming motility protein BswR, play a crucial role in the biofilm-mediated antibiotic resistance phenomenon. In this in silico study, LasI, LasR, and BswR were the prime targets for binding studies by promising drug candidates like linalool, ferutinin, citronellal, and carvacrol. These monoterpenoid compounds are carefully considered for this study due to their reported anti-microbial activity. Among all, carvacrol exhibited the highest binding energies with LasI (−5.932 kcal/mol), LasR (−7.469 kcal/mol), and BswR (−4.42 kcal/mol). Furthermore, the MMGBSA scores between carvacrol and LasI, LasR, and BswR individually are −33.14, −54.22, and −41.86 kcal/mol, which further corroborated the strong binding. During 100 ns of simulation, the ligand binds to the active sites of these proteins through the H-bonds at Ile107 of LasI, Tyr47 of LasR, and Leu57 of BswR. In addition, the root-mean-square deviation values of the ligand-protein complex are within the appropriate range of less than 5 Å. Absorption, Distribution, Metabolism, Excretion, and Toxicity analysis confirmed that carvacrol has the most negligible toxicity to mammalian cells. Hence, this finding is the first report to show that carvacrol can inhibit the Pseudomonas aeruginosa biofilms.
An integrated analytical–numerical framework for studying nonlinear PDEs: The GBF case study
Authors: Khater Mostafa M. A.
Published: November 2024

In this study, we investigate the complex dynamics of the [Formula: see text]-dimensional generalized Burgers–Fisher (GBF) model, a nonlinear partial differential equation that encapsulates the interplay between wave propagation, diffusion, and reaction processes. Our work employs a combination of the modified Khater (MKhat) method, the unified (UF) method, and He’s variational iteration (HVI) scheme to derive and validate analytical and numerical solutions. We present a comprehensive analysis of solitary wave, shock wave, and diffusion-driven phenomena within the GBF framework. The novelty of our study lies in the integration of these methods to provide deeper insights into the model’s physical implications, specifically highlighting the interactions between nonlinear advection, diffusion, and reaction mechanisms. This approach not only enhances the accuracy and applicability of the derived solutions, but also contributes to the advancement of nonlinear wave theory and related interdisciplinary fields.