bluuebunny/crossref_metadata_2025 huggingface dataset:
On Extending the Life of Floating Offshore Wind Turbines Via Sheltering Effects of Upstream Wave Energy Converters
Authors: Liu Ding Peng , Manuel Lance , Coe Ryan G.
Published: August 2024

Offshore renewable energy, derived from wind and waves, is increasingly being considered in many regions of the world. Co-location of offshore wind turbine (OWT) and wave energy converter (WEC) arrays allows the shared use of space and offers beneficial interaction, leading to efficient utilization of marine resources and more sustainable ocean energy solutions. By extracting energy from waves, WECs can offer sheltering effects and reduced hydrodynamic loads on downstream OWTs. This can enhance the structural reliability of the OWTs against fatigue and extend the service life. To quantify such extension in service life, a comprehensive reliability analysis framework is proposed that incorporates metocean data analysis, fatigue damage assessment, and an integrated reliability-based fatigue life estimation. We employ power-take-off matrices of different WEC devices to approximate absorbed wave power in irregular sea states. A metocean data analysis establishes the representative sea states for the incident and lee waves, where lee wave conditions are estimated by subtracting WEC absorbed power absorption from the incident power. The open-source time-domain simulation tool, OpenFAST, is employed to compute motions and loads on a downstream floating offshore wind turbine (FOWT), for sea states of interest. Fatigue damage assessment and associated life estimation are carried using a selected output stress response. An extended service life due to effective sheltering for the FOWT can be evaluated through the proposed fatigue reliability-based analysis that includes uncertainties from metocean conditions. By comparing three different types of WEC devices, the analysis showed a 14% to 25 % extension in service life can be achieved.
Remote neurostimulation through an endogenous ion channel using a near-infrared light–activatable nanoagonist
Authors: Tian Weifeng , Jia Qi , Lin Jiewen , Luo Jiamin , He Dongmei , Yang Jie , Guo Tao , Guo Huiling , Guo Yusheng , Zhang Wenjie , Chen Feiyu , Ye Ying , Liu Jingjing , Xu Mindong , Deng Chengjie , Cui Boxiang , Su Deyuan , Wang Hao , Lu Yi , Xiao Jianru , Liu Heng , Yang Jian , Hou Zhiyao , Wang Shu
Published: August 2024

The development of noninvasive approaches to precisely control neural activity in mammals is highly desirable. Here, we used the ion channel transient receptor potential ankyrin-repeat 1 (TRPA1) as a proof of principle, demonstrating remote near-infrared (NIR) activation of endogenous neuronal channels in mice through an engineered nanoagonist. This achievement enables specific neurostimulation in nongenetically modified mice. Initially, target-based screening identified flavins as photopharmacological agonists, allowing for the photoactivation of TRPA1 in sensory neurons upon ultraviolet A/blue light illumination. Subsequently, upconversion nanoparticles (UCNPs) were customized with an emission spectrum aligned to flavin absorption and conjugated with flavin adenine dinucleotide, creating a nanoagonist capable of NIR activation of TRPA1. Following the intrathecal injection of the nanoagonist, noninvasive NIR stimulation allows precise bidirectional control of nociception in mice through remote activation of spinal TRPA1. This study demonstrates a noninvasive NIR neurostimulation method with the potential for adaptation to various endogenous ion channels and neural processes by combining photochemical toolboxes with customized UCNPs.
Magnesium induced structural reorganization in the active site of adenylate kinase
Authors: Nam Kwangho , Thodika Abdul Raafik Arattu , Tischlik Sonja , Phoeurk Chanrith , Nagy Tamás Milán , Schierholz Léon , Ådén Jörgen , Rogne Per , Drescher Malte , Sauer-Eriksson A. Elisabeth , Wolf-Watz Magnus
Published: August 2024

Phosphoryl transfer is a fundamental reaction in cellular signaling and metabolism that requires Mg
2+
as an essential cofactor. While the primary function of Mg
2+
is electrostatic activation of substrates, such as ATP, the full spectrum of catalytic mechanisms exerted by Mg
2+
is not known. In this study, we integrate structural biology methods, molecular dynamic (MD) simulations, phylogeny, and enzymology assays to provide molecular insights into Mg
2+
-dependent structural reorganization in the active site of the metabolic enzyme adenylate kinase. Our results demonstrate that Mg
2+
induces a conformational rearrangement of the substrates (ATP and ADP), resulting in a 30° adjustment of the angle essential for reversible phosphoryl transfer, thereby optimizing it for catalysis. MD simulations revealed transitions between conformational substates that link the fluctuation of the angle to large-scale enzyme dynamics. The findings contribute detailed insight into Mg
2+
activation of enzymes and may be relevant for reversible and irreversible phosphoryl transfer reactions.
A nonconjugated radical polymer enables bimodal memory and in-sensor computing operation
Authors: Ko Jaehyoung , Kim Daeun , Nguyen Quynh H. , Lee Changhyeon , Kim Namju , Lee Hoyeon , Eo Joohwan , Kwon Ji Eon , Jeon Seung-Yeol , Jang Byung Chul , Im Sung Gap , Joo Yongho
Published: August 2024

This study reports intrinsic multimodal memristivity of a nonconjugated radical polymer with ambient stability. Organic memristive devices represent powerful candidates for biorealistic data storage and processing. However, there exists a substantial knowledge gap in realizing the synthetic biorealistic systems capable of effectively emulating the cooperative and multimodal activation processes in biological systems. In addition, conventional organic memristive materials are centered on conjugated small and macromolecules, making them synthetically challenging or difficult to process. In this work, we first describe the intrinsic resistive switching of the radical polymer that resulted in an exceptional state retention of >10
5
s and on/off ratio of >10
6
. Next, we demonstrate its bimodal cooperative switching, in response to the proton accumulation as a biological input. Last, we expand our system toward an advanced in-sensor computing system. Our research demonstrates a nonconjugated radical polymer with intrinsic memristivity, which is directly applicable to future electronics including data storage, neuromorphics, and in-sensor computing.
Active shape programming drives
Drosophila
wing disc eversion
Authors: Fuhrmann Jana F. , Krishna Abhijeet , Paijmans Joris , Duclut Charlie , Cwikla Greta , Eaton Suzanne , Popović Marko , Jülicher Frank , Modes Carl D. , Dye Natalie A.
Published: August 2024

How complex 3D tissue shape emerges during animal development remains an important open question in biology and biophysics. Here, we discover a mechanism for 3D epithelial shape change based on active, in-plane cellular events that is analogous to inanimate “shape programmable” materials, which undergo blueprinted 3D shape transformations from in-plane gradients of spontaneous strains. We study eversion of the
Drosophila
wing disc pouch, when the epithelium transforms from a dome into a curved fold, quantifying 3D tissue shape changes and mapping spatial patterns of cellular behaviors on the evolving geometry using cellular topology. Using a physical model inspired by shape programming, we find that active cell rearrangements are the major contributor to pouch eversion and validate this conclusion using a knockdown of MyoVI, which reduces rearrangements and disrupts morphogenesis. This work shows that shape programming is a mechanism for animal tissue morphogenesis and suggests that patterns in nature could present design strategies for shape-programmable materials.
Informing an investment case for Japanese encephalitis vaccine introduction in Bangladesh
Authors: Duque Mariana Perez , Naser Abu M. , dos Santos Gabriel Ribeiro , O’Driscoll Megan , Paul Kishor K. , Rahman Mahmudur , Alam Mohammad S. , Al-Amin Hasan M. , Rahman Mohammed Z. , Hossain Mohammad E. , Paul Repon C. , Luby Stephen P. , Cauchemez Simon , Vanhomwegen Jessica , Gurley Emily S. , Salje Henrik
Published: August 2024

Japanese encephalitis virus (JEV) is a major threat to human health. Bangladesh is considering introducing a JEV vaccine; however, the investment case is hampered by a limited understanding of key aspects of JEV ecology. We conducted a seroprevalence study in a high-incidence region using an assay that limits cross-reactivity with dengue virus. We also trapped mosquitoes and collected information about potential host species. We used mathematical models to recover risk factors for infection and underlying probabilities of severe disease and death. We observed 19.0% [95% confidence interval (CI):17.1 to 21.1] of JEV antibodies. On average, 0.7% (95% CI: 0.2 to 2.0) of the susceptible population gets infected yearly, with pig proximity being the main human infection risk factor. Our traps captured 10 different mosquito species that have been linked with JEV transmission. We estimated that 1 in 1000 infections results in severe disease, 1 in 10,000 results in death, and 76% of severe cases are missed by surveillance.
Mediastinal lymphadenopathy due to VEXAS syndrome
Authors: Burgei Jonathan , Alsheimer Katie M , Lantry Julia , Hehn Boyd
Published: August 2024

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a rare disease first reported in 2020, most commonly seen in men aged 56–75 years old. Common clinical features include skin lesions (83.5%), fever (63.6%), relapsing chondritis (36.4%), venous thrombosis (34.7%) and lymph node enlargement (33.9%). The patient is a man in his 40s who presented with testicular and lower extremity pain, followed by a rash and bicytopenia. He was initiated on corticosteroids and sulfasalazine. He was found to have mediastinal lymphadenopathy and underwent an endobronchial ultrasound and transbronchial needle aspiration followed by a video-assisted thoracic surgery biopsy which were unrevealing. Eventually, an ubiquitin-like modifier activating enzyme (UBA-1) gene analysis was performed that was consistent with VEXAS syndrome. Patients with VEXAS syndrome usually present with a red or violaceous rash and dyspnoea. Laboratory abnormalities include anaemia, elevated mean corpuscular volume, thrombocytopenia and elevated inflammatory markers. Diagnosis is based on the genetic mutation and associated symptoms. The treatment includes steroids and Janus kinase (JAK) inhibitors, specifically ruxolitinib.
Deep sequencing as a diagnostic tool in patients with suspected primary vitreoretinal lymphoma
Authors: Choo Charlene , Cote Olivia , Bostwick Karina , Regueiro Matthew , Wells Jill , Grossniklaus Hans E , Gonzales John , Yeh Steven , Hinterwirth Armin , Doan Thuy , Shantha Jessica G
Published: August 2024

Purpose

To compare the diagnostic utility of metagenomic deep sequencing (MDS) to cytology, flow cytometry and gene rearrangement by PCR in ocular samples of patients with suspected vitreoretinal lymphoma (VRL).

Methods

Patients with suspected VRL underwent ocular sampling of one or both eyes at the Emory Eye Center from September 2017 to June 2022. Ocular samples were evaluated with MDS and conventional diagnostics. MDS was performed at the Ralph and Sophie Heintz Laboratory at the F.I. Proctor Foundation. Relevant demographic and clinical data were retrospectively collected from medical records. Patients were diagnosed with VRL based on clinical assessment and conventional diagnostic testing.

Results

This study included 13 patients with suspected VRL who underwent diagnostic vitrectomy, including 1 patient who had an additional subretinal biopsy. Six patients (46.2%) were diagnosed with VRL. Among patients diagnosed with VRL, MDS detected pathogenic mutations in 5 out of 6 patients (83.3%) while cytology was positive for VRL in 4 out of 6 patients (66.7%), flow cytometry in 4 out of 4 patients (100.0%) and PCR in 4 out of 4 patients (100.0%). MDS detected mutations in
MYD88
in 2 out of 6 patients diagnosed with VRL. In 7 patients (53.8%) not diagnosed with VRL, MDS detected pathogenic lymphoma mutations in 2 patients (28.6%).

Discussion

MDS detected pathogenic mutations in five out of six patients diagnosed with VRL, including in two patients with negative cytology, demonstrating its potential to improve diagnostic rates of VRL as an adjunctive test.
Longitudinal assessment of female carriers of choroideremia using multimodal retinal imaging
Authors: Gocuk Sena A , Ayton Lauren N , Edwards Thomas L , McGuinness Myra B , Maclaren Robert E , Taylor Laura J , Jolly Jasleen K
Published: August 2024

Background/aims

Female choroideremia carriers present with a spectrum of disease severity. Unlike in men, the rate of disease progression has not been well characterised in carriers. This longitudinal study aimed to determine the rate of retinal degeneration in choroideremia carriers, using multimodal imaging and microperimetry.

Methods

Choroideremia carriers previously seen at Oxford Eye Hospital (United Kingdom) between 2012 and 2017 returned for testing between 2015 and 2023, providing up to 11 years’ follow-up data. Participants had optical coherence tomography, fundus-tracked microperimetry and fundus autofluorescence (FAF) imaging performed.

Results

Thirty-four eyes of 17 choroideremia carriers were examined using multimodal imaging. Median age was 44 (range: 15–73) years at baseline and median follow-up duration was 7 (range: 1–11) years. At baseline, phenotype was classified as fine (n=5 eyes), coarse (n=13 eyes), geographic (n=12 eyes) or male pattern (n=4 eyes). Thirteen patients showed no change in phenotype classification, four showed slight changes associated with choroideremia-related retinal degeneration. Despite this, carriers with severe retinal phenotypes had a statistically significant decline in average retinal sensitivity (−0.7 dB and −0.8 dB per year, respectively, p<0.001), area of geographic loss defined by FAF (+2.5 mm
2
and +3.7 mm
2
per year, respectively, p<0.001) and thinning of the photoreceptor complex (up to −2.8 microns and −10.3 microns per year, p<0.001).

Conclusion

Choroideremia carriers, particularly those with severe retinal phenotypes, exhibit progressive retinal degeneration, as evident by multimodal imaging biomarkers and functional testing. Clinicians should not rely on retinal severity classification alone to assess disease progression.
Frailty: a global health challenge in need of local action
Authors: Dlima Schenelle Dayna , Hall Alex , Aminu Abodunrin Quadri , Akpan Asangaedem , Todd Chris , Vardy Emma R L C
Published: August 2024

Frailty is a complex, age-related clinical condition that involves multiple contributing factors and raises the risk of adverse outcomes in older people. Given global population ageing trends, the growing prevalence and incidence of frailty pose significant challenges to health and social care systems in both high-income and lower-income countries. In this review, we highlight the disproportionate representation of research on frailty screening and management from high-income countries, despite how lower-income countries are projected to have a larger share of older people aged ≥60. However, more frailty research has been emerging from lower-income countries in recent years, paving the way for more context-specific guidelines and studies that validate frailty assessment tools and evaluate frailty interventions in the population. We then present further considerations for contextualising frailty in research and practice in lower-income countries. First, the heterogeneous manifestations of frailty call for research that reflects different geographies, populations, health systems, community settings and policy priorities; this can be driven by supportive collaborative systems between high-income and lower-income countries. Second, the global narrative around frailty and ageing needs re-evaluation, given the negative connotations linked with frailty and the introduction of intrinsic capacity by the World Health Organization as a measure of functional reserves throughout the life course. Finally, the social determinants of health as possible risk factors for frailty in lower-income countries and global majority populations, and potential socioeconomic threats of frailty to national economies warrant proactive frailty screening in these populations.
Treating infertility as a missing capability, not a disease: a capability approach
Authors: Bayefsky Michelle Jessica , Caplan Arthur
Published: August 2024

Infertility patients and patient advocates have long argued for classifying infertility as a disease, in the hopes that this recognition would improve coverage for and access to fertility treatment. However, for many fertility patients, including older women, single women and same-sex couples, infertility does not represent a true disease state. Therefore, while calling infertility a ‘disease’ may seem politically advantageous, it might actually exclude patients with ‘social’ or ‘relational’ infertility from treatment. What is needed is a new conceptual framing of infertility that better reflects the profound significance of being infertile for many people and the importance of addressing infertility in order to improve their lives. In this paper, we argue that the capability approach provides this moral underpinning. The capability approach is concerned with what people are able todo, and whether they are able to act in a way that is in keeping with their own values and goals. The ability to procreate and build a family is a fundamental capacity and can be a major part of self-fulfilment, regardless of sexual orientation or family arrangement. Since the capability approach asks us to conceive of equality in terms of equal capabilities, it provides a strong ethical impetus for society to help those who cannot conceive on their own to do so with assisted reproduction.
Genotype–phenotype correlation of
SQSTM1
variants in patients with amyotrophic lateral sclerosis
Authors: Wang Shichan , Jiang Qirui , Zheng Xiaoting , Wei Qianqian , Lin Junyu , Yang Tianmi , Xiao Yi , Li Chunyu , Shang Huifang
Published: August 2024

Background

Several variants of sequestosome 1 (
SQSTM1
) were screened in patients with amyotrophic lateral sclerosis (ALS), while the pathogenicity and genotype–phenotype correlation remains unclear.

Methods

We screened variants of
SQSTM1
gene in 2011 Chinese patients with ALS and performed a burden analysis focusing on the rare variants. Furthermore, we conducted a comprehensive analysis of patients with variants of
SQSTM1
gene in patients with ALS from our cohort and published studies.

Results

In our cohort, we identified 32 patients with 25 different
SQSTM1
variants with a mutant frequency of 1.6%. Notably, 26% (5/19) of the patients with ALS with
SQSTM1
variant in our cohort had comorbid cognitive impairment and 43% (3/7) of them had behavioural variant frontotemporal dementia (FTD). Our meta-analysis found a total frequency of
SQSTM1
variants in 7183 patients with ALS was 2.4%; burden analysis indicated that patients with ALS had enrichment of ultra-rare (minor allele frequency<0.01%) probably pathogenic variants in
SQSTM1
. Most variants were missense variants and distributed in various domains of p62 protein, some of which might be related to comorbidities of Paget’s disease of bone and FTD.

Conclusion

Our study established the largest cohort of patients with ALS with
SQSTM1
variants, expanded the mutation spectrum and investigated the genotype–phenotype correlations of
SQSTM1
variants.
Hidden in plain sight: the covering of patients’ eyes and a microethics of medical photography
Authors: Slobogin Christine
Published: August 2024

This article uses the author’s experience of researching historical photographs of facial injury and surgical reconstruction to think through the ethics of writing about and publishing images of patients anonymised by excising or covering their eyes. This article specifically highlights tensions between theBritish Medical Journal’s guidelines for patient anonymity in imagery and those of the archives of the British Association of Plastic, Reconstructive and Aesthetic Surgeons. The rules for reproducing these sensitive images are not standardised across disciplines nor across journals and medical archives. But by using lived academic experience, visual analysis and philosophical enquiry, a flexible personal directive (or microethics) for working with these images can be reached.

In order to more fully understand where the present-day suggestion of and debates around blocking out patients’ eyes for anonymity come from, this ethical analysis is tied back to the historical precedent of Harold Gillies’ 1920 publicationPlastic Surgery of the Face, in which civilians’ eyes are covered. Theories of looking and of photography unpick some of the complex ideas that these images raise regarding patient agency in medical imagery. This article will have direct application for any researcher grappling with similarly difficult material wondering how to frame their own microethics or ethics in practice for discussing, showing or publishing these types of images.
Effects of intensified training with insufficient recovery on joint level and single muscle fibre mechanical function: the role of myofibrillar Ca2+ sensitivity
Authors: Roussel Olivia P. , Pignanelli Christopher , Hubbard Emma F. , Coates Alexandra M. , Cheng Arthur J. , Burr Jamie F. , Power Geoffrey A.
Published: August 2024

Intense exercise training with insufficient recovery time is associated with reductions in neuromuscular performance. However, it is unclear how single muscle fibre mechanical function and myofibrillar Ca2+ sensitivity contribute to these impairments. We investigated the effects of overload training on joint-level neuromuscular performance and cellular-level mechanical function. Fourteen athletes (4 female and 10 male) underwent a 3-week intensified training protocol consisting of up to 150% of their regular training hours with three additional high-intensity training sessions per week. Neuromuscular performance of the knee extensors was assessed via maximal voluntary contraction (MVC) force, electrically evoked twitch contractions, and a force-frequency relationship. Muscle biopsies were taken from the vastus lateralis to assess single fibre mechanical function. Neither MVC force nor twitch parameters were altered following training (all p > 0.05), but a rightward shift in the force–frequency curve was observed with average reduction in force of 6%–27% across frequencies 5–20 Hz (all p < 0.05). In single fibres, maximal force output was not reduced following training, but there was a rightward shift in the force–pCa curve driven by a 6% reduction in Ca2+ sensitivity ( p < 0.05). These data indicate intensified training leads to impaired Ca2+ sensitivity at the single fibre level, which in part explains impaired neuromuscular function at the joint level during lower frequencies of activation. This is an important consideration for athletes, as performance is often assessed at maximal levels of activation, and these underlying impairments in force generation may be less obvious.
Decoding apatite in volcanic carbonatitic breccia from Mongra, NW of Amba Dongar Carbonatite Complex, Gujarat, India: insights to genesis and rare earth element budgets
Authors: Mohanty Sunit , Ravy Divyareshmi Thottungal , Zaitsev Victor A. , Ghatak Arundhuti
Published: August 2024

Chemical variations in apatite in context to carbonatites and trace element partitioning between apatites and carbonatite-rich liquids are important in assessing the petrogenesis and evolution of the carbonatites as well as the associated carbonatitic breccia owing to apatite's sensitivity to the surrounding magma composition. Volcanic carbonatitic breccia is one of the constituent rock types found outside the ring structure of the Amba Dongar Carbonatite Complex (ADC) situated in western India. In the present work, we report the mineral chemistry of apatites from the carbonatitic breccias of the Mongra region (ADC outer core) and compare them with apatites from ADC carbonatites. Apatite chemistry from Mongra displays a larger concentration of rare earth elements, manganese and chlorine when compared with those of ADC carbonatites. The morphology and distinct zoning of these apatites represent late-stage magmatic processes with high heavy rare earth element concentrations (high lutetium), followed by the interaction of fluids from the surrounding alkaline rocks. Variation in sulfur concentration in the apatites of this study indicates crystallization under mildly reducing conditions. Integrated field observations, petrography and apatite mineral chemistry from the Mongra region allow for an understanding of the genesis of apatites in the ADC outer core, with possible implications for late-stage mineral–melt interactions.
Optimizing Delegation in Collaborative Human-AI Hybrid Teams
Authors: Fuchs Andrew , Passarella Andrea , Conti Marco
Published: August 2024

When humans and autonomous systems operate together as what we refer to as a hybrid team, we of course wish to ensure the team operates successfully and effectively. We refer to team members as agents. In our proposed framework, we address the case of hybrid teams in which, at any time, only one team member (the control agent) is authorized to act as control for the team. To determine the best selection of a control agent, we propose the addition of an AI manager (via Reinforcement Learning) which learns as an outside observer of the team. The manager learns a model of behavior linking observations of agent performance and the environment/world the team is operating in, and from these observations makes the most desirable selection of a control agent. From our review of current state of the art, we present a novel manager model for oversight of hybrid teams by our support for diverse agents and decision-maker operations across multiple time steps and decisions. In our model, we restrict the manager’s task by introducing a set of constraints. The manager constraints indicate acceptable team operation, so a violation occurs if the team enters a condition which is unacceptable and requires manager intervention. To ensure minimal added complexity or potential inefficiency for the team, the manager should attempt to minimize the number of times the team reaches a constraint violation and requires subsequent manager intervention. Therefore, our manager is optimizing its selection of authorized agents to boost overall team performance while minimizing the frequency of manager intervention. We demonstrate our manager’s performance in a simulated driving scenario representing the case of a hybrid team of agents composed of a human driver and autonomous driving system. We perform experiments for our driving scenario with interfering vehicles, indicating the need for collision avoidance and proper speed control. Our results indicate a positive impact on our manager, with some cases resulting in increased team performance up to

\(\approx 187\%\)

that of the best solo agent performance.
Pen and palm model to envision the coexistence of induced-fit and substrate-strain theories of enzyme action
Authors: Varikasuvu Seshadri Reddy , Ranvee Lavanya , Varshney Saurabh , Mondal Himel
Published: August 2024

Understanding how enzymes work can be tricky, but a new teaching method using everyday objects like pens and palms helps make it easier. Two main theories explain this: the induced-fit model and the substrate-strain model. To visualize this, imagine a pen as the substrate and your palm as the enzyme. When you hold the pen with your fingers (induced-fit), it’s like the enzyme changing shape to hold the substrate. Pressing the pen’s button with your thumb (substrate-strain) is like the enzyme applying pressure to make the pen ready to write. This simple analogy helps students better understand these complex processes, making learning more engaging and accessible.
Sex differences in grey matter, white matter, and regional brain perfusion in young, healthy adults
Authors: Muer Jessica D. , Didier Kaylin D. , Wannebo Brett M. , Sanchez Sophie , Khademi Motlagh Hedyeh , Haley Travis L. , Carter Katrina J. , Banks Nile F. , Eldridge Marlowe W. , Serlin Ronald C. , Wieben Oliver , Schrage William G.
Published: August 2024

Cerebrovascular and neurological diseases exhibit sex-specific patterns in prevalence, severity, and regional specificity, some of which are associated with altered cerebral blood flow (CBF). Females often exhibit higher resting CBF, but understanding the impact of sex per se on CBF is hampered by study variability in age, comorbidities, medications, and control for menstrual cycle or hormone therapies. A majority of studies report whole brain CBF without differentiating between grey and white matter, or without assessing regional CBF. Thus, fundamental sex differences in regional or whole-brain CBF remain unclarified. While controlling for the above confounders, we tested the hypothesis that females will exhibit higher total grey and white matter perfusion as well as regional grey matter perfusion. Adults 18-30 years old (females=22, males=26), were studied using arterial spin labeling (ASL) magnetic resonance imaging (MRI) scans followed by Computational Anatomy Toolbox (CAT12) analysis in Statistical Parametric Mapping (SPM12) to quantify CBF relative to brain volume. Females displayed 40% higher perfusion globally (females =62±9, males=45±10mL/100g/min, p<0.001), grey matter (females=75±11, males=54±12mL/100g/min, p<0.001), and white matter (females=44±6, males=32±7mL/100g/min, p<0.001). Females exhibited greater perfusion than males in 67 of the 68 regions tested, ranging from 14-66% higher. A second MRI approach (4D flow) focused on large arteries confirmed the sex difference in global CBF. These data indicate strikingly higher basal CBF in females at global, grey, and white matter levels and across dozens of brain regions, and offer new clarity into fundamental sex differences in global and regional CBF regulation prior to aging or pathology.
Two Pediatric Cases of Primary Ciliary Dyskinesia Caused by Loss‐of‐Function Variants in Oral‐Facial‐Digital Syndrome Gene, OFD1
Authors: Xu Yifei , Tsurinaga Yuki , Matsumoto Tsubasa , Muta Ryuji , Yano Taichi , Sakaida Hiroshi , Masuda Sawako , Ueda Koki , Feng Guofei , Gotoh Shimpei , Ogawa Satoru , Ikejiri Makoto , Nakatani Kaname , Nagao Mizuho , Tanabe Masaki , Takeuchi Kazuhiko
Published: August 2024

Primary ciliary dyskinesia (PCD) is a hereditary disease caused by genes related to motile cilia. We report two male pediatric cases of PCD caused by hemizygous pathogenic variants in the OFD1 centriole and centriolar satellite protein (OFD1) gene. The variants were NM_003611.3: c.[2789_2793delTAAAA] (p.[Ile930LysfsTer8]) in Case 1 and c.[2632_2635delGAAG] (p.[Glu878LysfsTer9]) in Case 2. Both cases had characteristic recurrent respiratory infections. Neither case had symptoms of oral‐facial‐digital syndrome type I. We identified a variant (c.2632_2635delGAAG) that has not been previously reported in any case of OFD1‐PCD.
Hybrid Dyakonov Surface Waves at Uniaxial Crystal‐Temperature‐Sensitive Material Interfaces
Authors: Sana Tahseen , Alkanhal Majeed A. S. , Ali Ahtisham , Ullah Hafeez , Ghaffar Abdul , Khan Yasin , Yaqoob Muhammad Zeshan
Published: August 2024

A theoretical investigation of the temperature‐dependent hybrid surface waves guided by the uniaxial crystal‐temperature‐sensitive material (TSM) interface is carried out in the present study. The uniaxial crystal is realized as a metamaterial having a direction‐dependent permittivity tensor, with the optical axis (OA) parallel to the interface. Indium antimonide (InSb) is characterized as TSM, and the temperature‐dependent electromagnetic (EM) characteristics of InSb are modeled using the extended Drude model. Analytical and numerical calculations have been performed to obtain the characteristics equation for the temperature‐dependent hybrid surface waves. The contour plot technique has been implemented in Mathematica for the computation of dispersion relation. The influence of the temperature and propagation angle on the dispersion curve, effective mode index, phase speed, and propagation length was analyzed. It is reported that the proposed interface supports the two types of surface waves (i.e., (i) pure Dyakonov surface waves (DSWs) for the temperature range (i.e., T ∈ [200, 240] K) and (ii) hybrid plasmons waves for the temperature range (i.e., T ∈ [290, 360] K)). The computed results can be used to design temperature‐assisted optical waveguides, thermo‐optical sensors, and chemical sensing/communication devices.
Analysis of the Influence of Depression on the Occupational Performance of People Diagnosed with Multiple Sclerosis and Its Impact on Caregiver Burden
Authors: Rodríguez Menéndez Sergio , Perez-de-Heredia-Torres Marta , Jaraba Berné David , Menéndez González Manuel , Martínez-Piédrola Rosa Mª
Published: August 2024

Background. One of the most common symptoms in multiple sclerosis (MS) is depression, which causes disruption to daily participation. MS as a degenerative disease causes caregiver strain. The aim of this study is to analyze the influence of depression on the occupational performance of people with MS and to study whether these aspects influence caregiver strain. Materials and Methods. A descriptive cross‐sectional observational study was carried out. A total of 124 people with a diagnosis of multiple sclerosis were assessed and administered the Beck Depression Inventory‐II, the Canadian Occupational Performance Measure, and the Zarit Caregiver Burden Scale. Results. MS type influences performance, involvement, and caregiver burden. High levels of depression are associated with low levels of participation and performance. The types of MS with the highest caregiver burden are relapsing–remitting and secondary progressive. Conclusions. The type of MS negatively influences occupational performance. Depression and occupational performance are related to caregiver strain. The greater the depressive symptoms, the worse the performance, and the more caregiver strain.
Replaceable Displacement‐Amplifying Rotary Friction Damper: Experimental and Numerical Investigation
Authors: Zhang Xicheng , Liu Leilei , Qiu Zhihao , Cui Lanhao , Hu Chengming
Published: August 2024

Timber structures are vulnerable to failure and collapse under seismic action. To improve the seismic performance of such structures, a replaceable displacement amplification rotary friction damper was proposed and designed. Six specimens were fabricated, each varying in pretension strains and employing three different composite friction materials as control parameters, followed by low cyclic loading tests. The study investigated the working mechanism, hysteresis performance, energy dissipation capacity, performance stability, and displacement amplification effect of the dampers. A finite element model was developed to analyze the hysteresis performance of the damper and evaluate the impact of various parameters on its overall effectiveness. Furthermore, a comparative analysis of the damper’s hysteresis characteristics was conducted. The theoretical calculations and finite element analysis were validated using experimental results, showing a relative error within 10%. The specimens demonstrated a notable displacement amplification capability, which increased as the intermediate connector length decreased. By reducing the length by 200 mm, the maximum damping force could be amplified by 5.5 times, while the nodal rotation values increased by 3.92 times. Additionally, for every 50 με increment in pretension strain, energy consumption increases by an average of 148%, and for each unit increase in the friction coefficient, energy consumption increases by an average of 172%.
A Systematic Review of Economic Evaluations in Clinical Nursing Practices
Authors: Guan Yushan , Ru Nan , Kang Ruifu , Jia Xiangping , Xu Tingting , Meng Zhaolin
Published: August 2024

Background. The misallocation of scarce healthcare resources globally raises concerns regarding the underuse of high‐value care and the overuse of low‐value care. Economic evaluations can help policy makers determine whether an intervention presents a better value for money and desirable clinical benefits, thus realizing value‐based care. Aim. We aimed to conduct a systematic review of the economic evaluations of clinical nursing practices to advance knowledge on value‐based care. Methods. A systematic review was conducted using MEDLINE, Embase, Web of Science, Cochrane Central Register of Controlled Trials, CINAHL, NHS Economic Evaluation Database, Health Technology Assessment, and Tufts CEA Registry for full economic evaluations of clinical nursing practices from January 2013 to January 2023. Outcomes were incremental cost‐effectiveness ratios, incremental cost‐utility ratios, incremental cost‐benefit ratios, incremental net benefit, and the differences in costs for cost‐minimization studies. Methodological quality was evaluated using the Consensus Health Economic Criteria–extended checklist. Results were synthesized using permutation matrices for all studies. The protocol was registered with PROSPERO (CRD42023415918). Results. Thirty‐five studies were included in this review, with 27 studies categorized as good methodological quality and 8 as moderate quality. Clinical nursing practices were dominant (i.e., more effective and less costly) in 19 studies, potentially cost‐effective depending on willingness‐to‐pay thresholds in 15 studies, and were dominated (i.e., less effective and more costly) in 1 study. Conclusion. Our study advanced knowledge on value‐based care for clinical nursing practices. Results suggest that most clinical nursing practices studied may be clearly economically favourable or potentially favourable. Implications for Nursing Management. The results of this review provide valuable insights into value‐based care in nursing and facilitate the decision‐making of healthcare policymakers regarding health resource allocation to achieve value‐based care.
DAZAP1 Phase Separation Regulates Mitochondrial Metabolism to Facilitate Invasion and Metastasis of Oral Squamous Cell Carcinoma
Authors: Zhang Jiayi , Ni Zihui , Zhang Yu , Guo Yan , Zhai Rundong , Wang Mengqi , Gong Zizhen , Wang Mengyao , Zeng Fanrui , Gu Ziyue , Chen Qianming , Liu Laikui , Wang Zhiyong , Zhu Weiwen
Published: August 2024

Tumor invasion and metastasis are the underlying causes of high mortality rate due to oral squamous cell carcinoma (OSCC). Energy metabolism reprogramming has been identified as a crucial process mediating tumor metastasis, thus indicating an urgent need for an in-depth investigation of the specific mechanisms of tumor energy metabolism. Here, we identified an RNA-binding protein, DAZ-associated protein 1 (DAZAP1), as a tumor-promoting factor with an important role in OSCC progression. DAZAP1 was significantly upregulated in OSCC, which enhanced the migration and invasion of OSCC cells and induced the epithelial–mesenchymal transition (EMT). RNA sequencing analysis and experimental validation demonstrated that DAZAP1 regulates mitochondrial energy metabolism in OSCC. Mechanistically, DAZAP1 underwent liquid–liquid phase separation to accumulate in the nucleus where it enhanced cytochrome c oxidase 16 (COX16) expression by regulating pre-mRNA alternative splicing, thereby promoting OSCC invasion and mitochondrial respiration. In mouse OSCC models, loss of DAZAP1 suppressed EMT, downregulated COX16, and reduced tumor growth and metastasis. In samples from patients with OSCC, expression of DAZAP1 positively correlated with COX16 and a high expression of both proteins was associated with poor patient prognosis. Together, these findings revealed a mechanism by which DAZAP1 supports mitochondrial metabolism and tumor development of OSCC, suggesting the potential of therapeutic strategies targeting DAZAP1 to block OSCC invasion and metastasis.

Significance: The RNA-binding protein DAZAP1 undergoes phase separation to enhance COX16 expression and mediate metabolic reprogramming that enables tumor metastasis, highlighting DAZAP1 as a potential metabolic target for cancer therapy.
Dual Inhibition of SYK and EGFR Overcomes Chemoresistance by Inhibiting CDC6 and Blocking DNA Replication
Authors: Mandal Jayaprakash , Jones Tiffany Nicole , Liberto Juliane Marie , Gaillard Stephanie , Wang Tian-Li , Shih Ie-Ming
Published: August 2024

Targeting multiple signaling pathways has been proposed as a strategy to overcome resistance to single-pathway inhibition in cancer therapy. A previous study in epithelial ovarian cancers identified hyperactivity of spleen tyrosine kinase (SYK) and EGFR, which mutually phosphorylate and activate each other. Given the potential for pharmacologic inhibition of both kinases with clinically available agents, this study aimed to assess the antitumor efficacy of both pharmacologic and genetic SYK and EGFR coinhibition using a multifaceted approach. We assessed the coinactivation effects in chemoresistant ovarian cancer cell lines, patient-derived organoids, and xenograft models. Dual inhibition of SYK and EGFR in chemoresistant ovarian cancer cells elicited a synergistic antitumor effect. Notably, the combined inhibition activated the DNA damage response, induced G1 cell-cycle arrest, and promoted apoptosis. The phosphoproteomic analysis revealed that perturbation of SYK and EGFR signaling induced a significant reduction in both phosphorylated and total protein levels of cell division cycle 6, a crucial initiator of DNA replication. Together, this study provides preclinical evidence supporting dual inhibition of SYK and EGFR as a promising treatment for chemoresistant ovarian cancer by disrupting DNA synthesis and impairing formation of the prereplication complex. These findings warrant further clinical investigation to explore the potential of this combination therapy in overcoming drug resistance and improving patient outcomes.

Significance: SYK and EGFR coinhibition exerts synergistic anticancer effects in chemoresistant ovarian cancer, providing a strategy to treat chemotherapy-resistant ovarian cancers using clinically available agents by targeting critical signaling pathways involved in DNA replication.
Table S8 from p53R172H and p53R245W Hotspot Mutations Drive Distinct Transcriptomes in Mouse Mammary Tumors Through a Convergent Transcriptional Mediator
Authors: McDaniel Joy M. , Morrissey Rhiannon L. , Dibra Denada , Patel Lalit R. , Xiong Shunbin , Zhang Yun , Chau Gilda P. , Su Xiaoping , Qi Yuan , El-Naggar Adel K. , Lozano Guillermina
Published: August 2024

MEME motif enrichment analysis results summarizing transcription factor motifs significantly enriched in the promoters of significantly upregulated genes of human breast tumors (from METABRIC Consortium) harboring a TP53R175H or TP53R248Q/W mutation.
Supplementary Fig.1 from Tumor Vessel Normalization via PFKFB3 Inhibition Alleviates Hypoxia and Increases Tumor Necrosis in Rectal Cancer upon Radiotherapy
Authors: Edelmann Marcus , Fan Shuang , De Oliveira Tiago , Goldhardt Tina , Sartorius Dorothée , Midelashvili Teona , Conrads Karly , Paul Niels B. , Beißbarth Tim , Fleischer Johannes R. , Blume Moritz L. , Bohnenberger Hanibal , Josipovic Natasa , Papantonis Argyris , Linnebacher Michael , Dröge Leif H. , Ghadimi Michael , Rieken Stefan , Conradi Lena-Christin
Published: August 2024

Supplementary Fig.1
Epileptic Encephalopathy due to CACNA1A Variant: A Case Report and Diagnostic Challenges from Resource-Limited Settings
Authors: Chipongo Hilary , Chaki Samina , Mclarty Ronald
Published: August 2024

Introduction: Epilepsy is one of the most common neurological disorders present in sub-Saharan Africa and most of these cases are underdiagnosed due to a lack of resources. Epileptic encephalopathies are a broad spectrum of seizure disorders characterized by epileptic activity itself impairing cognitive and behavioral function more than what is expected from the underlying pathology alone. Epileptic encephalopathy resulting from the CACNA1A variant is extremely challenging to treat and prognosis is poor if prompt diagnosis is not made. Case Presentation: This is a 7-year-old male patient of African descent with a history of recurrent seizures since infancy. He has been kept on several anticonvulsants without success to control seizure attacks. The patient had more than three attacks in a single month despite being on anticonvulsants. EEG (electro-encephalography) was done and genetic studies showed a diagnosis consistent with CACNA1A variant-associated epileptic encephalopathy. Anticonvulsants were revised and a combination of new medications as suggested by current guidelines was initiated, and the patient is followed up closely on a monthly basis. Conclusion: Despite being challenging to treat epileptic encephalopathies associated with CACNA1A variants all patients initiated with antiepileptic therapy should be followed closely and monitored for control of seizure attacks. If EEG alone does not point out the diagnosis, appropriate investigations such as genetic studies should be considered. Early diagnosis is crucial for the prognosis of such kind of cases, especially in resource-limited settings where diagnostic equipments are scarce. All clinicians in these areas should have a high suspicion index in pediatric patients with recurrent seizure attacks to rule out epileptic encephalopathies.
Rotor angle deviation regulator to enhance the rotor angle stability of synchronous generators
Authors: Murad Nor Syaza Farhana Mohamad , Kamarudin Muhammad Nizam , Zakaria Muhammad Iqbal
Published: August 2024

Occurrences of disturbance affect the rotor angle operation of a synchronous generator in the generation system of a power system. The disturbance will disrupt the synchronous generator's rotor oscillation and result in rotor angle instability, which will degrade the power system's performance. This paper aims to develop a Lyapunov-based rotor angle deviation regulator for the nonlinear swing equation of a synchronous generator. The proposed regulator is expected to assure asymptotic stability of the rotor angle and robustness to uncertainty. Backstepping and Lyapunov redesign techniques are employed in developing the regulator. To validate the effectiveness and robustness of the regulator, a simulation in MATLAB/Simulink is carried out. The simulation result shows that the asymptotic stability and robustness of the regulator are guaranteed regardless of the disturbance.
Comparative design of harmonic current reduction in variable speed drive using space vector pulse width modulation and hybrid pulse width modulation
Authors: Siregar Yulianta , Situmeang Farel , Mohamed Nur Nabila
Published: August 2024

In industry and commerce, three-phase induction motors are frequently utilized as the primary power source for machinery. However, to increase motor performance efficiency, induction motors also need a tool for speed control. The variable speed drive (VSD) is one tool used to control the rotation speed of three-phase induction motors. Since VSD is a non-linear load, harmonic distortion will result from it. The space vector pulse width modulation (SVPWM) injection method and the hybrid pulse width modulation method were the two techniques employed by the author in this study to lower the current in the VSD. With the SVPWM injection approach, the variable speed drive's current total harmonic distortion (THD) values in the R, S, and T phases dropped to 3.77%, 3.53%, and 2.19% from 7.14%, 7.17%, and 7.58%.