bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration Merdeka Belajar concept in development STEMC module for electrochemical and renewable energy at vocational school SMK SMTI Banda Aceh
Authors: Azhari A , Irwandi I , Jalil Z , Ilhamsyah Y , Sulastri S , Muhibuddin M , Rasul M S
Published: October 2023

Indonesia’s energy consumption needs to reduce its dependence on fossil energy. The Ministry of Education and Culture plays a role in developing renewable energy through vocational education by improving the quality of vocational education graduates through the Merdeka Learning curriculum. The three advantages of the Merdeka Learning curriculum are that it is simpler, in-depth, independent, relevant, and interactive. The STEM Research Center, Syiah Kuala University has initiated STEMC which can fulfill its excellence. STEMC consists of ISLE-based STEM learning activities which are one of the inquiry learning models. Electrochemistry and renewable energy educational materials have been developed using this model, to study the concepts of electric current in wires, electrolysis, and fuel cells. SMTI Banda Aceh Vocational School students are enthusiastic and happy to take part in the practicum stages. They better understand the concept of science because it combines theory and real practice. This learning module is designed with stages that help the constructivism process to increase the effectiveness of learning to be more meaningful. This module also helps students solve real-life problems by honing cognitive skills, designing experiments, utilizing technology, applying knowledge, and combining cognitive, affective, and psychomotor knowledge. As well as arousing curiosity and triggering students’ creative imagination and critical thinking.
Sub-micrometer real-time imaging of trajectory of alpha particles using GAGG plate and CMOS camera
Authors: Yamamoto Seiichi , Yoshino Masao , Nakanishi Kohei , Yogo Katsunori , Kamada Kei , Yoshikawa Akira , Koshikawa Nanase , Kataoka Jun
Published: October 2023

High-resolution and real-time imaging of the trajectories of
alpha particles is desired in nuclear medicine and nuclear
engineering. Although an imaging method using a scintillator plate
combined with a magnifying unit and a cooled electron multiplying
charge-coupled device (EM-CCD) camera is a possible method of
obtaining high-resolution trajectory images, the spatial resolution
of the system is limited to ∼2 μm. To overcome the spatial
resolution limitations of this method on trajectory imaging, we used
a cooled complementally metal oxide (CMOS) camera in which the
sensor had a much larger number of pixels, which were also
smaller. Using the CMOS camera based imaging system, we could
measure the trajectories of alpha particles in real time with the
spatial resolution of 0.34 μm FWHM. With smoothing of the
images to reduce image noise, spatial resolution was still kept to
less than 0.75 μm. We conclude that this CMOS camera-based
alpha-particle trajectory-imaging system is promising for
alpha-particle or other particles imaging where ultrahigh spatial
resolution is required.
Alphabet cardinality and adaptive evolution
Authors: Srivastava Malvika , Rozhoňová Hana , Payne Joshua L
Published: October 2023

One of the most fundamental characteristics of a fitness landscape is its dimensionality, which is defined by genotype length and alphabet cardinality—the number of alleles per locus. Prior work has shown that increasing landscape dimensionality can promote adaptation by forming new ‘uphill’ mutational paths to the global fitness peak, but can also frustrate adaptation by increasing landscape ruggedness. How these two topographical changes interact to influence adaptation is an open question. Here, we address this question in the context of alphabet cardinality, using theoretical fitness landscapes with tuneable fitness correlations, as well as three empirical fitness landscapes for proteins. We find that the primary effect of increasing alphabet cardinality is the introduction of a new global fitness peak. Controlling for this effect, we find that increasing alphabet cardinality promotes adaptation on uncorrelated fitness landscapes, but frustrates adaptation on correlated fitness landscapes. The primary explanation is that the increased ruggedness that accompanies alphabet expansion is characterized by an increase in mean peak height on uncorrelated fitness landscapes, but a decrease in mean peak height in correlated fitness landscapes. Moreover, in two of the empirical fitness landscapes we observe no effect of increasing alphabet cardinality on adaptation, despite an increase in the number of peaks and a decrease in mean peak height, calling into question the utility of these common measures of landscape ruggedness as indicators of evolutionary outcomes.
Cortical growth from infancy to adolescence in preterm and term-born children
Authors: Kelly Claire E , Thompson Deanne K , Adamson Chris L , Ball Gareth , Dhollander Thijs , Beare Richard , Matthews Lillian G , Alexander Bonnie , Cheong Jeanie L Y , Doyle Lex W , Anderson Peter J , Inder Terrie E
Published: October 2023

Early life experiences can exert a significant influence on cortical and cognitive development. Very preterm birth exposes infants to several adverse environmental factors during hospital admission, which affect cortical architecture. However, the subsequent consequence of very preterm birth on cortical growth from infancy to adolescence has never been defined; despite knowledge of critical periods during childhood for establishment of cortical networks. Our aims were to: chart typical longitudinal cortical development and sex differences in cortical development from birth to adolescence in healthy term-born children; estimate differences in cortical development between children born at term and very preterm; and estimate differences in cortical development between children with normal and impaired cognition in adolescence.

This longitudinal cohort study included children born at term (≥37 weeks’ gestation) and very preterm (<30 weeks’ gestation) with MRI scans at ages 0, 7 and 13 years (n = 66 term-born participants comprising 34 with one scan, 18 with two scans and 14 with three scans; n = 201 very preterm participants comprising 56 with one scan, 88 with two scans and 57 with three scans). Cognitive assessments were performed at age 13 years. Cortical surface reconstruction and parcellation were performed with state-of-the-art, equivalent MRI analysis pipelines for all time points, resulting in longitudinal cortical volume, surface area and thickness measurements for 62 cortical regions. Developmental trajectories for each region were modelled in term-born children, contrasted between children born at term and very preterm, and contrasted between all children with normal and impaired cognition.

In typically developing term-born children, we documented anticipated patterns of rapidly increasing cortical volume, area and thickness in early childhood, followed by more subtle changes in later childhood, with smaller cortical size in females than males. In contrast, children born very preterm exhibited increasingly reduced cortical volumes, relative to term-born children, particularly during ages 0–7 years in temporal cortical regions. This reduction in cortical volume in children born very preterm was largely driven by increasingly reduced cortical thickness rather than area. This resulted in amplified cortical volume and thickness reductions by age 13 years in individuals born very preterm. Alterations in cortical thickness development were found in children with impaired language and memory.

This study shows that the neurobiological impact of very preterm birth on cortical growth is amplified from infancy to adolescence. These data further inform the long-lasting impact on cortical development from very preterm birth, providing broader insights into neurodevelopmental consequences of early life experiences.
Premovement activity in the mesocortical system links peak force but not initiation of force generation under incentive motivation
Authors: Sugawara Sho K , Yamamoto Tetsuya , Nakayama Yoshihisa , Hamano Yuki H , Fukunaga Masaki , Sadato Norihiro , Nishimura Yukio
Published: October 2023

Motivation facilitates motor performance; however, the neural substrates of the psychological effects on motor performance remain unclear. We conducted a functional magnetic resonance imaging experiment while human subjects performed a ready-set-go task with monetary incentives. Although subjects were only motivated to respond quickly, increasing the incentives improved not only reaction time but also peak grip force. However, the trial-by-trial correlation between reaction time and peak grip force was weak. Extensive areas in the mesocortical system, including the ventral midbrain (VM) and cortical motor-related areas, exhibited motivation-dependent activity in the premovement “Ready” period when the anticipated monetary reward was displayed. This premovement activity in the mesocortical system correlated only with subsequent peak grip force, whereas the activity in motor-related areas alone was associated with subsequent reaction time and peak grip force. These findings suggest that the mesocortical system linking the VM and motor-related regions plays a role in controlling the peak of force generation indirectly associated with incentives but not the initiation of force generation.
Brain plasticity underlying sleep-dependent motor consolidation after motor imagery
Authors: Di Rienzo Franck , Debarnot Ursula , Daligault Sébastien , Delpuech Claude , Doyon Julien , Guillot Aymeric
Published: October 2023

Motor imagery can, similarly to physical practice, improve motor performance through experience-based plasticity. Using magnetoencephalography, we investigated changes in brain activity associated with offline consolidation of motor sequence learning through physical practice or motor imagery. After an initial training session with either physical practice or motor imagery, participants underwent overnight consolidation. As control condition, participants underwent wake-related consolidation after training with motor imagery. Behavioral analyses revealed that overnight consolidation of motor learning through motor imagery outperformed wake-related consolidation (95% CI [0.02, 0.07], P < 0.001, RP2 = 0.05). As regions of interest, we selected the generators of event-related synchronization/desynchronization of alpha (8–12 Hz) and beta (15–30 Hz) oscillations, which predicted the level of performance on the motor sequence. This yielded a primary sensorimotor-premotor network for alpha oscillations and a cortico-cerebellar network for beta oscillations. The alpha network exhibited increased neural desynchronization after overnight consolidation compared to wake-related consolidation. By contrast, the beta network exhibited an increase in neural synchronization after wake-related consolidation compared to overnight consolidation. We provide the first evidence of parallel brain plasticity underlying behavioral changes associated with sleep-dependent consolidation of motor skill learning through motor imagery and physical practice.
Is proton-pump inhibitor effective in preventing postoperative bleeding after esophageal endoscopic submucosal dissection?
Authors: Tanaka Ippei , Tarasawa Kunio , Saito Hiroaki , Hirasawa Dai , Fujimori Kenji , Fushimi Kiyohide , Matsuda Tomoki
Published: October 2023

Although proton-pump inhibitor (PPI) administration was reported to be effective in preventing delayed bleeding after gastric endoscopic submucosal dissection (ESD), its effectiveness in esophageal ESD is still unknown. We assessed whether PPI or vonoprazan administration was effective in preventing posterior hemorrhage after esophageal ESD. This retrospective cohort study used the Japanese Diagnosis Procedure Combination (DPC) database, and patients who underwent esophageal ESD between January 2012 and December 2020 were enrolled. The participants were divided into two groups: patients who were prescribed PPI or vonoprazan (PPI or vonoprazan group) and those who were not prescribed PPI (no acid suppression). Propensity score matching analysis was performed, and the delayed bleeding rate was compared between the groups. We analyzed 54,345 patients, of whom 8237 (15.16%) were in the no acid suppression group and 46,108 (84.84%) in the PPI or vonoprazan group (PPI: 34,380 and vonoprazan: 11,728). Delayed bleeding occurred in 1126 patients (2.07%). A total of 8237 pairs were created after matching. Delayed bleeding was not significantly different between the no acid suppression group and PPI or vonoprazan group, respectively (odds ratio: 1.20, 95% confidential interval: 0.93–1.54, P = 0.227). A sub-analysis according to the dose of PPI or vonoprazan, tumor location, and prescription of antithrombotic or anticoagulant medications was performed, but no significant effects of PPI or vonoprazan administration were found. PPI or vonoprazan did not prevent delayed bleeding; thus, the prescription of PPI and vonoprazan after esophageal ESD may not be recommended for the prevention of delayed bleeding.
Taste-Based Gender Favouritism in High-Stake Decisions: Evidence from The Price is Right
Authors: Atanasov Pavel , Dana Jason D , Klein Teeselink Bouke
Published: October 2023

Gender discrimination is present across various fields, but identifying the underlying mechanism is challenging. We demonstrate own-gender favouritism in a field setting that allows for clean identification of tastes versus beliefs: the One Bid game on the TV show The Price Is Right. Players must guess an item’s value without exceeding it, leaving the last bidder with a dominant ‘cutoff’ strategy of overbidding another player by ${\$}$1. We show that last bidders are significantly more likely to cut off opposite-gender opponents. This behaviour is explained by own-gender favouritism rather than beliefs that cutting off opposite-gender opponents is more profitable.
Characterization of de novo malignancy after orthotopic heart transplantation: single-centre outcomes over 20 years
Authors: Bakir Nadia H , Florea Ioana B , Phillipps Jordan , Schilling Joel D , Damiano Marci S , Ewald Gregory A , Kotkar Kunal D , Itoh Akinobu , Damiano Ralph J , Moon Marc R , Masood Muhammad F
Published: October 2023

OBJECTIVES

Malignancy is the leading cause of late mortality after orthotopic heart transplantation (OHT), and the burden of post-transplantation cancer is expected to rise in proportion to increased case volume following the 2018 heart allocation score change. In this report, we evaluated factors associated with de novo malignancy after OHT with a focus on skin and solid organ cancers.

METHODS

Patients who underwent OHT at our institution between 1999 and 2018 were retrospectively reviewed (n = 488). Terminal outcomes of death and development of skin and/or solid organ malignancy were assessed as competing risks. Fine–Gray subdistribution hazards regression was used to evaluate the association between perioperative patient and donor characteristics and late-term malignancy outcomes.

RESULTS

By 1, 5 and 10 years, an estimated 2%, 17% and 27% of patients developed skin malignancy, while 1%, 5% and 12% of patients developed solid organ malignancy. On multivariable Fine–Gray regression, age [1.05 (1.03–1.08); P < 0.001], government payer insurance [1.77 (1.20–2.59); P = 0.006], family history of malignancy [1.66 (1.15–2.38); P = 0.007] and metformin use [1.73 (1.15–2.59); P = 0.008] were associated with increased risk of melanoma and basal or squamous cell carcinoma. Age [1.08 (1.04–1.12); P < 0.001] and family history of malignancy [2.55 (1.43–4.56); P = 0.002] were associated with an increased risk of solid organ cancer, most commonly prostate and lung cancer.

CONCLUSIONS

Vigilant cancer and immunosuppression surveillance is warranted in OHT recipients at late-term follow-up. The cumulative incidence of skin and solid organ malignancies increases temporally after transplantation, and key risk factors for the development of post-OHT malignancy warrant identification and routine monitoring.
Isolated loss of the AUTS2 long isoform, brain-wide or targeted to Calbindin-lineage cells, generates a specific suite of brain, behavioral, and molecular pathologies
Authors: Song Yunshu , Seward Christopher H , Chen Chih-Ying , LeBlanc Amber , Leddy Analise M , Stubbs Lisa
Published: October 2023

Rearrangements within the AUTS2 region are associated with a rare syndromic disorder with intellectual disability, developmental delay, and behavioral abnormalities as core features. In addition, smaller regional variants are linked to wide range of neuropsychiatric disorders, underscoring the gene's essential role in brain development. Like many essential neurodevelopmental genes, AUTS2 is large and complex, generating distinct long (AUTS2-l) and short (AUTS2-s) protein isoforms from alternative promoters. Although evidence suggests unique isoform functions, the contributions of each isoform to specific AUTS2-linked phenotypes have not been clearly resolved. Furthermore, Auts2 is widely expressed across the developing brain, but cell populations most central to disease presentation have not been determined. In this study, we focused on the specific roles of AUTS2-l in brain development, behavior, and postnatal brain gene expression, showing that brain-wide AUTS2-l ablation leads to specific subsets of the recessive pathologies associated with mutations in 3′ exons (exons 8–19) that disrupt both major isoforms. We identify downstream genes that could explain expressed phenotypes including hundreds of putative direct AUTS2-l target genes. Furthermore, in contrast to 3′ Auts2 mutations which lead to dominant hypoactivity, AUTS2-l loss-of-function is associated with dominant hyperactivity and repetitive behaviors, phenotypes exhibited by many human patients. Finally, we show that AUTS2-l ablation in Calbindin 1-expressing cell lineages is sufficient to yield learning/memory deficits and hyperactivity with abnormal dentate gyrus granule cell maturation, but not other phenotypic effects. These data provide new clues to in vivo AUTS2-l functions and novel information relevant to genotype–phenotype correlations in the human AUTS2 region.
Toxoplasma gondii Causes Adverse Pregnancy Outcomes by Damaging Uterine Tissue-Resident NK Cells That Secrete Growth-Promoting Factors
Authors: Zhang Famin , Sun Wenze , Zhao Ji , Zhang Chenlin , Sheng Keyuan , Wang Cong , Song Lingling , Zhang Xiran , Cao Yuanyuan , Luo Qingli , Shen Jilong , Yu Li
Published: October 2023

Vertical transmission of the intracellular parasite, Toxoplasma gondii can lead to adverse pregnancy outcomes especially when infection occurs in early pregnancy. Decidual natural killer (dNK) cells accumulate at the maternal-fetal interface in large numbers during early pregnancy. Their nutritional roles during infection with T. gondii remain poorly defined. In the present study, we demonstrated that a functional deficiency of the uterine tissue-resident NK (trNK) cells, a subset of dNK cells, contributes to the adverse pregnancy outcomes induced by T. gondii in early pregnancy. Adverse pregnancy outcomes could be ameliorated by adoptive transfer of trNK cells. Moreover, fetal growth restriction could be improved after supplementation of growth-promoting factors. In addition to the widely recognized disturbance of the immune balance at the interface between the mother and the fetus, our study reveals a novel mechanism in T. gondii that contributes to the adverse pregnancy outcomes.
Requeening queenright honey bee colonies with queen cells in honey supers
Authors: Holmes Leslie A , Kearns Jeffery D , Ovinge Lynae P , Wolf Veiga Patricia , Hoover Shelley E
Published: October 2023

Many Canadian beekeepers replace a subset of their honey bee queens annually. However, introducing a new queen to a honey bee colony is a management practice with a high degree of uncertainty. Despite the consensus that it is most effective to introduce queens to queenless colonies, some commercial beekeepers claim success with introducing queen cells into the honey super of queenright colonies. We tested the success rate of this practice by introducing queen cells to 100 queenright colonies in southern Alberta during a honey flow. The genotypes of the resultant offspring drones were determined using the microsatellite marker A76 to identify their laying queen mothers. Our results show that new queens successfully supersede original queens in 6% of queenright colonies, suggesting that the practice does not result in the new queen taking over leadership in most colonies. Additionally, supersedure by daughter queens is more common (13%) than new queen supersedure when introducing queen cells to queenright colonies during a honey flow. However, there could be a benefit to the practice of requeening queenright colonies with queen cells in honey supers if the colonies that accepted a new queen (whether a daughter of or unrelated to the old queen) were colonies with a failing queen.
Causal Semantics for Implicative Verbs
Authors: Nadathur Prerna
Published: October 2023

Implicative verbs (e.g., manage, dare) are characterized by complement inferences (Karttunen, 1971). English manage entails its complement; the entailment reverses polarity with matrix negation, and is accompanied by a projective inference to the complement’s non-triviality (Coleman, 1975; Karttunen & Peters, 1979). I use data from Finnish and English to argue that the implicative inferential profile is derived from backgrounded relations of causal necessity and causal sufficiency (defined over the structure of a formal causal model; Pearl 2000; Schulz 2011) which link the lexical content of an implicative verb to the realization of its complement. The proposal builds on Baglini & Francez’s (2016) causal analysis of manage, but significantly revises the earlier proposal to offer a treatment which accounts not only for English manage, but extends to the lexical semantics of the full implicative class, including ‘polarity-reversing’ verbs like fail, lexically specific verbs like dare, and their Finnish counterparts. Unlike earlier analyses, the proposed causal semantics also provides a natural explanation of the commonalities between two-way entailing verbs like manage and a related class of weaker ‘one-way’ implicatives such as Finnish jaksaa (‘have the strength’), which entail complement truth values under only one matrix polarity, but generate strong pragmatic implicatures in the two-way implicative pattern under the non-entailing polarity.
Instruments to measure patient satisfaction with comprehensive medication management (CMM) services: a scoping review
Authors: Resende Lorayne Caroline , Michel Barbosa Mariana , Rezende Cristiane de Paula , Pantuza Laís Lessa Neiva , Reis Edna Afonso , Nascimento Mariana Martins Gonzaga
Published: October 2023

Objectives

To map the instruments to measure patient satisfaction with comprehensive medication management (CMM) services and to compare them according to their development characteristics and applicability of patient-reported outcome measures (PRO) measures.

Methods

A scoping review was conducted using the methodology proposed by the Joanna Briggs Institute and the PRISMA Extension for Scoping Reviews (PRISMA-ScR). Studies that developed or applied a patient satisfaction measurement instrument in CMM services, published from 1990 onwards were selected. The critical appraisal of the instruments identified was carried out using an 18 item checklist developed to systematically evaluate PRO measures.

Key findings

A total of 28 studies were selected; in most (17), the applied instruments had been developed by the authors. Nine of them were validated, most of which used open-ended and closed questions in self-administered printed instruments. The best-qualified instrument reached 11 out of the 18 evaluated items, highlighting the difficulty in the definition of the satisfaction construct.

Conclusions

The review made it possible to identify the instruments available to measure patient satisfaction with CMM services and to comparatively highlight their characteristics and psychometric properties. It also pointed out the need to improve or develop a patient satisfaction instrument for CMM services. However, improvement is needed in many of the evaluated domains of the instruments to meet the desirable requirements for a PRO measure. These gaps should be taken into consideration in future research, aiming to build a robust and standardized instrument for the CMM service.
Refugee Journalism in Indonesia: Self-Representation, Resistance, and Writing across Borders
Authors: Missbach Antje , Joniad J N , Adiputera Yunizar
Published: October 2023

By presenting the political engagements of a young refugee from Myanmar who was stuck in Indonesia for nine years, this article discusses the role, value, and importance of refugee writing. Refugees are prohibited from working in Indonesia. Any form of income-generation can result in serious pitfalls, including detention and other punishments. Writing—for international newspapers, blogs, and journals—presents a unique opportunity for earning money while also providing a platform for voicing refugee concerns and engaging in activism beyond borders. Yet, politically motivated writing also comes with certain risks, i.e., exposing the refugee authors to authorities. While this collaboratively written account portrays the struggles and the small and big successes in gaining a voice and communicating across borders of one refugee activist, it remains cautious in prescribing writing as an effective tool for all refugees stuck in transit, thus acknowledging also their ongoing destitution and precarity.
Pelvic organ prolapse after delivery: effects on sexual function, quality of life, and psychological health
Authors: Li Jie , Zhao Xiaoling , Li Juanhua , Liu Yuanwen , Li Tiantian
Published: October 2023

Background

Living with pelvic organ prolapse (POP) after delivery negatively impacted women’s daily living and was detrimental to their psychological health.

Aim

The purpose of the present study was to explore the effects of POP after delivery on women’s sexual function, quality of life (QoL), and psychological health within the first year following delivery.

Methods

A cross-sectional study was conducted with 640 female participants at obstetric clinic in 2 hospitals in Shenzhen, China.

Outcomes

All women completed following questionnaires: short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) on sexual function, Pelvic Floor Distress Inventory-20 (PFDI-20) on well-being and QoL, Symptom Checklist-90-Revised (SCL-90-R) on psychological health, and International Consultation on Incontinence Questionnaire Short Form.

Results

Women with symptomatic POP (N = 250) had higher mean scores (P < .05) than those without symptoms (N = 390) in PISQ-12, PFDI-20, and SCL-90-R domains. In the symptomatic POP group (N = 250), the sexually dysfunctional group (N = 137) had significantly higher mean scores (P < .001) than the sexually functional group (N = 113) in PISQ-12, PFDI-20, and SCL-90-R domains. Women with POP duration ≥6 months (N = 132) had significantly higher mean scores (P < .001) than women with POP duration <6 months (N = 118) in PISQ-12, PFDI-20, and SCL-90-R domains. The multiple linear regression model of PISQ-12 showed that constipation history, regular pelvic floor muscle training, parity, and symptomatic POP were independently correlated with the questionnaire score (P < .05).

Clinical Implications

The significantly pervasive nature of POP often leads to the neglect of a substantial percentage of sexual problems and related emotional suffering, emphasizing the critical importance of raising awareness about this issue among clinicians and the general public.

Strengths and Limitations

The current study brought attention to significant aspects of postpartum POP; the findings suggest issues concerning POP occurrences and their impacts on sexual function, QoL, and psychological health. Primary constraints are linked to the utilization of self-report assessments.

Conclusion

The current study reveals a robust correlation between POP in postpartum women and compromised sexual function, QoL, and psychological health.
Uncertainty-based knowing how logic
Authors: Areces Carlos , Fervari Raul , Saravia Andrés R , Velázquez-Quesada Fernando R
Published: October 2023

We introduce a novel semantics for a multi-agent epistemic operator of knowing how, based on an indistinguishability relation between plans. Our proposal is, arguably, closer to the standard presentation of knowing that modalities in classical epistemic logic. We study the relationship between this new semantics and previous approaches, showing that our setting is general enough to capture them. We also study the logical properties of the new semantics. First, we define a sound and complete axiomatization. Second, we define a suitable notion of bisimulation and prove correspondence theorems. Finally, we investigate the computational complexity of the model checking and satisfiability problems for the new logic.
Probable low-frequency quasi-periodic oscillations in blazars from the ZTF survey
Authors: Banerjee Anuvab , Negi Vibhore , Joshi Ravi , Kumar Nagendra , Wiita Paul J , Chand Hum , Rawat Nikita , Wu Xue-Bing , Ho Luis C
Published: October 2023

We investigate the possible presence of quasi-periodic oscillation (QPO) signals in 2103 blazars from the Zwicky Transient Facility (ZTF) time-domain survey. We detect a low-frequency QPO signal in five blazars observed over these 3.8-yr-long optical r-band ZTF light curves. These periods range from 144 to 196 d detected at ≳4σ significance levels in both the Lomb–Scargle periodogram and weighted wavelet Z-transform analyses. We find consistent results using the phase dispersion minimization technique. A similar peak is detected in the g-band light curves at a slightly lower significance of 3σ. Such nearly periodic signals on these time-scales in optical wavebands most likely originate from a precessing jet with high Lorentz factor, closely aligned to the observer’s line of sight or the movement of plasma blobs along a helical structure in the jet.
Phase shift between joint rotation and actuation reflects dominant forces and predicts muscle activation patterns
Authors: Sutton G P , Szczecinski N S , Quinn R D , Chiel H J
Published: October 2023

During behavior, the work done by actuators on the body can be resisted by the body's inertia, elastic forces, gravity, or viscosity. The dominant forces that resist actuation have major consequences on the control of that behavior. In the literature, features and actuation of locomotion, for example, have been successfully predicted by nondimensional numbers (e.g. Froude number and Reynolds number) that generally express the ratio between two of these forces (gravitational, inertial, elastic, and viscous). However, animals of different sizes or motions at different speeds may not share the same dominant forces within a behavior, making ratios of just two of these forces less useful. Thus, for a broad comparison of behavior across many orders of magnitude of limb length and cycle period, a dimensionless number that includes gravitational, inertial, elastic, and viscous forces is needed. This study proposes a nondimensional number that relates these four forces: the phase shift (ϕ) between the displacement of the limb and the actuator force that moves it. Using allometric scaling laws, ϕ for terrestrial walking is expressed as a function of the limb length and the cycle period at which the limb steps. Scale-dependent values of ϕ are used to explain and predict the electromyographic (EMG) patterns employed by different animals as they walk.
Ribosomal dysregulation: A conserved pathophysiological mechanism in human depression and mouse chronic stress
Authors: Zhang Xiaolu , Eladawi Mahmoud Ali , Ryan William George , Fan Xiaoming , Prevoznik Stephen , Devale Trupti , Ramnani Barkha , Malathi Krishnamurthy , Sibille Etienne , Mccullumsmith Robert , Tomoda Toshifumi , Shukla Rammohan
Published: October 2023

The underlying biological mechanisms that contribute to the heterogeneity of major depressive disorder (MDD) presentation remain poorly understood, highlighting the need for a conceptual framework that can explain this variability and bridge the gap between animal models and clinical endpoints. Here, we hypothesize that comparative analysis of molecular data from different experimental systems of chronic stress, and MDD has the potential to provide insight into these mechanisms and address this gap. Thus, we compared transcriptomic profiles of brain tissue from postmortem MDD subjects and from mice exposed to chronic variable stress (CVS) to identify orthologous genes. Ribosomal protein genes (RPGs) were down-regulated, and associated ribosomal protein (RP) pseudogenes were up-regulated in both conditions. A seeded gene co-expression analysis using altered RPGs common between the MDD and CVS groups revealed that down-regulated RPGs homeostatically regulated the synaptic changes in both groups through a RP-pseudogene-driven mechanism. In vitro analysis demonstrated that the RPG dysregulation was a glucocorticoid-driven endocrine response to stress. In silico analysis further demonstrated that the dysregulation was reversed during remission from MDD and selectively responded to ketamine but not to imipramine. This study provides the first evidence that ribosomal dysregulation during stress is a conserved phenotype in human MDD and chronic stress-exposed mouse. Our results establish a foundation for the hypothesis that stress-induced alterations in RPGs and, consequently, ribosomes contribute to the synaptic dysregulation underlying MDD and chronic stress-related mood disorders. We discuss the role of ribosomal heterogeneity in the variable presentations of depression and other mood disorders.
Feasibility of Low-Load Resistance Training Using Blood Flow Restriction for People With Advanced Multiple Sclerosis: A Prospective Cohort Study
Authors: Mañago Mark M , Cohen Evan T , Alvarez Enrique , Hager Emily R , Owens Johnny G , Bade Michael
Published: October 2023

Objective

The objective of this study was to determine the feasibility of low-load resistance training with blood flow restriction (BFR) for people with advanced disability due to multiple sclerosis (MS).

Methods

In this prospective cohort study, 14 participants with MS (Expanded Disability Status Scale [EDSS] score = 6.0 to 7.0; mean age = 55.4 [SD = 6.2] years; 71% women) were asked to perform 3 lower extremity resistance exercises (leg press, calf press, and hip abduction) bilaterally twice weekly for 8 weeks using BFR. Feasibility criteria were as follows: enrollment of 20 participants, ≥80% retention and adherence, ≥90% satisfaction, and no serious adverse events related to the intervention. Other outcomes included knee extensor, ankle plantar flexor, and hip abductor muscle strength, 30-Second Sit-to-Stand Test, Berg Balance Scale, Timed 25-Foot Walk Test, 12-Item MS Walking Scale, Modified Fatigue Impact Scale, Patient-Specific Functional Scale, and daily step count.

Results

Sixteen participants consented, and 14 completed the intervention, with 93% adherence overall. All participants were satisfied with the intervention. A minor hip muscle strain was the only intervention-related adverse event. There were muscle strength improvements on the more-involved (16%–28%) and less-involved (12%–19%) sides. There were also changes in the 30-Second Sit-to-Stand Test (1.9 repetitions; 95% CI = 1.0 to 2.8), Berg Balance Scale (5.3 points; 95% CI = 3.2 to 7.4), Timed 25-Foot Walk Test (−3.3 seconds; 95% CI = −7.9 to 1.3), Modified Fatigue Impact Scale (−8.8 points; 95% CI = −16.5 to −1.1), 12-Item MS Walking Scale (−3.6 points; 95% CI = −11.5 to 4.4), Patient-Specific Functional Scale (2.9 points; 95% CI = 1.9 to 3.8), and daily step count (333 steps; 95% CI = −191 to 857).

Conclusion

Low-load resistance training using BFR in people with MS and EDSS scores of 6.0 to 7.0 appears feasible, and subsequent investigation into its efficacy is warranted.

Impact

Although efficacy data are needed, combining BFR with low-load resistance training may be a viable alternative for people who have MS and who do not tolerate conventional moderate- to high-intensity training because of more severe symptoms, such as fatigue and weakness.

Lay Summary

Low-load strength training with BFR was feasible in people who have advanced disability due to MS. Using BFR may provide an alternative for people with MS who do not tolerate higher intensity training due to more severe symptoms, such as fatigue and weakness.
Taxifolin inhibits NETosis through activation of Nrf2 and provides protective effects in models of lupus and antiphospholipid syndrome
Authors: Rysenga Christine E , May-Zhang Linda , Zahavi Miela , Knight Jason S , Ali Ramadan A
Published: October 2023

Objectives

Taxifolin (dihydroquercetin) is a bioactive plant flavonoid that exhibits anti-inflammatory and anti-oxidative properties. We hypothesized that taxifolin might be an effective dietary supplement to ameliorate symptoms arising from thrombo-inflammatory diseases such as lupus and APS.

Methods

We used in vitro assays and a mouse model to determine mechanisms by which taxifolin inhibits neutrophil extracellular trap (NET) formation (i.e. NETosis) and venous thrombosis in lupus and APS.

Results

At doses ranging from 0.1 to 1 µg/ml, taxifolin inhibited NETosis from control neutrophils stimulated with autoantibodies isolated from lupus and APS patients, and its suppressive effects were mitigated by blocking the antioxidant transcription factor Nrf2 (nuclear factor erythroid 2–related factor 2). Furthermore, taxifolin at a dose as low as 20 mg/kg/day reduced in vivo NETosis in thrombo-inflammatory mouse models of lupus and APS while also significantly attenuating autoantibody formation, inflammatory cytokine production and large-vein thrombosis.

Conclusion

Our study is the first to demonstrate the protective effects of taxifolin in the context of lupus and APS. Importantly, our study also suggests a therapeutic potential to neutralize neutrophil hyperactivity and NETosis that could have relevance to a variety of thrombo-inflammatory diseases.
Metabolome Revealed the Potential Mechanism of Fusarium Wilt Resistance in Bitter Gourd (Momordica charantia) Based on Liquid Chromatography with Mass Spectrometry
Authors: Guan Feng , Shi Bo , Zhang Jiangyun , Wan Xinjian
Published: October 2023

Fusarium wilt fungus infection of bitter gourd, a major melon vegetable crop, results in massive yield reduction. Through extensive testing, some Fusarium wilt-resistant bitter melon varieties have been produced, but the molecular mechanism of their resistance to the fungus remains unknown. Importantly, after bitter melon plants are infected with Fusarium oxysporum f. sp. momordicae (FOM), apart from altering their gene expression levels, numerous metabolites are produced because of the interaction with the fungus. In the current study, an untargeted metabolomics analysis was performed to investigate the metabolic difference between resistant and susceptible bitter gourd varieties at various timepoints postinoculation with FOM based on liquid chromatography with mass spectrometry. A total of 1,595 positive ion mode and 922 negative ion mode metabolites were identified. Between the resistant and susceptible bitter gourd varieties, 213 unique differentially abundant metabolites (DAMs) were identified, and they were mainly enriched in the alpha-linolenic acid metabolism pathway. By comparing the postinoculation with preinoculation timepoints in the resistant and susceptible bitter gourd varieties, 93 and 159 DAMs were identified, respectively. These DAMs were mainly related to beta-alanine metabolism, among others. Multiple metabolites in the biosynthesis of the phenylpropanoid pathway showed greater variability in the susceptible than the resistant varieties, which may be related to senescence and mortality in the susceptible variety. These results provide new insights into the understanding of metabolite changes after FOM infection and a theoretical foundation for the elucidation of the bitter gourd disease resistance mechanism.
Insurance Denial of Care for Randomized Controlled Trial-Eligible Patients
Authors: McClelland Shearwood , Brately Melissa , Zuhour Raed J. , Sun Yilun , Spratt Daniel E.
Published: October 2023

Introduction:

Insurance denials for clinical trials serve as a pertinent barrier for patients to remain trial-eligible, thus hindering the development of therapies and the overall advancement of health care. We present results from an ongoing oncology randomized clinical trial regarding insurance denials and peer-to-peer authorization (P2PA) success rate in allowing patients to remain trial-eligible.

Methods:

The ongoing Spine Patient Optimal Radiosurgery Treatment for Symptomatic Metastatic Neoplasms Phase II trial randomizes spine cancer patients to treatment with spine radiosurgery/stereotactic body radiation therapy (SBRT) versus conventional external beam radiation therapy (EBRT). Trial-eligible patients during the first 3 months of enrollment are examined to determine whether the option of SBRT was denied by their insurance. Advocacy for overcoming SBRT denial in P2PA centered on SBRT being recommended as a preferred treatment modality in the National Comprehensive Cancer Network guidelines, and the recent level I evidence demonstrating the advantages of SBRT over EBRT for symptomatic spine cancer.

Results:

Of 15 trial-eligible patients, 3 (20%) experienced insurance denials for SBRT. P2PA resulted in the reversal of denials in all 3 patients, allowing each to remain trial-eligible for randomization between SBRT and cEBRT.

Conclusions:

Despite a clinical oncologic treatment modality for which recent Level 1 evidence is available, the insurance denial rate was 20%. A vigilant P2PA strategy focusing on highlighting National Comprehensive Cancer Network guidelines and the supporting Level 1 evidence resulted in a very high rate of reversing initial denial.
A Novel Machine Learning Approach to Predict Textbook Outcome in Colectomy
Authors: Ashraf Ganjouei Amir , Romero-Hernandez Fernanda , Conroy Patricia C. , Miller Phoebe , Calthorpe Lucia , Wang Jaeyun Jane , Lin Jackie , Feng Jean , Kirkwood Kimberly S. , Alseidi Adnan , Sarin Ankit , Adam Mohamed A.
Published: October 2023

BACKGROUND:

Several calculators exist to predict risk of postoperative complications. However, in low-risk procedures such as colectomy, a tool to determine the probability of achieving the ideal outcome could better aid clinical decision making, especially for high-risk patients. A textbook outcome is a composite measure that serves as a surrogate for the ideal surgical outcome.

OBJECTIVE:

To identify the most important factors for predicting textbook outcome in patients with non-metastatic colon cancer undergoing colectomy and to create a textbook outcome decision support tool using machine learning algorithms.

DESIGN:

This was a retrospective analysis study.

SETTINGS:

Data were collected from the American College of Surgeons National Quality Improvement Program database.

PATIENTS:

Adult patients undergoing elective colectomy for non-metastatic colon cancer (2014-2020) were included

MAIN OUTCOME MEASURES:

Textbook outcome was the main outcome, defined as no mortality, no 30-day readmission, no postoperative complications, no 30-days reinterventions, and a hospital length of stay ≤5 days. Four models (logistic regression, decision tree, random forest, and XGBoost) were trained and validated. Ultimately, a web-based calculator was developed as proof-of-concept for clinical application.

RESULTS:

A total of 20,498 patients who underwent colectomy for non-metastatic colon cancer were included. Overall, textbook outcome was achieved in 66% of patients. Textbook outcome was more frequently achieved after robotic colectomy (77%), followed by laparoscopic colectomy (68%), and open colectomy (39%, p < 0.001). XGBoost was the best performing model (AUC = 0.72). The top 5 preoperative variables to predict textbook outcome were surgical approach, patient age, preoperative hematocrit, preoperative oral antibiotic bowel preparation, and female sex.

LIMITATIONS:

This study was limited by its retrospective nature of the analysis.

CONCLUSIONS:

Using textbook outcome as the preferred outcome may be a useful tool in relatively low-risk procedures such as colectomy and the proposed web-based calculator may aid surgeons in preoperative evaluation and counseling, especially for high-risk patients.
Home-Use Hyaluronic Acid Jet Injectors: Unreliable and Unsafe
Authors: Juch Rosalie N. S. , Bik Liora , Boeijink Neill , de Vos Judith , Dobbe Iwan J. G. G. , Bloemen Paul R. , van Doorn Martijn B. A. , Velthuis Peter , Aalders Maurice C. G. , Wolkerstorfer Albert
Published: October 2023

BACKGROUND

Needle-free hyaluronic acid (HA) jet injectors are gaining popularity for rejuvenation treatment. The devices are widely available online and are used for self-injection or in beauty salons by nonphysicians. However, little is known about their performance and safety.

OBJECTIVE

To explore the injection efficiency and cutaneous biodistribution patterns administered with home-use compared with medical jet injectors and to assess safety aspects.

MATERIALS AND METHODS

The authors injected HA into ex vivo human skin with 4 home-use and 2 medical injectors. The intracutaneous dose of HA was calculated, and the cutaneous biodistribution of HA was assessed using a 3-dimensional Fluorescent Imaging Cryomicrotome System (3D-FICS). Safety aspects were evaluated based on the presence of a manual, CE (conformité européenne) mark, and sterility.

RESULTS

The intracutaneous dose delivered by the home-use injectors was markedly lower compared with the medical injectors. 3D imaging for home-use injectors showed superficial epidermal distribution with low distribution volumes. For medical injectors, volumes were substantially larger and mainly middermal. All evaluated safety aspects were lacking.

CONCLUSION

Results of this study suggest that the specific combinations of home-use injectors and HA used in this study are unreliable and unsafe, which casts doubts on the performance of these treatments in general.
Evaluation and Management of Pericarditis in Rheumatic Diseases
Authors: Kawano Yumeko , Pabón Maria A. , Feldman Candace H. , Cuddy Sarah , Lilly Leonard S. , Garshick Michael S. , Weber Brittany
Published: October 2023

This review summarizes the evaluation for underlying rheumatic conditions in patients presenting with acute pericarditis, treatment considerations for specific rheumatic conditions, and the role of imaging in diagnosis and monitoring. Pericarditis may be one of the initial presentations of a rheumatic disease or identified in a patient with known rheumatic disease. There is also growing evidence for using anti-inflammatory and immunosuppressive agents for treating recurrent pericarditis, which can overlap with the treatment of rheumatic diseases.
Interleukin-1 Inhibition for the Prevention and Treatment of Heart Failure
Authors: Jafree Ehsan , Del Buono Marco Giuseppe , Canada Justin M. , Carbone Salvatore , Kron Jordana , Arena Ross , Van Tassell Benjamin , Abbate Antonio , Trankle Cory R.
Published: October 2023

Heart failure (HF) is a complex syndrome that remains a leading cause of morbidity and mortality worldwide. Abundant evidence suggests inflammation plays a key role in the development and perpetuation of HF, but there are currently no anti-inflammatory treatments approved for use in HF. Interleukin-1, the prototypical proinflammatory cytokine, has been implicated in adverse cardiac remodeling and left ventricular dysfunction. Multiple early phase clinical trials using interleukin-1 blockade in patients at risk for or diagnosed with HF have suggested favorable safety and efficacy in reducing inflammatory biomarkers, as well as positive signals in surrogate and clinical end points. Additional large scale clinical trials are urgently needed to confirm the safety and efficacy of this therapeutic approach specifically in HF. In this narrative review, we discuss current evidence regarding interleukin-1 blockade in the prevention and treatment of HF.