bluuebunny/crossref_metadata_2025 huggingface dataset:
Empirical study on the impact of the digital economy on the efficiency of agricultural product circulation under the dual carbon goals
Authors: Luo Qianwen , Wang Yujie , Chen Bo
Published: July 2024

Under the dual carbon goals, it has become an urgent practical issue to enhance the efficiency of agricultural product circulation while reducing environmental damage. This paper first constructs a theoretical model to analyze the relationship between the digital economy, green technological innovation, and agricultural product circulation efficiency. Based on panel data from 29 provinces in China (excluding Hong Kong, Macao, Taiwan, Tibet, and Hainan) from 2015 to 2021, this study utilizes a two-way fixed-effects model and a threshold regression model to analyze the impact of the digital economy on agricultural product circulation efficiency. Meanwhile, the mediating role of green technological innovation is explored in-depth through a mediating effect model. The results indicate that regional heterogeneity exists at the development level of the digital economy and in the efficiency of agricultural product circulation. The digital economy can significantly enhance the efficiency of agricultural product circulation, and green technological innovation plays a mediating role in this process. The impact of the digital economy on agricultural product circulation efficiency exhibits a dual threshold effect, where the promotion effect weakens after crossing two threshold values. Finally, this paper proposes countermeasures based on regional development status, including strengthening the application of the digital economy in agricultural product circulation, promoting green technological innovation, and reducing the thresholds for digital economy development.
Experimental study of the effect of the addition of Posidonia Oceanica fiber on the thermal and acoustic insulation properties of plaster
Authors: Jedidi Malek
Published: July 2024

In this work, plaster and natural Posidonia Oceanica (PO) fibers are combined to create a composite material that was recently produced. This work’s primary objective is to assess the mechanical and thermophysical performance of the composite material in order to determine whether or not it may be used as a thermal and acoustic insulation material in buildings. For this end, prismatic and parallelepipedic specimens of different dimensions were made with fiber percentages ranging from 0% to 20%. In addition, parallelepiped panels (600 mm × 600 mm × 40 mm3) were also prepared containing 10% of PO fibers. Mechanical properties (flexual strength, compressive strength), thermal properties and sound absorption coefficient were investigated. For each test specimen, the density was calculated for a proportion of fibers ranging from 0% to 20%. The results indicated a marked improvement in the compressive and flexural strength of the fiber-reinforced mixtures. This improvement is respectively 14.5% and 33.8% for mixtures containing 10% of PO fibers. Additionally, the addition of PO fibers significantly decreases density (by 40.5%), thermal conductivity (by 68.5%) and thermal diffusivity (by 36.9%) of the different mixtures. The ideal mechanical characteristics are attained when 5%–10% of the volume is made up of Posidonia Oceanica fibers. The results of the sound absorption coefficient test show that the mixture of plaster with 10% fibers has a good sound absorption coefficient of 0.78 for high frequencies between 1000 Hz and 4000 Hz. This work has shown conclusively that the incorporation of PO fibers, up to a maximum of 10% with plaster, makes it possible to obtain a lightweight composite that can potentially be used as a new insulating construction material.
AEDN-YOLO: an efficient one-stage detection network for strip steel surface defects
Authors: Wei Mingjun , Chen Beilong , Liu Jianuo , Yuan Na , Liu Jinyun , Ji Zhanlin
Published: July 2024

Steel surface defect detection is one of the key tasks in industrial production and quality control. Research on defect detection using deep learning algorithms has shown promising results. However, due to the complex backgrounds, large differences in defect sizes, and diverse defect types present in steel strip surface defect images, existing deep learning algorithms struggle to achieve precise detection. To address these challenges, this paper proposes an efficient detection model named AEDN-YOLO. Firstly, an adaptive feature extraction (AFE) module is designed, embedded into C2f to better capture irregularly shaped objects. Secondly, the Triplet Attention module is incorporated into the bottom layer of the backbone network to enhance the model’s ability to locate defect features accurately. Additionally, replace the standard convolution in the neck network with GSConv, which not only accelerates feature fusion to improve detection speed but also enlarges the model’s receptive field to enhance detection accuracy. Finally, add a small target detection layer to enhance the detection capability for tiny defects. The model achieves mAP of 81.7% and 72.7% on the NEU-DET and GC10-DET datasets, respectively, with a detection speed of 72.1 FPS. Compared to mainstream defect detection algorithms, the proposed algorithm enables accurate and efficient detection of steel surface defects.
A review of optimization of energy involved in rolling stock of a sub-urban rail transport system
Authors: Ishaq Mohammad , Shukla Praveen Kumar , Ashfaq Haroon
Published: July 2024

Railway systems stand out as highly efficient modes of transportation compared to others, leading to a rising demand for the sake of research and development aimed at reducing their energy consumption. This pursuit not only enhances sustainability but also addresses the pressing issue of climate change. A multitude of studies delve into modeling, analyzing, and optimizing energy usage within railway systems, showcasing a diverse array of methodologies and techniques for formulating, and solving optimization problems. This review paper undertakes a comparative examination of approximately 36 relevant studies focusing on railway energy consumption encompassing both traction and auxiliary energy. The research emphasizes various modeling techniques employed in simulating train movement and energy consumption; alongside different optimization methods focused at improving operational efficiency on railway tracks. It meticulously scrutinizes the most prevalent optimization methods, techniques and variables are utilized. Through an extensive review of literature, it becomes apparent that deterministic approaches, particularly based on the Davis equations, dominate the modeling landscape, accounting for over 80% of the approaches. However, when it comes to optimization, meta-heuristic approaches take precedence, with Genetic Algorithms being a prominent choice. These findings underscore the significance of meta-heuristic approaches, crucial for enhancing both human activities and mitigating energy consumption, especially in a heavy energy-consuming sector like railway transportation.
Trainability issues in quantum policy gradients
Authors: Sequeira André , Paulo Santos Luis , Soares Barbosa Luis
Published: July 2024

This research explores the trainability of Parameterized Quantum Circuit-based policies in Reinforcement Learning, an area that has recently seen a surge in empirical exploration. While some studies suggest improved sample complexity using quantum gradient estimation, the efficient trainability of these policies remains an open question. Our findings reveal significant challenges, including standard Barren Plateaus with exponentially small gradients and gradient explosion. These phenomena depend on the type of basis-state partitioning and the mapping of these partitions onto actions. For a polynomial number of actions, a trainable window can be ensured with a polynomial number of measurements if a contiguous-like partitioning of basis-states is employed. These results are empirically validated in a multi-armed bandit environment.
Using syndromic surveillance to rapidly assess the impact of a June 2023 wildfire smoke event on respiratory-related emergency department visits, Massachusetts, United States
Authors: Fitzsimmons Kathleen , Mahin Maya , Parikh Megha , Ergas Rosa , Guo Jing , Warner Michelle , Pacheco Michelle , Sparer-Fine Emily
Published: July 2024

A statewide air quality advisory was issued in Massachusetts for 6–7 June 2023 due to smoke originating from wildfires in Canada. Of particular concern was fine particulate matter, which has an aerodynamic diameter of ⩽2.5 μm (PM2.5) and has been linked to adverse respiratory outcomes. The objective of this study was to rapidly assess the impact of this wildfire smoke event on respiratory-related emergency department (ED) visits among Massachusetts residents. For exposure, daily air quality index (AQI) data from the US Environmental Protection Agency were used. Massachusetts counties, where for each day from 6 to 8 June 2023, the daily AQI was ⩾101 (i.e. unhealthy air quality), were considered exposed. For each exposed period, two unexposed reference periods where AQI < 101 (i.e. ‘good’ or ‘moderate’ air quality) were identified within the two weeks prior to the exposed period, with the same days of the week and in the same county. Data from the Massachusetts Department of Public Health’s syndromic surveillance system were used to examine daily counts of ED visits for asthma, air-quality-related respiratory illness, and all causes by county of residence, age group, race, and Hispanic/Latino ethnicity. For each outcome, the numbers of ED visits were compared between the exposed and reference periods. Overall, there were no large increases in ED visits for any conditions examined during this wildfire smoke event. However, residents who were aged 18–64 years, Hispanic/Latino or White experienced small but not statistically significant increases in asthma-related ED visits. These potential differences in the effect on asthma-related ED visits by age and race/ethnicity may be relevant for analyses of future events. This study provides an example of how real-time, publicly available exposure data can be used in conjunction with outcome data from syndromic surveillance to rapidly examine the impact of wildfires and other acute environmental events on health.
Centralized Administration in Ukraine for Ukraine
Authors: Kibita Nataliya
Published: July 2024

The 1917 February Revolution opened a window of opportunity to establish a centralized Ukrainian administration and form Ukrainian gubernias into one polity. In the period between the February Revolution and spring 1918, all main political parties active in Ukraine, including the Bolsheviks, understood the political benefits of a Kyiv-based administration. In 1918–1919, Ukraine-based Bolsheviks focused their efforts on persuading the resistant Russian Bolshevik leadership to accept Ukraine as a separate administrative unit that needed a territorial administration. Lenin’s acceptance of the Ukrainian Socialist Soviet Republic generated an expectation of genuine administrative self-government among Ukrainian Bolshevik leaders, legitimized their claims for policymaking authority, and thus created a new dynamic in the relationship between the latter and the Russian Bolshevik leadership. The chapter illustrates that in the case of Bolshevism, the struggle for the same ideas did not equate to the struggle for the interests of the same institutions.
‘The More We Centralize, the Less Order There Is in the State’
Authors: Kibita Nataliya
Published: July 2024

With the break-up of the Soviet Union, the new dual executive branch of Ukraine faced the urgent task of establishing de facto control over the Ukrainian economy and the regions. However, to accomplish this task, the executive branch chose the old Soviet diktat. It focused on extracting resources from the regions through administrative control over the economy, while neglecting active regional policy. It continued to prioritize heavy industry and maintained nearly full control over agriculture. The executive branch was wrong to assume that the regions would accept Kyiv’s diktat unconditionally. Throughout 1992–1994, the regions continued explaining to the government that the command-administrative methods was not the way to consolidate either centralized control over the economy in Ukraine or Ukrainian statehood. Instead, argued the regions, Kyiv should focus on market reforms, install transparent mechanisms for implementing central policies and laws, and build the economy from the bottom up by prioritizing the needs of the regions and producers. For objective reasons, regionalism was unavoidable. But it was up to the Ukrainian leadership to convince the regions to accept its authority, rather than for the regions to unconditionally accept Kyiv’s diktat. In 1992–1994, institutional inertia prevailed, and the old dilemma of how to distribute power between the Ukrainian centre and the regions remained unresolved.
Legal Realism in France
Authors: Troper Michel
Published: July 2024

Realism has acquired in France some characteristics that, without contrasting it with Italian realism, distinguish it significantly from it. First, it is a radically skeptical version of the realist theory of interpretation, namely the idea that it is only through legal interpretation that a meaning is determined, so that before an interpretation has taken place a text has no meaning at all. This goes against the common idea that a text has several possible meanings among which the interpreter makes a choice. It also goes against the idea that the interpreter is bound by some norm, at least the norm that empowers it to give an interpretation, because that norm too is a product of an interpretation. Second, the French version of realism proposes to extend the theory of interpretation not only to texts but to facts. Third, it contends that the hierarchy of norms is a product of legal interpretation. Finally, French realism argues that, while any interpretation by an authentic interpreter is valid, most interpreters do not act out of sheer whim or ideology because they are subject to specific causal influences and constraints.
Einstein's Entanglement
Authors: Stuckey W M , Silberstein Michael , McDevitt Timothy
Published: July 2024

Einstein introduced quantum entanglement in 1935 and referred to it as “spooky actions at a distance” because it seemed to conflict with his theory of special relativity. Today, some refer to it as “the greatest mystery in physics,” and the 2022 Physics Nobel Prize was even awarded for experimental confirmation of the “spookiness.” While the mystery is experimentally well established, its solution remains elusive because it is commonly believed that quantum entanglement entails one or more of the following:

In this book, a rigorous solution to the mystery of quantum entanglement is provided that entails none of those things. The key to this seemingly impossible feat is—to use Einstein’s own language—a “principle” explanation that foregoes the need for any “constructive” explanation of quantum entanglement, such as those listed above. Ironically, the proposed principle explanation is Einstein’s own relativity principle as grounded in quantum information theory. So, contrary to popular belief, quantum mechanics and special relativity are far from inconsistent, as both are a consequence of the exact same relativity principle.
Preface
Authors: Stuckey W M , Silberstein Michael , McDevitt Timothy
Published: July 2024

The 2022 Nobel Prize in Physics was awarded “for experiments with entangled photons, establishing the violation of Bell inequalities” that have created tremendous confusion among physicists and philosophers about “how Nature works.” With the violation of Bell inequalities due to quantum entanglement (hereafter just “entanglement”), we now know that Einstein’s view of a universe that functions exclusively according to locally real causal mechanisms is wrong. Ironically, we propose to replace Einstein’s desired “constructive” explanation of entanglement with a “principle” explanation based on his own relativity principle. In other words, we solve Einstein’s mystery of entanglement just like Einstein solved the mystery of length contraction, i.e., using the relativity principle. Chapters that can be skipped based on the interests and background of the reader are recommended.
A Principle Response from Quantum Information Theorists
Authors: Stuckey W M , Silberstein Michael , McDevitt Timothy
Published: July 2024

Chapter 6 explains the axiomatic reconstruction of QM via information-theoretic principles. Hardy’s reconstruction is featured because it shows that the quantum probability theory of QM obtains by adding the word “continuous” to the fifth axiom of classical probability theory. As explained in Chapter 0, continuity is responsible for superposition, so the quantum bit (qubit) differs from the classical bit because the states of a qubit are superpositions. The Planck postulate is shown to follow from Brukner and Zeilinger’s principle of Information Invariance & Continuity at the foundation of their reconstruction, so QM can be understood as a principle theory based on NPRF + h. We show that ‘average-only’ projection is one way to characterize the ‘weirdness’ of the qubit. Grinbaum’s reconstruction based on relational quantum mechanics is introduced.
Superquantum Probabilities: Why No PR-Box?
Authors: Stuckey W M , Silberstein Michael , McDevitt Timothy
Published: July 2024

Chapter 8 introduces Popescu and Rohrlich’s no-signalling PR-box of superquantum joint probabilities violating the CHSH Bell inequality more strongly than QM. We present Mermin’s derivation of the CHSH Bell inequality. Using Tanya and Jeff Bub’s quantum guessing game, we show how the PR-box violates conservation per NPRF whence Bell state entanglement. This is shown to be the reason the PR-box violates the CHSH-Bell inequality more strongly than QM. Therefore, we conclude that the PR-box is akin to a perpetual motion machine.
What’s Really Going On?
Authors: Stuckey W M , Silberstein Michael , McDevitt Timothy
Published: July 2024

In Chapter 9 we answer Zeilinger’s question, “What’s really going on?” concerning how Nature works. In other words, we present an ontology over which the constraints NPRF + h and NPRF + c range and operate. We contrast contextuality with reductionism and relationalism, then discuss relational quantum mechanics. We explain our version of multiscale contextual emergence called quantum-classical contextuality. Accordingly, bodily (classical) objects interact via the exchange of quanta of energy-momentum. NPRF + c constrains the distribution of worldtubes of bodily objects in spacetime while NPRF + h constrains the distribution of quanta exchanged between bodily objects. Thus, NPRF + h is an “all-at-once” or “atemporal” constraint on the distribution of quanta among bodily objects in spacetime. We call such a constraint an adynamical global constraint (AGC). Feynman’s path integral formalism for QM is contrasted with Schrödinger’s equation. We present our Poincaré symmetric ontology.
Interpreting Quantum Mechanics in a Realist Fashion
Authors: Stuckey W M , Silberstein Michael , McDevitt Timothy
Published: July 2024

In Sub-Chapter 9A we explain what makes an interpretation of QM realist and how our interpretation of QM is realist and psi-epistemic. We contrast this with relational quantum mechanics. What is fundamental in our interpretation is 4D quantum–classical contextuality as given by “all-at-once” AGCs.
Young Adult Patient and Caregiver Perspectives on Transition Readiness in an Inflammatory Bowel Disease Clinic
Authors: Strobel Thomas M , Narayani Nikita A , Nicholson Maribeth R , Riera Diana C , Rakos Tanner G , Fulton Nisa P , Trotter-Busing Jordan A , Horst Sara N , Dalal Robin L , Pabla Baldeep S , Scoville Elizabeth A , Schwartz David A , Beaulieu Dawn B
Published: July 2024

Background

When it comes to readiness to transition to an adult subspecialty clinic, perspectives between patients with inflammatory bowel disease (IBD) and their caregivers may differ and influence the ability to successfully transition. Patients with IBD have been shown to suffer from poor transfers of care. There is a need to more efficiently and accurately assess transition readiness to improve the transfer process.

Methods

Patients transferring to an adult subspecialty clinic and their caregivers were each administered the Transition Readiness Assessment Questionnaire and IBD Self-Efficacy Scale—Adolescent. Differences between patient and caregiver responses and agreement among each dyad were tested.

Results

There were 29 dyads of patients and caregivers who enrolled. There was no difference between patient and caregiver total scores. The average level of agreement between patients and caregivers was 78%. There was no association between patient response and their age, gender, ethnicity, age at time of transfer, age at diagnosis, or number of emergency room visits in the prior year.

Conclusions

Patient-reported readiness to transition to adult care was confirmed by their caregivers using validated readiness assessment tools. As transition clinics must focus on high-yield interventions, a readiness survey of young adult patients without a survey of their caregivers may be adequate. However, as experts in each patient’s journey, caregivers may be utilized when setting goals and priorities for a transition readiness program. The surveys used in this study can be used broadly to aid subspecialty clinics that are trying to improve the transition process.
Enigmatic Pachytene PIWI-Interacting RNAs
Authors: Xu Ming-Min , Li Xin Zhiguo
Published: July 2024

PIWI-interacting RNAs (piRNAs), a class of small RNAs, are renowned for their roles in sequencing-dependent targeting and suppressing transposable elements (TEs). Nevertheless, a majority of mammalian piRNAs, expressing at pachytene stage of meiosis, known as pachytene piRNAs, are devoid of discernible targets, casting a veil of enigma over their functional significance. Overturning the notion that this unusual class of piRNAs functions beyond TE silencing, we recently demonstrated that pachytene piRNAs play an essential and conserved role in silencing young and actively transposing TEs across amniotes. However, only 1% of pachytene piRNAs target active TEs. The biological significance of the abundant non-TE piRNAs, coproduced from the same precursors as TE piRNAs, remains unclear. Here, we provide a comprehensive summary of the potential roles of non-TE piRNAs, and thus propose that these non-TE piRNAs either bolster the action of TE piRNAs or provide the host genome a preexisting mechanism to suppress the potential invasion of novel TEs in the future.
The Young and the Resilient: Investigating Coral Thermal Resilience in Early Life Stages
Authors: Walker Nia S , Isma Lys , García Nepsis , True Aliyah , Walker Taylor , Watkins Joyah
Published: July 2024

Synopsis

Global ocean warming is affecting keystone species distributions and fitness, resulting in the degradation of marine ecosystems. Coral reefs are one of the most diverse and productive marine ecosystems. However, reef-building corals, the foundational taxa of coral reef ecosystems, are severely threatened by thermal stress. Models predict 40–80% of global coral cover will be lost by 2100, which highlights the urgent need for widespread interventions to preserve coral reef functionality. There has been extensive research on coral thermal stress and resilience, but 95% of studies have focused on adult corals. It is necessary to understand stress during early life stages (larvae, recruits, and juveniles), which will better inform selective breeding programs that aim to replenish reefs with resilient stock. In this review, we surveyed the literature on coral thermal resilience in early life stages, and we highlight that studies have been conducted on relatively few species (commonly Acropora spp.) and in limited regions (mainly Australia). Reef-building coral management will be improved by comprehensively understanding coral thermal resilience and fitness across life stages, as well as in diverse species and regions.
Pathogenesis of IgA nephropathy as a tissue-specific autoimmune disease
Authors: Nihei Yoshihito , Kitamura Daisuke
Published: July 2024

Glomerulonephritis (GN) is a group of heterogeneous immune-mediated kidney diseases that causes inflammation within the glomerulus. Autoantibodies (auto-Abs) are considered to be central effectors in the pathogenesis of several types of GN. Immunoglobulin A nephropathy (IgAN) is the most common GN worldwide and is characterized by the deposition of IgA in the glomerular mesangium of the kidneys, which is thought to be mediated by immune complexes containing non-specific IgA. However, we recently reported that IgA auto-Abs specific to mesangial cells (anti-mesangium IgA) were found in the sera of gddY mice, a spontaneous IgAN model, and patients with IgAN. We identified two autoantigens (β2-spectrin and CBX3) that are selectively expressed on the mesangial cell surface and targeted by anti-mesangial IgA. Our findings redefined IgAN as a tissue-specific autoimmune disease. Regarding the mechanisms of production of anti-mesangium IgA, studies using gddY mice have revealed that the production of anti-CBX3 IgA is induced by particular strains of commensal bacteria in the oral cavity, possibly through their molecular mimicry to CBX3. Here, we discuss a new concept of IgAN pathogenesis from the perspective of this disease as autoimmune GN caused by tissue-specific auto-Abs.
Antibacterial characteristics and mechanistic insights of combined tea polyphenols, Nisin, and epsilon-polylysine against feline oral pathogens: a comprehensive transcriptomic and metabolomic analysis
Authors: Bai Huasong , Liu Tong , Wang Hengyan , Wang Zhanzhong
Published: July 2024

Aims

This study evaluates the antibacterial characteristics and mechanisms of combined tea polyphenols (TPs), Nisin, and ε-polylysine (PL) against Streptococcus canis, Streptococcus minor, Streptococcus mutans, and Actinomyces oris, common zoonotic pathogens in companion animals.

Methods and results

Pathogenic strains were isolated from feline oral cavities and assessed using minimum inhibitory concentration (MIC) tests, inhibition zone assays, growth kinetics, and biofilm inhibition studies. Among single agents, PL exhibited the lowest MIC values against all four pathogens. TP showed significant resistance against S. minor, and Nisin against S. mutans. The combination treatment (Comb) of TP, Nisin, and PL in a ratio of 13:5:1 demonstrated broad-spectrum antibacterial activity, maintaining low MIC values, forming large inhibition zones, prolonging the bacterial lag phase, reducing growth rates, and inhibiting biofilm formation. RNA sequencing and metabolomic analysis indicated that TP, Nisin, and PL inhibited various membrane-bound carbohydrate-specific transferases through the phosphoenolpyruvate-dependent phosphotransferase system in S. canis, disrupting carbohydrate uptake. They also downregulated glycolysis and the citric acid cycle, inhibiting cellular energy metabolism. Additionally, they modulated the activities of peptidoglycan glycosyltransferases and d-alanyl-d-alanine carboxypeptidase, interfering with peptidoglycan cross-linking and bacterial cell wall stability.

Conclusions

The Comb therapy significantly enhances antibacterial efficacy by targeting multiple bacterial pathways, offering potential applications in food and pharmaceutical antimicrobials.
Determination of Toxic Elements in Botanical Dietary Supplement Ingredient Reference Materials
Authors: Fong Sam Jennifer , Kuszak Adam J , Gray Patrick J , Wise Stephen A
Published: July 2024

Background

The National Institute of Standards and Technology (NIST) has produced over 40 botanical dietary supplement Standard Reference Materials (SRMs) and reference materials (RMs) with values assigned for chemical markers and/or active compounds. Although environmental accumulation or inadvertent introduction of toxic elements (arsenic, cadmium, lead, and mercury) is a potential source of exposure in botanical dietary supplement products, the majority of the dietary supplement SRMs/RMs do not have values assigned for the four major toxic elements.

Objective

To determine As, Cd, Pb, and Hg content in the current inventory of NIST botanical dietary supplement SRMs/RMs.

Methods

Fifteen SRMs/RMs suites of plant part, extract, and finished products (i.e., solid oral dosage form [SODF]) were analyzed for As, Cd, Pb, and Hg using nitric acid microwave-assisted digestion followed by quantification using inductively coupled plasma–mass spectrometry.

Results

Results for control samples were in good agreement with certified values indicating that the analyses of 38 individual botanical SRMs/RMs were in control. Characterization of linked plant/extract SRMs/RMs derived from the same source materials demonstrated that while extraction processes can often yield extracts with lower toxic element content for Hg or As, it is also possible for mass fraction levels to remain unchanged or even to increase after extraction.

Conclusions

The results fill significant knowledge gaps in toxic element content ranges for SRMs/RMs where no NIST assigned values existed, in particular for Hg content and for extract and SODF matrixes. With comprehensive toxic element content now available, researchers can better select appropriate dietary supplement SRMs/RMs for use as controls in the analysis of dietary supplement ingredients and products.

Highlights

Results for As, Cd, Pb, and Hg are reported for 38 dietary supplement SRMs/RMs including six suites of plant, extract, and SODF and nine pairs of plant and extract from the same batch of plant material.
Operations of a Student-Run Asylum Clinic: Frameworks, Challenges, and Recommendations
Authors: Gu Kathleen , Kim Dylan K , Kleidermacher Lauren E , Berhe Anne D , Sanjurjo Alexander D , Leone Ryan M , Dreux Simone R , Lin Allison P , Yuan Mina , Yang Eunice , Viswanathan Ashwin , Lorence Isabella M , Wang Melissa , Molyneux Kevin , Saha Prantik , Devlin Michael J
Published: July 2024

Student-run asylum clinics within medical schools represent a promising alternative to costly medicolegal services for people seeking asylum by providing pro bono forensic medical evaluations. However, there exist significant operational barriers to creating and developing such clinics, which depend largely on volunteerism and limited financial budgets. This policy and practice note not only presents a framework aimed at navigating these barriers in developing a student-run asylum clinic but also outlines critical challenges and recommendations for addressing them. We describe three principal components of clinic structure: community outreach and service, administration of forensic medical evaluations, and continuity of care. We also highlight challenges, such as access to a physical space for evaluations, maintenance of interpreter access and quality, standardization of clinician evaluator expectations, clinician evaluator availability, and evaluator wellbeing. Recommendations include the incorporation of a diversity of referral sources, opportunities for clinician-clinician shadowing, evaluation quality assessment, affidavit standardization, and development of interdisciplinary partnership.
Durations of Antibiotic Treatment for Acute Otitis Media and Variability in Prescribed Durations Across Two Large Academic Health Systems
Authors: Katz Sophie E , Jenkins Timothy C , Stein Amy B , Thomas Gale , Koenig Nancy , Starnes Gary Lucas , Newland Jason G , Banerjee Ritu , Frost Holly M
Published: July 2024

Background

Acute otitis media (AOM) accounts for roughly 25% of antibiotics prescribed to children annually. Despite national guidelines that recommend short (5–7 days) durations of antibiotics for children 2 years and older with AOM, most receive long (10 day) courses. This study aims to evaluate antibiotic durations prescribed for children aged 2–17 years with uncomplicated AOM across two pediatric academic health systems, and to assess the variability in prescribed durations between and within each system.

Methods

Electronic medical record data from 135 care locations at two health systems were retrospectively analyzed. Outpatient encounters for children aged 2–17 years with a diagnosis of AOM from 2019 to 2022 were included. The primary outcome was the percent of 5-day prescriptions. Secondary outcomes included the proportion of 7-day prescriptions, 10-day prescriptions, prescriptions for nonfirst-line antibiotics, cases associated with treatment failure, AOM recurrence, and adverse drug events.

Results

Among 73 198 AOM encounters for children 2 years and older, 61 612 (84%) encounters resulted in an antibiotic prescription. Most prescriptions were for 10 days (45 689; 75%), 20% were for 7 days (12 060), and only 5% were for 5 days (3144). Treatment failure, AOM recurrence, adverse drug events, hospitalizations, and office, emergency department or urgent-care visits for AOM within 30 days after the index visit were rare.

Conclusions

Despite national guidelines that recommend shorter durations for children with uncomplicated AOM, 75% of our cohort received 10-day durations. Shortening durations of therapy for AOM could reduce antibiotic exposure and should be a priority of pediatric antibiotic stewardship programs.
Fluoroquinolone Prophylaxis in Children With Cancer: A Pro/Con Discussion
Authors: Vasileiadi Eleana , Lloyd Kevin M , Fisher Brian T , Hanisch Benjamin
Published: July 2024

There are conflicting recommendations on whether to use or not to use fluoroquinolone prophylaxis in pediatric oncology patients. An international pediatric clinical practice guideline (CPG) recommends administering levofloxacin prophylaxis in patients with acute myeloblastic leukemia and relapsed acute lymphoblastic leukemia receiving intensive chemotherapy as this practice has been found to reduce episodes of fever and bacteremia. A separate European CPG does not recommend levofloxacin prophylaxis because of concerns for adverse effects, including potentiation of fluoroquinolone resistance and possible increased resistance to other classes of antibiotics. The nuance of the decision to give or not give prophylaxis is discussed in the context of published evidence defining the risks and benefits of levofloxacin prophylaxis for pediatric leukemia patients at high risk for bacterial infection. Knowledge gaps are also identified to guide further investigations to optimize the use of fluoroquinolone prophylaxis in pediatric patients receiving chemotherapy for cancer or undergoing a hematopoietic cell transplantation.
Evolution of drought and frost responses in cool season grasses (Pooideae): was drought tolerance a precursor to frost tolerance?
Authors: Stolsmo Sylvia Pal , Lindberg Camilla Lorange , Ween Rebekka Eriksen , Schat Laura , Preston Jill Christine , Humphreys Aelys Muriel , Fjellheim Siri
Published: July 2024

Frost tolerance has evolved many times independently across flowering plants. However, conservation of several frost tolerance mechanisms among distant relatives suggests that apparently independent entries into freezing climates may have been facilitated by repeated modification of existing traits (‘precursor traits’). One possible precursor trait for freezing tolerance is drought tolerance, because palaeoclimatic data suggest plants were exposed to drought before frost and several studies have demonstrated shared physiological and genetic responses to drought and frost stress. Here, we combine ecophysiological experiments and comparative analyses to test the hypothesis that drought tolerance acted as a precursor to frost tolerance in cool-season grasses (Pooideae). Contrary to our predictions, we measured the highest levels of frost tolerance in species with the lowest ancestral drought tolerance, indicating that the two stress responses evolved independently in different lineages. We further show that drought tolerance is more evolutionarily labile than frost tolerance. This could limit our ability to reconstruct the order in which drought and frost responses evolved relative to each other. Further research is needed to determine whether our results are unique to Pooideae or general for flowering plants.
mTOR in Acquired and Genetic Models of Epilepsy
Authors: Wong Michael , Bordey Angelique , Danzer Steve C.
Published: July 2024

Mutations in genes regulating the mechanistic target of rapamycin (mTOR) signaling pathway have emerged as a common cause of childhood epilepsy, including focal cortical dysplasia, hemimegalencephaly, and tuberous sclerosis complex. Dysregulation of mTOR signaling is also implicated in nongenetic causes of epilepsy, such as following status epilepticus or traumatic brain injury. In this chapter, we describe the evidence linking the mTOR pathway to genetic and acquired epilepsies, the variety of animal models developed to examine mTOR pathway signaling in the brain, and the general patterns of brain pathology produced by pathway disruption. We also examine potential mechanisms by which disrupted mTOR signaling regulates brain development, neuronal excitability, and epileptogenesis. The variety of tissues and cellular functions regulated by mTOR, and the breadth of epilepsies linked to disrupted mTOR signaling, all implicate the pathway as an important modulator of epileptogenesis.
GABAA-Receptor Signaling and Ionic Plasticity in the Generation and Spread of Seizures
Authors: Kaila Kai , Trevelyan Andrew , Raimondo Joseph , Ala-Kurikka Tommi , Huberfeld Gilles , Avoli Massimo , de Curtis Marco
Published: July 2024

According to a classical concept in epilepsy research, seizures are triggered by an “imbalance” between excitatory (glutamatergic) and inhibitory (GABAergic) synaptic transmission. Recent work has shown, however, that not only the efficacy but also the qualitative mode of action of GABAergic signaling is controlled by ionic plasticity, which is mediated by activity-dependent changes in the driving force of currents across GABAA receptors (GABAARs). We will briefly describe the basics of neuronal Cl− and pH/HCO3− regulation, and the main functions of neuronal carbonic anhydrases and the Cl− transporters, KCC2 and NKCC1. A major topic of discussion is how depolarizing currents carried by bicarbonate and by sodium across GABAARs and ionotropic glutamate receptors, respectively, act in a synergistic manner, leading to massive neuronal uptake of Cl− and large extracellular K+ transients. These transmembrane ion fluxes form a major constituent of a positive feedback cycle, in which neuronal excitability is boosted by, and contributes to, the ionic shifts. Initially, this leads to an erosion of the inhibitory restraint in the region surrounding the ictal core, followed by a subsequent transformation to functionally excitatory GABA action (which is independent on NKCC1). In line with this, a wealth of evidence shows that intense activation of cortical interneurons often has a seizure-promoting effect. The synaptic and non-synaptic mechanisms associated with GABAergic excitation shed light on the complex spatiotemporal profiles of seizure generation and propagation, and they provide a rational basis for the loss of efficacy of GABA-enhancing antiseizure drugs on ongoing seizure activity.
Connexins, Pannexins, and Epilepsy
Authors: Zhang Liang , Zoidl Georg R. , Carlen Peter L.
Published: July 2024

Connexins are proteins that form gap junctions which “connect” cells together, permitting the passage of small molecules and electricity. Since epilepsy is thought of as a disease of neuronal hypersynchrony, it is natural to consider these molecules with the gap junctions they form as playing a significant role in epilepsy. Over time, the “connections” of connexins to epilepsy are becoming more complicated and deeper. Adding to the complexity was the discovery of a family of membrane channels, the pannexins, which were initially mistaken for a second family of gap junction forming proteins. However, they, too, clearly play a major role in epilepsy. Herein we start with an introduction to the complex biology of both protein classes, followed by discussions of their multiple roles in epilepsy. These include such phenomena as direct intercellular communication between neurons and more recently, between glia, now increasingly recognized as key players in epilepsy. Also, the functions of membrane channels formed by connexins (hemichannels) and pannexins in promoting seizure activity and pathological consequences are discussed.
Transition to Seizure from Cellular, Network, and Dynamical Perspectives
Authors: Chang Wei-Chih , Kudlacek Jan , Jiruska Premysl , Jefferys John G. R.
Published: July 2024

The cellular and network mechanisms of seizure emergence (ictogenesis) remain unknown. Recent studies brought new fundamental insights about the complex nature of seizure genesis and the dynamical principles that govern the shift of epileptic networks dynamics into the seizure state. In this chapter, we describe new perspectives on how to approach understanding ictogenesis. Primarily, we focus on the latest data about the dynamical pathways and pathophysiological processes that drive the transition to seizure. In addition, we review recent evidence about the existence of long-term fluctuations in seizure likelihood which represent a missing piece in the mosaic of ictogenesis. We demonstrate that combining the cellular and network mechanisms at multiple temporal scales (ranging from epileptogenesis to seizure initiation) is a crucial step to a unified theory of seizure genesis.
Optogenetic Modulation of Focal Seizures
Authors: Lévesque Maxime , Avoli Massimo , Kokaia Merab
Published: July 2024

Optogenetics rests on the activation of light-gated ion channels or pumps in transgenic animals, and it is used to reversibly excite or silence specific neuronal populations, with millisecond precision and with a higher spatial accuracy than electrical stimulation. To date, epilepsy researchers have used optogenetics to study this neurological disorder, and in particular focal seizures that originate from a discrete brain area as in mesial temporal lobe epilepsy. Here, we will review findings obtained by employing optogenetics in in vitro and in vivo models of focal epileptiform synchronization. We will also address the use of this technique to control acute and chronic spontaneous seizures induced by the administration of chemoconvulsants in animal models of mesial temporal lobe epilepsy, such as the kainic acid and the pilocarpine model. These findings reveal that optogenetic activation or inhibition of excitatory or inhibitory cells can exert paradoxical effects on seizure occurrence depending on the frequency and timing of light stimulation, as well as on the targeted neuronal populations. We also consider the limitations associated with the use of optogenetics and the potential issues that must be solved before this approach is translated to human application. We conclude that optogenetics, despite some limitations, represents an innovative and promising approach to improve our understanding of brain function in health and disease.
Balancing Seizure Control with Cognitive Side Effects Using Changes in Theta
Authors: Toprani Sheela , Gurkoff Gene G. , Shahlaie Kiarash , Girgis Fady , Saez Ignacio , Kennedy Jeffrey , Moxon Karen A.
Published: July 2024

This chapter discusses the growing evidence that seizure generation and cognitive deficits have a similar pathological source characterized by, but not limited to, deficits in theta oscillations and their influence on interneurons that is part of a larger pathological brain network. The authors discuss new tools and techniques that are being used to identify this larger pathological network, how it overlaps with cognitive networks, and how therapies need to be developed that consider both the seizure network and the overlap with cognitive networks. A new framework is presented that describes oscillatory states in epilepsy as alternating between hyper- and hyposynchrony rather than solely the spontaneous transition to hyperexcitability characterized by the seizures. This framework suggests a pathological imbalance between excitation and inhibition in favor of synchronous inhibition during interictal theta oscillations that could account for both the seemingly spontaneous nature of seizures and comorbid cognitive deficits. The chapter concludes that there is a need to understand epilepsy as impacting extensive brain networks in order to optimize outcome for patients.
Role of Ion Concentration Dynamics in Epileptic Seizures
Authors: González Oscar C. , Timofeev Igor , Bazhenov Maxim
Published: July 2024

The regulation of transmembrane ion flux is crucial for maintaining physiological neuronal activity and preventing the occurrence of epileptic seizures. The net effect (e.g., depolarization or hyperpolarization) of the transmembrane ion flux is determined by the relative ion concentration gradients established across the cellular membrane. Because of the tight regulation of neuronal excitability and dynamics by changes in the ion concentrations, the brain has evolved multiple mechanisms to precisely regulate and maintain these concentration gradients. It has been demonstrated that the breakdown in the maintenance of ion gradients may lead to development of seizure discharges and may underly various forms of pathological neuronal activity. It is now well established that during a seizure discharge, the extracellular potassium concentration substantially increases, while the concentrations of extracellular sodium and calcium decrease. More recently, experimental recordings and computational models have demonstrated preictal increases in the intracellular chloride concentration in pyramidal neurons. This chapter discusses the effects of the ion concentration dynamics on seizure initiation, progression, and termination with the goal of providing novel insights into the underlying biophysical mechanisms of epileptic seizures.
Computational EEG Analysis of Human Epileptogenic Networks
Authors: Gnatkovsky Vadym , Schindler Kaspar
Published: July 2024

With the modern development of electroencephalogram (EEG) recording technology (stereo-EEG, grid, strip, and microelectrodes), computational EEG analysis started to play an essential role in assisting traditional visual EEG evaluation. The number of recording electrodes and the temporal resolution of these modern recording technologies are far beyond the human capability to rapidly extract and integrate all necessary information for studies of epileptogenic networks. This chapter describes the state of the art of computational EEG analysis. It reviews and discusses different computational approaches and achievements in the approximation of the epileptogenic zone, in seizure pattern recognition, seizure classification, and in the understanding of seizure generation mechanisms.
Clinical Features and Molecular Mechanisms Underlying Autoantibody-Mediated Seizures
Authors: Mathy Alexandre , Irani Sarosh R.
Published: July 2024

The last two decades have seen the discovery of a plethora of cell-surface autoantibodies causally implicated in clinically distinctive central nervous system (CNS) diseases. These autoantibody-mediated neurological disorders frequently present with multifocal neurological and psychiatric symptoms with both focal and generalized seizures as a core feature. This chapter describes the clinical spectrum of autoantibody-mediated CNS disorders, focusing on autoantibodies which target the extracellular domains of cell-surface antigens, including NMDAR and LGI1. In addition, the preclinical immune mechanisms underlying the genesis and propagation of these conditions are explored, and the chapter reviews how these autoantibodies directly modulate neuronal and circuit functions to explain the observed clinical features.