bluuebunny/crossref_metadata_2025 huggingface dataset:
Unprecedented nor-seco-polycyclic polyprenylated acylphloroglucinols counteract myocardial cell injury via activation of the Akt/mTOR signaling pathway
Authors: Wei Jiangchun , Fan Pingping , Jin Xingpiao , Li Xinping , Li Zhiyue , Chen Xuanluan , Zeng Hanxiao , Wu Zhengzhi , Zhang Yonghui , Hu Zhengxi
Published: July 2024

Five nor-seco-PPAPs with a novel linear 5-5/6/5 tetracyclic skeleton (1–5) were isolated from Hypericum monogynum. 1 may elicit its protective effect against H2O2-induced myocardial cell injury via activation of the Akt/mTOR signaling pathway.
NIR afterglow nanosystem for photodynamic therapy
Authors: Shu Bingxin , Zhao Shubi , Zhang Yuling , Sun Qinchao , Huang Zhen
Published: July 2024

The Ru/CYQ@CPPO exhibits afterglow and recharging effect. There was reasonable correlation between afterglow luminescence and the inhibitory rate of tumor cells, which indicates that Ru/CYQ@CPPO holds for facilitating non-invasive, personalized PDT.
Green synthesis, in silico modeling, and biological evaluation of N-substituted (Z)-5-arylidene imidazolidine/thiazolidine-2,4-dione/4-thione derivatives catalyzed by Bu SO3H core–shell nanostructures
Authors: Akhavan Malihe , Esam Zohreh , Mirshafa Atefeh , Lotfi Maryam , Pourmand Saeed , Ashori Froug , Rabani Motahare , Ekbatani Golbahar , Tourani Saeed , Beheshti Reza , Keshavarzian Zahra , Ghanbarimasir Zahra , Bekhradnia Ahmadreza
Published: July 2024

The newly designed magnetic nanocatalyst Fe3O4@CPTMS@guanidine–BuSO3H in a one-pot multicomponent reaction is reported to obtain N-substituted (Z)-5-arylidene imidazolidine/thiazolidine-2,4-dione/4-thione as a highly selective antiproliferation agent.
Persistent luminescence nanoparticles with high intensity for colorectal cancer surgery navigation and precision resection
Authors: Yan Zichao , Wang Yifei , Qiu Minghan , Long Kai , Zhang Zhouyu , Sun Mengjie , Yin Chang , Wang Wei , Wang Hua-qing , Yuan Zhi
Published: July 2024

We used persistent luminescence nanoparticle-based surgical navigation to accurately remove colon cancer tumors in the small intestine.
Observation of the planar Hall effect in the quasi-two-dimensional topological insulator candidate Ni3Bi2Se2
Authors: Ma Yuzhe , Sun Wen , Xu Qiunan , Wang Xinming , Aqeel Aisha , Li Guowei
Published: July 2024

Single crystals of the topological insulator candidate Ni3Bi2Se2 were grown, which exhibit a clear planar Hall effect (PHE) with π-period. The parametric plot indicates that the observed PHE primarily arises from in-plane orbital magnetoresistance.
Molecular aspects of Interleukin-36 cytokine activation and regulation
Authors: Keller Jennifer , O’ Siorain James R. , Kündig Thomas M. , Mellett Mark
Published: July 2024

Interleukin-36 (IL-36) cytokines are structurally similar to other Interleukin-1 superfamily members and are essential to convey inflammatory responses at epithelial barriers including the skin, lung, and gut. Due to their potent effects on immune cells, IL-36 cytokine activation is regulated on multiple levels, from expression and activation to receptor binding. Different IL-36 isoforms convey specific responses as a consequence of particular danger- or pathogen-associated molecular patterns. IL-36 expression and activation are regulated by exogenous pathogens, including fungi, viruses and bacteria but also by endogenous factors such as antimicrobial peptides or cytokines. Processing of IL-36 into potent bioactive forms is necessary for host protection but can elevate tissue damage. Indeed, exacerbated IL-36 signalling and hyperactivation are linked to the pathogenesis of diseases such as plaque and pustular psoriasis, emphasising the importance of understanding the molecular aspects regulating IL-36 activation. Here, we summarise facets of the electrochemical properties, regulation of extracellular cleavage by various proteases and receptor signalling of the pro-inflammatory and anti-inflammatory IL-36 family members. Additionally, this intriguing cytokine subfamily displays many characteristics that are unique from prototypical members of the IL-1 family and these key distinctions are outlined here.
Comment utiliser des progestatifs chez la femelle
Authors: Topie Emmanuel , Gogny Anne
Published: July 2024

Les analogues synthétiques de la progestérone sont utilisés depuis des décennies chez la chienne et chez la chatte afin de prévenir ou d’interrompre l’œstrus. Les molécules les plus fréquemment utilisées sont l’acétate de mégestrol, l’acétate de médroxyprogestérone, l’acétate de delmadinone et l’acétate de proligestone.

Les effets secondaires rapportés des progestatifs dépendent de la molécule administrée, de la dose, de la durée du traitement et de l’âge de l’animal. Ils incluent : agitation ou léthargie, alopécie, augmentation de l’appétit et prise de poids, affection utérine, affections mammaires, diabète, acromégalie et immunodépression.

Cependant, utilisés à faible dose et pour une durée courte, idéalement inférieure à 6 mois, les progestatifs représentent un moyen de contraception réversible possible chez la chienne et la chatte.

Par ailleurs, l’utilisation de l’acétate de mégestrol une fois par jour pendant une semaine à la dose de 0,1 mg/kg, puis pendant une autre semaine consécutive à la dose journalière de 0,05 mg/kg représente un traitement prometteur de la subinvolution des sites d’insertion placentaire chez la chienne.

Une complémentation en progestérone naturelle peut être nécessaire en cas de suspicion d’insuffisance lutéale chez la chienne. L’option de choix est alors l’administration par voie orale de progestérone micronisée afin de pouvoir suivre l’efficacité du traitement par dosage de la progestérone plasmatique et de moduler le traitement au besoin.
Five Questions to Help Prompt End-of-Life Planning in Neuromuscular Disease
Authors: Lipanot Benjamin J. , Bosslet Gabriel
Published: July 2024

Patients with neuromuscular disease are living longer lives but continue to have significant and often unpredictable morbidity and mortality. End-of-life planning for these patients is thus an essential part of their medical care. This planning should include the following topics: health care surrogates, swallowing and nutrition, daytime respiratory support, and all aspects of when end of life is near. Adult-onset and early-onset diseases may require different approaches to these topics. All patients with neuromuscular disease will benefit from these discussions to best reach patient-centered goals. We present health care providers these five questions and explanations as a guide.
Study on the aging characteristics of PET for SF6 gas-insulated transformer
Authors: Zhang Daning , Xu Haisong , Yang Dingqian , Wang Qian , Mu Haibao , Zhang Guanjun
Published: July 2024

SF6 gas insulated transformers (GITs) are extensively utilized in underground substations within densely populated areas of large- and medium-sized cities, praised for their excellent non-flammability and operational reliability. However, the aging characteristics of gas–solid composite insulation (SF6–PET) within GITs remain unclear, complicating the effective evaluation of their aging condition. In this study, we performed accelerated thermal aging experiments on type 6020 polyethylene terephthalate (PET) films under an SF6 gas environment at 150 °C. We investigated the aging characteristics of PET materials at various stages using differential scanning calorimetry, tensile tests, near-infrared spectroscopy (NIRS), and frequency domain dielectric spectroscopy. Our findings indicate that the crystallinity and fracture elongation of PET materials initially increased before decreasing as aging progressed, while tensile strength steadily declined. In addition, the absorption rate observed in NIRS diminished with aging. Utilizing linear discriminant analysis, we achieved dimension reduction of characteristic parameters across different wavelengths, facilitating the classification of PET materials at diverse aging times. The tan δ–f curves of PET films initially decreased and subsequently rose with aging. By applying the Havriliak–Negami (H–N) dielectric relaxation model across three distinct frequency bands of the dielectric spectrum, a significant correlation was discerned between the aging state of PET materials and the characteristic relaxation peaks, τ1 and τ2. Fitting the H–N relaxation model and Arrhenius equation allowed us to negate the impact of “temperature drift,” yielding an interface polarization activation energy of Ea = 0.69 eV. This research on the aging performance of PET materials in an SF6 gas atmosphere provides a vital foundation for assessing the aging state of SF6-insulated GITs.
Insubordination and what happens after it
Authors: Sideltsev Andrei V.
Published: July 2024

One of the sources of irrealis markers is former markers of conditional sentences, both protases and apodoses,
both factual and counterfactual. The development, amply documented cross-linguistically, is that of insubordination: a former
marker of subordination is used as an irrealis marker in main clauses. However, the next stage of development is not commonly
observed: when irrealis markers that came into being as the result of insubordination and are used in main clauses spread back to
their original locus, conditional sentences. The paper deals with a clear attestation of this pattern in Hittite, an extinct
Indo-European language. It is argued that the development is part of a linguistic cycle of the ‘broken’ kind, i.e., that the cycle
changed by other processes simultaneously operating in the language.
How pragmatically (in)definite are you and
one?
Authors: Sorlin Sandrine
Published: July 2024

This chapter focuses on two specific pronominal
‘imposters’, you and one as used in
Orwell’s semi-autobiographical text Down and Out in Paris and
London (1933). It
studies the ‘definite-indefinite’ and ‘specific-generic’ potential of the
pronouns via the same theoretical framework put forward in Sorlin (2022) with regard to the
second-person pronoun, the better to appreciate the similarities and
differences between the two pronouns. The aim of this chapter is to
investigate the way the two pronouns foreground (and background) their
egocentric and altruistic orientation and to what pragmatic purposes. The
pronominal comparison within the same corpus allows to perceive why
one tends to be used in lieu of you
(and vice versa) in strategic places of the essay.
Projected impact of solar radiation modification geoengineering on water deficit risk over major Central African river basins
Authors: Fotso-Nguemo Thierry C , Chouto Steven , Nghonda Jean P , Diedhiou Arona , Kravitz Ben , Yepdo Zéphirin D , Djuidje Flore K , Abiodun Babatunde J
Published: July 2024

The economy of Central African countries strongly depends on rain-fed agriculture and hydropower generation. However, most countries in this subregion do not yet have the irrigation technologies that are already applied in many more advanced nations, which further exposes them to the serious risk of severe drought caused by global warming. This study investigates the potential impact of solar radiation modification (SRM) geoengineering on the water availability over the four major river basins that cross most of Central African countries (i.e. Niger Basin, Lake Chad Basin, Cameroon Atlantic Basin (CAB) and Congo Basin). For this purpose a potential water availability index was computed based on an ensemble-mean simulations carried out in the framework of Phase 6 of the Geoengineering Model Intercomparison Project considering two SRM simulation experiments: the stratospheric sulphate aerosol injection (G6sulfur) and the global solar dimming (G6solar). The climate change simulation results in a robust decreases by up to 60% in water availability, most pronounced over the CAB under the high radiative forcing scenario. Therefore, in a business-as-usual world, the reduction in water availability combined with the rapid population growth expected by 2050 in the studied subregion, could result in a significant water deficit over Central African countries towards the end of the 21st century. This water deficit could affect all activities that depend on water resources, such as water supply, agriculture and hydropower generation. Furthermore, the results also show that SRM methods have the potential to significantly reduce this deficit by increasing water availability (as compared to climate change) by up to 50% over the affected river basins, with a more accentuated increase found in the CAB when the global solar dimming is applied. These results suggest good possibilities of adaptation for populations living in the geographical areas of these river basins.
Investigating the Impact of Annealing Temperature on CdS Nanoparticles: Optimizing Solar Photovoltaic Efficiency
Authors: Kumar Mahato Prabin , Chaudhuri Swarat , Lal Patel Shankar , Patra Prashanta
Published: July 2024

The development of solar photovoltaic (PV) technology in the era of nanotechnology plays a crucial role in the advancement of renewable energy technologies. CdS is a vibrant candidate for numerous applications and the properties of CdS nanoparticles could be tailored and enhanced by annealing treatment. The present work unveils the impact of air annealing temperature on the tailoring of microstructural and optical properties of CdS nanoparticles. A facile chemical co-precipitation technique is employed to synthesize the CdS nanoparticles followed by annealing at 200°C and 400°C for 1 hour. The XRD patterns exhibit that nanoparticles are crystallized in hexagonal wurtzite crystal structure with (002) and (101) preferred orientations depending upon the annealing condition where the interplanar spacing and crystallite size corresponds to preferred peaks concerned ranging from 3.15-3.34 Å and 13-24 nm, respectively. Optical analysis reveals that transmittance is found less than 20% up to 500 nm and then abruptly increases in higher visible regions. The absorbance of nanoparticles is improved with annealing whereas band gap decreased from 2.19 eV to 2.02 eV. EDS pattern of as-grown samples confirmed the impurity-free synthesis of CdS nanoparticles. The FESEM micrographs revealed the formation of nano spherical grains for as-grown samples while nanoflake-like grain structures are visible for 400°C annealed nanoparticles. The novelty of this study lies in its comprehensive exploration of the impact of annealing temperature on the microstructure and optical characteristics of CdS nanoparticles.
LC Based Active Cell Balancing for Efficient Energy Management in Automotive Batteries
Authors: Ackshaya V , Naveen Shankar S , Sri Balaji G , Mathankumar M
Published: July 2024

When every single cell in the body has the same voltage and capacity, it is said to be in cell balance. Maintaining the identical state-of-charge for each cell in a multi-cell pack by balancing contributes to the pack’s maximum capacity and service life. Two basic techniques of balancing exist: Overcharged cells lose charge due to passive balancing, which dissipates the stored energy as heat. Active balancing distributes energy from abundant cells to least cells to preserve battery pack energy. Battery management systems (BMS) use resistors to achieve passive cell balancing, which balances the states of charge in individual cells. Every cell has a resistor connected in parallel with it. The matching resistor is triggered when a cell is charged too much, releasing extra energy as heat. Until all cells have voltages that are comparable, this process is repeated. Active balancing is more efficient than passive balancing, and less expensive. In BMS, energy is transferred between cells to balance their state of charge, a process known as active cell balancing. It controls the flow of energy by using electronic parts like capacitors and inductors. Active balancing can quickly balance cells or correct large voltage imbalances since it is more sophisticated and effective than passive balancing. A cell’s state of charge (SOC) represents its current capacity as a function of its rated capacity. This technology optimizes battery performance, prolonging overall lifespan and promoting reliable energy management in electric vehicles. By minimizing voltage deviations, LC-based balancing contributes to increased driving range and sustained battery health.
Smart and Sustainable Energy Systems: Enhanced Transmission of EEG Signals in Telemedicine Applications using Soft Output Viterbi Turbo Decoder
Authors: Santhosh Kumar K. B. , Sujatha B. R. , Sushma N. , Rao Kolli Venkateswara
Published: July 2024

In the era of telemedicine, where remote treatment is gaining traction, the reliable transmission of biomedical signals is paramount. Turbo Coding has emerged as a pivotal method due to its robust performance and quality of service. However, the inherent complexity of Turbo decoders presents a significant hurdle. This paper investigates the efficacy of Soft Output Viterbi Algorithm (SOVA), Logarithmic MAP (Log-MAP), and Maximum A posteriori Probability (MAP) decoding techniques within Turbo decoding, crucial for real-time telemedicine applications. Focusing specifically on EEG signal transmission, we employ wireless channels and Turbo coding to enhance reliability. Viterbi decoding is leveraged to mitigate complexity, with an in-depth analysis of the SOVA algorithm’s Bit Error Rate performance across various parameters. This research enhances telemedicine by improving the reliability of biomedical signal transmission. Through efficient decoding techniques like Soft Output Viterbi Turbo Decoder, it ensures timely and accurate healthcare delivery. By reducing the need for patient travel and optimizing energy consumption, it aligns with Smart and Sustainable Energy Systems goals. This contributes to global healthcare accessibility and sustainability by minimizing carbon footprint and resource utilization. Ultimately, it promotes efficient, dependable, and eco-friendly healthcare solutions for all.
A Smart and Efficient Cooling System Design for High-Performance Electric Vehicle Battery Packs
Authors: Gokul Raj K , Nikhil Srinivas T , Jeswanth M G , Mohana Sundaram N
Published: July 2024

This project aims to develop an efficient cooling system for high-performance Electric Vehicle (EV) battery packs, addressing the critical need for optimal thermal management to ensure battery performance, safety, and longevity. The proposed system employs a blend of active and passive cooling techniques to maintain the optimal temperature during the movement of vehicle. Microcontrollers are utilized to control the cooling system, monitor temperature sensors, and make real-time adjustments, ensuring the battery pack stay within the desired temperature limits. The methodology includes the design of the cooling system, the selection of appropriate cooling methods, integration of temperature sensors, and implementation using microcontroller-based hardware. A key feature is the real-time adjustments made by the microcontrollers, allowing for precise temperature control. The effectiveness of the cooling system is rigorously evaluated through testing under various operating conditions to validate enhanced battery performance, safety and overall efficiency. The combination of active and passive cooling, coupled with microcontroller-based control and real-time monitoring, represents a holistic approach to maintaining optimal battery temperature. This research not only advances the technology required for EVs but also contributes to the broader goal of sustainable and efficient transportation.
Sustainable Parking Innovations: Enhancing Security with IoT and Facial Image Recognition
Authors: Deenakonda Mamatha , Vijetha Inti V V , Chakravarthi B N Ch V , Rajyalakshmi Ch , Palleswari Y.T.R. , Siva A. , Kethan Sai Pranay M.
Published: July 2024

Technology has advanced quickly today. The parking lot is one location where technology is used. The world’s most technologically advanced parking lots can currently recognize a vehicle plate image, but it is believed that by using Internet of Things (IoT) technology that is connected with facial recognition photographs, it will be even better. The manual screening done by security agents is one of the parking issues. Naturally, this will take time, and the level of security is also poor because there is no verification when you enter. Only at the moment of exit are checks made, and the officer making the check is not always the same and does not have the vehicle owner’s memory. The adoption of this facial image recognition technology is expected to increase the parking system’s security. This service does not require training data. The proposed system makes use of real-time data, low-cost sensors, and user-friendly applications to enable users to track parking availability in real time. The aim is to streamline the parking search process by automating the identification of optimal parking spots, whether it be the ideal floor, location, or lot, thereby minimizing manual search time. The integration of low-cost sensors not only enhances cost-effectiveness but also reduces the ecological footprint associated with traditional parking systems and also promotes a more resilient and eco-friendly urban environment for the benefit of both users and lot owners.
Truncated smooth function spaces
Authors: Domínguez Oscar , Tikhonov Sergey
Published: July 2024

We introduce truncated Besov and Triebel–Lizorkin function spaces and study their main properties: embeddings, interpolation, duality, lifting, traces. These new scales allow us to improve several known results in functional analysis and PDE’s. In particular, we obtain a full solution to the trace/extension problem in the critical case as well as sharp Sobolev-type embeddings with critical smoothness parameters.
𝐾𝑈-local zeta-functions of finite CW-complexes
Authors: Salch A.
Published: July 2024

Begin with the Hasse-Weil zeta-function of a smooth projective variety over

Q

\mathbb {Q}

. Replace the variety with a finite CW-complex, replace étale cohomology with complex

K
K

-theory

K

U
∗

KU^*

, and replace the

p
p

-Frobenius operator with the

p
p

th Adams operation on

K
K

-theory. This simple idea yields a kind of “

K
U

KU

-local zeta-function” of a finite CW-complex. For a wide range of finite CW-complexes

X
X

with torsion-free

K
K

-theory, we show that this zeta-function admits analytic continuation to a meromorphic function on the complex plane, with a nice functional equation, and whose special values in the left half-plane recover the

K
U

KU

-local stable homotopy groups of

X
X

away from

2
2

.

We then consider a more general and sophisticated version of the

K
U

KU

-local zeta-function, one which is suited to finite CW-complexes

X
X

with nontrivial torsion in their

K
K

-theory. This more sophisticated

K
U

KU

-local zeta-function involves a product of

L
L

-functions of complex representations of the torsion subgroup of

K

U
0

(
X
)

KU^0(X)

, similar to how the Dedekind zeta-function of a number field factors as a product of Artin

L
L

-functions of complex representations of the Galois group. For a wide range of such finite CW-complexes

X
X

, we prove analytic continuation of the zeta-function, and we show that the special values in the left half-plane recover the

K
U

KU

-local stable homotopy groups of

X
X

away from

2
2

if and only if the skeletal filtration on the torsion subgroup of

K

U
0

(
X
)

KU^0(X)

splits completely.
Introduction
Authors: Snowdon Paul F
Published: July 2024

The Introduction to this volume serves as a guide to the sixteen chapters that it contains. This book consists of papers written between 1980 and the present, all dealing with philosophical issues raised by perceptual experience and our thought about it. All of them have been previously published and are reprinted, more or less, in their original form. The book is divided into one part called “Issues” and another part called “Philosophers,” corresponding to differences in their focus. Snowdon goes in depth to describe the theoretical challenges, approaches, and themes that animate the set of interrelated problems addressed in the chapters. Sprinkled throughout are an array of candid reflections that serve both to illuminate substantive connections between the chapters as well as the historical and circumstantial contexts that occasioned their writing.
The Objects of Perceptual Experience
Authors: Snowdon Paul F
Published: July 2024

According to a widely held view, the concept of seeing an external object is best analysed by appeal to causation. This causalist analysis combines a positive and a negative claim: (1) if P (a subject) sees O (an object) then O is causally responsible for an experience (call it E) undergone by S; and (2) it is not sufficient for P to see O that O be causally responsible for an experience E undergone by P. It is argued here that any such analysis is mistaken: causation is no part of our ordinary concept of seeing. The causalist analysis could be correct only if there were a visual experience common to both genuine perceptions and illusions. But in order for a common element to be part of our concept of seeing, disjunctivism would have to be analytically false. Even if disjunctivism could be shown to be empirically false, no such demonstration can flow from an analysis of the concept of seeing.
What Is Realism?
Authors: Snowdon Paul F
Published: July 2024

In the paper by Michael Ayers to which the present chapter is a reply, Ayers argues that (1) there is a scholastic-Cartesian framework concerning the relation of thought and experience to their objects, in terms of which two philosophical approaches can be defined, namely the Cartesian stance and direct realism, both of which should be rejected by a plausible realism. In §I of this reply, it is argued that Ayers’s elucidation of the issues he is considering, in terms of idealism, but, more importantly, in terms of the scholastic-Cartesian framework he sets up, is not helpful. Ayers also contends that (2) the currently popular direct realist approach to perception, namely disjunctivism, should be rejected. §II of this reply attempts to counter Ayers’s objections. Finally, Ayers contends that (3) “Reality structures experience and so thought. We are that closely in touch with it. The supposed problem of comparing ‘conceptual scheme’ with reality does not arise.” In §III it is shown that two of the claims in (3) are hard to reconcile with the general approach to thought and experience that Ayers seems to adopt.
McDowell on Scepticism, Disjunctivism, and Transcendental Arguments
Authors: Snowdon Paul F
Published: July 2024

McDowell’s disjunctive account of perceptual knowledge contains a novel addition to his interesting response to scepticism by placing within it a transcendental argument. It is not clear that such addition strengthens it. McDowell’s disjunctivism seems to involve both epistemological and experience-theoretical commitments. It is a two-sided structure, from which questions could be raised about the assumed relation between the two sides. The purpose of this chapter is to make some progress with evaluating McDowell’s contribution to the discussion on perceptual knowledge and illuminate more general aspects of the debate about disjunctivism.
Private Experience and Sense Data
Authors: Snowdon Paul F
Published: July 2024

In the mid-1930s, Ludwig Wittgenstein was immersed in problems about experience, or perhaps one might say, our thought about experience. One record of his developing thinking are the notes that Rush Rhees made of the lectures by Wittgenstein on these topics, published under the title, “The Language of Sense Data and Private Experience,” in Philosophical Occasions. The ideas that Wittgenstein developed in these notes and lectures culminated in the discussion of the same topics in Philosophical Investigations. What views about sense data and private experience is Wittgenstein proposing? Wittgenstein suggests that bad philosophy is produced by the “bewitchment of intelligence by language.” In addition, he brings out a genuine contrast between the status of the idea of the private object account of perception and the idea of private objects as involved in the experience of sensations. It is natural to read Wittgenstein’s brief discussion of the so-called “visual room” in Philosophical Investigations as another engagement with the sense datum model of perception.
Blind Rule-Following, Properly Construed
Authors: Miller Alexander
Published: July 2024

This chapter develops responses to Paul Boghossian’s Inference Problem and Crispin Wright’s Minor Premise Problem (as outlined in Chapter 3). It does this by arguing that in each case the problem makes an assumption that Wittgenstein justifiably rejects in the second paragraph of Philosophical Investigations §201. The assumption in question is that following a rule necessarily involves interpretation. It connects the idea that there is a way of following a rule which does not involve interpretation to the notion of blind rule-following. Whereas Boghossian and Wright take the idea of following a rule blindly to involve the rejection of the idea that accepting a rule is an intentional state, the chapter argues that it leaves this idea intact but reasserts the lesson of §201. Blind rule-following is rule-following that is not based on an interpretation of the rule. The work seemingly done by “interpretation” is in fact done by the notion of training in a practice or custom.
A Non-Reductionist Response to Kripke’s Wittgenstein’s Sceptical Argument
Authors: Miller Alexander
Published: July 2024

This chapter uses the notion of blind rule-following defended in Chapter 4 to provide a non-reductionist response to the sceptical argument about meaning adumbrated in Chapter 2 above. Accepting a rule is a matter of intending to exercise an ability to conform one’s behaviour to the dictates of the rule; understanding a linguistic expression in a particular way is a matter of having an intention to exercise an ability to use the expression in accord with a correctness condition. Crucially, exercise of the relevant abilities needn’t be mediated by interpretation. The chapter shows how this form of non-reductionism avoids the objections to primitivism raised by Kripke’s Wittgenstein in the course of the sceptical argument. It argues that recent work fails to respect the insights of §201(b). It finishes by responding to a number of objections.
Kripke’s Wittgenstein’s Sceptical Argument
Authors: Miller Alexander
Published: July 2024

This chapter outlines and expands on the sceptical paradox developed in chapter 2 of Kripke’s Wittgenstein on Rules and Private Language. It does so in the context of the ACER model of rule-following introduced in Chapter 1 above. According to this argument, there are no facts about an agent’s psychological and/or social history capable of making it true that the agent accepts one rule rather than another (or means one thing rather than another by a linguistic expression or has a mental state with one content rather than another). Particular attention is paid to Kripke’s attack on reductive dispositionalist theories of meaning and to his objections to non-reductionist views which regard facts about meaning as primitive and sui generis. The chapter also considers “sceptical solutions”, according to which the integrity of meaning-ascribing practices can be preserved even in the absence of meaning-constituting facts. It is argued that such a position—whether construed as an error theory or as a form of non-factualism—is inherently unstable.
Estimating the magnitude and healthcare costs of melanoma in situ and thin invasive melanoma overdiagnosis in Australia
Authors: Lindsay Daniel , Bell Katy J L , Olsen Catherine M , Whiteman David C , Pathirana Thanya , Collins Louisa G
Published: July 2024

Background

Research suggests that a high proportion of melanoma in situ (MIS) may be overdiagnosed, potentially contributing to overtreatment, patient harm and inflated costs for individuals and healthcare systems. However, Australia-wide estimates of the magnitude of melanoma overdiagnosis are potentially outdated and there has been no estimation of the cost to the healthcare system.

Objectives

To estimate the magnitude and cost of overdiagnosed MIS and thin invasive melanomas in Australia.

Methods

Using two different methods to calculate lifetime risk, we used routinely collected national-level data to estimate overdiagnosed MIS and thin invasive melanomas (stage IA) in Australia in 2017 and 2021, separately for men and women. We multiplied the number of overdiagnosed melanomas by the estimated annual cost of a MIS or thin invasive melanoma, to quantify the financial burden of melanoma overdiagnosis to the Australian healthcare system in the year following diagnosis.

Results

We estimated that 67–70% of MIS were overdiagnosed in 2017, rising to 71–76% in 2021, contributing to between 19 829 [95% confidence interval (CI) 19 553–20 105] and 20 811 (95% CI 20 528–21 094) cases of overdiagnosed MIS. In 2021, the estimated costs in Australia ranged between $17.7 million Australian dollars (AUD; 95% CI 17.4–17.9 million) and AUD$18.6 million (95% CI 18.3–18.8 million). We estimated that 22–29% of thin invasive melanomas were overdiagnosed in 2017, rising to 28–34% in 2021, contributing to between 2831 (95% CI 2726–2935) and 3168 (95% CI 3058–3279) overdiagnosed thin invasive melanomas. In 2021, the estimated costs from thin invasive melanoma overdiagnoses ranged between AUD$2.5 million (95% CI 2.4–2.6 million) and AUD$2.8 million (95% CI 2.7–2.9 million).

Conclusions

Melanoma overdiagnosis is a growing clinical and public health problem in Australia, producing significant economic costs in the year following overdiagnosis. Limiting melanoma overdiagnosis may prevent unnecessary healthcare resource use and improve financial sustainability within the Australian healthcare system.
A random mutagenesis screen enriched for missense mutations in bacterial effector proteins
Authors: Urbanus Malene L , Zheng Thomas M , Khusnutdinova Anna N , Banh Doreen , O’Connor Mount Harley , Gupta Alind , Stogios Peter J , Savchenko Alexei , Isberg Ralph R , Yakunin Alexander F , Ensminger Alexander W
Published: July 2024

To remodel their hosts and escape immune defenses, many pathogens rely on large arsenals of proteins (effectors) that are delivered to the host cell using dedicated translocation machinery. Effectors hold significant insight into the biology of both the pathogens that encode them and the host pathways that they manipulate. One of the most powerful systems biology tools for studying effectors is the model organism, Saccharomyces cerevisiae. For many pathogens, the heterologous expression of effectors in yeast is growth inhibitory at a frequency much higher than housekeeping genes, an observation ascribed to targeting conserved eukaryotic proteins. Abrogation of yeast growth inhibition has been used to identify bacterial suppressors of effector activity, host targets, and functional residues and domains within effector proteins. We present here a yeast-based method for enriching for informative, in-frame, missense mutations in a pool of random effector mutants. We benchmark this approach against three effectors from Legionella pneumophila, an intracellular bacterial pathogen that injects a staggering >330 effectors into the host cell. For each protein, we show how in silico protein modeling (AlphaFold2) and missense-directed mutagenesis can be combined to reveal important structural features within effectors. We identify known active site residues within the metalloprotease RavK, the putative active site in SdbB, and previously unidentified functional motifs within the C-terminal domain of SdbA. We show that this domain has structural similarity with glycosyltransferases and exhibits in vitro activity consistent with this predicted function.
Development of a sequential sampling plan for classifying Thrips tabaci (Thysanoptera: Thripidae) populations in onion fields
Authors: Komondy Lidia , Hoepting Christy A , Pethybridge Sarah J , Fuchs Marc , Nault Brian A
Published: July 2024

Onion thrips, Thrips tabaci Lindeman, is a global pest of onion crops, causing substantial economic damage by diminishing bulb yields and transmitting plant pathogens. Insecticides are used to manage T. tabaci infestations with control decisions traditionally based on action thresholds that require visually counting thrips on a fixed, predetermined number of onion plants per field. However, this approach for treatment decisions is inefficient when thrips populations are well above or below the action threshold. The aim of this research was to develop a sequential sampling plan that would provide a rapid and reliable classification of thrips populations in commercial onion fields above or below prespecified management thresholds. The study was conducted in a total of 24 commercial onion fields in New York in 2021 and 2022. Taylor’s power law and Wald’s Sequential Probability Ratio Test were used in concert to develop each sampling plan. Simulated and historical field data of thrips populations were used to further validate the efficacy of each sampling plan. Results demonstrated the sequential sampling plan required an average of 78% fewer samples to make a control decision compared with the traditional fixed-sampling approach. Treatment decisions were reached in 72% of cases after inspecting only 10 plants, while only 6% of the cases required examining more than 25 plants. Comparisons with fixed-sample sizes ranging from 23 to 68 plants revealed a 96% agreement in decision-making and a 78% reduction in sampling effort when using the sequential sampling plans.
(330) COMPARING PDE5IS EFFICACY FOR ERECTILE DYSFUNCTION TREATMENT USING A NOVEL TRIFECTA OUTCOME
Authors: Capogrosso Dr Paolo , Belladelli Dr Federico , Pozzi Dr Edoardo , Corsini Dr Christian , Bertini Dr Alessandro , Raffo Dr Massimiliano , Negri Dr Fausto , Cattafi Dr Francesco , Oddo Dr Marco , Malvestiti Dr Marco , Ramadani Dr Riccardo , Candela Dr Luigi , Boeri Dr Luca , d'Arma Alessia , Montorsi Prof Francesco , Dehò Prof Federico , Salonia Prof Andrea
Published: July 2024

Objectives

Current data suggest that all available PDE5-inhibitors (PDE5is) appear equivalent for treating erectile dysfunction (ED). We aimed to compare the effectiveness of PDE5is in terms of a novel TRIFECTA outcome, including erectile function (EF), orgasmic function (OF), and psychological well-being.

Methods

We analysed 328 ED patients assessed at a single centre in 2010-2023. Patients were prescribed with either sildenafil, tadalafil, vardenafil or avanafil on-demand at the maximum effective dose for at least 1 month and with a minimum of 6 sexual attempts. The choice of PDE5i was based on clinical judgment and patient preference. All patients completed International Index of Erectile Function (IIEF) and Becks Inventory for Depression (BDI) at baseline and follow-up. The TRIFECTA outcome was defined as achieving an IIEF-EF>=26 + IIEF-OF >=8 + BDI score<11 (indicating good psychological well-being). Kaplan-Meier estimated the probability of achieving TRIFECTA over time according to different PDE5is and Cox-regression analysis tested predictors of treatment efficacy.

Results

Median (IQR) age was 55(43-62) years. Median IIEF-EF, IIEF-OF and BDI score were 16(8-23), 8(5-10) and 6(2-11), with 53%(174) patients reporting moderate-severe ED and 28%(91) having depressive symptoms (BDI>11). Overall, 16%(52), 39%(127), 28%(91) and 18%(58) received sildenafil, tadalafil, vardenafil and avanafil. The median treatment duration was 8(3-15) months. Overall, TRIFECTA was achieved in only 15%(48) of cases. Kaplan-Meier (figure) showed estimated TRIFECTA rates at 6 months of 20%(95%CI:8-45), 4%(95%CI:1-13), 12%(95%CI:5-28) and 18%(95%CI:6-46) for sildenafil, tadalafil, vardenafil and avanafil (p<0.0001). At Cox-regression tadalafil was associated with a lower probability of achieving TRIFECTA over time (HR: 0.31, p=0.009) after adjusting for baseline characteristics.

Conclusions

PDE5is on-demand for ED are associated with a low overall probability of treatment success in terms of EF, OF and psychological well-being (TRIFECTA). According to our data sildenafil, vardenafil and avanafil should be preferred over tadalafil in order to achieve a TRIFECTA in the short term.

Conflicts of Interest

None.
Artificial Intelligence in Military Medicine
Authors: Leone Ryan M , Chambers James A , Donham Benjamin P , Junker Caesar A
Published: July 2024

Artificial intelligence (AI) has garnered significant attention for its pivotal role in the national security and health care sectors. However, its utilization in military medicine remains relatively unexplored despite its immense potential. AI operates through evolving algorithms that process extensive datasets, continuously improving accuracy and emulating human learning processes. Generative AI, a type of machine learning, uses algorithms to generate new content, such as images, text, videos, audio, and computer code. These models employ deep learning to encode simplified representations of training data and generate new work resembling the original without being identical. Although many AI applications in military medicine are theoretical, the U.S. Military has implemented several initiatives, often without widespread awareness among its personnel. This article aims to shed light on two resilience initiatives spearheaded by the Joint Artificial Intelligence Center, which is now the Chief Digital and Artificial Intelligence Office. These initiatives aim to enhance commanders’ dashboards for predicting troop behaviors and develop models to forecast troop suicidality. Additionally, it outlines 5 key AI applications within military medicine, including (1) clinical efficiency and routine decision-making support, (2) triage and clinical care algorithms for large-scale combat operations, (3) patient and resource movements in the medical common operating picture, (4) health monitoring and biosurveillance, and (5) medical product development. Even with its promising potential, AI brings forth inherent risks and limitations that require careful consideration and discussion. The article also advocates for a forward-thinking approach for the U.S. Military to effectively leverage AI in advancing military health and overall operational readiness.
Aspergillus Endophthalmitis Secondary to Infectious Scleritis: Utility of Diagnostic PCR
Authors: Elwood Kevin F. , Warner Evan J. , Chang Jonathan S. , Kopplin Laura J.
Published: July 2024

Purpose:

To describe a case of delayed-onset Aspergillus fumigatus endophthalmitis secondary to infectious fungal scleritis diagnosed with broad range polymerase chain reaction (PCR) from scleral nodular debridement and vitreous sampling during vitrectomy.

Methods:

Retrospective case report with slit lamp photography, optical coherence tomography, and fundus photography.

Results:

A 76-year-old man presented with right eye worsening vision and pain concerning for progressive nodular scleritis and endophthalmitis eight months following a reportedly innocuous tree branch injury. Following the injury, he underwent an MRI, surgical exploration, subconjunctival antibiotic administration, and culturing due to persistent foreign body sensation. Cultures were negative, and the patient was started on oral NSAIDs, oral prednisone, and periocular triamcinolone injections following negative/normal infectious and rheumatologic workup for scleritis. The patient was referred for worsened scleritis with development of endophthalmitis. He underwent lamellar sclerectomy, debridement, and culture of purulent material from scleral nodules in coordination with diagnostic vitrectomy, vitreous sampling, and subconjunctival and intravitreal antibiotic and antifungal treatment. Broad range PCR was positive for Aspergillus fumigatus and targeted antifungal treatment initiated. The eye did not regain visual function and was enucleated for progressive pain six months following diagnosis.

Conclusion:

Fungal scleritis and endophthalmitis results in significant morbidity. Diagnostic vitrectomy and broad range PCR can aid in prompt diagnosis and targeted treatment, and may be useful in refractory cases.
Orbital Oncocytic Carcinoma: A Comprehensive Case Series and Literature Review
Authors: Li Jing , Yang Runzi , Liu Rui , Wang Nan , Zhang Hong , Guo Qihan , Ma Jianmin
Published: July 2024

Purpose:

This case series and literature review evaluated the baseline variables, clinical symptoms, pathological characteristics, and prognosis of patients with orbital oncocytic carcinoma.

Methods:

This retrospective case series collected the medical histories and other related data from 13 patients pathologically diagnosed with oncocytic carcinoma.

Results:

The average age of patients with orbital oncocytic carcinoma was 64.8 years, with a significantly higher rate of males than females. Furthermore, unilateral disease was more common than bilateral disease. All patients had surrounding tissue invasion, most commonly to extraocular muscles (69.2%) and bones (53.8%). The clinical manifestations were proptosis (30.8%), swelling of the lesion area (23.1%), vision loss (23.1%), diplopia (23.1%), periocular mass (23.1%), tears (15.4%), eye pain (7.7%), ptosis (7.7%), and visual field loss (7.7%). Microscopic examination revealed many large eosinophilic cells. There were obvious nuclei and abundant mitotic figures. The cancer cells expressed cytokeratin, but not P63 or S-100. The follow-up duration was 2–53 months, and the metastasis rate was 16.7%. The patients exhibited a good prognosis. The main treatment methods included surgical resection, surgery combined with radiotherapy, and the enucleation of ocular contents.

Conclusions:

Orbital oncocytic carcinoma has the immunohistochemical characteristics of eosinophilic tumor cells, with expression of cytokeratin but not P63 or S-100. The prognosis is favorable. Surgical resection, surgery combined with radiotherapy, and enucleation of intraocular material are effective treatment options. Nevertheless, long-term follow-up and close observation for metastases are required.
“By Us for Us”: Lessons Learned in Developing a National Training and Technical Assistance Center by and for CHWs
Authors: Wennerstrom Ashley , Witmeier Kelsey N. , Wortmann Kira , Holderby-Fox Lisa Renee , Haywood Catherine G. , Ohly Sherri L.
Published: July 2024

In 2021, the Centers for Disease Control and Prevention (CDC) funded 67 health departments to implement community health worker (CHW) programs to enhance COVID-19 response. The CDC also funded a unique CHW-led Technical Assistance and Training (TTA) Center called Envision, which supported health departments to implement CHW programs and promote CHW workforce sustainability. After 1 year, Envision evaluators interviewed Envision staff to assess barriers and facilitators in developing the Center and the degree to which CHW leadership was operationalized. Thematic analysis revealed 3 themes regarding relationships, CHW values in practice, and operational challenges. Findings informed program updates. CHWs, funders, and policymakers may learn from these experiences.