bluuebunny/crossref_metadata_2025 huggingface dataset:
A converse of dynamical Mordell–Lang conjecture in positive characteristic
Authors: Lee Jungin , Nam GyeongHyeon
Published: July 2024

In this paper, we prove the converse of the dynamical Mordell–Lang conjecture in positive characteristic: For every subset

S
⊂

N

0

S \subset \mathbb {N}_0

which is a union of finitely many arithmetic progressions along with finitely many

p
p

-sets of the form
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartSet sigma-summation Underscript j equals 1 Overscript m Endscripts c Subscript j Baseline p Superscript k Super Subscript j Superscript n Super Subscript j Superscript Baseline colon n Subscript j Baseline element-of double-struck upper N 0 EndSet">

{

∑

j
=
1

m

c
j

p

k
j

n
j

:

n
j

∈

N

0

}

\left \{ \sum _{j=1}^{m} c_j p^{k_jn_j} : n_j \in \mathbb {N}_0 \right \}

(

c
j

∈

Q

c_j \in \mathbb {Q}

,

k
j

∈

N

0

k_j \in \mathbb {N}_0

), there exist a split torus

X
=

G

m
k

X = \mathbb {G}_m^k

defined over

K
=

F

p

¯

(
t
)

K=\overline {\mathbb {F}_p}(t)

, an endomorphism

Φ
\Phi

of

X
X

,

α
∈
X
(
K
)

\alpha \in X(K)

and a closed subvariety

V
⊆
X

V \subseteq X

such that

{
n
∈

N

0

:

Φ
n

(
α
)
∈
V
(
K
)
}

=
S

\left \{ n \in \mathbb {N}_0 : \Phi ^n(\alpha ) \in V(K) \right \} = S

.
Regularity for one-phase Bernoulli problems with discontinuous weights and applications
Authors: Ferreri Lorenzo , Velichkov Bozhidar
Published: July 2024

We study a one-phase Bernoulli free boundary problem with weight function admitting a discontinuity along a smooth jump interface. In any dimension

N
≥
2

N\ge 2

, we show the

C

1
,
α

C^{1, \alpha }

regularity of the free boundary outside of a singular set of Hausdorff dimension at most

N
−
3

N-3

. In particular, we prove that the free boundaries are

C

1
,
α

C^{1, \alpha }

regular in dimension

N
=
2

N=2

, while in dimension

N
=
3

N=3

the singular set can contain at most a finite number of points. We use this result to construct singular free boundaries in dimension

N
=
2

N=2

, which are minimizing for one-phase functionals with weight functions in

L
∞

L^\infty

that are arbitrarily close to a positive constant.
Sobolev inequalities and regularity of the linearized complex Monge-Ampère and Hessian equations
Authors: Wang Jiaxiang , Zhou Bin
Published: July 2024

Let

u
u

be a smooth, strictly

k
k

-plurisubharmonic function on a bounded domain

Ω
∈

C

n

\Omega \in \mathbb C^n

with

2
≤
k
≤
n

2\leq k\leq n

. The purpose of this paper is to study the regularity of solution to the linearized complex Monge-Ampère and Hessian equations when the complex

k
k

-Hessian

H
k

[
u
]

H_k[u]

of

u
u

is bounded from above and below. We first establish an estimate of Green’s functions associated to the linearized equations. Then we prove a class of new Sobolev inequalities. With these inequalities, we use Moser’s iteration to investigate the a priori estimates of Hessian equations and their linearized equations, as well as the Kähler scalar curvature equation. In particular, we obtain the Harnack inequality for the linearized complex Monge-Ampère and Hessian equations under an extra integrability condition on the coefficients.
Some Sellarsian Myths
Authors: Snowdon Paul F
Published: July 2024

This chapter locates Sellars’s discussion of perception in Empiricism and the Philosophy of Mind within the context of his discussion of the myth of the given. It argues that his criticisms of the traditional sense datum theory are insightful but in some respects indecisive. It is further argued that Sellars’s account of our thought about perception contains important insights in his treatment of looks-judgements, but that he mis-describes in a fundamental way our understanding of such talk, and that more mistakes creep into his account when he links our thought about perception to the second myth of Jones.
Introduction
Authors: Pearson Giles
Published: July 2024

The Introduction highlights two reasons, besides its intrinsic interest, that Aristotle’s account of what-emotions-are is worth investigating. First, emotions play a significant role in many aspects of his thought—e.g. his ethics, politics, philosophy of mind, aesthetics, and rhetoric—and so the account will bear on a number of important aspects of his thinking. Second, Aristotle’s account challenges many current philosophical views of emotions in a number of important respects and several of these will be developed in this book. The Introduction also marks out a key question about Aristotle’s account of the emotions that the book does not address—namely, which intentional state or states he thinks can apprehend objects of emotions—and shows that the book’s project—concerning what he thinks emotions are—can remain neutral on the correct answer to that question. The Introduction also sketches the contents of the book, chapter by chapter.
Emotions as Representational Hedonic States
Authors: Pearson Giles
Published: July 2024

Part I (Chapters 2–5) develops the core interpretation of Aristotle’s view of emotions as representational pleasures or distresses that form in response to other intentional states that apprehend their objects. This chapter first addresses what Aristotle means when he claims that emotions ‘are accompanied by’ (hepetai) pleasure or pain. Although a few options are available, it is argued that it is at any rate clear that for at least a good range of cases Aristotle thinks that emotions are (at least in part) pleasures or pains. But what sort of pleasures or pains? The view that they are non-representational sensations or feelings is resisted. Instead, it is argued that Aristotle holds that the pleasures or pains of emotions are representational states in their own right (and hence ‘distress’ is better than ‘pain’). The chapter closes by arguing that there should be no general prejudice against such a view.
Pleasure and Distress as Contributing to the Individuation of Emotion-Types
Authors: Pearson Giles
Published: July 2024

If Aristotle thinks that emotions require both (1) an intentional state that apprehends their object and (2) a representational pleasure/distress directed at that object (so Chapter 2), the next question is: what is the relation between these two elements? This chapter considers the suggestion, advanced by several commentators, that the two are simply two different ways of characterizing the same thing. This view, which I label the ‘Identification view’, is resisted on two grounds. First, and most simply, some of Aristotle’s specifications of emotions indicate that he thinks the two are separate states. Second, the way Aristotle individuates emotions (roughly, by a combination of pleasure/distress and the emotion’s evaluative object) dictates that he cannot hold the Identification view. The chapter also argues that the considerations adduced here concerning the individuation of emotions can help construct an argument against current judgementalist and perceptualist views, insofar as the latter must involve extraneous representational additions.
Anger (Orgē)
Authors: Pearson Giles
Published: July 2024

Part II of the book (Chapters 6–8) considers Aristotle on the relation between emotions and desires. This chapter tackles anger orgē. From Aristotle’s account of anger in Rhetoric II.2—a desire for revenge accompanied by distress at an apparent slight—it is clear that he holds that anger involves both a desire and a concurrent distress. However, it is argued that this need not undermine the idea that he thinks emotions are representational pleasures/distresses alone. So long as he holds that anger essentially incorporates both a desire and an emotion (a representational distress), he can, quite legitimately, treat it as an emotion qua distress, even if it also involves a desire. The chapter also considers a representational pleasure Aristotle connects to anger (directed at the hope of revenge). And it closes by examining the connection between the distress of anger and its desire and investigating why Aristotle maintains anger essentially involves both.
The Material or Bodily Dimension of Emotions
Authors: Pearson Giles
Published: July 2024

Part III of the book (Chapters 9–10) considers some further challenges to the interpretation thus far developed. This chapter addresses the fact that Aristotle clearly holds that emotions essentially involve a material dimension. Some have thought that the way Aristotle specifies this (esp. in De anima I.1) shows he thinks emotions cannot be adequately defined at all without explicit reference to their material aspect. Against this, it is argued that Aristotle thinks emotions can be legitimately specified simply in terms of representational pleasures/distresses (directed at apparent instantiations of the emotion’s evaluative object). The chapter shows it is plausible that Aristotle thinks such definitions are extensionally equivalent to ones that include reference to their material dimension, and are themselves explanatorily significant. And it is argued that he thinks the material aspect need only be highlighted in certain contexts—in natural science investigations or when explanatorily helpful—but is unnecessary/unhelpful to specify in many other legitimate kinds of investigation.
Explaining Recalcitrant Emotions with Aristotle
Authors: Pearson Giles
Published: July 2024

A notorious touchstone in recent discussions of emotions has been how different accounts can deal with recalcitrant emotions. This chapter argues that Aristotle’s view has a significant advantage over accounts that identify emotions with perceptual states, judgements, or quasi-judgements (such as passive assent or inclination to assent). All such views fail either to explain the existence of (all plausible cases of) recalcitrant emotions or to account for their irrationality (when they are irrational); even if that irrationality is specified in practical or motivational terms. By contrast, it is argued that Aristotle’s view, as developed in this book, enables him to do both these things. It is also argued that recalcitrant emotions are not necessarily irrational, but could be rational if they conflict with an irrationally formed judgement. This view is defended against those who take rationality to be simply a matter of coherence.
Introduction
Authors: Marvin Laurence W
Published: July 2024

Chapter 1 outlines the reasons why Pope Innocent III called for a crusade. Its planning began in 1213, culminating in a general ecumenical council. In 1215 the participants at the Fourth Lateran council determined various details of the projected crusade, including a timeline for departure and financing, although they did not identify a specific operational target. The chapter also describes the Latin Christian and Islamic world of the Near East prior to the crusade. It explores the kind of men who went on it, as well as how western armies were organized and led. The chapter does the same thing for Ayyubid armies, explaining how they were organized, and the forces available to the Ayyubid rulers to defend themselves. The chapter explains the nature of “brown-water” or riverine warfare, which was a unique feature of this crusade since the major portion of it was fought along the Nile river. The chapter also explains how we can view this crusade through the various levels of military planning and thought: grand strategy, strategy, campaigns, operations, and tactics. Finally, the chapter describes in brief the most important primary sources of the crusade.
From Europe to the Holy Land, 1217–18
Authors: Marvin Laurence W
Published: July 2024

Chapter 2 explains how the various groups which made up the Latin Christian army got from their embarkation points to the Holy Land. Frisian and Germans departed from the Netherlands in late May 1217. Along the Atlantic coast they encountered rough weather and nautical mishaps. In Lisbon, a portion of this force led by William of Holland attacked the Muslim-held fortress of Alcácer do Sal, which surrendered after a dramatic siege. Those who had not participated in the siege of Alcácer made their way further down the coast, conducting raids against Faro, Rota, and Cadiz. Forces from other parts of Europe made their way from Mediterranean ports in the summer and early fall of 1217 to the city of Acre. In late 1217 the crusaders conducted three raids in Muslim Syria, including against Mount Tabor. After that, the presumptive leader of the crusade, Andrew, king of Hungary, departed. In the winter and spring of 1218 other groups arrived in Acre and participated in talks to determine a specific operational target for the crusade. After much debate, the crusaders decided to attack the city of Damietta on the Egyptian coast in order to threaten Cairo. The goal was to convince the Ayyubid sultan, al-‘Adil, to return Jerusalem in exchange for not losing Cairo. Since Andrew’s departure, the pope had not formally designated another commander nor had the magnates of the army agreed upon one.
Winter 1219 through the Battle of Fariskur, August 29, 1219
Authors: Marvin Laurence W
Published: July 2024

Chapter 4 emphasizes the period from early February 1219 through the crusader defeat at Fariskur in August. The crusaders could not attack Damietta directly because of al-Kamil’s camp and underwater obstructions. Pelagius began asserting more control over certain aspects of the crusade, which made him unpopular and caused tensions between him and King John. The Egyptians suffered a crisis when al-Kamil uncovered a plot by Ibn al-Mashtub and other emirs to overthrow him and replace him with one of his younger brothers. Al-Kamil abandoned his camp, allowing the crusaders to cross the Nile without casualties and seize al-Adilya and its extensive supplies. They established it as their forward base but for protection against Egyptian relief forces, dug a circumvallation from al-Adilya to Damietta’s walls. The crusaders drew close to Damietta’s walls and essentially surrounded it. They launched multiple assaults by sea and land but were thrown back, and in turn suffered numerous Egyptian attacks. In August 1219 the common crusaders demanded a change of operational strategy, so the army marched out to confront al-Kamil’s army at Fariskur. The sultan seemingly abandoned his camp to the Latin Christian advance, but as the crusade army tarried there to loot, its members ran short of water. The Ayyubid army attacked the crusaders, causing a tactical rout as the crusaders panicked and retreated to Damietta. Despite the severe defeat the strategic situation had not changed.
Cracks, 1220–21
Authors: Marvin Laurence W
Published: July 2024

Chapter 6 explains why the crusaders did not conduct an offensive in 1220. Both primary and secondary sources often criticize the crusaders for not advancing on Cairo immediately. The crusaders did not do so for sound reasons, among them the season, the army’s exhaustion, disputes over spoils and territory in Damietta, and al-Mu‘azzam’s attacks against crusader targets in Syria like Caesarea. The disposition of plunder caused conflicts and aggravated tensions between King John and Pelagius. After threats against Pelagius, some money was paid out. In February John departed for Acre to defend against al-Mu‘azzam, and to press his son’s case for the kingship of Cilician Armenia. As the only trusted military leader, his absence made the army unwilling to advance on Cairo, even as reinforcements arrived in the spring and summer. The crusaders believed that Frederick II, King of the Germans and Emperor of the Romans designate, would arrive with reinforcements, and take command. Pelagius unsuccessfully initiated a summer offensive because without a reliable military leader, the army refused. Al-Mu‘azzam’s efforts in Latin Syria caused crusaders to go defend it, ending the possibility of an offensive. In the first half of 1221, with Frederick now emperor, the crusaders believed he would arrive. Rumors of mysterious allies, notably Prester John or King David, also buoyed the Latin Christians. By the early summer Frederick’s deputy, Louis, Duke of Bavaria, came with reinforcements. The leaders of the army decided to attack al-Kamil at Mansoura rather than Cairo. Pelagius recalled King John to Egypt.
The Failed Campaign, Negotiations, and the End of the Crusade
Authors: Marvin Laurence W
Published: July 2024

Chapter 7 explains how and why the offensive of 1221 ended as it did. The crusaders, pushed by Pelagius and Louis, prepared to advance without Frederick. This went against the pope’s and emperor’s wishes since the pope wanted Frederick to lead in person. John did not support an offensive either. His relationship with Pelagius never improved. By mid-July al-Kamil, aware of the Latin Christian army’s imminent advance, offered a deal like that of fall 1219. The crusaders made unrealistic counter-offers. The army marched to Fariskur and then Shirimsah. John recommended staying there, but all continued south. The army discounted the Mahalla canal opening on the Nile’s west side as an ingress point. By late July the army arrived at the intersection of the Nile and Tinnīs branch across from Mansoura. It could not cross to a hostile riverbank, so the men constructed a fortified camp. Forces led by al-Kamil’s brothers began arriving. Al-Kamil used the Mahalla canal to get ships behind the crusaders, strangling them logistically. After much dissention the crusaders retreated north as al-Kamil’s troops flooded the Nile’s eastern bank. During the retreat men got stuck or drowned and Muslim forces surrounded them. By August 28 the army was trapped near al-Barāmūn. It surrendered on August 30. The terms were generous given the circumstances. The two sides exchanged hostages. In Damietta some talked of refusing to turn over the city. Eventually the Latin Christians surrendered Damietta, and all either walked or sailed to Acre.
Conclusion
Authors: Marvin Laurence W
Published: July 2024

The conclusion analyzes why the Damietta Crusade failed. Its result did not blunt Latin Christian desire to crusade in the eastern Mediterranean. In 1249 King Louis IX led another army to Egypt and encountered more initial success but suffered a worse defeat than the first, with Louis himself taken captive. The Damietta Crusade is a snapshot of early-thirteenth-century Latin Christian grand strategic, strategic, operational, and tactical thinking. Its grand strategy and strategy were sound. Operationally its participants lacked the vision to accept a diplomatic solution and insisted on taking Damietta as recompense for the blood and treasure expended. The crusade thus failed at the operational level but was not the sole cause of the crusade’s defeat. Powell’s “leadership question” contributed: Pelagius and John never got along, but neither was unambiguously in charge nor was any other noble. Frederick II’s repeated delays sapped initiative and morale. The most effective leader on either side was al-Kamil, who exercised effective strategic and operational leadership, and proved to be adroit diplomatically. Ethnic and social tensions in the army contributed to the crusade’s failure, as well as the consistent departure of seasoned veterans who served only for a year or less. The campaign’s brown-water nature complicated things, despite the crusaders’ superior nautical expertise. Local knowledge of water ways and terrain trumped maritime skill. The crusade suggests that people have always served, fought, and died to achieve goals they did not understand or that changed along with the circumstances.
Bidirectional Associations between Probable Eating Disorders and Mental Health Conditions Among Military Service Members and Veterans
Authors: Sharifian Neika , Ray Travis N , Jacobson Isabel G , Klimek-Johnson Patrycja , McMaster Hope S , Geronimo-Hara Toni Rose , Rull Rudolph P , Maguen Shira ,   for the Millennium Cohort Study Team, Baccetti Anna , Belding Jenn , Boparai Satbir , Carey Felicia R , Castañeda Sheila F , Villalobos Javier , Kolaja Claire , Magallon Sandra , Rivera Anna , Roesch Scott , Seay Julia , Sheppard Beverly , Trone Daniel , Walstrom Jennifer , Zhu Katie
Published: July 2024

Although prior research has examined the prevalence of eating disorders (EDs) such as binge eating disorder (BED) and bulimia nervosa (BN) among military personnel, less is known regarding temporal associations between EDs and other mental health conditions. Using longitudinal data from 179,694 service members and veterans from the Millennium Cohort Study, temporal associations between EDs (BN, BED) and mental health conditions (posttraumatic stress disorder, anxiety, depression, and problem drinking) were investigated using a cross-lagged panel model approach. Results indicated consistent bidirectional associations between most mental health conditions and EDs; however, the magnitude of these cross-lagged associations varied across BN and BED. Cross-lagged effects of mental health conditions on subsequent BED were significantly stronger than BED to mental health condition cross-lagged effects. In contrast, cross-lagged effects of BN on subsequent mental health conditions were stronger than mental health conditions to BN. Preventive screening for those at risk for BN may have a stronger impact on mitigating downstream mental health conditions, while interventions among those with mental health conditions may play a greater role in eliminating maladaptive coping strategies including binge eating. Study findings underscore the importance of early detection of mental health conditions and EDs to maximize readiness among service members.
Principles and practices of returning individual research results to participants in large studies of pregnancy and childhood
Authors: Mash Clay , McAllister Kimberly A , Wonnum Sundania , Vargas Ashley J , Dowling Gaya , Arteaga S Sonia , Blaisdell Carol J , Hardy Kristina K , Das Irene Prabhu , Raju Tonse N K , Gillman Matthew W
Published: July 2024

Investigators conducting human subject research have typically conveyed only clinically actionable results back to individual participants. Shifting scientific culture around viewing participants as partners in research, however, is prompting investigators to consider returning as much data or results as the participant would like, even if they are not clearly actionable. Expanding return of individual results may add value for individual participants and their communities, refine future research questions and methods, build trust, and enhance retention of participants. Yet, gaps remain in understanding the implications of these changes for groups of “vulnerable” participants, including pregnant and pediatric participants. Here we present the findings of a National Institutes of Health workshop on returning individual research results, particularly as applicable to pregnant and pediatric participants. Research participants who were panelists at the workshop agreed that they desired to receive their results. Workshop findings and current literature indicate that participants have differing preferences for what results they receive. One way to address the limits of current practice is to develop flexible digital platforms that convey individual results along with researchers’ availability to answer questions, and to provide as much information as possible about actionable steps for controlling environmental exposures associated with disease risk.
Evaluating the desirability of outcome ranking and response adjusted for duration of antibiotic risk for clinical trials of antibiotics in pediatric pneumonia
Authors: VanBuren John M , Banks Russell K , Kuppermann Nathan , Gerber Jeffrey S , Ruddy Richard M , Casper T Charles , Florin Todd A ,   Pediatric Emergency Care Applied Research Network (PECARN)
Published: July 2024

Objective outcomes for pediatric community-acquired pneumonia (CAP) are lacking. The desirability of outcome ranking (DOOR) and response adjusted for duration of antibiotic risk (RADAR) outcome encompass clinical benefit and adverse effects, while also accounting for antibiotic exposure. We evaluated DOOR and RADAR (DOOR/RADAR) through simulations and compared sample-size considerations to noninferiority designs in a hypothetical trial comparing antibiotics and no antibiotics (ie, placebo) for children with mild CAP. We also evaluated a trial comparing different durations of antibiotic therapy. Three scenarios were considered: 1 with no difference in DOOR between the 2 groups, 1 in which placebo is more efficacious, and another in which amoxicillin is more efficacious than placebo. The power to detect a difference between arms was greater using DOOR/RADAR compared with DOOR alone. Assuming a sample size of 200, DOOR had 2.5%, 50%, and 65% power to detect a statistical difference between arms for scenarios 1-3, respectively, significantly less than DOOR/RADAR. Importantly, DOOR/RADAR incorrectly identified placebo as superior in scenario 3, where amoxicillin was truly efficacious. Sample size requirements for noninferiority designs were larger to achieve similar levels of power as DOOR and DOOR/RADAR. DOOR/RADAR has the potential to lead to an incorrect conclusion declaring placebo superior when amoxicillin is efficacious.
The Racial Ideology of the British Police: Protecting and Maintaining the Racial Interests of the White Institution
Authors: Wicks Nikhaela
Published: July 2024

Previous canonical writings on racism and policing have focussed on the shift from overt to covert articulations (Loftus 2010; Holdaway and O’Neill 2013), finding that racism is communicated primarily by white, heterosexist men in ‘white spaces’ (Loftus 2008). This paper moves beyond individualistic conceptions of racism to explore how police officers subscribe to a white racial ideology (Bonilla-Silva 2018). By drawing upon over 600 h of observations and interviews and discussions with over 60 officers, this paper explores four police discourses that underplay, defend and maintain the unequal racial status quo in policing: (1) individualization, (2) historicization, (3) discursive deracialization and (4) racial stories.
Fruit anatomy and histogenesis in Mediterranean species of Arbutus (Ericaceae: Arbutoideae): ecological and morphogenetic aspects
Authors: Yatsenko Olga V , Sorokin Alexey N , Romanov Mikhail S , Bobrov Alexey V F Ch , Iovlev Petr S , Zdravchev Nikita S , Timchenko Anton S , Mikhaylova Anna A , Vasekha Natalia D , Kandidov Maxim V , Kuptsov Kirill V
Published: July 2024

Details of fruit anatomy and pericarp histogenesis were studied in Mediterranean species of Arbutus with the aim to determine the morphogenetic fruit type, to reveal the functional and ecological significance of fruit structure, and to suggest the most probable scenarios of fruit structural transformations in Arbutoideae (Ericaceae). The pericarp of the coenocarpous berries of Arbutus is differentiated into: one-layered exocarp, multilayered parenchymatous mesocarp with scattered solitary and groups of sclereids, and one-layered endocarp composed of thin-walled cells. The warts covering the fruit surface are formed by parenchymatous cells of the mesocarp and the exocarp. The process of pericarp development in Arbutus is divided into four periods, which correlate with the phenology and climatic factors of the Mediterranean region. The origin of the dormancy period in the middle part of fruit development in Arbutus is interpreted as an important adaptation to the arid Mediterranean climate. The data obtained suggest that both the berry of Arbutus and the pyrenariums of Arctostaphylos and Arctous are highly specialized fruit types that could not have derived from each other. The capsule of Hamamelis type of Enkianthoideae is recognized as the original fruit type of the berries and pyrenariums of Arbutoideae.
Presynaptic hyperexcitability reversed by positive allosteric modulation of a GABABR epilepsy variant
Authors: Minere Marielle , Mortensen Martin , Dorovykh Valentina , Warnes Gary , Nizetic Dean , Smart Trevor G , Hannan Saad B
Published: July 2024

GABABRs are key membrane proteins that continually adapt the excitability of the nervous system. These G-protein coupled receptors are activated by the brain's premier inhibitory neurotransmitter GABA. They are obligate heterodimers composed of GABA-binding GABABR1 and G-protein-coupling GABABR2 subunits. Recently, three variants (G693W, S695I, I705N) have been identified in the gene (GABBR2) encoding for GABABR2. Individuals that harbour any of these variants exhibit severe developmental epileptic encephalopathy and intellectual disability, but the underlying pathogenesis that is triggered in neurons remains unresolved.

Using a range of confocal imaging, flow cytometry, structural modelling, biochemistry, live cell Ca2+ imaging of presynaptic terminals, whole-cell electrophysiology of human embryonic kidney (HEK)-293 T cells and neurons and two-electrode voltage clamping of Xenopus oocytes, we have probed the biophysical and molecular trafficking and functional profiles of G693W, S695I and I705N variants.

We report that all three point mutations impair neuronal cell surface expression of GABABRs, reducing signalling efficacy. However, a negative effect evident for one variant perturbed neurotransmission by elevating presynaptic Ca2+ signalling. This is reversed by enhancing GABABR signalling via positive allosteric modulation.

Our results highlight the importance of studying neuronal receptors expressed in nervous system tissue and provide new mechanistic insights into how GABABR variants can initiate neurodevelopmental disease whilst highlighting the translational suitability and therapeutic potential of allosteric modulation for correcting these deficits.
The representation of noun–verb distinction in left posterior middle temporal gyrus: evidence from representation similarity analyses
Authors: Zhang Wenjia , Chen Xuemei , Wang Suiping
Published: July 2024

Nouns and verbs are fundamental grammatical building blocks of languages. A key question is whether and where the noun–verb division was represented in the brain. Previous studies mainly used univariate analyses to examine this issue. However, the interpretation of activated brain regions in univariate analyses may be confounded with general cognitive processing and/or confounding variables. We addressed these limitations by using partial representation similarity analysis (RSA) of Chinese nouns and verbs with different levels of imageability. Participants were asked to complete the 1-back grammatical class probe (GCP; an explicit measure) and the 1-back word probe (WP; an implicit measure) tasks while undergoing functional magnetic resonance imaging. RSA results showed that the activation pattern in the left posterior middle temporal gyrus (LpMTG) was significantly correlated with the grammatical class representational dissimilarity matrix in the GCP task after eliminating the potential confounding variables. Moreover, the LpMTG did not overlap with the frontal–parietal regions that were activated by verbs vs. nouns or the task effect (CRP vs. WP) in univariate analyses. These results highlight the role of LpMTG in distinguishing nouns from verbs rather than general cognitive processing.
Volleyball training improves working memory in children aged 7 to 12 years old: an fNIRS study
Authors: Zhong Xiaoke , Dai Yuanfu , Xu Mingchao , Jiang Changhao
Published: July 2024

This study aimed to investigate the effect of a 12-wk extracurricular volleyball training on working memory from both behavioral and cerebral aspects. A total of 80 children were randomized assigned to (i) the experimental group, who engaged in extracurricular volleyball training for 60 min, thrice a week for 12 wk, and (ii) the control group, who maintained their regular daily routine. Working memory was evaluated in both groups using the N-back task before and after the intervention. Furthermore, functional near-infrared spectroscopy was employed to monitor the level of oxygenated hemoglobin in the prefrontal cortex. The experimental group performed better in the behavioral task than the control group, as evidenced by a shorter response time and a higher correct rate. The functional near-infrared spectroscopy results suggested that the activation of the left dorsolateral prefrontal cortex was significantly higher in the experimental group than in the control group. In addition, correlation analyses showed that the enhancement of left dorsolateral prefrontal cortex activation was significantly correlated with decreasing response time and improving response accuracy in the N-back task. These findings suggest that the left dorsolateral prefrontal cortex is likely the neural substrate for improved working memory performance elicited by 12-wk open skill exercise.
Revisiting the Evidence Base That Informs the Use of Adjunctive Therapy for Enterococcus faecalis Endocarditis: A Systematic Review and Meta-Analysis
Authors: Prosty Connor , Sorin Mark , Katergi Khaled , Khalaf Roy , Fogarty Clare , Turenne Malick , Lee Todd C , McDonald Emily G
Published: July 2024

Background

Guidelines recommend adjunctive gentamicin for the treatment of Enterococcus faecalis infective endocarditis (EFIE) despite a risk of toxicity. We sought to revisit the evidence for adjunctive therapy in EFIE and to synthesize the comparative safety and effectiveness of aminoglycosides versus ceftriaxone by systematic review and meta-analysis.

Methods

For historical context, we reviewed seminal case series and in vitro studies on the evolution from penicillin monotherapy to modern-day regimens for EFIE. Next, we searched MEDLINE and Embase from inception to 16 January 2024 for studies of EFIE that compared adjunctive aminoglycosides versus ceftriaxone or adjunctive versus monotherapy. Where possible, clinical outcomes were compared between regimens using random effects meta-analysis. Otherwise, data were narratively summarized.

Results

The meta-analysis was limited to 10 observational studies at high risk of bias (911 patients). Relative to adjunctive ceftriaxone, gentamicin had similar all-cause mortality (risk difference [RD], –0.8%; 95% confidence interval [CI], −5.0 to 3.5), relapse (RD, −0.1%; 95% CI, −2.4 to 2.3), and treatment failure (RD, 1.1%; 95% CI, −1.6 to 3.7) but higher discontinuation due to toxicity (RD, 26.3%; 95% CI, 19.8 to 32.7). The 3 studies that compared adjunctive therapy to monotherapy included only 30 monotherapy patients, and heterogeneity precluded meta-analysis.

Conclusions

Adjunctive ceftriaxone appeared to be equally effective and less toxic than gentamicin for the treatment of EFIE. The existing evidence does not clearly establish the superiority of either adjunctive therapy or monotherapy. Pending randomized evidence, if adjunctive therapy is to be used, ceftriaxone appears to be a reasonable option.
Percutaneous mechanical support in catheter ablation of ventricular arrhythmias: hype or hope?
Authors: Kautzner Josef , Hašková Jana , Stojadinovič Predrag , Peichl Petr , Wichterle Dan
Published: July 2024

Catheter ablation (CA) has become an established treatment strategy for managing recurrent ventricular tachycardias (VTs) in patients with structural heart disease. In recent years, percutaneous mechanical circulatory support (PMCS) devices have been increasingly used intra-operatively to improve the ablation outcome. One indication would be rescue therapy for patients who develop haemodynamic deterioration during the ablation. However, more efforts are focused on identifying subjects who are at high risk of such deterioration and could benefit from the pre-emptive use of the PMCS. The third reason to use PMCS could be the inability to identify diffuse substrate, especially in non-ischaemic cardiomyopathy. This paper reviews available experiences using various types of PMCS in different clinical scenarios. Although PMCS allows mapping during VT, it does not significantly influence acute outcomes and not convincingly long-term outcomes. On the contrary, the complication rate appears to be higher in PMCS cohorts. Our data suggest that even in patients with severe left ventricular dysfunction, the substrate modification can be performed without the need for general anaesthesia and risk of haemodynamic decompensation. In end-stage heart failure associated with the electrical storm, implantation of a left ventricular assist device (or PMCS with a transition to the left ventricular assist device) might be the preferred strategy before CA. In high-risk patients who are not potential candidates for these treatment options, radiotherapy could be considered as a bail-out treatment of recurrent VTs. These approaches should be studied in prospective trials.
The evolution of reduced facilitation in a four-species bacterial community
Authors: Piccardi Philippe , Ulrich Eric , Garcia-Garcerà Marc , Martino Rita Di , Testa Samuele E A , Mitri Sara
Published: July 2024

Microbial evolution is typically studied in monocultures or in communities of competing species. But microbes do not always compete and how positive inter-species interactions drive evolution is less clear: Initially facilitative communities may either evolve increased mutualism, increased reliance on certain species according to the Black Queen Hypothesis (BQH), or weaker interactions and resource specialization. To distinguish between these outcomes, we evolved four species for 44 weeks either alone or together in a toxic pollutant. These species initially facilitated each other, promoting each other’s survival and pollutant degradation. After evolution, two species (Microbacterium liquefaciens and Ochrobactrum anthropi) that initially relied fully on others to survive continued to do so, with no evidence for increased mutualism. Instead, Agrobacterium tumefaciens and Comamonas testosteroni (Ct) whose ancestors interacted positively, evolved in community to interact more neutrally and grew less well than when they had evolved alone, suggesting that the community limited their adaptation. We detected several gene loss events in Ct when evolving with others, but these events did not increase its reliance on other species, contrary to expectations under the BQH. We hypothesize instead that these gene loss events are a consequence of resource specialization. Finally, co-evolved communities degraded the pollutant worse than their ancestors. Together, our results support the evolution of weakened interactions and resource specialization, similar to what has been observed in competitive communities.
Dynamics of the lipid body lipidome in the oleaginous yeast Yarrowia sp
Authors: Joshi Apoorva Ravindra , Barvkar Vitthal T , Kashikar Akanksha , Gaikwad Prashant , Ravikumar Ameeta
Published: July 2024

Time-dependent changes in the lipid body (LB) lipidome of two oleaginous yeasts, Yarrowia lipolytica NCIM 3589 and Yarrowia bubula NCIM 3590 differing in growth temperature was investigated. LB size and lipid content were higher in Y. lipolytica based on microscopy, Feret, and integrated density analysis with lipid accumulation and mobilization occurring at 48 h in both strains. Variations in LB lipidome were reflected in interfacial tension (59.67 and 68.59 mN m−1) and phase transition temperatures (30°C–100°C and 60°C–100°C) for Y. lipolytica and Y. bubula, respectively. Liquid Chromatography-Mass Spectroscopy (LC–MS) analysis revealed neutral lipids (NLs), phospholipids, sphingolipids, sterols, and fatty acids as the major classes present in both strains while fatty acid amides were seen only in Y. lipolytica. Amongst the lipid classes, a few species were present in abundance with a number of lipids being less dominant. Permutational multivariate analysis of variance (PERMANOVA) and Analysis of covariance (ANOCOVA) analysis suggest 22 lipids belonging to NLs, fatty acid amides, and free fatty acids were found to be statistically different between the two strains. Analysis of the ratios between different lipid components suggest changes in LB size and mobilization as a function of time. The results indicate influence of temperature and strain variation on the dynamics of LB lipidome in Yarrowia species.
Racial/Ethnic Differences in Loneliness Among Older Adults: The Role of Income and Education as Mediators
Authors: Taylor Harry Owen , Chen Yu-Chih , Tsuchiya Kazumi , Cudjoe Thomas K M , Qin Weidi , Nguyen Ann W , Roy Arka
Published: July 2024

Background and Objectives

Loneliness is a major public health concern; however, limited research has examined the mechanisms contributing to racial/ethnic inequities in loneliness. Race/ethnicity has been hypothesized to be a distal factor influencing loneliness, and racial/ethnic inequities in loneliness may be attributable to socioeconomic factors (e.g., income and education). Our study seeks to confirm these hypotheses by examining mechanisms that contribute to racial/ethnic inequities in loneliness. In other words, if racial/ethnic differences in loneliness among older adults are mediated by income and education.

Research Design and Methods

Data came from the Health and Retirement Study Leave-Behind Questionnaire, 2014–2016. Loneliness was measured by the UCLA 3-item loneliness scale. Race/ethnicity categories were White, Black, and Hispanic/Latino. The mediator variables were household income and education. Multivariable linear regression models were used to determine differences in loneliness by race/ethnicity. The Karlson–Holm–Breen (KHB) mediation method was used to determine if income and education mediated racial/ethnic differences in loneliness.

Results

In models examining income and education together, a complete mediation was found between White and Black older adults, in that income and education completely mediated differences in loneliness between these groups. A partial mediation was found between White and Hispanic, and Black and Hispanic older adults. When examining income and education separately, we found that income solely accounted for racial/ethnic differences in loneliness compared to education.

Discussion and Implications

Our study is the first to explicitly determine if socioeconomic factors mediate race/ethnicity differences in loneliness among a national sample of older adults. These findings illustrate that income may have greater proximate effects for loneliness among older adults in comparison to education. Additionally, these findings can inform evidence-based interventions to reduce loneliness among older adults. Interventions that enhance quality of life and provide opportunities for socialization for racialized low-income older adults may help decrease racial/ethnic inequities in loneliness.
Revisiting G 1/19 Three Years Later: A Missed Opportunity?
Authors: Fischer Michael M
Published: July 2024

Decision G 1/19 of the EPO’s Enlarged Board of Appeal has changed the patentability of computer-implemented simulations. It has also had an impact on the patentability of computer-implemented inventions in Europe more generally, which has become more restrictive as existing case law has not been confirmed. Moreover, G 1/19 has started a process in which previously well-defined legal terms are becoming increasingly blurred. The author identifies the problems associated with this development and points to early case law, such as T 208/84 and the German Federal Supreme Court’s (BGH) Logikverifikation, which the Enlarged Board of Appeal could easily have followed but chose not to. Finally, the author presents his own ‘Three Motives Model’ as a possible solution and compares it with a previous, similar model based on a ‘Virtual Analog Rule’ for patent eligibility suggested by Joseph. S. Bird in the US in 2015.
Effectiveness of e-learning material on essential components of evidence-based medicine among laypersons: a randomized controlled trial
Authors: Okabayashi Satoe , Kitazawa Kyoko , Noma Hisashi , Takahashi Yoshimitsu , Iwami Taku , Kawamura Takashi , Nakayama Takeo
Published: July 2024

Evidence-based medicine (EBM) is helpful for laypersons’ decision-making. This study aimed to evaluate the effectiveness of e-learning materials on the essential components of EBM for laypersons. We conducted a web-based, open-label, randomized controlled trial with laypersons in Japan aged ≥20 years who used the internet. Participants were randomly assigned to the intervention group with the e-learning material and the control group with only the ‘Introduction’ section of the same material. The primary and secondary outcomes were the self-created acquirement test scores (responding correctly with confidence) immediately after using the material and after 4 weeks. A multiple linear regression analysis was conducted. Of the 122 participants, 62 were randomly assigned to the intervention group and 59 to the control group; finally, 59 and 58, respectively, were included in the full analysis set. The mean (standard deviation) of the acquirement test score immediately after learning was 14.11 and (3.11) and 11.07 (3.88) in the intervention and control groups, respectively, indicating statistical significance (multivariable P < 0.001). The secondary long-term outcome was also statistically significant. The results showed that the e-learning material was effective for laypersons in acquiring the essential components of EBM. The material may increase laypersons’ confidence in appraising health information, which can be used in decision-making.
Polar Multiplicities and Integral Dependence
Authors: Cid-Ruiz Yairon
Published: July 2024

We provide new criteria for the integrality and birationality of an extension of graded algebras in terms of the general notion of polar multiplicities of Kleiman and Thorup. As an application, we obtain a new criterion for when a module is a reduction of another in terms of certain mixed Buchsbaum–Rim multiplicities. Furthermore, we prove several technical results regarding polar multiplicities.
SARS-CoV-2 Monoclonal Antibody Treatment Followed by Vaccination Shifts Human Memory B-Cell Epitope Recognition, Suggesting Antibody Feedback
Authors: Bloom Nathaniel , Ramirez Sydney I , Cohn Hallie , Parikh Urvi M , Heaps Amy , Sieg Scott F , Greninger Alex , Ritz Justin , Moser Carlee , Eron Joseph J , Bajic Goran , Currier Judith S , Klekotka Paul , Wohl David A , Daar Eric S , Li Jonathan , Hughes Michael D , Chew Kara W , Smith Davey M , Crotty Shane , Coelho Camila H ,   for the Accelerating COVID-19 Therapeutic Interventions and Vaccines–2/A5401 (ACTIV-2/A5401) Study Team, Hosey Lara , Roa Jhoanna , Patel Nilam , Erhardt Bill , Adams Stacey
Published: July 2024

Therapeutic monoclonal antibodies (mAbs) have been studied in humans, but the impact on immune memory of mAb treatment during an ongoing infection remains unclear. We evaluated the effect of infusion of the anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) mAb bamlanivimab on memory B cells (MBCs) in SARS-CoV-2–infected individuals. Bamlanivimab treatment skewed the repertoire of MBCs targeting spike toward non-RBD epitopes. Furthermore, the relative affinity of RBD MBCs was weaker in mAb-treated individuals compared to placebo-treated individuals over time. Subsequently, after mRNA coronavirus disease 2019 vaccination, MBC differences persisted and mapped to a specific reduction in recognition of the class II RBD site, the same RBD epitope recognized by bamlanivimab. These findings indicate a substantial role of antibody feedback in regulating MBC responses to infection, and single mAb administration can continue to impact MBC responses to additional antigen exposures months later.