bluuebunny/crossref_metadata_2025 huggingface dataset:
Interplay of electromagnetically induced transparency and Doppler broadening in hot atomic vapors
Authors: Zhang (张理达) Lida , Stiesdal Nina , Busche Hannes , Gaard Hansen Mikkel , Pohl Thomas , Hofferberth Sebastian
Published: July 2024

For multi-level systems in hot atomic vapors the interplay between the Doppler shift due to atomic motion and the wavenumber mismatch between driving laser fields strongly influences transmission and absorption properties of the atomic medium. In a three-level atomic ladder-system, Doppler broadening limits the visibility of electromagnetically-induced transparency (EIT) when the probe and control fields are co-propagating, while EIT is recovered under the opposite condition of counter-propagating geometry and

k

p

<

k

c

, with

k

p

and

k

c

being the wavenumbers of the probe and control fields, respectively. This effect has been studied and experimentally demonstrated as an efficient mechanism to realize non-reciprocal probe light transmission, which may enable applications as magnetic-field free optical isolators. Here, we describe the basics of this effect and discuss a simple picture for the underlying mechanism. We illustrate how the non-reciprocity scales with wavelength mismatch and show how to experimentally demonstrate the effect in a simple Rydberg-EIT system using thermal Rubidium atoms.
Double diffraction imaging of x-ray induced structural dynamics in single free nanoparticles
Authors: Sauppe M , Bischoff T , Bomme C , Bostedt C , Colombo A , Erk B , Feigl T , Flückiger L , Gorkhover T , Heilrath A , Kolatzki K , Kumagai Y , Langbehn B , Müller J P , Passow C , Ramm D , Rolles D , Rompotis D , Schäfer-Zimmermann J , Senfftleben B , Treusch R , Ulmer A , Zimbalski J , Möller T , Rupp D
Published: July 2024

Because of their high photon flux, x-ray free-electron lasers (FEL) allow to resolve the structure of individual nanoparticles via coherent diffractive imaging (CDI) within a single x-ray pulse. Since the inevitable rapid destruction of the sample limits the achievable resolution, a thorough understanding of the spatiotemporal evolution of matter on the nanoscale following the irradiation is crucial. We present a technique to track x-ray induced structural changes in time and space by recording two consecutive diffraction patterns of the same single, free-flying nanoparticle, acquired separately on two large-area detectors opposite to each other, thus examining both the initial and evolved particle structure. We demonstrate the method at the extreme ultraviolet (XUV) and soft x-ray Free-electron LASer in Hamburg (FLASH), investigating xenon clusters as model systems. By splitting a single XUV pulse, two diffraction patterns from the same particle can be obtained. For focus intensities of about

2
×

10

12

 W cm−2 we observe still largely intact clusters even at the longest delays of up to 650 picoseconds of the second pulse, indicating that in the highly absorbing systems the damage remains confined to one side of the cluster. Instead, in case of five times higher flux, the diffraction patterns show clear signatures of disintegration, namely increased diameters and density fluctuations in the fragmenting clusters. Future improvements to the accessible range of dynamics and time resolution of the approach are discussed.
The Rosenzweig–Porter model revisited for the three Wigner–Dyson symmetry classes
Authors: Čadež Tilen , Kumar Nandy Dillip , Rosa Dario , Andreanov Alexei , Dietz Barbara
Published: July 2024

Interest in the Rosenzweig–Porter model, a parameter-dependent random-matrix model which interpolates between Poisson and Wigner–Dyson (WD) statistics describing the fluctuation properties of the eigenstates of typical quantum systems with regular and chaotic classical dynamics, respectively, has come up again in recent years in the field of many-body quantum chaos. The reason is that the model exhibits parameter ranges in which the eigenvectors are Anderson-localized, non-ergodic (fractal) and ergodic extended, respectively. The central question is how these phases and their transitions can be distinguished through properties of the eigenvalues and eigenvectors. We present numerical results for all symmetry classes of Dyson’s threefold way. We analyzed the fluctuation properties in the eigenvalue spectra, and compared them with existing and new analytical results. Based on these results we propose characteristics of the short- and long-range correlations as measures to explore the transition from Poisson to WD statistics. Furthermore, we performed in-depth studies of the properties of the eigenvectors in terms of the fractal dimensions, the Kullback–Leibler (KL) divergences and the fidelity susceptibility. The ergodic and Anderson transitions take place at the same parameter values and a finite size scaling analysis of the KL divergences at the transitions yields the same critical exponents for all three WD classes, thus indicating superuniversality of these transitions.
Secant loci of scrolls over curves
Authors: Hitching George
Published: July 2024

Given a curve

C
C

and a linear series

ℓ
\ell

on

C
C

, the secant locus

V
e

e
−
f

(
ℓ
)

V^{e-f}_e( \ell )

parametrises effective divisors of degree

e
e

which impose at most

e
−
f

e-f

conditions on

ℓ
\ell

. For

E
→
C

E \to C

a vector bundle of rank

r
r

, we define determinantal subschemes
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper H Subscript e Superscript e minus f Baseline left-parenthesis script l right-parenthesis subset-of-or-equal-to normal upper H normal i normal l normal b Superscript e Baseline left-parenthesis double-struck upper P upper E right-parenthesis">

H
e

e
−
f

(
ℓ
)
⊆

H
i
l
b

e

(

P

E
)

H^{e-f}_e ( \ell )\subseteq \mathrm {Hilb}^e ( \mathbb {P}E )

and
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper Q Subscript e Superscript e minus f Baseline left-parenthesis upper V right-parenthesis subset-of-or-equal-to normal upper Q normal u normal o normal t Superscript 0 comma e Baseline left-parenthesis upper E Superscript asterisk Baseline right-parenthesis">

Q
e

e
−
f

(
V
)
⊆

Q
u
o
t

0
,
e

(

E
∗

)

Q^{e-f}_e(V)\subseteq \mathrm {Quot}^{0, e} ( E^* )

which generalise

V
e

e
−
f

(
ℓ
)

V^{e-f}_e( \ell )

, giving several examples. We describe the Zariski tangent spaces of

Q
e

e
−
f

(
V
)

Q^{e-f}_e(V)

, and give examples showing that smoothness of

Q
e

e
−
f

(
V
)

Q^{e-f}_e(V)

is not necessarily controlled by injectiveness of a Petri map. We generalise the Abel–Jacobi map and the notion of linear series to the context of Quot schemes.

We give some sufficient conditions for nonemptiness of generalised secant loci, and a criterion in the complete case when

f
=
1

f = 1

in terms of the Segre invariant

s
1

(
E
)

s_1 (E)

. This leads to a geometric characterisation of semistability similar to that in [Quot schemes, Segre invariants, and inflectional loci of scrolls over curves, Geom. Dedicata 205 (2020), 1–19]. Using these ideas, we also give a partial answer to a question of Lange on very ampleness of

O

P

E

(
1
)

\mathcal {O}_{\mathbb {P}E}(1)

, and show that for any curve,

Q
e

e
−
1

(
V
)

Q^{e-1}_e(V)

is either empty or of the expected dimension for sufficiently general

E
E

and

V
V

. When

Q
e

e
−
1

(
V
)

Q^{e-1}_e(V)

has and attains expected dimension zero, we use formulas of Oprea–Pandharipande and Stark to enumerate

Q
e

e
−
1

(
V
)

Q^{e-1}_e(V)

.

We mention several possible avenues of further investigation.
A multi-bin rarefying method for evaluating alpha diversities in TCR sequencing data
Authors: Li Mo , Hua Xing , Li Shuai , Wu Michael C , Zhao Ni
Published: July 2024

Motivation

T cell receptors (TCRs) constitute a major component of our adaptive immune system, governing the recognition and response to internal and external antigens. Studying the TCR diversity via sequencing technology is critical for a deeper understanding of immune dynamics. However, library sizes differ substantially across samples, hindering the accurate estimation/comparisons of alpha diversities. To address this, researchers frequently use an overall rarefying approach in which all samples are sub-sampled to an even depth. Despite its pervasive application, its efficacy has never been rigorously assessed.

Results

In this paper, we develop an innovative “multi-bin” rarefying approach that partitions samples into multiple bins according to their library sizes, conducts rarefying within each bin for alpha diversity calculations, and performs meta-analysis across bins. Extensive simulations using real-world data highlight the inadequacy of the overall rarefying approach in controlling the confounding effect of library size. Our method proves robust in addressing library size confounding, outperforming competing normalization strategies by achieving better-controlled type-I error rates and enhanced statistical power in association tests.

Availability and implementation

The code is available at https://github.com/mli171/MultibinAlpha. The datasets are freely available at https://doi.org/10.21417/B7001Z and https://doi.org/10.21417/AR2019NC.
Bromodomain-containing 4 is a Positive Regulator of the Inflammatory Cytokine Response in the Gut
Authors: Franzè Eleonora , Laudisi Federica , Maresca Claudia , Di Grazia Antonio , Iannucci Andrea , Pacifico Teresa , Ortenzi Angela , Sica Giuseppe , Lolli Elisabetta , Stolfi Carmine , Monteleone Ivan , Monteleone Giovanni
Published: July 2024

Background and Aim

Bromodomain-containing protein 4 [BRD4], one of the components of the bromodomain and extraterminal domain [BET] family, is a transcriptional and epigenetic regulator of cellular proliferation and cytokine production. In this study, we assessed whether BRD4 regulates the cytokine response in inflammatory bowel diseases [IBD].

Materials and Methods

BRD4 expression was analysed in intestinal mucosal samples of patients with ulcerative colitis [UC], patients with Crohn’s disease [CD], normal controls [CTRs], and mice with chemically-induced colitis, by real-time polymerase chain reaction [PCR], western blotting, and confocal microscopy. Cytokine production was evaluated in lamina propria mononuclear cells [LPMCs] of IBD patients and mucosal tissues of colitic mice treated with BRD4 inhibitors. Finally, we evaluated the effect of JQ1, an inhibitor of the BRD4 signalling pathway, on the course of murine colitis.

Results

BRD4 RNA and protein expression was up-regulated in the inflamed mucosa of patients with UC and patients with CD as compared with the uninvolved areas of the same patients and CTRs, and in the inflamed colon of colitic mice. Knockdown of BRD4 with a specific antisense oligonucleotide in IBD LPMCs led to reduced expression of TNF-α, IL-6, IFN-γ, and IL-17A. Administration of JQ1 to colitic mice inhibited the inflammatory cytokine response and attenuated the ongoing colitis.

Conclusions

This is the first study showing the up-regulation of BRD4 in IBD and suggesting the role of such a protein in the positive control of the inflammatory cytokine response in the gut.
Development and Investigation of a Non-invasive Disease Severity Index for Inflammatory Bowel Disease
Authors: Swaminathan Akhilesh , Borichevsky Grace Mary , Frampton Chris , Kettle Anthony James , Peyrin-Biroulet Laurent , Siegel Corey Allan , Day Andrew Stewart , Gearry Richard Blair
Published: July 2024

Introduction

The disease severity index [DSI] encapsulates the inflammatory bowel disease [IBD] burden but requires endoscopic investigations. This study developed a non-invasive DSI using faecal calprotectin [DSI-fCal] and faecal myeloperoxidase [DSI-fMPO] instead of colonoscopy.

Methods

Adults with IBD were recruited prospectively. Baseline biomarker concentrations were used to develop DSI-fCal and DSI-fMPO, and these were correlated with the original DSI, IBD symptoms, endoscopic activity, and quality of life [QoL]. Areas under the receiver operating characteristic curves [AUROC] assessed DSI-fCal and DSI-fMPO as predictors of clinical and biochemical remission at 6 months [symptom remission and fCal < 150 μg/g, respectively], and a complicated IBD-course at 24 months [disease relapse needing escalation of biologics or immunomodulators, recurrent corticosteroids, IBD hospitalisations, and/or surgeries]. Multivariable logistic regression assessed the utility of DSI-fCal and DSI-fMPO in predicting a complicated IBD course at 24 months.

Results

In total, 171 patients were included (Crohn’s disease = 99, female = 90, median age = 46 years, interquartile range [IQR] 36–59]). DSI-fCal and DSI-fMPO correlated with the original DSI [r > 0.9, p < 0.001], endoscopic indices [r = 0.45–0.49, p < 0.001], IBD symptoms [r = 0.53–0.58, p < 0.001] and QoL [r = -0.57–0.58, p < 0.001]. Baseline DSI-fCal [AUROC = 0.79, 95% CI 0.65–0.92] and DSI-fMPO [AUROC = 0.80, 95% CI 0.67–0.93] were associated with 6-month clinical and biochemical remission. DSI-fCal [AUROC = 0.83, 95% CI 0.77–0.89] and DSI-fMPO [AUROC = 0.80, 95% CI 0.73–0.87] performed similarly in predicting a complicated IBD course to the original DSI [pdifference > 0.05]. The non-invasive DSI was independently associated with a complicated IBD course on multivariable analyses [DSI-fCal28, aOR = 6.04, 95% CI 2.42–15.08; DSI-fMPO25, aOR = 7.84, 95% CI 2.96–20.73].

Conclusions

The DSI-fCal and DSI-fMPO perform similarly in prognosticating the longitudinal disease course as the original DSI, whilst avoiding a need for an endoscopic assessment.
Microbial anabolic and catabolic utilization of hydrocarbons in deep subseafloor sediments of Guaymas Basin
Authors: Nagakura Toshiki , Morono Yuki , Ito Motoo , Mangelsdorf Kai , Pötz Stefanie , Schnabel Ellen , Kallmeyer Jens
Published: July 2024

Guaymas Basin, located in the Gulf of California, is a hydrothermally active marginal basin. Due to steep geothermal gradients and localized heating by sill intrusions, microbial substrates like short-chain fatty acids and hydrocarbons are abiotically produced from sedimentary organic matter at comparatively shallow depths. We analyzed the effect of hydrocarbons on uptake of hydrocarbons by microorganisms via nano-scale secondary ion mass spectrometry (NanoSIMS) and microbial sulfate reduction rates (SRR), using samples from two drill sites sampled by IODP Expedition 385 (U1545C and U1546D). These sites are in close proximity of each other (ca. 1 km) and have very similar sedimentology. Site U1546D experienced the intrusion of a sill that has since then thermally equilibrated with the surrounding sediment. Both sites currently have an identical geothermal gradient, despite their different thermal history. The localized heating by the sill led to thermal cracking of sedimentary organic matter and formation of potentially bioavailable organic substrates. There were low levels of hydrocarbon and nitrogen uptake in some samples from both sites, mostly in surficial samples. Hydrocarbon and methane additions stimulated SRR in near-seafloor samples from Site U1545C, while samples from Site U1546D reacted positively only on methane. Our data indicate the potential of microorganisms to metabolize hydrocarbons even in the deep subsurface of Guaymas Basin.
Natural forests support higher mycological diversity and more edible mushroom species than plantation forests in Ethiopia
Authors: Megersa Shasho , Yohannes Yonas , Dejene Tatek , Martín-Pinto Pablo
Published: July 2024

To identify measures to protect and conserve macrofungal communities in Ethiopian forests, we need a more comprehensive understanding of macrofungal diversity, functions, and fruiting body production. In this study, we assessed macrofungal communities in three forest types in Gambo Forest District, South-Central Ethiopia. We surveyed 18 plots (each 1000 m2) located in a clear-cut and replanted plantation forest, an old plantation forest, and a natural forest. We identified a total of 132 macrofungal species, of which 75% were saprotrophic, 16% were ectomycorrhizal, and 9% were plant pathogens. We identified 40 edible species, including economically important species, such as those from the genus of Agaricus, Morchella, Cantharellus, Suillus, and Termitomyces. The three forests were significantly different (P < .001) in terms of their macrofungal community composition, with natural forest having the highest species richness and unique community assemblages. In total, 86 macrofungal species were collected from natural forest, of which 28 species were edible. The macrofungal diversity of clear-cut and old plantation forests did not differ significantly. Our findings suggest that prioritizing the restoration or preservation of fragmented natural forests rather than the expansion of exotic tree plantations would be a more effective strategy for conserving and enhancing macrofungal species diversity and the production of economically valuable edible species.
Chromosome-Scale Genome Assembly for Soft-Stem Bulrush (Schoenoplectus tabernaemontani) Confirms a Clade-Specific Whole-Genome Duplication in Cyperaceae
Authors: Li Yang , Ning Yu , Zheng Yan Chao , Lou Xuan Yu , Pan Zhe , Dong Shu Bin
Published: July 2024

Schoenoplectus tabernaemontani (C. C. Gmelin) Palla is a typical macrophyte in diverse wetland ecosystems. This species holds great potential in decontamination applications and carbon sequestration. Previous studies have shown that this species may have experienced recent polyploidization. This would make S. tabernaemontani a unique model to study the processes and consequences of whole-genome duplications in the context of the well-documented holocentric chromosomes and dysploidy events in Cyperaceae. However, the inference was not completely solid because it lacked homology information that is essential to ascertain polyploidy. We present here the first chromosome-level genome assembly for S. tabernaemontani. By combining Oxford Nanopore Technologies (ONT) long reads and Illumina short reads, plus chromatin conformation via the Hi-C method, we assembled a genome spanning 507.96 Mb, with 99.43% of Hi-C data accurately mapped to the assembly. The assembly contig N50 value was 3.62 Mb. The overall BUSCO score was 94.40%. About 68.94% of the genome was comprised of repetitive elements. A total of 36,994 protein-coding genes were predicted and annotated. Long terminal repeat retrotransposons accounted for ∼26.99% of the genome, surpassing the content observed in most sequenced Cyperid genomes. Our well-supported haploid assembly comprised 21 pseudochromosomes, each harboring putative holocentric centromeres. Our findings corroborated a karyotype of 2n = 2X = 42. We also confirmed a recent whole-genome duplication occurring after the divergence between Schoenoplecteae and Bolboschoeneae. Our genome assembly expands the scope of sequenced genomes within the Cyperaceae family, encompassing the fifth genus. It also provides research resources on Cyperid evolution and wetland conservation.
A Chromosome-Level Genome Assembly and Annotation for theOecanthus rufescens(Orthoptera: Oecanthidae)
Authors: Jing Xuan , Zhao Hui-Yao , Zheng Yan-Na , Nie Yi-Meng , Ma Li-Bin , Huang Yuan
Published: July 2024

Oecanthus is a genus of cricket known for its distinctive chirping and distributed across major zoogeographical regions worldwide. This study focuses on Oecanthus rufescens, and conducts a comprehensive examination of its genome through genome sequencing technologies and bioinformatic analysis. A high-quality chromosome-level genome of O. rufescens was successfully obtained, revealing significant features of its genome structure. The genome size is 877.9 Mb, comprising ten pseudo-chromosomes and 70 other sequences, with a GC content of 41.38% and an N50 value of 157,110,771 bp, indicating a high level of continuity. BUSCO assessment results demonstrate that the genome's integrity and quality are high (of which 96.8% are single-copy and 1.6% are duplicated). Comprehensive genome annotation was also performed, identifying approximately 310 Mb of repetitive sequences, accounting for 35.3% of the total genome sequence, and discovering 15,481 tRNA genes, 4,082 rRNA genes, and 1,212 other noncoding genes. Furthermore, 15,031 protein-coding genes were identified, with BUSCO assessment results showing that 98.4% (of which 96.3% are single-copy and 1.6% are duplicated) of the genes were annotated.
Carbapenem combination therapy versus standard of care for persistent methicillin-susceptible Staphylococcus aureus bacteraemia
Authors: Shah Sunish , Clarke Lloyd G , Ludwig Justin , Burgdorf Sarah , Arbulu Guerra Ricardo D , Shields Ryan K
Published: July 2024

Background

Successful use of carbapenems in combination with cefazolin or oxacillin for treatment of MSSA bacteraemia has been described; however, comparative data to standard treatment approaches are lacking.

Methods

This was a multicentre, retrospective study of adult patients with MSSA bacteraemia for >48 h. Standard treatment was considered monotherapy with cefazolin, oxacillin or nafcillin. Combination therapy was defined as the addition of ertapenem or meropenem to standard treatment for at least 24 h. The primary outcome was duration of bacteraemia defined as time from administration of an antibiotic with in vitro activity to first negative blood culture. Time to blood culture sterilization was compared through risk-set matching with aid of a propensity score.

Results

Overall, 238 patients were included; 66% (157/238) received standard treatment and 34% (81/238) received combination therapy. The median (IQR) time to carbapenem initiation was 4.7 (3.63–6.5) days. Patients who received combination therapy were younger (P = 0.012), more likely to have endocarditis (P = 0.034) and had longer median duration of bacteraemia (P < 0.001). After applying risk-set matching, patients who received combination therapy experienced faster time to blood culture sterilization compared with control patients [HR = 1.618 (95% CI; 1.119–2.339) P = 0.011]. Using a paired hazard model, 90 day mortality rates were not statistically different among patients who received combination therapy versus matched controls [HR = 1.267 (95% CI; 0.610–2.678), P = 0.608].

Discussion

Carbapenem combination therapy resulted in faster time to blood culture sterilization, but no differences in overall mortality rates. Randomized trials are critical to determine the utility of carbapenem combination therapy.
The interactive effects of medicinal dyes with conventional antimicrobials against skin pathogens
Authors: Ramfol Rhea , van Vuuren Sandy
Published: July 2024

Aims

This study aimed to explore potential synergistic effects of medicinal dyes with antimicrobials against pathogens responsible for skin infections.

Methods and results

Antimicrobial testing was conducted using minimum inhibitory concentrations and minimum bactericidal/fungicidal concentration assays. The fractional inhibitory index (ΣFIC) of combinations was calculated, and isobolograms were constructed on selected combinations. Toxicity studies were conducted using the brine-shrimp lethality assay. Combination (1:1 ratio) studies noted that 26% of dye-antibiotic combinations were synergistic against the Gram-positive strains, 15% against the Gram-negative strains, and 14% against the yeasts. The Mercurochrome: Betadine® combination noted synergy at ratios against all the Staphylococcus aureus strains with ΣFIC values ranging from 0.05 to 0.48. The combination of Gentian violet with Gentamycin noted a 15-fold decrease in toxicity, and a selectivity index of 977.50 against the Escherichia coli (DSM 22314) strain. Time-kill studies were conducted on the combinations with the highest safe selectivity index (SI) value and lowest safe SI value i.e. Gentian violet with Gentamycin and Malachite green with Neomycin. Both combinations demonstrated better antimicrobial activity in comparison to the independent values and the controls.

Conclusion

This study highlights the potential for medicinal dye combinations as a treatment for skin infections.
A Quantitative Review of Certified Burn Therapist’s Involvement in the JBCR Publications and ABA Leadership
Authors: Warthman Renée , O’Neil Audrey M , Murray Derek , Nedelec Bernadette , Islas Claudia , Foster Kevin N
Published: July 2024

The Burn Therapist Certification (BT-C) was introduced in 2018 to acknowledge occupational therapists (OT) and physical therapists (PT) with specialized knowledge, skill, and experience in the promotion of quality burn rehabilitation. Currently, BT-Cs make up 11.7% of therapists working in burn rehabilitation (n = 39/333). The purpose of this review is to report on the contributions of BT-Cs to organizational leadership of the American Burn Association (ABA) and in the generation of new knowledge through peer-reviewed publications. Despite the small percentage of burn therapists who are certified, they have a disproportionately large involvement in leadership within the ABA and burn research in the Journal of Burn Care and Rehabilitation (JBCR). From 2018 to 2023, BT-Cs have contributed to nearly one-half (n = 26/56) of therapy authored publications in the JBCR and almost one-third (n = 65/202) of accepted abstracts at the ABA annual meeting. Certified burn therapists demonstrate substantial involvement throughout the ABA, including maintaining an 85% membership rate and, on average, serve in 53% (n = 31/59) of the therapy allotted committee positions. Therapist pursuit of certification can have a profound impact on the burn community through publication, leadership, and development of care standards. Although therapists have indicated a desire to pursue certification, barriers related to a lack of association and center support have been identified. The burn community has endorsed certification as a mark of excellence for nurses and physicians. Maximizing the value of a transdisciplinary approach to burn care is also dependent on the excellence of therapies. If the burn community desires improved engagement and contribution from therapies, it should support therapist certification.
Keratan sulfate proteoglycan: putative template for neuroblast migratory and axonal fascicular pathways and fetal expression in globus pallidus, thalamus, and olfactory bulb
Authors: Sarnat Harvey B , Yu Weiming
Published: July 2024

Keratan sulfate (KS) is a proteoglycan secreted in the fetal brain astrocytes and radial glia into extracellular parenchyma as granulofilamentous deposits. KS surrounds neurons except dendritic spines, repelling glutamatergic and facilitating GABAergic axons. The same genes are expressed in both neuroblast migration and axonal growth. This study examines timing of KS during morphogenesis of some normally developing human fetal forebrain structures. Twenty normal human fetal brains from 9-41 weeks gestational age were studied at autopsy. KS was examined by immunoreactivity in formalin-fixed paraffin sections, plus other markers including synaptophysin, S-100β protein, vimentin and nestin. Radial and tangential neuroblast migratory pathways from subventricular zone to cortical plate were marked by KS deposits as early as 9wk GA, shortly after neuroblast migration initiated. During later gestation this reactivity gradually diminished and disappeared by term. Long axonal fascicles of the internal capsule and short fascicles of intrinsic bundles of globus pallidus and corpus striatum also appeared as early as 9-12wk, as fascicular sleeves before axons even entered. Intense KS occurs in astrocytic cytoplasm and extracellular parenchyma at 9wk in globus pallidus, 15wk thalamus, 18wk corpus striatum, 22wk cortical plate, and hippocampus postnatally. Corpus callosum and anterior commissure do not exhibit KS at any age. Optic chiasm shows reactivity at the periphery but not around intrinsic subfasciculi. We postulate that KS forms a chemical template for many long and short axonal fascicles before axons enter and neuroblast migratory pathways at initiation of migration. Cross-immunoreactivity with aggrecan may render difficult molecular distinction.
Intraorganizational mobility and employees’ work-related contact patterns: evidence from panel data in the European Commission
Authors: Vantaggiato Francesca P , Murdoch Zuzana , Kassim Hussein , Geys Benny , Connolly Sara
Published: July 2024

Programs to encourage staff to move within public-sector organizations have become increasingly widespread in recent decades. Yet, although there are some anecdotal accounts, the effects of such intraorganizational mobility remain largely unexplored. Building on insights from organization theory and social psychology, we argue that intraorganizational mobility entails an important trade-off: it undermines movers’ depth of work-related contacts within the (new) department, while it increases the breadth of their work-related contacts outside it. Our empirical analysis evaluates this trade-off using a two-way fixed effects model for a longitudinal dataset of movers (N = 149) and stayers (N = 473) across two survey waves among European Commission officials in 2014 and 2018. Our main findings confirm that intraorganizational mobility is connected in opposing ways to employees’ intra- and extra-departmental work-related contact patterns. In line with theoretical expectations, we find these relationships to be stronger for employees who have previously experienced intraorganizational moves (“repeat-movers”).
Learning local cascading failure pattern from massive network failure data
Authors: Xiao Xun , Ye Zhisheng , Revie Matthew
Published: July 2024

This article proposes a novel multivariate point process regression model for a large-scale physically distributed network infrastructure with two failure modes, i.e. primary failures caused by the long-term usage and degradation of assets, and cascading failures triggered by primary failures in a short period. We exploit large-scale field pipe failure data from a UK-based water utility to support the rationale of considering the two failure modes. The two modes are not self-revealed in the data. To make the inference of the large-scale problem possible, we introduce a time window for cascading failures, based on which the likelihood of the pipe failure process can be decomposed into two parts, one for the primary failures and the other for the cascading failure processes modulated by the primary failure processes. The window length for cascading failures is treated as a tuning parameter, and determined through maximizing the likelihood based on all failure data. To illustrate the effectiveness of the model, two case studies are presented based on real data from the UK-based water utility. Interesting features of the cascading failures are identified from massive field pipe failure data. The results provide insights on advanced modelling and practical decision-making for both researchers and practitioners.
Effect of semaglutide on kidney function across different levels of baseline HbA1c, blood pressure, body weight and albuminuria in SUSTAIN 6 and PIONEER 6
Authors: Apperloo Ellen M , Cherney David Z I , Kuhlman Anja Birk , Mann Johannes F E , Rasmussen Søren , Rossing Peter , Tuttle Katherine R , Vrhnjak Blaz , Heerspink Hiddo J L
Published: July 2024

Background

This post hoc analysis explored the effects of semaglutide on estimated glomerular filtration (eGFR) slope by baseline glycemic control, blood pressure (BP), body mass index (BMI) and albuminuria status in people with type 2 diabetes and high cardiovascular risk.

Methods

Pooled SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) and PIONEER 6 (A Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes) data were analyzed for change in eGFR slope by baseline hemoglobin A1c (HbA1c) (<8%/≥8%; <64/≥64 mmol/mol), systolic BP (<140/90/≥140/90 mmHg) and BMI (<30/≥30 kg/m2). SUSTAIN 6 data were analyzed by baseline urinary albumin:creatinine ratio (UACR; <30/30–300/>300 mg/g).

Results

The estimated absolute treatment differences overall in eGFR slope (95% confidence intervals) favored semaglutide versus placebo in the pooled analysis [0.59 (0.29; 0.89) mL/min/1.73 m2/year] and in SUSTAIN 6 [0.60 (0.24; 0.96) mL/min/1.73 m2/year]; the absolute benefit was consistent across all HbA1c, BP, BMI and UACR subgroups (all P-interaction >.5).

Conclusion

A clinically meaningful reduction in risk of chronic kidney disease progression was observed with semaglutide versus placebo regardless of HbA1c, BP, BMI, and UACR levels.
Multicenter Analysis of Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients
Authors: Foca Marc , Demirhan Salih , Munoz Flor M , Valencia Deray Kristen G , Bocchini Claire E , Sharma Tanvi S , Sherman Gilad , Muller William J , Heald-Sargent Taylor , Danziger-Isakov Lara , Blum Samantha , Boguniewicz Juri , Bacon Samantha , Joseph Tuhina , Smith Jodi , Ardura Monica I , Su Yin , Maron Gabriela M , Ferrolino Jose , Herold Betsy C
Published: July 2024

Background

Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes.

Methods

A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned. Episodes of CMV DNA in blood (DNAemia), CMV disease, drug-related toxicities, as well as other infections in the first year posttransplant and demographic and clinical data were collected. CMV DNAemia in the first year after prophylaxis or during prophylaxis (breakthrough) was analyzed by multivariate hazard models.

Results

Among the 749 patients enrolled, 131 (17.5%) had CMV DNAemia at any time in the first year; 85 (11.4%) had breakthrough DNAemia, and 46 (6.1%) had DNAemia after prophylaxis. CMV disease occurred in 30 (4%). In a multivariate model, liver transplantation compared to kidney or heart, intermediate or high risk based on donor/recipient serologies, neutropenia, and valganciclovir dose modifications attributed to toxicity were associated with increased risk of total and/or breakthrough DNAemia. Bacteremia was also associated with increased hazard ratio for CMV DNAemia. In a separate multivariate analysis, rejection occurred more often in those with breakthrough CMV DNAemia (P = .002); liver transplants, specifically, had increased rejection if CMV DNAemia occurred in the first year (P = .004). These associations may be bidirectional as rejection may contribute to infection risk.

Conclusions

CMV DNAemia in the first year posttransplantation occurs despite valganciclovir prophylaxis and is associated with medication toxicity, bacteremia, and rejection. Pediatric studies of newer antivirals, especially in higher-risk subpopulations, appear to be warranted.
A Diagnostic Stewardship Intervention to Improve Utilization of 1,3 β-D-Glucan Testing at a Single Academic Center: Five-Year Experience
Authors: Colson Jordan D , Kendall Jonathan A , Yamamoto Takeru , Mizusawa Masako
Published: July 2024

Background

(1,3)- β-D-glucan (BDG) testing is one of the noninvasive tests to aid diagnosis of invasive fungal infections (IFIs). The study results have been heterogenous, and diagnostic performance varies depending on the risks for IFI. Thus, it is important to select appropriate patients for BDG testing to prevent false-positive results. An algorithmic diagnostic stewardship intervention was instituted at a single academic medical center to improve BDG test utilization.

Methods

The BDG test order in the electronic health record was replaced with the BDG test request order, which required approval to process the actual test order. The approval criteria were (1) immunocompromised or intensive care unit patient and (2) on empiric antifungal therapy, or inability to undergo invasive diagnostic procedures. A retrospective observational study was conducted to evaluate the efficacy of the intervention by comparing the number of BDG tests performed between 1 year pre- and post-intervention. Safety was assessed by chart review of the patients for whom BDG test requests were deemed inappropriate and rejected.

Results

The number of BDG tests performed per year decreased by 85% from 156 in the pre-intervention period to 24 in the post-intervention period. The average monthly number of BDG tests performed was significantly lower between those periods (P = .002). There was no delay in IFI diagnosis or IFI-related deaths in the patients whose BDG test requests were rejected. The sustained effectiveness of the intervention was observed for 5 years.

Conclusions

Institution of the diagnostic stewardship intervention successfully and safely improved BDG test utilization.
Effectiveness of BNT162b2 XBB Vaccine Against XBB and JN.1 Sublineages
Authors: Tartof Sara Y , Slezak Jeff M , Puzniak Laura , Frankland Timothy B , Ackerson Bradley K , Jodar Luis , McLaughlin John M
Published: July 2024

We provide updated results (11 October 2023 through 29 February 2024) from our previously conducted test-negative case-control study in Kaiser Permanente Southern California to evaluate sublineage-specific effectiveness of the BNT162b2 XBB1.5-adapted vaccine. Results suggest that XBB1.5-adapted vaccines may have reduced effectiveness against JN.1 versus XBB sublineages.
Nondifferentiable activity in the brain
Authors: Tsubo Yasuhiro , Shinomoto Shigeru
Published: July 2024

Spike raster plots of numerous neurons show vertical stripes, indicating that neurons exhibit synchronous activity in the brain. We seek to determine whether these coherent dynamics are caused by smooth brainwave activity or by something else. By analyzing biological data, we find that their cross-correlograms exhibit not only slow undulation but also a cusp at the origin, in addition to possible signs of monosynaptic connectivity. Here we show that undulation emerges if neurons are subject to smooth brainwave oscillations while a cusp results from nondifferentiable fluctuations. While modern analysis methods have achieved good connectivity estimation by adapting the models to slow undulation, they still make false inferences due to the cusp. We devise a new analysis method that may solve both problems. We also demonstrate that oscillations and nondifferentiable fluctuations may emerge in simulations of large-scale neural networks.
Atrial anatomical variations on computed tomography angiography associated with atrial fibrillation and those predicting recurrence following pulmonary vein isolation
Authors: Abazid Rami M , Smettie Osama , Romsa Jonathan G , Warrington James , Akincioglu Cigdem , Tzemos Nikolaos , Vezina William C , Khan Habib Rehman
Published: July 2024

Background

We aim to investigate the atrial anatomical variations in patients with and without atrial fibrillation (AF) using cardiac-computed tomography angiography (CCTA) and identify features associated with AF recurrence following pulmonary vein isolation.

Materials and Methods

We retrospectively reviewed 502 CCTAs of patients with AF performed prior to a pulmonary vein isolation procedure with 1058 CCTAs of patients without AF performed to rule out coronary artery disease between 2014 and 2017. Anatomical variations of both atria including left atrial diverticula (LAD), right atrial diverticula (RAD), Bachmann bundle shunt (BBS), and pulmonary vein anatomy were assessed.

Results

We found that patients with AF were older (67 ± 14 vs 63 ± 13 years, P = .039), had a higher prevalence of diabetes (24.4%) versus (14.7%), P = .006, and cerebrovascular accidents (3.8%) versus (0.9%), P = .044 when compared with patients without AF. Furthermore, on CCTAs patients with AF demonstrated a significantly higher prevalence of BBS (11% vs 4.1%, P < .001), LAD (19% vs 7.7%, P < .001), and RAD (9.8% vs 2.1%, P < .001) when compared to patients without AF. Logistic multivariable regression analyses of CCTA findings demonstrated increased odd ratios (OR) in those with AF of BBS (OR = 3.51, 95% CI, 2.32-5.35, P < .001), LAD (OR = 2.94, 95% CI, 2.12-4.07, P < .001), RAD (OR = 1.54, 95% CI, 1.19-2.11, P = .03), LA diameter (OR = 2.42, 95% CI, 1.65-3.39, P < .001). Importantly, multivariate Cox regression showed that the LA dimension is a predictor of AF recurrence (HR = 1.019, 95% CI, 1.001-1.051, P = .02).

Conclusion

AF patients have a higher prevalence of BBS, LAD, and RAD in comparison to patients without AF. Mean LA diameter predicts AF recurrence after the pulmonary vein isolation procedure.
Research progresses on mitochondrial-targeted biomaterials for bone defect repair
Authors: Wang Shuze , Liu Jialin , Zhou Linxi , Xu Hao , Zhang Dan , Zhang Xing , Wang Qiang , Zhou Qing
Published: July 2024

In recent years, the regulation of the cell microenvironment has opened up new avenues for bone defect repair. Researchers have developed novel biomaterials to influence the behavior of osteoblasts and immune cells by regulating the microenvironment, aiming to achieve efficient bone repair. Mitochondria, as crucial organelles involved in energy conversion, biosynthesis and signal transduction, play a vital role in maintaining bone integrity. Dysfunction of mitochondria can have detrimental effects on the transformation of the immune microenvironment and the differentiation of stem cells, thereby hindering bone tissue regeneration. Consequently, targeted therapy strategies focusing on mitochondria have emerged. This approach offers a wide range of applications and reliable therapeutic effects, thereby providing a new treatment option for complex and refractory bone defect diseases. In recent studies, more biomaterials have been used to restore mitochondrial function and promote positive cell differentiation. The main directions are mitochondrial energy metabolism, mitochondrial biogenesis and mitochondrial quality control. In this review, we investigated the biomaterials used for mitochondria-targeted treatment of bone defect repair in recent years from the perspective of progress and strategies. We also summarized the micro-molecular mechanisms affected by them. Through discussions on energy metabolism, oxidative stress regulation and autophagy regulation, we emphasized the opportunities and challenges faced by mitochondria-targeted biomaterials, providing vital clues for developing a new generation of bone repair materials.
XIILiterature 1780–1830: The Romantic Period
Authors: Davis Amanda Blake , Wride Sarah , Fancett Anna , Senkiw Anna
Published: July 2024

This chapter has three sections: 1. General and Prose; 2. The Novel; 3. Drama. Section 1 is by Amanda Blake Davis; section 2 is by Sarah Wride and Anna Fancett; section 3 is by Anna Senkiw. There is no poetry section this year; Romantic poetry for this year will be added to next year’s contribution.
An epidermal growth factor receptor‐targeting immunotoxin based on IgG shows potent antitumor activity against head and neck cancer
Authors: Huang Mei , Park Jisoo , Seo Jina , Ko Sanghwan , Yang Yoon Hee , Lee Yeaji , Kim Hyo Jeong , Lee Bok‐Soon , Lee Yun Sang , Ko Byoung Joon , Jung Sang Teak , Park Deachan , Yoo Tae Hyeon , Kim Chul‐Ho
Published: July 2024

The epidermal growth factor receptor (EGFR) is an important target for cancer therapies. Many head and neck cancer (HNC) cells have been reported to overexpress EGFR; therefore, anti‐EGFR therapies have been attempted in patients with HNC. However, its clinical efficacy is limited owing to the development of drug resistance. In this study, we developed an EGFR‐targeting immunotoxin consisting of a clinically proven anti‐EGFR IgG (cetuximab; CTX) and a toxin fragment (LR‐LO10) derived from Pseudomonas exotoxin A (PE) using a novel site‐specific conjugation technology (peptide‐directed photo‐crosslinking reaction), as an alternative option. The immunotoxin (CTX‐LR‐LO10) showed specific binding to EGFR and properties of a typical IgG, such as stability, interactions with receptors of immune cells, and pharmacokinetics, and inhibited protein synthesis via modification of elongation factor‐2. Treatment of EGFR‐positive HNC cells with the immunotoxin resulted in apoptotic cell death and the inhibition of cell migration and invasion. The efficacy of CTX‐LR‐LO10 was evaluated in xenograft mouse models, and the immunotoxin exhibited much stronger tumor suppression than CTX or LR‐LO10. Transcriptome analyses revealed that the immunotoxins elicited immune responses and altered the expression of genes related to its mechanisms of action. These results support the notion that CTX‐LR‐LO10 may serve as a new therapeutic agent targeting EGFR‐positive cancers.
FOXK2 facilitates the airway remodeling during chronic asthma by promoting glycolysis in a SIRT2‐dependent manner
Authors: Shan Lishen , Chen Li , Shen Wenxin , Zhou Qianlan , Liu Si , Han Lina , Zhang Qinzhen , Dai Bing , Zhao Yuhong
Published: July 2024

Asthma is a chronic pulmonary disease with the worldwide prevalence. The structural alterations of airway walls, termed as “airway remodeling”, are documented as the core contributor to the airway dysfunction during chronic asthma. Forkhead box transcription factor FOXK2 is a critical regulator of glycolysis, a metabolic reprogramming pathway linked to pulmonary fibrosis. However, the role of FOXK2 in asthma waits further explored. In this study, the chronic asthmatic mice were induced via ovalbumin (OVA) sensitization and repetitive OVA challenge. FOXK2 was upregulated in the lungs of OVA mice and downregulated after adenovirus‐mediated FOXK2 silencing. The lung inflammation, peribronchial collagen deposition, and glycolysis in OVA mice were obviously attenuated after FOXK2 knockdown. Besides, the expressions of FOXK2 and SIRT2 in human bronchial epithelial cells (BEAS‐2B) were increasingly upregulated upon TGF‐β1 stimulation and downregulated after FOXK2 knockdown. Moreover, the functional loss of FOXK2 remarkably suppressed TGF‐β1‐induced epithelial‐mesenchymal transition (EMT) and glycolysis in BEAS‐2B cells, as manifested by the altered expressions of EMT markers and glycolysis enzymes. The glycolysis inhibitor 2‐deoxy‐d‐glucose (2‐DG) inhibited the EMT in TGF‐β1‐induced cells, making glycolysis a driver of EMT. The binding of FOXK2 to SIRT2 was validated, and SIRT2 overexpression blocked the FOXK2 knockdown‐mediated inhibition of EMT and glycolysis in TGF‐β1‐treated cells, which suggests that FOXK2 regulates EMT and glycolysis in TGF‐β1‐treated cells in a SIRT2‐dependnet manner. Collectively, this study highlights the protective effect of FOXK2 knockdown on airway remodeling during chronic asthma.
Aerobic training attenuates cardiac remodeling in mice post‐myocardial infarction by inhibiting the p300/CBP‐associated factor
Authors: Huang Chuan , Ding Xinyu , Shao Jingrong , Yang Mengxue , Du Dongdong , Hu Jiayi , Wei Ya , Shen Qiu , Chen Ze , Zuo Shengkai , Wan Chunxiao
Published: July 2024

Aerobic training (AT), an effective form of cardiac rehabilitation, has been shown to be beneficial for cardiac repair and remodeling after myocardial infarction (MI). The p300/CBP‐associated factor (PCAF) is one of the most important lysine acetyltransferases and is involved in various biological processes. However, the role of PCAF in AT and AT‐mediated cardiac remodeling post‐MI has not been determined. Here, we found that the PCAF protein level was significantly increased after MI, while AT blocked the increase in PCAF. AT markedly improved cardiac remodeling in mice after MI by reducing endoplasmic reticulum stress (ERS). In vivo, similar to AT, pharmacological inhibition of PCAF by Embelin improved cardiac recovery and attenuated ERS in MI mice. Furthermore, we observed that both IGF‐1, a simulated exercise environment, and Embelin protected from H2O2‐induced cardiomyocyte injury, while PCAF overexpression by viruses or the sirtuin inhibitor nicotinamide eliminated the protective effect of IGF‐1 in H9C2 cells. Thus, our data indicate that maintaining low PCAF levels plays an essential role in AT‐mediated cardiac protection, and PCAF inhibition represents a promising therapeutic target for attenuating cardiac remodeling after MI.