bluuebunny/crossref_metadata_2025 huggingface dataset:
On Ruzsa’s discrete Brunn-Minkowski conjecture
Authors: van Hintum Peter , Keevash Peter , Tiba Marius
Published: August 2024

We prove a conjecture by Ruzsa from 2006 on a discrete version of the Brunn-Minkowski inequality, stating that for any

A
,
B
⊂

Z

k

A,B\subset \mathbb {Z}^k

and

ϵ
>
0

\epsilon >0

with

B
B

not contained in

n

k
,
ϵ

n_{k,\epsilon }

parallel hyperplanes we have
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartAbsoluteValue upper A plus upper B EndAbsoluteValue Superscript 1 slash k Baseline greater-than-or-equal-to StartAbsoluteValue upper A EndAbsoluteValue Superscript 1 slash k Baseline plus left-parenthesis 1 minus epsilon right-parenthesis StartAbsoluteValue upper B EndAbsoluteValue Superscript 1 slash k">

|

A
+
B

|

1

/

k

≥

|

A

|

1

/

k

+

(
1
−
ϵ
)

|

B

|

1

/

k

|A+B|^{1/k}\geq |A|^{1/k}+\left (1-\epsilon \right )|B|^{1/k}

.
Symplectic capacities of disc cotangent bundles of flat tori
Authors: Benedetti Gabriele , Bimmermann Johanna , Zehmisch Kai
Published: August 2024

We show that on the unit disc cotangent bundle of flat Riemannian tori, all normalized capacities coincide with twice the systole. The same result holds for flat, reversible Finsler tori and normalized capacities that are greater than or equal to the Hofer–Zehnder capacity.
The equivalence of smooth and synthetic notions of timelike sectional curvature bounds
Authors: Beran Tobias , Kunzinger Michael , Ohanyan Argam , Rott Felix
Published: August 2024

Timelike sectional curvature bounds play an important role in spacetime geometry, both for the understanding of classical smooth spacetimes and for the study of Lorentzian (pre-)length spaces introduced by Kunzinger and Sämann [Ann. Global Anal. Geom. 54 (2018), pp. 399-447]. In the smooth setting, a bound on the sectional curvature of timelike planes can be formulated via the Riemann curvature tensor. In the synthetic setting, bounds are formulated by comparing various geometric configurations to the corresponding ones in constant curvature spaces. The first link between these notions in the Lorentzian context was established by Harris [Indiana Univ. Math. J. 31 (1982), pp. 289–308], which was instrumental in the proof of powerful results in spacetime geometry (see Beem et al. [Toponogov splitting theorem for Lorentzian manifolds, Springer, Berlin, 1985; J. Differential Geom. 22 (1985), pp. 29–42]; Galloway and Ling [Gen. Relativity Gravitation 50 (2018), p. 7]). For general semi-Riemannian manifolds, the equivalence between sectional curvature bounds and synthetic bounds was established by Alexander and Bishop [Comm. Anal. Geom. 16 (2008), pp. 251–282]; however in this approach the sectional curvatures of both timelike and spacelike planes have to be considered. In this article, we fill a gap in the literature by proving the full equivalence between sectional curvature bounds on timelike planes and synthetic timelike bounds on strongly causal spacetimes. As an essential tool, we establish Hessian comparison for the time separation and signed distance functions.
Complex algebraic stacks and morphisms of intersection complexes
Authors: Huynh Matthew
Published: August 2024

We generalize a construction of Barthel-Brasselet-Fieseler-Gabber-Kaup in the setting of complex varieties to the setting of finite type, complex algebraic stacks. Given two such stacks

X

,

Y

\mathcal {X}, \mathcal {Y}

with affine stabilizers, and a morphism between them, we construct a morphism from the pullback of the intersection complex of

Y

\mathcal {Y}

to the intersection complex of

X

\mathcal {X}

. As an application, we show that the Borel-Moore fundamental class of a closed substack

Z

\mathcal {Z}

in a Deligne-Mumford stack

X

\mathcal {X}

lifts to a class in the intersection cohomology of

X

\mathcal {X}

.
Sign regular matrices and variation diminution: Single-vector tests and characterizations, following Schoenberg, Gantmacher–Krein, and Motzkin
Authors: Choudhury Projesh , Yadav Shivangi
Published: August 2024

Variation diminution (VD) is a fundamental property in total positivity theory, first studied in 1912 by Fekete–Pólya for one-sided Pólya frequency sequences, followed by Schoenberg, and by Motzkin who characterized sign regular (SR) matrices using VD and some rank hypotheses. A classical theorem by Gantmacher–Krein characterized the strictly sign regular (SSR)

m
×
n

m \times n

matrices for

m
>
n

m>n

using this property.

In this article we strengthen these results by characterizing all

m
×
n

m \times n

SSR matrices using VD. We further characterize strict sign regularity of a given sign pattern in terms of VD together with a natural condition motivated by total positivity. We then refine Motzkin’s characterization of SR matrices by omitting the rank condition and specifying the sign pattern. This concludes a line of investigation on VD started by Fekete–Pólya [Rend. Circ. Mat. Palermo 34 (1912), pp. 89–120] and continued by Schoenberg [Math. Z. 32 (1930), pp. 321–328], Motzkin [Beiträge zur Theorie der linearen Ungleichungen, PhD Dissertation, Jerusalem, 1936], Gantmacher–Krein [Oscillyacionye matricy i yadra i malye kolebaniya mehaničeskih sistem, Gosudarstv. Izdat. Tehn.-Teor. Lit., Moscow-Leningrad, 1950], Brown–Johnstone–MacGibbon [J. Amer. Statist. Assoc. 76 (1981), pp. 824–832], and Choudhury [Bull. Lond. Math. Soc. 54 (2022), pp. 791–811; Bull. Sci. Math. 186 (2023), p. 21].

In fact we show stronger characterizations, by employing single test vectors with alternating sign coordinates – i.e., lying in the alternating bi-orthant. We also show that test vectors chosen from any other orthant will not work.
No bounded geometry wandering domains for sufficiently regular automorphisms
Authors: Merenkov Sergei
Published: August 2024

A question whether sufficiently regular manifold automorphisms may have wandering domains with controlled geometry is answered in the negative for quasiconformal or smooth homeomorphisms of

n
n

-tori,

n
≥
2

n\ge 2

, and hyperbolic surfaces. Besides control on geometry of wandering domains, the assumptions are either analytic, e.g., minimal sets having measure zero or supporting invariant conformal structures, or geometric, such as uniform relative separation of wandering domains.
Bounded, compact and Schatten class Hankel operators on Fock-type spaces
Authors: Zeng Zhicheng , Hu Zhangjian , Wang Xiaofeng
Published: August 2024

In this paper, we consider Hankel operators, with locally integrable symbols, densely defined on a family of Fock-type spaces whose weights are

C
3

C^3

-logarithmic growth functions with mild smoothness conditions. It is shown that a Hankel operator is bounded on such a Fock space if and only if its symbol function has bounded distance to analytic functions BDA which is initiated by Luecking [J. Funct. Anal. 110 (1992), pp. 247–271]. We also characterize the compactness and Schatten class membership of Hankel operators. Besides, we give characterizations of the Schatten class membership of Toeplitz operators with positive measure symbols for the small exponent

0
>
p
>
1

0>p>1

. Our proofs depend strongly on the technique of Hömander’s

L
2

L^2

estimates for the

∂
¯

\overline {\partial }

operator and the decomposition theory of BDA spaces as well as integral estimates involving the reproducing kernel.
Dimerization activates the Inversin complex in C. elegans
Authors: Beyrent Erika , Wei Derek T. , Beacham Gwendolyn M. , Park Sangwoo , Zheng Jian , Paszek Matthew J. , Hollopeter Gunther
Published: August 2024

Genetic, colocalization, and biochemical studies suggest that the ankyrin repeat-containing proteins Inversin (INVS) and ANKS6 function with the NEK8 kinase to control tissue patterning and maintain organ physiology. It is unknown whether these three proteins assemble into a static “Inversin complex” or one that adopts multiple bioactive forms. Through the characterization of hyperactive alleles in C. elegans, we discovered that the Inversin complex is activated by dimerization. Genome engineering of an RFP tag onto the nematode homologues of INVS (MLT-4) and NEK8 (NEKL-2) induced a gain-of-function, cyst-like phenotype that was suppressed by monomerization of the fluorescent tag. Stimulated dimerization of MLT-4 or NEKL-2 using optogenetics was sufficient to recapitulate the phenotype of a constitutively active Inversin complex. Further, dimerization of NEKL-2 bypassed a lethal MLT-4 mutant, demonstrating that the dimeric form is required for function. We propose that dynamic switching between at least two functionally distinct states – an active dimer and an inactive monomer – gates the output of the Inversin complex.
Proviral role of ATG2 autophagy related protein in tomato bushy stunt virus replication through bulk phospholipid transfer into the viral replication organelle
Authors: Kang Yuanrong , Pogany Judit , Nagy Peter D.
Published: August 2024

Subversion of cellular membranes and membrane proliferation are used by positive-strand RNA viruses to build viral replication organelles (VROs) that support virus replication. The biogenesis of the membranous VROs requires major changes in lipid metabolism and lipid transfer in infected cells. In this work, we show that tomato bushy stunt virus (TBSV) hijacks Atg2 autophagy related protein with bulk lipid transfer activity into VROs via interaction with TBSV p33 replication protein. Deletion of Atg2 in yeast and knockdown of Atg2 in Nicotiana benthamiana resulted in decreased TBSV replication. We found that subversion of Atg2 by TBSV was important to enrich VRO membranes with phosphatidylethanolamine (PE), phosphatidylserine (PS) and PI(3)P phosphoinositide. Interestingly, inhibition of autophagy did not affect the efficient recruitment of Atg2 into VROs, and overexpression of Atg2 enhanced TBSV replication, indicating autophagy-independent subversion of Atg2 by TBSV. These findings suggest that the proviral function of Atg2 lipid transfer protein is in VRO membrane proliferation. In addition, we find that Atg2 interacting partner Atg9 with membrane lipid-scramblase activity is also coopted for tombusvirus replication. Altogether, the subversion of Atg2 bridge-type lipid transfer protein provides a new mechanism for tombusviruses to greatly expand VRO membranes to support robust viral replication.
Fame at Any Cost—Sandy Hook
Authors: Rahman Tahir , Abugel Jeffrey
Published: August 2024

Adam Lanza was diagnosed with autism spectrum disorder at a young age. He had sensory issues, language delays, anxiety, and repetitive behaviors. Lanza developed an internet cognitive isoform—a process by which the brain uses cognitive shortcuts to make inferences about the world—which often turn out to be incorrect. The brain takes ambiguous or complex information and interprets it in the simplest possible terms. He held extreme overvalued beliefs in which he relished prior shooters, including Jared Loughner, James Holmes, Eric Harris, and Dylan Klebold. Misanthropic sentiments have also been espoused by Elliot Rodger, as well as Ted Kaczynski (the Unabomber). This scorn for others formed the basis of their extreme overvalued beliefs. Lanza’s thinking became more refined over time, his warped moral stance increasingly binary, simplistic, and absolute, culminating in a plan to murder children at Sandy Hook Elementary School.
Revisiting Histories, Rethinking Spaces
Authors: Berruezo-Sánchez Diana
Published: August 2024

This chapter revisits the many misconceptions about the African diaspora in Spain, including the common idea that the black African diaspora is a recent phenomenon in Spain. Using space as a means to frame the lives and social relationships of black Africans living in early modern Spanish cities, the chapter offers new readings of the everyday lives of black Africans by exposing how they organised confraternities and formed communities that developed distinctive identities and priorities. Focusing on the black confraternity in Seville and its campaign to parade in major religious festivals, it explores the ways that black communities resisted attempts by white confraternities to confine and restrict them, turning spatial litigation into racial litigation. This chapter shows that black men and women took pride in their communities, their Christianity, and their blackness, and demonstrates their agency in navigating the racial, religious, economic, and cultural landscapes of early modern Spanish cities.
NanoMGT: Marker gene typing of low complexity mono-species metagenomic samples using noisy long reads
Authors: Hallgren Malte B , Clausen Philip T L C , Aarestrup Frank M
Published: August 2024

Rapid advancements in sequencing technologies have led to significant progress in microbial genomics, yet challenges persist in accurately identifying microbial strain diversity in metagenomic samples, especially when working with noisy long-read data from platforms like Oxford Nanopore Technologies (ONT). In this article, we introduce NanoMGT, a tool designed to enhance marker gene typing in low-complexity mono-species samples, leveraging the unique properties of long reads. NanoMGT excels in its ability to accurately identify mutations amidst high error rates, ensuring the reliable detection of multiple strain-specific marker genes. Our tool implements a novel scoring system that rewards mutations co-occurring across different reads and penalizes densely grouped, likely erroneous variants, thereby achieving a good balance between sensitivity and precision. A comparative evaluation of NanoMGT, using a simulated multi-strain sample of seven bacterial species, demonstrated superior performance relative to existing tools and the advantages of using a threshold-based filtering approach to calling minority variants in ONT’s sequencing data. NanoMGT’s potential as a post-binning tool in metagenomic pipelines is particularly notable, enabling researchers to more accurately determine specific alleles and understand strain diversity in microbial communities. Our findings have significant implications for clinical diagnostics, environmental microbiology, and the broader field of genomics. The findings offer a reliable and efficient approach to marker gene typing in complex metagenomic samples.
Therapeutic potential of Garcinia kola against experimental toxoplasmosis in rats
Authors: Ahidjo Nene , Maidawa Yaya Frederic , Njamnshi Wepnyu Y , Rissia-Ngo Pambe Judith C , Ndianteng Ethel W , Nwasike Caroline N C , Kemmo Christelle , Choupo Arnaud C , Meka’a Zang Luc Yvan , Pieme Anatole C , Vecchio Lorella , Ngadjui Bonaventure T , Njamnshi Alfred K , Seke Etet Paul F
Published: August 2024

Cerebral toxoplasmosis, the most common opportunistic infection in immunocompromised individuals, is increasingly reported in immunocompetent individuals due to mutant strains of Toxoplasma gondii, which, furthermore, are reported to be resistant to available treatments. We assessed the therapeutic potential of Garcinia kola, a medicinal plant reported to have antiplasmodial and neuroprotective properties, against experimental toxoplasmosis in rats. Severe toxoplasmosis was induced in male Wistar rats (156.7 ± 4.1 g) by injecting them with 10 million tachyzoites in suspension in 500 µl of saline (intraperitoneal), and exclusive feeding with a low-protein diet [7% protein (weight by weight)]. Then, animals were treated with hexane, dichloromethane, and ethyl acetate fractions of Garcinia kola. Footprints were analysed and open-field and elevated plus maze ethological tests were performed when symptoms of severe disease were observed in the infected controls. After sacrifice, blood samples were processed for Giemsa staining, organs were processed for haematoxylin and eosin staining, and brains were processed for Nissl staining and cell counting. Compared with non-infected animals, the infected control animals had significantly lower body weights (30.27%↓, P = 0.001), higher body temperatures (P = 0.033) during the sacrifice, together with signs of cognitive impairment and neurologic deficits such as lower open-field arena centre entries (P < 0.001), elevated plus maze open-arm time (P = 0.029) and decreased stride lengths and step widths (P < 0.001), as well as neuronal loss in various brain areas. The ethyl acetate fraction of Garcinia kola prevented or mitigated most of these signs. Our data suggest that the ethyl acetate fraction of Garcinia kola has therapeutic potential against cerebral toxoplasmosis.
Integrative approach of omics and imaging data to discover new insights for understanding brain diseases
Authors: Yoon Jong Hyuk , Lee Hagyeong , Kwon Dayoung , Lee Dongha , Lee Seulah , Cho Eunji , Kim Jaehoon , Kim Dayea
Published: August 2024

Treatments that can completely resolve brain diseases have yet to be discovered. Omics is a novel technology that allows researchers to understand the molecular pathways underlying brain diseases. Multiple omics, including genomics, transcriptomics and proteomics, and brain imaging technologies, such as MRI, PET and EEG, have contributed to brain disease-related therapeutic target detection. However, new treatment discovery remains challenging. We focused on establishing brain multi-molecular maps using an integrative approach of omics and imaging to provide insights into brain disease diagnosis and treatment. This approach requires precise data collection using omics and imaging technologies, data processing and normalization. Incorporating a brain molecular map with the advanced technologies through artificial intelligence will help establish a system for brain disease diagnosis and treatment through regulation at the molecular level.
A case of dermatopathia pigmentosa reticularis masquerading as dyskeratosis congenita: the importance of nailing the correct diagnosis
Authors: Le Quynh , Le Fevre Anna , Tan Tiong Yang , Robertson Susan
Published: August 2024

We report a challenging case where an initial clinical diagnosis of dyskeratosis congenita was revised to dermatopathia pigmentosa reticularis after exome sequencing.
Information flow and catalytic dyad in SARS-CoV2 main protease Mpro enzyme using embedded discrete Markov chains and centrality measures
Authors: Olivares-Quiroz Luis Agustín
Published: August 2024

In this work, we use a network representation of the globular crystalline structure of a given protein as a graph structure with N nodes and E edges in order to analyze quantitatively the flow information and to identify key sites within the globular structure. Each node nj represents a $ C_{\alpha}^{i}$ carbon of the main backbone whereas the node’s degree ki is a measure of its physical interactions. In order to identify biologically relevant and active nodes, we compute local per residue closeness $ C_{c}(i)$, betweenness $ C_{b}(i)$ and eigenvector centralities $ C_{e}(i)$. Further analysis is done by embedding a stochastic dynamic discrete Markov chain in order to evaluate the dynamics of a set of normal random walkers (NRW’s) within the network. From this, we compute the mean first passage time matrix M and the stationary occupation probability vector ψi for each node. These two measures provide very useful information on the dynamical process embed within the $ C_{\alpha}$ network. We apply this to SARS-CoV2 Mpro main protease which is a key enzyme in the virus replication cycle. In particular, we focus our attention to the properties of the catalytic dyad integrated by His41-Cys145 in Mpro main protease since this active site has been under intense scrutiny as a pharmaceutical target. In addition, our results show the existence of additional relevant aminoacids that might play a fundamental role on signal propagation and allosteric pathways in SARS-CoV main proteases.
Automated detection of maxillary sinus opacifications compatible with sinusitis from CT images
Authors: Kwon Kyung Won , Kim Jihun , Kang Dongwoo
Published: August 2024

Background

Sinusitis is a commonly encountered clinical condition that imposes a considerable burden on the healthcare systems. A significant number of maxillary sinus opacifications are diagnosed as sinusitis, often overlooking the precise differentiation between cystic formations and inflammatory sinusitis, resulting in inappropriate clinical treatment. This study aims to improve diagnostic accuracy by investigating the feasibility of differentiating maxillary sinusitis, retention cysts, and normal sinuses.

Methods

We developed a deep learning-based automatic detection model to diagnose maxillary sinusitis using ostiomeatal unit CT images. Of the 1080 randomly selected coronal-view CT images, including 2158 maxillary sinuses, datasets of maxillary sinus lesions comprised 1138 normal sinuses, 366 cysts, and 654 sinusitis based on radiographic findings, and were divided into training (n = 648 CT images), validation (n = 216), and test (n = 216) sets. We utilized a You Only Look Once based model for object detection, enhanced by the transfer learning method. To address the insufficiency of training data, various data augmentation techniques were adopted, thereby improving the model’s robustness.

Results

The trained You Only Look Once version 8 nano model achieved an overall precision of 97.1%, with the following class precisions on the test set: normal = 96.9%, cyst = 95.2%, and sinusitis = 99.2%. With an average F1-score of 95.4%, the F1-score was the highest for normal, then sinusitis, and finally, cysts. Upon evaluating a performance on difficulty level, the precision decreased to 92.4% on challenging test dataset.

Conclusions

The developed model is feasible for assisting clinicians in screening maxillary sinusitis lesions.
Pericoronary adipose tissue for predicting long-term outcomes
Authors: van Rosendael Sophie E , Kamperidis Vasileios , Maaniitty Teemu , de Graaf Michiel A , Saraste Antti , McKay-Goodall George E , Jukema J Wouter , Knuuti Juhani , Bax Jeroen J
Published: August 2024

Aims

Pericoronary adipose tissue (PCAT) attenuation obtained by coronary computed tomography angiography (CCTA) has been associated with coronary inflammation and outcomes. Whether PCAT attenuation is predictive of major adverse cardiac events (MACE) during long-term follow-up is unknown.

Methods and results

Symptomatic patients with coronary artery disease (CAD) who underwent CCTA were included, and clinical outcomes were evaluated. PCAT was measured at all lesions for all three major coronary arteries using semi-automated software. A comparison between patients with and without MACE was made on both a per-lesion and a per-patient level. The predictive value of PCAT attenuation for MACE was assessed in Cox regression models. In 483 patients (63.3 ± 8.5 years, 54.9% men), 1561 lesions were analysed over a median follow-up duration of 9.5 years. The mean PCAT attenuation was not significantly different between patients with and without MACE. At a per-patient level, the adjusted hazard ratio (HR) and 95% confidence interval (CI) for MACE were 0.970 (95% CI: 0.933–1.008, P = 0.121) when the average of all lesions per patient was analysed, 0.992 (95% CI: 0.961–1.024, P = 0.622) when only the most obstructive lesion was evaluated, and 0.981 (95% CI: 0.946–1.016, P = 0.285) when only the lesion with the highest PCAT attenuation per individual was evaluated. Adjusted HRs for vessel-specific PCAT attenuation in the right coronary artery, left anterior descending artery, and left circumflex artery were 0.957 (95% CI: 0.830–1.104, P = 0.548), 0.989 (95% CI: 0.954–1.025, P = 0.550), and 0.739 (95% CI: 0.293–1.865, P = 0.522), respectively, in predicting long-term MACE.

Conclusion

In patients referred to CCTA for clinically suspected CAD, PCAT attenuation did not predict MACE during long-term follow-up.
Risk-adjusted discrete increases in length of stay by complication following anatomic lung resection: an analysis of 32 133 cases across the USA
Authors: Stuart Christina M , Bronsert Michael R , Dyas Adam R , Mott Nicole M , Healy Garrett L , Anioke Tochi , Henderson William G , Randhawa Simran K , David Elizabeth A , Mitchell John D , Meguid Robert A
Published: August 2024

OBJECTIVES

Prior studies have associated morbidity following anatomic lung resection with prolonged postoperative length of stay; however, each complication’s individual impact on length of stay as a continuous variable has not been studied. The purpose of this study was to determine the risk-adjusted increase in length of stay associated with each individual postoperative complications following anatomic lung resection.

METHODS

Patients who underwent anatomic lung resection cataloged in the prospectively collected American College of Surgeons National Surgical Quality Improvement Program participant use file, 2005–2018, were targeted. The association between preoperative characteristics, postoperative complications and length of stay in days was tested. A negative binomial model adjusting for the effect of preoperative characteristics and 18 concurrent postoperative complications was used to generate incidence rate ratios. This model was fit to generate risk-adjusted increases in length of stay by complication.

RESULTS

Of 32 133 patients, 5065 patients (15.8%) experienced at least one post-operative complication. The most frequent complications were pneumonia (n = 1829, 5.7%), the need for transfusion (n = 1794, 5.6%) and unplanned reintubation (n = 1064, 3.3%). The occurrence of each of the 18 individual complications was associated with significantly increased length of stay. This finding persisted after risk-adjustment, with the greatest risk-adjusted increases being associated with prolonged ventilation (+17.4 days), followed by septic shock (+17.2 days), acute renal failure (+16.5 days) and deep surgical site infection (+13.2 days).

CONCLUSIONS

All 18 postoperative complications studied following anatomic lung resection were associated with significant risk-adjusted increases in length of stay, ranging from an increase of 17.4 days with prolonged ventilation to 2.6 days following the need for transfusion.
Advancements in nutritional composition of milk and species identification
Authors: Yu Mingxue , Li Baiyi , Hong Tiannuo , Li Ziqi , Ru Xin , Bian Wenbo , Zhu Wenqi , Chen Lu , Han Juan
Published: August 2024

Milk product market is currently experiencing profound diversification, marked by an increasing presence of specialty milk and dairy products alongside traditional cow milk. These specialty varieties include yak, sheep, buffalo, and goat milk. Given their limited availability, these specialty milks often command higher prices than cow milk, rendering them susceptible to adulteration through substitution with the latter. Such fraudulent practices result in significant economic damage and pose risks to public health. Consequently, numerous identification methods have been devised to trace the origin of dairy products. Although the prevailing methods predominantly focus on analyzing the nutrient composition of these products, this review aims to explore more cost-effective, sensitive, accurate, and efficient techniques. This endeavor begins with a comprehensive analysis of the common nutrients found in different dairy sources available on the market. Subsequently, this study elucidates various techniques employed for adulterating milk sources, with a specific emphasis on targeting these nutrients. Furthermore, a systematic comparative analysis was performed to evaluate the strengths and weaknesses of the diverse detection methods. This review provides a theoretical framework essential for the subsequent development of detection technologies for milk source identification.
Estimating the Impact of Tuberculosis Pathways on Transmission—What Is the Gap Left by Passive Case Finding?
Authors: Horton Katherine C , McCaffrey Ty , Richards Alexandra S , Schwalb Alvaro , Houben Rein M G J
Published: August 2024

Current passive case-finding policies have not resulted in the expected decline in tuberculosis incidence. Recognition of the variety of disease pathways experienced by individuals with tuberculosis highlights how many are not served by the current prevention and care system and how much transmission is missed.
The Emergent Invasive Serotype 4 ST10172 Strain Acquires vanG-Type Vancomycin-Resistance Element: A Case of a 66-Year-Old With Bacteremic Pneumococcal Pneumonia
Authors: Chochua Sopio , Beall Bernard , Lin Wuling , Tran Theresa , Rivers Joy , Li Zhongya , Arvay Melissa L , Kobayashi Miwako , Houston Jessica , Arias Sabra , McGee Lesley
Published: August 2024

We report a single case of invasive pneumococcal disease (IPD) by serotype 4, multilocus sequence type 10172 (ST10172) isolate with vanG-type resistance genes and reduced vancomycin susceptibility. The isolate was recovered during 2022 from a 66-year-old resident with bacteremic pneumococcal pneumonia within a Centers for Disease Control and Prevention Active Bacterial Core surveillance (ABCs) site hospital. The patient had received 23-valent pneumococcal polysaccharide vaccine and there was no evidence of concurrent or prior receipt of vancomycin in the previous year. Serotype 4/ST10172 IPD has shown increases within western ABCs sites, and the recent acquisition of a vanG element warrants close monitoring of this lineage.
Predicting antibiotic susceptibility in urinary tract infection with artificial intelligence—model performance in a multi-centre cohort
Authors: Lee Alfred Lok Hang , To Curtis Chun Kit , Chan Ronald Cheong Kin , Wong Janus Siu Him , Lui Grace Chung Yan , Cheung Ingrid Yu Ying , Chow Viola Chi Ying , Lai Christopher Koon Chi , Ip Margaret , Lai Raymond Wai Man
Published: August 2024

Objective

To develop an artificial intelligence model to predict an antimicrobial susceptibility pattern in patients with urinary tract infection (UTI).

Materials and methods

26 087 adult patients with culture-proven UTI during 2015–2020 from a university teaching hospital and three community hospitals in Hong Kong were included. Cases with asymptomatic bacteriuria (absence of diagnosis code of UTI, or absence of leucocytes in urine microscopy) were excluded. Patients from 2015 to 2019 were included in the training set, while patients from the year 2020 were included as the test set.

Three first-line antibiotics were chosen for prediction of susceptibility in the bacterial isolates causing UTI: namely nitrofurantoin, ciprofloxacin and amoxicillin-clavulanate. Baseline epidemiological factors, previous antimicrobial consumption, medical history and previous culture results were included as features. Logistic regression and random forest were applied to the dataset. Models were evaluated by F1-score and area under the curve-receiver operating characteristic (AUC-ROC).

Results

Random forest was the best algorithm in predicting susceptibility of the three antibiotics (nitrofurantoin, amoxicillin-clavulanate and ciprofloxacin). The AUC-ROC values were 0.941, 0.939 and 0.937, respectively. The F1 scores were 0.938, 0.928 and 0.906 respectively.

Conclusions

Random forest model may aid judicious empirical antibiotics use in UTI. Given the reasonable performance and accuracy, these accurate models may aid clinicians in choosing between different first-line antibiotics for UTI.
Treating Scars After Burns With Pulsed Electric Fields in the Rat Model
Authors: Mann Din , Bar-Shai Nurit , Levkov Klimentiy , Gabay Batel , Vitkin Edward , Nyska Abraham , Yarmush Martin , Shalom Avshalom , Golberg Alexander
Published: August 2024

Reducing scar size after severe burn injuries is an important and challenging medical, technological, and social problem. We have developed a battery-powered pulsed electric field (PEF) device and surface needle electrode applicator to deliver PEFs to the healing dorsal burn wound in rats. The pulsed electric field was used to treat residual burn wounds caused by metal contact in rats starting 10 days after the injury for 4 months every 11 or 22 days for 4 months using varying time applied voltages at 250-350 V range, 400 mA current, 40 pulses, 70 μs duration each, delivered at pulse repetition frequency 10 Hz at 5 locations inside the wound. We found 40%-45% reduction in the scar size in comparison with untreated controls in both upper and lower dorsal locations on rats’ backs 2 months after the last PEF application. We have not detected significant histopathological differences in the center of the scars besides the thickness of the newly generated epidermis, which was thicker in the PEF-treated group. We showed that minimally invasively applied PEFs through needle electrodes are effective method and device for treating residual burn wounds in the rat model, reducing the size of the resulting scars, without any adverse reaction.
‘China’s Disequilibrium’ in ISDS: an interplay of China’s trade-offs and domestic institutions to investment treaty policy
Authors: Lin Yating
Published: August 2024

This article explores China’s limited engagement in Investor-State Dispute Settlment (ISDS) despite its significant foreign investment inflows, termed “China’s Disequilibrium”. Despite having liberal ISDS provisions in its Bilateral Investment Treaties(BITs), China has faced only nine claims and has never lost a case. Using a political-economic framework, the article examines domestic factors influencing China's stance on ISDS, highlighting its shift from ideological resistance to acceptance. The paper argues that China’s ambivalent mood to ISDS render it to adopt a bifurcated strategy: internationally, it incrementally liberalizes investor-State Arbitration to protect Chinese investors abroad; domestically, it relies on local remedy to protect foreign investors and discourages the use of investment treaty arbitration. This approach contrasts with other jurisdictions and partly explains China’s Disequilibrium in ISDS.
Spontaneous bilothorax without previous surgery or trauma, a case report
Authors: Neetichow Tarashene , Angthong Wirana , Tongyoo Assanee
Published: August 2024

Bilothorax is a rare condition that can lead to severe infection and death. Most cases present with right-sided pleural effusion and the etiology can be biliary obstruction, infection, or iatrogenic complications. The diagnosis of bilothorax is confirmed by the ratio of pleural fluid to serum bilirubin >1. A 33-year-old Asian female presented with progressive dyspnea from right pleural effusion, which was confirmed to be biloma by pleural fluid to serum bilirubin ratio of 15.9. Imaging showed right-sided subdiaphragmatic nodule, which was subsequently biopsied on laparoscopy revealing hemorrhagic endometriotic lesion. However, there was no obvious diaphragmatic defect connecting pleural and peritoneal cavities. Additionally, no biliary leakage was identified by magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP). The treatment included antibiotics, tube thoracostomy, ERCP with stent, thermal ablation of endometriotic nodules under laparoscopy, and hormonal therapy for endometriosis. Bilothorax is rare case itself but the etiology secondary to endometriosis makes this case particularly unique.
The Book Collection of John Ostewyk, Chaplain of St Magnus the Martyr, London, 1495
Authors: Payne M T W
Published: August 2024

This note offers a transcription, and brief discussion, of the probate inventory of John Ostewyk, a priest in the parish of St Magnus the Martyr in London, who died in 1495. Among his belongings, the appraisers found seventeen named volumes and twenty pamphlets. These are additional to books mentioned in his will. Some of the volumes can be identified with surviving editions.
Update of the History of the Shakespeare First Folio
Authors: West Anthony James
Published: August 2024

This update of the Shakespeare First Folio History (2001) volume by Anthony West gives selected events in the story of the First Folio since 2001, complementing the update of West’s Census volume in the previous issue of this journal.
William Worcestre, Sir John Fastolf and Latin Learning
Authors: Rundle David
Published: August 2024

Sir John Fastolf is known for his association with books in the vernaculars of French and English. It is, though, known that there was also an interest in Latin learning in his circle, and this article provides new evidence concerning that. It introduces a set of manuscripts which passed from the hands of Fastolf’s secretary, William Worcestre, to the foundation of Magdalen College, Oxford. Their passage to Oxford is placed in the context of the battle over Fastolf’s will, with its desire to establish a college at his house of Caister in Norfolk. A college did not necessarily imply a learned function but what Worcestre perceived to be the intentions for that foundation are placed in a wider context of his belief in his late master’s interest in promoting Latin education.
The Military Medicine Leadership Life Cycle: A Model for Longitudinal Leadership Development for Staff Physicians
Authors: Hartzell Joshua D , Servey Jessica , Wilson Ramey , Mount George , Barry Erin S , Durning Steven J
Published: August 2024

Leadership development is a challenge for all health care systems. Military Medicine has unique challenges with increased frequency of physician turnover and more junior leaders taking on positions of leadership earlier in their careers. Military medical corps officers are also challenged with leading in clinical, academic, and operational settings. Effective leadership within the Military Healthcare System requires an intentional and ongoing leadership development process across the careers of military medical corps officers. This article describes the leadership lifecycle of military medical corps officers, highlighting existing leadership development opportunities and providing an example of a leadership lifecycle from junior staff to senior executive for other organizations. The article concludes with specific recommendations that will allow military medicine to continue to strengthen the leadership skills of its officers to meet ever growing challenges.
The ratio of [Eu/α] differentiates accreted/in situ Milky Way stars across metallicities, as indicated by both field stars and globular clusters
Authors: Monty Stephanie , Belokurov Vasily , Sanders Jason L , Hansen Terese T , Sakari Charli M , McKenzie Madeleine , Myeong GyuChul , Davies Elliot Y , Ardern-Arentsen Anke , Massari Davide
Published: August 2024

We combine stellar orbits with the abundances of the heavy, r-process element europium and the light, $\alpha$-element, silicon to separate in situ and accreted populations in the Milky Way (MW) across all metallicities. At high orbital energy, the accretion-dominated halo shows elevated values of [Eu/Si], while at lower energies, where many of the stars were born in situ, the levels of [Eu/Si] are lower. These systematically different levels of [Eu/Si] in the MW and the accreted halo imply that the scatter in [Eu/$\alpha$] within a single galaxy is smaller than previously thought. At the lowest metallicities, we find that both accreted and in situ populations trend down in [Eu/Si], consistent with enrichment via neutron star mergers. Through compiling a large data set of abundances for 54 globular clusters (GCs), we show that differences in [Eu/Si] extend to populations of in situ/accreted GCs. We interpret this consistency as evidence that in r-process elements GCs trace the star formation history of their hosts, motivating their use as sub-Gyr timers of galactic evolution. Furthermore, fitting the trends in [Eu/Si] using a simple galactic chemical evolution model, we find that differences in [Eu/Si] between accreted and in situ MW field stars cannot be explained through star formation efficiency alone. Finally, we show that the use of [Eu/Si] as a chemical tag between GCs and their host galaxies extends beyond the Local Group, to the halo of M31 – potentially offering the opportunity to do Galactic Archaeology in an external galaxy.
BioFlow-Insight: facilitating reuse of Nextflow workflows with structure reconstruction and visualization
Authors: Marchment George , Brancotte Bryan , Schmit Marie , Lemoine Frédéric , Cohen-Boulakia Sarah
Published: August 2024

Bioinformatics workflows are increasingly used for sharing analyses, serving as a cornerstone for enhancing the reproducibility and shareability of bioinformatics analyses. In particular, Nextflow is a commonly used workflow system, permitting the creation of large workflows while offering substantial flexibility. An increasing number of Nextflow workflows are being shared on repositories such as GitHub. However, this tremendous opportunity to reuse existing code remains largely underutilized. In cause, the increasing complexity of workflows constitute a major obstacle to code reuse. Consequently, there is a rising need for tools that can help bioinformaticians extract valuable information from their own and others’ workflows. To facilitate workflow inspection and reuse, we developed BioFlow-Insight to automatically analyze the code of Nextflow workflows and generate useful information, particularly in the form of visual graphs depicting the workflow’s structure and representing its individual analysis steps. BioFlow-Insight is an open-source tool, available as both a command-line interface and a web service. It is accessible at https://pypi.org/project/bioflow-insight/ and https://bioflow-insight.pasteur.cloud/.
Ceftolozane/Tazobactam for the Treatment of Adults With Cystic Fibrosis: Results From a French Prospective Cohort Study
Authors: Burgel Pierre-Régis , Bourge Xavier , Mackosso Carole , Parquin Francois
Published: August 2024

Background

People with cystic fibrosis (pwCF) are particularly susceptible to respiratory infections, including those caused by multidrug-resistant (MDR) pathogens. Ceftolozane/tazobactam (C/T) is an antibacterial agent combination active against MDR gram-negative bacteria that has shown promising results in isolates from pwCF. This subanalysis is the first extensive observation of real-world C/T use in pwCF.

Methods

The multicenter observational CONDUCT study included consecutive patients, some with cystic fibrosis, who received ≥1 dose of C/T at 28 centers throughout France. Patients were treated according to hospital standards and followed up until the end of C/T treatment (EOT).

Results

Among 260 patients who had received ≥1 dose of C/T, 63 were pwCF, including 12 with previous lung transplant. The median age was 34 years and 55.6% of patients were female. Pseudomonas aeruginosa was the most frequently isolated pathogen (n = 40/41 [97.6%]). Most tested P aeruginosa strains (n = 65/73 [91.5%]) and all other isolated strains (Escherichia coli, Citrobacter koseri, Proteus mirabilis, and Serratia marcescens) were susceptible to C/T. Most patients completed the treatment duration, including those with historical β-lactam hypersensitivity. Reasons for stopping treatment were planned EOT and improvement in condition; overall, 88.9% of patients (n = 56/63) experienced improvement in condition. No new safety signals were identified. Mean forced expiratory volume in 1 second improved from 1.33 L to 1.47 L before and after C/T treatment, respectively (n = 52; P = .057).

Conclusions

C/T treatment was well tolerated and effective in pwCF, including those with previous β-lactam hypersensitivity.
Clinical immunity to malaria involves epigenetic reprogramming of innate immune cells
Authors: Nideffer Jason , Ty Maureen , Donato Michele , John Rek , Kajubi Richard , Ji Xuhuai , Nankya Felistas , Musinguzi Kenneth , Press Kathleen Dantzler , Yang Nora , Camanag Kylie , Greenhouse Bryan , Kamya Moses , Feeney Margaret E , Dorsey Grant , Utz Paul J , Pulendran Bali , Khatri Purvesh , Jagannathan Prasanna
Published: August 2024

The regulation of inflammation is a critical aspect of disease tolerance and naturally acquired clinical immunity to malaria. Here, we demonstrate using RNA sequencing and epigenetic landscape profiling by cytometry by time-of-flight, that the regulation of inflammatory pathways during asymptomatic parasitemia occurs downstream of pathogen sensing—at the epigenetic level. The abundance of certain epigenetic markers (methylation of H3K27 and dimethylation of arginine residues) and decreased prevalence of histone variant H3.3 correlated with suppressed cytokine responses among monocytes of Ugandan children. Such an epigenetic signature was observed across diverse immune cell populations and not only characterized active asymptomatic parasitemia but also correlated with future long-term disease tolerance and clinical immunity when observed in uninfected children. Pseudotime analyses revealed a potential trajectory of epigenetic change that correlated with a child's age and recent parasite exposure and paralleled the acquisition of clinical immunity. Thus, our data support a model whereby exposure to Plasmodium falciparum induces epigenetic changes that regulate excessive inflammation and contribute to naturally acquire clinical immunity to malaria.
Robust differential gene expression patterns in the prefrontal cortex of male mice exposed to an occupationally relevant dose of laboratory-generated wildfire smoke
Authors: Schuller Adam , Oakes Jessica , LaRocca Tom , Matz Jacqueline , Eden Matthew , Bellini Chiara , Montrose Luke
Published: August 2024

Wildfires have become common global phenomena concurrent with warmer and drier climates and are now major contributors to ambient air pollution worldwide. Exposure to wildfire smoke has been classically associated with adverse cardiopulmonary health outcomes, especially in vulnerable populations. Recent work has expanded our understanding of wildfire smoke toxicology to include effects on the central nervous system and reproductive function; however, the neurotoxic profile of this toxicant remains ill-explored in an occupational context. Here, we sought to address this by using RNA sequencing to examine transcriptomic signatures in the prefrontal cortex of male mice modeling career wildland firefighter smoke exposure. We report robust changes in gene expression profiles between smoke-exposed samples and filtered air controls, evidenced by 2,862 differentially expressed genes (51.2% increased). We further characterized the functional relevance of these genes highlighting enriched pathways related to synaptic transmission, neuroplasticity, blood–brain barrier integrity, and neurotransmitter metabolism. Additionally, we identified possible contributors to these alterations through protein–protein interaction network mapping, which revealed a central node at ß-catenin and secondary hubs centered around mitochondrial oxidases, the Wnt signaling pathway, and gene expression machinery. The data reported here will serve as the foundation for future experiments aiming to characterize the phenotypic effects and mechanistic underpinnings of occupational wildfire smoke neurotoxicology.