bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation in human gut microbiota impacts tamoxifen pharmacokinetics
Authors: Alam Yasmine , Hakopian Sheron , Ortiz de Ora Lizett , Tamburini Ian , Avelar-Barragan Julio , Jung Sunhee , Long Zane , Chao Alina , Whiteson Katrine , Jang Cholsoon , Bess Elizabeth 
Published: November 2024

ABSTRACT

Tamoxifen is the most prescribed drug used to prevent breast cancer recurrence, but patients show variable responses to tamoxifen. Such differential inter-individual response has a significant socioeconomic impact as one in eight women will develop breast cancer and nearly half a million people in the United States are treated with tamoxifen annually. Tamoxifen is orally delivered and must be activated by metabolizing enzymes in the liver; however, clinical studies show that neither genotype nor hepatic metabolic enzymes are sufficient to predict why some patients have sub-therapeutic levels of the drug. Here, using gnotobiotic- and antibiotics-treated mice, we show that tamoxifen pharmacokinetics are heavily influenced by gut bacteria and prolonged exposure to tamoxifen. Interestingly, 16S rRNA gene sequencing shows tamoxifen does not affect overall microbiota composition and abundance. Metabolomics, however, reveals differential metabolic profiles across the microbiomes of different donors cultured with tamoxifen, suggesting an enzymatic diversity within the gut microbiome that influences response to tamoxifen. Consistent with this notion, we found that β-glucuronidase (GUS) enzymes vary in their hydrolysis activity of glucuronidated tamoxifen metabolites across the gut microbiomes of people. Together, these findings highlight the importance of the gut microbiome in tamoxifen’s pharmacokinetics.

IMPORTANCE
One in eight women will develop breast cancer in their lifetime, and tamoxifen is used to suppress breast cancer recurrence, but nearly 50% of patients are not effectively treated with this drug. Given that tamoxifen is orally administered and, thus, reaches the intestine, this variable patient response to the drug is likely related to the gut microbiota composed of trillions of bacteria, which are remarkably different among individuals. This study aims to understand the impact of the gut microbiome on tamoxifen absorption, metabolism, and recycling. The significance of our research is in defining the role that gut microbes play in tamoxifen pharmacokinetics, thus paving the way for more tailored and effective therapeutic interventions in the prevention of breast cancer recurrence.
Genome-wide quantification of polycistronic transcription in
Leishmania major
Authors: Grünebast Janne , Lorenzen Stephan , Clos Joachim 
Published: November 2024

ABSTRACT

Leishmania major
is a human-pathogenic, obligate parasite and the etiological agent of the most prevalent, cutaneous form of leishmaniasis, which is an important neglected, tropical disease with ~1.2 million new infections per year.
Leishmania
, and the whole order Trypanosomatida, are early eukaryotes with highly diverged gene expression and regulation pathways, setting them apart from their mammalian hosts and from most other eukaryotes. Using precision run-on sequence analysis, we performed a genome-wide mapping and density analysis of RNA polymerases in isolated nuclei of the protozoan parasite
Leishmania major
. We map transcription initiation sites at divergent strand switch regions and head-tail regions within the chromosomes and correlate them with known sites of chromatin modifications. We confirm continuous, polycistronic RNA synthesis in all RNA polymerase II-dependent gene arrays but find small varying RNA polymerase activities in polycistronic transcription units (PTUs), excluding gene-specific transcription regulation, but not PTU-specific variations. Lastly, we find evidence for transcriptional pausing of all three RNA polymerase classes, hinting at a possible mechanism of transcriptional regulation.

IMPORTANCE

Leishmania
spp. are pathogens of humans and animals and cause one of the most important neglected tropical diseases. Regulation of gene expression in
Leishmania
but also in the related
Trypanosoma
is radically different from all eukaryotic model organisms, dispensing with regulated, gene-specific transcription, and relying instead on highly regulated translation. Our work sheds light on the initiation, elongation, and termination of transcription, maps unidirectional, polycistronic transcription units, provides evidence for transcriptional pausing at or near starting points of RNA synthesis, and quantifies the varying transcription rates of the polycistronic transcription units. Our results will further the understanding of these important pathogens and should provide a valuable resource for researchers in the field of eukaryotic microbiology.
p18 encoded by FgGMTV1 is responsible for asymptomatic infection in
Fusarium graminearum
Authors: Zhang Lihang , Li Pengfei , Wang Yanfei , Wang Shuangchao , Guo Lihua 
Published: November 2024

ABSTRACT

The intricate interplay between mycoviruses and their fungal hosts frequently culminates in asymptomatic infections, but the virus-derived factors underlying these infections remain poorly understood. Our study introduces p18, a novel protein encoded by the DNA-C segment of the genomovirus FgGMTV1, which facilitates the transition from virus-induced hypovirulence to asymptomatic infection within
Fusarium graminearum
upon its expression. We have confirmed the expression of p18 during FgGMTV1 infection and observed its presence in both the nucleus and cytoplasm. Remarkably, strains with a p18 null mutation show a significant reduction in colony expansion, conidial production, and virulence, leading to a hypovirulent phenotype. Our results also indicate that p18 hinders the accumulation of FgGMTV1, thus determining asymptomatic infection and enabling vertical transmission through conidia. Furthermore, the p18 null mutant virus converts
F. graminearum
from virulent to hypovirulent strains on wheat leaves after horizontal transmission. This work not only expands our knowledge of the genomovirus proteome but also provides insights into the strategies of viral evolution and adaptation. Moreover, we propose an innovative approach for creating hypovirulent strains utilizing engineered mycoviruses for the biocontrol of plant pathogenic fungi.

IMPORTANCE

Mycovirus-fungus interplay often leads to asymptomatic infections. Our study identifies p18, a novel protein from the genomovirus FgGMTV1, as a key determinant of asymptomatic infection in
Fusarium graminearum
. A p18-null mutant exhibits a pronounced hypovirulent phenotype. By modulating viral accumulation, p18 promotes asymptomatic infection and facilitates vertical transmission via conidia. This insight deepens our understanding of mycovirus-fungus interactions and introduces a novel strategy for biocontrol using engineered mycoviruses.
IOC consensus statement: interpersonal violence and safeguarding in sport
Authors: Tuakli-Wosornu Yetsa A , Burrows Kirsty , Fasting Kari , Hartill Mike , Hodge Ken , Kaufman Keith , Kavanagh Emma , Kirby Sandra L , MacLeod Jelena G , Mountjoy Margo , Parent Sylvie , Tak Minhyeok , Vertommen Tine , Rhind Daniel J A 
Published: November 2024

ObjectiveInterpersonal violence (IV) in sport is challenging to define, prevent and remedy due to its subjectivity and complexity. The 2024 International Olympic Committee Consensus on Interpersonal Violence and Safeguarding aimed to synthesise evidence on IV and safeguarding in sport, introduce a new conceptual model of IV in sport and offer more accessible safeguarding guidance to all within the sports ecosystem by merging evidence with insights from Olympic athletes.MethodsA 15-member expert panel performed a scoping review following Joanna Briggs Institute methodologies. A seminal works-driven approach was used to identify relevant grey literature. Four writing groups were established focusing on: definitions/epidemiology, individual/interpersonal determinants, contextual determinants and solutions. Writing groups developed referenced scientific summaries related to their respective topics, which were discussed by all members at the consensus meeting. Recommendations were then developed by each group, presented as voting statements and circulated for confidential voting following a Delphi protocol with ≥80% agreement defined a priori as reaching consensus.ResultsOf 48 voting statements, 21 reached consensus during first-round voting. Second-round and third-round voting saw 22 statements reach consensus, 5 statements get discontinued and 2 statements receive minority dissension after failing to reach agreement. A total of 43 statements reached consensus, presented as overarching (n=5) and topical (n=33) consensus recommendations, and actionable consensus guidelines (n=5).ConclusionThis evidence review and consensus process elucidated the characterisation and complexity of IV and safeguarding in sport and demonstrates that a whole-of-system approach is needed to fully comprehend and prevent IV. Sport settings that emphasise mutual care, are athlete centred, promote healthy relationships, embed trauma- and violence-informed care principles, integrate diverse perspectives and measure IV prevention and response effectiveness will exemplify safe sport. A shared responsibility between all within the sports ecosystem is required to advance effective safeguarding through future research, policy and practice.
Changes in peak oxygen consumption in Fabry disease and associations with cardiomyopathy severity
Authors: Roy Ashwin , Thompson Sophie E , Hodson James , van Vliet Jan , Condon Nicola , Alvior Amor Mia , O’Shea Christopher , Vijapurapu Ravi , Nightingale Tom E , Clift Paul F , Townend Jonathan , Geberhiwot Tarekegn , Steeds Richard Paul 
Published: November 2024

BackgroundFabry disease (FD) causes multiorgan sphingolipid accumulation, with cardiac involvement responsible for the largest burden of morbidity and mortality. Exercise intolerance in FD is prevalent, yet the mechanisms of this are poorly understood. The aim of this study was to assess exercise intolerance in FD and identify whether this correlates with the phase of cardiomyopathy.MethodsThis was a retrospective observational study of adults with FD undergoing cardiopulmonary exercise testing (CPEX) between September 2011 and September 2023 at a national referral centre in the UK. The primary outcome measure was peak oxygen uptake (V̇O2peak), with forced expiratory volume in 1 s (FEV1) used to quantify respiratory impairment. Age-normalised/sex-normalised values were additionally calculated, based on published normal ranges for subgroups of age and sex. The cardiomyopathy phase was classified on a 4-point scale by two FD experts using contemporaneous imaging and biochemistry results.ResultsCPEX was completed by 42 patients, with a median age of 54 years and of whom 62% were male. Patients were approximately equally distributed across the four cardiomyopathy phases. At phase I, the mean (±SD) V̇O2peakwas 28.7±7.7 mL/kg/min, which represented a significant underperformance of 23%, relative to age-normalised and sex-normalised values (expected mean: 37.3±3.2 mL/kg/min, p=0.006). V̇O2peakdeclined significantly across the cardiomyopathy phases (p=0.010), reaching a mean of 21.2±6.1 mL/kg/min at phase IV. Normalised FEV1was not found to show a corresponding significant change with cardiomyopathy phase (p=0.683). Impaired left atrial global longitudinal strain as well as biochemical markers of inflammation were associated with impaired V̇O2peak.ConclusionsThis study identifies significantly impaired aerobic capacity in FD, even in those without phenotypic cardiomyopathy. No corresponding changes in respiratory impairment were observed, suggesting that exercise intolerance may be due to early cardiac sphingolipid accumulation and subsequent atrial and ventricular dysfunction, which increases as cardiomyopathy progresses. As such, peak V̇O2peakholds promise as a therapeutic marker of response to FD-specific therapy.
Theoretical study on low-lying hidden-bottom and double-bottom tetraquark states
Authors: Jiang Lin-Juan , An Chun-Sheng , Deng Cheng-Rong , Li Gang , Xie Ju-Jun 
Published: November 2024

AbstractWe perform a theoretical study on the spectrum of the low-lying hidden-bottom ($$q\bar{q}b\bar{b}$$

q

q

¯

b

b

¯

with $$q=$$

q
=

u, d and s) and double-bottom ($$q\bar{q}bb$$

q

q

¯

b
b

) tetraquark states within a nonrelativistic quark model, in which the instanton-induced interaction is taken as the residual spin-dependent hyperfine interaction between quarks. All the model parameters are fixed by fitting the spectrum of the ground hadron states. The numerical results indicate that masses of several $$X_{q\bar{q}}$$

X

q

q

¯

, $$Z_{b}$$

Z
b

, and $$Z_{bs}$$

Z

bs

tetraquark states are below and near thresholds of corresponding meson-meson channels, thus these states may form components of exotic meson states with reasonable probabilities. Especially, in present model, masses of several obtained states with quantum number $$I^G(J^P)=1^+(1^{+})$$

I
G

(

J
P

)

=

1
+

(

1
+

)

are close to $$Z_b^\pm (10610)$$

Z
b
±

(
10610
)

, so one may expect these states to be non-negligible components of the experimentally observed $$Z_{b}$$

Z
b

states. Concerning to the double-bottom tetraquark states, the present results are in general consistent with other previous works. Two possible stable $$T_{bb}$$

T

bb

states with quark content $$bb\bar{n}\bar{n}$$

b
b

n

¯

n

¯

($$n=u$$

n
=
u

or d quark) lying at energies 10558 MeV and 10650 MeV are found, and one possible stable $$bb\bar{n}\bar{s}$$

b
b

n

¯

s

¯

state is found, whose energy is $$\sim 10687$$

∼
10687

MeV.
Neutralino dark matter in the extension of MSSM with two triplets and singlet
Authors: Yang Zhong-Jun , Yang Jin-Lei , Zhao Shu-Min , Wu Xing-Gang , Feng Tai-Fu 
Published: November 2024

AbstractIn an extension of MSSM with two triplets and a singlet, called the TNMSSM, there are seven neutralinos which can enrich the study of cold dark matter if one expects that the weakly interacting massive particle (WIMP) is responsible for the observation of Planck satellite. Such a model, compared to the MSSM, can naturally offer a solution to the $$\mu $$
μ
problem, and its lightest neutralino, which is bino-like, can also provide a correct relic density by using the coannihilation mechanism due to the newly added triplinos. Taking into account the related experimental measurements, such as the bound on the SM-like Higgs mass, the B meson rare decays, the anomalous magnetic moment of the muon $$a_\mu $$

a
μ

, the Large Hadron Collider (LHC) measurements and the latest dark matter direct detection experiment LUX-ZEPLIN (LZ), the TNMSSM parameter space can be strictly limited. In respect to all the constraints mentioned above, we find that a bino-like neutralino with a mass in the region $$[100, 450]~\textrm{GeV}$$

[
100
,
450
]

GeV

can successfully account for the correct dark matter relic density. Additionally, most of the viable parameter space can be tested in the near future experiments such as the Xenon-nT experiment or LHC.
Seeking a coherent explanation of LHC excesses for compressed spectra
Authors: Agin Diyar , Fuks Benjamin , Goodsell Mark D. , Murphy Taylor 
Published: November 2024

AbstractThe most recent searches by the ATLAS and CMS Collaborations in final states with soft leptons and missing transverse energy show mild excesses predominantly associated with dilepton invariant masses of about $$10{-}20$$

10
-
20

GeV, which can result from decays of electroweakinos that are heavier than the lightest neutralino by $$\mathcal {O}(10)$$

O
(
10
)

GeV. On the other hand, these analyses are insensitive to electroweakino mass splittings smaller than about 5 GeV. In previous work, we demonstrated that while recent searches in the monojet channel can exclude some of the smallest $$\mathcal {O}(1)$$

O
(
1
)

GeV mass splitting configurations for electroweakinos, they also exhibit excesses that can overlap with the soft-lepton excesses in certain models, including a simplified scenario with pure higgsinos. In this work we dive deeper into these excesses, studying the analyses in detail and exploring an array of models that go beyond the simplified scenarios considered by the experimental collaborations. We show that, in the Minimal Supersymmetric Standard Model, the overlapping excesses are not unique to the pure-higgsino limit, instead persisting in realistic parameter space featuring a bino-like lightest supersymmetric particle with some wino admixture. On the other hand, for the Next-to-Minimal Supersymmetric Standard Model with a singlino-like lightest supersymmetric particle and higgsino-like next-to-lightest supersymmetric particle(s), the excess in the two-lepton channel fits rather well with the parameter space predicting the correct relic abundance through freeze out, but the monojet fit is much poorer. Interestingly, the excesses either do not overlap or do not exist at all for two non-supersymmetric models seemingly capable of producing the correct final states.
On the randomness of time ordered quantum measurements
Authors: Almlöf Jonas , Lettner Thomas , Gyger Samuel , Vall Llosera Gemma , Nilsson Tigge , Zwiller Val 
Published: November 2024

AbstractA new method for efficient, high-quality randomness extraction is presented. The method relies on quantum processes such as the emission of single photons and their subsequent detection, where each detection event has an associated detection time. By establishing a list of time differences between a fixed number of events, a unique order can be established.We note that, by utilising the number of ways to order the resulting list of time differences between the quantum events, the efficiency can be increased many-fold compared to current methods. The method delivers fundamentally uniform randomness and therefore, in principle, does not need debiasing.
Remobilization of inverted normal faults drives active extension in the axial zone of the southern Apennine mountain belt (Italy)
Authors: Camanni G. , De Landro G. , Mazzoli S. , Michele M. , Muzellec T. , Ascione A. , Schaff D. P. , Tarantino S. , Zollo A. 
Published: November 2024

The Irpinia region is one of the most seismically active areas of Italy owing to ongoing, late-orogenic extension in the axial zone of the Apennine mountain belt. However, the 3D architecture and the nature of the faults that drive this extension are still uncertain, posing challenges to seismic hazard assessment. Here, we address these uncertainties by integrating a new catalogue of high-resolution micro-seismicity (M
L
< 3.5) complemented by earthquake focal mechanisms, with existing 3D seismic velocity models and geological data. We found that micro-seismicity is primarily taking place along a segmented, approximately 60 km long, deep-seated, Mesozoic normal fault that was inverted during the shortening stages of the Apennine orogeny and then extensionally reactivated during the Quaternary. These findings suggest that multiple events of reactivation of long-lived faults can weaken their strength, making them prone to co-seismic remobilization under newly imposed strain fields in active mountain belts.
Developing the Fear of Disasters Scale and Exploring Its Psychometric Properties
Authors: Güzel Aysun 
Published: November 2024

Aims: The present methodological study attempted to develop the Fear of Disasters Scale (FDS) and reveal its psychometric properties.Methods: While explanatory factor analysis (EFA) was carried out on the data of 265 voluntary participants, the data of 75 participants were used to explore the test–retest reliability of the scale. Confirmatory factor analysis (CFA) was carried out on the data of 150 participants. All analyses were performed on the Statistical Package for the Social Sciences (SPSS) 25.0 and linear structural relations (LISRELs) programs.Results: Cronbach’s α value was calculated to be 0.93. The test–retest reliability analysis resulted in a significant, very strong, and positive correlation (p < 0.001; r = 0.92). The CFA yielded the following fit indices for the scale: p > 0.05, χ2/df = 1.51, root mean square error of approximation (RMSEA) = 0.05, standardized root mean square residual (SRMR) = 0.02, goodness of fit index (GFI) = 0.96, normed fit index (NFI) = 0.97.Conclusions: The findings revealed that the one‐factor instrument with seven items is valid and reliable for measuring fear of disasters (FD) in the sample.
CTCA Prior to Invasive Coronary Angiography in Patients With Previous Bypass Surgery: Patient-Related Outcomes, Imaging Resource Utilization, and Cardiac Events at 3 Years From the BYPASS-CTCA Trial
Authors: Kelham Matthew , Beirne Anne-Marie , Rathod Krishnaraj S. , Andiapen Mervyn , Wynne Lucinda , Learoyd Annastazia E. , Forooghi Nasim , Ramaseshan Rohini , Moon James C. , Davies Ceri , Bourantas Christos V. , Baumbach Andreas , Manisty Charlotte , Wragg Andrew , Ahluwalia Amrita , Pugliese Francesca , Mathur Anthony , Jones Daniel A. 
Published: November 2024

BACKGROUND:
In patients with previous coronary artery bypass grafting, computed tomography cardiac angiography (CTCA) before invasive coronary angiography (ICA) was demonstrated in the BYPASS-CTCA trial (Randomized Controlled Trial to Assess Whether Computed Tomography Cardiac Angiography Can Improve Invasive Coronary Angiography in Bypass Surgery Patients) to reduce procedure time and incidence of contrast-associated acute kidney injury, with greater levels of patient satisfaction. Patient-related outcomes, utilization of further diagnostic imaging resources, and longer-term incidence of major adverse cardiac events were key secondary end points not yet reported.

METHODS:
Patients with prior coronary artery bypass grafting referred for ICA were randomized 1:1 to undergo CTCA before ICA or ICA alone and followed up for a median of 3 (2.2-3.4) years. Angina status was assessed using the Seattle Angina Questionnaire and overall quality of life using the EQ-5D-5L. The incidence of noninvasive imaging use and major adverse cardiac events were compared between the 2 groups.

RESULTS:

In all, 688 patients were randomized, 344 to CTCA+ICA and 344 to ICA only. The mean age of participants was 69.8 years, with 45% undergoing ICA for acute coronary syndromes and the remainder stable angina. At 3 months follow-up, patients in the CTCA+ICA group were more likely to be angina-free (51.7% versus 43.2%;
P
=0.03) with greater quality of life (EQ-5D-5L index, 81.6 versus 74.4;
P
=0.001), although these improvements did not persist. At 3 years follow-up, imaging resource use (35.8% versus 45.1%; odds ratio, 0.68 [95% CI, 0.50–0.92];
P
=0.013) and incidence of major adverse cardiac events were lower in the CTCA+ICA group (35.8% versus 43.5%; hazard ratio, 0.73 [95% CI, 0.58–0.93];
P
=0.010).

CONCLUSIONS:
In patients with prior coronary artery bypass grafting undergoing ICA, CTCA before ICA leads to reductions in the use of imaging resources and the rate of major cardiac events out to 3 years, but with similar patient-related outcome measures. Together with the initial findings of BYPASS-CTCA, these data are supportive of routinely undertaking a CTCA before ICA in patients with prior coronary artery bypass grafting.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03736018.