bluuebunny/crossref_metadata_2025_split huggingface dataset:
Motility-activating mutations upstream of
flhDC
reduce acid shock survival of
Escherichia coli
Authors: Schumacher Kilian , Braun Djanna , Kleigrewe Karin , Jung Kirsten 
Published: April 2024

ABSTRACT

Many neutralophilic bacterial species try to evade acid stress with an escape strategy, which is reflected in the increased expression of genes coding for flagellar components. Extremely acid-tolerant bacteria, such as
Escherichia coli
, survive the strong acid stress, e.g., in the stomach of vertebrates. Recently, we were able to show that the induction of motility genes in
E. coli
is strictly dependent on the degree of acid stress, i.e., they are induced under mild acid stress but not under severe acid stress. However, it was not known to what extent fine-tuned expression of motility genes is related to fitness and the ability to survive periods of acid shock. In this study, we demonstrate that the expression of FlhDC, the master regulator of flagellation, is inversely correlated with the acid shock survival of
E. coli
. We encountered this phenomenon when analyzing mutants from the Keio collection, in which the expression of
flhDC
was altered by an insertion sequence element. These results suggest a fitness trade-off between acid tolerance and motility.

IMPORTANCE

Escherichia coli
is extremely acid-resistant, which is crucial for survival in the gastrointestinal tract of vertebrates. Recently, we systematically studied the response of
E. coli
to mild and severe acidic conditions using Ribo-Seq and RNA-Seq. We found that motility genes are induced at pH 5.8 but not at pH 4.4, indicating stress-dependent synthesis of flagellar components. In this study, we demonstrate that motility-activating mutations upstream of
flhDC
, encoding the master regulator of flagella genes, reduce the ability of
E. coli
to survive periods of acid shock. Furthermore, we show an inverse correlation between motility and acid survival using a chromosomal isopropyl β-D-thio-galactopyranoside (IPTG)-inducible
flhDC
promoter and by sampling differentially motile subpopulations from swim agar plates. These results reveal a previously undiscovered trade-off between motility and acid tolerance and suggest a differentiation of
E. coli
into motile and acid-tolerant subpopulations, driven by the integration of insertion sequence elements.
Excessive subsidence of oceanic basins caused by recycled oceanic crust in the mantle source: A new perspective on the oceanic topography within Southeast Asia
Authors: Yang Fan , Huang Xiao-Long , Xu Yi-Gang , Zhang Le , He Peng-Li , Yu Yang , Liu Liang 
Published: April 2024

Abstract
Additional subsidence of oceanic basins compared to the half-space cooling prediction is thought to be a dynamic response to the underlying mantle convection induced by slab sinking. Here, we identified a significantly elevated proportion (10%–20%) of recycled oceanic crust (ROC) in the source of mid-ocean-ridge basalts (MORBs) from the South China Sea (SCS), illustrating the ROC accumulation within a confined upper-mantle range, possibly as a result of the long-term surrounding subduction events. The presence of this lithological heterogeneity in the ROC leads to an increase in mantle density by 0.45%–0.90% at most, thereby contributing to the observed excessive subsidence in the SCS basin when compared to other small basins affected by dynamic topography, while open oceans experience subsidence primarily due to thermal cooling. We propose that the ROC-induced density change in the upper mantle is crucial for generating the topographic anomalies in oceanic basins influenced by subducted slabs, alongside dynamic topography caused by mantle flow.
Effect of active-duty military service on neonatal birth outcomes: a systematic review
Authors: Morris Kirsten A L , McKee M 
Published: April 2024

IntroductionIncreasing numbers of women serve in the armed forces in countries worldwide. Stress experienced during pregnancy is associated with adverse birth outcomes including preterm delivery (PTD) and low birth weight (LBW). Several characteristics of military employment and lifestyle can increase stress acting on active-duty servicewomen (ADSW) and hence may increase the risk of adverse neonatal outcomes. This paper reviews the prevalence of PTD, preterm labour (PTL), LBW and stillbirth in babies born to ADSW in the armed forces.MethodsThis systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Medline, EMBASE, Web of Science, Global Health and CINAHL Plus databases were searched from inception to July 2021 (November 2023, EMBASE) using subject heading and keyword searches for English language journal articles on babies born to ADSW in any military branch and any country. The Joanna Briggs Institute prevalence critical appraisal tool assessed risk of bias in included papers. Studies were paired with a comparator non-active-duty population to generate a prevalence ratio as the effect measure. A narrative synthesis was conducted.Results21 observational studies fulfilled the eligibility criteria. They were all conducted in the US military, involved a total of 650 628 participants, and were published between 1979 and 2023. Their results indicate increased LBW in ADSW compared with non-service women. There was insufficient evidence to conclude or rule out whether ADSW have increased rates of PTD or PTL.ConclusionsADSW may be at increased risk of having an LBW baby. However, caution is needed if seeking to generalise the findings beyond the US context. This review highlights a growing need for female-specific research in other armed forces and, specifically, into reproductive health. Such research is necessary to inform military maternity pathways and policies in ways that safeguard mothers and their babies while enhancing military readiness.
The Bayes factor surface for searches for new physics
Authors: Fowlie Andrew 
Published: April 2024

AbstractThe Bayes factor surface is a new way to present results from experimental searches for new physics. Searches are regularly expressed in terms of phenomenological parameters – such as the mass and cross-section of a weakly interacting massive particle. Bayes factor surfaces indicate the strength of evidence for or against models relative to the background only model in terms of the phenomenological parameters that they predict. They provide a clear and direct measure of evidence, may be easily reinterpreted, but do not depend on choices of prior or parameterization. We demonstrate the Bayes factor surface with examples from dark matter, cosmology, and collider physics.
Appendectomy and Risk of Prostate Cancer in the Health Professionals Follow-up Study
Authors: Zhang Yiwen , Feng Xiaotong , Giovannucci Edward L. 
Published: April 2024

Abstract

Background:
Appendectomy is a common surgical procedure to treat appendicitis. Limited studies have examined its association with prostate cancer, with one large cohort study suggesting a significantly increased risk of overall and advanced prostate cancer, especially among younger men.

Methods:
A total of 49,104 men in the Health Professionals Follow-up Study were followed from 1986 to 2016. Cox proportional hazards models were applied to evaluate the association between self-reported history of appendectomy and risk of overall and subtype-specific prostate cancer, adjusted for multiple risk factors.

Results:
During 30 years of follow-up, we documented 7,253 overall prostate cancer cases, including 579 advanced and 1,092 lethal events. Compared to men without appendectomy, those who reported at baseline having had appendectomy were not at higher risk of overall [HR, 1.01; 95% confidence interval (CI), 0.95–1.07], advanced (HR, 0.99; 95% CI, 0.81–1.23), or lethal (HR, 1.04; 95% CI, 0.89–1.20) prostate cancer. The association remained null when stratified by age.

Conclusions:
We found no evidence of an association between appendectomy and the risk of overall and clinically important prostate cancer.

Impact:
We showed that appendectomy was not associated with overall or advanced prostate cancer after adjusting for multiple risk factors in a large population of men with 30 years of follow-up.
Genomic Profiling to Contextualize the Results of Intervention for Smoldering Multiple Myeloma
Authors: Kazandjian Dickran , Diamond Benjamin , Papadimitriou Marios , Hill Elizabeth , Sklavenitis-Pistofidis Romanos , Ziccheddu Bachisio , Blaney Patrick , Chojnacka Monika , Durante Michael , Maclachlan Kylee , Young Ryan , Usmani Saad , Davies Faith , Getz Gad , Ghobrial Irene , Korde Neha , Morgan Gareth , Maura Francesco , Landgren Ola 
Published: April 2024

Abstract

Purpose:
Early intervention for high-risk smoldering multiple myeloma (HR-SMM) achieves deep and prolonged responses. It is unclear if beneficial outcomes are due to the treatment of less complex, susceptible disease or inaccuracy in clinical definition of cases entered.

Experimental Design:
In this study, we interrogated whole-genome and whole-exome sequencing for 54 patients across two HR-SMM interventional studies (NCT01572480 and NCT02279394).

Results:
We reveal that the genomic landscape of treated HR-SMM is generally simple as compared with newly diagnosed multiple myeloma counterparts with less inactivation of tumor suppressor genes, RAS pathway mutations, MYC disruption, and APOBEC contribution. The absence of these events parallels that of indolent precursor conditions, possibly explaining overall excellent outcomes. However, some patients harboring genomic complexity fail to sustain response and experience resistant, progressive disease. Overall, clinical risk scores do not effectively discriminate between genomically indolent and aggressive disease.

Conclusions:
Genomic profiling can contextualize the advantage of early intervention in SMM and guide personalization of therapy.
See related commentary by Weinhold and Rasche, p. 4263
Hematopoietic Clonal Evolution Goes Spatial
Authors: Austin Rebecca , Aifantis Iannis 
Published: April 2024

Summary:The spatial distribution of cells carrying clonal hematopoiesis mutations in the bone marrow and the potential role of interactions with the microenvironment are largely unknown. This study takes clonal evolution to the spatial level by describing a novel technique examining the spatial location of mutated clones in the bone marrow and the first evidence that mutated hematopoietic clones are spatially constrained and have heterogenous locations within millimeters of distance.See related article by Young et al., p. 153 (10).
Abstract 4183: Gender Difference in the Relationship Between Socioeconomic Deprivation and Fatal Compared to Non-fatal Myocardial Infarction
Authors: Jhund Pardeep , Macintyre Kate , McMurray John 
Published: April 2024

Introduction: Although socioeconomic deprivation (SED) has been identified as an important risk factor for myocardial infarction (MI), it is not clear whether it predicts outcome after adjustment for traditional risk factors. The relative importance of SED as a predictor of fatal versus non-fatal outcomes and in men versus women is also uncertain.
Hypothesis: We hypothesized that SED is an independent predictor of both first hospitalization for MI and MI death (and equally so in men and women).
Methods: We examined outcomes in 15,378 men and women initially surveyed between 1972–76 in Renfrew and Paisley, Scotland, and followed until 3/31/2004. Hazards ratios (HR) for a first admission with a MI (as principal diagnosis) and death from MI were calculated using Cox Regression. All analyses were adjusted for age, body mass index, systolic and diastolic blood pressure, cholesterol, smoking, ECG ischemia, and a history of diabetes, angina or stroke. Deprivation was defined using the seven category Carstairs deprivation index. Deprivation categories (depcat) 6 and 7 (the most deprived depcats) were combined to increase power due to small numbers of individuals in group 7. Log rank tests were used to compare the overall trend across depcats.
Results: During >=28 years follow-up, 1873 men and women had a first MI hospitalization and 2370 a MI death. Compared to the most affluent (depcat 1), the risk of MI death in men and women combined in depcat 6/7 was 37% higher (hazard ratio (HR) 1.37 (P=0.001)), trend P<0.0001. The HR for men alone in depcat 6/7 versus depcat 1 was 1.35 (P=0.018) and similarly 1.38 for women alone (P=0.027). For men and women in depcat 6/7 (compared to depcat 1), the HR for a first MI hospitalization was 1.34 (P= 0.007), P<0.0001. The HR was 1.1 for men (P=0.5) and 1.74 for women (P=0.002).
Conclusion: SED is associated with an increased risk of MI death which is of similar magnitude in men and women, even after accounting for “traditional” risk factors. By contrast, SED is associated with a smaller risk of 1st hospitalization for MI in men than women. This explanation for this gender difference is uncertain but may represent a differential effect of SED on survival to hospital admission in men and women.
2009 Sol Sherry Distinguished Lecture in Thrombosis—Hemostasis and Thrombosis—Two Sides of the Same Coin?
Authors: Mackman Nigel 
Published: April 2024

Blood coagulation is essential for life. The clotting cascade is divided into extrinsic (tissue factor and factor VIIa), intrinsic (factors XIIa, XIa, IXa, and FVIIIa), and common (factor Xa, factor Va, and thrombin) pathways that generate cross-linked fibrin. Hemostasis is a physiological process that prevents excess bleeding after vessel injury. Under normal conditions, all coagulation factors, except tissue factor, reside in the blood. Tissue factor is expressed in the vessel wall and activates the clotting system after injury. Thrombosis is a pathological process that leads to occlusion of blood vessels. Thrombosis can be triggered by rupture of an atherosclerotic plaque or by tissue factor–positive microparticles in the blood. Mice lacking components of the extrinsic or common pathways do not survive, which indicates that these pathways are essential for hemostasis. In contrast, mice lacking either factor XI or factor XII have no hemostatic defects, which suggests that these factors are not required for hemostasis. Mice deficient in either factor VIII or IX survive but exsanguinate after tail transection, consistent with a role in amplification of the cascade.
Surprisingly, mice lacking either factor XII or factor XI were protected in thrombosis models demonstrating a role in thrombosis. These results reveal mechanistic differences between hemostasis and thrombosis. At present, the identity of the activators of the intrinsic pathway has not been defined but may include extracellular RNA released from damaged cells and polyphosphate secreted from activated platelets. A better understanding of the different pathways may lead to the development of novel antithrombotic drugs.
These designations were based on the “ex vivo” activation of coagulation. An “extrinsic” factor called tissue thromboplastin (also known as factor III or tissue factor) initiated clotting via the extrinsic pathway, and this reaction formed the basis of the prothrombin time assay. In contrast, addition of blood to a negatively charged surface, such as kaolin, activated the clotting cascade via the intrinsic pathway. This is called the activated partial thromboplastin time and is driven by factor XIIa (also known as Hageman factor). However, individuals deficient in factor XII, such as John Hageman, were not bleeders. This suggested that factor XIIa was not required for in vivo clotting. In 1991, Gailani and Broze found that thrombin could activate factor XI and factor XII was largely removed from diagrams of the clotting cascade. Studies on mice lacking different clotting factors demonstrated essential roles in hemostasis for components of the extrinsic and common pathways.
Abstract 4945: Eptifibatide is Non-inferior to Abciximab in Acute Coronary Syndromes: Results From the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)
Authors: Akerblom Axel , James Stefan K , Koutouzis Michael , Lagerqvist Bo , Stenestrand Ulf , Svennblad Bodil , Oldgren Jonas 
Published: April 2024

Introduction: Glycoprotein IIb/IIIa inhibitors are recommended by international guidelines with high level of evidence in patients with Acute Coronary Syndromes (ACS) undergoing treatment with percutaneous coronary interventions. No prospective randomized trial comparing abciximab and eptifibatide has been published.
Hypothesis: We hypothesized that eptifibatide is non-inferior to abciximab.
Methods: We included all ACS patients in Sweden undergoing percutaneous coronary interventions receiving either eptifibatide or abciximab during 2004 to 2006 from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). The primary endpoint was death and myocardial (re-)infarction during one year follow-up with adjustment for baseline differences with a multivariable logistic regression analysis including propensity score. The pre-specified non-inferiority margin was set to 1.29.
Results: ACS patients were stratified in two treatment groups (eptifibatide n=3703 and abciximab n=10252) which showed similar baseline characteristics with mean age of 65 years, female representation of 27% and diabetes in 20.5% respectively 19.4%. The eptifibatide cohort had a lower proportion of ST-elevation myocardial infarctions (45.8% vs. 67.6%). The combined endpoint occurred in 543 (14.7%) and 1607 (15.7 %) of eptifibatide and abciximab treated patients respectively. The unadjusted odds ratio (95 %CI) for eptifibatide versus abciximab was 0.92 [0.83 – 1.03]. Multivariable adjustment (n=13882) showed non-inferiority with an odds ratio of 1.07 [0.95 – 1.19]. In patients with ST-elevation myocardial infarctions the non-inferiority remained with adjusted odds ratio of 1.03 [0.89 – 1.20] (n=8598).
Conclusions: This large scale registry study shows that eptifibatide is non-inferior to abciximab as adjunctive therapy in invasively managed ACS patients with respect to death or myocardial infarction during one year, justifying its broad use in clinical practice.
Abstract 5269: Asymmetric Dimethylarginine Triggers Vasculo-Renal Interaction in CKD Mice
Authors: Kajimoto Hidemi , Kai Hisashi , Yasuoka Suguru , Anegawa Takahiro , Aoki Hiroki , Imaizumi Tsutomu 
Published: April 2024

Background: Patients with chronic kidney disease (CKD) also suffer increased morbidity and mortality from cardiovascular diseases (CVD). Endothelial dysfunction is a major factor underlying the pathogenesis of CVD. Asymmetric dimethylarginine (ADMA), an endogenous endothelial nitric oxide synthase (eNOS) inhibitor, is elevated in CKD. We hypothesized that ADMA has a role in endothelial dysfunction in CKD.
Methods and Results: We created a CKD model by performing 5/6 nephrectomy (Nx) in mice. Blood and 24-hour urine were collected for measurements of renal function and ADMA, and NOx levels at 4 weeks after Nx. Nx induced renal failure (serum blood urea nitrogen, controls: 26.9±1.6 mg/dL, Nx mice: 61.0±3.8 mg/dL, p <0.001; serum creatinine, controls: 0.19±0.01 mg/dl, Nx mice: 0.31±0.03 mg/dL, p <0.01) without changing blood pressure. The serum ADMA level was higher (p <0.01) in Nx mice (1.20±0.05 nmol/mL) than in controls (1.00±0.05 nmol/mL). Urinary NOx was lower in Nx mice (controls: 2153±189 nmol/L, Nx mice: 706±335 nmol/L, p <0.05). Isometric tension study using aortic rings showed that endothelium-mediated relaxation induced by acetylcholine was impaired in Nx mice. Furthermore, pretreatment with exogenously administered ADMA at a serum concentration comparable to that in Nx mice reduced acetylcholine-induced relaxation in the aorta of controls. Western blotting showed the phosphorylated eNOS level of the aorta was lower in Nx mice than in controls, whereas eNOS levels were similar. The expression level of dimethylarginine dimethylaminohydrolase-1 (DDAH-1), a degradation enzyme of ADMA, was reduced in the kidney, but not in the aorta of Nx mice. In an ex vivo experiment using cultured human umbilical vein endothelial cells, ADMA treatment with a concentration corresponding to the serum level in Nx mice reduced the eNOS phosphorylation level.
Conclusions: Elevated levels of circulating ADMA, probably resulting from decreased DDAH-1 expression in the kidney, appear to impair endothelial function by inhibiting eNOS activity in CKD. ADMA may thus have a triggering role in the vasculo-renal interaction in CKD.
Abstract 5465: SIRT1 Decreases Lox-1 Mediated Foam Cell Formation in Atherogenesis
Authors: Stein M A , Lohmann Christine , Schäfer Nicola , Hofmann Janin , Rohrer Lucia , Breitenstein Alexander , Besler Christian , Becher Burkhard , Hottiger Michael O , McBurney Michael W , Luscher Thomas F , Matter Christian M 
Published: April 2024

Background - Atherosclerosis is a chronic inflammatory disease that results from interaction between oxLDL, activated endothelial cells, monocyte-derived macrophages, T cells, and the arterial wall. Infiltrating macrophages become foam cells upon uptake of oxidized low-density lipoproteins (oxLDL) via scavenger receptors such as lectin-like oxLDL receptor-1 (Lox-1). SIRT1 is a class III deacetylase that senses caloric restriction, improves insulin secretion in islet cells, and reduces accumulation of fatty acids in white adipose. The relevance of endogenous SIRT1 on atherosclerosis remains unknown.
Methods - To investigate the role of SIRT1 in these cellular and molecular processes, we compared hypercholesterolemic ApoE−/− SIRT1+/+ and ApoE−/− SIRT1+/− mice that were kept on a high-cholesterol diet for 12 weeks. Peritoneal-elicited macrophages, human aortic endothelial cells (HAEC) and RAW macrophages were used to verify our in vivo findings. Bone-marrow transplantations were performed to assess the relevance of macrophage-derived SIRT1 on atherogenesis.

Results - Our plaque analyses reveal that SIRT1 prevents atherogenesis without affecting total plasma cholesterol or lipid subfractions. ApoE−/− SIRT1+/− mice show increased features of plaque vulnerability with thinner fibrous caps and enhanced plaque inflammation (increased number of macrophages and T cells as well as induced expression of adhesion molecules and inflammatory cytokines). Furthermore, peritoneal-elicited macrophages from heterozygous mice accumulate increased levels of oxLDL. In vitro, we show that the atheroprotective effects of SIRT1 are mediated via NF-
κ
B inhibition: in HAEC SIRT1 inhibits NF-
κ
B signaling and diminishes expression of adhesion molecules; in macrophages the inhibitory effect reduces expression of Lox-1. Bone-marrow transplantations demonstrate that macrophage.-derived SIRT1 is crucial for preventing disease progression.

Conclusions - Our data show that SIRT1 prevents atherosclerotic plaque formation. The availability of specific SIRT1-activating drugs suggests that pharmacological activation of SIRT1 may become an attractive anti-atherogenic strategy.