bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of ischaemic heart disease in heart failure
Authors: Montone Rocco A , Volterrani Maurizio , Zhang Jian , Crea Filippo
Published: December 2023

Ischaemic heart disease represents the most important cause underlying the occurrence of heart failure. Pathophysiological mechanisms explaining the association between myocardial ischaemia and heart failure are multiple and complex, ranging from multivessel obstructive coronary artery disease (CAD) to microvascular dysfunction in the absence of obstructive CAD. Of importance, understanding the exact mechanism of disease is crucial to obtain a proper diagnosis and start appropriate therapy. For this reason, the beginning of this chapter analyses the pathophysiology of ischaemic heart failure across a wide spectrum of heart failure presentations, from heart failure with reduced ejection fraction to heart failure with preserved ejection fraction. The chapter then discusses the diagnostic approach to the patient with heart failure of suspected ischaemic origin. Finally, the chapter reports on the evidence supporting the currently available therapeutic options, highlighting the knowledge gaps in management of these patients.
From hypertension to heart failure
Authors: Manolis Athanasios J , Lopatin Yuri
Published: December 2023

Although different conditions and diseases may lead to the development of heart failure, arterial hypertension due to its high prevalence represents a major risk factor. Through several mechanisms, including endothelial dysfunction, accelerated atherosclerosis, and left ventricular hypertrophy, a patient with hypertension may go on to develop heart failure, with devastating effects in terms of cardiovascular morbidity and mortality. This chapter reviews the cardiovascular continuum that leads a patient with hypertension to progress to heart failure, as well as practical issues related to the therapeutic approach and management.
Peripartum cardiomyopathy
Authors: Sliwa Karen , Bauersachs Johann
Published: December 2023

This chapter provides the definition and describes the investigations and management recommendations for physicians dealing with peripartum cardiomyopathy (PPCM). It gives details on risk stratification and morbidity and mortality. PPCM is a disease that occurs globally in all ethnic groups. It is a diagnosis of exclusion but should be suspected in any peripartum women presenting with symptoms and signs of heart failure towards the end of their pregnancy or in the months following delivery. These women should be thoroughly assessed and alternative causes should be excluded. Urgent cardiac investigation with electrocardiography and natriuretic peptide measurement (if available) should be performed. Echocardiography is the next step in investigation, prior to more advanced imaging where this is available. Patients with abnormal cardiac investigations should be urgently referred to a cardiology team for expert management. Just under half of women with PPCM experience myocardial recovery. PPCM is a disease with substantial maternal and neonatal morbidity and mortality; mortality rates range widely from 0% to 30%, depending on ethnic background and geographical region. Compared to other cardiomyopathies, PPCM patients have better prognosis in terms of survival and recovery of left ventricular function.
Obesity
Authors: Badimon Lina , Anker Stefan D , Haehling Stephan von
Published: December 2023

Obesity is a growing cardiovascular health problem, which is highly prevalent in the general population, as well as in patients with heart failure. Obesity is a risk factor for developing heart failure. Among patients with manifest heart failure, it affects 36–51% and 26–37% of patients with heart failure with preserved and reduced ejection fraction, respectively. The accumulation of adipocytes in obesity fuels a pro-inflammatory response that propagates into a low-grade systemic inflammation, with a large variety of metabolic alterations. In the myocardium, mitochondrial uncoupling is increased, which—together with decreased glucose utilization—impairs myocardial energetics, and consequently mechanical performance. Adipose tissue itself has little metabolic demand, but obesity also comes with increased lean tissue, yielding oxygen requirements and carbon dioxide production. Still, database analyses have shown a survival benefit for patients with heart failure, known as the obesity paradox. This chapter summarizes the available knowledge of the metabolic effects of obesity and its effects on the course of heart failure.
Toxins and infections
Authors: Gavazzi Antonello , Nunes Maria Carmo , Pinto Fausto
Published: December 2023

Toxins, systemic infections, and cardiac infections represent relatively uncommon causes of impaired cardiac function and heart failure (HF). Several exogenous and endogenous toxins are possible causes of progressive cardiac deterioration. Substances of abuse, prescribed and illicit drugs, and environmental agents are the most frequently involved. Any severe systemic infection may induce HF but frequently represents the precipitating cause in a patient with previous heart disease. Cardiac infections may be due to several different agents: viruses, bacteria, fungi, helminths, and protozoa. Among viral cardiac infections, the most clinically relevant are myocarditis caused usually by enteroviruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and human immunodeficiency virus, with subsequent myocardial dysfunction and overt HF. Among parasitic infections, protozoan trypanosomiasis, in particular Chagas disease causing myocarditis leading to cardiomyopathy, and helminthic infection, including schistosomiasis causing pulmonary hypertension and right-sided ventricular HF, are the most prevalent. Different and complex pathophysiological mechanisms, involving inflammation, immunity, and genetic susceptibility, are operative.
Ventricular remodelling
Authors: Díez Javier , Brunner-La Rocca Hans-Peter
Published: December 2023

The term ventricular remodelling refers to alterations in size, shape, and function due to the response of the ventricle to sustained stress. Initially, the remodelling response to pathological stress helps in compensating the cardiac performance, but over time the response becomes maladaptive and leads to ventricular dysfunction. Thus, adverse ventricular remodelling is critically involved in the development of heart failure and its poor clinical outcome. Depending on the underlying pathology, the ventricle can remodel either concentrically or eccentrically. At the myocardial level, the adverse remodelling process implies tissue alterations involving the cardiomyocyte, interstitium, and microcirculation, as well as metabolic and electrophysiological alterations. Multiple mechanisms participate in the development of these alterations, highlighting the complexity and heterogeneity of the remodelling process. Understanding these mechanisms is necessary for both preventing and effectively reversing ventricular remodelling with therapy in heart failure patients.
Immune-mediated mechanisms
Authors: Hofmann Ulrich , Frantz Stefan , Frangogiannis Nikolaos
Published: December 2023

The association between inflammation and acute and chronic heart failure has been established for several decades. Yet this has not been translated into clinical application. Mixed results from several anti-cytokine trials in chronic heart failure have dampened for a long time the enthusiasm to conduct further clinical studies testing the therapeutic potential of immune-modulatory drugs in heart failure. In the meantime, experimental studies on various acute and chronic heart injury and failure models have provided a much better mechanistic understanding of the innate and adaptive immune systems in heart failure. Several large prospective interventional trials have shown a clinical benefit from inhibition of inflammation in atherosclerotic vascular disease. However, such clinical evidence is still widely lacking in relation to heart failure treatment.
Heart failure clinical assessment
Authors: Komajda Michel , Ponikowski Piotr , Shlyakhtho Evgeny
Published: December 2023

According to current European Society of Cardiology Guidelines, heart failure (HF) is a clinical syndrome characterized by typical symptoms/signs caused by a structural/functional cardiac abnormality, resulting in reduced cardiac output and/or elevated intracardiac pressures at rest or during stress. Clinical assessment of chronic HF is based on a stepwise approach: (1) assessment of symptomatic severity using the New York Heart Association classification; (2) comprehensive history taking and clinical examination, as well as identification of comorbidities which are frequent and may impact management; (3) assessment of the aetiology, as HF is the final common pathway of cardiac disorders and can also complicate many non-cardiovascular diseases; and (4) assessment of the risk of death or hospitalization, as mortality is high and hospitalization is recurrent and prolonged. The diagnostic workup of chronic HF cannot be based on clinical assessment only but also requires additional investigations, including electrocardiogram, chest X-ray, plasma natriuretic peptide levels, and imaging, most often based on transthoracic echocardiography. Acute heart failure (AHF) is a life-threatening condition which describes the rapid onset or worsening of symptoms and signs of HF. It can occur de novo or during the course of chronic HF (acute-on-chronic HF). Clinical classification is based on the presence/absence of signs of hypoperfusion and congestion. The diagnostic workup of AHF should be initiated immediately after the first medical contact, and clinical assessment should rule in/out cardiogenic shock or respiratory failure, identify an acute and potentially curable aetiology, and be complemented by appropriate investigations in order to start appropriate therapy.
Cardiac magnetic resonance in heart failure: diagnostic and prognostic assessment
Authors: Baritussio Anna , Sharrack Noor , Plein Sven , Bucciarelli-Ducci Chiara
Published: December 2023

Cardiac magnetic resonance (CMR) is a highly versatile imaging modality, with high spatial resolution and tissue contrast, allowing for detailed morphological and functional assessment of the heart and vasculature. CMR is increasingly used in the assessment of patients with heart failure (HF), from diagnosis to treatment planning and risk stratification. In HF patients, CMR provides whole-heart cine imaging for accurate measurement of biventricular dimensions and function, and a range of methods for myocardial tissue characterization that help determine the aetiology of HF. This chapter discusses the role of CMR in chronic HF to include standard and advanced acquisition protocols, diagnostic workup, differential diagnoses, and insights into how CMR helps guide treatment planning decisions.
Digitalis glycosides
Authors: Bavendiek Udo , Bauersachs Johann
Published: December 2023

The potential of digitalis glycosides in heart failure therapy has been long known. In the only large placebo-controlled, randomized trial, namely the DIG trial, digoxin had a neutral effect on overall mortality in patients with heart failure with reduced ejection fraction (HFrEF), but led to significantly reduced heart failure hospitalization. As standard HFrEF treatment in the DIG trial did not include beta-blockers and mineralocorticoid receptor antagonists, and the therapeutic window of digitalis glycosides is narrow, with a risk of serious side effects, the value of digitalis glycosides in HFrEF therapy is currently uncertain. Nevertheless, digitalis glycosides are still applied frequently worldwide, and this chapter provides recommendations for digitalis use in patients with HFrEF and/or atrial fibrillation. Two ongoing large trials will define the role of digitalis glycosides on top of modern HFrEF treatment: the Digoxin Evaluation in Chronic Heart Failure: Investigational Study In Outpatients in the Netherlands (DECISION) and the DIGitoxin to Improve ouTcomes in patients with advanced chronic Heart Failure (DIGIT-HF).
Ancillary pharmacological treatment options
Authors: Agewall Stefan , van Gelder Isabelle C , Savelieva Irina
Published: December 2023

Heart failure (HF) is not a single pathological diagnosis, but a clinical syndrome consisting of cardinal symptoms (e.g. breathlessness, ankle swelling, fatigue) that may be accompanied by signs (e.g. elevated jugular venous pressure, pulmonary crackles, peripheral oedema). It is due to a structural and/or functional abnormality of the heart that results in elevated intracardiac pressures and/or inadequate cardiac output at rest and/or during exercise. Identification of the aetiology of the underlying cardiac dysfunction is mandatory in the diagnosis of HF, as the specific pathology can determine subsequent treatment. Most commonly, HF is due to myocardial dysfunction: either systolic or diastolic, or both. However, pathology of the valves, pericardium, and endocardium, as well as abnormalities of heart rhythm and conduction, can also cause or contribute to HF. This chapter focuses on ancillary pharmacological treatment options such as anticoagulant treatment, statin treatment, and treatment with antiarrhythmic drugs.
Advanced heart failure: management
Authors: Tomasoni Daniela , Adamo Marianna , Metra Marco
Published: December 2023

Advanced heart failure (HF) represents the stage of HF when conventional therapies are no longer effective in controlling patients’ symptoms and stabilizing the clinical course. In the present chapter, we focus on the importance of optimizing guideline-directed medical therapy, in order to improve prognosis at this advanced stage. Firstly, intolerance to neurohormonal antagonists is often a hallmark of advanced HF and identifies patients with a very poor prognosis, who need non-conventional therapies. Secondly, patients with advanced HF often present volume overload, diuretic resistance, and kidney failure. We summarize the management of congestion in advanced HF patients, from diuretics to renal replacement therapy as a bail-out strategy. In addition, intermittent administration of intravenous inotropes may be considered as a palliative strategy to alleviate haemodynamic symptoms and improve quality of life. Omecamtiv mecarbil, an orally available myosin activator, reduced the composite endpoint of cardiovascular (CV) death or HF hospitalization in patients with heart failure and reduced ejection fraction, with a major benefit in those with severe HF, representing a new opportunity for the future.
Mechanical circulatory support
Authors: Mehra Mandeep , Gustafsson Finn
Published: December 2023

Mechanical circulatory support (MCS) has evolved dramatically over the last 50 years. Circulatory pumps are routinely being used to treat the spectrum of presentations ranging from cardiogenic shock (short-term, for acute haemodynamic restoration) advanced heart failure (long-term, to improve quality and duration of life). Short-term pumps typically are used to assist the circulation in cardiogenic shock or as a back-up in high-risk cardiac interventions. The evidence base for such application is in evolution and most application algorithms are still dependent on individual centre-based criteria. Left and right ventricular mechanical performance, lung function, and systemic perfusion are the most important clinical factors in the decision tree. For durable MCS, left ventricular assist systems (LVAS) are the mainstay for use. Implantable, continuous flow LVAS are effective and reliable in leading to improved survival and quality of life but do require monitoring for complications related to haemocompatibility (pump thrombosis, strokes and non-surgical bleeding), heart failure and infection. A considerable body of evidence from adequately powered, randomized and observational clinical studies support the use of current LVAS, particularly the HeartMate 3 pump. The primary indication for proceeding with LVAS is in advanced HF refractory to routine medical therapy, irrespective of whether the patient is a candidate for transplantation or not. In selected patients LV recovery may even allow for explant of the LVAS without recurrence of advanced HF, however this is uncommon. Patients with biventricular failure may be treated with a total artificial heart and the ongoing developments in this field are reviewed.
Dyskalaemia in heart failure
Authors: Ferreira João Pedro , Damman Kevin , Mullens Wilfried , Butler Javed
Published: December 2023

Potassium (K+) is the most abundant cation in humans and is essential for normal cellular function. Alterations in K+ regulation can lead to neuromuscular, gastrointestinal, and cardiac abnormalities. Dyskalaemia (i.e. hypokalaemia and hyperkalaemia) in heart failure (HF) is common. The cause is multifactorial, but includes comorbidities, medications, and HF by itself. Dyskalaemia has important prognostic implications, with a U-shaped relationship. This chapter presents practical and easy-to-implement strategies for patients with HF to deal with both hypo- and hyperkalaemia as well as guidance for the use of potassium-binders.
Liver and gut dysfunction
Authors: Lopatin Yuri , Savarese Gianluigi
Published: December 2023

Liver and gut dysfunction are common in heart failure (HF) patients, and their presence is associated with disease progression and worse outcomes. The complex relationships between the heart, the liver, and the gut in HF have not yet been fully established. This chapter presents the histological findings of congestive hepatopathy and acute cardiogenic liver injury, their clinical manifestations, biochemical profiles, and diagnostic and treatment modalities. We consider the mechanisms of the impact of gut microbiota on the development and progression of HF. The perspectives of targeting gut dysfunction in HF are also discussed.
Multidisciplinary approach to heart failure management
Authors: Hill Loreena , Koehler Friedrich , Jaarsma Tiny , Polovina Marija , McCreary Katherine , Coats Andrew JS
Published: December 2023

Abstract)

At least three decades has passed since the inception of the first multidisciplinary team (MDT) intervention. During this time, studies incorporating different MDT models of care delivery, using different components of varying intensity and provided by different disciplines, have tested the ability to improve patient outcomes. Nevertheless, current international guidelines, recommend all patients receive MDT programmes of care, in order to reduce the likelihood of re-hospitalization and mortality. This chapter discusses the rationale for the MDT approach and its main characteristics in care delivery. Historical aspects as well as ongoing innovations, such as tele-monitoring, will be presented. Many patients with heart failure have additional comorbidities, requiring close collaboration and clear lines of communication between specialisms, for example endocrinologists, renal physicians, and specialist palliative care professionals. A MDT approach can ensure patient-centred care appropriate to need is provided, no matter what the setting. The future of Heart Failure Association accredited Quality of Care Centres will foster this approach, demonstrating the MDT as a vital part of the armoury against HF progression.
Planteome 2024 Update: Reference Ontologies and Knowledgebase for Plant Biology
Authors: Cooper Laurel , Elser Justin , Laporte Marie-Angelique , Arnaud Elizabeth , Jaiswal Pankaj
Published: December 2023

The Planteome project (https://planteome.org/) provides a suite of reference and crop-specific ontologies and an integrated knowledgebase of plant genomics data. The plant genomics data in the Planteome has been obtained through manual and automated curation and sourced from more than 40 partner databases and resources. Here, we report on updates to the Planteome reference ontologies, namely, the Plant Ontology (PO), Trait Ontology (TO), the Plant Experimental Conditions Ontology (PECO), and integration of species/crop-specific vocabularies from our partners, the Crop Ontology (CO) into the TO ontology graph. Currently, 11 CO vocabularies are integrated into the Planteome with the addition of yam, sorghum, and potato since 2018. In addition, the size of the annotation database has increased by 34%, and the number of bioentities (genes, proteins, etc.) from 125 plant taxa has increased by 72%. We developed new tools to facilitate user requests and improvements to the CO vocabularies, and to allow fast searching and browsing of PO terms and definitions. These enhancements and future changes to automate the TO-CO mappings and knowledge discovery tools ensure that the Planteome will continue to be a valuable resource for plant biology.
Spatial regulation of DNA damage tolerance protein Rad5 interconnects genome stability maintenance and proteostasis networks
Authors: Lehmann Carl P , González-Fernández Paula , Tercero José Antonio
Published: December 2023

The Rad5/HLTF protein has a central role in the tolerance to DNA damage by mediating an error-free mode of bypassing unrepaired DNA lesions, and is therefore critical for the maintenance of genome stability. We show in this work that, following cellular stress, Rad5 is regulated by relocalization into two types of nuclear foci that coexist within the same cell, which we termed ‘S’ and ‘I’. Rad5 S-foci form in response to genotoxic stress and are associated with Rad5’s function in maintaining genome stability, whereas I-foci form in the presence of proteotoxic stress and are related to Rad5’s own proteostasis. Rad5 accumulates into S-foci at DNA damage tolerance sites by liquid-liquid phase separation, while I-foci constitute sites of chaperone-mediated sequestration of Rad5 at the intranuclear quality control compartment (INQ). Relocalization of Rad5 into each type of foci involves different pathways and recruitment mechanisms, but in both cases is driven by the evolutionarily conserved E2 ubiquitin-conjugating enzyme Rad6. This coordinated differential relocalization of Rad5 interconnects DNA damage response and proteostasis networks, highlighting the importance of studying these homeostasis mechanisms in tandem. Spatial regulation of Rad5 under cellular stress conditions thus provides a useful biological model to study cellular homeostasis as a whole.
A Multinational Case Series Describing Successful Treatment of Persistent Severe Acute Respiratory Syndrome Coronavirus 2 Infection Caused by Omicron Sublineages With Prolonged Courses of Nirmatrelvir/Ritonavir
Authors: Snell Luke B , McGreal-Bellone Aimee , Nye Clemency , Gage Sarah , Bakrania Prijay , Williams Tom G S , Aarons Emma , Botgros Alina , Douthwaite Samuel T , Mallon Patrick , Milligan Iain , Moore Catherine , O’Kelly Brendan , Underwood Jonathan , de Barra Eoghan , Nebbia Gaia
Published: December 2023

The optimum treatment for persistent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not known. Our case series, across 5 hospitals in 3 countries, describes 11 cases where persistent SARS-CoV-2 infection was successfully treated with prolonged courses (median, 10 days [range, 10–18 days]) of nirmatrelvir/ritonavir (Paxlovid). Most cases (9/11) had hematological malignancy and 10 (10/11) had received CD20-depleting therapy. The median duration of infection was 103 days (interquartile range, 85–138 days). The majority (10/11) were hospitalized, and 7 (7/11) had severe/critical disease. All survived and 9 of 11 demonstrated viral clearance, almost half (4/9) of whom received nirmatrelvir/ritonavir as monotherapy. This case series suggests that prolonged nirmatrelvir/ritonavir has a role in treating persistent infection.
Higher Sensitivity of Xpert MTB/RIF Ultra Over Tuberculosis Culture for the Diagnosis of Spinal Tuberculosis With Open or Computed Tomography–Guided Biopsies
Authors: Waters Robyn , Laubscher Maritz , Dunn Robert N , Adikary Nawaal , Coussens Anna K , Held Michael
Published: December 2023

Background

Diagnostic specimens for spinal tuberculosis (STB) are mostly collected via open surgery. Percutaneous computed tomography (CT)–guided biopsies are used in times of limited surgical availability. However, poor diagnostic accuracy of Mycobacterium tuberculosis (Mtb) culture has been reported with this method, due to limited sample volume and the paucibacillary nature of STB. We evaluated Xpert MTB/RIF Ultra on open and CT-guided biopsies as compared with the gold standard Mtb culture and histopathology.

Methods

We conducted a prospective diagnostic accuracy study of Xpert Ultra, as compared with tuberculosis culture and histopathology, in adults with signs and symptoms of STB at a tertiary academic hospital in South Africa from November 2020 to December 2021. Diagnostic testing was performed on 31 patients with available samples.

Results

Xpert Ultra had a sensitivity of 94.7% (95% CI, 75.3%–99.7%) and specificity of 100% (95% CI, 75.7%–100.0%) against a reference standard of Mtb culture and histopathology. Xpert Ultra had high diagnostic accuracy in open and CT-guided biopsy samples with sensitivity and specificity of 100% and 100% (open) and 89% and 100% (CT), respectively. Mtb culture had limited specificity for CT-guided biopsies (43%; 95% CI, 15.8%–74.9%). HIV-1 coinfection did not affect Mtb abundance measures by Xpert Ultra or culture. Xpert Ultra was also superior to culture for STB diagnosis in patients concurrently treated for pulmonary tuberculosis.

Conclusions

Xpert Ultra detected more STB cases than culture for CT-guided biopsy samples. There was also no difference in sensitivity for open biopsies, irrespective of HIV-1 status, making it an important tool for rapid diagnosis, especially during times or in locations where open surgery is not possible or concurrent pulmonary tuberculosis treatment is initiated.
KAgoshima Galactic Object survey with Nobeyama 45 m telescope by Mapping in Ammonia lines (KAGONMA): Discovery of parsec-scale CO depletion in the Canis Major star-forming region
Authors: Hirata Yushi , Murase Takeru , Nishi Junya , Shimajiri Yoshito , Omodaka Toshihiro , Nakano Makoto , Sunada Kazuyoshi , Ito Takumi , Handa Toshihiro
Published: December 2023

In observational studies of infrared dark clouds, the number of detections of CO freeze-out on to dust grains (CO depletion) at the pc scale is extremely limited, and the conditions for its occurrence are, therefore, still unknown. We report a new object where pc-scale CO depletion is expected. As part of the Kagoshima Galactic Object survey with Nobeyama 45 m telescope by Mapping in Ammonia lines (KAGONMA), we have made mapping observations of NH3 inversion transition lines towards the star-forming region associated with Canis Major OB1, including IRAS 07077−1026, IRAS 07081−1028, and PGCC G224.28−0.82. By comparing the spatial distributions of NH3 (1,1) and C18O (J = 1–0), an intensity anti-correlation was found in IRAS 07077−1026 and IRAS 07081−1028 on the ∼1 pc scale. Furthermore, we obtained a lower abundance of C18O at least in IRAS 07077−1026 than in the other parts of the star-forming region. After examining high-density gas dissipation, photodissociation, and CO depletion, we concluded that the intensity anti-correlation in IRAS 07077−1026 is due to CO depletion. On the other hand, in the vicinity of the center of PGCC G224.28−0.82, the emission line intensities of both NH3 (1,1) and C18O (J = 1–0) were strongly detected, although the gas temperature and density were similar to IRAS 07077−1026. This indicates that there are situations where C18O (J = 1–0) cannot trace dense gas on the pc scale and implies that the conditional differences in which C18O (J = 1–0) can and cannot trace dense gas are unclear.
HISTONE DEACETYLASE19 Controls Ovule Number Determination and Transmitting Tract Differentiation
Authors: Manrique Silvia , Cavalleri Alex , Guazzotti Andrea , Villarino Gonzalo H , Simonini Sara , Bombarely Aureliano , Higashiyama Tetsuya , Grossniklaus Ueli , Mizzotti Chiara , Pereira Ana Marta , Coimbra Silvia , Sankaranarayanan Subramanian , Onelli Elisabetta , Masiero Simona , Franks Robert G , Colombo Lucia
Published: December 2023

The gynoecium is critical for the reproduction of flowering plants as it contains the ovules and the tissues that foster pollen germination, growth, and guidance. These tissues, known as the reproductive tract (ReT), comprise the stigma, style, and transmitting tract (TT). The ReT and ovules originate from the carpel margin meristem (CMM) within the pistil. SHOOT MERISTEMLESS (STM) is a key transcription factor for meristem formation and maintenance. In all above-ground meristems, including the CMM, local STM downregulation is required for organ formation. However, how this downregulation is achieved in the CMM is unknown. Here, we have studied the role of HISTONE DEACETYLASE 19 (HDA19) in Arabidopsis (Arabidopsis thaliana) during ovule and ReT differentiation based on the observation that the hda19-3 mutant displays a reduced ovule number and fails to differentiate the TT properly. Fluorescence-activated cell sorting coupled with RNA-sequencing revealed that in the CMM of hda19-3 mutants, genes promoting organ development are downregulated while meristematic markers, including STM, are upregulated. HDA19 was essential to downregulate STM in the CMM, thereby allowing ovule formation and TT differentiation. STM is ectopically expressed in hda19-3 at intermediate stages of pistil development, and its downregulation by RNA interference alleviated the hda19-3 phenotype. Chromatin immunoprecipitation assays indicated that STM is a direct target of HDA19 during pistil development and that the transcription factor SEEDSTICK is also required to regulate STM via histone acetylation. Thus, we identified factors required for the downregulation of STM in the CMM, which is necessary for organogenesis and tissue differentiation.
mRNA cleavage by 21-nucleotide phasiRNAs determines temperature-sensitive male sterility in rice
Authors: Shi Chuanlin , Zou Wenli , Zhu Yiwang , Zhang Jie , Teng Chong , Wei Hua , He Huiying , He Wenchuang , Liu Xiangpei , Zhang Bin , Zhang Hong , Leng Yue , Guo Mingliang , Wang Xianmeng , Chen Wu , Zhang Zhipeng , Qian Hongge , Cui Yan , Jiang Hongshuang , Chen Ying , Fei Qili , Meyers Blake C , Liang Wanqi , Qian Qian , Shang Lianguang
Published: December 2023

Temperature-sensitive male sterility is one of the core components for hybrid rice (Oryza sativa) breeding based on the 2-line system. We previously found that knockout of ARGONAUTE 1d (AGO1d) causes temperature-sensitive male sterility in rice by influencing phased small interfering RNA (phasiRNA) biogenesis and function. However, the specific phasiRNAs and their targets underlying the temperature-sensitive male sterility in the ago1d mutant remain unknown. Here, we demonstrate that the ago1d mutant displays normal female fertility but complete male sterility at low temperature. Through a multiomics analysis of small RNA (sRNA), degradome, and transcriptome, we found that 21-nt phasiRNAs account for the greatest proportion of the 21-nt sRNA species in rice anthers and are sensitive to low temperature and markedly downregulated in the ago1d mutant. Moreover, we found that 21-nt phasiRNAs are essential for the mRNA cleavage of a set of fertility- and cold tolerance–associated genes, such as Earlier Degraded Tapetum 1 (EDT1), Tapetum Degeneration Retardation (TDR), OsPCF5, and OsTCP21, directly or indirectly determined by AGO1d-mediated gene silencing. The loss of function of 21-nt phasiRNAs can result in upregulation of their targets and causes varying degrees of defects in male fertility and grain setting. Our results highlight the essential functions of 21-nt phasiRNAs in temperature-sensitive male sterility in rice and suggest their promising application in 2-line hybrid rice breeding in the future.
Deep proteomics reveals incorporation of unedited proteins into mitochondrial protein complexes in Arabidopsis
Authors: Rugen Nils , Senkler Michael , Braun Hans-Peter
Published: December 2023

The mitochondrial proteome consists of numerous types of proteins which either are encoded and synthesized in the mitochondria, or encoded in the cell nucleus, synthesized in the cytoplasm and imported into the mitochondria. Their synthesis in the mitochondria, but not in the nucleus, relies on the editing of the primary transcripts of their genes at defined sites. Here, we present an in-depth investigation of the mitochondrial proteome of Arabidopsis (Arabidopsis thaliana) and a public online platform for the exploration of the data. For the analysis of our shotgun proteomic data, an Arabidopsis sequence database was created comprising all available protein sequences from the TAIR10 and Araport11 databases, supplemented with sequences of proteins translated from edited and nonedited transcripts of mitochondria. Amino acid sequences derived from partially edited transcripts were also added to analyze proteins encoded by the mitochondrial genome. Proteins were digested in parallel with six different endoproteases to obtain maximum proteome coverage. The resulting peptide fractions were finally analyzed using liquid chromatography coupled to ion mobility spectrometry and tandem mass spectrometry. We generated a “deep mitochondrial proteome” of 4,692 proteins. 1,339 proteins assigned to mitochondria by the SUBA5 database (https://suba.live) accounted for >80% of the total protein mass of our fractions. The coverage of proteins by identified peptides was particularly high compared to single-protease digests, allowing the exploration of differential splicing and RNA editing events at the protein level. We show that proteins translated from nonedited transcripts can be incorporated into native mitoribosomes and the ATP synthase complex. We present a portal for the use of our data, based on “proteomaps” with directly linked protein data. The portal is available at www.proteomeexplorer.de.
Distance to vaccine sites is tied to decreased COVID-19 vaccine uptake
Authors: Mazar Asaf , Jaro Daniel , Tomaino Geoff , Carmon Ziv , Wood Wendy
Published: December 2023

COVID-19 remains a leading cause of mortality in the United States, despite the widespread availability of vaccines. Conventional wisdom ties failure to vaccinate primarily to vaccine-skeptic beliefs (e.g. conspiracy theories, partisanship). Yet in this research, we find that vaccination is also hindered by travel distance to vaccine sites (a form of friction, or structural barriers). In study 1, Californians living farther from vaccine sites had lower vaccination rates, and this effect held regardless of partisanship. In study 2, Chicago zip codes saw an uptick in vaccination following vaccine site opening. These results proved robust in multiverse analyses accounting for a wide range of covariates, outcomes, and distance indicators. COVID-19 vaccination is hampered not only by vaccine hesitancy but also by structural barriers like distance. Efforts to boost vaccination could benefit from minimizing friction.
Policy sequencing can increase public support for ambitious climate policy
Authors: Montfort Simon , Fesenfeld Lukas , Stadelmann-Steffen Isabelle , Ingold Karin
Published: December 2023

Public support for ambitious climate policies and carbon prices that have direct costs for voters may depend on policy sequencing. Policy sequencing theory suggests that the strategic ordering of policies into sequences that initially create benefits can subsequently increase support for higher carbon prices. However, systematic quantitative evidence about the effects of sequencing on public support is lacking. We provide novel theoretical and empirical insights on the mechanisms through which strategic policy sequencing affects public support for climate policies. We generated these insights using geospatial data and a representative conjoint experiment with Swiss voters conducted just before the popular vote on an amendment to the Federal Act on the Reduction of Greenhouse Gas Emissions in June 2021. Our evidence shows that the perceived effectiveness of prior policy-induced benefits is related to more public support for higher carbon prices across sectors. Moreover, we find that more opportunity structures for low-emission alternatives—like higher EV charging station density—are associated with increased public support for carbon prices in the sector where the former material benefits occur. Our results also imply that positive policy perceptions of prior climate policies are related to increased support, particularly among conservative voters and those who do not regard climate change as a salient issue. Thus, strategic policy sequencing could be an effective strategy for broadening public support for ambitious climate policies.
Renal outcomes after contrast exposure in patients with diabetes who use sodium–glucose cotransporter 2 inhibitors
Authors: Chen Chih-Wei , Su Fu-You , Wang Ping-Ping , Chuang Ming-Tsang , Lin Yi-Cheng , Kao Chih-Chin , Huang Chun-Yao
Published: December 2023

Background

Contrast-induced nephropathy has become increasingly prevalent as the age and prevalence of comorbidities in the general population have increased. Most cases of contrast-induced nephropathy are reversible; however, some may progress to acute kidney disease, and subsequently, to chronic kidney disease. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are known for their renoprotective effects. However, whether the use of these inhibitors affects the risk of contrast-induced kidney injury remains unclear.

Methods

Data were collected from the Taipei Medical University Clinical Research Database. We included patients with diabetes who had contrast exposure between 2016 and 2020 because of computed tomography or coronary angiography. The primary outcome was the risk of a major adverse kidney event (MAKE), which encompassed acute kidney disease, chronic kidney disease progression, and the need for renal replacement therapy. Overlap weighting was performed to reduce the effects of potential confounders.

Results

This study included 12 421 patients, who were divided into two groups: SGLT2i users (n = 920) and nonusers (n = 11 501). The follow-up period after contrast exposure was 6 months. The risk of a MAKE was lower in SGLT2i users than in nonusers (incidence, 36.9 vs. 49.9 per 1000 person-months, respectively; P = .0011). Furthermore, the incidence of acute kidney disease or chronic kidney disease progression was significantly lower in the SGLT2i users than in nonusers. However, no significant between-group difference was noted in the incidence of other MAKEs.

Conclusions

SGLT2i may be safely used in diabetic patients needing contrast exposure. The risk of a MAKE may be lower in SGLT2i users than in nonusers.
Hip dysplasia as risk factor for clinically relevant and radiographic hip osteoarthritis: 10-year results from the CHECK cohort
Authors: Vinge Rebecka , Riedstra Noortje , Tiderius Carl Johan , Bierma-Zeinstra Sita , Agricola Rintje , Runhaar Jos
Published: December 2023

Objectives

To investigate hip dysplasia as a risk factor for clinically relevant and incident radiographic hip OA.

Methods

From a prospective cohort (CHECK) of 1002 middle-aged, new consulters for hip and/or knee pain, 468 hips (251 individuals) were selected based on hip pain, available lateral center edge angle (LCEA) and absence of definite radiographic hip OA (Kellgren and Lawrence [KL] grade <2) at baseline, as well as available follow-up measures. Clinically relevant hip OA was defined by an expert diagnosis based on clinical and radiographic data obtained between years 5 and 10 from baseline. Incident radiographic hip OA was defined by KL grade ≥2 or a total hip replacement at the 10-year follow-up. Associations between hip dysplasia (LCEA ≤20°) and outcomes were expressed as an odds ratio (OR) adjusted for age, sex and BMI.

Results

At baseline, participants had a mean age of 55.5 (5.4) years, 88% were female and, on hip level, the prevalence of hip dysplasia was 3.6% (n = 17). After 10 years, hip dysplasia was associated with an increased risk for clinically relevant hip OA (OR 2.80; 95% CI: 1.15, 6.79), but not for incident radiographic hip OA (OR 0.78; 95% CI: 0.26, 2.30).

Conclusion

In the long term, baseline hip dysplasia was associated with an increased risk for clinically relevant hip OA, but not for incident radiographic hip OA. With this in mind, we suggest that future research investigating the link between hip dysplasia and OA strives to include a definition for OA that is clinically relevant.
Investigation of the protective activity of baicalein on the lungs via regulation of various cellular responses in rats exposed to experimental sepsis
Authors: Dicle Yalcin , Aydin Elif , Seker Ugur
Published: December 2023

Backgrounds

In the present study, a cecal ligation and puncture (CLP)-induced experimental sepsis rat model was used to explore the effects of baicalein on inflammatory cytokine levels and oxidative stress as well as the possible regulatory role of nuclear factor-kappa B (NF-κB).

Methods

For that purpose, 42 Wistar albino rats were equally divided into control, sham, sepsis, B50 + S, B100 + S, S + B50, and S + B100 groups. The B50 + S and B100 + S groups received baicalein before the induction of sepsis, while the S + B50 and S + B100 groups received baicalein afterwards. Experimental sepsis in related groups is generated through ligation of cecum and a puncture in cecal wall. Serum samples were used for tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) analyses, and tissue Malondialdehyde (MDA), Superoxide dismutase (SOD), Glutathione (GSH), IL-6, and NF-κB levels were measured.

Results

Compared to the control group, there were significantly increases in the serum TNF-α, IL-6, tissue MDA, and NF-κB levels and decreases in the tissue SOD and GSH levels in the septic group (P < 0.05). Compared to the septic group, inflammation and oxidative stress were reduced in the baicalein-treated groups. Although all of the pre- and post-treatment protocols alleviated inflammation and oxidative stress to varying degrees, pre-treatment with 100 mg/kg was the most successful.

Conclusions

Findings of this study indicated that baicalein has the potential to reduce sepsis-related oxidative stress and inflammation in the lungs and that pathological outcomes could be regulated via NF-κB transcription factor activity.
Selective elimination of younger erythrocytes in blood circulation and associated molecular changes in benzo (a) pyrene induced mouse model of lung cancer
Authors: Chauhan Pooja , Bhardwaj Nitin , Rajaura Sumit , Gupta Neelujain
Published: December 2023

Background

Anemia is a common feature in cancer patients. The present research was conducted to explore the mechanisms of induction of anemia in a mouse model of lung cancer.

Methods

The lung cancer was induced by treating orally with BaP (50 mg/kg body weight, twice a week for four weeks). The erythrocyte kinetics were studied using a double in vivo biotinylation (DIB) technique. ROS production and apoptosis analysis were done by staining with the CMH2DCFDA stain and anti-mouse Annexin V antibody, followed by flow cytometry. The expression of antioxidant, apoptotic, anti-apoptotic and inflammatory genes was analyzed by quantitative PCR (RT-qPCR).

Results

BaP-induced tumour reduced body weight and induced persistent haemolytic anaemia. The kinetics data suggest that, though reticulocyte production was enhanced, the proportion of young erythrocytes did not increase in the same proportion. The young aged erythrocytes were selectively eliminated from blood circulation, but intermediate and old aged erythrocytes persisted for a longer duration. The tumour progression leads to a significant increase in ROS production and apoptosis in the erythrocytes. The molecular data suggests that the expression levels of antioxidants (SOD1, catalase, and GPX1) and erythropoietin (Epo) were significantly increased. The anti-inflammatory genes Interleukin-6 (IL-6), Interleukin-10 (IL-10) were significantly decreased.Apoptotic genes Bax, and caspase 3 were significantly decreased while Bcl 2 was significantly increased in the blood of tumour-bearing mice.

Conclusions

The overall data suggest that erythrocyte turnover is severely modulated with the progression of tumor. The apoptosis, ROS levels, antioxidant, anti-apoptotic, and Epo gene expressions were increased, but proapoptotic and anti-inflammatory gene expression were suppressed.
Vein hierarchy mediates the 2D relationship between leaf size and drought tolerance across subtropical forest tree species
Authors: He Pengcheng , Ye Qing , Hua Lei , Zhu Shidan , Liu Hui , Ning Qiurui , Hu Qin , Li Qiang , Qin Xinsheng
Published: December 2023

Previous studies have observed a 2D relationship (i.e. decoupled correlation) between leaf size (LS) and leaf economics as well as a tight correlation between leaf economics and drought tolerance. However, the underlying mechanism maintaining the relationship between LS and drought tolerance remains largely unknown. Here, we measured LS, water potential at 50% loss of hydraulic conductance, hydraulic safety margin and different orders of vein traits across 28 tree species in a subtropical forest in Southern China. We found that LS and drought tolerance were in two independent dimensions (R2 = 0.00, P > 0.05). Primary and secondary vein traits (i.e. vein diameter and density) explained the variation of LS, with R2 ranging from 0.37 to 0.70 (all Ps < 0.01), while minor vein traits accounted for the variation of leaf drought tolerance, with R2 ranging from 0.30 to 0.43 (all Ps < 0.01). Our results provide insight into the 2D relationship between LS and drought tolerance and highlight the importance of vein hierarchy in plant leaf functioning.
Lived Experiences of Hospitalized Patients With Coronavirus Disease at Tibebe Ghion Comprehensive Specialized Hospital, Bahir Dar, North West Ethiopia, A Phenomenological Study
Authors: Yihun Abebe , Ambaw Fentie , Yigzaw Zeamanuel Anteneh
Published: December 2023

Background

Hospitalized patients with coronavirus disease experienced different challenges at treatment centers; however, there is no evidence in Ethiopia on patients’ experiences at COVID-19 treatment centers. Therefore, the aim of this study was to explore the lived experiences of hospitalized patients with coronavirus disease at Tibebe Ghion Comprehensive Specialized Hospital, Bahir Dar, Ethiopia, in 2021.

Methods

A qualitative phenomenological study design with a heterogeneous purposive sampling technique was used. Fifteen hospitalized patients participated from March 15 to April 1, 2021. The information was gathered through an in-depth interview technique with an audio recorder. Thematic analysis was used to analyze the data using Atlas Ti version 7.09 software.

Result

Hospitalized patients with the coronavirus disease had a variety of experiences with various phenomena. Lived experiences were identified with 2 major themes: the psychoemotional theme has 2 subthemes (psychological and emotional experience), and the context-related experience has 5 subthemes (socioeconomic, patient–health care provider, health facility–related, exposure prevention, and governmental-related factors).

Conclusion

The study identified 2 major themes: 7 subthemes and 10 categories. Study participants faced different challenges, mainly hopelessness, anxiety, a lack of caregiver, isolation, a shortage of medications, poor communication between the patient and health care provider, and a lack of health insurance. Therefore, we recommend giving psychological support, improving communication between patients and health care professionals, and ensuring health insurance.