bluuebunny/crossref_metadata_2025_split huggingface dataset:
Con7 is a key transcription regulator for conidiogenesis in the plant pathogenic fungus
Fusarium graminearum
Authors: Shin Soobin , Park Jiyeun , Yang Lin , Kim Hun , Choi Gyung Ja , Lee Yin-Won , Kim Jung-Eun , Son Hokyoung 
Published: April 2024

ABSTRACT

The mycelium of the plant pathogenic fungus
Fusarium graminearum
exhibits distinct structures for vegetative growth, asexual sporulation, sexual development, virulence, and chlamydospore formation. These structures are vital for the survival and pathogenicity of the fungus, necessitating precise regulation based on environmental cues. Initially identified in
Magnaporthe oryzae
, the transcription factor Con7p regulates conidiation and infection-related morphogenesis, but not vegetative growth. We characterized the Con7p ortholog
Fg
Con7, and deletion of
FgCON7
resulted in severe defects in conidium production, virulence, sexual development, and vegetative growth. The mycelia of the deletion mutant transformed into chlamydospore-like structures with high chitin level accumulation. Notably, boosting
FgABAA
expression partially alleviated developmental issues in the
FgCON7
deletion mutant. Chromatin immunoprecipitation (ChIP)–quantitative PCR (qPCR) analysis confirmed a direct genetic link between
FgABAA
and
FgCON7
. Furthermore, the chitin synthase gene
Fg6550
(FGSG_06550) showed significant upregulation in the
FgCON7
deletion mutant, and altering
FgCON7
expression affected cell wall integrity. Further research will focus on understanding the behavior of the chitin synthase gene and its regulation by
Fg
Con7 in
F. graminearum
. This study contributes significantly to our understanding of the genetic pathways that regulate hyphal differentiation and conidiation in this plant pathogenic fungus.

IMPORTANCE

The ascomycete fungus
Fusarium graminearum
is the primary cause of head blight disease in wheat and barley, as well as ear and stalk rot in maize. Given the importance of conidia and ascospores in the disease cycle of
F. graminearum
, precise spatiotemporal regulation of these biological processes is crucial. In this study, we characterized the
Magnaporthe oryzae
Con7p ortholog and discovered that
Fg
Con7 significantly influences various crucial aspects of fungal development and pathogenicity. Notably, overexpression of
FgABAA
partially restored developmental defects in the
FgCON7
deletion mutant. ChIP-qPCR analysis confirmed a direct genetic link between
FgABAA
and
FgCON7
. Furthermore, our research revealed a clear correlation between
Fg
Con7 and chitin accumulation and the expression of chitin synthase genes. These findings offer valuable insights into the genetic mechanisms regulating conidiation and the significance of mycelial differentiation in this plant pathogenic fungus.
Proteomic and transcriptomic analysis of selenium utilization in
Methanococcus maripaludis
Authors: Funkner Katrina , Poehlein Anja , Jehmlich Nico , Egelkamp Richard , Daniel Rolf , von Bergen Martin , Rother Michael 
Published: April 2024

ABSTRACT

Methanococcus maripaludis
utilizes selenocysteine- (Sec-) containing proteins (selenoproteins), mostly active in the organism’s primary energy metabolism, methanogenesis. During selenium depletion,
M. maripaludis
employs a set of enzymes containing cysteine (Cys) instead of Sec. The genes coding for these Sec-/Cys-containing isoforms were the only genes known of which expression is influenced by the selenium status of the cell. Using proteomics and transcriptomics, approx. 7% and 12%, respectively, of all genes/proteins were found differentially expressed/synthesized in response to the selenium supply. Some of the genes identified involve methanogenesis, nitrogenase functions, and putative transporters. An increase of transcript abundance for putative transporters under selenium depletion indicated the organism’s effort to tap into alternative sources of selenium.
M. maripaludis
is known to utilize selenite and dimethylselenide as selenium sources. To expand this list, a selenium-responsive reporter strain was assessed with nine other, environmentally relevant selenium species. While the effect of some was very similar to that of selenite, others were effectively utilized at lower concentrations. Conversely, selenate and seleno
-
amino acids were only utilized at unphysiologically high concentrations and two compounds were not utilized at all. To address the role of the selenium-regulated putative transporters,
M. maripaludis
mutant strains lacking one or two of the putative transporters were tested for the capability to utilize the different selenium species. Of the five putative transporters analyzed by loss-of-function mutagenesis, none appeared to be absolutely required for utilizing any of the selenium species tested, indicating they have redundant and/or overlapping specificities or are not dedicated selenium transporters.

IMPORTANCE

While selenium metabolism in microorganisms has been studied intensively in the past, global gene expression approaches have not been employed so far. Furthermore, the use of different selenium sources, widely environmentally interconvertible via biotic and abiotic processes, was also not extensively studied before.
Methanococcus maripaludis
JJ is ideally suited for such analyses, thanks to its known selenium usage and available genetic tools. Thus, an overall view on the selenium regulon of
M. maripaludis
was obtained via transcriptomic and proteomic analyses, which inspired further experimentation. This led to demonstrating the use of selenium sources
M. maripaludis
was previously not known to employ. Also, an attempt—although so far unsuccessful—was made to pinpoint potential selenium transporter genes, in order to deepen our understanding of trace element utilization in this important model organism.
Caregiving experiences of family caregivers of patients with schizophrenia in a community: a qualitative study in Beijing
Authors: Pan Zhaolu , Li Ting , Jin Guanghui , Lu Xiaoqin 
Published: April 2024

ObjectivesThis study aims to understand the caregiving experiences of family caregivers of people with schizophrenia in a community.DesignA qualitative study based on phenomenological analysis was conducted through in-depth interviews.SettingThis study was carried out from May to June 2023 in two community health service centres in urban Beijing, China.ParticipantsWe selected 16 family caregivers for interviews using purposive sampling method.ResultsFour themes and 10 subthemes were identified: (1) psychosocial distress of family caregivers (feeling unprepared and helpless at the beginning, confronting negative emotions in long-term care and straying away from social life); (2) adverse impacts on the whole family (poor cooperation within the family, insufficient family involvement in professional care); (3) coping with family caregiving (accepting the reality of the patients’ illness, struggling with family life balance and having realistic expectations); (4) concerns about future care (daily living support, physical health management).ConclusionFamily caregivers experienced psychosocial distress and family stress in the process of caregiving. They had to cope with caregiving stress and were concerned about the long-term care of people with schizophrenia. These findings provide implications for intervention programmes to strengthen social support, family involvement, and active coping for caregivers and develop long-term care mechanisms for people with schizophrenia.
Combination of diuretics for acute heart failure: a protocol for a systematic review of randomised clinical trials with network meta-analysis and trial sequential analysis
Authors: Nahiz Nihal , Lukoschewitz Jasmin Dam , Seven Ekim , Olsen El Caidi Nora , Hove Jens Dahlgaard , Jakobsen Janus , Grand Johannes 
Published: April 2024

IntroductionAcute heart failure (AHF) is a critical, costly condition with high mortality rates, affecting millions annually. Despite advances in cardiovascular care, AHF treatment lacks robust evidence. AHF commonly manifests with sudden heart failure symptoms such as pulmonary congestion, and the pathophysiology involves fluid overload. Initial treatment is based on intravenous diuretics typically, but the optimal combination of drugs remains uncertain.Methods and analysisWe will systematically review randomised controlled trials enrolling patients with AHF and volume overload undergoing in-hospital diuretic treatment. We aim to investigate any diuretic intervention. Our search strategy includes the following databases: Embase, Medline, Latin American and Caribbean Health Sciences Literature, Web of Science and the Cochrane Central Register of Controlled Trials. The primary outcome is all-cause mortality. Secondary outcomes are serious adverse events, hospital readmission and kidney failure. Study results reported at the most extended follow-up will be used for all outcomes. If appropriate, we will conduct meta-analysis, trial sequential analysis and network meta-analysis.Ethics and disseminationNo ethics approval is required for this study. The results will be published in a peer-reviewed journal in this field.PROSPERO registration numberCRD42023463979.
Solving poverty or tackling healthcare inequalities? Qualitative study exploring local interpretations of national policy on health inequalities under new NHS reforms in England
Authors: Alderwick Hugh , Hutchings Andrew , Mays Nicholas 
Published: April 2024

ObjectivesMajor reforms to the organisation of the National Health Service (NHS) in England established 42 integrated care systems (ICSs) to plan and coordinate local services. The changes are based on the idea that cross-sector collaboration is needed to improve health and reduce health inequalities—and similar policy changes are happening elsewhere in the UK and internationally. We explored local interpretations of national policy objectives on reducing health inequalities among senior leaders working in three ICSs.DesignWe carried out qualitative research based on semistructured interviews with NHS, public health, social care and other leaders in three ICSs in England.Setting and participantsWe selected three ICSs with varied characteristics all experiencing high levels of socioeconomic deprivation. We conducted 32 in-depth interviews with senior leaders of NHS, local government and other organisations involved in the ICS’s work on health inequalities. Our interviewees comprised 17 leaders from NHS organisations and 15 leaders from other sectors.ResultsLocal interpretations of national policy objectives on health inequalities varied, and local leaders had contrasting—sometimes conflicting—perceptions of the boundaries of ICS action on reducing health inequalities. Translating national objectives into local priorities was often a challenge, and clarity from national policy-makers was frequently perceived as limited or lacking. Across the three ICSs, local leaders worried that objectives on tackling health inequalities were being crowded out by other short-term policy priorities, such as reducing pressures on NHS hospitals. The behaviour of national policy-makers appeared to undermine their stated priorities to reduce health inequalities.ConclusionsVaried and vague interpretations of NHS policy on health inequalities are not new, but lack of clarity among local health leaders brings major risks—including interventions being poorly targeted or inadvertently widening inequalities. Greater conceptual clarity is likely needed to guide ICS action in future.
Impact of pandemic-related movement restriction on public access defibrillation in Japan: a retrospective cohort study
Authors: Omatsu Kentaro , Yamashita Akira , Inaba Hideo 
Published: April 2024

ObjectivesTo analyse monthly changes in public access defibrillation (PAD) incidence and outcomes of out-of-hospital cardiac arrest (OHCA) during the 2020–2021 COVID-19 pandemic compared with those during the 2016–2019 prepandemic period with consideration of pandemic-related movement restriction.DesignRetrospective cohort study.SettingAn extended database was created by combining and reconciling the nationwide Utstein-style OHCA and the emergency medical service (EMS) transportation databases in Japan.ParticipantsWe analysed 226 182 EMS-witnessed, non-newborn and out-of-home OHCA cases in Japan.Primary and secondary outcome measuresThe primary outcomes were the PAD incidence and neurologically favourable 1-month survival rate. The secondary outcomes were bystander cardiopulmonary resuscitation (CPR) provision and dispatcher-assisted CPR attempts.ResultsThe proportion of out-of-home OHCA cases slightly decreased during the pandemic (from 33.7% to 31.9%). Although the pandemic was associated with a decreased PAD incidence, 2-year trend analyses by an interaction test showed that the PAD incidence was lower during the first nationwide declaration of a state of emergency (p<0.001) and in the pandemic’s second year (p<0.01). Regardless of location, delays in basic life support (BLS) actions and EMS contact with patients were more common and the rate of PAD-induced return of spontaneous circulation was lower during the pandemic. PAD incidence reduction was significant only in locations with a recommendation of automated external defibrillator placement (p<0.001). In other locations, a pronounced delay in BLS was found during the pandemic. The neurologically favourable survival rate was reduced in parallel with the reduced PAD incidence during the pandemic (r=0.612, p=0.002).ConclusionsProlonged and repeated movement restrictions during the COVID-19 pandemic worsened the OHCA outcomes concurrently with disturbed BLS actions, including the reduced PAD incidence in out-of-home settings. Maintaining BLS training, re-arranging automated external defibrillator placement and establishing a local alert system for recruiting well-trained citizens to the scene are essential.
Role of patient characteristics in adherence to first-line treatment guidelines in breast, lung and prostate cancer: insights from the Nordic healthcare system
Authors: Sandström Niclas , Leppälä Emilia , Jekunen Antti , Johansson Mikael , Andersén Heidi 
Published: April 2024

ObjectivesThis study investigates the influence of socioeconomic status, health literacy, and numeracy on treatment decisions and the occurrence of adverse events in patients with breast, lung, and prostate cancer within a Nordic healthcare setting.DesignA follow-up to a cross-sectional, mixed-methods, single-centre study.SettingA Nordic, tertiary cancer clinic.ParticipantsA total of 244 participants with breast, lung and prostate cancer were initially identified, of which 138 first-line treatment participants were eligible for this study. First-line treatment participants (n=138) surpassed the expected cases (n=108).InterventionsNot applicable as this was an observational study.Primary and secondary outcome measuresThe study’s primary endpoint was the rate of guideline adherence. The secondary endpoint involved assessing treatment toxicity in the form of adverse events.ResultsGuideline-adherent treatment was observed in 114 (82.6%) cases. First-line treatment selection appeared uninfluenced by participants’ education, occupation, income or self-reported health literacy. A minority (3.6%) experienced difficulties following treatment instructions, primarily with oral cancer medications.ConclusionsThe findings indicated lesser cancer health disparities regarding guideline adherence and treatment toxicity within the Nordic healthcare framework. A causal connection may not be established; however, the findings contribute to discourse on equitable cancer health provision.
'An eye for an eye' therapeutic strategy for cavernous sinus dural arteriovenous fistula: a single-center experience
Authors: Xu Liang , Zheng Jingwei , Ling Chenhan , Chen Xianyi , Fang Bing , Qian Cong , Xu Jing , Yu Jun 
Published: April 2024

BackgroundIn cavernous sinus dural arteriovenous fistulas (CS-DAVF), ophthalmological symptoms are usually the main clinical presentation, caused by abnormal drainage of the superior ophthalmic vein (SOV). Early opacification of the SOV during cerebral angiography inevitably signifies the fistula’s shunt point at the confluence of the SOV and CS. We aimed to leverage this anatomical feature to achieve precise embolization, thereby enhancing the embolization success rate and preventing CS-related symptoms and complications resulting from overpacking.MethodsThis single-center, case series study was conducted between May 2017 and September 2023, and included the largest sample of CS-DAVF patients treated via the transfemoral vein-SOV approach. We retrospectively reviewed the data of 32 CS-DAVF patients with inferior petrosal sinus (IPS) occlusion.ResultsThe study demonstrated an excellent immediate postoperative complete embolization rate (31/32, 97%). Only three patients (3/32, 9%) developed temporary endovascular treatment-related complications. The average operation time was 131.6±61.6 min, with an average of 1.2±1.1 coils and 1.8±1.2 mL Onyx glue used per patient. CS-DAVF-associated ophthalmological symptoms resolved in all patients. We also identified a rare anatomical variation, where 77% of the patients had a facial vein draining into the external jugular vein.ConclusionsTransfemoral vein-SOV embolization should be considered a crucial alternative approach in CS-DAVF patients with occluded IPS and predominantly SOV drainage. This approach showed an excellent immediate postoperative complete embolization rate and satisfactory long-term outcomes along with clinical safety. We therefore strongly advocate for this ‘an eye for an eye’ treatment strategy.
Particle detectors based on glass: toward the Multigap Resistive Plate Chambers
Authors: De Gruttola Daniele 
Published: April 2024

AbstractGlass found a large application in particle physics, and it can be considered as a key turning point in the technology of gaseous detectors, in particular in the development that lead from parallel plate chambers to resistive plate chambers and multigap resistive plate chambers (MRPCs). One of the crucial parameters to take into account when building such a detector is the resistivity of the material used to collect the signal produced by a particle crossing the detector. In this paper a (not comprehensive) history of the gaseous detectors will be presented, in order to describe the use of glass in the MRPC, including a few examples of experiments making use of this technology.
2-Distance coloring of planar graphs with maximum degree 5
Authors: Chen Ming , Jiang Lu , Wang Min , Zhou Shan 
Published: April 2024

A 2-distance coloring of a graph is a proper [Formula: see text]-coloring in which any two vertices with distance at most two get different colors. The 2-distance number is the smallest number [Formula: see text] such that [Formula: see text] has a 2-distance [Formula: see text]-coloring, denoted as [Formula: see text]. In 1977, Wegner conjectured that for each planar graph [Formula: see text] with maximum degree [Formula: see text], [Formula: see text] if [Formula: see text], [Formula: see text] if [Formula: see text], and [Formula: see text] if [Formula: see text]. In 2001, Thomassen supported the conjecture by proving the case [Formula: see text]. The conjecture is still open even for [Formula: see text]. In this paper, we show that [Formula: see text] for the case [Formula: see text] which improves the upper bound 18 recently obtained by Hou et al.
Encompassing geoheritage's multiple voices, multiple venues and multi-disciplinarity
Authors: Clary Renee M. , Pyle Eric J. , Andrews William 
Published: April 2024

Abstract
Geoheritage is recognized globally as a critical concept that celebrates unique geological sites, their history and scientific value, educational potential and geotourism opportunities. Importantly, geoheritage encompasses a wide range of geodiversity, which exists in a variety of scales – from local outcrops to internationally recognized UNESCO sites – and within a continuum of scientific value, historical merit, indigenous meaning, educational potential and geotourism possibilities. We celebrate a selected example of geoheritage sites across the world that have been noticed, recognized and utilized. The breadth and geodiversity of some of these sites indicate we should broaden our geoheritage definition and include historical collections and largely inaccessible sites. Notably, all geoscientists and educators must remain diligent to ensure the sustainability of these sites so that future generations can enjoy our geological and cultural heritage.
Targeting SMAD3 Improves Response to Oxaliplatin in Esophageal Adenocarcinoma Models by Impeding DNA Repair
Authors: Ballout Farah , Lu Heng , Bhat Nadeem , Chen Lei , Peng Dunfa , Chen Zheng , Chen Steven , Sun Xiaodian , Giordano Silvia , Corso Simona , Zaika Alexander , McDonald Oliver , Livingstone Alan S. , El-Rifai Wael 
Published: April 2024

Abstract

Purpose:
TGFβ signaling is implicated in the progression of most cancers, including esophageal adenocarcinoma (EAC). Emerging evidence indicates that TGFβ signaling is a key factor in the development of resistance toward cancer therapy.

Experimental Design:
In this study, we developed patient-derived organoids and patient-derived xenograft models of EAC and performed bioinformatics analysis combined with functional genetics to investigate the role of SMAD family member 3 (SMAD3) in EAC resistance to oxaliplatin.

Results:
Chemotherapy nonresponding patients showed enrichment of SMAD3 gene expression when compared with responders. In a randomized patient-derived xenograft experiment, SMAD3 inhibition in combination with oxaliplatin effectively diminished tumor burden by impeding DNA repair. SMAD3 interacted directly with protein phosphatase 2A (PP2A), a key regulator of the DNA damage repair protein ataxia telangiectasia mutated (ATM). SMAD3 inhibition diminished ATM phosphorylation by enhancing the binding of PP2A to ATM, causing excessive levels of DNA damage.

Conclusions:
Our results identify SMAD3 as a promising therapeutic target for future combination strategies for the treatment of patients with EAC.
Metabolic Signaling in Cancer Metastasis
Authors: Krieg Sarah , Fernandes Sara Isabel , Kolliopoulos Constantinos , Liu Ming , Fendt Sarah-Maria 
Published: April 2024

Abstract

Metastases, which are the leading cause of death in patients with cancer, have metabolic vulnerabilities. Alterations in metabolism fuel the energy and biosynthetic needs of metastases but are also needed to activate cell state switches in cells leading to invasion, migration, colonization, and outgrowth in distant organs. Specifically, metabolites can activate protein kinases as well as receptors and they are crucial substrates for posttranslational modifications on histone and nonhistone proteins. Moreover, metabolic enzymes can have moonlighting functions by acting catalytically, mainly as protein kinases, or noncatalytically through protein–protein interactions. Here, we summarize the current knowledge on metabolic signaling in cancer metastasis.

Significance:
Effective drugs for the prevention and treatment of metastases will have an immediate impact on patient survival. To overcome the current lack of such drugs, a better understanding of the molecular processes that are an Achilles heel in metastasizing cancer cells is needed. One emerging opportunity is the metabolic changes cancer cells need to undergo to successfully metastasize and grow in distant organs. Mechanistically, these metabolic changes not only fulfill energy and biomass demands, which are often in common between cancer and normal but fast proliferating cells, but also metabolic signaling which enables the cell state changes that are particularly important for the metastasizing cancer cells.