bluuebunny/crossref_metadata_2025_split huggingface dataset:
How Streptococcus suis escapes antibiotic treatments
Authors: Uruén Cristina , García Carla , Fraile Lorenzo , Tommassen Jan , Arenas Jesús 
Published: November 2022

AbstractStreptococcus suisis a zoonotic agent that causes sepsis and meningitis in pigs and humans.S. suisinfections are responsible for large economic losses in pig production. The lack of effective vaccines to prevent the disease has promoted the extensive use of antibiotics worldwide. This has been followed by the emergence of resistance against different classes of antibiotics. The rates of resistance to tetracyclines, lincosamides, and macrolides are extremely high, and resistance has spread worldwide. The genetic origin ofS. suisresistance is multiple and includes the production of target-modifying and antibiotic-inactivating enzymes and mutations in antibiotic targets.S. suisgenomes contain traits of horizontal gene transfer. Many mobile genetic elements carry a variety of genes that confer resistance to antibiotics as well as genes for autonomous DNA transfer and, thus,S. suiscan rapidly acquire multiresistance. In addition,S. suisforms microcolonies on host tissues, which are associations of microorganisms that generate tolerance to antibiotics through a variety of mechanisms and favor the exchange of genetic material. Thus, alternatives to currently used antibiotics are highly demanded. A deep understanding of the mechanisms by whichS. suisbecomes resistant or tolerant to antibiotics may help to develop novel molecules or combinations of antimicrobials to fight these infections. Meanwhile, phage therapy and vaccination are promising alternative strategies, which could alleviate disease pressure and, thereby, antibiotic use.
FABP4-mediated lipid droplet formation in Streptococcus uberis-infected macrophages supports host defence
Authors: Wan Zhixin , Fu Shaodong , Wang Zhenglei , Xu Yuanyuan , Zhou Yuanyuan , Lin Xinguang , Lan Riguo , Han Xiangan , Luo Zhenhua , Miao Jinfeng 
Published: November 2022

AbstractFoamy macrophages containing prominent cytoplasmic lipid droplets (LDs) are found in a variety of infectious diseases. However, their role in Streptococcus uberis-induced mastitis is unknown. Herein, we report that S. uberis infection enhances the fatty acid synthesis pathway in macrophages, resulting in a sharp increase in LD levels, accompanied by a significantly enhanced inflammatory response. This process is mediated by the involvement of fatty acid binding protein 4 (FABP4), a subtype of the fatty acid-binding protein family that plays critical roles in metabolism and inflammation. In addition, FABP4 siRNA inhibitor cell models showed that the deposition of LDs decreased, and the mRNA expression of Tnf, Il1b and Il6 was significantly downregulated after gene silencing. As a result, the bacterial load in macrophages increased. Taken together, these data demonstrate that macrophage LD formation is a host-driven component of the immune response to S. uberis. FABP4 contributes to promoting inflammation via LDs, which should be considered a new target for drug development to treat infections.
Identification of protein profile in metacyclic and amastigote-like stages of Leishmania tropica: a proteomic approach
Authors: Ashrafmansouri Marzieh , Amiri-Dashatan Nasrin , Ahmadi Nayebali 
Published: November 2022

AbstractLeishmaniasis is a tropical disease that leads to various clinical phenotypes. This study aimed to investigate protein expression changes in metacyclic and amastigote-like stages of L. tropica isolated from Iranian cutaneous leishmaniasis patients. Isolated samples were cultured and species type identified using PCR–RFLP technique. The promastigotes were grown in RPMI1640 media and differentiated to metacyclic and amastigote-like forms, followed by the extracted proteins of both successive stages carried out for proteomics and bioinformatics analysis. Using SWATH-MS quantitative proteomics technique, a total 176 and 155 distinct proteins were identified in metacyclic and axenic amastigote stages, respectively. Of these, 65 proteins were altered significantly (p-value < 0.05 and fold change ≥ 2) between studied stages. Several gene ontology (GO) categories were enriched for biological process during conversion of metacyclic promastigotes into amastigote-like, which “metabolic process” (GO: 0044281, P-Value: 6.52e-5), and “translation” (GO: 0006412, p-value: 5.01e–14) were disclosed as the top category in up and down-regulated proteins, respectively. Also, the KEGG pathway analysis indicated “metabolic pathways” and “ribosome” term as the most important pathways in up and down-regulated proteins, respectively. According to protein interaction network analysis, enolase (ENOL) has been detected as main hub proteins during differentiation, followed by Putative NADH-dependent fumarate reductase (LmjF.35.1180) and 40S ribosomal protein S2 (LmjF.32.0450). Overall, protein changes possibly play important roles in L. tropica biology. Anabolic pathways were down-regulated, whereas catabolic pathways were up-regulated during L. tropica differentiation. These protein expression changes could provide parasite survival in host macrophages, and could use as novel potential drug and vaccine targets for leishmaniasis.
Graphical Abstract
mTORC1-c-Myc pathway rewires methionine metabolism for HCC progression through suppressing SIRT4 mediated ADP ribosylation of MAT2A
Authors: Zhao Liang , Su Huizhao , Liu Xiaomeng , Wang Hongquan , Feng Yukuan , Wang Yan , Chen Haiqiang , Dai Luo , Lai Shihui , Xu Siqi , Li Chong , Hao Jihui , Tang Bo 
Published: November 2022

Abstract
Background
Exploiting cancer metabolism during nutrient availability holds immense potential for the clinical and therapeutic benefits of hepatocellular carcinoma (HCC) patients. Dietary methionine is a metabolic dependence of cancer development, but how the signal transduction integrates methionine status to achieve the physiological demand of cancer cells remains unknown.

Methods
Low or high levels of dietary methionine was fed to mouse models with patient-derived xenograft or diethyl-nitrosamine induced liver cancer. RNA sequence and metabolomics were performed to reveal the profound effect of methionine restriction on gene expression and metabolite changes. Immunostaining, sphere formation assays, in vivo tumourigenicity, migration and self-renewal ability were conducted to demonstrate the efficacy of methionine restriction and sorafenib.

Results
We discovered that mTORC1-c-Myc-SIRT4 axis was abnormally regulated in a methionine-dependent manner and affected the HCC progression. c-Myc rewires methionine metabolism through TRIM32 mediated degradation of SIRT4, which regulates MAT2A activity by ADP-ribosylation on amino acid residue glutamic acid 111. MAT2A is a key enzyme to generate S-adenosylmethionine (SAM). Loss of SIRT4 activates MAT2A, thereby increasing SAM level and dynamically regulating gene expression, which triggers the high proliferation rate of tumour cells. SIRT4 exerts its tumour suppressive function with targeted therapy (sorafenib) by affecting methionine, redox and nucleotide metabolism.

Conclusions
These findings establish a novel characterization of the signaling transduction and the metabolic consequences of dietary methionine restriction in malignant liver tissue of mice. mTORC1, c-Myc, SIRT4 and ADP ribosylation site of MAT2A are promising clinical and therapeutic targets for the HCC treatment.
Right ventricular free wall longitudinal strain is independently associated with mortality in mechanically ventilated patients with COVID-19
Authors: McErlane James , McCall Philip , Willder Jennifer , Berry Colin , Shelley Ben ,   the COVID-RV investigators, Reece A. , Kitchen C. , Gillies M. , Dabek V. , Irvine V. , MacBrayne J. , Sim K. , Scott T. , Trumper E. , Savage F. , Allan A. , Falconer J. , Coutts A. , McDonald A. , Rutherford J. , Christie D. , Jardine C. , Puxty A. , Hughes M. , Cathcart S. , Sim M. , Docking B. , Thornton M. , Greatorex B. , Rae J. , Barr C. , Bradley C. , Barrett F. , Campbell R. , Clarke N. , Mascarenhas M. , Matheson J. , McDonald D. , O Hara M. , O keeffe L. , Gemmell L. , Price R. , McHendry M. , McLaughlan D. , Herman C. , Elliot H. , Meehan S. , Allan J. , Finn D. , Brannan G. , Wood S. , Watson T. , Ross K. , Tatarkowska N. , Boyle R. , Lee E. , Strachan D. , Morrison A. , Lucie P. , Lochrin C. , Clements S. , Vigni D. , Stanley B. , Messow C. M. 
Published: November 2022

Abstract
Background
Right ventricular (RV) dysfunction has been commonly reported in patients with Coronavirus disease 2019 (COVID-19), and is associated with mortality in mixed cohorts of patients requiring and not requiring invasive mechanical ventilation (IMV). Using RV-speckle tracking echocardiography (STE) strain analysis, we aimed to identify the prevalence of RV dysfunction (diagnosed by abnormal RV-STE) in patients with COVID-19 that are exclusively undergoing IMV, and assess association between RV dysfunction and 30 day mortality. We performed a prospective multicentre study across 10 ICUs in Scotland from 2/9/20 to 22/3/21. One-hundred-and-four echocardiography scans were obtained from adult patients at a single timepoint between 48 h after intubation, and day 14 of intensive care unit admission. We analysed RV-STE using RV free-wall longitudinal strain (RVFWLS), with an abnormal cutoff of  > −20%. We performed survival analysis using Kaplan–Meier, log rank, and multivariate cox-regression (prespecified covariates were age, gender, ethnicity, severity of illness, and time since intubation).

Results
Ninety-four/one-hundred-and-four (90.4%) scans had images adequate for RVFWLS. Mean RVFWLS was −23.0% (5.2), 27/94 (28.7%) of patients had abnormal RVFWLS. Univariate analysis with Kaplan–Meier plot and log-rank demonstrated that patients with abnormal RVFWLS have a significant association with 30-day mortality (p = 0.047). Multivariate cox-regression demonstrated that abnormal RVFWLS is independently associated with 30-day mortality (Hazard-Ratio 2.22 [1.14–4.39], p = 0.020).

Conclusions
Abnormal RVFWLS (> −20%) is independently associated with 30-day mortality in patients with COVID-19 undergoing IMV. Strategies to prevent RV dysfunction, and treatment when identified by RVFWLS, may be of therapeutic benefit to these patients.
Trial Registration: Retrospectively registered 21st Feb 2021. ClinicalTrials.gov Identifier: NCT04764032.
Adverse outcomes with extracorporeal adsorbent blood treatments in toxic systemic inflammation: a perspective on possible mechanisms
Authors: Matson James , Lange Paul , Honore Patrick M. , Chung Kevin K. 
Published: November 2022

Abstract
Background
Extracorporeal blood purification (EBP) treatments may be used in patients with sepsis and related conditions to mitigate toxic systemic inflammation, prevent or reverse vital organ injury, and improve outcome. These treatments lack demonstrable efficacy, but are generally considered safe. However, since late 2020, four clinical studies of EBP treatment using adsorbent devices in inflammatory disease reported significantly increased patient mortality associated with the adsorbent treatments. Criticisms of study design and execution were published, but revealed no decisive flaws. None of these critiques considered possible toxic effects of the adsorbent treatments per se.

Perspective and conclusion
In adsorbent EBP treatment of systemic inflammatory disease the adsorbent media are deployed in patient blood or plasma flow for the purpose of broad spectrum, non-specific adsorptive removal of inflammatory mediators. Adsorption and sequestration of inflammatory mediators by adsorbent media is intended to reduce mediator concentrations in circulating blood and neutralize their activity. However, in the past two decades developments in both biomedical engineering and the science of cytokine molecular dynamics suggest that immobilization of inflammatory proteins on solid scaffolds or molecular carriers may stabilize protein structure and preserve or amplify protein function. It is unknown if these mechanisms are operative in EBP adsorbent treatments. If these mechanisms are operative, then the adsorbent medium could become reactive, promoting inflammatory activity which could result in negative outcomes. Considering the recent reports of harm with adsorbent treatments in diverse inflammatory conditions, caution urges investigation of these potentially harmful mechanisms in these devices. Candidate mechanisms for possible inquiry are discussed.
Effective maNagement of depression among patients witH cANCEr (ENHANCE): a protocol for a hybrid systematic review and network meta-analysis of randomised controlled trials of interventions for depressive symptoms
Authors: Pertl Maria M. , Perez Sergio , Collier Sonya , Guinan Emer , Monahan Garret , Verling Katie , Wallace Emma , Walsh Aisling , Doyle Frank 
Published: November 2022

Abstract
Background
Depression is common among patients with cancer and is associated with lower treatment participation, lower satisfaction with care, poorer quality of life, greater symptom burden and higher healthcare costs. Various types of interventions (e.g. pharmacological, psychotherapy) are used for the treatment of depression. However, evidence for these among patients with cancer is limited. Furthermore, the relative effectiveness and acceptability of different approaches are unknown because a direct comparison between all available treatments has not been carried out. We will address this by conducting a network meta-analysis (NMA) of interventions for depression among people with cancer using a hybrid overview of reviews and systematic review methodology.

Methods
We will search for and extract data from systematic reviews of randomised controlled trials (RCTs) of depression interventions for patients with cancer from inception, before performing a supplemental search for more recent RCTs. We will include RCTs comparing pharmacological, psychotherapy, exercise, combination therapy, collaborative care or complementary and alternative medicine interventions with pill placebo, no treatment, waitlist, treatment as usual or minimal treatment control groups, or directly in head-to-head trials, among adults who currently have cancer or have a history of any cancer and elevated depressive symptoms (scores above a cut-off on validated scales or meeting diagnostic criteria). Our primary outcomes will be change in depressive symptoms (standardised mean difference) and intervention acceptability (% who withdrew). Our secondary outcomes will be 6-month change in depressive symptoms, health-related quality of life, adverse events and mortality. We will independently screen for eligibility, extract data and assess risk of bias using the RoB 2 tool. We will use frequentist random-effects multivariate NMA in Stata, rankograms and surface under the cumulative ranking curves to synthesise evidence and obtain a ranking of intervention groups. We will explore heterogeneity and inconsistency using local and global measures and evaluate the credibility of results using the Confidence in NEtwork Meta-Analysis (CINeMA) framework.

Discussion
Our findings will provide the best available evidence for managing depression among patients with cancer. Such information will help to inform clinical guidelines, evidence-based treatment decisions and future research by identifying gaps in the current literature.

Systematic review registration
Submitted to PROSPERO (record number: 290145), awaiting registration.
Evidence for pharmacological interventions to reduce cardiovascular risk for patients with chronic kidney disease: a study protocol of an evidence map
Authors: Colombijn Julia M. T. , Idema Demy L. , van der Braak Kim , Spijker Rene , Meijvis Sabine C. A. , Bots Michiel L. , Hooft Lotty , Verhaar Marianne C. , Vernooij Robin W. M. 
Published: November 2022

Abstract
Background
Patients with chronic kidney disease (CKD) require a personalised strategy for cardiovascular risk management (CVRM) to reduce their high risk of cardiovascular morbidity and mortality. Despite their high risk, patients with CKD appear to be underrepresented in randomised controlled trials (RCTs) for pharmacological CVRM interventions to reduce cardiovascular risk (pharmacological CVRM interventions). As a result, it remains unclear whether the efficacy of these interventions found in patients without CKD is similarly applicable to patients with CKD. This evidence map aims to provide an overview of the availability of the evidence from pharmacological CVRM trials for patients with CKD by assessing how often patients with reduced kidney function are specifically excluded or included from RCTs on pharmacological CVRM interventions and whether studies report efficacy estimates of interventions specifically for kidney patients.

Methods
We will perform a systematic literature search in ClinicalTrials.gov to identify relevant planned, ongoing, and completed RCTs on a broad range of CVRM medications after which we will retrieve the published protocols and papers via ClinicalTrials.gov itself, Embase, MEDLINE, or Google Scholar. We will include RCTs that investigate the efficacy of platelet inhibitors, anticoagulants, antihypertensives, glucose-lowering medication, and lipid-lowering medication on all-cause mortality, cardiovascular mortality, cardiovascular morbidity, and end-stage kidney disease in patients with a cardiovascular history or a major risk factor for cardiovascular disease. Two reviewers will independently screen trial records and their corresponding full-text publications to determine eligibility and extract data. Outcomes of interest are the exclusion of patients with reduced kidney function from RCTs and whether the study population was restricted to kidney patients or subgroup analyses were performed on kidney function. Results will be visualised in an evidence map.

Discussion
The availability of evidence on the efficacy and safety of pharmacological CVRM interventions in patients with CKD might be limited. Hence, we will identify knowledge gaps for future research. At the same time, the availability of evidence, or lack thereof, might warrant caution from healthcare decision-makers in making strong recommendations based on the extrapolation of results from studies to patients who were explicitly excluded from participation.

Systematic review registration
PROSPERO CRD42022296746.
Roles of N6-methyladenosine (m6A) modifications in gynecologic cancers: mechanisms and therapeutic targeting
Authors: Chen Jiahua , Guo Bao , Liu Xiaojing , Zhang Jing , Zhang Junhui , Fang Yuan , Zhu Suding , Wei Bing , Cao Yunxia , Zhan Lei 
Published: November 2022

AbstractUterine and ovarian cancers are the most common gynecologic cancers. N6−methyladenosine (m6A), an important internal RNA modification in higher eukaryotes, has recently become a hot topic in epigenetic studies. Numerous studies have revealed that the m6A-related regulatory factors regulate the occurrence and metastasis of tumors and drug resistance through various mechanisms. The m6A-related regulatory factors can also be used as therapeutic targets and biomarkers for the early diagnosis of cancers, including gynecologic cancers. This review discusses the role of m6A in gynecologic cancers and summarizes the recent advancements in m6A modification in gynecologic cancers to improve the understanding of the occurrence, diagnosis, treatment, and prognosis of gynecologic cancers.
Anticipatory and consummatory pleasure in eating disorders
Authors: Dolan Sarah C. , Reilly Erin E. , Brown Tiffany A. , Shott Megan E. , Frank Guido K. W. 
Published: November 2022

Abstract
Background
Recent research suggests that anhedonia, or the inability to experience pleasure, is elevated in individuals with eating disorders (EDs). However, past literature has only studied anhedonia in EDs as a unidimensional construct rather than separately examining anticipatory (i.e., prediction of pleasure for a future event) and consummatory (i.e., enjoyment of a present event) pleasure. Given that these subcomponents of pleasure have distinct neurobiological correlates, studying pleasure as a multifaceted construct may yield important insights into the underlying mechanisms of binge eating or food restriction.

Methods
A sample of 124 women with anorexia nervosa, bulimia nervosa, or other specified feeding or eating disorder and 84 control women (CW) completed self-report measures of anticipatory pleasure, consummatory pleasure, ED symptoms, depression, harm avoidance, and anxiety.

Results
Individuals with EDs endorsed significantly lower anticipatory pleasure than CW, but there were no significant group differences in consummatory pleasure. Further, there were no significant differences in self-reported pleasure among ED diagnostic groups. Within the ED sample, anticipatory pleasure but not consummatory pleasure was positively related to binge eating frequency and significantly negatively correlated with cognitive ED symptoms, state and trait anxiety, and harm avoidance. Both anticipatory and consummatory pleasure was negatively associated with depression.

Conclusion
The results of the current study suggest that lower pleasure across the ED spectrum may be due to deficits in anticipatory, but not consummatory, pleasure. Future research should continue to explore the behavioral, affective, and neural correlates of anticipatory pleasure in EDs to characterize better how it relates to the onset and maintenance of binge eating and other eating disorder pathology.
Visuospatial perspective-taking in social-emotional development: enhancing young children’s mind and emotion understanding via block building training
Authors: Caldwell Melissa Pearl , Cheung Him , Cheung Sum-Kwing , Li Jian-Bin , Carrey Siu Tik-Sze 
Published: November 2022

AbstractBackgroundTheory of Mind (ToM) refers to the ability to represent one's own and others' mental states, and emotion understanding involves appropriately comprehending and responding to others' emotional cues in social interactions. Individual differences in mind and emotion understanding have been associated strongly with verbal ability and interaction and, as such, existing training for children's ToM and emotion understanding is mostly language-based. Building on the literature on embodied cognition, this study proposes that mind and emotion understanding could be facilitated by one's visuospatial experience in simulating other's frames of reference.MethodsThis protocol consists of two training studies. Study 1 will examine if visuospatial perspective-taking training promotes ToM and emotion understanding. Participants will consist of 96 4.5-year-olds and will be randomly assigned to one of two training groups: the altercentric block building group (trained to be visuospatial perspective-takers), or the egocentric block building group (no visuospatial perspective-taking is involved). Study 2 will compare the engagement of visuospatial perspective-taking and verbal interaction in the development of mind and emotion understanding. Participants will consist of 120 4.5-year-olds. They will be randomly assigned to one of three training groups: the socialized altercentric block building (both visuospatial perspective-taking and verbal interaction), the parallel altercentric block building (visuospatial perspective-taking only), or the paired dialogic reading (verbal interaction only).ConclusionsIn terms of theoretical implications, the potential causal relationship between visuospatial perspective-taking and ToM and emotion understanding may shed new insights on what underlies the development of mental state understanding. The findings of this study also have practical implications: researchers and educators may popularize visuospatial perspective-taking training in the form of block-building games if it is found to be effective in complementing conventional language-based theory-of-mind training.