bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolism of novel potential syntrophic acetate-oxidizing bacteria in thermophilic methanogenic chemostats
Authors: Zeng Yan , Zheng Dan , Li Lan-Peng , Wang Miaoxiao , Gou Min , Kamagata Yoichi , Chen Ya-Ting , Nobu Masaru Konishi , Tang Yue-Qin 
Published: January 2024

ABSTRACT

Acetate is a major intermediate in the anaerobic digestion of organic waste to produce CH
4
. In methanogenic systems, acetate degradation is carried out by either acetoclastic methanogenesis or syntrophic degradation by acetate oxidizers and hydrogenotrophic methanogens. Due to challenges in the isolation of syntrophic acetate-oxidizing bacteria (SAOB), the diversity and metabolism of SAOB and the mechanisms of their interactions with methanogenic partners are not fully characterized. In this study, the
in situ
activity and metabolic characteristics of potential SAOB and their interactions with methanogens were elucidated through metagenomics and metatranscriptomics. In addition to the reported SAOB classified in the genera
Tepidanaerobacter
,
Desulfotomaculum
, and
Thermodesulfovibrio
, we identified a number of potential SAOB that are affiliated with
Clostridia
, Thermoanaerobacteraceae, Anaerolineae, and Gemmatimonadetes. The potential SAOB possessing the glycine-mediated acetate oxidation pathway dominates SAOB communities. Moreover, formate appeared to be the main product of the acetate degradation by the most active potential SAOB. We identified the methanogen partner of these potential SAOB in the acetate-fed chemostat as
Methanosarcina thermophila
. The dominated potential SAOB in each chemostat had similar metabolic characteristics, even though they were in different fatty-acid-fed chemostats. These novel syntrophic lineages are prevalent and may play critical roles in thermophilic methanogenic reactors. This study expands our understanding of the phylogenetic diversity and
in situ
biological functions of uncultured syntrophic acetate degraders and presents novel insights into how they interact with methanogens.

IMPORTANCE
Combining reactor operation with omics provides insights into novel uncultured syntrophic acetate degraders and how they perform in thermophilic anaerobic digesters. This improves our understanding of syntrophic acetate degradation and contributes to the background knowledge necessary to better control and optimize anaerobic digestion processes.
Identification and characterization of methoxy- and dimethoxyhydroquinone 1,2-dioxygenase from
Phanerochaete chrysosporium
Authors: Kato Hiroyuki , Takahashi Yasushi , Suzuki Hiromitsu , Ohashi Keisuke , Kawashima Ryunosuke , Nakamura Koki , Sakai Kiyota , Hori Chiaki , Takasuka Taichi E. , Kato Masashi , Shimizu Motoyuki 
Published: January 2024

ABSTRACT

White-rot fungi, such as
Phanerochaete chrysosporium
, are the most efficient degraders of lignin, a major component of plant biomass. Enzymes produced by these fungi, such as lignin peroxidases and manganese peroxidases, break down lignin polymers into various aromatic compounds based on guaiacyl, syringyl, and hydroxyphenyl units. These intermediates are further degraded, and the aromatic ring is cleaved by 1,2,4-trihydroxybenzene dioxygenases. This study aimed to characterize homogentisate dioxygenase (HGD)-like proteins from
P. chrysosporium
that are strongly induced by the G-unit fragment of vanillin. We overexpressed two homologous recombinant HGDs, PcHGD1 and PcHGD2, in
Escherichia coli
. Both PcHGD1 and PcHGD2 catalyzed the ring cleavage in methoxyhydroquinone (MHQ) and dimethoxyhydroquinone (DMHQ). The two enzymes had the highest catalytic efficiency (
k
cat
/
K

m

) for MHQ, and therefore, we named PcHGD1 and PcHGD2 as MHQ dioxygenases 1 and 2 (PcMHQD1 and PcMHQD2), respectively, from
P. chrysosporium
. This is the first study to identify and characterize MHQ and DMHQ dioxygenase activities in members of the HGD superfamily. These findings highlight the unique and broad substrate spectra of PcHGDs, rendering them attractive candidates for biotechnological applications.

IMPORTANCE

This study aimed to elucidate the properties of enzymes responsible for degrading lignin, a dominant natural polymer in terrestrial lignocellulosic biomass. We focused on two homogentisate dioxygenase (HGD) homologs from the white-rot fungus,
P. chrysosporium
, and investigated their roles in the degradation of lignin-derived aromatic compounds. In the
P. chrysosporium
genome database, PcMHQD1 and PcMHQD2 were annotated as HGDs that could cleave the aromatic rings of methoxyhydroquinone (MHQ) and dimethoxyhydroquinone (DMHQ) with a preference for MHQ. These findings suggest that MHQD1 and/or MHQD2 play important roles in the degradation of lignin-derived aromatic compounds by
P. chrysosporium
. The preference of PcMHQDs for MHQ and DMHQ not only highlights their potential for biotechnological applications but also underscores their critical role in understanding lignin degradation by a representative of white-rot fungus,
P. chrysosporium
.
Trends in inequalities in childhood overweight and obesity prevalence: a repeat cross-sectional analysis of the Health Survey for England
Authors: Broadbent Philip , Shen Yue , Pearce Anna , Katikireddi Srinivasa Vittal 
Published: January 2024

ObjectiveTo examine trends in socio-economic and ethnic inequalities in childhood overweight and obesity in the England between 1995 and 2019 in survey data and to compare these to administrative data.DesignObservational repeated cross-sectional study using the Health Survey for England (HSE) and National Child Measurement Programme (NCMP).OutcomeAge and sex standardised overweight, obesity and overweight including obesity.AnalysisInequalities assessed by parental education, family structure, ethnicity (binary non-white vs white) and area-level Index of Multiple Deprivation. Estimates stratified by age and sex. Trends compared against NCMP data (age 4–5 and 10–11 years).ResultsPrevalence of childhood overweight including obesity increased from 26.0% in 1995 to 31.7% in 2019, with the highest and fastest growing levels in those aged 11–15 years, rising from 29.7% to 38.0%. Despite a plateau in overall childhood obesity since 2004, differences between groups demonstrated widening inequalities over time. Inequalities widened by area-level deprivation, household educational attainment, household structure and ethnicity driven primarily by increased prevalence among socioeconomically disadvantaged children. For example, the gap between children from households with no qualifications versus degree-level qualifications increased from −1.1% to 13.2%, and the gap between single-parent households and couple households increased from 0.5% to 5.3%. HSE trends in prevalence of childhood overweight and obesity by deprivation quintile were consistent with those in NCMP.ConclusionOverall levels of child overweight and obesity increased between 1995 and 2004. Since then, increases in prevalence among less advantaged groups have driven widening of inequalities.
Characteristics and outcomes of patients enrolled in the Connect 360 benralizumab patient support programme in the UK: a retrospective cohort study
Authors: Morris Tamsin , Wood Robert , Silvey Mark , Diomatari Christina , Lipworth Joe , Menon Shruti 
Published: January 2024

BackgroundPatient support programmes (PSPs) allow patients with chronic diseases to receive treatment and support at home. This study describes the Connect 360 PSP delivery and impact on patient-reported outcomes, satisfaction and adherence/persistence among benralizumab-treated patients with severe eosinophilic asthma (SEA).MethodsA non-interventional retrospective cohort study using data collected during routine care in the Connect 360 PSP. All consenting enrollees (≥18 years) were included in the study.Results746 patients formed the study cohort. Mean (SD) age was 53.7 (14.5) years on PSP entry; 38.3% were female (38.7% unknown). 79.6% of patients were experienced biological therapy users. Oral corticosteroid (OCS) use was reported in 48.4% of patients at baseline and 34.8% at 48 weeks. 8.2% of patients reported asthma hospitalisation in the previous 6 months at 24 weeks vs 3.0% at 48 weeks. Mean (SD) 6-item Asthma Control Questionnaire (ACQ-6) scores were 2.7 (1.5) at baseline vs 1.6 (1.3) at 48 weeks. Mean (SD) patient satisfaction scores remained high (4.5 of 5 (1.0) at baseline; 4.7 of 5 (0.6) at 48 weeks). 28.3% of patients were considered adherent at 24 weeks, increasing to 98.3% when supplemented with sales/delivery data (sensitivity analysis). Discontinuation from PSP/benralizumab was low at 24 (3.4%/3.0%) and 48 (12.6%/5.8%) weeks.ConclusionsConnect 360 PSP achieved high levels of satisfaction and persistence, with indications of positive outcomes including OCS use, hospitalisation and ACQ-6. The study was conducted during COVID-19, so it provides reassurance that patients with SEA receiving benralizumab may be supported safely and effectively at home.
A mucus production programme promotes classical pancreatic ductal adenocarcinoma
Authors: Tonelli Claudia , Yordanov Georgi N , Hao Yuan , Deschênes Astrid , Hinds Juliene , Belleau Pascal , Klingbeil Olaf , Brosnan Erin , Doshi Abhishek , Park Youngkyu , Hruban Ralph H , Vakoc Christopher R , Dobin Alexander , Preall Jonathan , Tuveson David A 
Published: January 2024

ObjectiveThe optimal therapeutic response in cancer patients is highly dependent upon the differentiation state of their tumours. Pancreatic ductal adenocarcinoma (PDA) is a lethal cancer that harbours distinct phenotypic subtypes with preferential sensitivities to standard therapies. This study aimed to investigate intratumour heterogeneity and plasticity of cancer cell states in PDA in order to reveal cell state-specific regulators.DesignWe analysed single-cell expression profiling of mouse PDAs, revealing intratumour heterogeneity and cell plasticity and identified pathways activated in the different cell states. We performed comparative analysis of murine and human expression states and confirmed their phenotypic diversity in specimens by immunolabeling. We assessed the function of phenotypic regulators using mouse models of PDA, organoids, cell lines and orthotopically grafted tumour models.ResultsOur expression analysis and immunolabeling analysis show that a mucus production programme regulated by the transcription factor SPDEF is highly active in precancerous lesions and the classical subtype of PDA — the most common differentiation state. SPDEF maintains the classical differentiation and supports PDA transformationin vivo. The SPDEF tumour-promoting function is mediated by its target genes AGR2 andERN2/IRE1β that regulate mucus production, and inactivation of the SPDEF programme impairs tumour growth and facilitates subtype interconversion from classical towards basal-like differentiation.ConclusionsOur findings expand our understanding of the transcriptional programmes active in precancerous lesions and PDAs of classical differentiation, determine the regulators of mucus production as specific vulnerabilities in these cell states and reveal phenotype switching as a response mechanism to inactivation of differentiation states determinants.
Danger, Danger, Gaston Labat! Does zero-shot artificial intelligence correlate with anticoagulation guidelines recommendations for neuraxial anesthesia?
Authors: Hurley Nathan C , Gupta Rajnish K , Schroeder Kristopher M , Hess Aaron S 
Published: January 2024

Introduction
Artificial intelligence and large language models (LLMs) have emerged as potentially disruptive technologies in healthcare. In this study GPT-3.5, an accessible LLM, was assessed for its accuracy and reliability in performing guideline-based evaluation of neuraxial bleeding risk in hypothetical patients on anticoagulation medication. The study also explored the impact of structured prompt guidance on the LLM’s performance.

Methods
A dataset of 10 hypothetical patient stems and 26 anticoagulation profiles (260 unique combinations) was developed based on American Society of Regional Anesthesia and Pain Medicine guidelines. Five prompts were created for the LLM, ranging from minimal guidance to explicit instructions. The model’s responses were compared with a “truth table” based on the guidelines. Performance metrics, including accuracy and area under the receiver operating curve (AUC), were used.

Results
Baseline performance of GPT-3.5 was slightly above chance. With detailed prompts and explicit guidelines, performance improved significantly (AUC 0.70, 95% CI (0.64 to 0.77)). Performance varied among medication classes.

Discussion
LLMs show potential for assisting in clinical decision making but rely on accurate and relevant prompts. Integration of LLMs should consider safety and privacy concerns. Further research is needed to optimize LLM performance and address complex scenarios. The tested LLM demonstrates potential in assessing neuraxial bleeding risk but relies on precise prompts. LLM integration should be approached cautiously, considering limitations. Future research should focus on optimization and understanding LLM capabilities and limitations in healthcare.
Effects of combined dexamethasone and dexmedetomidine as adjuncts to peripheral nerve blocks: a systematic review with meta-analysis and trial sequential analysis
Authors: Maagaard Mathias , Andersen Jakob Hessel , Jaeger Pia , Mathiesen Ole 
Published: January 2024

Background/importanceThe effects of combining dexamethasone and dexmedetomidine on block duration are unclear.ObjectiveTo investigate the effects of combining dexamethasone and dexmedetomidine on block duration.Evidence reviewSystematic review of randomized controlled trials (RCTs) from Medline, Embase, CENTRAL, CINAHL, the Web of Science, and BIOSIS until June 8, 2023. RCTs with adults undergoing surgery with a peripheral nerve block randomized to combined dexamethasone and dexmedetomidine versus placebo or other adjuncts were eligible. Primary outcome was duration of analgesia. We performed meta-analysis, trial sequential analysis, risk of bias-2, and Grading Recommendations Assessment, Development, and Evaluation assessment.FindingsWe included 9 RCTs with 14 eligible comparisons. The combination of dexamethasone and dexmedetomidine was compared with placebo in three RCTs (173 participants), dexamethasone in seven (569 participants), and dexmedetomidine in four (281 participants). The duration of analgesia was likely increased with the combination versus placebo (mean difference 460 min, 95% CI 249 to 671) and versus dexmedetomidine (mean difference 388 min, 95% CI 211 to 565). The duration was likely similar with the combination versus dexamethasone (mean difference 50 min, 95% CI −140 to 239). The certainty of the evidence was moderate because most trials were at high risk of bias.ConclusionsCombined dexamethasone and dexmedetomidine likely increased the duration of analgesia when compared with placebo and dexmedetomidine. The combination likely provided a similar duration of analgesia as dexamethasone. Based on this systematic review, it seems reasonable to use dexamethasone as the sole adjunct if the goal is to increase the duration of analgesia.
Learning Failure-Inducing Models for Testing Software-Defined Networks
Authors: Ollando Raphaël , Shin Seung Yeob , Briand Lionel C. 
Published: January 2024

Software-defined networks (SDN) enable flexible and effective communication systems that are managed by centralized software controllers. However, such a controller can undermine the underlying communication network of an SDN-based system and thus must be carefully tested. When an SDN-based system fails, in order to address such a failure, engineers need to precisely understand the conditions under which it occurs. In this article, we introduce a machine learning-guided fuzzing method, named FuzzSDN, aiming at both (1) generating effective test data leading to failures in SDN-based systems and (2) learning accurate failure-inducing models that characterize conditions under which such system fails. To our knowledge, no existing work simultaneously addresses these two objectives for SDNs. We evaluate FuzzSDN by applying it to systems controlled by two open-source SDN controllers. Furthermore, we compare FuzzSDN with two state-of-the-art methods for fuzzing SDNs and two baselines for learning failure-inducing models. Our results show that (1) compared to the state-of-the-art methods, FuzzSDN generates at least 12 times more failures, within the same time budget, with a controller that is fairly robust to fuzzing and (2) our failure-inducing models have, on average, a precision of 98% and a recall of 86%, significantly outperforming the baselines.
Structural and Temperature Dependent-Magnetic and Dielectric Properties of CoNd
x
Fe2−x
O4 (0 ≤ x ≤ 0.1) Nanoparticles
Authors: Singh Bittu , Babu Kuppam Mohan , Bhaskaraiah M. , Kavuluri Pushpalatha , Joshi Rajendra , Chandra Bhuwan 
Published: January 2024

We present an investigation into the structural and magnetic properties of neodymium-doped cobalt ferrites, described by the general formula CoNd
x
Fe2−x
O4 (where x = 0, 0.02, 0.04, 0.06, 0.08 & 0.10). CoNd
x
Fe2−x
O4 nanoparticles were synthesized using sol-gel auto-combustion method with tartaric acid employed as a chelating agent. The strength of the X-ray diffraction (XRD) peak diminishes as the concentration of Nd3+ increases from 0 to 0.10 mol%, implying that crystallization is hindered due to relatively large ion radii. The crystallite size decreases from 22 nm to 12 nm, with an increase in Nd3+ concentration from 0 to 0.1 mol% in CoFe2O4. Scanning electron microscopy (SEM) studies reveal irregularly shaped particles with a homogenous distribution. The hysteresis loop obtained from the Vibrating-sample magnetometer (VSM) indicates the formation of soft magnetic materials, with magnetization values decreasing from 53 emu g−1 (x = 0) to 40 emu g−1 (x = 0.10) at 3 K and from 32 emu g−1 (x = 0) to 20 emu g−1 (x = 0.10) at 300 K. Interestingly, the highest coercivity and highest anisotropy constant (K) were observed for the sample x = 0.04.
Association of Fibroids, Endometriosis, and Gynecologic Surgeries with Breast Cancer Incidence and Hormone Receptor Subtypes
Authors: Zeldin Jordan , Sandler Dale P. , Ogunsina Kemi , O'Brien Katie M. 
Published: January 2024

Abstract

Background:
Fibroids and endometriosis are sex hormone–mediated and exhibit cancer-like behavior. Breast cancer may be more common in women who have had these conditions, but the literature is conflicting and does not always address factors like hysterectomy/oophorectomy status, race/ethnicity, menopause, and hormone receptor subtypes.

Methods:
Data are from the Sister Study, a cohort of 50,884 U.S. women enrolled in 2003 to 2009 and followed through 2020. Cox proportional hazards models with time-varying exposures and covariates assessed the relationship of fibroids or endometriosis with breast cancer. Logistic regression examined the association with estrogen receptor (ER) status among cases.

Results:
Fibroids (19,932 cases) were positively associated with breast cancer [fully adjusted HR: 1.07; 95% confidence interval (CI): 1.01–1.14], notably among Black participants (HR: 1.34; 95% CI: 1.07–1.69) and women who had a hysterectomy (HR: 1.18; 95% CI: 1.05–1.31). Endometriosis (3,970 cases) was not associated with breast cancer (HR: 0.99; 95% CI: 0.91–1.08). Among 4,419 breast cancer cases, fibroids were positively associated with ER+ subtypes (OR: 1.34; 95% CI: 1.10–1.65), while endometriosis was negatively associated with ER+ subtypes (OR: 0.78; 95% CI: 0.61–1.01).

Conclusions:
We observed a modest positive association between fibroids and breast cancer, particularly ER+ breast cancer. No relationship with endometriosis and breast cancer incidence was found.

Impact:
Fibroids, even in those with a family history of breast cancer, might modify breast cancer risk stratification tools. Future studies should further assess this link and interrogate shared risk factors.
Germline USP36 Mutation Confers Resistance to EGFR-TKIs by Upregulating MLLT3 Expression in Patients with Non–Small Cell Lung Cancer
Authors: Guan Shaoxing , Chen Xi , Wei Yuru , Wang Fei , Xie Wen , Chen Youhao , Liang Heng , Zhu Xia , Yang Yunpeng , Fang Wenfeng , Huang Yan , Zhao Hongyun , Zhang Xiaoxu , Liu Shu , Zhuang Wei , Huang Min , Wang Xueding , Zhang Li 
Published: January 2024

Abstract

Purpose:
Although somatic mutations were explored in depth, limited biomarkers were found to predict the resistance of EGFR tyrosine kinase inhibitors (EGFR-TKI). Previous studies reported N6-methyladenosine (m6A) levels regulated response of EGFR-TKIs; whether the germline variants located in m6A sites affected resistance of EGFR-TKIs is still unknown.

Experimental Design:
Patients with non–small cell lung cancer (NSCLC) with EGFR-activating mutation were enrolled to investigate predictors for response of EGFR-TKIs using a genome-wide-variant-m6A analysis. Bioinformatics analysis and series of molecular biology assays were used to uncover the underlying mechanism.

Results:
We identified the germline mutation USP36 rs3744797 (C &gt; A, K814N) was associated with survival of patients with NSCLC treated with gefitinib [median progression-free survival (PFS): CC vs. CA, 16.30 vs. 10.50 months, P &lt; 0.0001, HR = 2.45] and erlotinib (median PFS: CC vs. CA, 14.13 vs. 9.47 months, P = 0.041, HR = 2.63). Functionally, the C &gt; A change significantly upregulated USP36 expression by reducing its m6A level. Meanwhile, rs3744797_A (USP36 MUT) was found to facilitate proliferation, migration, and resistance to EGFR-TKIs via upregulating MLLT3 expression in vitro and in vivo. More importantly, MLLT3 and USP36 levels are tightly correlated in patients with NSCLC, which were associated with prognosis of patients. Mechanistically, USP36 MUT stabilized MLLT3 by deubiquitinating MLLT3 in nucleoli and consequently activating its downstream signaling (HIF1α and Snai). Furthermore, inhibition of MLLT3 alleviated USP36 variant–induced EGFR-TKIs resistance in EGFR-mutant NSCLC.

Conclusions:
These findings characterized rs3744797 as an oncogenic variant in mediating EGFR-TKI resistance and tumor aggressiveness through deubiquitinating MLLT3, highlighting the variant as a predictive biomarker for EGFR-TKI response in NSCLC.