bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering antifungal and antibiofilm mechanisms of isobavachalcone against Cryptococcus neoformans through RNA-seq and functional analyses
Authors: Qian Weidong , Lu Jiaxing , Gao Chang , Liu Qiming , Li Yongdong , Zeng Qiao , Zhang Jian , Wang Ting , Chen Si 
Published: April 2024

AbstractCryptococcus neoformans has been designated as critical fungal pathogens by the World Health Organization, mainly due to limited treatment options and the prevalence of antifungal resistance. Consequently, the utilization of novel antifungal agents is crucial for the effective treatment of C. neoformans infections. This study exposed that the minimum inhibitory concentration (MIC) of isobavachalcone (IBC) against C. neoformans H99 was 8 µg/mL, and IBC dispersed 48-h mature biofilms by affecting cell viability at 16 µg/mL. The antifungal efficacy of IBC was further validated through microscopic observations using specific dyes and in vitro assays, which confirmed the disruption of cell wall/membrane integrity. RNA-Seq analysis was employed to decipher the effect of IBC on the C. neoformans H99 transcriptomic profiles. Real-time quantitative reverse transcription PCR (RT-qPCR) analysis was performed to validate the transcriptomic data and identify the differentially expressed genes. The results showed that IBC exhibited various mechanisms to impede the growth, biofilm formation, and virulence of C. neoformans H99 by modulating multiple dysregulated pathways related to cell wall/membrane, drug resistance, apoptosis, and mitochondrial homeostasis. The transcriptomic findings were corroborated by the antioxidant analyses, antifungal drug sensitivity, molecular docking, capsule, and melanin assays. In vivo antifungal activity analysis demonstrated that IBC extended the lifespan of C. neoformans-infected Caenorhabditis elegans. Overall, the current study unveiled that IBC targeted multiple pathways simultaneously to inhibit growth significantly, biofilm formation, and virulence, as well as to disperse mature biofilms of C. neoformans H99 and induce cell death.
Detection of P. malariae using a new rapid isothermal amplification lateral flow assay
Authors: Assefa Ashenafi , Wamae Kevin , Hennelly Christopher M. , Ngasala Billy , Muller Meredith , Kalonji Albert , Phanzu Fernandine , Cunningham Clark H. , Lin Jessica T. , Parr Jonathan B. 
Published: April 2024

Abstract
Background
While Plasmodium falciparum and Plasmodium vivax cause the majority of malaria cases and deaths, infection by Plasmodium malariae and other Plasmodium species also causes morbidity and mortality. Current understanding of these infections is limited in part by existing point-of-care diagnostics that fail to differentiate them and have poor sensitivity for low-density infections. Accurate diagnosis currently requires molecular assays performed in well-resourced laboratories. This report describes the development of a P. malariae diagnostic assay that uses rapid, isothermal recombinase polymerase amplification (RPA) and lateral-flow-strip detection.

Methods
Multiple combinations of custom RPA primers and probes were designed using publicly available P. malariae genomic sequences, and by modifying published primer sets. Based on manufacturer RPA reaction conditions (TwistDx nfo kit), an isothermal assay was optimized targeting the multicopy P. malariae 18S rRNA gene with 39 °C incubation and 30-min run time. RPA product was visualized using lateral strips (FAM-labeled, biotinylated amplicon detected by a sandwich immunoassay, visualized using gold nanoparticles). Analytical sensitivity was evaluated using 18S rRNA plasmid DNA, and clinical sensitivity determined using qPCR-confirmed samples collected from Tanzania, Ethiopia, and the Democratic Republic of the Congo.

Results
Using 18S rRNA plasmid DNA, the assay demonstrates a detection limit of 10 copies/µL (~ 1.7 genome equivalents) and 100% analytical specificity. Testing in field samples showed 95% clinical sensitivity and 88% specificity compared to qPCR. Total assay time was less than 40 min.

Conclusion
Combined with simplified DNA extraction methods, the assay has potential for future field-deployable, point-of-care use to detect P. malariae infection, which remains largely undiagnosed but a neglected cause of chronic malaria. The assay provides a rapid, simple readout on a lateral flow strip without the need for expensive laboratory equipment.
Comparison of the effect of ultrasounic-harmonic scalpel and electrocautery in the treatment of axillary lymph nodes during radical surgery for breast cancer
Authors: Tian Yujia , Han Lifei , Ma Xiao , Guo Rui , GeSang Zhuoga , Zhai Yabo , Hu Haolin 
Published: April 2024

Abstract
Objective
To compare the efficacy of ultrasounic-harmonic scalpel and electrocautery in the treatment of axillary lymph nodes during radical surgery for breast cancer.

Methods
A prospective study was conducted in the Department of Breast Surgery, Zhongda Hospital Affiliated to Southeast University. A total of 128 patients with pathologically confirmed breast cancer who were treated by the same surgeon from July 2023 to November 2023 were included in the analysis. All breast operations were performed using electrocautery, and surgical instruments for axillary lymph nodes were divided into ultrasounic-harmonic scalpel group and electrocautery group using a random number table. According to the extent of lymph node surgery, it was divided into four groups: sentinel lymph node biopsy, lymph node at station I, lymph node at station I and II, and lymph node dissection at station I, II and III. Under the premise of controlling variables such as BMI, age and neoadjuvant chemotherapy, the effects of ultrasounic-harmonic scalpel and electrocautery in axillary surgery were compared.

Results
Compared with the electrosurgical group, there were no significant differences in lymph node operation time, intraoperative blood loss, postoperative axillary drainage volume, axillary drainage tube indwelling time, postoperative pain score on the day after surgery, and the incidence of postoperative complications (p>0.05).

Conclusion
There is no significant difference between ultrasounic-harmonic scalpel and electrocautery in axillary lymph node treatment for breast cancer patients, which can provide a basis for the selection of surgical energy instruments.
Modelled cost-effectiveness analysis of the Support and Treatment After Replacement (STAR) care pathway for chronic pain after total knee replacement compared with usual care
Authors: Cole Sophie , Noble Sian , Gooberman-Hill Rachael , Pinedo-Villanueva Rafael 
Published: April 2024

Abstract
Background
The aim of the study was to estimate the long-term cost-effectiveness of the Support and Treatment After Replacement (STAR) care pathway for chronic pain after total knee replacement compared with usual postoperative care.

Methods
Study design: A decision-analytic (cohort Markov) model was used for the simulation with time dependent annual transition probabilities and a time horizon of five years.
Setting: Patients treated by National Health Service (NHS) hospitals in England and Wales.
Study population: Adults classified as having chronic pain three months after undergoing a total knee replacement.
Intervention: The STAR care pathway following a total knee replacement.
Comparator: Usual postoperative care following a total knee replacement.
Perspective: The study was undertaken from the perspective of the NHS.
Outcome measures: Quality-adjusted life years and healthcare costs.
Discounting: A rate of 3.5% for both costs and health utility.

Results
Model results indicate that the STAR intervention would dominate current practice by providing a gain in quality-adjusted life years (QALYs) of 0.086 and a reduction of £375 (per person) in costs over the first five years. The incremental net monetary benefit of the STAR intervention was estimated at £2,086 (at a threshold of £20,000 per QALY). Probabilistic sensitivity analysis suggests the STAR intervention is likely to be cost-effective with a probability of 0.62.
The results remain robust to changes in model assumptions on comparator utility and the timing of the start of the intervention. If hospital admission costs are assumed not to be reduced by the STAR intervention, it would no longer be cost saving, but it would likely be cost-effective based on probabilistic sensitivity analysis (0.59).

Conclusion
Evidence from the economic model suggests that the STAR care pathway is likely to be cost-effective and potentially dominant from an NHS perspective.

Trial registration
The STAR trial is registered with ISRCTN, ISRCTN92545361.
C-reactive protein to albumin ratio as a prognostic tool for predicting intravenous immunoglobulin resistance in children with kawasaki disease: a systematic review of cohort studies
Authors: Liu Jue , Chen Xingguang , Yang Minling , Shen Fangfang , Zhu Feng , Jin Jian , Teng Yiqun 
Published: April 2024

Abstract
Background
Intravenous immunoglobulin (IVIG) is the primary treatment for Kawasaki disease (KD). However, 10–20% of KD patients show no response to IVIG treatment, making the early prediction of IVIG resistance a key focus of KD research. Our aim is to explore the application of the C-reactive protein to albumin ratio (CAR) for predicting IVIG resistance in children with KD through meta-analysis.

Methods
Cochrane Library, PubMed, MEDLINE, EMbase, CNKI, WanFang, the Chinese Biomedical Database, and CQVIP were searched up to November 2023 for cohort studies on predicting IVIG-resistant KD using the CAR. Articles were selected based on pre-established inclusion and exclusion criteria after extracting literature data and assessing them using the QUADAS-2.0 tool for evaluating the accuracy of diagnostic tests. Stata 15.0 software was used for meta-analysis.

Results
Four Chinese and English literature reports were included in this meta-analysis. The results revealed the presence of a threshold effect and high heterogeneity among the included studies. The combined sensitivity for CAR predicting IVIG-resistant KD was calculated as 0.65 (95% CI 0.58–0.72), specificity as 0.71 (95% CI 0.57–0.81), and the area under the curve (AUC) as 0.70 (95% CI 0.66–0.74) using the random-effects model. The combined positive likelihood ratio was 2.22 (95% CI 1.35–3.65), the combined negative likelihood ratio was 0.49 (95% CI 0.35–0.69), and the diagnostic odds ratio was 5 (95% CI 2–10).

Conclusion
CAR is an auxiliary predictive indicator with moderate diagnostic value that provides guidance in the early treatment of the disease, demonstrating a certain predictive value that warrants further investigation. However, CAR cannot yet be considered as a definitive diagnostic or exclusionary marker for IVIG-resistant KD. Therefore, multi-center, large sample, and high-quality long-term follow-up trials are warranted to confirm the current findings.
Soluble CD27 is an intrathecal biomarker of T-cell-mediated lesion activity in multiple sclerosis
Authors: Cencioni Maria T. , Magliozzi Roberta , Palmisano Ilaria , Suwan Keittisak , Mensi Antonella , Fuentes-Font Laura , Villar Luisa M. , Fernández-Velasco José I. , Migallón Noelia Villarrubia , Costa-Frossard Lucienne , Monreal Enric , Ali Rehiana , Romozzi Marina , Mazarakis Nicholas , Reynolds Richard , Nicholas Richard , Muraro Paolo A. 
Published: April 2024

Abstract
Objective
Soluble CD27 is a promising cerebrospinal fluid inflammatory biomarker in multiple sclerosis. In this study, we investigate relevant immune and neuro-pathological features of soluble CD27 in multiple sclerosis.

Methods
Protein levels of soluble CD27 were correlated to inflammatory cell subpopulations and inflammatory cytokines and chemokines detected in cerebrospinal fluid of 137 patients with multiple sclerosis and 47 patients with inflammatory and non-inflammatory neurological disease from three independent cohorts. Production of soluble CD27 was investigated in cell cultures of activated T and B cells and CD27-knockout T cells. In a study including matched cerebrospinal fluid and post-mortem brain tissues of patients with multiple sclerosis and control cases, levels of soluble CD27 were correlated with perivascular and meningeal infiltrates and with neuropathological features.

Results
We demonstrate that soluble CD27 favours the differentiation of interferon-γ-producing T cells and is released through a secretory mechanism activated by TCR engagement and regulated by neutral sphingomyelinase. We also show that the levels of soluble CD27 correlate with the representation of inflammatory T cell subsets in the CSF of patients with relapsing-remitting multiple sclerosis and with the magnitude of perivascular and meningeal CD27 + CD4 + and CD8 + T cell infiltrates in post-mortem central nervous system tissue, defining a subgroup of patients with extensive active inflammatory lesions.

Interpretation
Our results demonstrate that soluble CD27 is a biomarker of disease activity, potentially informative for personalized treatment and monitoring of treatment outcomes.
A modified action framework to develop and evaluate academic-policy engagement interventions
Authors: Mäkelä Petra , Boaz Annette , Oliver Kathryn 
Published: April 2024

Abstract
Background
There has been a proliferation of frameworks with a common goal of bridging the gap between evidence, policy, and practice, but few aim to specifically guide evaluations of academic-policy engagement. We present the modification of an action framework for the purpose of selecting, developing and evaluating interventions for academic-policy engagement.

Methods
We build on the conceptual work of an existing framework known as SPIRIT (Supporting Policy In Health with Research: an Intervention Trial), developed for the evaluation of strategies intended to increase the use of research in health policy. Our aim was to modify SPIRIT, (i) to be applicable beyond health policy contexts, for example encompassing social, environmental, and economic policy impacts and (ii) to address broader dynamics of academic-policy engagement. We used an iterative approach through literature reviews and consultation with multiple stakeholders from Higher Education Institutions (HEIs) and policy professionals working at different levels of government and across geographical contexts in England, alongside our evaluation activities in the Capabilities in Academic Policy Engagement (CAPE) programme.

Results
Our modifications expand upon Redman et al.’s original framework, for example adding a domain of ‘Impacts and Sustainability’ to capture continued activities required in the achievement of desirable outcomes. The modified framework fulfils the criteria for a useful action framework, having a clear purpose, being informed by existing understandings, being capable of guiding targeted interventions, and providing a structure to build further knowledge.

Conclusion
The modified SPIRIT framework is designed to be meaningful and accessible for people working across varied contexts in the evidence-policy ecosystem. It has potential applications in how academic-policy engagement interventions might be developed, evaluated, facilitated and improved, to ultimately support the use of evidence in decision-making.
Pamiparib as consolidation treatment after concurrent chemoradiotherapy of limited-stage small cell lung cancer: a single-arm, open-label phase 2 trial
Authors: Mao Jiuang , Ni Jianjiao , Chu Li , Chu Xiao , Xu Dayu , Yang Xi , Zhu Zhengfei 
Published: April 2024

Abstract
Background
Small cell lung cancer (SCLC) is highly invasive with poor prognosis, and its treatment has historically been hindered due to the absence of targetable driver genomic alterations. However, the high genomic instability and replication stress in SCLC have made poly(ADP-ribose) polymerases (PARPs) inhibitors a focus of research. Pamiparib is an orally available PARP1/2 inhibitor with high selectivity, strong PARP trapping activity, and excellent brain penetration. Utilizing pamiparib as consolidation maintenance therapy in limited-stage SCLC holds promise for improving survival outcomes and offering a viable therapeutic approach.

Methods
This single-arm, open-label phase II trial will enroll patients aged 18–75 years with histologically/cytologically confirmed, limited-stage SCLC who have not progressed following definitive platinum-based cCRT and have an ECOG PS of 0 or 1. Patients will be excluded if they have histologically confirmed mixed SCLC or NSCLC, or have undergone previous tumor resection, or can be treated with surgery or stereotactic body radiation therapy/stereotactic ablative radiation therapy. Participants will receive pamiparib 40 mg twice daily every 3 weeks within 2 to 6 weeks after cCRT for up to 1 year or until disease progression according to RECIST v1.1. The primary endpoint is the 1-year progression-free survival (PFS) rate assessed by investigators per RECIST v1.1. Secondary endpoints include PFS, objective response rate, and duration of response assessed by investigators per RECIST 1.1, overall survival, time to distant metastasis, and safety.

Discussion
The study will provide valuable data on the feasibility, safety, and effectiveness of pamiparib as a consolidation therapy after cCRT in patients with LS-SCLC. The correlation between molecular typing or gene expression profile of the disease and curative response will be further explored.

Trial registration
NCT05483543 at clinicaltrials.gov.
Are enlarged peroneal tubercle and accessory anterolateral talar facet associated with calcaneal spur?
Authors: Kasai Yuichi , Paholpak Permsak , Wisanuyotin Taweechok , Sukitthanakornkul Nuttharada , Hanarwut Parika , Chaiyamoon Arada , Iamsaard Sitthichai , Nishimura Akinobu 
Published: April 2024

Abstract
Background
As the anatomical variations of the foot, enlarged peroneal tubercle (EPT) and accessory anterolateral talar facet (AALTF) have attracted the attention of foot surgeons in recent years. However, EPT and AALTF have not been examined for a relationship with calcaneus spur (CS) as a common osteophyte.

Methods
The subjects were 369 individuals who died in northeastern Thailand and were preserved as skeletal specimens. The authors examined for the presence of left and right EPT, AALTF, and calcaneus spur (CS). We divided the EPT (+) group with EPT and the EPT (-) group without it and also divided the AALTF (+) group with AALTF and the AALTF (-) group without it. The age at death and the presence of CS were compared statistically between the EPT (+) and EPT (-) groups and between the AATLF (+) and AALTF (-) groups.

Results
Out of the total 369 cases, EPT was found in 117 cases (31.7%), AALTF was positive in 91 cases (24.7%), and CS was found in 194 cases (52.3%). In comparison between EPT (+) and EPT (-) groups, CS was significantly higher (p < 0.0001) in the EPT (+) group, but there was no significant difference in age at death. In comparison between AALTF (+) and AALTF (-) groups, there was no significant difference in age at death or CS.

Conclusion
This study showed a strong relationship between EPT and CS, and the prevalence of EPT and AALTF by age in Thailand was first reported. We believe it helps to know the pathogenesis and biomechanism of EPT and AALTF.

Trial registration
Not applicable.
Neo-epitope detection identifies extracellular matrix turnover in systemic inflammation and sepsis: an exploratory study
Authors: Fan YiWen , Moser Jill , van Meurs Matijs , Kiers Dorien , Sand Jannie Marie Bülow , Leeming Diana Julie , Pickkers Peter , Burgess Janette K. , Kox Matthijs , Pillay Janesh 
Published: April 2024

Abstract
Background
Sepsis is associated with high morbidity and mortality, primarily due to systemic inflammation-induced tissue damage, resulting organ failure, and impaired recovery. Regulated extracellular matrix (ECM) turnover is crucial for maintaining tissue homeostasis in health and in response to disease-related changes in the tissue microenvironment. Conversely, uncontrolled turnover can contribute to tissue damage. Systemic Inflammation is implicated to play a role in the regulation of ECM turnover, but the relationship between the two is largely unclear.

Methods
We performed an exploratory study in 10 healthy male volunteers who were intravenously challenged with 2 ng/kg lipopolysaccharide (LPS, derived from Escherichia coli) to induce systemic inflammation. Plasma samples were collected before (T0) and after (T 1 h, 3 h, 6 h and 24 h) the LPS challenge. Furthermore, plasma was collected from 43 patients with septic shock on day 1 of ICU admission. Circulating neo-epitopes of extracellular matrix turnover, including ECM degradation neo-epitopes of collagen type I (C1M), type III (C3M), type IV (C4Ma3), and type VI (C6M), elastin (ELP-3) and fibrin (X-FIB), as well as the ECM synthesis neo-epitopes of collagen type III (PRO-C3), collagen type IV (PRO-C4) and collagen type VI (PRO-C6) were measured by ELISA. Patient outcome data were obtained from electronic patient records.

Results
Twenty-four hours after LPS administration, all measured ECM turnover neo-epitopes, except ELP-3, were increased compared to baseline levels. In septic shock patients, concentrations of all measured ECM neo-epitopes were higher compared to healthy controls. In addition, concentrations of C6M, ELP-3 and X-FIB were higher in patients with septic shock who ultimately did not survive (N = 7) compared to those who recovered (N = 36).

Conclusion
ECM turnover is induced in a model of systemic inflammation in healthy volunteers and was observed in patients with septic shock. Understanding interactions between systemic inflammation and ECM turnover may provide further insight into mechanisms underlying acute and persistent organ failure in sepsis.
Selective omission of sentinel lymph node biopsy in mastectomy for ductal carcinoma in situ: identifying eligible candidates
Authors: Bae Soong June , Kook Yoonwon , Jang Ji Soo , Baek Seung Ho , Moon Sohyun , Kim Jung Hyun , Lee Seung Eun , Kim Min Ji , Ahn Sung Gwe , Jeong Joon 
Published: April 2024

Abstract
Background
Sentinel lymph node biopsy (SLNB) is recommended for patients with ductal carcinoma in situ (DCIS) undergoing mastectomy, given the concerns regarding upstaging and technical difficulties of post-mastectomy SLNB. However, this may lead to potential overtreatment, considering favorable prognosis and de-escalation trends in DCIS. Data regarding upstaging and axillary lymph node metastasis among these patients remain limited.

Methods
We retrospectively reviewed patients with DCIS who underwent mastectomy with SLNB or axillary lymph node dissection at Gangnam Severance Hospital between January 2010 and December 2021. To explore the feasibility of omitting SLNB, we assessed the rates of DCIS upgraded to invasive carcinoma and axillary lymph node metastasis. Binary Cox regression analysis was performed to identify clinicopathologic factors associated with upstaging and axillary lymph node metastasis.

Results
Among 385 patients, 164 (42.6%) experienced an invasive carcinoma upgrade: microinvasion, pT1, and pT2 were confirmed in 53 (13.8%), 97 (25.2%), and 14 (3.6%) patients, respectively. Seventeen (4.4%) patients had axillary lymph node metastasis. Multivariable analysis identified age ≤ 50 years (adjusted odds ratio [OR], 12.73; 95% confidence interval [CI], 1.18–137.51; p = 0.036) and suspicious axillary lymph nodes on radiologic evaluation (adjusted OR, 9.31; 95% CI, 2.06–41.99; p = 0.004) as independent factors associated with axillary lymph node metastasis. Among patients aged > 50 years and/or no suspicious axillary lymph nodes, only 1.7–2.3%) experienced axillary lymph node metastasis.

Conclusions
Although underestimation of the invasive component was relatively high among patients with DCIS undergoing mastectomy, axillary lymph node metastasis was rare. Our findings suggest that omitting SLNB may be feasible for patients over 50 and/or without suspicious axillary lymph nodes on radiologic evaluation.