bluuebunny/crossref_metadata_2025_split huggingface dataset:
A risk prediction model mediated by genes of APOD/APOC1/SQLE associates with prognosis in cervical cancer
Authors: Zhang Ya , Qin Yuankun , Li Danqing , Yang Yingjie 
Published: December 2022

AbstractCervical cancer is one of the most common gynecological malignancies. Due to the high heterogeneity of cervical cancer accelerating cancer progression, it is necessary to identify new prognostic markers and treatment regimens for cervical cancer to improve patients’ survival rates. We purpose to construct and verify a risk prediction model for cervical cancer patients. Based on the analysis of data from the Gene Expression Omnibus database (GEO) and The Cancer Genome Atlas (TCGA), differences of genes in normal and cancer samples were analyzed and then used analysis of WGCNA along with consistent clustering to construct single-factor + multi-factor risk models. After regression analysis, the target genes were obtained as prognostic genes and prognostic risk models were constructed, and the validity of the risk model was confirmed using the receiver operating characteristic curve (ROC) and Kaplan–Meier curve. Subsequently, the above model was verified on the GSE44001 data validation followed by independent prognostic analysis. Enrichment analysis was conducted by grouping the high and low risks of the model. In addition, differences in immune analysis (immune infiltration, immunotherapy), drug sensitivity, and other levels were counted by the high and low risks groups. In our study, three prognostic genes including APOD, APOC1, and SQLE were obtained, and a risk model was constructed along with validation based on the above-mentioned analysis. According to the model, immune correlation and immunotherapy analyses were carried out, which will provide a theoretical basis and reference value for the exploration and treatment of cervical cancer.
Health literacy in asthma and chronic obstructive pulmonary disease (COPD) care: a narrative review and future directions
Authors: Poureslami Iraj , FitzGerald J. Mark , Tregobov Noah , Goldstein Roger S. , Lougheed M. Diane , Gupta Samir 
Published: December 2022

AbstractRespiratory self-care places considerable demands on patients with chronic airways disease (AD), as they must obtain, understand and apply information required to follow their complex treatment plans. If clinical and lifestyle information overwhelms patients’ HL capacities, it reduces their ability to self-manage. This review outlines important societal, individual, and healthcare system factors that influence disease management and outcomes among patients with asthma and chronic obstructive pulmonary disease (COPD)—the two most common ADs. For this review, we undertook a comprehensive literature search, conducted reference list searches from prior HL-related publications, and added insights from international researchers and scientists with an interest in HL. We identified methodological limitations in currently available HL measurement tools in respiratory care. We also summarized the issues contributing to low HL and system-level cultural incompetency that continue to be under-recognized in AD management and contribute to suboptimal patient outcomes. Given that impaired HL is not commonly recognized as an important factor in AD care, we propose a three-level patient-centered model (strategies) designed to integrate HL considerations, with the goal of enabling health systems to enhance service delivery to meet the needs of all AD patients.
Higher systolic blood pressure is specifically associated with better islet beta-cell function in T2DM patients with high glycemic level
Authors: Xia Zhang , Song Lijuan , Fang Dongdong , You Wenjun , Li Feng , Zheng Deqiang , Li Yuhao , Lin Lu , Dou Jingtao , Su Xin , Zhai Qi , Zuo Yingting , Zhang Yibo , Gaisano Herbert Y. , Jiang Jiajia , He Yan 
Published: December 2022

Abstract
Background
Patients with type 2 diabetes mellitus (T2DM) usually have higher blood viscosity attributed to high blood glucose that can decrease blood supply to the pancreas. A mild increase in blood pressure (BP) has been reported as a potential compensatory response that can maintain blood perfusion in the islet. However, how BP influences beta-cell function in T2DM subjects remains inconsistent. This study aimed to examine the relationship between BP and beta-cell function in patients with T2DM under different HbA1c levels.

Methods
This is a cross-sectional study of 615 T2DM patients, whose clinical data were extracted from hospital medical records. Beta-cell function was assessed by insulin secretion-sensitivity index-2 (ISSI2). Multivariable linear regression analysis and restricted cubic splines (RCS) analysis were performed to identify the association between systolic BP (SBP) and ISSI2. Mediation analysis was performed to determine whether higher SBP could reduce blood glucose by enhancing beta-cell function.

Results
After adjustment of potential confounders, in participants with HbA1c ≥ 10%, the SBP between 140 to150 mmHg had the highest log ISSI2 (b = 0.227, 95% CI 0.053–0.402), an association specific to participants with < 1 year duration of diabetes. RCS analyses demonstrated an inverted U-shaped association between SBP and ISSI2 with the SBP at 144 mmHg corresponding to the best beta-cell function. This higher SBP was “paradoxically” associated with lower 2 h postprandial blood glucose (PBG) when SBP < 150 mmHg that was almost exclusively mediated by ISSI2 (mediating effect = − 0.043, 95%CI − 0.067 to − 0.018; mediating effect percentage = 94.7%, P < 0.01). SBP was however not associated with improvement in ISSI2 or 2 h PBG in participants with HbA1c < 10%.

Conclusions
In early stage of diabetes, a slightly elevated SBP (140–150 mmHg) was transiently associated with better beta-cell function in T2DM patients with HbA1c ≥ 10% but not in those with HbA1c < 10%.
Development of a thiostrepton-free system for stable production of PLD in Streptomyces lividans SBT5
Authors: Wang Juntan , Zhu Haihua , Shang Huiyi , Guo Bishan , Zhang Mengxue , Wang Fayun , Zhang Lipan , Xu Jun , Wang Hui 
Published: December 2022

Abstract
Background
Phospholipase D (PLD) is highly valuable in the food and medicine industries, where it is used to convert low-cost phosphatidylcholine into high-value phospholipids (PLs). Despite being overexpressed in Streptomyces, PLD production requires expensive thiostrepton feeding during fermentation, limiting its industrialization. To address this issue, we propose a new thiostrepton-free system.

Results
We developed a system using a combinatorial strategy containing the constitutive promoter kasOp* and PLD G215S mutation fused to a signal peptide sigcin of Streptoverticillium cinnamoneum pld. To find a candidate vector, we first expressed PLD using the integrative vector pSET152 and then built three autonomously replicating vectors by substituting Streptomyces replicons to increase PLD expression. According to our findings, replicon 3 with stability gene (sta) inserted had an ideal result. The retention rate of the plasmid pOJ260-rep3-pld* was 99% after five passages under non-resistance conditions. In addition, the strain SK-3 harboring plasmid pOJ260-rep3-pld* produced 62 U/mL (3.48 mg/g) of PLD, which further improved to 86.8 U/mL (7.51 mg/g) at 32 °C in the optimized medium, which is the highest activity achieved in the PLD secretory expression to date.

Conclusions
This is the first time that a thiostrepton-free PLD production system has been reported in Streptomyces. The new system produced stable PLD secretion and lays the groundwork for the production of PLs from fermentation stock. Meanwhile, in the Streptomyces expression system, we present a highly promising solution for producing other complex proteins.
Integrated single-cell transcriptomics of cerebrospinal fluid cells in treatment-naïve multiple sclerosis
Authors: Straeten Frederike , Zhu Jing , Börsch Anna-Lena , Zhang Baohong , Li Kejie , Lu I-Na , Gross Catharina , Heming Michael , Li Xiaolin , Rubin Rebekah , Ouyang Zhengyu , Wiendl Heinz , Mingueneau Michael , Meyer zu Hörste Gerd 
Published: December 2022

AbstractMultiple sclerosis (MS) is a chronic and often disabling autoimmune disease of the central nervous system (CNS). Cerebrospinal fluid (CSF) surrounds and protects the CNS. Analysis of CSF can aid the diagnosis of CNS diseases, help to identify the prognosis, and underlying mechanisms of diseases. Several recent studies have leveraged single-cell RNA-sequencing (scRNA-seq) to identify MS-associated changes in CSF cells that are considerably more altered than blood cells in MS. However, not all alterations were replicated across all studies. We therefore integrated multiple available scRNA-seq datasets of CSF cells from MS patients with early relapsing–remitting (RRMS) disease. We provide a searchable and interactive resource of this integrated analysis (https://CSFinMS.bxgenomics.com) facilitating diverse visualization and analysis methods without requiring computational skills. In the present joint analysis, we replicated the known expansion of B lineage and the recently described expansion of natural killer (NK) cells and some cytotoxic T cells and decrease of monocytes in the CSF in MS. The previous observation of the abundance of Th1-like Th17 effector memory cells in the CSF was not replicated. Expanded CSF B lineage cells resembled class-switched plasmablasts/-cells (e.g., SDC1/CD138, MZB1) as expected. Our integrative analysis thus validates increased cell type diversity and B cell maturation in the CSF in MS and improves accessibility of available data.
Supporting factors and structural barriers in the continuity of breastfeeding in the hospital workplace
Authors: Jiravisitkul Paveewan , Thonginnetra Saraiorn , Kasemlawan Naruporn , Suntharayuth Thitiphong 
Published: December 2022

AbstractBackgroundThe World Health Organization recommends that babies should receive exclusive breastfeeding (EBF) for six months, and mothers should be encouraged to breastfeed until their infant is aged two years or older. The breastfeeding rate in Thailand is currently much lower than the target. One critical factor is lactating mothers returning to work, especially in a hospital workplace with high job stress. In this study, we aimed to identify supporting factors and obstacles to sustaining breastfeeding in hospital-type workplaces.MethodsWe conducted a mixed methods study between February 2021 and August 2021 at Chulabhorn Hospital, Thailand. Quantitative data were collected using questionnaires, and qualitative data were gathered in a focus group discussion among purposefully chosen participants, including mothers with both successful and unsuccessful continuation of breastfeeding after returning to work. We conducted multivariate analysis and thematic analysis in quantitative and qualitative data analysis, respectively.ResultsQuestionnaires were completed by 65 permanent employees of the hospital, and seven of these participated in focus group discussion. The rate of exclusive breastfeeding from birth to six months was sixty six percent, and was measured by the responses from questionnaires, which defined as a practice whereby the infants receive only breastmilk without mixing it with other food. Seventy-seven percent of participants were continuing to breastfeed when they returned to work, with 24% (12/50) having to stop after three months. Factors associated with exclusive breastfeeding was caesarean delivery (OR 7.9; 95% CI 2.00, 31.08). Additionally, childcare at the workplace and the attitude of colleagues were found to be supporting factors for sustaining breastfeeding. Barriers included inadequate private facilities (location and equipment), lack of a breastfeeding break, workload, and inconvenient uniform.ConclusionsEffort is needed to sustain breastfeeding after maternal return to work. Our findings are crucial in determining how best to support nursing mothers in breastfeeding after returning to work, particularly during the ongoing COVID-19 pandemic. A breastfeeding-friendly policy with clear operating guidelines in the workplace is critical to sustaining breastfeeding. Learning from others who have had a positive experience will ensure that all breastfeeding women are better supported in the workplace in future.
X-ray fluorescence spectroscopy (XRF) for metallome analysis of herbarium specimens
Authors: Purwadi Imam , Casey Lachlan W. , Ryan Chris G. , Erskine Peter D. , van der Ent Antony 
Published: December 2022

Abstract
Background
“Herbarium X-ray Fluorescence (XRF) Ionomics” is a new quantitative approach for extracting the elemental concentrations from herbarium specimens using handheld XRF devices. These instruments are principally designed for dense sample material of infinite thickness (such as rock or soil powder), and their built-in algorithms and factory calibrations perform poorly on the thin dry plant leaves encountered in herbaria. While empirical calibrations have been used for ‘correcting’ measured XRF values post hoc, this approach has major shortcomings. As such, a universal independent data analysis pipeline permitting full control and transparency throughout the quantification process is highly desirable. Here we have developed such a pipeline based on Dynamic Analysis as implemented in the GeoPIXE package, employing a Fundamental Parameters approach requiring only a description of the measurement hardware and derivation of the sample areal density, based on a universal standard.

Results
The new pipeline was tested on potassium, calcium, manganese, iron, cobalt, nickel, and zinc concentrations in dry plant leaves. The Dynamic Analysis method can correct for complex X-ray interactions and performs better than both the built-in instrument algorithms and the empirical calibration approach. The new pipeline is also able to identify and quantify elements that are not detected and reported by the device built-in algorithms and provides good estimates of elemental concentrations where empirical calibrations are not straightforward.

Conclusions
The new pipeline for processing XRF data of herbarium specimens has a greater accuracy and is more robust than the device built-in algorithms and empirical calibrations. It also gives access to all elements detected in the XRF spectrum. The new analysis pipeline has made Herbarium XRF approach even more powerful to study the metallome of existing plant collections.
Rare disease education in Europe and beyond: time to act
Authors: Tumiene Birute , Peters Harm , Melegh Bela , Peterlin Borut , Utkus Algirdas , Fatkulina Natalja , Pfliegler György , Graessner Holm , Hermanns Sanja , Scarpa Maurizio , Blay Jean-Yves , Ashton Sharon , McKay Lucy , Baynam Gareth 
Published: December 2022

AbstractPeople living with rare diseases (PLWRD) still face huge unmet needs, in part due to the fact that care systems are not sufficiently aligned with their needs and healthcare workforce (HWF) along their care pathways lacks competencies to efficiently tackle rare disease-specific challenges. Level of rare disease knowledge and awareness among the current and future HWF is insufficient. In recent years, many educational resources on rare diseases have been developed, however, awareness of these resources is still limited and rare disease education is still not sufficiently taken into account by some crucial stakeholders as academia and professional organizations. Therefore, there is a need to fundamentally rethink rare disease education and HWF development across the whole spectrum from students to generalists, specialists and experts, to engage and empower PLWRD, their families and advocates, and to work towards a common coherent and complementary strategy on rare disease education and training in Europe and beyond. Special consideration should be also given to the role of nurse coordinators in care coordination, interprofessional training for integrated multidisciplinary care, patient and family-centered education, opportunities given by digital learning and fostering of social accountability to enforce the focus on socially-vulnerable groups such as PLWRD. The strategy has to be developed and implemented by multiple rare disease education and training providers: universities, medical and nursing schools and their associations, professional organizations, European Reference Networks, patient organizations, other organizations and institutions dedicated to rare diseases and rare cancers, authorities and policy bodies.
Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Authors: Kim Dong Won , Tu Kevin J. , Wei Alice , Lau Ashley J. , Gonzalez-Gil Anabel , Cao Tianyu , Braunstein Kerstin , Ling Jonathan P. , Troncoso Juan C. , Wong Philip C. , Blackshaw Seth , Schnaar Ronald L. , Li Tong 
Published: December 2022

Abstract
Background
Amongst risk alleles associated with late-onset Alzheimer’s disease (AD), those that converged on the regulation of microglia activity have emerged as central to disease progression. Yet, how canonical amyloid-β (Aβ) and tau pathologies regulate microglia subtypes during the progression of AD remains poorly understood.

Methods
We use single-cell RNA-sequencing to profile microglia subtypes from mice exhibiting both Aβ and tau pathologies across disease progression. We identify novel microglia subtypes that are induced in response to both Aβ and tau pathologies in a disease-stage-specific manner. To validate the observation in AD mouse models, we also generated a snRNA-Seq dataset from the human superior frontal gyrus (SFG) and entorhinal cortex (ERC) at different Braak stages.

Results
We show that during early-stage disease, interferon signaling induces a subtype of microglia termed Early-stage AD-Associated Microglia (EADAM) in response to both Aβ and tau pathologies. During late-stage disease, a second microglia subtype termed Late-stage AD-Associated Microglia (LADAM) is detected. While similar microglia subtypes are observed in other models of neurodegenerative disease, the magnitude and composition of gene signatures found in EADAM and LADAM are distinct, suggesting the necessity of both Aβ and tau pathologies to elicit their emergence. Importantly, the pattern of EADAM- and LADAM-associated gene expression is observed in microglia from AD brains, during the early (Braak II)- or late (Braak VI/V)- stage of the disease, respectively. Furthermore, we show that several Siglec genes are selectively expressed in either EADAM or LADAM. Siglecg is expressed in white-matter-associated LADAM, and expression of Siglec-10, the human orthologue of Siglecg, is progressively elevated in an AD-stage-dependent manner but not shown in non-AD tauopathy.

Conclusions
Using scRNA-Seq in mouse models bearing amyloid-β and/or tau pathologies, we identify novel microglia subtypes induced by the combination of Aβ and tau pathologies in a disease stage-specific manner. Our findings suggest that both Aβ and tau pathologies are required for the disease stage-specific induction of EADAM and LADAM. In addition, we revealed Siglecs as biomarkers of AD progression and potential therapeutic targets.
Spatiotemporal evolution of the clear cell renal cell carcinoma microenvironment links intra-tumoral heterogeneity to immune escape
Authors: Golkaram Mahdi , Kuo Fengshen , Gupta Sounak , Carlo Maria I. , Salmans Michael L. , Vijayaraghavan Raakhee , Tang Cerise , Makarov Vlad , Rappold Phillip , Blum Kyle A. , Zhao Chen , Mehio Rami , Zhang Shile , Godsey Jim , Pawlowski Traci , DiNatale Renzo G. , Morris Luc G. T. , Durack Jeremy , Russo Paul , Kotecha Ritesh R. , Coleman Jonathan , Chen Ying-Bei , Reuter Victor E. , Motzer Robert J. , Voss Martin H. , Liu Li , Reznik Ed , Chan Timothy A. , Hakimi A. Ari 
Published: December 2022

Abstract

Background
Intratumoral heterogeneity (ITH) is a hallmark of clear cell renal cell carcinoma (ccRCC) that reflects the trajectory of evolution and influences clinical prognosis. Here, we seek to elucidate how ITH and tumor evolution during immune checkpoint inhibitor (ICI) treatment can lead to therapy resistance.

Methods
Here, we completed a single-arm pilot study to examine the safety and feasibility of neoadjuvant nivolumab in patients with localized RCC. Primary endpoints were safety and feasibility of neoadjuvant nivolumab. Then, we spatiotemporally profiled the genomic and immunophenotypic characteristics of 29 ccRCC patients, including pre- and post-therapy samples from 17 ICI-treated patients. Deep multi-regional whole-exome and transcriptome sequencing were performed on 29 patients at different time points before and after ICI therapy. T cell repertoire was also monitored from tissue and peripheral blood collected from a subset of patients to study T cell clonal expansion during ICI therapy.

Results
Angiogenesis, lymphocytic infiltration, and myeloid infiltration varied significantly across regions of the same patient, potentially confounding their utility as biomarkers of ICI response. Elevated ITH associated with a constellation of both genomic features (HLA LOH, CDKN2A/B loss) and microenvironmental features, including elevated myeloid expression, reduced peripheral T cell receptor (TCR) diversity, and putative neoantigen depletion. Hypothesizing that ITH may itself play a role in shaping ICI response, we derived a transcriptomic signature associated with neoantigen depletion that strongly associated with response to ICI and targeted therapy treatment in several independent clinical trial cohorts.

Conclusions
These results argue that genetic and immune heterogeneity jointly co-evolve and influence response to ICI in ccRCC. Our findings have implications for future biomarker development for ICI response across ccRCC and other solid tumors and highlight important features of tumor evolution under ICI treatment.

Trial registration
The study was registered on ClinicalTrial.gov (NCT02595918) on November 4, 2015.
Association of medial arch support of foot orthoses with knee valgus angle at initial contact during cutting maneuvers in female athletes: a controlled laboratory study
Authors: Toyooka Seikai , Tsukada Keisuke , Yasui Youich , Saho Yasuaki , Okawa Yasuaki , Ando Shuji , Nakagawa Takumi , Kawano Hirotaka , Miyamoto Wataru 
Published: December 2022

Abstract
Background
The effect of medial arch support foot orthoses on kinematics and kinetics of the knee joint has remained unknown.

Methods
Sixteen female collegiate-level athletes volunteered to participate. Participants were asked to perform a 30° sidestep cut using orthoses of 3 different medial arch heights, comprising of the following: (1) “low,” a full flat foot orthosis without arch support, (2) “mid,” a commercially available foot orthosis with general height arch support, and (3) “high,” a foot orthosis with double the commercially available height for arch support to observe the effect on the knee when overcorrected. Kinematics and kinetics of the knee joint were collected by a markerless motion capture system with 2 force plates and compared between orthosis types using linear regression analysis, assuming a correlation between the measurements of the same cases in the error term.

Results
The knee valgus angle at initial contact was 2.3 ± 5.2 degrees for “low” medial arch support height, 2.1 ± 5.8 degrees for “mid,” and 0.4 ± 6.6 degrees for “high”. Increased arch support height significantly decreased the knee valgus angle at initial contact (p = 0.002). Other kinematic and kinetic measurements did not differ between groups.

Conclusions
The valgus angle of the knee at initial contact was decreased by the height of the medial arch support provided by foot orthosis during cutting manoeuvres. Increasing the arch support height may decrease knee valgus angle at initial contact. Medial arch support of foot orthosis may be effective in risk reduction of ACL injury.
Clinical trial registration numbers and date of registration: UMIN000046071, 15/11/2021.