bluuebunny/crossref_metadata_2025_split huggingface dataset:
An attacin antimicrobial peptide, Hill_BB_C10074, from Hermetia illucens with anti-Pseudomonas aeruginosa activity
Authors: Fahmy Leila , Ali Youssif M. , Seilly David , McCoy Reece , Owens Róisín M. , Pipan Miha , Christie Graham , Grant Andrew J 
Published: December 2023

Abstract
Background
There is a global need to develop new therapies to treat infectious diseases and tackle the rise in antimicrobial resistance. To date, the larvae of the Black Solider Fly, Hermetia illucens, have the largest repertoire of antimicrobial peptides derived from insects. Antimicrobial peptides are of particular interest in the exploration of alternative antimicrobials due to their potent action and reduced propensity to induce resistance compared with more traditional antibiotics.

Results
The predicted attacin from H. illucens, Hill_BB_C10074, was first identified in the transcriptome of H. illucens populations that had been fed a plant-oil based diet. In this study, recombinant Hill_BB_C10074 (500 µg/mL), was found to possess potent antimicrobial activity against the serious Gram-negative pathogen, Pseudomonas aeruginosa. Sequence and structural homology modelling predicted that Hill_BB_C10074 formed a homotrimeric complex that may form pores in the Gram-negative bacterial outer membrane. In vitro experiments defined the antimicrobial action of Hill_BB_C10074 against P. aeruginosa and transmission electron microscopy and electrochemical impedance spectroscopy confirmed the outer membrane disruptive power of Hill_BB_C10074 which was greater than the clinically relevant antibiotic, polymyxin B.

Conclusions
Combining predictive tools with in vitro approaches, we have characterised Hill_BB_C10074 as an important insect antimicrobial peptide and promising candidate for the future development of clinical antimicrobials.
Humoral and T cell responses to SARS-CoV-2 reveal insights into immunity during the early pandemic period in Pakistan
Authors: Masood Kiran Iqbal , Qaiser Shama , Abidi Syed Hani , Khan Erum , Mahmood Syed Faisal , Hussain Areeba , Ghous Zara , Imtiaz Khekahsan , Ali Natasha , Hasan Muhammad , Memon Haris Ali , Yameen Maliha , Ali Shiza , Baloch Sadaf , Lakhani Gulzar , Alves Paula M. , Iqbal Najeeha Talat , Ahmed Kumail , Iqbal Junaid , Bhutta Zulfiqar A. , Hussain Rabia , Rottenberg Martin , Simas J. Pedro , Veldhoen Marc , Ghias Kulsoom , Hasan Zahra 
Published: December 2023

Abstract
Background
Protection against SARS-CoV-2 is mediated by humoral and T cell responses. Pakistan faced relatively low morbidity and mortality from COVID-19 through the pandemic. To examine the role of prior immunity in the population, we studied IgG antibody response levels, virus neutralizing activity and T cell reactivity to Spike protein in a healthy control group (HG) as compared with COVID-19 cases and individuals from the pre-pandemic period (PP).

Methods
HG and COVID-19 participants were recruited between October 2020 and May 2021. Pre-pandemic sera was collected before 2018. IgG antibodies against Spike and its Receptor Binding Domain (RBD) were determined by ELISA. Virus neutralization activity was determined using a PCR-based micro-neutralization assay. T cell – IFN-γ activation was assessed by ELISpot.

Results
Overall, the magnitude of anti-Spike IgG antibody levels as well as seropositivity was greatest in COVID-19 cases (90%) as compared with HG (39.8%) and PP (12.2%). During the study period, Pakistan experienced three COVID-19 waves. We observed that IgG seropositivity to Spike in HG increased from 10.3 to 83.5% during the study, whilst seropositivity to RBD increased from 7.5 to 33.3%. IgG antibodies to Spike and RBD were correlated positively in all three study groups. Virus neutralizing activity was identified in sera of COVID-19, HG and PP. Spike reactive T cells were present in COVID-19, HG and PP groups. Individuals with reactive T cells included those with and without IgG antibodies to Spike.

Conclusions
Antibody and T cell responses to Spike protein in individuals from the pre-pandemic period suggest prior immunity against SARS-CoV-2, most likely from cross-reactive responses. The rising seroprevalence observed in healthy individuals through the pandemic without known COVID-19 may be due to the activation of adaptive immunity from cross-reactive memory B and T cells. This may explain the more favourable COVID-19 outcomes observed in this population.
Latencies to the first interictal epileptiform discharges recorded by the electroencephalography in different epileptic patients
Authors: Liu Chenyu , Qi Yi , Wang Liang , Zhang Ce , Kang Li , Shang Suhang , Dang Jingxia 
Published: December 2023

Abstract
Purpose
Interictal epileptiform discharges (IEDs) captured in electroencephalography (EEG) have a high diagnostic value for epileptic patients. Extending the recording time may increase the possibility of obtaining IEDs. The purpose of our research was to determine how long it took for various epileptic individuals to receive their first IEDs.

Methods
We retrospectively analyzed patients who were diagnosed with epilepsy and had no anti-seizure medications (ASMs) between September 2018 and March 2019 in the neurology department of the First Affiliated Hospital of Xi'an Jiaotong University. Each individual underwent a 24-h long-term video electroencephalographic monitoring (VEM) procedure. Clinical information including age, gender, age of seizure onset, frequency of seizures, the interval between last seizure and VEM, and results of neuroimaging were gathered. We also calculated the times from the start of the VEM to the first definite IEDs.

Results
A total of 241 patients were examined, including 191 with focal-onset epilepsy and 50 with generalized epilepsy. In individuals with focal-onset epilepsy, the median latency to the first IED was 63.0 min (IQR 19.0–299.0 min), as compared to 30.0 min (IQR 12.5–62.0 min) in patients with generalized epilepsy (p < 0.001). The latency to the first IED is significantly related to the age of seizure onset (HR = 0.988, p = 0.049), the interval between last seizure and VEM (HR = 0.998, p = 0.013). But it is not correlated with seizure frequency, gender and age.

Conclusions
IEDs were discovered during 24-h EEG monitoring in 222/241(92.1%) of the epilepsy patients that were included. Compared to focal-onset epilepsy, generalized epilepsy demonstrated a much shorter latency to IED. Patients with late-onset epilepsy or those without recent episodes may require longer EEG monitoring periods.
Temporal trends in age- and stage-specific incidence of colorectal adenocarcinomas in Germany
Authors: Waldmann Annika , Borchers Pia , Katalinic Alexander 
Published: December 2023

Abstract
Background
A national colorectal cancer (CRC) screening programme was launched in 2002 in Germany. A comprehensive evaluation of the programme effectiveness using real-world data is still lacking. In addition, there are regional reports on increasing colorectal cancer incidence in younger populations. Therefore, we aimed to describe and compare the overall, age- and stage-specific incidence trends for colorectal, colon and rectal cancer.

Methods
We used data from seven population-based cancer registries in Germany. We report absolute and relative changes in incidence rates between the early screening phase (2003–2005) and the most recent time period available (2015–2017), as well as annual percent changes. We analysed incidences according to tumour site (colorectum, colon, and rectum) and to six age groups (young adults: 15–34, 35–39, 40–49, screening-entitled/older adults: 50–54, 55–69 and 70 + years old).

Results
In our sample of 271,011 colorectal adenocarcinomas, about two-thirds were located in the colon and 95% of them occurred in the age group 50+ (50–54: 5%, 55–69: 32.8%, 70+: 57.2%). For the time period 2003–2005 the age-specific incidence rates of individuals in the age group 55–69 were about 76/100,00 for colon and 54/100,000 for rectal cancer (age group 70 + colon: 179/100,000; rectum: 84/100,000). The incidence rates in young adults were less than 13% of that of individuals in the age group 55–69 (< 5% of individuals aged 70+; <33% of individuals aged 50–54).
Over time, incidence decreased in individuals at the age of 55+, for all subsites considered as well as for early and late stage cancers (with few exceptions), while incidence of young adult CRC (both early and late stage) increased steepest in the youngest age groups. For late stage rectal cancer, a shift was observed in all age groups from UICC stage IV to stage III being the most frequent stage.

Conclusions
Six years after the introduction of the national colonoscopy screening program, late stage CRC incidence began to decline substantially in the screening-eligible age groups (55-69, 70+). It is likely that this decline and the increase in early stage CRC observed in younger age groups can be attributed to the program. Long lasting public awareness campaigns for CRC screening might have led to opportunistic screening in younger adults. Whether these benefits outweigh the possible harm of screening in younger age groups remains unclear.
The validity and IRT psychometric analysis of Chinese version of Difficult Doctor-Patient Relationship Questionnaire (DDPRQ-10)
Authors: Du Jianhua , Wang Yufei , Wu Aoxue , Jiang Yinan , Duan Yanping , Geng Wenqi , Wan Lin , Li Jiarui , Hu Jiaojiao , Jiang Jing , Shi Lili , Wei Jing 
Published: December 2023

Abstract
Objective
The doctor-patient relationship (DPR) plays a crucial role in the Chinese healthcare system, functioning to improve medical quality and reduce medical costs. This study examined the psychometric properties of the Chinese version of the Difficult Doctor-Patient Relationship Questionnaire (DDPRQ-10) among general hospital inpatients in China.

Methods
The research recruited 38 resident doctors responsible for 120 participants, and factor analyses were used to assess the construct validity of the scale. Convergent validity was evaluated by examining the correlation between DDPRQ-10 and depressive symptoms, burnout, and self-efficacy, using the Patient Health Questionnaire Depression Scale-9 item (PHQ-9), and the Maslach Burnout Inventory (MBI). Both multidimensional item response theory (MIRT) and unidimensional item response theory (IRT) frameworks were used to estimate the parameters of each item.

Results
The Chinese version of DDPRQ-10 showed satisfactory internal consistency (Cronbach's alpha = 0.931), and fitted in a modified two-factor model of positive feelings and negative feelings (χ2/df = 1.494, GFI = 0.925, RMSEA = 0.071, SRMR = 0.008, CFI = 0.985, NFI = 0.958, NNFI = 0.980, TLI = 0.980, IFI = 0.986). Significant correlations with PHQ-9 with DDPRQ-10 and both subscales were revealed (r = 0.293 ~ 0.333, p < .001), while DDPRQ-10 score also significantly correlated with doctors’ MBI score (r = -0.467, p < .001). The MIRT model of full scale and IRT models of both subscales showed high discrimination of all items (a = 2.30 ~ 10.18), and the test information within the range of low-quality relationship was relatively high.

Conclusion
The Chinese version of DDPRQ-10 displayed satisfactory reliability and validity and thus was appropriate for measuring the DPR in Chinese medical settings.
Mean difference in timing of first antenatal checks across regions and associated factors among pregnant women attending health facilities in Ethiopia: evidence from Ethiopian demographic health survey, 2019
Authors: Feyisa Gemechu Chemeda , Dagne Alemayehu , Woyessa Delelegn , Ephrem Tenna , Ahmed Ausman , G/Senbet Habtamu , Chane Getachew , Wake Senahara Korsa 
Published: December 2023

Abstract
Introduction
Early initiation of antenatal care visits is an essential component of services to improve maternal health. Conducting a detailed study about the mean difference in timing at first antenatal checks across regions and factors associated with timing at first antenatal checks among women attending antenatal in Ethiopia is essential to ensure maternal and newborn health. Therefore, this study aimed to describe the mean difference in timing at first antenatal visits and associated factors among pregnant women attending different health facilities across regions in Ethiopia.

Method
The Ethiopian Demographic and Health Survey (EDHS) conducted a community-based cross-sectional study in 2019. In this study, data about the timing of the first antenatal check-ups were requested from the Demographic Health Survey in February 2023, and the required variables were downloaded in SAS and SPSS formats from the data set. A total of 2935 women from nine regional states and two city administrations with an age range of 15 to 49 years were included in the study. The mean difference in timing at first antenatal check-ups, its correlation and various factors were estimated using multiple linear regressions to identify factors.

Result
The majority of the 2034 (69.3%) of pregnant women who participated in the study were rural residents. The mean (± SD) age of the pregnant women was 29 (± 6.5) years. Approximately 32.5% of pregnant women visited their first antenatal check after 4 months of pregnancy. The results showed that counselling by health workers during a previous pregnancy (p < 0.01) significantly predicts timing at first antenatal checks in months holding previous delivery, previous antenatal care at both government and private facilities, ever attended school, and highest educational level. Timing at the first antenatal check-in months is expected to decrease by 0.99 months for every counselling session at each pregnancy. The results of the analysis suggested that the regression model significantly predicted timing at the first antenatal check (p = 0.001).

Conclusion
The mean difference in timing at the first antenatal check in months among Ethiopian pregnant women relatively significantly varies in two regions. Previous pregnancy counselling by health workers positively influences the timing of first antenatal check-ups for subsequent antenatal check follow-ups in Ethiopia.
Cordymin alleviates osteoporosis induced by hindlimb unloading via regulating the gut - microelements -bone axis --for non-clinical studies
Authors: Qi Wei , Ma Tiancheng , Ji Yufei , Jia Hong , Sun Qiang , Zhang Dawei 
Published: December 2023

Abstract
Introduction
The purpose of this study was to evaluate the protective effects of cordymin on osteoporosis induced by hindlimb unloading(HLU) in rats and whether cordymin can prevent bone loss from HLU.

Materials and methods
We employed the hindlimb suspension rats model to mimic physiological changes concomitant with space travel.The mechanical strength in the femoral neck,cancellous bone volume, gut microbiota structure,serum calcium and phosphorus contents, bone mineral content and bone mineral content can be changed after hindlimb unloading. Oral cordymin was administered for 4 weeks,cordymin treatment significantly increased the mechanical strength through elevated bone volume/tissue volume (BV/TV), trabecular number (Tb. N), trabecular thickness (Tb. Th) and decreased trabecular separation (Tb. Sp).

Results
Importantly, 16 S rRNA sequencing showed cordymin treatment regulated the various genera that were imbalanced in hindlimb unloading rats. At the same time,The plasma total calcium and inorganic phosphate concentrations in hindlimb unloading rats decreased and bone mineral content in the lumbar vertebrae and femur increased after treatment with cordymin.

Conclusion
These data indicate that the cordymin might exert bone protective effects indirectly via modulating the complex relationship between gut microbiota, microelements and bone loss.
Coexpression network analysis identified MT3 as a hub gene that promotes the chemoresistance of oral cancer by regulating the expression of YAP1
Authors: Luo Jingyi , Liu Xin , Zhang Yifei , Yin Miao , Xu Li , Cao Menglei , Cheng Bo , Yang Sisi 
Published: December 2023

Abstract
Background
Oral cancer is considered one of the most malignant types of tumors and is known for its high likelihood of recurrence and metastasis. During clinical treatment, patients with oral cancer often develop resistance to chemotherapy, making the treatment process challenging. The purpose of this study was to investigate the genes related to chemotherapy resistance and their mechanisms in oral cancer patients.

Methods
The “limma” package was used to identify the differentially expressed genes between tumor and normal tissues from TCGA dataset. Subsequently, the “WGCNA” package was utilized to discover genes associated with chemoresistance. Cisplatin-resistant oral cancer cell lines were obtained through exposure to gradually increasing doses of cisplatin. SiRNA was used to knock down the MT3 and YAP1 genes to validate their functions. Finally, the therapeutic efficacy of combining a YAP1 inhibitor with cisplatin was confirmed by inoculating an oral cancer cell line in mice.

Results
In our study, we analyzed 43 OSCC samples and identified 724 different genes using the weighted gene coexpression network analysis (WGCNA) method. Among these genes, MT3 stood out as strongly associated with chemotherapy resistance. Patients with high MT3 expression had worse prognoses, and MT3 levels were elevated in drug-resistant patients. Knocking down MT3 reversed tumor cell chemoresistance. We also observed that MT3 increased the expression of YAP1, potentially contributing to chemotherapy resistance by inducing tumor stemness through YAP1. In animal models, using YAP1 inhibitors improved the effectiveness of cisplatin in treating chemoresistant oral cancer.

Conclusions
MT3 is related to chemotherapy resistance, which may be caused by its promotion of YAP1 expression and induction of tumor cell stemness. Inhibiting the activity of MT3 and YAP1 is helpful for increasing chemotherapy sensitivity.
Identifying potential pathogenesis and immune infiltration in diabetic foot ulcers using bioinformatics and in vitro analyses
Authors: Xu Yuanyuan , Xu Jianchang , Chen Sirong , Zhou Anbang , Huang Guangjing , Huang Shidao , Yu Dianbo , Wu Biaoliang 
Published: December 2023

Abstract
Background
Diabetic foot ulcers (DFU) are among the fastest-growing diseases worldwide. Recent evidence has emphasized the critical role of microRNA (miRNA)-mRNA networks in various chronic wounds, including DFU. In this study, we aimed to clarify the miRNA-mRNA axes associated with the occurrence of DFU.

Methods
Expression profiles of miRNAs and mRNAs were extracted from the Gene Expression Omnibus. Differentially expressed genes and differentially expressed miRNAs were identified, and miRNA-mRNA regulatory axes were constructed through integrated bioinformatics analyses. We validated the miRNA-mRNA axes using quantitative real-time PCR (qPCR) and dual-luciferase reporter assays. We conducted an immune infiltration analysis and confirmed the bioinformatics results using immunofluorescence staining. Single-sample gene set enrichment analysis (ssGSEA) was used to analyze the metabolic mechanisms.

Results
miR-182-5p-CHL1/MITF and miR-338-3p-NOVA1 interactions were identified using in silico analysis. The qPCR results showed apparent dysregulation of these miRNA-mRNA axes in DFU. The dual-luciferase reporter assay confirmed that miR-182-5p targeted CHL1 and MITF, and miR-338-3p targeted NOVA1. We conducted an immune infiltration analysis and observed that key genes correlated with decreased infiltration of M1 macrophages and resting mast cells in DFU. Immunofluorescence staining verified the co-localization of CHL1 and tryptase, while MITF and CD68 showed weak positive correlations. Metabolic pathways related to these three genes were identified using ssGSEA.

Conclusions
In summary, the miR-182-5p-CHL1/MITF and miR-338-3p-NOVA1 pathway interactions and decreased infiltration of M1 macrophages and resting mast cells may provide novel clues to the pathogenesis of DFU.

Trial registration
The clinical trial included in this study was registered in the Chinese Clinical Trial Registry (ChiCTR2200066660) on December 13, 2022.
CSE triggers ferroptosis via SIRT4-mediated GNPAT deacetylation in the pathogenesis of COPD
Authors: Li Congping , Chen Fei , Lin Liangfen , Li Jiwei , Zheng Yamei , Chen Qingyun 
Published: December 2023

Abstract
Background
It is now understood that ferroptosis plays a significant role in the progression of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke extract (CSE). However, the mechanisms underlying this relationship remain largely unclear.

Methods
In this study, we established a COPD mouse model through exposure to cigarette smoke particulates, followed by H&E staining, analysis of bronchoalveolar lavage fluid, and immunohistochemistry assay. A549 cells were exposed to increasing concentrations of CSE, with the addition of the ferroptosis activator erastin or the inhibitor Fer-1. Cell viability, LDH (lactate dehydrogenase) release, inflammatory cytokines, total ROS (reactive oxygen species), and lipid ROS were measured using the corresponding assay kits. The acetylation level of GNPAT was determined through immunoprecipitation. We assessed the expression levels of molecules involved in plasmalogen biosynthesis (FAR1, AGPS, and GNPAT), GPX4, and SIRT4 using quantitative real-time PCR, western blot analysis, and immunofluorescence staining.

Results
CSE-induced lung tissue damage was initially observed, accompanied by oxidative stress, ferroptosis, and increased plasmalogen biosynthesis molecules (FAR1, AGPS, and GNPAT). CSE also induced ferroptosis in A549 cells, resulting in reduced cell viability, GSH, and GPX4 levels, along with increased LDH, ROS, MDA (malondialdehyde) levels, oxidized lipids, and elevated FAR1, AGPS, and GNPAT expression. Knockdown of GNPAT mitigated CSE-induced ferroptosis. Furthermore, we found that CSE regulated the acetylation and protein levels of GNPAT by modulating SIRT4 expression. Importantly, the overexpression of GNPAT countered the inhibitory effects of SIRT4 on ferroptosis.

Conclusions
Our study revealed GNPAT could be deacetylated by SIRT4, providing novel insights into the mechanisms underlying the relationship between CSE-induced ferroptosis and COPD.
Automated design of dynamic programming schemes for RNA folding with pseudoknots
Authors: Marchand Bertrand , Will Sebastian , Berkemer Sarah J. , Ponty Yann , Bulteau Laurent 
Published: December 2023

AbstractAlthough RNA secondary structure prediction is a textbook application of dynamic programming (DP) and routine task in RNA structure analysis, it remains challenging whenever pseudoknots come into play. Since the prediction of pseudoknotted structures by minimizing (realistically modelled) energy is NP-hard, specialized algorithms have been proposed for restricted conformation classes that capture the most frequently observed configurations. To achieve good performance, these methods rely on specific and carefully hand-crafted DP schemes. In contrast, we generalize and fully automatize the design of DP pseudoknot prediction algorithms. For this purpose, we formalize the problem of designing DP algorithms for an (infinite) class of conformations, modeled by (a finite number of) fatgraphs, and automatically build DP schemes minimizing their algorithmic complexity. We propose an algorithm for the problem, based on the tree-decomposition of a well-chosen representative structure, which we simplify and reinterpret as a DP scheme. The algorithm is fixed-parameter tractable for the treewidth tw of the fatgraph, and its output represents a $${\mathcal {O}}(n^{tw+1})$$

O
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algorithm (and even possibly $${\mathcal {O}}(n^{tw})$$

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in simple energy models) for predicting the MFE folding of an RNA of length n. We demonstrate, for the most common pseudoknot classes, that our automatically generated algorithms achieve the same complexities as reported in the literature for hand-crafted schemes. Our framework supports general energy models, partition function computations, recursive substructures and partial folding, and could pave the way for algebraic dynamic programming beyond the context-free case.