bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of human and porcine gammaherpesvirus-encoded BILF1 receptor endocytosis
Authors: Mavri Maša , Glišić Sanja , Senćanski Milan , Vrecl Milka , Rosenkilde Mette M. , Spiess Katja , Kubale Valentina 
Published: February 2023

AbstractBackgroundThe viral G-protein-coupled receptor (vGPCR) BILF1 encoded by the Epstein–Barr virus (EBV) is an oncogene and immunoevasin and can downregulate MHC-I molecules at the surface of infected cells. MHC-I downregulation, which presumably occurs through co-internalization with EBV-BILF1, is preserved among BILF1 receptors, including the three BILF1 orthologs encoded by porcine lymphotropic herpesviruses (PLHV BILFs). This study aimed to understand the detailed mechanisms of BILF1 receptor constitutive internalization, to explore the translational potential of PLHV BILFs compared with EBV-BILF1.MethodsA novel real-time fluorescence resonance energy transfer (FRET)-based internalization assay combined with dominant-negative variants of dynamin-1 (Dyn K44A) and the chemical clathrin inhibitor Pitstop2 in HEK-293A cells was used to study the effect of specific endocytic proteins on BILF1 internalization. Bioluminescence resonance energy transfer (BRET)-saturation analysis was used to study BILF1 receptor interaction with β-arrestin2 and Rab7. In addition, a bioinformatics approach informational spectrum method (ISM) was used to investigate the interaction affinity of BILF1 receptors with β-arrestin2, AP-2, and caveolin-1.ResultsWe identified dynamin-dependent, clathrin-mediated constitutive endocytosis for all BILF1 receptors. The observed interaction affinity between BILF1 receptors and caveolin-1 and the decreased internalization in the presence of a dominant-negative variant of caveolin-1 (Cav S80E) indicated the involvement of caveolin-1 in BILF1 trafficking. Furthermore, after BILF1 internalization from the plasma membrane, both the recycling and degradation pathways are proposed for BILF1 receptors.ConclusionsThe similarity in the internalization mechanisms observed for EBV-BILF1 and PLHV1-2 BILF1 provide a foundation for further studies exploring a possible translational potential for PLHVs, as proposed previously, and provides new information about receptor trafficking.Graphical Abstract
Comparative transcriptome analysis reveals the regulatory mechanisms of two tropical water lilies in response to cold stress
Authors: Ma Xiangyu , Jin Qijiang , Wang Yanjie , Wang Xiaowen , Wang Xuelian , Yang Meihua , Ye Chunxiu , Yang Zhijuan , XU Yingchun 
Published: February 2023

Abstract
Background
Tropical water lily is an aquatic plant with high ornamental value, but it cannot overwinter naturally at high latitudes. The temperature drop has become a key factor restricting the development and promotion of the industry.

Results
The responses of Nymphaea lotus and Nymphaea rubra to cold stress were analyzed from the perspective of physiology and transcriptomics. Under the cold stress, Nymphaea rubra had obvious leaf edge curling and chlorosis. The degree of peroxidation of its membrane was higher than that of Nymphaea lotus, and the content of photosynthetic pigments also decreased more than that of Nymphaea lotus. The soluble sugar content, SOD enzyme activity and CAT enzyme activity of Nymphaea lotus were higher than those of Nymphaea rubra. This indicated that there were significant differences in the cold sensitivity of the two varieties. GO enrichment and KEGG pathway analysis showed that many stress response genes and pathways were affected and enriched to varying degrees under the cold stress, especially plant hormone signal transduction, metabolic pathways and some transcription factor genes were from ZAT gene family or WKRY gene family. The key transcription factor ZAT12 protein in the cold stress response process has a C2H2 conserved domain, and the protein is localized in the nucleus. Under the cold stress, overexpression of the NlZAT12 gene in Arabidopsis thaliana increased the expression of some cold-responsive protein genes. The content of reactive oxygen species and MDA in transgenic Arabidopsis thaliana was lower, and the content of soluble sugar was higher, indicating that overexpression of NlZAT12 can improve the cold tolerance of Arabidopsis thaliana.

Conclusion
We demonstrate that ethylene signalling and reactive oxygen species signalling play critical roles in the response of the two cultivars to cold stress. The key gene NlZAT12 for improving cold tolerance was identified. Our study provides a theoretical basis for revealing the molecular mechanism of tropical water lily in response to cold stress.
Elevated atmospheric CO2 concentrations caused a shift of the metabolically active microbiome in vineyard soil
Authors: Rosado-Porto David , Ratering Stefan , Wohlfahrt Yvette , Schneider Bellinda , Glatt Andrea , Schnell Sylvia 
Published: February 2023

AbstractBackgroundElevated carbon dioxide concentrations (eCO2), one of the main causes of climate change, have several consequences for both vine and cover crops in vineyards and potentially also for the soil microbiome. Hence soil samples were taken from a vineyard free-air CO2enrichment (VineyardFACE) study in Geisenheim and examined for possible changes in the soil active bacterial composition (cDNA of 16S rRNA) using a metabarcoding approach. Soil samples were taken from the areas between the rows of vines with and without cover cropping from plots exposed to either eCO2or ambient CO2(aCO2).ResultsDiversity indices and redundancy analysis (RDA) demonstrated that eCO2changed the active soil bacterial diversity in grapevine soil with cover crops (p-value 0.007). In contrast, the bacterial composition in bare soil was unaffected. In addition, the microbial soil respiration (p-values 0.04—0.003) and the ammonium concentration (p-value 0.003) were significantly different in the samples where cover crops were present and exposed to eCO2. Moreover, under eCO2conditions, qPCR results showed a significant decrease in 16S rRNA copy numbers and transcripts for enzymes involved in N2fixation and NO2−reduction were observed using qPCR. Co-occurrence analysis revealed a shift in the number, strength, and patterns of microbial interactions under eCO2conditions, mainly represented by a reduction in the number of interacting ASVs and the number of interactions.ConclusionsThe results of this study demonstrate that eCO2concentrations changed the active soil bacterial composition, which could have future influence on both soil properties and wine quality.
Resilience and stability of the CF- intestinal and respiratory microbiome during nutritional and exercise intervention
Authors: Knoll Rebecca L. , Jarquín-Díaz Víctor Hugo , Klopp Jonas , Kemper Alissa , Hilbert Katja , Hillen Barlo , Pfirrmann Daniel , Simon Perikles , Bähner Viola , Nitsche Oliver , Gehring Stephan , Markó Lajos , Forslund Sofia K. , Poplawska Krystyna 
Published: February 2023

Abstract
Background
Impaired respiratory and intestinal microbiome composition is linked to cystic fibrosis lung disease severity. In people with cystic fibrosis (pwCF), regular exercise is recommended to delay disease progression and preserve a stable lung function. An optimal nutritional status is vital for best clinical outcomes. Our study investigated whether regular and monitored exercise and nutritional support promotes CF microbiome health.

Methods
A personalized nutrition and exercise program promoted nutritional intake and physical fitness in 18 pwCF for 12 months. Throughout the study, patients performed strength and endurance training monitored by a sports scientist via an internet platform. After three months, food supplementation with Lactobacillus rhamnosus LGG was introduced. Nutritional status and physical fitness were assessed before the study started, after three and nine months. Sputum and stool were collected, and microbial composition was analyzed by 16S rRNA gene sequencing.

Results
Sputum and stool microbiome composition remained stable and highly specific to each patient during the study period. Disease-associated pathogens dominated sputum composition. Lung disease severity and recent antibiotic treatment had the highest impact on taxonomic composition in stool and sputum microbiome. Strikingly, the long-term antibiotic treatment burden had only a minor influence.

Conclusion
Despite the exercise and nutritional intervention, respiratory and intestinal microbiomes proved to be resilient. Dominant pathogens drove the composition and functionality of the microbiome. Further studies are required to understand which therapy could destabilize the dominant disease-associated microbial composition of pwCF.
Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio as prognostic predictors for delirium in critically ill patients: a systematic review and meta-analysis
Authors: Sarejloo Shirin , Shojaei Niloofar , Lucke-Wold Brandon , Zelmanovich Rebecca , Khanzadeh Shokoufeh 
Published: February 2023

Abstract
Introduction
In this systematic review and meta-analysis, we aim to analyze the current literature to evaluate neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) values among critically ill patients who develop delirium as compared to those who do not.

Methods
PubMed, Web of Science, and Scopus were used to conduct a systematic search for relevant publications published before June 12, 2022. The Newcastle–Ottawa scale was used for quality assessment. Because a significant level of heterogeneity was found, we used the random-effects model to generate pooled effects.

Results
Twenty-four studies including 11,579 critically ill patients, of whom 2439 were diagnosed with delirium, were included in our meta-analysis. Compared with the non-delirious group, the delirious group's NLR levels were significantly higher (WMD = 2.14; CI 95% = 1.48–2.80, p < 0.01). In the subgroup analysis according to the type of critical condition, the NLR levels in patients of delirious group were significantly more than those of non-delirious group in studies on POD, PSD and PCD (WMD = 1.14, CI 95% = 0.38–1.91, p < 0.01, WMD = 1.38, CI 95% = 1.04–1.72, p < 0.001, and WMD = 4.22, CI 95% = 3.47–4.98, p < 0.001, respectively). However, compared with the non-delirious group, the delirious group's PLR levels were not significantly different (WMD = 1.74; CI 95% = -12.39–15.86, p = 0.80).

Conclusion
Our findings support NLR to be a promising biomarker that can be readily integrated into clinical settings to aid in the prediction and prevention of delirium.
Changes in emergency psychiatric consultations in time of COVID-19: a retrospective observational study in the Verona Academic Hospital over the two pandemic years 2020–2021
Authors: Bodini Luca , Bonetto Chiara , Maccagnani Antonio , Bonora Antonio , Polati Enrico , Ricci Giorgio , Paolillo Ciro , Amaddeo Francesco , Lasalvia Antonio 
Published: February 2023

Abstract
Background
During the first months of the COVID-19 pandemic, local health authorities in most Italian regions prescribed a reduction of ordinary outpatient and community mental health care. The aim of this study was to assess the impact of the COVID-19 pandemic on access to the emergency departments (ED) for psychiatric consultation in the pandemic years 2020 and 2021 compared to 2019.

Methods
This is a retrospective study conducted by using routinely collected administrative data of the two EDs of the Verona Academic Hospital Trust (Verona, Italy). All ED psychiatry consultations registered from 01.01.2020 to 31.12.2021 were compared with those registered in the pre-pandemic year (01.01.2019 to 31.12.2019). The association between each recorded characteristic and the year considered was estimated by chi-square or Fisher’s exact test.

Results
A significant reduction was observed between 2020 and 2019 (-23.3%) and between 2021 and 2019 (-16.3%). This reduction was most evident in the lockdown period of 2020 (-40.3%) and in the phase corresponding to the second and third pandemic waves (-36.1%). In 2021, young adults and people with diagnosis of psychosis showed an increase in requests for psychiatric consultation.

Conclusions
Fear of contagion may have been an important factor in the overall reduction in psychiatric consultations. However, psychiatric consultations for people with psychosis and for young adults increased. This finding underlines the need for mental health services to implement alternative outreach strategies aimed to support, in times of crisis, these vulnerable segments of the population.
Emergency department care experiences among members of equity-deserving groups: quantitative results from a cross-sectional mixed methods study
Authors: Bartels Susan A. , MacKenzie Meredith , Douglas Stuart L. , Collier Amanda , Pritchard Jodie , Purkey Eva , Messenger David , Walker Melanie 
Published: February 2023

Abstract
Background
Emergency departments (EDs) serve an integral role in healthcare, particularly for vulnerable populations. However, marginalized groups often report negative ED experiences, including stigmatizing attitudes and behaviours. We engaged with historically marginalized patients to better understand their ED care experiences.

Method
Participants were invited to complete an anonymous mixed-methods survey about a previous ED experience. We analysed quantitative data including controls and equity-deserving groups (EDGs) - those who self-identified as: (a) Indigenous; (b) having a disability; (c) experiencing mental health issues; (d) a person who uses substances; (e) a sexual and gender minority; (f) a visible minority; (g) experiencing violence; and/or (h) facing homelessness - to identify differences in their perspectives. Differences between EDGs and controls were calculated with chi squared tests, geometric means with confidence ellipses, and the Kruskal-Wallis H test.

Results
We collected a total of 2114 surveys from 1973 unique participants, 949 controls and 994 who identified as equity-deserving. Members of EDGs were more likely to attribute negative feelings to their ED experience (p < 0.001), to indicate that their identity impacted the care received (p < 0.001), and that they felt disrespected and/or judged while in the ED (p < 0.001). Members of EDGs were also more likely to indicate that they had little control over healthcare decisions (p < 0.001) and that it was more important to be treated with kindness/respect than to receive the best possible care (p < 0.001).

Conclusion
Members of EDGs were more likely to report negative ED care experiences. Equity-deserving individuals felt judged and disrespected by ED staff and felt disempowered to make decisions about their care. Next steps will include contextualizing findings using participants’ qualitative data and identifying how to improve ED care experiences among EDGs to make it more inclusive and better able to meet their healthcare needs.
Propensity score analysis with missing data using a multi-task neural network
Authors: Yang Shu , Du Peipei , Feng Xixi , He Daihai , Chen Yaolong , Zhong Linda L. D. , Yan Xiaodong , Luo Jiawei 
Published: February 2023

AbstractBackgroundPropensity score analysis is increasingly used to control for confounding factors in observational studies. Unfortunately, unavoidable missing values make estimating propensity scores extremely challenging. We propose a new method for estimating propensity scores in data with missing values.Materials and methodsBoth simulated and real-world datasets are used in our experiments. The simulated datasets were constructed under 2 scenarios, the presence (T = 1) and the absence (T = 0) of the true effect. The real-world dataset comes from LaLonde’s employment training program. We construct missing data with varying degrees of missing rates under three missing mechanisms: MAR, MCAR, and MNAR. Then we compare MTNN with 2 other traditional methods in different scenarios. The experiments in each scenario were repeated 20,000 times. Our code is publicly available athttps://github.com/ljwa2323/MTNN.ResultsUnder the three missing mechanisms of MAR, MCAR and MNAR, the RMSE between the effect and the true effect estimated by our proposed method is the smallest in simulations and in real-world data. Furthermore, the standard deviation of the effect estimated by our method is the smallest. In situations where the missing rate is low, the estimation of our method is more accurate.ConclusionsMTNN can perform propensity score estimation and missing value filling at the same time through shared hidden layers and joint learning, which solves the dilemma of traditional methods and is very suitable for estimating true effects in samples with missing values. The method is expected to be broadly generalized and applied to real-world observational studies.
Technology-enabled virtual ward for COVID management of the elderly and immunocompromised in Singapore: a descriptive cohort
Authors: Ko Stephanie Q. , Kumar Shoban Krishna , Jacob Jonathan , Hooi Benjamin M. Y. , Soo Michelle , Nashi Norshima , Cruz Maria Teresa D. , Wah Yeo Ai , Xin Wong Zhi , Smitasin Nares , Lum Lionel , Archuleta Sophia 
Published: February 2023

Abstract
Background
To address the hospital bed demand for Delta and Omicron surges in Singapore, the National University Health System (NUHS) developed a COVID Virtual Ward to relieve bed pressures on its three acute hospitals—National University Hospital, Ng Teng Fong General Hospital, Alexandra Hospital. To serve a multilingual population, the COVID Virtual Ward featuring protocolized teleconsultation of high-risk patients, use of a vital signs chatbot, supplemented by home visits where necessary. This study aims to evaluate the safety, outcomes and utilisation of the Virtual Ward as a scalable response to COVID-19 surges.

Methods
This is a retrospective cohort study of all patients admitted to the COVID Virtual Ward between 23 September to 9 November 2021. Patients were defined as “early discharge” if they were referred from inpatient COVID-19 wards and “admission avoidance” if they were referred directly from primary care or emergency services. Patient demographics, utilisation measures and clinical outcomes were extracted from the electronic health record system. The primary outcomes were escalation to hospital and mortality. Use of the vital signs chatbot was evaluated by examining compliance levels, need for automated reminders and alerts triggered. Patient experience was evaluated using data extracted from a quality improvement feedback form.

Results
238 patients were admitted to the COVID Virtual Ward from 23 September to 9 November, of whom 42% were male, 67.6% of Chinese ethnicity. 43.7% were over the age of 70, 20.5% were immunocompromised, and 36.6% were not fully vaccinated. 17.2% of patients were escalated to hospital and 2.1% of patients died. Patients who were escalated to hospital were more likely to be immunocompromised or to have a higher ISARIC 4C-Mortality Score. There were no missed deteriorations. All patients received teleconsults (median of 5 teleconsults per patient, IQR 3–7). 21.4% of patients received home visits. 77.7% of patients engaged with the vital signs chatbot, with a compliance rate of 84%. All patients would recommend the programme to others in their situation.

Conclusions
Virtual Wards are a scalable, safe and patient-centered strategy to care for high risk COVID-19 patients at home.

Trial Registration

NA.
Glycosylation spectral signatures for glioma grade discrimination using Raman spectroscopy
Authors: Quesnel Agathe , Coles Nathan , Angione Claudio , Dey Priyanka , Polvikoski Tuomo M. , Outeiro Tiago F. , Islam Meez , Khundakar Ahmad A. , Filippou Panagiota S. 
Published: February 2023

Abstract
Background
Gliomas are the most common brain tumours with the high-grade glioblastoma representing the most aggressive and lethal form. Currently, there is a lack of specific glioma biomarkers that would aid tumour subtyping and minimally invasive early diagnosis. Aberrant glycosylation is an important post-translational modification in cancer and is implicated in glioma progression. Raman spectroscopy (RS), a vibrational spectroscopic label-free technique, has already shown promise in cancer diagnostics.

Methods
RS was combined with machine learning to discriminate glioma grades. Raman spectral signatures of glycosylation patterns were used in serum samples and fixed tissue biopsy samples, as well as in single cells and spheroids.

Results
Glioma grades in fixed tissue patient samples and serum were discriminated with high accuracy. Discrimination between higher malignant glioma grades (III and IV) was achieved with high accuracy in tissue, serum, and cellular models using single cells and spheroids. Biomolecular changes were assigned to alterations in glycosylation corroborated by analysing glycan standards and other changes such as carotenoid antioxidant content.

Conclusion
RS combined with machine learning could pave the way for more objective and less invasive grading of glioma patients, serving as a useful tool to facilitate glioma diagnosis and delineate biomolecular glioma progression changes.
Distribution, dynamic evolution, and clinical outcomes of patients with advanced breast cancer according to HER2 expression
Authors: Shi Qin , Yu Jing , Liu Deyue , Ren Fang , Wu Jiayi , Shen Kunwei 
Published: February 2023

Abstract
Background
Novel antibody‒drug conjugates (ADC) have shown great efficacy in HER2-low advanced breast cancer. However, the clinical features of HER2-low disease still need to be clarified. The current study aims to evaluate the distribution and dynamic change in HER2 expression in patients with disease recurrence and the clinical outcome of those patients.

Methods
Patients with pathologically diagnosed relapsed breast cancer between 2009 and 2018 were included. Samples were considered HER2-zero when the immunohistochemistry (IHC) score was 0, HER2-low when the IHC score was 1 + or 2 + with negative fluorescence in situ hybridization (FISH) results, and HER2-positive when the IHC score was 3 + or the FISH results were positive. Breast cancer-specific survival (BCSS) was compared among the three HER2 groups. Changes in HER2 status were also evaluated.

Results
A total of 247 patients were included. Among recurrent tumors, 53 (21.5%) were HER2-zero, 127 (51.4%) were HER2-low, and 67 (27.1%) were HER2-positive. The HER2-low subtype represented 68.1% of the HR-positive breast cancer group and 31.3% of the HR-negative group (P < 0.001). This three-group classification of HER2 status was prognostic in advanced breast cancer (P = 0.0011), with HER2-positive patients having the best clinical outcome after disease recurrence (P = 0.024), while only marginal survival advantages were observed in HER2-low patients versus HER2-zero patients (P = 0.051). In the subgroup analysis, the survival difference was observed only in patients with HR-negative recurrent tumors (P = 0.0006) or with distant metastasis (P = 0.0037). The overall discordance rate of HER2 status between primary and recurrent tumors was 38.1%, with 25 (49.0%) primary HER2-zero patients and 19 (26.8%) HER2-positive patients shifting to HER2-low at recurrence.

Conclusion
Nearly half of the advanced breast cancer patients had HER2-low disease, which indicates a poorer prognosis than HER2-positive disease and marginally better outcomes than HER2-zero disease. During disease progression, one-fifth of tumors convert to HER2-low entities, and the corresponding patients may benefit from ADC treatment.