bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data
Authors: Li Shuang , Schmid Katharina T. , de Vries Dylan H. , Korshevniuk Maryna , Losert Corinna , Oelen Roy , van Blokland Irene V. ,   BIOS Consortium, sc-eQTLgen Consortium, Groot Hilde E. , Swertz Morris A. , van der Harst Pim , Westra Harm-Jan , van der Wijst Monique G.P. , Heinig Matthias , Franke Lude 
Published: April 2023

AbstractBackgroundExpression quantitative trait loci (eQTL) studies show how genetic variants affect downstream gene expression. Single-cell data allows reconstruction of personalized co-expression networks and therefore the identification of SNPs altering co-expression patterns (co-expression QTLs, co-eQTLs) and the affected upstream regulatory processes using a limited number of individuals.ResultsWe conduct a co-eQTL meta-analysis across four scRNA-seq peripheral blood mononuclear cell datasets using a novel filtering strategy followed by a permutation-based multiple testing approach. Before the analysis, we evaluate the co-expression patterns required for co-eQTL identification using different external resources. We identify a robust set of cell-type-specific co-eQTLs for 72 independent SNPs affecting 946 gene pairs. These co-eQTLs are replicated in a large bulk cohort and provide novel insights into how disease-associated variants alter regulatory networks. One co-eQTL SNP, rs1131017, that is associated with several autoimmune diseases, affects the co-expression of RPS26 with other ribosomal genes. Interestingly, specifically in T cells, the SNP additionally affects co-expression of RPS26 and a group of genes associated with T cell activation and autoimmune disease. Among these genes, we identify enrichment for targets of five T-cell-activation-related transcription factors whose binding sites harbor rs1131017. This reveals a previously overlooked process and pinpoints potential regulators that could explain the association of rs1131017 with autoimmune diseases.ConclusionOur co-eQTL results highlight the importance of studying context-specific gene regulation to understand the biological implications of genetic variation. With the expected growth of sc-eQTL datasets, our strategy and technical guidelines will facilitate future co-eQTL identification, further elucidating unknown disease mechanisms.
A robust reprogramming strategy for generating hepatocyte-like cells usable in pharmaco-toxicological studies
Authors: Garcia-Llorens Guillem , Martínez-Sena Teresa , Pareja Eugenia , Tolosa Laia , Castell José V. , Bort Roque 
Published: April 2023

Abstract
Background
High-throughput pharmaco-toxicological testing frequently relies on the use of established liver-derived cell lines, such as HepG2 cells. However, these cells often display limited hepatic phenotype and features of neoplastic transformation that may bias the interpretation of the results. Alternate models based on primary cultures or differentiated pluripotent stem cells are costly to handle and difficult to implement in high-throughput screening platforms. Thus, cells without malignant traits, optimal differentiation pattern, producible in large and homogeneous amounts and with patient-specific phenotypes would be desirable.

Methods
We have designed and implemented a novel and robust approach to obtain hepatocytes from individuals by direct reprogramming, which is based on a combination of a single doxycycline-inducible polycistronic vector system expressing HNF4A, HNF1A and FOXA3, introduced in human fibroblasts previously transduced with human telomerase reverse transcriptase (hTERT). These cells can be maintained in fibroblast culture media, under standard cell culture conditions.

Results
Clonal hTERT-transduced human fibroblast cell lines can be expanded at least to 110 population doublings without signs of transformation or senescence. They can be easily differentiated at any cell passage number to hepatocyte-like cells with the simple addition of doxycycline to culture media. Acquisition of a hepatocyte phenotype is achieved in just 10 days and requires a simple and non-expensive cell culture media and standard 2D culture conditions. Hepatocytes reprogrammed from low and high passage hTERT-transduced fibroblasts display very similar transcriptomic profiles, biotransformation activities and show analogous pattern behavior in toxicometabolomic studies. Results indicate that this cell model outperforms HepG2 in toxicological screening. The procedure also allows generation of hepatocyte-like cells from patients with given pathological phenotypes. In fact, we succeeded in generating hepatocyte-like cells from a patient with alpha-1 antitrypsin deficiency, which recapitulated accumulation of intracellular alpha-1 antitrypsin polymers and deregulation of unfolded protein response and inflammatory networks.

Conclusion
Our strategy allows the generation of an unlimited source of clonal, homogeneous, non-transformed induced hepatocyte-like cells, capable of performing typical hepatic functions and suitable for pharmaco-toxicological high-throughput testing. Moreover, as far as hepatocyte-like cells derived from fibroblasts isolated from patients suffering hepatic dysfunctions, retain the disease traits, as demonstrated for alpha-1-antitrypsin deficiency, this strategy can be applied to the study of other cases of anomalous hepatocyte functionality.
The COVID-19 pandemic posed many dilemmas for policymakers, which sometimes resulted in unprecedented decision-making
Authors: Ash Nachman , Triki Noa , Waitzberg Ruth 
Published: April 2023

Abstract
Background
The COVID-19 pandemic evolved through five phases, beginning with ‘the great threat’, then moving through ‘the emergence of variants', ‘vaccines euphoria’, and ‘the disillusionment’, and culminating in ‘a disease we can live with’. Each phase required a different governance response. With the progress of the pandemic, data were collected, evidence was created, and health technology was developed and disseminated. Policymaking shifted from protecting the population by limiting infections with non-pharmaceutical interventions to controlling the pandemic by prevention of severe disease with vaccines and drugs for those infected. Once the vaccine became available, the state started devolving the responsibility for the individual’s health and behavior.

Main body
Each phase of the pandemic posed new and unique dilemmas for policymakers, which resulted in unprecedented decision-making. Restrictions to individual’s rights such as a lockdown or the ‘Green Pass policy’ were unimaginable before the pandemic. One of the most striking decisions that the Ministry of Health made was approving the third (booster) vaccine dose in Israel, before it was approved by the FDA or any other country. It was possible to make an informed, evidence-based decision due to the availability of reliable and timely data. Transparent communication with the public probably promoted adherence to the booster dose recommendation. The boosters made an important contribution to public health, even though their uptake was less than the uptake for the initial doses. The decision to approve the booster illustrates seven key lessons from the pandemic: health technology is key; leadership is crucial (both political and professional); a single body should coordinate the actions of all stakeholders involved in the response, and these should collaborate closely; policymakers need to engage the public and win their trust and compliance; data are essential to build a suitable response; and nations and international organizations should collaborate in preparing for and responding to pandemics, because viruses travel without borders.

Conclusion
The COVID-19 pandemic posed many dilemmas for policymakers. The lessons learned from the actions taken to deal with them should be incorporated into preparedness for future challenges.
Access control scheme based on blockchain and attribute-based searchable encryption in cloud environment
Authors: Yan Liang , Ge Lina , Wang Zhe , Zhang Guifen , Xu Jingya , Hu Zheng 
Published: April 2023

AbstractWith the rapid development of cloud computing technology, how to achieve secure access to cloud data has become a current research hotspot. Attribute-based encryption technology provides the feasibility to achieve the above goal. However, most of the existing solutions have high computational and trust costs. Furthermore, the fairness of access authorization and the security of data search can be difficult to guarantee. To address these issues, we propose a novel access control scheme based on blockchain and attribute-based searchable encryption in cloud environment. The proposed scheme achieves fine-grained access control with low computation consumption by implementing proxy encryption and decryption, while supporting policy hiding and attribute revocation. The encrypted file is stored in the IPFS and the metadata ciphertext is stored on the blockchain, which ensures data integrity and confidentiality. Simultaneously, the scheme enables the secure search of ciphertext keyword in an open and transparent blockchain environment. Additionally, an audit contract is designed to constrain user access behavior to dynamically manage access authorization. Security analysis proves that our scheme is resistant to chosen-plaintext attacks and keyword-guessing attacks. Theoretical analysis and experimental results show that our scheme has high computational and storage efficiency, which is more advantageous than other schemes.
Genome profiling of uropathogenic E. coli from strictly defined community-acquired UTI in paediatric patients: a multicentric study
Authors: Mohapatra Sarita , Ghosh Dipannita , Vivekanandan Perumal , Chunchanur Sneha , Venugopal Shwetha , Tak Vibhor , Panigrahy Rajashree , Chaudhuri Susmita , Pundir Swati , Sharma Tanya , Kocher Deepak , Singh Harpreet , Gautam Hitender , Sood Seema , Das Bimal Kumar , Kapil Arti , Kumar Arvind , Kumari Rajesh , Kalaivani Mani , Rangaiah Ambica , Salve Harshal Ramesh , Malhotra Sumit , Kant Shashi , Hari Pankaj ,   Investigators of CAUTION-ED STUDY (Community-acquired UTI & Emerging Drug Resistance), Mohapatra Sarita , Sneha K. C. , Shwetha J. V. , Tak Vibhor , Panigrahy Rajashree , Chaudhuri Susmita 
Published: April 2023

Abstract
Background
Urinary tract infection (UTI) in children is a common bacterial infection. The emergence of extended-spectrum beta-lactamases (ESBLs) poses a major challenge against the treatment of uropathogens. We aimed to characterize the E. coli isolates recovered from children with UTI for their resistance profile and circulating sequence types (ST).

Methods
Children (> 1.5–18 years of age) from different community health centres of India with symptoms of UTI were enrolled. Isolates causing significant bacteriuria were identified by Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) and tested for antimicrobial susceptibility by the automated system, VITEK-2 (Biomeriux, Durhum, US). Nineteen E. coli isolates (15 ESBL positive and 4 ESBL negative) were sequenced in Oxford Nanopore platform followed by core-genome phylogeny, accessory genome cluster analysis, identification of sequence types, mobile genetic elements, genetic antimicrobial resistance markers. The correlation between detection of antimicrobial resistance genes with phenotypic resistance profiles was also investigated.

Results
Eleven percent of children had significant bacteriuria [male:female—1:1, > 50% were 11–18 years of age group]. E. coli was predominant (86%) followed by K. pneumoniae (11%). Susceptibility of E. coli was highest against fosfomycin (100%) followed by carbapenems (90.7%) and nitrofurantoin (88.8%). ST131 (15.8%) and ST167 (10.5%) found as high-risk clones with the presence of plasmid [IncFIB (63.1%), IncFIA (52.6%)], and composite transposon [Tn2680 (46.6%)] in many isolates. Few isolates coharboured multiple beta-lactamases including blaNDM-5 (33.3%), blaOXA-1 (53.3%), blaCTX-M-15 (60%) and blaTEM-4 (60%).

Conclusions
This study highlights horizontal transmission of resistance genes and plasmids in paediatric patients at community centers across the nation harbouring multidrug-resistant genes such as blaNDM-5 and blaCTX-M-15 associated with high-risk clones ST131 and ST167. The data is alarming and emphasizes the need for rapid identification of resistance markers to reduce the spread in community. To our knowledge, this is the first multicentric study targeting paediatric UTI patients from the community setting of India.
Jasmine tea extract enhances human retinal pigment epithelial cells survival after UVB irradiation
Authors: Shang Hu , Guo Yaling , Wu Liangyu , Lin Jinke 
Published: April 2023

AbstractTo examine the protecting effect of jasmine tea extract (JTE) against ultraviolet B (UVB) induced damage on human retinal pigment epithelial (RPE) cells, the RPE cells were subjected to UVB exposure and sequential JTE administration. The cell viability, intracellular reactive oxygen species (ROS), and apoptosis were determined by MTT, 2ʹ,7ʹ-dichlorodihydrofluorescein diacetate and flow cytometer assays, respectively. Further, the cells treated with UVB irradiation and sequential JTE administration were subjected to RNA-sequencing analysis in order to identify genes and pathways involved in the UVB-induced damage and JTE protecting mechanisms. The results showed that JTE effectively attenuated the UVB-induced cell injury by reducing the excessive intracellular ROS generation, and inhibiting the expression of apoptotic genes such as Bax, Caspase-3/9. This finding may offer a promising candidate for the prevention of UVB exposure related eye diseases.
The effect of insurance status on treatment modality in advanced oral cavity cancer
Authors: Sivarajah Shanmugappiriya , Ghods-Esfahani Daniel , Quimby Alexandra , Makki Fawaz , Montagna Giacomo , Seikaly Hadi 
Published: April 2023

Background Insurance status has been shown to impact survival outcomes. We sought to determine whether insurance affects the choice of treatment modality among patients with advanced (T4) oral cavity squamous cell carcinoma. Methods This is a retrospective, population-based cohort study using the Survival, Epidemiology, and End Results Program database. The population included all adult (age ≥ 18) patients with advanced (T4a or T4b) oral cavity squamous cell carcinoma diagnosed from 2007 to 2016. The main outcome was the odds of receiving definitive treatment, defined as primary surgical resection. Insurance status was categorized into uninsured, any Medicaid, and insured groups. Univariable, multivariable, and subgroup analyses were performed. Results The study population consisted of 2628 patients, of whom 1915 (72.9%) were insured, 561 (21.3%) had Medicaid, and 152 (5.8%) were uninsured. The multivariable model showed that patients who were 80 years or older, unmarried, received treatment in the pre-Affordable Care Act (ACA) period, and who were on Medicaid or uninsured were significantly less likely to receive definitive treatment. Insured patients were significantly more likely to receive definitive treatment compared to those on Medicaid or uninsured (OR = 0.59, 95% CI 0.46–0.77, p < 0.0001 [Medicaid vs. Insured]; and OR = 0.48, 95% CI 0.31–0.73 p = 0.001 [Uninsured vs. Insured]), however these differences did not persist when considering only those patients treated following the 2014 expansion of the ACA. Conclusions Insurance status is significantly associated with treatment modality among adults with advanced stage (T4a) oral cavity squamous cell carcinoma. These findings support the premise of expanding insurance coverage in the US. Graphical Abstract
Patient perspectives on non-response to psychotherapy for borderline personality disorder: a qualitative study
Authors: Woodbridge Jane , Townsend Michelle L. , Reis Samantha L. , Grenyer Brin F. S. 
Published: April 2023

Abstract
Background
Despite increasing evidence for the effectiveness of psychotherapy for Borderline Personality Disorder (BPD), estimates show that approximately half of those in treatment do not clinically improve or reach reliable change criteria. There are limited qualitative descriptions of treatment factors associated with non-response from the perspectives of those struggling to improve.

Method
Eighteen people (72.2% female, mean age 29.4 (SD = 8)) with experience of receiving psychotherapeutic treatment for BPD were interviewed to obtain their perspectives on hindering factors in treatment and what may be helpful to reduce non-response. The data in this qualitative study was analysed thematically.

Results
Four domains were created from the insights patients shared on non-response and what may be needed to mitigate it. The focus of Domain 1 was that therapy cannot be effective until two factors are in place. First, the patient needs sufficient safety and stability in their environment in order to face the challenges of therapy. Second, they need to be able to access therapy. Domain 2 described factors the patients themselves contribute. The themes in this domain were described as phases that need to be progressed through before therapy can be effective. These phases were ceasing denial that help is warranted and deserved, taking responsibility for behaviours that contribute to unwellness, and committing to the hard work that is required for change. Domain 3 described how the lack of a safe alliance and ruptures in the safety of the relationship with the therapist can contribute to non-response. Domain 4 was comprised of factors that patients identified as supportive of moving through the barriers to response. The first theme in this domain was prioritising the safety of the therapy relationship. The second theme was giving a clear diagnosis and taking a collaborative approach in sessions. The final theme described the importance of focusing on practical goals with the patient to create tangible life changes.

Conclusion
This study found that non-response is complex and multifaceted. First, it is clear that systems need to be in place to support access to adequate care and foster life stability. Second, considerable effort may be needed at the engagement phase of therapy to clarify expectations. Third, attention to specific interpersonal challenges between patients and therapists is an important focus. Finally, structured work to improve relationships and vocational outcomes is indicated.
Towards a novel strategy for soot removal from water-soluble materials: the synergetic effect of hydrogels and cyclomethicone on gelatine emulsion-based photographs
Authors: Ortega Saez Natalia , Arno Robbe , Marchetti Andrea , Cauberghs Sabine , Janssens Koen , Van der Snickt Geert , Al-Emam Ehab 
Published: April 2023

Abstract
Gels are a popular cleaning method for paper conservators and a lot of research has been done concerning gel cleaning of paper objects over the last 15 years. Despite the close interconnection between the conservation fields of paper and photographic material, research on using gels for cleaning photographs is very scarce. However, gels can provide an excellent cleaning method for photographic material. Cleaning silver gelatine prints with aqueous solvents is very complex due to the hydrophilic properties and fragility of the gelatine layer which makes mechanical cleaning difficult. The properties of gels ensure better control over the flow and evaporation of the solvent, facilitating the cleaning process. This study is the first insight into the viability of using gellan gum gel and polyvinyl acetate-borax (PVAc-borax) gel to clean contaminants from the surface of silver gelatine photographs. It is based on self-made samples that were artificially aged and contaminated with soot. Water, ethanol (EtOH), and Kodak Photo-flo were studied as solvents to remove the soot from the silver gelatine-based prints. These solvents were loaded into the aforementioned gels and applied to the samples in two different methods. These gel cleaning methods were subsequently compared with traditional cleaning methods. In addition, the usage of cyclomethicone D4 as a protective mask for the gelatine layer was studied. Measuring methods used to evaluate the cleaning were visual comparison, microscopic observation, and densitometry. ATR-FTIR measurements were also conducted to investigate potential side-effects of the cleaning methods on the prints, such as unwanted chemical transformations or the presence of gel residues after the treatments. Most of the gel cleaning methods within this study proved to be inadequate, with the exception of the gellan gum gel loaded with 30% EtOH. It was used as a granulated gel applied mechanically on a print saturated with cyclomethicone (octamethylcyclotetrasiloxane D4). Cyclomethicone proved to be a very effective protective barrier for the water-sensitive gelatine layer with minimal reduction in cleaning effectiveness.
Morpho-anatomical, and chemical characterization of some calcareous Mediterranean red algae species
Authors: Ismail Mona M. , Ismail Gehan A. , Elshobary Mostafa E. 
Published: April 2023

AbstractClimatic changes are anticipated to have a detrimental effect on calcifying marine species. Calcareous red algae may be especially vulnerable to seasonal variations since they are common and essential biologically, but there is little research on the morpho-anatomical, and chemical characterization of such species. This study conducted the seasonal investigation of the three dominant Mediterranean calcified red algae. Morphological and 18S rRNA analysis confirmed the identification of collected species asCorallina officinalis, Jania rubens,andAmphiroa rigida. In general,C. officinaliswas represented in the four seasons and flourishing maximum in autumn (70% of total species individuals). WhileJ. rubensspecies was represented in winter, autumn, and spring and completely absent in summer.A. rigidawas abundant only in the summer season by 40%. A full morphological and anatomical description of these species were examined, and their chemical compositions (carbohydrate, protein, lipid, pigments, and elements content) were assessed in different seasons, where carbohydrates were the dominant accumulates followed by proteins and lipids. Pearson correlation analysis confirmed a positive correlation between salinity level and nitrogenous nutrients of the seawater with the pigment contents (phycobiliproteins, carotenoids, and chlorophyll a) of the studied seaweeds. The results proved that calcified red algae were able to deposit a mixture of calcium carbonates such as calcite, vaterite, calcium oxalate, calcite-III I calcium carbonate, and aragonite in variable forms depending on the species.