bluuebunny/crossref_metadata_2025_split huggingface dataset:
AI/ML combined with next-generation sequencing of VHH immune repertoires enables the rapid identification of de novo humanized and sequence-optimized single domain antibodies: a prospective case study
Authors: Arras Paul , Yoo Han Byul , Pekar Lukas , Clarke Thomas , Friedrich Lukas , Schröter Christian , Schanz Jennifer , Tonillo Jason , Siegmund Vanessa , Doerner Achim , Krah Simon , Guarnera Enrico , Zielonka Stefan , Evers Andreas 
Published: October 2023

Introduction: In this study, we demonstrate the feasibility of yeast surface display (YSD) and nextgeneration sequencing (NGS) in combination with artificial intelligence and machine learning methods (AI/ML) for the identification of de novo humanized single domain antibodies (sdAbs) with favorable early developability profiles.Methods: The display library was derived from a novel approach, in which VHH-based CDR3 regions obtained from a llama (Lama glama), immunized against NKp46, were grafted onto a humanized VHH backbone library that was diversified in CDR1 and CDR2. Following NGS analysis of sequence pools from two rounds of fluorescence-activated cell sorting we focused on four sequence clusters based on NGS frequency and enrichment analysis as well as in silico developability assessment. For each cluster, long short-term memory (LSTM) based deep generative models were trained and used for the in silico sampling of new sequences. Sequences were subjected to sequence- and structure-based in silico developability assessment to select a set of less than 10 sequences per cluster for production.Results: As demonstrated by binding kinetics and early developability assessment, this procedure represents a general strategy for the rapid and efficient design of potent and automatically humanized sdAb hits from screening selections with favorable early developability profiles.
Dietary intake of total vegetable, fruit, cereal, soluble and insoluble fiber and risk of all-cause, cardiovascular, and cancer mortality: systematic review and dose–response meta-analysis of prospective cohort studies
Authors: Yao Feifei , Ma Jianping , Cui Yong , Huang Cuihong , Lu Ruiqi , Hu Fulan , Zhu Xiaoming , Qin Pei 
Published: October 2023

ObjectivesTo conduct a systematic review and meta-analysis of prospective cohort studies to investigate the association between total, vegetable, fruit, cereal, soluble and insoluble fiber intake and risk of all causes, cardiovascular disease (CVD), and cancer mortality and quantitatively assess the dose–response relation.MethodsEligible studies were identified by searching PubMed, Embase and Web of science before August 2023. Random effects models were used to calculate summary relative risk (RR) and 95% confidence intervals (CI) and restricted cubic splines to model the linear/non-linear association.ResultsThe summary RR for all-cause, CVD and cancer mortality of dietary fiber was 0.90 (95% CI: 0.86,0.93), 0.87 (0.84,0.91), 0.91 (0.88,0.93), respectively. Significant association was observed for all-cause and CVD mortality with fruit, vegetable cereal and soluble fiber intake and cancer mortality with cereal fiber intake. No significant association was found for insoluble fiber, vegetable or fruit fiber intake and cancer mortality. Dose-response analysis showed a significant non-linear relation of dietary fiber intake with all-cause mortality, and linear relation for others.ConclusionsHigher dietary fiber including different type and food sources of fiber intake were associated with lower risk of mortality. Our findings provide more comprehensive evidence on dietary fiber intake with mortality.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier: CRD42022338837.
Does perioperative allogeneic blood transfusion worsen the prognosis of patients with hepatocellular carcinoma? A meta-analysis of propensity score-matched studies
Authors: Hu Lingbo , Li Zhenyu , Qiao Yingli , Wang Aidong 
Published: October 2023

BackgroundAllogeneic blood transfusion is required in a part of liver resection. The effect of allogeneic blood transfusion on the prognosis of patients with hepatocellular carcinoma (HCC) remains controversial. To investigate whether perioperative allogeneic blood transfusion (PBT) affects the long-term prognosis of patients with HCC, we conducted a meta-analysis that included only propensity score-matched (PSM) studies.MethodsThe Cochrane Library, Embase, PubMed, and Web of Science databases were systematically searched to identify PSM studies that compared the long-term outcomes of allogeneic blood transfusion in resected HCC patients. Overall survival (OS) and recurrence-free survival (RFS) rates were calculated.ResultsThis meta-analysis included 9 PSM studies with 12 datasets involving 2476 patients. Lower OS and RFS in HCC patients receiving allogeneic blood transfusion were observed than those in patients not receiving blood transfusion (OS: hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.10–1.64; p &lt; 0.01; RFS: HR, 1.29; 95% CI, 1.07–1.56; p &lt; 0.01). Subgroup analysis revealed that among patients with BCLC A HCC, those receiving allogeneic blood transfusion had lower OS and RFS (OS: HR, 2.27; 95% CI, 1.61–3.21; RFS: HR, 2.11; 95% CI, 1.30–3.41). OS and RFS were similar in both groups of patients with BCLC B and C HCC.ConclusionThe receipt of perioperative allogeneic blood transfusion is associated with a decrease in OS and RFS. These results seem to be reliable for patients in BCLC stage A. But more high-quality research is needed to confirm this conclusion.
Real-world outcomes of diffuse large B-cell lymphoma in the biosimilar era
Authors: Nair Reena , Bhat Gull Mohammad , Agrawal Narendra , Sengar Manju , Malhotra Pankaj , Nityanand Soniya , Lele Chitra , Reddy Pramod , Kankanwadi Suresh , Maharaj Narendra 
Published: October 2023

BackgroundDiffuse large B-cell lymphoma (DLBCL) is an aggressive and the most common type of non-Hodgkin lymphoma (NHL). The clinical use of rituximab has improved the treatment response and survival of patients with DLBCL. The introduction of rituximab biosimilar into healthcare system has helped in providing a cost-effective treatment to B-cell lymphoid malignancies as standard of care and has improved access to patients worldwide. The aim of this study was to observe the real-world effectiveness and safety of Reditux™ and Ristova®in DLBCL patients.MethodsObservational study in adults with DLBCL receiving Reditux™ or Ristova®across 29 centers in India (2015–2022). Effectiveness and safety were assessed up to 2 years after first dose.ResultsOut of 1,365 patients considered for analysis, 1,250 (91.6%) were treated with Reditux™ and 115 (8.42%) with Ristova®. At 2 years, progression-free survival (PFS) 69% [hazard ratio (HR), 1.16; 95% CI, 0.80–1.67], overall survival (OS) 78.7% (HR, 1.20; 95% CI, 0.78–1.86), response rates, quality of life (QoL), and overall safety in both the cohorts were comparable. The best overall response rate (BORR) at 6 months was comparable with no statistically significant differences between the Reditux™ and the Ristova®cohorts (89.2% vs. 94.3%). In multivariate analysis, BCL-2 and VAS were significant prognostic factors for PFS.ConclusionReditux™ and Ristova®were comparable in real-world setting.Clinical Trial RegistrationISRCTN registry, identifier (ISRCTN13301166)
Predicting head and neck cancer treatment outcomes with pre-treatment quantitative ultrasound texture features and optimising machine learning classifiers with texture-of-texture features
Authors: Safakish Aryan , Sannachi Lakshmanan , DiCenzo Daniel , Kolios Christopher , Pejović-Milić Ana , Czarnota Gregory J. 
Published: October 2023

AimCancer treatments with radiation present a challenging physical toll for patients, which can be justified by the potential reduction in cancerous tissue with treatment. However, there remain patients for whom treatments do not yield desired outcomes. Radiomics involves using biomedical images to determine imaging features which, when used in tandem with retrospective treatment outcomes, can train machine learning (ML) classifiers to create predictive models. In this study we investigated whether pre-treatment imaging features from index lymph node (LN) quantitative ultrasound (QUS) scans parametric maps of head &amp; neck (H&amp;N) cancer patients can provide predictive information about treatment outcomes.Methods72 H&amp;N cancer patients with bulky metastatic LN involvement were recruited for study. Involved bulky neck nodes were scanned with ultrasound prior to the start of treatment for each patient. QUS parametric maps and related radiomics texture-based features were determined and used to train two ML classifiers (support vector machines (SVM) and k-nearest neighbour (k-NN)) for predictive modeling using retrospectively labelled binary treatment outcomes, as determined clinically 3-months after completion of treatment. Additionally, novel higher-order texture-of-texture (TOT) features were incorporated and evaluated in regards to improved predictive model performance.ResultsIt was found that a 7-feature multivariable model of QUS texture features using a support vector machine (SVM) classifier demonstrated 81% sensitivity, 76% specificity, 79% accuracy, 86% precision and an area under the curve (AUC) of 0.82 in separating responding from non-responding patients. All performance metrics improved after implementation of TOT features to 85% sensitivity, 80% specificity, 83% accuracy, 89% precision and AUC of 0.85. Similar trends were found with k-NN classifier.ConclusionBinary H&amp;N cancer treatment outcomes can be predicted with QUS texture features acquired from index LNs. Prediction efficacy improved by implementing TOT features following methodology outlined in this work.
Microenvironmental immune cell alterations across the spectrum of nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma
Authors: Panayi Christos , Akarca Ayse U. , Ramsay Alan D. , Shankar Ananth G. , Falini Brunangelo , Piris Miguel A. , Linch David , Marafioti Teresa 
Published: October 2023

BackgroundThe clinicopathological spectrum of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), also known as nodular lymphocyte predominant B-cell lymphoma, partially overlaps with T-cell/histiocyte-rich large B-cell lymphoma (THRLCBL). NLPHL histology may vary in architecture and B-cell/T-cell composition of the tumour microenvironment. However, the immune cell phenotypes accompanying different histological patterns remain poorly characterised.MethodsWe applied a multiplexed immunofluorescence workflow to identify differential expansion/depletion of multiple microenvironmental immune cell phenotypes between cases of NLPHL showing different histological patterns (as described by Fan et al, 2003) and cases of THRLBCL.ResultsFOXP3-expressing T-regulatory cells were conspicuously depleted across all NLPHL cases. As histology progressed to variant Fan patterns C and E of NLPHL and to THRLBCL, there were progressive expansions of cytotoxic granzyme-B-expressing natural killer and CD8-positive T-cells, PD1-expressing CD8-positive T-cells, and CD163-positive macrophages including a PDL1-expressing subset. These occurred in parallel to depletion of NKG2A-expressing natural killer and CD8-positive T-cells.DiscussionThese findings provide new insights on the immunoregulatory mechanisms involved in NLPHL and THLRBCL pathogenesis, and are supportive of an increasingly proposed biological continuum between these two lymphomas. Additionally, the findings may help establish new biomarkers of high-risk disease, which could support a novel therapeutic program of immune checkpoint interruption targeting the PD1:PDL1 and/or NKG2A:HLA-E axes in the management of high-risk NLPHL and THRLBCL.
Revealing the dynamic landscape of drug-drug interactions through network analysis
Authors: Jeong Eugene , Malin Bradley , Nelson Scott D. , Su Yu , Li Lang , Chen You 
Published: October 2023

Introduction: The landscape of drug-drug interactions (DDIs) has evolved significantly over the past 60 years, necessitating a retrospective analysis to identify research trends and under-explored areas. While methodologies like bibliometric analysis provide valuable quantitative perspectives on DDI research, they have not successfully delineated the complex interrelations between drugs. Understanding these intricate relationships is essential for deciphering the evolving architecture and progressive transformation of DDI research structures over time. We utilize network analysis to unearth the multifaceted relationships between drugs, offering a richer, more nuanced comprehension of shifts in research focus within the DDI landscape.Methods: This groundbreaking investigation employs natural language processing, techniques, specifically Named Entity Recognition (NER) via ScispaCy, and the information extraction model, SciFive, to extract pharmacokinetic (PK) and pharmacodynamic (PD) DDI evidence from PubMed articles spanning January 1962 to July 2023. It reveals key trends and patterns through an innovative network analysis approach. Static network analysis is deployed to discern structural patterns in DDI research, while evolving network analysis is employed to monitor changes in the DDI research trend structures over time.Results: Our compelling results shed light on the scale-free characteristics of pharmacokinetic, pharmacodynamic, and their combined networks, exhibiting power law exponent values of 2.5, 2.82, and 2.46, respectively. In these networks, a select few drugs serve as central hubs, engaging in extensive interactions with a multitude of other drugs. Interestingly, the networks conform to a densification power law, illustrating that the number of DDIs grows exponentially as new drugs are added to the DDI network. Notably, we discovered that drugs connected in PK and PD networks predominantly belong to the same categories defined by the Anatomical Therapeutic Chemical (ATC) classification system, with fewer interactions observed between drugs from different categories.Discussion: The finding suggests that PK and PD DDIs between drugs from different ATC categories have not been studied as extensively as those between drugs within the same categories. By unearthing these hidden patterns, our study paves the way for a deeper understanding of the DDI landscape, providing valuable information for future DDI research, clinical practice, and drug development focus areas.
Narrative abilities in individuals with Down syndrome: single case-profiles
Authors: Neitzel Isabel 
Published: October 2023

IntroductionNarrative abilities are an important part of our everyday lives and social interaction with others. Nevertheless, narration is a complex ability influenced by language and cognition. This makes it difficult for individuals with language and cognitive impairment, such as in children and adolescents with Down syndrome. Previous studies have shown distinct narrative impairments in individuals with Down syndrome; nevertheless, this research was based on overall group means in most cases. To identify individual strengths and weaknesses and to draw conclusions for speech and language therapy, the narrative profile of every participant should be considered equally. Following this approach, the current study aims to describe single case narrative profiles in individuals with Down syndrome.MethodsThe narrative transcripts of 28 children and adolescents with Down syndrome (aged 10;0–20;1), based on a non-verbal picture book, were rated using the Narrative Scoring Scheme across seven macro- and microstructural categories. Point scores across the whole group are displayed – nevertheless, the paper specifically addresses the individual narrative profiles of the participants. The participants could be assigned to narrative profile groups which show different characteristics, strengths and weaknesses. Group comparisons and correlations were computed for the relation to language abilities (especially vocabulary) and nonverbal cognitive abilities.ResultsThe results of the two profile groups with minimal and developing narrative skills differ significantly not only concerning narrative outcomes in the Narrative Scoring Scheme but also for language abilities and developmental stage of nonverbal cognition. Individuals that show floor effects in narrative abilities are characterized by an overall weakness in language and cognition. In contrast, a group of approximately equal size shows distinct strengths in their narrative profiles which are in line with their vocabulary strengths, MLU and nonverbal cognition.DiscussionThe current study uses a new approach to identify individual narrative profiles in a group of individuals with Down syndrome. The results of the investigation underline the existence of narrative impairments in many individuals with Down syndrome but also point to individual strengths of the participants. Furthermore, the study outcomes suggest that narrative abilities might be representative for overall language and cognition in individuals with Down syndrome. However, intervention studies addressing narration are missing.
Assessment of users’ behavior in Lithuanian online communities
Authors: Skarzauskiene Aelita , Mačiulienė Monika 
Published: October 2023

IntroductionOnline communities are gaining importance in modern society by actively structuring public opinion and initiating discussions about various socio-economical issues. As information and communication technologies advance, the online communities are confronted with novel technological and societal hurdles (the spread of misinformation, lack of active participation). To boost their efficacy and productivity, it’s crucial to enhance our understanding of user behavior, communication avenues and potential future trends of development.ObjectiveOnline platforms serve a function beyond simply sharing information or knowledge; they act as influential social networks affecting various societal sectors, including politics, culture and the economy. There is a need to recognize online communities not as static entities, but as dynamic, evolving systems of collective intelligence.MethodsA representative quantitative study was carried out between 1 to 30 of October 2022 through direct, in-person interviews conducted at the respondent’s residence (known as an Omnibus survey). The sample of respondents is representative of the entire population of Lithuania regarding essential socio-demographic characteristics. By thoroughly analyzing data gathered from a comprehensive quantitative study, the study raises awareness of the issues surrounding online communities, while also shedding light on social networking behavior within these virtual spaces.DiscussionDespite the multitude of challenges inherent to virtual communication, there remains a significant knowledge gap in comprehending general user behavior within these online communities. The current research aims to bridge this gap by investigating user behavior in Lithuanian online communities.
Association between COVID-19 vaccination and critical outcomes among older adults with dementia: a comparative cohort study
Authors: Radomyslsky Zorian , Kivity Sara , Lidar Shira , Bentur Netta , Korn Liat , Nissanholtz-Gannot Rachel , Sternberg Shelley , Halevi Hochwald Inbal , Reges Orna , Alon Yaniv , Saban Mor 
Published: October 2023

BackgroundAs COVID-19 vaccines became available, understanding their potential benefits in vulnerable populations has gained significance. This study explored the advantages of COVID-19 vaccination in individuals with cognitive disorders by analyzing health-related variables and outcomes.MethodsA prospective cohort study analyzed electronic medical records of 25,733 older adults with cognitive disorders and 65,544 older adults without cognitive disorders from March 2020 to February 2022. COVID-19 vaccination status was the primary exposure variable, categorized as fully vaccinated or unvaccinated. The primary outcomes measured were all-cause mortality and hospitalization rates within 14 and 400 days post-vaccination. Data on vaccination status, demographics, comorbidities, testing history, and clinical outcomes were collected from electronic health records. The study was ethically approved by the relevant medical facility’s Institutional Review Board (0075-22-MHS).ResultsVaccinated individuals had significantly lower mortality rates in both groups. In the research group, the mortality rate was 52% (n = 1852) for unvaccinated individuals and 7% (n = 1,241) for vaccinated individuals (p &lt; 0.001). Similarly, in the control group, the mortality rate was 13.58% (n = 1,508) for unvaccinated individuals and 1.85% (n = 936) for vaccinated individuals (p &lt; 0.001), despite higher COVID-19 positivity rates. In the research group, 30.26% (n = 1,072) of unvaccinated individuals tested positive for COVID-19, compared to 37.16% (n = 6,492) of vaccinated individuals (p &lt; 0.001). In the control group, 17.31% (n = 1922) of unvaccinated individuals were COVID-19 positive, while 37.25% (n = 18,873) of vaccinated individuals tested positive (p &lt; 0.001). Vaccination also showed potential benefits in mental health support. The usage of antipsychotic drugs was lower in vaccinated individuals (28.43%, n = 4,967) compared to unvaccinated individuals (37.48%, n = 1,328; 95% CI [0.92–1.28], p &lt; 0.001). Moreover, vaccinated individuals had lower antipsychotic drug prescription rates (23.88%, n = 4,171) compared to unvaccinated individuals (27.83%, n = 968; 95% CI [−1.02 to −0.63], p &lt; 0.001). Vaccination appeared to have a positive impact on managing conditions like diabetes, with 38.63% (n = 6,748) of vaccinated individuals having diabetes compared to 41.55% (n = 1,472) of unvaccinated individuals (95% CI [0.24, 0.48], p &lt; 0.001).DiscussionThe findings highlight the importance of vaccination in safeguarding vulnerable populations during the pandemic and call for further research to optimize healthcare strategies for individuals with cognitive disorders.
Nitrogen-Activated CLV3/ESR-Related 4 (CLE4) Regulates Shoot, Root, and Stolon Growth in Potato
Authors: Gancheva Maria S. , Lutova Lyudmila A. 
Published: October 2023

In potato, high levels of nitrogen (N) can lead to excessive vegetative growth at the expense of tuber development, resulting in lower yield and poor-quality tubers. We found that Solanum tuberosum CLE4 (StCLE4) is expressed most strongly in the roots grown in N-rich media, and it positively regulates potato root growth under N-deficient conditions. We noted that StCLE4 functions as a negative regulator of normal shoot apex development similar to CLV3 in Arabidopsis. Transcriptomic analysis revealed that overexpression of StCLE4 resulted in the repression of the StIT1 gene, a regulator of potato tuber initiation. StCLE4-overexpressing stolons were converted into branches, that were similar to a mild phenotype of the it1 (identity of tuber 1) mutant. We also found that NIN-like proteins, key regulators of nitrate signaling bind to the regulatory sequence of StIT1 in a yeast one-hybrid assay. Taken together, our findings suggest that StCLE4 regulates shoot, root, and stolon growth in potato.
نمذجة نقل أيونات CaBr2 من خلال غشاء الترشيح النانوي الخزفي
Authors: حجرات رشا , الفساطلة هديل , الهقيش روان , نادر سلام 
Published: October 2023

تم استخدام معادلة Nernst-Planck لمحاولة فهم سلوك فصل Ca2+ وBr1-. أيونات باستخدام غشاء الترشيح النانوي. تم تشغيل النموذج لمسام غشاء مختلفة، وتدفق حجمي مختلف بناءً على قيم مساحة السطحية للغشاء، وتركيز أيونات مختلفة؛ لدراسة سلوك الفصل الأفضل. بشكل عام، كلما زاد نصف قطر مسام الغشاء، انخفض فصل Ca2+ وBr1-. أيونات؛ حيث كان نسبة فصل أيون Ca2+ أعلى من نسبة فصل أيونBr1-. بينما زاد نسبة فصل Ca2+و Br1-أيونات مع زيادة التدفق الحجمي بناءً على مساحة الغشاء الطحية. من ناحية أخرى، كان تركيز Br- داخل الطبقة النشطة للغشاء أعلى من تركيز أيونات .Ca2+ وبالتالي فإن نسبة فصل الأيونات يتأثر بنصف قطر مسام الغشاء بجانب التدفق الحجمي بناءً على المساحة السطحية للغشاء.