bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ide-cel vs standard regimens in triple-class–exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses
Authors: Ailawadhi Sikander , Arnulf Bertrand , Patel Krina , Cavo Michele , Nooka Ajay K. , Manier Salomon , Callander Natalie , Costa Luciano J. , Vij Ravi , Bahlis Nizar J. , Moreau Philippe , Solomon Scott , Abrahamsen Ingerid Weum , Baz Rachid , Broijl Annemiek , Chen Christine , Jagannath Sundar , Raje Noopur , Scheid Christof , Delforge Michel , Benjamin Reuben , Pabst Thomas , Iida Shinsuke , Berdeja Jesús , Giralt Sergio , Truppel-Hartmann Anna , Chen Yanping , Zhong Xiaobo , Wu Fan , Piasecki Julia , Eliason Laurie , Dhanda Devender , Felten Jasper , Caia Andrea , Cook Mark , Popa McKiver Mihaela , Rodríguez-Otero Paula 
Published: August 2024

Abstract
Outcomes are poor in triple-class–exposed (TCE) relapsed and refractory multiple myeloma (R/RMM). In the phase 3 KarMMa-3 trial, patients with TCE R/RMM and 2 to 4 prior regimens were randomized 2:1 to idecabtagene vicleucel (ide-cel) or standard regimens (SRs). An interim analysis (IA) demonstrated significantly longer median progression-free survival (PFS; primary end point; 13.3 vs 4.4 months; P &lt; .0001) and higher overall response rate (ORR) with ide-cel vs SRs. At final PFS analysis (median follow-up, 30.9 months), ide-cel further improved median PFS vs SRs (13.8 vs 4.4 months; hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.38-0.63). PFS benefit with ide-cel vs SRs was observed regardless of number of prior lines of therapy, with greatest benefit after 2 prior lines (16.2 vs 4.8 months, respectively). ORR benefit was maintained with ide-cel vs SRs (71% vs 42%; complete response, 44% vs 5%). Patient-centric design allowed crossover from SRs (56%) to ide-cel upon progressive disease, confounding overall survival (OS) interpretation. At IA of OS, median was 41.4 (95% CI, 30.9 to not reached [NR]) vs 37.9 (95% CI, 23.4 to NR) months with ide-cel and SRs, respectively (HR, 1.01; 95% CI, 0.73-1.40); median OS in both arms was longer than historical data (9-22 months). Two prespecified analyses adjusting for crossover showed OS favoring ide-cel. This trial highlighted the importance of individualized bridging therapy to ensure adequate disease control during ide-cel manufacturing. Ide-cel improved patient-reported outcomes vs SRs. No new safety signals were reported. These results demonstrate the continued favorable benefit-risk profile of ide-cel in early-line and TCE R/RMM. This trial was registered at www.ClinicalTrials.gov as #NCT03651128.
Genomic analysis of adult thrombotic microangiopathies in less than 3 days: from rapid to fast genomics to treatment
Authors: Yousfi Nadhir , Mousseaux Cyril , Hamza Abderaouf , Laville Pierre , Mille Marie , Philippe Nicolas , Dancer Marine , Bouder Christophe , Luque Yosu , Rafat Cédric , Mesnard Laurent 
Published: August 2024

Abstract
Using nanopore sequencing, we showed the feasibility and impact of rapid genomic screening for managing thrombotic microangiopathies in 18 prospective cases, achieving diagnoses in &lt;3 days. We compared the results with standard exome sequencing, cost efficiency, and complement blockade initiation.
The use of biostimulants as a key to sustainable hydroponic lettuce farming under saline water stress
Authors: İkiz Boran , Dasgan Hayriye Yildiz , Balik Sibel , Kusvuran Sebnem , Gruda Nazim S. 
Published: August 2024

Abstract
Backround
The utilization of high-quality water in agriculture is increasingly constrained by climate change, affecting availability, quality, and distribution due to altered precipitation patterns, increased evaporation, extreme weather events, and rising salinity levels. Salinity significantly challenges salt-sensitive vegetables like lettuce, particularly in a greenhouse. Hydroponics water quality ensures nutrient solution stability, enhances nutrient uptake, prevents contamination, regulates pH and electrical conductivity, and maintains system components. This study aimed to mitigate salt-induced damage in lettuce grown via the floating culture method under 50 mM NaCl salinity by applying biostimulants.

Results
We examined lettuce’s physiological, biochemical, and agronomical responses to salt stress after applying biostimulants such as amino acids, arbuscular mycorrhizal fungi, plant growth-promoting rhizobacteria (PGPR), fulvic acid, and chitosan. The experiment was conducted in a greenhouse with a randomized complete block design, and each treatment was replicated four times. Biostimulant applications alleviated salt’s detrimental effects on plant weight, height, leaf number, and leaf area. Yield increases under 50 mM NaCl were 75%, 51%, 31%, 34%, and 33% using vermicompost, PGPR, fulvic acid, amino acid, and chitosan, respectively. Biostimulants improved stomatal conductance (58–189%), chlorophyll content (4–10%), nutrient uptake (15–109%), and water status (9–107%). They also reduced MDA content by 26–42%. PGPR (1.0 ml L‒1), vermicompost (2 ml L‒1), and fulvic acid (40 mg L‒1) were particularly effective, enhancing growth, yield, phenol, and mineral content while reducing nitrate levels under saline conditions.

Conclusions
Biostimulants activated antioxidative defense systems, offering a sustainable, cost-effective solution for mitigating salt stress in hydroponic lettuce cultivation.
Optimized deep CNN for detection and classification of diabetic retinopathy and diabetic macular edema
Authors: Thanikachalam V , Kabilan K , Erramchetty Sudheer Kumar 
Published: August 2024

AbstractDiabetic Retinopathy (DR) and Diabetic Macular Edema (DME) are vision related complications prominently found in diabetic patients. The early identification of DR/DME grades facilitates the devising of an appropriate treatment plan, which ultimately prevents the probability of visual impairment in more than 90% of diabetic patients. Thereby, an automatic DR/DME grade detection approach is proposed in this work by utilizing image processing. In this work, the retinal fundus image provided as input is pre-processed using Discrete Wavelet Transform (DWT) with the aim of enhancing its visual quality. The precise detection of DR/DME is supported further with the application of suitable Artificial Neural Network (ANN) based segmentation technique. The segmented images are subsequently subjected to feature extraction using Adaptive Gabor Filter (AGF) and the feature selection using Random Forest (RF) technique. The former has excellent retinal vein recognition capability, while the latter has exceptional generalization capability. The RF approach also assists with the improvement of classification accuracy of Deep Convolutional Neural Network (CNN) classifier. Moreover, Chicken Swarm Algorithm (CSA) is used for further enhancing the classifier performance by optimizing the weights of both convolution and fully connected layer. The entire approach is validated for its accuracy in determination of grades of DR/DME using MATLAB software. The proposed DR/DME grade detection approach displays an excellent accuracy of 97.91%.
Behavioral, cognitive and emotional determinants of getting vaccinated for COVID-19 and the mediating role of institutional trust among young adults in Cyprus
Authors: Konstantinou Pinelopi , Kyprianidou Maria , Christodoulou Andria , McHugh Louise , Constantinou Marios , Epiphaniou Eleni , Vahey Nigel , Nicolaou Christiana , Middleton Nicos , Karekla Maria , Kassianos Angelos P. 
Published: August 2024

Abstract
Background
Vaccination uptake is a complex behavior, influenced by numerous factors. Behavioral science theories are commonly used to explain the psychosocial determinants of an individual’s health behavior. This study examined the behavioural, cognitive, and emotional determinants of COVID-19 vaccination intention based on well-established theoretical models: Acceptance and Commitment Therapy (ACT), Capability, Opportunity, Motivation, and Behaviour (COM-B) and the Health Belief Model (HBM). Additionally, it examined the mediating role of institutional trust in the relationship between determinants of these models and vaccination intentions.

Methods
A cross-sectional study was conducted from January to May 2022, where university students in Cyprus completed an online survey.

Results
A total of 484 university students completed the online survey, with 23.8% reporting being vaccinated with fewer than three vaccination doses and/or no intention to vaccinate further. Hierarchical logistic regression analysis showed that higher scores in institutional trust, perceived severity, motivation, physical and psychological capability were significantly associated with higher odds of intending to vaccinate. Higher psychological flexibility and not being infected with COVID-19 were also associated with higher odds of vaccination intention, but not in the final model when all determinants were included. Additionally, significant indirect effects of psychological and physical capability, motivation and perceived severity on vaccination intention were found to be mediated by institutional trust.

Conclusions
When tackling COVID-19 vaccination hesitancy, behavioural, cognitive, and emotional aspects should be considered. Stakeholders and policymakers are advised to implement targeted vaccination programs in young people while at the same time building trust and improving their capabilities and motivation towards getting vaccinated.
A double-masked, sham-controlled trial of rose bengal photodynamic therapy for the treatment of fungal and acanthamoeba keratitis: Rose Bengal Electromagnetic Activation with Green Light for Infection Reduction (REAGIR) study
Authors: Prajna NV , Lalitha P , Sharma S , de Freitas D , Höfling-Lima A , Varnado N , Abdelrahman S , Cavallino V , Arnold BF , Lietman TM , Rose-Nussbaumer J 
Published: August 2024

Abstract
Background
Infectious keratitis secondary to fungus or acanthamoeba often has a poor outcome despite receiving the best available medical therapy. In vitro rose bengal photodynamic therapy (RB-PDT) appears to be effective against fungal and acanthamoeba isolates (Atalay HT et al., Curr Eye Res 43:1322–5, 2018, Arboleda A et al. Am J Ophthalmol 158:64-70, 2014). In one published series, RB-PDT reduced the need for therapeutic penetrating keratoplasty in severe bacterial, fungal, and acanthamoeba keratitis not responsive to medical therapy.

Methods
This international, randomized, sham and placebo controlled 2-arm clinical trial randomizes patients with smear positive fungal and acanthamoeba and smear negative corneal ulcers in a 1:1 fashion to one of two treatment arms: 1) topical antimicrobial plus sham RB-PDT or 2) topical antimicrobial plus RB-PDT.

Discussion
We anticipate that RB-PDT will improve best spectacle-corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via ClinicalTrials.gov website, meetings, and journal publications. Our data will also be available upon reasonable request.

Trial registration
NCT, NCT05110001, Registered on November 5, 2021.
Intra- and interspecific variation of Amblyomma ticks from southern Africa
Authors: Smit Andeliza , Mulandane Fernando , Labuschagne Martinet , Wójick Stephané Heike , Malabwa Choolwe , Sili Gourgelia , Mandara Stephen , Dlamkile Zinathi , Ackermann Rebecca , Rose Vineer Hannah , Stoltsz Wilhelm Heinrich , Huber Karine , Horak Ivan Gerard , Morar-Leather Darshana , Makepeace Benjamin Lawrence , Neves Luis 
Published: August 2024

Abstract
Background
Amblyomma spp. ticks, known for their long mouthparts, bright ornate appearance and aggressive hunting behaviour, are vectors of a number of important pathogens. In southern Africa, 17 Amblyomma spp. are currently documented. Of these species, Amblyomma hebraeum and Amblyomma variegatum have been well studied due to their wide geographical range and their status as competent vectors of pathogens that are of veterinary and medical importance. Studies on other Amblyomma spp. in southern Africa have been neglected, fostering ongoing debates on the validity of certain species such as Amblyomma pomposum. This study investigated the inter- and intra-species variation of Amblyomma ticks collected in southern Africa, focusing on resolving the dispute about A. pomposum and A. variegatum being distinct species.

Methods
Four Amblyomma tick species were collected from Angola, Mozambique, South Africa, Zambia and Zimbabwe, and were identified morphologically as Amblyomma eburneum (208), A. hebraeum (4758), A. pomposum (191) and A. variegatum (2577) using identification keys. Gene amplification targeting the 12S and 16S rRNA, cytochrome oxidase I, cytochrome B and internal transcribed spacer-2 genes was conducted for 204 ticks, for which varying success was achieved during amplification for each of the markers. Maximum likelihood analyses were performed in IQ-TREE.

Results
The phylogenetic topologies and ABGD analyses of each individual gene clustered A. pomposum within the A. variegatum clade, while clearly separating A. eburneum and A. hebraeum from all other species. None of the genetic markers indicated intraspecific structuring on the basis of geographical origin, despite great distances between sampling sites.

Conclusion
Our study concludes that there is insufficient molecular evidence to differentiate A. pomposum and A. variegatum from each other. We highlight the need for whole mitochondrial genome sequencing of these two species to resolve the ongoing controversies. Furthermore, we propose mating and hybrid viability studies between the two species to confirm their reproductive isolation.

Graphical Abstract
Validation of the C-X-C chemokine receptor 3 (CXCR3) as a target for PET imaging of T cell activation
Authors: Martin Sebastian , Wendlinger Lennard , Zitti Béatrice , Hicham Mehdi , Postupalenko Viktoriia , Marx Léo , Giordano-Attianese Greta , Cribioli Elisabetta , Irving Melita , Litvinenko Alexandra , Faizova Radmila , Viertl David , Schottelius Margret 
Published: August 2024

Abstract
Purpose
CXCR3 is expressed on activated T cells and plays a crucial role in T-cell recruitment to the tumor microenvironment (TME) during cell-based and immune checkpoint inhibitor (ICI) immunotherapy. This study utilized a 64Cu-labeled NOTA-α-CXCR3 antibody to assess CXCR3 expression in the TME and validate it as a potential T cell activation biomarker in vivo.

Procedures
CXCR3+ cells infiltrating MC38 tumors (B57BL/6 mice, untreated and treated with αPD-1/αCTLA-4 ICI) were quantified using fluorescence microscopy and flow cytometry. A commercial anti-mouse CXCR3 antibody (α-CXCR3) was site-specifically conjugated with 2,2,2-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid (NOTA) and radiolabeled with 64Cu. Saturation binding of [64Cu]Cu-NOTA-α-CXCR3 was investigated using CHO cells stably transfected with murine CXCR3. Biodistribution and PET imaging studies both at baseline and after 1 to 3 cycles of ICI, respectively, were carried out using different molar activities (10 GBq/µmol to 300 GBq/µmol) of [64Cu]Cu-NOTA-α-CXCR3.

Results
Flow cytometry analysis at baseline confirmed the presence of CXCR3 + T-cells in MC38 tumors, which was significantly increased at day five after ICI (treated 33.8 ± 17.4 vs. control 8.8 ± 6.2 CD3+CXCR3+ cells/mg). These results were qualitatively and quantitatively confirmed by immunofluorescence of tumor cryoslices. In vivo PET imaging of MC38 tumor bearing mice before, during and after ICI using [64Cu]Cu-NOTA-α-CXCR3 (Kd = 3.3 nM) revealed a strong dependence of CXCR3-specificity of tracer accumulation in secondary lymphoid organs on molar activity. At 300 GBq/µmol (1.5 µg of antibody/mouse), a specific signal was observed in lymph nodes (6.33 ± 1.25 control vs. 3.95 ± 1.23%IA/g blocking) and the spleen (6.04 ± 1.02 control vs. 3.84 ± 0.79%IA/g blocking) at 48 h p.i. Spleen-to-liver ratios indicated a time dependent systemic immune response showing a steady increase from 1.08 ± 0.19 (untreated control) to 1.54 ± 0.14 (three ICI cycles).

Conclusions
This study demonstrates the feasibility of in vivo imaging of CXCR3 upregulation under immunotherapy using antibodies. However, high molar activities and low antibody doses are essential for sensitive detection in lymph nodes and spleen. Detecting therapy-induced changes in CXCR3+ T cell numbers in tumors was challenging due to secondary antibody-related effects. Nonetheless, CXCR3 remains a promising target for imaging T cell activation, with anticipated improvements in sensitivity using alternative tracers with high affinities and favorable pharmacokinetics.
Validation of the PCL-5 in Dutch trauma-exposed adults
Authors: Hoeboer Chris M. , Karaban Irina , Karchoud Jeanet F. , Olff Miranda , van Zuiden Mirjam 
Published: August 2024

AbstractBackgroundThe PTSD Checklist for DSM-5 (PCL-5) is an internationally widely used self-report questionnaire that can be used to screen for probable diagnosis of posttraumatic stress disorder (PTSD). Information on the psychometric properties of the Dutch PCL-5 is currently lacking.ObjectiveWe aimed to validate the Dutch PCL-5 in a sample of Dutch adults with prior (suspected) serious injury and establish the optimal cut-off for probable PTSD diagnosis herein.MethodsData for the current study were collected as part of a long-term follow-up measurement of the TraumaTIPS cohort, where adults admitted to an emergency department following (suspected) serious injury completed a follow-up measurement 12–15 years post-trauma. OfN = 333 eligible participants,n = 192 (57.7%) consented and completed the PCL-5 alongside self-report instruments measuring depression (QIDS), PTSD (IES-R), and quality of life (WHO-QOL and EQ-6D). In total,n = 185 participants also completed a clinician administered interview for PTSD (CAPS-5). Most participants were men (66%) and on average 54 years old (SD = 12.41). We evaluated the diagnostic utility of the PCL-5 using Youden index and tested reliability and convergent validity.ResultsThe PCL-5 demonstrated excellent diagnostic accuracy with a cut-off point of 16 resulting in an optimal Youden index (0.90) for screening purposes with a high sensitivity (1.00) and specificity (0.90). A cut-off of 22 yielded a slightly lower Youden index (0.84) but better positive predictive value (0.50 instead of 0.33) than the cut-off of 16. A cut-off of 29 resulted in the most accurate prevalence estimates. The PCL-5 showed a high internal consistency (Cronbach’s α = 0.94), excellent inter-item and item-total correlations and good convergent validity (r > .5 for CAPS-5, IES-R and QIDS).ConclusionsThe PCL-5 is a reliable and valid measurement for PTSD symptoms and probable diagnosis and shows excellent screening abilities in Dutch adults with prior (suspected) serious injury, with a lower optimal cut-off compared to previously found in clinical populations. We recommend a cut-off of 22 for screening purposes and a cut-off of 29 for prevalence estimates in Dutch trauma-exposed adults.
Oak seedling microbiome assembly under climate warming and drought
Authors: Hoefle Daniel , Sommer Milena , Wassermann Birgit , Faticov Maria , Serra Demetrio , Berg Gabriele , Tack Ayco J.M. , Abdelfattah Ahmed 
Published: August 2024

AbstractDespite that climate change is currently one of the most pervasive challenges, its effects on the plant-associated microbiome is still poorly studied. The aim of this study was to evaluate the impact of the independent and combinatory effect of climate warming and drought on the microbiome assembly of oak from seed to seedling. In a multifactorial experimental set up, acorns were subjected to different temperatures (15 °C, 20 °C, and 25 °C) and soil moisture levels (drought (15%) and control (60%)) from germination until the seedling stage, after which the bacterial and fungal communities associated to the rhizosphere and phyllosphere were characterized by amplicon sequencing and qPCR. The results showed a stronger effect of temperature on fungal than on bacterial diversity and the effect was more pronounced in the phyllosphere. Under drought condition, temperature had a significantly negative effect on phyllosphere fungal diversity. In the rhizosphere, temperature had a significant effect on the fungal community composition which was primarily caused by species turnover. Regardless of temperature, Actinobacteriota was significantly enriched in drought, a group of bacteria known to increase plant drought tolerance. This study provides new insights into the effect of climate change on the plant microbiome in natural ecosystems.
Effect of Time-Restricted Eating on β-Cell Function in Adults With Type 2 Diabetes
Authors: Kramer Caroline Kaercher , Zinman Bernard , Feig Denice S , Retnakaran Ravi 
Published: August 2024

Abstract

Context
Time-restricted eating (TRE), which consists of restricting the eating window to typically 4 to 8 hours (while fasting for the remaining hours of the day), has been proposed as a nonpharmacological strategy with cardiometabolic benefits but little is known about its metabolic effect on type 2 diabetes mellitus (T2DM).

Objective
We evaluated whether TRE can improve pancreatic β-cell function and metabolic status in overweight individuals with early T2DM.

Methods
In a randomized, crossover trial, 39 participants (mean 2.9 years of diabetes duration, baseline glycated hemoglobin A1c [HbA1c] 6.6% ± 0.7% and body mass index [BMI] 32.4 ± 5.7) were randomly assigned to either an initial intervention consisting of 6 weeks of TRE (20 h-fasting/4 h-eating) or standard lifestyle. The primary outcome of β-cell function was assessed by the Insulin Secretion-Sensitivity Index-2 (ISSI-2) derived from an oral glucose tolerance test.

Results
As compared to standard lifestyle, TRE induced a 14% increase in ISSI-2 (+14.0 ± 39.2%; P = .03) accompanied by a 14% reduction of hepatic insulin resistance as evaluated by HOMA-IR (−11.6% [−49.3 to 21.9]; P = .03). Fasting glucose did not differ between interventions, but TRE yielded a statistically significant reduction in HbA1c (−0.32 ± 0.48%; P &lt; .001). These metabolic improvements were coupled with a reduction of body weight of 3.86% (−3.86 ± 3.1%; P &lt; .001) and waist circumference of 3.8 cm (−3.8 ± 7.5 cm; P = .003).

Conclusion
TRE improved β-cell function and insulin resistance in overweight patients with early diabetes, accompanied by beneficial effects on adiposity.