bluuebunny/crossref_metadata_2025_split huggingface dataset:
Humoral immunity to SARS-CoV-2 in kidney transplant recipients and dialysis patients: IgA and IgG patterns unraveled after SARS-CoV-2 infection and vaccination
Authors: De Bouver Caroline , Bouziotis Jason , Wijtvliet Veerle P. W. M. , Ariën Kevin K. , Mariën Joachim , Heyndrickx Leo , Couttenye Marie M. , de Fijter Hans J. W. , Mestrez Fabienne , Treille Serge , Mat Olivier , Collart Frederic , Allard Sabine D. , Vingerhoets Lies , Moons Pieter , Abramowicz Daniel , De Winter Benedicte Y. , Pipeleers Lissa , Wissing Karl Martin , Ledeganck Kristien J. 
Published: June 2024

Abstract
Background
Infection with SARS-CoV-2 in high-risk groups such as kidney transplant and dialysis patients is shown to be associated with a more serious course of the disease. Four years after the start of the COVID-19 pandemic, crucial knowledge on the immune responses in these patient groups is still lacking. Therefore, this study aimed at investigating the humoral immune response after a SARS-CoV-2 infection compared to vaccination as well as the evolution of immunoglobulins over time.

Methods
Kidney transplant recipients, patients on haemodialysis or on peritoneal dialysis and healthy controls were included in this longitudinal multicenter study. SARS-CoV-2 anti-RBD, anti-NP and anti-S1S2 immunoglobulin G (IgG) and A (IgA) as well as the neutralizing antibody capacity were measured.

Results
Kidney transplant recipients had a significantly better humoral response to SARS-CoV-2 after infection (86.4%) than after a two-dose mRNA vaccination (55.8%) while seroconversion was comparable in patients on haemodialysis after infection (95.8%) versus vaccination (89.4%). In individuals without prior COVID-19, the IgG levels after vaccination were significantly lower in kidney transplant recipients when compared to all other groups. However, the IgA titres remained the highest in this patient group at each time point, both after infection and vaccination. A history COVID-19 was associated with higher antibody levels after double-dose vaccination in all patient categories and, while decreasing, titres remained high six months after double-dose vaccination.

Conclusion
Kidney transplant recipients had a more robust humoral response to SARS-CoV-2 following infection compared to a two-dose mRNA vaccination, while patients on haemodialysis exhibited comparable seroconversion rates. Notably, individuals with prior COVID-19 exhibited higher IgG levels in response to vaccination. Hybrid immunity is thus the best possible defence against severe COVID-19 disease and seems also to hold up for these populations. Next, it is not clear whether the higher IgA levels in the kidney transplant recipients is beneficial for neutralizing SARS-CoV-2 or if it is a sign of disease severity.
The potential impact of the Comprehensive and Progressive Agreement for Trans-Pacific Partnership on Thailand’s hepatitis C treatment program
Authors: Tenni Brigitte , Lexchin Joel , Akaleephan Chutima , Kittitrakul Chalermsak , Gleeson Deborah 
Published: June 2024

Abstract
Background
Thailand has expressed interest in joining the Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP), a twelve-country plurilateral trade agreement whose original incarnation included the United States of America (USA). When the USA withdrew from this agreement, key intellectual property clauses relevant to pharmaceuticals were suspended. These could be reinstated should the CPTPP Parties decide to do so.

Methods
This study uses two scenarios to cost the impact the CPTPP would have had on Thailand’s 2020 hepatitis C treatment regime if Thailand joined the CPTPP and suspended clauses were reinstated.

Results
Joining the CPTPP could have increased the cost more than tenfold if suspended CPTPP clauses were reinstated and Thailand was not willing or able to issue compulsory licenses. Based on the 2020 budget, the price for this possible scenario could have reduced hepatitis C treatment coverage by 90%.

Conclusions
Acceding to trade agreements such as the CPTPP that require increasing intellectual property protection, could compromise Thailand’s hepatitis C program and other national treatment programs reliant on affordable generic medicines. The CPTPP could also prevent Thailand from relying on its own pharmaceutical capabilities to manufacture medicines needed to sustain its treatment programs.
Clinical and genetic characterization of patients with eye diseases included in the Spanish Rare Diseases Patient Registry
Authors: Lopez-de la Rosa Alberto , Telleria Juan J. , Posada de la Paz Manuel , Hermosilla-Gimeno Isabel M. , Rivas Miren Agurtzane , Gilabert Raúl , Coco-Martín Rosa M. 
Published: June 2024

Abstract
Background
The low prevalence of rare diseases poses a significant challenge in advancing their understanding. This study aims to delineate the clinical and genetic characteristics of patients with rare eye diseases (RED) enrolled in the Spanish Rare Diseases Patient Registry.

Methods
A total of 864 patients from the registry database were included. Diseases were categorized into inherited retinal dystrophies (n=688); anterior segment diseases (n=48); congenital malformations (n=27); and syndromic diseases with ocular involvement including muscular (n=46), neurological (n=34), or metabolic (n=13); inflammatory diseases (n=4); and tumors (n=4). Data on visual acuity (VA) and/or visual field (VF), symptoms and signs, concurrent diseases in syndromic cases, age of onset and at diagnosis, affected genes, disability rating, inability to work and dependency grade recognition were collected.

Results
A mean diagnostic delay of 7 years from symptom onset was observed. Commonly reported symptoms included photophobia, night blindness, and progressive vision loss (≥57% of patients). Cataract was the most prevalent secondary disease (46%), with pseudophakia being the most common ocular surgery (26%). Hearing loss and cardiovascular diseases were the most prevalent concurrent systemic diseases (≥13%). Certificates of disability, incapacity for work, and dependency were held by 87%, 42%, and 19% of patients, respectively. Among the 719 patients with available VA data, 193 (27%) were blind, and 188 (26%) had moderate to severe visual impairment. Over half of the patients (54%) exhibited VF defects, and 216 (25%) had concentric contraction ≤5° or abolished VF. Most had genetic diseases with autosomal recessive (55%), autosomal dominant (30%), X-linked (9%), and mitochondrial (6%) patterns. One patient had mutations in both recessive USH2A and dominant RHO genes simultaneously. Of the 656 patients (75.7%) who underwent genetic testing, only 461 (70.3%) received a positive result (pathogenic or likely pathogenic mutations explaining the phenotype). We found 62 new gene variants related to RED not previously reported in databases of genetic variants related to specific phenotypes.

Conclusions
This study delineates the clinical and genotypic profiles of RED in Spain. Genetic diseases, particularly retinal disorders, predominate, but a significant proportion of affected patients remain genetically undiagnosed, hindering potential gene therapy endeavors. Despite notable improvements in reducing diagnosis delays, it is still remarkable. RED frequently lead to disability and blindness among young populations.
Experimental and theoretical quantum chemical studies of 2-(2-acetamidophenyl)-2-oxo-N-(pyridin-2-ylmethyl)acetamide and its copper(II) complex: molecular docking simulation of the designed coordinated ligand with insulin-like growth factor-1 receptor (IGF-1R)
Authors: El-Sayed Doaa S. , Sinha Leena , Soayed Amina A. 
Published: June 2024

AbstractNewly synthesized ligand 2-(2- acetamidophenyl)-2-oxo-N-(pyridin-2-ylmethyl)acetamide and its copper(II) complex were characterized by elemental analyses, FT-IR, UV–Vis., ESR, 1H-NMR, and thermal analysis along with the theoretical quantum chemical studies. Combined experimental and theoretical DFT (density functional theory) studies showed the ligand to be a tridentate ligand with three coordinate bonds. The complex was suggested to be in a distorted octahedral structure with dx2-y2 ground state. The activation energy, ΔE*; entropy ΔS*; enthalpy ΔH* and order of reaction has been derived from differential thermogravimetric (DTA) curve, using Horowitz–Metzeger method. The nujol mull electronic spectrum of the ligand and Cu(II) complex have been recorded and the difference of the excited and ground state densities has also been theoretically calculated and plotted to investigate the movement of electrons on excitation. The Cu(II) complex was evaluated for its antibacterial activity against two bacterial species, namely Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Antifungal screening was performed against two species (Condida albicans and Aspergillus flavus). The complex under investigation was found to possess notable biological activity. Molecular docking investigation predicted different types of non-covalent interactions of the synthesized ligand towards Insulin-like growth factor 1 receptor (ID: 5FXR).
Qualitative and quantitative MRI analysis of alveolar soft part sarcoma: correlation with histological grade and Ki-67 expression
Authors: Yuan Junhui , Xie Deshun , Fang Shaobo , Meng Fan , Wu Yue , Shan Dongqiu , Shao Nannan , Wang Bangmin , Tian Zhichao , Wang Yuanyuan , Xu Chunmiao , Chen Xuejun 
Published: June 2024

Abstract
Objective
To investigate the correlation between MRI findings and histological features for preoperative prediction of histological grading and Ki-67 expression level in alveolar soft part sarcoma (ASPS).

Methods
A retrospective analysis was conducted on 63 ASPS patients (Jan 2017–May 2023). All patients underwent 3.0-T MRI examinations, including conventional sequences, dynamic contrast-enhanced scans with time-intensity curve analysis, and diffusion-weighted imaging with apparent diffusion coefficient (ADC) measurements. Patients were divided into low-grade (histological Grade I) and high-grade (histological Grade II/III) groups based on pathology. Immunohistochemistry was used to assess Ki-67 expression levels in ASPS. Statistical analysis included chi-square tests, Wilcoxon rank-sum test, binary logistic regression analysis, Spearman correlation analysis, and receiver operating characteristic curve analysis of various observational data.

Results
There were 29 low-grade and 34 high-grade patients (26 males and 37 females) and a wide age range (5–68 years). Distant metastasis, tumor enhancement characteristics, and ADC values were independent predictors of high-grade ASPS. High-grade ASPS had lower ADC values (p = 0.002), with an area under the curve (AUC), sensitivity, and specificity of 0.723, 79.4%, and 58.6%, respectively, for high-grade prediction. There was a negative correlation between ADC values and Ki-67 expression (r = −0.526; p < 0.001). When the cut-off value of ADC was 0.997 × 10−3 mm²/s, the AUC, sensitivity, and specificity for predicting high Ki-67 expression were 0.805, 65.6%, and 83.9%, respectively.

Conclusion
Qualitative and quantitative MRI parameters are valuable for predicting histological grading and Ki-67 expression levels in ASPS.

Critical relevance statement
This study will help provide a more nuanced understanding of ASPS and guide personalized treatment strategies.

Key Points

There is limited research on assessing ASPS prognosis through MRI.

Metastasis, enhancement, and ADC correlated with histological grade; ADC related to Ki-67 expression.

MRI provides clinicians with valuable information on ASPS grading and proliferation activity.

Graphical Abstract
Next-generation sequencing profiling of miRNAs in individuals with 22q11.2 deletion syndrome revealed altered expression of miR-185-5p
Authors: Dantas Anelisa Gollo , Nunes Beatriz Carvalho , Nunes Natália , Galante Pedro , Asprino Paula Fontes , Ota Vanessa Kiyomi , Melaragno Maria Isabel 
Published: June 2024

Abstract
Background
The 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with highly variable phenotypic manifestations, even though most patients present the typical 3 Mb microdeletion, usually affecting the same ~ 106 genes. One of the genes affected by this deletion is DGCR8, which plays a crucial role in miRNA biogenesis. Therefore, the haploinsufficiency of DGCR8 due to this microdeletion can alter the modulation of the expression of several miRNAs involved in a range of biological processes.

Results
In this study, we used next-generation sequencing to evaluate the miRNAs profiles in the peripheral blood of 12 individuals with typical 22q11DS compared to 12 healthy matched controls. We used the DESeq2 package for differential gene expression analysis and the DIANA-miTED dataset to verify the expression of differentially expressed miRNAs in other tissues. We used miRWalk to predict the target genes of differentially expressed miRNAs. Here, we described two differentially expressed miRNAs in patients compared to controls: hsa-miR-1304-3p, located outside the 22q11.2 region, upregulated in patients, and hsa-miR-185-5p, located in the 22q11.2 region, which showed downregulation. Expression of miR-185-5p is observed in tissues frequently affected in patients with 22q11DS, and previous studies have reported its downregulation in individuals with 22q11DS. hsa-miR-1304-3p has low expression in blood and, thus, needs more validation, though using a sensitive technology allowed us to identify differences in expression between patients and controls.

Conclusions
Thus, lower expression of miR-185-5p can be related to the 22q11.2 deletion and DGCR8 haploinsufficiency, leading to phenotypic consequences in 22q11.2DS patients, while higher expression of hsa-miR-1304-3p might be related to individual genomic variances due to the heterogeneous background of the Brazilian population.
Exploring bi-directional impacts of Lisdexamfetamine dimesylate on psychological comorbidities and quality of life in people with Binge Eating Disorder
Authors: Griffiths Kristi R. , Boulet Stephanie , Barakat Sarah , Touyz Stephen , Hay Phillipa , Maguire Sarah , Kohn Michael R. 
Published: June 2024

Abstract
Background
Lisdexamfetamine dimesylate (LDX) has demonstrated safety and efficacy for treatment of Binge Eating Disorder (BED). However, to date, trials have not included participants with co-occurring psychiatric disorders. This study explores how LDX affects eating disorder psychopathology, symptoms of common psychiatric comorbidities of BED (ADHD, depression, anxiety), and psychological quality of life, in people with moderate to severe BED.

Methods
These are secondary analyses of an open-label LDX trial conducted in 41 adults (18–40 years) over eight-weeks. Participants received LDX titrated to 50 or 70 mg. Clinical assessments and self-report questionnaires were conducted at baseline and 8-week follow-up.

Results
Eating disorder psychopathology and psychological quality of life improved after 8-weeks of LDX. No significant group-level changes in depression, anxiety or ADHD severity scores were observed. However, the majority within the small subsets with elevated depression and ADHD symptoms experienced reduced depressive and inattentive symptom severity, respectively.

Conclusions
We provide proof-of-concept evidence that LDX may provide broader psychological benefits to individuals with BED, beyond reducing their BE frequency. Effects of LDX on anxiety should be monitored closely by clinicians. Early indications suggest that LDX may be effectively used in people with BED, with and without co-occurring psychiatric conditions, however tolerability may be lower in highly complex cases.
Trial registration: Australian and New Zealand Clinical Trials Registry (anzctr.org.au) #ACTRN12618000623291.
Biocontrol potential of epiphytic bacteria against Xanthomonas citri pathotypes A and A*
Authors: Fathi Zahra , Rezaei Rasool , Charehgani Habiballah , Ghaderi Fariba , Ghalavoz Maryam Ghalamzan 
Published: June 2024

Abstract
Background
Citrus canker caused by the bacterium Xanthomonas citri (Hasse 1915) is known as a dangerous disease that has serious economic impacts on citrus production in many tropical and subtropical countries. In Iran, Citrus canker disease has caused significant damage to various citrus fruits, particularly limes. Nowadays, employing antagonistic bacteria as an effective and environmentally friendly method for plant disease management has gained special importance.

Results
Citrus leaf samples were collected from different regions of Iran, and after isolating epiphytic bacteria, ex planta and in planta investigations concerning antagonistic activities of the isolates against Xanthomonas citri pathotypes A and A* were performed. A total of 94 epiphytic bacterial isolates were isolated from citrus aerial parts. Based on biochemical, physiological, morphological, and genotypic tests, it was determined that these bacteria belong to the Bacillus and Staphylococcus genera. The highest inhibition activity against the pathogenic bacterium was related to isolates D4 and D5. Using the molecular method and the resulting dendrogram, it was found that these isolates were most similar to Bacillus amyloliquefaciens. The present findings demonstrated that pathogenicity test on key lime leaves infected with X. citri pathotypes A and A*, along with the application of the biocontrol strain B. amyloliquefaciens, resulted in a significant reduction in the number of canker lesions.

Conclusion
The results strongly suggested that the identified antagonistic bacterial isolates hold promising potential as biocontrol agents for managing citrus bacterial canker disease.
Phase IIA study of high-affinity TCR-T (TAEST16001) targeting NY-ESO-1 in soft tissue sarcoma.
Authors: Liu Jiayong , Gao Tian , Pan Qiuzhong , Bai Chujie , Han Zhaosheng , Tan Zhichao , Peng Ruiqing , Xu Bushu , Wen Xizhi , Cen Huafang , Yan Chaoxian , Lau Johnson Yiu-Nam , Zeng Lun , Wu Xueyun , Ou Yusheng , Gong Haiping , Huang Yingjie , Fan Zhengfu , Zhang Xing 
Published: June 2024

11548 Background: TAEST16001 cells are genetically engineered autologous T cells expressing high-affinity NY-ESO-1-specific T-cell receptor (TCR) targeting NY-ESO-1 (expressed in a wide range of tumors) positive soft tissue sarcoma (STS) in the context of HLA-A*02:01. A phase I study of in patients with advanced STS (NCT04318964) demonstrated safety and preliminary indication of efficacy at ASCO 2022. Here, we will present our encouraging phase IIa results. Methods: This is an open-labeled, single arm study to evaluate efficacy and safety of TAEST16001 cells in patients with advanced STS (NCT05549921). Enrolled patients underwent apheresis, their isolated T cells expanded in vitro after transduction with a lentiviral vector expressing high affinity NY-ESO-1 TCR. Patients received 3-day lymphodepleting chemotherapy (cyclophosphamide 15 mg/kg/day and fludarabine 20 mg/m2/day). TAEST16001 cells were administered at 1.2 × 1010± 30% cells (determined through our phase I data) and they also received 14-day IL-2 s.c. injection. Target efficacy ( per RECIST 1.1) was set at overall response rate (ORR) =25% for the first stage cohort of 12 patients. Results: As of January 2024, 8 patients were enrolled (M:F 4: 4; mean age: 40 yrs.; median prior regimens: 3 (range:2-5)). TAEST16001 cells demonstrated a manageable safety profile consistent with previous phase I study. The common (n>1) reported grade (G) 3 adverse events were lymphocytopenia (n=8), decreased WBC count (n=7), neutropenia (n=6), elevated γ-GT (n=3), hypokalemia (n=2). Six patients had cytokine release syndrome (CRS) (G3: 1; G2: 1; G1: 4), and 2 patients also experienced G1 ICANS, all resolved completely after symptomatic treatment. Importantly, after at least two tumor assessments, 4 had confirmed partial response, 3 had stable disease, and 1 had progressive disease. The ORR at cut-off date was 50%. The median time to initial response was 1.1 months (1.1 to 2.2) and median duration of response was 5.0 months (1.5 to 8.8). Most patients are still being follow-up. When pooling the data for the same dose in phase I part, ORR at dose of 1.2 × 1010 was 54.5% (6/11). Conclusions: TAEST16001 demonstrated an acceptable safety profile. The encouraging efficacy data (ORR=50%) exceeded our pre-specified target efficacy (ORR=25%). The review committee has recommended TAEST16001 to proceed early to the next stage of clinical development. Clinical trial information: NCT05549921 .
Phase 2a results of SQ3370, a doxorubicin-based click chemistry therapeutic in patients with advanced STS: Planned interim analysis.
Authors: Bui Nam , Kwatra Vineet , Ryan Christopher W. , Gordon Erlinda Maria , Aleckovic Masa , Srinivasan Sangeetha , Nguyen Tri-Hung , Mejia Oneto Jose Manuel , Abella-Dominicis Esteban , Chawla Sant P. 
Published: June 2024

11555 Background: Shasqi is a clinical stage biotech that uses click chemistry, a Nobel Prize winning technology, to selectively activate cancer treatments at the tumor. The Click Activated Protodrugs Against Cancer (CAPAC) platform comprises of 1) tumor targeting agents, which carry an activator, and 2) attenuated cancer drugs, which are selectively activated at the tumor by the targeting agent through click chemistry, maximizing therapeutic index and minimizing toxicities. We have demonstrated clinical proof of concept with SQ3370, which uses an intratumorally injected SQL70 biopolymer (bp) with a doxorubicin (Dox) protodrug (SQP33) injected systemically. As previously reported RP2D of SQP33=12x Dox. (NCT04106492). Methods: Dox naïve patients (pts) received 10/20 mL bp and protodrug IV QD x 3 or 5. Key eligibility: locally advanced or metastatic soft tissue sarcomas (STS). The objective was to explore bp dose and schedule of the RDP2 (same dose per cycle) in advanced or metastatic STS. Results: Fourteen patients with predominantly metastatic (11/14) STS, all unresectable, were enrolled at the 1st interim analysis. Median age 58 years (32-89), ECOG=1 (11/14). Therapy was well tolerated. The most common TEAE was nausea and fatigue (all grade ≤ 2), with 1 subject in each group having a manageable grade ≤ 3 TEAE-related discontinuations. The majority of subjects did not suffer clinical myelosuppression grade ≤ 1 neutropenia (10/14), anemia (13/14), or thrombocytopenia (13/14), with DCR 71% (CI 95% 44-92%) and ORR 14.3% (CI 95%1.7-40%). Detailed PK, immune assessment and safety findings will be presented. Conclusions: SQ3370 is the first clinical click chemistry-based cancer therapy, and this is the 1st clinical trial to explore doses greater than 3x Dox in STS patients. The results show that the bp activates protodrug, which is not a vesicant, and releases Dox in patients. Click chemistry favorably alters PK and safety of the Dox payload. At 12x Dox, using the commonly administered 3-week schedule, Dox was very well tolerated. Click-chemistry maintains expected clinical activity, and preliminary data suggest enhanced safety (reduced myelosuppression) as well as unlocking immunological effects (intratumoral and systemic), without the myelosuppressive effects typically seen with Dox. Clinical trial information: NCT04106492 . [Table: see text]