bluuebunny/crossref_metadata_2025_split huggingface dataset:
B-184 Purifying High-Quality Genomic DNA From Frozen Blood Samples Stored up to 1.5 Years at -20°C
Authors: Wood A , Wang Y 
Published: October 2024

Abstract

Background
Maintaining DNA integrity in blood samples, from transport to storage to processing, is crucial to the success of downstream applications, especially regarding diagnostic applications. Additionally, due to the invasive nature of collecting blood samples, minimizing resampling to avoid excess patient pain and cost of collection and transportation are important to consider. Having the option to store and maintain portions of blood samples in the freezer enables future retesting without recollection. Since -20°C freezers generally are more affordable, require less energy, and have smaller footprints than -80°C freezers, demonstrating frozen blood stability at -20°C temperatures could decrease sampling burdens for labs with facility constraints.

Methods
Whole blood was collected into 9mL vacuum tubes (HemaSure-OMXP) from healthy donors. Aliquots of whole blood and buffy coat samples were stored at -20°C and thawed for genomic DNA extractions (QIAamp DNA Blood Mini Kit, Qiagen) at a range of different timepoints; frozen whole blood samples were processed at 0, 49, 141, and 148 days and frozen buffy coat samples were processed at 7, 27, 36, 185, 246, 373, 394, 584, and 604 days. Purified gDNA was quantified with Qubit (Broad Range dsDNA Assay, ThermoFisher) and qualified with Nanodrop One Microvolume UV-Vis Spectrophotometer (ThermoFisher) and TapeStation (Genomic DNA ScreenTape, Agilent Technologies).

Results
No significant decrease was observed for DNA yield and quality between fresh and frozen whole blood samples. Average DNA yields from 200 μL whole blood were 4.5 ± 2.2 μg and 5.3 ± 1.2 μg for fresh and frozen blood respectively. Average DNA integrity (DIN) was 6.9 ± 0.4 and 7.1 ± 0.3 for fresh and frozen blood respectively. Donor differences in blood samples can help explain the variance in DNA yields reported. No significant decrease was observed for DNA yield and quality in buffy coat samples frozen for longer at -20°C. In total, 84 whole blood and 25 buffy coat samples were processed in this study.

Conclusions
Although buffy coat samples tended to have higher yields than whole blood, due to the higher amount of white blood cells present, both sample types provided sufficient amounts of gDNA for downstream applications. Freezing blood samples for future testing can be effective at reducing the need for resampling without sacrificing the nucleic acid yield or quality of fresh samples. Additionally, as technological advancements are made for equipment and assays, frozen blood samples can be retested and compared to previous results for improved diagnostic decisions, done without requiring recollection from labs and patients.
B-227 Customized molecular tests for minimal residual disease: a tool for therapeutic decisions in follicular lymphoma patients
Authors: Tohami T , Yankolovitz D , Ortenberg R , Tawil H , Abadi U 
Published: October 2024

Abstract

Background
Monitoring of minimal residual disease (MRD) is based on accurate laboratory tests which can recognize a small fraction of malignant cells that survived the course of treatment. Several studies of the B-non-Hodgkin lymphoma group have been presented that MRD positivity at the end of treatment is a negative prognostic index. Follicular lymphoma (FL) is a chronic indolent malignancy, which response highly to immuno-chemotherapy followed by prolonged remissions but with inevitable relapse in most patients. The GALLIUM study showed that immuno-chemotherapy combinations, 6 cycles of bendamustine-obinutuzumab (BO), is the most efficacious treatment, but with severe side effects .In addition, 90% of patients achieved negative MRD from peripheral blood (PB) or bone marrow (BM) after only 3 BO cycles. These findings raise the possibility for MRD based treatment approach, where the duration of chemotherapy could be decided according to MRD status at mid-induction (MI). Identification of a marker in the PB and/or BM of each FL patient which will be use to the design of a sensitive RQ-PCR test for MRD detection for follow-up.

Methods
Qualitative PCR for translocation 14:18 and for the VDJ rearrangement sequence of the immunoglobulin heavy chain was used for marker identification. MRD monitoring was done by RQ-PCR. MRD monitoring for VDJ was designed specifically to each patients based on his VDJ sequence. MRD was assessed on PB and BM at MI.

Results
Marker for monitoring was identified at 11/21 patients in this study. After 3 combined therapy cycles, 7 patients were found to have MRD negativity by RQ-PCR therefore continue with immuno-therapy only. MRD positivity was assessed in BM of 3 patients (0.11%, 0.022%, and 0.133%). These 3 patients continued with the combined therapy. RQ-PCR sensitivity was 10-4-10-5.

Conclusions
This study will reveal the ability to use sensitive and specific MRD that has to be designed for each patient according to his marker and enable the establishment of a treatment with a high safety profile for FL patients. Correlation between MRD status and clinical and safety parameters will be assessed at the end of the study, 30 months after the first treatment, taking into account MRD status from different time point of the follow-up period.
B-236 New real-time PCR test for APOE genotyping in patients with Alzheimer’s disease before anti-amyloid therapy
Authors: Sabalza M , Meißner D , Denker A , Stallmann S , Milbredt S , Saschenbrecker S , Steller U 
Published: October 2024

Abstract

Background
In 2023, the US Food and Drug Administration approved LEQEMBI, a monoclonal antibody therapy targeting beta-amyloid plaques, for patients with early-stage Alzheimer’s disease (AD). However, anti-amyloid drug trials demonstrated an elevated risk for amyloid-related imaging abnormalities with cerebral edema (ARIA-E) in carriers of the AD risk allele apolipoprotein E epsilon 4 (APOE-ɛ4), especially in ɛ4/ɛ4 homozygous individuals [1-3]. Here, we report on the evaluation of a new real-time polymerase chain reaction (PCR) test for APOE genotyping.

Methods
The EURORealTime APOE (EUROIMMUN), which enables simultaneous testing for all six APOE genotypes (ɛ2/ɛ2, ɛ2/ɛ3, ɛ2/ɛ4, ɛ3/ɛ3, ɛ3/ɛ4, and ɛ4/ɛ4) by real-time PCR, was performed using genomic DNA (gDNA) isolated from EDTA blood samples. The PCR amplification results were evaluated using the EURORealTime Analysis Software (EUROIMMUN). Samples from healthy blood donors (HBD) were used to assess intra-assay, inter-assay and between-lot precision (n=6) as well as analytical sensitivity (n=21), with each APOE genotype represented by at least one sample. Assay accuracy was analyzed by comparing genotype assignments to the results of the CE-IVD-marked EUROArray APOE (EUROIMMUN) and bidirectional Sanger sequencing using 110 samples (100 AD, 10 HBD). APOE genotype frequencies were compared between patients (100 AD) and controls (250 HBD).

Results
Precision testing of the EURORealTime APOE resulted in 100% correct genotype calls. Assessment of the analytical sensitivity revealed valid and correct genotype assignment in all 21 samples, confirming 1 ng/µl as the recommended minimum gDNA concentration. The analytical accuracy amounted to 100% based on agreement with the two reference methods in 110/110 cases. Comparison of the APOE genotype distribution showed a higher proportion of ɛ4 allele carriers (i.e., ɛ2/ɛ4, ɛ3/ɛ4, and ɛ4/ɛ4) in AD patients than in HBD (50.0% vs. 25.2%). The prevalence of the ɛ4/ɛ4 genotype in these cohorts was 25.0% for AD patients compared with 2.8% for HBD.

Conclusions
The well-established high prevalence of the APOE-ɛ4/ɛ4 genotype in AD patients, together with the increased risk of ARIA-E in these homozygous carriers, substantiates the relevance of APOE genotyping prior to anti-amyloid treatment. The EURORealTime APOE test provides sensitive and reliable determination of APOE alleles, thus presenting a suitable tool to improve risk stratification for potential LEQEMBI recipients.
B-342 Teclistamab interference in serum protein electrophoresis and serum immunofixation electrophoresis in patients with recurrent or relapsed multiple myeloma
Authors: Whitt A , McCoy M H , Jortani S A 
Published: October 2024

Abstract

Background
Serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (IFE) analyses are mainstays in the initial diagnosis, risk stratification, and evaluating treatment response in patients with multiple myeloma (MM) in accordance with the International Myeloma Working Group criteria. Published reports have demonstrated that therapeutic monoclonal antibodies (mAbs) used to treat MM (e.g. anti-CD38 IgG-kappa) are detectable by SPEP and IFE, which may interfere with accurate evaluation of complete response. Recently, Teclistamab (Tecvayli®; Janssen Biotech, Horsham Township, PA), a humanized bispecific IgG-lambda mAb targeting B-cell maturation antigen (BCMA) and CD3 on T cells was approved for treating patients with penta-refractory MM. In contrast with other IgG-kappa therapeutic mAbs, the degree to which Teclistamab may interfere with detection and quantification of monoclonal proteins is unknown. Therefore, we sought to assess the interference of Teclistamab therapy on routine SPEP and IFE analysis.

Methods
Patients treated with Teclistamab were identified by retrospective review of electronic medical records. Teclistamab (90 mg/mL) was spiked into a remnant patient sample with IgG lambda MM at a final concentration of 10 μg/mL, which corresponds to ½Cmax values in patients infused with Teclistamab. SPEP and IFE were performed using the Helena SPIFE Touch instrument. Computer-assisted densitometry was used to quantify monoclonal proteins in the gamma region of SPEP gels.

Results
In several patients with refractory MM treated with Teclistamab, IFE analysis revealed IgG lambda or lambda light chain monoclonal proteins, which were inconsistent with previously-identified monoclonal proteins (e.g. IgG kappa). In one patient diagnosed with IgG lambda MM, spiking 10 μg/mL Teclistamab increased M-spike abundance by approximately 0.15 g/dL when quantified by SPEP.

Conclusions
In patients with relapsed or refractory MM, treatment with Teclistamab may confound accurate clinical assessment of complete response by SPEP and IFE methods. Increased awareness of this preanalytical interference is necessary to guide clinical decision making.
Restoring the English March: interpreting 17th- and 18th-century drum music
Authors: Chapman John A 
Published: October 2024

Abstract
The English March (EM) defined the sound of the nation for four centuries, but its rhythm and sound have been almost entirely lost, despite the availability of music from the 17th and 18th centuries. Attempts over the past half-century to interpret the music have produced unsatisfactory translations, because they have had to augment the music provided and have not convincingly defined the rudiments depicted in the original sources. I argue that applying rules derived from white mensural notation and Arbeau’s Orchésographie to the EM’s rhythm produces a strong 34 interpretation. Additionally, a study of three surviving versions of the EM and a survey of 18th- and 19th-century drum rudiments allows us to form a complete picture of the rudimental complexity of the EM. The resulting beating represents the closest interpretation to the original EM that current resources allow, and therefore constitutes a major advance in the interpretation of early British military music.
A low-cost alternative to LiDAR for site index models: applying repeated digital aerial photogrammetry data in the modelling of forest top height growth
Authors: Janiec Piotr , Hawryło Paweł , Tymińska-Czabańska Luiza , Miszczyszyn Jakub , Socha Jarosław 
Published: October 2024

AbstractEnvironmental and forest structural information derived from remote sensing data has been found suitable for modelling forest height growth and site index and therefore forest productivity assessment, with the advances in airborne laser scanning (ALS) playing a major role in this development. While there is growing interest in the use of ALS-derived point clouds, point clouds from high-resolution digital aerial photography (DAP) are also often used for mapping and estimating forest ecosystem properties due to their lower acquisition costs. In this study, we document the applicability of bi-temporal DAP data for developing top height (TH) growth models for Scots pine stands. Our results indicate that DAP data can function as an alternative to traditional TH measurements used in growth modelling when corrected based on a limited sample of field-measured reference TH values. As the correction cannot be constant for each DAP dataset due to the different parameters during data acquisition, we propose a straightforward method for the bias correction of DAP-derived TH estimates. By undertaking iterative random sampling, we were able to find the minimum number of reference measurements needed to calculate the TH correction in order to achieve the desired accuracy of the TH estimations based on DAP. Here, we used ALS data as the reference data; however, the ALS measurements can be replaced by any other reliable source of TH values. The presented method for determining TH can be used not only for site index and forest growth modelling but also in forest inventories.
A vacuolar invertase gene SlVI modulates sugar metabolism and postharvest fruit quality and stress resistance in tomato
Authors: Wu Yu , Chen Haonan , Wu Mengbo , Zhou Yuanyi , Yu Chuying , Yang Qihong , Rolland Filip , Van de Poel Bram , Bouzayen Mondher , Hu Nan , Wang Yikui , Liu Mingchun 
Published: October 2024

Abstract
Sugars act as signaling molecules to modulate various growth processes and enhance plant tolerance to various abiotic and biotic stresses. Moreover, sugars contribute to the postharvest flavor in fleshy fruit crops. To date, the regulation of sugar metabolism and its effect in plant growth, fruit ripening, postharvest quality, and stress resistance remains not fully understood. In this study, we investigated the role of tomato gene encoding a vacuolar invertase, hydrolyzing sucrose to glucose and fructose. SlVI is specifically expressed during the tomato fruit ripening process. We found that overexpression of SlVI resulted in increased leaf size and early flowering, while knockout of SlVI led to increased fruit sucrose content, enhanced fruit firmness, and elevated resistance of postharvest fruit to Botrytis cinerea. Moreover, the content of naringenin and total soluble solids was significantly increased in SlVI knockout fruit at postharvest stage. Transcriptome analysis showed a negative feedback regulation triggered by sucrose accumulation in SlVI knockout fruit resulting in a downregulation of BAM3 and AMY2, which are critical for starch degradation. Moreover, genes associated with cell wall, cutin, wax, and flavonoid biosynthesis and pathogen resistance were upregulated in SlVI knockout fruit. Conversely, the expression levels of genes involved in cell wall degradation were decreased in knockout fruit. These results are consistent with the enhanced postharvest quality and resistance. Our findings not only provide new insights into the relationship between tomato fruit sucrose content and postharvest fruit quality, but also suggest new strategies to enhance fruit quality and extend postharvest shelf life.
Effect of add-on naldemedine treatment in patients with cancer and opioid-induced constipation insufficiently responding to magnesium oxide: a pooled, subgroup analysis of two randomized controlled trials
Authors: Kessoku Takaomi , Akamatsu Toshikazu , Morioka Yasuhide , Yokota Takaaki , Kobayashi Masayuki , Uchida Kohei , Koretaka Yuichi , Nakajima Atsushi 
Published: October 2024

Abstract

Objective
To evaluate the additive effect of naldemedine tosylate (naldemedine) on opioid-induced constipation in cancer patients insufficiently responding to magnesium oxide treatment.

Methods
We combined two randomized, double-blind, placebo-controlled, phase IIb and III trials of naldemedine and conducted a post hoc subgroup analysis. We evaluated the effect and safety of naldemedine in 116 patients who received naldemedine in addition to magnesium oxide (naldemedine group) and 117 patients who received placebo in addition to magnesium oxide (placebo group). Both groups included patients insufficiently responding to magnesium oxide for opioid-induced constipation. Effect was assessed using spontaneous bowel movement responder rate, complete spontaneous bowel movement responder rate, changes in spontaneous bowel movements and complete spontaneous bowel movements. Safety was also assessed.

Results
During the 2-week treatment period, the responder rates for spontaneous bowel movement and complete spontaneous bowel movement were 73.3 and 43.1% in naldemedine group, respectively, which were significantly higher (P &lt; 0.0001) than 41.9 and 14.5% in placebo group, respectively. Median time to first spontaneous bowel movement and first complete spontaneous bowel movement was significantly shorter (P &lt; 0.0001) in the naldemedine group (4.0 and 21.3 h, respectively) than in the placebo group (27.7 and 211.7 h, respectively). The incidence of adverse events and diarrhoea was significantly higher (P &lt; 0.05) in the naldemedine group than in the placebo group, while the incidence of serious adverse events and severe diarrhoea was not significantly different between the naldemedine and placebo groups.

Conclusion
The study suggested the addition of naldemedine as an effective treatment option for opioid-induced constipation in cancer patients insufficiently responding to magnesium oxide treatment.
A randomized phase III study evaluating dexamethasone-based mouthwash to prevent chemotherapy-induced stomatitis in patients with breast cancer
Authors: Kuba Sayaka , Soutome Sakiko , Hagiwara Yasuhiro , Kikawa Yuichiro , Iwamoto Takayuki , Sangai Takafumi , Harao Michiko , Yamaguchi Takeshi , Taji Tomoe , Igarashi Ataru , Kajimoto Yusuke , Sakurai Naomi , Yamanouchi Kosho , Watanabe Kenichi , Maeda Noriko , Suzuki Masahiko , Maeda Shigeto , Toh Uhi , Ebata Akiko , Iwakuma Nobutaka , Matsunuma Ryoichi , Yamaguchi Miki , Mukai Hirofumi ,   CSPOR-BC, Kuba Sayaka 
Published: October 2024

Abstract
Stomatitis, which is a common side effect of chemotherapy, currently lacks a standardized approach for its prevention. Therefore, this multicenter, randomized, open-label, controlled phase III trial aims to assess the efficacy and safety of a dexamethasone-based mouthwash for preventing chemotherapy-induced stomatitis in patients with early breast cancer. We will randomly assign 230 patients with early breast cancer scheduled to receive chemotherapy in a 1:1 ratio to either the dexamethasone-based mouthwash group (10 ml, 0.1 mg/ml; swish for 2 min and spit 4 times daily for 8 weeks) or the mouthwash-with-tap-water group. The incidence of stomatitis, measured using electronic patient-reported outcomes, is the primary endpoint.
Epithelioid sarcoma of the pretragus: a rare pediatric entity with an unusual site
Authors: El Mohtarim Rihane , Sassi Samia , El Ansari Nawal , Rguieg Naji , El Ghafouli Sara , Rouas Lamiaa , Lamalmi Najat 
Published: October 2024

Abstract
Epithelioid sarcoma (ES) is a rare soft tissue tumor that is commonly misdiagnosed. It is a mesenchymal tumor that shows both mesenchymal and epithelial features. It tends to occur in the distal upper extremity in children and young adults but may appear in any location and any age group. Less than 1% of ES involve the head and neck. Clinically, the tumor can be mistakenly confused with a benign lesion as it can mimic nonspecific ulcers or infected warts. Histologically, ES is characterized by a nodular architecture and epithelioid appearance of cells centered with necrosis, mimicking a granulomatous process. We present the clinical history of a 12-year-old male who presented with an ES of the pretragus with a brief review of the literature to raise awareness on this rare entity and to discuss the challenges in managing histopathological differential diagnosis in front of this unusual clinical presentation.
Flowers meet Newton: testing the role of gravitational pull in resupination of orchid flowers
Authors: Cardoso João C F , Johnson Steven D , Oliveira Paulo E 
Published: October 2024

Abstract
Resupination refers to the developmental orientation changes of flowers through ~180°, leaving them effectively upside-down. It is a widespread trait present in 14 angiosperm families, including the Orchidaceae, where it is a gravitropic phenomenon actively controlled by auxins. Here, we demonstrate that the passive gravitational pull on flower parts can have an additional influence on resupination. We studied a lady’s slipper orchid in which some flowers naturally fail to resupinate. We conducted a manipulative experiment removing floral parts and showed that both the probability of complete resupination and the degree of flower vertical movement (from 0° to 180°) are related to the mass of floral organs. During flower development, the tip of the ovary slightly curves actively (14.75°) due to gravitropism. This promotes a lever arm effect so that the gravitational pull acting on flower mass creates a torque that bends the ovary, orienting the flower into a resupinate position that is accessible to pollinators. The role of the mass of floral organs in resupination provides new insights into flower development and its role in pollination mechanisms.
Obtaining 3D Atomic Reconstructions from Electron Microscopy Images Using a Bayesian Genetic Algorithm: Possibilities, Insights, and Limitations
Authors: Stoops Tom , De Backer Annick , Lobato Ivan , Van Aert Sandra 
Published: October 2024

Abstract
The Bayesian genetic algorithm (BGA) is a powerful tool to reconstruct the 3D structure of mono-atomic single-crystalline metallic nanoparticles imaged using annular dark field scanning transmission electron microscopy. The number of atoms in a projected atomic column in the image is used as input to obtain an accurate and atomically precise reconstruction of the nanoparticle, taking prior knowledge and the finite precision of atom counting into account. However, as the number of parameters required to describe a nanoparticle with atomic detail rises quickly with the size of the studied particle, the computational costs of the BGA rise to prohibitively expensive levels. In this study, we investigate these computational costs and propose methods and control parameters for efficient application of the algorithm to nanoparticles of at least up to 10 nm in size.