bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of immunocapture and nanoflow LC–MS/MS to overcome the barriers to the quantitation of oxytocin in plasma of women in third stage labour
Authors: Bijttebier Sebastiaan , Nguyen Tri‐Hung , McIntosh Michelle P. , Kirkpatrick Carl , Remmerie Bart , Dillen Lieve , Lambert Pete 
Published: June 2024

AimsPostpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. To prevent PPH, the WHO recommends administration of oxytocin (OT) immediately after birth, i.e. during the third stage of labour (TSL). Previous studies demonstrate that methods to quantify OT in biological matrices, e.g. enzyme‐linked immunosorbent assays (ELISA), radioimmunoassays (RIA) and liquid chromatography–tandem mass spectrometry (LC–MS/MS) lack the specificity and/or sensitivity to accurately quantify OT in plasma from women administered OT during TSL. This is due to increased metabolic clearance of OT in late‐stage pregnancy and at the time of childbirth, resulting in extremely low OT plasma concentrations. This study describes the development of an ultra‐sensitive bioanalytical method that overcomes the issues previously reported and enables accurate pharmacokinetic analyses of exogenously administered OT in TSL.MethodsA selective and sensitive assay to quantify OT in TSL plasma was developed. Immunoprecipitation (IP) was applied to selectively extract OT from the TSL plasma, thereby generating clean extracts compatible with nanoflow LC (nLC). nLC–MS/MS was chosen for its high sensitivity and ability to differentiate between OT and potentially co‐captured OT‐like immunoreactive products.ResultsThe presented methodology is accurate and precise, with a good linear fit between 100–10 000 fg mL−1 OT. TSL plasma samples from a clinical phase 1 study (NCT02999100) were analysed successfully, enabling OT quantification down to 100 fg mL−1.ConclusionsThe presented IP–nLC–MS/MS method succeeded in overcoming the sensitivity challenge related to the assay of OT in TSL plasma and thereby revealing the PK profiles of OT in TSL plasma clinical study samples.
Serum mass spectrometry for treatment monitoring in patients with multiple myeloma receiving ARI0002h CAR T‐cells
Authors: Ortiz de Landazuri Iñaki , Oliver‐Caldés Aina , Español‐Rego Marta , Agulló Cristina , Contreras María Teresa , Zabaleta Aintzane , Puig Noemí , Cabañas Valentín , González‐Calle Verónica , Zugasti Inés , Inogés Susana , Rodríguez Otero Paula , Martin‐Antonio Beatriz , Reguera Juan Luis , López‐Diaz de Cerio Ascensión , Aróstegui Juan Ignacio , Uribe‐Herranz Mireia , Benítez‐Ribas Daniel , Rodríguez‐Lobato Luis Gerardo , González Europa Azucena , Tovar Natalia , Charry Paola , Navarro Sergio , Rosiñol Laura , Tréboles Karen , Mora Génesis , Yagüe Jordi , Moraleda José María , Urbano‐Ispizua Álvaro , Mateos María Victoria , Pascal Mariona , Paiva Bruno , Juan Manel , Fernández de Larrea Carlos 
Published: June 2024

SummaryChimeric antigen receptor (CAR) T‐cell therapies have increased the patients with relapsed/refractory multiple myeloma (RRMM) in whom standard electrophoretic techniques fail to detect the M‐protein. Quantitative immunoprecipitation mass spectrometry (QIP‐MS) can accurately measure serum M‐protein with high sensitivity, and identify interferences caused by therapeutic monoclonal antibodies. Here, we investigate the outcome of QIP‐MS in 33 patients treated with the academic BCMA‐directed CAR T‐cell ARI0002h (Cesnicabtagene Autoleucel). QIP‐MS offered more detailed insights than serum immunofixation (sIFE), identifying glycosylated M‐proteins and minor additional peaks. Moreover, the potential interferences owing to daratumumab or tocilizumab treatments were successfully detected. When analysing different assay platforms during patient's monitoring after ARI0002h administration, we observed that QIP‐MS showed a high global concordance (78.8%) with sIFE, whereas it was only moderate (55.6%) with bone marrow (BM)‐based next‐generation flow cytometry (NGF). Furthermore, QIP‐MS consistently demonstrated the lowest negativity rate across the different timepoints (27.3% vs. 60.0% in months 1 and 12, respectively). Patients with QIP‐MS(+)/BM‐based NGF(−) showed a non‐significant shorter median progression free survival than those with QIP‐MS(−)/BM‐based NGF(−). In summary, we show the first experience to our knowledge demonstrating that QIP‐MS could be particularly useful as a non‐invasive technique when evaluating response after CAR T‐cell treatment in MM.
Controversies in endoscopic ultrasonography‐guided management of walled‐off necrosis
Authors: Nakai Yousuke , Saito Tomotaka , Hamada Tsuyoshi , Sato Tatsuya , Hakuta Ryunosuke , Takahara Naminatsu , Isayama Hiroyuki , Yasuda Ichiro , Fujishiro Mitsuhiro 
Published: June 2024

Walled‐off necrosis (WON) develops as local complications after acute necrotizing pancreatitis. Although less invasive interventions such as endoscopic ultrasonography (EUS)‐guided drainage and endoscopic necrosectomy are selected over surgical interventions, delayed and step‐up interventions are still preferred to avoid procedure‐related adverse events. However, there is a controversy about the appropriate timing of drainage and subsequent necrosectomy. The advent of large‐caliber lumen‐apposing metal stents has also brought about potential advantages of proactive interventions, which still needs investigation in future trials. When step‐up interventions of necrosectomy and additional drainage are necessary, a structured or protocoled approach for WON has been reported to improve safety and effectiveness of endoscopic and/or percutaneous treatment, but has not been standardized yet. Finally, long‐term outcomes such as recurrence of WON, pancreatic endocrine, and exocrine function are increasingly investigated in association with disconnected pancreatic duct syndrome. In this review we discuss current evidence and controversy on EUS‐guided management of WON.
Estimation of the direct health and indirect societal costs of diabetes in the UK using a cost of illness model
Authors: Hex Nick , MacDonald Rachael , Pocock Jessica , Uzdzinska Barbara , Taylor Matthew , Atkin Marc , Wild Sarah H. , Beba Hannah , Jones Ross 
Published: June 2024

AbstractAimsThe direct cost of diabetes to the UK health system was estimated at around £10 billion in 2012. This analysis updates that estimate using more recent and accurate data sources.MethodsA pragmatic review of relevant data sources for UK nations was conducted, including population‐level data sets and published literature, to generate estimates of costs separately for Type 1, Type 2 and gestational diabetes. A comprehensive cost framework, developed in collaboration with experts, was used to create a population‐based cost of illness model.The key driver of the analysis was prevalence of diabetes and its complications. Estimates were made of the excess costs of diagnosis, treatment and diabetes‐related complications compared with the general UK population. Estimates of the indirect costs of diabetes focused on productivity losses due to absenteeism and premature mortality.ResultsThe direct costs of diabetes in 2021/22 for the UK were estimated at £10.7 billion, of which just over 40% related to diagnosis and treatment, with the rest relating to the excess costs of complications. Indirect costs were estimated at £3.3 billion.ConclusionsDiabetes remains a considerable cost burden in the UK, and the majority of those costs are still spent on potentially preventable complications. Although rates of some complications are reducing, prevalence continues to increase and effective approaches to primary and secondary prevention continue to be needed. Improvements in data capture, data quality and reporting, and further research on the human and financial implications of increasing incidence of Type 2 diabetes in younger people are recommended.
In situ studies on temperature‐dependent deformation mechanisms of Al2O3 prepared by spark plasma sintering
Authors: Shen Chao , Niu Tongjun , Cho Jaehun , Sun Tianyi , Shang Anyu , Zhang Yifan , Wang Haiyan , Zhang Xinghang 
Published: June 2024

AbstractAlumina (α‐Al2O3) is one of the most versatile engineering ceramics, and its mechanical properties have been extensively studied. However, the micromechanical properties of Al2O3 with a fine microstructure are less well understood. Here, we present one of the first investigations that probe the micromechanical properties of fine‐grained polycrystalline Al2O3 fabricated via spark plasma sintering, employing in situ microcompression tests inside a scanning electron microscope. This study explores the influence of temperature variations on the deformation mechanisms, particularly the involvement of microcracks and dislocation activities throughout the deformation process. As temperature rises, substantial deformability occurs in the inherently brittle Al2O3 at intermediate temperature, where the improved plastic deformability mainly arose from prominent dislocation activities accompanied by grain boundary sliding. This study sheds light on understanding the relationship between defect evolution and mechanical behavior in Al2O3 with fine grain sizes.
Evaluating Airflow Sensor Methods: Precision in Indirect Calorimetry
Authors: Titheradge Praneel , Robergs Robert 
Published: June 2024

ABSTRACTThis study assesses the impact of three volumetric gas flow measurement methods—turbine (fT); pneumotachograph (fP), and Venturi (fV)—on predictive accuracy and precision of expired gas analysis indirect calorimetry (EGAIC) across varying exercise intensities. Six males (Age: 38 ± 8 year; Height: 178.8 ± 4.2 cm; : 42 ± 2.8 mL O2 kg−1 min−1) and 14 females (Age = 44.6 ± 9.6 year; Height = 164.6 ± 6.9 cm; = 45 ± 8.6 mL O2 kg−1 min−1) were recruited. Participants completed physical exertion on a stationary cycle ergometer for simultaneous pulmonary minute ventilation () measurements and EGAIC computations. Exercise protocols and subsequent conditions involved a 5‐min cycling warm‐up at 25 W min−1, incremental exercise to exhaustion ( ramp test), then a steady‐state exercise bout induced by a constant Watt load equivalent to 80% ventilatory threshold (80% VT). A linear mixed model revealed that exercise intensity significantly affected measurements (p < 0.0001), whereas airflow sensor method (p = 0.97) and its interaction with exercise intensity (p = 0.91) did not. Group analysis of precision yielded a CV % = 21%; SEM = 5 mL O2 kg−1 min−1. Intra‐ and interindividual analysis of precision via Bland–Altman revealed a 95% confidence interval (CI) precision benchmark of 3–5 mL kg−1 min−1. Agreement among methods decreased at power outputs eliciting up to 150 L min−1, indicating a decrease in precision and highlighting potential challenges in interpreting biological variability, training response heterogeneity, and test–retest comparisons. These findings suggest careful consideration of airflow sensor method variance across metabolic cart configurations.
A national surveillance system for continuous monitoring of blood transfusion safety: German haemovigilance data
Authors: Berg Philipp , Heiden Margarethe , Müller Susanne , Meyer Britta , Witzenhausen Cornelia , Ruppert‐Seipp Gabriele , Kehr Sarah , Funk Markus B. 
Published: June 2024

AbstractBackground and ObjectivesHaemovigilance (HV) systems aim to improve transfusion outcomes in patients and donor safety. An important question for blood regulators is how to ensure an effective HV system.Materials and MethodsWe retrospectively analysed the HV reports submitted to Paul‐Ehrlich‐Institut over the last two decades.ResultsBetween 2011 and 2020, 50.86 million units of blood components were used, and 8931 suspected serious donor and recipient adverse reactions (SARs), 874 serious adverse events (SAEs) and 12,073 donor look‐backs were reported. Following implementation of specific risk‐minimization measures (RMMs) between 2000 and 2010, SAR reporting rates decreased for transfusion‐transmitted viral infections (TTVIs), transfusion‐related acute lung injury (TRALI) and transfusion‐transmitted bacterial infections (TTBIs), while increasing for other serious adverse transfusion reactions. Within this decade, the overall blood component use decreased.ConclusionLong‐term data collection forms the basis to establish trends and changes in reporting and to evaluate the effect of RMM. Standardized criteria for reaction types, seriousness and imputability assessments and availability of a denominator are important elements. Central data collection and independent assessment allow for monitoring HV data in a nationwide context over time. Stakeholder involvement and transparent feedback on the benefit of RMM will help to achieve the objectives of HV.
Does metformin prolong pregnancy in preterm pre-eclampsia? A study protocol for a South African, hospital-based double-blind, randomised, placebo-controlled trial
Authors: Cluver Catherine Anne , Bergman Lina , Imberg Henrik , Mol Ben W , Hall David , Bekker Adrie , Gordon Adrienne , Brownfoot Fiona , Kaitu’u-Lino Tu’uhevaha J , Walker Susan P , Tong Stephen 
Published: June 2024

IntroductionPreterm pre-eclampsia is a leading cause of maternal morbidity and mortality. The Pre-eclampsia Intervention 2 (PI 2) trial suggested that metformin sustained release (XR) may prolong gestation by a week in pregnant women undergoing expectant management (7.6 days, geometric mean ratio 1.39, 95% CI 0.99 to 1.95; p=0.057). These findings should be confirmed with a larger sample size, and we need to know if such a prolongation improves neonatal outcome. Here, we describe the protocol for such a follow-up trial.MethodsThe PI 3 trial is a phase III, intention-to-treat, double-blind, placebo-controlled randomised clinical trial to assess if metformin XR can prolong gestation and improve neonatal outcomes in women undergoing expectant management for preterm pre-eclampsia. We will recruit women who are between 26+0 and 31+6 weeks pregnant. Women will be randomised to receive either 3 g metformin XR or an identical placebo in divided daily doses. The primary outcome is prolongation of pregnancy. Secondary outcomes are neonatal birth weight and length of neonatal care admission (an indicator of neonatal health at birth). All other outcomes will be exploratory. We will record tolerability and adverse events. We plan a sample size of 500 participants to be powered for the primary and secondary outcomes.Ethics and disseminationPI 3 has ethical approval (Health Research Ethics Committee 2, Stellenbosch University, Protocol number M21/03/007, Project ID 21639, Federal Wide Assurance Number 00001372, Institutional Review Board Number IRB0005239), and is registered with the Pan African Clinical Trial Registry (PACTR202104532026017) and the South African Medicine Control Council (20211211). Data will be presented at international conferences and published in peer-reviewed journals.Trial registration numberPACTR202104532026017)
Product Market Competition and Stock Price Crash Risk: Evidence from China
Authors: Ma Yunbiao , Yang Xiaotong , Zhang Yuan , Zhu Bing 
Published: June 2024

Synopsis The research problem This study analyzes the relationship between product market competition (PMC) and stock price crash risk in China, especially for firms with weak corporate governance and a lower-quality information environment. Motivation Emerging capital markets like China have less-developed financial systems and institutions compared to developed capital markets like Europe and the United States, making them more susceptible to stock price crash risk. The impact of product market competition (PMC) on corporate decision-making has attracted considerable attention from scholars, especially given the increasingly intense and complex strategic competition in global markets and uncertainty in the world today. However, the effect of PMC on a firm’s stock price crash risk has not been thoroughly explored. Therefore, this study investigated how PMC affects managers’ tendency to hoard bad news and how this behavior contributes to the risk of stock price crashes. The test hypotheses We tested two competing hypotheses: PMC is negatively correlated with crash risk, and PMC is positively correlated with crash risk. Target population This study should be of interest to stakeholders, including firm managers, practitioners, regulatory authorities, policymakers, and investors. Adopted methodology This study employed ordinary least squares (OLS), difference-in-differences analysis (DID), and path analysis. Analysis Using a sample of Chinese A-share listed manufacturing firms from 2000 to 2021, this study found that competitive pressure from the product market encouraged managers to hide bad news, thereby increasing future stock price crash risk. Moreover, we performed additional tests to examine how PMC affected stock price crash risk. Findings We found robust evidence that PMC significantly increases stock price crash risk. Further tests showed that the effect of PMC on crash risk is more pronounced for firms with weak corporate governance and a lower-quality information environment. We also provide evidence that firms in highly competitive industries tend to disclose fewer negative words in the management discussion and analysis section of the annual report and fewer risk factors in the internal control report. Moreover, we show that operational risk is the underlying driver through which PMC affects crash risk.
Abstract PO-035: Genome-wide CRISPR knockout screen identifies sialylation as a tumor suppressive mechanism in B-cell malignancies
Authors: Sheshadri Namratha , Li Rongrong , Tariq Muhammad Usama , Shen Jianliang , Jung Jaeyong , Yan Junrong , Lu Kevin , Shen Zhiyuan , Xie Ping , Zong Wei-Xing 
Published: June 2024

Abstract
Ba/F3 is a murine pro-B cell line that is dependent on interleukin-3 (IL-3) for its survival and proliferation. It has been widely used for identifying oncogenes and mechanisms of drug-resistance. Using this cell line, we conducted a genome-wide CRISPR knockout screen to identify genes whose loss can confer IL-3 independence, hence may be implied as tumor suppressor genes (TSGs). We identified several genes that map to human chromosome 6q, a frequent deletion hotspot in B-cell malignancies, that may act as TSGs. One of these putative novel TSGs is Slc35a1, which encodes the membrane solute carrier that facilitates the transport of nucleotide sugar (CMP-sialic acid) into the Golgi apparatus for subsequent sialylation. Interestingly, in addition to Slc35a1, pathway analysis of hits from the CRISPR screen identified several genes in the sialic acid metabolism pathway, Nans, Cmas, and St3gal5. We confirmed that their silencing led to decreased protein sialyation and could confer IL-3-independent cell survival and growth in Ba/F3 cells. We continued to characterize Slc35a1 since its homozygous and heterozygous deletions are seen in 7-40% of different types of B-cell malignancies, including approximately 40% of patients with Diffuse Large B-cell Lymphoma. Slc35a1 deletion in murine and human cell-lines conferred cytokine-independent growth. Tail-vein injection of Slc35a1-silenced Ba/F3 cells resulted in allograft tumor growth presenting with splenomegaly and lymphadenopathy. Using Maackia amurensis lectin II (MAL II) to pull down sialylated proteins for mass spectrometry, we identified proteins that were differentially sialylated in Slc35a1 wild-type and knockout cells, among which are the α and β subunits of the integrin receptor, lymphocyte functional antigen 1 (LFA-1). As integrin desialylation can promote its constitutive activation, we are currently studying the impact of LFA-1 sialylation on B-cell function and transformation. We have also developed mouse models with B-cell specific ablation of Nans and Slc35a1 to further evaluate the role of sialylation on B-cell development and tumorigenesis in vivo. Overall, our study demonstrates that sialylation may function as a tumor suppressive mechanism and serve as a therapeutic target in B-cell cancers.
Citation Format: Namratha Sheshadri, Rongrong Li, Muhammad Usama Tariq, Jianliang Shen, Jaeyong Jung, Junrong Yan, Kevin Lu, Zhiyuan Shen, Ping Xie, Wei-Xing Zong. Genome-wide CRISPR knockout screen identifies sialylation as a tumor suppressive mechanism in B-cell malignancies [abstract]. In: Proceedings of the Fourth AACR International Meeting on Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2024 Jun 19-22; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(3_Suppl):Abstract nr PO-035.
PENGETAHUAN, SIKAP, DAN PERILAKU PASIEN GLAUKOMA DI PMN RS MATA CICENDO TERHADAP PENYAKIT GLAUKOMA
Authors: Akbari Anamika Lingga Anjani , Rifada R. Maula , Gustianty Elsa 
Published: June 2024

Pendahuluan: Glaukoma merupakan penyebab kedua kebutaan terbanyak secara global. Sebagian besar kasus glaukoma bersifat asimptomatik, sehingga pasien tidak sadar dengan penyakitnya sampai munculnya gangguan penglihatan hingga kebutaan. Melalui pengetahuan, sikap, dan perilaku (PSP) pasien yang baik dapat mendukung pengendalian keparahan penyakit glaukoma. Akan tetapi, di Indonesia penelitian yang menunjukkan tingkat PSP pasien glaukoma terhadap penyakit glaukoma masih tergolong sedikit. Oleh karena itu, penelitian ini bertujuan untuk menilai tingkat PSP pasien glaukoma di PMN RS Mata Cicendo terhadap penyakit glaukoma.
Metode: Studi ini menggunakan metode kuantitatif dengan desain penelitian deskriptif cross-sectional melalui pengisian kuesioner pada 59 pasien glaukoma di PMN RS Mata Cicendo pada bulan Februari 2023. Pada penelitian ini terdapat tiga variabel yang dinilai, yaitu pengetahuan, sikap, dan perilaku.
Hasil: Pasien glaukoma menunjukkan pengetahuan baik (35,6%), cukup (59,5%), dan kurang (5,1%) dengan hanya 42,4% pasien yang bersikap positif dan 49,2% pasien berperilaku baik. Secara keseluruhan tingkat PSP pasien adalah 47%. PSP yang baik banyak ditemukan pada pasien dengan durasi pengobatan ≥6 bulan.
Simpulan: Tingkat PSP pasien glaukoma terhadap penyakit glaukoma yang sudah cukup baik tetap harus ditingkatkan dengan strategi edukasi agar tingkat sikap dan perilaku pasien jauh lebih baik.
MULTIPLE EYELID LUMPS IN INFANT WITH DYSLIPIDEMIA IN RESOURCE-LIMITED SETTING ANAMBAS ARCHIPELAGO DISTRICT
Authors: Febrianti Santi 
Published: June 2024

Objective: Present a case of recurrent multiple eyelid lumps in the infant with dyslipidemia in the limited resources area.
Case Report: A case report on a three-year-old child who had several painless red tumors in his eyelids and was well-nourished. The patient had a similar complaint three times in the last seven months in different sites. No history of atopy, chronic blepharitis, trauma, or eyelid surgery. Laboratory findings showed elevated levels of cholesterol. Warm compresses, antibiotic topical, and erythromycin 50 mg/kgbw/day divided into three doses were the patient's initial therapeutic interventions. For managing dyslipidemia we planned to modification of lifestyle, diet, and activities for two weeks, then evaluate the level of cholesterol. We evaluated and educated the patient’s parent to refer him to an ophthalmologist for further management. However, we had difficulty referring patients to the provincial hospital with an ophthalmologist due to the islands’ geographical location, infrequent and weather-affected transportation, as well as family economics.
Discussions: A hordeolum is a common inflammation of the eyelid margin. Recurrence of hordeolum is usually associated with underlying causes such as systemic disease. Dyslipidemia leads to hypersecretion of meibum which will cause highly concentrated meibum in Meibomian glands, that leads to blockage of ducts of Meibomian glands and Meibomian gland dysfunction (MGD). Initial treatment of hordeolum is indeed conservative, typically limited to the application of warm compresses several times a day and topical antibiotics.
Conclusions: Dyslipidemia is usually associated with recurrent hordeolum. The management of hordeolum is conservative.