bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacologic Targeting of Histone H3K27 Acetylation/BRD4-dependent Induction of ALDH1A3 for Early-phase Drug Tolerance of Gastric Cancer
Authors: Lee Jin , Mashima Tetsuo , Kawata Naomi , Yamamoto Noriko , Morino Shun , Inaba Saori , Nakamura Ayane , Kumagai Koshi , Wakatsuki Takeru , Takeuchi Kengo , Yamaguchi Kensei , Seimiya Hiroyuki 
Published: April 2024

Abstract

Anticancer drug-tolerant persister (DTP) cells at an early phase of chemotherapy reshape refractory tumors. Aldehyde dehydrogenase 1 family member A3 (ALDH1A3) is commonly upregulated by various anticancer drugs in gastric cancer patient-derived cells (PDC) and promotes tumor growth. However, the mechanism underlying the generation of ALDH1A3-positive DTP cells remains elusive. Here, we investigated the mechanism of ALDH1A3 expression and a combination therapy targeting gastric cancer DTP cells. We found that gastric cancer tissues treated with neoadjuvant chemotherapy showed high ALDH1A3 expression. Chromatin immunoprecipitation (ChIP)-PCR and ChIP sequencing analyses revealed that histone H3 lysine 27 acetylation was enriched in the ALDH1A3 promoter in 5-fluorouracil (5-FU)-tolerant persister PDCs. By chemical library screening, we found that the bromodomain and extraterminal (BET) inhibitors OTX015/birabresib and I-BET-762/molibresib suppressed DTP-related ALDH1A3 expression and preferentially inhibited DTP cell growth. In DTP cells, BRD4, but not BRD2/3, was recruited to the ALDH1A3 promoter and BRD4 knockdown decreased drug-induced ALDH1A3 upregulation. Combination therapy with 5-FU and OTX015 significantly suppressed in vivo tumor growth. These observations suggest that BET inhibitors are efficient DTP cell–targeting agents for gastric cancer treatment.

Significance:
Drug resistance hampers the cure of patients with cancer. To prevent stable drug resistance, DTP cancer cells are rational therapeutic targets that emerge during the early phase of chemotherapy. This study proposes that the epigenetic regulation by BET inhibitors may be a rational therapeutic strategy to eliminate DTP cells.
Percutaneous Balloon–Expandable Stent Implantation to Treat Transverse Aortic Arch Obstruction: Medium- to Long-Term Outcomes of a Retrospective Multicenter Study
Authors: Salavitabar Arash , Eisner Mariah , Armstrong Aimee K. , Boe Brian A. , Chisolm Joanne L. , Cheatham John P. , Cheatham Sharon L. , Forbes Thomas , Jones Thomas K. , Krings Gregor J. , Morray Brian H. , Steinberg Zachary L. , Akam-Venkata Jyothsna , Voskuil Michiel , Berman Darren P. 
Published: April 2024

BACKGROUND:
Transverse aortic arch obstruction is a challenging lesion for which stent implantation provides a potentially important alternate therapy. The objectives were to evaluate the technical, procedural, and medium-to-long-term clinical outcomes of percutaneous stent implantation of transverse aortic arch obstruction.

METHODS:
This is a retrospective, multicenter study of transverse aortic arch stent implantation. Univariable and multivariable analyses were performed.

RESULTS:

Index catheterization included 187 stent implants in 146 patients. The median age is 14.3 years (interquartile range, 9.3–19), weight is 53 kg (30–69), and follow-up is 53 months (12–120). The most common stent design was open cell (n=90, 48%). Stents overlapped 142 arch vessels (37 carotid arteries) in 118 (81%) cases. Technical and procedural success rates were 100% and 88%, respectively. Lower weight (
P
=0.018), body surface area (
P
=0.013), and minimum-to-descending aortic diameter ratio (
P
<0.001) were associated with higher baseline aortic gradient. The residual gradient was inversely associated with implant and final dilation diameters (
P
<0.001). The combined incidence of aortic injury and stent-related complications was 14%. There were no reports of abnormal brain scans or stroke. Blood pressure cuff gradient, echocardiographic arch velocity, and hypertension rates improved within 1-year follow-up with increased antihypertensive medication use. Reintervention was reported in 60 (41%) patients at a median of 84 (22–148) months to first reintervention. On multivariable logistic regression, residual aortic gradient >10 mm Hg was associated with increased odds of reintervention at all time points when controlling for each final dilation diameter, weight, and minimum-to-descending aortic diameter ratio.

CONCLUSIONS:
Transverse aortic arch stent implantation has high rates of technical, procedural, and medium-to-long-term clinical success. Aortic gradient >10 mm Hg is associated with increased odds of reintervention at 1-year and most recent follow-ups. Open cell stent design was frequently used for its advantages in conformability, perfusion of arch vessels, low fracture rate, and the ability to perform effective angioplasty of side cells.
Precision brain morphometry using cluster scanning
Authors: Elliott Maxwell L. , Nielsen Jared A. , Hanford Lindsay C. , Hamadeh Aya , Hilbert Tom , Kober Tobias , Dickerson Bradford C. , Hyman Bradley T. , Mair Ross W. , Eldaief Mark C. , Buckner Randy L. 
Published: April 2024

Abstract
Measurement error limits the statistical power to detect group differences and longitudinal change in structural MRI morphometric measures (e.g., hippocampal volume, prefrontal cortical thickness). Recent advances in scan acceleration enable extremely fast T1-weighted scans (~1 minute) that achieve morphometric errors that are close to the errors in longer traditional scans. As acceleration allows multiple scans to be acquired in rapid succession, it becomes possible to pool estimates to increase measurement precision, a strategy known as “cluster scanning.” Here, we explored brain morphometry using cluster scanning in a test-retest study of 40 individuals (12 younger adults, 18 cognitively unimpaired older adults, and 10 adults diagnosed with mild cognitive impairment or Alzheimer’s Dementia). Morphometric errors from a single compressed sensing (CS) 1.0 mm scan (CS) were, on average, 12% larger than a traditional scan using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) protocol. Pooled estimates from four clustered CS acquisitions led to errors that were 34% smaller than ADNI despite having a shorter total acquisition time. Given a fixed amount of time, a gain in measurement precision can thus be achieved by acquiring multiple rapid scans instead of a single traditional scan. Errors were further reduced when estimates were pooled from eight CS scans (51% smaller than ADNI). Neither pooling across a break nor pooling across multiple scans of different spatial resolutions boosted this benefit. We discuss the potential of cluster scanning to improve morphometric precision, boost statistical power, and produce more sensitive disease progression biomarkers.
Gauge-Optimal Approximate Learning for Small Data Classification
Authors: Vecchi Edoardo , Bassetti Davide , Graziato Fabio , Pospíšil Lukáš , Horenko Illia 
Published: April 2024

Abstract
Small data learning problems are characterized by a significant discrepancy between the limited number of response variable observations and the large feature space dimension. In this setting, the common learning tools struggle to identify the features important for the classification task from those that bear no relevant information and cannot derive an appropriate learning rule that allows discriminating among different classes. As a potential solution to this problem, here we exploit the idea of reducing and rotating the feature space in a lower-dimensional gauge and propose the gauge-optimal approximate learning (GOAL) algorithm, which provides an analytically tractable joint solution to the dimension reduction, feature segmentation, and classification problems for small data learning problems. We prove that the optimal solution of the GOAL algorithm consists in piecewise-linear functions in the Euclidean space and that it can be approximated through a monotonically convergent algorithm that presents—under the assumption of a discrete segmentation of the feature space—a closed-form solution for each optimization substep and an overall linear iteration cost scaling. The GOAL algorithm has been compared to other state-of-the-art machine learning tools on both synthetic data and challenging real-world applications from climate science and bioinformatics (i.e., prediction of the El Niño Southern Oscillation and inference of epigenetically induced gene-activity networks from limited experimental data). The experimental results show that the proposed algorithm outperforms the reported best competitors for these problems in both learning performance and computational cost.
Common Concern of Humankind and Its Legal Consequences for Climate Stability
Authors: Amat-i-Puigsech Didac 
Published: April 2024

Abstract
One of the main challenges for modern international law is its capacity to deal with global public interests. In a world characterized by growing interdependence, the international community requires instruments to regulate the global commons, provide global public goods, and enforce its fundamental values. In this context, this article contributes to the debate on the legal consequences of recognizing climate stability as a global public good. While these goods are regulated on a case-by-case basis, some of them have the status of being common concerns of humankind. Since the icj and the ilc have not clarified the content of this legal status, I discuss the main academic perspectives and propose a new standpoint. Considering the current stage of public international law, I argue that the common concern status does not generate new state obligations but impacts the content of those commitments already included in the international climate change regime.
Machine learning-based wood anatomy identification: towards anatomical feature recognition
Authors: He Xin , Pelt Daniël M. , Gao JingRan , Gravendeel Barbara , Zhu PeiQi , Chen SongYang , Qiu Jian , Lens Frederic 
Published: April 2024

Summary
Computer vision-based wood identification has been successfully applied to recognize tree species using digital images of wood sections or surfaces. However, this image-to-species approach can only recognize a limited number of species due to two main reasons: 1) the lack of a good reference database requiring high-quality standardized images from multiple individuals of hundreds or even thousands of traded timber species, and 2) species not included in the reference database cannot be identified without expert knowledge. Another bottleneck is that the feature extraction process used by these species recognition approaches is a black box, thereby creating a discrepancy between machine learning features and wood anatomical features. This discrepancy prevents wood anatomists from understanding how these machine-learning algorithms work. Here, we survey currently existing methods used in feature extraction, classification, and deep learning methods applied in wood identification along with their pitfalls and opportunities. As an example of how the field could move forward, we launch the idea of building an image-to-features-to-species identification approach based on microscopic wood images as well as text files comprising wood anatomical descriptions. If we can manage machine learning-based algorithms to recognize the main wood anatomical traits that experts use to identify species in a (semi-)automated way, this would boost wood identification in two ways: (1) extensive reference databases for each species would become less crucial as the databases are ordered at the trait level, (2) timber identification would become more feasible for species that have not yet been included in the reference database as long as wood anatomical descriptions are available.
Assessing children’s health literacy: A curricular approach
Authors: Otten Claire , Kemp Nenagh , Cruickshank Vaughan , Peralta Louisa , Hawkins Melanie , Nash Rose 
Published: April 2024

Objectives: Increasing childhood health literacy (HL) is a crucial means of improving health outcomes and reducing preventable deaths globally. Understanding how to best support children’s HL development in schools is essential. However, identifying pedagogical strategies that develop children’s HL relies on a fit-for-purpose measure. Currently, no universally accepted approach for measuring HL among children exists. The purpose of this paper was to propose and discuss how a curricular approach to assessing children’s HL could provide a means to overcoming the challenges with existing children HL measures. Design/Methods: The discussion is framed by the key components of assessment – outcome of interest, and collection, analysis and interpretation of data – and is underpinned by contemporary HL and educational research. Setting: The Australian Curriculum is used to discuss the approach in practice. Results: A curricular approach to HL assessment suggests that HL assessment may work best when it is relevant to the child and their context, is integrated with other areas of the curriculum, allows children to demonstrate a wide range of HL skills and contains an element of open-endedness. Measurement could be guided by a rubric (underpinned by a taxonomy), and interpretation of scores consistently aligned with the learning intentions outlined in the curriculum. Conclusion: A curricular approach provides a contextually adaptive framework from which HL assessment tools for children can be developed.
The Role of Internal Control Disclosure in Financial Reporting Precision and the Quality of Audited Financial Reports
Authors: Deng Mingcherng , Wen Xiaoyan 
Published: April 2024

We study the impact of internal control disclosure in a model in which a client company privately invests corporate resources in its internal control system that subsequently determines its financial reporting precision. Without internal control disclosure, the capital market cannot observe the precision and must price the client value based on its conjecture. With internal control disclosure requirements, the effectiveness of internal controls is disclosed, which reveals the precision to the market. Thus, internal control disclosure provides the client with another channel to influence the market pricing. Contrary to the conventional wisdom, we find that the client tends to invest less in its internal control system with disclosure requirements. As a result of lower precision, internal control disclosure may lower the informativeness of audited financial reports, albeit ex-post communicating more information to the market. We also find that internal control disclosure reduces the client’s ex-ante payoff when the auditor bears a high misstatement cost due to audit failure. JEL Classification: M41, M48
Identification and characterization of migraine in pregnancy: A Norwegian registry-based cohort study
Authors: Mitter Vera R. , Lupattelli Angela , Bjørk Marte-Helene , Nordeng Hedvig M.E. 
Published: April 2024

Background Migraine is common in women of reproductive age. Migraine’s episodic manifestation and acute and preventive pharmacological treatment options challenge studying drug safety for this condition during pregnancy. To improve such studies, we aimed to develop algorithms to identify and characterize migraines in electronic healthcare registries and to assess the level of care. Methods We linked four registries to detect pregnancies from 2009–2018 and used three algorithms for migraine identification: i) diagnostic codes, ii) triptans dispensed, and iii) a combination of both. We assessed migraine severity using dispensed drugs as proxies. ICD-10 diagnostic subcodes of migraine (G43) allowed the allocation of four subtypes: complicated and/or status migrainosus; with aura; without aura; other/unspecified. Results We included 535,089 pregnancies in 367,908 women with available one-year lookback. The prevalence of migraines identified was 2.9%–4.3% before, and 0.8%–1.5% during pregnancy, depending on algorithm used. Pregnant women with migraine were mostly managed in primary care. Conclusions Primary care data in combination with drug dispensation records were instrumental for identification of migraine in electronic healthcare registries. Data from secondary care and drug dispensations allow better characterization of migraines. Jointly, these algorithms may contribute to improved perinatal pharmacoepidemiological studies in this population by addressing confounding by maternal migraine indication.
Clonal relapse dynamics in acute myeloid leukemia following allogeneic hematopoietic cell transplantation
Authors: Wienecke Clara Philine , Heida Bennet , Venturini Letizia , Gabdoulline Razif , Krüger Katja , Teich Katrin , Büttner Konstantin , Wichmann Martin , Puppe Wolfram , Neziri Blerina , Reuter Marlene , Dammann Elke , Stadler Michael , Ganser Arnold , Hambach Lothar , Thol Felicitas , Heuser Michael 
Published: April 2024

Abstract
Patients with acute myeloid leukemia (AML) who experience relapse following allogeneic hematopoietic cell transplantation (alloHCT) face unfavorable outcomes regardless of the chosen relapse treatment. Early detection of relapse at the molecular level by measurable residual disease (MRD) assessment enables timely intervention, which may prevent hematological recurrence of the disease. It remains unclear whether molecular MRD assessment can detect MRD before impending relapse and, if so, how long in advance. This study elucidates the molecular architecture and kinetics preceding AML relapse by using error-corrected next-generation sequencing (NGS) in 74 patients with AML relapsing after alloHCT, evaluating 140 samples from peripheral blood collected 0.6 to 14 months before relapse. At least 1 MRD marker became detectable in 10%, 38%, and 64% of patients at 6, 3, and 1 month before relapse, respectively. By translating these proportions into monitoring intervals, 38% of relapses would have been detected through MRD monitoring every 3 months, whereas 64% of relapses would have been detected with monthly intervals. The relapse kinetics after alloHCT are influenced by the functional class of mutations and their stability during molecular progression. Notably, mutations in epigenetic modifier genes exhibited a higher prevalence of MRD positivity and greater stability before relapse, whereas mutations in signaling genes demonstrated a shorter lead time to relapse. Both DTA (DNMT3A, TET2, and ASXL1) and non-DTA mutations displayed similar relapse kinetics during the follow-up period after alloHCT. Our study sets a framework for MRD monitoring after alloHCT by NGS, supporting monthly monitoring from peripheral blood using all variants that are known from diagnosis.
Obinutuzumab vs rituximab for transplant-eligible patients with mantle cell lymphoma
Authors: Sarkozy Clémentine , Callanan Mary , Thieblemont Catherine , Obéric Lucie , Burroni Barbara , Bouabdallah Krimo , Damaj Gandhi , Tessoulin Benoit , Ribrag Vincent , Houot Roch , Morschhauser Franck , Griolet Samuel , Joubert Clémentine , Cacheux Victoria , Delwail Vincent , Safar Violaine , Gressin Remy , Cheminant Morgane , Delfau-Larue Marie-Hélène , Hermine Olivier , Macintyre Elizabeth , Le Gouill Steven 
Published: April 2024

Abstract
Obinutuzumab (O) and rituximab (R) are 2 CD antibodies that have never been compared in a prospective randomized trial of mantle cell lymphoma (MCL). Herein, we report the long-term outcome of the LyMa-101 trial, in which newly diagnosed patients with MCL were treated with chemotherapy plus O before transplantation, followed by O maintenance (O group). We then compared these patients with those treated with the same treatment design with R instead of O (R group). A propensity score matching (PSM) was used to compare the 2 populations (O vs R groups) in terms of measurable residual disease (MRD) at the end of induction (EOI), progression-free survival (PFS), and overall survival (OS). In LyMa-101, the estimated 5-year PFS and OS after inclusion (n = 85) were 83.4% (95% confidence interval [CI], 73.5-89.8) and 86.9% (95% CI, 77.6-92.5), respectively. At EOI, patients treated in the O group had more frequent bone marrow MRD negativity than those treated in the R group (83.1% vs 63.4%; χ2, P = .007). PSM resulted in 2 sets of 82 patients with comparable characteristics at inclusion. From treatment initiation, the O group had a longer estimated 5-year PFS (P = .029; 82.8% vs 66.6%; hazard ratio [HR], 1.99; 95% confidence interval (CI), 1.05-3.76) and OS (P = .039; 86.4% vs 71.4%; HR, 2.08; 95% CI, 1.01-4.16) compared with the R group. Causes of death were comparable in the 2 groups, the most common cause being lymphoma. O before transplantation and in maintenance provides better disease control and enhances PFS and OS compared with R in transplant-eligible patients with MCL. These trials were registered at www.clinicaltrials.gov as #NCT00921414 and NCT02896582.
Outcomes of HLA-mismatched HSCT with TCRαβ/CD19 depletion or post-HSCT cyclophosphamide for inborn errors of immunity
Authors: Lum Su Han , Albert Michael H. , Gilbert Patrick , Sirait Tiarlan , Algeri Mattia , Muratori Rafaella , Fournier Benjamin , Laberko Alexandra , Karakukcu Musa , Unal Elrem , Ayas Mouhab , Yadav Satya Prakash , Fisgin Tunc , Elfeky Reem , Fernandes Juliana , Faraci Maura , Cole Theresa , Schulz Ansgar , Meisel Roland , Zecca Marco , Ifversen Marianne , Biffi Alessandra , Diana Jean-Sebastien , Vallée Tanja , Giardino Stefano , Ersoy Gizem Zengin , Moshous Despina , Gennery Andrew R. , Balashov Dmitry , Bonfim Carmem , Locatelli Franco , Lankester Arjan , Neven Bénédicte , Slatter Mary 
Published: April 2024

Abstract
HLA-mismatched transplants with either in vitro depletion of CD3+ T-cell receptor (TCR)αβ/CD19 (TCRαβ) cells or in vivo T-cell depletion using posttransplant cyclophosphamide (PTCY) have been increasingly used for patients with inborn errors of immunity (IEIs). We performed a retrospective multicenter study via the EBMT registry on 306 children with IEIs undergoing their first transplant between 2010 and 2019 from an HLA-mismatched donor using TCRαβ (n = 167) or PTCY (n = 139). The median age for hematopoietic stem cell transplantation (HSCT) was 1.2 years (range, 0.03-19.6 years). The 3-year overall survival (OS) was 78% (95% confidence interval (CI), 71-84) after TCRαβ and 66% (57-74) after PTCY (P = .013). Pre-HSCT morbidity score (hazard ratio [HR], 2.27; 1.07-4.80, P = .032) and non-busulfan/treosulfan conditioning (HR, 3.12; 1.98-4.92, P &lt; .001) were the only independent predictors of unfavorable OS. The 3-year event-free survival (EFS) was 58% (50%-66%) after TCRαβ and 57% (48%-66%) after PTCY (P = .804). The cumulative incidence of severe acute graft-versus-host disease (GvHD) was higher after PTCY (15%, 9%-21%) than TCRαβ (6%, 2%-9%, P = .007), with no difference in chronic GvHD (PTCY, 11%, 6%-17%; TCRαβ, 7%, 3%-11%, P = .173). The 3-year GvHD-free EFS was 53% (44%-61%) after TCRαβ and 41% (32%-50%) after PTCY (P = .080). PTCY had significantly higher rates of veno-occlusive disease (14.4% vs TCRαβ 4.9%, P = .009), acute kidney injury (12.7% vs 4.6%, P = .032), and pulmonary complications (38.2% vs 24.1%, P = .017). Adenoviremia (18.3% vs PTCY 8.0%, P = .015), primary graft failure (10% vs 5%, P = .048), and second HSCT (17.4% vs 7.9%, P = .023) were significantly higher in TCRαβ. In conclusion, this study demonstrates that both approaches are suitable options in patients with IEIs, although they are characterized by different advantages and outcomes.
High efficacy of CD19 CAR T cells in patients with transformed Waldenström macroglobulinemia
Authors: Durot Eric , Roos-Weil Damien , Chauchet Adrien , Decroocq Justine , Di Blasi Roberta , Gastinne Thomas , Bensaber Hedi , Cheminant Morgane , Jacquet Caroline , Guidez Stéphanie , Gros François-Xavier , Bachy Emmanuel , Coste Arthur , Cony-Makhoul Pascale , Treon Steven P. , Delmer Alain , Reshef Ran , Le Gouill Steven , Castillo Jorge J. , Houot Roch 
Published: April 2024

Abstract
Histologic transformation of Waldenström macroglobulinemia (HT-WM) carries a poor prognosis with standard treatments. Here, we report the first series of HT-WM treated with chimeric antigen receptor T cells showing a high efficacy and no unexpected toxicity.