bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transformer-based time-to-event prediction for chronic kidney disease deterioration
Authors: Zisser Moshe , Aran Dvir 
Published: February 2024

Abstract

Objective
Deep-learning techniques, particularly the Transformer model, have shown great potential in enhancing the prediction performance of longitudinal health records. Previous methods focused on fixed-time risk prediction, however, time-to-event prediction is often more appropriate for clinical scenarios. Here, we present STRAFE, a generalizable survival analysis Transformer-based architecture for electronic health records.

Materials and Methods
The input for STRAFE is a sequence of visits with SNOMED-CT codes in OMOP-CDM format. A Transformer-based architecture was developed to calculate probabilities of the occurrence of the event in each of 48 months. Performance was evaluated using a real-world claims dataset of over 130 000 individuals with stage 3 chronic kidney disease (CKD).

Results
STRAFE showed improved mean absolute error (MAE) compared to other time-to-event algorithms in predicting the time to deterioration to stage 5 CKD. Additionally, STRAFE showed an improved area under the receiver operating curve compared to binary outcome algorithms. We show that STRAFE predictions can improve the positive predictive value of high-risk patients by 3-fold. Finally, we suggest a novel visualization approach to predictions on a per-patient basis.

Discussion
Time-to-event predictions are the most appropriate approach for clinical predictions. Our deep-learning algorithm outperformed not only other time-to-event prediction algorithms but also fixed-time algorithms, possibly due to its ability to train on censored data. We demonstrated possible clinical usage by identifying the highest-risk patients.

Conclusions
The ability to accurately identify patients at high risk and prioritize their needs can result in improved health outcomes, reduced costs, and more efficient use of resources.
Laser-Assisted Drug Delivery in the Treatment of Hypertrophic Scars and Keloids: A Systematic Review
Authors: Bernabe Rendell M , Choe Deborah , Calero Tiffany , Lin Joshua , Pham Christopher , Dang Justin , Madrigal Paloma , Yenikomshian Haig A , Gillenwater T Justin 
Published: February 2024

Abstract
Hypertrophic scars and keloids are the results of an exaggerated healing process and are often associated with significant patient morbidity. Fractional ablative lasers create microchannels in the skin and penetrate into the substance of the scar, inducing a normal healing response in zones of created damage. Focal delivery of scar-modulating agents into the scar through these microchannels—a process termed laser-assisted drug delivery (LADD)—is a promising and developing treatment modality. In this systematic review, we aim to critically examine the evidence of LADD in the treatment of hypertrophic scars and keloids. The evidence suggests that LADD improves outcomes in hypertrophic scars and keloids. LADD is a more effective treatment modality than the topical application of agents in hypertrophic scars and equally effective as the intralesional injection of agents in keloids. There were few reports of adverse events. Evidence supports the use of LADD as an adjunct to non-surgical measures or a treatment modality to be used before more invasive measures such as surgical excision. However, the quality of evidence supporting this conclusion is inconsistent and lacks power. Additional studies are required to optimize dosages, laser settings, and agent choices for the treatment of these lesions.
Revisiting the effects of maternal education on adolescents’ academic performance: Doubly robust estimation in a network-based observational study
Authors: McNealis Vanessa , Moodie Erica E M , Dean Nema 
Published: February 2024

Abstract
In many contexts, particularly when study subjects are adolescents, peer effects can invalidate typical statistical requirements in the data. For instance, it is plausible that a student’s academic performance is influenced both by their own mother’s educational level as well as that of their peers. Since the underlying social network is measured, the Add Health study provides a unique opportunity to examine the impact of maternal college education on adolescent school performance, both direct and indirect. However, causal inference on populations embedded in social networks poses technical challenges, since the typical no interference assumption no longer holds. While inverse probability-of-treatment weighted (IPW) estimators have been developed for this setting, they are often highly unstable. Motivated by the question of maternal education, we propose doubly robust (DR) estimators combining models for treatment and outcome that are consistent and asymptotically normal if either model is correctly specified. We present empirical results that illustrate the DR property and the efficiency gain of DR over IPW estimators even when the treatment model is misspecified. Contrary to previous studies, our robust analysis does not provide evidence of an indirect effect of maternal education on academic performance within adolescents’ social circles in Add Health.
Rare finding of a symptomatic epidermoid cyst of the diaphragm – a case report
Authors: Welsh Fraser , Weilert Frank , Grunewald Bernd , Lanka Laxmi , Patil Sudha 
Published: February 2024

Abstract
Cystic lesions of the diaphragm are rare and accordingly present a diagnostic challenge. Specific radiological features with which to clinch a diagnosis may be elusive. Herein we present the case of a patient who presented with symptoms attributable to a cyst in the left upper abdomen, irritating the diaphragm. Surgery was considered appropriate for diagnostic and symptomatic purposes. Final histology demonstrated an epidermoid cyst. Resolution of symptoms was reported after surgery. Diaphragmatic epidermoid cysts appear to be a rare entity with only three prior cases reported in the literature. Given the rarity of this lesion and the lack of unique features by which they can be characterized, accurately diagnosing epidermoid cysts of the diaphragm is likely to remain difficult without surgery, although they are presumed to have a benign behaviour.
Multi-regulated GDP-l-galactose phosphorylase calls the tune in ascorbate biosynthesis
Authors: Baldet Pierre , Mori Kentaro , Decros Guillaume , Beauvoit Bertrand , Colombié Sophie , Prigent Sylvain , Pétriacq Pierre , Gibon Yves 
Published: February 2024

Abstract
Ascorbate is involved in numerous vital processes, in particular in response to abiotic but also biotic stresses whose frequency and amplitude increase with climate change. Ascorbate levels vary greatly depending on species, tissues, or stages of development, but also in response to stress. Since its discovery, the ascorbate biosynthetic pathway has been intensely studied and it appears that GDP-l-galactose phosphorylase (GGP) is the enzyme with the greatest role in the control of ascorbate biosynthesis. Like other enzymes of this pathway, its expression is induced by various environmental and also developmental factors. Although mRNAs encoding it are among the most abundant in the transcriptome, the protein is only present in very small quantities. In fact, GGP translation is repressed by a negative feedback mechanism involving a small open reading frame located upstream of the coding sequence (uORF). Moreover, its activity is inhibited by a PAS/LOV type photoreceptor, the action of which is counteracted by blue light. Consequently, this multi-level regulation of GGP would allow fine control of ascorbate synthesis. Indeed, experiments varying the expression of GGP have shown that it plays a central role in response to stress. This new understanding will be useful for developing varieties adapted to future environmental conditions.
Ascorbate degradation: pathways, products, and possibilities
Authors: Ford Christopher M , Sweetman Crystal , Fry Stephen C 
Published: February 2024

Abstract
A role for l-ascorbate as the precursor of several plant compounds adds to its already broad metabolic utility. There are many examples of plant species in which oxalate and l-threonate are formed from l-ascorbate breakdown, and a number of roles have been proposed for this: structural, physiological, and biochemical. On the other hand, the synthesis of l-tartrate from l-ascorbate remains limited to a very few species, amongst which we must be grateful to count the domesticated grapevine Vitis vinifera and its relatives on which wine production is based. Pathways for the degradation of ascorbate were first proposed ~50 years ago and have formed the basis of more recent biochemical and molecular analyses. The present review seeks to summarize some of these findings and to propose opportunities for future research.
Rainbow phlebotomy collection and urine aliquots for emergency department add-on testing in the era of pandemic-driven supply shortages
Authors: Potter Scott , Rudolf Joseph W , Pearson Lauren N 
Published: February 2024

Abstract

Background
Rainbow blood draws for add-on testing in the emergency department (ED) are a common practice at our institution. We sought to determine the prevalence of this practice among reference laboratory clients and characterize the impact of pandemic-driven supply shortages.

Methods
This cross-sectional study surveyed 354 client laboratories to understand specimen collection practices in specific clinical environments and how these practices may have been affected by supply chain shortages. Data analysis by descriptive statistics was performed in Qualtrics.

Results
A total of 138 laboratories took the survey (39% response rate) with 57% indicating that their ED performed rainbow draws. Of these, 16% have a formal policy regarding rainbow draws, and 76% of respondents indicated that their institution was required to modify practices due to pandemic-driven supply shortages. A total of 19% indicated they routinely collect multiple urine aliquots for add-on testing.

Conclusion
Rainbow draws and collection of urine aliquots in the ED for add-on testing are relatively common practices, with few institutions maintaining formal policies regarding the practice. Pandemic-driven supply chain shortages affected a majority of respondent laboratories and local cost-benefit analysis regarding extra specimen collection is recommended to limit waste of laboratory resources.
Modalities combining two negations
Authors: Luis Castiglioni JosÉ , Ertola-Biraben Rodolfo C 
Published: February 2024

Abstract
In the context of positive logic expanded with the dual of intuitionistic negation, obtaining intuitionistic negation itself as a consequence, those two connectives allow to introduce modal concepts such as necessity and possibility. We study the resulting modal logic, paying attention to different extensions of it. We provide a syntactic approach and both algebraic and Kripke semantics.
Resection of DNA double-strand breaks activates Mre11–Rad50–Nbs1- and Rad9–Hus1–Rad1-dependent mechanisms that redundantly promote ATR checkpoint activation and end processing in Xenopus egg extracts
Authors: Tatsukawa Kensuke , Sakamoto Reihi , Kawasoe Yoshitaka , Kubota Yumiko , Tsurimoto Toshiki , Takahashi Tatsuro S , Ohashi Eiji 
Published: February 2024

Abstract
Sensing and processing of DNA double-strand breaks (DSBs) are vital to genome stability. DSBs are primarily detected by the ATM checkpoint pathway, where the Mre11–Rad50–Nbs1 (MRN) complex serves as the DSB sensor. Subsequent DSB end resection activates the ATR checkpoint pathway, where replication protein A, MRN, and the Rad9–Hus1–Rad1 (9–1–1) clamp serve as the DNA structure sensors. ATR activation depends also on Topbp1, which is loaded onto DNA through multiple mechanisms. While different DNA structures elicit specific ATR-activation subpathways, the regulation and mechanisms of the ATR-activation subpathways are not fully understood. Using DNA substrates that mimic extensively resected DSBs, we show here that MRN and 9–1–1 redundantly stimulate Dna2-dependent long-range end resection and ATR activation in Xenopus egg extracts. MRN serves as the loading platform for ATM, which, in turn, stimulates Dna2- and Topbp1-loading. Nevertheless, MRN promotes Dna2-mediated end processing largely independently of ATM. 9–1–1 is dispensable for bulk Dna2 loading, and Topbp1 loading is interdependent with 9–1–1. ATR facilitates Mre11 phosphorylation and ATM dissociation. These data uncover that long-range end resection activates two redundant pathways that facilitate ATR checkpoint signaling and DNA processing in a vertebrate system.
Joint inference of clonal structure using single-cell genome and transcriptome sequencing data
Authors: Bai Xiangqi , Duren Zhana , Wan Lin , Xia Li C 
Published: February 2024

Abstract
Latest advancements in the high-throughput single-cell genome (scDNA) and transcriptome (scRNA) sequencing technologies enabled cell-resolved investigation of tissue clones. However, it remains challenging to cluster and couple single cells for heterogeneous scRNA and scDNA data generated from the same specimen. In this study, we present a computational framework called CCNMF, which employs a novel Coupled-Clone Non-negative Matrix Factorization technique to jointly infer clonal structure for matched scDNA and scRNA data. CCNMF couples multi-omics single cells by linking copy number and gene expression profiles through their general concordance. It successfully resolved the underlying coexisting clones with high correlations between the clonal genome and transcriptome from the same specimen. We validated that CCNMF can achieve high accuracy and robustness using both simulated benchmarks and real-world applications, including an ovarian cancer cell lines mixture, a gastric cancer cell line, and a primary gastric cancer. In summary, CCNMF provides a powerful tool for integrating multi-omics single-cell data, enabling simultaneous resolution of genomic and transcriptomic clonal architecture. This computational framework facilitates the understanding of how cellular gene expression changes in conjunction with clonal genome alternations, shedding light on the cellular genomic difference of subclones that contributes to tumor evolution.
Fractionated radiotherapy for spinal tumors: A literature review regarding spinal glioma, ependymoma, and meningioma
Authors: Bodensohn Raphael , Haehl Erik , Belka Claus , Niyazi Maximilian 
Published: February 2024

Abstract
Radiation therapy plays a vital role in the management of primary spinal tumors in adults. However, due to the rarity of these tumor types, the literature on optimal treatment indications and radiation doses is limited. Many treatment recommendations are extrapolated from their cranial counterparts, where more data are available. Despite the absence of prospective data, numerous retrospective studies have provided valuable insights to guide treatment decisions until more comprehensive data become available. This review provides an overview of the most relevant literature, with a specific focus on spinal gliomas, ependymomas, and meningiomas, in the context of the role of radiation therapy.
Astrocytomas of the spinal cord
Authors: Tonn Joerg-Christian , Teske Nico , Karschnia Philipp 
Published: February 2024

Abstract
Tumors of astrocytic origin represent one of the most frequent entities among the overall rare group of spinal cord gliomas. Initial clinical symptoms are often unspecific, and sensorimotor signs localizing to the spinal cord occur with progressing tumor growth. On MRI, a hyperintense intrinsic spinal cord signal on T2-weighted sequences with varying degrees of contrast enhancement raises suspicion for an infiltrative neoplasm. Blood and CSF analysis serves to exclude an infectious process, nutritional deficits, or metabolic disorders. When such other differential diagnoses have been ruled out, a neuropathological tissue-based analysis is warranted to confirm the diagnosis of a spinal cord astrocytoma and guide further patient management. As such, maximal safe resection forms the basis of any treatment. Meticulous preoperative planning is necessary to weigh the potential improvement in survival against the risk of functional deterioration. Intraoperative neuromonitoring and ultrasound may aid in achieving a more extensive resection. Depending on the assigned WHO tumor grade spanning from grade 1 to grade 4, the use of radiotherapy and chemotherapy might be indicated but also wait-and-scan approaches appear reasonable in tumors of lower grade. Close imaging follow-up is necessary given that recurrence inevitably occurs in astrocytomas of grades 2–4. Prognosis is so far dictated by tumor grade and histopathological findings, but also by age and clinical performance of the patient. Targeted therapies resting upon an in-depth tissue analysis are emerging in recurrent tumors, but no prospective study is available so far given the rarity of spinal cord astrocytomas.
Separation surgery for metastatic spine tumors: How less became more
Authors: Zhang Xiaoran , Giantini Larsen Alexandra , Kharas Natasha , Bilsky Mark H , Newman William Christopher 
Published: February 2024

Abstract
Metastatic epidural spinal cord compression (MESCC) is an increasingly common clinical entity in cancer patients and is associated with significant morbidity and neurologic sequalae. Management of MESCC has undergone many significant paradigms shifts over the past 50 years and was at times managed exclusively with either surgery or radiation. Historically, aggressive surgical techniques to achieve en bloc or intralesional gross tumor resections were pursued but were associated with significant morbidity and poor tumor control rates when combined with conventional external beam radiation. However, improvements in radiation treatment delivery in the form of stereotactic body radiation therapy have allowed for the safe delivery of high-dose conformal photon beam radiation providing histology-independent ablative responses. This shifted the goals of surgery away from maximal tumor resection toward simple spinal cord decompression with reconstitution of the thecal to create a tumor target volume capable of being irradiated within the constraints of spinal cord tolerance. This new approach of creating space between the thecal sac and the tumor was termed separation surgery and when combined with postoperative SBRT, it is referred to as hybrid therapy. Herein, we will describe the evolution of the management of MESCC, the technique of separation surgery and its outcomes, and finish with an illustrative case example.
Tracked and self-reported nighttime smartphone use, general health, and healthcare utilization: results from the SmartSleep Study
Authors: Drews Henning Johannes , Sejling Christoffer , Andersen Thea Otte , Varga Tibor V , Jensen Andreas Kryger , Rod Naja Hulvej 
Published: February 2024

Abstract

Study Objectives
Nighttime smartphone use is an increasing public health concern. We investigated whether nighttime smartphone use is associated with general health and primary healthcare utilization.

Methods
Four thousand five hundred and twenty individuals (age 35.6 ± 9.7 years, 35% male) provided self-reported information on smartphone use frequency, symptoms of depression, and general health (one-item perceived health and cross-symptom composite score). A subset of the study sample (n = 3221) tracked their nighttime smartphone use. Primary healthcare utilization, i.e. the number of weeks in which at least one service from the patient’s general practitioner (GP) was billed in 2020, was extracted from Danish population registries. Statistical analysis comprised logistic and multiple linear regression, controlling for sociodemographics.

Results
Three hundred and nineteen individuals (7%) reported using their smartphone almost every night or more. More frequent self-reported nighttime smartphone use was associated with poor general health across all measures. Using the smartphone almost every night or more was associated with 2.8 [95% CI: 1.9, 4.1] fold higher odds of reporting poor health and with an average of 1.4 [95% CI: 0.7, 2.1] additional GP utilizations per year compared to no use. Associations were also found for the cross-symptom composite score across all symptoms. Further adjustment for symptoms of depression attenuated some associations. Smartphone use towards the end of the sleep period (sleep-offset use) was associated with poorer self-reported general health, but not with healthcare utilization.

Conclusions
Nighttime smartphone use frequency is associated with poor general health and healthcare utilization. Further studies should investigate the underlying causal structure and nighttime smartphone use as a transdiagnostic intervention target.
Leaf thermotolerance of Hevea brasiliensis clones: intra- versus interclonal variation and relationships with other functional traits
Authors: Hazir Mohd Hafiz Mohd , Gloor Emanuel , Docherty Emma , Galbraith David 
Published: February 2024

Abstract
Land surface temperature is predicted to increase by 0.2 °C per decade due to climate change, although with considerable regional variability, and heatwaves are predicted to increase markedly in the future. These changes will affect where crops can be grown in the future. Understanding the thermal limits of plant physiological functioning and how flexible such limits are is thus important. Here, we report on the measurements of a core foliar thermotolerance trait, T50, defined as the temperature at which the maximum quantum yield (Fv/Fm) of photosystem II declines by 50%, across nine different Malaysian Hevea brasiliensis clones. We explore the relative importance of interclonal versus intraclonal variation in T50 as well as its association with leaf and hydraulic traits. We find very low variation in T50 within individual clones (mean intraclonal coefficient of variation (CoV) of 1.26%) and little variation across clones (interclonal CoV of 2.1%). The interclonal variation in T50 was lower than for all other functional traits considered. The T50 was negatively related to leaf mass per area and leaf dry matter content, but it was not related to hydraulic traits such as embolism resistance (P50) or hydraulic safety margins (HSM50). The range of T50 observed (42.9–46.2 °C) is well above the current maximum air temperatures Tmax,obs (T50 − Tmax,obs &gt;5.8 °C), suggesting that H. brasiliensis is likely thermally safe in this south-east Asian region of Malaysia.