bluuebunny/crossref_metadata_2025 huggingface dataset:
Complicating the Role of Relationships in Reducing Student Absenteeism
Authors: Stokes Kimberly L , Lenhoff Sarah Winchell , Singer Jeremy
Published: September 2024

A strong connection between schools and families is vital for student success and well-being. Previous studies on school–family relationships found that open communication between parties may aid in supporting students’ needs and ability to attend school. In this paper, authors analyze how leveraging relationships to gain an increased understanding of a family’s attendance barriers is more beneficial than relationships built on accountability. From interviews with 38 caregivers, 29 students, and 40 staff members in an urban school district with high rates of chronic absenteeism, authors found that efforts to build relationships with families focused on accountability and caregiver education about their children’s attendance and the importance of attending school. Families sometimes perceived these efforts as superficial and ineffective. Authors discuss how school districts and key school personnel, such as social workers, can intentionally use the power of relationships to identify student and family needs and connect them with resources.
Liver-targeted Angptl4 silencing by antisense oligonucleotide treatment attenuates hyperlipidaemia and atherosclerosis development in APOE*3-Leiden.CETP mice
Authors: Modder Melanie , het Panhuis Wietse In , Li Mohan , Afkir Salwa , Dorn Alexandra L , Pronk Amanda C M , Streefland Trea C M , Lalai Reshma A , Pierrou Stefan , Nilsson Stefan K , Olivecrona Gunilla , Kooijman Sander , Rensen Patrick C N , Schönke Milena
Published: September 2024

Aims

Angiopoietin-like 3 (ANGPTL3) and 4 (ANGPTL4) inhibit lipoprotein lipase to regulate tissue fatty acid (FA) uptake from triglyceride (TG)-rich lipoproteins such as very low density lipoproteins (VLDL). While pharmacological inhibition of ANGPTL3 is being evaluated as a lipid-lowering strategy, systemic ANGPTL4 inhibition is not pursued due to adverse effects. This study aims to compare the therapeutic potential of liver-specific Angptl3 and Angptl4 silencing to attenuate hyperlipidemia and atherosclerosis development in APOE*3-Leiden.CETP mice, a well-established humanized model for lipoprotein metabolism.

Methods and results

Mice were subcutaneously injected twice per week with saline or liver-targeted antisense oligonucleotides against Angptl3, Angptl4, both, or a scrambled oligonucleotide. Plasma lipid levels, VLDL clearance, and hepatic VLDL production were determined, and atherosclerosis development was assessed. For toxicological evaluation, cynomolgus monkeys were treated with three dosages of liver-targeted ANGPTL4-silencing oligonucleotides. Liver-targeted Angptl4 silencing reduced plasma TGs (−48%) and total cholesterol (−56%), explained by higher VLDL-derived FA uptake by brown adipose tissue and lower VLDL production by the liver. Accordingly, Angptl4 silencing reduced atherosclerotic lesion size (−86%) and improved lesion stability. Hepatic Angptl3 silencing similarly attenuated hyperlipidemia and atherosclerosis development. While Angptl3 and Angptl4 silencing lowered plasma TGs in the refed and fasted state, respectively, combined Angptl3/4 silencing lowered plasma TGs independent of the nutritional state. In cynomolgus monkeys, anti-ANGPTL4 ASO treatment was well tolerated without adverse effects.

Conclusion

Liver-targeted Angptl4 silencing potently attenuates hyperlipidemia and atherosclerosis development in APOE*3-Leiden.CETP mice, and liver-targeted ANGPTL4 silencing is well tolerated in non-human primates. These data warrant further clinical development of liver-targeted ANGPTL4 silencing.
How mentoring and a shift in mindset and practices can help navigate fast-paced science
Authors: Bercht Anna Lena , Kamm Ruth
Published: September 2024

In the competitive realm of academia, the pursuit of meaningful knowledge often collides with the imperative to publish quickly and frequently, sidelining patient investigation and deep understanding. This article aims to share critical insights into this issue, sparking further discussions about the challenges of fast-paced science and cultivating a more ethical scientific landscape, one that values exploration and ingenuity over rushed output and flashy headlines. The narrative traces the growing disillusionment of the first author with the prevailing publish-or-perish culture and her concerns about its impact on research quality and genuine collaboration. The article showcases how a mentoring programme for women postdoctoral researchers and network activities have aided her in navigating these challenges and carving out her career path. Her experiences are enriched by the perspectives of the second author, the coordinator of the mentoring programme. Through one-on-one mentoring, get-togethers, and workshops, the first author gained the inspiration, skills, and encouragement necessary to rekindle her commitment to science. The lesson learned is the importance of providing scientists with a guided, safe, and brave space for open dialogue about individual concerns and general working conditions in academia. Examples are provided that illustrate potential strategies and practices for challenging the status quo. By nurturing an environment that puts quality before quantity, academia can pave the way for transformative discoveries and profound understanding across all career levels.
“I Flip, Therefore I Am”: Smartphone Detoxing as a Practice of Sovereignty
Authors: Markussen Håvard Rustad
Published: September 2024

This article theorizes smartphone detoxing as a practice of sovereignty. The article begins by arguing that the smartphone enables the exercise of psychopolitical control, a new mode of neoliberal governmentality under which individuals are governed through the algorithmic modification of behavior. Against this background, smartphone detoxing can be seen as a practice of sovereignty in the sense that it aims to recover the subject's autonomy and rationality—qualities that are lost as humans become smartphone addicts. Ironically, however, smartphone detoxing is also a neoliberal practice in the sense that it plays on an ethos of self-care and cultivates market-oriented notions of freedom. As such, the article contends that the detoxing subject is a post-smartphone subject that performs political subjectivity by negotiating the tension between sovereignty and neoliberalism. To explore how smartphone detoxing performs political subjectivity in practice, the article analyses the testimonies of four influencers who share their detoxing journeys on YouTube. The analysis finds that detoxers recover sovereignty by rediscovering the Self, reconnecting with Others, and reclaiming time, and that they—through these very practices—also strive for the neoliberal virtues of wellness, authenticity and productivity.
Is Lycorma delicatula (Hemiptera: Fulgoridae) a blooming threat to citrus?
Authors: Molfini Marco , West Mari , Gómez-Marco Francesc , Torres Jorge Braz , Hoddle Mark
Published: September 2024

Examining the host range of emerging invasive insects is essential to assess their invasion potential and to anticipate the negative impacts of their spread. The ongoing North American invasion of spotted lanternfly (SLF) [Lycorma delicatula (White, 1845)] threatens agricultural, urban, and natural areas. The survival and development of SLF nymphs on Washington navel orange [Citrus sinensis (L.) Osbeck (Sapindales: Rutaceae)] trees were assessed in a quarantine facility. Results indicated that SLF nymphs can develop to at least the third instar by feeding exclusively on Washington navel orange. This finding suggests that, at least up to the third stage of nymphal development, Washington navel orange might be a suitable host for SLF, highlighting the possibility that this invasive pest represents an unrecognized threat to this globally important crop and possibly to other Citrus species.
Using Multi-Objective Optimization to build non-Random Forest
Authors: Klikowska Joanna , Woźniak Michał
Published: September 2024

The use of multi-objective optimization to build classifier ensembles is becoming increasingly popular. This approach optimizes more than one criterion simultaneously and returns a set of solutions. Thus the final solution can be more tailored to the user’s needs. The work proposes the MOONF method using one or two criteria depending on the method’s version. Optimization returns solutions as feature subspaces that are then used to train decision tree models. In this way, the ensemble is created non-randomly, unlike the popular Random Subspace approach (such as the Random Forest classifier). Experiments carried out on many imbalanced datasets compare the proposed methods with state-of-the-art methods and show the advantage of the MOONF method in the multi-objective version.
Performance evaluation of a low-throughput qPCR-based Legionella assay for utility as an onsite industrial water system monitoring method
Authors: Corrigan Alexsandra , Niemaseck Benjamin , Moore Mackenzie , McIlwaine Douglas , Duguay Jeremy
Published: September 2024

Legionella is a bacterial genus found in natural aquatic environments, as well as domestic and industrial water systems. Legionella presents potential human health risks when aerosolized and inhaled by at-risk individuals and is commonly monitored at locations with likelihood of proliferation and human exposure. Legionella monitoring is widely performed using culture-based testing, which faces limitations including turnaround time and interferences. Molecular biology methodologies, including quantitative polymerase chain reaction (qPCR), are being explored to supplement or replace culture-based testing because of faster turnaround and lower detection limits, allowing for more rapid water remediation measures. In this study, three methods were compared by testing industrial water samples: culture-based testing by a certified lab, high throughput qPCR testing (HT qPCR), and field deployable low throughput qPCR testing (LT qPCR). The qPCR test methods reported more positive results than culture testing, indicating improved sensitivity and specificity. The LT qPCR test is portable with quick turnaround times, and can be leveraged for environmental surveillance, process optimization, monitoring, and onsite case investigations. The LT qPCR test had high negative predictive value and would be a useful tool for negative screening of Legionella samples from high-risk environments and/or outbreak investigations to streamline samples for culture testing.

One-Sentence Summary

This study compared three test methods for Legionella to evaluate performance of a low throughput quantitative polymerase chain reaction (LT qPCR) test for Legionella that can be used onsite; the study found that the high throughput (HT) and LT qPCR tests used in this study gave more positive results than culture testing, and the results indicated a similar negative predictive value for the HT and LT qPCR tests, supporting that the LT qPCR method could be useful for negative screening of Legionella samples in industrial water systems onsite.
Development of mixed linear models to analyze and describe the impact of malathion on the larval growth of Megaselia scalaris (Diptera: Phoridae) under various feeding media and environmental conditions
Authors: Castillo-Alanís Luz Alejandra , Torres-Saez de Nanclares Ximena Alexa , Pedraza-Lara Carlos Salvador , Colorado-Hernández José Luis , Quijano-Mateos Alejandra , Ávalos-Hernández Omar , Bravo-Gómez María Elena
Published: September 2024

Forensic entomology plays a crucial role in estimating the minimum postmortem interval through the study of insect larvae found at crime scenes. The precision of this estimation relies on various biotic and abiotic elements that simultaneously influence insect growth and development, encompassing factors such as temperature, humidity, photoperiod, diet, and the existence of xenobiotics in decomposing tissues. Despite numerous studies on the influence of these factors, including the impact of xenobiotics, there are currently no robust tools available for making corrections to this estimation considering concurrently all variables. In an attempt to propose an exploratory and descriptive statistical model to analyze the simultaneous effect and interaction of different variables on larval growth, this study aimed to compare the effect of malathion on the growth of Megaselia scalaris (Loew, 1866) (Diptera: Phoridae) raised in malathion-spiked porcine muscle, under controlled and uncontrolled temperature and humidity conditions (environmental conditions). Larvae were also reared using various growth media. A split-plot design that combined crossed and nested factors was employed; 2 linear mixed models were developed to assess the relationships between the variables. The model provides valuable insights into the complex interactions among xenobiotics, growth media, and environmental conditions in the size and development of M. scalaris.
Radiation-associated cardiovascular disease in patients with cancer: current insights from a cardio-oncologist
Authors: Uehara Masae , Bekki Norifumi , Shiga Taro
Published: September 2024

Radiation-associated cardiovascular disease (RACD), a complex disease characterized with pericarditis, myocardial damage, valvular heart diseases, heart failure, vasculopathy and ischemic heart disease, has a generally poor prognosis. While RACD may be acute, it often manifests in the late years or even decades following radiation exposure to the chest. With an increasing number of cancer survivors, RACD is likely to become an important issue in cardio-oncology. This review discusses pre-radiation therapy (RT) preparation, peri-RT patient management and long follow-up planning post-RT from a cardiology perspective. Additionally, a novel technique of stereotactic radiotherapy, which has been applied for the treatment of intractable cardiac arrhythmias, is presented. Appropriate patient examination and management during and after RT are essential to support patients undergoing cancer treatment to improve long life expectancy. A multidisciplinary team is needed to determine how to manage patients who receive RT to reduce RACD, to detect early phases of RACD and to provide the best treatment for RACD. Recent studies increasingly report advances in diagnosis using new equipment that has the potential to detect early phases of RACD, along with growing evidence for the optimal treatment for RACD. This review provides an overview of recent studies and guidelines to report on the latest findings, and to identify unresolved issues surrounding RACD that require validation in future studies.
Robust model averaging prediction of longitudinal response with ultrahigh-dimensional covariates
Authors: Jiang Binyan , Lv Jing , Li Jialiang , Cheng Ming−Yen
Published: September 2024

Model averaging is an attractive ensemble technique to construct fast and accurate prediction. Despite of having been widely practiced in cross-sectional data analysis, its application to longitudinal data is rather limited so far. We consider model averaging for longitudinal response when the number of covariates is ultrahigh. To this end, we propose a novel two-stage procedure in which variable screening is first conducted and then followed by model averaging. In both stages, a robust rank-based estimation function is introduced to cope with potential outliers and heavy-tailed error distributions, while the longitudinal correlation is modelled by a modified Cholesky decomposition method and properly incorporated to achieve efficiency. Asymptotic properties of our proposed methods are rigorously established, including screening consistency and convergence of the model averaging predictor, with uncertainties in the screening step and selected model set both taken into account. Extensive simulation studies demonstrate that our method outperforms existing competitors, resulting in significant improvements in screening and prediction performance. Finally, we apply our proposed framework to analyse a human microbiome dataset, showing the capability of our procedure in resolving robust prediction using massive metabolites.
Challenges associated with low rectal malignant obstruction stenting: a case report
Authors: Cabrera-Bou Victor , Lincango Eddy P , Cabrera Alessandra E , Diaz-Pagan Gabriel , Kostick Nathan , Sobel Noah , Serrano Luis F , Kondylis Philip
Published: September 2024

An ongoing debate exists regarding the feasibility of placing self-expanding metallic stents (SEMS) within 5 cm of the anal verge. Traditionally, SEMS have been considered contraindicated for patients with a malignant rectal obstruction within this region due to potential impact on the anorectal ring or anal canal, which can cause incontinence, proctalgia, and tenesmus. However, in the case of a 63-year-old female who presented with distention, abdominal pain, and diminishing stool output, the rectal exam identified a bulky fixed mass. Imaging studies revealed large bowel obstruction and high-grade stricture, with a minuscule residual lumen. Endoscopy identified a bulky mass obscuring the lumen at 5 cm from the anal verge, and biopsy confirmed adenocarcinoma. Despite the traditionally held contraindication, a 2.5 cm × 9.0 cm colonic stent was successfully deployed, leading to brisk colonic decompression. This allowed the patient to promptly undergo chemoradiotherapy.
The value of electrophysiological testing in the adjunctive diagnosis of premature ejaculation
Authors: Chen Zhimin , Zheng Zhenming , Zhang Xiansheng
Published: September 2024

Background

Although the four-class system of classifying premature ejaculation (PE), including lifelong PE (LPE), acquired PE (APE), natural variable PE (NPE), and subjective PE (SPE), has existed for many years, objective classification standards in clinical practice are lacking.

Aim

In this study, we sought to investigate the use of electrophysiologic parameters to assist in the classification of PE, thereby guiding subsequent treatment.

Methods

From July 2023 to April 2024, 187 study participants were enrolled. For each participant, the biological sensory threshold (BST), penile sympathetic skin response (PSSR), and dorsal nerve somatosensory evoked potential (DNSEP) were recorded.

Outcomes

The differences in the PSSR latencies (PL) and DNSEP latencies (DL), the PSSR amplitudes (PA) and DNSEP amplitudes (DA), and the BST were compared among the LPE, APE, SPE, NPE, and healthy control (HC) groups.

Results

The participants were divided into the LPE (46 cases), APE (53 cases), SPE (20 cases), NPE (33 cases), and HC (35 cases) groups. The results showed shorter latencies of the PSSR (PL) and DNSEP (DL), larger amplitudes of the PSSR (PA) and DNSEP (DL), and smaller BST in the LPE group than in the NPE, SPE, APE, and HC groups (P < .05). In addition, the larger PA and shorter PL in the APE group than in the NPE and HC groups (P < .05). However, the electrophysiological parameters were not significantly different among the NPE, SPE, and HC groups (P > .05). In addition, PL <1262.0 milliseconds and DL <41.85 milliseconds were strong predictors of LPE, 1262.0 milliseconds < PL <1430.0 milliseconds was a predictor of APE, and PL >1430.0 milliseconds suggested possible SPE or NPE.

Clinical implications

Analysis of the electrophysiological parameters of PE may be helpful for classification and treatment.

Strengths and Limitations

No previous study, to our knowledge, has analyzed the electrophysiological parameters of the four types of PE. The main limitation is the small sample size.

Conclusion

APE is characterized by increased sympathetic excitability, whereas LPE is characterized by increased penile sensitivity and increased sympathetic excitability. However, penile sensitivity and sympathetic excitability in SPE and NPE patients may not differ significantly from normal.
Variant Readings of Luke 22:15-20 and the Relationship of Codex Bezae to Curetonian Syriac
Authors: James Rob
Published: September 2024

The text of Luke 22:15–20 exists in several variant forms. Often these are classified simply as the ‘longer’ and ‘shorter’ form of the text. This paper argues that these designations are misleading as there are several important variations within the shorter form. Some of these variations are in Syriac and have often been ignored, with some scholars dismissing them as not relevant to the question of the original composition of Luke. By examining the probable origin of the additional verses of the longer text, and by analysing the variations that exist within the shorter text, especially including taking the Syriac evidence seriously, this paper suggests that the longer version is the more original. An examination of the Syriac texts leads to the ability to show that Bezae (in both Greek and Latin) and Curetonian (in Syriac) share a closer common ancestor than may be generally assumed, given their different languages. The paper ends by showing how these two MSS are related to one another.
Conflict of Laws and Arbitral Discretion
Authors: Hayward Benjamin
Published: September 2024

Arbitration is the dispute resolution method of choice in international commerce, but it rests on a complex legal foundation. In many international commercial contracts, the parties will choose the law governing any future disputes. However, where the parties do not choose a governing law, the prevailing approach in arbitration is to afford arbitrators broad and largely unfettered discretion to choose the law considered most appropriate or most applicable. The uncertainty resulting from this discretion potentially affects the parties’ rights and obligations, the performance of their contract, the presentation of their cases, and negotiations undertaken to settle their disputes. This text critically reviews the prevailing approach to the conflict of laws in international commercial arbitration. The text adopts a focused and detail-oriented analysis—being based on a study of more than 130 sets of arbitral laws and rules from around the world, and drawing heavily on arbitral case law. It takes as its focus the needs and expectations of commercial parties, who are the ultimate users of international commercial arbitration. This book identifies the difficulties that result from resolving conflicts of laws through broad and unconstrained arbitral discretions. It establishes that a bright-line test would be a preferable way to resolve arbitral conflicts of laws. Specifically, it recommends a modified Art 4 Rome Convention rule as the ideal basis for law reform in this area of arbitral procedure.
A Proposed Bright-Line Test—The Closest Connection Test
Authors: Hayward Benjamin
Published: September 2024

This chapter recommends the closest connection test as the basis for the reform of arbitral conflicts of laws. It assesses thirteen different ways in which the governing substantive law can be identified, based primarily on the conflicts rules addressed in Chapter 2. To facilitate this analysis, these thirteen methodologies are divided into three groups: ‘Category A rules’ are those considered out-of-favour in the modern international commercial arbitration environment; ‘Category B rules’ are those enjoying some contemporary endorsement in arbitral conflicts of laws, but which remain controversial; and ‘Category C rules’ are those rules considered mainstream in contemporary arbitral conflicts discourse. Only Category A’s international instruments rule and Category C’s closest connection test emerge as potentially feasible bright-line tests. On further comparison of these two alternatives, the closest connection test emerges as the optimal conflict of laws rule for international commercial arbitration.
Six Roles for Inclination
Authors: Barnett Zach
Published: September 2024

Initially, you judge that p. You then learn that most experts disagree. All things considered, you believe that the experts are probably right. Still, p continues to seem right to you, in some sense. You don’t yet see what, if anything, is wrong with your original reasoning. In such a case, we’ll say that you are ‘inclined’ toward p. This paper explores various roles that this state of inclination can play, both within epistemology and more broadly. Specifically, it will be argued that: (i) inclinations can promote the accuracy of inquiring groups; (ii) they can support rational participation within philosophy despite pervasive disagreement; (iii) they allow us to make sense of an important way in which two people can continue to disagree even after they ‘conciliate’; (iv) inclinations carry information about individuals’ independent judgments and for this reason must be accounted for when updating on the opinions of others; (v) inclinations are connected to understanding in a way that belief is not; (vi) and awareness of the inclination-belief distinction enables us to respond to a provocative challenge purporting to show that critical thinking, or ‘thinking for oneself’, typically reduces expected accuracy and hence should be discouraged.
GA-NIFS: NIRSpec reveals evidence for non-circular motions and AGN feedback in GN20
Authors: Übler Hannah , D’Eugenio Francesco , Perna Michele , Arribas Santiago , Jones Gareth C , Bunker Andrew J , Carniani Stefano , Charlot Stéphane , Maiolino Roberto , Rodríguez del Pino Bruno , Willott Chris J , Böker Torsten , Cresci Giovanni , Kumari Nimisha , Lamperti Isabella , Parlanti Eleonora , Scholtz Jan , Venturi Giacomo
Published: September 2024

We present rest-frame optical data of the $z\sim 4$ submillimetre galaxy GN20 obtained with the JWST Near Infrared Spectrograph (NIRSpec) in integral field spectroscopy mode. The H$\alpha$ emission is asymmetric and clumpy and extends over a projected distance of >15 kpc. To first order, the large-scale ionized gas kinematics are consistent with a turbulent ($\sigma \sim 90$ km s$^{-1}$), rotating disc ($v_{\rm rot}\sim 500$ km s$^{-1}$), congruent with previous studies of its molecular and ionized gas kinematics. However, we also find clear evidence for non-circular motions in the H$\alpha$ kinematics. We discuss their possible connection with various scenarios, such as external perturbations, accretion, or radial flows. In the centre of GN20, we find broad-line emission (full width at half-maximum $\sim 1000{-}2000$ km s$^{-1}$) in the H$\alpha$ + [N ii] complex, suggestive of fast, active galactic nucleus-driven winds or, alternatively, of the broad-line region of an active black hole. Elevated values of [N ii] $\lambda 6583$/H$\alpha \ \gt\ 0.4$ and of the Hα equivalent width EW(H$\alpha)\ \gt\ 6$ Å throughout large parts of GN20 suggest that feedback from the active black hole is able to photoionize the interstellar medium. Our data corroborate that GN20 offers a unique opportunity to observe key processes in the evolution of the most massive present-day galaxies acting in concert, over 12 billion years ago.
RT-SNDETR: real-time supernova detection via end-to-end image transformers
Authors: Pan Zhi-Ren , Qiu Bo , Li Guang-Wei
Published: September 2024

In large-scale astronomical surveys, traditional supernova detection pipelines rely on complex and relatively inefficient image differencing techniques. This paper proposes an end-to-end deep-learning supernova detection network, the Real-Time SuperNova DEtection TRansformer (RT-SNDETR). This network partially replaces traditional pipelines by integrating image differencing, source detection, and Real-bogus classification, achieving a speed 51.49 times that of the fastest image differencing method, SFFT. Additionally, it remains competitive with methods like YOLO v8, offering a well-balanced trade-off between speed and accuracy. Experimental results highlight RT-SNDETR’s superior performance, with an average precision(AP) of 96.30 per cent on synthetic samples and 76.60 per cent on real supernova samples. It significantly outperforms other detection networks, including RT-DETR (+5.6 per cent AP on synthetic/+5.1 per cent AP on real samples) and Cascade R-CNN (+8.9 per cent AP on synthetic/ +28.6 per cent AP on real samples). The incorporation of CycleGAN-based data generation methods plays a significant role in enhancing RT-SNDETR’s performance. These methods simulate realistic PSF variations, enabling the object detection network to learn more robust features and improving its generalization to real supernovae data. Additionally, by integrating unsupervised domain adaptation techniques, RT-SNDETR achieves an AP of 81.70 per cent on real SDSS supernova survey samples. This study demonstrates RT-SNDETR’s potential to significantly enhance both the speed and accuracy of supernova detection, making it a highly effective solution for large-scale astronomical surveys.
ARTEMIS: a method for topology-independent superposition of RNA 3D structures and structure-based sequence alignment
Authors: Bohdan Davyd R , Bujnicki Janusz M , Baulin Eugene F
Published: September 2024

Non-coding RNAs play a major role in diverse processes in living cells with their sequence and spatial structure serving as the principal determinants of their function. Superposition of RNA 3D structures is the most accurate method for comparative analysis of RNA molecules and for inferring structure-based sequence alignments. Topology-independent superposition is particularly relevant, as evidenced by structurally similar RNAs with sequence permutations such as tRNA and Y RNA. To date, state-of-the-art methods for RNA 3D structure superposition rely on intricate heuristics, and the potential for topology-independent superposition has not been exhausted. Recently, we introduced the ARTEM method for unrestrained pairwise superposition of RNA 3D modules and now we developed it further to solve the global RNA 3D structure alignment problem. Our new tool ARTEMIS significantly outperforms state-of-the-art tools in both sequentially-ordered and topology-independent RNA 3D structure superposition. Using ARTEMIS we discovered a helical packing motif to be preserved within different backbone topology contexts across various non-coding RNAs, including multiple ribozymes and riboswitches. We anticipate that ARTEMIS will be essential for elucidating the landscape of RNA 3D folds and motifs featuring sequence permutations that thus far remained unexplored due to limitations in previous computational approaches.
DORQ-seq: high-throughput quantification of femtomol tRNA pools by combination of cDNA hybridization and Deep sequencing
Authors: Kristen Marco , Lander Marc , Kilz Lea-Marie , Gleue Lukas , Jörg Marko , Bregeon Damien , Hamdane Djemel , Marchand Virginie , Motorin Yuri , Friedland Kristina , Helm Mark
Published: September 2024

Due to its high modification content tRNAs are notoriously hard to quantify by reverse transcription and RNAseq. Bypassing numerous biases resulting from concatenation of enzymatic treatments, we here report a hybrid approach that harnesses the advantages of hybridization-based and deep sequencing–based approaches. The method renders obsolete any RNAseq related workarounds and correction factors that affect accuracy, sensitivity, and turnaround time. Rather than by reverse transcription, quantitative information on the isoacceptor composition of a tRNA pool is transferred to a cDNA mixture in a single step procedure, thereby omitting all enzymatic conversations except for the subsequent barcoding PCR. As a result, a detailed tRNA composition matrix can be obtained from femtomolar amounts of total tRNA. The method is fast, low in cost, and its bioinformatic data workup surprisingly simple. These properties make the approach amenable to high-throughput investigations including clinical samples, as we have demonstrated by application to a collection of variegated biological questions, each answered with novel findings. These include tRNA pool quantification of polysome-bound tRNA, of tRNA modification knockout strains under stress conditions, and of Alzheimer patients’ brain tissues.
MBNL splicing factors regulate the microtranscriptome of skeletal muscles
Authors: Piasecka Agnieszka , Szcześniak Michał W , Sekrecki Michał , Kajdasz Arkadiusz , Sznajder Łukasz J , Baud Anna , Sobczak Krzysztof
Published: September 2024

Muscleblind like splicing regulators (MBNLs) govern various RNA-processing steps, including alternative splicing, polyadenylation, RNA stability and mRNA intracellular localization. In myotonic dystrophy type 1 (DM1), the most common muscular dystrophy in adults, MBNLs are sequestered on toxic RNA containing expanded CUG repeats, which leads to disruption of MBNL-regulated processes and disease features of DM1. Herein, we show the significance of MBNLs in regulating microtranscriptome dynamics during the postnatal development of skeletal muscles and in microRNA (miRNA) misregulation observed in mouse models and patients with DM1. We identify multiple miRNAs sensitive to MBNL proteins insufficiency and reveal that many of them were postnatally regulated, which correlates with increases in the activity of these proteins during this process. In adult Mbnl1-knockout mice, miRNA expression exhibited an adult-to-newborn shift. We hypothesize that Mbnl1 deficiency influences miRNA levels through a combination of mechanisms. First, the absence of Mbnl1 protein results in alterations to the levels of pri-miRNAs. Second, MBNLs affect miRNA biogenesis by regulating the alternative splicing of miRNA primary transcripts. We propose that the expression of miR-23b, miR-27b and miR-24-1, produced from the same cluster, depends on the MBNL-sensitive inclusion of alternative exons containing miRNA sequences. Our findings suggest that MBNL sequestration in DM1 is partially responsible for altered miRNA activity. This study provides new insights into the biological roles and functions of MBNL proteins as regulators of miRNA expression in skeletal muscles.
DNA palette code for time-series archival data storage
Authors: Yan Zihui , Zhang Haoran , Lu Boyuan , Han Tong , Tong Xiaoguang , Yuan Yingjin
Published: September 2024

The long-term preservation of large volumes of infrequently accessed cold data poses challenges to the storage community. Deoxyribonucleic acid (DNA) is considered a promising solution due to its inherent physical stability and significant storage density. The information density and decoding sequence coverage are two important metrics that influence the efficiency of DNA data storage. In this study, we propose a novel coding scheme called the DNA palette code, which is suitable for cold data, especially time-series archival datasets. These datasets are not frequently accessed, but require reliable long-term storage for retrospective research. The DNA palette code employs unordered combinations of index-free oligonucleotides to represent binary information. It can achieve high net information density encoding and lossless decoding with low sequencing coverage. When sequencing reads are corrupted, it can still effectively recover partial information, preventing the complete failure of file retrieval. The in vitro testing of clinical brain magnetic resonance imaging (MRI) data storage, as well as simulation validations using large-scale public MRI datasets (10 GB), planetary science datasets and meteorological datasets, demonstrates the advantages of our coding scheme, including high net information density, low decoding sequence coverage and wide applicability.
Infections Following Gender-Affirming Vaginoplasty: A Single-Center Experience
Authors: Sheth Radhika , Bhaskara Apoorva , Brown Haley , Varley Cara D , Streifel Amber , Maier Marissa , Sikka Monica K , Evans Christopher
Published: September 2024

We describe the epidemiology and incidence of infections following gender-affirming vaginoplasty. Urinary tract and surgical site infections were the most common infections with incidences of 17.5% and 5.5%, respectively. We also identified a significant gap in human immunodeficiency virus screening and prescription of preexposure prophylaxis.
Ion-induced cloud modulation through new particle formation and runaway cloud condensation nuclei production
Authors: Chandrakar Kamal Kant , Cantrell Will , Shaw Raymond A
Published: September 2024

Cloud formation in the Pi Convection–Cloud Chamber is achieved via ionization in humid conditions, without the injection of aerosol particles to serve as cloud condensation nuclei (CCN). Abundant ions, turbulence, and supersaturated water vapor combine to produce new particles, which grow to become CCN sized and eventually are activated to form clouds. Coupling between the new particle formation and cloud droplets causes predator-prey type oscillations in aerosol and droplet concentrations under turbulent conditions. Leading terms are identified in the budgets for Aitken and accumulation mode aerosols and for cloud droplets. The cloud coupling is proposed to be a result of cloud-induced runaway CCN production through aerosol scavenging. The experiments suggest potential applications to marine cloud brightening, in which ions rather than sea-salt aerosols are generated.
Low abundances of TiO and VO on the dayside of KELT-9 b: Insights from ground-based photometric observations
Authors: Hayashi Yuya , Narita Norio , Fukui Akihiko , Changeat Quentin , Kawauchi Kiyoe , Ikuta Kai , Palle Enric , Murgas Felipe , Parviainen Hannu , Esparza-Borges Emma , Peláez-Torres Alberto , Meni Gallardo Pedro Pablo , Morello Giuseppe , Fernández-Rodríguez Gareb , Abreu García Néstor , Muñoz Torres Sara , Calatayud Borrás Yéssica , Montañés Rodríguez Pilar , Livingston John H , Watanabe Noriharu , de Leon Jerome P , Kawai Yugo , Isogai Keisuke , Mori Mayuko
Published: September 2024

We present ground-based photometric observations of secondary eclipses of the hottest known planet KELT-9 b using MuSCAT2 and Sinistro. We detect secondary eclipse signals in i and $z_{\rm s}$ with eclipse depths of $373^{+74}_{-75}$ and $638^{+199}_{-178}$ parts per million, respectively. We perform an atmospheric retrieval on the emission spectrum combined with the data from HST/WFC3, Spitzer, TESS, and CHEOPS to obtain the temperature profile and chemical abundances, including TiO and VO, which have been thought to produce temperature inversion structures in the dayside of ultra-hot Jupiters. While we confirm a strong temperature inversion structure, we find low abundances of TiO and VO with mixing ratios of $\rm {log(TiO)}=-7.80^{+0.15}_{-0.30}$ and $\rm {log(VO)}=-9.60^{+0.64}_{-0.57}$, respectively. The low abundances of TiO and VO are consistent with theoretical predictions for such an ultra-hot atmosphere. In such low abundances, TiO and VO have little effect on the temperature structure of the atmosphere. The abundance of ${\rm e}^{-}$, which serves as a proxy for ${\rm H}^{-}$ ions in this study, is found to be high, with $\rm {log(e^-)}=-4.89\pm {0.06}$. These results indicate that the temperature inversion in KELT-9 b’s dayside atmosphere is likely not caused by ${\rm TiO/VO}$, but rather by the significant abundance of ${\rm H}^{-}$ ions. The best-fitting model cannot fully explain the observed spectrum, and chemical species not included in the retrieval may introduce modeling biases. Future observations with broader wavelength coverage and higher spectral resolution are expected to provide more accurate diagnostics on the presence and abundances of ${\rm TiO/VO}$. These advanced observations will overcome the limitations of current data from HST and photometric facilities, which are constrained by narrow wavelength coverage and instrumental systematics.
CYP7B1 deficiency impairs myeloid cell activation in autoimmune disease of the central nervous system
Authors: Song Huanhuan , Lv Aowei , Zhu Zhibao , Li Runyun , Zhao Qiuping , Yu Xintong , Jiang Junyi , Lin Xiang , Zhang Cunjin , Li Rui , Yan Yaping , Chen Wanjin , Wang Ning , Fu Ying
Published: September 2024

Dysregulation of cholesterol metabolism underlies neurodegenerative disease and is increasingly implicated in neuroinflammatory diseases, such as multiple sclerosis (MS). Cytochrome P450 family 7 subfamily B member 1 (CYP7B1) is a key enzyme in alternative cholesterol metabolism. A recessive mutation in the gene CYP7B1 is known to cause a neurodegenerative disease, hereditary spastic paraplegia type 5 and oxysterol accumulation. However, the role of CYP7B1 in neuroinflammation has been little revealed. In this study, we induced experimental autoimmune encephalomyelitis (EAE), as a murine model of MS, using CYP7B1 homozygous knockout (KO) mice. We found that CYP7B1 deficiency can significantly attenuate EAE severity. CYP7B1 deficiency is sufficient to reduce leukocyte infiltration into the central nervous system, suppress proliferation of pathogenic CD4+ T cells, and decrease myeloid cell activation during EAE. Additionally, live-animal imaging targeting translocator protein expression, an outer mitochondrial membrane protein biomarker of neuroinflammation, showed that CYP7B1 deficiency results in suppressed neuroinflammation. Using human monocyte-derived microglia-like cellular disease model and primary microglia of CYP7B1 KO mice, we also found that activation of microglia of CYP7B1 deficiency was impaired. These cumulative results suggest that CYP7B1 can regulate neuroinflammation, thus providing potential new targets for therapeutic intervention.
Large language models reduce public knowledge sharing on online Q&A platforms
Authors: del Rio-Chanona R Maria , Laurentsyeva Nadzeya , Wachs Johannes
Published: September 2024

Large language models (LLMs) are a potential substitute for human-generated data and knowledge resources. This substitution, however, can present a significant problem for the training data needed to develop future models if it leads to a reduction of human-generated content. In this work, we document a reduction in activity on Stack Overflow coinciding with the release of ChatGPT, a popular LLM. To test whether this reduction in activity is specific to the introduction of this LLM, we use counterfactuals involving similar human-generated knowledge resources that should not be affected by the introduction of ChatGPT to such extent. Within 6 months of ChatGPT’s release, activity on Stack Overflow decreased by 25% relative to its Russian and Chinese counterparts, where access to ChatGPT is limited, and to similar forums for mathematics, where ChatGPT is less capable. We interpret this estimate as a lower bound of the true impact of ChatGPT on Stack Overflow. The decline is larger for posts related to the most widely used programming languages. We find no significant change in post quality, measured by peer feedback, and observe similar decreases in content creation by more and less experienced users alike. Thus, LLMs are not only displacing duplicate, low-quality, or beginner-level content. Our findings suggest that the rapid adoption of LLMs reduces the production of public data needed to train them, with significant consequences.
The 2024 British Society for Rheumatology guideline for management of systemic sclerosis—executive summary
Authors: Denton Christopher P , De Lorenzis Enrico , Roblin Elen , Goldman Nina , Alcacer-Pitarch Begonya , Blamont Emma , Buch Maya H , Carulli Maresa , Cotton Caroline , Del Galdo Francesco , Derrett-Smith Emma , Douglas Karen , Farrington Sue , Fligelstone Kim , Gompels Luke , Griffiths Bridget , Herrick Ariane , Hughes Michael , Pain Clare , Pantano Georgina , Pauling John D , Prabu Athiveeraramapandian , O’Donoghue Nuala , Renzoni Elisabetta A , Royle Jeremy , Samaranayaka Muditha , Spierings Julia , Tynan Aoife , Warburton Louise , Ong Voon H
Published: September 2024

This guideline was developed according to the British Society for Rheumatology Guidelines Protocol by a Guideline Development Group comprising healthcare professionals with expertise in SSc and people with lived experience, as well as patient organization representatives. It is an update of the previous 2015 SSc guideline. The recommendations were developed and agreed by the group and are underpinned by published evidence, assessed by systematic literature review and reinforced by collective expert opinion of the group. It considers all aspects of SSc including general management, treatment of organ-based complications, including cardiopulmonary, renal and gastrointestinal tract manifestations, as well as broader impact of disease. Whilst it is focused on adults with SSc we expect that the guideline will be relevant to people of all ages and expert input and review by paediatric rheumatologists and other relevant specialists considered where the guideline was, or may not be, applicable to young people with SSc and juvenile-onset disease. In addition to providing guidance on disease assessment and management the full guideline also considers service organization within the National Health Service and future approaches to audit of the guideline. The lay summary that accompanies this abstract can be found in Supplemental information 1.
Associations between loneliness, disease activity and disease impact in inflammatory arthritis: a nationwide cross-sectional study among more than 12 000 patients
Authors: Vestergaard Sofie Bech , Esbensen Bente Appel , Midtgaard Julie , Cromhout Pernille Fevejle , Aadahl Mette , Glintborg Bente , de Thurah Annette
Published: September 2024

Objectives

To investigate the prevalence of loneliness among patients with IA with a specific focus on the associations with disease activity and impact.

Methods

We used data from a Danish cross-sectional survey comprising information on socio-demographics, mental health status, and social contacts among 12 713 patients with IA [rheumatoid arthritis (RA)/psoriatic arthritis (PsA)/axial spondylarthritis (axSpA)]. Data were linked to the DANBIO Rheumatology Registry and the National Patient Registry. Loneliness was measured by asking: ‘Are you ever alone, although you would prefer to be together with others?’. Association with disease activity and disease impact (Patient Global Assessment, pain, fatigue, physical function) was estimated using multivariable logistic regression [age, sex, cohabitation status, educational level, mental health status (depression, anxiety) and co-morbidity].

Results

: Approximately one-third reported loneliness. Prevalence was lowest for patients with RA [31.6% (95%CI: 30.5; 32.6)] compared with PsA and axSpA [36.0 (34.0; 38.0)] and [36.3 (34.1; 38.4), respectively]. It was highest among axSpA patients reporting high levels of depression [66.2% (60.0; 72.8)]. A positive association was observed between loneliness and disease activity. For disease impact, prevalence estimates were between 40% and 60% when patients experienced high levels of pain, fatigue, low levels of physical function, and high Patient Global Assessment.

Conclusions

Loneliness was highly prevalent in IA and associated with disease activity and impact. Therefore, loneliness is an important target for future mental health interventions in IA.