bluuebunny/crossref_metadata_2025_split huggingface dataset:
The overestimation of the effect sizes of psychotherapies for depression in waitlist controlled trials: a meta-analytic comparison with usual care controlled trials
Authors: Cuijpers Pim , Miguel Clara , Harrer Mathias , Ciharova Marketa , Karyotaki Eirini 
Published: November 2024

AbstractAimsThere is considerable evidence that waiting list (WL) control groups overestimate the effect sizes of psychotherapies for depression. It is not clear, however, what are the exact causes for this overestimation. We decided to conduct a meta-analytic study to compare trials on psychotherapy for depression with a WL control group against trials with a care-as-usual (CAU) control group.MethodsWe used an existing meta-analytic database of randomized trials comparing psychological treatments of adult depression with control groups and selected trials using a WL or a CAU control group. We used subgroup and meta-regression analyses to examine differences in effect sizes between WL and CAU controlled trials.ResultsWe included 333 randomized controlled trials (472 comparisons; total number participants: 41,480), 141 with a WL and 195 with a CAU control group (3 included both). We found several significant differences between WL and CAU controlled trials (in type of therapy examined, treatment format, recency, target group, recruitment strategy, number of treatment arms and number of depression outcome measures). The overall effect size indicating the difference between treatment and control at post-test for all comparisons wasg= 0.77 (95% confidence interval [CI]: 0.71; 0.84) with high heterogeneity (I2= 84; 95% CI: 82; 85). A highly significant difference was observed between studies with a CAU control group (g= 0.63; 95% CI: 0.55; 0.71;I2= 85; 95% CI: 83; 86) and studies with a WL (g= 0.95; 95% CI: 0.85; 1.04;I2= 80; 95% CI: 78; 82;pfor difference < 0.001). This difference remained significant in all sensitivity analyses, including a meta-regression analysis in which we adjusted for all differences in characteristics of studies with a WL versus CAU control group. We also found that pre-post effect sizes in WL control conditions (g= 0.37; 95% CI: 0.28; 0.46) were significantly smaller than change within CAU conditions (g= 0.64; 95% CI: 0.50; 0.78). We found few indications that pre-post effect sizes within therapy conditions differed between WL and CAU controlled trials.ConclusionsWL control conditions considerably overestimate the effect sizes of psychological treatments, compared to trials using CAU control conditions. This overestimation is probably caused by a smaller improvement within the WL condition compared to the improvement in the CAU condition. WL control conditions should be avoided in randomized trials examining psychological treatments of adult depression.
Ten minute trips: a case study examining student perceptions of the value of virtual reality in A-level Classical Civilisation
Authors: Johnson Tom 
Published: November 2024

Abstract
Virtual Reality is regularly heralded as a tool which will revolutionise teaching and education, yet little research has been done into its use and, in particular, into its use with secondary school students. Through a case study of a Year 13 Classical Civilisation class this article investigates student perceptions of the use of Virtual Reality in the Classics classroom and its impact upon their learning. This study demonstrated students' positive attitudes towards the use of Virtual Reality and that it appeared to have a positive and lasting impact upon their understanding of Ancient Greek sanctuaries. The study is limited in its scale – both in terms of student numbers and time period – but it can, I hope, offer encouragement for greater use of, and research into, Virtual Reality within the secondary Classics classroom.
Isotopic Constraints on Nitrous Oxide Emissions From the US Corn Belt
Authors: Griffis T. J. , Yu Z. , Baker J. M. , Millet D. B. 
Published: November 2024

AbstractAgriculture is the dominant source of anthropogenic nitrous oxide (N2O) –a greenhouse gas and a stratospheric ozone depleting substance. The US Corn Belt is a large global N2O source, but there remain large uncertainties regarding its source attribution and biogeochemical pathways. Here, we interpret high frequency stable N2O isotope observations from a very tall tower to improve our understanding of regional source attribution. We detected significant seasonal variability in δ15Nbulk (6.47–7.33‰) and the isotope site preference (δ15NSP = δ15Nα–δ15Nβ, 18.22–25.19‰) indicating a predominance of denitrification during the growing period but of nitrification during the snowmelt period. Isotope mixing models and atmospheric inversions both indicate that indirect emissions contribute substantially (>35%) to total N2O emissions. Despite the relatively large uncertainties, the upper bound of bottom‐up indirect emission estimates are at the lower bound of the isotopic constraint, implying significant discrepancies that require further investigation.
Transpolar Arcs Are Not Always Cusp‐Aligned: Evidence of HiLDA‐Aligned Arcs
Authors: Katrougkalou Maria Chloi , Kullen Anita , Cai Lei , Roth Lorenz , Zhang Yongliang 
Published: November 2024

AbstractTranspolar arcs (TPAs) are often cusp‐aligned. Especially when multiple TPAs appear simultaneously, they join at the auroral signature of the cusp. Here we investigate the dayside connection point of TPAs using Defense Meteorological Satellite Program measurements and identify three cases where the tip of the TPA ends in a localized brightening. One is a typical cusp spot with a TPA attached. The cusp appears just poleward of the oval with a near circular shape. In the second case, multiple cusp spots are observed over a 3 MLT wide region, each connected to a TPA. In the third case, the brightening at the tip of a TPA is identified as high‐latitude dayside aurora (HiLDA). Cusp aurora appears between the HiLDA and the duskside oval. Plasma flows and particle characteristics indicate a lobe origin of the HiLDA. Our results indicate a more complicated connection between TPAs and dayside aurora than previously anticipated.
Targeted protein degradation: advances in drug discovery and clinical practice
Authors: Zhong Guangcai , Chang Xiaoyu , Xie Weilin , Zhou Xiangxiang 
Published: November 2024

AbstractTargeted protein degradation (TPD) represents a revolutionary therapeutic strategy in disease management, providing a stark contrast to traditional therapeutic approaches like small molecule inhibitors that primarily focus on inhibiting protein function. This advanced technology capitalizes on the cell’s intrinsic proteolytic systems, including the proteasome and lysosomal pathways, to selectively eliminate disease-causing proteins. TPD not only enhances the efficacy of treatments but also expands the scope of protein degradation applications. Despite its considerable potential, TPD faces challenges related to the properties of the drugs and their rational design. This review thoroughly explores the mechanisms and clinical advancements of TPD, from its initial conceptualization to practical implementation, with a particular focus on proteolysis-targeting chimeras and molecular glues. In addition, the review delves into emerging technologies and methodologies aimed at addressing these challenges and enhancing therapeutic efficacy. We also discuss the significant clinical trials and highlight the promising therapeutic outcomes associated with TPD drugs, illustrating their potential to transform the treatment landscape. Furthermore, the review considers the benefits of combining TPD with other therapies to enhance overall treatment effectiveness and overcome drug resistance. The future directions of TPD applications are also explored, presenting an optimistic perspective on further innovations. By offering a comprehensive overview of the current innovations and the challenges faced, this review assesses the transformative potential of TPD in revolutionizing drug development and disease management, setting the stage for a new era in medical therapy.
A protein vaccine of RBD integrated with immune evasion mutation shows broad protection against SARS-CoV-2
Authors: An Ran , Yang Hao , Tang Cong , Li Qianqian , Huang Qing , Wang Haixuan , Wang Junbin , Zhou Yanan , Yang Yun , Chen Hongyu , Yu Wenhai , Li Bai , Wu Daoju , Zhang Yong , Luo Fangyu , Quan Wenqi , Xu Jingwen , Lin Dongdong , Liang Xiaoming , Yan Yuhuan , Yuan Longhai , Du Xuena , Yuan Yuxia , Li Yanwen , Sun Qiangming , Wang Youchun , Lu Shuaiyao 
Published: November 2024

AbstractVariants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge and evade immunity, resulting in breakthrough infections in vaccinated populations. There is an urgent need for the development of vaccines with broad protective effects. In this study, we selected hotspot mutations in the receptor-binding domain (RBD) that contribute to immune escape properties and integrated them into the original RBD protein to obtain a complex RBD protein (cRBD), and we found cRBDs have broad protective effects against SARS-CoV-2 variants. Three cRBDs were designed in our study. Compared with the BA.1 RBD protein, the cRBDs induced the production of higher levels of broader-spectrum neutralizing antibodies, suggesting stronger and broader protective efficacy. In viral challenge experiments, cRBDs were more effective than BA.1 RBD in attenuating lung pathologic injury. Among the three constructs, cRBD3 showed optimal broad-spectrum and protective effects and is a promising candidate for a broad-spectrum SARS-CoV-2 vaccine. In conclusion, immunization with cRBDs triggered immunity against a wide range of variants, including those that emerged after we had completed designing the cRBDs. This study preliminarily explores and validates the feasibility of incorporating hotspot mutations that contribute to immune evasion into the RBD to expand the activity spectrum of antigen-induced antibodies.
Dependence of NPPS creates a targetable vulnerability in RAS-mutant cancers
Authors: Xia Rui-xue , Zou Pei-chen , Xie Jun-ting , Tang Ya-bin , Gong Miao-miao , Fan Fu , Aihemaiti Ayinazhaer , Liu Yu-qing , Shen Ying , Zhou Bin-bing S. , Zhu Liang , Lei Hui-min 
Published: November 2024

Abstract
RAS is the most frequently mutated oncoprotein for cancer driving. Understanding of RAS biology and discovery of druggable lynchpins in RAS pathway is a prerequisite for targeted therapy of RAS-mutant cancers. The recent identification of KRASG12C inhibitor breaks the “undruggable” curse on RAS and has changed the therapy paradigm of KRAS-mutant cancers. However, KRAS mutations, let alone KRASG12C mutation, account for only part of RAS-mutated cancers. Targeted therapies for cancers harboring other RAS mutations remain the urgent need. In this study we explored the pivotal regulatory molecules that allow for broad inhibition of RAS mutants. By comparing the expression levels of nucleotide pyrophosphatase (NPPS) in a panel of cell lines and the functional consequence of increased NPPS expression in RAS-mutant cells, we demonstrated that cancer cells with various kinds of RAS mutations depended on NPPS for growth and survival, and that this dependence conferred a vulnerability of RAS-mutant cancer to treatment of NPPS inhibition. RAS-mutant cells, compared with RAS-wildtype cells, bored and required an upregulation of NPPS. Transcriptomics and metabolomics analyses revealed a NPPS-dependent hyperglycolysis in RAS-mutant cells. We demonstrated that NPPS promoted glucose-derived glycolytic intermediates in RAS-mutant cells by enhancing its interaction with hexokinase 1 (HK1), the enzyme catalyzing the first committed step of glycolysis. Pharmacological inhibition of NPPS-HK1 axis using NPPS inhibitor Enpp-1-IN-1 or HK1 inhibitor 2-deoxyglucose (2-DG), or genetic interfere with NPPS suppressed RAS-mutant cancers in vitro and in vivo. In conclusion, this study reveals an unrecognized mechanism and druggable lynchpin for modulation of pan-mutant-RAS pathway, proposing a new potential therapeutic approach for treating RAS-mutant cancers.
Smad transcription factors as mediators of 7 transmembrane G protein-coupled receptor signalling
Authors: Chia Zheng-Jie , Kumarapperuma Hirushi , Zhang Ruizhi , Little Peter J. , Kamato Danielle 
Published: November 2024

AbstractThe Smad transcription factors are well known for their role at the core of transforming growth factor-β (TGF-β) signalling. However, recent evidence shows that the Smad transcription factors play a vital role downstream of other classes of receptors including G protein-coupled receptors (GPCR). The versatility of Smad transcription factors originated from the two regions that can be differently activated by the TGF-β receptor superfamily or through the recruitment of intracellular kinases stimulated by other receptors classes such as GPCRs. The classic GPCR signalling cascade is further expanded to conditional adoption of the Smad transcription factor under the stimulation of Akt, demonstrating the unique involvement of the Smad transcription factor in GPCR signalling pathways in disease environments. In this review, we provide a summary of the signalling pathways of the Smad transcription factors as an important downstream mediator of GPCRs, presenting exciting opportunities for discovering new therapeutic targets for diseases.
Mosaic chromosomal alterations (mCAs) in individuals with monoclonal B-cell lymphocytosis (MBL)
Authors: Sekar Aswin , Griffin Rosalie , Parikh Sameer A. , Genovese Giulio , Robinson Dennis P. , Norman Aaron D. , Olson Janet E. , Rabe Kari G. , Hoel Mingma S. , Boddicker Nicholas J. , Hampel Paul J. , Kay Neil E. , Cerhan James R. , Braggio Esteban , Hanson Curtis A. , Vachon Celine M. , Shanafelt Tait D. , Ebert Benjamin L. , Slager Susan L. 
Published: November 2024

AbstractMBL is a precursor condition to chronic lymphocytic leukemia (CLL), characterized by monoclonal B-cells in blood. Mosaic chromosomal alterations (mCAs) are a form of clonal hematopoiesis that include gains, losses, and copy-neutral loss-of-heterozygosity of large DNA segments. Both MBL and mCAs have been found to increase the risk of CLL and lymphoid malignancies, and the aim of our study was to investigate how mCAs relate to MBL, which is currently unknown. We analyzed genetic, flow cytometric, and hematologic data from 4632 individuals from the Mayo Clinic Biobank and CLL Database. MBL was detected using flow cytometry and classified as high-count (HC) or low-count (LC) MBL based on clone size. mCAs were detected primarily from whole blood DNA using sensitive SNP-array-based analyses. mCAs commonly altered in CLL (deletion of 6q, 11q, 13q, 17p, and trisomy 12) were specific (>99%) to individuals with MBL and CLL. HC-MBL and LC-MBL individuals were 881-fold and 8-fold, respectively, more likely to harbor CLL-associated mCAs than those without MBL. The cell fraction bearing these mCAs typically exceeded the B-cell fraction, suggesting their origin prior to the B-cell lineage. Integrating genetic and blood count data enabled detecting HC-MBL with high specificity in a biobank sample. These results quantify the contribution of mCAs to MBL and could enable large studies of HC-MBL without the need for flow cytometric screening.
Measurable residual mutated IDH1 before allogeneic transplant for acute myeloid leukemia
Authors: Gui Gege , Ravindra Niveditha , Hegde Pranay S. , Andrew Georgia , Mukherjee Devdeep , Wong Zoë , Auletta Jeffery J. , El Chaer Firas , Chen Evan C. , Chen Yi-Bin , Corner Adam , Devine Steven M. , Iyer Sunil G. , Jimenez Jimenez Antonio Martin , De Lima Marcos J. G. , Litzow Mark R. , Kebriaei Partow , Saber Wael , Spellman Stephen R. , Zeger Scott L. , Page Kristin M. , Dillon Laura W. , Hourigan Christopher S. 
Published: November 2024

Abstract
Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. Persistence of mutated NPM1 or FLT3-ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoietic cell transplant (alloHCT) associates with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as IDH1, at this treatment landmark however remain incompletely defined. We performed testing for residual IDH1 variants (IDH1m) in pre-transplant CR1 blood of 148 adult patients undergoing alloHCT for IDH1-mutated AML at a CIBMTR reporting site between 2013 and 2019. No statistically significant post-transplant differences were observed between those testing IDH1m positive (n = 53, 36%) and negative pre-transplant (overall survival (OS): p = 0.4; relapse: p = 0.5). For patients with IDH1 mutated AML co-mutated with NPM1 and/or FLT3-ITD, only detection of persistent mutated NPM1 and/or FLT3-ITD was associated with significantly higher rates of relapse (p = 0.01). These data, from the largest study to date, do not support the detection of IDH1 mutation in CR1 blood prior to alloHCT as evidence of AML MRD for increased post-transplant relapse risk.
Replication stress induces POLQ-mediated structural variant formation throughout common fragile sites after entry into mitosis
Authors: Wilson Thomas E. , Ahmed Samreen , Winningham Amanda , Glover Thomas W. 
Published: November 2024

AbstractGenomic structural variants (SVs) greatly impact human health, but much is unknown about the mechanisms that generate the largest class of nonrecurrent alterations. Common fragile sites (CFSs) are unstable loci that provide a model for SV formation, especially large deletions, under replication stress. We study SV junction formation as it occurs in human cell lines by applying error-minimized capture sequencing to CFS DNA harvested after low-dose aphidicolin treatment. SV junctions form throughout CFS genes at a 5-fold higher rate after cells pass from G2 into M-phase. Neither SV formation nor CFS expression depend on mitotic DNA synthesis (MiDAS), an error-prone form of replication active at CFSs. Instead, analysis of tens of thousands of de novo SV junctions combined with DNA repair pathway inhibition reveal a primary role for DNA polymerase theta (POLQ)-mediated end-joining (TMEJ). We propose an important role for mitotic TMEJ in nonrecurrent SV formation genome wide.
Microscale chemical imaging to characterize and quantify corrosion processes at the metal-electrolyte interface
Authors: Albert Cristhiana C. , Mundra Shishir , Ferreira Sanchez Dario , Furcas Fabio E. , Rajyaguru Ashish D. , Isgor O. Burkan , Grolimund Daniel , Angst Ueli M. 
Published: November 2024

AbstractWe introduce an experimental setup to chemically image corrosion processes at metal-electrolyte interfaces under stagnant, confined conditions—relevant in a wide range of situations. The setup is based on a glass capillary, in which precipitation of corrosion products in the interfacial aqueous phase can be monitored over time with optical microscopy, and chemically and structurally characterized with microscopic synchrotron-based techniques (X-ray fluorescence, X-ray diffraction, and X-ray absorption spectroscopy). Moreover, quantification of precipitates through X-ray transmission measurements provides in-situ corrosion rates. We illustrate this setup for iron corrosion in a pH 8 electrolyte, revealing the critical role of O2 and iron diffusion in governing the precipitation of ferrihydrite and its transformation to goethite. Corrosion and coupled reactive transport processes can thus be monitored and fundamentally investigated at the metal-electrolyte interface, with micrometer-scale resolution. This capillary setup has potential applications for in-situ corrosion studies of various metals and environments.
Classification of dynamical Lie algebras of 2-local spin systems on linear, circular and fully connected topologies
Authors: Wiersema Roeland , Kökcü Efekan , Kemper Alexander F. , Bakalov Bojko N. 
Published: November 2024

AbstractMuch is understood about 1-dimensional spin chains in terms of entanglement properties, physical phases, and integrability. However, the Lie algebraic properties of the Hamiltonians describing these systems remain largely unexplored. In this work, we provide a classification of all Lie algebras generated by the terms of 2-local spin chain Hamiltonians, or so-called dynamical Lie algebras, on 1-dimensional linear and circular lattice structures. We find 17 unique dynamical Lie algebras. Our classification includes some well-known models such as the transverse-field Ising model and the Heisenberg chain, and we also find more exotic classes of Hamiltonians that appear new. In addition to the closed and open spin chains, we consider systems with a fully connected topology, which may be relevant for quantum machine learning approaches. We discuss the practical implications of our work in the context of variational quantum computing, quantum control and the spin chain literature.
Offline ensemble co-reactivation links memories across days
Authors: Zaki Yosif , Pennington Zachary T. , Morales-Rodriguez Denisse , Bacon Madeline E. , Ko BumJin , Francisco Taylor R. , LaBanca Alexa R. , Sompolpong Patlapa , Dong Zhe , Lamsifer Sophia , Chen Hung-Tu , Carrillo Segura Simón , Christenson Wick Zoé , Silva Alcino J. , Rajan Kanaka , van der Meer Matthijs , Fenton André , Shuman Tristan , Cai Denise J. 
Published: November 2024

AbstractMemories are encoded in neural ensembles during learning1–6 and are stabilized by post-learning reactivation7–17. Integrating recent experiences into existing memories ensures that memories contain the most recently available information, but how the brain accomplishes this critical process remains unclear. Here we show that in mice, a strong aversive experience drives offline ensemble reactivation of not only the recent aversive memory but also a neutral memory formed 2 days before, linking fear of the recent aversive memory to the previous neutral memory. Fear specifically links retrospectively, but not prospectively, to neutral memories across days. Consistent with previous studies, we find that the recent aversive memory ensemble is reactivated during the offline period after learning. However, a strong aversive experience also increases co-reactivation of the aversive and neutral memory ensembles during the offline period. Ensemble co-reactivation occurs more during wake than during sleep. Finally, the expression of fear in the neutral context is associated with reactivation of the shared ensemble between the aversive and neutral memories. Collectively, these results demonstrate that offline ensemble co-reactivation is a neural mechanism by which memories are integrated across days.