bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-molecule characterization of Sen1 translocation properties provides insights into eukaryotic factor-dependent transcription termination
Authors: Wang Shuang , Han Zhong , Strick Terence R 
Published: January 2024

Abstract
Sen1 is an essential helicase for factor-dependent transcription termination in Saccharomyces cerevisiae, whose molecular-motor mechanism has not been well addressed. Here, we use single-molecule experimentation to better understand the molecular-motor determinants of its action on RNA polymerase II (Pol II) complex. We quantify Sen1 translocation activity on single-stranded DNA (ssDNA), finding elevated translocation rates, high levels of processivity and ATP affinities. Upon deleting the N- and C-terminal domains, or further deleting different parts of the prong subdomain, which is an essential element for transcription termination, Sen1 displays changes in its translocation properties, such as slightly reduced translocation processivities, enhanced translocation rates and statistically identical ATP affinities. Although these parameters fulfil the requirements for Sen1 translocating along the RNA transcript to catch up with a stalled Pol II complex, we observe significant reductions in the termination efficiencies as well as the factions of the formation of the previously described topological intermediate prior to termination, suggesting that the prong may preserve an interaction with Pol II complex during factor-dependent termination. Our results underscore a more detailed rho-like mechanism of Sen1 and a critical interaction between Sen1 and Pol II complex for factor-dependent transcription termination in eukaryotes.
Translation variation across genetic backgrounds reveals a post-transcriptional buffering signature in yeast
Authors: Teyssonniere Elie M , Shichino Yuichi , Mito Mari , Friedrich Anne , Iwasaki Shintaro , Schacherer Joseph 
Published: January 2024

Abstract
Gene expression is known to vary among individuals, and this variability can impact the phenotypic diversity observed in natural populations. While the transcriptome and proteome have been extensively studied, little is known about the translation process itself. Here, we therefore performed ribosome and transcriptomic profiling on a genetically and ecologically diverse set of natural isolates of the Saccharomyces cerevisiae yeast. Interestingly, we found that the Euclidean distances between each profile and the expression fold changes in each pairwise isolate comparison were higher at the transcriptomic level. This observation clearly indicates that the transcriptional variation observed in the different isolates is buffered through a phenomenon known as post-transcriptional buffering at the translation level. Furthermore, this phenomenon seemed to have a specific signature by preferentially affecting essential genes as well as genes involved in complex-forming proteins, and low transcribed genes. We also explored the translation of the S. cerevisiae pangenome and found that the accessory genes related to introgression events displayed similar transcription and translation levels as the core genome. By contrast, genes acquired through horizontal gene transfer events tended to be less efficiently translated. Together, our results highlight both the extent and signature of the post-transcriptional buffering.
Leveraging external control data in the design and analysis of neuro-oncology trials: Pearls and perils
Authors: Polley Mei-Yin C , Schwartz Daniel , Karrison Theodore , Dignam James J 
Published: January 2024

Abstract

Background
Randomized controlled trials have been the gold standard for evaluating medical treatments for many decades but they are often criticized for requiring large sample sizes. Given the urgent need for better therapies for glioblastoma, it has been argued that data collected from patients treated with the standard regimen can provide high-quality external control data to supplement or replace concurrent control arm in future glioblastoma trials.

Methods
In this article, we provide an in-depth appraisal of the use of external control data in the context of neuro-oncology trials. We describe several clinical trial designs with particular attention to how external information is utilized and address common fallacies that may lead to inappropriate adoptions of external control data.

Results
Using 2 completed glioblastoma trials, we illustrate the use of an assessment tool that lays out a blueprint for assembling a high-quality external control data set. Using statistical simulations, we draw caution from scenarios where these approaches can fall short on controlling the type I error rate.

Conclusions
While this approach may hold promise in generating informative data in certain settings, this sense of optimism should be tampered with a healthy dose of skepticism due to a myriad of design and analysis challenges articulated in this review. Importantly, careful planning is key to its successful implementation.
Long-Term Survival in Patients With Relapsed/Refractory Advanced Renal Cell Carcinoma Treated With Tivozanib: Analysis of the Phase III TIVO-3 Trial
Authors: Beckermann Kathryn E , Asnis-Alibozek Aviva G , Atkins Michael B , Escudier Bernard , Hutson Thomas E , Kasturi Vijay , McDermott David F , Pal Sumanta K , Porta Camillo , Rini Brian I , Verzoni Elena 
Published: January 2024

Abstract

Background
Tivozanib is an oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) with efficacy in advanced renal cell carcinoma (RCC). Long-term exploratory analyses from the TIVO-3 trial in relapsed/refractory (R/R) RCC including patients (26%) with prior immuno-oncology (IO) therapy are reported.

Methods
Patients with R/R advanced RCC that progressed with 2 or 3 prior systemic therapies (≥1 VEGFR TKI) were randomized to tivozanib 1.5 mg QD or sorafenib 400 mg BID, stratified by IMDC risk and previous therapy. Safety, investigator-assessed long-term progression-free survival (LT-PFS), and serial overall survival (OS) were assessed.

Results
Mean time on treatment was 11.0 months with tivozanib (n = 175) and 6.3 months with sorafenib (n = 175). Fewer grade ≥3 treatment-related adverse events occurred with tivozanib (46%) than sorafenib (55%). Dose modification rates were lower with tivozanib than sorafenib across age/prior IO subgroups; prior IO therapy did not impact dose reductions or discontinuations in either arm. Landmark LT-PFS rates were higher with tivozanib (3 years: 12.3% vs 2.4%; 4 years: 7.6% vs 0%). After 22.8 months mean follow-up, the OS HR was 0.89 (95% CI, 0.70-1.14); when conditioned on 12-month landmark PFS, tivozanib showed significant OS improvement over sorafenib (HR, 0.45; 95% CI, 0.22-0.91; 2-sided P = .0221).

Conclusions
Tivozanib demonstrated a consistent safety profile and long-term survival benefit in patients with R/R advanced RCC who were alive and progression free at 12 months. These post hoc exploratory analyses of LT-PFS and conditional OS support a clinically meaningful improvement with tivozanib versus sorafenib in this advanced RCC population.
Pathogen perception and signaling in plant immunity
Authors: Dodds Peter N , Chen Jian , Outram Megan A 
Published: January 2024

Abstract
Plant diseases are a constant and serious threat to agriculture and ecological biodiversity. Plants possess a sophisticated innate immunity system capable of detecting and responding to pathogen infection to prevent disease. Our understanding of this system has grown enormously over the past century. Early genetic descriptions of plant disease resistance and pathogen virulence were embodied in the gene-for-gene hypothesis, while physiological studies identified pathogen-derived elicitors that could trigger defense responses in plant cells and tissues. Molecular studies of these phenomena have now coalesced into an integrated model of plant immunity involving cell surface and intracellular detection of specific pathogen-derived molecules and proteins culminating in the induction of various cellular responses. Extracellular and intracellular receptors engage distinct signaling processes but converge on many similar outputs with substantial evidence now for integration of these pathways into interdependent networks controlling disease outcomes. Many of the molecular details of pathogen recognition and signaling processes are now known, providing opportunities for bioengineering to enhance plant protection from disease. Here we provide an overview of the current understanding of the main principles of plant immunity, with an emphasis on the key scientific milestones leading to these insights.
Pointing Calibration of GroundBIRD Telescope Using Moon Observation Data
Authors: Sueno Y , Baselmans J J A , Coppens A H M , Génova-Santos R T , Hattori M , Honda S , Karatsu K , Kutsuma H , Lee K , Nagasaki T , Oguri S , Otani C , Peel M , Suzuki J , Tajima O , Tanaka T , Tsujii M , Thoen D J , Won E 
Published: January 2024

Abstract
Understanding telescope pointing (i.e. line of sight) is important for observing the cosmic microwave background (CMB) and astronomical objects. The Moon is a candidate astronomical source for pointing calibration. Although the visible size of the Moon (30′) is larger than that of the planets, we can frequently observe the Moon once a month with a high signal-to-noise ratio. We developed a method for performing pointing calibration using observational data from the Moon. We considered the tilts of the telescope axes as well as the encoder and collimation offsets for pointing calibration. In addition, we evaluated the effects of the nonuniformity of the brightness temperature of the Moon, which is a dominant systematic error. As a result, we successfully achieved a pointing accuracy of 3.3′. This is one order of magnitude smaller than an angular resolution of 36′. This level of accuracy competes with past achievements in other ground-based CMB experiments using observational data from the planets.
Outside Options in the Labour Market
Authors: Caldwell Sydnee , Danieli Oren 
Published: January 2024

Abstract
This paper develops a method to estimate workers’ outside employment opportunities. We outline a matching model with two-sided heterogeneity, from which we derive a sufficient statistic, the “outside options index” (OOI), for the effect of outside options on earnings, holding worker productivity constant. The OOI uses the cross-sectional concentration of similar workers across job types to quantify workers’ outside options as a function of workers’ commuting costs, preferences, and skills. Using German micro-data, we find that differences in options explain 20% of the gender earnings gap, and that gender gaps in options are mostly due to differences in the implicit costs of commuting and moving.
Patient burden and joint inflammation during development of RA from arthralgia: is it similar in ACPA-positive and ACPA-negative disease?
Authors: Khidir Sarah J H , Krijbolder Doortje I , Glas Herman K , van Mulligen Elise , van der Helm-van Mil Annette H M 
Published: January 2024

Abstract

Objectives
ACPA-positive and ACPA-negative RA differ in underlying risk factors but have a similar clinical presentation at RA diagnosis. It is unknown what the ACPA-associated differences or similarities are during the symptomatic at-risk stage of RA, i.e. clinically suspect arthralgia (CSA). To deepen insights into these differences/similarities, we compared the course of symptoms/impairments and subclinical joint inflammation in the CSA phase during progression to inflammatory arthritis (IA) or to CSA resolution.

Methods
A total of 845 CSA patients were followed for a median of 24 months; 136 patients developed IA and an additional 355/505 patients had resolution of CSA according to rheumatologists. Patient burden (pain, morning stiffness, fatigue, functional disabilities, presenteeism) was assessed at baseline and 4, 12 and 24 months and at IA development. Subclinical joint inflammation in the hands and feet was assessed over time with 1.5T MRI. Linear and Poisson mixed models were used.

Results
In both ACPA-positive and ACPA-negative patients, patient burden increased towards IA development and decreased towards CSA resolution. However, patient burden was lower in ACPA-positive vs ACPA-negative disease at all timepoints. Conversely, subclinical joint inflammation tended to increase more rapidly during development of ACPA-positive IA [incidence rate ratio (IRR) 1.52 (95% CI 0.94, 2.47), P = 0.089] and remained higher over time in ACPA-positive CSA patients achieving resolution compared with ACPA-negative patients [IRR 1.52 (95% CI 1.07, 2.15), P = 0.018]. Although correlation coefficients between changes in patient burden and subclinical joint inflammation during progression to IA were weak, they were consistently higher in ACPA-positive than ACPA-negative disease, e.g. ρ = 0.29 vs 0.12 for functional disabilities.

Conclusion
During RA development and CSA resolution, ACPA-positive CSA patients have lower patient burden but more subclinical joint inflammation than ACPA-negative CSA patients. These data strengthen the notion that the development of ACPA-positive and ACPA-negative RA is pathophysiologically different and encourage further research on these differences.
Heterogeneous Brain Abnormalities in Schizophrenia Converge on a Common Network Associated With Symptom Remission
Authors: Wang Yingru , Yang Yinian , Xu Wenqiang , Yao Xiaoqing , Xie Xiaohui , Zhang Long , Sun Jinmei , Wang Lu , Hua Qiang , He Kongliang , Tian Yanghua , Wang Kai , Ji Gong-Jun 
Published: January 2024

Abstract

Background and Hypothesis
There is a huge heterogeneity of magnetic resonance imaging findings in schizophrenia studies. Here, we hypothesized that brain regions identified by structural and functional imaging studies of schizophrenia could be reconciled in a common network.

Study Design
We systematically reviewed the case-control studies that estimated the brain morphology or resting-state local function for schizophrenia patients in the literature. Using the healthy human connectome (n = 652) and a validated technique “coordinate network mapping” to identify a common brain network affected in schizophrenia. Then, the specificity of this schizophrenia network was examined by independent data collected from 13 meta-analyses. The clinical relevance of this schizophrenia network was tested on independent data of medication, neuromodulation, and brain lesions.

Study Results
We identified 83 morphological and 60 functional studies comprising 7389 patients with schizophrenia and 7408 control subjects. The “coordinate network mapping” showed that the atrophy and dysfunction coordinates were functionally connected to a common network although they were spatially distant from each other. Taking all 143 studies together, we identified the schizophrenia network with hub regions in the bilateral anterior cingulate cortex, insula, temporal lobe, and subcortical structures. Based on independent data from 13 meta-analyses, we showed that these hub regions were specifically connected with regions of cortical thickness changes in schizophrenia. More importantly, this schizophrenia network was remarkably aligned with regions involving psychotic symptom remission.

Conclusions
Neuroimaging abnormalities in cross-sectional schizophrenia studies converged into a common brain network that provided testable targets for developing precise therapies.
Cultural Resistance to Policy Change: Welfare Privatization, Policy Feedback, and the Moral Economy of Welfare
Authors: Frederiksen Morten 
Published: January 2024

Abstract
Social policy research posits that people adapt to policy change by aligning their preferences and institutional expectations through habituation. At face value, this policy feedback theory conflicts with theories of moral economy, which suggests that people share durable cultural repertoires regarding the meaning of the good life and good society. Deploying a large number of qualitative interviews, this study analyzes whether and how people resist or adapt to welfare privatization polices in Sweden and Denmark. The analysis identifies and compares cultural repertoires incompatible across the state–market boundary in the contexts of health care and education. Equality and efficiency are identified as key values in the moral economy of welfare, whereas profit and selectivity are market values that interviewees resist and reject in the context of welfare. In contrast, many justify the individual right to buy welfare in the market. The findings suggest that policy changes that cross sectorial boundaries become legitimate only if multiple notions of cultural worth are involved. Attempts to justify privatization policies take place as cultural reconfiguration and interpretation, rather than changed preferences and expectations.
Uterine Immunoprivileged Cells Restore Cardiac Function of Male Recipients After Myocardial Infarction
Authors: Peng Zexu , Ludke Ana , Wu Jun , Li Shuhong , Alibhai Faisal J , Zhang Yichong , Fan Yunfei , Song Huifang , He Sheng , Xie Jun , Li Ren-Ke 
Published: January 2024

Abstract
It has been documented that the uterus plays a key cardio-protective role in pre-menopausal women, which is supported by uterine cell therapy, to preserve cardiac functioning post-myocardial infarction, being effective among females. However, whether such therapies would also be beneficial among males is still largely unknown. In this study, we aimed to fill in this gap in knowledge by examining the effects of transplanted uterine cells on infarcted male hearts. We identified, based on major histocompatibility complex class I (MHC-I) expression levels, 3 uterine reparative cell populations: MHC-I(neg), MHC-I(mix), and MHC-I(pos). In vitro, MHC-I(neg) cells showed higher levels of pro-angiogenic, pro-survival, and anti-inflammatory factors, compared to MHC-I(mix) and MHC-I(pos). Furthermore, when cocultured with allogeneic mixed leukocytes, MHC-I(neg) had lower cytotoxicity and leukocyte proliferation. In particular, CD8+ cytotoxic T cells significantly decreased, while CD4+CD25+ Tregs and CD4-CD8- double-negative T cells significantly increased when cocultured with MHC-I(neg), compared to MHC-I(mix) and MHC-I(pos) cocultures. In vivo, MHC-I(neg) as well as MHC-I(mix) were found under both syngeneic and allogeneic transplantation in infarcted male hearts, to significantly improve cardiac function and reduce the scar size, via promoting angiogenesis in the infarcted area. All of these findings thus support the view that males could also benefit from the cardio-protective effects observed among females, via cell therapy approaches involving the transplantation of immuno-privileged uterine reparative cells in infarcted hearts.
The seroprevalence of toxocariasis and related risk factors in children in Ho Chi Minh City, Vietnam: results from a school-based cross-sectional study
Authors: Ha Thieu V , Vo Tien T N , Dang Duy K H , Tran Y M L , Kim Thanh V , Le Duc H , Do Lan-Anh T , Tang Hong K 
Published: January 2024

Abstract

Background
Children are especially vulnerable to Toxocara infection and its severe complications; however, there have not been any published data on the disease prevalence and treatment effectiveness in the population of Vietnamese children. This study was conducted to determine the prevalence of toxocariasis and explore factors associated with Toxocara infection in children aged 3–15 y in Ho Chi Minh City, Vietnam.

Methods
We conducted a cross-sectional study using a multistage cluster sampling approach in public schools. Blood samples were collected, and toxocariasis cases were confirmed, based on a history of contact with dogs/cats and positive anti-Toxocara antibody detection via ELISA. We calculated the percentage of seropositive children across gender, grade levels, districts and caregiver education. Multiple regression models were employed to identify potential risk factors.

Results
Anti-Toxocara antibodies were found in 14.2% of the 986 children studied. Significant variations in seropositivity were observed across grade levels, districts and caregiver education levels. Multivariable analysis identified caregiver education, contact with dogs/cats and improper handling of pet feces as seropositivity risk factors.

Conclusion
This was the first community-based prevalence study of toxocariasis in a pediatric population in Vietnam. Implementation of preventive measures such as public education, routine fecal examinations and chemotherapeutic treatment of animals is highly recommended.
Treatment with sodium butyrate induces autophagy resulting in therapeutic benefits for spinocerebellar ataxia type 3
Authors: Watchon Maxinne , Robinson Katherine J. , Luu Luan , An Yousun , Yuan Kristy C. , Plenderleith Stuart K. , Cheng Flora , Don Emily K. , Nicholson Garth A. , Lee Albert , Laird Angela S. 
Published: January 2024

AbstractSpinocerebellar ataxia type 3 (SCA3, also known as Machado Joseph disease) is a fatal neurodegenerative disease caused by the expansion of the trinucleotide repeat region within the ATXN3/MJD gene. Mutation of ATXN3 causes formation of ataxin‐3 protein aggregates, neurodegeneration, and motor deficits. Here we investigated the therapeutic potential and mechanistic activity of sodium butyrate (SB), the sodium salt of butyric acid, a metabolite naturally produced by gut microbiota, on cultured SH‐SY5Y cells and transgenic zebrafish expressing human ataxin‐3 containing 84 glutamine (Q) residues to model SCA3. SCA3 SH‐SY5Y cells were found to contain high molecular weight ataxin‐3 species and detergent‐insoluble protein aggregates. Treatment with SB increased the activity of the autophagy protein quality control pathway in the SCA3 cells, decreased the presence of ataxin‐3 aggregates and presence of high molecular weight ataxin‐3 in an autophagy‐dependent manner. Treatment with SB was also beneficial in vivo, improving swimming performance, increasing activity of the autophagy pathway, and decreasing the presence of insoluble ataxin‐3 protein species in the transgenic SCA3 zebrafish. Co‐treating the SCA3 zebrafish with SB and chloroquine, an autophagy inhibitor, prevented the beneficial effects of SB on zebrafish swimming, indicating that the improved swimming performance was autophagy‐dependent. To understand the mechanism by which SB induces autophagy we performed proteomic analysis of protein lysates from the SB‐treated and untreated SCA3 SH‐SY5Y cells. We found that SB treatment had increased activity of Protein Kinase A and AMPK signaling, with immunoblot analysis confirming that SB treatment had increased levels of AMPK protein and its substrates. Together our findings indicate that treatment with SB can increase activity of the autophagy pathway process and that this has beneficial effects in vitro and in vivo. While our results suggested that this activity may involve activity of a PKA/AMPK‐dependent process, this requires further confirmation. We propose that treatment with sodium butyrate warrants further investigation as a potential treatment for neurodegenerative diseases underpinned by mechanisms relating to protein aggregation including SCA3.