bluuebunny/crossref_metadata_2025_split huggingface dataset:
Landscape of RNA pseudouridylation in archaeon Sulfolobus islandicus
Authors: Li Yuqian , Wu Songlin , Ye Keqiong 
Published: February 2024

Abstract
Pseudouridine, one of the most abundant RNA modifications, is synthesized by stand-alone or RNA-guided pseudouridine synthases. Here, we comprehensively mapped pseudouridines in rRNAs, tRNAs and small RNAs in the archaeon Sulfolobus islandicus and identified Cbf5-associated H/ACA RNAs. Through genetic deletion and in vitro modification assays, we determined the responsible enzymes for these modifications. The pseudouridylation machinery in S. islandicus consists of the stand-alone enzymes aPus7 and aPus10, and six H/ACA RNA-guided enzymes that account for all identified pseudouridines. These H/ACA RNAs guide the modification of all eleven sites in rRNAs, two sites in tRNAs, and two sites in CRISPR RNAs. One H/ACA RNA shows exceptional versatility by targeting eight different sites. aPus7 and aPus10 are responsible for modifying positions 13, 54 and 55 in tRNAs. We identified four atypical H/ACA RNAs that lack the lower stem and the ACA motif and confirmed their function both in vivo and in vitro. Intriguingly, atypical H/ACA RNAs can be modified by Cbf5 in a guide-independent manner. Our data provide the first global view of pseudouridylation in archaea and reveal unexpected structures, substrates, and activities of archaeal H/ACA RNPs.
A sensitive and scalable fluorescence anisotropy single stranded RNA targeting approach for monitoring riboswitch conformational states
Authors: Rivera Maira , Ayon Omma S , Diaconescu-Grabari Suzana , Pottel Joshua , Moitessier Nicolas , Mittermaier Anthony , McKeague Maureen 
Published: February 2024

Abstract
The capacity of riboswitches to undergo conformational changes in response to binding their native ligands is closely tied to their functional roles and is an attractive target for antimicrobial drug design. Here, we established a probe-based fluorescence anisotropy assay to monitor riboswitch conformational switching with high sensitivity and throughput. Using the Bacillus subtillis yitJ S-Box (SAM-I), Fusobacterium nucleatum impX RFN element of (FMN) and class-I cyclic-di-GMP from Vibrio cholerae riboswitches as model systems, we developed short fluorescent DNA probes that specifically recognize either ligand-free or -bound riboswitch conformational states. We showed that increasing concentrations of native ligands cause measurable and reproducible changes in fluorescence anisotropy that correlate with riboswitch conformational changes observed by native gel analysis. Furthermore, we applied our assay to several ligand analogues and confirmed that it can discriminate between ligands that bind, triggering the native conformational change, from those that bind without causing the conformational change. This new platform opens the possibility of high-throughput screening compound libraries to identify potential new antibiotics that specifically target functional conformational changes in riboswitches.
Urinary C4d and progression of kidney disease in IgA vasculitis
Authors: Yu Guizhen , Zhao Jie , Wang Meifang , Chen Yang , Feng Shi , Li Bingjue , Wang Cuili , Wang Yucheng , Jiang Hong , Chen Jianghua 
Published: February 2024

ABSTRACT

Background
Immunoglobulin A (IgA) vasculitis nephritis (IgAVN) is the most common secondary IgA nephropathy (IgAN). Urinary C4d have been identified associated with the development and progression in primary IgAN; however, its role in kidney disease progression of IgAVN is still unclear.

Methods
This study enrolled 139 patients with IgAVN, 18 healthy subjects, 23 focal segmental glomerulosclerosis patients and 38 IgAN patients. Urinary C4d levels at kidney biopsy were measured using enzyme-linked immunosorbent assay. The association between urinary C4d/creatinine and kidney disease progression event, defined as 40% estimated glomerular filtration rate decline or end-stage kidney disease, was assessed using Cox proportional hazards models and restricted cubic splines.

Results
The levels of urinary C4d/creatinine (Cr) in IgAVN and IgAN patients were higher than in healthy controls. Higher levels of urinary C4d/Cr were associated with higher proteinuria and severe Oxford C lesions, and glomerular C4d deposition. After a median follow-up of 52.79 months, 18 (12.95%) participants reached composite kidney disease progression event. The risk of kidney disease progression event was higher with higher levels of Ln(urinary C4d/Cr). After adjustment for clinical data, higher levels of urinary C4d/Cr were associated with kidney disease progression in IgAVN [per Ln-transformed urinary C4d/Cr, hazard ratio 1.573, 95% confidence interval (CI) 1.101–2.245; P = .013]. Compared with the lower C4d/Cr group, the hazard ratio was 5.539 (95% CI 1.135–27.035; P = .034) for the higher levels group.

Conclusions
Higher levels of urinary C4d/Cr were associated with kidney disease progression event in patients with IgAVN.
Atezolizumab Plus Carboplatin and Etoposide in Patients with Untreated Extensive-Stage Small-Cell Lung Cancer: Interim Results of the MAURIS Phase IIIb Trial
Authors: Bria Emilio , Morgillo Floriana , Garassino Marina Chiara , Ciardiello Fortunato , Ardizzoni Andrea , Stefani Alessio , Verderame Francesco , Morabito Alessandro , Chella Antonio , Tonini Giuseppe , Gilli Marina , Del Signore Ester , Berardi Rossana , Mencoboni Manlio , Bearz Alessandra , Delmonte Angelo , Migliorino Marta Rita , Gridelli Cesare , Pazzola Antonio , Iero Manuela , De Marinis Filippo 
Published: February 2024

Abstract

Background
MAURIS is an Italian multicenter, open-label, phase IIIb ongoing trial, aiming at evaluating the safety and effectiveness of atezolizumab + carboplatin/etoposide in patients with newly diagnosed, extensive-stage small-cell lung cancer (ES-SCLC). The primary objective is the safety evaluation.

Materials and Methods
Patients received atezolizumab + carboplatin/etoposide Q3W for 4-6 cycles in the induction phase, followed by atezolizumab maintenance Q3W. We presented the interim analysis on safety (referring to the induction phase) and clinical effectiveness, in all patients (N = 154) and in subgroups that received ≤3 (N = 23), 4 (N = 43), and 5-6 cycles (N = 89) of induction.

Results
At a median follow-up of 10.5 months, 139 patients (90.3%) discontinued treatment. Serious adverse events occurred in 29.9% of patients overall, and the rate was lower in patients with 5-6 cycles (19.1%) than in those with 4 (34.9%) or ≤3 (63.6%) cycles. Immune-mediated adverse events were reported in 14.9%, 15.7%, 11.6%, and 18.2% of patients, overall and by subgroup, respectively. The median overall survival and progression-free survival were 10.7 and 5.5 months, respectively. Overall, 111 patients (71.6%) had a tumor response.

Conclusions
Interim results provide further evidences about safety and efficacy profile of atezolizumab + carboplatin/etoposide treatment in a ES-SCLC patient population closer to that observed in clinical practice.

Clinical Trial Registration
Eudract No. 2019-001146-17, NCT04028050.
Increased α-ketoglutarate links the C3–C4 intermediate state to C4 photosynthesis in the genus Flaveria
Authors: Tang Qiming , Huang Yuhui , Ni Xiaoxiang , Lyu Ming-Ju Amy , Chen Genyun , Sage Rowan , Zhu Xin-Guang 
Published: February 2024

Abstract
As a complex trait, C4 photosynthesis has multiple independent origins in evolution. Phylogenetic evidence and theoretical analysis suggest that C2 photosynthesis, which is driven by glycine decarboxylation in the bundle sheath cell, may function as a bridge from C3 to C4 photosynthesis. However, the exact molecular mechanism underlying the transition between C2 photosynthesis to C4 photosynthesis remains elusive. Here, we provide evidence suggesting a role of higher α-ketoglutarate (AKG) concentration during this transition. Metabolomic data of 12 Flaveria species, including multiple photosynthetic types, show that AKG concentration initially increased in the C3–C4 intermediate with a further increase in C4 species. Petiole feeding of AKG increases the concentrations of C4-related metabolites in C3–C4 and C4 species but not the activity of C4-related enzymes. Sequence analysis shows that glutamate synthase (Fd-GOGAT), which catalyzes the generation of glutamate using AKG, was under strong positive selection during the evolution of C4 photosynthesis. Simulations with a constraint-based model for C3–C4 intermediate further show that decreasing the activity of Fd-GOGAT facilitated the transition from a C2-dominant to a C4-dominant CO2 concentrating mechanism. All these results provide insight into the mechanistic switch from C3–C4 intermediate to C4 photosynthesis.
Double blocking of carbon metabolism causes a large increase of Calvin–Benson cycle compounds in cyanobacteria
Authors: Domínguez-Lobo María Teresa , Roldán Miguel , Gutiérrez-Diánez Alba María , Florencio Francisco Javier , Muro-Pastor María Isabel 
Published: February 2024

Abstract
Carbon-flow-regulator A (CfrA) adapts carbon flux to nitrogen conditions in nondiazotrophic cyanobacteria. Under nitrogen deficiency, CfrA leads to the storage of excess carbon, which cannot combine with nitrogen, mainly as glycogen. cfrA overexpression from the arsenite-inducible, nitrogen-independent ParsB promoter allows analysis of the metabolic effects of CfrA accumulation. Considering that the main consequence of cfrA overexpression is glycogen accumulation, we examined carbon distribution in response to cfrA expression in Synechocystis sp. PCC 6803 strains impaired in synthesizing this polymer. We carried out a comparative phenotypic analysis to evaluate cfrA overexpression in the wild-type strain and in a mutant of ADP-glucose pyrophosphorylase (ΔglgC), which is unable to synthesize glycogen. The accumulation of CfrA in the wild-type background caused a photosynthetic readjustment although growth was not affected. However, in a ΔglgC strain, growth decreased depending on CfrA accumulation and photosynthesis was severely affected. An elemental analysis of the H, C, and N content of cells revealed that cfrA expression in the wild-type caused an increase in the C/N ratio, due to decreased nitrogen assimilation. Metabolomic study indicated that these cells store sucrose and glycosylglycerol, in addition to the previously described glycogen accumulation. However, cells deficient in glycogen synthesis accumulated large amounts of Calvin–Benson cycle intermediates as cfrA was expressed. These cells also showed increased levels of some amino acids, mainly alanine, serine, valine, isoleucine, and leucine. The findings suggest that by controlling cfrA expression, in different conditions and strains, we could change the distribution of fixed carbon, with potential biotechnological benefits.
The emergence of MedTok: a qualitative analysis of popular medical TikTok videos
Authors: Rosen Ross , Vasiloudes Vasilis , Mhaskar Rahul 
Published: February 2024

Abstract
Social media is increasingly being used by the public as a medium for health information. Unfortunately, misinformation has become widely available on these sites, often being provided using content that is designed to be more popular and engaging, and it is difficult for the public to differentiate between what is true and what is false. TikTok is one of these platforms and has been rapidly growing over the last few years. As an increasing number of people look to TikTok for their health information, it is important that quality information is accessible and popular on the platform. We conducted a review of TikTok videos using the top 10 videos to show when searching for 13 common conditions. Characteristics of both the creator and video were recorded and analyzed. Videos on conditions commonly diagnosed younger were commonly produced by younger creators with the condition, often based on their own experiences. Conversely, videos on conditions commonly diagnosed older were commonly produced by healthcare professionals providing educational information. Though for conditions affecting older individuals healthcare professionals may be able to create didactic, educational videos, for those affecting younger individuals, it may be beneficial to partner with younger creators, or “influencers,” to produce more viral content. Further studies may expand on these ideas to encompass more facets of healthcare. As this study did not analyze the quality of the information in the videos, future research should also focus on determining the quality of popular content on TikTok and other social media platforms.
Evolution of fiscal systems: convergence or divergence?
Authors: Péligry Paloma , Ragot Xavier 
Published: February 2024

Abstract
We analyze the convergence or divergence of the diversity of fiscal systems after the financial crisis of 2007. Studying twenty-nine countries, we first document the evolution of the taxation of households, firms, labor, consumption, and capital. We identify three types of fiscal systems: liberal, intermediate, and high-redistribution, which can be ranked in ascending order of tax rates, confirming known typologies in the diversity of capitalism literature. Only the tax rate on corporate profits shows signs of downward convergence over the period. The other tax rates show rather signs of divergence. Second, a divergence is observed among the liberal and high-redistribution groups over the period. The European countries are converging toward the high-redistribution model, with the exception of Great Britain, which is moving toward the liberal model. Thus, the financial crisis seems to contribute not to the convergence, but to the divergence of fiscal systems.
MSC-Derived Small Extracellular Vesicles Exert Cardioprotective Effect Through Reducing VLCFAs and Apoptosis in Human Cardiac Organoid IRI Model
Authors: Poh Boon Min , Liew Lee Chuen , Soh Yan Ni Annie , Lai Ruenn Chai , Lim Sai Kiang , Ho Ying Swan , Soh Boon Seng 
Published: February 2024

Abstract
Cardiovascular diseases (CVDs) are the leading cause of death worldwide, accounting for 31% of all deaths globally. Myocardial ischemia-reperfusion injury (IRI), a common complication of CVDs, is a major cause of mortality and morbidity. Studies have shown efficacious use of mesenchymal stem cells-derived small extracellular vesicles (MSCs-EVs) to mitigate IRI in animals, but few research has been done on human-related models. In this study, human embryonic stem cell-derived chambered cardiac organoid (CCO) was used as a model system to study the effects of MSC-EVs on myocardial IRI. The results revealed that MSC-EVs treatment reduced apoptosis and improved contraction resumption of the CCOs. Metabolomics analysis showed that this effect could be attributed to EVs’ ability to prevent the accumulation of unsaturated very long-chain fatty acids (VLCFAs). This was corroborated when inhibition of fatty acid synthase, which was reported to reduce VLCFAs, produced a similar protective effect to EVs. Overall, this study uncovered the mechanistic role of MSC-EVs in mitigating IRI that involves preventing the accumulation of unsaturated VLCFA, decreasing cell death, and improving contraction resumption in CCOs.
Loss of chaperone‐mediated autophagy does not alter age‐related bone loss in male mice
Authors: Hendrixson James A. , James Alicen , Akel Nisreen S. , Laster Dominique J. , Crawford Julie A. , Berryhill Stuart B. , Onal Melda 
Published: February 2024

AbstractChaperone‐mediated autophagy (CMA) is a lysosome‐dependent degradation pathway that eliminates proteins that are damaged, partially unfolded, or targeted for selective proteome remodeling. CMA contributes to several cellular processes, including stress response and proteostasis. Age‐associated increase in cellular stressors and decrease in CMA contribute to pathologies associated with aging in various tissues. CMA contributes to bone homeostasis in young mice. An age‐associated reduction in CMA was reported in osteoblast lineage cells; however, whether declining CMA contributes to skeletal aging is unknown. Herein we show that cellular stressors stimulate CMA in UAMS‐32 osteoblastic cells. Moreover, the knockdown of an essential component of the CMA pathway, LAMP2A, sensitizes osteoblasts to cell death caused by DNA damage, ER stress, and oxidative stress. As elevations in these stressors are thought to contribute to age‐related bone loss, we hypothesized that declining CMA contributes to the age‐associated decline in bone formation by sensitizing osteoblast lineage cells to elevated stressors. To test this, we aged male CMA‐deficient mice and controls up to 24 months of age and examined age‐associated changes in bone mass and architecture. We showed that lack of CMA did not alter age‐associated decline in bone mineral density as measured by dual x‐ray absorptiometry (DXA). Moreover, microCT analysis performed at 24 months of age showed that vertebral cancellous bone volume, cortical thickness, and porosity of CMA‐deficient and control mice were similar. Taken together, these results suggest that reduction of CMA does not contribute to age‐related bone loss.
Sulfide quinone oxidoreductase contributes to voltage sensing of the mitochondrial permeability transition pore
Authors: Griffiths Keren K. , Wang Aili , Jonas Elizabeth A. , Levy Richard J. 
Published: February 2024

AbstractPathological opening of the mitochondrial permeability transition pore (mPTP) is implicated in the pathogenesis of many disease processes such as myocardial ischemia, traumatic brain injury, Alzheimer's disease, and diabetes. While we have gained insight into mPTP biology over the last several decades, the lack of translation of this knowledge into successful clinical therapies underscores the need for continued investigation and use of different approaches to identify novel regulators of the mPTP with the hope of elucidating new therapeutic targets. Although the mPTP is known to be a voltage‐gated channel, the identity of its voltage sensor remains unknown. Here we found decreased gating potential of the mPTP and increased expression and activity of sulfide quinone oxidoreductase (SQOR) in newborn Fragile X syndrome (FXS) mouse heart mitochondria, a model system of coenzyme Q excess and relatively decreased mPTP open probability. We further found that pharmacological inhibition and genetic silencing of SQOR increased mPTP open probability in vitro in adult murine cardiac mitochondria and in the isolated‐perfused heart, likely by interfering with voltage sensing. Thus, SQOR is proposed to contribute to voltage sensing by the mPTP and may be a component of the voltage sensing apparatus that modulates the gating potential of the mPTP.
Risk Factors and Clinical Prognosis Associated With RSV-ALRI Intensive Care Unit Admission in Children <2 Years of Age: A Multicenter Study
Authors: Lim Su Ann , Chan Mei , Hu Nan , McMullan Brendan , Britton Philip N. , Bartlett Adam , Kandasamy Rama , Saravanos Gemma L. , Prentice Bernadette , Jaffe Adam , Owens Louisa , Homaira Nusrat 
Published: February 2024

Background:
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections (ALRIs) in children <2 years of age. Currently, there are limited data on risk factors for very severe RSV-ALRI requiring intensive care unit (ICU) admission.

Methods:
We conducted a case-control study of children <2 years old admitted with RSV-ALRI to the Sydney Children’s Hospital Network, comprising 2 large tertiary pediatric hospitals. Cases were children with laboratory-confirmed RSV-ALRI admitted to ICU, and controls were (1:2, matched on date of admission) children hospitalized with RSV-ALRI but not requiring ICU transfer. Data on risk factors were retrieved from the electronic medical record system. Adjusted odds ratios (aORs) with 95% confidence intervals (95% CI) associated with risk factors for ICU admission and the association with clinical and treatment factors were determined from logistic regression models.

Results:
A total of 44 (44%) of 100 cases and 90 (48.1%) of 187 controls were male. Age <6 months and preterm births were associated with a 2.10-fold (95% CI: 1.14–3.79) and 2.35-fold (95% CI: 1.26–4.41) increased risk in ICU admissions, respectively. The presence of any chronic health condition was a significant risk factor for ICU admission. The clinical presentations on admission more commonly seen in cases were apnea (aOR: 5.01, 95% CI: 1.50–17.13) and respiratory distress (aOR: 15.91, 95% CI: 4.52–55.97). Cases were more likely to be hospitalized for longer duration and require respiratory support.

Conclusions:
Our results can be translated into a clinical risk algorithm to identify children at risk of very severe RSV disease.
A novel stratification scheme combined with internal arteries in CT imaging for guiding postoperative adjuvant transarterial chemoembolization in hepatocellular carcinoma: a retrospective cohort study
Authors: Li Xinming , Liang Xiangjing , Li Zhipeng , Liang Jianye , Qi Zhendong , Zhong Liming , Geng Zhijun , Liang Wen , Quan Xianyue , Liang Changhong , Liu Zaiyi 
Published: February 2024

Background:
Although postoperative adjuvant transarterial chemoembolization (PA-TACE) improves survival outcomes in a subset of patients with resected hepatocellular carcinoma (HCC), the lack of reliable biomarkers for patient selection remains a significant challenge. The present study aimed to evaluate whether computed tomography (CT) imaging can provide more value for predicting benefits from PA-TACE and to establish a new scheme for guiding PA-TACE benefits.

Methods:
In this retrospective study, patients with HCC who had undergone preoperative contrast-enhanced CT and curative hepatectomy were evaluated. Inverse probability of treatment weight was performed to balance the difference of baseline characteristics. Cox models were used to test the interaction among PA-TACE, imaging features and pathological indicators. An HCC imaging and pathological classification (HIPC) scheme incorporating these imaging and pathological indicators was established.

Results:
This study included 1,488 patients (median age, 52 y [IQR, 45–61 y]; 1,309 male). Microvascular invasion (MVI) positive, and diameter>5 cm tumors achieved a higher recurrence-free survival (RFS), and overall survival (OS) benefit, respectively, from PA-TACE than MVI negative, and diameter ≤5 cm tumors. Patients with internal arteries (IA) positive benefited more than those with IA negative in terms of RFS (P=0.016) and OS (P=0.018). PA-TACE achieved significant RFS and OS improvements in HIPC3 (IA present and diameter, or two or three tumors) patients but not in HIPC1 (diameter ≤5 cm, MVI negative) and HIPC2 (other single tumor) patients. Our scheme may decrease the number of patients receiving PA-TACE by approximately 36.5% compared to the previous suggestion.

Conclusions:
IA can provide more value for predicting the benefit of PA-TACE treatment. The proposed HIPC scheme can be used to stratify patients with and without survival benefits from PA-TACE.