bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of hearing loss and structural changes in specific cortical regions: a Mendelian randomization study
Authors: Liu Xiaoduo , Shi Lubo , Li Enze , Jia Shuo 
Published: March 2024

Abstract

Introduction
Previous studies have suggested a correlation between hearing loss (HL) and cortical alterations, but the specific brain regions that may be affected are unknown.

Methods
Genome-wide association study (GWAS) data for 3 subtypes of HL phenotypes, sensorineural hearing loss (SNHL), conductive hearing loss, and mixed hearing loss, were selected as exposures, and GWAS data for brain structure-related traits were selected as outcomes. The inverse variance weighted method was used as the main estimation method.

Results
Negative associations were identified between genetically predicted SNHL and brain morphometric indicators (cortical surface area, cortical thickness, or volume of subcortical structures) in specific brain regions, including the bankssts (β = −0.006 mm, P = 0.016), entorhinal cortex (β = −4.856 mm2, P = 0.029), and hippocampus (β = −24.819 cm3, P = 0.045), as well as in brain regions functionally associated with visual perception, including the pericalcarine (β = −10.009 cm3, P = 0.013).

Conclusion
Adaptive changes and functional remodeling of brain structures occur in patients with genetically predicted HL. Brain regions functionally associated with auditory perception, visual perception, and memory function are the main brain regions vulnerable in HL.
Small nucleolar RNA host gene 18 controls vascular smooth muscle cell contractile phenotype and neointimal hyperplasia
Authors: Niu Kaiyuan , Zhang Chengxin , Yang Mei , Maguire Eithne Margaret , Shi Zhenning , Sun Shasha , Wu Jianping , Liu Chenxin , An Weiwei , Wang Xinxin , Gao Shan , Ge Shenglin , Xiao Qingzhong 
Published: March 2024

Abstract

Aims
Long non-coding RNA (LncRNA) small nucleolar RNA host gene 18 (SNHG18) has been widely implicated in cancers. However, little is known about its functional involvement in vascular diseases. Herein, we attempted to explore a role for SNHG18 in modulating vascular smooth muscle cell (VSMC) contractile phenotype and injury-induced neointima formation.

Methods and results
Analysis of single-cell RNA sequencing and transcriptomic datasets showed decreased levels of SNHG18 in injured and atherosclerotic murine and human arteries, which is positively associated with VSMC contractile genes. SNHG18 was upregulated in VSMCs by TGFβ1 through transcription factors Sp1 and SMAD3. SNHG18 gene gain/loss-of-function studies revealed that VSMC contractile phenotype was positively regulated by SNHG18. Mechanistic studies showed that SNHG18 promotes a contractile VSMC phenotype by up-regulating miR-22-3p. SNHG18 up-regulates miR-22 biogenesis and miR-22-3p production by competitive binding with the A-to-I RNA editing enzyme, adenosine deaminase acting on RNA-2 (ADAR2). Surprisingly, we observed that ADAR2 inhibited miR-22 biogenesis not through increasing A-to-I editing within primary miR-22, but by interfering with the binding of microprocessor complex subunit DGCR8 to primary miR-22. Importantly, perivascular SNHG18 overexpression in the injured vessels dramatically up-regulated the expression levels of miR-22-3p and VSMC contractile genes, and prevented injury-induced neointimal hyperplasia. Such modulatory effects were reverted by miR-22-3p inhibition in the injured arteries. Finally, we observed a similar regulator role for SNHG18 in human VSMCs and a decreased expression level of both SNHG18 and miR-22-3p in diseased human arteries; and we found that the expression level of SNHG18 was positively associated with that of miR-22-3p in both healthy and diseased human arteries.

Conclusion
We demonstrate that SNHG18 is a novel regulator in governing VSMC contractile phenotype and preventing injury-induced neointimal hyperplasia. Our findings have important implications for therapeutic targeting snhg18/miR-22-3p signalling in vascular diseases.
Essential dextrin structure as donor substrate for 4-α-glucanotransferase in glycogen debranching enzyme
Authors: Uno Rentaro , Makino Yasushi , Matsubara Hiroshi 
Published: March 2024

Abstract
Glycogen debranching enzyme is a single polypeptide with distinct catalytic sites for 4-α-glucanotransferase and amylo-α-1,6-glucosidase. To allow phosphorylase to degrade the inner tiers of highly branched glycogen, 4-α-glucanotransferase converts the phosphorylase-limit biantennary branch G-G-G-G-(G-G-G-G↔)G-G- (G: d-glucose, hyphens: α-1,4-linkages; double-headed arrow: α-1,6-linkage) into the G-G-G-G-(G↔)G-G- residue, which is then subjected to amylo-α-1,6-glucosidase to release the remaining G↔ residue. However, while the essential side-chain structure of the 4-α-glucanotransferase donor substrate has been determined to be the G-G-G-G↔ residue (Watanabe, Y., et al. (2008) J. Biochem.143, 435–440), its essential main-chain structure remains to be investigated. In this study, we probed the 4-α-glucanotransferase donor-binding region using novel fluorogenic dextrins Gm-(G4↔)G-Gn-F (F: 1-deoxy-1-[(2-pyridyl)amino]-d-glucitol) and maltohexaose (G6) as the donor and acceptor substrates, respectively. 4-α-Glucanotransferase exhibited maximum activity towards G4-(G4↔)G-F and G4-(G4↔)G-G-F, indicating that recognition of the G4-(G4↔)G-moiety was essential for full enzyme function. Notably, when the 4-α-glucanotransferase activity towards G4-(G4↔)G-G-F was taken as unity, those towards nonbranching dextrins were &lt; 0.001. This indicated that the disproportionation activities towards maltooligosaccharides (Gm) are abnormal behaviours of 4-α-glucanotransferase. Notably, however, these activities have been traditionally measured to identify the 4-α-glucanotransferase mutations causing glycogen storage disease type III. This study provides a basis for more accurate identification.
Discordant responses of bone formation and absorption markers in Japanese infants with vitamin D deficiency: a comprehensive matched case–control study
Authors: Takahashi Keigo , Ikeda Kazushige , Hara-Isono Kaori , Nitta Akihisa , Nagano Nobuhiko , Arimitsu Takeshi 
Published: March 2024

Abstract
Vitamin D deficiency during infancy has been associated with increased bone turnover rate and bone mineral loss. However, few studies have examined bone turnover markers (BTMs) for both bone formation and resorption in infants with vitamin D deficiency. Here, we analyzed serum concentrations of 25OHD, intact parathormone (iPTH), and BTMs including total alkaline phosphatase (ALP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), and serum type I collagen N-telopeptide (NTx) as well as basic clinical characteristics of 456 infants (626 samples) aged less than 12 mo born at Saitama City Hospital, Japan (latitude 35.9° North) between January 2021 and December 2022. One hundred sixteen infants (147 samples) were classified as having vitamin D deficiency (25OHD &lt; 12.0 ng/mL), and 340 infants (479 samples) had sufficient vitamin D levels (25OHD ≥ 12.0 ng/mL). In addition to 25OHD and ALP, both TRACP-5b and sNTx were measured in 331 infants (418 samples), while 90 infants (105 samples) had only TRACP-5b measured and 101 infants (103 samples) had only sNTx measured. Statistical comparison of 104 subjects each in the vitamin D deficiency and sufficiency groups after matching for the background characteristics revealed that the vitamin D deficiency group had significantly higher levels of ALP and iPTH compared with the sufficiency group (P = &lt;.0001, .0012, respectively). However, no significant differences were found in TRACP-5b and NTx levels between the 2 groups (P = .19, .08, respectively). Our findings suggest discordant responses between bone formation and resorption markers in subclinical vitamin D deficiency during infancy.
Overexpressing GLUTAMINE SYNTHETASE 1;2 maintains carbon and nitrogen balance under high-ammonium conditions and results in increased tolerance to ammonium toxicity in hybrid poplar
Authors: Leng Xue , Wang Hanzeng , Cao Lina , Chang Ruhui , Zhang Shuang , Xu Caifeng , Yu Jiajie , Xu Xiuyue , Qu Chunpu , Xu Zhiru , Liu Guanjun 
Published: March 2024

Abstract
The glutamine synthetase/glutamic acid synthetase (GS/GOGAT) cycle plays important roles in N metabolism, growth, development, and stress resistance in plants. Excess ammonium (NH4+) restricts growth, but GS can help to alleviate its toxicity. In this study, the 84K model clone of hybrid poplar (Populus alba × P. tremula var. glandulosa), which has reduced biomass accumulation and leaf chlorosis under high-NH4+ stress, showed less severe symptoms in transgenic lines overexpressing GLUTAMINE SYNTHETASE 1;2 (GS1;2-OE), and more severe symptoms in RNAi lines (GS1;2-RNAi). Compared with the wild type, the GS1;2-OE lines had increased GS and GOGAT activities and higher contents of free amino acids, soluble proteins, total N, and chlorophyll under high-NH4+ stress, whilst the antioxidant and NH4+ assimilation capacities of the GS1;2-RNAi lines were decreased. The total C content and C/N ratio in roots and leaves of the overexpression lines were higher under stress, and there were increased contents of various amino acids and sugar alcohols, and reduced contents of carbohydrates in the roots. Under high-NH4+ stress, genes related to amino acid biosynthesis, sucrose and starch degradation, galactose metabolism, and the antioxidant system were significantly up-regulated in the roots of the overexpression lines. Thus, overexpression of GS1;2 affected the carbon and amino acid metabolism pathways under high-NH4+ stress to help maintain the balance between C and N metabolism and alleviate the symptoms of toxicity. Modification of the GS/GOGAT cycle by genetic engineering is therefore a potential strategy for improving the NH4+ tolerance of cultivated trees.
The beneficial rhizobacterium Bacillus velezensis SQR9 regulates plant nitrogen uptake via an endogenous signaling pathway
Authors: Chen Yu , Li Yucong , Fu Yansong , Jia Letian , Li Lun , Xu Zhihui , Zhang Nan , Liu Yunpeng , Fan Xiaorong , Xuan Wei , Xu Guohua , Zhang Ruifu 
Published: March 2024

Abstract
Nitrogen fertilizer is widely used in agriculture to boost crop yields. Plant growth-promoting rhizobacteria (PGPRs) can increase plant nitrogen use efficiency through nitrogen fixation and organic nitrogen mineralization. However, it is not known whether they can activate plant nitrogen uptake. In this study, we investigated the effects of volatile compounds (VCs) emitted by the PGPR strain Bacillus velezensis SQR9 on plant nitrogen uptake. Strain SQR9 VCs promoted nitrogen accumulation in both rice and Arabidopsis. In addition, isotope labeling experiments showed that strain SQR9 VCs promoted the absorption of nitrate and ammonium. Several key nitrogen-uptake genes were up-regulated by strain SQR9 VCs, such as AtNRT2.1 in Arabidopsis and OsNAR2.1, OsNRT2.3a, and OsAMT1 family members in rice, and the deletion of these genes compromised the promoting effect of strain SQR9 VCs on plant nitrogen absorption. Furthermore, calcium and the transcription factor NIN-LIKE PROTEIN 7 play an important role in nitrate uptake promoted by strain SQR9 VCs. Taken together, our results indicate that PGPRs can promote nitrogen uptake through regulating plant endogenous signaling and nitrogen transport pathways.
Identification and characterization of two O-methyltransferases involved in biosynthesis of methylated 2-(2-phenethyl)chromones in agarwood
Authors: Wu Wenli , Yan Tingting , Sun Xiaochen , Wilson Iain , Li Gaiyun , Hong Zhou , Shao Fenjuan , Qiu Deyou 
Published: March 2024

Abstract
The 2-(2-phenethyl)chromones (PECs) are the signature constituents responsible for the fragrance and pharmacological properties of agarwood. O-Methyltransferases (OMTs) are necessary for the biosynthesis of methylated PECs, but there is little known about OMTs in Aquilaria sinensis. In this study, we identified 29 OMT genes from the A. sinensis genome. Expression analysis showed they were differentially expressed in different tissues and responded to drill wounding. Comprehensive analysis of the gene expression and methylated PEC content revealed that AsOMT2, AsOMT8, AsOMT11, AsOMT16, and AsOMT28 could potentially be involved in methylated PECs biosynthesis. In vitro enzyme assays and functional analysis in Nicotiana benthamiana demonstrated that AsOMT11 and AsOMT16 could methylate 6-hydroxy-2-(2-phenylethyl)chromone to form 6-methoxy-2-(2-phenylethyl)chromone. A transient overexpression experiment in the variety ‘Qi-Nan’ revealed that AsOMT11 and AsOMT16 could significantly promote the accumulation of three major methylated PECs. Our results provide candidate genes for the mass production of methylated PECs using synthetic biology.
Probiotics in autism spectrum disorders: a systematic review of clinical studies and future directions
Authors: Barba-Vila Olga , García-Mieres Helena , Ramos Belén 
Published: March 2024

Abstract

Context
It is hypothesized that gut dysbiosis, a typical feature of patients with autism spectrum disorder (ASD), could be involved in the origin of this neurodevelopmental disorder. Therefore, the use of probiotics to restore gastrointestinal (GI) equilibrium might be a promising therapeutic strategy due to its capacity to balance the gut-brain axis and behavioral responses.

Objective
To summarize current knowledge on the use of probiotics to treat core clinical ASD symptoms and concomitant GI signs, compare the design of published studies with those of ongoing trials, assess the near future of this field, and provide recommendations for improving novel studies.

Data sources
The literature search was conducted in February 2020 and updated in March 2021, using a broad range of bibliographic and clinical trial–specific databases.

Data extraction
Data were extracted using a standardized form, and articles reporting on 28 clinical studies (already published or still ongoing) were included. The risk of bias in clinical studies was evaluated using the Cochrane Collaboration Risk of Bias Assessment tool for randomized trials and the Risk of Bias in Nonrandomized Studies–Interventions tool for nonrandomized trials.

Results
The results suggest that probiotics improve ASD-like social deficits, GI symptoms, and gut microbiota profile. However, inconsistencies among studies and their methodological limitations make it difficult to draw any conclusions regarding the efficacy of probiotics in ASD. This review provides specific suggestions for future research to improve the quality of the studies.

Conclusions
Although ongoing studies have improved designs, the available knowledge does not permit solid conclusions to be made regarding the efficacy of probiotics in ameliorating the symptoms (psychiatric and/or GI) associated with ASD. Thus, more high-quality research and new approaches are needed to design effective probiotic strategies for ASD.
Innovations in the repayment structure of microcredit contracts
Authors: Barboni Giorgia 
Published: March 2024

Abstract
Microfinance contracts typically require a fixed repayment schedule that, while ensuring repayment discipline, may inhibit entrepreneurship and business growth. In this article, I review the recent developments in the literature studying innovations in the repayment structure of microcredit contracts. Introducing flexible repayment schedules improves business outcomes by allowing microcredit borrowers to increase investment and to respond to income fluctuations to a higher extent. Although financial innovations hold the promise to foster business growth, and evidence suggests that their demand appears concentrated among financially sophisticated borrowers, they are feared to increase credit risk and hence their adoption among microfinance institutions is very limited. I explore potential challenges lenders face in offering these innovations and outline pathways towards a profitable implementation of such contracts.
Frequency and characteristics of severe relapses in giant cell arteritis
Authors: Lozachmeur Nicolas , Dumont Anael , Deshayes Samuel , Boutemy Jonathan , Maigné Gwénola , Martin Silva Nicolas , Nguyen Alexandre , Gallou Sophie , Philip Rémi , Aouba Achille , de Boysson Hubert 
Published: March 2024

Abstract

Objectives
To assess the frequency and characteristics of severe relapse in patients with GCA in a real-life setting.

Methods
In a monocentric database of 530 patients, we retrospectively analysed patients who experienced at least one relapse and distinguished severe from non-severe relapses. Severe relapse was defined by the occurrence of an ischaemic event (ophthalmologic, neurologic, digestive, limb ischaemia), the occurrence of an aortic complication (i.e. new or worsening of aortic dilation, aortic dissection), or new or worsening vascular stenosis.

Results
From the cohort of 530 patients, 242 (45.7%) patients experienced relapse at least once, including 13 (2.5% of the cohort) who experienced severe relapse. Among the 464 recorded relapses, 14 (3% of all relapses) were severe. Severe relapse corresponded to the following vascular events: a peripheral limb ischaemia in six patients, a visual event in three patients (including two acute anterior ischaemic anterior neuropathies), an aortic complication in three patients, a mesenteric ischaemia in one patient and an ischaemic stroke in one patient. When compared with the 229 patients who experienced non-severe relapses, severe relapse patients were younger at diagnosis (P = 0.02), and showed more frequently limb claudication at baseline (P &lt; 0.0001) and fewer GCA-related cranial signs (P &lt; 0.0001). At diagnosis, more large-vessel vasculitis on imaging (82% vs 36%, P = 0.002) were observed in patients with severe relapse. The death rate did not differ between patients with severe and non-severe relapses.

Conclusion
In a real-life setting, relapse affects nearly half of GCA patients, but severe relapse is rare.
Optimal carbon storage during drought
Authors: Stefaniak Elisa Z , Tissue David T , Dewar Roderick C , Medlyn Belinda E 
Published: March 2024

Abstract
Allocation of non-structural carbohydrates to storage allows plants to maintain a carbon pool in anticipation of future stress. However, to do so, plants must forego use of the carbon for growth, creating a trade-off between storage and growth. It is possible that plants actively regulate the storage pool to maximize fitness in a stress-prone environment. Here, we attempt to identify the patterns of growth and storage that would result during drought stress under the hypothesis that plants actively regulate carbon storage. We use optimal control theory to calculate the optimal allocation to storage and utilization of stored carbon over a single drought stress period. We examine two fitness objectives representing alternative life strategies: prioritization of growth and prioritization of storage, as well as the strategies in between these extremes. We find that optimal carbon storage consists of three discrete phases: ‘growth’, ‘storage without growth’ and the ‘stress’ phase where there is no carbon source. This trajectory can be defined by the time point when the plant switches from growth to storage. Growth-prioritizing plants switch later and fully deplete their stored carbon over the stress period, while storage-prioritizing plants either do not grow or switch early in the drought period. The switch time almost always occurs before the soil water is depleted, meaning that growth stops before photosynthesis. We conclude that the common observation of increasing carbon storage during drought could be interpreted as an active process that optimizes plant performance during stress.
Is Everyone Beating Around the Bush?: A Qualitative Study Examining the Status of Shared Decision-Making Between Veterans Affairs Providers and Surgical Patients in the ICU
Authors: Millis M. Andrew , Vitous C. Ann , Ferguson Cara , Marzoughi Maedeh , Kim Erin , Bradley Sarah E. , Duby Ashley , Suwanabol Pasithorn A. 
Published: March 2024

Objective:
We sought to determine if and how providers use elements of shared decision-making (SDM) in the care of surgical patients in the intensive care unit (ICU).

Background:
SDM is the gold standard for decision-making in the ICU. However, it is unknown if this communication style is used in caring for critically ill surgical patients.

Methods:
Qualitative interviews were conducted with providers who provide ICU-level care to surgical patients in Veterans Affairs hospitals. Interviews were designed to examine end-of-life care among veterans who have undergone surgery and require ICU-level care.

Results:
Forty-eight providers across 14 Veterans Affairs hospitals were interviewed. These participants were diverse with respect to age, race, and sex. Participant dialogue was deductively mapped into 8 established SDM components: describing treatment options; determining roles in the decision-making process; fostering partnerships; health care professional preferences; learning about the patient; patient preferences; supporting the decision-making process; and tailoring the information. Within these components, participants shared preferred tools and tactics used to satisfy a given SDM component. Participants also noted numerous barriers to achieving SDM among surgical patients.

Conclusions:
Providers use elements of SDM when caring for critically ill surgical patients. Additionally, this work identifies facilitators that can be leveraged and barriers that can be addressed to facilitate better communication and decision-making through SDM. These findings are of value for future interventions that seek to enhance SDM among surgical patients both in the ICU and in other settings.
Rectal Cancer Survival for Residual Carcinoma In Situ Vs. Pathologic Complete Response After Neoadjuvant Therapy
Authors: Kohrman Nathan M. , Wlodarczyk Jordan R. , Ding Li , McAndrew Nicholas P. , Algaze Sandra D. , Cologne Kyle G. , Lee Sang W. , Koller Sarah E 
Published: March 2024

BACKGROUND:
Pathologic complete response after neoadjuvant chemoradiotherapy for rectal cancer is associated with improved survival. It is unclear whether residual carcinoma in situ portends a similar outcome.

OBJECTIVE:
To compare survival of patients with locally advanced rectal cancer who received neoadjuvant therapy and achieved pathologic carcinoma in situ versus pathologic complete response.

DESIGN:
Retrospective cohort study.

SETTING:
National public database.

PATIENTS:
A total of 4,594 patients in the National Cancer Database from 2006 to 2016 with locally advanced rectal cancer who received neoadjuvant therapy, underwent surgery, and had node-negative, ypTis or ypT0 on final pathology were included. 4,321 (94.1%) had ypT0 and 273 (5.9%) had ypTis on final pathology.

MAIN OUTCOME MEASURES:
Overall survival.

RESULTS:
Median age was 60 years. 1,822 patients (39.7%) were female. 54.5% (n = 2,503) had stage II disease and 45.5% (n = 2,091) had stage III disease on initial staging. The ypTis group had decreased overall survival compared to the ypT0 group (HR 1.42, 95% CI 1.04-1.95, p = 0.028). Other factors associated with decreased overall survival were an older age at diagnosis, increasing Charlson-Deyo score, and poorly differentiated tumor grade. Variables associated with improved survival were female sex, private insurance, and receipt of both neoadjuvant and adjuvant chemotherapy. For the total cohort, there was no difference in survival between clinical stage 2 versus stage 3.

LIMITATIONS:
Standard therapy versus total neoadjuvant therapy were unable to be abstracted. Overall survival was defined as time from surgery to death from any cause or last contact, allowing for some erroneously misclassified deaths.

CONCLUSIONS:
ypTis is associated with worse overall survival than ypT0 for locally advanced rectal cancer patients who receive neoadjuvant chemoradiotherapy followed by surgery. For this cohort, clinical stage was not a significant predictor of survival. Prospective trials comparing survival for these pathologic outcomes are needed. See Video Abstract.