bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advanced maternal age leads to changes within the insulin/IGF system and lipid metabolism in the reproductive tract and preimplantation embryo: insights from the rabbit model
Authors: Trohl Juliane , Schindler Maria , Buske Maximilian , de Nivelle Johanna , Toto Nienguesso Alicia , Navarrete Santos Anne 
Published: November 2023

Abstract
Reproductive potential in women declines with age. The impact of ageing on embryo–maternal interactions is still unclear. Rabbits were used as a reproductive model to investigate maternal age-related alterations in reproductive organs and embryos on Day 6 of pregnancy. Blood, ovaries, endometrium, and blastocysts from young (16–20 weeks) and advanced maternal age phase (&gt;108 weeks, old) rabbits were analysed at the mRNA and protein levels to investigate the insulin-like growth factor (IGF) system, lipid metabolism, and stress defence system. Older rabbits had lower numbers of embryos at Day 6 of pregnancy. Plasma insulin and IGF levels were reduced, which was accompanied by paracrine regulation of IGFs and their receptors in ovaries and endometrium. Embryos adapted to hormonal changes as indicated by reduced embryonic IGF1 and 2 levels. Aged reproductive organs increased energy generation from the degradation of fatty acids, leading to higher oxidative stress. Stress markers, including catalase, superoxide dismutase 2, and receptor for advanced glycation end products were elevated in ovaries and endometrium from aged rabbits. Embryonic fatty acid uptake and β-oxidation were increased in both embryonic compartments (embryoblast and trophoblast) in old rabbits, associated with minor changes in the oxidative and glycative stress defence systems. In summary, the insulin/IGF system, lipid metabolism, and stress defence were dysregulated in reproductive tissues of older rabbits, which is consistent with changes in embryonic metabolism and stress defence. These data highlight the crucial influence of maternal age on uterine adaptability and embryo development.
CropGS-Hub: a comprehensive database of genotype and phenotype resources for genomic prediction in major crops
Authors: Chen Jiaxin , Tan Cong , Zhu Min , Zhang Chenyang , Wang Zhihan , Ni Xuemei , Liu Yanlin , Wei Tong , Wei XiaoFeng , Fang Xiaodong , Xu Yang , Huang Xuehui , Qiu Jie , Liu Huan 
Published: November 2023

Abstract
The explosive amount of multi-omics data has brought a paradigm shift both in academic research and further application in life science. However, managing and reusing the growing resources of genomic and phenotype data points presents considerable challenges for the research community. There is an urgent need for an integrated database that combines genome-wide association studies (GWAS) with genomic selection (GS). Here, we present CropGS-Hub, a comprehensive database comprising genotype, phenotype, and GWAS signals, as well as a one-stop platform with built-in algorithms for genomic prediction and crossing design. This database encompasses a comprehensive collection of over 224 billion genotype data and 434 thousand phenotype data generated from &gt;30 000 individuals in 14 representative populations belonging to 7 major crop species. Moreover, the platform implemented three complete functional genomic selection related modules including phenotype prediction, user model training and crossing design, as well as a fast SNP genotyper plugin-in called SNPGT specifically built for CropGS-Hub, aiming to assist crop scientists and breeders without necessitating coding skills. CropGS-Hub can be accessed at https://iagr.genomics.cn/CropGS/.
A modular dCas9-based recruitment platform for combinatorial epigenome editing
Authors: Swain Tessa , Pflueger Christian , Freytag Saskia , Poppe Daniel , Pflueger Jahnvi , Nguyen Trung Viet , Li Ji Kevin , Lister Ryan 
Published: November 2023

Abstract
Targeted epigenome editing tools allow precise manipulation and investigation of genome modifications, however they often display high context dependency and variable efficacy between target genes and cell types. While systems that simultaneously recruit multiple distinct ‘effector’ chromatin regulators can improve efficacy, they generally lack control over effector composition and spatial organisation. To overcome this we have created a modular combinatorial epigenome editing platform, called SSSavi. This system is an interchangeable and reconfigurable docking platform fused to dCas9 that enables simultaneous recruitment of up to four different effectors, allowing precise control of effector composition and spatial ordering. We demonstrate the activity and specificity of the SSSavi system and, by testing it against existing multi-effector targeting systems, demonstrate its comparable efficacy. Furthermore, we demonstrate the importance of the spatial ordering of the recruited effectors for effective transcriptional regulation. Together, the SSSavi system enables exploration of combinatorial effector co-recruitment to enhance manipulation of chromatin contexts previously resistant to targeted editing.
The Efg1–Bud22 dimer associates with the U14 snoRNP contacting the 5′ rRNA domain of an early 90S pre-ribosomal particle
Authors: Beine-Golovchuk Olga , Kallas Martina , Kunze Ruth , Griesel Sabine , Baßler Jochen 
Published: November 2023

Abstract
The DEAD-box helicase Dbp4 plays an essential role during the early assembly of the 40S ribosome, which is only poorly understood to date. By applying the yeast two-hybrid method and biochemical approaches, we discovered that Dbp4 interacts with the Efg1–Bud22 dimer. Both factors associate with early pre-90S particles and smaller complexes, each characterized by a high presence of the U14 snoRNA. A crosslink analysis of Bud22 revealed its contact to the U14 snoRNA and the 5′ domain of the nascent 18S rRNA, close to its U14 snoRNA hybridization site. Moreover, depletion of Bud22 or Efg1 specifically affects U14 snoRNA association with pre-ribosomal complexes. Accordingly, we concluded that the role of the Efg1–Bud22 dimer is linked to the U14 snoRNA function on early 90S ribosome intermediates chaperoning the 5′ domain of the nascent 18S rRNA. The successful rRNA folding of the 5′ domain and the release of Efg1, Bud22, Dpb4, U14 snoRNA and associated snoRNP factors allows the subsequent recruitment of the Kre33-Bfr2-Enp2-Lcp5 module towards the 90S pre-ribosome.
The replication enhancer crtS depends on transcription factor Lrp for modulating binding of initiator RctB to ori2 of Vibrio cholerae
Authors: Doan Alexander , Chatterjee Soniya , Kothapalli Roopa , Khan Zaki , Sen Shaanit , Kedei Noemi , Jha Jyoti K , Chattoraj Dhruba K , Ramachandran Revathy 
Published: November 2023

Abstract
Replication of Vibrio cholerae chromosome 2 (Chr2) initiates when the Chr1 locus, crtS (Chr2 replication triggering site) duplicates. The site binds the Chr2 initiator, RctB, and the binding increases when crtS is complexed with the transcription factor, Lrp. How Lrp increases the RctB binding and how RctB is subsequently activated for initiation by the crtS-Lrp complex remain unclear. Here we show that Lrp bends crtS DNA and possibly contacts RctB, acts that commonly promote DNA-protein interactions. To understand how the crtS-Lrp complex enhances replication, we isolated Tn-insertion and point mutants of RctB, selecting for retention of initiator activity without crtS. Nearly all mutants (42/44) still responded to crtS for enhancing replication, exclusively in an Lrp-dependent manner. The results suggest that the Lrp-crtS controls either an essential function or more than one function of RctB. Indeed, crtS modulates two kinds of RctB binding to the origin of Chr2, ori2, both of which we find to be Lrp-dependent. Some point mutants of RctB that are optimally modulated for ori2 binding without crtS still remained responsive to crtS and Lrp for replication enhancement. We infer that crtS-Lrp functions as a unit, which has an overarching role, beyond controlling initiator binding to ori2.
Fibrates and the risk of cardiovascular outcomes in chronic kidney disease patients
Authors: Goto Hirohito , Iseri Ken , Hida Noriko 
Published: November 2023

ABSTRACT

Background
The high risk of major adverse cardiovascular events (MACE) in patients with chronic kidney disease (CKD) has been well described. However, the efficacy of fibrates on the risk of MACE in patients with CKD remains unclear.

Methods
We conducted a nested case–control study using data from a large administrative database that included more than 1.5 million Japanese patients. We defined cases as CKD patients with incidences of MACE and matched them with controls based on age, sex, calendar year of cohort entry and CKD stage. Fibrate exposure timing was categorized as current, recent or past. A conditional logistic regression analysis was used to investigate the association between fibrate use and the risk of MACE.

Results
Our study included 47 490 patients with CKD, with 15 830 MACE identified during a median follow-up of 9.4 months. The numbers of fibrates used during the study period were 556 (3.5%) in the case group and 1109 (3.5%) in the control group. Fibrate use was significantly associated with a decreased risk of MACE [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.75–0.94], particularly for current (OR 0.81; 95% CI 0.68–0.97) and recent use (OR 0.65; 95% CI 0.48–0.90). Regarding the class effect of fibrates, pemafibrate use, but not bezafibrate or fenofibrate use, was significantly associated with a decreased risk of MACE (OR 0.73; 95% CI 0.528–0.997).

Conclusion
Recent and current fibrate use, especially pemafibrate use, was associated with a reduced risk of MACE in patients with CKD. This suggests the potential benefits of continuous fibrate therapy and the possible superiority of pemafibrate over other fibrates. However, further investigations in different populations are required to confirm the generalizability of these findings.
Patient-derived glioblastoma organoids reflect tumor heterogeneity and treatment sensitivity
Authors: Verduin Maikel , Hoosemans Linde , Vanmechelen Maxime , van Heumen Mike , Piepers Jolanda A F , Astuti Galuh , Ackermans Linda , Schijns Olaf E M G , Kampen Kim R , Tjan-Heijnen Vivianne C G , de Barbanson Buys A , Postma Alida A , Eekers Danielle B P , Broen Martijn P G , Beckervordersandforth Jan , Staňková Katerina , de Smet Frederik , Rich Jeremy , Hubert Christopher G , Gimenez Gregory , Chatterjee Aniruddha , Hoeben Ann , Vooijs Marc A 
Published: November 2023

Abstract

Background
Treatment resistance and tumor relapse are the primary causes of mortality in glioblastoma (GBM), with intratumoral heterogeneity playing a significant role. Patient-derived cancer organoids have emerged as a promising model capable of recapitulating tumor heterogeneity. Our objective was to develop patient-derived GBM organoids (PGO) to investigate treatment response and resistance.

Methods
GBM samples were used to generate PGOs and analyzed using whole-exome sequencing (WES) and single-cell karyotype sequencing. PGOs were subjected to temozolomide (TMZ) to assess viability. Bulk RNA sequencing was performed before and after TMZ.

Results
WES analysis on individual PGOs cultured for 3 time points (1–3 months) showed a high inter-organoid correlation and retention of genetic variants (range 92.3%–97.7%). Most variants were retained in the PGO compared to the tumor (range 58%–90%) and exhibited similar copy number variations. Single-cell karyotype sequencing demonstrated preservation of genetic heterogeneity. Single-cell multiplex immunofluorescence showed maintenance of cellular states. TMZ treatment of PGOs showed a differential response, which largely corresponded with MGMT promoter methylation. Differentially expressed genes before and after TMZ revealed an upregulation of the JNK kinase pathway. Notably, the combination treatment of a JNK kinase inhibitor and TMZ demonstrated a synergistic effect.

Conclusions
Overall, these findings demonstrate the robustness of PGOs in retaining the genetic and phenotypic heterogeneity in culture and the application of measuring clinically relevant drug responses. These data show that PGOs have the potential to be further developed into avatars for personalized adaptive treatment selection and actionable drug target discovery and as a platform to study GBM biology.
Effect of Inhaled Ciclesonide in Non–Critically Ill Hospitalized Patients With Coronavirus Disease 2019: A Multicenter Observational Study in Japan
Authors: Suzuki Jun , Endo Shiro , Suzuki Takayuki , Sasahara Teppei , Hatakeyama Shuji , Morisawa Yuji , Hayakawa Mineji , Yamakawa Kazuma , Endo Akira , Ogura Takayuki , Hirayama Atsushi , Yasunaga Hideo , Tagami Takashi 
Published: November 2023

Abstract

Background
Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic. Although systemic steroids play an important role in treating patients with severe COVID-19, the role of inhaled corticosteroids in non–critically ill, hospitalized patients with COVID-19 remains unclear.

Methods
We analyzed findings in non–critically ill, hospitalized patients with COVID-19 who were &gt;18 years old and were admitted to 64 Japanese hospitals between January and September 2020. We performed propensity score matching analysis to evaluate 28-day and in-hospital mortality rates with or without inhaled ciclesonide within 2 days of admission. Sensitivity analyses using inverse probability weighting analysis, and generalized estimating equation method were also performed.

Results
Eligible patients (n = 3638) were divided into ciclesonide (n = 290) and control (n = 3, 393) groups. The 1-to-4 propensity score matching analysis included 271 ciclesonide users and 1084 nonusers. There were no significant differences between the 2 groups for 28-day (3.3% vs 2.3%; risk difference, 1.0% [95% confidence interval, −1.2 to 3.3]) or in-hospital (4.8% vs 2.6%; risk difference, 2.2 [−.5 to 4.9]) mortality rates. The sensitivity analysis showed similar outcomes.

Conclusions
From this multicenter observational study in Japan, inhaled ciclesonide did not decrease 28-day or in-hospital mortality rates in non–critically ill, hospitalized patients with COVID-19. Future large, multinational, randomized trials are required to confirm our results.
Comparison of Adjuvant Clindamycin vs Linezolid for Severe Invasive Group A Streptococcus Skin and Soft Tissue Infections
Authors: Heil Emily L , Kaur Harpreet , Atalla Anthony , Basappa Sapna , Mathew Minu , Seung Hyunuk , Johnson J Kristie , Schrank Gregory M 
Published: November 2023

Abstract

Background
Linezolid may be an option for severe group A Streptococcus (GAS) infections based on its potent in vitro activity and antitoxin effects, but clinical data supporting its use over clindamycin are limited. This study evaluated treatment outcomes in patients with severe GAS skin and soft tissue infections who received either linezolid or clindamycin.

Methods
This retrospective single-center cohort study examined patients with GAS isolated from blood and/or tissue cultures with invasive soft tissue infection or necrotizing fasciitis who underwent surgical debridement and received linezolid or clindamycin for at least 48 hours. The primary outcome was percentage change in Sequential Organ Failure Assessment (SOFA) score from baseline through 72 hours of hospitalization.

Results
After adjustment for time to first surgical intervention among patients with a baseline SOFA score &gt;0 (n = 23 per group), there was no difference in reduction of SOFA score over the first 72 hours in patients receiving clindamycin vs linezolid. In the entire cohort (n = 26, clindamycin; n = 29, linezolid), there was no difference in inpatient mortality (2% vs 1%) or any secondary outcomes, including duration of vasopressor therapy, intensive care unit length of stay, and antibiotic-associated adverse drug events.

Conclusions
There was no difference in reduction of critical illness as measured by SOFA score between baseline and 72 hours among patients treated with clindamycin vs linezolid. Given its more favorable side effect profile, linezolid may be a viable option for the treatment of serious GAS infections and should be further studied.
Hepatitis E Virus Infection Epidemiology in Recipients of Allogeneic Hematopoietic Cell Transplant
Authors: Courjon Johan , Portillo Vera , Yerly Sabine , Vetter Pauline , Schibler Manuel , Mappoura Maria , Morin Sarah , Giannotti Federica , Mamez Anne-Claire , van Delden Christian , Kaiser Laurent , Chalandon Yves , Masouridi-Levrat Stavroula , Neofytos Dionysios 
Published: November 2023

Abstract
Among 292 recipients of allogeneic hematopoietic cell transplant (2018–2022), 64 (21.9%) tested positive for anti–hepatitis E virus (HEV) immunoglobulin G. Among 208 recipients tested by plasma/serum HEV polymerase chain reaction (2012–2022), 3 (1.4%) primary HEV infections were diagnosed; in 1 patient, plasma HEV polymerase chain reaction relapsed positive for 100 days. HEV infection remains rare albeit associated with persistent viral replication.
Treatment of Hypercalcemic Hyperparathyroidism After Kidney Transplantation Is Associated With Improved Allograft Survival
Authors: Wang Rongzhi , Reed Rhiannon D , Price Griffin , Abraham Peter , Lewis Marshall , McMullin Jessica Liu , MacLennan Paul , Killian Cozette , Locke Jayme E , Ong Song , Kumar Vineeta , Gillis Andrea , Lindeman Brenessa , Chen Herbert , Fazendin Jessica 
Published: November 2023

Abstract

Background
Hyperparathyroidism (HPT) and malignancy are the most common causes of hypercalcemia. Among kidney transplant (KT) recipients, hypercalcemia is mostly caused by tertiary HPT. Persistent tertiary HPT after KT is associated with allograft failure. Previous studies on managing tHPT were subjected to survivor treatment selection bias; as such, the impact of tertiary HPT treatment on allograft function remained unclear. We aim to assess the association between hypercalcemic tertiary HPT treatment and kidney allograft survival.

Materials and Methods
We identified 280 KT recipients (2015-2019) with elevated post-KT adjusted serum calcium and parathyroid hormone (PTH). KT recipients were characterized by treatment: cinacalcet, parathyroidectomy, or no treatment. Time-varying Cox regression with delayed entry at the time of first elevated post-KT calcium was conducted, and death-censored and all-cause allograft failure were compared by treatment groups.

Results
Of the 280 recipients with tHPT, 49 underwent PTx, and 98 received cinacalcet. The median time from KT to first elevated calcium was 1 month (IQR: 0-4). The median time from first elevated calcium to receiving cinacalcet and parathyroidectomy was 0(IQR: 0-3) and 13(IQR: 8-23) months, respectively. KT recipients with no treatment had shorter dialysis vintage (P = .017) and lower PTH at KT (P = .002), later onset of hypercalcemia post-KT (P &lt; .001). Treatment with PTx (adjusted hazard ratio (aHR) = 0.18, 95%CI 0.04-0.76, P = .02) or cinacalcet (aHR = 0.14, 95%CI 0.004-0.47, P = .002) was associated with lower risk of death-censored allograft failure. Moreover, receipt of PTx (aHR = 0.28, 95%CI 0.12-0.66, P &lt; .001) or cinacalcet (aHR = 0.38, 95%CI 0.22-0.66, P &lt; .001) was associated with lower risk of all-cause allograft failure.

Conclusions
This study demonstrates that treatment of hypercalcemic tertiary HPT post-KT is associated with improved allograft survival. Although these findings are not specific to hypercalcemia of malignancy, they do demonstrate the negative impact of hypercalcemic tertiary HPT on kidney function. Hypercalcemic HPT should be screened and aggressively treated post-KT.
Expansin SlExp1 and endoglucanase SlCel2 synergistically promote fruit softening and cell wall disassembly in tomato
Authors: Su Guanqing , Lin Yifan , Wang Chunfeng , Lu Jiao , Liu Zimeng , He Zhiren , Shu Xiu , Chen Wenbo , Wu Rongrong , Li Baijun , Zhu Changqing , Rose Jocelyn K C , Grierson Donald , Giovannoni James J , Shi Yanna , Chen Kunsong 
Published: November 2023

Abstract
Fruit softening, an irreversible process that occurs during fruit ripening, can lead to losses and waste during postharvest transportation and storage. Cell wall disassembly is the main factor leading to loss of fruit firmness, and several ripening-associated cell wall genes have been targeted for genetic modification, particularly pectin modifiers. However, individual knockdown of most cell wall–related genes has had minimal influence on cell wall integrity and fruit firmness, with the notable exception of pectate lyase. Compared to pectin disassembly, studies of the cell wall matrix, the xyloglucan–cellulose framework, and underlying mechanisms during fruit softening are limited. Here, a tomato (Solanum lycopersicum) fruit ripening–associated α-expansin (SlExpansin1/SlExp1) and an endoglucanase (SlCellulase2/SlCel2), which function in the cell wall matrix, were knocked out individually and together using clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9-mediated genome editing. Simultaneous knockout of SlExp1 and SlCel2 enhanced fruit firmness, reduced depolymerization of homogalacturonan-type pectin and xyloglucan, and increased cell adhesion. In contrast, single knockouts of either SlExp1 or SlCel2 did not substantially change fruit firmness, while simultaneous overexpression of SlExp1 and SlCel2 promoted early fruit softening. Collectively, our results demonstrate that SlExp1 and SlCel2 synergistically regulate cell wall disassembly and fruit softening in tomato.
Transcription factors PuPRE6/PuMYB12 and histone deacetylase PuHDAC9-like regulate sucrose levels in pear
Authors: Gao Siyang , Yin Mingxin , Xu Mingyang , Zhang He , Li Shuai , Han Yinxiao , Ji Shujuan , Li Xinyue , Du Guodong 
Published: November 2023

Abstract
The improvement of fruit quality, in particular sugar content, has been a major goal of plant breeding programmes for many years. Here, 2 varieties of the Ussurian pear (Pyrus ussuriensis), Nanguo, and its high-sucrose accumulation bud sport, Nanhong, were used to study the molecular mechanisms regulating sucrose transport in fruits. Comparative transcriptome analysis showed that in Nanhong fruit, an MYB transcription factor, PuMYB12, and a sucrose transporter protein, PuSUT4-like, were expressed at higher levels, while a paclobutrazol resistance transcription factor, PuPRE6, and a histone deacetylase (HDAC), PuHDAC9-like, were expressed at lower levels in Nanguo fruit. PuSUT4-like silencing and overexpression experiments in Nanguo pear showed that PuSUT4-like is essential for sucrose transportation. PuPRE6 and PuMYB12 act as antagonistic complexes to regulate PuSUT4-like transcription and sucrose accumulation. The histone deacetylation levels of the PuMYB12 and PuSUT4-like promoters were higher in Nanguo fruit than in Nanhong fruit, and Y1H assays showed that HDAC PuHDAC9-like bound directly to the promoters of PuMYB12 and PuSUT4-like. Our results uncovered transcription regulation and epigenetic mechanisms underlying sucrose accumulation in pears.