bluuebunny/crossref_metadata_2025_split huggingface dataset:
40S Ribosomal protein S6 kinase integrates daylength perception and growth regulation in Arabidopsis thaliana
Authors: Boix Marc , Garcia-Rodriguez Alba , Castillo Laia , Miró Bernat , Hamilton Ferga , Tolak Sanata , Pérez Adrián , Monte-Bello Carolina , Caldana Camila , Henriques Rossana 
Published: May 2024

Abstract
Plant growth occurs via the interconnection of cell growth and proliferation in each organ following specific developmental and environmental cues. Therefore, different photoperiods result in distinct growth patterns due to the integration of light and circadian perception with specific Carbon (C) partitioning strategies. In addition, the TARGET OF RAPAMYCIN (TOR) kinase pathway is an ancestral signaling pathway that integrates nutrient information with translational control and growth regulation. Recent findings in Arabidopsis (Arabidopsis thaliana) have shown a mutual connection between the TOR pathway and the circadian clock. However, the mechanistical network underlying this interaction is mostly unknown. Here, we show that the conserved TOR target, the 40S ribosomal protein S6 kinase (S6K) is under circadian and photoperiod regulation both at the transcriptional and post-translational level. Total S6K (S6K1 and S6K2) and TOR-dependent phosphorylated-S6K protein levels were higher during the light period and decreased at dusk especially under short day conditions. Using chemical and genetic approaches, we found that the diel pattern of S6K accumulation results from 26S proteasome-dependent degradation and is altered in mutants lacking the circadian F-box protein ZEITLUPE (ZTL), further strengthening our hypothesis that S6K could incorporate metabolic signals via TOR, which are also under circadian regulation. Moreover, under short days when C/energy levels are limiting, changes in S6K1 protein levels affected starch, sucrose and glucose accumulation and consequently impacted root and rosette growth responses. In summary, we propose that S6K1 constitutes a missing molecular link where day-length perception, nutrient availability and TOR pathway activity converge to coordinate growth responses with environmental conditions.
Auxin signaling in the cambium promotes tissue adhesion and vascular formation during Arabidopsis graft healing
Authors: Serivichyaswat Phanu T , Kareem Abdul , Feng Ming , Melnyk Charles W 
Published: May 2024

Abstract
The strong ability of plants to regenerate wounds is exemplified by grafting when two plants are cut and joined together to grow as one. During graft healing, tissues attach, cells proliferate, and the vasculatures connect to form a graft union. The plant hormone auxin plays a central role, and auxin-related mutants perturb grafting success. Here, we investigated the role of individual cell types and their response to auxin during Arabidopsis (Arabidopsis thaliana) graft formation. By employing a cell-specific inducible misexpression system, we blocked auxin response in individual cell types using the bodenlos mutation. We found that auxin signaling in procambial tissues was critical for successful tissue attachment and vascular differentiation. In addition, we found that auxin signaling was required for cell divisions of the procambial cells during graft formation. Loss of function mutants in cambial pathways also perturbed attachment and phloem reconnection. We propose that cambial and procambial tissues drive tissue attachment and vascular differentiation during successful grafting. Our study thus refines our knowledge of graft development and furthers our understanding of the regenerative role of the cambium.
Activation of feedforward wiring in adult hippocampal neurons by the basic-helix-loop-helix transcription factor Ascl4
Authors: Luo Wenshu , Egger Matteo , Cruz-Ochoa Natalia , Tse Alice , Maloveczky Gyula , Tamás Bálint , Lukacsovich David , Seng Charlotte , Amrein Irmgard , Lukacsovich Tamás , Wolfer David , Földy Csaba 
Published: May 2024

Abstract
Although evidence indicates that the adult brain retains a considerable capacity for circuit formation, adult wiring has not been broadly considered and remains poorly understood. In this study, we investigate wiring activation in adult neurons. We show that the basic-helix-loop-helix transcription factor Ascl4 can induce wiring in different types of hippocampal neurons of adult mice. The new axons are mainly feedforward and reconfigure synaptic weights in the circuit. Mice with the Ascl4-induced circuits do not display signs of pathology and solve spatial problems equally well as controls. Our results demonstrate reprogrammed connectivity by a single transcriptional factor and provide insights into the regulation of brain wiring in adults.
Intranasal influenza-vectored COVID-19 vaccines confer broad protection against SARS-CoV-2 XBB variants in hamsters
Authors: Chen Junyu , Chen Congjie , Yuan Lunzhi , Chen Yaode , Wang Xijing , Tang Ningxin , Wei Dongmei , Ye Xiangzhong , Xia Ningshao , Chen Yixin 
Published: May 2024

Abstract
The XBB.1.5 subvariant has garnered significant attention due to its exceptional immune evasion and transmissibility. Significantly, the evolutionary trajectory of SARS-CoV-2 has shown continual progression, with a recent global shift observed from XBB to BA.2.86, exemplified by the emergence of the predominant JN.1 subvariant. This phenomenon highlights the need for vaccines that can provide broad-spectrum antigenic coverage. In this study, we utilized a NS1-deleted (dNS1) influenza viral vector to engineer an updated live-attenuated vectored vaccine called dNS1-XBB-RBD. This vaccine encodes the receptor-binding domain (RBD) protein of the XBB.1.5 strain. Our findings demonstrate that the dNS1-XBB-RBD vaccine elicits a similar systemic and mucosal immune response compared to its prototypic form, dNS1-RBD. In hamsters, the dNS1-XBB-RBD vaccine provided robust protection against the SARS-CoV-2 immune-evasive strains XBB.1.9.2.1 and Beta. Remarkably, nasal vaccination with dNS1-RBD, which encodes the ancestor RBD gene, also effectively protected hamsters against both the XBB.1.9.2.1 and Beta strains. These results provide valuable insights about nasal influenza-vectored vaccine and present a promising strategy for the development of a broad-spectrum vaccine against COVID-19 in the future.
Paediatric non-infectious granulomatous uveitis: a retrospective cohort study
Authors: Nguyen Ai Tien , Rousseau Antoine , Bodaghi Bahram , Rossi-Semerano Linda , Galeotti Caroline , Da Cunha Elodie , Eid Laura , Labetoulle Marc , Barreau Emmanuel , Titah Cherif , Toutée Adélaïde , Koné-Paut Isabelle , Dusser Perrine , Borocco Charlotte 
Published: May 2024

Abstract

Introduction
Paediatric granulomatous uveitis (PGU) is rare. In addition, lack of awareness often leads to delayed diagnosis and poor visual outcome. Identifying the underlying cause and deciding how best to treat each patient is challenging.

Objective
The objective of this study was to evaluate the demographics, aetiologies, complications, treatments, and visual prognosis of paediatric non-infectious granulomatous uveitis.

Methods
A retrospective chart review of non-infectious PGU occurring in children before the age of 16 years (recruited from the Paediatric Rheumatology Unit, Bicêtre Hospital, France, from 2001 to 2023) was undertaken.

Results
We included 50 patients with 90 affected eyes: 29 with idiopathic uveitis, 15 with sarcoidosis, 5 with JIA, and 1 with Vogt-Koyanagi-Harada disease. The median age at diagnosis was 9.8 years (range 7.2–12.5). The M:F sex ratio was 0.52. The most common types of PGU were: panuveitis (56%), bilateral (84%), and chronic (84%). Sarcoidosis was the most frequent diagnosis after idiopathic disease, particularly in the presence of lymphopenia and hypergammaglobulinemia. Uveomeningitis was present in 12% of cases. Upon diagnosis, ocular complications were present in 68 of 90 eyes (76%), particularly in cases of panuveitis. The most commonly used treatments were systemic CSs (72%) and MTX (80%). Twenty-three percent of eyes were in remission at last follow-up, 68% were inactive and 4% remained active. The median duration of follow-up was 5.8 years.

Conclusion
We report the largest cohort of PGU. The cases of PGU were mostly idiopathic and had a high rate of complications. Sarcoid and idiopathic panuveitis are serious illnesses in which disease-modifying therapy should be initiated at diagnosis to improve management.
Kenya Psychosis-Risk Outcomes Study (KePROS): Development of an Accelerated Medicine Partnership Schizophrenia-Aligned Project in Africa
Authors: Mamah Daniel , Mutiso Victoria , Musyimi Christine , Harms Michael P , Anokhin Andrey P , Chen ShingShiun , Torous John , Muyela Levi , Nashed Jerome , Al-Hosni Yazen , Odera Arthur , Yarber Alaina , Golosheykin Semyon , Faghankhani Masoomeh , Sneed Megan , Ndetei David M 
Published: May 2024

Abstract

Background and Hypothesis
The Accelerating Medicines Partnership Schizophrenia (AMP SCZ) funds a longitudinal study of 43 research sites across 5 continents to develop tools to stratify developmental trajectories of youth at clinical high risk for psychosis (CHR) and identify homogenous targets for future clinical trials. However, there are no sites in Africa, leaving a critical gap in our knowledge of clinical and biological outcomes among CHR individuals.

Study Design
We describe the development of the Kenya Psychosis-Risk Outcomes Study (KePROS), a 5-year NIH-funded project in Kenya designed to harmonize with AMP SCZ. The study will recruit over 100 CHR and 50 healthy participants and conduct multiple clinical and biomarker assessments over 2 years. Capacity building is a key component of the study, including the construction of an electroencephalography (EEG) laboratory and the upgrading of a local 3 T magnetic resonance imaging (MRI) machine. We detail community recruitment, study methodologies and protocols, and unique challenges with this pioneering research in Africa.

Study Results
This paper is descriptive only. Planned future analyses will investigate possible predictors of clinical outcomes and will be compared to results from other global populations.

Conclusions
KePROS will provide the research community with a rich longitudinal clinical and biomarker dataset from an African country in the developing Global South, which can be used alongside AMP SCZ data to delineate CHR outcome groups for future treatment development. Training in mental health assessment and investment in cutting-edge biomarker assessment and other technologies is needed to facilitate the inclusion of African countries in large-scale research consortia.
Influence of Clinical and Genetic Factors on Propofol Dose Requirements: A Genome-wide Association Study
Authors: Ahlström Sirkku , Reiterä Paula , Jokela Ritva , Olkkola Klaus T. , Kaunisto Mari A. , Kalso Eija 
Published: May 2024

Background
Propofol is a widely used intravenous hypnotic. Dosing is based mostly on weight, with great interindividual variation in consumption. Suggested factors affecting propofol requirements include age, sex, ethnicity, anxiety, alcohol consumption, smoking, and concomitant valproate use. Genetic factors have not been widely explored.

Methods
This study considered 1,000 women undergoing breast cancer surgery under propofol and remifentanil anesthesia. Depth of anesthesia was monitored with State Entropy (GE Healthcare, Finland). Propofol requirements during surgery were recorded. DNA from blood was genotyped with a genome-wide array. A multivariable linear regression model was used to assess the relevance of clinical variables and select those to be used as covariates in a genome-wide association study. Imputed genotype data were used to explore selected loci further. In silico functional annotation was used to explore possible consequences of the discovered genetic variants. Additionally, previously reported genetic associations from candidate gene studies were tested.

Results
Body mass index, smoking status, alcohol use, remifentanil dose (ln[mg · kg−1 · min−1]), and average State Entropy during surgery remained statistically significant in the multivariable model. Two loci reached genome-wide significance (P < 5 × 10−8). The most significant associations were for single-nucleotide polymorphisms rs997989 (30 kb from ROBO3), likely affecting expression of another nearby gene, FEZ1, and rs9518419, close to NALCN (sodium leak channel); rs10512538 near KCNJ2 encoding the Kir2.1 potassium channel showed suggestive association (P = 4.7 × 10−7). None of these single-nucleotide polymorphisms are coding variants but possibly affect the regulation of nearby genes. None of the single-nucleotide polymorphisms previously reported as affecting propofol pharmacokinetics or pharmacodynamics showed association in the data.

Conclusions
In this first genome-wide association study exploring propofol requirements, This study discovered novel genetic associations suggesting new biologically relevant pathways for propofol and general anesthesia. The roles of the gene products of ROBO3/FEZ1, NALCN, and KCNJ2 in propofol anesthesia warrant further studies.

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Update on corneal crosslinking for keratoconus and corneal ectasia
Authors: Greenstein Steven A. , Hersh Peter S. 
Published: May 2024

Purpose of review
To review corneal crosslinking for keratoconus and corneal ectasia, and recent developments in the field. This study will review the mechanism of crosslinking, clinical approaches, current results, and potential future innovations.

Recent findings
Corneal crosslinking for keratoconus was first approved by U.S. FDA in 2016. Recent studies have confirmed the general long-term efficacy of the procedure in decreasing progression of keratoconus and corneal ectasia. New types of crosslinking protocols, such as transepithelial treatments, are under investigation. In addition, adjunctive procedures have been developed to improve corneal contour and visual function in these patients.

Summary
Crosslinking has been found to be well tolerated and effective with the goal of decreasing progression of ectatic corneal diseases, keratoconus and corneal ectasia after refractive surgery. Studies have shown its long-term efficacy. New techniques of crosslinking and adjunctive procedures may further improve treatments and results.
Pediatric refractive surgery: current opinion in ophthalmology
Authors: Kim Abigail J. , Shahraki Kourosh , Suh Donny W. 
Published: May 2024

Purpose of review
Pediatric refractive surgery has been growing at a steady pace since its introduction in the early 1980 s. This article will review common laser refractive surgeries performed on pediatric patients along with controversies regarding the practice.

Recent findings
Pediatric refractive surgery is reserved for a small population of children who fail amblyopic treatment due to high anisometropic refractive errors. Publications over the years have treated these children with various types of laser refractive surgery.

Summary
Laser pediatric refractive surgery appears to be well tolerated and effective for the population of children that need it. It provides an alternative for anisometropic amblyopia treatment for children who would have otherwise not been able to improve their vision.
Consequences of Clot Formation and Hyphema Post–Internal Trabeculotomy for Glaucoma
Authors: Chihara Etsuo , Chihara Tomoyuki 
Published: May 2024

Précis:
Clot formation and hyphema following internal trabeculotomy represent distinct clinical entities. The eyes with clot formation exhibited a more pronounced postsurgical intraocular pressure spike, longer residual intracameral bleeding, and a higher risk of reoperation.

Purpose:
The aim of this study was to investigate the consequences of clot formation and hyphema in the anterior chamber after internal trabeculotomy.

Materials and Methods:
In this retrospective interventional comparative study, we investigated the surgical outcomes of internal trabeculotomy in 142 eyes of 142 patients at Sensho-kai Eye Institute.

Results:
Concurrent clot formation and L≥2 hyphema (height of hyphema ≥1 mm) was observed in 22 eyes. In these cases, the postsurgical IOP was 29.3 mm Hg at 1 week, significantly higher than the 16.1 mm Hg in eyes that had L≥2 hyphema but without clot formation (P=0.0002). However, the 1-week postsurgical IOP in L≥2 hyphema and clot (−) eyes, which measured 16.1 mm Hg was not significantly greater than that in L<2 hyphema and clot (−) eyes, which measured 18.7 mm Hg (P=0.162). Thus, clot formation was identified as a significant factor contributing to high postsurgical IOP at 1 week. The resolution time for anterior chamber bleeding in eyes with concurrent clot formation and L≥2 hyphema was 12.3 days, longer than the 5.8 days observed in L≥2 hyphema eyes without clot formation (P=0.016). Among the 22 eyes with concurrent L≥2 hyphema and clot formation, 8 required anterior chamber washout. Three of the 10 eyes that underwent washout necessitated additional trabeculectomy, a rate significantly higher than that in nonwashout eyes (P<0.001).

Conclusions:
After internal trabeculotomy, the sequelae of concurrent clot formation and L≥2 hyphema in the anterior chamber were more severe than those of simple hyphema without clots. Clot formation negatively affected postoperative IOP.
Single stage management of suspected gallbladder cancer guided by intraoperative frozen section analysis: a retrospective cohort study
Authors: Banh Serena , Fehervari Matyas , Flod Sara , Soleimani-Nouri Payam , Leyte Golpe Antonio , Ahmad Raida , Pai Madhava , Spalding Duncan R.C. 
Published: May 2024

Background:
The management of radiologically suspected gallbladder cancers (GBC) that lack definitive radiological features usually involves performing a first-stage routine laparoscopic cholecystectomy, followed by an open second-stage liver resection (segments IVB and V) and hilar lymphadenectomy (extended cholecystectomy) if subsequent formal histology confirms a malignancy. Performing a cholecystectomy with an intraoperative frozen section to guide the need for conversion to an extended cholecystectomy as a single-stage procedure has multiple benefits compared to a two-stage approach. However, the safety and efficacy of this approach have not yet been evaluated in a tertiary setting.

Methods:
A retrospective cohort study was performed using a database of all consecutive patients with suspected GBC who had been referred to our tertiary unit. Following routine cholecystectomy, depending on the operative findings, the gallbladder specimen was removed and sent for frozen-section analysis. If malignancy was confirmed, the depth of tumour invasion was evaluated, followed by simultaneous extended cholecystectomy, when appropriate. The sensitivity and specificity of frozen section analysis for the diagnosis of GBC were measured using formal histopathology as a reference standard.

Results:
A total of 37 consecutive cholecystectomies were performed. In nine cases, GBC was confirmed by intraoperative frozen section analysis, three of which had standard cholecystectomy only as their frozen section showed adenocarcinoma to be T1a or below (n=2) or were undetermined (n=1). In the remaining six cases, malignant invasion beyond the muscularis propria (T1b or above) was confirmed; thus, a synchronous extended cholecystectomy was performed. The sensitivity (95% CI: 66.4–100%) and specificity (95% CI: 87.7–100%) for identifying GBC using frozen section analysis were both 100%. The net cost of the single-stage pathway in comparison to the two-stage pathway resulted in overall savings of £3894.

Conclusion:
Intraoperative frozen section analysis is a reliable tool for guiding the use of a safe, single-stage approach for the management of GBC in radiologically equivocal cases. In addition to its lower costs compared to a conventional two-stage procedure, intraoperative analysis also affords the benefit of a single hospital admission and single administration of general anaesthesia, thus greatly enhancing the patient’s experience and relieving the burden on waiting lists.
Association of glucagon-like peptide-1 receptor agonists with risk of cancers-evidence from a drug target Mendelian randomization and clinical trials
Authors: Sun Yuming , Liu Yongjia , Dian Yating , Zeng Furong , Deng Guangtong , Lei Shaorong 
Published: May 2024

Background:
Glucagon-like peptide-1 receptor (GLP1R) agonists have been approved by Food and Drug Administration for management of obesity. However, the causal relationship of GLP1R agonists (GLP1RA) with cancers still unclear.

Methods:
The available cis-eQTLs for drugs target genes (GLP1R) were used as proxies for exposure to GLP1RA. Mendelian randomizations (MR) were performed to reveal the association of genetically-proxied GLP1RA with 14 common types cancer from large-scale consortia. Type 2 diabetes was used as positive control, and the GWASs data including 80 154 cases and 853 816 controls. Replicating the findings in the FinnGen study and then pooled with meta-analysis. Finally, all the related randomized controlled trails (RCTs) on GLP1RA were systematically searched from PubMed, Embase, and the Cochrane Library to comprehensively synthesize the evidence to validate any possible association with cancers.

Result:
A total of 22 significant cis-eQTL single-nucleotide polymorphisms were included as genetic instrument. The association of genetically-proxied GLP1RA with significantly decreased type 2 diabetes risk [OR (95%)=0.82 (0.79–0.86), P<0.001], which ensuring the effectiveness of identified genetic instruments. The authors found favorable evidence to support the association of GLP1RA with reduced breast cancer and basal cell carcinoma risk [0.92 (0.88–0.96), P<0.001, 0.92 (0.85–0.99), P=0.029, respectively], and with increased colorectal cancer risk [1.12 (1.07–1.18), P<0.001]. In addition, there was no suggestive evidence to support the association of GLP1RA with ovarian cancer [0.99 (0.90–1.09), P=0.827], lung cancer [1.01 (0.93–1.10), P=0760], and thyroid cancer [0.83 (0.63–1.10), P=0.187]. Our findings were consistent with the meta-analysis. Finally, 80 RCTs were included in the systematic review, with a low incidence of different kinds of cancer.

Conclusions:
Our study suggests that GLP1RA may decrease the risk of breast cancer and basal cell carcinoma, but increase the risk of colorectal cancer. However, according to the systematic review of RCTs, the incidence of cancer in patients treated with GLP1RA is low. Larger sample sizes of RCTs with long-term follow-up are necessary to establish the incidence of cancers and evaluate the risk-benefit ratios.