bluuebunny/crossref_metadata_2025_split huggingface dataset:
A highly conserved tRNA modification contributes to
C. albicans
filamentation and virulence
Authors: Böttcher Bettina , Kienast Sandra D. , Leufken Johannes , Eggers Cristian , Sharma Puneet , Leufken Christine M. , Morgner Bianka , Drexler Hannes C. A. , Schulz Daniela , Allert Stefanie , Jacobsen Ilse D. , Vylkova Slavena , Leidel Sebastian A. , Brunke Sascha 
Published: April 2024

ABSTRACT

tRNA modifications play important roles in maintaining translation accuracy in all domains of life. Disruptions in the tRNA modification machinery, especially of the anticodon stem loop, can be lethal for many bacteria and lead to a broad range of phenotypes in baker’s yeast. Very little is known about the function of tRNA modifications in host-pathogen interactions, where rapidly changing environments and stresses require fast adaptations. We found that two closely related fungal pathogens of humans, the highly pathogenic
Candida albicans
and its much less pathogenic sister species,
Candida dubliniensis
, differ in the function of a tRNA-modifying enzyme. This enzyme, Hma1, exhibits species-specific effects on the ability of the two fungi to grow in the hypha morphology, which is central to their virulence potential. We show that Hma1 has tRNA-threonylcarbamoyladenosine dehydratase activity, and its deletion alters ribosome occupancy, especially at 37°C—the body temperature of the human host. A
C. albicans HMA1
deletion mutant also shows defects in adhesion to and invasion into human epithelial cells and shows reduced virulence in a fungal infection model. This links tRNA modifications to host-induced filamentation and virulence of one of the most important fungal pathogens of humans.

IMPORTANCE

Fungal infections are on the rise worldwide, and their global burden on human life and health is frequently underestimated. Among them, the human commensal and opportunistic pathogen,
Candida albicans,
is one of the major causative agents of severe infections. Its virulence is closely linked to its ability to change morphologies from yeasts to hyphae. Here, this ability is linked—to our knowledge for the first time—to modifications of tRNA and translational efficiency. One tRNA-modifying enzyme, Hma1, plays a specific role in
C. albicans
and its ability to invade the host. This adds a so-far unknown layer of regulation to the fungal virulence program and offers new potential therapeutic targets to fight fungal infections.
Outbreak of
Streptococcus pyogenes emm89
ST646 in a head and neck surgical oncology ward
Authors: Hayama Brian , Harada Sohei , Suzuki Masahiro , Doi Yohei , Nomura Yusuke , Aoki Kotaro , Takehana Kazumi , Akatsuchi Tomomi , Enokida Taisuke , Takeda Koichi , Seto Akira , Mitani Hiroki , Ohkushi Daisuke 
Published: April 2024

ABSTRACT

Streptococcus pyogenes
causes a variety of human infections, and hospital outbreaks with this pathogen have also been reported. The purpose of this study is to describe the clinical characteristics of an outbreak of
S. pyogenes
involving 15 patients and four healthcare workers (HCWs), as well as the molecular characteristics of the causative isolates. The course and response to the outbreak were reviewed, and information on the characteristics of the patients was extracted retrospectively from the medical records. Whole-genome sequencing of the 16 causative isolates (14 from patients and two from HCWs) was also performed. All 15 patients were postoperative of head and neck cancer with tracheotomy, and 12 had invasive infections, primarily surgical site infections, all of which resolved without causing serious illness. All but the first case was detected more than 7 days after admission.
S. pyogenes
was detected in two patients after empiric antimicrobial administration was performed on all inpatients and HCWs, and the outbreak was finally contained in approximately 2 months. All isolates detected in patients and HCWs belonged to
emm89
/clade 3, a hypervirulent clone that has emerged worldwide and was classified as sequence type 646. These isolates had single nucleotide polymorphism (SNP) differences of zero to one, indicating clonal transmission. This study demonstrated an outbreak of
S. pyogenes emm89
/clade 3 in a ward of patients with head and neck cancer. The global emergence of hypervirulent isolates may increase the risk of outbreaks among high-risk patients.

IMPORTANCE

This study describes an outbreak of
Streptococcus pyogenes
that occurred in a ward caring for patients with head and neck cancer and tracheostomies. Many cases of invasive infections occurred in a short period, and extensive empiric antimicrobial administration on patients and healthcare workers was performed to control the outbreak. Whole-genome sequencing analysis of the causative strains confirmed that it was a monoclonal transmission of strains belonging to
emm89
/clade 3. The epidemiology and clinical characteristics of
S. pyogenes
infections have changed with the replacement of the prevalent clones worldwide. In the 1980s, there was a reemergence of
S. pyogenes
infections in high-income countries due to the spread of hypervirulent emm1 strains.
emm89
/clade 3 has recently been spreading worldwide and shares common features with emm1, including increased production of two toxins, NADase, and streptolysin O. The outbreak reported here may reflect the high spreading potential and virulence of
emm89
/clade 3.
Incidence and analysis of intraoperative complications in femtosecond laser-assisted cataract surgery: a large-scale cohort study to establish the learning curve
Authors: Zhang Xiaobo , Xu Wen , Shentu Xingchao , Chen Peiqing , Yu Yibo , Lai Kairan , Li Jiayong , Wang Wei , Chen Xinyi , Yao Ke 
Published: April 2024

Aims
To assess the safety of femtosecond laser-assisted cataract surgery (FLACS) based on surgical parameters and intraoperative complications analysis and to determine the length of the learning curve for FLACS.

Methods
A prospective consecutive cohort study was conducted on Chinese patients who underwent either FLACS (3289 cases) or contemporaneous conventional phacoemulsification cataract surgery (2130 cases). The laser group was divided into four subgroups in chronological order. We recorded intraoperative complication incidences and compared with surgical parameters between groups. Subgroup analysis was conducted to explore the learning curve of FLACS.

Results
The laser group had a 4.93% incidence of incomplete capsulotomies and a 1.22% incidence of anterior capsule tears. Subgroup analysis showed significant differences in 8 aspects between the first 250 cases (50 cases per surgeon) and the last 2539 cases, but only 2 aspects differed between the second 250 cases (50 cases per surgeon) and the last 2539 cases. There were no significant differences between the third 250 cases (50 cases per surgeon) and the last 2539 cases.

Conclusions
The intraoperative complications of FLACS were reported, and the learning curve is associated with a significant reduction in the incidence of intraoperative complications. The length of the basic learning curve of FLACS is 100 cases, and the length of the advanced learning curve was 150 cases. This study demonstrated that FLACS is characterised by a relatively straightforward and secure operative technique.
Peripapillary atrophy area predicts the decrease of macular choroidal thickness in young adults during myopia progression
Authors: Li Menghan , Shi Ya , Chen Qiuying , Hu Guangyi , Xie Jiamin , Ye Luyao , Fan Ying , Zhu Jianfeng , He Jiangnan , Xu Xun 
Published: April 2024

ObjectiveThis study aimed to investigate the influence of peripapillary atrophy (PPA) area and axial elongation on the longitudinal changes in macular choroidal thickness (ChT) in young individuals with myopia.Methods and analysisIn this longitudinal investigation, 431 eyes—342 categorised as non-high myopia (non-HM) and 89 as HM—were examined for 2 years. Participants were examined with swept-source optical coherence tomography. The macular ChT, PPA area and axial length (AL) were measured at baseline and follow-up visits. Multiple regression analysis was performed to identify factors associated with ChT changes. The areas under the receiver operating characteristic curves were analysed to ascertain the predictive capacity of the PPA area and axial elongation for the reduction in macular ChT.ResultsInitial measurements revealed that the average macular ChT was 240.35±56.15 µm in the non-HM group and 198.43±50.27 µm in the HM group (p<0.001). It was observed that the HM group experienced a significantly greater reduction in average macular ChT (−7.35±11.70 µm) than the non-HM group (−1.85±16.95 µm, p=0.004). Multivariate regression analysis showed that a greater reduction of ChT was associated with baseline PPA area (β=−26.646, p<0.001) and the change in AL (β=−35.230, p<0.001). The combination of the baseline PPA area with the change in AL was found to be effective in predicting the decrease in macular ChT, with an area under the curve of 0.741 (95% CI 0.694 to 0.787).ConclusionOver 2 years, eyes with HM exhibit a more significant decrease in ChT than those without HM. Combining the baseline PPA area with the change in AL could be used to predict the decrease of macular ChT.
Parental stress, depression, anxiety and participation in care in neonatal intensive care unit: a cross-sectional study in Italy comparing mothers versus fathers
Authors: Bua Jenny , Dalena Paolo , Mariani Ilaria , Girardelli Martina , Ermacora Maddalena , Manzon Ursula , Plet Sabrina , Travan Laura , Lazzerini Marzia 
Published: April 2024

BackgroundThis study aimed at documenting the levels of stress, depression, anxiety and participation in care among mothers versus fathers of newborns hospitalised in a third-level neonatal intensive care unit (NICU) in Northern Italy.MethodsParental stress, depression and anxiety were assessed by the Parental Stressor Scale in NICU (PSS:NICU), the Edinburgh Postnatal Depression Scale (EPDS) and the State-Trait Anxiety Inventory (STAI). Participation in care was evaluated with the Index of Parental Participation. Differences between mothers and fathers were assessed with the Mood’s median test and z-test, respectively for continuous and discrete variables. Multivariate analyses controlling for potential confounders were performed to confirm gender differences.Results191 parents (112 mothers and 79 fathers) were enrolled. Mothers reported significantly higher median scores for stress (2.9 vs 2.2, p<0.001) and trait anxiety (37 vs 32, p=0.004) and higher depression rates (EPDS ≥12: 43.8% vs 19.0%, p<0.001). ‘High stress’ (PSS:NICU ≥3) was reported by 45.5% of mothers compared with 24.1% of fathers (p=0.004). The frequency of the three conditions simultaneously was significantly higher among mothers (20.0% vs 3.8%, p=0.016), with the vast majority of mothers (76.0%) suffering from at least one condition compared with less than half of fathers (45.3%, p<0.001). Participation in care was more frequent in mothers (median score: 19 vs 15, p<0.001), with the exception of activities related to advocacy (median 5 vs 4, p=0.053). In a multivariate analysis, gender differences in mental health outcomes did not change.ConclusionsRoutine screening of mental distress among parents of infants in NICU is warranted, and gender differences need to be acknowledged in order to deliver tailored support and to promote collaboration with the family of vulnerable newborns. Knowledge and skills on how to prevent and cope with mental distress of parents should be part of the core curriculum of staff working in NICU.
Causal associations of antioxidants with Alzheimer’s disease and cognitive function: a Mendelian randomisation study
Authors: Wang Jiao , Huang Yingyue , Bei Chunhua , Yang Huiling , Lin Zihong , Xu Lin 
Published: April 2024

BackgroundCirculating antioxidants are associated with a lower risk of Alzheimer’s disease (AD) in observational studies, suggesting potential target areas for intervention. However, whether the associations are causal remains unclear. Here, we studied the causality between antioxidants and AD or cognitive function using two-sample Mendelian randomisation (MR).MethodsSingle nucleotide polymorphisms strongly (p<5×10−8) associated with antioxidants (vitamin A, vitamin C, zinc, selenium, β-carotene and urate) and outcomes (AD, cognitive performance and reaction time) were obtained from the largest and most recent genome-wide association studies (GWAS). MR inverse variance weighting (IVW) and MR pleiotropy residual sum and outlier test (MR-PRESSO) were used for data analysis.ResultsHigher genetically determined selenium level was associated with 5% higher risk of AD (OR 1.047, 95% CI 1.005 to 1.091, p=0.028) using IVW. Higher genetically determined urate level was associated with worse cognitive performance (β=−0.026, 95% CI −0.044 to −0.008, p=0.005) using MR-PRESSO. No association between the other antioxidants and AD, cognitive performance and reaction time was found. Similar results were found in the sensitivity analyses.ConclusionOur results suggest that lifelong exposure to higher selenium may be associated with a higher risk of AD, and higher urate levels could be associated with worse cognitive performance. Further analyses using larger GWAS of antioxidants are warranted to confirm these observations. Our results suggest that caution is needed in the interpretation of traditional observational evidence on the neuroprotective effects of antioxidants.
PD-1 downregulation enhances CAR-T cell antitumor efficiency by preserving a cell memory phenotype and reducing exhaustion
Authors: Ouyang Wanyan , Jin Shi-Wei , Xu Nan , Liu Wei-Yang , Zhao Han , Zhang Liuqingqing , Kang Liqing , Tao Yi , Liu Yuanfang , Wang Yan , Wang Jin , Liu Feng , Yu Lei , Liu Zhiqiang , Mi Jian-Qing 
Published: April 2024

BackgroundDespite the encouraging outcome of chimeric antigen receptor T cell (CAR-T) targeting B cell maturation antigen (BCMA) in managing relapsed or refractory multiple myeloma (RRMM) patients, the therapeutic side effects and dysfunctions of CAR-T cells have limited the efficacy and clinical application of this promising approach.MethodsIn this study, we incorporated a short hairpin RNA cassette targeting PD-1 into a BCMA-CAR with an OX-40 costimulatory domain. The transduced PD-1KDBCMA CAR-T cells were evaluated for surface CAR expression, T-cell proliferation, cytotoxicity, cytokine production, and subsets when they were exposed to a single or repetitive antigen stimulation. Safety and efficacy were initially observed in a phase I clinical trial for RRMM patients.ResultsCompared with parental BCMA CAR-T cells, PD-1KDBCMA CAR-T cell therapy showed reduced T-cell exhaustion and increased percentage of memory T cells in vitro. Better antitumor activity in vivo was also observed in PD-1KDBCMA CAR-T group. In the phase I clinical trial of the CAR-T cell therapy for seven RRMM patients, safety and efficacy were initially observed in all seven patients, including four patients (4/7, 57.1%) with at least one extramedullary site and four patients (4/7, 57.1%) with high-risk cytogenetics. The overall response rate was 85.7% (6/7). Four patients had a stringent complete response (sCR), one patient had a CR, one patient had a partial response, and one patient had stable disease. Safety profile was also observed in these patients, with an incidence of manageable mild to moderate cytokine release syndrome and without the occurrence of neurological toxicity.ConclusionsOur study demonstrates a design concept of CAR-T cells independent of antigen specificity and provides an alternative approach for improving the efficacy of CAR-T cell therapy.
The LHC as a Neutrino-Ion Collider
Authors: Cruz-Martinez Juan M. , Fieg Max , Giani Tommaso , Krack Peter , Mäkelä Toni , Rabemananjara Tanjona R. , Rojo Juan 
Published: April 2024

AbstractProton-proton collisions at the LHC generate a high-intensity collimated beam of neutrinos in the forward (beam) direction, characterised by energies of up to several TeV. The recent observation of LHC neutrinos by FASER$$\nu $$
ν
and SND@LHC signifies that this previously overlooked particle beam is now available for scientific investigation. Here we quantify the impact that neutrino deep-inelastic scattering (DIS) measurements at the LHC would have on the parton distributions (PDFs) of protons and heavy nuclei. We generate projections for DIS structure functions for FASER$$\nu $$
ν
and SND@LHC at Run III, as well as for the FASER$$\nu $$
ν
2, AdvSND, and FLArE experiments to be hosted at the proposed Forward Physics Facility (FPF) operating concurrently with the High-Luminosity LHC (HL-LHC). We determine that up to one million electron-neutrino and muon-neutrino DIS interactions within detector acceptance can be expected by the end of the HL-LHC, covering a kinematic region in x and $$Q^2$$

Q
2

overlapping with that of the Electron-Ion Collider. Including these DIS projections in global (n)PDF analyses, specifically PDF4LHC21, NNPDF4.0, and EPPS21, reveals a significant reduction in PDF uncertainties, in particular for strangeness and the up and down valence PDFs. We show that LHC neutrino data enable improved theoretical predictions for core processes at the HL-LHC, such as Higgs and weak gauge boson production. Our analysis demonstrates that exploiting the LHC neutrino beam effectively provides CERN with a “Neutrino-Ion Collider” without requiring modifications in its accelerator infrastructure.
UC and BUC plane partitions
Authors: Zhang Shengyu , Yan Zhaowen 
Published: April 2024

AbstractThis paper is concerned with the investigation of UC and BUC plane partitions based upon the fermion calculus approach. We construct generalized the vertex operators in terms of free charged fermions and neutral fermions and present the interlacing (strict) 2-partitions. Furthermore, it is showed that the generating functions of UC and BUC plane partitions can be written as product forms.
A generalized static spherically symmetric anisotropic compact stellar model
Authors: Govender Megandhren , Das Shyam 
Published: April 2024

AbstractWe report here a new exact solution of the Einstein field equations that describes a static spherically symmetric, anisotropic compact stellar fluid sphere. A generalized metric form corresponding to the $$g_{rr}$$

g

rr

component and a specific anisotropic profile generates the model. The new class of generalized solutions reduces to Finch-Skea, Vaidya Tikekar and Schwarzschild interior solutions for specific cho-ices of the model parameters. The model parameters have been determined from the continuity of the interior and exterior metrics at the surface of the star and setting the radial pressure at the boundary to zero. Recent observed measurements from some pulsars as sources have been utilized to validate our model.
High Fidelity Makeup via 2D and 3D Identity Preservation Net
Authors: Liu Jinliang , Zheng Zhedong , Yang Zongxin , Yang Yi 
Published: April 2024

In this article, we address the challenging makeup transfer task, aiming to transfer makeup from a reference image to a source image while preserving facial geometry and background consistency. Existing deep neural network-based methods have shown promising results in aligning facial parts and transferring makeup textures. However, they often neglect the facial geometry of the source image, leading to two adverse effects: (1) alterations in geometrically relevant facial features, causing face flattening and loss of personality, and (2) difficulties in maintaining background consistency, as networks cannot clearly determine the face-background boundary. To jointly tackle these issues, we propose the High Fidelity Makeup via two-dimensional (2D) and 3D Identity Preservation Network (IP23-Net), to the best of our knowledge, a novel framework that leverages facial geometry information to generate more realistic results. Our method comprises a 3D Shape Identity Encoder, which extracts identity and 3D shape features. We incorporate a 3D face reconstruction model to ensure the three-dimensional effect of face makeup, thereby preserving the characters’ depth and natural appearance. To preserve background consistency, our Background Correction Decoder automatically predicts an adaptive mask for the source image, distinguishing the foreground and background. In addition to popular benchmarks, we introduce a new large-scale High Resolution Synthetic Makeup Dataset containing 335,230 diverse high-resolution face images to evaluate our method’s generalization ability. Experiments demonstrate that IP23-Net achieves high-fidelity makeup transfer while effectively preserving background consistency. The code will be made publicly available.
A Novel Dual ATM/DNA-PK Inhibitor, XRD-0394, Potently Radiosensitizes and Potentiates PARP and Topoisomerase I Inhibitors
Authors: Gilmer Tona M. , Lai Chun-Hsiang , Guo Kexiao , Deland Katherine , Ashcraft Kathleen A. , Stewart Amy E. , Wang Yaode , Fu Jianmin , Wood Kris C. , Kirsch David G. , Kastan Michael B. 
Published: April 2024

Abstract
A majority of patients with cancer receive radiotherapy as part of their treatment regimens whether using external beam therapy or locally-delivered radioisotopes. While often effective, some tumors are inadequately controlled with radiation and radiotherapy has significant short-term and long-term toxicities for cancer survivors. Insights into molecular mechanisms involved in cellular responses to DNA breaks introduced by radiation or other cancer therapies have been gained in recent years and approaches to manipulate these responses to enhance tumor cell killing or reduce normal tissue toxicity are of great interest. Here, we report the identification and initial characterization of XRD-0394, a potent and specific dual inhibitor of two DNA damage response kinases, ATM and DNA-PKcs. This orally bioavailable molecule demonstrates significantly enhanced tumor cell kill in the setting of therapeutic ionizing irradiation in vitro and in vivo. XRD-0394 also potentiates the effectiveness of topoisomerase I inhibitors in vitro. In addition, in cells lacking BRCA1/2 XRD-0394 shows single-agent activity and synergy in combination with PARP inhibitors. A phase Ia clinical trial (NCT05002140) with XRD-0394 in combination with radiotherapy has completed. These results provide a rationale for future clinical trials with XRD-0394 in combination with radiotherapy, PARP inhibitors, and targeted delivery of topoisomerase I inhibitors.