bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deeper than DEEP: a spectroscopic survey of z &gt; 3 Ly α emitters in the Extended Groth Strip
Authors: Stawinski Stephanie M Urbano , Cooper M C , Finkelstein Steven L , Jung Intae , Pérez-González Pablo G , Bagley Micaela B , Casey Caitlin M , Cooper Olivia R , Hathi Nimish P , Holwerda Benne W , Koekemoer Anton M , Kartaltepe Jeyhan S , Fernández Vital , Larson Rebecca L , Lucas Ray A , Yung L Y Aaron 
Published: February 2024

ABSTRACT
We present a spectroscopic survey of Ly α emitters in the Extended Groth Strip (EGS) field, targeting the regime near the Epoch of Reionization. Using Keck/DEep Imaging Multi-Object Spectrograph, we observed 947 high-z candidates with photometric redshifts from 3 &lt; zphot &lt; 7 and down to an H-band (Hubble Space Telescope/Wide Field Camera 3 F160W) magnitude limit of &lt;27.5. Observations were taken over the course of eight nights, with integration times ranging from 4 to 7.8 h. Our survey secured 137 unique redshifts, 126 of which are Ly α emitters at 2.8 &lt; z &lt; 6.3 with a mean redshift of $\overline{z} = 4.3$. We provide a comprehensive redshift catalogue for our targets, as well as the reduced one- and two-dimensional spectra for each object. These observations will provide an important auxiliary data set for the JWST Directors Discretionary Early Release Science programme the Cosmic Evolution Early Release Science Survey, which recently completed near- and mid-infrared imaging and spectroscopy of galaxies in the EGS field.
Radio spectral properties of star-forming galaxies between 150 and 5000 MHz in the ELAIS-N1 field
Authors: An Fangxia , Vaccari M , Best P N , Ocran E F , Ishwara-Chandra C H , Taylor A R , Leslie S K , Röttgering H J A , Kondapally R , Haskell Paul , Collier J D , Bonato M 
Published: February 2024

ABSTRACT
By combining high-sensitivity LOFAR 150 MHz, uGMRT 400 MHz and 1250 MHz, GMRT 610 MHz, and VLA 5 GHz data in the ELAIS-N1 field, we study the radio spectral properties of radio-detected star-forming galaxies (SFGs) at observer-frame frequencies of 150–5000 MHz. We select ∼3500 SFGs that have both LOFAR 150 MHz and GMRT 610 MHz detections, and obtain a median two-point spectral index of $\alpha _{150}^{610}=-0.51\pm 0.01$. The photometric redshift of these SFGs spans z = 0.01−6.21. We also measure the two-point radio spectral indices at 150–400–610–1250 MHz and 150–610–5000 MHz, respectively, for the GMRT 610-MHz-detected SFGs, and find that, on average, the radio spectrum of SFGs is flatter at low frequency than at high frequency. At observer-frame 150–5000 MHz, we find that the radio spectrum slightly steepens with increasing stellar mass. However, we only find that the radio spectrum flattens with increasing optical depth at V band at $\nu \lesssim 1$ GHz. We suggest that spectral ageing due to the energy loss of CR electrons and thermal free–free absorption could be among the possible main physical mechanisms that drive the above two correlations, respectively. In addition, both of these mechanisms could physically explain why the radio spectrum is flatter at low frequency than at high frequency.
Introducing urea into tirapazamine derivatives to enhance anticancer therapy
Authors: Xu Yajun , Lv Jianlin , Kong Chaoying , Liu Ya , Wang Kun , Tang Zhaohui , Chen Xuesi 
Published: February 2024

ABSTRACT
Tirapazamine (TPZ) has been approved for multiple clinical trials relying on its excellent anticancer potential. However, as a typical hypoxia-activated prodrug (HAP), TPZ did not exhibit survival advantages in Phase III clinical trials when used in combination therapy due to the insufficient hypoxia levels in patients’ tumors. In this study, to improve the therapeutic effects of TPZ, we first introduced urea to synthesize a series of urea-containing derivatives of TPZ. All urea-containing TPZ derivatives showed increased hypoxic cytotoxicity (9.51–30.85-fold) compared with TPZ, while maintaining hypoxic selectivity. TPZP, one of these derivatives, showed 20-fold higher cytotoxicity than TPZ while maintaining a similar hypoxic cytotoxicity ratio. To highly efficiently deliver TPZP to the tumors and reduce its side effects on healthy tissues, we further prepared TPZP into a nanodrug with fibrin-targeting ability: FT11-TPZP-NPs. CA4-NPs, a vascular disrupting agent, was used to increase the fibrin level within tumors and exacerbate tumor hypoxia. By being combined with CA4-NPs, FT11-TPZP-NPs can accumulate in the hypoxia-aggravated tumors and activate sufficiently to kill tumor cells. After a single-dose treatment, FT11-TPZP-NPs + CA4-NPs showed a high inhibition rate of 98.1% against CT26 tumor models with an initial volume of ∼480 mm3 and four out of six tumors were completely eliminated; it thereby exerted a significant antitumor effect. This study provides a new strategy for improving the therapeutic effect of TPZ and other HAPs in anticancer therapy.
Uncovering key salt-tolerant regulators through a combined eQTL and GWAS analysis using the super pan-genome in rice
Authors: Wei Hua , Wang Xianmeng , Zhang Zhipeng , Yang Longbo , Zhang Qianqian , Li Yilin , He Huiying , Chen Dandan , Zhang Bin , Zheng Chongke , Leng Yue , Cao Xinglan , Cui Yan , Shi Chuanlin , Liu Yifan , Lv Yang , Ma Jie , He Wenchuang , Liu Xiangpei , Xu Qiang , Yuan Qiaoling , Yu Xiaoman , Wang Tianyi , Qian Hongge , Li Xiaoxia , Zhang Bintao , Zhang Hong , Chen Wu , Guo Mingliang , Dai Xiaofan , Wang Yuexing , Zheng Xiaoming , Guo Longbiao , Xie Xianzhi , Qian Qian , Shang Lianguang 
Published: February 2024

ABSTRACT
For sessile plants, gene expression plays a pivotal role in responding to salinity stress by activating or suppressing specific genes. However, our knowledge of genetic variations governing gene expression in response to salt stress remains limited in natural germplasm. Through transcriptome analysis of the Global Mini-Core Rice Collection consisting of a panel of 202 accessions, we identified 22 345 and 27 610 expression quantitative trait loci associated with the expression of 7787 and 9361 eGenes under normal and salt-stress conditions, respectively, leveraging the super pan-genome map. Notably, combined with genome-wide association studies, we swiftly pinpointed the potential candidate gene STG5—a major salt-tolerant locus known as qSTS5. Intriguingly, STG5 is required for maintaining Na+/K+ homeostasis by directly regulating the transcription of multiple members of the OsHKT gene family. Our study sheds light on how genetic variants influence the dynamic changes in gene expression responding to salinity stress and provides a valuable resource for the mining of salt-tolerant genes in the future.
Culture, conditions and care support mental health of healthcare workers during crises
Authors: Maple J L , Whiteside M , Smallwood N , Putland M , Baldwin P , Bismark M , Harrex W , Johnson D , Karimi L , Willis K 
Published: February 2024

Abstract

Background
The coronavirus disease 2019 (COVID-19) pandemic has presented immense challenges to health systems worldwide and significantly impacted the mental health of frontline healthcare workers.

Aims
This study drew on the experiences of frontline healthcare workers to examine organizational strategies needed to support the mental health and well-being of healthcare workers during times of crisis.

Methods
Semi-structured focus groups or individual interviews were conducted with healthcare workers to examine their perspectives on organizational strategies for enhancing staff mental health and well-being during crises. Data were analysed thematically. Following this, evidence for the identified strategies was reviewed to assess alignment with participant views and recommendations.

Results
Thirty-two healthcare workers from diverse disciplines (10 allied health, 11 nursing, 11 medical) participated in the study. Data analysis identified three broad themes contributing to supporting mental health and well-being. These themes can be encapsulated as the ‘Three Cs’—culture (building an organizational culture that prioritizes mental health); conditions (implementing proactive organizational strategies during crises) and care (ensuring fit-for-purpose strategies to support mental health and well-being).

Conclusions
Study findings underscore the necessity of an integrated and systemic organizational approach to address mental health and well-being in the healthcare workplace. This approach must be long term with the components of the ‘Three Cs’, particularly cultural change and conditions, viewed as a part of a suite of strategies to ensure crisis preparedness. It is imperative that organizations collaborate with their staff, providing support and fostering a safe and inclusive work environment that ultimately benefits patients, their care and staff well-being.
Changes in Body Mass Index Over Time in People With and Without HIV Infection
Authors: Lam Jennifer O , Leyden Wendy A , Alexeeff Stacey , Lea Alexandra N , Hechter Rulin C , Hu Haihong , Marcus Julia L , Pitts Lakecia , Yuan Qing , Towner William J , Horberg Michael A , Silverberg Michael J 
Published: February 2024

Abstract

Background
Excess weight gain is an important health concern among people with HIV (PWH) on antiretroviral therapy (ART). The extent to which ART contributes to body mass index (BMI) changes is incompletely understood.

Methods
We conducted a retrospective study of PWH initiating ART and demographically matched people without HIV (PWoH). Data on baseline BMI (kg/m2; categorized as underweight/normal, overweight, or obese) and ART class (integrase strand transfer inhibitor [INSTI], non-nucleoside reverse transcriptase inhibitor [NNRTI], protease inhibitor [PI]) were obtained from electronic health records. BMI was evaluated longitudinally using piecewise linear splines in mixed effects models by HIV status, baseline BMI, and ART class. Models were adjusted for sociodemographics, comorbidities, and substance use.

Results
The study included 8256 PWH and 129 966 PWoH (mean baseline age, 40.9 and 42.2 years, respectively; 88% men). In adjusted models, the average annual change in BMI in the first 2 years after ART initiation was 0.53 for PWH and 0.12 for PWoH (P &lt; .001). BMI increases among PWH were observed for all ART classes: 0.69 for INSTIs, 0.69 for PIs, and 0.40 for NNRTIs vs 0.12 among PWoH. For PWH initiating INSTIs, BMI increases were observed regardless of baseline BMI. Overall BMI changes &gt;2 years after ART initiation were similar by HIV status (0.02 average annual increase for PWH and PWoH).

Conclusions
PWH initiating ART gained excess weight in the first 2 years, emphasizing the importance of monitoring weight and cardiometabolic health among ART-treated PWH.
Personalized Infant Risk Prediction for Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Requiring Intensive Care Unit Admission
Authors: Snyder Brittney M , Achten Niek B , Gebretsadik Tebeb , Wu Pingsheng , Mitchel Edward F , Escobar Gabriel , Bont Louis J , Hartert Tina V 
Published: February 2024

Abstract

Background
Currently, there are no available tools to identify infants at the highest risk of significant morbidity and mortality from respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) who would benefit most from RSV prevention products. The objective was to develop and internally validate a personalized risk prediction tool for use among all newborns that uses readily available birth/postnatal data to predict RSV LRTI requiring intensive care unit (ICU) admission.

Methods
We conducted a population-based birth cohort study of infants born from 1995 to 2007, insured by the Tennessee Medicaid Program, and who did not receive RSV immunoprophylaxis during the first year of life. The primary outcome was severe RSV LRTI requiring ICU admission during the first year of life. We built a multivariable logistic regression model including demographic and clinical variables available at or shortly after birth to predict the primary outcome.

Results
In a population-based sample of 429 365 infants, 713 (0.2%) had severe RSV LRTI requiring ICU admission. The median age of admission was 66 days (interquartile range, 37–120). Our tool, including 19 variables, demonstrated good predictive accuracy (area under the curve, 0.78; 95% confidence interval, 0.77-0.80) and identified infants who did not qualify for palivizumab, based on American Academy of Pediatrics guidelines, but had higher predicted risk levels than infants who qualified (27% of noneligible infants with &gt;0.16% predicted probabilities [lower quartile for eligible infants]).

Conclusions
We developed a personalized tool that identified infants at increased risk for severe RSV LRTI requiring ICU admission, expected to benefit most from immunoprophylaxis.
Pregnancy in antiphospholipid syndrome: what should a rheumatologist know?
Authors: Andreoli Laura , Regola Francesca , Caproli Alessia , Crisafulli Francesca , Fredi Micaela , Lazzaroni Maria-Grazia , Nalli Cecilia , Piantoni Silvia , Zatti Sonia , Franceschini Franco , Tincani Angela 
Published: February 2024

Abstract
This review focuses on the management of reproductive issues in women who have antiphospholipid syndrome (APS) or are carriers of antiphospholipid antibodies (aPL). The importance of aPL detection during preconception counselling relies on their pathogenic potential for placental insufficiency and related obstetric complications. The risk of adverse pregnancy outcomes can be minimized by individualized risk stratification and tailored treatment aimed at preventing placental insufficiency. Combination therapy of low-dose acetylsalicylic acid and heparin is the mainstay of prophylaxis during pregnancy; immunomodulation, especially with hydroxychloroquine, should be considered in refractory cases. Supplementary ultrasound surveillance is useful to detect fetal growth restriction and correctly tailor the time of delivery. The individual aPL profile must be considered in the stratification of thrombotic risk, such as during assisted reproduction techniques requiring hormonal ovarian stimulation or during the follow-up after pregnancy in order to prevent the first vascular event.
Revealing novel genomic insights and therapeutic targets for juvenile idiopathic arthritis through omics
Authors: Fan Jingxian , Li Xiumei , Yang Jie , Zhang Sipeng , Qu Hui-Qi , Ji Dandan , Glessner Joseph T , Hao Jian , Ding Zhiyong , Wang Nan , Meng Xinyi , Xia Qianghua , Hakonarson Hakon , Wei Wei , Li Jin 
Published: February 2024

Abstract

Background
The genetic architecture of JIA remains only partially comprehended. There is a clear imperative for continued endeavours to uncover insights into the underlying causes of JIA.

Methods
This study encompassed a comprehensive spectrum of endeavours, including conducting a JIA genome-wide association study (GWAS) meta-analysis that incorporated data from 4550 JIA cases and 18 446 controls. We employed in silico and genome-editing approaches to prioritizing target genes. To investigate pleiotropic effects, we conducted phenome-wide association studies. Cell-type enrichment analyses were performed by integrating bulk and single-cell sequencing data. Finally, we delved into potential druggable targets for JIA.

Results
Fourteen genome-wide significant non-HLA loci were identified, including four novel loci, each exhibiting pleiotropic associations with other autoimmune diseases or musculoskeletal traits. We uncovered strong genetic correlation between JIA and BMD traits at 52 genomic regions, including three GWAS loci for JIA. Candidate genes with immune functions were captured by in silico analyses at each novel locus, with additional findings identified through our experimental approach. Cell-type enrichment analysis revealed 21 specific immune cell types crucial for the affected organs in JIA, indicating their potential contribution to the disease. Finally, 24 known or candidate druggable target genes were prioritized.

Conclusions
Our identification of four novel JIA-associated genes, CD247, RHOH, COLEC10 and IRF8, broadens the novel potential drug repositioning opportunities. We established a new genetic link between COLEC10, TNFRSF11B and JIA/BMD. Additionally, the identification of RHOH underscores its role in positive thymocyte selection, thereby illuminating a critical facet of JIA’s underlying biological mechanisms.
Efficacy and safety of neoadjuvant sintilimab in combination with FLOT chemotherapy in patients with HER2-negative locally advanced gastric or gastroesophageal junction adenocarcinoma: an investigator-initiated, single-arm, open-label, phase II study
Authors: Li Ning , Li Zhi , Fu Qiang , Zhang Bin , Zhang Jian , Wan Xiang-Bin , Lu Chao-Min , Wang Jin-Bang , Deng Wen-Ying , Ma Yi-Jie , Bie Liang-Yu , Wang Meng-Yu , Li Jing , Xia Qing-Xin , Wei Chen , Luo Su-Xia 
Published: February 2024

Background:
The addition of immune checkpoint inhibitors to neoadjuvant chemotherapy in operable advanced gastric or gastroesophageal junction (G/GEJ) cancer aroused wide interest. This study was designed to assess the efficacy and safety of neoadjuvant sintilimab, a programmed cell death protein-1 (PD-1) inhibitor, in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy for HER2-negative locally advanced G/GEJ cancer.

Methods:
Eligible patients with clinical stage cT4 and/or cN+M0 G/GEJ cancer were enroled in this phase II study. Patients received neoadjuvant sintilimab (200 mg every 3 weeks) for three cycles plus FLOT (50 mg/m2 docetaxel, 80 mg/m2 oxaliplatin, 200 mg/m2 calcium levofolinate, 2600 mg/m2 5-fluorouracil every 2 weeks) for four cycles before surgery, followed by four cycles of adjuvant FLOT with same dosages after resection. The primary endpoint was the pathological complete response (pCR) rate.

Results:
Thirty-two patients were enroled between August 2019 and September 2021, with a median follow-up of 34.8 (95% CI, 32.8–42.9) months. Thirty-two (100%) patients received neoadjuvant therapy, and 29 underwent surgery with an R0 resection rate of 93.1%. The pCR (TRG0) was achieved in 5 (17.2%; 95% CI, 5.8–35.8%) patients, and the major pathological response was 55.2%. Twenty-three (79.3%) patients had T downstaging, 21 (72.4%) had N downstaging, and 19 (65.5%) had overall TNM downstaging. Six (20.7%) patients experienced recurrence. Patients achieving pCR showed better event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) than non-pCR. The estimated 3-year EFS rate, 3-year DFS rate, and 3-year OS rate were 71.4% (95% CI, 57.2–89.2%), 78.8% (95% CI, 65.1–95.5%), and 70.9% (95% CI, 54.8–91.6%), respectively. The objective response rate and disease control rate were 84.4% (95% CI, 68.3–93.1%) and 96.9% (95% CI, 84.3–99.5%), respectively. Twenty-five (86.2%) received adjuvant therapy. The main grade ≥3 treatment-related adverse events (TRAEs) were lymphopenia (34.4%), neutropenia (28.1%), and leukopenia (15.6%). no patients died from TRAE. The LDH level exhibited a better predictive value to pathological responses than PD-L1 and MSI status.

Conclusions:
The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant sintilimab plus FLOT in HER2-negative locally advanced G/GEJ cancer, which suggested a potential therapeutic option for this population.
Vascular Complications and Outcomes Following Transcatheter Aortic Valve Replacement in Patients on Chronic Steroid Therapy. A meta-analysis
Authors: Ang Song Peng , Chia Jia Ee , Jaiswal Vikash , Hanif Muhammed , Vadhera Ananya , Gautam Sudarshan , Raut Anuradha , Rafaqat Saira , Borra Vamsikalyan Reddy , Khandait Harshwardhan , Shrestha Abhigan Babu , Iglesias Jose 
Published: February 2024

Background:Chronic steroid (CS) therapy was reportedly linked to increased vascular complications following percutaneous coronary intervention. However, its association with vascular complications after transcatheter aortic valve replacement (TAVR) remained uncertain, with conflicting results being reported.Objective:We aimed to compare the rate of vascular complications and outcomes between patients with and without (CS) use after TAVR.Methods:We conducted a comprehensive literature search in PubMed, Embase and Cochrane databases from their inception until 18th April 2022 for relevant studies. Endpoints were described according to Valve Academic Research Consortium-2 definitions. Effect sizes were pooled using DerSimonian and Laird random-effects model as risk ratio (RR) with 95% confidence intervals (CI).Results:5 studies with 6136 patients undergoing TAVR were included in the analysis. The included studies were published between 2015 and 2022. The mean ages of patients in both study groups were similar, with the CS group averaging 80 years and the non-steroid group averaging 82 years. Notably, a higher proportion of patients in the CS group were female (56%) compared to the non-steroid group (54%). CS use was associated with a significantly higher risk of major vascular complications (12.5% vs. 6.7%, RR 2.32, 95% CI 1.73-3.11,P<0.001), major bleeding (16.8% vs. 13.1%, RR 1.61, 95% CI 1.27-2.05,P<0.001), and aortic annulus rupture (2.3% vs. 0.6%, RR 4.66, 95% CI 1.67-13.01,P<0.001). There was no significant difference in terms of minor vascular complications (RR 1.43, 95% CI 1.00-2.04,P=0.05), in-hospital mortality (2.3% vs. 1.4%, RR 1.86, 95% CI 0.74-4.70,P=0.19), and 30-day mortality (2.9% vs. 3.1%, RR 1.14, 95% CI 0.53-2.46,P=0.74) between both groups.Conclusion:Our study showed that CS therapy is associated with increased major vascular complications, major bleeding, and annulus rupture following TAVR. Further large multicenter studies or randomized controlled trials are warranted to validate these findings.