bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orphan gene BR2 positively regulates bolting resistance through the vernalization pathway in Chinese cabbage
Authors: Zu Ye , Jiang Mingliang , Zhan Zongxiang , Li Xiaonan , Piao Zhongyun 
Published: July 2024

Abstract
Orphan genes (OGs) are unique to the specific species or lineage, and whose homologous sequences cannot be found in other species or lineages. Furthermore, these genes lack recognizable domains or functional motifs, which make their characterization difficult. Here, we identified a Brassica rapa OG named BOLTING RESISTANCE 2 (BR2) that could positively modulate bolting resistance. The expression of BR2 was developmentally regulated and the BR2 protein was localized to the cell membrane. BR2 overexpression not only markedly delayed flowering time in Arabidopsis transgenic plants, but substantially affected the development of leaves and flower organs. Flowering repressor AtFLC gene was significantly up-regulated transcribed in Arabidopsis BR2 overexpression lines, while AtFT and AtSOC1 expression was decreased. In addition, the BR2 expression was enhanced in bolting-resistant type Chinese cabbage and was reduced in non-resistant type. Moreover, chilling stress inhibited the BR2 expression levels. Overexpression of BR2 also delayed flowering time in Chinese cabbage. In vernalized Chinese cabbage BR2 overexpression plants, BrVIN3.b and BrFRI were significantly down-regulated, while BrFLC5 was substantially up-regulated. Key floral factors, including three BrSOC1s, two BrLFYs, and four BrFTs were down-regulated. The expression changes of these key genes were consistent with the delayed flowering phenotype of Chinese cabbage BR2 overexpressing plants. Thus, we predicted that BR2 may predominantly function via the vernalization pathway. Our findings propose that the OG BR2 acts as a novel modulator of flowering time in Chinese cabbage, which provides a new insight on the breeding of varieties that are resistant to bolting.
Ibuprofen as an adjuvant to conventional antimicrobials and essential oil compounds against skin pathogens
Authors: Simbu Shivar , Orchard Ané , van de Venter Maryna , van Vuuren Sandy 
Published: July 2024

Abstract

Aims
Antimicrobial resistance continues to be a growing concern, resulting in increased use of drug combinations. Antibiotic adjuvants are an emerging strategy that may potentiate an antibiotics efficacy. Ibuprofen’s polypharmacological properties have been investigated for their antimicrobial and host-modulating potential. This study aimed to investigate the potential of a novel multidrug combination involving ibuprofen, essential oil compounds (EOCs), and conventional antimicrobials against skin pathogens.

Methods and Results
The minimum inhibitory concentrations of ibuprofen, conventional antimicrobials, and EOCs were determined and then combined and tested against 14 (reference and clinical) skin pathogens. The cytotoxicity was analysed using the MTT assay, whilst the anti-inflammatory effects were evaluated using lipopolysaccharide activated RAW264.7 murine macrophages. Four pairwise (Ibuprofen and antibiotic) (ΣFIC 0.33–0.50) and three triple (Ibuprofen and antibiotic with EOC) (ΣFIC 0.44–0.47) synergistic antimicrobial interactions were identified. These combinations demonstrated cell viability of 77.59%–100%. No combination significantly reduced nitric oxide production.

Conclusion
The results from this study provide insight into the potential of a multidrug combination involving ibuprofen with conventional antimicrobials and EOCs against common skin pathogens.
A rare presentation of inguinal mass in postmenopausal women: leiomyoma of round ligament mimicking an irreducible inguinal hernia
Authors: Alshuqayfi Hind A , Alotaibi Abdulaziz F , Alkhaldi May S , Alghazwi Abdulaziz A , Alghazwi Mohammed A , Ibrahim Arwa H , Alsolami Sana S 
Published: July 2024

Abstract
Tumors of the round ligament rarely happen; leiomyomas are considered the most common. Round ligament leiomyomas are benign tumors mimicking inguinal hernia, lymph nodes, or other inguinal masses. They are usually asymptomatic and take place in premenopausal female patients. This paper will present a case of a postmenopausal female patient who presented to our outpatient surgical clinic complaining of a right groin mass for 3 months. She was clinically diagnosed as a case of an irreducible inguinal hernia. After investigations, it turned out to be a round ligament leiomyoma, confirmed by the histopathological examination. There are broad differential diagnoses of inguinal masses. Although imaging exams could help diagnose leiomyomas, surgical excision followed by histopathological assessment is the best to confirm the diagnoses.
Classical computation over quantum architectures
Authors: Della Schiava Alex , Piazza Carla , Romanello Riccardo 
Published: August 2024

Abstract
The lack of purely Quantum Programming Languages constitutes a hurdle in the general description of quantum computational processes; the implementation is heavily dependent on the considered quantum computational model. To bypass the obstacle, this paper pursues a new direction, investigating the compilation of classical programming paradigms over different quantum computational models: Gate-Based, Measurement-Based and Adiabatic Quantum Computation. Since graphs can be exploited to describe both classical and quantum computations, the problem of graph encoding on quantum hardware is tightly connected to our purposes. As such, it holds a major relevance in our quest for quantum compilation. While studying these topics through the lenses of Graph Theory, declarative programming emerges as the ideal candidate for such endeavour. In this paper we consider some existing quantum computational models and for each of them we identify the main subtleties in the compilation of classical languages. In turn, we break these complexities down into easier problems to stimulate further developments in this area of research. As it turns out, the observations for each model differ widely. Nevertheless, as for the tasks here considered, no model seems to claim supremacy over the others. In contrast, declarative programming maintains the spot as the ideal candidate for quantum compilation, independently of the model.
Hyperfine structure of the methanol molecule as traced by Class I methanol masers
Authors: Agafonova I I , Bayandina O S , Gong Y , Henkel C , Kim Kee-Tae , Kozlov M G , Lankhaar B , Levshakov S A , Menten K M , Ubachs W , Val’tts I E , Yang W 
Published: July 2024

ABSTRACT
We present results on simultaneous observations of Class I methanol masers at 25, 36, and 44 GHz towards 22 Galactic targets carried out with the Effelsberg 100-m telescope. The study investigates relations between the hyperfine (HF) structure of the torsion–rotation transitions in CH$_3$OH and maser activity. By analysing the radial velocity shifts between different maser lines together with the patterns of the HF structure based on laboratory measurements and quantum-chemical calculations, we find that in any source only one specific HF transition forms the maser emission and that this transition changes from source to source. The physical conditions leading to this selective behaviour are still unclear. Using accurate laboratory rest frequencies for the 25 GHz transitions, we have refined the centre frequencies for the HF multiplets at 36, 44, and 95 GHz: $f_{\scriptscriptstyle 36} = (36169.2488\pm 0.0002_{\scriptscriptstyle \rm stat} \pm 0.0004_{\scriptscriptstyle \rm sys})$ MHz. $f_{\scriptscriptstyle 44} = (44069.4176\pm 0.0002_{\scriptscriptstyle \rm stat} \pm 0.0004_{\scriptscriptstyle \rm sys})$ MHz, and $f_{\scriptscriptstyle 95} = (95169.4414\pm 0.0003_{\scriptscriptstyle \rm stat} \pm 0.0004_{\scriptscriptstyle \rm sys})$ MHz. Comparison with previous observations of 44 GHz masers performed 6–10 yr ago with a Korean 21-m Korean Very Long Baseline Interferometry Network telescope towards the same targets confirms the kinematic stability of Class I maser line profiles during this time interval and reveals a systematic radial velocity shift of $0.013\pm 0.005$ km s$^{-1}$ between the two telescopes.
Growth of high-redshift supermassive black holes from heavy seeds in the BRAHMA cosmological simulations: implications of overmassive black holes
Authors: Bhowmick Aklant K , Blecha Laura , Torrey Paul , Somerville Rachel S , Kelley Luke Zoltan , Vogelsberger Mark , Weinberger Rainer , Hernquist Lars , Sivasankaran Aneesh 
Published: July 2024

ABSTRACT
JWST has revealed a large population of accreting black holes (BHs) in the early Universe. Recent work has shown that even after accounting for possible systematic biases, the high-z$M_*{\!-\!}M_{\rm \rm bh}$ relation can be above the local scaling relation by $\gt 3\sigma$. To understand the implications of these overmassive high-z BHs, we study the BH growth at $z\sim 4{\!-\!}7$ using the $[18~\mathrm{Mpc}]^3$BRAHMA cosmological simulations with systematic variations of heavy seed models that emulate direct collapse black hole (DCBH) formation. In our least restrictive seed model, we place $\sim 10^5~{\rm M}_{\odot }$ seeds in haloes with sufficient dense and metal-poor gas. To model conditions for direct collapse, we impose additional criteria based on a minimum Lyman Werner flux (LW flux $=10~J_{21}$), maximum gas spin, and an environmental richness criterion. The high-z BH growth in our simulations is merger dominated, with a relatively small contribution from gas accretion. The simulation that includes all the above seeding criteria fails to reproduce an overmassive high-z$M_*{\!-\!}M_{\rm bh}$ relation consistent with observations (by factor of $\sim 10$ at $z\sim 4$). However, more optimistic models that exclude the spin and environment based criteria are able to reproduce the observed relations if we assume $\lesssim 750~\mathrm{Myr}$ delay times between host galaxy mergers and subsequent BH mergers. Overall, our results suggest that current JWST observations may be explained with heavy seeding channels if their formation is more efficient than currently assumed DCBH conditions. Alternatively, we may need higher initial seed masses, additional contributions from lighter seeds to BH mergers, and / or more efficient modes for BH accretion.
Efficacy and safety of sarilumab in patients with rheumatoid arthritis stratified by age (&lt;65 and ≥65 years): A post hoc analysis of Japanese Phase 3 clinical trials
Authors: Tanaka Yoshiya , Takahashi Toshiya , van Hoogstraten Hubert , Kato Naoto , Kameda Hideto 
Published: July 2024

ABSTRACT

Objectives
This study aimed to assess the efficacy and safety of sarilumab in older patients with active rheumatoid arthritis (RA).

Methods
This is a post hoc analysis of KAKEHASI (NCT02293902) and HARUKA (NCT02373202) trials with stratification by age (&lt;65 and ≥65 years). Patients with moderately to severely active RA were treated with sarilumab in combination with methotrexate or with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or as monotherapy. The primary end points in KAKEHASI and HARUKA trials were the American College of Rheumatology 20% improvement criteria (ACR20) responses at Week 24 and safety, respectively. Secondary end points were other RA disease activity measures, including Clinical Disease Activity Index (CDAI).

Results
Approximately 20% of patients were aged ≥65 years in treatment arms across both trials, except the sarilumab + csDMARD arm (40%, 12/30). ACR20 response rates were similar between age groups across sarilumab treatment arms, and similar results were obtained for the CDAI scores. Safety profiles were similar between age groups except for a higher incidence of serious adverse events in patients aged ≥65 years in the sarilumab + methotrexate arm.

Conclusions
In Japanese patients with RA enrolled in Phase 3 studies for sarilumab, no clear difference in efficacy or safety was observed between patients aged &lt;65 and ≥65 years.
Phase 1 study of concomitant tumor treating fields and temozolomide chemoradiation for newly diagnosed glioblastoma
Authors: Goldlust Samuel A , Singer Samuel , Cappello Lori A , AlMekkawi Ahmad K , Lee Kangmin D , Ingenito Anthony C , Lewis Brett E , Nyirenda Themba , Azmi Hooman , Kaptain George J 
Published: July 2024

Abstract

Background
Glioblastoma (GBM) is the most common and aggressive primary brain tumor and has limited effective therapies. Tumor treating fields (TTF; Optune Gio®) is an FDA-approved device with data supporting a significant survival benefit and minimal toxicity when added to maintenance chemotherapy. Uptake in clinical practice is not universal and might improve if a shorter duration of treatment is feasible. This phase 1 trial was designed to determine the safety and preliminary efficacy of TTF concomitant to chemoradiation.

Methods
Patients with newly diagnosed, histologically confirmed GBM were eligible. Following surgery, patients were treated with TTF concomitant to standard chemoradiation. The device continued through 2 monthly cycles of maintenance temozolomide with imaging and clinical assessments at regular intervals to assess toxicity and response. The primary endpoint was the safety and tolerability of combined modality treatment based upon the incidence and severity of adverse events. Secondary endpoints were overall survival (OS) and progression-free survival (PFS).

Results
Thirteen patients were enrolled. Dermatologic adverse events were frequent but limited to grade 1/2. There was only 1 serious adverse event possibly related to TTF and no patients were unable to complete the prescribed course of multimodality treatment due to TTF-associated toxicity. Twelve patients were evaluable for median and 6-month progression-free survival which were 8.5 months (mo) and 66.7%, respectively. Median and 12 mo overall survival were 16.0 mo and 83.3%, respectively.

Conclusions
TTF can be safely delivered in conjunction with chemoradiation. The potential for a finite TTF course merits further evaluation.
HNF4α improves hepatocyte regeneration by upregulating PXR
Authors: Qiu Shantong , Pan Yangyang , Cui Yan , Li Mei , Yue Tao , Pu Sisi , Zhang Qian , Wang Meng 
Published: July 2024

AbstractHepatocyte nuclear factor 4 alpha (HNF4α) and the pregnane X receptor (PXR) are involved in hepatocyte regeneration. It is not clear whether HNF4α is involved in hepatocyte regeneration through the regulation of PXR. This study aims to explore the regulatory relationship between HNF4a and PXR, and whether it affects hepatocyte regeneration. A mouse PXR gene reporter and an HNF4α overexpression plasmid were constructed and transfected into mouse hepatoma cells (Hepa1‐6). Overexpression of HNF4α, detection of the PXR gene reporter fluorescence value, PXR gene, and protein expression analysis were conducted to explore the regulatory relationship between HNF4α and PXR. Apoptosis and cell cycle data were measured to verify whether HNF4α is involved in hepatocyte regeneration through PXR. The luciferase gene reporter assay results indicated when HNF4α was overexpressed, the fluorescence value of the PXR gene reporter was higher than that in the control at 24 h. With increasing HNF4α expression, the PXR gene and protein expression increased, indicating that HNF4α binds to the PXR promoter and upregulates PXR expression. Apoptosis and cell cycle analysis results demonstrated that when the expression of HNF4α increased, the expression of PXR increased, the apoptosis rate decreased, and the proliferation rate increased. Meanwhile, when the upward trend of PXR gene expression was inhibited by ketoconazole, the proliferation rate decreased. By inhibiting HNF4α and creating a partial hepatectomy (PHx), we demonstrated that HNF4α can upregulate PXR to promote liver regeneration in vivo. Therefore, HNF4α is shown to improve hepatocyte regeneration by upregulating PXR, which provides a reference for future research on the combined application of drugs for the treatment of liver injury.
The Cost-effectiveness of Valganciclovir Prophylaxis Versus Preemptive Therapy in CMV R+ Kidney Transplant Recipients Over the First Year Posttransplantation
Authors: Villeneuve Claire , Rerolle Jean-Phillipe , Couzi Lionel , Westeel Pierre-Francois , Etienne Isabelle , Esposito Laure , Kamar Nassim , Büchler Mathias , Thierry Antoine , Marquet Pierre , Monchaud Caroline 
Published: July 2024

Background.
In kidney transplant recipients with positive serology (R+) for the cytomegalovirus (CMV), 2 strategies are used to prevent infection, whose respective advantages over the other are still debated. This study aimed to evaluate the cost-effectiveness and cost utility of antiviral prophylaxis against CMV versus preemptive therapy, considering CMV infection–free survival over the first year posttransplantation as the main clinical outcome.

Methods.
Clinical, laboratory, and economic data were collected from 186 kidney transplant patients CMV (R+) included in the cohort study (85 patients who benefited from CMV prophylaxis and 101 from preemptive therapy). Costs were calculated from the hospital perspective and quality-adjusted life years (QALYs) using the EQ5D form. Using nonparametric bootstrapping, the incremental cost-effectiveness ratio (ICER) and cost utility were estimated (euros) for each case of infection avoided and each QALY gained for 1 y, respectively.

Results.
Prophylaxis significantly decreased the risk of CMV infection over the first year posttransplantation (hazard ratio 0.22, 95% confidence interval = 0.12-0.37, P < 0.01). Compared with preemptive therapy, prophylaxis saved financial resources (€1155 per patient) and was more effective (0.42 infection avoided per patient), resulting in an ICER = €2769 per infection avoided. Prophylaxis resulted in a net gain of 0.046 in QALYs per patient and dominated over preemptive therapy with €1422 cost-saving for 1 QALY gained.

Conclusions.
This study shows that CMV prophylaxis, although considered as a more expensive strategy, is more cost-effective than preemptive therapy for the prevention of CMV infections in renal transplant patients. Prophylaxis had a positive effect on quality of life at reasonable costs and resulted in net savings for the hospital.
Expanding the Donor Pool to the Ultimate Level: Introducing the Revolutionary Hybrid Dual Graft Liver Transplant Using Domino and Living Donors
Authors: Zidan Ahmed , Momani Hammam , Sengupta Bodhisatwa , Abdullah Rehab , Bader Razan , Khan Iftikhar , Tawfeeq Mansour , Al Qahtani Mohammed 
Published: July 2024

Background.Innovative solutions are crucial as the demand for liver transplants continues to outpace available grafts. Dual graft liver transplantation offers a promising avenue to address graft volume challenges while minimizing donor risks. This report introduces a groundbreaking approach, combining a full organ domino donor graft with a living donor graft for a hybrid dual graft liver transplant.Brief Report.A 2-y-old child with Maple syrup urine disease and a 40-y-old adult with end-stage liver disease became the focus of this unique case. A hybrid dual graft liver transplant was executed, uniting the domino donor’s full organ graft with a living donor’s left lateral segment. Precise vascular and biliary reconstructions facilitated a successful transplant.Conclusions.The hybrid dual graft liver transplant, merging domino donor and living donor grafts, presents a viable strategy to combat graft shortages, particularly in regions predominantly reliant on living donor transplants. Despite challenges, this pioneering approach should be embraced by established liver transplant centers because it enables concurrent living donor liver transplantation while prioritizing donor safety and recipient outcomes.
Individualized melanoma risk prediction using machine learning with electronic health records
Authors: Wan Guihong , Khattab Sara , Roster Katie , Nguyen Nga , Yan Boshen , Rashdan Hannah , Estiri Hossein , Semenov Yevgeniy R. 
Published: July 2024

ABSTRACTBackgroundMelanoma is a lethal form of skin cancer with a high propensity for metastasizing, making early detection crucial. This study aims to develop a machine learning model using electronic health record data to identify patients at high risk of developing melanoma to prioritize them for dermatology screening.MethodsThis retrospective study included patients diagnosed with melanoma (cases), as well as matched patients without melanoma (controls), from Massachusetts General Hospital (MGH), Brigham and Women’s Hospital (BWH), Dana-Farber Cancer Institute (DFCI), and other hospital centers within the Research Patient Data Registry at Mass General Brigham healthcare system between 1992 and 2022. Patient demographics, family history, diagnoses, medications, procedures, laboratory tests, reasons for visits, and allergy data six months prior to the date of first melanoma diagnosis or date of censoring were extracted. A machine learning framework for health outcomes (MLHO) was utilized to build the model. Performance was evaluated using five-fold cross-validation of the MGH cohort (internal validation) and by using the MGH cohort for model training and the non-MGH cohort for independent testing (external validation). The Area Under the Receiver Operating Characteristic Curve (AUC-ROC) and the Area Under the Precision-Recall Curve (AUC-PR), along with 95% Confidence Intervals (CIs), were computed.ResultsThis study identified 10,778 patients with melanoma and 10,778 matched patients without melanoma, including 8,944 from MGH and 1,834 from non-MGH hospitals in each cohort, both with an average follow-up duration of 9 years. In the internal and external validations, the model achieved AUC-ROC values of 0.826 (95% CI: 0.819–0.832) and 0.823 (95% CI: 0.809–0.837) and AUC-PR scores of 0.841 (95% CI: 0.834–0.848) and 0.822 (95% CI: 0.806–0.839), respectively. Important risk features included a family history of melanoma, a family history of skin cancer, and a prior diagnosis of benign neoplasm of skin. Conversely, medical examination without abnormal findings was identified as a protective feature.ConclusionsMachine learning techniques and electronic health records can be effectively used to predict melanoma risk, potentially aiding in identifying high-risk patients and enabling individualized screening strategies for melanoma.