bluuebunny/crossref_metadata_2025_split huggingface dataset:
IbNF‐YA1 is a key factor in the storage root development of sweet potato
Authors: Xue Luyao , Wang Yuxin , Fan Yue , Jiang Zhicheng , Wei Zihao , Zhai Hong , He Shaozhen , Zhang Huan , Yang Yufeng , Zhao Ning , Gao Shaopei , Liu Qingchang 
Published: March 2024

SUMMARYAs a major worldwide root crop, the mechanism underlying storage root yield formation has always been a hot topic in sweet potato [Ipomoea batatas (L.) Lam.]. Previously, we conducted the transcriptome database of differentially expressed genes between the cultivated sweet potato cultivar “Xushu18,” its diploid wild relative Ipomoea triloba without storage root, and their interspecific somatic hybrid XT1 with medium‐sized storage root. We selected one of these candidate genes, IbNF‐YA1, for subsequent analysis. IbNF‐YA1 encodes a nuclear transcription factor Y subunit alpha (NF‐YA) gene, which is significantly induced by the natural auxin indole‐3‐acetic acid (IAA). The storage root yield of the IbNF‐YA1 overexpression (OE) plant decreased by 29.15–40.22% compared with the wild type, while that of the RNAi plant increased by 10.16–21.58%. Additionally, IAA content increased significantly in OE plants. Conversely, the content of IAA decreased significantly in RNAi plants. Furthermore, real‐time quantitative reverse transcription‐PCR (qRT‐PCR) analysis demonstrated that the expressions of the key genes IbYUCCA2, IbYUCCA4, and IbYUCCA8 in the IAA biosynthetic pathway were significantly changed in transgenic plants. The results indicated that IbNF‐YA1 could directly target IbYUCCA4 and activate IbYUCCA4 transcription. The IAA content of IbYUCCA4 OE plants increased by 71.77–98.31%. Correspondingly, the storage root yield of the IbYUCCA4 OE plant decreased by 77.91–80.52%. These findings indicate that downregulating the IbNF‐YA1 gene could improve the storage root yield in sweet potato.
Computed tomographic features of canine intracranial and jugular foraminal masses involving the combined glossopharyngeal, vagus, and accessory nerve roots
Authors: Lluesma Begoña , Whitley Nathaniel T. , Hughes Jonathan R. 
Published: March 2024

AbstractA chronic cough, gag, or retch is a common presenting clinical complaint in dogs. Those refractory to conservative management frequently undergo further diagnostic tests to investigate the cause, including CT examination of their head, neck, and thorax for detailed morphological assessment of their respiratory and upper gastrointestinal tract. This case series describes five patients with CT characteristics consistent with an intracranial and jugular foraminal mass of the combined glossopharyngeal (IX), vagus (X), and accessory (XI) cranial nerves and secondary features consistent with their paresis. The consistent primary CT characteristics included an intracranial, extra‐axial, cerebellomedullary angle, and jugular foraminal soft tissue attenuating, strongly enhancing mass (5/5). Secondary characteristics included smooth widening of the bony jugular foramen (5/5), mild hyperostosis of the petrous temporal bone (3/5), isolated severe atrophy of the ipsilateral sternocephalic, cleidocephalic, and trapezius muscles (5/5), atrophy of the ipsilateral thyroarytenoideus and cricoarytenoideus muscles of the vocal fold (5/5), and an ipsilateral “dropped” shoulder (4/5). Positional variation of the patient in CT under general anesthesia made the “dropped” shoulder of equivocal significance. The reported clinical signs and secondary CT features reflect a unilateral paresis of the combined cranial nerves (IX, X, and XI) and are consistent with jugular foramen syndrome/Vernet's syndrome reported in humans. The authors believe this condition is likely chronically underdiagnosed without CT examination, and this case series should enable earlier CT diagnosis in future cases.
Commuting tuple of multiplication operators homogeneous under the unitary group
Authors: Ghara Soumitra , Kumar Surjit , Misra Gadadhar , Pramanick Paramita 
Published: March 2024

AbstractLet be the group of unitary matrices. We find conditions to ensure that a ‐homogeneous ‐tuple is unitarily equivalent to multiplication by the coordinate functions on some reproducing kernel Hilbert space , . We describe this class of ‐homogeneous operators, equivalently, nonnegative kernels quasi‐invariant under the action of . We classify quasi‐invariant kernels transforming under with two specific choice of multipliers. A crucial ingredient of the proof is that the group has exactly two inequivalent irreducible unitary representations of dimension and none in dimensions , . We obtain explicit criterion for boundedness, reducibility, and mutual unitary equivalence among these operators.
Scedosporiosis and lomentosporiosis: modern perspectives on these difficult-to-treat rare mold infections
Authors: Neoh Chin Fen , Chen Sharon C-A , Lanternier Fanny , Tio Shio Yen , Halliday Catriona L. , Kidd Sarah E. , Kong David C. M. , Meyer Wieland , Hoenigl Martin , Slavin Monica A. 
Published: March 2024

SUMMARYAlthoughScedosporiumspecies andLomentospora prolificansare uncommon causes of invasive fungal diseases (IFDs), these infections are associated with high mortality and are costly to treat with a limited armamentarium of antifungal drugs. In light of recent advances, including in the area of new antifungals, the present review provides a timely and updated overview of these IFDs, with a focus on the taxonomy, clinical epidemiology, pathogenesis and host immune response, disease manifestations, diagnosis, antifungal susceptibility, and treatment. An expansion of hosts at risk for these difficult-to-treat infections has emerged over the last two decades given the increased use of, and broader population treated with, immunomodulatory and targeted molecular agents as well as wider adoption of antifungal prophylaxis. Clinical presentations differ not only between genera but also across the differentScedosporiumspecies.L. prolificansis intrinsically resistant to most currently available antifungal agents, and the prognosis of immunocompromised patients with lomentosporiosis is poor. Development of, and improved access to, diagnostic modalities for early detection of these rare mold infections is paramount for timely targeted antifungal therapy and surgery if indicated. New antifungal agents (e.g., olorofim, fosmanogepix) with novel mechanisms of action and less cross-resistance to existing classes, availability of formulations for oral administration, and fewer drug-drug interactions are now in late-stage clinical trials, and soon, could extend options to treat scedosporiosis/lomentosporiosis. Much work remains to increase our understanding of these infections, especially in the pediatric setting. Knowledge gaps for future research are highlighted in the review.
Retracted and republished from: “The current state of research on influenza antiviral drug development: drugs in clinical trial and licensed drugs”
Authors: Li Yanbai , Huo Shanshan , Yin Zhe , Tian Zuguang , Huang Fang , Liu Peng , Liu Yue , Yu Fei 
Published: March 2024

ABSTRACT

Influenza viruses (IVs) threaten global human health due to the high morbidity, infection, and mortality rates. Currently, the influenza drugs recommended by the Food and Drug Administration are oseltamivir, zanamivir, peramivir, and baloxavir marboxil. These recommended antivirals are currently effective for major subtypes of IVs as the compounds target conserved domains in neuraminidase or polymerase acidic (PA) protein. However, this trend may gradually change due to the selection of antiviral drugs and the natural evolution of IVs. Therefore, there is an urgent need to develop drugs related to the treatment of influenza to deal with the next pandemic. Here, we summarized the cutting-edge research in mechanism of action, inhibitory activity, and clinical efficacy of drugs that have been approved and drugs that are still in clinical trials for influenza treatment. We hope this review will provide up-to-date and comprehensive information on influenza antivirals and generate hypotheses for screens and development of new broad-spectrum influenza drugs in the near future.
Structural analysis of resistance-nodulation cell division transporters
Authors: Klenotic Philip A. , Yu Edward W. 
Published: March 2024

SUMMARY
Infectious bacteria have both intrinsic and acquired mechanisms to combat harmful biocides that enter the cell. Through adaptive pressures, many of these pathogens have become resistant to many, if not all, of the current antibiotics used today to treat these often deadly infections. One prominent mechanism is the upregulation of efflux systems, especially the resistance-nodulation-cell division class of exporters. These tripartite systems consist of an inner membrane transporter coupled with a periplasmic adaptor protein and an outer membrane channel to efficiently transport a diverse array of substrates from inside the cell to the extracellular space. Detailed mechanistic insight into how these inner membrane transporters recognize and shuttle their substrates can ultimately inform both new antibiotic and efflux pump inhibitor design. This review examines the structural basis of substrate recognition of these pumps and the molecular mechanisms underlying multidrug extrusion, which in turn mediate antimicrobial resistance in bacterial pathogens.
Modelling the potential clinical and economic impact of universal antenatal hepatitis C (HCV) screening and providing treatment for pregnant women with HCV and their infants in Egypt: a cost-effectiveness study
Authors: Hachicha-Maalej Nadia , Lepers Clotilde , Collins Intira Jeannie , Mostafa Aya , Ades Anthony E , Judd Ali , Scott Karen , Gibb Diana M , Pett Sarah , Indolfi Giuseppe , Yazdanpanah Yazdan , El Sayed Manal H , Deuffic-Burban Sylvie 
Published: March 2024

Backgrounds and aimsPregnant women and children are not included in Egypt’s hepatitis C virus (HCV) elimination programmes. This study assesses the cost-effectiveness of several screening and treatment strategies for pregnant women and infants in Egypt.DesignA Markov model was developed to simulate the cascade of care and HCV disease progression among pregnant women and their infants according to different screening and treatment strategies, which included: targeted versus universal antenatal screening; treatment of women in pregnancy or deferred till after breast feeding; treatment of infected children at 3 years vs 12 years. Current practice is targeted antenatal screening with deferred treatment for the mother and child. We also explored prophylactic treatment after birth for children of diagnosed HCV-infected women. Discounted lifetime cost, life expectancy (LE) and disability-adjusted life-years (DALYs) were calculated separately for women and their infants, and then combined.ResultsCurrent practice led to the highest cost (US$314.0), the lowest LE (46.3348 years) and the highest DALYs (0.0512 years) per mother–child pair. Universal screening and treatment during pregnancy followed by treatment of children at 3 years would be less expensive and more effective (cost saving) compared with current practice (US$219.3, 46.3525 and 0.0359 years). Prophylactic treatment at birth for infants born to HCV RNA-positive mothers would also be similarly cost saving, even with treatment uptake as low as 15% (US$218.6, 46.3525 and 0.0359 years). Findings were robust to reasonable changes in parameters.ConclusionUniversal screening and treatment of HCV in pregnancy, with treatment of infected infants at age 3 years is cost saving compared with current practice in the Egyptian setting.
Treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis: a comprehensive review
Authors: Villard Christina , Jorns Carl , Bergquist Annika 
Published: March 2024

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease, characterised by persistent biliary inflammation resulting in fibrosis and multifocal strictures of the biliary tree. The course of disease is highly variable, ranging from asymptomatic disease to the development of end-stage biliary cirrhosis and an increased risk of biliary tract cancer (BTC), particularly cholangiocarcinoma (CCA).PSC is the most important risk factor for CCA in younger people, with a reported lifetime prevalence ranging from 6% to 13%. Perihilar CCA (pCCA), involving the hepatic duct bifurcation, is the most common CCA amounting to approximately 50% of all cases, whereas intrahepatic CCA (iCCA), located within the hepatic parenchyma, represents less than 10%.CCA is an aggressive tumour, and only a minority of patients are amenable to surgical resection with curative intent. Radical liver resection and liver transplantation are potentially curative therapeutic options in patients with PSC in the absence of metastatic or locally advanced disease. Liver transplantation with neoadjuvant chemoradiation could be considered in selected patients with unresectable pCCA and without pretreatment in patients with PSC with bile duct high-grade dysplasia. Recent reports demonstrating favourable outcomes in transplanted patients with small iCCA and patients with locally advanced disease following neoadjuvant therapy have challenged the previously described poor outcome in transplanted patients with iCCA.Treatment for CCA is challenged by the inherent difficulties in enabling an early diagnosis and thereby preventing an otherwise dismal prognosis. This comprehensive review aims to describe therapeutic considerations and challenges in patients with PSC-CCA.
GD2-Targeting CAR T-cell Therapy for Patients with GD2+ Medulloblastoma
Authors: Ciccone Roselia , Quintarelli Concetta , Camera Antonio , Pezzella Michele , Caruso Simona , Manni Simona , Ottaviani Alessio , Guercio Marika , Del Bufalo Francesca , Quadraccia Maria Cecilia , Orlando Domenico , Di Cecca Stefano , Sinibaldi Matilde , Aurigemma Mariasole , Iaffaldano Laura , Sarcinelli Andrea , D'Amore Maria Luisa , Ceccarelli Manuela , Nazio Francesca , Marabitti Veronica , Giorda Ezio , Pezzullo Marco , De Stefanis Cristiano , Carai Andrea , Rossi Sabrina , Alaggio Rita , Del Baldo Giada , Becilli Marco , Mastronuzzi Angela , De Angelis Biagio , Locatelli Franco 
Published: March 2024

Abstract

Purpose:
Medulloblastoma (MB), the most common childhood malignant brain tumor, has a poor prognosis in about 30% of patients. The current standard of care, which includes surgery, radiation, and chemotherapy, is often responsible for cognitive, neurologic, and endocrine side effects. We investigated whether chimeric antigen receptor (CAR) T cells directed toward the disialoganglioside GD2 can represent a potentially more effective treatment with reduced long-term side effects.

Experimental Design:
GD2 expression was evaluated on primary tumor biopsies of MB children by flow cytometry. GD2 expression in MB cells was also evaluated in response to an EZH2 inhibitor (tazemetostat). In in vitro and in vivo models, GD2+ MB cells were targeted by a CAR-GD2.CD28.4-1BBζ (CAR.GD2)-T construct, including the suicide gene inducible caspase-9.

Results:
GD2 was expressed in 82.68% of MB tumors. The SHH and G3–G4 subtypes expressed the highest levels of GD2, whereas the WNT subtype expressed the lowest. In in vitro coculture assays, CAR.GD2 T cells were able to kill GD2+ MB cells. Pretreatment with tazemetostat upregulated GD2 expression, sensitizing GD2dimMB cells to CAR.GD2 T cells cytotoxic activity. In orthotopic mouse models of MB, intravenously injected CAR.GD2 T cells significantly controlled tumor growth, prolonging the overall survival of treated mice. Moreover, the dimerizing drug AP1903 was able to cross the murine blood–brain barrier and to eliminate both blood-circulating and tumor-infiltrating CAR.GD2 T cells.

Conclusions:
Our experimental data indicate the potential efficacy of CAR.GD2 T-cell therapy. A phase I/II clinical trial is ongoing in our center (NCT05298995) to evaluate the safety and therapeutic efficacy of CAR.GD2 therapy in high-risk MB patients.
Solid Organ Transplant Recipients Exhibit More TET2-Mutant Clonal Hematopoiesis of Indeterminate Potential Not Driven by Increased Transplantation Risk
Authors: Silver Alexander J. , Vlasschaert Caitlyn , Mack Taralynn , Sharber Brian , Xu Yaomin , Bick Alexander G. , Pinson C. Wright , Savona Michael R. 
Published: March 2024

Abstract

Purpose:
Solid organ transplant recipients comprise a unique population of immunosuppressed patients with increased risk of malignancy, including hematologic neoplasms. Clonal hematopoiesis of indeterminate potential (CHIP) represents a known risk factor for hematologic malignancy and this study describes the prevalence and patterns of CHIP mutations across several types of solid organ transplants.

Experimental Design:
We use two national biobank cohorts comprised of &gt;650,000 participants with linked genomic and longitudinal phenotypic data to describe the features of CHIP across 2,610 individuals who received kidney, liver, heart, or lung allografts.

Results:
We find individuals with an allograft before their biobank enrollment had an increased prevalence of TET2 mutations (OR, 1.90; P = 4.0e−4), but individuals who received transplants post-enrollment had a CHIP mutation spectrum similar to that of the general population, without enrichment of TET2. In addition, we do not observe an association between CHIP and risk of incident transplantation among the overall population (HR, 1.02; P = 0.91). And in an exploratory analysis, we do not find evidence for a strong association between CHIP and rates of transplant complications such as rejection or graft failure.

Conclusions:
These results demonstrate that recipients of solid organ transplants display a unique pattern of clonal hematopoiesis with enrichment of TET2 driver mutations, the causes of which remain unclear and are deserving of further study.
BRCA1-Mediated Dual Regulation of Ferroptosis Exposes a Vulnerability to GPX4 and PARP Co-Inhibition in BRCA1-Deficient Cancers
Authors: Lei Guang , Mao Chao , Horbath Amber D. , Yan Yuelong , Cai Shirong , Yao Jun , Jiang Yan , Sun Mingchuang , Liu Xiaoguang , Cheng Jun , Xu Zhihao , Lee Hyemin , Li Qidong , Lu Zhengze , Zhuang Li , Chen Mei-Kuang , Alapati Anagha , Yap Timothy A. , Hung Mien-Chie , You Mingjian James , Piwnica-Worms Helen , Gan Boyi 
Published: March 2024

Abstract
Resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) limits the therapeutic efficacy of PARP inhibition in treating breast cancer susceptibility gene 1 (BRCA1)-deficient cancers. Here we reveal that BRCA1 has a dual role in regulating ferroptosis. BRCA1 promotes the transcription of voltage-dependent anion channel 3 (VDAC3) and glutathione peroxidase 4 (GPX4); consequently, BRCA1 deficiency promotes cellular resistance to erastin-induced ferroptosis but sensitizes cancer cells to ferroptosis induced by GPX4 inhibitors (GPX4i). In addition, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and defective GPX4 induction unleash potent ferroptosis in BRCA1-deficient cancer cells upon PARPi and GPX4i co-treatment. Finally, we show that xenograft tumors derived from patients with BRCA1-mutant breast cancer with PARPi resistance exhibit decreased GPX4 expression and high sensitivity to PARP and GPX4 co-inhibition. Our results show that BRCA1 deficiency induces a ferroptosis vulnerability to PARP and GPX4 co-inhibition and inform a therapeutic strategy for overcoming PARPi resistance in BRCA1-deficient cancers.
Significance: BRCA1 deficiency promotes resistance to erastin-induced ferroptosis via blocking VDAC3 yet renders cancer cells vulnerable to GPX4i-induced ferroptosis via inhibiting GPX4. NCOA4 induction and defective GPX4 further synergizes GPX4i with PARPi to induce ferroptosis in BRCA1-deficient cancers and targeting GPX4 mitigates PARPi resistance in those cancers.
See related commentary by Alborzinia and Friedmann Angeli, p. 1372
Spatially Segregated Macrophage Populations Predict Distinct Outcomes in Colon Cancer
Authors: Matusiak Magdalena , Hickey John W. , van IJzendoorn David G.P. , Lu Guolan , Kidziński Lukasz , Zhu Shirley , Colburg Deana R.C. , Luca Bogdan , Phillips Darci J. , Brubaker Sky W. , Charville Gregory W. , Shen Jeanne , Loh Kyle M. , Okwan-Duodu Derick K. , Nolan Garry P. , Newman Aaron M. , West Robert B. , van de Rijn Matt 
Published: March 2024

Abstract
Tumor-associated macrophages are transcriptionally heterogeneous, but the spatial distribution and cell interactions that shape macrophage tissue roles remain poorly characterized. Here, we spatially resolve five distinct human macrophage populations in normal and malignant human breast and colon tissue and reveal their cellular associations. This spatial map reveals that distinct macrophage populations reside in spatially segregated micro-environmental niches with conserved cellular compositions that are repeated across healthy and diseased tissue. We show that IL4I1+ macrophages phagocytose dying cells in areas with high cell turnover and predict good outcome in colon cancer. In contrast, SPP1+ macrophages are enriched in hypoxic and necrotic tumor regions and portend worse outcome in colon cancer. A subset of FOLR2+ macrophages is embedded in plasma cell niches. NLRP3+ macrophages co-localize with neutrophils and activate an inflammasome in tumors. Our findings indicate that a limited number of unique human macrophage niches function as fundamental building blocks in tissue.
Significance: This work broadens our understanding of the distinct roles different macrophage populations may exert on cancer growth and reveals potential predictive markers and macrophage population-specific therapy targets.