bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Dual Transcriptomic Approach Reveals Contrasting Patterns of Differential Gene Expression During Drought in Arbuscular Mycorrhizal Fungus and Carrot
Authors: Keller-Pearson Michelle , Bortolazzo Anthony , Willems Luke , Smith Brendan , Peterson Annika , Ané Jean-Michel , Silva Erin M. 
Published: September 2023

While arbuscular mycorrhizal (AM) fungi are known for providing host plants with improved drought tolerance, we know very little about the fungal response to drought in the context of the fungal–plant relationship. In this study, we evaluated the drought responses of the host and symbiont, using the fungus Rhizophagus irregularis with carrot ( Daucus carota) as a plant model. Carrots inoculated with spores of R. irregularis DAOM 197198 were grown in a greenhouse. During taproot development, carrots were exposed to a 10-day water restriction. Compared with well-watered conditions, drought caused diminished photosynthetic activity and reduced plant growth in carrot with and without AM fungi. Droughted carrots had lower root colonization. For R. irregularis, 93% of 826 differentially expressed genes (DEGs) were upregulated during drought, including phosphate transporters, several predicted transport proteins of potassium, and the aquaporin RiAQPF2. In contrast, 78% of 2,486 DEGs in AM carrot were downregulated during drought, including the symbiosis-specific genes FatM, RAM2, and STR, which are implicated in lipid transfer from the host to the fungus and were upregulated exclusively in AM carrot during well-watered conditions. Overall, this study provides insight into the drought response of an AM fungus in relation to its host; the expression of genes related to symbiosis and nutrient exchange were downregulated in carrot but upregulated in the fungus. This study reveals that carrot and R. irregularis exhibit contrast in their regulation of gene expression during drought, with carrot reducing its apparent investment in symbiosis and the fungus increasing its apparent symbiotic efforts. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
New Biochemical Principles for NLR Immunity in Plants
Authors: Chai Jijie , Song Wen , Parker Jane E. 
Published: September 2023

While working for the United States Department of Agriculture on the North Dakota Agricultural College campus in Fargo, North Dakota, in the 1940s and 1950s, Harold H. Flor formulated the genetic principles for coevolving plant host-pathogen interactions that govern disease resistance or susceptibility. His ‘gene-for-gene’ legacy runs deep in modern plant pathology and continues to inform molecular models of plant immune recognition and signaling. In this review, we discuss recent biochemical insights to plant immunity conferred by nucleotide-binding domain/leucine-rich-repeat (NLR) receptors, which are major gene-for-gene resistance determinants in nature and cultivated crops. Structural and biochemical analyses of pathogen-activated NLR oligomers (resistosomes) reveal how different NLR subtypes converge in various ways on calcium (Ca2+) signaling to promote pathogen immunity and host cell death. Especially striking is the identification of nucleotide-based signals generated enzymatically by plant toll-interleukin 1 receptor (TIR) domain NLRs. These small molecules are part of an emerging family of TIR-produced cyclic and noncyclic nucleotide signals that steer immune and cell-death responses in bacteria, mammals, and plants. A combined genetic, molecular, and biochemical understanding of plant NLR activation and signaling provides exciting new opportunities for combatting diseases in crops. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Biocontrol Efficacy and Induced Resistance of Paenibacillus polymyxa J2-4 Against Meloidogyne incognita Infection in Cucumber
Authors: Shi Qianqian , Zhang Jie , Fu Qi , Hao Guangyang , Liang Chen , Duan Fangmeng , Zhao Honghai , Song Wenwen 
Published: September 2023

Meloidogyne incognita is one of the most destructive agricultural pathogens around the world, resulting in severe damage to yield and quality in agricultural production. Biological control promises to be a great potential alternative to chemical agents against M. incognita. Paenibacillus polymyxa J2-4, isolated from ginger plants injured by M. incognita, has shown excellent biocontrol efficacy against M. incognita in cucumber. In vitro experiments with the strain J2-4 resulted in a correct mortality rate of 88.79% (24 h) and 98.57% (48 h) for second-stage juveniles (J2s) of M. incognita. Strain J2-4 significantly suppressed nematode infection on potted plants, with a 65.94% reduction in galls and a 51.64% reduction in eggs compared with the control. The split-root assay demonstrated that strain J2-4 not only reduced J2s’ invasion but also inhibited nematode development through the dependence on salicylic acid and jasmonic acid signaling of strain J2-4 induction of plant resistance in local and systemic roots of cucumbers. Genomic analysis of strain J2-4 indicated biosynthetic gene clusters encoding polymyxin, fusaricidin B, paenilan, and tridecaptin. In addition, genetic analysis showed that none of the genes encoding virulence factors were detected in the genome of J2-4 compared with the pathogenic Bacillus species. Taking all the data together, we conclude that P. polymyxa J2-4 has potential as a biological control agent against M. incognita on cucumbers and can be considered biologically safe when used in agriculture.
Adrenomedullin/FOXO3 enhances sunitinib resistance in clear cell renal cell carcinoma by inhibiting FDX1 expression and cuproptosis
Authors: Wang Xin , Jia Jiang‐Hua , Zhang Ming , Meng Qing‐Song , Yan Bo‐Wen , Ma Zi‐Yue , Wang Dong‐Bin 
Published: September 2023

AbstractCuproptosis, a new type of copper‐induced cell death, is involved in the antitumor activity and resistance of multiple chemotherapeutic drugs. Our previous study revealed that adrenomedullin (ADM) was engaged in sunitinib resistance in clear cell renal cell carcinoma (ccRCC). However, it has yet to be investigated whether and how ADM regulates sunitinib resistance by cuproptosis. This study found that the ADM expression was elevated in sunitinib‐resistant ccRCC tissues and cells. Furthermore, the upregulation of ADM significantly enhanced the chemoresistance of sunitinib compared with their respective control. Moreover, cuproptosis was involved in ADM‐regulated sunitinib resistance by inhibiting mammalian ferredoxin 1 (FDX1) expression. Mechanically, the upregulated ADM activates the p38/MAPK signaling pathway to promote Forkhead box O3 (FOXO3) phosphorylation and its entry into the nucleus. Consequently, the increased FOXO3 in the nucleus inhibited FDX1 transcription and cell cuproptosis, promoting chemoresistance. Collectively, cuproptosis has a critical effector role in ccRCC progress and chemoresistance and thus is a relevant target to eradicate the cell population of sunitinib resistance.
Quizartinib inhibits necroptosis by targeting receptor‐interacting serine/threonine protein kinase 1
Authors: Li Min , Wei Jun , Zhu Guofeng , Fu Shufang , He Xiaoyan , Hu Xinqian , Yu Yajie , Mou Yan , Wang Jia , You Xiaoling , Xiao Xin , Gu Tanrong , Ye Zhi , Zha Yunhong 
Published: September 2023

AbstractSystemic inflammatory response syndrome (SIRS), at least in part driven by necroptosis, is characterized by life‐threatening multiple organ failure. Blocking the progression of SIRS and consequent multiple organ dysfunction is challenging. Receptor‐interacting serine/threonine protein kinase 1 (RIPK1) is an important cell death and inflammatory mediator, making it a potential treatment target in several diseases. Here, using a drug repurposing approach, we show that inhibiting RIPK1 is also an effective treatment for SIRS. We performed cell‐based high‐throughput drug screening of an US Food and Drug Administration (FDA)‐approved drug library that contains 1953 drugs to identify effective inhibitors of necroptotic cell death by SYTOX green staining. Dose–response validation of the top candidate, quizartinib, was conducted in two cell lines of HT‐22 and MEFs. The effect of quizartinib on necroptosis‐related proteins was evaluated using western blotting, immunoprecipitation, and an in vitro RIPK1 kinase assay. The in vivo effects of quizartinib were assessed in a murine tumor necrosis factor α (TNFα)‐induced SIRS model. High‐throughput screening identified quizartinib as the top “hit” in the compound library that rescued cells from necroptosis in vitro. Quizartinib inhibited necroptosis by directly inhibiting RIPK1 kinase activity and blocking downstream complex IIb formation. Furthermore, quizartinib protected mice against TNFα‐induced SIRS. Quizartinib, as an FDA‐approved drug with proven safety and efficacy, was repurposed for targeted inhibition of RIPK1. This work provides essential preclinical data for transferring quizartinib to the treatment of RIPK1‐dependent necroptosis‐induced inflammatory diseases, including SIRS.
Prevalence and correlates of frailty in older hypertensive outpatients according to different tools: the HYPER-FRAIL pilot study
Authors: Rivasi Giulia , Ceolin Ludovica , Turrin Giada , Tortu’ Virginia , D’Andria Maria Flora , Testa Giuseppe Dario , Montali Sara , Tonarelli Francesco , Brunetti Enrico , Bo Mario , Romero-Ortuno Roman , Mossello Enrico , Ungar Andrea 
Published: September 2023

Objectives:
To date, few studies have investigated frailty in hypertensive individuals. This study aimed at identifying the prevalence of frailty in a sample of hypertensive older outpatients using six different identification tools. Clinical correlates of frailty and agreement between different frailty definitions were also investigated.

Methods:
The HYPER-FRAIL pilot study recruited hypertensive patients aged at least 75 years from two geriatric outpatient clinics of Careggi Hospital, Florence, Italy. Four frailty scales [Fried Frailty Phenotype, Frailty Index, Clinical Frailty Scale (CFS), Frailty Postal Score] and two physical performance tests [Short Physical Performance Battery (SPPB) and usual gait speed] were applied. The Cohen's kappa coefficient was calculated to assess agreement between measures. Multiple logistic regression was used to identify clinical features independently associated with frailty.

Results:
Among 121 participants (mean age 81, 60% women), frailty prevalence varied between 33 and 50% according to the tool used. Moderate agreement was observed between Fried Frailty Phenotype, Frailty Index and SPPB, and between Frailty Index and CFS. Agreement was minimal or weak between the remaining measures (K < 0.60). Use of walking aids and depressive symptoms were independently associated with frailty, regardless of the definition used. Frailty correlates also included dementia, disability and comorbidity burden, but not office and 24-h blood pressure values.

Conclusion:
Frailty is highly prevalent among older hypertensive outpatients, but agreement between different frailty tools was moderate-to-weak. Longitudinal studies are needed to assess the prognostic role of different frailty tools and their clinical utility in the choice of antihypertensive treatment.
Measuring the longitudinal impact of a transgender and gender diverse curriculum on nurse practitioner students' and nurse practitioners' cultural competence, knowledge, skills, and attitudes
Authors: Mueller Rebecca C. 
Published: September 2023

ABSTRACTNurse practitioners (NPs) are well positioned to provide inclusive, person-centered care to patients who are transgender and gender diverse (TGD); however, few NPs have been trained on how to do so. This study demonstrates the longitudinal effect of an educational intervention that used readings, lecture, a patient panel, and a standardized patient encounter on NPs' and nurse practitioner students' cultural competency, knowledge, skills, and attitudes toward patients who are TGD. The study followed participants for 3 months and used the Sexual Orientation Counselor Competency Scale version 3 tool to measure changes across three data points. Significant improvements were demonstrated in cultural competency and clinical skills, with knowledge and attitude increases that did not reach significances. The findings from this study have implications for the inclusion of TGD content in graduate nursing curriculum and continuing education activities and provide educators with best practices to integrate this content into learning activities.
Cystic partially differentiated nephroblastoma in an 18-month-old girl: a case report
Authors: Alhassoun Alia , Bara Albaraa H. , Ibrahim Mohammad N. , Berro Selman M. , Khalil Mays G. 
Published: September 2023

Introduction and importance:
Cystic partially differentiated nephroblastoma (CPDN) is a rare cystic tumor that affects the kidney. It has a low potential for malignancy. It usually presents as an abdominal mass. It may be difficult to confirm the diagnosis of CPDN without a histopathological study.

Case presentation:
The authors report a case of an 18-month-old girl with abdominal distention, which was noticed by her parents. An abdominal computed tomography scan showed a large multilocular cystic mass arising from the lower pole of the left kidney. A left total nephrectomy was performed. Immature blastemal elements without evidence of malignant cells were observed on histological analysis.

Conclusion:
The authors report a case of an 18-month-old girl with CPDN managed by total nephrectomy. CPDN should be considered in the differential diagnosis of patients with cystic renal lesions. The authors would also like to affirm that partial or total nephrectomy should be done in all cases of CPDN and other cystic renal tumors.
Systemic sclerosis sine scleroderma with atypical clinical course: a rare case report
Authors: Samha Raghad , Ghaddar Sawsane A. , Raya Maria , Abdalhadi Safaa 
Published: September 2023

Introduction and importance:
Systemic sclerosis (SSc) is divided into three subtypes: limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc), and systemic sclerosis sine scleroderma (ssSSc). ssSSc is a rare subtype of SSc that presents with internal organ manifestations but no cutaneous findings.

Case presentation:
We report the case of a 58-year-old patient with a history of pulmonary hypertension who presented with symptoms of fatigue, inflammatory polyarthritis, and joint swelling. Following a comprehensive clinical examination and laboratory tests, the patient was diagnosed with ssSSc.

Clinical discussion:
Due to its atypical clinical course, we present this case report, which commenced with idiopathic pulmonary hypertension. Subsequently, after 7 months, the patient presented complaints of polyarthritis with positive antinuclear antibodies. Raynaud’s phenomenon was identified 2 months later during the rheumatology clinic examination. Typically, the clinical course encompasses all three features simultaneously, without any gap between them.

Conclusion:
Diagnosis of ssSSc remains challenging, and it is essential to consider this disease form in all cases involving unexplained fibrotic involvement of the internal organs.
Primary Sarcoidosis of the Temporal Bone a Clinical Pathologic Correlation
Authors: Fallon Keelin , Akalin Ali , Wu Peggy , Remenschneider Aaron K. 
Published: September 2023

Objective:
This report describes a case of sarcoidosis that presented as a lytic bone lesion in the squamous part of the temporal bone.

Patients:
A 64-year-old woman presented with right-sided aural fullness, pulsatile tinnitus, and intermittent otalgia.

Interventions:
CT and MRI were performed without contrast and suggested an osseodestructive, lytic bone lesion. An excisional biopsy was performed, showing granulomatous infiltration suggestive of osseous sarcoidosis.

Main Outcome Measures:
Removal of mass and resolution of symptoms.

Results:
Initial findings from patient imaging suggested a lytic bone lesion. An excisional biopsy was required for diagnosis and was performed with little patient morbidity. Biopsy findings showed granulomatous infiltration suggestive of osseous sarcoidosis. Osseous involvement of sarcoidosis is a rare manifestation and typically occurs secondary to other disease manifestations. After the removal of the mass and a short unrelated course of steroids, the patient’s symptoms resolved.

Conclusions:
Sarcoidosis should be added to the differential diagnosis of lytic bone lesions in the temporal bone.
Effect of Neurotoxin Exposure on Blood Biomarkers of Neurodegeneration and Alzheimer Disease
Authors: Schubert Carla R. , Paulsen Adam J. , Pinto A. Alex , Chappell Richard J. , Chen Yanjun , Ferrucci Luigi , Hancock Laura M. , Cruickshanks Karen J. , Merten Natascha 
Published: September 2023

Aim:
To determine whether exposure to neurotoxins in midlife is associated with changes in blood-based biomarkers of neurodegeneration and Alzheimer disease pathology.

Methods:
Blood cadmium, lead, neurofilament light (NfL) chain, total tau (TTau), and amyloid beta (Aβ) 40 and Aβ42 concentrations were measured in 1516 participants in the Beaver Dam Offspring Study. Linear mixed-effect models were used to determine associations between baseline cadmium and lead levels and baseline NfL, TTau, and Aβ42/Aβ40, and 10-year change in concentrations using repeated measures of these biomarkers as the outcome.

Results:
In women, higher cadmium and lead levels were associated with higher baseline TTau concentrations. A higher baseline cadmium level was associated with lower baseline Aβ42/Aβ40 in both men and women. In age-sex-adjusted models, a doubling in baseline cadmium level was associated with a 0.2% (95% CI: 0.0, 0.3) higher increase per year in NfL concentrations. In men, a doubling of baseline lead level was associated with a 0.9% (95% CI: 0.1, 1.7) higher increase per year in TTau concentration.

Conclusions:
Participants with relatively higher levels of cadmium and lead had blood biomarker concentrations consistent with more neuronal damage and Alzheimer disease pathology. Environmental exposure to neurotoxins may contribute to neurodegeneration.
eMIND: Enabling automatic collection of protein variation impacts in Alzheimer’s disease from the literature
Authors: Gupta Samir , Qin Xihan , Wang Qinghua , Cowart Julie , Huang Hongzhan , Wu Cathy H , Vijay-Shanker K , Arighi Cecilia N 
Published: September 2023

AbstractAlzheimer’s disease and related dementias (AD/ADRDs) are among the most common forms of dementia, and yet no effective treatments have been developed. To gain insight into the disease mechanism, capturing the connection of genetic variations to their impacts, at the disease and molecular levels, is essential. The scientific literature continues to be a main source for reporting experimental information about the impact of variants. Thus, development of automatic methods to identify publications and extract the information from the unstructured text would facilitate collecting and organizing information for reuse. We developed eMIND, a deep learning-based text mining system that supports the automatic extraction of annotations of variants and their impacts in AD/ADRDs. In particular, we use this method to capture the impacts of protein-coding variants affecting a selected set of protein properties, such as protein activity/function, structure and post-translational modifications. We conducted an evaluation on the efficacy of eMIND to extract variant impact relations and obtained a recall of 0.84 and a precision of 0.94. The publications and extracted information are integrated into the UniProtKB computationally mapped bibliography to expand annotations on protein entries. eMIND’s text-mined output are presented using controlled vocabularies and ontologies for variant, disease and impact along with the evidence sentences. A sample of annotated abstracts can be accessed at URL:https://research.bioinformatics.udel.edu/itextmine/emind.
Rapid and synchronous chemical induction of replicative-like senescence via a small molecule inhibitor
Authors: Palikyras Spiros , Sofiadis Konstantinos , Stavropoulou Athanasia , Danieli-Mackay Adi , Varamogianni-Mamatsi Vassiliki , Hörl David , Nasiscionyte Simona , Zhu Yajie , Josipovic Natasa , Papadakis Antonis , Zirkel Anne , O’Connell Aoife , Loughran Gary , Keane James , Michel Audrey , Wagner Wolfgang , Beyer Andreas , Harz Hartmann , Leonhardt Heinrich , Lukinavicius Grazvydas , Nikolaou Christoforos , Papantonis Argyris 
Published: September 2023

AbstractCellular senescence is now acknowledged as a key contributor to organismal ageing and late-life disease. Although popular, the study of senescencein vitrocan be complicated by the prolonged and asynchronous timing of cells committing to it and its paracrine effects. To address these issues, we repurposed the small molecule inhibitor inflachromene (ICM) to induce senescence to human primary cells. Within six days of treatment with ICM, senescence hallmarks, including the nuclear eviction of HMGB1 and -B2, are uniformly induced across IMR90 cell populations. By generating and comparing various high throughput datasets from ICM-induced and replicative senescence, we uncovered significant similarity of the two states. Notably though, ICM suppresses the proinflammatory secretome associated with senescence, thus alleviating most paracrine effects. In summary, ICM induces a senescence-like phenotype rapidly and synchronously thereby allowing the study of its core regulatory program without any confounding heterogeneity.
Household geckos as a potential vector forSalmonellatransmission in Malawi
Authors: Wilson Catherine N. , Musicha Patrick , Beale Mathew A. , Diness Yohane , Kanjerwa Oscar , Salifu Chifundo , Katuah Zefaniah , Duncan Patricia , Nyangu John , Mungu Andrew , Deleza Muonaouza , Banda Lawrence , Elviss Nicola , Jewell Christopher P. , Pinchbeck Gina , Thomson Nicholas R. , Feasey Nicholas A. , Fèvre Eric M. 
Published: September 2023

AbstractSalmonellawas isolated from 23/79 (29.1%) gecko stool samples from households in southern Malawi. Whole genome sequencing of 47 isolates revealed 27Salmonellaserovars spanning two subspecies. Our results demonstrate that geckos play an important role in the carriage and potentially, transmission ofSalmonellawithin households.
Machine Learning connects structure, bitterness & mechanism to antimalarial activity
Authors: Sambu S 
Published: September 2023

AbstractMachine learning allows us to identify patterns we might otherwise have missed in the data. It therefore provides an ample solution to the age-old problem of lossless research. When the pattern is robust and the signal is durable, it is possible to use relatively modest amounts of data to build powerful well-learned models. By constructing a classifier using gradient-boosted machines, it was shown that the model was robust, yielded high quality metrics and demonstrated consistent probability assignments for chemistries that have a suitable chemical backbone qualified for inclusion in antiplasmodic libraries. Critical to model development was the utilization of molecular fingerprinting and extraction of physico-chemical parameters relevant to the mechanism driving antiplasmodic activity. Subsequently, such an approach allows the model to uncover the link between bitterness, molecular structure and therapeutic value. This approach to evaluating antiplasmodic activity in chemistries provides a low-cost tool usable in identifying new classes of molecules for use in reducing malaria morbidity that often affects vulnerable members of the community the most. Additionally, given their relatively broad, low colligation and potent efficacies, these molecules may provide strong safety margins and durability netting high returns for health equity.