bluuebunny/crossref_metadata_2025 huggingface dataset:
Ran-GTP/-GDP-dependent nuclear accumulation of NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 and TGACG-BINDING FACTOR2 controls salicylic acid-induced leaf senescence
Authors: Pham Giang , Shin Dong-Min , Kim Yoon , Kim Soo-Hwan
Published: April 2022

Leaf senescence is the final stage of leaf development and can be triggered by various external factors, such as hormones and light deprivation. In this study, we demonstrate that the overexpression of the GTP-bound form of Arabidopsis (Arabidopsis thaliana) Ran1 (a Ras-related nuclear small G-protein, AtRan1) efficiently promotes age-dependent and dark-triggered leaf senescence, while Ran-GDP has the opposite effect. Transcriptome analysis comparing AtRan1-GDP- and AtRan1-GTP-overexpressing transgenic plants (Ran1T27Nox and Ran1G22Vox, respectively) revealed that differentially expressed genes (DEGs) related to the senescence-promoting hormones salicylic acid (SA), jasmonic acid, abscisic acid, and ethylene (ET) were significantly upregulated in dark-triggered senescing leaves of Ran1G22Vox, indicating that these hormones are actively involved in Ran-GTP/-GDP-dependent, dark-triggered leaf senescence. Bioinformatic analysis of the promoter regions of DEGs identified diverse consensus motifs, including the bZIP motif, a common binding site for TGACG-BINDING FACTOR (TGA) transcription factors. Interestingly, TGA2 and its interactor, NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (NPR1), which are two positive transcriptional regulators of SA signaling, differed in their extent of accumulation in the nucleus versus cytoplasm of Ran1T27Nox and Ran1G22Vox plants. Moreover, SA-induced, Ran-GTP-/-GDP-dependent functions of NPR1 included genome-wide global transcriptional reprogramming of genes involved in cell death, aging, and chloroplast organization. Furthermore, the expression of AtRan1-GTP in SA signaling-defective npr1 and SA biosynthesis-deficient SA-induction deficient2 genetic backgrounds abolished the effects of AtRan1-GTP, thus retarding age-promoted leaf senescence. However, ET-induced leaf senescence was not mediated by Ran machinery-dependent nuclear shuttling of ETHYLENE-INSENSITIVE3 and ETHYLENE-INSENSITIVE3-LIKE1 proteins. We conclude that Ran-GTP/-GDP-dependent nuclear accumulation of NPR1 and TGA2 represents another regulatory node for SA-induced leaf senescence.
Cyan fluorescent proteins derived from mNeonGreen
Authors: Zarowny Landon , Clavel Damien , Johannson Ryan , Duarte Kévin , Depernet Hadrien , Dupuy Jérôme , Baker Heather , Brown Alex , Royant Antoine , Campbell Robert E
Published: April 2022

mNeonGreen, an engineered green fluorescent protein (GFP) derived from lancelet, is one of the most brightly fluorescent homologs of Aequorea victoria jellyfish GFP (avGFP) yet reported. In this work, we investigated whether this bright fluorescence might be retained in homologs of mNeonGreen with modified chromophore structures and altered fluorescent hues. We found mNeonGreen to be generally less tolerant than avGFP to chromophore modification by substitution of the key chromophore-forming tyrosine residue with other aromatic amino acids. However, we were ultimately successful in creating a variant, designated as NeonCyan1, with a tryptophan-derived cyan fluorescent protein (CFP)-type chromophore, and two additional mutants with distinct spectral hues. Structural, computational, and photophysical characterization of NeonCyan1 and its variants provided insight into the factors that control the fluorescence emission color. Though not recommended as replacements for contemporary CFP variants, we demonstrate that NeonCyan1 variants are potentially suitable for live cell imaging applications.
Valuation of dry and wet aged beef by U.S. consumers
Authors: Ortez Mario , Widmar Nicole Olynk , Thompson Nathan M , Kim Yuan H Brad
Published: April 2022

Aged-beef has historically been available in high-end establishments, but investigation into consumer preferences for aging is increasingly important as it has become more readily available. Consumer perceptions of and willingness-to-pay (WTP) for aged-beef under two methods dry-aging and wet-aging, were studied in a representative sample of n = 1,275 US residents alongside USDA quality grades. In general, US residents are not knowledgeable regarding aged-beef but have a positive direct-stated perception of the practice. Respondents self-reported familiarity with USDA grades Prime and Choice and perceived them as superior beef attributes. Half of respondents were randomly assigned to receive a low information treatment about beef aging, while the other half saw a high information treatment with additional information about beef aging. A likelihood ratio test indicated that the two information groups could not be pooled for analysis, and a two-class latent class model was estimated for both the low information and high information treatments. Respondents in class 1, in both information treatments, had stronger preferences for beef and were more receptive of beef aging, with the exception of wet-aged beef in the low information treatment, which they were not willing to pay a premium for. The second latent class, which is probabilistically smaller, had negative WTP estimates for both aging methods under both information treatments provided. Additional information regarding beef aging was found to have a positive impact on mean WTP for dry-aged beef in latent class 2. All models revealed positive mean WTP point estimates which ordinally behaved as expected with USDA Prime commanding the highest premium and Select the least.
SNP rs7130280 in lncRNA NONHSAT159216.1 confers susceptibility to Behçet’s disease uveitis in a Chinese Han population
Authors: Zhang Jun , Qi Jian , Shu Jia , Su Guannan , Cao Qingfeng , Zhou Chunjiang , Wang Yao , Yang Peizeng
Published: April 2022

Objective

Long noncoding RNA (lncRNA) plays a crucial role in the process of immune-mediated diseases. However, the defined involvement of lncRNA on Behçet’s disease (BD) is not well known. The aim of this study was to investigate the effects of lncRNA-related single nucleotide polymorphisms (SNPs) on BD susceptibility in Chinese populations.

Methods

A two-stage case–control association study was conducted in a cohort of 1152 BD individuals and 1152 healthy controls. Genotyping was performed by a MassARRAY System. Quantified expression of the lncRNA–miRNA–mRNA molecular axis was detected by real-time PCR and western blot. The cell proliferation was measured by CCK-8 assay.

Results

Two-stage association analysis showed a significantly decreased frequency of A allele of SNP rs7130280 in BD patients compared with healthy controls [OR 0.72 (95% CI 0.64, 0.81), Pc = 1.15 × 10−6]. Functionally, SNP rs7130280 could influence the secondary structure and relative expression of NONHSAT159216.1 in human THP-1/U937 macrophages and in peripheral blood mononuclear cells from healthy volunteers. In vitro, overexpression of the rs7130280 A allele also suppressed cell proliferation. Mechanistically, rs7130280 A allele could inhibit the expression of miR-6778-5p, thus enhancing its downstream molecular RPS6KA4/IL10 in a competing endogenous RNA sponge manner.

Conclusion

Our findings suggest that NONHSAT159216.1 rs7130280 G>A might be associated with a low risk of BD and participates in a potential lncRNA–miRNA–mRNA regulatory network.
Cadherin-11 Influences Differentiation in Human Mesenchymal Stem Cells by Regulating the Extracellular Matrix Via the TGFβ1 Pathway
Authors: Passanha Fiona R , Geuens Thomas , LaPointe Vanessa L S
Published: April 2022

For regenerative medicine, directing stem cell fate is one of the key aims. Human mesenchymal stem cells (hMSCs) are versatile adult stem cells that have been proposed for several clinical applications, making directing their fate of utmost importance. For most clinical applications, their differentiation toward the adipogenic lineage is an undesired outcome. Understanding the mechanisms that regulate hMSC commitment toward the adipogenic lineage might help open up new avenues for fine-tuning implanted hMSCs for regenerative medicine applications. We know that cadherin-11 is required for hMSC commitment to the adipogenic lineage; therefore, we sought to investigate the mechanisms through which cadherin-11 regulates adipogenic differentiation. We observed that hMSCs lacking cadherin-11 had decreased expression of type VI collagen and increased expression of fibronectin. We provide evidence of increased transforming growth factor beta 1 and the subsequent translocation of phosphorylated SMAD2/3 into the nucleus by cells that lack cadherin-11, which could be attributed to the changes in extracellular matrix composition. Taken together, our study implicates cadherin-11 in regulating extracellular matrix production and thereby helping improve cell- and material-based regenerative medicine approaches.
First Report of Carbendazim-Resistant Field Isolates of Ustilaginoidea virens on Rice in East China
Authors: Song Jie-Hui , Zhang Si-Jie , Wang Yan , Chen Yun-Tong , Luo Jun-Fei , Huo Zhong-Yang , Dai Qi-Gen , Xu Ke
Published: April 2022

Rice false smut caused by the filamentous fungus Ustilaginoidea virens is a devastating grain disease in rice. Carbendazim is usually used to control rice fungal disease. In this study, sensitivities of 264 isolates of U. virens collected from rice fields to carbendazim were determined. Most isolates were completely inhibited at 10.0 µg/ml of carbendazim except for 14 resistant isolates (5.3%). The average effective concentration for one half inhibition of mycelial growth (EC50) value for the sensitive isolates was 0.61 ± 0.03 (SEM) μg/ml, whereas the EC50 value for the resistant isolates ranged from 57.6 to >500 µg/ml. The average mycelial growth rate of five resistant isolates was not different from sensitive isolates, but the conidia production of resistant isolates decreased. Cross-resistance assays showed that there was no cross-resistance between carbendazim and DMI fungicides or QoI fungicides. Sequencing analysis of the partial β-tubulin gene from all 14 carbendazim-resistant isolates revealed that there was no nucleotide change at codon 198 or 200. The molecular mechanism of carbendazim-resistant field isolates of U. virens needs to be further studied. As far as we know, this is the first report of carbendazim resistance in U. virens in East China.
First Report of ‘Candidatus Phytoplasma brasiliense’ in North America and in a New Host, Globe Sedge (Cyperus globulosus)
Authors: Di Lella Brandon , Mou De-Fen , Helmick Ericka E. , Bahder Brian W.
Published: April 2022

A survey of weeds was undertaken in a palm nursery affected by lethal bronzing (LB) to identify a reservoir host of the causal phytoplasma. Three common species were identified; Urochloa maxima (Guineagrass), Sporobolus indicus (smut grass), and Cyperus esculentus (yellow nutsedge) and sampled over a period of 2 years. Each species was sampled 36 times and all three species were negative for the LB phytoplasma. However, three specimens of C. esculentus tested positive for the phytoplasma species ‘Candidatus Phytoplasma brasiliense’. These findings represent the first documented case of ‘Ca. P. brasiliense’ in North America, specifically in Florida, U.S.A., as well as a new host record for the phytoplasma and the first monocot host documented. Because of the impact this phytoplasma has on papaya and hibiscus in South America, it presents a unique threat to ornamental and agricultural sectors in south Florida. An area-wide survey for the phytoplasma and potential vectors is recommended.
When Will You Succeed Casting Patients With Early-onset Scoliosis? Prospective Evaluation of Predictive Radiographic Parameters
Authors: Glotzbecker Michael P. , Du Jerry Y. , Dumaine Anne M. , Ramo Brandon A. , Kelly Derrek M. , Birch Craig M. , Sturm Peter F. ,   PSSG
Published: April 2022

Background:

In a recent retrospective study, in cast correction of the major curve correlated with final curve size in patients with early-onset scoliosis treated with casting. We therefore sought to perform a prospective study with controlled methodology to determine if there are parameters associated with reduction of coronal deformity.

Methods:

A prospective, observational study was conducted between 2014 and 2019 at selected sites willing to comply with a standard radiographic and follow-up protocol. Radiographic data was collected at time points of precast, in traction, initial in-cast, and at minimum 1 year follow-up. Multivariate linear regression models were utilized to control for potential confounders using a stepwise procedure. Twenty-nine patients met inclusion criteria.

Results:

On multivariate analysis, traction major curve (P=0.043) and initial in-cast (P=0.011) major curve Cobb angles were independently associated with final out of cast major curve Cobb angle. The only factor that was independently associated with failure to cure (<15-degree major curve) was traction major curve Cobb angle (P=0.046). A threshold traction major curve Cobb angle of 20 degrees was found to have good accuracy with 81% sensitivity and 73% specificity (receiver operator curve area: 0.869, P<0.001). A traction major curve Cobb angle over 20 degrees would accurately predict failure of casting treatment to cure scoliosis in 79% of cases. A threshold in-cast major curve Cobb angle of 21 degrees was found to have slightly less accuracy than traction with 69% sensitivity, 82% specificity, and 74% accuracy (receiver operator curve area: 0.830, P=0.004).

Conclusions:

Radiographic measurements in traction and initially in the cast are predictive of curve size at follow-up for children with early-onset scoliosis treated with casting. The standardization and utility of traction films should be further explored.

Level of Evidence:

Level II.
In-hospital and 1-Year Outcomes of Repeated Percutaneous Coronary Intervention for In-stent Restenosis With Acute Coronary Syndrome Presentation
Authors: Nozari Younes , Mojtaba Ghorashi Seyyed , Alidoust Mostafa , Hamideh Mortazavi Seyedeh , Jalali Arash , Omidi Negar , Fazeli Amir , Aghajani Hassan , Salarifar Mojtaba , Reza Amirzadegan Ali
Published: April 2022

Background:

In-stent restenosis (ISR) is the Achilles’ heel of percutaneous coronary intervention (PCI). There have been controversial data about outcomes of repeated PCI (redo-PCI) for ISR. This study aims to determine the predictors of major adverse cardiac events (MACE) in patients underwent redo-PCI for ISR.

Methods:

In this retrospective study, all patients with acute coronary syndrome who were underwent successful PCI for ISR at Tehran Herat Center (between 2004 and 2019) were eligible for inclusion. Patients with moderate to severe valvular heart disease and/or hematological disorders were excluded. Participants were divided into 2 groups based on the occurrence of the MACE [composite of cardiovascular death, myocardial infarction (MI), coronary artery bypass grafting, target vessel revascularization, and target lesion revascularization]; then, the study variables were compared between the 2 groups. Finally, the predictors of MACE were identified using Cox regression analysis.

Results:

Of 748 redo-PCI patients (mean age: 65.2 ± 10.1; 71.0% males), 631 patients had met the inclusion criteria. Fifty-four patients (9.8%) developed MACE within a 1-year follow-up period. Multivessel disease, primary PCI, Ad-hoc PCI, history of non–ST-segment elevation MI, and diabetes mellitus were independent predictors for MACE. In a subgroup analysis, 30 patients who experienced third PCI (target lesion revascularization/target vessel revascularization) were followed more as 1-year MACE. Among these patients, 14 MACEs were observed during the last follow-up (till June 2020).

Conclusions:

Multivessel disease, primary PCI, and history of non–ST-segment elevation MI were the predictors of higher 1-year MACE, whereas Ad-hoc PCI and diabetes mellitus had a protective effect on MACE.
Intensification of Middle- and High-Molecular-Weight Toxins Removal in Dialysis Process
Authors: Poorkhalil Ali , Farrokhzad Hasan , Poorkhalil Amir , Bizari Davood , Van der Bruggen Bart
Published: April 2022

A novel extracorporeal circuit for hemodialysis is described, which enhances the removal of middle- and high-molecular-weight toxins. To enhance the removal of especially high-molecular toxins, a recirculation pathway for dialysate flow is added to conventional circuit. The influence of an increase in the ratio of recirculation to dialysate flow rate and the ultrafiltration rate (UFR) on the removal of toxins was investigated to evaluate the removal of different toxins in clinical conditions. Removal of toxins was also modeled by an analytical method and solved by the MATLAB software (The MathWorks, Inc., Natick, MA). A significant increase in removal of urea (up to 31%) and vitamin B12 (11%) was achieved when the UFR is low (≤50 ml/h) or zero. The model showed an excellent agreement with the experimental results, which indicates its applicability for the removal of different toxins in an extracorporeal circuit. Increase in recirculation flow, while adjusting the UFR near zero, improves the mass transfer coefficient and can lead to enhanced especially middle- and high-molecular-weight toxin removal.
Lung Volume Reduction Surgery Reduces Pulmonary Arterial Hypertension Associated With Severe Lung Emphysema and Hypercapnia
Authors: Akil Ali , Ziegeler Stephan , Rehers Stephanie , Lavae-Mokhtari Mahyar , Richter Lars , Dickgreber Nicolas Johannes , Ernst Erik Christian , Fischer Stefan
Published: April 2022

Lung volume reduction surgery (LVRS) represents a standard surgical approach for patients with severe pulmonary emphysema. One of the relevant risk factors for LVRS is the presence of pulmonary arterial hypertension (PAH). The aim of this study is to assess the postoperative changes in pulmonary arterial pressure (PAP) after LVRS for patients with severe pulmonary emphysema compared with preoperative measures. N = 61 consecutive patients with severe pulmonary emphysema and preoperative evidence for PAH (pulmonary arterial systolic pressure [PASP] ≥ 35 mmHg) were prospectively included into this study. In all patients, thoracoscopic LVRS was performed. PASP was assessed by echocardiography before surgery, early postoperatively, and 3 months after surgery. Data were prospectively recorded and analyzed retrospectively. Primary end points were the postoperative changes in PASP as well as the 90 day mortality rate. Secondary endpoints included: pulmonary function test, exercise capacity, quality of life, and dyspnea symptoms (Borg scale). Early after surgery, a significant reduction in PASP was observed at the day of discharge and at 3 month follow-up. In n = 34 patients, no tricuspid valve regurgitation was detectable anymore suggesting normal PAP. In n = 3 patients, venovenous extracorporeal lung support (VV ECLS) was already implemented preoperatively. In the remaining cases, VV ECLS was applied intraoperatively and continued postoperatively. Mean duration of postoperative ECLS support was 2 days. Four patients died due to acute right heart failure, two patients from sepsis with multiorgan failure, and one patient from acute pulmonary embolism. Ninety day mortality was 11.5 %. A significant improvement was postoperatively observed regarding the performance status, dyspnea scale, as well as quality of life. This study suggests a beneficial effect of LVRS on PAP, which may ultimately help to protect and stabilize right ventricular function. Further studies, implementing pre- and postoperative right heart catheterizations including invasive PAP evaluation, are necessary to support the findings in this study in greater detail.
Exploratory Analysis of Associations Between Whole Blood Mitochondrial Gene Expression and Cancer-Related Fatigue Among Breast Cancer Survivors
Authors: Kleckner Amber S. , Kleckner Ian R. , Culakova Eva , Wojtovich Andrew P. , Klinedinst N. Jennifer , Kerns Sarah L. , Hardy Sara J. , Inglis Julia E. , Padula Gilbert D. A. , Mustian Karen M. , Janelsins Michelle C. , Dorsey Susan G. , Saligan Leorey N. , Peppone Luke J.
Published: April 2022

Background

Cancer-related fatigue is a prevalent, debilitating, and persistent condition. Mitochondrial dysfunction is a putative contributor to cancer-related fatigue, but relationships between mitochondrial function and cancer-related fatigue are not well understood.

Objectives

We investigated the relationships between mitochondrial DNA (mtDNA) gene expression and cancer-related fatigue, as well as the effects of fish and soybean oil supplementation on these relationships.

Methods

A secondary analysis was performed on data from a randomized controlled trial of breast cancer survivors 4–36 months posttreatment with moderate–severe cancer-related fatigue. Participants were randomized to take 6 g fish oil, 6 g soybean oil, or 3 g each daily for 6 weeks. At pre- and postintervention, participants completed the Functional Assessment of Chronic Illness Therapy–Fatigue questionnaire and provided whole blood for assessment of mtDNA gene expression. The expression of 12 protein-encoding genes was reduced to a single dimension using principal component analysis for use in regression analysis. Relationships between mtDNA expression and cancer-related fatigue were assessed using linear regression.

Results

Among 68 participants, cancer-related fatigue improved and expression of all mtDNA genes decreased over 6 weeks with no effect of treatment group on either outcome. Participants with lower baseline mtDNA gene expression had greater improvements in cancer-related fatigue. No significant associations were observed between mtDNA gene expression and cancer-related fatigue at baseline or changes in mtDNA gene expression and changes in cancer-related fatigue.

Discussion

Data from this exploratory study add to the growing literature that mitochondrial dysfunction may contribute to the etiology and pathophysiology of cancer-related fatigue.
Low-grade Fibromyxoid Sarcoma of the Vulva and Vagina
Authors: Costigan Danielle , Dal Cin Paola , Fletcher Christopher D.M. , Nucci Marisa R. , Parra-Herran Carlos , Chapel David B.
Published: April 2022

Low-grade fibromyxoid sarcoma (LGFMS) is a malignancy with propensity for late relapse that principally affects deep soft tissues of the extremities and trunk. Its occurrence in the lower female genital tract is rare, and thus it may not be always considered in the differential diagnosis. We describe the salient features of 7 vulvovaginal LGFMS identified in the authors’ consultation files. Clinical information was obtained from referring pathologists. Archival slides were reviewed, and immunohistochemistry and fluorescence in situ hybridization were performed in cases with available material. Median age was 40 years (range, 34 to 58 y). Primary sites included vulva (n=6) and vagina (n=1). Tumors were 1.2 to 8.7 cm (median, 5.0 cm) in size and grossly circumscribed with firm to focally gelatinous cut surfaces. Microscopically, 5/7 had infiltrative edges. All tumors showed fibrous and myxoid areas, with lobulated myxoid foci in 5/7, comprising storiform, patternless, or (less often) fascicular arrangement of spindled to stellate cells with bland, slender to ovoid nuclei. In all cases, mitoses were <1/2.4 mm2, and necrosis was absent. Capillary “arcades” were seen in 3/7. Margins were positive in 3/6. Immunohistochemistry showed positive epithelial membrane antigen in 4/6 and MUC4 in 5/6. Fluorescence in situ hybridization detected FUS rearrangement in 5/7. Both tumors without FUS rearrangement were also negative for EWSR1 rearrangement. All 5 patients with available follow-up were alive and disease-free 10 to 150 months (median, 57 mo) after diagnosis. However, a review of vulvovaginal/pelvic LGFMS previously reported shows recurrences as late as 45 years after initial diagnosis. Pathologists need to be aware that LGFMS can arise in the vulvovaginal region. Tumor lobulation, capillary arcades, and positive MUC4 are helpful features distinguishing LGFMS from other bland myxoid spindle cell neoplasms in the lower female genital tract. Molecular testing can be useful in challenging cases. Complete excision is feasible for most vulvovaginal LGFMS. Long-term surveillance is required as local and/or distant spread can occur decades after diagnosis.
Clinicopathologic Spectrum of Secondary Solid Tumors of the Prostate of Nonurothelial Origin
Authors: Acosta Andres M. , Gordetsky Jennifer B. , Collins Katrina , Osunkoya Adeboye O. , Sangoi Ankur R. , Miyamoto Hiroshi , Kao Chia-Sui , Trpkov Kiril , Van Leenders Geert J.L.H. , Wobker Sara E. , Maclean Fiona , Lal Priti , Daniel Reba E. , Brimo Fadi , Wasco Matthew , Hirsch Michelle S. , Baniak Nicholas , Diaz-Perez Julio A. , Cornejo Kristine M. , Choy Bonnie , Mehra Rohit , Williamson Sean R. , Epstein Jonathan I. , Matoso Andres
Published: April 2022

Secondary involvement of the prostate by urothelial or hematolymphoid neoplasms is relatively common and well-described. In contrast, less is known about the clinicopathologic spectrum of secondary solid tumors of the prostate of nonurothelial origin. This study evaluated a series of secondary nonurothelial solid tumors of the prostate diagnosed at 21 institutions. Eighty-five patients with a median age at diagnosis of 64 years were included. Sixty-two patients had clinically manifest disease (62/85, 73%), 10 were diagnosed incidentally (10/85, 12%), and 13 (13/85, 15%) had no detailed clinical data available about symptomatology at presentation. Among patients with clinically manifest disease, the most common symptoms and signs were lower urinary tract symptoms (either obstructive of irritative; 36/62, 58%), abdominal or pelvic pain or discomfort (16/62, 26%), and hematuria (12/62, 19%). Metastasis and direct invasion occurred at roughly similar frequencies (47% vs. 42%) in this series, and in 11% of the cases, the mechanism of spread to the prostate was unclear/uncertain. Overall, among tumors with confirmed sites of origin, the most common primary sites were gastrointestinal tract (53/85, 62%), lung (9/85, 11%), skin (6/85, 7%), and testis (4/85, 5%). Among metastases, the most common tumor types were lung carcinomas (9/40, 23%), colorectal adenocarcinomas (7/40, 18%), melanoma (6/40, 15%), and germ cell tumors (6/40, 15%). This study demonstrated that secondary involvement of the prostate by solid tumors of nonurothelial origin is commonly symptomatic and that the most frequent sites of origin are the gastrointestinal tract, lung, skin, and testis. These findings are worth considering when lesions with unusual cytomorphology and/or architecture are encountered in prostate specimens.
Low-Grade Oncocytic Renal Tumor With Massive Liver Metastasis: Do Not Trust a Negative CK7 and Misdiagnose Oncocytoma: A Cautionary Tale and Current Classification of Oncocytic Renal Tumors
Authors: Burke Allen , Legesse Teklu , Paulk Adina
Published: April 2022

We report a renal tumor originally diagnosed as oncocytoma that recurred with biopsy-proven multiple liver metastases. Review of the initial tumor revealed a predominantly CK7-negative neoplasm that had areas resembling oncocytoma, areas resembling eosinophilic chromophobe renal cell carcinoma, and areas with intermediate features. The case illustrates that the distinction between eosinophilic chromophobe renal cell carcinoma and “oncocytic tumor of uncertain malignant potential” is in some cases subjective. Criteria need better definition and should not be based on cytokeratin 7 staining pattern alone. A discussion of the current classification of oncocytic renal tumors is included, as well as a discussion of the differential diagnosis of renal neoplasms with eosinophilic cytoplasm.
Kikuchi Disease Masquerading as a T-Cell Lymphoma
Authors: Aqil Barina , Kaur Amandeep
Published: April 2022

Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis, is most prevalent in Asia and has been increasingly recognized in other parts of the world. It usually occurs more frequently in females and presents as fever and localized cervical lymphadenopathy. It resolves spontaneously, usually over a period of several weeks up to 6 months. Its initial clinical features are commonly similar to that of a lymphoma, and it can be misdiagnosed both by clinicians and pathologists. Kikuchi disease has been associated with systemic lupus erythematosus. We report a case of Kikuchi disease that occurred in a 25-year-old female patient that masqueraded as a T-cell lymphoma.
Desmoplastic Small Round Cell Tumor Is an Important Mimic of High-Grade Carcinoma in Colonic Biopsy Samples
Authors: Hissong Erika , Yantiss Rhonda K.
Published: April 2022

Desmoplastic small round cell tumor (DSRCT) is a rare but aggressive malignancy that usually occurs within the intra-abdominal cavities of young adult males. Most DSRCTs can be reliably diagnosed based on the presence of characteristic morphology; coexpression of epithelial, myogenic, and neural markers; and detection of the reciprocal translocation t(11;22)(p13:21) associated with the EWS::WT1 fusion. However, occasional tumors lack classic features, affect older adults, or are located outside the abdominal cavity. Mucosal biopsy samples can pose challenges when both the stromal and epithelial components are not represented. Herein, we present a case of DSRCT that simulated clinical and histologic features of a colonic adenocarcinoma. Biopsy sampling revealed nests of cytokeratin-positive epithelioid cells that simulated a high-grade carcinoma with neuroendocrine features. This case report emphasizes the importance of considering this rare entity when presented with high-grade epithelioid tumors that occur in young patients.
Proteinuria in Deceased Kidney Transplant Donors for Prediction of Chronic Lesions in Pretransplant Biopsies: A Prospective Observational Study
Authors: Haupenthal Frederik , Kläger Johannes , Bauernfeind Florian , Heinzel Andreas , Doberer Konstantin , Mayer Katharina , Naar Luis , Eigenschink Michael , Hu Karin , Regele Heinz , Szekeres Thomas , Berlakovich Gabriela , Reindl-Schwaighofer Roman , Bond Gregor
Published: April 2022

Background.

Pretransplant kidney graft biopsies have been suggested for organ quality assessment. Data on the association between donor proteinuria and organ quality of deceased donors are not available.

Methods.

In this prospective study, we analyzed 147 pretransplant kidney biopsies from 88 deceased adult donors procured and transplanted consecutively at the Medical University Vienna between July 2017 and May 2020. Lesions in each renal compartment were scored from 0 to 5 with each ascending score representing a 20% increase in organ damage. A chronic lesions score was calculated including glomerulosclerosis, intima fibrosis, hyalinosis, interstitial fibrosis, and tubular atrophy.

Results.

The median chronic lesion score was 2 (interquartile range [IQR] 1–4) and the median donor urinary protein to creatinine ratio (UPCR) was 382 mg/dL (IQR 222–703). There was a positive correlation between UPCR and number of chronic lesions (β 0.15, 95% confidence interval, 0.03-0.28; P = 0.019). Biopsies with 2 or more lesions had a median UPCR of 486 mg/dL (IQR 251–717) compared with 274 mg/dL (IQR 211–556; P = 0.016) in biopsies with <2 lesions. The risk for detection of 2 or more lesions rose by 18% for every log increase in UPCR (risk ratio 1.18, 95% confidence interval, 1.03-1.25; P = 0.017). Multivariable and sensitivity analysis revealed an independent and robust association between chronic lesions and UPCR.

Conclusions.

Donor UPCR is associated with chronic lesions in pretransplant deceased donor kidney graft biopsies. This finding justifies further investigation of donor proteinuria for the assessment of organ quality and outcome.
Reducing fatigue-related symptoms in Long COVID-19: a preliminary report of a lymphatic drainage intervention
Authors: H. Heald Adrian , Perrin Raymond , Walther Andreas , Stedman Mike , Hann Mark , Mukherjee Annice , Riste Lisa
Published: April 2022

Introduction

In the early days of the first global wave of the COVID-19 pandemic, the potential for a postviral syndrome to manifest following COVID-19 infection was first recognized. Here, we present an analysis of a case series of the first 20 patients’ data collected in clinical practice to evaluate the potential of a possible alternative treatment for Long COVID.

Methods

Face-to-face treatment sessions with Perrin techniqueTM practitioners occurred weekly involving effleurage/other manual articulatory techniques. The individuals being treated also undertook daily self-massage along with gentle mobility exercises. Patients recorded symptom severity using the self-report 54-item profile of fatigue-related states (PFRS) before and after treatment.

Results

The mean age of male patients was 41.8 years (range, 29–53 years), and for female patients, 39.3 years (range, 28–50 years). None of the participants had a prior diagnosis of chronic fatigue syndrome, and all were new attendees to the clinics at the time of initial assessment. The average number of treatment sessions was 9.7 in men and 9.4 in women. The reduction in PFRS scores was 41.8% in men and 60.5% in women. The highest subscale scores on average were for fatigue, with the lowest for somatic symptoms. All subscale scores showed, on average, a similar reduction of approximately 50% postintervention, with the reduction in score relating to a decrease in the severity of symptoms.

Conclusion

Our findings suggest that a specific manual lymphatic drainage intervention may help to reduce fatigue symptoms related to Long COVID, perhaps preventing acute symptoms through early intervention.
Naltrexone alters cardiovascular function following acute forced swimming in mice
Authors: Longoria Candace R. , Qadiri Qudratullah S. , Matthews Evan L. , Campbell Sara C. , Guers John J.
Published: April 2022

Purpose

Naltrexone (NTX) is an opioid antagonist that can reverse the physiological effects of opioid receptors when bound. Opioid receptors have been found to play a role in cardiovascular (CV) function, and thus, binding of NTX may alter CV activity at rest and in response to acute and chronic exercise (EX). We hypothesized that opioid receptor blockade will alter the typical CV responses following acute EX.

Methods

We assessed the effects of opioid receptor blockade on CV function via echocardiography in mice following an acute bout of forced swimming (FSw), a model of rodent EX. We administered opioid receptor antagonist, NTX, or saline in mice before FSw and in the absence of an FSw perturbation. Furthermore, we assessed how NTX can influence maximal EX capacity on a rodent treadmill.

Results

Our data shows that NTX administration does not decrease maximal EX capacity in mice (P > 0.05). However, NTX attenuated cardiac output following FSw (FSw = 52.5 ± 2.5 ml/min vs. FSw + NTX = 32.7 ± 5.2 ml/min; P < 0.05) when compared with saline control (33.5 ± 3.8 ml/min). Further, the administration of NTX in the non-EX condition significantly (P < 0.05) reduced ejection fraction.

Conclusion

These data suggest that normal opioid receptor activation is necessary for typical CV function following FSw.
Cool birds: first evidence of energy-saving nocturnal torpor in free-living common swifts
Apus apus
resting in their nests
Authors: Wellbrock Arndt H. J. , Eckhardt Luca R. H. , Kelsey Natalie A. , Heldmaier Gerhard , Rozman Jan , Witte Klaudia
Published: April 2022

Daily torpor is a means of saving energy by controlled lowering of the metabolic rate (MR) during resting, usually coupled with a decrease in body temperature. We studied nocturnal daily torpor under natural conditions in free-living common swifts
Apus apus
resting in their nests as a family using two non-invasive approaches. First, we monitored nest temperature (
T
nest
) in up to 50 occupied nests per breeding season in 2010–2015. Drops in
T
nest
were the first indication of torpor. Among 16 673 observations, we detected 423 events of substantial drops in
T
nest
of on average 8.6°C. Second, we measured MR of the families inside nest-boxes prepared for calorimetric measurements during cold periods in the breeding seasons of 2017 and 2018. We measured oxygen consumption and carbon dioxide production using a mobile indirect respirometer and calculated the percentage reduction in MR. During six torpor events observed, MR was gradually reduced by on average 56% from the reference value followed by a decrease in
T
nest
of on average 7.6°C. By contrast, MR only decreased by about 33% on nights without torpor. Our field data gave an indication of daily torpor, which is used as a strategy for energy saving in free-living common swifts.
Large abdominal mechanoreceptive sense organs in small plant-dwelling insects
Authors: Ehlers Sarah , Baum Daniel , Mühlethaler Roland , Hoch Hannelore , Bräunig Peter
Published: April 2022

The Hemiptera, with approximately 98 000 species, is one of the largest insect orders. Most species feed by sucking sap from plant tissues and are thus often vectors for economically important phytopathogens. Well known within this group are the large cicadas (Cicadomorpha: Cicadoidea: Cicadidae) because they produce extremely loud airborne sounds. Less well known are their mostly tiny relatives, the leafhoppers, spittlebugs, treehoppers and planthoppers that communicate by silent vibrational signals. While the generation of these signals has been extensively investigated, the mechanisms of their perception are poorly understood. This study provides a complete description and three-dimensional reconstruction of a large and complex array of mechanoreceptors in the first abdominal segments of the Rhododendron leafhopper
Graphocephala fennahi
(Cicadomorpha: Membracoidea: Cicadellidae). Further, we identify homologous organs in the spittlebug
Philaenus spumarius
(Cicadomorpha: Cercopoidea: Aphrophoridae) and the planthopper
Issus coleoptratus
(Fulgoromorpha: Fulgoroidea: Issidae). Such large abdominal sensory arrays have not been found in any other insect orders studied so far. This indicates that these sense organs, together with the signal-producing tymbal organ, constitute a synapomorphy of the Tymbalia (Hemiptera excl. Sternorrhyncha). Our results contribute to the understanding of the evolution from substrate-borne to airborne communication in insects.
Dietary isotopes of Madagascar's extinct megafauna reveal Holocene browsing and grazing guilds
Authors: Hansford James P. , Turvey Samuel T.
Published: April 2022

Megafauna play a disproportionate role in developing and maintaining their biomes, by regulating plant dispersal, community structure and nutrient cycling. Understanding the ecological roles of extinct megafaunal communities, for example through dietary reconstruction using isotope analysis, is necessary to determine pre-human states and set evidence-based restoration goals. We use
δ
13
C and
δ
15
N isotopic analyses to reconstruct Holocene feeding guilds in Madagascar's extinct megaherbivores, which included elephant birds, hippopotami and giant tortoises that occurred across multiple habitats and elevations. We compare isotopic data from seven taxa and two elephant bird eggshell morphotypes against contemporary regional floral baselines to infer dietary subsistence strategies. Most taxa show high consumption of C
3
and/or CAM plants, providing evidence of widespread browsing ecology. However,
Aepyornis hildebrandti
, an elephant bird restricted to the central highlands region, has isotope values with much higher
δ
13
C values than other taxa. This species is interpreted as having obtained up to 48% of its diet from C
4
grasses. These findings provide new evidence for distinct browsing and grazing guilds in Madagascar's Holocene megaherbivore fauna, with implications for past regional distribution of ecosystems dominated by endemic C
4
grasses.
Multi-scale mechanistic modelling of the host defence in invasive aspergillosis reveals leucocyte activation and iron acquisition as drivers of infection outcome
Authors: Ribeiro Henrique AL , Vieira Luis Sordo , Scindia Yogesh , Adhikari Bandita , Wheeler Matthew , Knapp Adam , Schroeder William , Mehrad Borna , Laubenbacher Reinhard
Published: April 2022

Aspergillus species are ubiquitous environmental moulds, with spores inhaled daily by most humans. Immunocompromised hosts can develop an invasive infection resulting in high mortality. There is, therefore, a pressing need for host-centric therapeutics for this infection. To address it, we created a multi-scale computational model of the infection, focused on its interaction with the innate immune system and iron, a critical nutrient for the pathogen. The model, parameterized using published data, was found to recapitulate a wide range of biological features and was experimentally validatedin vivo. Conidial swelling was identified as critical in fungal strains with high growth, whereas the siderophore secretion rate seems to be an essential prerequisite for the establishment of the infection in low-growth strains. In immunocompetent hosts, high growth, high swelling probability and impaired leucocyte activation lead to a high conidial germination rate. Similarly, in neutropenic hosts, high fungal growth was achieved through synergy between high growth rate, high swelling probability, slow leucocyte activation and high siderophore secretion. In summary, the model reveals a small set of parameters related to fungal growth, iron acquisition and leucocyte activation as critical determinants of the fate of the infection.
Lipid biophysics and/or soft matter-inspired approach for controlling enveloped virus infectivity
Authors: Al-dalawi Lamyaa , Dunham Stephen P. , Rauch Cyril
Published: April 2022

Proven as a natural barrier against viral infection, pulmonary surfactant phospholipids have a biophysical and immunological role within the respiratory system, acting against microorganisms including viruses. Enveloped viruses have, in common, an outer bilayer membrane that forms the underlying structure for viral membrane proteins to function in an optimal way to ensure infectivity. Perturbating the membrane of viruses using exogenous lipids can be envisioned as a generic way to reduce their infectivity. In this context, the potential of exogenous lipids to be used against enveloped virus infectivity would be indicated by the resulting physical stress imposed to the viral membrane, and conical lipids, i.e. lyso-lipids, would be expected to generate stronger biophysical disturbances. We confirm that when treated with lyso-lipids the infectivity three strains of influenza virus (avian H2N3, equine H3N8 or pandemic human influenza H1N1) is reduced by up to 99% in a cell-based model. By contrast, lipids with a similar head group but two aliphatic chains were less effective (reducing infection by only 40–50%). This work opens a new path to merge concepts from different research fields, i.e. ‘soft matter physics' and virology.
Ergodic descriptors of non-ergodic stochastic processes
Authors: Mangalam Madhur , Kelty-Stephen Damian G.
Published: April 2022

The stochastic processes underlying the growth and stability of biological and psychological systems reveal themselves when far-from-equilibrium. Far-from-equilibrium, non-ergodicity reigns. Non-ergodicity implies that the average outcome for a group/ensemble (i.e. of representative organisms/minds) is not necessarily a reliable estimate of the average outcome for an individual over time. However, the scientific interest in causal inference suggests that we somehow aim at stable estimates of the cause that will generalize to new individuals in the long run. Therefore, the valid analysis must extract an ergodic stationary measure from fluctuating physiological data. So the challenge is to extract statistical estimates that may describe or quantify some of this non-ergodicity (i.e. of the raw measured data) without themselves (i.e. the estimates) being non-ergodic. We show that traditional linear statistics such as the standard deviation, coefficient of variation and root mean square can break ergodicity. Time series of statistics addressing sequential structure and its potential nonlinearity: fractality and multi-fractality, change in a time-independent way and fulfil the ergodic assumption. Complementing traditional linear indices with fractal and multi-fractal indices would empower the study of stochastic far-from-equilibrium biological and psychological dynamics.
Geometric algebra generation of molecular surfaces
Authors: Alfarraj Azzam , Wei Guo-Wei
Published: April 2022

Geometric algebra is a powerful framework that unifies mathematics and physics. Since its revival in the 1960s, it has attracted great attention and has been exploited in fields like physics, computer science and engineering. This work introduces a geometric algebra method for the molecular surface generation that uses the Clifford–Fourier transform (CFT) which is a generalization of the classical Fourier transform. Notably, the classical Fourier transform and CFT differ in the derivative property inRkforkeven. This distinction is due to the non-commutativity of geometric product of pseudoscalars with multivectors and has significant consequences in applications. We use the CFT inR3to benefit from the derivative property in solving partial differential equations (PDEs). The CFT is used to solve the mode decomposition process in PDE transform. Two different initial cases are proposed to make the initial shapes in the present method. The proposed method is applied first to small molecules and proteins. To validate the method, the molecular surfaces generated are compared to surfaces of other definitions. Applications are considered to protein electrostatic surface potentials and solvation free energy. This work opens the door for further applications of geometric algebra and CFT in biological sciences.
Predicting how US public opinion on moral issues will change from 2018 to 2020 and beyond
Authors: Strimling Pontus , Vartanova Irina , Eriksson Kimmo
Published: April 2022

The General Social Survey, conducted every 2 years, measures public opinion on a wide range of moral issues. The data from the 2020 survey are expected to be released in mid-October 2021. In advance of this data release, we make predictions for how public opinion will have shifted since 2018. We also predict further public opinion shifts for the coming decade up until the year 2030. These predictions are based on the theory that an opinion will become more popular over time if it holds an argument advantage, that is, if it is better justified by generally accepted kinds of arguments than the opposite opinion is. While this theory has successfully accounted for historical opinion trends, this is the first time it is used to predict future shifts. To assess the accuracy of our forecast we will compare it with the benchmark forecast that predicts the same public opinion in 2020 as in 2018.