bluuebunny/crossref_metadata_2025 huggingface dataset:
Intratumoral and Peritumoral Radiomics Based on Functional Parametric Maps from Breast DCE‐MRI for Prediction of HER‐2 and Ki‐67 Status
Authors: Li Chunli , Song Lirong , Yin Jiandong
Published: May 2021

Background

Radiomics has been applied to breast magnetic resonance imaging (MRI) for gene status prediction. However, the features of peritumoral regions were not thoroughly investigated.

Purpose

To evaluate the use of intratumoral and peritumoral regions from functional parametric maps based on breast dynamic contrast‐enhanced MRI (DCE‐MRI) for prediction of HER‐2 and Ki‐67 status.

Study Type

Retrospective.

Population

A total of 351 female patients (average age, 51 years) with pathologically confirmed breast cancer were assigned to the training (n = 243) and validation (n = 108) cohorts.

Field Strength/Sequence

3.0T, T1 gradient echo.

Assessment

Radiomic features were extracted from intratumoral and peritumoral regions on six functional parametric maps calculated using time‐intensity curves of DCE‐MRI. The intraclass correlation coefficients (ICCs) were used to determine the reproducibility of feature extraction. Based on the intratumoral, peritumoral, and combined intra‐ and peritumoral regions, three radiomics signatures (RSs) were built using the least absolute shrinkage and selection operator (LASSO) logistic regression model, respectively.

Statistical Tests

Wilcoxon rank‐sum test, minimum redundancy maximum relevance, LASSO, receiver operating characteristic curve (ROC) analysis, and DeLong test.

Results

The intratumoral and peritumoral RSs for prediction of HER‐2 and Ki‐67 status achieved areas under the ROC (AUCs) of 0.683 (95% confidence interval [CI], 0.574–0.793) and 0.690 (95% CI, 0.577–0.804), and 0.714 (95% CI, 0.616–0.812) and 0.692 (95% CI, 0.590–0.794) in the validation cohort, respectively. The combined RSs yielded AUCs of 0.713 (95% CI, 0.604–0.823) and 0.749 (95% CI, 0.656–0.841), respectively. There were no significant differences in prediction performance among intratumoral, peritumoral, and combined RSs. Most (69.7%) of the features had good agreement (ICCs >0.8).

Data Conclusion

Radiomic features of intratumoral and peritumoral regions on functional parametric maps based on breast DCE‐MRI had the potential to identify HER‐2 and Ki‐67 status.

Level of Evidence: 3

Technical Efficacy Stage: 2
Elucidation of the structure of supramolecular polymorphs in peptide nanofibres using Raman spectroscopy
Authors: Sloan‐Dennison Sian , Lampel Ayala , Raßlenberg Eileen , Ulijn Rein V. , Smith Ewen , Faulds Karen , Graham Duncan
Published: May 2021

Peptide fibre formation via molecular self‐assembly is a key step in a range of cellular processes and increasingly considered as an approach to produce supramolecular biomaterials. We previously demonstrated the self‐assembly of the tripeptide lysine‐dityrosine (KYY) as a substrate for the formation of proton‐conducting melanin‐like materials. Point based Raman scattering is one of several techniques which were used to characterise the secondary structure of the KYY nanofibre but as is often the case with this type of fibre, the spectra are rather complex and in addition there were variations in intensity between samples making interpretation difficult. Using Raman mapping we show that, as a drop of KYY in solution dries, it self‐assembles into two different fibre forms and the simpler spectra obtained for each are easier to interpret. The tyrosine amide marker bands, 852 and 828 cm−1, are present in both forms with similar intensities indicating the formation of a similar secondary structure in both forms with some stacking of the tyrosine rings. However, the tyrosine marker bands at 1614 and 1661 cm−1 vary considerably in intensity between the two forms. It is concluded that both forms consist of stacked polypeptide units joined by hydrogen bonds to form structures similar to β‐sheet structures in longer peptides. There are other clear differences such the large intensity difference in the lysine side chain band at 1330 cm−1 and the relative intensities of the bands at 982 and 1034 cm−1. These differences are attributed to changes in the conformation of tyrosine side chains causing different electron withdrawing effects on the ring.
Perfusion Patterns of Peripheral Pulmonary Granulomatous Lesions Using Contrast‐Enhanced Ultrasound (CEUS) and Their Correlation with Immunohistochemically Detected Vascularization Patterns
Authors: Safai Zadeh Ehsan , Keber Corinna U. , Dietrich Christoph F. , Westhoff Christina C. , Günter Christina , Beutel Björn , Alhyari Amjad , Trenker Corinna , Görg Christian
Published: May 2021

Purpose

To describe the perfusion patterns of peripheral pulmonary granulomatous lesions (PPGLs) by contrast‐enhanced ultrasound (CEUS) and their correlation with vascularization patterns (VPs) represented by immunohistochemical (CD34) endothelial staining.

Patients and methods

From January 2007 until September 2020, 10 consecutive patients with histologically confirmed PPGLs were investigated by CEUS. The time to enhancement, classified as early pulmonary‐arterial (PA) pattern of enhancement versus delayed bronchial‐arterial (BA) pattern of enhancement, the extent of enhancement, classified as marked or reduced, the homogeneity of enhancement, classified as homogeneous or inhomogeneous, and the decrease of enhancement, classified as rapid washout (<120 seconds) or a late washout (≥120 seconds), were analyzed retrospectively. Furthermore, the tissue samples from the study patients and as a control group, 10 samples of normal lung tissue obtained by autopsy, and 10 samples of lung tissue with acute pneumonia obtained by autopsy were immunohistochemically stained with CD34 antibody. The presence of avascular areas (AAs) and the VPs were evaluated in all tissue samples.

Results

On CEUS, all PPGLs showed a reduced inhomogeneous BA pattern of enhancement and a rapid washout (<120 seconds). On CD34 staining, all PPGLs showed central AAs in granulomas and a chaotic VP similar to angiogenesis in lung tumors. The lung tissue in control groups revealed on CD34 staining a regular alveolar VP.

Conclusion

The PPGLs on CEUS show an identical perfusion pattern similar to those of malignant lesions. Furthermore, for the first time, neoangiogenesis was demonstrated as a histopathological correlate to BA pattern of enhancement on CEUS.
T‐cell mediated responses against alpha‐foetoprotein in hepatocellular carcinoma: Relationship with hepatitis C virus infection, tumour phenotype and patients’ survival
Authors: Pinato David J. , Fessas Petros , Gibbin Antonello , Occhino Giuseppa , Boccato Elisa , Smirne Carlo , Minisini Rosalba , Pirisi Mario
Published: May 2021

Background

Alpha‐foetoprotein (AFP) is a potential immunotherapeutic target in hepatocellular carcinoma (HCC). However, T‐cell response (TR) to AFP is suppressed in HCC due to immune evasion. It is unknown whether HCV infection may pre‐condition TR against AFP, or whether TR may influence the clinical course of HCC.

Methods

We prospectively enrolled 18 HCV+ treatment‐naïve patients with cirrhosis (CC), 18 HCV+ HCC cases and 17 HCV‐ HCC cases. TR was quantified by ELISPOT using assays specific to interleukin (IL) 2, IL10 and granulocyte‐monocyte colony stimulating factor (GM‐CSF) on ex‐vivo peripheral blood mononuclear cells (PBMC) stimulated in vitro with AFP peptides. Cytokine ratios were compared between groups and with clinicopathological features of HCC, including overall survival (OS).

Results

The proportion of AFP‐specific responses was not different across the studied groups for any of the assayed cytokines. AFP‐specific IL‐2 responses were increased in larger (P = .02), multifocal tumours (P = .01) and correlated with advanced disease (P = .01). TRs did not correlate with other clinicopathological factors and did not predict for OS.

Conclusion

Tumour stage but not HCV infection is related to the emergence of anti‐AFP TRs. These data enable formulation of a rationale for the further development of anti‐AFP immunotherapy in HCC, facilitating optimal patient selection for future studies.
Coupled dynamics of iron, manganese, and phosphorus in brackish coastal sediments populated by cable bacteria
Authors: Hermans Martijn , Astudillo Pascual Marina , Behrends Thilo , Lenstra Wytze K. , Conley Daniel J. , Slomp Caroline P.
Published: May 2021

Coastal waters worldwide suffer from increased eutrophication and seasonal bottom water hypoxia. Here, we assess the dynamics of iron (Fe), manganese (Mn), and phosphorus (P) in sediments of the eutrophic, brackish Gulf of Finland populated by cable bacteria. At sites where bottom waters are oxic in spring, surface enrichments of Fe and Mn oxides and high abundances of cable bacteria were observed in sediments upon sampling in early summer. At one site, Fe and P were enriched in a thin layer (~ 3 mm) just below the sediment–water interface. X‐ray absorption near edge structure and micro X‐ray fluorescence analyses indicate that two‐thirds of the P in this layer was associated with poorly crystalline Fe oxides, with an additional contribution of Mn(II) phosphates. The Fe enriched layer was directly overlain by a Mn oxide‐rich surface layer (~ 2 mm). The Fe oxide layer was likely of diagenetic origin, formed through dissolution of Fe monosulfides and carbonates, potentially induced by cable bacteria in the preceding months when bottom waters were oxic. Most of the Mn oxides were likely deposited from the water column as part of a cycle of repeated deposition and remobilization. Further research is required to confirm whether cable bacteria activity in spring indeed promotes the formation of distinct layers enriched in Fe, Mn, and P minerals in Gulf of Finland sediments. The temporal variations in biogeochemical cycling in this seasonally hypoxic coastal system, potentially controlled by cable bacteria activity, have little impact on permanent sedimentary Fe, Mn, and P burial.
Information sharing in a Cournot–Bertrand duopoly
Authors: Kopel Michael , Putz Eva Maria
Published: May 2021

Studies on information sharing in oligopolies focus on either Cournot or Bertrand markets. We consider a Cournot–Bertrand market where owners provide strategic managerial incentives and can share the details of their compensation contracts. We find that the Cournot firm punishes its manager for sales, whereas the Bertrand firm rewards sales. Both firms share contract information if the firms' products are sufficiently differentiated. However, if product differentiation is low, then either the Cournot firm or the Bertrand firm keeps the contract information private. Mandating information sharing can lead to an increase in consumer and social welfare but harms firms' profits.
Detecting Sensitive Mobility Features for Parkinson's Disease Stages Via Machine Learning
Authors: Mirelman Anat , Ben Or Frank Mor , Melamed Michal , Granovsky Lena , Nieuwboer Alice , Rochester Lynn , Del Din Silvia , Avanzino Laura , Pelosin Elisa , Bloem Bastiaan R. , Della Croce Ugo , Cereatti Andrea , Bonato Paolo , Camicioli Richard , Ellis Theresa , Hamilton Jamie L. , Hass Chris J. , Almeida Quincy J. , Inbal Maidan , Thaler Avner , Shirvan Julia , Cedarbaum Jesse M. , Giladi Nir , Hausdorff Jeffrey M.
Published: May 2021

Background

It is not clear how specific gait measures reflect disease severity across the disease spectrum in Parkinson's disease (PD).

Objective

To identify the gait and mobility measures that are most sensitive and reflective of PD motor stages and determine the optimal sensor location in each disease stage.

Methods

Cross‐sectional wearable‐sensor records were collected in 332 patients with PD (Hoehn and Yahr scale I−III) and 100 age‐matched healthy controls. Sensors were adhered to the participant's lower back, bilateral ankles, and wrists. Study participants walked in a ~15‐meter corridor for 1 minute under two walking conditions: (1) preferred, usual walking speed and (2) walking while engaging in a cognitive task (dual‐task). A subgroup (n = 303, 67% PD) also performed the Timed Up and Go test. Multiple machine‐learning feature selection and classification algorithms were applied to discriminate between controls and PD and between the different PD severity stages.

Results

High discriminatory values were found between motor disease stages with mean sensitivity in the range 72%–83%, specificity 69%–80%, and area under the curve (AUC) 0.76–0.90. Measures from upper‐limb sensors best discriminated controls from early PD, turning measures obtained from the trunk sensor were prominent in mid‐stage PD, and stride timing and regularity were discriminative in more advanced stages.

Conclusions

Applying machine‐learning to multiple, wearable‐derived features reveals that different measures of gait and mobility are associated with and discriminate distinct stages of PD. These disparate feature sets can augment the objective monitoring of disease progression and may be useful for cohort selection and power analyses in clinical trials of PD. © 2021 International Parkinson and Movement Disorder Society
Efficacy and safety of probiotics and prebiotics in liver transplantation: A systematic review and meta‐analysis
Authors: Ma Ming , Wang Xiaodong , Li Junjie , Jiang Wentao
Published: May 2021

Probiotics were used for liver transplantation (LT) patients to reduce postoperative infection, but clinical trials examining the combined use of prebiotics and probiotics are limited. This meta‐analysis aimed to compare the safety and efficacy of combined use of prebiotics and probiotics in patients undergoing LT. PubMed, Cochrane, and Embase databases were reviewed for the combined use of prebiotics and probiotics in patients undergoing LT. The weighted mean difference (WMD), risk ratio (RR), and 95% CI were calculated. A total of 6 related studies comprising 345 patients were included. Most prebiotics and probiotics were given for 7.14 days. The overall infection rate (RR = 0.29; 95% CI, 0.14.0.60; P value for heterogeneity [PH] = .066; test for heterogeneity [I2] = 51.7%) and the incidence of urinary tract infection (RR = 0.14; 95% CI, 0.04–0.47, PH = .724; I2 = 0%) were lower in the probiotics group when compared with those in the control group. Furthermore, probiotics significantly reduced the hospital length of stay (WMD = −1.37; 95% CI, −1.92 to 0.82; PH = .506; I2 = 0%) and the duration of antimicrobial therapy (WMD = −4.31; 95% CI, −5.41 to 3.22; PH = .019; I2 = 69.8%) in patients undergoing LT. These findings suggested that the combined use of prebiotics and probiotics (Lactobacillus and Bifidobacterium) was effective in lowering the incidence of bacterial infections and shortening the hospital length of stay and duration of antibiotic therapy in patients undergoing LT, when compared with conventional nutrition.
Back pain associated with centrally administered parenteral nutrition
Authors: Swartz Sheila , Dummann Kacy , Guell Caitlin , Lubinsky Mark , Kozeniecki Michelle
Published: May 2021

Parenteral nutrition (PN) is well recognized for its ability to provide nutrition to patients without the ability to digest enterally; however, PN must also be seen as a medication with associated adverse drug events similar to any other pharmacological agent that is administered to patients. Here we present a case report of localized lower back pain with central PN infusion. The initial areas of concern were the intravenous lipid emulsion, peripherally inserted central catheter placement, osmolarity of the formula, and the additives. The patient's back pain was ultimately felt to be an adverse reaction to the multivitamin component of the infusion based on an elimination trial of the PN components.
Mixed‐method research protocol: Development and evaluation of a nursing intervention in patients discharged from the intensive care unit
Authors: Cuzco Cecilia , Castro Rebollo Pedro , Marín Pérez Raquel , Núñez Delgado Ana Isabel , Romero García Marta , Martínez Momblan M. Antonia , Estrada Reventós Dolors , Martínez Estalella Gemma , Delgado‐Hito Pilar
Published: May 2021

Aim

(a) To understand patients’ lived experience at intensive care unit (ICU) discharge and (b) to evaluate the impact of a nursing empowerment intervention (NEI) on patients’ anxiety and depression levels at ICU discharge.

Design

A mixed‐methods approach will be applied.

Methods

In the qualitative phase, the hermeneutic phenomenological method will be used. Participants will be patients from three university hospitals who will be selected by purposive sampling. Data will be gathered through in‐depth interviews and analysed using content analysis. The qualitative data obtained will be employed to develop the nursing intervention. Subsequently, a multicenter, parallel‐group, experimental pre‐test/post‐test design with a control group will be used to measure the effectiveness of the nursing empowerment intervention in the quantitative phase by means of the Hospital Anxiety and Depression Scale (HADS). Simple random probabilistic sampling will include 172 patients in this phase.
The Effect of Roux‐en‐Y Gastric Bypass on Bone Marrow Adipose Tissue and Bone Mineral Density in Postmenopausal, Nondiabetic Women
Authors: Beekman Kerensa M. , Akkerman Erik M. , Streekstra Geert J. , Veldhuis‐Vlug Annegreet G. , Acherman Yair , Gerdes Victor E. , den Heijer Martin , Maas Mario , Bravenboer Nathalie , Bisschop Peter H.
Published: May 2021

Objectives

This study aimed to determine the effect of bariatric surgery‐induced weight loss on bone marrow adipose tissue (BMAT) and bone mineral density (BMD) in postmenopausal, nondiabetic women.

Methods

A total of 14 postmenopausal, nondiabetic women with obesity who were scheduled for laparoscopic Roux‐en‐Y gastric bypass surgery (RYGB) were included in this study. Vertebral bone marrow fat signal fraction was determined by quantitative chemical shift magnetic resonance imaging, and vertebral volumetric BMD (vBMD) was determined by quantitative computed tomography before surgery and 3 and 12 months after surgery. Data were analyzed by linear mixed model.

Results

Body weight [mean (SD)] decreased after surgery from 108 (13) kg at baseline to 89 (12) kg at 3 months and 74 (11) kg at 12 months (P < 0.001). BMAT decreased after surgery from 51% (8%) at baseline to 50% (8%) at 3 months and 46% (7%) at 12 months (P = 0.004). vBMD decreased after surgery from 101 (26) mg/cm3 at baseline to 94 (28) mg/cm3 at 3 months (P = 0.003) and 94 (28) mg/cm3 at 12 months (P = 0.035). Changes in BMAT and vBMD were not correlated (ρ = −0.10 and P = 0.75). Calcium and vitamin D concentrations did not change after surgery.

Conclusions

RYGB decreases both BMAT (after 12 months) and vBMD (both after 3 months and 12 months) in postmenopausal, nondiabetic women. Changes in BMAT and vBMD were not correlated. These findings suggest that BMAT does not contribute to bone loss following RYGB.
Smoothened loss is a characteristic of neuroendocrine prostate cancer
Authors: Wang Lili , Li Haiying , Li Zhang , Li Ming , Tang Qi , Wu Chunxiao , Lu Zhiming
Published: May 2021

Purpose

Hedgehog (Hh) signaling promotes castration‐resistant prostate cancer by supporting androgen‐independent prostate cancer cell development and growth; however, its role in neuroendocrine prostate cancer (NEPC) has not yet been explored. In this study, we assessed the expression of key genes involved in Hh signaling in prostate cancer and investigated the potential role of smoothened (SMO) in the pathogenesis of NEPC.

Methods

Six public datasets, each containing cases of prostate adenocarcinoma (AdPC) and NEPC, were analyzed to compare the differential messenger RNA (mRNA) expression of six classic Hh signaling genes. The SMO, synaptophysin, chromogranin A (CHGA) and androgen receptor (AR) proteins were evaluated in human tissues from 5 cases of NEPC, 2 cases of AdPC mixed with NEPC, 2 cases of AdPC with neuroendocrine differentiation and 22 cases of high‐grade AdPC as determined by an immunohistochemistry assay. Gene set enrichment analysis (GSEA) was performed to identify relevant genetic signatures associated with SMO expression based on the public datasets. Stable SMO‐knockdown LNCaP and C4‐2B cells were established with a lentiviral system, and the expression of SMO, Gli1, AR, prostate‐specific antigen (PSA), and REST was assessed by real‐time polymerase chain reaction and western blot. Secreted PSA in the conditioned medium was assessed by ELISA. Gli1 was ectopically expressed performed by the transfection of Gli1 complementary DNA into SMO‐knockdown LNCaP cells, and western blot was used to assess of AR and PSA expression.

Results

The mRNA level of SMO was dramatically downregulated in NEPC samples compared with AdPC samples in all 6 public datasets. SMO protein loss was observed in 100% of NEPC samples but in only 9% (2 of 22) of high‐grade AdPC samples. GSEA results showed that SMO loss was closely correlated with AR signaling activity. Stable SMO knockdown significantly attenuated AR signaling activity and suppressed AR expression, while Gli1 overexpression partially reversed the inhibitory effects of SMO knockdown on AR signaling activity and AR expression in LNCaP and C4‐2B cells.

Conclusion

These results demonstrate that SMO loss is a characteristic of NEPC and that detecting SMO by IHC could aid pathologists in NEPC diagnosis. SMO loss may promote NEPC pathogenesis by modulating AR signaling.
Genomic profiles and clinical outcomes in primary versus secondary metastatic hormone‐sensitive prostate cancer
Authors: Nizialek Emily , Lim Su Jin , Wang Hao , Isaacsson Velho Pedro , Yegnasubramanian Srinivasan , Antonarakis Emmanuel S.
Published: May 2021

Background

Clinical outcomes may differ among patients presenting with primary (de novo) metastatic hormone‐sensitive prostate cancer (mHSPC) versus secondary (metachronous) mHSPC occurring after local therapy. It is unknown what molecular features distinguish these potentially distinct presentations.

Methods

A single‐center retrospective study of mHSPC patients classified as primary mHSPC (n = 121) or secondary mHSPC (n = 106). A targeted set of genes was analyzed:BRCA2,PTEN,RB1,TP53,SPOP,CDK12, any two out ofPTEN/RB1/TP53alterations, and homologous recombination deficiency mutations.TP53mutations were categorized as loss‐of‐function (LOF) versus dominant‐negative (DN). The impacts of genetic features on progression‐free survival (PFS) and overall survival (OS) were assessed using univariate and multivariate Cox proportional hazards regression.

Results

Median PFS was 15 and 30 months for men with primary and secondary mHSPC, respectively (hazard ratio: 0.57, 95% confidence interval: 0.41–0.78;p < .01). OS did not show a significant difference between groups. There were more men with Gleason 8–10 disease in the primary versus secondary mHSPC groups (83% vs. 68%; p < .01). In univariate and multivariate analyses,TP53 DN mutations showed a statistically significant association with OS for the entire mHSPC population. Conversely,SPOPmutations were associated with improved OS. Additionally,TP53mutations (DN and LOF) were associated with worse OS for secondary mHSPC. A combination ofPTEN/RB1/TP53mutations was associated with worse OS and PFS for secondary mHSPC, while no genomic alteration affected outcomes for primary mHSPC.

Conclusions

TP53DN mutations, but not allTP53alterations, were the strongest predictor of negative outcomes in men with mHSPC, whileSPOPmutations were associated with improved outcomes. In subgroup analyses, specific alterations were prognostic of outcomes in secondary, but not primary, mHSPC.
Suppression of Pseudomonas syringae pv. tomato infection by rhizosphere fungi
Authors: Elsharkawy Mohsen M , Khedr Amr A , Mehiar Farid , El‐Kady Elsayed M , Baazeem Alaa , Shimizu Masafumi
Published: May 2021

BACKGROUND

Induced resistance against several plant pathogens was reported using different beneficial plant growth‐promoting microorganisms. The potential of five fungal isolates, Trichoderma harzianum GT 3‐2, Fusarium equiseti GF 18‐3, F. equiseti GF 19‐1, Phoma sp. GS 10‐1 and Phoma sp. GS 14‐1, to stimulate tomato growth and resistance against bacterial speck disease caused by Pseudomonas syringae pathovar (pv.) tomato DC3000 was evaluated.

RESULTS

Based on the results of disease severity and growth promotion experiments, GF 18‐3 exhibited the best results among all fungal isolates. Treatment with barley grain inocula (BGI) and culture filtrate (CF) of the isolates promoted tomato growth and suppressed the pathogen in pot trials. Furthermore, expressions of the pathogenesis‐related genes (PR‐1, β‐1,3‐glucanase A, β‐1,3‐glucanase B and LOX) were relatively higher than the control in the leaves of tomato plants treated with both BGI and CF. The transcription levels remained consistently higher than the control plants for 6 days post‐inoculation with pathogen.

CONCLUSION

Taken together, the results indicate that the tested fungal isolates have the potential to promote tomato growth and induce systemic resistance against the bacterial speck disease. Analysis of certain PR gene expression revealed significant activation in both BGI and CF treatments, leading to stimulated resistance against the pathogen. © 2021 Society of Chemical Industry.
Population pharmacokinetic modeling of molibresib and its active metabolites in patients with solid tumors: A semimechanistic autoinduction model
Authors: Krishnatry Anu Shilpa , Voelkner Alexander , Dhar Arindam , Prohn Marita , Ferron‐Brady Geraldine
Published: May 2021

Molibresib (GSK525762) is an investigational, orally bioavailable, small‐molecule bromodomain and extraterminal (BET) protein inhibitor for the treatment of advanced solid tumors. Molibresib was initially evaluated in a first‐time‐in‐human (FTIH) study BET115521 consisting of two parts: Part 1 of the study (dose escalation) was conducted in 94 patients with nuclear protein in testis midline carcinoma and other solid tumors, and Part 2 (expansion cohort) was conducted in 99 patients with different solid tumor types. Molibresib is metabolized by cytochrome P450 3A4 enzymes to produce two major active metabolites that are equipotent to the parent molecule. The metabolites are measured together after full conversion of one to the other and reported as an active metabolite composite (GSK3529246). The molibresib pharmacokinetic (PK) profile has been characterized by a decrease in exposure over time, with the decrease more pronounced at higher doses, and accompanied by a slight increase of the metabolite concentrations. Autoinduction of molibresib metabolism was suspected and confirmed in vitro. Here we report the development of a semimechanistic liver‐compartment population PK model using PK data from the FTIH study, which adequately describes the autoinduction of molibresib clearance and the PK of both molibresib and GSK3529246. Covariate analysis indicated body weight had a significant effect on the volume of distribution of molibresib and GSK3529246, and higher levels of aspartate aminotransferase resulted in the lower clearance of GSK3529246. This model was used to simulate individual patient exposures based on covariate information for use in future alternative dosing strategies and exposure–response analyses.
Designing of cyanobenzene based small molecules with suitable photovoltaic parameters for organic solar cells
Authors: Khan Memoona , Jilani Faiza , Ayub Amna , Naseem Zubera , Ayub Ali Raza , Mahr Muhammad Shabir , Iqbal Javed
Published: May 2021

In this research work, a theoretical analysis of the photovoltaic properties of nonfullerene organic solar cells is performed. Four molecules have been designed by incorporating different donor units around the central cyanobenzene based acceptor core through thiophene spacer by mimicking the structure of R. DFT and TD‐DFT have been used to explore the following properties of solar cell material: opto‐electronic properties, reorganization energy, transition density matrix, and open circuit voltage. The designed molecules have side groups triphenylamine (M1), 2‐(5‐(4 [diphenylamino]phenyl) thiophen‐2‐yl) acrylonitrile (M2), 4‐(5‐(ethynylthiophen‐2‐yl)‐N,N‐diphenylaniline (M3), and 4‐(benzo[c][1,2,5]thiadiazol‐4‐yl)‐N,N‐diphenylaniline (M4). Among all the designed molecules, M4 has shown bathochromic shift with λmax 663 nm due to extended conjugation between end‐capped donor units and central electron‐deficient core. Similarly, among all of the designed molecules M4 also shown lower mobility of electron (λe) and hole (λh) which are 0.0047 and 0.0050 eV, respectively, that are also comparable to R. The lower reorganization energy of M4 exhibits the higher transfer of charge among all other designed molecules. Moreover, the open circuit voltage of M4 was 1.56 eV according to that of PC61BM acceptor. Results showed that designed Acceptor‐π spacer‐Donor molecule opened a new pathway for the solar cell material with modified and advanced properties.
Prescribed time tracking control of constrained Euler–Lagrange systems: An adaptive proportional–integral solution
Authors: Cui Qian , Cao Hongwei , Wang Yujuan , Song Yongduan
Published: May 2021

Most autonomous systems can be described by Euler–Lagrange (EL) model. This article investigates the problem of prescribed time tracking control for EL systems in the presence of modeling uncertainties, prescribed performance requirements and time‐varying state constraints. Two proportional–integral (PI)‐like control schemes with time‐varying gains are developed with several favorable features: (1) achieving prescribed tracking precision within finite time in the presence of modeling uncertainties; (2) state constraints being obeyed all the time; (3) both the final tracking accuracy and the setting time being preassigned irrespective of initial condition or any other constraining parameter; and (4) bearing simple PI structure with analytical formula for robust‐adaptive tuning gains, and demanding inexpensive online computation. The benefits and effectiveness of the proposed control are also validated via numerical simulation.
In situ Sub‐Cellular Identification of Functional Amyloids in Bacteria and Archaea by Infrared Nanospectroscopy
Authors: Otzen Daniel E. , Dueholm Morten S. , Najarzadeh Zahra , Knowles Tuomas P. J. , Ruggeri Francesco Simone
Published: May 2021

Formation of amyloid structures is originally linked to human disease. However, amyloid materials are found extensively in the animal and bacterial world where they stabilize intra‐ and extra‐cellular environments like biofilms or cell envelopes. To date, functional amyloids have largely been studied using optical microscopy techniques in vivo, or after removal from their biological context for higher‐resolution studies in vitro. Furthermore, conventional microscopies only indirectly identify amyloids based on morphology or unspecific amyloid dyes. Here, the high chemical and spatial (≈20 nm) resolution of Infrared Nanospectroscopy (AFM‐IR) to investigate functional amyloid from Escherichia coli (curli), Pseudomonas (Fap), and the Archaea Methanosaeta (MspA) in situ is exploited. It is demonstrated that AFM‐IR identifies amyloid protein within single intact cells through their cross β‐sheet secondary structure, which has a unique spectroscopic signature in the amide I band of protein. Using this approach, nanoscale‐resolved chemical images and spectra of purified curli and Methanosaeta cell wall sheaths are provided. The results highlight significant differences in secondary structure between E. coli cells with and without curli. Taken together, these results suggest that AFM‐IR is a new and powerful label‐free tool for in situ investigations of the biophysical state of functional amyloid and biomolecules in general.
One species with a disjunct distribution or two with convergent evolution? Taxonomy of two South American garlics
Authors: Sassone Agostina B. , Arroyo Mary T.K. , Arroyo‐Leuenberger Silvia C. , García Nicolás , Román María José
Published: May 2021

The establishment of species boundaries has been a difficult task for biologists since the beginning of classifications. Within South American Allioideae (= Alliaceae), the delimitation of genera and species has long been a major challenge. Consequently, species‐level nomenclature in these groups has been difficult to elucidate. Ipheion and Tristagma are two closely related South American genera for which the delimitation and circumscription of several species continue to be unclear. Tristagma sessile, a species inhabiting the Andes and the Coast Range in Chile, and Ipheion recurvifolium, a species native to Uruguay only found close to sea level, have been considered as one species with an intracontinental disjunct distribution. The divergent habitats and distributions of these taxa have stirred the question of whether they are a single species. The present study aims to elucidate the evolutionary relationships and status of the Chilean and Pampean taxa. We also analysed the name Tristagma leichtlinii, which has long been a source of confusion. Based on their phylogenetic relationships, geographical distributions, flowering periods, and DNA content, we conclude that the two taxa are different species and assignable to separate genera. We propose that the morphological similarity of Ipheion recurvifolium and Tristagma sessile, amply corroborated in this study, might be the sum of shared synapomorphies (between Ipheion and Tristagma) and convergent features. We update the biogeographic history of the two genera and propose that similar pollinators might underpin the convergence in floral traits. We outline the differences among genera and species, present a taxonomic review with a new lectotype and consider the conservation status of the studied species.
Causal emergence from effective information
Authors: Dewhurst Joe ,   Philosophy Documentation Center
Published: May 2021

The past few years have seen several novel information-theoretic measures of causal emergence developed within the scientific community. In this paper I will introduce one such measure, called ‘effective information’, and describe how it is used to argue for causal emergence. In brief, the idea is that certain kinds of complex system are structured such that an intervention characterised at the macro-level will be more informative than one characterised at the micro-level, and that this constitutes a form of causal emergence. Having introduced this proposal, I will then assess the extent to which it is genuinely ‘causal’ and/or ‘emergent’, and argue that it supports only an epistemic form of causal emergence that is not as exciting as it first seems.
Delphinidin modulates JAK/STAT3 and MAPKinase signaling to induce apoptosis in HCT116 cells
Authors: Zhang Zhiyong , Pan Yan , Zhao Yan , Ren Mudan , Li Yarui , Lu Guifang , Wu Kaichun , He Shuixiang
Published: May 2021

Delphinidin is an anthocyanin that belongs to the group of flavonoids that exert numerous biological activities. However, the molecular mechanisms underlying the anticancer effects of delphinidin remain poorly understood. In our study we analyzed delphinidin modulate STAT‐3 and MAPKinase signaling thereby inhbits cell proliferation and promote apoptosis. Our study demonstrated that delphinidin treatment significantly reduced the viability of human colon cancer HCT116 in a concentration‐dependent manner. We noticed that delphinidin effectively induced oxidative stress‐mediated apoptosis by generating intracellular ROS, decreasing antioxidant levels, inducing lipid peroxidation, and single‐strand break on colon cancer cells. In this study, we observed that delphinidin treatment alters the mitochondrial membrane potential, thereby induces apoptosis was closely associated with the induction of pro‐apoptotic Bax, Caspase‐ 3,8 & 9, cytochrome C, and inhibition of anti‐apoptotic protein expression. Studies on STAT‐3 and MAPKinase signaling showed delphinidin inhibited the phosphorylation of these transcription factors' activity. Inhibition of STAT‐3, p38, and ERK1/2 phosphorylation and modulation pro‐apoptotic protein expression might be responsible for the anticancer activity of delphinidin in colon cancer cells.
Advances of nanomaterials‐based strategies for fighting against COVID‐19
Authors: Zeng Chunxi , Hou Xucheng , Bohmer Margaret , Dong Yizhou
Published: May 2021

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has infected over 100 million people globally due to its high infectivity. After decades of efforts on the studies of nanomaterials, researchers have applied nanomaterials‐based strategies to combat the pandemic of the coronavirus disease 2019 (COVID‐19). First, nanomaterials facilitate the development of easy, fast, and low‐cost diagnostic assays to detect SARS‐CoV‐2 and related biomarkers. Second, nanomaterials enable the efficient delivery of viral antigens to antigen‐presenting cells or serve as adjuvants in the host, leading to vaccine development at an unprecedented pace. Lastly, nanomaterials‐based treatments may inhibit SARS‐CoV‐2 replication and reduce inflammation. Overall, nanomaterials have played important roles in controlling this COVID‐19 pandemic. Here, we provide a brief overview of the representative examples of nanomaterials‐based diagnostics, vaccines, and therapeutics in the fight against COVID‐19.
The effect of CRISPR constructs microinjection on the expression of developmental genes in Rag1 knocked‐out mice embryo
Authors: Salimi Maryam , Shirazi Abolfazl , Sineh Sepehr Koushan , Norouzian Mohsen , Ebrahimi Vahid , Mehravar Maryam , Majidi Mohammad , Mehrazar Mohammad M.
Published: May 2021

Despite all the advances in the production of transgenic mice, the production efficiency of these animal models is still low. Given that the expression of developmental genes has a critical role in growth and development of embryo, we determined the expression pattern of pluripotency, trophectoderm and imprinting genes in the Rag1 (recombination‐activating gene 1) knocked‐out blastocysts resulting from microinjection of CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR‐associated protein 9) constructs into the zygote cytoplasm of C57bl6 mice. Following microinjection, the embryos were cultured and the gene expression of developed blastocysts and natural blastocysts (Sham and control groups) were evaluated using real‐time PCR. The agarose gel to confirm the deletion in the Rag1 gene in Rag1 knocked‐out blastocyst. Our results showed that the expression of trophectoderm genes (‐TEAD‐4 and Cdx2), pluripotency genes (Nanog and Oct‐4) and imprinting gene (H19) in the Rag1 knocked‐out group was significantly lower compared with the embryos obtained from Natural fertilization. According to these findings, manipulation, embryo culture and microinjection of CRISPR constructs into the zygote cytoplasm of mice led to reduced expression of imprinting, pluripotency and trophectoderm genes. Therefore, the Rag1 knocked‐out embryos produced by the CRISPR/Cas9 system are of low quality, which reduces the chances of live birth in these animals and may cause various abnormalities in fetuses.
Effects of Amaranthus hypochondriacus supplementation during gestation and lactation on the apparent total tract digestibility of nutrients, lactational feed intake, and litter performance in sows
Authors: Xia Jun , Chen Linlin , Huang Pengfei , Mou Qi , Yang Ying , Li Jiaming , Xu Minglang , Li Jianzhong , Yang Huansheng , Yin Yulong
Published: May 2021

The purpose of this study was to investigate the effects of Amaranthus hypochondriacus (AH) inclusion in the diets of gestating and lactating sows on the lactational feed intake, nutrient digestibility, and growth performance of suckling piglets. During gestation, 40 multiparous Landrace sows were restrictively fed with either a control diet or a diet including 30% AH. Both diets had similar levels of digestible energy and crude protein, but the 30% AH diet had higher crude fibre levels than the control diet. After breeding, lactating sows were fed ad libitum with one of two isoenergetic and isonitrogenous diets, either a control diet or a diet containing 10% AH. In gestating sows, AH supplementation was found to be associated with decreased digestibility of crude protein and dry matter (p < .001), resulting in lesser backfat depth (p < .001). However, in lactating sows, AH supplementation had little effect on digestibility and milk composition; moreover, it increased the feed intake (p < .001) and decreased backfat loss (p < .001) in sows. On the 21st day of lactation, suckling piglets in AH group showed significantly greater average daily gains (p < .001), and average body weight and litter weight significantly increased compared with sows fed the control diet. In conclusion, AH‐supplementation increased lactational feed intake in sows and improved the growth performance of suckling piglets.
Conformal Regge theory at finite boost
Authors: Caron-Huot Simon , Sandor Joshua
Published: May 2021

Abstract

The Operator Product Expansion is a useful tool to represent correlation functions. In this note we extend Conformal Regge theory to provide an exact OPE representation of Lorenzian four-point correlators in conformal field theory, valid even away from Regge limit. The representation extends convergence of the OPE by rewriting it as a double integral over continuous spins and dimensions, and features a novel “Regge block”. We test the formula in the conformal fishnet theory, where exact results involving nontrivial Regge trajectories are available.
Towards general scalar-Yukawa renormalisation group equations at three-loop order
Authors: Steudtner Tom
Published: May 2021

Abstract

For arbitrary four-dimensional quantum field theories with scalars and fermions, renormalisation group equations in the$$ \overline{\mathrm{MS}} $$MS¯scheme are investigated at three-loop order in perturbation theory. Collecting literature results, general expressions are obtained for field anomalous dimensions, Yukawa interactions, as well as fermion masses. The renormalisation group evolution of scalar quartic, cubic and mass terms is determined up to a few unknown coefficients. The combined results are applied to compute the renormalisation group evolution of the gaugeless Litim-Sannino model.
A variational restriction theorem
Authors: Kovač Vjekoslav , Oliveira e Silva Diogo
Published: May 2021

We establish variational estimates related to the problem of restricting the Fourier transform of a three-dimensional function to the two-dimensional Euclidean sphere. At the same time, we give a short survey of the recent field of maximal Fourier restriction theory.
Paternal outcrossing success differs among faba bean genotypes and impacts breeding of synthetic cultivars
Authors: Brünjes Lisa , Link Wolfgang
Published: May 2021

Key message

Faba bean genotypes showed significant and marked genetic differences in their success as pollen donors to cross-fertilized seeds. The findings may improve exploitation of heterosis in synthetic cultivars.

In partially allogamous crops such as faba bean (Vicia faba L.), increasing the share of heterosis in a synthetic cultivar can improve yield and yield stability. The share of heterosis in such synthetic cultivars is increased by higher degrees of cross-fertilization. This trait is defined as percentage of cross-fertilized seeds among all seeds and is a crucial parameter in breeders’ yield predictions. Current approaches use degree of cross-fertilization to predict inbreeding and share of heterosis, they even consider genotype-specific degrees; yet, all genotypes are assumed to contribute equally to the cross-fertilized seeds. Here, we expect faba bean genotypes to differ in their success rates as pollen donors, i.e. in paternal outcrossing success. To quantify the variation of both, the degree of cross-fertilization and the paternal outcrossing success, we assessed these parameters in inbred lines and F1 hybrids, grown in four polycrosses composed of eight genotypes each. We identified the paternal genotype of 500 to 800 seeds per genotype and polycross using SNP markers. In both traits, we found marked and significant variation among inbred lines and among F1 hybrids, as well as between inbred lines and F1. Based on our findings, we discuss how differential paternal outcrossing success influences the amount of inbreeding in synthetic cultivars. Our findings offer the potential for a better management and exploitation of heterotic yield increase in faba bean.
Estimating the cumulative risk of postnatal depressive symptoms: the role of insomnia symptoms across pregnancy
Authors: Pietikäinen Johanna T. , Härkänen Tommi , Polo-Kantola Päivi , Karlsson Hasse , Paunio Tiina , Karlsson Linnea , Paavonen E. Juulia
Published: May 2021

Purpose

Insomnia symptoms during late pregnancy are a known risk for postnatal depressive symptoms (PDS). However, the cumulative effect of various risk factors throughout pregnancy has not been explored. Our aim was to test how various insomnia symptoms (sleep latency, duration, quality, frequent night awakenings, early morning awakenings) and other risk factors (e.g., history of depression, symptoms of depression and anxiety, as well as sociodemographic factors) in early, mid-, and late pregnancy predict PDS.

Methods

Using data from the FinnBrain Birth Cohort Study and logistic regression analyses, we investigated the associations of distinct insomnia symptoms at gw 14, 24, and 34 with depressive symptoms (Edinburgh Postnatal Depression Scale score ≥ 11) 3 months postnatally. We also calculated separate and combined predictive models of PDS for each pregnancy time point and reported the odds ratios for each risk group.

Results

Of the 2224 women included in the study, 7.1% scored EPDS ≥ 11 3 months postnatally. Our predictive models indicated that sleep latency of ≥ 20 min, anxiety in early pregnancy, and insufficient sleep during late pregnancy predicted the risk of PDS. Furthermore, we found highly elevated odds ratios in early, mid-, and late pregnancy for women with multiple PDS risk factors.

Conclusion

Screening of long sleep latency and anxiety during early pregnancy, in addition to depression screening, could be advisable. Odds ratios of risk factor combinations demonstrate the magnitude of cumulating risk of PDS when multiple risk factors are present.