bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14932: Effects of Cardiac Resynchronization Therapy in Ischemic Cardiomyopathy Patients by Revascularization Procedures in MADIT-CRT
Authors: Husaini Mustafa , Biton Yitschak , McNitt Scott , Zareba Wojciech , Moss Arthur J , Goldenberg Ilan , Barsheshet Alon , Kutyifa Valentina
Published: July 2021

Background:
The Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) showed that patients with ischemic cardiomyopathy (ICM) had similar reductions in clinical events with implanted CRT-D vs. ICD-only when compared to patients with non-ischemic cardiomyopathy (NICM). Frequency of revascularizations may serve as a surrogate for severity of coronary artery disease in patients with ICM and severely reduced left ventricular ejection fraction. However, it is unknown whether the number of revascularizations plays a role in clinical outcomes in ICM patients implanted with CRT-D vs. ICD-only.

Methods:
Using a multivariable analysis of MADIT-CRT data, we evaluated the effect of CRT-D vs. ICD-only on combined heart failure (HF) or death and combined ventricular tachycardia (VT), ventricular fibrillation (VF) or death in ICM patients by the number of pre-enrollment revascularizations (1 or ≥ 2 revascularizations) compared to those with no need for revascularization. Follow-up over a median period of 5.6 years for HF/death and 4.0 years for VT/VF/death was assessed among 1374 ICM patients with a Left Bundle Branch Block (LBBB).

Results:
There was a significant and similar risk reduction with CRT-D vs. ICD-only in HF/death in all three sub-groups: ICM with no need for revascularization (HR 0.45 [0.26-0.80]; p < 0.006), ICM with one revascularization (HR 0.46 [0.31-0.69]; p <0.001), and ICM with 2 or more revascularization (HR 0.50 [0.30-0.84]; p = 0.008). However, significant risk reduction of VT/VF/death with CRT-D vs. ICD-only was only observed in patients with no need for revascularization (HR 0.52 [0.30-0.89]; p = 0.017), less so in those with ICM with one revascularization (HR 0.72 [0.49-1.06]; p = 0.10), and no reduction was seen in those with ICM with 2 or more revascularization (HR 0.94 [0.54-1.62]; p = 0.81). Conclusions: In ischemic cardiomyopathy patients, CRT-D vs. ICD-only is associated with a significant risk reduction in heart failure events or death irrespective of the frequency of pre-enrollment revascularization procedures; however, the benefit of CRT-D vs. ICD-only to reduce ventricular tachyarrhythmias is attenuated with the increasing number of revascularization procedures.
Abstract 15436: Remote Ischemic Conditioning Modulates Myocardial Perfusion and Coronary Vascular Resistance in Ischemic and Non-ischemic Myocardial Territories in Humans
Authors: Pryds Kasper , Ranghøj Nielsen Roni , Rahbek Schmidt Michael , Molich Hoff Camilla , Tolbod Poulsen Lars , Bouchelouche Kirsten , Frøkiær Jørgen , Bøtker Hans Erik
Published: July 2021

Purpose:
Remote ischemic conditioning (RIC) confers protection against myocardial ischemia-reperfusion injury through cellular protective pathways but may also involve modulation of the myocardial perfusion (MP). We investigated whether RIC modulates MP and coronary vascular resistance (CVR) in ischemic and non-ischemic myocardial territories in humans.

Methods:
In a prospective, single blinded study, we studied 49 patients with suspected stable coronary artery disease. MP was quantified by
82
Rb-PET before and after RIC, and CVR was calculated as mean arterial pressure divided by MP. RIC was conducted as 4 cycles of 5 min upper arm ischemia followed by 5 min of reperfusion. A subsequent adenosine
82
Rb-PET stress scanning identified non-ischemic, reversibly and irreversibly ischemic myocardial segments by summed difference scores, and quantified coronary flow reserve (CFR).

Results:
Stress
82
Rb-PET data were available for 47 patients and identified 682 non-ischemic, 38 reversibly ischemic, and 37 irreversibly ischemic myocardial segments. Mean CFR was decreased in reversibly ischemic myocardial segments. Global MP and CVR were not affected by RIC (p=0.64 and p=0.53). RIC decreased MP and increased CVR in reversibly ischemic myocardial segments but not in non-ischemic or irreversibly ischemic myocardial segments (Table). Overall, CFR correlated with a change in MP and CVR by RIC (r
2
=0.08, p<0.001 and r
2
=0.10, p<0.001), and allowed identification of a cut-off of CFR<2.3 for a decrease in MP by RIC.

Conclusion:
RIC modulated MP and CVR dependent on the ischemic status of the myocardium and the vasodilatative capacity of the microcirculation. These findings support the assumption that gentle perfusion may be involved in the cardioprotective mechanisms underlying RIC.
Abstract 15554: Heart Failure-Related Hyperphosphorylation of Ser199 on Cardiac Troponin I Causes Divergent Effects on Cardiac Function at Baseline and During Ischemia-Reperfusion
Authors: Li Yuejin , Zhu Guangshuo , Takahashi Cyrus , Bedja Djahida , Ramirez-Correa Genaro , Paolocci Nazareno , Kass David A , Murphy Anne M
Published: July 2021

Background:
Phosphorylation of cardiac troponin I (cTnI) on Ser199 is significantly increased in human heart failure (HF), however its cardiac impact in vivo remains unknown. In addition, selective proteolysis of cTnI is a marker of myocardial injury and contributes to cardiac dysfunction in ischemia/reperfusion (I/R), and Ser199 phosphorylation affects cTnI proteolysis in vitro, thus whether Ser199 phosphorylation affects cardiac performance during I/R is of great interest.

Methods and Results:
We generated transgenic mice (TgS200D) carrying cTnI S200D mutation to mimic the site-specific hyperphosphorylation of murine Ser200 (equivalent to human Ser199). Cardiac function was first assessed in vivo using echocardiography. TgS200D mice demonstrated unaltered ejection fraction (EF), significantly prolonged isovolumic relaxation time, and normal left ventricular (LV) chamber size and wall thickness (n=10). LV pressure-volume studies showed preserved dp/dtmax, significantly decreased -dp/dtmin and increased relaxation time constant in TgS200D when compared to non-transgenic (NTg) control group at baseline (n=10). With increasing heart rates, the two groups showed similar enhancement in both systolic and diastolic function, suggesting the positive force-frequency relation is preserved in TgS200D (n=5). After isoproterenol injection (i.v. 40ng/min/kg), although a comparable increase in dp/dtmax was observed in both groups, there was no enhancement of -dp/dtmin in TgS200D in contrast to 15% of increase in NTg (n=5, p=0.019). After ischemia (30 min)/reperfusion (60 min), LV developed pressure was recovered by ~90% in isolated TgS200D hearts but only ~40% in NTg (n=5, p=0.003). Immunoblotting detected cTnI cleavage only in NTg hearts.

Conclusions:
Our results indicate that hyperphosphorylation of cTnI Ser199 1) impairs basal diastolic function but preserves systolic function, without LV hypertrophy or dilation; 2) blunts cardiac lusitropic response to β-adrenergic stimulation with isoproterenol; 3) protects heart against I/R injury, likely via preventing cTnI degradation. We propose a dual role of cTnI Ser199 hyperphosphorylaiton: contributing to HF with preserved EF but protecting heart during I/R.
Abstract 16145: Significance of High-sensitivity Cardiac Troponin T Levels Between the Limit of Blank and the Limit of Detection in the General Population: A Meta-analysis
Authors: Parikh Ravi , Seliger Stephen L , de Lemos James , Nambi Vijay , Christenson Robert , Ayers Colby , Sun Wensheng , Gottdiener John S , Kuller Lewis H , Ballantyne Christie M , deFilippi Christopher
Published: July 2021

Introduction:
A substantial minority of asymptomatic individuals will have very low but measurable levels of cardiac troponin T using a high sensitive assay (hs-cTnT). It is controversial if levels in this range provide physiologic and prognostic information. We hypothesized that hs-cTnT levels between the limit of blank (LOB) (3 ng/L) and limit of detection (LOD) (5 ng/L) are associated with increased incidence of heart failure (HF) and cardiovascular death compared to levels below the LOB (<3 ng/L).

Methods:
hs-cTnT was measured in subjects without prevalent HF from the Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities (ARIC) study, and Dallas Heart Study (DHS). Participants were divided into two groups: levels below the LOB (n=7272) and levels between the LOB and LOD (n=3451). Cross sectional and longitudinal associations with demographics, traditional cardiovascular risk factors, and cardiovascular outcomes were made. A fixed-effect meta-analysis was performed using regression coefficients and variance estimates from fully adjusted models from all three cohorts.

Results:
Participants with hs-cTnT between the LOB and LOD were older, more likely to be male, and had higher prevalence of cardiovascular risk factors and structural abnormalities such as higher coronary artery calcium score and left ventricular mass. A meta-analysis of the three cohorts showed participants with hs-cTnT between the LOB and LOD were at increased risk of new-onset HF (HR=1.18, 95% CI: 1.02, 1.38) and cardiovascular death (HR=1.29, 95% CI: 1.06, 1.57) after adjusting for demographics and traditional risk factors when compared to participants with hs-cTnT below the LOB (Figure).

Conclusions:
hs-cTnT levels between the LOB and LOD are associated with a higher prevalence of traditional risk factors, cardiac pathology, and worse outcomes compared with levels below the LOB. Therefore, in general population cohorts, hs-cTnT should be reported down to the LOB.
Abstract 16279: Serine Protease Inhibitor (serpin) Reactive Site Loop Peptides Prevent Transplant Vasculopathy and Inflammatory Vasculitis
Authors: Morshed Sufi R , Ambadapadi Sriram , Munaswamy-Ramanujam Ganesh , Chen Hao , Zheng Donghang , Feldman Emily , Tibbetts Scott , Lucas Alexandra
Published: July 2021

Aim:
Ser
ine
p
rotease
in
hibitors (
Serpins
) regulate key clotting and inflammatory pathways. Two anti-inflammatory
Serpins
, neuroserpin (NSP) and Serp-1 markedly reduce arterial inflammation and plaque growth in a rodent aortic transplant vasculitis model after single dose infusion. NSP is a mammalian serpin that inhibits thrombolytic proteases and Serp-1 is a virus-derived serpin that inhibits both thrombotic and thrombolytic proteases. We postulated that proteolytic cleavage of the reactive site loop (RSL) produces active peptide derivatives with expanded functions. 8 peptide sequences encompassing predicted cleavage sites for Serp-1 and NSP were synthesized and tested in mouse aortic allograft transplant and herpesvirus (MHV68) vasculitis models. The main aim was to assess therapeutic potential for RSL peptides derived from NSP and Serp-1 in vascular inflammation.

Methods:
We assessed the capacity of 8 predicted serpin RSL peptides, 4 from Serp-1 and 4 from NSP to reduce vascular inflammation. 40 C57BL/6 mice had aortic allograft transplant with a single IV injection of each single peptide. 29 IFN-γR KO mice had MHV-68 infection and were treated for 10 days with S-2 (ISRMAV), S-7 (GTTASSDTAITLIPR), Inverse S-7 (RPILTIATDSSATTG), S-8 (MAVLYPQVIVDHPFFFLIRNR) peptides, or Saline control.

Results:
RSL peptides with R or RN sequences, but not RM, and with 0-+1 charge significantly reduced vascular inflammatory cell invasion and plaque growth after aortic transplant from C57Bl/6 donor to BALB/c recipient transplant mice (5-6 transplants/peptide) (P < 0.01). S-1, S-3, S-7 & S-8 peptides reduced inflammation and plaque in aortic transplant. Hydrophobicity and negative charge in S-6 peptide increased thrombosis. S-7 peptide also significantly improved survival in a lethal MHV68 infection vasculitic model (150 days survival; P < 0.043), while inactive S-2 peptide, Inverse S-7 and S-8 had no effect (P = NS; 40 days) (P< 0.043).

Conclusions:
In conclusion, a series of serpin RSL peptides were synthesized based upon natural protease cleavage sites. RSL peptides have demonstrated significant efficacy in reducing inflammatory vasculitis after transplant or after lethal mouse herpesviral (MHV) infections, extending serpin regulatory activity.
Abstract 16300: Efficacy and Safety of Anticoagulation Following Bioprosthetic Aortic Valve Replacement: A Meta-analysis
Authors: Riaz Haris , Khan Muhammad S , Riaz Talha , Idrees Jay , Riaz Irbaz Bin , Khan Mohammad Q , Sanghi Vedha , Raza Sajjad , Krasuski Richard
Published: July 2021

Background:
The American College of Cardiology (ACC) guidelines recommend three months of anticoagulation (AC) after replacement of the aortic valve with a bioprosthesis (BP). However, there remains great variability in the current clinical practice and conflicting results from clinical studies. To assist clinical decision making, we pooled the existing evidence to assess whether AC in the setting of a new BP was associated with improved outcomes and/or greater risk of bleeding.

Methods:
We searched the PubMed database from the inception of these databases until April 2015 to identify original studies (observational studies or clinical trials) that assessed AC with warfarin in comparison with either aspirin or no antiplatelet or anticoagulant therapy. We included the studies if their outcomes included thromboembolism or stroke/transient ischemic attacks (TIA) and bleeding events. Quality assessment was performed in accordance with the Newland Ottawa scale and random effects was used to pool the data from the available studies. I2 testing was done to assess the heterogeneity of the included studies.

Results:
After screening through 170 papers, a total of 13 studies (cases=6431, controls=18210) were included in the final analyses. Use of warfarin use was associated with a significantly increased risk of overall bleeding (OR= 1.96, 95% CI 1.25-3.08, P<0.0001) or bleeding risk at 3 months (OR= 1.92, 95% CI 1.10-3.34), P<0.0001) compared with aspirin or placebo. With regard to composite primary outcome variables (risk of venous thromboembolism, stroke or TIA) at 3 months, no significant difference was seen with warfarin (OR= 1.13, 95% CI 0.82-1.56, P=0.67). Moreover AC was also not shown to improve outcomes at time interval >3 months (OR= 1.12, 95% CI 0.80-1.58, P=0.79).

Conclusion:
Contrary to the current guidelines, a meta-analysis of prior studies suggests that AC in the setting of an aortic bioprosthesis significantly increases bleeding risk without a favorable impact on thromboembolic events. Larger, randomized controlled studies should be performed to further guide this clinical practice.
Mechanism of Persistent Ischemic Mitral Regurgitation After Annuloplasty
Authors: Zhu Fang , Otsuji Yutaka , Yotsumoto Goichi , Yuasa Toshinori , Ueno Takayuki , Yu Bo , Koriyama Chihaya , Hamasaki Shuichi , Biro Sadatoshi , Kisanuki Akira , Minagoe Shinichi , Levine Robert A. , Sakata Ryuzo , Tei Chuwa
Published: July 2021

Background—

We hypothesized that surgical annuloplasty for ischemic mitral regurgitation (MR) that displaces the posterior annulus anteriorly can potentially augment posterior leaflet (PML) tethering, leading to persistent MR. Relationships between leaflet configurations and persistent ischemic MR after the annuloplasty were investigated.

Methods and Results—

In 31 patients with surgical annuloplasty for ischemic MR and 20 controls, posterior and apical displacement of the leaflet coaptation, the anterior leaflet (AML) and PML tethering angles relative to the line connecting annuli, coaptation length (CL), and the MR grade were quantified before and early after surgery in echocardiographic left ventricular long-axis views. Six of the 31 patients showed persistent MR despite annuloplasty. Compared with patients without persistent MR, those with MR showed no improvement in the left ventricular ejection fraction and systolic volume, similar reduction in the annular area, significant increase in posterior displacement of the coaptation (
P
<0.01), no improvement in AML tethering, greater worsening in PML tethering (
P
<0.01), and no increase in the CL. All tethering variables were significantly correlated with both preoperative and postoperative MR in univariate analysis, and reduced CL was the primary independent determinant of both preoperative and postoperative MR. Although increased AML tethering was the primary determinant of the preoperative CL (r
2
=0.46,
P
<0.0001), increased PML tethering was the primary determinant afterward (r
2
=0.60,
P
<0.0001).

Conclusion—

Although tethering of both leaflets is the major determinant of ischemic MR before surgical annuloplasty, both leaflets tethering but with predominant and augmented PML tethering is related to persistent ischemic MR after the annnuloplasty.
Abstract T P89: Curcumin Encapsulated Stem Cell Exosomes Attenuate Ischemic Brain Injury in Type 1 Diabetic Akita Mice
Authors: Kalani Anuradha , Kamat Pradip K , Tyagi Neetu
Published: July 2021

Background and Purpose:
Stroke in type-1 diabetes mellitus (T1DM) is severe in terms of exacerbated brain damage and severe functional decline as compared to non-diabetic stroke. Curcumin possesses remarkable medicinal properties and stem cells exosomes (nano-vesicles; 40-100 nm) have paracrine effects with neovascularization properties. The therapy available for stroke (tissue plasminogen activator) is not effective in diabetic stroke and leads to excessive vasodilation and hemorrhagic transformations. Therefore, we tested the hypothesis that encapsulating curcumin to mouse embryonic stem cell exosomes mitigates type-1 diabetic stroke injury.

Methods:
We employed 8-10 weeks old male genetic T1DM Ins2+/- Akita mice. Ischemia was performed for 40 min and reperfusion for 7 days in the following mice groups: 1) Sham
Akita
, 2) Sham
Akita
+
cur-exo
, 3) IR
Akita
, 4) IR
Akita
+
cur-exo
. Exosomes were isolated from mouse embryonic stem cells culture conditioned media and encapsulated with curcumin (
cur-exo
). Therapeutic
exo-cur
units were used for mice treatment intranasally for 7 days. Brain cryo-sections were analyzed for vascular (VCAM, VE-cadherin), glial (GFAP), neuronal (Tuj1, nNOS) coupling in ipsilateral area. Neuronal loss, neurodegeneration was analyzed with NeuN, fluorojade-C staining. White matter damage was examined with luxol fast blue. Intra-carotid FITC-BSA infusion was used to assess venular leakage. Passive avoidance and auditory brainstem response tests were used to determine cognitive functions.

Results:
Treatment with
cur-exo
alleviated Infarct volume, edema, and vascular damage in IR
Akita
+
cur-exo
mice as compared to IR
Akita
mice. The axonal-glia damage and venular permeability were exacerbated in IR
Akita
mice, as compared to sham
Akita
, which were mitigated after
cur-exo
treatment.
Cur-exo
also ameliorated neurodegeneration and promoted neuronal survival as determined through immunolocalization studies. Further,
cur-exo
remarkably restored cognitive functions (p<0.001, n=6).

Conclusion:
Our results suggested that combining the therapeutic efficacy of curcumin and stem cells exosomes represent a novel treatment for stroke during T1DM.

Acknowledgement:
This work was supported by NIH grant HL107640.
A new species of Erythrogonia Melichar, 1926 (Insecta: Hemiptera: Cicadellidae: Cicadellini) from the Mantiqueira mountain range, southeastern Brazil, associated with olive orchards
Authors: FROZA JOYCE A. , QUINTAS VICTOR , MEJDALANI GABRIEL
Published: July 2021

A new species of the diverse Neotropical sharpshooter genus Erythrogonia Melichar, 1926 is described and illustrated from the Mantiqueira mountain range, municipality of Maria da Fé, state of Minas Gerais, southeastern Brazil. The new taxon is associated with olive orchards and has been implicated as a vector of the bacterium Xylella fastidiosa Wells et al., 1987, which causes a disease known in Brazil as olive leaf scorch syndrome. Erythrogonia sinvali sp. nov. can be distinguished from the other 90 known species of the genus by the following combination of features: (1) crown black without conspicuous contrasting spots; (2) frons with large yellow median spot; (3) pronotum black with large yellow area covering most of disk; (4) forewing dark red, without contrasting spots or stripes, costal margin narrowly black, apical portion dark brown; (5) aedeagus elongate, curved dorsally, with pair of spiniform apical processes; (6) paraphyses greatly reduced; (7) basal portion of male anal tube with pair of spiniform curved processes; (8) posterior margin of female abdominal sternite VII broadly emarginate and with broad central lobe; (9) female sternite VIII with sclerotized areas, including a transverse bar located at bases of ovipositor valvulae I, followed by a pair of elongate sclerites and a posterior bilobed sclerite. Both males and females of the new species are described in detail. A putative group of five species within Erythrogonia is preliminarily proposed, including the new taxon, E. separata Melichar, 1926, E. dorsalis (Signoret, 1853), E. calva (Taschenberg, 1884), and E. melichari Schmidt, 1928. Among these species, the male terminalia of E. sinvali sp. nov. are more similar to those of E. separata.
A new species of the genus Themarictera Hendel (Diptera: Tephritidae: Phytalmiinae: Acanthonevrini) from Madagascar
Authors: KORNEYEV SEVERYN V. , HANCOCK DAVID L. , HAUSER MARTIN , KORNEYEV VALERY A. , GAIMARI STEPHEN D.
Published: July 2021

Themarictera rinhai sp. n. is described from Madagascar. Previously Themarictera was a monotypic genus with only the species, T. flaveolata (Fabricius, 1805) having several synonyms, from continental Africa. A key for identification of both species is provided.
Revision of the Laonice bahusiensis complex (Annelida: Spionidae) with a description of three new species
Authors: SIKORSKI ANDREY V. , RADASHEVSKY VASILY I. , CASTELLI ALBERTO , PAVLOVA LYUDMILA V. , NYGREN ARNE , MALYAR VASILY V. , BORISOVA POLINA B. , MIKAC BARBARA , ROUSOU MARIA , MARTIN DANIEL , GIL JOÃO , PACCIARDI LORENZO , LANGENECK JOACHIM
Published: July 2021

The morphological reexamination of specimens previously identified as Laonice bahusiensis Söderström, 1920 from North European and Mediterranean collections, supported by the molecular analysis of freshly collected material, enabled the recognition of four different species in the region: the genuine L. bahusiensis, L. irinae n. sp. from North European waters, and L. grimaldii n. sp. and L. mediterranea n. sp. from the Mediterranean Sea. The morphology of these species is described and illustrated, and their distributions are clarified based on old and new materials. A key for their identification is also provided. The Bayesian analysis of the COI sequences (483 bp) showed that these four species form a clade, namely the L. bahusiensis species complex, morphologically characterized by the continuous dorsal crests on postbranchiate chaetigers in the adults. The genetic p-distances between the species of the complex ranged from 13.27% to 17.99%, while the intraspecific variability ranged from 0.6% to 1.57%. Together with the sister species Laonice cirrata (Sars, 1851), the L. bahusiensis complex formed the Laonice (Laonice) clade, which is morphologically characterized by the prostomium fused with the anterior peristomial margin. However, the monophyly of the L. bahusiensis complex, as well as that of the clade Laonice (Laonice), needs to be further supported through the analysis of a greater set of genes from a larger number of species.
MiR-32 Suppresses the Development of Lung Cancer via Modulating PI3K/Akt
Authors: Liu Qing-Feng , Zhang Ye , Deng Lei , Zhang Tao , Xiao Jian-Ping , Zhou Zong-Mei , Bi Nan
Published: July 2021

Our team utilized qRT-PCR for prospecting miR-32 expression level in primary lung carcinoma tissues and cell lines, as well as Kaplan–Meier method for dissecting the relation of miR-32 expression with the prognosis of lung carcinoma. We transfected lung cancer A549 cells with miR-32 mimic/inhibitor and mimic/inhibitor NC, and appraised the influences of miR-32 on the phenotype changes of lung carcinoma cells via MTT assay, wound healing assay and cell apoptosis assay, separately. Then the target gene of miR-32 was predicted via bioinformatics. Finally, Western blotting was adopted for analyzing the impact of alteration of miR-32 expression on the PI3K/Akt axis in A549 cells. In lung carcinoma tissues as well as cells, miR-32 expression is down-regulated, and miR-32 partakes in the progress of lung carcinoma via PI3K/Akt pathway.
Gemcitabine Nanoparticles Improve the Activity of Ovarian Cancer Cells by Inhibiting CA-125 and Apoptosis-Related Proteins
Authors: Yi Sisi , Feng Chen , Hu Xiaohua
Published: July 2021

In recent years, the risk of ovarian cancer (OC) has become increasingly prevalent. Gemcitabine (GE) provides excellent inhibitory action on some solid tumors, but how it affects OC remains elusive. In the present research, we prepared GE nanoparticles (GEN) and analyzed OC cell viability
under its intervention, hoping to conceive novel ideas for future clinical treatment of OC. Through experiments, we observed that the encapsulation efficiency and drug loading of GEN were observably higher than those of GE alone, and the release rate presented a stable slow release state.
Under GEN intervention, the viability of OC cells was decreased, the apoptosis rate was elevated, and the apoptosis-related proteins were activated, while CA-125 was suppressed. Therefore, we can see that GEN exert favorable inhibitory action on OC cell viability, whose mechanism may be achieved
through activating apoptosis-related proteins and inhibiting CA-125, which may be a new scheme for OC treatment in the future.
Infant negative affect moderates longitudinal associations between maternal gatekeeping and toddlers’ social–emotional difficulties
Authors: Altenburger Lauren E. , Schoppe-Sullivan Sarah J.
Published: July 2021

Maternal gatekeeping is characterized by the extent to which mothers engage in behaviors that ultimately serve to inhibit (i.e., gate close) or encourage (i.e., gate open) father involvement in childrearing. This study considered direct and indirect associations between observed and reported maternal gatekeeping and children’s social–emotional difficulties. Data come from a sample of 182 parents who transitioned to parenthood in 2008–2010 and their young children. Results of longitudinal path analyses indicated mothers’ perceptions of maternal gate closing at 3-months postpartum were associated with greater dysregulation (β = .21, 95% CI [.08, .35], p = .002) and externalizing (β = .25, 95% CI [.10, .41], p = .001) in 26-month-old toddlers. Observed maternal gate opening at 3-months postpartum predicted lower dysregulation (β = −.18, 95% CI [−.32, −.05], p = .008) in 26-month-old toddlers. Observed fathers’ parenting quality did not mediate associations between maternal gatekeeping and child social–emotional difficulties. However, a statistically significant interaction between infant negative affect and observed maternal gate opening emerged as a predictor of toddler dysregulation, such that the adjusted negative effect of observed maternal gate opening on toddler dysregulation was strongest when infant negative affect was low. Statistically significant interactions between fathers’ perceptions of gate closing and infant negative affect also emerged as predictors of toddler dysregulation and externalizing. Infants high in negative affect exposed to maternal gate closing were at the greatest risk for externalizing and dysregulation difficulties. Implications for maternal gatekeeping theory and research are discussed.
Marshallsussmanite, NaCaMnSi3O8(OH), a new pectolite-group mineral providing insight into hydrogen bonding in pyroxenoids
Authors: Origlieri Marcus J. , Downs Robert T. , Hoffman Derek R. , Ducea Mihai N. , Post Jeffrey E.
Published: July 2021

Marshallsussmanite (IMA2013-067) is a new pyroxenoid mineral from the Wessels mine, Kalahari Manganese Field, Northern Cape Province, South Africa. Marshallsussmanite has ideal formula NaCaMnSi3O8(OH) and triclinic P$\bar{1}$symmetry. Marshallsussmanite forms vitreous pink bladed crystals to 2.1 cm. The mineral shows perfect cleavage on both {100} and {001}. The chemical composition from electron microprobe (average of 20 analyses) and inductively coupled plasma mass spectrometer analysis (average of three analyses) is Li2O 0.43, Na2O 8.06, MgO 0.08, CaO 15.33, MnO 21.79, SiO251.71; totalling 97.40 wt.%. The empirical formula, normalized to 3 Si and assuming 1 H apfu is Li0.100Na0.906Ca0.953Mg0.007Mn1.071Si3O8(OH). Unit-cell parameters from single crystal X-ray diffraction area= 7.7854(4),b= 6.9374(4),c= 6.8516(3) Å, α = 90.683(3)°, β = 94.330(3)°, γ = 102.856(3)°,V= 359.59(3) Å3;Z= 2. The crystal structure refinement converged withRobs= 0.0248 and site occupancy refinement gives crystal chemistry [Na0.948Li0.052][Ca0.793Mn0.207] [Mn0.937Ca0.063]Si3O8(OH). Marshallsussmanite is a single chain silicate with a repeat interval of three tetrahedra (i.e.dreierchain). Marshallsussmanite is a member of the pectolite group of pyroxenoids, which also includes barrydawsonite-(Y), cascandite, pectolite, serandite and tanohataite. Parallel silicate chains form layers, intercalated with well-ordered cation layers. Calcium and Mn both exhibit octahedral coordination, while Na has four bonded interactions in a coordination sphere (radius 3 Å) of seven separate O atoms. Procrystal electron density and bond valence modelling results are compared. The mineral has an unusually strong hydrogen bond with O4⋅⋅⋅O3 separation of 2.458(2) Å. Unlike pectolite and serandite, O4 in marshallsussmanite acts as an H-bond donor and O3 is an H-bond acceptor. Cation ordering in pyroxenoids has a substantial impact on the H position and corresponding H-bonding schemata.
Performance of Web tools for predicting changes in protein stability caused by mutations
Authors: Marabotti Anna , Del Prete Eugenio , Scafuri Bernardina , Facchiano Angelo
Published: July 2021

Background

Despite decades on developing dedicated Web tools, it is still difficult to predict correctly the changes of the thermodynamic stability of proteins caused by mutations. Here, we assessed the reliability of five recently developed Web tools, in order to evaluate the progresses in the field.

Results

The results show that, although there are improvements in the field, the assessed predictors are still far from ideal. Prevailing problems include the bias towards destabilizing mutations, and, in general, the results are unreliable when the mutation causes a ΔΔG within the interval ± 0.5 kcal/mol. We found that using several predictors and combining their results into a consensus is a rough, but effective way to increase reliability of the predictions.

Conclusions

We suggest all developers to consider in their future tools the usage of balanced data sets for training of predictors, and all users to combine the results of multiple tools to increase the chances of having correct predictions about the effect of mutations on the thermodynamic stability of a protein.
Two homologous Salmonella serogroup C1-specific genes are required for flagellar motility and cell invasion
Authors: Zhou Xiujuan , Liu Bin , Liu Yanhong , Shi Chunlei , Fratamico Pina M. , Zhang Lida , Wang Dapeng , Zhang Jianhua , Cui Yan , Xu Ping , Shi Xianming
Published: July 2021

Background

Salmonella is a major bacterial pathogen associated with a large number of outbreaks of foodborne diseases. Many highly virulent serovars that cause human illness belong to Salmonella serogroup C1, and Salmonella ser. Choleraesuis is a prominent cause of invasive infections in Asia. Comparative genomic analysis in our previous study showed that two homologous genes, SC0368 and SC0595 in Salmonella ser. Choleraesuis were unique to serogroup C1. In this study, two single-deletion mutants (Δ0368 and Δ0595) and one double-deletion mutant (Δ0368Δ0595) were constructed based on the genome. All these mutants and the wild-type strain were subjected to RNA-Seq analysis to reveal functional relationships of the two serogroup C1-specific genes.

Results

Data from RNA-Seq indicated that deletion of SC0368 resulted in defects in motility through repression of σ28 in flagellar regulation Class 3. Consistent with RNA-Seq data, results from transmission electron microcopy (TEM) showed that flagella were not present in △0368 and △0368△0595 mutants resulting in both swimming and swarming defects. Interestingly, the growth rates of two non-motile mutants △0368 and △0368△0595 were significantly greater than the wild-type, which may be associated with up-regulation of genes encoding cytochromes, enhancing bacterial proliferation. Moreover, the △0595 mutant was significantly more invasive in Caco-2 cells as shown by bacterial enumeration assays, and the expression of lipopolysaccharide (LPS) core synthesis-related genes (rfaB, rfaI, rfaQ, rfaY, rfaK, rfaZ) was down-regulated only in the △0368△0595 mutant. In addition, this study also speculated that these two genes might be contributing to serotype conversion for Salmonella C1 serogroup based on their apparent roles in biosynthesis of LPS and the flagella.

Conclusion

A combination of biological and transcriptomic (RNA-Seq) analyses has shown that the SC0368 and SC0595 genes are involved in biosynthesis of flagella and complete LPS, as well as in bacterial growth and virulence. Such information will aid to revealing the role of these specific genes in bacterial physiology and evolution within the serogroup C1.
Genotyping and lipid profiling of 601 cultivated sunflower lines reveals novel genetic determinants of oil fatty acid content
Authors: Chernova Alina I. , Gubaev Rim F. , Singh Anupam , Sherbina Katrina , Goryunova Svetlana V. , Martynova Elena U. , Goryunov Denis V. , Boldyrev Stepan V. , Vanyushkina Anna A. , Anikanov Nikolay A. , Stekolshchikova Elena A. , Yushina Ekaterina A. , Demurin Yakov N. , Mukhina Zhanna M. , Gavrilova Vera A. , Anisimova Irina N. , Karabitsina Yulia I. , Alpatieva Natalia V. , Chang Peter L. , Khaitovich Philipp , Mazin Pavel V. , Nuzhdin Sergey V.
Published: July 2021

Background

Sunflower is an important oilseed crop domesticated in North America approximately 4000 years ago. During the last century, oil content in sunflower was under strong selection. Further improvement of oil properties achieved by modulating its fatty acid composition is one of the main directions in modern oilseed crop breeding.

Results

We searched for the genetic basis of fatty acid content variation by genotyping 601 inbred sunflower lines and assessing their lipid and fatty acid composition. Our genome-wide association analysis based on the genotypes for 15,483 SNPs and the concentrations of 23 fatty acids, including minor fatty acids, revealed significant genetic associations for eleven of them.

Identified genomic regions included the loci involved in rare fatty acids variation on chromosomes 3 and 14, explaining up to 34.5% of the total variation of docosanoic acid (22:0) in sunflower oil.

Conclusions

This is the first large scale implementation of high-throughput lipidomic profiling to sunflower germplasm characterization. This study contributes to the genetic characterization of Russian sunflower collections, which made a substantial contribution to the development of sunflower as the oilseed crop worldwide, and provides new insights into the genetic control of oil composition that can be implemented in future studies.
Transcriptomics unravels molecular players shaping dorsal lip hypertrophy in the vacuum cleaner cichlid, Gnathochromis permaxillaris
Authors: Lecaudey Laurène Alicia , Singh Pooja , Sturmbauer Christian , Duenser Anna , Gessl Wolfgang , Ahi Ehsan Pashay
Published: July 2021

Background

Teleosts display a spectacular diversity of craniofacial adaptations that often mediates ecological specializations. A considerable amount of research has revealed molecular players underlying skeletal craniofacial morphologies, but less is known about soft craniofacial phenotypes. Here we focus on an example of lip hypertrophy in the benthivorous Lake Tangnayika cichlid, Gnathochromis permaxillaris, considered to be a morphological adaptation to extract invertebrates out of the uppermost layer of mud bottom. We investigate the molecular and regulatory basis of lip hypertrophy in G. permaxillaris using a comparative transcriptomic approach.

Results

We identified a gene regulatory network involved in tissue overgrowth and cellular hypertrophy, potentially associated with the formation of a locally restricted hypertrophic lip in a teleost fish species. Of particular interest were the increased expression level of apoda and fhl2, as well as reduced expression of cyp1a, gimap8, lama5 and rasal3, in the hypertrophic lip region which have been implicated in lip formation in other vertebrates. Among the predicted upstream transcription factors, we found reduced expression of foxp1 in the hypertrophic lip region, which is known to act as repressor of cell growth and proliferation, and its function has been associated with hypertrophy of upper lip in human.

Conclusion

Our results provide a genetic foundation for future studies of molecular players shaping soft and exaggerated, but locally restricted, craniofacial morphological changes in fish and perhaps across vertebrates. In the future, we advocate integrating gene regulatory networks of various craniofacial phenotypes to understand how they collectively govern trophic and behavioural adaptations.
Optimizing interleukin-2 concentration, seeding density and bead-to-cell ratio of T-cell expansion for adoptive immunotherapy
Authors: Ghaffari Sasan , Torabi-Rahvar Monireh , Aghayan Sajjad , Jabbarpour Zahra , Moradzadeh Kobra , Omidkhoda Azadeh , Ahmadbeigi Naser
Published: July 2021

Background

The successful ex vivo expansion of T-cells in great numbers is the cornerstone of adoptive cell therapy. We aimed to achieve the most optimal T-cell expansion condition by comparing the expansion of T-cells at various seeding densities, IL-2 concentrations, and bead-to-cell ratios. we first expanded the peripheral blood mononuclear cells (PBMCs) of a healthy donor at a range of 20 to 500 IU/mL IL-2 concentrations, 125 × 103to 1.5 × 106cell/mL, and 1:10 to 10:1 B:C (Bead-to-cell) ratios and compared the results. We then expanded the PBMC of three healthy donors using the optimized conditions and examined the growth kinetics. On day 28, CD3, CD4, and CD8 expression of the cell populations were analyzed by flow cytometry.

Results

T-cells of the first donor showed greater expansion results in IL-2 concentrations higher than 50 IU/mL compared to 20 IU/mL (P = 0.02). A seeding density of 250 × 103cell/mL was superior to higher or lower densities in expanding T-cells (P = 0.025). Also, we witnessed a direct correlation between the B:C ratio and T-cell expansion, in which, in 5:1 and 10:1 B:C ratios T-cell significantly expanded more than lower B:C ratios. The results of PBMC expansions of three healthy donors were similar in growth kinetics. In the optimized condition, 96–98% of the lymphocyte population expressed CD3. While the majority of these cells expressed CD8, the mean expression of CD4 in the donors was 19.3, 16.5, and 20.4%.

Conclusions

Our methodology demonstrates an optimized culture condition for the production of large quantities of polyclonal T-cells, which could be useful for future clinical and research studies.
How to forget a “traumatic” experience: a case report of transient global amnesia after nasopharyngeal swab for Coronavirus disease 19
Authors: Ravaglia Sabrina , Zito Antonio , Ahmad Lara , Canavero Isabella
Published: July 2021

Background

Transient global amnesia (TGA) is a clinical syndrome characterized by a temporary short-term memory loss with inability to retain new memories, usually lasting 2 to 8 h. TGA may be related to several medical procedures, including angiography, general anesthesia, gastroscopy.

Case presentation

We report a 58-year-old woman who experiencing TGA one hour after the execution of her first-time nasopharyngeal swab for COVID-19. Brain MRI showed a typical punctate Diffusion Weight Image (DWI) hippocampal lesion.

Conclusions

This is the first report of TGA after the execution of nasopharyngeal swab for COVID-19. This association lengthen the list of medical procedures associated with TGA, and we discuss the possible plausible mechanisms by which a nasopharyngeal swab could trigger TGA.
Psychometric properties of the Persian version of the weight-related experiential avoidance (AAQW): overweight and obese treatment seeker at the clinical setting
Authors: Pirmoradi Mohammad Reza , Asgharzadeh Ali , Birashk Behrooz , Gharaee Banafshe , Salehian Razieh , Ostadrahimi Ali Reza , Akbarzadeh Abolfazl
Published: July 2021

Background

The present study aimed to investigate the psychometric properties of the Persian version of the weight-related experiential avoidance (AAQW) in overweight and obese treatment seeker in the clinical setting.

Methods

This sample consists of 220 male and female overweight or obesity treatment seeker from Overweight and obesity centers who agreed to fill out the self-reported measures.

Results

Confirmatory factor analysis (CFA) supported 3-factor structures of AAQW, including (weight as a barrier to living, Food as Control, and weight-stigma). Furthermore, the internal consistency of AAQW indicates an acceptable range (α = .70); Also, expected associations between AAQW and external correlates (e.g., BES, AAQ-II, KIMS, BDI-II, and CFQ) supported the measure’s convergent validity in a sample of overweight and obese treatment seeker in the clinical setting.

Conclusions

Overall, our study offers that the Persian version of weight-related experiential avoidance has psychometrically valid and reliable tools to assess experiential avoidance. Furthermore, weight-related experiential avoidance is associated with higher severity of binge eating symptoms, higher psychological inflexibility levels, experiential avoidance, and more cognitive fusion and depression symptomology.
Previous life experiences and social relations affecting individuals wish for support when establishing healthy habits – a qualitative study of Norwegian Healthy Life Centre participants
Authors: Gjertsen Thea Ingebjørg , Helvik Anne-S. , Følling Ingrid S.
Published: July 2021

Background

Interventions to reduce and prevent overweight, obesity and T2D has been advocated worldwide. In Norway, Healthy Life Centres have been established to help individuals to reduce and prevent diseases, offering physical activity and dietary advice to establish healthy habits. Previous life experiences, social support and help from health personnel could play a role in the process of establishing healthy habits. The aim of this study was to explore how two groups of Healthy Life Centre participants described their previous life experiences, social relations and wish for support from Healthy Life Centre personnel.

Methods

A qualitative design was used, including 49 individual semi-structured interviews. The interviews for this study were performed in two different samples, one sample of participants applying for HLC participation in 2013 (n = 23) and one sample of participants invited to HLC participation in 2015 (n = 26). The data was analyzed using systematic text condensation.

Results

Three main themes in a chronological (past, present and future) order were identified: 1. Previous life experiences stamping life situation (past time). 2. Social relations being a support or a burden in everyday life (present time) and 3. Expressing wishes for HLC support (future).

Conclusions

In the process of establishing healthy habits, the need for help from personnel may be differentiated based on previous life experiences and present social relations.
Lippia javanica (Zumbani) herbal tea infusion attenuates allergic airway inflammation via inhibition of Th2 cell activation and suppression of oxidative stress
Authors: Mfengu Mvuyisi O. M. , Shauli Mathulo , Engwa Godwill A. , Musarurwa Hannibal T. , Sewani-Rusike Constance R.
Published: July 2021

Background

Lippia javanica (lemon bush) is commonly used in the treatment of respiratory ailments, including asthma in southern African countries but there is no scientific evidence to support this claim. This study investigated the anti-inflammatory, antioxidant and anti-asthmatic effects of L. javanica using a rat model of asthma.

Methods

A 5% w/v L. javanica tea infusion was prepared and characterised by liquid chromatography–mass spectrometer (LC-MS). Animals were intraperitoneally sensitized with ovalbumin (OVA) and subsequently challenged intranasal with OVA on day 15 except the control group. Animals were grouped (n = 5/group) for treatment: unsensitised control, sensitised control, sensitised + prednisolone and sensitised + L. javanica at 50 mg/kg/day and 100 mg/kg/day – equivalent to 1 and 2 cups of tea per day, respectively. After 2 weeks of treatment, bronchoalveolar lavage fluid (BALF) was collected for total and differential white blood cell (WBC) count. Nitric oxide (NO), lipid peroxidation and antioxidants were also assessed in BALF. Ovalbumin specific IgE antibody and inflammatory cytokines: IL-4, IL-5, IL-13 and TNF-alpha were measured in serum. Lung and muscle tissues were histological examined.

Results

L. javanica was rich in phenolic compounds. OVA sensitisation resulted in development of allergic asthma in rats. L. javanica treatment resulted in a reduction in total WBC count as well as eosinophils, lymphocytes and neutrophils in BALF. L. javanica inhibited Th2-mediated immune response, which was evident by a decrease in serum IgE and inflammatory cytokines: IL-4, IL-5, IL-13 and TNF-α. L. javanica treatment also reduced malondialdehyde (MDA) and NO, and increased superoxide dismutase, glutathione and total antioxidant capacity. Histology showed significant attenuation of lung infiltration of inflammatory cells, alveolar thickening, and bronchiole smooth muscle thickening.

Conclusion

L. javanica suppressed allergic airway inflammation by reducing Th2-mediated immune response and oxidative stress in OVA-sensitized rats which may be attributed to the presence of phenolic compound in the plant. This finding validates the traditional use of L. javanica in the treatment of respiratory disorders.
An engineered genetic circuit for lactose intolerance alleviation
Authors: Cheng Mingyue , Cheng Zhangyu , Yu Yiyan , Liu Wangjie , Li Ruihao , Guo Zhenyi , Qin Jiyue , Zeng Zhi , Di Lin , Mo Yufeng , Pan Chunxiu , Liang Yuanhao , Li Jinman , Tong Yigang , Yan Yunjun , Zhan Yi , Ning Kang
Published: July 2021

Background

Lactose malabsorption occurs in around 68% of the world’s population, causing lactose intolerance (LI) symptoms, such as abdominal pain, bloating, and diarrhea. To alleviate LI, previous studies have mainly focused on strengthening intestinal β-galactosidase activity while neglecting the inconspicuous drop in the colon pH caused by the fermentation of non-hydrolyzed lactose by the gut microbes. A drop in colon pH will reduce the intestinal β-galactosidase activity and influence intestinal homeostasis.

Results

Here, we synthesized a tri-stable-switch circuit equipped with high β-galactosidase activity and pH rescue ability. This circuit can switch in functionality between the expression of β-galactosidase and expression of L-lactate dehydrogenase in response to an intestinal lactose signal and intestinal pH signal, respectively. We confirmed that the circuit functionality was efficient in bacterial cultures at a range of pH levels, and in preventing a drop in pH and β-galactosidase activity after lactose administration to mice. An impact of the circuit on gut microbiota composition was also indicated.

Conclusions

Due to its ability to flexibly adapt to environmental variation, in particular to stabilize colon pH and maintain β-galactosidase activity after lactose influx, the tri-stable-switch circuit can serve as a promising prototype for the relief of lactose intolerance.