bluuebunny/crossref_metadata_2025 huggingface dataset:
Ivabradine improves survival and attenuates cardiac remodeling in isoproterenol‐induced myocardial injury
Authors: Simko Fedor , Baka Tomas , Repova Kristina , Aziriova Silvia , Krajcirovicova Kristina , Paulis Ludovit , Adamcova Michaela
Published: October 2020

This study investigated whether ivabradine, a selective If current inhibitor reducing heart rate (HR), is able to improve survival and prevent left ventricular (LV) remodeling in isoproterenol‐induced heart damage. Wistar rats were treated for 6 weeks: controls (n = 10), ivabradine (10 mg/kg/day orally; n = 10), isoproterenol (5 mg/kg/day intraperitoneally; n = 40), and isoproterenol plus ivabradine (n = 40). Isoproterenol increased mortality, induced hypertrophy of both ventricles and LV fibrotic rebuilding, and reduced systolic blood pressure (SBP). Ivabradine significantly increased survival rate (by 120%) and prolonged average survival time (by 20%). Furthermore, ivabradine reduced LV weight and hydroxyproline content in soluble and insoluble collagen fraction, reduced HR and attenuated SBP decline. We conclude that ivabradine improved survival in isoproterenol‐damaged hearts.
Multiaxial notch fatigue life prediction based on the dominated loading control mode under variable amplitude loading
Authors: Tao Zhi‐Qiang , Zhang Ming , Zhu Yu , Cai Tian , Zhang Zi‐Ling , Liu Hu , Bai Bin , Li Dao‐Hang
Published: October 2020

A new calculation approach is suggested to the fatigue life evaluation of notched specimens under multiaxial variable amplitude loading. Within this suggested approach, if the computed uniaxial fatigue damage by the pure torsional loading path is larger than that by the axial tension–compression loading path, a shear strain‐based multiaxial fatigue damage parameter is assigned to calculate multiaxial fatigue damage; otherwise, an axial strain‐based multiaxial fatigue damage parameter is assigned to calculate multiaxial fatigue damage. Furthermore, the presented method employs shear strain‐based and axial strain‐based multiaxial fatigue damage parameters in substitution of equivalent strain amplitude to consider the influence of nonproportional additional hardening. The experimental data of GH4169 superalloy and 7050‐T7451 aluminium alloy notched components are used to illustrate the presented multiaxial fatigue lifetime estimation approach for notched components, and the results reveal that estimations are accurate.
Lipid production is more than doubled by manipulating a diacylglycerol acyltransferase in algae
Authors: Zhang Yu , Pan Yufang , Ding Wei , Hu Hanhua , Liu Jin
Published: October 2020

Oleaginous algae have the ability to synthesize a high level of triacylglycerol (TAG) and are considered as the next‐generation feedstock for biofuel production. Manipulating algal lipid biosynthetic pathways has potential to overproduce TAG and represents a feasible way toward bringing down algae‐derived biofuels production cost. Here we dissected functional roles and engineering potential of six diacylglycerol acyltransferase (DGAT) genes from the marine alga Phaeodactylum tricornutum. PtDGAT1, PtDGAT2B, and PtDGAT3, residing at the chloroplast endoplasmic reticulum (ER) readily for utilizing both chloroplast‐ and ER‐derived diacylglycerol, were transcriptionally correlated with TAG accumulation. Heterologous expression in yeast, in vitro assay and overexpression in P. tricornutum all supported that PtDGAT1 surpassed the other five PtDGATs in synthesizing TAG. Compared to wild type P. tricornutum, the PtDGAT1‐overexpressing strain produced more than doubled TAG and total lipids, which reached 57% and 73% of dry weight, respectively, record‐high levels ever achieved in this alga. Our results demonstrated the strategy of screening proper engineering targets and manipulating a single gene to pull carbon flux to lipids for TAG hyper‐accumulation without growth compromise. The engineered alga with a great trait improvement may serve as a potent lipid producer for production uses.
MKK7 deficiency in mature neurons impairs parental behavior in mice
Authors: Shin Tadashi , Hiraoka Yuichi , Yamasaki Tokiwa , Marth Jamey D. , Penninger Josef M. , Kanai‐Azuma Masami , Tanaka Kohichi , Kofuji Satoshi , Nishina Hiroshi
Published: October 2020

c‐Jun N‐terminal kinases (JNKs) are constitutively activated in mammalian brains and are indispensable for their development and neural functions. MKK7 is an upstream activator of all JNKs. However, whether the common JNK signaling pathway regulates the brain's control of social behavior remains unclear. Here, we show that female mice in which Mkk7 is deleted specifically in mature neurons (Mkk7flox/floxSyn‐Cre mice) give birth to a normal number of pups but fail to raise them due to a defect in pup retrieval. To explore the mechanism underlying this abnormality, we performed comprehensive behavioral tests. Mkk7flox/floxSyn‐Cre mice showed normal locomotor functions and cognitive ability but exhibited depression‐like behavior. cDNA microarray analysis of mutant brain revealed an altered gene expression pattern. Quantitative RT‐PCR analysis demonstrated that mRNA expression levels of genes related to neural signaling pathways and a calcium channel were significantly different from controls. In addition, loss of neural MKK7 had unexpected regulatory effects on gene expression patterns in oligodendrocytes. These findings indicate that MKK7 has an important role in regulating the gene expression patterns responsible for promoting normal social behavior and staving off depression.
Surface plasmon resonance triggered promising visible light photocatalysis of LiNbO3 ceramic supported Ag nanoparticles
Authors: Singh Gurpreet , Kumar Manish , Singh Manmohan , Vaish Rahul
Published: October 2020

LiNbO3 ceramic was fabricated using solid‐state reaction route. Silver nanoparticles (NPs) were loaded on LiNbO3 at room temperature using silver nitrate and polyethylene glycol reagents, without the use of external heat and light energy. The X‐ray diffraction showed only LiNbO3 phase in Ag‐loaded LiNbO3 sample with no peak related to Ag metal due to small fraction of Ag loading. X‐ray energy diffraction spectroscopy elemental color mapping confirmed the uniform loading of Ag metal on LiNbO3 particles. Ag metal was loaded in the form of NPs as visualized under transmission electron microscope. Ag NPs‐loaded LiNbO3 showed enhanced absorption of visible light owing to the phenomenon of surface plasmon resonance (SPR). The loading of Ag NPs had no effect on the band gap energy of LiNbO3 ceramic. X‐ray photoelectron spectroscopy technique confirmed the metallic chemical state of Ag in Ag NPs‐loaded LiNbO3. Ag NPs‐loaded LiNbO3 degraded 97% rhodamine‐B model dye from the solution when irradiated for 240 minutes under visible light. The dye degradation follows pseudo‐first‐order kinetic having k‐value (kinetic rate constant) of as 0.013 min−1. The •OH (hydroxyl) and (superoxide) radicals were the main active species behind the photocatalytic activity of Ag NPs‐loaded LiNbO3. Thus, Ag NPs‐loaded LiNbO3 could be a potential material for degrading organic dyes from water.
Loganetin and 5‐fluorouracil synergistically inhibit the carcinogenesis of gastric cancer cells via down‐regulation of the Wnt/β‐catenin pathway
Authors: Zhou Huaixiang , Hu Xiaoge , Li Na , Li Guangyan , Sun Xiaotian , Ge Feimin , Jiang Jiahong , Yao Jingchun , Huang Dongsheng , Yang Liu
Published: October 2020

Although most gastrointestinal tumours are sensitive to 5‐fluorouracil (5FU), drug resistance is commonly occurred after 5FU therapy in gastric cancer (GC). Loganetin is the primary active compound in Cornus officinali. However, the synergetic effects of loganetin and 5FU on GC remain unknown. Here, we investigated the synergetic effects and the underlying mechanism of loganetin and 5FU on proliferation, stem‐like properties, migration, and invasion of GC both in vitro and in vivo. We found that loganetin alone inhibited the proliferation, stem‐like properties, migration and invasion of GC cells in vitro. Importantly, the loganetin remarkably enhanced the anti‐cancer effect of 5FU on GC cells and the Wnt/β‐catenin pathway might be involved in this process. Animal experiments further confirmed the synergistic effects of 5FU and loganetin on inhibiting cell growth and metastasis of GC. These results suggested that loganetin could synergistically increase the effect of 5FU against GC, which sheds light on effective combinational drug strategies for GC treatment.
Salivary biomarkers for discriminating periodontitis in the presence of diabetes
Authors: Miller Craig S. , Ding Xiuhua , Dawson Dolph R. , Ebersole Jeffrey L.
Published: October 2020

Aim

Salivary biomarkers can help in assessment of periodontitis; however, concentrations may be altered in the presence of diabetes. Hence, the ability of salivary biomarkers to discriminate periodontally healthy type II diabetics (T2DM) from T2DM who have periodontitis was examined.

Methods

Ninety‐two participants (29 with T2DM with chronic periodontitis, DWP; 32 T2DM without chronic periodontitis, DWoP; and 31 Not Periodontitis, NP) provided saliva and clinical parameters of periodontal health were recorded. Salivary concentrations of interleukin (IL)‐1β, IL‐6, matrix metalloproteinase‐8 (MMP‐8), macrophage inflammatory protein‐1α (MIP‐1α), adiponectin and resistin were measured by immunoassay.

Results

Salivary analyte concentrations for IL‐1β, MMP‐8 and resistin correlated with clinical parameters of periodontitis, with MMP‐8 demonstrating the strongest positive correlation with PD ≥5 mm (p < 0.0001). Periodontal health was reflected in salivary analyte concentrations by group, with concentrations of IL‐1β and MMP‐8 showing significant associations with periodontitis (p ≤ 0.04) that increased in concentration from health to DWoP to DWP. Odds ratio (OR) analyses showed that MMP‐8 discriminated periodontitis from NP (OR of 8.12; 95% CI: 1.01–65.33; p = 0.03) and in the presence of T2DM (DWP vs DWoP, OR = 5.09; 95% CI: 1.24–20.92; p = 0.03).

Conclusion

Salivary MMP‐8 and IL‐1β discriminate periodontitis in T2DM.
Keratinized tissue gain after free gingival graft augmentation procedures around teeth and dental implants: A prospective observational study
Authors: Golmayo Pilar , Barallat Lucía , Losada Meritxell , Valles Cristina , Nart Jose , Pascual‐La Rocca Andrés
Published: October 2020

Aim

The primary goal was to compare the amount of keratinized tissue width (KTW) gain after free gingival graft (FGG) procedures around implants and teeth after 6 and 12 months of healing.

Materials and Methods

Patients with mucogingival defects (<2 mm of KT) around teeth and implants underwent a gingival augmentation procedure by means of a FGG. Clinical measurements were performed with an individual stent to determine keratinized tissue width (KTW), length (KTL), graft shrinkage (GS) and gingival margin position (GMP) at 2 weeks, 6 weeks, 3 months, 6 months and 12 months after surgery.

Results

Twenty‐nine patients (35 sites) participated in this prospective study. After surgery, KTW decreased and GS increased significantly in both treatment groups during the whole follow‐up period, but the biggest changes were observed at 6 weeks. When comparing both treatment groups, implant sites showed significantly more reduction in KTW and more GS. Thus, at 12 months, KTW and GS reduced 2.03 ± 2.1 mm and 36.74 ± 38.2% in the teeth group and 2.91 ± 12.03 mm and 61.8 ± 36.25% around implants, respectively.

Conclusions

A significantly greater reduction in KTW and more GS might be expected at implant sites.
Enhanced leaky sex expression in response to pollen limitation in the dioecious plant Mercurialis annua
Authors: Cossard Guillaume G. , Pannell John R.
Published: October 2020

In dioecious plants, males and females frequently show ‘leaky’ sex expression, with individuals occasionally producing flowers of the opposite sex. This leaky sex expression may have enabled the colonization of oceanic islands by dioecious plant species, and it is likely to represent the sort of variation upon which selection acts to bring about evolutionary transitions from dioecy to hermaphroditism. Although leakiness is commonly reported for dioecious species, it is not known whether it has plastic component. The question is interesting because males or females with an ability to enhance their leakiness plastically in the absence of mates would have an advantage of being able to produce progeny by self‐fertilization. Here, we demonstrate that leaky sex expression in the wind‐pollinated dioecious herb Mercurialis annua is plastically responsive to its mating context. We compared experimental populations of females growing either with or without males. Females growing in the absence of males were leakier in their sex expression than controls growing with males, producing more than twice as many male flowers. Our results thus provide a striking instance of plasticity in the reproductive behaviour of plants that is likely adaptive. We consider how females might sense their mating environment as a function of pollen availability, and we discuss possible constraints on the evolution of plasticity in sex expression when the environmental signals that individuals receive are unreliable.
Histological and immunohistochemical characterization of 17 gonadal tumours in koi carp (Cyprinus carpio koi)
Authors: Sirri Rubina , Tura Giorgia , Budai Jane , Beraldo Paola , Fiorentino Michelangelo , Barbé Tim , Galeotti Marco , Sarli Giuseppe , Mandrioli Luciana
Published: October 2020

Reports on abdominal tumours in koi carp are scarce and most are from the gonads. Their histological diagnosis is challenging due to the occurrence of mixed populations of neoplastic cells and the few availability of cross‐reactive antibodies in fish tissues. The present study aims to provide a histopathological characterization of seventeen gonadal tumours, enriched by a wide antibody panel (vimentin, CD117, placental alkaline phosphatase—PLAP, AE1/AE3 cytokeratin, E‐cadherin, proliferating cell nuclear antigen—PCNA, müllerian‐inhibiting substance—MIS, GATA4 and Inhibin‐α) applied on whole and tissue microarray (TMA) sections. Abdominal enlargement was associated with tumours filling 30%–80% of the abdominal cavity; frequently, the gonads had been completely replaced by neoplastic tissue. Twelve cases were characterized as sex cord‐stromal tumours (SCSTs), three as germ cell tumours (GCTs), one as mixed germ cell sex cord‐stromal tumour (MGCSCST) and one as carcinoma. By immunohistochemistry, PLAP enabled confirmation of GCTs, ovarian carcinoma and the objective identification of a further cell component in 8 out of the 12 SCSTs that were reclassified as mixed tumours. The use of an immunohistochemical panel can help in refining the histological diagnosis, but the morphological diagnosis still represents the main tool for the characterization of these tumours in koi carp.
Cryptic evidence for the former presence of lawsonite in blueschist and eclogite
Authors: Chapman Timothy , Clarke Geoffrey L.
Published: October 2020

Cryptic geochemical indicators of prograde lawsonite breakdown are established in basic and metasedimentary Eocene blueschist and eclogite in New Caledonia utilizing phase equilibria modelling and synchrotron X‐ray fluorescence mapping. Lawsonite–epidote‐bearing eclogite has garnet with concentric zones depleted in the LREE and MREE, and clinozoisite with high‐Sr rims, which geochemically record a prograde stage of lawsonite stability. These records persist in eclogite that now lacks lawsonite, and may be used to validate texturally based interpretations for prograde lawsonite stability. The compositional trends depend on extrinsic and intrinsic variables, including bulk rock composition, which determine the rock‐forming and accessory minerals that host Sr and the REEs. Distinct prograde reaction histories are recorded by two eclogite terranes in NE New Caledonia due to subtle distinctions in their protolith whole‐rock compositions.
An effective hydroquinone alternative for topical skin lightening
Authors: Draelos Zoe Diana , Deliencourt‐Godefroy Geraldine , Lopes Lénaïg
Published: October 2020

Background

Many skin lightening preparations containing hydroquinone, kojic acid, arbutin, and deoxyarbutin are toxic to melanocytes.

Objective

This research examined a new skin lightening agent from a family of gem difluorocompounds 2‐[2‐(2,4‐difluorophenyl)‐2‐propen‐1‐yl]‐1,3‐propanediol that also function as tyrosinase inhibitors. This ingredient does not exhibit melanocyte toxicity yet is capable of inducing skin lightening. This research compared the gem difluorocompound, TFC‐1067, to hydroquinone evaluating both tolerability and efficacy for lightening facial dyschromia.

Method

48 nonpregnant and non‐nursing healthy female subjects age 25‐70 years skin types I‐IV with mild‐to‐moderate facial dyschromia were randomized to receive either study product or 2% hydroquinone cream. Subject and investigator tolerability and efficacy assessments were made at baseline, week 4, week 8, and week 12. Dermaspectrophotometer readings from normal skin and a pigmented target area were obtained. All subjects underwent facial photography at each visit.

Results

TFC‐1067 and 2% hydroquinone produced statistically significant skin lightening after 8 weeks of use, but only hydroquinone lightened the normal skin. This pattern continued into week 12 where both products significantly lightened dyschromic skin, but hydroquinone also lightened the normal skin, which is not always desirable.
COMMON‐ENEMY EFFECTS: MULTIDISCIPLINARY ANTECEDENTS AND ECONOMIC PERSPECTIVES
Authors: De Jaegher Kris
Published: October 2020

A disparate literature hypothesizes what can broadly be described as the common‐enemy effect: the fact that the interaction with a common enemy (formed by Nature, an individual, or a group) increases cooperation. This review identifies the multidisciplinary antecedents of this effect, and then distinguishes between several strands of literature applying noncooperative game theory to account for it. A first strand argues that the threat posed by a common enemy makes each player's cooperative effort more critical. In a second strand a behavioral common‐enemy effect caused by group interaction is studied experimentally. A third strand models the common‐enemy effect as the formation of a coalition of players against another player in a contest. A fourth strand formalizes the principle that the ‘enemy of my enemy is my friend’, either in a model of social relations, interdependent altruistic preferences, or indirect reciprocity in repeated games. The connections between these strands of literature are investigated, and questions for future research are proposed.
Variceal recurrence 4 years post endoscopic band ligation in hepatitis C patients who achieved sustained virological response with oral direct‐acting antiviral therapy
Authors: Ibrahim El‐Sayed , Abdel‐Samiee Mohamed , Youssef Mohamed I. , El‐Shazly Helmy , A.El‐Gendy Abd‐ElAleem , Sakr Ayman Ahmed , Elwazzan Doaa , Nassar Mervat Ragab , Aly Elshormilisy Amr , Madkour Ahmad , Kamal Mostafa , Amrousy Yasmine M. , Elkhadry Sally Waheed , Abdelsameea Eman
Published: October 2020

Oral Direct‐acting antivirals (DAAs) are safe, highly effective altering disease burden and prognosis in hepatitis C patients. Sustained virologic response (SVR) is achieved nowadays in more than 90% of the treated patients and related to the improvements in functions of the liver, fibrosis plus survival. Furthermore, portal hypertension is thought to be improved with achievement of virological response, parallel to the improvements in hepatic inflammation and fibrosis. We aimed to assess the recurrence rate of oesophageal varices by long‐term follow‐up in patients treated with different DAAs regimens who had achieved SVR. We studied 176 Child A cirrhotic HCV patients who achieved SVR after DAAs treatment and had a history of endoscopic oesophageal varices obliteration and were on maximum tolerated propranolol dose. They were subjected to follow‐up upper gastrointestinal endoscopy repeated every 6 months for 4 years. Fifty‐two patients (29.5%) had recurrence of oesophageal varices observed during the 4‐years follow‐up upper GIT endoscopy. On multivariate analysis, platelet count was the only significant variable, P‐value = .007*. HbA1C, HOMA IR, BMI 1 and BMI 2 showed non‐significant differences between the studied groups. By ROC analysis, we identified baseline platelet count of 96 000/µL with 100% sensitivity (95% confidence interval [CI] [91%‐100%]) and 74% specificity (95% CI [65%‐81%]). Spearman correlation showed a positive correlation between AFP, age, AST, Bilirubin, creatinine, INR. Patients who achieved SVR post DAAs showed a significant decrease in oesophageal varices recurrence post endoscopic obliteration. Baseline platelet count was found to be a strong independent predictor for oesophageal varices recurrence.
Hepatitis C virus: Testing rate and attrition at linkage to specialized care, Catalonia, Spain 2011‐2016
Authors: Reyes‐Urueña Juliana , Celly Ana , Moreno Sergio , Majó Xavier , Colom Joan , Casabona Jordi
Published: October 2020

Hepatitis C virus (HCV) screening through primary care providers (PCP) might increase linkage to specialized care. This study aimed to calculate HCV testing rate and prevalence of anti‐HCV according to socio‐demographic factors in primary care in Catalonia, Spain, from 2011 to 2016, and to identify the rate and determinants of attrition at linkage to specialized care. Patient data from 274 primary care centres (3414 PCP) were analysed, including socio‐demographic information, morbidity, laboratory tests and treatments (1‐Jan‐2011 to 31‐Dec‐2016). Both descriptive and inferential statistics were used to examine HCV testing rate, HCV seroprevalence and rate of attrition at linkage to specialized care. In the study period, there were 839 072 people tested for HCV infection and 21 156 with first‐time positive anti‐HCV test results. Rate of HCV testing was 143.54/103 pop (95% CI: 143.26‐143.83). Women had higher HCV testing rate (158.65/103 women [95% CI: 158.24‐159.07]), compared to men (128.10/103 men [95% CI: 127.72‐128.49]). The highest HCV testing rate was among people aged 25‐34 (284.11/103 pop [CIs: 283.10‐285.12]). The anti‐HCV seroprevalence was 3.62/103 pop (CIs: 3.57‐3.67). The highest prevalence was found among men (4.20/103 men [CIs: 4.12‐4.27]), people aged 45‐54 (7.19/103 pop [CIs: 7.01‐7.37]), people aged 75‐84 (7.26/103 pop [CIs: 6.99‐7.53]), Spanish (3.68/103 [CIs: 3.61‐3.75]), European and Northern Americans (5.64/103 [CIs: 5.33‐5.96]) and Asians (9.78/103 [CIs: 9.21‐10.35]). From those who had a positive anti‐HCV result, 49.8% (N = 10 528) were not linked to specialized care. Appropriate clinical care pathways and referral systems need to be established to ensure optimal linkage to specialized care for people newly diagnosed with HCV in primary care.
The pharmacokinetics and antiparasitic activity of ivermectin in Hutsul and Toric horses
Authors: Vyniarska Alla , Ziółkowski Hubert , Madej‐Śmiechowska Hanna , Jaroszewski Jerzy J.
Published: October 2020

The aim of this study was to compare the pharmacokinetics of ivermectin and its antiparasitic activity in two horse breeds. Eight Hutsul and 14 Toric horses were administered ivermectin orally at a dose of 0.2 mg/kg body weight. Blood samples were collected for 96 hr, and faecal samples were collected one day before and on days 14 and 21 after drug administration. Ivermectin concentrations in plasma samples were determined by high‐performance liquid chromatography. Ivermectin concentration was significantly higher in Toric than in Hutsul horses 90 min after ivermectin administration and was maintained at higher level for up to 96 hr. The area under the concentration versus the time curve from 0 to the last sampling point (AUC0→t) and the maximum plasma concentration (Cmax) were significantly higher in Toric than in Hutsul horses (1792.09 ± 246.22 μg × hr/L vs. 716.99 ± 255.81 μg × hr/L and 62.72 ± 17.97 ng/ml vs. 35.34 ± 13.61 ng/ml, respectively). No parasitic eggs were found in the faecal samples collected from both groups of horses on days 14 and 21 after drug administration. The obtained results indicate that although the pharmacokinetics of ivermectin may differ significantly between horse breeds, these differences do not affect the effectiveness of therapy.
Qualification of tumour mutational burden by targeted next‐generation sequencing as a biomarker in hepatocellular carcinoma
Authors: Wong Ching Ngar , Fessas Petros , Dominy Kathy , Mauri Francesco A. , Kaneko Takahiro , Parcq Persephone Du , Khorashad Jamshid , Toniutto Pierluigi , Goldin Robert D. , Avellini Claudio , Pinato David J.
Published: October 2020

Background & Aims

Tumour mutational burden (TMB) predicts improved response and survival to immunotherapy. In this pilot study, we optimized targeted next‐generation sequencing (tNGS) to estimate TMB in hepatocellular carcinoma (HCC).

Methods

We sequenced 48 non‐paired samples (21 fresh‐frozen [FF] and 27 paraffin‐embedded [FFPE]), among which 11 FFPE samples were pretreated with uracil‐DNA glycosylase (UDG). Thirty samples satisfied post‐sequencing quality control. High/low TMB was defined by median number of mutations/Mb (Mut/Mb), across different minimum allele frequency (MAF) thresholds (≥0.05, ≥0.1 and ≥0.2).

Results

Eligible patients (n = 29) were cirrhotic (84%) with TNM stage I‐II HCC (75%). FFPE samples had higher TMB (median 958.39 vs 2.51 Mut/Mb, P < .0001), estimated deamination counts (median 1335.50 vs 0, P < .0001) and C > T transitions at CpG sites (median 60.3% vs 9.1%, P = .002) compared to FF. UDG‐treated samples had lower TMB (median 4019.92 vs 353 Mut/Mb, P = .041) and deamination counts (median 6393.5 vs 328.5, P = .041) vs untreated FFPE. At 0.2 MAF threshold with UDG treatment, median TMB was 5.48 (range 1.68‐16.07) and did not correlate with salient pathologic features of HCC, including survival.

Conclusion

While tNGS on fresh HCC samples appears to be the optimal source of tumour DNA, the low median TMB values observed may limit the role of TMB as a predictor of response to immunotherapy in HCC.
Coral reef productivity and diversity—Contributions from enhanced photosynthesis via demand for carbohydrate from the host
Authors: Adams Melanie S. , Demmig‐Adams Barbara , Li Ruiqi , Zarate Daniel , Li Jingchun
Published: October 2020

Coral reefs’ high productivity has been attributed mainly to photosymbioses between the coral animal and algae of the family Symbiodiniaceae, with recognition that the host can increase algal photosynthesis by concentrating nutrients and enhancing the efficiency of light absorption. Here, we propose that an additional effect, consumption of carbohydrate by the host, may also enhance algal photosynthesis. We examine evidence from symbiosis between terrestrial plants and root fungi that indicates a link between carbohydrate consumption by the symbiotic partner and photosynthetic upregulation in the plant system. In addition, we review evidence from free‐living algae manipulated to exude carbohydrate into the external medium, which was associated with strong upregulation of photosynthetic capacity. We offer suggestions on how host‐induced carbohydrate release may increase photosynthesis rates in the symbionts in the intact photosymbiosis and how this relationship evolved.
Beyond the patch‐clamp resolution: functional activity of nonelectrogenic vacuolar NHX proton/potassium antiporters and inhibition by phosphoinositides
Authors: Gradogna Antonella , Scholz‐Starke Joachim , Pardo José M. , Carpaneto Armando
Published: October 2020

We combined the patch‐clamp technique with ratiometric fluorescence imaging using the proton‐responsive dye BCECF as a luminal probe.

Upon application of a steep cytosol‐directed potassium ion (K+) gradient in Arabidopsis mesophyll vacuoles, a strong and reversible acidification of the vacuolar lumen was detected, whereas no associated electrical currents were observed, in agreement with electroneutral cation/H+ exchange.

Our data show that this acidification was generated by NHX antiport activity, because: it did not distinguish between K+ and sodium (Na+) ions; it was sensitive to the NHX inhibitor benzamil; and it was completely absent in vacuoles from nhx1 nhx2 double knockout plants. Our data further show that NHX activity could be reversed, was voltage‐independent and specifically impaired by the low‐abundance signaling lipid PI(3,5)P2, which may regulate salt accumulation in plants by acting as a common messenger to coordinately shut down secondary active carriers responsible for cation and anion uptake inside the vacuole.

Finally, we developed a theory based on thermodynamics, which supports the data obtained by our novel experimental approach.

This work, therefore, represents a proof‐of‐principle that can be applied to the study of proton‐dependent exchangers from plants and animals, which are barely detectable using conventional techniques.
Selection patterns on early‐life phenotypic traits in Pinus sylvestris are associated with precipitation and temperature along a climatic gradient in Europe
Authors: Ramírez‐Valiente José Alberto , Solé‐Medina Aida , Pyhäjärvi Tanja , Savolainen Outi , Cervantes Sandra , Kesälahti Robert , Kujala Sonja T. , Kumpula Timo , Heer Katrin , Opgenoorth Lars , Siebertz Jan , Danusevicius Darius , Notivol Eduardo , Benavides Raquel , Robledo‐Arnuncio Juan José
Published: October 2020

Understanding the dynamics of selection is key to predicting the response of tree species to new environmental conditions in the current context of climate change. However, selection patterns acting on early recruitment stages and their climatic drivers remain largely unknown in most tree species, despite being a critical period of their life cycle.

We measured phenotypic selection on Pinus sylvestris seed mass, emergence time and early growth rate over 2 yr in four common garden experiments established along the latitudinal gradient of the species in Europe.

Significant phenotypic plasticity and among‐population genetic variation were found for all measured phenotypic traits. Heat and drought negatively affected fitness in the southern sites, but heavy rainfalls also decreased early survival in middle latitudes. Climate‐driven directional selection was found for higher seed mass and earlier emergence time, while the form of selection on seedling growth rates differed among sites and populations. Evidence of adaptive and maladaptive phenotypic plasticity was found for emergence time and early growth rate, respectively.

Seed mass, emergence time and early growth rate have an adaptive role in the early stages of P. sylvestris and climate strongly influences the patterns of selection on these fitness‐related traits.
A predator–prey model with Crowley–Martin functional response: A nonautonomous study
Authors: Tripathi Jai Prakash , Bugalia Sarita , Tiwari Vandana , Kang Yun
Published: October 2020

We investigate a nonautonomous predator–prey model system with a Crowley–Martin functional response. We perform rigorous mathematical analysis and obtain conditions for (a) global attractivity and permanence in the form of integrals which improve the traditional conditions obtained by using bounds of involved parameters; and (b) the existence of periodic solutions applying continuation theorem from coincidence degree theory which has stronger results than using Brouwer fixed point theorem. Our result also indicates that the global attractivity of periodic solution is positively affected by the predator's density dependent death rate. We employ partial rank correlation coefficient method to focus on how the output of the model system analysis is influenced by variations in a particular parameter disregarding the uncertainty over the remaining parameters. We discuss the relations between results (permanence and global attractivity) for autonomous and nonautonomous systems to get insights on the effects of time‐dependent parameters.

Recommendations for Resource Managers:

The natural environment fluctuates because of several factors, for example, mating habits, food supplies, seasonal effects of weathers, harvesting, death rates, birth rates, and other important population rates. The temporal fluctuations in physical environment (periodicity) plays a major role in community and population dynamics along with the impacts of population densities.

Periodic system may suppress the permanence of its corresponding autonomous system with parameters being the averages of periodic parameters.

As the human needs crosses a threshold level, then we require to observe the sustainability of resources of the associated exploited system. Therefore, the concept of stability and permanence become our main concern in an exploited model system (system with harvesting).

The mutual interference at high prey density may leave negative effect on the permanence of the system.

In harvested system, permanence becomes an important issue because if we harvest too many individuals then species may be driven to extinction. Interestingly, in many biological/agricultural systems, harvesting (due to fishing in marine system, hunting or disease) of a particular species/crop can only be more beneficial at certain times (e.g., the time and stage of harvest of a particular crop play greater role in its production and hence the particular crop is many times harvested at its physiological maturity or at harvest maturity).
Prognostic value of pretreatment cardiovascular biomarkers in head and neck squamous cell carcinoma
Authors: de Oliveira Karine Gadioli , Thebit Marcela Marçal , Andrade Tadeu Uggere , Campos Fabiana Vasconcelos , Podestá Jose Roberto Vasconcelos , Zeidler Sandra Lucia Ventorin Von , Bissoli Nazaré Souza , Gouvea Sonia Alves
Published: October 2020

Objectives

To examine the prognostic significance of pretreatment C‐reactive protein (CRP), N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), and cardiac troponin T (cTnT) levels on all‐cause mortality 3 years after head and neck squamous cell carcinoma (HNSCC) diagnosis.

Subjects and Methods

Data from 118 consecutive HNSCC patients, treated between 2012 and 2015, were evaluated prospectively. The impact of CRP, high‐sensitive (hs)‐cTnT, and NT‐proBNP levels on the 3‐year overall survival was estimated using the Kaplan–Meier method and Cox proportional hazard models.

Results

During the 36‐month follow‐up, 37 patients (31.35%) died. Multivariate analysis revealed that elevated CRP (Hazard ratio: 3.71, 95% CI: 1.44–9.53, p = .007) and NT‐proBNP levels (Hazard ratio: 5.04, 95% CI: 2.02–12.55, p = .001) were associated with negative prognosis, independent on age, sex, smoking and alcohol status, TNM classification, tumor site, body mass index (BMI), systolic blood pressure (SBP), and treatment modality (except for radiotherapy). hs‐cTnT had no influence over the prognosis, but it was correlated with TNM classification and SBP. CRP was significantly correlated with BMI and TNM classification, and NT‐proBNP with SBP and hs‐cTnT.

Conclusions

Pretreatment CRP and NT‐proBNP levels were identified as independent prognostic markers for poor clinical outcome 3 years after HNSCC diagnosis.
Impaired visual acuity caused by uncorrected refractive errors and amblyopia in a German paediatric cohort
Authors: Brandt Manuela , Truckenbrod Carolin , Meigen Christof , Vogel Mandy , Poulain Tanja , Kiess Wieland , Wahl Siegfried
Published: October 2020

Purpose

This study describes the prevalence of visual impairment caused by uncorrected distance refractive error and the spectacle coverage in a large cohort of German children and adolescents. Furthermore, we determined the prevalence of amblyopia and amblyopia treatment.

Methods

Optometrists carried out visual acuity (VA) testing, non‐cycloplegic autorefraction, VA retesting with the refractive correction obtained by autorefraction, and if necessary subjective refraction and cover‐test in 1,874 subjects (901 girls/973 boys), aged 3 to 16 years. Additionally, a questionnaire on the history of previous eye care was completed.

Results

Distance visual impairment (VI) with VA worse than 6/18 Snellen in the better eye was present in 0.5% (95% confidence interval [95% CI]: 0.2% to 0.9%) of children. Logistic regression showed a significant positive association between VI and older age (OR = 1.21, P = 0.03). Gender differences were not found (P = 0.77). The spectacle coverage of all participants was 74.8% (95% CI: 65.2% to 82.8%). Amblyopia was found in 29 participants (1.5%; 95% CI: 1.0% to 2.2%) with no age or sex differences. The causes of unilateral amblyopia (27 cases, 93.1%) were anisometropia in 55.6% of children, strabismus in 25.9% and the combination of these factors in 18.5%. All children with bilateral amblyopia (2 cases, 6.9%) showed bilateral high ametropia. We observed 15 children with current amblyopia, who had been treated with occlusion therapy in the past (62.2%; 95% CI: 42.7% to 83.6%).

Conclusions

The prevalence of impaired VA caused by uncorrected refractive error and amblyopia is comparable with previous studies conducted in urban areas worldwide. Adding the measurement of refractive error to existing medical check‐ups, possibly using autorefraction, would be desirable.
Overexpression of GmMYB14 improves high‐density yield and drought tolerance of soybean through regulating plant architecture mediated by the brassinosteroid pathway
Authors: Chen Limiao , Yang Hongli , Fang Yisheng , Guo Wei , Chen Haifeng , Zhang Xiaojuan , Dai Wenjun , Chen Shuilian , Hao Qingnan , Yuan Songli , Zhang Chanjuan , Huang Yi , Shan Zhihui , Yang Zhonglu , Qiu Dezhen , Liu Xiaorong , Tran Lam‐Son Phan , Zhou Xinan , Cao Dong
Published: October 2020

MYB transcription factors (TFs) have been reported to regulate the biosynthesis of secondary metabolites, as well as to mediate plant adaption to abiotic stresses, including drought. However, the roles of MYB TFs in regulating plant architecture and yield potential remain poorly understood. Here, we studied the roles of the dehydration‐inducible GmMYB14 gene in regulating plant architecture, high‐density yield and drought tolerance through the brassinosteroid (BR) pathway in soybean. GmMYB14 was shown to localize to nucleus and has a transactivation activity. Stable GmMYB14‐overexpressing (GmMYB14‐OX) transgenic soybean plants displayed a semi‐dwarfism and compact plant architecture associated with decreased cell size, resulting in a decrease in plant height, internode length, leaf area, leaf petiole length and leaf petiole angle, and improved yield in high density under field conditions. Results of the transcriptome sequencing suggested the involvement of BRs in regulating GmMYB14‐OX plant architecture. Indeed, GmMYB14‐OX plants showed reduced endogenous BR contents, while exogenous application of brassinolide could partly rescue the phenotype of GmMYB14‐OX plants. Furthermore, GmMYB14 was shown to directly bind to the promoter of GmBEN1 and up‐regulate its expression, leading to reduced BR content in GmMYB14‐OX plants. GmMYB14‐OX plants also displayed improved drought tolerance under field conditions. GmBEN1 expression was also up‐regulated in the leaves of GmMYB14‐OX plants under polyethylene glycol treatment, indicating that the GmBEN1‐mediated reduction in BR level under stress also contributed to drought/osmotic stress tolerance of the transgenic plants. Our findings provided a strategy for stably increasing high‐density yield and drought tolerance in soybean using a single TF‐encoding gene.
An investigation into uterine capacity based on litter and placental characteristics in two sow lines with different prolificacy (Danish Landrace x Danish Yorkshire versus German Saddleback)
Authors: König Nicola Lea , Wähner Martin , Seeger Johannes , Sigmarsson Haukur Lindberg , Kauffold Johannes
Published: October 2020

Litter size in modern so called hyperprolific pig (Sus scrofa Linnaeus) breeds such as of crossbred Danish Landrace x Danish Yorkshire (LY/YL) sows increased remarkably over recent years, however, commonly associated with reduced piglet birth weight and higher within litter birth weight variability likely due to a limited uterine capacity. Since investigation into this issue is patchy, the aim of this study was to investigate uterine capacity based on litter and placental characteristics in two sow lines with different prolificacy, that is crossbred Danish genetic (Danish Landrace x Danish Yorkshire; DG; n = 14) and purebred German Saddleback (GS) sows (n = 12). Parameters recorded were litter size, piglet birth weight and vitality, placental weight and surface area as well as placental vascularization. Litters of DG were on average larger than of GS (p < .001). Piglets of DG weighed on average less than GS (p < .001) and were less vital (p < .001–.142). Increasing litter size was associated with reduced piglet birth weight and increased within litter birth weight variability in GS, but not in DG. DG had on average a lower placental weight (p < .001) and smaller placentae (p < .001) than GS, but the placenta was on average more efficient than of GS (based on the quotient of piglet and corresponding placental weight; p < .001). Vascularization of placentae was on average not or only slightly different between breeds (p < .05 – .982). Remarkably, however, vascularization of the lateral and apical chorionic epithelium of the chorionic ridges as the immediate foetal/maternal interface was on average slightly higher in DG than GS (p < .05–.111). Results thus demonstrate that uterine capacity based on litter and placental characteristics is higher in DG than GS sows.
Association of diabetes, education level, and care dependency with use of temporary vascular access in patients with chronic kidney disease
Authors: Chen Hung‐Chih , Lai Meng‐Jie , Wu Wan‐Chen , Lee Chi‐Yu , Lin Hsuan‐Jen , Lin Chung‐Chih , Chang Chiz‐Tzung , Wang Charles C. N. , Chou Che‐Yi
Published: October 2020

Objective

Temporary vascular access (TVA) is frequently used during the first dialysis in patients with chronic kidney disease (CKD), and it is associated with an increased risk of infection, central vein stenosis, and mortality. Here, factors associated with TVA in patients with CKD were explored.

Methods

This study included patients in a single‐center CKD care program who initiated long‐term renal replacement therapy. The primary outcome was TVA use at first dialysis. Factors possibly associated with TVA use were analyzed using Cox regression.

Results

Temporary vascular access was used in 53.2% of the patients at first dialysis. In total, 73.2% (n = 865) and 26.8% (n = 317) of the patients were on hemodialysis and peritoneal dialysis, respectively. Multivariate Cox regression analysis showed that TVA use in patients with CKD was associated with diabetes (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.28‐1.81, p < 0.001), lower albumin (HR 0.82, 95% CI 0.75‐0.91, p < 0.001), lower education level (HR 0.75, 95% CI 0.56‐1.00, p = 0.055), and total care dependency (HR 1.92, CI 1.44‐3.43, p = 0.003).

Conclusion

Diabetes, education level, and care dependency are associated with TVA at dialysis initiation in patients with CKD.
Measurement of dermal water content by confocal RAMAN spectroscopy to investigate intrinsic aging and photoaging of human skin in vivo
Authors: Kourbaj Ghaith , Bielfeldt Stephan , Seise Matthias , Wilhelm Klaus‐Peter
Published: October 2020

Background

In vivo confocal Raman spectroscopy (CRS) revealed a clear correlation of age and dermal water content, indicating increasing water content of the dermis with increasing age. This enhancement of water has been interpreted as an age‐dependent depletion, of proteins, mainly of collagen. Chronical sun exposure is known to destroy the collagen network of the skin, which leads to the signs of photoaging as the formation of wrinkles. Noninvasive in vivo measuring techniques for photoaging are limited. Therefore, sensitive techniques to quantify even mild degrees of photoaging in a clinical setting are of high interest. We used CRS to measure the water content in human dermis in vivo, assuming that additionally to the increase of water content in intrinsic aging, photoaging would lead to further collagen depletion and an additional increase in water content of the dermis.

Materials and Methods

A panel of 24 female subjects of different age‐groups and scores of photoaging was recruited. A ranking of high resolution dorsal forearm photographs was used to classify the degree of photoaging with high precision. After that, CRS water content and collagen measurements were performed in the photoexposed dorsal as well as the photoprotected volar dermis of the subjects.

Results

A positive correlation of water content in the dermis with age could be confirmed (r = .550). Further, a positive correlation between water content of dorsal dermis and photoaging ranks was observed (Pearson's r = .417).

Conclusion

Assessment of water content in the dermis with confocal Raman spectroscopy was found to be a promising method to measure the degree of photoaging in human subjects in vivo.
Reflectance confocal microscopy role in mycosis fungoides follow‐up
Authors: Melhoranse Gouveia Bruna , Wells Jillian , Kim Jennifer , Collgros Helena , Guitera Pascale , Longo Caterina , Fernandez‐Penas Pablo
Published: October 2020

Background

Reflectance confocal microscopy (RCM) is a useful tool for many skin cancers, allowing non‐invasive evaluation over time and identifying areas of active disease. Its role to follow‐up mycosis fungoides (MF) patients has not yet been evaluated.

Objective

To assess the level of agreement between RCM and histopathology and to develop a RCM checklist that could help monitoring MF patients.

Method

Prospective study in a cutaneous lymphoma clinic of a tertiary hospital in Australia. RCM and biopsies were performed on the same area at baseline, before commencing or changing treatment, and at 6 months after starting treatment. Normal skin sites were also analysed and acted as controls. RCM features and histopathological findings were blindly evaluated by the confocalist and pathologist. Correlation between RCM and histology was measured by overall per cent of agreement (OPA), kappa and ROC curves. Additionally, RCM images before and after treatment were assessed blinded from clinical information and correlated to clinical assessment.

Results

Thirty‐eight MF lesions were included. Nineteen of these 38 were re‐assessed by RCM 6 months later. Fifty biopsies were performed (38 at baseline and 12 after 6 months). The combination of four RCM features corresponding to Pautrier's microabscess, epidermal and junctional lymphocytes and interface dermatitis formed the RCM checklist for MF that predicted the severity of disease with AUC of 0.95 (P = .003).

Conclusion

Reflectance confocal microscopy can assess activity within a lesion and over time and assist in the clinical management of patients with MF.