bluuebunny/crossref_metadata_2025 huggingface dataset:
Intestinal protection by proanthocyanidins involves anti-oxidative and anti-inflammatory actions in association with an improvement of insulin sensitivity, lipid and glucose homeostasis
Authors: Koudoufio Mireille , Feldman Francis , Ahmarani Lena , Delvin Edgard , Spahis Schohraya , Desjardins Yves , Levy Emile
Published: February 2021

Recent advances have added another dimension to the complexity of cardiometabolic disorders (CMD) by directly implicating the gastrointestinal tract as a key player. In fact, multiple factors could interfere with intestinal homeostasis and elicit extra-intestinal CMD. As oxidative stress (OxS), inflammation, insulin resistance and lipid abnormalities are among the most disruptive events, the aim of the present study is to explore whether proanthocyanidins (PACs) exert protective effects against these disorders. To this end, fully differentiated intestinal Caco-2/15 cells were pre-incubated with PACs with and without the pro-oxidant and pro-inflammatory iron/ascorbate (Fe/Asc). PACs significantly reduce malondialdehyde, a biomarker of lipid peroxidation, and raise antioxidant SOD2 and GPx via the increase of NRF2/Keap1 ratio. Likewise, PACs decrease the inflammatory agents TNFα and COX2 through abrogation of NF-κB. Moreover, according to crucial biomarkers, PACs result in lipid homeostasis improvement as reflected by enhanced fatty acid β-oxidation, diminished lipogenesis, and lowered gluconeogenesis as a result of PPARα, γ and SREBP1c modulation. Since these metabolic routes are mainly regulated by insulin sensitivity, we have examined the insulin signaling pathway and found an upregulation of phosphoPI3K/Akt and downregulation of p38-MAPK expressions, indicating beneficial effects in response to PACs. Taken together, PACs display the potential to counterbalance OxS and inflammation in Fe/Asc-exposed intestinal cells, in association with an improvement of insulin sensitivity, which ameliorates lipid and glucose homeostasis.
Reflected wave intensity increases based on aortic diameter after endovascular aortic therapy in a goat model
Authors: Takano Tomohiro , Iwai-Takano Masumi , Tsuboko Yusuke , Shiraishi Yasuyuki , Yambe Tomoyuki , Igarashi Takashi , Yokoyama Hitoshi
Published: February 2021

Reflected wave increases after endovascular aortic repair (EVAR) in patients with aortic aneurysm. This affects the left ventricular (LV) diastolic function and leads to a poor prognosis. This study aimed to evaluate the relationship between increased reflected wave amplitude and aortic diameter after EVAR. EVAR was performed in seven healthy goats. We assessed wave intensity (WI), aortic diameter, and stiffness parameter β. Moreover, we evaluated the relationship between negative reflected wave (NW, reflected waves toward the heart from the periphery by WI) and other parameters after EVAR. Results showed an increase in stiffness parameter β (3.5 ± 0.3 vs 15.9 ± 4.7, p = 0.018) and a decrease in the change of aortic diameter (6.9 ± 0.7 vs 2.7 ± 0.4%, p = 0.018) after EVAR. The NW was significantly amplified after EVAR from baseline (−589.8 ± 143.4 to  − 1192.3 ± 303.7 mmHg-m/sec3, p = 0.043). The NW showed a significant correlation with maximum aortic diameter (R = 0.707, p = 0.038) and minimum aortic diameter (R = 0.724, p = 0.033). The reflected wave was enhanced after EVAR and was correlated to the aortic diameter at the stent-graft site. It is important to consider that patients with smaller aortic diameters in landing zone who undergo EVAR may develop LV dysfunction.
Fungal diversity and community structure from coastal and barrier island beaches in the United States Gulf of Mexico
Authors: Walker Allison K. , Robicheau Brent M.
Published: February 2021

Fungi are an important and understudied component of coastal biomes including sand beaches. Basic biogeographic diversity data are lacking for marine fungi in most parts of the world, despite their important role in decomposition. We examined intertidal fungal communities at several United States (US) Gulf of Mexico sand beach sites using morphology and ITS rDNA terminal restriction fragment length polymorphism (T-RFLP) analyses. Fungal biogeographical patterns from sand beach detritus (wood, emergent plant [mangrove/ saltmarsh], or marine [algae, seagrass]) from Florida, Mississippi, and Texas were investigated using diversity indices and multivariate analyses. Fungal diversity increased with decreasing latitude at our study sites. Substrate type strongly influenced fungal community structure in this region, with different fungal communities on detrital marine versus emergent substrates, as well as detrital marine versus wood substrates. Thirty-five fungi were identified morphologically, including new regional and host records. Of these, 86% were unique to an individual collection (i.e., sampled once from one site). Rarefaction curves from pooled morphological data from all sites estimate the number of samples required to characterize the mycota of each substrate. As sampling occurred before the Deepwater Horizon oil spill (April-2010), our findings contribute pre-oil spill sand beach biodiversity data and marine fungal distribution trends within this economically important oceanographic region.
PGMD/curcumin nanoparticles for the treatment of breast cancer
Authors: Kumari Mankamna , Sharma Nikita , Manchanda Romila , Gupta Nidhi , Syed Asad , Bahkali Ali H. , Nimesh Surendra
Published: February 2021

The present study aims at developing PGMD (poly-glycerol-malic acid-dodecanedioic acid)/curcumin nanoparticles based formulation for anticancer activity against breast cancer cells. The nanoparticles were prepared using both the variants of PGMD polymer (PGMD 7:3 and PGMD 6:4) with curcumin (i.e. CUR NP 7:3 and CUR NP 6:4). The size of CUR NP 7:3 and CUR NP 6:4 were found to be ~ 110 and 218 nm with a polydispersity index of 0.174 and 0.36, respectively. Further, the zeta potential of the particles was − 18.9 and − 17.5 mV for CUR NP 7:3 and CUR NP 6:4, respectively. The entrapment efficiency of both the nanoparticles was in the range of 75–81%. In vitro anticancer activity and the scratch assay were conducted on breast cancer cell lines, MCF-7 and MDA-MB-231. The IC50of the nanoformulations was observed to be 40.2 and 33.6 μM at 48 h for CUR NP 7:3 and CUR NP 6:4, respectively, in MCF-7 cell line; for MDA-MB-231 it was 43.4 and 30.5 μM. Acridine orange/EtBr and DAPI staining assays showed apoptotic features and nuclear anomalies in the treated cells. This was further confirmed by western blot analysis that showed overexpression of caspase 9 indicating curcumin role in apoptosis.
Author Correction: Coronavirus disease 2019 (COVID-19) in Italy: features on chest computed tomography using a structured report system
Authors: Grassi Roberto , Fusco Roberta , Belfiore Maria Paola , Montanelli Alessandro , Patelli Gianluigi , Urraro Fabrizio , Petrillo Antonella , Granata Vincenza , Sacco Palmino , Mazzei Maria Antonietta , Feragalli Beatrice , Reginelli Alfonso , Cappabianca Salvatore
Published: February 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The simply modified intrascleral fixation using round flange (SMURF) technique for intrascleral intraocular lens fixation
Authors: Kim Soa , Kim Jee Taek
Published: February 2021

We describe a simply modified intrascleral fixation using round flange (SMURF) technique and report the clinical outcomes of the surgery. Forty-one eyes of 41 consecutive patients, with intraocular lens (IOL) dislocation, crystalline lens subluxation, and zonular weakness, who underwent surgery using the SMURF technique were included. The modified technique included the use of a conventional 27-gauge needle, a non-bent needle, oblique sclerotomy, direct threading of the leading haptic, and simple placement of the following haptic. IOLs were successfully placed and showed good centring. There were no cases of wound leakage or hypotony during the early postoperative period. Postoperative complications included vitreous haemorrhage in one eye (2.4%), intraocular pressure elevation in one eye (2.4%), and iris capture in six eyes (14.6%). There were no cases of postoperative retinal detachment, cystoid macular oedema, endophthalmitis, or IOL dislocation during the follow-up period. We proposed a few modifications in the intrascleral flanged technique for IOL fixation. The modified technique is a simple, easy, and minimally invasive procedure for successful IOL intrascleral fixation.
Association of maternal pre-pregnancy low or increased body mass index with adverse pregnancy outcomes
Authors: Tang Jie , Zhu Xinhong , Chen Yanbing , Huang Dongming , Tiemeier Henning , Chen Ruoling , Bao Wei , Zhao Qingguo
Published: February 2021

This study investigated the association between pre-pregnancy body mass index (BMI) and adverse pregnancy outcomes among women participated in the National Free Preconception Health Examination Project in Guangdong Province, China, and explored these associations according to maternal age. Pre-pregnancy BMI was classified into underweight (BMI < 18.5 kg/m2), healthy weight (18.5–23.9 kg/m2), overweight (24.0–27.9 kg/m2), and obesity (≥ 28.0 kg/m2) according to Chinese criteria. Outcomes were preterm birth (PTB, delivery before 37 weeks of gestation), large for gestational age (LGA, birthweight above the 90th percentile for gestational age by infants’ sex), small for gestational age (SGA, birthweight below the 10th percentile for gestational age by infants’ sex), primary caesarean delivery, shoulder dystocia or birth injury, and stillbirth. Adjusted incidence risk ratios (aIRR) were calculated for underweight, overweight and obesity, respectively. Compared with healthy weight, underweight was associated with increased risk of PTB (aIRR 1.06, 95%CI 1.04–1.09) and SGA (1.23, 1.22–1.26) but inversely associated with LGA (0.83, 0.82–0.85), primary caesarean delivery (0.88, 0.87–0.90) and stillbirth (0.73, 0.53–0.99). Overweight was associated with increased risk of LGA (1.17, 1.14–1.19), primary caesarean delivery (1.18, 1.16–1.20) and stillbirth (1.44, 1.03–2.06), but inversely associated with SGA (0.92, 0.90–0.95) and shoulder dystocia or birth injury (0.86, 0.79–0.93). Obesity was associated with increased risk of PTB (1.12, 1.05–1.20), LGA (1.32, 1.27–1.37), primary caesarean delivery (1.45, 1.40–1.50), but inversely associated with SGA (0.92, 0.87–0.97). The aIRRs for underweight, overweight and obesity in relation to these adverse pregnancy outcomes ranged from 0.65 to 1.52 according to maternal age. In Chinese population, maternal pre-pregnancy BMI was significantly associated with the risk of adverse pregnancy outcomes and the risk differs according to maternal age. Further investigation is warranted to determine whether and how counselling and interventions for women with low or increased BMI before pregnancy can reduce the risk of adverse pregnancy outcomes.
The tendency to stop collecting information is linked to illusions of causality
Authors: Moreno-Fernández María Manuela , Blanco Fernando , Matute Helena
Published: February 2021

Previous research proposed that cognitive biases contribute to produce and maintain the symptoms exhibited by deluded patients. Specifically, the tendency to jump to conclusions (i.e., to stop collecting evidence soon before making a decision) has been claimed to contribute to delusion formation. Additionally, deluded patients show an abnormal understanding of cause-effect relationships, often leading to causal illusions (i.e., the belief that two events are causally connected, when they are not). Both types of bias appear in psychotic disorders, but also in healthy individuals. In two studies, we test the hypothesis that the two biases (jumping to conclusions and causal illusions) appear in the general population and correlate with each other. The rationale is based on current theories of associative learning that explain causal illusions as the result of a learning bias that tends to wear off as additional information is incorporated. We propose that participants with higher tendency to jump to conclusions will stop collecting information sooner in a causal learning study than those participants with lower tendency to jump to conclusions, which means that the former will not reach the learning asymptote, leading to biased judgments. The studies provide evidence in favour that the two biases are correlated but suggest that the proposed mechanism is not responsible for this association.
Nubian Levallois technology associated with southernmost Neanderthals
Authors: Blinkhorn James , Zanolli Clément , Compton Tim , Groucutt Huw S. , Scerri Eleanor M. L. , Crété Lucile , Stringer Chris , Petraglia Michael D. , Blockley Simon
Published: February 2021

Neanderthals occurred widely across north Eurasian landscapes, but between ~ 70 and 50 thousand years ago (ka) they expanded southwards into the Levant, which had previously been inhabited by Homo sapiens. Palaeoanthropological research in the first half of the twentieth century demonstrated alternate occupations of the Levant by Neanderthal and Homo sapiens populations, yet key early findings have largely been overlooked in later studies. Here, we present the results of new examinations of both the fossil and archaeological collections from Shukbah Cave, located in the Palestinian West Bank, presenting new quantitative analyses of a hominin lower first molar and associated stone tool assemblage. The hominin tooth shows clear Neanderthal affinities, making it the southernmost known fossil specimen of this population/species. The associated Middle Palaeolithic stone tool assemblage is dominated by Levallois reduction methods, including the presence of Nubian Levallois points and cores. This is the first direct association between Neanderthals and Nubian Levallois technology, demonstrating that this stone tool technology should not be considered an exclusive marker of Homo sapiens.
Genetic characteristics of Bursaphelenchus xylophilus third-stage dispersal juveniles
Authors: Chen Qiaoli , Zhang Ruizhi , Li Danlei , Wang Feng
Published: February 2021

The third-stage dispersal juvenile (DJ3) of pinewood nematode (PWN) is highly associated with low-temperature survival and spread of the nematode. Oil-Red-O staining showed that its lipid content was significantly higher compared with other PWN stages. Weighted gene coexpression network analysis identified that genes in the pink module were highly related to DJ3 induced in the laboratory (DJ3-lab). These genes were arranged according to their gene significance (GS) to DJ3-lab. Of the top 30 genes with the highest GS, seven were found to be highly homologous to the cysteine protease family cathepsin 1 (CATH1). The top 30 genes with the highest weight value to each of the seven genes in the pink module were selected, and finally 35 genes were obtained. Between these seven CATH1 homologous genes and their 35 highly related genes, 15 were related to fat metabolism or autophagy. These autophagy-related genes were also found to be highly correlated with other genes in the pink module, suggesting that autophagy might be involved in the mechanism of longevity in DJ3 and the formation of DJ3 by regulating genes related to fat metabolism.
Oestrogen replacement fails to fully revert ovariectomy-induced changes in adipose tissue monoglycerides, diglycerides and cholesteryl esters of rats fed a lard-enriched diet
Authors: Boldarine Valter Tadeu , Joyce Ellen , Pedroso Amanda Paula , Telles Mônica Marques , Oyama Lila Missae , Bueno Allain Amador , Ribeiro Eliane Beraldi
Published: February 2021

Menopause may be accompanied by abdominal obesity and inflammation, conditions accentuated by high-fat intake, especially of saturated fat (SFA)-rich diets. We investigated the consequences of high-SFA intake on the fatty acid (FA) profile of monoglycerides, diglycerides and cholesteryl esters from retroperitoneal white adipose tissue (RET) of rats with ovariectomy-induced menopause, and the effect of oestradiol replacement. Wistar rats were either ovariectomized (Ovx) or sham operated (Sham) and fed either standard chow (C) or lard-enriched diet (L) for 12 weeks. Half of the Ovx rats received 17β-oestradiol replacement (Ovx + E2). Body weight and food intake were measured weekly. RET neutral lipids were chromatographically separated and FAs analysed by gas chromatography. Ovariectomy alone increased body weight, feed efficiency, RET mass, leptin and insulin levels, leptin/adiponectin ratio, HOMA-IR and HOMA-β indexes. OvxC + E2 showed attenuation in nearly all blood markers. HOMA-β index was restored in OvxL + E2. OvxC showed significantly disturbed SFA and polyunsaturated FA (PUFA) profile in RET cholesteryl esters (CE). OvxC also showed increased monounsaturated FA (MUFA) in the monoglyceride diglyceride (Mono–Di) fraction. Similar changes were not observed in OvxL, although increased SFA and decreased PUFA was observed in Mono–Di. Overall, HRT was only partially able to revert changes induced by ovariectomy. There appears to be increased mobilization of essential FA in Ovx via CE, which is a dynamic lipid species. The same results were not found in Mono–Di, which are more inert. HRT may be helpful to preserve FA profile in visceral fat, but possibly not wholly sufficient in reverting the metabolic effects induced by menopause.
Extracellular vesicle concentrations of glial fibrillary acidic protein and neurofilament light measured 1 year after traumatic brain injury
Authors: Flynn Spencer , Leete Jacqueline , Shahim Pashtun , Pattinson Cassandra , Guedes Vivian A. , Lai Chen , Devoto Christina , Qu Bao-Xi , Greer Kisha , Moore Brian , van der Merwe Andre , Ekanayake Vindhya , Gill Jessica , Chan Leighton
Published: February 2021

Traumatic brain injury (TBI) is linked to long-term symptoms in a sub-set of patients who sustain an injury, but this risk is not universal, leading us and others to question the nature of individual variability in recovery trajectories. Extracellular vesicles (EVs) are a promising, novel avenue to identify blood-based biomarkers for TBI. Here, our aim was to determine if glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) measured 1-year postinjury in EVs could distinguish patients from controls, and whether these biomarkers relate to TBI severity or recovery outcomes. EV GFAP and EV NfL were measured using an ultrasensitive assay in 72 TBI patients and 20 controls. EV GFAP concentrations were elevated in moderate and severe TBI compared to controls (p’s < 0.001) and could distinguish controls from moderate (AUC = 0.86) or severe TBI (AUC = 0.88). Increased EV GFAP and EV NfL levels were associated with lower 1-year Glasgow Outcome Scale–Extended (GOS-E) score (p’s < 0.05). These findings suggest that blood-derived EV concentrations of GFAP and NfL drawn even 1 year after injury are higher in TBI patients compared to controls, and are related to injury severity and poor recovery outcomes, suggesting that TBIs alter the activity of these biomarkers, likely contributing to individual variability in recovery.
Publisher Correction: Inhibition of eNOS by L-NAME resulting in rat hind limb developmental defects through PFKFB3 mediated angiogenetic pathway
Authors: Wu Ziqiang , Yao Huan , Xu Huan , Wang Yang , Hu Wangming , Lou Guanhua , Zhang Lingling , Huang Cong , Jiang Cen , Zhou Shiyi , Shi Yaping , Chen Xiongbing , Yang Lan , Xu Yiming , Wang Yong
Published: February 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Monitoring blood potassium concentration in hemodialysis patients by quantifying T-wave morphology dynamics
Authors: Palmieri Flavio , Gomis Pedro , Ferreira Dina , Ruiz José Esteban , Bergasa Beatriz , Martín-Yebra Alba , Bukhari Hassaan A. , Pueyo Esther , Martínez Juan Pablo , Ramírez Julia , Laguna Pablo
Published: February 2021

We investigated the ability of time-warping-based ECG-derived markers of T-wave morphology changes in time ($$d_{w}$$

d
w

) and amplitude ($$d_a$$

d
a

), as well as their non-linear components ($${d_w^{{\mathrm{NL}}}}$$

d
w
NL

and $${d_a^{\mathrm{NL}}}$$

d
a
NL

), and the heart rate corrected counterpart ($$d_{w,c}$$

d

w
,
c

), to monitor potassium concentration ($$[K^{+}]$$

[

K
+

]

) changes ($$\Delta [K^+]$$

Δ
[

K
+

]

) in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD). We compared the performance of the proposed time-warping markers, together with other previously proposed $$[K^{+}]$$

[

K
+

]

markers, such as T-wave width ($$T_w$$

T
w

) and T-wave slope-to-amplitude ratio ($$T_{S/A}$$

T

S
/
A

), when computed from standard ECG leads as well as from principal component analysis (PCA)-based leads. 48-hour ECG recordings and a set of hourly-collected blood samples from 29 ESRD-HD patients were acquired. Values of $$d_w$$

d
w

, $$d_a$$

d
a

, $${d_w^{\mathrm{NL}}}$$

d
w
NL

, $${d_a^{\mathrm{NL}}}$$

d
a
NL

and $$d_{w,c}$$

d

w
,
c

were calculated by comparing the morphology of the mean warped T-waves (MWTWs) derived at each hour along the HD with that from a reference MWTW, measured at the end of the HD. From the same MWTWs $$T_w$$

T
w

and $$T_{S/A}$$

T

S
/
A

were also extracted. Similarly, $$\Delta [K^+]$$

Δ
[

K
+

]

was calculated as the difference between the $$[K^{+}]$$

[

K
+

]

values at each hour and the $$[K^{+}]$$

[

K
+

]

reference level at the end of the HD session. We found that $$d_{w}$$

d
w

and $$d_{w,c}$$

d

w
,
c

showed higher correlation coefficients with $$\Delta [K^+]$$

Δ
[

K
+

]

than $$T_{S/A}$$

T

S
/
A

—Spearman’s ($$\rho$$
ρ
) and Pearson’s (r)—and $$T_w$$

T
w

—Spearman’s ($$\rho$$
ρ
)—in both SL and PCA approaches being the intra-patient median $$\rho \ge 0.82$$

ρ
≥
0.82

and $$r \ge 0.87$$

r
≥
0.87

in SL and $$\rho \ge 0.82$$

ρ
≥
0.82

and $$r \ge 0.89$$

r
≥
0.89

in PCA respectively. Our findings would point at $$d_{w}$$

d
w

and $$d_{w,c}$$

d

w
,
c

as the most suitable surrogate of $$\Delta [K^+]$$

Δ
[

K
+

]

, suggesting that they could be potentially useful for non-invasive monitoring of ESRD-HD patients in hospital, as well as in ambulatory settings. Therefore, the tracking of T-wave morphology variations by means of time-warping analysis could improve continuous and remote $$[K^{+}]$$

[

K
+

]

monitoring of ESRD-HD patients and flagging risk of $$[K^{+}]$$

[

K
+

]

-related cardiovascular events.
Altered functional properties of the codling moth Orco mutagenized in the intracellular loop-3
Authors: Bobkov Yuriy V. , Walker III William B. , Cattaneo Alberto Maria
Published: February 2021

Amino acid substitutions within the conserved polypeptide sequence of the insect olfactory receptor co-receptor (Orco) have been demonstrated to influence its pharmacological properties. By sequence analysis and phylogenetic investigation, in the Lepidopteran subgroup Ditrysia we identified a fixed substitution in the intracellular loop-3 (ICL-3) of a conserved histidine to glutamine. By means of HEK293 cells as a heterologous system, we functionally expressed Orco from the Ditrysian model Cydia pomonella (CpomOrco) and compared its functional properties with a site-directed mutagenized version where this ICL-3-glutamine was reverted to histidine (CpomOrcoQ417H). The mutagenized CpomOrcoQ417H displayed decreased responsiveness to VUAA1 and reduced response efficacy to an odorant agonist was observed, when co-transfected with the respective OR subunit. Evidence of reduced responsiveness and sensitivity to ligands for the mutagenized Orco suggest the fixed glutamine substitution to be optimized for functionality of the cation channel within Ditrysia. In addition, contrary to the wild type, the mutagenized CpomOrcoQ417H preserved characteristics of VUAA-binding when physiologic conditions turned to acidic. Taken together, our findings provide further evidence of the importance of ICL-3 in forming basic functional properties of insect Orco- and Orco/OR-channels, and suggest involvement of ICL-3 in the potential functional adaptation of Ditrysian Orcos to acidified extra-/intracellular environment.
Projected plastic waste loss scenarios between 2000 and 2030 into the largest freshwater-lake system in Southeast Asia
Authors: Finnegan Alexander Matthew David , Gouramanis Christos
Published: February 2021

Freshwater plastic pollution is critically understudied in Southeast Asia (SEA). Recent modelling studies indicate that SEA rivers contribute vast quantities of plastic to the world’s oceans, however, these fail to capture the complexity of individual systems. We determine the volume of mismanaged plastic waste (MPW) entering Tonle Sap Basin (TSB)—the largest freshwater lake–river system in SEA, between 2000 and 2030. Using economic, population and waste data at provincial and national levels, coupled with high resolution population and flood datasets, we estimate that ca. 221,700 tons of plastic entered between 2000 and 2020, and 282,300 ± 8700 tons will enter between 2021 and 2030. We demonstrate that policy interventions can reduce MPW up to 76% between 2021 and 2030. The most-stringent scenario would prevent 99% of annual MPW losses by 2030, despite substantially higher waste volumes and population. If successfully implemented, Cambodia will prevent significant losses in natural capital, material value and degradation in TSB worth at least US$4.8 billion, with additional benefits for the Mekong River and South China Sea.
Predictors of brain infarction in adult patients on extracorporeal membrane oxygenation: an observational cohort study
Authors: Iacobelli Riccardo , Fletcher-Sandersjöö Alexander , Lindblad Caroline , Keselman Boris , Thelin Eric Peter , Broman Lars Mikael
Published: February 2021

Non-hemorrhagic brain infarction (BI) is a recognized complication in adults treated with extracorporeal membrane oxygenation (ECMO) and associated with increased mortality. However, predictors of BI in these patients are poorly understood. The aim of this study was to identify predictors of BI in ECMO-treated adult patients. We conducted an observational cohort study of all adult patients treated with venovenous or venoarterial (VA) ECMO at our center between 2010 and 2018. The primary endpoint was a computed tomography (CT) verified BI. Logistic regression models were employed to identify BI predictors. In total, 275 patients were included, of whom 41 (15%) developed a BI. Pre-ECMO Simplified Acute Physiology Score III, pre-ECMO cardiac arrest, VA ECMO and conversion between ECMO modes were identified as predictors of BI. In the multivariable analysis, VA ECMO demonstrated independent risk association. VA ECMO also remained the independent BI predictor in a sub-group analysis excluding patients who did not undergo a head CT scan during ECMO treatment. The incidence of BI in adult ECMO patients may be higher than previously believed and is independently associated with VA ECMO mode. Larger prospective trials are warranted to validate these findings and ascertain their clinical significance.
Case control study comparing the HPV genome in patients with oral cavity squamous cell carcinoma to normal patients using metagenomic shotgun sequencing
Authors: Ganly Ian , Pei Zhiheng , Hao Yuhan , Ma Yingfei , Rosenthal Matthew , Wu Zhenglin , Migliacci Jocelyn , Huang Bin , Katabi Nora , Tseng Wenzhi , Brown Stuart , Tang Yi-Wei , Yang Liying
Published: February 2021

The aim of this study was to carry out a case control study comparing the HPV genome in patients with oral cavity squamous cell carcinoma (OC-SCC) to normal patients using metagenomic shotgun sequencing. We recruited 50 OC-SCC cases which were then matched with a control patient by age, gender, race, smoking status and alcohol status. DNA was extracted from oral wash samples from all patients and whole genome shotgun sequencing performed. The raw sequence data was cleaned, reads aligned with the human genome (GRCH38), nonhuman reads identified and then HPV genotypes identified using HPViewer. In the 50 patients with OC-SCC, the most common subsite was tongue in 26 (52%). All patients were treated with primary resection and neck dissection. All but 2 tumors were negative on p16 immunohistochemistry. There were no statistically significant differences between the cases and controls in terms of gender, age, race/ethnicity, alcohol drinking, and cigarette smoking. There was no statistically significant difference between the cancer samples and control samples in the nonhuman DNA reads (medians 4,228,072 vs. 5,719,715, P value = 0.324). HPV was detected in 5 cases (10%) of OC-SCC (genotypes 10, 16, 98) but only 1 tumor sample (genotype 16) yielded a high number of reads to suggest a role in the etiology of OC-SCC. HPV was detected in 4 control patients (genotypes 16, 22, 76, 200) but all had only 1–2 HPV reads per human genome. Genotypes of HPV are rarely found in patients with oral cancer.
Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice
Authors: Lee Han-Chung , Hamzah Hamizun , Leong Melody Pui-Yee , Md Yusof Hadri , Habib Omar , Zainal Abidin Shahidee , Seth Eryse Amira , Lim Siong-Meng , Vidyadaran Sharmili , Mohd Moklas Mohamad Aris , Abdullah Maizaton Atmadini , Nordin Norshariza , Hassan Zurina , Cheah Pike-See , Ling King-Hwa
Published: February 2021

Ruxolitinib is the first janus kinase 1 (JAK1) and JAK2 inhibitor that was approved by the United States Food and Drug Administration (FDA) agency for the treatment of myeloproliferative neoplasms. The drug targets the JAK/STAT signalling pathway, which is critical in regulating the gliogenesis process during nervous system development. In the study, we assessed the effect of non-maternal toxic dosages of ruxolitinib (0–30 mg/kg/day between E7.5-E20.5) on the brain of the developing mouse embryos. While the pregnant mice did not show any apparent adverse effects, the Gfap protein marker for glial cells and S100β mRNA marker for astrocytes were reduced in the postnatal day (P) 1.5 pups' brains. Gfap expression and Gfap+ cells were also suppressed in the differentiating neurospheres culture treated with ruxolitinib. Compared to the control group, adult mice treated with ruxolitinib prenatally showed no changes in motor coordination, locomotor function, and recognition memory. However, increased explorative behaviour within an open field and improved spatial learning and long-term memory retention were observed in the treated group. We demonstrated transplacental effects of ruxolitinib on astrogenesis, suggesting the potential use of ruxolitinib to revert pathological conditions caused by gliogenic-shift in early brain development such as Down and Noonan syndromes.
Molecular communication of the membrane insertase YidC with translocase SecYEG affects client proteins
Authors: Steudle Anja , Spann Dirk , Pross Eva , Shanmugam Sri Karthika , Dalbey Ross E. , Kuhn Andreas
Published: February 2021

The membrane insertase YidC inserts newly synthesized proteins by its hydrophobic slide consisting of the two transmembrane (TM) segments TM3 and TM5. Mutations in this part of the protein affect the insertion of the client proteins. We show here that a quintuple mutation, termed YidC-5S, inhibits the insertion of the subunit a of the FoF1 ATP synthase but has no effect on the insertion of the Sec-independent M13 procoat protein and the C-tail protein SciP. Further investigations show that the interaction of YidC-5S with SecY is inhibited. The purified and fluorescently labeled YidC-5S did not approach SecYEG when both were co-reconstituted in proteoliposomes in contrast to the co-reconstituted YidC wild type. These results suggest that TM3 and TM5 are involved in the formation of a common YidC-SecYEG complex that is required for the insertion of Sec/YidC-dependent client proteins.
Structural design principles for specific ultra-high affinity interactions between colicins/pyocins and immunity proteins
Authors: Shushan Avital , Kosloff Mickey
Published: February 2021

The interactions of the antibiotic proteins colicins/pyocins with immunity proteins is a seminal model system for studying protein–protein interactions and specificity. Yet, a precise and quantitative determination of which structural elements and residues determine their binding affinity and specificity is still lacking. Here, we used comparative structure-based energy calculations to map residues that substantially contribute to interactions across native and engineered complexes of colicins/pyocins and immunity proteins. We show that the immunity protein α1–α2 motif is a unique structurally-dissimilar element that restricts interaction specificity towards all colicins/pyocins, in both engineered and native complexes. This motif combines with a diverse and extensive array of electrostatic/polar interactions that enable the exquisite specificity that characterizes these interactions while achieving ultra-high affinity. Surprisingly, the divergence of these contributing colicin residues is reciprocal to residue conservation in immunity proteins. The structurally-dissimilar immunity protein α1–α2 motif is recognized by divergent colicins similarly, while the conserved immunity protein α3 helix interacts with diverse colicin residues. Electrostatics thus plays a key role in setting interaction specificity across all colicins and immunity proteins. Our analysis and resulting residue-level maps illuminate the molecular basis for these protein–protein interactions, with implications for drug development and rational engineering of these interfaces.
Identification of sarcomatoid differentiation in renal cell carcinoma by machine learning on multiparametric MRI
Authors: Mazin Asim , Hawkins Samuel H. , Stringfield Olya , Dhillon Jasreman , Manley Brandon J. , Jeong Daniel K. , Raghunand Natarajan
Published: February 2021

Sarcomatoid differentiation in RCC (sRCC) is associated with a poor prognosis, necessitating more aggressive management than RCC without sarcomatoid components (nsRCC). Since suspected renal cell carcinoma (RCC) tumors are not routinely biopsied for histologic evaluation, there is a clinical need for a non-invasive method to detect sarcomatoid differentiation pre-operatively. We utilized unsupervised self-organizing map (SOM) and supervised Learning Vector Quantizer (LVQ) machine learning to classify RCC tumors on T2-weighted, non-contrast T1-weighted fat-saturated, contrast-enhanced arterial-phase T1-weighted fat-saturated, and contrast-enhanced venous-phase T1-weighted fat-saturated MRI images. The SOM was trained on 8 nsRCC and 8 sRCC tumors, and used to compute Activation Maps for each training, validation (3 nsRCC and 3 sRCC), and test (5 nsRCC and 5 sRCC) tumor. The LVQ classifier was trained and optimized on Activation Maps from the 22 training and validation cohort tumors, and tested on Activation Maps of the 10 unseen test tumors. In this preliminary study, the SOM-LVQ model achieved a hold-out testing accuracy of 70% in the task of identifying sarcomatoid differentiation in RCC on standard multiparameter MRI (mpMRI) images. We have demonstrated a combined SOM-LVQ machine learning approach that is suitable for analysis of limited mpMRI datasets for the task of differential diagnosis.
Extraction of short chain chitooligosaccharides from fungal biomass and their use as promoters of arbuscular mycorrhizal symbiosis
Authors: Crosino Andrea , Moscato Elisa , Blangetti Marco , Carotenuto Gennaro , Spina Federica , Bordignon Simone , Puech-Pagès Virginie , Anfossi Laura , Volpe Veronica , Prandi Cristina , Gobetto Roberto , Varese Giovanna Cristina , Genre Andrea
Published: February 2021

Short chain chitooligosaccharides (COs) are chitin derivative molecules involved in plant-fungus signaling during arbuscular mycorrhizal (AM) interactions. In host plants, COs activate a symbiotic signalling pathway that regulates AM-related gene expression. Furthermore, exogenous CO application was shown to promote AM establishment, with a major interest for agricultural applications of AM fungi as biofertilizers. Currently, the main source of commercial COs is from the shrimp processing industry, but purification costs and environmental concerns limit the convenience of this approach. In an attempt to find a low cost and low impact alternative, this work aimed to isolate, characterize and test the bioactivity of COs from selected strains of phylogenetically distant filamentous fungi: Pleurotus ostreatus, Cunninghamella bertholletiae and Trichoderma viride. Our optimized protocol successfully isolated short chain COs from lyophilized fungal biomass. Fungal COs were more acetylated and displayed a higher biological activity compared to shrimp-derived COs, a feature that—alongside low production costs—opens promising perspectives for the large scale use of COs in agriculture.
Agarose-resolvable InDel markers based on whole genome re-sequencing in cucumber
Authors: Adedze Yawo Mawunyo Nevame , Lu Xia , Xia Yingchun , Sun Qiuyue , Nchongboh Chofong G. , Alam Md. Amirul , Liu Menghua , Yang Xue , Zhang Wenting , Deng Zhijun , Li Wenhu , Si Longting
Published: February 2021

Insertion and Deletion (InDel) are common features in genomes and are associated with genetic variation. The whole-genome re-sequencing data from two parents (X1 and X2) of the elite cucumber (Cucumis sativus) hybrid variety Lvmei No.1 was used for genome-wide InDel polymorphisms analysis. Obtained sequence reads were mapped to the genome reference sequence of Chinese fresh market type inbred line ‘9930’ and gaps conforming to InDel were pinpointed. Further, the level of cross-parents polymorphism among five pairs of cucumber breeding parents and their corresponding hybrid varieties were used for evaluating hybrid seeds purity test efficiency of InDel markers. A panel of 48 cucumber breeding lines was utilized for PCR amplification versatility and phylogenetic analysis of these markers. In total, 10,470 candidate InDel markers were identified for X1 and X2. Among these, 385 markers with more than 30 nucleotide difference were arbitrary chosen. These markers were selected for experimental resolvability through electrophoresis on an Agarose gel. Two hundred and eleven (211) accounting for 54.81% of markers could be validated as single and clear polymorphic pattern while 174 (45.19%) showed unclear or monomorphic genetic bands between X1 and X2. Cross-parents polymorphism evaluation recorded 68 (32.23%) of these markers, which were designated as cross-parents transferable (CPT) InDel markers. Interestingly, the marker InDel114 presented experimental transferability between cucumber and melon. A panel of 48 cucumber breeding lines including parents of Lvmei No. 1 subjected to PCR amplification versatility using CPT InDel markers successfully clustered them into fruit and common cucumber varieties based on phylogenetic analysis. It is worth noting that 16 of these markers were predominately associated to enzymatic activities in cucumber. These agarose-based InDel markers could constitute a valuable resource for hybrid seeds purity testing, germplasm classification and marker-assisted breeding in cucumber.
Molecular detection and whole genome characterization of Canine Parainfluenza type 5 in Thailand
Authors: Charoenkul Kamonpan , Nasamran Chanakarn , Janetanakit Taveesak , Chaiyawong Supassama , Bunpapong Napawan , Boonyapisitsopa Supanat , Tangwangvivat Ratanaporn , Amonsin Alongkorn
Published: February 2021

Parainfluenza virus type 5 (PIV-5) causes respiratory infection in several animal species and humans. Canine parainfluenza virus type 5 (CPIV-5) causes respiratory disease in domestic dogs worldwide. In this study, we conducted a cross-sectional survey of CPIV-5 in dogs with respiratory symptoms from small animal hospitals in Thailand from November 2015 to December 2018. Our results showed that 32 out of 571 nasal swab samples (5.6%) were positive for CPIV-5 by RT-PCR specific to the NP gene. To characterize the viruses, three representative CPIV-5 were subjected to whole genome sequencing, and an additional ten CPIV-5 were subjected to HN, F, SH and V/P gene sequencing. Pairwise sequence comparison and phylogenetic analysis showed that Thai CPIV-5 was closely related to the CPIV-5 isolated from China and Korea. In conclusion, this study constitutes a whole genome characterization of CPIV-5 from dogs in Thailand. The surveillance of CPIV-5 should be further investigated at a larger scale to determine the dynamics, distribution and potential zoonotic transmission of CPIV-5.
A summary of eye-related visits to a tertiary emergency department
Authors: Rai Ravneet S. , Mehta Nitish , Larochelle Ryan , Rathi Siddarth , Schuman Joel S.
Published: February 2021

Timely ophthalmologic consultation is important to ensure patients receive high quality ophthalmologic care in the Emergency Department (ED). Tele-ophthalmology may prove useful in safely and efficiently managing ED eye-related complaints. Prior to implementing such a solution, current consultation patterns must be understood. We aimed to assess case-mix acuity and consultation workflow patterns in the ophthalmology consult service at a tertiary emergency department in New York City. The medical records of patients with eye-related complaints who presented to the ED between January 1, 2015 and December 31, 2015 were reviewed. Visits were retrospectively assigned acuities and the ophthalmologic subspecialty involved in the case was recorded. The number of ophthalmologic consultations ordered and consultant response times were analyzed. Patients who were transferred to the ED for eye-related complaints were included. The ED received 1090 eye-related complaints in this period. 60% were retrospectively assigned low acuity, 27% were assigned medium acuity, and 13% were assigned high acuity. Ophthalmology was consulted on 19% of low, 18% of medium, and 48% of high acuity cases. 44% of complaints involved the anterior segment and 30% involved oculoplastics. 2/3 of transfer patients initially assigned high acuity were downgraded to low acuity upon examination. On average, the consult note was created and signed within 109 and 153 min, respectively, after consult order. ED consults are heavily weighted towards pathology of low-to-medium acuity affecting the anterior segment and ocular adnexa. Currently available tele-ophthalmology technology can potentially address a large volume of eye-related visits.
Social signals mediate oviposition site selection in Drosophila suzukii
Authors: Elsensohn Johanna E. , Aly Marwa F. K. , Schal Coby , Burrack Hannah J.
Published: February 2021

The information that female insects perceive and use during oviposition site selection is complex and varies by species and ecological niche. Even in relatively unexploited niches, females interact directly and indirectly with conspecifics at oviposition sites. These interactions can take the form of host marking and re-assessment of prior oviposition sites during the decision-making process. Considerable research has focused on the niche breadth and host preference of the polyphagous invasive pest Drosophila suzukii Matsumura (Diptera: Drosophilidae), but little information exists on how conspecific signals modulate oviposition behavior. We investigated three layers of social information that female D. suzukii may use in oviposition site selection—(1) pre-existing egg density, (2) pre-existing larval occupation, and (3) host marking by adults. We found that the presence of larvae and host marking, but not egg density, influenced oviposition behavior and that the two factors interacted over time. Adult marking appeared to deter oviposition only in the presence of an unmarked substrate. These results are the first behavioral evidence for a host marking pheromone in a species of Drosophila. These findings may also help elucidate D. suzukii infestation and preference patterns within crop fields and natural areas.
Purification and characterization of bacteriocins-like inhibitory substances from food isolated Enterococcus faecalis OS13 with activity against nosocomial enterococci
Authors: El-Gendy Ahmed O. , Brede Dag A. , Essam Tamer M. , Amin Magdy A. , Ahmed Shaban H. , Holo Helge , Nes Ingolf F. , Shamikh Yara I.
Published: February 2021

Nosocomial infections caused by enterococci are an ongoing global threat. Thus, finding therapeutic agents for the treatment of such infections are crucial. Some Enterococcus faecalis strains are able to produce antimicrobial peptides called bacteriocins. We analyzed 65 E. faecalis isolates from 43 food samples and 22 clinical samples in Egypt for 17 common bacteriocin-encoding genes of Enterococcus spp. These genes were absent in 11 isolates that showed antimicrobial activity putatively due to bacteriocins (three from food, including isolate OS13, and eight from clinical isolates). The food-isolated E. faecalis OS13 produced bacteriocin-like inhibitory substances (BLIS) named enterocin OS13, which comprised two peptides (enterocin OS13α OS13β) that inhibited the growth of antibiotic-resistant nosocomial E. faecalis and E. faecium isolates. The molecular weights of enterocin OS13α and OS13β were determined as 8079 Da and 7859 Da, respectively, and both were heat-labile. Enterocin OS13α was sensitive to proteinase K, while enterocin OS13β was resistant. Characterization of E. faecalis OS13 isolate revealed that it belonged to sequence type 116. It was non-hemolytic, bile salt hydrolase-negative, gelatinase-positive, and sensitive to ampicillin, penicillin, vancomycin, erythromycin, kanamycin, and gentamicin. In conclusion, BLIS as enterocin OS13α and OS13β represent antimicrobial agents with activities against antibiotic-resistant enterococcal isolates.
Dissociating implicit and explicit ensemble representations reveals the limits of visual perception and the richness of behavior
Authors: Hansmann-Roth Sabrina , Kristjánsson Árni , Whitney David , Chetverikov Andrey
Published: February 2021

Our senses provide us with a rich experience of a detailed visual world, yet the empirical results seem to suggest severe limitations on our ability to perceive and remember. In recent attempts to reconcile the contradiction between what is experienced and what can be reported, it has been argued that the visual world is condensed to a set of summary statistics, explaining both the rich experience and the sparse reports. Here, we show that explicit reports of summary statistics underestimate the richness of ensemble perception. Our observers searched for an odd-one-out target among heterogeneous distractors and their representation of distractor characteristics was tested explicitly or implicitly. Observers could explicitly distinguish distractor sets with different mean and variance, but not differently-shaped probability distributions. In contrast, the implicit assessment revealed that the visual system encodes the mean, the variance, and even the shape of feature distributions. Furthermore, explicit measures had common noise sources that distinguished them from implicit measures. This suggests that explicit judgments of stimulus ensembles underestimate the richness of visual representations. We conclude that feature distributions are encoded in rich detail and can guide behavior implicitly, even when the information available for explicit summary judgments is coarse and limited.