bluuebunny/crossref_metadata_2025 huggingface dataset:
Coordination Insertion Mechanism of Ring‐Opening Polymerization of Lactide Catalyzed by Stannous Octoate†
Authors: Rao Weihan , Cai Caiyun , Tang Jingyu , Wei Yiman , Gao Caiyun , Yu Lin , Ding Jiandong
Published: February 2021

Main observation and conclusion

Ring‐opening polymerization (ROP) of cyclic esters in the presence of stannous octoate (Sn(Oct)2) is the main way to obtain biodegradable aliphatic polyesters, an important family of biodegradable polymers which have been widely used and still rapidly developed in the fields of biomedical polymers and environment‐friendly materials. The underlying mechanism is thought via a coordination‐insertion way, but the pathway is still open owing to the absence of direct experimental evidence. Herein, we inquire this issue through density functional theory (DFT) calculations. According to our DFT calculations and the following Curtin‐Hammett evaluation, the carbonyl oxygen has a significant advantage over the ester oxygen, and thus the ring is opened mainly through pathway A instead of pathway B. The stannous octoate is identified as a catalyst rather than an initiator. We eventually summarize the main stages during the whole polymerization of lactide.
The myosin regulatory light chain Myl5 localizes to mitotic spindle poles and is required for proper cell division
Authors: Ramirez Ivan , Gholkar Ankur A. , Velasquez Erick F. , Guo Xiao , Tofig Bobby , Damoiseaux Robert , Torres Jorge Z.
Published: February 2021

Myosins are ATP‐dependent actin‐based molecular motors critical for diverse cellular processes like intracellular trafficking, cell motility, and cell invasion. During cell division, myosin MYO10 is important for proper mitotic spindle assembly, the anchoring of the spindle to the cortex, and positioning of the spindle to the cell mid‐plane. However, myosins are regulated by myosin regulatory light chains (RLCs), and whether RLCs are important for cell division has remained unexplored. Here, we have determined that the previously uncharacterized myosin RLC Myl5 associates with the mitotic spindle and is required for cell division. We show that Myl5 localizes to the leading edge and filopodia during interphase and to mitotic spindle poles and spindle microtubules during early mitosis. Importantly, depletion of Myl5 led to defects in mitotic spindle assembly, chromosome congression, and chromosome segregation and to a slower transition through mitosis. Furthermore, Myl5 bound to MYO10 in vitro and co‐localized with MYO10 at the spindle poles. These results suggest that Myl5 is important for cell division and that it may be performing its function through MYO10.
Photodynamic sensitizers modulate cytoskeleton structural dynamics in neuronal cells
Authors: Dubey Tushar , Chinnathambi Subashchandrabose
Published: February 2021

The neuronal cytoskeleton plays a crucial role in maintaining cell integrity and functioning of neurons. Cytoskeleton deformities have been reported to be associated with neurodegenerative diseases thus; cytoskeleton can be targeted for therapeutic strategies. The therapeutic application of photosensitive molecule is termed as photodynamic therapy (PDT). PDT has been applied in the field of dermatology, cancer biology, and antimicrobial therapy. PDT induces several changes in cells, which include induction of apoptosis, DNA damage, and induction of inflammatory response. PDT has been also reported to modulate cytoskeleton such as actin dynamics. The in vitro studies suggested that PDT using dyes such as Toluidine Blue and Rose Bengal effectively modulated the actin cytoskeleton, neurite outgrowth, tubulin, and Tau aggregation. In this review, we focused on the effect of photosensitized molecules on various cytoskeleton proteins. We hypothesize that PDT could have potency against Alzheimer's disease and other neurodegenerative disorders.
Systematic Review and Patient‐Level Meta‐Analysis of SARS‐CoV‐2 Viral Dynamics to Model Response to Antiviral Therapies
Authors: Gastine Silke , Pang Juanita , Boshier Florencia A.T. , Carter Simon J. , Lonsdale Dagan O. , Cortina‐Borja Mario , Hung Ivan F.N. , Breuer Judy , Kloprogge Frank , Standing Joseph F.
Published: February 2021

Severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) viral loads change rapidly following symptom onset, so to assess antivirals it is important to understand the natural history and patient factors influencing this. We undertook an individual patient‐level meta‐analysis of SARS‐CoV‐2 viral dynamics in humans to describe viral dynamics and estimate the effects of antivirals used to date. This systematic review identified case reports, case series, and clinical trial data from publications between January 1, 2020, and May 31, 2020, following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. A multivariable Cox proportional hazards (Cox‐PH) regression model of time to viral clearance was fitted to respiratory and stool samples. A simplified four parameter nonlinear mixed‐effects (NLME) model was fitted to viral load trajectories in all sampling sites and covariate modeling of respiratory viral dynamics was performed to quantify time‐dependent drug effects. Patient‐level data from 645 individuals (age 1 month to 100 years) with 6,316 viral loads were extracted. Model‐based simulations of viral load trajectories in samples from the upper and lower respiratory tract, stool, blood, urine, ocular secretions, and breast milk were generated. Cox‐PH modeling showed longer time to viral clearance in older patients, men, and those with more severe disease. Remdesivir was associated with faster viral clearance (adjusted hazard ratio (AHR) = 9.19, P < 0.001), as well as interferon, particularly when combined with ribavirin (AHR = 2.2, P = 0.015; AHR = 6.04, P = 0.006). Combination therapy should be further investigated. A viral dynamic dataset and NLME model for designing and analyzing antiviral trials has been established.
Therapeutic nanostructures and nanotoxicity
Authors: Sarma Anupam , Bania Ratnali , Devi Juti Rani , Deka Satyendra
Published: February 2021

Nanotechnology, with its continuous advancement, leads to the development of nanoscale‐level therapeutics to mitigate many complex diseases. This results in the emergence of numerous novel nanomaterials and its composite products into the market such as liposome, polymeric nanoparticles, dendrimers, and nanostructured lipid carrier. However, their application is always determined by a high benefit to risk ratio. Very few research have been done on the toxicity assessment of nanoparticles in the biological system; therefore, the limited knowledge regarding the toxicity profile of nanotherapeutics is available leading to the ignorance of its side effects. Nanoparticles can distribute in the whole body through translocating in the bloodstream by crossing membrane barriers efficiently and shows effect in organs and tissues at cellular and molecular levels. The interaction of nanoparticle with cell may consequences into nanotoxicity. The narrow size distribution, large surface area to mass ratio and surface properties of nanoparticle are significantly associated with nanotoxicity. Nanoparticles can enter into the tissue and cell by invading the membranes and cause cellular injury as well as toxicity. Therefore, the exploration of mechanisms of nanotoxicity has prime importance now a day. The toxicity assessment should be an integral part of the development of nanotherapeutics using various toxicity evaluation models. This review has focused on the exploration of different nanostructures for therapeutic delivery system along with its physicochemical characteristics responsible for adverse effects on human biology, various toxicity evaluation models, and environmental and regulatory hurdles.
Distinct Immune Imprints of Post–Liver Transplantation Hepatitis C Persist Despite Viral Clearance
Authors: Aregay Amare , Engel Bastian , Port Kerstin , Vondran Florian W.R. , Bremer Birgit , Niehaus Christian , Khera Tanvi , Richter Nicolas , Jaeckel Elmar , Cornberg Markus , Taubert Richard , Wedemeyer Heiner
Published: February 2021

Recurrence or de novo infection of hepatitis C virus (HCV) after liver transplantation (LT) has been associated with progressive graft hepatitis that can be improved by treatment with novel direct‐acting antivirals. Cases of rejection episodes have been described during and after HCV treatment. The evolution of innate and adaptive immune response during and after cure of HCV LT is unknown. We studied 74 protein biomarkers in the plasma of LT patients receiving antiviral therapy. In addition, deep immune phenotyping of both the myeloid and lymphoid immune cell subsets in peripheral blood mononuclear cells was performed. We found that LT patients with active HCV infection displayed distinct alterations of inflammatory protein biomarkers, such as C‐X‐Cmotif chemokine 10 (CXCL10), caspase 8, C‐C motif chemokine 20 (CCL20), CCL19, interferon γ, CUB domain‐containing protein 1 (CDCP1), interleukin (IL)‐18R1, CXCL11, CCL3, IL8, IL12B, tumor necrosis factor‐beta, CXCL6, osteoprotegerin, IL10, fms‐related tyrosine kinase 3 ligand, hepatocyte growth factor, urokinase‐type plasminogen activator, neurotrophin‐3, CCL4, IL6, tumornecrosis factor receptor superfamily member 9, programmed death ligand 1, IL18, and monocyte chemotactic protein 1, and enrichment of peripheral immune cell subsets unlike patients without HCV infection who received transplants. Interestingly, patients who cleared HCV after LT did not normalize the altered inflammatory milieu nor did the peripheral immune cell subsets normalize to what would be seen in the absence of HCV recurrence. Overall, these data indicate that HCV‐specific imprints on inflammatory analytes and immune cell subsets after LT are not completely normalized by therapy‐induced HCV elimination. This is in line with the clinical observation that cure of HCV after LT did not trigger rejection episodes in many patients.
Renal Outcomes After Simultaneous Liver‐Kidney Transplantation: Results from the US Multicenter Simultaneous Liver‐Kidney Transplantation Consortium
Authors: Sharma Pratima , Sui Zhiyu , Zhang Min , Magee John C. , Barman Pranab , Patel Yuval , Schluger Aaron , Walter Kara , Biggins Scott W. , Cullaro Giuseppe , Wong Randi , Lai Jennifer C. , Jo Jennifer , Sinha Jasmine , VanWagner Lisa , Verna Elizabeth C.
Published: February 2021

Simultaneous liver‐kidney transplantation (SLKT) is increasingly common in the United States. However, little is known about the renal‐related outcomes following SLKT, which are essential to maximize the health of these allografts. We examined the factors impacting renal function following SLKT. This is an observational multicenter cohort study from the US Multicenter SLKT Consortium consisting of recipients of SLKT aged ≥18 years of transplantations performed between February 2002 and June 2017 at 6 large US centers in 6 different United Network for Organ Sharing regions. The primary outcome was incident post‐SLKT stage 4‐5 chronic kidney disease (CKD) defined as <30 mL/minute/1.73 m2 or listing for kidney transplant. The median age of the recipients (n = 570) was 58 years (interquartile range, 51‐64 years), and 37% were women, 76% were White, 33% had hepatitis C virus infection, 20% had nonalcoholic steatohepatitis (NASH), and 23% had alcohol‐related liver disease; 68% developed ≥ stage 3 CKD at the end of follow‐up. The 1‐year, 3‐year, and 5‐year incidence rates of post‐SLKT stage 4‐5 CKD were 10%, 12%, and 16%, respectively. Pre‐SLKT diabetes mellitus (hazard ratio [HR], 1.45; 95% CI, 1.00‐2.15), NASH (HR, 1.58; 95% CI, 1.01‐2.45), and delayed kidney graft function (HR, 1.72; 95% CI, 1.10‐2.71) were the recipient factors independently associated with high risk, whereas the use of tacrolimus (HR, 0.44; 95% CI, 0.22‐0.89) reduced the risk. Women (β = −6.22 ± 2.16 mL/minute/1.73 m2; P = 0.004), NASH (β = −7.27 ± 3.27 mL/minute/1.73 m2; P = 0.027), and delayed kidney graft function (β = −7.25 ± 2.26 mL/minute/1.73 m2; P = 0.007) were independently associated with low estimated glomerular filtration rate at last follow‐up. Stage 4‐5 CKD is common after SLKT. There remains an unmet need for personalized renal protective strategies, specifically stratified by sex, diabetes mellitus, and liver disease, to preserve renal function among SLKT recipients.
Nutritive Manganese and Zinc Overdosing in Aging C. elegans Result in a Metallothionein‐Mediated Alteration in Metal Homeostasis
Authors: Baesler Jessica , Michaelis Vivien , Stiboller Michael , Haase Hajo , Aschner Michael , Schwerdtle Tanja , Sturzenbaum Stephen R. , Bornhorst Julia
Published: February 2021

Scope

Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn‐Zn‐interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age‐dependent neurodegeneration.

Methods and Results

Chronic co‐exposure of C. elegans to Mn and Zn increases metal uptake, exceeding levels of single metal exposures. Supplementation with Mn and/or Zn also leads to an age‐dependent increase in metal content, a decline in overall mRNA expression, and metal co‐supplementation induced expression of target genes involved in Mn and Zn homeostasis, in particular metallothionein 1 (mtl‐1). Studies in transgenic worms reveal that mtl‐1 played a prominent role in mediating age‐ and diet‐dependent alterations in metal homeostasis. Metal dyshomeostasis is further induced in parkin‐deficient nematodes (Parkinson's disease (PD) model), but this did not accelerate the age‐dependent dopaminergic neurodegeneration.

Conclusions

A nutritive overdose of Mn and Zn can alter interactions between essential metals in an aging organism, and metallothionein 1 acts as a potential protective modulator in regulating homeostasis.
Membrane‐dependent amyloid aggregation of human BAX α9 (173–192)
Authors: Price David A. , Hill Tayler D. , Hutson Kaitlyn A. , Rightnowar Blaze W. , Moran Sean D.
Published: February 2021

Mitochondrial outer membrane permeabilization, which is a critical step in apoptosis, is initiated upon transmembrane insertion of the C‐terminal α‐helix (α9) of the proapoptotic Bcl‐2 family protein BAX. The isolated α9 fragment (residues 173–192) is also competent to disrupt model membranes, and the structures of its membrane‐associated oligomers are of interest in understanding the potential roles of this sequence in apoptosis. Here, we used ultrafast two‐dimensional infrared (2D IR) spectroscopy, thioflavin T binding, and transmission electron microscopy to show that the synthetic BAX α9 peptide (α9p) forms amyloid aggregates in aqueous environments and on the surfaces of anionic small unilamellar vesicles. Its inherent amyloidogenicity was predicted by sequence analysis, and 2D IR spectra reveal that vesicles modulate the β‐sheet structures of insoluble aggregates, motivating further examination of the formation or suppression of BAX amyloids in apoptosis.
Cardiolipin interacts with beta‐2‐glycoprotein I and forms an open conformation–Mechanisms analyzed using hydrogen/deuterium exchange
Authors: Tang Kuo‐Tung , Wu Ting‐Yuan , Chen Hsin‐Hua , Lin Chi‐Chien , Hsu Yuan‐Hao Howard
Published: February 2021

Beta‐2‐glycoprotein I (β2GPI) is the major antigen for the antiphospholipid antibodies in the antiphospholipid syndrome. The exposed epitope in domain I of β2GPI can be recognized by the anti‐β2GPI antibody. Here, we prepared the anionic di‐oleoyl‐phosphatidylserine (DOPS) and cardiolipin (CL) liposomes to interact with the β2GPI. The conformational changes of β2GPI upon binding with the liposomes were analyzed using hydrogen/deuterium exchange mass spectrometry. The exchange level of sequences 21–27 significantly increased after β2GPI had interacted with DOPS. This change indicated a reduced interaction between domain I and domain V, inferring to a protrusion of the sequences 21–27 from the ring conformation. After β2GPI had interacted with CL for 30 min, the exchange levels in 4 of the 5 domains increased significantly. The deuteration levels of sequences 1–20, 21–27, 196–205, 273–279 and 297–306 increased, suggesting that these regions had become more exposed, and the domain I was no longer in contact with domain V. The increasing deuteration levels in sequences 70–86, 153–162, 191–198, 196–205 and 273–279 indicated β2GPI undergoing conformational changes to expose these inner regions, suggesting a structural transition. Overall, DOPS and CL induced minor conformational changes of β2GPI at sequences 21–27 and forms an intermediate conformation after 10 min of interaction. After a complete protein–lipid interaction, high negatively charged CL membrane induced a major conformation transition of β2GPI.
Non-uniform Expansions of Real Numbers
Authors: Neunhäuserer Jörg
Published: February 2021

We introduce and study non-uniform expansions of real numbers, given by two non-integer bases.
Studies of transmembrane peptides by pulse dipolar spectroscopy with semi-rigid TOPP spin labels
Authors: Tkach Igor , Diederichsen Ulf , Bennati Marina
Published: February 2021

Electron paramagnetic resonance (EPR)-based pulsed dipolar spectroscopy measures the dipolar interaction between paramagnetic centers that are separated by distances in the range of about 1.5–10 nm. Its application to transmembrane (TM) peptides in combination with modern spin labelling techniques provides a valuable tool to study peptide-to-lipid interactions at a molecular level, which permits access to key parameters characterizing the structural adaptation of model peptides incorporated in natural membranes. In this mini-review, we summarize our approach for distance and orientation measurements in lipid environment using novel semi-rigid TOPP [4-(3,3,5,5-tetramethyl-2,6-dioxo-4-oxylpiperazin-1-yl)-L-phenylglycine] labels specifically designed for incorporation in TM peptides. TOPP labels can report single peak distance distributions with sub-angstrom resolution, thus offering new capabilities for a variety of TM peptide investigations, such as monitoring of various helix conformations or measuring of tilt angles in membranes.

Graphical Abstract
Laser-impact-induced splashing: an analysis of the splash crown evolution after Nd:YAG ns-pulse laser impact on a liquid tin pool
Authors: Hermens J. , Gelderblom H. , Liu B. , Duffhues J. , Rindt P. , Versolato O. O.
Published: February 2021

The splash created by intense laser pulse impact onto a liquid tin layer is studied experimentally using time-delayed stroboscopic shadowgraphy. An 8-ns infrared (1064 nm) laser pulse is focused onto a deep liquid tin pool. Various laser spot sizes (70, 120, and 130 $$\upmu$$
μ
m in diameter) and various laser pulse energies (ranging 2.5–30 mJ) are used, resulting in laser fluences of $$\sim$$
∼
 10–1000 J/cm$$^2$$

2

inducing pronounced splashing. Specifically, we study the time evolution of the splash crown-width. The crown width expansion velocity is found to be linearly dependent on the laser energy, and independent of the focal spot size. A collapse of all crown width evolution data onto a single master curve confirms that the hydrodynamic evolution of our laser-impact-induced splash is equivalent to droplet-impact-induced splashing. Laser-impact splashing is particularly relevant, e.g. for high-brightness laser-assisted discharge-produced plasma and laser-produced plasma sources of extreme ultraviolet light for nanolithography.
Efficacy and Safety of Intravenous rtPA in Ischemic Strokes Due to Small-Vessel Occlusion: Systematic Review and Meta-Analysis
Authors: Karaszewski Bartosz , Wyszomirski Adam , Jabłoński Bartosz , Werring David J. , Tomaka Dominika
Published: February 2021

Intravenous recombinant tissue plasminogen activator (iv-rtPA) has been routinely used to treat ischemic stroke for 25 years, following large clinical trials. However, there are few prospective studies on the efficacy and safety of this therapy in strokes attributed to cerebral small vessel disease (SVD). We evaluated functional outcome (modified Rankin scale, mRS) and symptomatic intracerebral hemorrhage (sICH) using all available data on the effects of iv-rtPA in SVD-related ischemic stroke (defined either using neuroimaging, clinical features, or both). Using fixed-effect and random-effects models, we calculated the pooled effect estimates with regard to excellent and favorable outcomes (mRS=0–1 and 0–2 respectively, at 3 months), and the rate of sICH. Twenty-three studies fulfilled the eligibility criteria, 11 of which were comparative, and there were only 3 randomized clinical trials. In adjusted analyses, there was an increased odds of excellent outcome (adjusted OR=1.53, 95% CI: 1.29–1.82, I2: 0%) or favorable outcome (adjusted OR=1.68, 95% CI: 1.31–2.15,I2: 0%) in patients who received iv-rtPA compared with placebo. Across the six studies which reported it, the incidence of sICH was higher in the treatment group (M-H RR = 8.83, 95% CI: 2.76–28.27). The pooled rate of sICH in patients with SVD administered iv-rtPA was only 0.72% (95% CI: 0.12%–1.64%). We conclude that when ischemic stroke attributed to SVD is considered separately, available data on the effects of iv-rtPA therapy are insufficient for the highest level of recommendation, but it seems to be safe. Although further therapeutic trials in SVD-related ischemic stroke appear to be justified, our findings should not prevent its continued use for this group of patients in clinical practice.
Bench-scale assessment of three copper-based algaecide products for cyanobacteria management in source water
Authors: Crafton Elizabeth , Glowczewski Jessica , Cutright Teresa , Ott Don
Published: February 2021

Three copper-based algaecide products were investigated for use in a drinking water source to address cyanobacteria growth. Bench-scale experiments were used to determine the optimal dose of each product given Lake Rockwell’s indigenous population and reservoir-specific characteristics. The optimal dose of Cutrine Ultra was determined to be a quarter dose (corresponding to 0.125 mg/L Cu) as it decreased 55% of the cyanobacteria population with limited release of microcystin and minimal rebound in the cyanobacteria population. The optimal dose for EarthTec was determined to be a half dose (i.e., 0.5 mg/L). The full dose was optimal for SeClear (1 mg/L Cu). The optimal doses had extracellular microcystin levels of 0.99 ± 0.09 µg/L (quarter dose Cutrine Ultra), 3.69 ± 0.43 µg/L (half dose EarthTec) and 0.92 ± 0.26 µg/L (full dose SeClear) by day 2. EarthTec and Cutrine Ultra facilitated a similar overall response, and the cyanobacteria population was predominately suppressed in the initial 2 days following treatment and then increased between 7 and 14 days after treatment (i.e., rebound). Both the suppression within the first 2 days and the rebound between 7 and 14 days after treatment were a function of dose (e.g., lower dose, larger increase in rebound). Although SeClear suppressed the cyanobacteria population during the initial 2 days after treatment (42,000 ± 3240 cells/mL at the baseline to 4822 ± 841), the cyanobacteria population rebounded significantly (p < 0.05) between 2 and 7 days after treatment.
TRIM41 is required to innate antiviral response by polyubiquitinating BCL10 and recruiting NEMO
Authors: Yu Zhou , Li Xuelian , Yang Mingjin , Huang Jiaying , Fang Qian , Jia Jianjun , Li Zheng , Gu Yan , Chen Taoyong , Cao Xuetao
Published: February 2021

Sensing of pathogenic nucleic acids by pattern recognition receptors (PRR) not only initiates anti-microbe defense but causes inflammatory and autoimmune diseases. E3 ubiquitin ligase(s) critical in innate response need to be further identified. Here we report that the tripartite motif-containing E3 ubiquitin ligase TRIM41 is required to innate antiviral response through facilitating pathogenic nucleic acids-triggered signaling pathway. TRIM41 deficiency impairs the production of inflammatory cytokines and type I interferons in macrophages after transfection with nucleic acid-mimics and infection with both DNA and RNA viruses. In vivo, TRIM41 deficiency leads to impaired innate response against viruses. Mechanistically, TRIM41 directly interacts with BCL10 (B cell lymphoma 10), a core component of CARD proteins−BCL10 − MALT1 (CBM) complex, and modifies the Lys63-linked polyubiquitylation of BCL10, which, in turn, hubs NEMO for activation of NF-κB and TANK-binding kinase 1 (TBK1) − interferon regulatory factor 3 (IRF3) pathways. Our study suggests that TRIM41 is the potential universal E3 ubiquitin ligase responsible for Lys63 linkage of BCL10 during innate antiviral response, adding new insight into the molecular mechanism for the control of innate antiviral response.
Surgical Treatment of Middle Cerebral Artery Aneurysms: Hints and Precautions for Young Cerebrovascular Surgeons
Authors: Sturiale Carmelo Lucio , Rapisarda Alessandro , Marchese Enrico , Puca Alfredo , Olivi Alessandro , Albanese Alessio
Published: February 2021

Background and Objective Clipping is still considered the treatment of choice for middle cerebral artery (MCA) aneurysms due to their angioarchitectural characteristics as they are often bifurcation dysplasias, needing a complex reconstruction rather than a simple exclusion. Thus, maintaining this surgical expertise is of paramount importance to train of young cerebrovascular surgeons. To balance for the increasingly limited experience due the worldwide general inclination toward the endovascular approaches, it is important to provide to the young neurosurgeons rules and operative nuances to guide this complex surgery. We describe the technical algorithm we use to teach our residents to approach ruptured and unruptured MCA aneurysms, which may help to develop a procedural memory useful to perform an effective and safe surgery.

Materials and Methods We reviewed our last 10 years' institutional experience of about 400 cases of ruptured and unruptured MCA aneurysms clipping, analyzing our technical refinements and the difficulties in residents and young neurosurgeons teaching, to establish fundamental key-points and design a didactic algorithm that includes operative instructions and safety rules.

Results We recognized seven pragmatic technical key points regarding craniotomy, sylvian fissure opening, basal cisternostomy, proximal vessel control, lenticulostriate arteries preservation, aneurysm neck microdissection, and clipping to use as a didactic algorithm for teaching residents, and as operative instructions for inexperienced neurosurgeons.

Conclusion In the setting of clipping MCA aneurysms, respect for surgical rules is of paramount importance to perform an effective and safe procedure, ensure the best aneurysm exclusion, and preserve the flow in collaterals and perforators.
Novel Use of Intraoperative Fluoroscopy in an Era of ICG for Complex Laparoscopic Cholecystectomy
Authors: Gandhi Jignesh A. , Shinde Pravin H. , Chaudhari Sadashiv N. , Banker Amay M.
Published: February 2021

Background Laparoscopic cholecystectomy (LC) is increasingly being used as a first-line treatment for acute cholecystitis. Bile duct injury (BDI) remains the most feared complication of the minimally invasive approach specially in cases with an inflamed calots triangle. While use of indocyanine dye (ICG) to delineate biliary anatomy serves to reduce BDI, the high cost of the technology prohibits its use in the developing world. We propose a novel use of common bile duct (CBD) stenting preoperatively in cases of cholecystitis secondary to choledocholithiasis as a means of identification and safeguarding the CBD.

Methods A retrospective review was conducted on 22 patients of Grade 2 or Grade 3 cholecystitis who underwent an early LC at our institution. All patients were stented preoperatively and the stent was used for a much-needed tactile feedback during dissection. A c-arm with intraoperative fluoroscopy was used to identify the CBD prior to clipping of the cystic duct.

Results The gall bladder was gangrenous in all the cases while two cases had evidence of end organ damage. This innovative use of CBD stenting allowed us to correctly delineate biliary anatomy in all of the cases and we report no instances of BDI despite a severely inflamed local environment.

Conclusion This technique can become a standard of care in all teaching institutions in developing countries further enhancing the safety of cholecystectomy in gangrenous cholecystitis with a distorted biliary anatomy.
Geometric differences between the crania of Australian hopping mice (
Authors: Alhajeri Bader H.
Published: February 2021

Half of the ten Australian hopping mice (Notomys) species have become extinct following the European colonisation of Australia, and most of the rest are threatened. This makes the study of their present diversity paramount. Although recent molecular phylogenies improved our understanding of the relationships among the species, detailed interspecific phenotypic comparisons are still lacking. This is the aim of the present study. Geometric morphometric methods were used to compare the crania of all five extant species (N. alexis, N. aquillo, N. cervinus, N. fuscus, and N. mitchellii) along with the extinct N. longicaudatus. Although previous work (based on traditional approaches) find intragenerically conserved crania, the present study discovers significant differences in cranial size and shape among Notomys species, with the ventral view being more distinct than the dorsal view. There was no evidence of sexual dimorphism in cranial size nor shape, and only a weak allometric effect. Most aspects of cranial shape differed among the species. The extant species pair that differed in cranial shape the most was N. aquilo – N. cervinus, differing in the foramen magnum, tympanic bulla, orbit, incisive foramen, and rostrum, along with cranial width, potentially a consequence of N. cervinus’ phylogenetic position, and N. aquilo’s s ecological uniqueness.
High-temperature resistant polypropylene films enhanced by atomic layer deposition
Authors: Wu Xudong , Tang Shaokai , Song Guanghui , Zhang Zihan , Tan Daniel Q
Published: February 2021

Last two decades has witnessed various technical programs towards the development of new dielectric films for high temperature and high energy density capacitor technology. Yet, the organic polypropylene film still holds its top position for film capacitors required for electric and electronic power applications such as power grid, hybrid electric vehicles, oil and gas exploration, and aviation. However, its low temperature stability determined by its structural nature limits its further adoption for more rising markets. This work thus developed a creative method (ultrathin coating of inorganic compound using atomic layer deposition) to increase the high temperature stability and the dielectric strength of such a strategically important polymer film from below 105 °C to above 140 °C. Several techniques also confirmed the effective minimization of the dimensional change and crystallinity loss at higher temperatures, i.e., Thermomechanical analysis, Dynamic mechanical analysis, Dynamic Scanning calorimetry, x-ray diffraction and electron microscopy techniques. This breakthrough discovery adds a huge value to the commercial PP films and relevant capacitor industry and will extend the operation of high-performance PP film capacitors to various high standard applications.
A survey on computational models for predicting protein–protein interactions
Authors: Hu Lun , Wang Xiaojuan , Huang Yu-An , Hu Pengwei , You Zhu-Hong
Published: February 2021

Proteins interact with each other to play critical roles in many biological processes in cells. Although promising, laboratory experiments usually suffer from the disadvantages of being time-consuming and labor-intensive. The results obtained are often not robust and considerably uncertain. Due recently to advances in high-throughput technologies, a large amount of proteomics data has been collected and this presents a significant opportunity and also a challenge to develop computational models to predict protein–protein interactions (PPIs) based on these data. In this paper, we present a comprehensive survey of the recent efforts that have been made towards the development of effective computational models for PPI prediction. The survey introduces the algorithms that can be used to learn computational models for predicting PPIs, and it classifies these models into different categories. To understand their relative merits, the paper discusses different validation schemes and metrics to evaluate the prediction performance. Biological databases that are commonly used in different experiments for performance comparison are also described and their use in a series of extensive experiments to compare different prediction models are discussed. Finally, we present some open issues in PPI prediction for future work. We explain how the performance of PPI prediction can be improved if these issues are effectively tackled.
NIBNA: a network-based node importance approach for identifying breast cancer drivers
Authors: Chaudhary Mandar S. , Pham Vu V.H. , Le Thuc D.
Published: February 2021

Motivation

Identifying meaningful cancer driver genes in a cohort of tumors is a challenging task in cancer genomics. Although existing studies have identified known cancer drivers, most of them focus on detecting coding drivers with mutations. It is acknowledged that non-coding drivers can regulate driver mutations to promote cancer growth. In this work, we propose a novel node importance-based network analysis (NIBNA) framework to detect coding and non-coding cancer drivers. We hypothesize that cancer drivers are crucial to the formation of community structures in cancer network, and removing them from the network greatly perturbs the network structure thereby critically affecting the functioning of the network. NIBNA detects cancer drivers using a three-step process: first, a condition-specific network is built by incorporating gene expression data and gene networks; second, the community structures in the network are estimated; and third, a centrality-based metric is applied to compute node importance.

Results

We apply NIBNA to the BRCA dataset, and it outperforms existing state-of-art methods in detecting coding cancer drivers. NIBNA also predicts 265 miRNA drivers, and majority of these drivers have been validated in literature. Further we apply NIBNA to detect cancer subtype-specific drivers, and several predicted drivers have been validated to be associated with cancer subtypes. Lastly, we evaluate NIBNA’s performance in detecting epithelial–mesenchymal transition drivers, and we confirmed 8 coding and 13 miRNA drivers in the list of known genes.

Availability and implementation

The source code can be accessed at https://github.com/mandarsc/NIBNA.

Supplementary information

Supplementary data are available at Bioinformatics online.
Monitoring of Chemical Markers in Extraction of Traditional Medicinal Plants (Piper nigrum, Curcuma longa) Using In Situ ReactIR
Authors: Sateesh Reddy K , Siva Bandi , Divya Reddy S , Kumar K , Pratap T V , Vidyasagar Reddy Konda , Venkateswara Rao B , Suresh Babu K
Published: February 2021

Background

The fingerprinting and quantification of marker compounds from medicinal plants is a domain of the herbal industry for quality/quantity control parameters.

Objective

The main objective of this study is the application of the in situ ReactIR technique for measuring the concentration of different components during the extraction process of different medicinal plants.

Method

In this study we have performed the extraction of two-marker compounds, viz. piperine from Piper nigrum and curcumin from Curcuma longa plants, using various solvents (dichloromethane and methanol). The progress of extraction was monitored using an in situ Fourier transform infrared (FTIR) probe instrument and an automated reactor.

Results

In this communication, using the in situ ReactIR technique we developed a method which demonstrates the relative quantification of marker analytes, optimizes extraction time and type of solvents to be used for different analytes during the extraction process.

Conclusions

To the best of our knowledge, this is the first report of relative quantification and structural information of marker compounds during the process of extraction using in situ FTIR.

Highlights

The present study highlights the real-time monitoring, in situ quantification, and structural information of marker compounds during the process of extraction of medicinal plants using in situ FTIR.
Structured water: effects on animals
Authors: Lindinger Michael I
Published: February 2021

This review focuses on the effects of structured water (SW) on animals when it is consumed on a daily basis. SW is liquid water that is given altered H-bonding structure by treatment with various forms of energy including magnetic fields and light. While most of the research has been conducted on ‘magnetized’ water, which has structure of short duration, recent research has examined effects of a SW with stability of at least 3.5 mo. A variety of laboratory and farm animals have been studied over the past 20 yr. Consistent (3 or more studies) responses among animals consuming SW for 1 mo or more include increased rate of growth, reduced markers of oxidative stress, improved glycemic and insulinemic responses in diabetics, improved blood lipid profile, improved semen and spermatozoa quality, and increased tissue conductivity as measured using bioelectrical impedance analysis. While it is known that fluids in and around cells and molecules are structured, it remains unknown if this endogenous water structuring is influenced by drinking SWs. The mechanisms by which SW affects biological systems are unknown and require investigation. Effects of SW, when taken up by biological systems, are likely associated with altered water structuring around biological surfaces, such as proteins and membranes.
Weaning causes a prolonged but transient change in immune gene expression in the intestine of piglets
Authors: de Groot Nienke , Fariñas Fernando , Cabrera-Gómez Carolina G , Pallares Francisco J , Ramis Guillermo
Published: February 2021

Controlling gut inflammation is important in managing gut disorders in the piglet after weaning. Establishing patterns of inflammation markers in the time subsequent to weaning is important for future research to determine whether interventions are effective in controlling gut inflammation. The objective of this study was to evaluate the intestinal inflammatory response during the postweaning period in piglets. A 45-d study included 108 piglets (weaned at 22 d, body weight 5.53 ± 1.19 kg), distributed in 12 pens with nine pigs per pen. Histomorphometry, gene expression of pro- and anti-inflammatory cytokines, and the quantity of immunoglobulin (Ig) A producing cells were measured in jejunum, ileum, and colon on days 0, 15, 30, and 45 postweaning. Cytokine gene expression in peripheral blood mononuclear cells and Ig quantities were analyzed in blood from piglets on days 0, 15, 30, and 45 postweaning. Histomorphometrical results showed a lower villus length directly after weaning. Results demonstrated a postweaning intestinal inflammation response for at least 15 d postweaning by upregulation of IgA producing cells and IFN-γ, IL-1α, IL-8, IL-10, IL-12α, and TGF-β in jejunum, ileum, and colon. IgM and IgA were upregulated at day 30 postweaning. IgG was downregulated at day 15 postweaning. The results indicate that weaning in piglets is associated with a prolonged and transient response in gene expression of pro- and anti-inﬂammatory cytokines and IgA producing cells in the intestine.
Limited Evidence for Parallel Evolution Among Desert-AdaptedPeromyscusDeer Mice
Authors: Colella Jocelyn P , Tigano Anna , Dudchenko Olga , Omer Arina D , Khan Ruqayya , Bochkov Ivan D , Aiden Erez L , MacManes Matthew D
Published: February 2021

Warming climate and increasing desertification urge the identification of genes involved in heat and dehydration tolerance to better inform and target biodiversity conservation efforts. Comparisons among extant desert-adapted species can highlight parallel or convergent patterns of genome evolution through the identification of shared signatures of selection. We generate a chromosome-level genome assembly for the canyon mouse (Peromyscus crinitus) and test for a signature of parallel evolution by comparing signatures of selective sweeps across population-level genomic resequencing data from another congeneric desert specialist (Peromyscus eremicus) and a widely distributed habitat generalist (Peromyscus maniculatus), that may be locally adapted to arid conditions. We identify few shared candidate loci involved in desert adaptation and do not find support for a shared pattern of parallel evolution. Instead, we hypothesize divergent molecular mechanisms of desert adaptation among deer mice, potentially tied to species-specific historical demography, which may limit or enhance adaptation. We identify a number of candidate loci experiencing selective sweeps in the P. crinitus genome that are implicated in osmoregulation (Trypsin, Prostasin) and metabolic tuning (Kallikrein, eIF2-alpha kinase GCN2, APPL1/2), which may be important for accommodating hot and dry environmental conditions.
Influence of Holocene habitat availability on Pacific gray whale (Eschrichtius robustus) population dynamics as inferred from whole mitochondrial genome sequences and environmental niche modeling
Authors: Brüniche-Olsen Anna , Bickham John W , Godard-Codding Celine A , Brykov Vladimir A , Kellner Kenneth F , Urban Jorge , DeWoody J Andrew
Published: February 2021

Environmental changes since the Pleistocene and commercial whaling in the last few centuries have drastically reduced many whale populations, including gray whales in the North Pacific. Herein we use complete mitogenome sequences from 74 individuals to evaluate gray whale phylogeography and historical demography, then use environmental niche modeling to assess how habitat availability has changed through time for Pacific gray whales. We identify a large degree of haplotype sharing between gray whales sampled in Russian and Mexican waters, coupled with very limited matrilineal population structure. Confirming previous studies, our environmental niche models showed a decrease in available habitat during the Last Glacial Maximum, but we find no genetic signals of recent population declines in mitochondrial genomes despite both sustained habitat loss and a commercial whaling bottleneck. Our results illustrate the complex dynamics of baleen whale biogeography since the Holocene as well as the difficulty in detecting recent demographic bottlenecks from mitochondrial DNA sequences.
Associations of sleep phenotypes with severe intentional self-harm: a prospective analysis of the UK Biobank cohort
Authors: Lei Binbin , Zhang Jihui , Chen Sijing , Chen Jie , Yang Lulu , Ai Sizhi , Chan Ngan Yin , Wang Jing , Dai Xi-jian , Feng Hongliang , Liu Yaping , Li Shirley Xin , Jia Fujun , Wing Yun-Kwok
Published: February 2021

Study objectives

We aimed to investigate the prospective associations of sleep phenotypes with severe intentional self-harm (ISH) in middle-aged and older adults.

Methods

A total of 499,159 participants (mean age: 56.55 ± 8.09 years; female: 54.4%) were recruited from the UK Biobank between 2006 and 2010 with follow-up until February 2016 in this population-based prospective study. Severe ISH was based on hospital inpatient records or a death cause of ICD-10 codes X60-X84. Patients with hospitalized diagnosis of severe ISH before the initial assessment were excluded. Sleep phenotypes, including sleep duration, chronotype, insomnia, sleepiness, and napping, were assessed at the initial assessments. Cox regression analysis was used to estimate temporal associations between sleep phenotypes and future risk of severe ISH.

Results

During a follow-up period of 7.04 years (SD: 0.88), 1,219 participants experienced the first hospitalization or death related to severe ISH. After adjusting for demographics, substance use, medical diseases, mental disorders, and other sleep phenotypes, short sleep duration (HR: 1.50, 95% CI: 1.23–1.83, p < .001), long sleep duration (HR: 1.56, 95% CI: 1.15–2.12, p = .004), and insomnia (usually: HR: 1.57, 95% CI: 1.31–1.89, p < .001) were significantly associated with severe ISH. Sensitivity analyses excluding participants with mental disorders preceding severe ISH yielded similar results.

Conclusion

The current study provides the empirical evidence of the independent prediction of sleep phenotypes, mainly insomnia, short- and long-sleep duration, for the future risk of severe ISH among middle-aged and older adults.
A statewide analysis of SARS-CoV-2 transmission in New York
Authors: Lasek-Nesselquist Erica , Singh Navjot , Russell Alexis , Lamson Daryl , Kelly John , Plitnick Jonathan , Pfeiffer Ryan D. , Tucker Nathan , Schneider Erasmus , George Kirsten St.
Published: February 2021

New York State, in particular the New York City metropolitan area, was the early epicenter of the SARS-CoV-2 pandemic in the United States. Similar to initial pandemic dynamics in many metropolitan areas, multiple introductions from various locations appear to have contributed to the swell of positive cases. However, representation and analysis of samples from New York regions outside the greater New York City area were lacking, as were SARS-CoV-2 genomes from the earliest cases associated with the Westchester County outbreak, which represents the first outbreak recorded in New York State. The Wadsworth Center, the public health laboratory of New York State, sought to characterize the transmission dynamics of SARS-CoV-2 across the entire state of New York from March to September with the addition of over 600 genomes from under-sampled and previously unsampled New York counties and to more fully understand the breadth of the initial outbreak in Westchester County. Additional sequencing confirmed the dominance of B.1 and descendant lineages (collectively referred to as B.1.X) in New York State. Community structure, phylogenetic, and phylogeographic analyses suggested that the Westchester outbreak was associated with continued transmission of the virus throughout the state, even after travel restrictions and the on-pause measures of March, contributing to a substantial proportion of the B.1 transmission clusters as of September 30th, 2020.