bluuebunny/crossref_metadata_2025 huggingface dataset:
Axonopathy precedes cell death in ocular damage mediated by blast exposure
Authors: Boehme Nickolas A. , Hedberg-Buenz Adam , Tatro Nicole , Bielecki Michael , Castonguay William C. , Scheetz Todd E. , Anderson Michael G. , Dutca Laura M.
Published: June 2021

Traumatic brain injuries (TBI) of varied types are common across all populations and can cause visual problems. For military personnel in combat settings, injuries from blast exposures (bTBI) are prevalent and arise from a myriad of different situations. To model these diverse conditions, we are one of several groups modeling bTBI using mice in varying ways. Here, we report a refined analysis of retinal ganglion cell (RGC) damage in male C57BL/6J mice exposed to a blast-wave in an enclosed chamber. Ganglion cell layer thickness, RGC density (BRN3A and RBPMS immunoreactivity), cellular density of ganglion cell layer (hematoxylin and eosin staining), and axon numbers (paraphenylenediamine staining) were quantified at timepoints ranging from 1 to 17-weeks. RNA sequencing was performed at 1-week and 5-weeks post-injury. Earliest indices of damage, evident by 1-week post-injury, are a loss of RGC marker expression, damage to RGC axons, and increase in glial markers expression. Blast exposure caused a loss of RGC somas and axons—with greatest loss occurring by 5-weeks post-injury. While indices of glial involvement are prominent early, they quickly subside as RGCs are lost. The finding that axonopathy precedes soma loss resembles pathology observed in mouse models of glaucoma, suggesting similar mechanisms.
Additional partial hepatectomy at the time of portal vein ligation accelerates the regeneration of the future liver remnant
Authors: Hua Chuanfeng , Wei Weiwei , Zhang Tianjiao , Xu Fengming , Dirsch Olaf , Homeyer André , Settmacher Utz , Dahmen Uta
Published: June 2021

Portal vein ligation (PVL) has been adopted to induce hypertrophy of the future liver remnant (FLR) in patients with primarily irresectable liver tumor. However, regeneration of the FLR is not always sufficient to allow curative resection of the portally-deprived tumor-bearing liver lobe. We hypothesize that simultaneous hepatectomy (PHx) and PVL augments regeneration of the FLR and that the effect is related to the extent of the additional resection. Seventy-two Lewis rats were enrolled into 3 groups: 20%PVL + 70%PHx; 70%PVL + 20%PHx; 90%PVL. Animals were observed for 1, 2, 3 and 7 days postoperatively (n = 6/time point). Liver enzymes, caudate liver/body-weight-ratio, BrdU-proliferation-index (PI), proliferating-cell-nuclear-antigen (PCNA)-mRNA-expression level and autophagy-related-proteins were evaluated. Compared with 90% PVL, additional PHx induced significantly more hypertrophy during the observation time, which was confirmed by significantly higher PI and higher level of PCNA-mRNA expression. Similarly, the additional PHx induced more autophagy in the FLR compared with PVL alone. However, both effects were not clearly related to the extent of additional resection. Additional resection augmented liver regeneration and autophagy substantially compared with PVL alone. Therefore, we concluded that autophagy might play a critical role in regulating hepatocyte proliferation and the size of the FLR after simultaneous PVL + PHx.
Bacteroides uniformis CECT 7771 alleviates inflammation within the gut-adipose tissue axis involving TLR5 signaling in obese mice
Authors: Fabersani Emanuel , Portune Kevin , Campillo Isabel , López-Almela Inmaculada , la Paz Sergio Montserrat-de , Romaní-Pérez Marina , Benítez-Páez Alfonso , Sanz Yolanda
Published: June 2021

This study investigated the immune mechanisms whereby administration of Bacteroides uniformis CECT 7771 reduces metabolic dysfunction in obesity. C57BL/6 adult male mice were fed a standard diet or a Western diet high in fat and fructose, supplemented or not with B. uniformis CECT 7771 for 14 weeks. B. uniformis CECT 7771 reduced body weight gain, plasma cholesterol, triglyceride, glucose, and leptin levels; and improved oral glucose tolerance in obese mice. Moreover, B. uniformis CECT 7771 modulated the gut microbiota and immune alterations associated with obesity, increasing Tregs and reducing B cells, total macrophages and the M1/M2 ratio in both the gut and epididymal adipose tissue (EAT) of obese mice. B. uniformis CECT 7771 also increased the concentration of the anti-inflammatory cytokine IL-10 in the gut, EAT and peripheral blood, and protective cytokines TSLP and IL-33, involved in Treg induction and type 2 innate lymphoid cells activation, in the EAT. It also restored the obesity–reduced TLR5 expression in the ileum and EAT. The findings indicate that the administration of a human intestinal bacterium with immunoregulatory properties on the intestinal mucosa helps reverse the immuno-metabolic dysfunction caused by a Western diet acting over the gut-adipose tissue axis.
Giant Mesozoic coelacanths (Osteichthyes, Actinistia) reveal high body size disparity decoupled from taxic diversity
Authors: Cavin Lionel , Piuz André , Ferrante Christophe , Guinot Guillaume
Published: June 2021

The positive correlation between speciation rates and morphological evolution expressed by body size is a macroevolutionary trait of vertebrates. Although taxic diversification and morphological evolution are slow in coelacanths, their fossil record indicates that large and small species coexisted, which calls into question the link between morphological and body size disparities. Here, we describe and reassess fossils of giant coelacanths. Two genera reached up to 5 m long, placing them among the ten largest bony fish that ever lived. The disparity in body size adjusted to taxic diversity is much greater in coelacanths than in ray-finned fishes. Previous studies have shown that rates of speciation and rates of morphological evolution are overall low in this group, and our results indicate that these parameters are decoupled from the disparity in body size in coelacanths. Genomic and physiological characteristics of the extant Latimeria may reflect how the extinct relatives grew to such a large size. These characteristics highlight new evolutionary traits specific to these “living fossils”.
Prediction of Yangtze River streamflow based on deep learning neural network with El Niño–Southern Oscillation
Authors: Ha Si , Liu Darong , Mu Lin
Published: June 2021

Accurate long-term streamflow and flood forecasting have always been an important research direction in hydrology research. Nowadays, climate change, floods, and other anomalies occurring more and more frequently and bringing great losses to society. The prediction of streamflow, especially flood prediction, is important for disaster prevention. Current hydrological models based on physical mechanisms can give accurate predictions of streamflow, but the effective prediction period is only about 1 month in advance, which is too short for decision making. The artificial neural network (ANN) has great potential for predicting runoff and is not only good at handling non-linear data but can also make long-period forecasts. However, most of ANN models are unstable in their predictions when faced with raw flow data, and have excessive errors in predicting extreme flows. Previous studies have shown a link between the El Niño–Southern Oscillation (ENSO) and the streamflow of the Yangtze River. In this paper, we use ENSO and the monthly streamflow data of the Yangtze River from 1952 to 2018 to predict the monthly streamflow of the Yangtze River in two extreme flood years and a small flood year by using deep neural networks. In this paper, three deep neural network frameworks are used: stacked long short-term memory, Conv long short-term memory encoder–decoder long short-term memory and Conv long short-term memory encoder–decoder gate recurrent unit. The results show that the use of ConvLSTM improves the stability of the model and increases the accuracy of the flood prediction. Besides, the introduction of ENSO to the experimental data resulted in a more accurate prediction of the time of the occurrence of flood peaks and flood flows. Furthermore, the best results were obtained on the convolutional long short-term memory + encoder–decoder gate recurrent unit model.
Purification of antibody fragments via interaction with detergent micellar aggregates
Authors: Dhandapani Gunasekaran , Wachtel Ellen , Das Ishita , Sheves Mordechai , Patchornik Guy
Published: June 2021

The research described in this report seeks to present proof-of-concept for a novel and robust platform for purification of antibody fragments and to define and optimize the controlling parameters. Purification of antigen-binding F(ab′)2fragments is achieved in the absence of chromatographic media or specific ligands, rather by using clusters of non-ionic detergent (e.g. Tween-60, Brij-O20) micelles chelated via Fe2+ions and the hydrophobic chelator, bathophenanthroline (batho). These aggregates, quantitatively capture the F(ab′)2fragment in the absence or presence ofE. colilysate and allow extraction of only the F(ab′)2domain at pH 3.8 without concomitant aggregate dissolution or coextraction of bacterial impurities. Process yields range from 70 to 87% by densitometry. Recovered F(ab′)2fragments are monomeric (by dynamic light scattering), preserve their secondary structure (by circular dichroism) and are as pure as those obtained via Protein A chromatography (from a mixture of F(ab′)2and Fc fragments). The effect of process parameters on Ab binding and Ab extraction (e.g. temperature, pH, ionic strength, incubation time, composition of extraction buffer) are reported, using a monoclonal antibody (mAb) and polyclonal human IgG’s as test samples.
Ancient DNA, lipid biomarkers and palaeoecological evidence reveals construction and life on early medieval lake settlements
Authors: Brown A. G. , Van Hardenbroek M. , Fonville T. , Davies K. , Mackay H. , Murray E. , Head K. , Barratt P. , McCormick F. , Ficetola G. F. , Gielly L. , Henderson A. C. G. , Crone A. , Cavers G. , Langdon P. G. , Whitehouse N. J. , Pirrie D. , Alsos I. G.
Published: June 2021

Direct evidence of ancient human occupation is typically established through archaeological excavation. Excavations are costly and destructive, and practically impossible in some lake and wetland environments. We present here an alternative approach, providing direct evidence from lake sediments using DNA metabarcoding, steroid lipid biomarkers (bile acids) and from traditional environmental analyses. Applied to an early Medieval Celtic settlement in Ireland (a crannog) this approach provides a site chronology and direct evidence of human occupation, crops, animal farming and on-site slaughtering. This is the first independently-dated, continuous molecular archive of human activity from an archeological site, demonstrating a link between animal husbandry, food resources, island use. These sites are under threat but are impossible to preserve in-situ so this approach can be used, with or without excavation, to produce a robust and full site chronology and provide direct evidence of occupation, the use of plants and animals, and activities such as butchery.
Evaluation of the immunomodulatory effects of cobalt, copper and magnesium ions in a pro inflammatory environment
Authors: Díez-Tercero Leire , Delgado Luis M. , Bosch-Rué Elia , Perez Roman A.
Published: June 2021

Biomaterials and scaffolds for Tissue Engineering are widely used for an effective healing and regeneration. However, the implantation of these scaffolds causes an innate immune response in which the macrophage polarization from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype is crucial to avoid chronic inflammation. Recent studies have showed that the use of bioactive ions such as cobalt (Co2+), copper (Cu2+) and magnesium (Mg2+) could improve tissue regeneration, although there is limited evidence on their effect on the macrophage response. Therefore, we investigated the immunomodulatory potential of Co2+, Cu2+and Mg2+in macrophage polarization. Our results indicate that Mg2+and concentrations of Cu2+lower than 10 μM promoted the expression of M2 related genes. However, higher concentrations of Cu2+and Co2+(100 μM) stimulated pro-inflammatory marker expression, indicating a concentration dependent effect of these ions. Furthermore, Mg2+were able to decrease M1 marker expression in presence of a mild pro-inflammatory stimulus, showing that Mg2+can be used to modulate the inflammatory response, even though their application can be limited in a strong pro-inflammatory environment.
Complete chloroplast genome of novel Adrinandra megaphylla Hu species: molecular structure, comparative and phylogenetic analysis
Authors: Nguyen Huu Quan , Nguyen Thi Ngoc Lan , Doan Thi Nhung , Nguyen Thi Thu Nga , Phạm Mai Huong , Le Tung Lam , Sy Danh Thuong , Chu Hoang Ha , Chu Hoang Mau
Published: June 2021

Adrinandra megaphylla Hu is a medicinal plant belonging to the Adrinandra genus, which is well-known for its potential health benefits due to its bioactive compounds. This study aimed to assemble and annotate the chloroplast genome of A. megaphylla as well as compare it with previously published cp genomes within the Adrinandra genus. The chloroplast genome was reconstructed using de novo and reference-based assembly of paired-end reads generated by long-read sequencing of total genomic DNA. The size of the chloroplast genome was 156,298 bp, comprised a large single-copy (LSC) region of 85,688 bp, a small single-copy (SSC) region of 18,424 bp, and a pair of inverted repeats (IRa and IRb) of 26,093 bp each; and a total of 51 SSRs and 48 repeat structures were detected. The chloroplast genome includes a total of 131 functional genes, containing 86 protein-coding genes, 37 transfer RNA genes, and 8 ribosomal RNA genes. The A. megaphylla chloroplast genome indicated that gene content and structure are highly conserved. The phylogenetic reconstruction using complete cp sequences, matK and trnL genes from Pentaphylacaceae species exhibited a genetic relationship. Among them, matK sequence is a better candidate for phylogenetic resolution. This study is the first report for the chloroplast genome of the A. megaphylla.
Liver stiffness regression after sustained virological response by direct-acting antivirals reduces the risk of outcomes
Authors: Piedade Juliana , Pereira Gustavo , Guimarães Lívia , Duarte Joana , Victor Lívia , Baldin Caroline , Inacio Cintia , Santos Ricardo , Chaves Úrsula , Nunes Estevão P. , Grinsztejn Beatriz , Veloso Valdilea G. , Fernandes Flavia , Perazzo Hugo
Published: June 2021

The role of liver stiffness measurement (LSM) after sustained virological response (SVR) in HCV patients treated by direct-acting antivirals (DAAs) remains unclear. We aimed to evaluate LSM regression value after SVR and to identify risk factors associated with liver related complications (LRC) or death. This retrospective study analyzed patients with LSM ≥ 10 kPa with LSM by transient elastography pre-DAAs and post-SVR. Patients with previous hepatic decompensation were excluded. Medical records were reviewed to identify primary outcomes. Kaplan–Meier curves and time-to-event Cox proportional-hazard models were performed. 456 patients [65% female, 62 years (IQR 57–68)] were included. During a follow-up of 2.3 years (IQR 1.6–2.7), 28 patients developed 37 outcomes [rate = 29.0 (95% CI 20.0–42.0) per 1000 person-years]. The cumulative incidence of outcomes was significantly lower in patients who regressed LSM ≥ 20% [3.4% (95% CI 1.8–7.0) vs. 9.0% (5.5–14.5), p = 0.028]. In a multivariate Cox-model [HR(95% CI)], male gender [HR = 3.00 (1.30–6.95), p = 0.010], baseline albumin < 3.5 mg/dL [HR = 4.49 (1.95–10.34), p < 0.001] and baseline unfavorable Baveno-VI [HR = 4.72 (1.32–16.83), p = 0.017] were independently associated and LSM regression ≥ 20% after SVR had a trend to reduce the risk of LRC or death [HR = 0.45 (0.21–1.02), p = 0.058]. The use of simple parameters before DAAs and repetition of LSM post-SVR can identify patients with different risks for severe outcome after HCV eradication.
Decompression effects on bone healing in rat mandible osteomyelitis
Authors: Sodnom-Ish Buyanbileg , Eo Mi Young , Oh Ji Hye , Seo Mi Hyun , Yang Hoon Joo , Lee Jong Ho , Kim Soung Min
Published: June 2021

Osteomyelitis (OM) of the jaw is usually caused by a chronic odontogenic infection. Decompression is the release the intraluminal pressure in the cystic cavity allowing gradual bone growth from the periphery. The aim of this study was to analyze the effectiveness of decompression in an OM jaw model. A 4-mm-diameter defect was made on mandibles of fourteen Sprague–Dawley rats and inoculated with S. aureus (20 μl of 1 × 107 CFU/ml) injection. Two weeks later, four groups were made as non-treatment (C1), only curettage (C2), curettage and decompression (E1), and curettage and decompression with normal saline irrigation (E2). After four weeks, each group was analyzed. Most micro-CT parameters, including bone mineral density [0.87 (± 0.08) g/cm3] with bone volume [0.73 (± 0.08) mm3] was higher in E2 group than that of C1 group (p = 0.04, p = 0.05, respectively). E2 group in histology showed the highest number of osteocytes than those of control groups, 91.00 (± 9.90) (p = 0.002). OPN were expressed strongly in the E1 (“5”: 76–100%) that those of other groups. Decompression drains induced advanced bone healing compared to that of curettage alone. Therefore, it could be recommended to use decompressive drain for enhancing the jaw OM management.
DC-SIGN binding to mannosylated B-cell receptors in follicular lymphoma down-modulates receptor signaling capacity
Authors: Valle-Argos Beatriz , Chiodin Giorgia , Bryant Dean J. , Taylor Joe , Lemm Elizabeth , Duriez Patrick J. , Rock Philip J. , Strefford Jonathan C. , Forconi Francesco , Burack Richard W. , Packham Graham , Stevenson Freda K.
Published: June 2021

In follicular lymphoma (FL), surface immunoglobulin (sIg) carries mandatory N-glycosylation sites in the variable regions, inserted during somatic hypermutation. These glycosylation sites are tumor-specific, indicating a critical function in FL. Added glycan unexpectedly terminates at high mannose (Mann) and confers capability for sIg-mediated interaction with local macrophage-expressed DC-SIGN lectin resulting in low-level activation of upstream B-cell receptor signaling responses. Here we show that despite being of low-level, DC-SIGN induces a similar downstream transcriptional response to anti-IgM in primary FL cells, characterized by activation of pathways associated with B-cell survival, proliferation and cell–cell communication. Lectin binding was also able to engage post-transcriptional receptor cross-talk pathways since, like anti-IgM, DC-SIGN down-modulated cell surface expression of CXCR4. Importantly, pre-exposure of a FL-derived cell line expressing sIgM-Mann or primary FL cells to DC-SIGN, which does not block anti-IgM binding, reversibly paralyzed the subsequent Ca2+ response to anti-IgM. These novel findings indicate that modulation of sIg function occurs in FL via lectin binding to acquired mannoses. The B-cell receptor alternative engagement described here provides two advantages to lymphoma cells: (i) activation of signaling, which, albeit of low-level, is sufficient to trigger canonical lymphoma-promoting responses, and (ii) protection from exogenous antigen by paralyzing anti-IgM-induced signaling. Blockade of this alternative engagement could offer a new therapeutic strategy.
Susceptibility of anurans, lizards, and fish to infection with Dracunculus species larvae and implications for their roles as paratenic hosts
Authors: Box Erin K. , Yabsley Michael J. , Garrett Kayla B. , Thompson Alec T. , Wyckoff Seth T. , Cleveland Christopher A.
Published: June 2021

Dracunculus spp. are parasitic nematodes that infect numerous species of mammals and reptiles. The life cycles of Dracunculus species are complex, and unknowns remain regarding the role of paratenic and transport hosts in transmission to definitive hosts. We had two primary objectives: to assess the susceptibility of several species of anurans, lizards, and fish as paratenic hosts for Dracunculus species, and to determine the long-term persistence of Dracunculus infections in African clawed frogs (Xenopus laevis). Animals were orally exposed to copepods infected with infectious third-stage larvae (L3s) of either Dracunculus insignis or D. medinensis. Dracunculus L3s were recovered from four anuran species, two lizard species, and one fish species, demonstrating that Dracunculus can infect tissues of a diversity of species. In long-term persistence trials, D. medinensis L3s were recovered from African clawed frogs tissues up to 58 days post-infection, and D. insignis L3s were recovered up to 244 days post-infection. Our findings regarding the susceptibility of novel species of frogs, lizards, and fish to infection with Dracunculus nematodes, and long-term persistence of L3s in paratenic hosts, address pressing knowledge gaps regarding Dracunculus infection in paratenic hosts and may guide future research regarding the transmission of Dracunculus to definitive mammalian hosts.
Impact of preprocedural coronary flow grade on duration of dual antiplatelet therapy in acute myocardial infarction
Authors: Kim Yong Hoon , Her Ae-Young , Kim Byeong-Keuk , Hong Sung-Jin , Ahn Chul-Min , Kim Jung-Sun , Ko Young-Guk , Choi Donghoon , Hong Myeong-Ki , Jang Yangsoo
Published: June 2021

We investigated the impact of pre-percutaneous coronary intervention (pre-PCI) thrombolysis in myocardial infarction (TIMI) flow grade (pre-TIMI) on 3-month (3-mo) and 12-mo of dual antiplatelet therapy (DAPT) in patients with acute myocardial infarction (AMI). This was a post hoc analysis of the TICO trial. A total of 2083 patients with AMI (pre-TIMI 0/1: n = 1143; pre-TIMI 2/3: n = 940) were evaluated. The primary outcome was the occurrence of net adverse clinical events (NACE), defined as a composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events (MACCE) within 12-mo following PCI. The secondary outcomes were the occurrence of the individual components of TIMI bleedings and MACCE. In the pre-TIMI 0/1 group, the primary and second outcomes were not significantly different between the 3-mo and 12-mo DAPT groups. However, in the pre-TIMI 2/3 group, the occurrences of TIMI minor (adjusted hazard ratio [aHR]: 0.294; p = 0.016) and major or minor bleeding (aHR: 0.483; p = 0.014) on intention-to-treat analysis were significantly higher in the 12-mo than in the 3-mo DAPT group. The occurrence of MACCE was similar between the two groups. A higher bleeding tendency in 12-mo DAPT compared with 3-mo DAPT was more obvious in the pre-TIMI 2/3 group than in the pre-TIMI 0/1 group.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02494895.
Contacts and behaviours of university students during the COVID-19 pandemic at the start of the 2020/2021 academic year
Authors: Nixon Emily , Trickey Adam , Christensen Hannah , Finn Adam , Thomas Amy , Relton Caroline , Montgomery Clara , Hemani Gibran , Metz Jane , Walker Josephine G. , Turner Katy , Kwiatkowska Rachel , Sauchelli Sarah , Danon Leon , Brooks-Pollock Ellen
Published: June 2021

University students have unique living, learning and social arrangements which may have implications for infectious disease transmission. To address this data gap, we created CONQUEST (COroNavirus QUESTionnaire), a longitudinal online survey of contacts, behaviour, and COVID-19 symptoms for University of Bristol (UoB) staff/students. Here, we analyse results from 740 students providing 1261 unique records from the start of the 2020/2021 academic year (14/09/2020–01/11/2020), where COVID-19 outbreaks led to the self-isolation of all students in some halls of residences. Although most students reported lower daily contacts than in pre-COVID-19 studies, there was heterogeneity, with some reporting many (median = 2, mean = 6.1, standard deviation = 15.0; 8% had ≥ 20 contacts). Around 40% of students’ contacts were with individuals external to the university, indicating potential for transmission to non-students/staff. Only 61% of those reporting cardinal symptoms in the past week self-isolated, although 99% with a positive COVID-19 test during the 2 weeks before survey completion had self-isolated within the last week. Some students who self-isolated had many contacts (mean = 4.3, standard deviation = 10.6). Our results provide context to the COVID-19 outbreaks seen in universities and are available for modelling future outbreaks and informing policy.
Prognostic analysis and beneficiary identification of adjuvant external beam radiotherapy for stage pT4b sigmoid colon cancer
Authors: Lin Yaobin , Wang Lei , Shao Lingdong , Zhang Xueqing , Lin Huaqin , Wang Youjia , Wu Junxin
Published: June 2021

The clinical efficacy of adjuvant radiotherapy in sigmoid colon cancer remains questioned. To evaluate the clinical efficacy of adjuvant external beam radiotherapy (EBRT) for patients with pathologic stage T4b sigmoid colon cancer. Patients with stage pT4b sigmoid colon cancer receiving adjuvant EBRT or not followed by surgery between 2004 and 2016 were extracted from the Surveillance, Epidemiology, and End Results database. Analysis of overall survival (OS) was performed using Kaplan–Meier curves and prognostic factors were identified using Cox proportional hazards regression models with 95% confidence intervals within the entire cohort. A risk-stratification system was then developed based on the β regression coefficient. Among 2073 patients, 284 (13.7%) underwent adjuvant EBRT. The median OS in the group receiving adjuvant EBRT was significantly longer than that in the non-radiotherapy group (p < 0.001). Age, serum carcinoembryonic antigen (CEA) level, perineural invasion, lymph node dissection (LND) number, and adjuvant EBRT were independent factors associated with OS. A risk‐stratification system was generated, which showed that low‐risk patients had a higher 5-year survival rate than high-risk patients (75.6% vs. 42.3%, p < 0.001). Adjuvant EBRT significantly prolonged the 5-year survival rate of high-risk patients (62.6% vs. 38.3%, p = 0.009) but showed no survival benefit among low‐risk patients (87.7% vs. 73.2%, p = 0.100). Our risk‐stratification model comprising age, serum CEA, perineural invasion, and LND number predicted the outcomes of patients with stage pT4b sigmoid colon cancer based on which subgroup of high-risk patients should receive adjuvant EBRT.
Intraocular asymmetry of visual field defects in primary angle-closure glaucoma, high-tension glaucoma, and normal-tension glaucoma in a Chinese population
Authors: Jiang Junhong , Ye Cong , Zhang Cong , Ye Wenqing , Wang Xiaoyan , Shang Xiao , Xu Xiang , Zhang Hongte , Zhang Shaodan , Zheng Jingwei , Zuo Jingjing , Hu Jingjing , Congdon Nathan , Lu Fan , Liang Yuanbo
Published: June 2021

Direct comparison data on spatial patterns of visual field (VF) defects among primary angle-closure glaucoma (PACG), high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) are not available. We aimed to compare the intraocular asymmetry of VF loss among patients with PACG, NTG and HTG across different severity levels. A total of 162 eyes of 114 patients with PACG, 111 eyes of 74 patients with HTG and 148 eyes of 102 patients with NTG were included. VF defects were categorized into 3 stages (early, moderate, and advanced), and each hemifield was divided into 5 regions according to the Glaucoma hemifield test (GHT). The mean total deviation (TD) of each GHT region was calculated. In the early stage, the paracentral, peripheral arcuate 1 and peripheral arcuate 2 regions in the superior hemifield in the NTG group had significantly worse mean TDs than their corresponding regions in the inferior hemifield. In the advanced stage, the central region in the superior hemifield in the PACG group had a significantly worse mean TD than that in the inferior hemifield. There was no significant difference in the mean TD for any of the five regions between hemifields across all severity levels in the in the HTG group. The superior hemifield was affected more severely than the inferior hemifield in all three subtypes of primary glaucoma. This asymmetric tendency was more pronounced in NTG than in PACG and HTG.
Low metformin dose and its therapeutic serum concentration in prediabetes
Authors: Sutkowska Edyta , Fortuna Paulina , Wisniewski Jerzy , Sutkowska Karolina , Hodurek Pawel , Gamian Andrzej , Kaluza Bernadetta
Published: June 2021

This prospective study aimed to analyze whether the patients with pre-diabetes (pre-DM) reach the TC (therapeutic concentration) of the metformin during repeated, low, constant drug dose. The guidelines do not recommend any metformin dose for this group of patients. Based on the previous study after a dose of 1700 mg/day the patients seem to reach the therapeutic drug concentration, which guarantees the glycemic effect. Twenty patients with new-diagnosed pre-DM were treated with a 1500 mg/day regimen of the metformin for 15 weeks. The serum concentration of the drug was assessed by liquid chromatography-mass spectrometry technique at 6 and 15 week of the treatment. The correlation of the serum metformin concentration with BMI (body mass index) and patients’ weight was also performed. The mean metformin concentration was: 4.65 μmol/L (± 2.41) and 5.41 μmol/L (± 3.44) (p = 0.27) after 6 and 15 weeks of the treatment respectively. There was a positive correlation between the serum concentration of the metformin and body weight (but not BMI) in the 15th week of the therapy (p = 0.04)- the higher body weight the higher concentration of the metformin. Patients with pre-diabetes can be successfully treated with a low dose of metformin, to reach the drug’s therapeutic concentration. Body weight can impact the metformin serum concentration during long-term treatment what should be taken into consideration when choosing the dose because of its pleiotropic effect e.g. on the cardiovascular system via reduction of the oxidative stress and would be not connected with the drug’s hypoglycemic effect.

ClinicalTrials.gov number: NCT03398356; date of first registration: 01/07/2018.
Automatic and unbiased segmentation and quantification of myofibers in skeletal muscle
Authors: Waisman Ariel , Norris Alessandra Marie , Elías Costa Martín , Kopinke Daniel
Published: June 2021

Skeletal muscle has the remarkable ability to regenerate. However, with age and disease muscle strength and function decline. Myofiber size, which is affected by injury and disease, is a critical measurement to assess muscle health. Here, we test and apply Cellpose, a recently developed deep learning algorithm, to automatically segment myofibers within murine skeletal muscle. We first show that tissue fixation is necessary to preserve cellular structures such as primary cilia, small cellular antennae, and adipocyte lipid droplets. However, fixation generates heterogeneous myofiber labeling, which impedes intensity-based segmentation. We demonstrate that Cellpose efficiently delineates thousands of individual myofibers outlined by a variety of markers, even within fixed tissue with highly uneven myofiber staining. We created a novel ImageJ plugin (LabelsToRois) that allows processing of multiple Cellpose segmentation images in batch. The plugin also contains a semi-automatic erosion function to correct for the area bias introduced by the different stainings, thereby identifying myofibers as accurately as human experts. We successfully applied our segmentation pipeline to uncover myofiber regeneration differences between two different muscle injury models, cardiotoxin and glycerol. Thus, Cellpose combined with LabelsToRois allows for fast, unbiased, and reproducible myofiber quantification for a variety of staining and fixation conditions.
Bioengineered model of the human motor unit with physiologically functional neuromuscular junctions
Authors: Rimington Rowan P. , Fleming Jacob W. , Capel Andrew J. , Wheeler Patrick C. , Lewis Mark P.
Published: June 2021

Investigations of the human neuromuscular junction (NMJ) have predominately utilised experimental animals, model organisms, or monolayer cell cultures that fail to represent the physiological complexity of the synapse. Consequently, there remains a paucity of data regarding the development of the human NMJ and a lack of systems that enable investigation of the motor unit. This work addresses this need, providing the methodologies to bioengineer 3D models of the human motor unit. Spheroid culture of iPSC derived motor neuron progenitors augmented the transcription of OLIG2, ISLET1 and SMI32 motor neuron mRNAs ~ 400, ~ 150 and ~ 200-fold respectively compared to monolayer equivalents. Axon projections of adhered spheroids exceeded 1000 μm in monolayer, with transcription of SMI32 and VACHT mRNAs further enhanced by addition to 3D extracellular matrices in a type I collagen concentration dependent manner. Bioengineered skeletal muscles produced functional tetanic and twitch profiles, demonstrated increased acetylcholine receptor (AChR) clustering and transcription of MUSK and LRP4 mRNAs, indicating enhanced organisation of the post-synaptic membrane. The number of motor neuron spheroids, or motor pool, required to functionally innervate 3D muscle tissues was then determined, generating functional human NMJs that evidence pre- and post-synaptic membrane and motor nerve axon co-localisation. Spontaneous firing was significantly elevated in 3D motor units, confirmed to be driven by the motor nerve via antagonistic inhibition of the AChR. Functional analysis outlined decreased time to peak twitch and half relaxation times, indicating enhanced physiology of excitation contraction coupling in innervated motor units. Our findings provide the methods to maximise the maturity of both iPSC motor neurons and primary human skeletal muscle, utilising cell type specific extracellular matrices and developmental timelines to bioengineer the human motor unit for the study of neuromuscular junction physiology.
An in vivo selection system with tightly regulated gene expression enables directed evolution of highly efficient enzymes
Authors: Nearmnala Parinthon , Thanaburakorn Manutsawee , Panbangred Watanalai , Chaiyen Pimchai , Hongdilokkul Narupat
Published: June 2021

In vivo selection systems are powerful tools for directed evolution of enzymes. The selection pressure of the systems can be tuned by regulating the expression levels of the catalysts. In this work, we engineered a selection system for laboratory evolution of highly active enzymes by incorporating a translationally suppressingcisrepressor as well as an inducible promoter to impart stringent and tunable selection pressure. We demonstrated the utility of our selection system by performing directed evolution experiments using TEM β-lactamase as the model enzyme. Five evolutionary rounds afforded a highly active variant exhibiting 440-fold improvement in catalytic efficiency. We also showed that, without thecisrepressor, the selection system cannot provide sufficient selection pressure required for evolving highly efficient TEM β-lactamase. The selection system should be applicable for the exploration of catalytic perfection of a wide range of enzymes.
An integrative measure of cognitive performance, but not individual task performance, is linked to male reproductive output in budgerigars
Authors: Medina-García Angela , Wright Timothy F.
Published: June 2021

Cognitive abilities such as learning and memory are key for survival and reproduction. Individuals with high cognitive abilities may be more successful at attracting mates and producing offspring. However, empirical tests of and evidence supporting this hypothesis remain scarce. We measured cognitive performance of male budgerigars in four tasks: problem solving, detour reaching, seed discrimination, and spatial memory. We then tested female choice for male cognition at three stages of the mating choice process: social pairing, extra-pair mating, and continued reproductive investment with a social mate. We also measured female reproductive output. We used an integrative measure of male cognitive performance that encapsulates performance across all tasks, the ‘composite cognitive score’ by summing performance on the four tasks. In the first stage, females did not choose their social mates based on any of the measures of male cognitive performance. In the second stage, however, males with higher composite cognitive scores sired and raised more offspring. In the third stage, females increased their reproductive investment after the first breeding attempt when paired with males with higher detour-reaching scores. These results suggest that female reproductive decisions may shape overall male cognitive performance.
Connectivity adaptations in dopaminergic systems define the brain maturity of investors
Authors: Ortiz-Teran Elena , Diez Ibai , Sepulcre Jorge , Lopez-Pascual Joaquin , Ortiz Tomas
Published: June 2021

Investment decisions rely on perceptions from external stimuli along with the integration of inner brain-body signals, all of which are shaped by experience. As experience is capable of molding both the structure and function of the human brain, we have used a novel neuroimaging connectomic-genetic approach to investigate the influence of investment work experience on brain anatomy. We found that senior investors display higher gray matter volume and increased structural brain connectivity in dopamine-related pathways, as well as a set of genes functionally associated with adrenaline and noradrenaline biosynthesis (SLC6A3, TH and SLC18A2), which is seemingly involved in reward processing and bodily stress responses during financial trading. These results suggest the key role of catecholamines in the way senior investors harness their emotions while raising bodily awareness as they grow in investment maturity.
Brain capillary structures of schizophrenia cases and controls show a correlation with their neuron structures
Authors: Saiga Rino , Uesugi Masayuki , Takeuchi Akihisa , Uesugi Kentaro , Suzuki Yoshio , Takekoshi Susumu , Inomoto Chie , Nakamura Naoya , Torii Youta , Kushima Itaru , Iritani Shuji , Ozaki Norio , Oshima Kenichi , Itokawa Masanari , Arai Makoto , Mizutani Ryuta
Published: June 2021

Brain blood vessels constitute a micrometer-scale vascular network responsible for supply of oxygen and nutrition. In this study, we analyzed cerebral tissues of the anterior cingulate cortex and superior temporal gyrus of schizophrenia cases and age/gender-matched controls by using synchrotron radiation microtomography or micro-CT in order to examine the three-dimensional structure of cerebral vessels. Over 1 m of cerebral blood vessels was traced to build Cartesian-coordinate models, which were then used for calculating structural parameters including the diameter and curvature of the vessels. The distribution of vessel outer diameters showed a peak at 7–9 μm, corresponding to the diameter of the capillaries. Mean curvatures of the capillary vessels showed a significant correlation to the mean curvatures of neurites, while the mean capillary diameter was almost constant, independent of the cases. Our previous studies indicated that the neurites of schizophrenia cases are thin and tortuous compared to controls. The curved capillaries with a constant diameter should occupy a nearly constant volume, while neurons suffering from neurite thinning should have reduced volumes, resulting in a volumetric imbalance between the neurons and the vessels. We suggest that the observed structural correlation between neurons and blood vessels is related to neurovascular abnormalities in schizophrenia.
Flexible, high mobility short-channel organic thin film transistors and logic circuits based on 4H–21DNTT
Authors: Bilgaiyan Anubha , Cho Seung-Il , Abiko Miho , Watanabe Kaori , Mizukami Makoto
Published: June 2021

The low mobility and large contact resistance in organic thin-film transistors (OTFTs) are the two major limiting factors in the development of high-performance organic logic circuits. Here, solution-processed high-performance OTFTs and circuits are reported with a polymeric gate dielectric and 6,6 bis (trans-4-butylcyclohexyl)-dinaphtho[2,1-b:2,1-f]thieno[3,2-b]thiophene (4H–21DNTT) for the organic semiconducting layer. By optimizing and controlling the fabrication conditions, a high saturation mobility of 8.8 cm2 V−1 s−1 was demonstrated as well as large on/off ratios (> 106) for relatively short channel lengths of 15 μm and an average carrier mobility of 10.5 cm2 V−1 s−1 for long channel length OTFTs (> 50 μm). The pseudo-CMOS inverter circuit with a channel length of 15 μm exhibited sharp switching characteristics with a high signal gain of 31.5 at a supply voltage of 20 V. In addition to the inverter circuit, NAND logic circuits were further investigated, which also exhibited remarkable logic characteristics, with a high gain, an operating frequency of 5 kHz, and a short propagation delay of 22.1 μs. The uniform and reproducible performance of 4H–21DNTT OTFTs show potential for large-area, low-cost real-world applications on industry-compatible bottom-contact substrates.
Flat hardness distribution in AA6061 joints by linear friction welding
Authors: Choi Jeong-Won , Li Weihao , Ushioda Kohsaku , Fujii Hidetoshi
Published: June 2021

It is known that one of the main concerns associated with the conventional welding of precipitation-strengthened Al alloys is the formation of softening regions, resulting in the deterioration of mechanical properties. In this study, we show that linear friction welding (LFW) can completely suppress softening regions in precipitation-strengthened AA6061-T6 alloy by introducing a large shear strain and by controlling the interfacial temperature. We found that the LFW process resulted in an extremely low interfacial temperature; it decreased as the applied pressure increased from 50 to 240 MPa. This approach can essentially suppress both softening and hardening regions, leading to uniform hardness distribution in Al joints. The high-pressure LFW process demonstrated here can thus provide an innovated guidance to obtain high-performance Al alloy joints and be extended to other precipitation-strengthened Al alloys, which undergo high-temperature softening.
Diet and general cognitive ability in the UK Biobank dataset
Authors: Hepsomali Piril , Groeger John A.
Published: June 2021

Accumulating evidence suggests that dietary interventions might have potential to be used as a strategy to protect against age-related cognitive decline and neurodegeneration, as there are associations between some nutrients, food groups, dietary patterns, and some domains of cognition. In this study, we aimed to conduct the largest investigation of diet and cognition to date, through systematically examining the UK Biobank (UKB) data to find out whether dietary quality and food groups play a role on general cognitive ability. This cross-sectional population-based study involved 48,749 participants. UKB data on food frequency questionnaire and cognitive function were used. Also, healthy diet, partial fibre intake, and milk intake scores were calculated. Adjusted models included age, sex, and BMI. We observed associations between better general cognitive ability and higher intakes of fish, and unprocessed red meat; and moderate intakes of fibre, and milk. Surprisingly, we found that diet quality, vegetable intake, high and low fibre and milk intake were inversely associated with general cognitive ability. Our results suggest that fish and unprocessed red meat and/or nutrients that are found in fish and unprocessed red meat might be beneficial for general cognitive ability. However, results should be interpreted in caution as the same food groups may affect other domains of cognition or mental health differently. These discrepancies in the current state of evidence invites further research to examine domain-specific effects of dietary patterns/food groups on a wide range of cognitive and affective outcomes with a special focus on potential covariates that may have an impact on diet and cognition relationship.
Spatial ecology of cane toads (Rhinella marina) in their native range: a radiotelemetric study from French Guiana
Authors: DeVore Jayna L. , Shine Richard , Ducatez Simon
Published: June 2021

Like most invasive species, cane toads have attracted less research in their native range than in invaded areas. We radio-tracked 34 free-ranging toads in French Guiana, a source region for most invasive populations, across two coastal and two rainforest sites. Coastal toads generally sheltered in pools of fresh or brackish water but nocturnally foraged on beaches, whereas rainforest toads sheltered in forested habitats, moving into open areas at night. Over five days of monitoring, native toads frequently re-used shelters and moved little between days (means = 10–63 m/site) compared to invasion-front toads from Australia (~ 250 m). Larger toads moved less between days, but displaced in more consistent directions. At night, foraging toads travelled up to 200 m before returning to shelters. Foraging distance was related to body condition at coastal sites, with toads in poorer body condition travelling farther. Rain increased the probability of coastal toads sheltering in the dry habitats where they foraged. Dispersal and rainfall were lower at coastal sites, and the strategies utilized by coastal toads to minimize water loss resembled those of invasive toads in semi-desert habitats. This global invader already exhibits a broad environmental niche and substantial behavioural flexibility within its native range.
Generation of restriction endonucleases barcode map to trace SARS-CoV-2 origin and evolution
Authors: Colombo Federico , Corsiero Elisa , Lewis Myles J. , Pitzalis Costantino
Published: June 2021

Since the first report of SARS-CoV-2 in China in 2019, there has been a huge debate about the origin. In this work, using a different method we aimed to strengthen the observation that no evidence of genetic manipulation has been found by (1) detecting classical restriction site (RS) sequence in human SARS-CoV-2 genomes and (2) comparing them with other recombinant SARS-CoV-like virus created for experimental purposes. Finally, we propose a novel approach consisting in the generation of a restriction endonucleases site map of SARS-CoV-2 and other related coronavirus genomes to be used as a fingerprint to trace the virus evolution.
Gemella haemolysans inhibits the growth of the periodontal pathogen Porphyromonas gingivalis
Authors: Miyoshi Tomohiro , Oge Shogo , Nakata Satoshi , Ueno Yuji , Ukita Hidehiko , Kousaka Reiko , Miura Yuki , Yoshinari Nobuo , Yoshida Akihiro
Published: June 2021

The oral microbiome plays an important role in the human microbial community and in maintaining the health of an individual. Imbalances in the oral microbiome may contribute to oral and systemic diseases. The progression of periodontal disease is closely related to the growth of bacteria, such as Porphyromonas gingivalis, in the oral cavity. However, the pathogen growth mechanism specific to periodontal disease remains unknown. This study aimed to identify bacteria associated with periodontal health by focusing on hemolytic bacteria. Unstimulated saliva samples were collected from ten periodontitis patients and five healthy subjects to detect and identify the presence of hemolytic bacteria. The saliva of healthy subjects contained a higher proportion of G. haemolysans than saliva samples from patients with periodontitis. Growth inhibition assays indicated that the protein components contained in the culture supernatant of G. haemolysans directly suppressed the growth of P. gingivalis. This study shows that the presence of G. haemolysans in saliva is associated with periodontal health and that it inhibits the growth of P. gingivalis in vitro.