bluuebunny/crossref_metadata_2025 huggingface dataset:
Shape-programmable liquid crystal elastomer structures with arbitrary three-dimensional director fields and geometries
Authors: Guo Yubing , Zhang Jiachen , Hu Wenqi , Khan Muhammad Turab Ali , Sitti Metin
Published: October 2021

Liquid crystal elastomers exhibit large reversible strain and programmable shape transformations, enabling various applications in soft robotics, dynamic optics, and programmable origami and kirigami. The morphing modes of these materials depend on both their geometries and director fields. In two dimensions, a pixel-by-pixel design has been accomplished to attain more flexibility over the spatial resolution of the liquid crystal response. Here we generalize this idea in two steps. First, we create independent, cubic light-responsive voxels, each with a predefined director field orientation. Second, these voxels are in turn assembled to form lines, grids, or skeletal structures that would be rather difficult to obtain from an initially connected material sample. In this way, the orientation of the director fields can be made to vary at voxel resolution to allow for programmable optically- or thermally-triggered anisotropic or heterogeneous material responses and morphology changes in three dimensions that would be impossible or hard to implement otherwise.
Joint single-cell multiomic analysis in Wnt3a induced asymmetric stem cell division
Authors: Sun Zhongxing , Tang Yin , Zhang Yanjun , Fang Yuan , Jia Junqi , Zeng Weiwu , Fang Dong
Published: October 2021

Wnt signaling usually functions through a spatial gradient. Localized Wnt3a signaling can induce the asymmetric division of mouse embryonic stem cells, where proximal daughter cells maintain self-renewal and distal daughter cells acquire hallmarks of differentiation. Here, we develop an approach, same cell epigenome and transcriptome sequencing, to jointly profile the epigenome and transcriptome in the same single cell. Utilizing this method, we profiled H3K27me3 and H3K4me3 levels along with gene expression in mouse embryonic stem cells with localized Wnt3a signaling, revealing the cell type-specific maps of the epigenome and transcriptome in divided daughter cells. H3K27me3, but not H3K4me3, is correlated with gene expression changes during asymmetric cell division. Furthermore, cell clusters identified by H3K27me3 recapitulate the corresponding clusters defined by gene expression. Our study provides a convenient method to jointly profile the epigenome and transcriptome in the same cell and reveals mechanistic insights into the gene regulatory programs that maintain and reset stem cell fate during differentiation.
Predicting temperature-dependent ultimate strengths of body-centered-cubic (BCC) high-entropy alloys
Authors: Steingrimsson B. , Fan X. , Yang X. , Gao M. C. , Zhang Y. , Liaw P. K.
Published: October 2021

This paper presents a bilinear log model, for predicting temperature-dependent ultimate strength of high-entropy alloys (HEAs) based on 21 HEA compositions. We consider the break temperature, Tbreak, introduced in the model, an important parameter for design of materials with attractive high-temperature properties, one warranting inclusion in alloy specifications. For reliable operation, the operating temperature of alloys may need to stay below Tbreak. We introduce a technique of global optimization, one enabling concurrent optimization of model parameters over low-temperature and high-temperature regimes. Furthermore, we suggest a general framework for joint optimization of alloy properties, capable of accounting for physics-based dependencies, and show how a special case can be formulated to address the identification of HEAs offering attractive ultimate strength. We advocate for the selection of an optimization technique suitable for the problem at hand and the data available, and for properly accounting for the underlying sources of variations.
Different types of spin currents in the comprehensive materials database of nonmagnetic spin Hall effect
Authors: Zhang Yang , Xu Qiunan , Koepernik Klaus , Rezaev Roman , Janson Oleg , Železný Jakub , Jungwirth Tomáš , Felser Claudia , van den Brink Jeroen , Sun Yan
Published: October 2021

Spin Hall effect (SHE) has its special position in spintronics. To gain new insight into SHE and to identify materials with substantial spin Hall conductivity (SHC), we performed high-precision high-throughput ab initio calculations of the intrinsic SHC for over 20,000 nonmagnetic crystals. The calculations revealed a strong relationship between the magnitude of the SHC and the crystalline symmetry, where a large SHC is typically associated with mirror symmetry-protected nodal line band structures. This database includes 11 materials with an SHC comparable to or even larger than that of Pt. Materials with different types of spin currents were additionally identified. Furthermore, we found that different types of spin current can be obtained by rotating applied electrical fields. This improves our understanding and is expected to facilitate the design of new types of spin-orbitronic devices.
Long-read sequencing reveals the structural complexity of genomic integration of HBV DNA in hepatocellular carcinoma
Authors: Zhuo Zhongling , Rong Weiqi , Li Hexin , Li Ying , Luo Xuanmei , Liu Ye , Tang Xiaokun , Zhang Lili , Su Fei , Cui Hongyuan , Xiao Fei
Published: October 2021

The integration of HBV DNA into the human genome can disrupt its structure in hepatocellular carcinoma (HCC), but the complexity of HBV genomic integration remains elusive. Here we applied long-read sequencing to precisely elucidate the HBV integration pattern in the human hepatocellular genome. The DNA library was sequenced using the long-read sequencing on GridION and PacBio Sequel II, respectively. The DNA and mRNA were sequenced using next-generation sequencing on Illumina NextSeq. BLAST (Basic Local Alignment Search Tool) and local scripts were used to analyze HBV integration patterns. We established an analytical strategy based on the long-read sequences, and analyzed the complexity of HBV DNA integration into the hepatocellular genome. A total of 88 integrated breakpoints were identified. HBV DNA integration into human genomic DNA was mainly fragmented with different orientations, rarely with a complete genome. The same HBV integration breakpoints were identified among the three platforms. Most breakpoints were observed at P, X, and S genes in the HBV genome, and observed at introns, intergenic sequences, and exons in the human genome. Tumor tissue harbored a much higher integrated number than the adjacent tissue, and the distribution of HBV integrated into human chromosomes was more concentrated. HBV integration shows different patterns between cancer cells and adjacent normal cells. We for the first time obtained the entire HBV integration pattern through long-read sequencing and demonstrated the value of long-read sequencing in detecting the genomic integration structures of viruses in host cells.
Parkinson’s disease patients benefit from bicycling - a systematic review and meta-analysis
Authors: Tiihonen Marianne , Westner Britta U. , Butz Markus , Dalal Sarang S.
Published: October 2021

Many Parkinson’s disease (PD) patients are able to ride a bicycle despite being severely compromised by gait disturbances up to freezing of gait. This review [PROSPERO CRD 42019137386] aimed to find out, which PD-related symptoms improve from bicycling, and which type of bicycling exercise would be most beneficial. Following a systematic database literature search, peer-reviewed studies with randomized control trials (RCT) and with non-randomized trials (NRCT) investigating the interventional effects of bicycling on PD patients were included. A quality analysis addressing reporting, design and possible bias of the studies, as well as a publication bias test was done. Out of 202 references, 22 eligible studies with 505 patients were analysed. An inverse variance-based analysis revealed that primary measures, defined as motor outcomes, benefitted from bicycling significantly more than cognitive measures. Additionally, secondary measures of balance, walking speed and capacity, and the PDQ-39 ratings improved with bicycling. The interventions varied in durations, intensities and target cadences. Conclusively, bicycling is particularly beneficial for the motor performance of PD patients, improving crucial features of gait. Furthermore, our findings suggest that bicycling improves the overall quality-of-life of PD patients.
Non-Markovian memory strength bounds quantum process recoverability
Authors: Taranto Philip , Pollock Felix A. , Modi Kavan
Published: October 2021

Generic non-Markovian quantum processes have infinitely long memory, implying an exact description that grows exponentially in complexity with observation time. Here, we present a finite memory ansatz that approximates (or recovers) the true process with errors bounded by the strength of the non-Markovian memory. The introduced memory strength is an operational quantity and depends on the way the process is probed. Remarkably, the recovery error is bounded by the smallest memory strength over all possible probing methods. This allows for an unambiguous and efficient description of non-Markovian phenomena, enabling compression and recovery techniques pivotal to near-term technologies. We highlight the implications of our results by analyzing an exactly solvable model to show that memory truncation is possible even in a highly non-Markovian regime.
Safety, tolerability and antiviral activity of the antisense oligonucleotide bepirovirsen in patients with chronic hepatitis B: a phase 2 randomized controlled trial
Authors: Yuen Man-Fung , Heo Jeong , Jang Jeong-Won , Yoon Jung-Hwan , Kweon Young-Oh , Park Sung-Jae , Tami Yvonne , You Shihyun , Yates Phillip , Tao Yu , Cremer Jennifer , Campbell Fiona , Elston Robert , Theodore Dickens , Paff Melanie , Bennett C. Frank , Kwoh T. Jesse
Published: October 2021

Chronic infection with hepatitis B virus (HBV) leads to an increased risk of death from cirrhosis and hepatocellular carcinoma. Functional cure rates are low with current treatment options (nucleos(t)ide analogs (NAs) and pegylated interferons). Bepirovirsen is an antisense oligonucleotide targeting all HBV messenger RNAs; in cell culture and animal models, bepirovirsen leads to reductions in HBV-derived RNAs, HBV DNA and viral proteins. This phase 2 double-blinded, randomized, placebo-controlled trial is the first evaluation of the safety and activity of an antisense oligonucleotide targeting HBV RNA in both treatment-naïve and virally suppressed individuals with chronic HBV infection. The primary objective was to assess the safety and tolerability of bepirovirsen in individuals with chronic hepatitis B (CHB) (NCT02981602). The secondary objective was to assess antiviral activity, including the change from baseline to day 29 in serum hepatitis B surface antigen (HBsAg) concentration. Participants with CHB infection ≥6 months and serum HBsAg ≥50 IU ml−1were enrolled from seven centers across Hong Kong and the Republic of Korea and randomized (3:1 within each dose cohort) to receive bepirovirsen or placebo via subcutaneous injection twice weekly during weeks 1 and 2 (days 1, 4, 8 and 11) and once weekly during weeks 3 and 4 (days 15 and 22). Participants were then followed for 26 weeks. Twenty-four participants were treatment-naïve and seven were receiving stable NA therapy. Treatment-emergent adverse events were mostly mild/moderate (most commonly injection site reactions). Eleven (61.1%) and three (50.0%) treatment-naïve participants experienced one or more treatment-emergent adverse event in the bepirovirsen and placebo groups, respectively. In participants receiving NA therapy, the corresponding numbers were three (60.0%) and one (50.0%). Transient, self-resolving alanine aminotransferase flares (≥2× upper limit of normal) were observed in eight treatment-naïve participants and three participants on stable NA regimens in the bepirovirsen treatment arms. HBsAg reductions were observed and were significant versus placebo for treatment-naïve participants receiving bepirovirsen 300 mg (P = 0.001), but not for the bepirovirsen 150 mg group (P = 0.245) or participants receiving stable NA therapy (P = 0.762). Two participants in each of the 300 mg dose groups achieved HBsAg levels below the lower limit of quantitation by day 29 (n = 3) or day 36 (n = 1). Bepirovirsen had a favorable safety profile. These preliminary observations warrant further investigation of the safety and activity of bepirovirsen in a larger CHB patient population.
A pilot study about the development and characterization of a Roux en Y gastric bypass model in obese Yucatan minipigs
Authors: Bergeat Damien , Blat S. , Gautier Y. , Guérin S. , Le Huërou-Luron I. , Thibault R. , Val-Laillet D.
Published: October 2021

Performing the Roux-en-Y gastric bypass (RYGBP) in obese Yucatan minipigs provides an opportunity to explore the mechanisms behind the effects of this surgery in controlled environmental and nutritional conditions. We hypothesized that RYGBP in these minipigs would induce changes at multiple levels, as in obese humans. We sought to characterize RYGBP in a diet-induced obese minipig model, compared with a pair-fed sham group. After inducing obesity with an ad libitum high-fat/high-sugar diet, we performed RYGBP (n = 7) or sham surgery (n = 6). Oral glucose tolerance tests (OGTT) were performed before and after surgery. Histological analyses were conducted to compare the alimentary limb at sacrifice with tissue sampled during RYGBP surgery. One death occurred in the RYGBP group at postoperative day (POD) 3. Before sacrifice, weight loss was the same across groups. GLP-1 secretion (OGTT) was significantly higher at 15, 30 and 60 min at POD 7, and at 30 and 60 min at POD 30 in the RYGBP group. Incremental insulin area under the curve increased significantly after RYGBP (p = 0.02). RYGBP induced extensive remodeling of the alimentary limb. Results show that RYGBP can be safely performed in obese minipigs, and changes mimic those observed in humans.
First report of an egg-predator nemertean worm in crabs from the south-eastern Pacific coast: Carcinonemertes camanchaco sp. nov
Authors: Leiva Natalia Verónica , Ñacari Luis , Baeza Juan Antonio , González María Teresa
Published: October 2021

Nemertean worms belonging to the genus Carcinonemertes have been tied to the collapse of crab fisheries in the northeastern Pacific Ocean. A new species is described from egg masses of two commercial crabs, Cancer porteri and Romaleon setosum, inhabiting the central-north Chilean coast. This is the first species of Carcinonemertes described from the southeastern Pacific Ocean. Total body length of Carcinonemertes camanchaco sp. nov. ranged from 2.38 to 4.93 and from 4.29 to 8.92 mm, in males and females, respectively. Among others, traits that distinguish this new species from other previously described congeneric species include: presence of two gonad rows on each side of the intestine, a simple (not decorated) mucus sheath, and a relatively wide stylet basis. Maximum likelihood and Bayesian inference phylogenetic analyses distinguished this new species from all other species of Carcinonemertes with available cox1 sequences in GenBank. Prevalence and mean (± SD) intensity of C. camanchaco sp. nov. was 24% and 2.6 (± 2.07) worms per egg mass in C. porteri and 38.1% and 3.8 (± 2.4) worms per egg mass in R. setosum. The formal description of this new species represents the first step towards the understanding of this worm's impact on the health of crab fisheries in the southeastern Pacific Ocean.
Integrated analysis of dysregulated microRNA and mRNA expression in intestinal epithelial cells following ethanol intoxication and burn injury
Authors: Herrnreiter C. J. , Li X. , Luck M. E. , Zilliox M. J. , Choudhry Mashkoor A.
Published: October 2021

Gut barrier dysfunction is often implicated in pathology following alcohol intoxication and burn injury. MicroRNAs (miRNAs) are negative regulators of gene expression that play a central role in gut homeostasis, although their role after alcohol and burn injury is poorly understood. We performed an integrated analysis of miRNA and RNA sequencing data to identify a network of interactions within small intestinal epithelial cells (IECs) which could promote gut barrier disruption. Mice were gavaged with ~ 2.9 g/kg ethanol and four hours later given a ~ 12.5% TBSA full thickness scald injury. One day later, IECs were harvested and total RNA extracted for RNA-seq and miRNA-seq. RNA sequencing showed 712 differentially expressed genes (DEGs) (padj < 0.05) in IECs following alcohol and burn injury. Furthermore, miRNA sequencing revealed 17 differentially expressed miRNAs (DEMs) (padj < 0.1). Utilizing the miRNet, miRDB and TargetScan databases, we identified both validated and predicted miRNA gene targets. Integration of small RNA sequencing data with mRNA sequencing results identified correlated changes in miRNA and target expression. Upregulated miRNAs were associated with decreased proliferation (miR-98-3p and miR-381-3p) and cellular adhesion (miR-29a-3p, miR-429-3p and miR3535), while downregulated miRNAs were connected to upregulation of apoptosis (Let-7d-5p and miR-130b-5p) and metabolism (miR-674-3p and miR-185-5p). Overall, these findings suggest that alcohol and burn injury significantly alters the mRNA and miRNA expression profile of IECs and reveals numerous miRNA–mRNA interactions that regulate critical pathways for gut barrier function after alcohol and burn injury.
hSSB2 (NABP1) is required for the recruitment of RPA during the cellular response to DNA UV damage
Authors: Boucher Didier , Kariawasam Ruvini , Burgess Joshua , Gimenez Adrian , Ocampo Tristan E. , Ferguson Blake , Naqi Ali , Walker Graeme J. , Bolderson Emma , Gamsjaeger Roland , O’Byrne Kenneth J. , Cubeddu Liza , Khanna Kum Kum , Richard Derek J.
Published: October 2021

Maintenance of genomic stability is critical to prevent diseases such as cancer. As such, eukaryotic cells have multiple pathways to efficiently detect, signal and repair DNA damage. One common form of exogenous DNA damage comes from ultraviolet B (UVB) radiation. UVB generates cyclobutane pyrimidine dimers (CPD) that must be rapidly detected and repaired to maintain the genetic code. The nucleotide excision repair (NER) pathway is the main repair system for this type of DNA damage. Here, we determined the role of the human Single-Stranded DNA Binding protein 2, hSSB2, in the response to UVB exposure. We demonstrate that hSSB2 levels increase in vitro and in vivo after UVB irradiation and that hSSB2 rapidly binds to chromatin. Depletion of hSSB2 results in significantly decreased Replication Protein A (RPA32) phosphorylation and impaired RPA32 localisation to the site of UV-induced DNA damage. Delayed recruitment of NER protein Xeroderma Pigmentosum group C (XPC) was also observed, leading to increased cellular sensitivity to UVB. Finally, hSSB2 was shown to have affinity for single-strand DNA containing a single CPD and for duplex DNA with a two-base mismatch mimicking a CPD moiety. Altogether our data demonstrate that hSSB2 is involved in the cellular response to UV exposure.
Intermittent radiotherapy as alternative treatment for recurrent high grade glioma: a modeling study based on longitudinal tumor measurements
Authors: Brüningk Sarah C. , Peacock Jeffrey , Whelan Christopher J. , Brady-Nicholls Renee , Yu Hsiang-Hsuan M. , Sahebjam Solmaz , Enderling Heiko
Published: October 2021

Recurrent high grade glioma patients face a poor prognosis for which no curative treatment option currently exists. In contrast to prescribing high dose hypofractionated stereotactic radiotherapy (HFSRT, $$\ge 6$$

≥
6

Gy $$\times$$
×
5 in daily fractions) with debulking intent, we suggest a personalized treatment strategy to improve tumor control by delivering high dose intermittent radiation treatment (iRT, $$\ge 6$$

≥
6

Gy $$\times$$
×
1 every 6 weeks). We performed a simulation analysis to compare HFSRT, iRT and iRT plus boost ($$\ge 6$$

≥
6

Gy $$\times$$
×
3 in daily fractions at time of progression) based on a mathematical model of tumor growth, radiation response and patient-specific evolution of resistance to additional treatments (pembrolizumab and bevacizumab). Model parameters were fitted from tumor growth curves of 16 patients enrolled in the phase 1 NCT02313272 trial that combined HFSRT with bevacizumab and pembrolizumab. Then, iRT +/− boost treatments were simulated and compared to HFSRT based on time to tumor regrowth. The modeling results demonstrated that iRT + boost(− boost) treatment was equal or superior to HFSRT in 15(11) out of 16 cases and that patients that remained responsive to pembrolizumab and bevacizumab would benefit most from iRT. Time to progression could be prolonged through the application of additional, intermittently delivered fractions. iRT hence provides a promising treatment option for recurrent high grade glioma patients for prospective clinical evaluation.
The surgical effect on overactive bladder symptoms in women with pelvic organ prolapse
Authors: Wu Ling-Ying , Huang Kuan-Hui , Yang Tsai-Hwa , Huang Hui-Shan , Wang Tzu-Shu , Lan Kuo-Chung , Chuang Fei-Chi
Published: October 2021

This study aimed to explore the effect of pelvic reconstruction surgery on the relation of pelvic organ prolapse (POP) and overactive bladder (OAB) and the impact of preoperative vaginal oestrogen supplement on vaginal tissue. A total of 100 postmenopausal women with symptomatic POP who underwent pelvic reconstruction surgery (laparoscopic sacrocolpopexy or transvaginal mesh) were enrolled in this study. Preoperative vaginal oestrogen was prescribed in 28 cases. The evaluation tools consisted of POP-Q, urodynamic study, Overactive Bladder Symptom Score (OABSS), and urinary NGF. Vaginal maturation index and vaginal specimens for hormone receptors study were investigated during operation to evaluate the effect of topical oestrogen. Follow-up assessments were performed at 1, 3, and 6 months after surgery. Preoperatively, 58 (58%) were POP with OAB. After reconstruction surgery, the OABSS decreased significantly (6.87 ± 0.85 vs 3.77 ± 0.61, p < 0.001) at postoperative 6 months in the group. Remarkable increasing trends of urinary NGF levels are noted till 3 months postoperatively, then decreasing to the baseline level at 6 months postoperative follow-up. Remarkable decrease of mRNA of the androgen receptor and significant higher expression of progesterone receptor (PR) were noted after use of the vaginal oestrogen cream. The severity of OAB in the POP women shows moderate degree according to OABSS. Pelvic reconstruction surgery can significantly improve the OAB symptoms. The surgery induced inflammation effect lasts for about 6 months. Short-term preoperative supplement of topical oestrogen brings alterations of the vaginal epithelium.
Cesarean section was not associated with mortality or morbidities advantage in very low birth weight infants: a nationwide cohort study
Authors: Kim Jin Kyu , Chang Yun Sil , Hwang Jong Hee , Lee Myung Hee , Park Won Soon
Published: October 2021

This study investigated the role of cesarean section (CS) in mortality and morbidity of very-low-birth-weight infants (VLBWIs) weighing less than 1500 g. This nationwide prospective cohort study of the Korean Neonatal Network consisted of 9,286 VLBWIs at 23–34 gestational weeks (GW) of age between 2013 and 2017. The VLBWIs were stratified into 23–24, 25–26, 27–28 and 29–34 GW, and the mortality and morbidity were compared according to the mode of delivery. The total CS rate was 78%, and was directly proportional to gestational age. The CS rate was the lowest at 61% in case of infants born at 23–24 GW and the highest at 84% in VLBWIs delivered at 29–34 GW. Contrary to the significantly lower total mortality (12%) and morbidities including sepsis (21%) associated with CS than vaginal delivery (VD) (16% and 24%, respectively), the mortality in the 25–26 GW (26%) and sepsis in the 27–28 GW (25%) and 29–34 GW (12%) groups were significantly higher in CS than in VD (21%, 20% and 8%, respectively). In multivariate analyses, the adjusted odds ratios (ORs) for mortality (OR 1.06, 95% CI 0.89–1.25) and morbidity including sepsis (OR 1.12, 95% CI 0.98–1.27) were not significantly reduced with CS compared with VD. The adjusted ORs for respiratory distress syndrome (1.89, 95% CI 1.59–2.23) and symptomatic patent ductus arteriosus (1.21, 95% CI 1.08–1.37) were significantly increased with CS than VD. In summary, CS was not associated with any survival or morbidity advantage in VLBWIs. These findings indicate that routine CS in VLBWIs without obstetric indications is contraindicated.
Mitochondrial superoxide dismutase overexpression and low oxygen conditioning hormesis improve the performance of irradiated sterile males
Authors: Dias Vanessa S. , Cáceres Carlos , Parker Andrew G. , Pereira Rui , Demirbas-Uzel Güler , Abd-Alla Adly M. M. , Teets Nicholas M. , Schetelig Marc F. , Handler Alfred M. , Hahn Daniel A.
Published: October 2021

The Sterile Insect Technique (SIT) is a successful autocidal control method that uses ionizing radiation to sterilize insects. However, irradiation in normal atmospheric conditions can be damaging for males, because irradiation generates substantial biological oxidative stress that, combined with domestication and mass-rearing conditions, may reduce sterile male sexual competitiveness and quality. In this study, biological oxidative stress and antioxidant capacity were experimentally manipulated in Anastrepha suspensa using a combination of low-oxygen conditions and transgenic overexpression of mitochondrial superoxide dismutase (SOD2) to evaluate their role in the sexual behavior and quality of irradiated males. Our results showed that SOD2 overexpression enhances irradiated insect quality and improves male competitiveness in leks. However, the improvements in mating performance were modest, as normoxia-irradiated SOD2 males exhibited only a 22% improvement in mating success compared to normoxia-irradiated wild type males. Additionally, SOD2 overexpression did not synergistically improve the mating success of males irradiated in either hypoxia or severe hypoxia. Short-term hypoxic and severe-hypoxic conditioning hormesis, per se, increased antioxidant capacity and enhanced sexual competitiveness of irradiated males relative to non-irradiated males in leks. Our study provides valuable new information that antioxidant enzymes, particularly SOD2, have potential to improve the quality and lekking performance of sterile males used in SIT programs.
Identification and characterization of a novel Enterococcus bacteriophage with potential to ameliorate murine colitis
Authors: Nishio Junko , Negishi Hideo , Yasui-Kato Mika , Miki Shoji , Miyanaga Kazuhiko , Aoki Kotaro , Mizusawa Takuma , Ueno Masami , Ainai Akira , Muratani Masafumi , Hangai Sho , Yanai Hideyuki , Hasegawa Hideki , Ishii Yoshikazu , Tanji Yasunori , Taniguchi Tadatsugu
Published: October 2021

Increase of the enteric bacteriophages (phage), components of the enteric virome, has been associated with the development of inflammatory bowel diseases. However, little is known about how a given phage contributes to the regulation of intestinal inflammation. In this study, we isolated a new phage associated with Enterococcus gallinarum, named phiEG37k, the level of which was increased in C57BL/6 mice with colitis development. We found that, irrespective of the state of inflammation, over 95% of the E. gallinarum population in the mice contained phiEG37k prophage within their genome and the phiEG37k titers were proportional to that of E. gallinarum in the gut. To explore whether phiEG37k impacts intestinal homeostasis and/or inflammation, we generated mice colonized either with E. gallinarum with or without the prophage phiEG37k. We found that the mice colonized with the bacteria with phiEG37k produced more Mucin 2 (MUC2) that serves to protect the intestinal epithelium, as compared to those colonized with the phage-free bacteria. Consistently, the former mice were less sensitive to experimental colitis than the latter mice. These results suggest that the newly isolated phage has the potential to protect the host by strengthening mucosal integrity. Our study may have clinical implication in further understanding of how bacteriophages contribute to the gut homeostasis and pathogenesis.
Evaluation of the influence of platelet-rich plasma (PRP), platelet lysate (PL) and mechanical loading on chondrogenesis in vitro
Authors: Pötter N. , Westbrock F. , Grad S. , Alini M. , Stoddart M. J. , Schmal H. , Kubosch D. , Salzmann G. , Kubosch E. J.
Published: October 2021

The aim of this work is to investigate the capability of PRP as an adjuvant therapy to autologous chondrocyte implantation (ACI) in combination with multi-axial load with respect to cartilage regeneration. Articular cartilage shows poor repair capacity and therapies for cartilage defects are still lacking. Well-established operative treatments include ACI, and growing evidence shows the beneficial effects of PRP. Platelets contain numerous growth factors, among them transforming growth factor beta (TGF-β). Dynamic mechanical loading is known to be essential for tissue formation, improving extracellular matrix (ECM) production. For our ACI model monolayer expanded human chondrocytes were seeded into polyurethane scaffolds and embedded in fibrin (hChondro), in PRP-Gel (PRP), or in fibrin with platelet lysate (PL), which was added to the media once a week with a concentration of 50 vol%. The groups were either exposed to static conditions or multi-axial forces in a ball-joint bioreactor for 1 h per day over 2 weeks, mimicking ACI under physiological load. The culture medium was collected and analyzed for glycosaminoglycan (GAG), nitrite and transforming growth factor beta 1 (TGF-β1) content. The cell-scaffold constructs were collected for DNA and GAG quantification; the expression of chondrogenic genes, TGF-β and related receptors, as well as inflammatory genes, were analyzed using qPCR. Loading conditions showed superior chondrogenic differentiation (upregulation of COL2A1, ACAN, COMP and PRG4 expression) than static conditions. PRP and PL groups combined with mechanical loading showed upregulation of COL2A1, ACAN and COMP. The highest amount of total TGF-β1 was quantified in the PL group. Latent TGF-β1 was activated in all loaded groups, while the highest amount was found in the PL group. Load increased TGFBR1/TGFBR2 mRNA ratio, with further increases in response to supplements. In general, loading increased nitrite release into the media. However, over time, the media nitrite content was lower in the PL group compared to the control group. Based on these experiments, we conclude that chondrogenic differentiation is strongest when simulated ACI is performed in combination with dynamic mechanical loading and PRP-gel or PL supplementation. An inflammatory reaction was reduced by PRP and PL, which could be one of the major therapeutic effects. Loading presumably can enhance the action of TGF-β1, which was predominantly activated in loaded PL groups. The combination of load and PRP represents an effective and promising synergy concerning chondrocyte-based cartilage repair.
A vehicle re-identification framework based on the improved multi-branch feature fusion network
Authors: Rong Leilei , Xu Yan , Zhou Xiaolei , Han Lisu , Li Linghui , Pan Xuguang
Published: October 2021

Vehicle re-identification (re-id) aims to solve the problems of matching and identifying the same vehicle under the scenes across multiple surveillance cameras. For public security and intelligent transportation system (ITS), it is extremely important to locate the target vehicle quickly and accurately in the massive vehicle database. However, re-id of the target vehicle is very challenging due to many factors, such as the orientation variations, illumination changes, occlusion, low resolution, rapid vehicle movement, and amounts of similar vehicle models. In order to resolve the difficulties and enhance the accuracy for vehicle re-id, in this work, we propose an improved multi-branch network in which global–local feature fusion, channel attention mechanism and weighted local feature are comprehensively combined. Firstly, the fusion of global and local features is adopted to obtain more information of the vehicle and enhance the learning ability of the model; Secondly, the channel attention module in the feature extraction branch is embedded to extract the personalized features of the targeting vehicle; Finally, the background and noise information on feature extraction is controlled by weighted local feature. The results of comprehensive experiments on the mainstream evaluation datasets including VeRi-776, VRIC, and VehicleID indicate that our method can effectively improve the accuracy of vehicle re-identification and is superior to the state-of-the-art methods.
Efficient marmoset genome engineering by autologous embryo transfer and CRISPR/Cas9 technology
Authors: Abe Yukiko , Nakao Harumi , Goto Motoki , Tamano Moe , Koebis Michinori , Nakao Kazuki , Aiba Atsu
Published: October 2021

Genetic engineering of non-human primates, which are most closely related to humans, has been expected to generate ideal animal models for human genetic diseases. The common marmoset (Callithrix jacchus) is a non-human primate species adequate for the production of genetically modified animals because of their small body size and high reproductive capacity. Autologous embryo transfer (AET) is routinely utilized in assisted reproductive technologies for humans but not for experimental animals. This study has developed a novel method for efficiently producing mutant marmosets using AET and CRISPR/Cas9 systems. The embryos were recovered from oviducts of naturally mated females, injected with Cas9/guide RNA, and transferred into the oviducts of the donors. This AET method can reduce the time for in vitro culture of embryos to less than 30 min. This method uses an embryo donor as the recipient, thus reducing the number of animals and allowing for “Reduction” in the 3R principles of humane experimental technique. Furthermore, this method can utilize nulliparous females as well as parous females. We applied our novel method and generated the 6 marmosets carrying mutations in the fragile X mental retardation 1 (FMR1) gene using only 18 females including 14 nulliparous females.
High sodium ionic conductivity in PEO/PVP solid polymer electrolytes with InAs nanowire fillers
Authors: Devi Chandni , Gellanki Jnaneswari , Pettersson Håkan , Kumar Sandeep
Published: October 2021

Solid-state sodium ion batteries are frequently referred to as the most promising technology for next-generation energy storage applications. However, developing a suitable solid electrolyte with high ionic conductivity, excellent electrolyte–electrode interfaces, and a wide electrochemical stability window, remains a major challenge. Although solid-polymer electrolytes have attracted great interest due to their low cost, low density and very good processability, they generally have significantly lower ionic conductivity and poor mechanical strength. Here, we report on the development of a low-cost composite solid polymer electrolyte comprised of poly(ethylene oxide), poly(vinylpyrrolidone) and sodium hexafluorophosphate, mixed with indium arsenide nanowires. We show that the addition of 1.0% by weight of indium arsenide nanowires increases the sodium ion conductivity in the polymer to 1.50 × 10−4 Scm−1 at 40 °C. In order to explain this remarkable characteristic, we propose a new transport model in which sodium ions hop between close-spaced defect sites present on the surface of the nanowires, forming an effective complex conductive percolation network. Our work represents a significant advance in the development of novel solid polymer electrolytes with embedded engineered ultrafast 1D percolation networks for near-future generations of low-cost, high-performance batteries with excellent energy storage capabilities.
Life expectancy of older people living in aged care facilities after a hip fracture
Authors: Liu Enwu , Killington Maggie , Cameron Ian D. , Li Raymond , Kurrle Susan , Crotty Maria
Published: October 2021

To the authors’ knowledge, no study has been conducted on life expectancy for aged care facility residents with hip fracture. We assessed life expectancy of 240 residents of aged care facilities in Australia who experienced recent hip fracture treated with surgery. 149 deaths occurred over a mean follow-up of 1.2 years. Being female and having better cognition were associated with longer life expectancy. Increased age was associated with shorter life expectancy. The cumulative mortality rate within three months after hip fracture was 25.0% while the cumulative mortality rate for the whole study period was 62.1%. Life expectancy was 8.2 years, 4.8 years and 2.8 years for 70, 80 and 90-years old female patients. Life expectancy was 3.8 years, 2.2 years and 1.3 years for 70, 80 and 90 years old male patients, respectively. In conclusion, age, gender and cognition level were associated with life expectancy of hip fracture patients living in aged care facilities and their life expectancy was much shorter than that of the general Australian population.
Signal complexity indicators of health status in clinical EEG
Authors: Shen Kelly , McFadden Alison , McIntosh Anthony R.
Published: October 2021

Brain signal variability changes across the lifespan in both health and disease, likely reflecting changes in information processing capacity related to development, aging and neurological disorders. While signal complexity, and multiscale entropy (MSE) in particular, has been proposed as a biomarker for neurological disorders, most observations of altered signal complexity have come from studies comparing patients with few to no comorbidities against healthy controls. In this study, we examined whether MSE of brain signals was distinguishable across patient groups in a large and heterogeneous set of clinical-EEG data. Using a multivariate analysis, we found unique timescale-dependent differences in MSE across various neurological disorders. We also found MSE to differentiate individuals with non-brain comorbidities, suggesting that MSE is sensitive to brain signal changes brought about by metabolic and other non-brain disorders. Such changes were not detectable in the spectral power density of brain signals. Our findings suggest that brain signal complexity may offer complementary information to spectral power about an individual’s health status and is a promising avenue for clinical biomarker development.
HLA-E circulating and genetic determinants in schizophrenia and bipolar disorder
Authors: Boukouaci Wahid , Lajnef Mohamed , Richard Jean-Romain , Wu Ching-Lien , Bouassida Jihène , Rafik Ismail , Foiselle Marianne , Straczek Céline , Mezouad Esma , Naamoune Soumia , Salah Sofiane , Bencharif Mohamed Amin , Ben Chaaben Arij , Barau Caroline , Le Corvoisier Philippe , Leboyer Marion , Tamouza Ryad
Published: October 2021

Schizophrenia (SZ) and bipolar disorders (BD) are severe mental illnesses that lack reliable biomarkers to guide diagnosis and management. As immune dysregulation is associated with these disorders, we utilized the immunoregulatory functions of the natural killer cell inhibitory HLA-E locus to investigate the relationships between HLA-E genetic and expression diversities with SZ and BD risk and severity. Four hundred and forty-four patients meeting DSM-IV criteria for SZ (N = 161) or BD (N = 283) were compared to 160 heathy controls (HC). Circulating levels of the soluble isoform of HLA-E molecules (sHLA-E) were measured and HLA-E*01:01 and HLA-E*01:03 variants genotyped in the whole sample. sHLA-E circulating levels were significantly higher in both SZ and in BD patients compared to HC (pc < 0.0001 and pc = 0.0007 for SZ and BD, respectively). High sHLA-E levels were also observed in stable SZ patients and in acute BD patients experiencing depressive episodes when comparisons were made between the acute and stable subgroups of each disorder. sHLA-E levels linearly increased along HLA-E genotypes (p = 0.0036). In conclusion, HLA-E variants and level may have utility as diagnostic biomarkers of SZ and BD. The possible roles of HLA diversity in SZ and BD etiology and pathophysiology are discussed.
Nobiletin-loaded composite penetration enhancer vesicles restore the normal miRNA expression and the chief defence antioxidant levels in skin cancer
Authors: Bayoumi Mahitab , Arafa Mona G. , Nasr Maha , Sammour Omaima A.
Published: October 2021

Skin cancer is one of the most dangerous diseases, leading to massive losses and high death rates worldwide. Topical delivery of nutraceuticals is considered a suitable approach for efficient and safe treatment of skin cancer. Nobiletin; a flavone occurring in citrus fruits has been reported to inhibit proliferation of carcinogenesis since 1990s, is a promising candidate in this regard. Nobiletin was loaded in various vesicular systems to improve its cytotoxicity against skin cancer. Vesicles were prepared using the thin film hydration method, and characterized for particle size, zeta potential, entrapment efficiency, TEM, ex-vivo skin deposition and physical stability. Nobiletin-loaded composite penetration enhancer vesicles (PEVs) and composite transfersomes exhibited particle size 126.70 ± 11.80 nm, 110.10 ± 0.90 nm, zeta potential + 6.10 ± 0.40 mV, + 9.80 ± 2.60 mV, entrapment efficiency 93.50% ± 3.60, 95.60% ± 1.50 and total skin deposition 95.30% ± 3.40, 100.00% ± 2.80, respectively. These formulations were selected for cytotoxicity study on epidermoid carcinoma cell line (A431). Nobiletin-loaded composite PEVs displayed the lowest IC50 value, thus was selected for the in vivo study, where it restored skin condition in DMBA induced skin carcinogenesis mice, as delineated by histological and immuno-histochemical analysis, biochemical assessment of skin oxidative stress biomarkers, in addition to miRNA21 and miRNA29A. The outcomes confirmed that nobiletin- loaded composite PEVs is an efficient delivery system combating skin cancer.
The combination of acute exercise and eye closure has a synergistic effect on alpha activity
Authors: Komiyama Takaaki , Goya Ryoma , Aoyama Chisa , Yokota Yusuke , Naruse Yasushi , Shimegi Satoshi
Published: October 2021

Acute aerobic exercise increases the brain cortical activity in alpha frequency. Eye closure also increases alpha activity. However, whether the two have an additive or a synergistic effect on alpha activity has never been explored. This study observed electroencephalography (EEG) from fifteen participants seated on the cycle ergometer before, during, and after a cycling exercise with the eyes open and with them closed. Exercise intensity was set to a target heart rate (120–130 bpm), corresponding to light-to-moderate intensity exercise. Each epoch was 6 min and the last 4 min (eyes closed in the first 2 min and eyes open in the second 2 min) were analyzed. The EEG power spectrum densities were calculated for alpha frequency band activity (8–13 Hz). At rest, alpha activity was significantly greater with the eyes closed than open. Exercise significantly increased alpha activity in both eye conditions. More importantly, in the occipital site, the alpha-increasing effect of their combination was significantly greater than the sum of the effect of each, showing a synergistic effect. We concluded that acute light-to-moderate intensity exercise with the eyes closed has a synergistic effect on alpha activity.
Chronic kidney disease is associated with increased risk of sudden sensorineural hearing loss and Ménière’s disease: a nationwide cohort study
Authors: Kim Jong-Yeup , Lee Suehyun , Cha Jaehun , Son Gilmyeong , Kim Dong-Kyu
Published: October 2021

Several studies have demonstrated the harmful effects of chronic kidney disease (CKD) on the audiovestibular system. Through a time-to-event analysis, we aimed to compare the association of CKD with sudden sensorineural hearing loss (SSNHL), and Ménière’s disease against a control population without CKD. We used a total of 1,025,340 patients from the Korean National Health Insurance Service database from 2002 to 2013. The CKD group (n = 2572) included patients diagnosed with CKD more than three times between January 2003 and December 2005. The non-CKD group (n = 5144) consisted of two patients without CKD for every patient with CKD. Each patient was monitored until December 2013. We calculated the incidence, survival rate, and hazards ratio (HR) of SSNHL and Ménière’s disease. In the CKD group, the incidence of SSNHL and Ménière’s disease was 1.39 and 3.64 per 1000 person-years, respectively. Patients with CKD showed an adjusted HR of 2.15 and 1.45 for SSNHL and Ménière’s disease, respectively. Middle-aged patients with CKD were associated with a higher incidence of developing SSNHL and Ménière’s disease than those without CKD. Female patients with CKD had a higher risk of developing SSNHL; however, there was no significant difference in the risk of Ménière’s disease in patients with CKD according to sex. Our findings suggest that CKD is associated with an increased incidence of SSNHL and Ménière’s disease. Therefore, audiovestibular surveillance should be considered in patients with CKD.
Machine learning for early discrimination between transient and persistent acute kidney injury in critically ill patients with sepsis
Authors: Luo Xiao-Qin , Yan Ping , Zhang Ning-Ya , Luo Bei , Wang Mei , Deng Ying-Hao , Wu Ting , Wu Xi , Liu Qian , Wang Hong-Shen , Wang Lin , Kang Yi-Xin , Duan Shao-Bin
Published: October 2021

Acute kidney injury (AKI) is commonly present in critically ill patients with sepsis. Early prediction of short-term reversibility of AKI is beneficial to risk stratification and clinical treatment decision. The study sought to use machine learning methods to discriminate between transient and persistent sepsis-associated AKI. Septic patients who developed AKI within the first 48 h after ICU admission were identified from the Medical Information Mart for Intensive Care III database. AKI was classified as transient or persistent according to the Acute Disease Quality Initiative workgroup consensus. Five prediction models using logistic regression, random forest, support vector machine, artificial neural network and extreme gradient boosting were constructed, and their performance was evaluated by out-of-sample testing. A simplified risk prediction model was also derived based on logistic regression and features selected by machine learning algorithms. A total of 5984 septic patients with AKI were included, 3805 (63.6%) of whom developed persistent AKI. The artificial neural network and logistic regression models achieved the highest area under the receiver operating characteristic curve (AUC) among the five machine learning models (0.76, 95% confidence interval [CI] 0.74–0.78). The simplified 14-variable model showed adequate discrimination, with the AUC being 0.76 (95% CI 0.73–0.78). At the optimal cutoff of 0.63, the sensitivity and specificity of the simplified model were 63% and 76% respectively. In conclusion, a machine learning-based simplified prediction model including routine clinical variables could be used to differentiate between transient and persistent AKI in critically ill septic patients. An easy-to-use risk calculator can promote its widespread application in daily clinical practice.