bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peptidoglycan maturation controls outer membrane protein assembly
Authors: Mamou Gideon , Corona Federico , Cohen-Khait Ruth , Housden Nicholas G. , Yeung Vivian , Sun Dawei , Sridhar Pooja , Pazos Manuel , Knowles Timothy J. , Kleanthous Colin , Vollmer Waldemar 
Published: June 2022

AbstractLinkages between the outer membrane of Gram-negative bacteria and the peptidoglycan layer are crucial for the maintenance of cellular integrity and enable survival in challenging environments1–5. The function of the outer membrane is dependent on outer membrane proteins (OMPs), which are inserted into the membrane by the β-barrel assembly machine6,7 (BAM). Growing Escherichia coli cells segregate old OMPs towards the poles by a process known as binary partitioning, the basis of which is unknown8. Here we demonstrate that peptidoglycan underpins the spatiotemporal organization of OMPs. Mature, tetrapeptide-rich peptidoglycan binds to BAM components and suppresses OMP foldase activity. Nascent peptidoglycan, which is enriched in pentapeptides and concentrated at septa9, associates with BAM poorly and has little effect on its activity, leading to preferential insertion of OMPs at division sites. The synchronization of OMP biogenesis with cell wall growth results in the binary partitioning of OMPs as cells divide. Our study reveals that Gram-negative bacteria coordinate the assembly of two major cell envelope layers by rendering OMP biogenesis responsive to peptidoglycan maturation, a potential vulnerability that could be exploited in future antibiotic design.
Label-free prediction of cell painting from brightfield images
Authors: Cross-Zamirski Jan Oscar , Mouchet Elizabeth , Williams Guy , Schönlieb Carola-Bibiane , Turkki Riku , Wang Yinhai 
Published: June 2022

AbstractCell Painting is a high-content image-based assay applied in drug discovery to predict bioactivity, assess toxicity and understand mechanisms of action of chemical and genetic perturbations. We investigate label-free Cell Painting by predicting the five fluorescent Cell Painting channels from brightfield input. We train and validate two deep learning models with a dataset representing 17 batches, and we evaluate on batches treated with compounds from a phenotypic set. The mean Pearson correlation coefficient of the predicted images across all channels is 0.84. Without incorporating features into the model training, we achieved a mean correlation of 0.45 with ground truth features extracted using a segmentation-based feature extraction pipeline. Additionally, we identified 30 features which correlated greater than 0.8 to the ground truth. Toxicity analysis on the label-free Cell Painting resulted a sensitivity of 62.5% and specificity of 99.3% on images from unseen batches. We provide a breakdown of the feature profiles by channel and feature type to understand the potential and limitations of label-free morphological profiling. We demonstrate that label-free Cell Painting has the potential to be used for downstream analyses and could allow for repurposing imaging channels for other non-generic fluorescent stains of more targeted biological interest.
Prospective intraoperative and histologic evaluation of cavernous sinus medial wall invasion by pituitary adenomas and its implications for acromegaly remission outcomes
Authors: Mohyeldin Ahmed , Katznelson Laurence J. , Hoffman Andrew R. , Asmaro Karam , Ahmadian Saman S. , Eltobgy Mostafa M. , Nayak Jayakar V. , Patel Zara M. , Hwang Peter H. , Fernandez-Miranda Juan C. 
Published: June 2022

AbstractRecurrence and biochemical remission rates vary widely among different histological subtypes of pituitary adenoma. In this prospective study, we evaluated 107 consecutive primary pituitary adenomas operated on by a single neurosurgeon including 28 corticotroph, 27 gonadotroph, 24 somatotroph, 17 lactotroph, 5 null-cell and 6 plurihormonal. In each case, we performed direct endoscopic intraoperative inspection of the medial wall of the cavernous sinus, which was surgically removed when invasion was visualized. This was performed irrespective of tumor functional status. Medial wall resection was performed in 47% of pituitary adenomas, and 39/50 walls confirmed pathologic evidence of invasion, rendering a positive predictive value of intraoperative evaluation of medial wall invasion of 78%. We show for the first-time dramatic disparities in the frequency of medial wall invasion among pathological subtypes. Somatotroph tumors invaded the medial wall much more often than other adenoma subtypes, 81% intraoperatively and 69% histologically, followed by plurihormonal tumors (40%) and gonadotroph cell tumors (33%), both with intraoperative positive predictive value of 100%. The least likely to invade were corticotroph adenomas, at a rate of 32% intraoperatively and 21% histologically, and null-cell adenomas at 0%. Removal of the cavernous sinus medial wall was not associated with permanent cranial nerve morbidity nor carotid artery injury, although 4 patients (all Knosp 3-4) experienced transient diplopia. Medial wall resection in acromegaly resulted in the highest potential for biochemical remission ever reported, with an average postoperative day 1 GH levels of 0.96 ug/L and surgical remission rates of 92% based on normalization of IGF-1 levels after surgery (mean = 15.56 months; range 3–30 months). Our findings suggest that tumor invasion of the medial wall of the cavernous sinus may explain the relatively low biochemical remission rates currently seen for acromegaly and illustrate the relevance of advanced intradural surgical approaches for successful and durable outcomes in endonasal pituitary surgery for functional adenomas.
Unsupervised learning architecture for classifying the transient noise of interferometric gravitational-wave detectors
Authors: Sakai Yusuke , Itoh Yousuke , Jung Piljong , Kokeyama Keiko , Kozakai Chihiro , Nakahira Katsuko T. , Oshino Shoichi , Shikano Yutaka , Takahashi Hirotaka , Uchiyama Takashi , Ueshima Gen , Washimi Tatsuki , Yamamoto Takahiro , Yokozawa Takaaki 
Published: June 2022

AbstractIn the data obtained by laser interferometric gravitational wave detectors, transient noise with non-stationary and non-Gaussian features occurs at a high rate. This often results in problems such as detector instability and the hiding and/or imitation of gravitational-wave signals. This transient noise has various characteristics in the time–frequency representation, which is considered to be associated with environmental and instrumental origins. Classification of transient noise can offer clues for exploring its origin and improving the performance of the detector. One approach for accomplishing this is supervised learning. However, in general, supervised learning requires annotation of the training data, and there are issues with ensuring objectivity in the classification and its corresponding new classes. By contrast, unsupervised learning can reduce the annotation work for the training data and ensure objectivity in the classification and its corresponding new classes. In this study, we propose an unsupervised learning architecture for the classification of transient noise that combines a variational autoencoder and invariant information clustering. To evaluate the effectiveness of the proposed architecture, we used the dataset (time–frequency two-dimensional spectrogram images and labels) of the Laser Interferometer Gravitational-wave Observatory (LIGO) first observation run prepared by the Gravity Spy project. The classes provided by our proposed unsupervised learning architecture were consistent with the labels annotated by the Gravity Spy project, which manifests the potential for the existence of unrevealed classes.
Ex-vivo study on the surface quality of corneal lenticule and stroma after low energy femtosecond laser lenticule extraction
Authors: Nanavaty Mayank A. , Naveed Hasan , Ashena Zahra , Mukhija Ritika 
Published: June 2022

AbstractThis study aimed to assess the surface quality of cap, stroma and lenticular surfaces created using low-energy femtosecond laser lenticule extraction (Ziemer FEMTO LDV Z8). Twenty-four porcine eyes were divided into four groups (n = 6 each): two with optimal laser power (32%) with posterior curvature equivalent to a spherical correction of -2D and -5D, respectively and the other two with high power (64%) with spherical correction of -2D and -5D respectively. Samples were analysed using scanning electron microscopy (SEM). Surface morphology was evaluated using a standard scoring system; surface relief, surface regularity, extent and position of irregularities were graded by four independent clinicians. Eyes with 32% power and -2D correction had significantly less size of the irregular area than those with -5D; however, no significant difference was found between the two groups with 64% power. When comparing eyes with -2D correction, the size of the irregular area was lesser with 32% power. Surface relief was lesser with -5D correction with 32% power than 64% power. Low-energy femtosecond laser lenticule extraction (Ziemer FEMTO LDV Z8) produces good surface quality results. There is a tendency for smoother surface stromal quality with lower power settings than a higher power.
Mitochondrial complex I dysfunction alters the balance of soluble and membrane-bound TNF during chronic experimental colitis
Authors: Peña-Cearra Ainize , Pascual-Itoiz Miguel Angel , Lavín Jose Luis , Fuertes Miguel , Martín-Ruiz Itziar , Castelo Janire , Palacios Ainhoa , Barriales Diego , Fullaondo Asier , Aransay Ana M , Rodríguez Hector , Anguita Juan , Abecia Leticia 
Published: June 2022

AbstractInflammatory bowel disease (IBD) is a complex, chronic, relapsing and heterogeneous disease induced by environmental, genomic, microbial and immunological factors. MCJ is a mitochondrial protein that regulates the metabolic status of macrophages and their response to translocated bacteria. Previously, an acute murine model of DSS-induced colitis showed increased disease severity due to MCJ deficiency. Unexpectedly, we now show that MCJ-deficient mice have augmented tumor necrosis factor α converting enzyme (TACE) activity in the context of chronic inflammation. This adaptative change likely affects the balance between soluble and transmembrane TNF and supports the association of the soluble form and a milder phenotype. Interestingly, the general shifts in microbial composition previously observed during acute inflammation were absent in the chronic model of inflammation in MCJ-deficient mice. However, the lack of the mitochondrial protein resulted in increased alpha diversity and the reduction in critical microbial members associated with inflammation, such as Ruminococcus gnavus, which could be associated with TACE activity. These results provide evidence of the dynamic metabolic adaptation of the colon tissue to chronic inflammatory changes mediated by the control of mitochondrial function.
Effect of thermal treatment at high temperature on phase stability and transformation of Yb2O3 and Y2O3 co-doped ZrO2 ceramics
Authors: Cao Zheng , An Shengli , Song Xiwen 
Published: June 2022

AbstractY2O3 doped ZrO2 (YSZ) ceramic material is used to protect alloy components worked in high-temperature. But its phase transformation between tetragonal phase and monoclinic phase occurred at 1150 °C leads to YSZ invalid. Therefore, enhancing the phase stability of YSZ is necessary for meeting the demands of the development of thermal barrier coatings (TBC). In this study, X-ray diffraction and Raman spectra were used to explore the phase stability and phase transformation of Yb2O3 and Y2O3 co-doped ZrO2 (YbYSZ) ceramics after heat treatment at 1300 °C with different times. The stability of tetragonal phase is improved by tetragonality decreasing with Yb3+ doped. Simultaneously, the incorporation of Yb3+ leads to O–O coupling, which is beneficial for increasing the concentration of oxygen vacancies near the substituted ions, thereby improving the stability of the crystal. The 6.5YbYSZ ceramic has the best stability after heat treatment at 1300 °C for different times.
The role of titanium surface micromorphology in MG-63 cell motility during osteogenesis
Authors: Jia Fang , Wang Shuxiu , Xu Shulan , Wu Wangxi , Zhou Lei , Zeng Jingsong 
Published: June 2022

AbstractDifferent surface micromorphologies influence osteoblast movements and impact the osteogenesis around implants. In this study, a biomimetic chip that simulates the microenvironment of the implant and bone in vitro was developed (tissue-on-chip of group T and group C) to study the correlation of cell movement velocity (CMV), direction (CMD), acceleration (CMA), and cell attachment number (CA) with the surface micromorphology of the Titanium material. Computational fluid dynamics (CFD) was used for flow analysis. Changes in intraosseous pressure (IOP), local blood perfusion index (LBPI), new bone microstructure, microvessel density (MVD), and bone-implant contact (BIC) in beagle dogs were detected as implant surface alterations. Surface skewness (Ssk) and surface arithmetic mean height (Sa) were the most important negative factors for high CMV, accounting for 51% and 32%, respectively, of all the influencing factors. Higher Ssk (SskT > 0, SskC < 0) and Sa (SaT > SaC) resulted in lower CMV (CMVT:CMVC = 0.41:1), greater CA (CAT:CAC = 1.44:1), and higher BIC (BICT:BICC = 3.06:1) (P < 0.05). The surface micromorphology influenced the CMD of MG-63 cells within 20 μm from the material surface. However, it could not regulate the IOP, LBPI, MVD, new bone microstructure, or CMD (P > 0.05).
Design, synthesis, and biological evaluation of tetrahydroquinolinones and tetrahydroquinolines with anticancer activity
Authors: Ryczkowska Małgorzata , Maciejewska Natalia , Olszewski Mateusz , Witkowska Milena , Makowiec Sławomir 
Published: June 2022

AbstractColorectal cancer (CRC) is the most commonly diagnosed cancer in Europe and the United States and the second leading cause of cancer related mortality. A therapeutic strategy used for the treatment of CRC involves targeting the intracellular levels of reactive oxygen species (ROS). In this study, we synthesized a series of novel tetrahydroquinolinones and assessed their ability to inhibit CRC growth and proliferation by evoking cellular stress through ROS. Our results revealed that (2-oxo-4-phenyl-5,6,7,8-tetrahydroquinolin-8-yl) N-(3-fluorophenyl)carbamate (20d) exhibited in vitro antiproliferative activity at micromolar concentrations. The compound also suppressed colony formation and the migration of HCT-116 cells, as well as deregulated the expression of several proteins involved in cell proliferation and metastasis. Furthermore,20dinduced massive oxidative stress by disrupting the balance of cells survival resulting in autophagy via the PI3K/AKT/mTOR signaling pathway. These findings suggest that this tetrahydroquinolinone can be an ideal lead compound for drug discovery based on quinone derivatives.
A machine learning based model accurately predicts cellular response to electric fields in multiple cell types
Authors: Sargent Brett , Jafari Mohammad , Marquez Giovanny , Mehta Abijeet Singh , Sun Yao-Hui , Yang Hsin-ya , Zhu Kan , Isseroff Roslyn Rivkah , Zhao Min , Gomez Marcella 
Published: June 2022

AbstractMany cell types migrate in response to naturally generated electric fields. Furthermore, it has been suggested that the external application of an electric field may be used to intervene in and optimize natural processes such as wound healing. Precise cell guidance suitable for such optimization may rely on predictive models of cell migration, which do not generalize. Here, we present a machine learning model that can forecast directedness of cell migration given a timeseries of previous directedness and electric field values. This model is trained using time series galvanotaxis data of mammalian cranial neural crest cells obtained through time-lapse microscopy of cells cultured at 37 °C in a galvanotaxis chamber at ambient pressure. Next, we show that our modeling approach can be used for a variety of cell types and experimental conditions with very limited training data using transfer learning methods. We adapt the model to predict cell behavior for keratocytes (room temperature, ~ 18–20 °C) and keratinocytes (37 °C) under similar experimental conditions with a small dataset (~ 2–5 cells). Finally, this model can be used to perform in silico studies by simulating cell migration lines under time-varying and unseen electric fields. We demonstrate this by simulating feedback control on cell migration using a proportional–integral–derivative (PID) controller. This data-driven approach provides predictive models of cell migration that may be suitable for designing electric field based cellular control mechanisms for applications in precision medicine such as wound healing.
Association of hemoglobin levels with bone mineral density for adults over 18 years of age: a cross-sectional study
Authors: Liu Enqi , Hou Xinzheng , Liu Siqi , Han Jing , Lv Hao 
Published: June 2022

AbstractThe overall objective of this study was to determine the association between hemoglobin (HGB) and bone mineral density (BMD) in the lumbar and thoracic spine of adults aged ≥ 18 years. This cross-sectional study utilized the non-institutionalized US population from the National Health and Nutrition Survey (NHANES) as the sample source. A multiple linear regression model was used to assess the relationship between HGB and BMD in the lumbar and thoracic spine, with analysis of subgroups conducted according to sex and race. Smooth curve fitting was performed to explore the potential nonlinear relationship. When nonlinearity was found, we further constructed a weighted two-piecewise linear regression model and used a recursive algorithm to calculate the inflection point. After accounting for relevant confounding variables, HGB was found to be negatively associated with lumbar spine BMD in multiple regression models. However, in the subgroup analyses stratified by sex and race, the relationship between HGB and thoracic spine BMD and lumbar spine BMD was only found in women and other races and races that were not recorded. In Non-Hispanic Asian subjects, the relationship between HGB and BMD in the lumbar spine and thoracic spine showed a U-shaped curve. In addition, the relationship between HGB and BMD in the lumbar spine formed an inverted U-shaped curve among participants in other races and those whose race was not reported. Our study shows that HGB has a non-linear relationship with lumbar and thoracic BMD. Further studies are required to elucidate the mechanisms underlying this association.
Enhanced HIV SOSIP Envelope yields in plants through transient co-expression of peptidyl-prolyl isomerase B and calreticulin chaperones and ER targeting
Authors: Rosenberg Yvonne J. , Jiang Xiaoming , Lees Jonathan P. , Urban Lori A. , Mao Lingjun , Sack Markus 
Published: June 2022

AbstractHigh yield production of recombinant HIV SOSIP envelope (Env) trimers has proven elusive as numerous disulfide bonds, proteolytic cleavage and extensive glycosylation pose high demands on the host cell machinery and stress imposed by accumulation of misfolded proteins may ultimately lead to cellular toxicity. The present study utilized the Nicotiana benthamiana/p19 (N.b./p19) transient plant system to assess co-expression of two ER master regulators and 5 chaperones, crucial in the folding process, to enhance yields of three Env SOSIPs, single chain BG505 SOSIP.664 gp140, CH505TF.6R.SOSIP.664.v4.1 and CH848-10.17-DT9. Phenotypic changes in leaves induced by SOSIP expression were employed to rapidly identify chaperone-assisted improvement in health and expression. Up to 15-fold increases were obtained by co-infiltration of peptidylprolvl isomerase (PPI) and calreticulin (CRT) which were further enhanced by addition of the ER-retrieval KDEL tags to the SOSIP genes; levels depending on individual SOSIP type, day of harvest and chaperone gene dosage. Results are consistent with reducing SOSIP misfolding and cellular stress due to increased exposure to the plant host cell’s calnexin/calreticulin network and accelerating the rate-limiting cis–trans isomerization of Xaa-Pro peptide bonds respectively. Plant transient co-expression facilitates rapid identification of host cell factors and will be translatable to other complex glycoproteins and mammalian expression systems.
A modified dynamic DEA model to assess the wastewater treatment efficiency: perspective from Yangtze River and Non-Yangtze River Basin
Authors: Ren Fangrong , Sun Yanan , Liu Jiawei , Chen Kejing , Shi Naixin 
Published: June 2022

AbstractThe wastewater treatment efficiency is crucial to constructing a livable ecological environment and promoting the sustainable development of economy and society. The differences in natural conditions, economic development and local policies between the Yangtze River Basin (YRB) and the Non-Yangtze River Basin (NYRB) increase the difficulty of wastewater treatment in governance. This study uses a modified Dynamic Data Envelopment Analysis (DEA) model to assess the wastewater treatment from 2013 to 2020, and divides the study period into two stages: the first stage (2013–2017) assesses the wastewater treatment efficiency of 18 provinces and cities in YRB and 12 provinces and cities in NYRB; the second stage (2018–2020) conducts statistical analysis of wastewater discharge pollutants in YRB and NYRB. The results conclude that the total wastewater treatment efficiency is generally low, but polarization is quite prominent. Among total wastewater treatment efficiency, NYRB scored 0.504, or slightly higher than YRB (0.398). In terms of expense efficiency, both NYRB and YRB scored below 0.4. In terms of chemical oxygen demand (COD) output efficiency, YRB (0.488) is better than NYRB (0.420). The second stage of statistical analysis presents that pollutant emissions are still high; the regions need to increase wastewater treatment investment and improve wastewater treatment efficiency.
Mobile phones are hazardous microbial platforms warranting robust public health and biosecurity protocols
Authors: Olsen Matthew , Nassar Rania , Senok Abiola , Moloney Susan , Lohning Anna , Jones Peter , Grant Gary , Morgan Mark , Palipana Dinesh , McKirdy Simon , Alghafri Rashed , Tajouri Lotti 
Published: June 2022

AbstractAdvancements in technology and communication have revolutionised the twenty-first century with the introduction of mobile phones and smartphones. These phones are known to be platforms harbouring microbes with recent research shedding light on the abundance and broad spectrum of organisms they harbour. Mobile phone use in the community and in professional sectors including health care settings is a potential source of microbial dissemination. To identify the diversity of microbial genetic signature present on mobile phones owned by hospital medical staff. Twenty-six mobile phones of health care staff were swabbed. DNA extraction for downstream next generation sequencing shotgun metagenomic microbial profiling was performed. Survey questionnaires were handed to the staff to collect information on mobile phone usage and users’ behaviours. Each of the 26 mobile phones of this study was contaminated with microbes with the detection of antibiotic resistance and virulent factors. Taken together the sum of microbes and genes added together across all 26 mobile phones totalised 11,163 organisms (5714 bacteria, 675 fungi, 93 protists, 228 viruses, 4453 bacteriophages) and 2096 genes coding for antibiotic resistance and virulent factors. The survey of medical staff showed that 46% (12/26) of the participants used their mobile phones in the bathroom. Mobile phones are vectors of microbes and can contribute to microbial dissemination and nosocomial diseases worldwide. As fomites, mobile phones that are not decontaminated may pose serious risks for public health and biosecurity.