bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of potential plasma protein biomarkers for bipolar II disorder: a preliminary/exploratory study
Authors: Lee Sheng-Yu , Wang Tzu-Yun , Lu Ru-Band , Wang Liang-Jen , Li Sung-Chou , Tu Chi-Ying , Chang Cheng-Ho , Chiang Yung-Chih , Tsai Kuo-Wang
Published: May 2021

The diagnostic peripheral biomarkers are still lacking for the bipolar II disorder (BD-II). We used isobaric tags for relative and absolute quantification technology to identify five upregulated candidate proteins [matrix metallopeptidase 9 (MMP9), phenylalanyl-tRNA synthetase subunit beta (FARSB), peroxiredoxin 2 (PRDX2), carbonic anhydrase 1 (CA-1), and proprotein convertase subtilisin/kexin type 9 (PCSK9)] for the diagnosis of BD-II. We analysed the differences in the plasma levels of these candidate proteins between BD-II patients and controls (BD-II, n = 185; Controls, n = 186) using ELISA. To establish a diagnostic model for the prediction of BD-II, the participants were divided randomly into a training group (BD-II, n = 149; Controls, n = 150) and a testing group (BD-II, n = 36; Controls, n = 36). Significant increases were found in all five protein levels between BD-II and controls in the training group. Logistic regression was analysed to form the composite probability score of the five proteins in the training group. Receiver-operating characteristic curve analysis revealed the diagnostic validity of the probability score [area under curve (AUC) = 0.89, P < 0.001]. The composite probability score of the testing group also showed good diagnostic validity (AUC = 0.86, P < 0.001). We propose that plasma levels of PRDX2, CA-1, FARSB, MMP9, and PCSK9 may be associated with BD-II as potential biomarkers.
Exploring exchange and direct procurement strategies for Natufian food processing tools of el-Wad Terrace, Israel
Authors: Rosenberg Danny , Gluhak Tatjana M. , Kaufman Daniel , Yeshurun Reuven , Weinstein-Evron Mina
Published: May 2021

We present the results of a detailed geochemical provenance study of 54 Natufian (ca. 15,000–11,700 cal. BP) basalt pestles from the site of el-Wad Terrace (EWT), Israel. It is the first time precise locations from where basalt raw materials were derived are provided. The results indicate that the Natufian hunter-gatherers used multiple sources of basaltic rocks, distributed over a large area surrounding the Sea of Galilee. This area is located at a considerable distance from EWT, ca. 60–120 km away, in a region where contemporaneous Natufian basecamps are few. We consider two possible models that suggest vehicles for the transportation of these artifacts to EWT, namely the exchange obtaining model (EOM) and the direct procurement model (DPM). We argue that these mechanisms are not mutually exclusive and may have operated together. We also suggest that at a time of increasing Natufian territoriality, a large area around the Sea of Galilee remained unclaimed. The paper concludes with a brief discussion of the implications for the two models. In particular, we note that the DPM implies that technological know-how for pestle production was maintained within the EWT community.
Machine learning-based mortality prediction model for heat-related illness
Authors: Hirano Yohei , Kondo Yutaka , Hifumi Toru , Yokobori Shoji , Kanda Jun , Shimazaki Junya , Hayashida Kei , Moriya Takashi , Yagi Masaharu , Takauji Shuhei , Yamaguchi Junko , Okada Yohei , Okano Yuichi , Kaneko Hitoshi , Kobayashi Tatsuho , Fujita Motoki , Yokota Hiroyuki , Okamoto Ken , Tanaka Hiroshi , Yaguchi Arino
Published: May 2021

In this study, we aimed to develop and validate a machine learning-based mortality prediction model for hospitalized heat-related illness patients. After 2393 hospitalized patients were extracted from a multicentered heat-related illness registry in Japan, subjects were divided into the training set for development (n = 1516, data from 2014, 2017–2019) and the test set (n = 877, data from 2020) for validation. Twenty-four variables including characteristics of patients, vital signs, and laboratory test data at hospital arrival were trained as predictor features for machine learning. The outcome was death during hospital stay. In validation, the developed machine learning models (logistic regression, support vector machine, random forest, XGBoost) demonstrated favorable performance for outcome prediction with significantly increased values of the area under the precision-recall curve (AUPR) of 0.415 [95% confidence interval (CI) 0.336–0.494], 0.395 [CI 0.318–0.472], 0.426 [CI 0.346–0.506], and 0.528 [CI 0.442–0.614], respectively, compared to that of the conventional acute physiology and chronic health evaluation (APACHE)-II score of 0.287 [CI 0.222–0.351] as a reference standard. The area under the receiver operating characteristic curve (AUROC) values were also high over 0.92 in all models, although there were no statistical differences compared to APACHE-II. This is the first demonstration of the potential of machine learning-based mortality prediction models for heat-related illnesses.
Whole genome analysis of extensively drug resistant Mycobacterium tuberculosis strains in Peru
Authors: Santos-Lazaro David , Gavilan Ronnie G. , Solari Lely , Vigo Aiko N. , Puyen Zully M.
Published: May 2021

Peru has the highest burden of multidrug-resistant tuberculosis in the Americas region. Since 1999, the annual number of extensively drug-resistant tuberculosis (XDR-TB) Peruvian cases has been increasing, becoming a public health challenge. The objective of this study was to perform genomic characterization of Mycobacterium tuberculosis strains obtained from Peruvian patients with XDR-TB diagnosed from 2011 to 2015 in Peru. Whole genome sequencing (WGS) was performed on 68 XDR-TB strains from different regions of Peru. 58 (85.3%) strains came from the most populated districts of Lima and Callao. Concerning the lineages, 62 (91.2%) strains belonged to the Euro-American Lineage, while the remaining 6 (8.8%) strains belonged to the East-Asian Lineage. Most strains (90%) had high-confidence resistance mutations according to pre-established WHO-confident grading system. Discordant results between microbiological and molecular methodologies were caused by mutations outside the hotspot regions analysed by commercial molecular assays (rpoB I491F and inhA S94A). Cluster analysis using a cut-off ≤ 10 SNPs revealed that only 23 (34%) strains evidenced recent transmission links. This study highlights the relevance and utility of WGS as a high-resolution approach to predict drug resistance, analyse transmission of strains between groups, and determine evolutionary patterns of circulating XDR-TB strains in the country.
Structural characterization of a Type B chloramphenicol acetyltransferase from the emerging pathogen Elizabethkingia anophelis NUHP1
Authors: Ghafoori Seyed Mohammad , Robles Alyssa M. , Arada Angelika M. , Shirmast Paniz , Dranow David M. , Mayclin Stephen J. , Lorimer Donald D. , Myler Peter J. , Edwards Thomas E. , Kuhn Misty L. , Forwood Jade K.
Published: May 2021

Elizabethkingia anophelisis an emerging multidrug resistant pathogen that has caused several global outbreaks.E. anophelisbelongs to the large family ofFlavobacteriaceae,which contains many bacteria that are plant, bird, fish, and human pathogens. Several antibiotic resistance genes are found within theE. anophelisgenome,including a chloramphenicol acetyltransferase (CAT). CATs play important roles in antibiotic resistance and can be transferred in genetic mobile elements. They catalyse the acetylation of the antibiotic chloramphenicol, thereby reducing its effectiveness as a viable drug for therapy. Here, we determined the high-resolution crystal structure of a CAT protein from theE. anophelisNUHP1 strain that caused a Singaporean outbreak. Its structure does not resemble that of the classical Type A CATs but rather exhibits significant similarity to other previously characterized Type B (CatB) proteins fromPseudomonas aeruginosa, Vibrio choleraeandVibrio vulnificus,which adopt a hexapeptide repeat fold.Moreover, the CAT protein fromE. anophelisdisplayed high sequence similarity to other clinically validated chloramphenicol resistance genes, indicating it may also play a role in resistance to this antibiotic. Our work expands the very limited structural and functional coverage of proteins fromFlavobacteriaceaepathogens which are becoming increasingly more problematic.
atpD gene sequencing, multidrug resistance traits, virulence-determinants, and antimicrobial resistance genes of emerging XDR and MDR-Proteus mirabilis
Authors: Algammal Abdelazeem M. , Hashem Hany R. , Alfifi Khyreyah J. , Hetta Helal F. , Sheraba Norhan S. , Ramadan Hazem , El-Tarabili Reham M.
Published: May 2021

Proteus mirabilis is a common opportunistic pathogen causing severe illness in humans and animals. To determine the prevalence, antibiogram, biofilm-formation, screening of virulence, and antimicrobial resistance genes in P. mirabilis isolates from ducks; 240 samples were obtained from apparently healthy and diseased ducks from private farms in Port-Said Province, Egypt. The collected samples were examined bacteriologically, and then the recovered isolates were tested for atpD gene sequencing, antimicrobial susceptibility, biofilm-formation, PCR detection of virulence, and antimicrobial resistance genes. The prevalence of P. mirabilis in the examined samples was 14.6% (35/240). The identification of the recovered isolates was confirmed by the atpD gene sequencing, where the tested isolates shared a common ancestor. Besides, 94.3% of P. mirabilis isolates were biofilm producers. The recovered isolates were resistant to penicillins, sulfonamides, β-Lactam-β-lactamase-inhibitor-combinations, tetracyclines, cephalosporins, macrolides, and quinolones. Using PCR, the retrieved strains harbored atpD, ureC, rsbA, and zapA virulence genes with a prevalence of 100%, 100%, 94.3%, and 91.4%, respectively. Moreover, 31.4% (11/35) of the recovered strains were XDR to 8 antimicrobial classes that harbored blaTEM, blaOXA-1, blaCTX-M, tetA, and sul1 genes. Besides, 22.8% (8/35) of the tested strains were MDR to 3 antimicrobial classes and possessed blaTEM, tetA, and sul1genes. Furthermore, 17.1% (6/35) of the tested strains were MDR to 7 antimicrobial classes and harbored blaTEM, blaOXA-1, blaCTX-M, tetA, and sul1 genes. Alarmingly, three strains were carbapenem-resistant that exhibited PDR to all the tested 10 antimicrobial classes and shared blaTEM, blaOXA-1, blaCTX-M, tetA, and sul1 genes. Of them, two strains harbored the blaNDM-1 gene, and one strain carried the blaKPC gene. In brief, to the best of our knowledge, this is the first study demonstrating the emergence of XDR and MDR-P.mirabilis in ducks. Norfloxacin exhibited promising antibacterial activity against the recovered XDR and MDR-P. mirabilis. The emergence of PDR, XDR, and MDR-strains constitutes a threat alarm that indicates the complicated treatment of the infections caused by these superbugs.
Empirical relationships between algorithmic SDA-M-based memory assessments and human errors in manual assembly tasks
Authors: Strenge Benjamin , Schack Thomas
Published: May 2021

The majority of manufacturing tasks are still performed by human workers, and this will probably continue to be the case in many industry 4.0 settings that aim at highly customized products and small lot sizes. Technical systems could assist on-the-job training and execution of these manual assembly processes, using augmented reality and other means, by properly treating and supporting workers’ cognitive resources. Recent algorithmic advancements automatized the assessment of task-related mental representation structures based on SDA-M, which enables technical systems to anticipate mistakes and provide corresponding user-specific assistance. Two studies have empirically investigated the relations between algorithmic assessments of individual memory structures and the occurrences of human errors in different assembly tasks. Hereby theoretical assumptions of the automatized SDA-M assessment approaches were deliberately violated in realistic ways to evaluate the practical applicability of these approaches. Substantial but imperfect correspondences were found between task-related mental representation structures and actual performances with sensitivity and specificity values ranging from 0.63 to 0.72, accompanied by prediction accuracies that were highly significant above chance level.
GPCR_LigandClassify.py; a rigorous machine learning classifier for GPCR targeting compounds
Authors: Ahmed Marawan , Hasani Horia Jalily , Kalyaanamoorthy Subha , Barakat Khaled
Published: May 2021

The current study describes the construction of various ligand-based machine learning models to be used for drug-repurposing against the family of G-Protein Coupled Receptors (GPCRs). In building these models, we collected > 500,000 data points, encompassing experimentally measured molecular association data of > 160,000 unique ligands against > 250 GPCRs. These data points were retrieved from the GPCR-Ligand Association (GLASS) database. We have used diverse molecular featurization methods to describe the input molecules. Multiple supervised ML algorithms were developed, tested and compared for their accuracy, F scores, as well as for their Matthews’ correlation coefficient scores (MCC). Our data suggest that combined with molecular fingerprinting, ensemble decision trees and gradient boosted trees ML algorithms are on the accuracy border of the rather sophisticated deep neural nets (DNNs)-based algorithms. On a test dataset, these models displayed an excellent performance, reaching a ~ 90% classification accuracy. Additionally, we showcase a few examples where our models were able to identify interesting connections between known drugs from the Drug-Bank database and members of the GPCR family of receptors. Our findings are in excellent agreement with previously reported experimental observations in the literature. We hope the models presented in this paper synergize with the currently ongoing interest of applying machine learning modeling in the field of drug repurposing and computational drug discovery in general.
Relaxation capacity of cartilage is a critical factor in rate- and integrity-dependent fracture
Authors: Han G. , Chowdhury U. , Eriten M. , Henak C. R.
Published: May 2021

Articular cartilage heals poorly but experiences mechanically induced damage across a broad range of loading rates and matrix integrity. Because loading rates and matrix integrity affect cartilage mechanical responses due to poroviscoelastic relaxation mechanisms, their effects on cartilage failure are important for assessing and preventing failure. This paper investigated rate- and integrity-dependent crack nucleation in cartilage from pre- to post-relaxation timescales. Rate-dependent crack nucleation and relaxation responses were obtained as a function of matrix integrity through microindentation. Total work for crack nucleation increased with decreased matrix integrity, and with decreased loading rates. Critical energy release rate of intact cartilage was estimated as 2.39 ± 1.39 to 2.48 ± 1.26 kJ m−2 in a pre-relaxation timescale. These findings showed that crack nucleation is delayed when cartilage can accommodate localized loading through poroviscoelastic relaxation mechanisms before fracture at a given loading rate and integrity state.
Controlling the corrosion and hydrogen gas liberation inside lead-acid battery via PANI/Cu-Pp/CNTs nanocomposite coating
Authors: Deyab M. A. , Mohsen Q.
Published: May 2021

The liberation of hydrogen gas and corrosion of negative plate (Pb) inside lead-acid batteries are the most serious threats on the battery performance. The present study focuses on the development of a new nanocomposite coating that preserves the Pb plate properties in an acidic battery electrolyte. This composite composed of polyaniline conductive polymer, Cu-Porphyrin and carbon nanotubes (PANI/Cu-Pp/CNTs). The structure and morphology of PANI/Cu-Pp/CNTs composite are detected using transmission electron microscopy (TEM), scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis. Based on the H2 gas evolution measurements and Tafels curves, the coated Pb (PANI/Cu-Pp/CNTs) has a high resistance against the liberation of hydrogen gas and corrosion. Electrochemical impedance spectroscopy (EIS) results confirm the suppression of the H2 gas evolution by using coated Pb (PANI/Cu-Pp/CNTs). The coated Pb (PANI/Cu-Pp/CNTs) increases the cycle performance of lead-acid battery compared to the Pb electrode with no composite.
Author Correction: TDCS effects on pointing task learning in young and old adults
Authors: Kaminski E. , Engelhardt M. , Hoff M. , Steele C. , Villringer A. , Ragert P.
Published: May 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Dominant egg surface bacteria of Holotrichia oblita (Coleoptera: Scarabaeidae) inhibit the multiplication of Bacillus thuringiensis and Beauveria bassiana
Authors: Wang Kui , Liu Qi , Liu Chunqin , Geng Lili , Wang Guirong , Zhang Jie , Shu Changlong
Published: May 2021

Holotrichia oblita (Coleoptera: Scarabaeidae) and some other scarab beetles are the main soil-dwelling pests in China. Bacillus thuringiensis (Bt) and Beauveria bassiana (Bb) are entomopathogens that have been used as biocontrol agents of various pests. However, scarab larvae especially H. oblita exhibited strong adaptability to these pathogens. Compared to other scarabs, H. oblita could form a specific soil egg case (SEC) structure surrounding its eggs, and young larvae complete the initial development process inside this structure. In this study, we investigated the role of SEC structure and microorganisms from SEC and egg surface in pathogen adaptability. 16S rRNA gene analysis revealed low bacterial richness and high community unevenness in egg surface, with Proteobacteria, Firmicutes, Bacteroidetes and Fusobacteria dominating. In terms of OTUs composition analysis, the data show that the egg surface contains a large number of unique bacteria, indicating that the egg bacterial community may be derived from maternal transmission. Furthermore, we found that all culturable bacteria isolated from egg surface possessed antimicrobial activity against both Bt and Bb. The Pseudomonas bacteria with a significantly higher abundance in egg surface showed strong Bt- and Bb antagonistic ability. In conclusion, this study demonstrated a unique and antimicrobial bacterial community of H. oblita egg surface, which may contribute to its adaptability. Furthermore, the specific SEC structure surrounding the H. oblita eggs will provide a stable microenvironment for the eggs and egg surface bacteria, which probably provides more advantages for H. oblita adaptation ability.
Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome
Authors: Victorino Daniella B. , Pinheiro Daniel J. L. L. , Scott-McKean Jonah J. , Barker Sarah , Stasko Melissa R. , Faber Jean , Scorza Carla A. , Costa Alberto C. S.
Published: May 2021

Mounting evidence implicates dysfunctional GABAAR-mediated neurotransmission as one of the underlying causes of learning and memory deficits observed in the Ts65Dn mouse model of Down syndrome (DS). The specific origin and nature of such dysfunction is still under investigation, which is an issue with practical consequences to preclinical and clinical research, as well as to the care of individuals with DS and anxiety disorder or those experiencing seizures in emergency room settings. Here, we investigated the effects of GABAAR positive allosteric modulation (PAM) by diazepam on brain activity, synaptic plasticity, and behavior in Ts65Dn mice. We found Ts65Dn mice to be less sensitive to diazepam, as assessed by electroencephalography, long-term potentiation, and elevated plus-maze. Still, diazepam pre-treatment displayed typical effectiveness in reducing susceptibility and severity to picrotoxin-induced seizures in Ts65Dn mice. These findings fill an important gap in the understanding of GABAergic function in a key model of DS.
Deep learning for gradability classification of handheld, non-mydriatic retinal images
Authors: Nderitu Paul , do Rio Joan M. Nunez , Rasheed Rajna , Raman Rajiv , Rajalakshmi Ramachandran , Bergeles Christos , Sivaprasad Sobha ,   for the SMART India Study Group, Bhende Pramod , Raman Rajiv , Rajalakshmi Ramachandran , Mohan Viswanathan , Ramasamy Kim , Das Taraprasad , Rani Padmaja K. , Roy Rupak , Das Supita , Mohan Deepa , Narendran V. , Manayath George , Anantharaman Giridhar , Gopalakrishnan Mahesh , Natarajan Sundaram , Krishnan Radhika , Mani Sheena Liz , Agarwal Manisha , Padhi Tapas , Behera Umesh , Bhattacharjee Harsha , Barman Manabjyoti , Chawla Gajendra , Sen Alok , Saxena Moneesh , Sil Asim K. , Chakabarty Subhratanu , Cherian Thomas , Reesha K. R. , Naigaonkar Rushikesh , Desai Abishek , Deshpande Col Madan , Kulkarni Sucheta , Conroy Dolores , Thethi Jitendra Pal , Ramakrishnan Radha , Surya Janani
Published: May 2021

Screening effectively identifies patients at risk of sight-threatening diabetic retinopathy (STDR) when retinal images are captured through dilated pupils. Pharmacological mydriasis is not logistically feasible in non-clinical, community DR screening, where acquiring gradable retinal images using handheld devices exhibits high technical failure rates, reducing STDR detection. Deep learning (DL) based gradability predictions at acquisition could prompt device operators to recapture insufficient quality images, increasing gradable image proportions and consequently STDR detection. Non-mydriatic retinal images were captured as part of SMART India, a cross-sectional, multi-site, community-based, house-to-house DR screening study between August 2018 and December 2019 using the Zeiss Visuscout 100 handheld camera. From 18,277 patient eyes (40,126 images), 16,170 patient eyes (35,319 images) were eligible and 3261 retinal images (1490 patient eyes) were sampled then labelled by two ophthalmologists. Compact DL model area under the receiver operator characteristic curve was 0.93 (0.01) following five-fold cross-validation. Compact DL model agreement (Kappa) were 0.58, 0.69 and 0.69 for high specificity, balanced sensitivity/specificity and high sensitivity operating points compared to an inter-grader agreement of 0.59. Compact DL gradability model performance was favourable compared to ophthalmologists. Compact DL models can effectively classify non-mydriatic, handheld retinal image gradability with potential applications within community-based DR screening.
Contribution of sewage to occurrence of phosphodiesterase-5 inhibitors in natural water
Authors: Hong Youngmin , Lee Ingyu , Tae Beomseok , Lee Wonseok , Pan Shu-Yuan , Snyder Seth W. , Kim Hyunook
Published: May 2021

Phosphodiesterase-5 inhibitors (PDE-5i, such as Sildenafil, Tadalafil and Vardenafil, mainly prescribed to treat erectile dysfunction) and their generic drug equivalents have been widely marketed and consumed in Korea. From the concentrations detected in wastewater, we could deduce that relatively large amounts of PDE-5i were consumed without a legal prescription. Thus, PDE-5i’s presence in the environment via sewage is unavoidable, and their environmental fate within a sewage treatment plant (STP) should be evaluated. In this study, we investigated the occurrence of three PDE-5i analogs in the influent and effluent of two STPs and the receiving water bodies. The PDE-5i concentration in total reached 62 ± 12 (STP#1) and 88 ± 37 ng L−1 (STP#2) in the sewage influent; about 70% of it was Sildenafil in both STPs. However, they were hardly removed by the STPs as the removal efficiency of the STPs was less than 10% ± 5%. Therefore, the pharmaceuticals were detected in the receiving water (lower than 7 ng L−1as a total amount) and the concentration slightly increased downstream of the STPs. A simple mass balance model applied for the compounds in the STP effluent and receiving water bodies also confirmed that the discharged PDE-5i were quite persistent. Lastly, we identified temporal and regional patterns in the consumption of the drugs from daily variations of PDE-5i in the influent to these two STPs. For instance, the levels of PDE-5i in the sewage significantly increased on weekends (from Friday to Saturday), and especially in the area where adult-entertainment businesses are common. We estimated that the amount of PDE-5i consumption in this area was 31% higher than that in the area with fewer nightlife spots. Considering that they are pharmaceutically active and resistant to treatment processes within an STP, it is advised that a regular monitoring and management program for PDE-5i should be developed to prevent the discharge of the pharmaceuticals into the water environment.
Toxoplasma gondii infection in domestic and wild felids as public health concerns: a systematic review and meta-analysis
Authors: Hatam-Nahavandi Kareem , Calero-Bernal Rafael , Rahimi Mohammad Taghi , Pagheh Abdol Sattar , Zarean Mehdi , Dezhkam Asiyeh , Ahmadpour Ehsan
Published: May 2021

Felidae as definitive hosts for Toxoplasma gondii play a major role in transmission to all warm-blooded animals trough oocysts dissemination. Therefore the current comprehensive study was performed to determine the global status of T. gondii infection in domestic and wild felids aiming to provide comprehensive data of interest for further intervention approaching the One Health perspective. Different databases were searched by utilizing particular key words for publications related to T. gondii infecting domestic and wild feline host species, worldwide, from 1970 to 2020. The review of 337 reports showed that the seroprevalence of T. gondii in domestic cats and wild felids was estimated in 37.5% (95% CI 34.7–40.3) (I2 = 98.3%, P < 0.001) and 64% (95% CI 60–67.9) (I2 = 88%, P < 0.0001), respectively. The global pooled prevalence of oocysts in the fecal examined specimens from domestic cats was estimated in 2.6% (95% CI 1.9–3.3) (I2 = 96.1%, P < 0.0001), and that in fecal samples from wild felids was estimated in 2.4% (95% CI 1.1–4.2) (I2 = 86.4%, P < 0.0001). In addition, from 13,252 examined soil samples in 14 reviewed studies, the pooled occurrence of T. gondii oocysts was determined in 16.2% (95% CI 7.66–27.03%). The observed high rates of anti-T. gondii antibodies seroprevalence levels and oocyst excretion frequency in the felids, along with soil (environmental) contamination with oocysts may constitute a potential threat to animal and public health, and data will result of interest in further prophylaxis programs.
Weakly supervised temporal model for prediction of breast cancer distant recurrence
Authors: Sanyal Josh , Tariq Amara , Kurian Allison W. , Rubin Daniel , Banerjee Imon
Published: May 2021

Efficient prediction of cancer recurrence in advance may help to recruit high risk breast cancer patients for clinical trial on-time and can guide a proper treatment plan. Several machine learning approaches have been developed for recurrence prediction in previous studies, but most of them use only structured electronic health records and only a small training dataset, with limited success in clinical application. While free-text clinic notes may offer the greatest nuance and detail about a patient’s clinical status, they are largely excluded in previous predictive models due to the increase in processing complexity and need for a complex modeling framework. In this study, we developed a weak-supervision framework for breast cancer recurrence prediction in which we trained a deep learning model on a large sample of free-text clinic notes by utilizing a combination of manually curated labels and NLP-generated non-perfect recurrence labels. The model was trained jointly on manually curated data from 670 patients and NLP-curated data of 8062 patients. It was validated on manually annotated data from 224 patients with recurrence and achieved 0.94 AUROC. This weak supervision approach allowed us to learn from a larger dataset using imperfect labels and ultimately provided greater accuracy compared to a smaller hand-curated dataset, with less manual effort invested in curation.
A detailed EIS study of boron doped diamond electrodes decorated with gold nanoparticles for high sensitivity mercury detection
Authors: McLaughlin Maeve H. S. , Pakpour-Tabrizi Alexander C. , Jackman Richard B.
Published: May 2021

This work compares the electrochemical impedance response of polished and unpolished boron doped diamond (BDD) electrodes, during mercury detection measurements. For each substrate type both bare electrodes and electrodes decorated with average diameter 30 nm AuNPs were used, to investigate the role of AuNPs during mercury sensing with diamond electrodes. In square wave anodic stripping voltammetry (SWASV) measurements for mercury detection, the mercury ions in the electrolyte are deposited onto, then stripped from the diamond electrode surface. To investigate the different electrode performances during these steps, the EIS measurements were made at the deposition and stripping potentials, alongside scans at open circuit potential for comparison. The performance of the electrodes is assessed in terms of their electron transfer rate (k0). The electrodes decorated with AuNPs are shown to have lower capacitance and higher reactivity than the bare pBDD and BDD electrodes, until the mercury concentration in the electrolyte is < 500 µM, when the sp2/sp3 carbon ratio at the surface of the electrodes has a greater influence on the sensitivity for mercury detection than the presence of AuNPs.
Surgical outcomes with high and low pulse energy femtosecond laser systems for cataract surgery
Authors: Lin Hung-Yuan , Chuang Ya-Jung , Lin Pi-Jung
Published: May 2021

Currently, there is no clear consensus in cataract surgery if low compared to high energy femto-lasers may enable better capsulotomy quality and induce lower inflammatory response. Therefore, the aim of this study was to compare the intra-operative outcomes achieved with high and low pulse energy femtosecond laser systems for cataract surgery. The charts of 200 eyes of 200 patients aged 68.3 ± 10.3 years who had undergone femtosecond laser-assisted cataract surgery using either group 1 high pulse energy: LenSx (Alcon Laboratories) (N = 100) or group 2 low pulse energy: FEMTO LDV Z8 (Ziemer) (N = 100) laser were reviewed retrospectively. Integrity of anterior capsulotomy, classified as (1) complete (free-floating or with minor microadhesions), (2) incomplete and (3) with capsular tears, intraoperative completeness of the clear corneal incisions (CCI, main incision and side port), incidences of intraoperative miosis and incidence of subconjunctival hemorrhage were evaluated and compared between the two groups. The proportion of complete capsulotomies was significantly higher in the group 2 than the group 1 (100% vs 94%; p = 0.03). The incidences of intraoperative miosis (0% vs 19%) and subconjunctival hemorrhage (1% vs 63%) were significantly lower in the group 2 than the group 1 (p < 0.001). Completeness of the main incision was comparable (97% vs 95%; p = 0.721) between the two groups. Although not statistically significant, the completeness of side-port incision was slightly better in the group 2 than the group 1 (91% vs 86%). Low energy laser system performed significantly better in terms of completeness of capsulotomy, intraoperative miosis and sub-conjunctival hemorrhage, compared with high energy laser; the CCI outcomes were comparable.
Conservation concerns associated with low genetic diversity for K’gari–Fraser Island dingoes
Authors: Conroy G. C. , Lamont R. W. , Bridges L. , Stephens D. , Wardell-Johnson A. , Ogbourne S. M.
Published: May 2021

The dingo population on world heritage-listed K’gari-Fraser Island (K’gari) is amongst the most well-known in Australia. However, an absence of population genetic data limits capacity for informed conservation management. We used 9 microsatellite loci to compare the levels of genetic diversity and genetic structure of 175 K’gari dingo tissue samples with 264 samples from adjacent mainland regions. Our results demonstrated that the K'gari population has significantly lower genetic diversity than mainland dingoes (AR,HE,PAR;p < 0.05) with a fourfold reduction in effective population size (Ne = 25.7 vs 103.8). There is also strong evidence of genetic differentiation between the island and mainland populations. These results are in accordance with genetic theory for small, isolated, island populations, and most likely the result of low initial diversity and founder effects such as bottlenecks leading to decreased diversity and drift. As the first study to incorporate a large sample set of K’gari dingoes, this provides invaluable baseline data for future research, which should incorporate genetic and demographic monitoring to ensure long-term persistence. Given that human-associated activities will continue to result in dingo mortality, it is critical that genetic factors are considered in conservation management decisions to avoid deleterious consequences for this iconic dingo population.
Exposure to airborne bacteria depends upon vertical stratification and vegetation complexity
Authors: Robinson Jake M. , Cando-Dumancela Christian , Antwis Rachael E. , Cameron Ross , Liddicoat Craig , Poudel Ravin , Weinstein Philip , Breed Martin F.
Published: May 2021

Exposure to biodiverse aerobiomes supports human health, but it is unclear which ecological factors influence exposure. Few studies have investigated near-surface green space aerobiome dynamics, and no studies have reported aerobiome vertical stratification in different urban green spaces. We used columnar sampling and next generation sequencing of the bacterial 16S rRNA gene, combined with geospatial and network analyses to investigate urban green space aerobiome spatio-compositional dynamics. We show a strong effect of habitat on bacterial diversity and network complexity. We observed aerobiome vertical stratification and network complexity that was contingent on habitat type. Tree density, closer proximity, and canopy coverage associated with greater aerobiome alpha diversity. Grassland aerobiomes exhibited greater proportions of putative pathogens compared to scrub, and also stratified vertically. We provide novel insights into the urban ecosystem with potential importance for public health, whereby the possibility of differential aerobiome exposures appears to depend on habitat type and height in the airspace. This has important implications for managing urban landscapes for the regulation of aerobiome exposure.
Cyanobiont genetic diversity and host specificity of cyanobiont-bearing dinoflagellate Ornithocercus in temperate coastal waters
Authors: Kim Miran , Choi Dong Han , Park Myung Gil
Published: May 2021

Cyanobacteria are ubiquitous in marine environments and play an important role as primary producers. Some cyanobacteria, the so-called cyanobionts (cyanobacterial symbionts), have a symbiotic relationship with unicellular organisms. Among these relationships, in particular, the nature (e.g., genetic diversity, host or cyanobiont specificity, and cyanobiont seasonality) of the cyanobiont-dinoflagellate host consortia remains poorly understood. In this study, 16S rDNA of cyanobionts in 138 single host cells isolated over four seasons from temperate waters were sequenced using the MiSeq platform. Genetic analysis of cyanobionts from the dinoflagellate host Ornithocercus revealed that three genetic types of Synechococcales cyanobionts occurred in a wide range of water temperatures (11–24 °C), and their distribution seemed to be closely associated with variations in salinity. Furthermore, a certain degree of host (or cyanobiont) specificity in cyanobionts (or the host) among Ornithocercus species as well as among other dinophysoid species (i.e. Amphisolenia, Citharistes, and Histioneis), was observed. In addition to the Synechococcales cyanobionts, this study identified OTU sequences affiliated with Vampirovibrionales and Chroococcidiopsidales in some Ornithocercus cells, suggesting that Ornithocercus species are an additional habitat for these bacterial groups.
Periplocin and cardiac glycosides suppress the unfolded protein response
Authors: Tokugawa Muneshige , Inoue Yasumichi , Ishiuchi Kan’ichiro , Kujirai Chisane , Matsuno Michiyo , Ri Masaki , Itoh Yuka , Miyajima Chiharu , Morishita Daisuke , Ohoka Nobumichi , Iida Shinsuke , Mizukami Hajime , Makino Toshiaki , Hayashi Hidetoshi
Published: May 2021

The unfolded protein response (UPR) controls protein homeostasis through transcriptional and translational regulation. However, dysregulated UPR signaling has been associated with the pathogenesis of many human diseases. Therefore, the compounds modulating UPR may provide molecular insights for these pathologies in the context of UPR. Here, we screened small-molecule compounds that suppress UPR, using a library of Myanmar wild plant extracts. The screening system to track X-box binding protein 1 (XBP1) splicing activity revealed that the ethanol extract of the Periploca calophylla stem inhibited the inositol-requiring enzyme 1 (IRE1)-XBP1 pathway. We isolated and identified periplocin as a potent inhibitor of the IRE1-XBP1 axis. Periplocin also suppressed other UPR axes, protein kinase R-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6). Examining the structure–activity relationship of periplocin revealed that cardiac glycosides also inhibited UPR. Moreover, periplocin suppressed the constitutive activation of XBP1 and exerted cytotoxic effects in the human multiple myeloma cell lines, AMO1 and RPMI8226. These results reveal a novel suppressive effect of periplocin or the other cardiac glycosides on UPR regulation, suggesting that these compounds will contribute to our understanding of the pathological or physiological importance of UPR.
Non-coding RNA suppresses FUS aggregation caused by mechanistic shear stress on pipetting in a sequence-dependent manner
Authors: Hamad Nesreen , Yoneda Ryoma , So Masatomo , Kurokawa Riki , Nagata Takashi , Katahira Masato
Published: May 2021

Fused in sarcoma/translocated in liposarcoma (FUS/TLS) is a multitasking RNA/DNA binding protein. FUS aggregation is implicated in various neurodegenerative diseases. RNA was suggested to modulate phase transition of FUS. Here, we found that FUS transforms into the amorphous aggregation state as an instant response to the shear stress caused by usual pipetting even at a low FUS concentration, 100 nM. It was revealed that non-coding RNA can suppress the transformation of FUS into aggregates. The suppressive effect of RNA on FUS aggregation is sequence-dependent. These results suggested that the non-coding RNA could be a prospective suppressor of FUS aggregation caused by mechanistic stress in cells. Our finding might pave the way for more research on the role of RNAs as aggregation inhibitors, which could facilitate the development of therapies for neurodegenerative diseases.
Implementation of a multidisciplinary infections conference improves the treatment of spondylodiscitis
Authors: Ntalos D. , Schoof B. , Thiesen D. M. , Viezens L. , Kleinertz H. , Rohde H. , Both A. , Luebke A. , Strahl A. , Dreimann M. , Stangenberg M.
Published: May 2021

Establishing a multidisciplinary approach regarding the treatment of spondylodiscitis and analyzing its effect compared to a single discipline approach. 361 patients diagnosed with spondylodiscitis were included in this retrospective pre-post intervention study. The treatment strategy was either established by a single discipline approach (n = 149, year 2003–2011) or by a weekly multidisciplinary infections conference (n = 212, year 2013–2018) consisting of at least an orthopedic surgeon, medical microbiologist, infectious disease specialist and pathologist. Recorded data included the surgical and antibiotic strategy, complications leading to operative revision, recovered microorganisms, as well as the total length of hospital and intensive care unit stay. Compared to a single discipline approach, performing the multidisciplinary infections conference led to significant changes in anti-infective and surgical treatment strategies. Patients discussed in the conference showed significantly reduced days of total antibiotic treatment (66 ± 31 vs 104 ± 31, p < 0.001). Moreover, one stage procedures and open transpedicular screw placement were more frequently performed following multidisciplinary discussions, while there were less involved spinal segments in terms of internal fixation as well as an increased use of intervertebral cages instead of autologous bone graft (p < 0.001). Staphylococcus aureus and Staphylococcus epidermidis were the most frequently recovered organisms in both patient groups. No significant difference was found comparing inpatient complications between the two groups or the total in-hospital stay. Implementation of a weekly infections conference is an effective approach to introduce multidisciplinarity into spondylodiscitis management. These conferences significantly altered the treatment plan compared to a single discipline approach. Therefore, we highly recommend the implementation to optimize treatment modalities for patients.
Carbon sphere-zinc sulphate nanohybrids for smart delivery of zinc in rice (Oryza sativa L)
Authors: Yuvaraj Muthuraman , Subramanian Kizhaeral Sevathapandian
Published: May 2021

The laboratory research was attempted to find nano zinc fertilizer utilizing the carbon sphere as a substrate. Typically the encapsulation techniques are followed in the drug delivery system, the limited work was done in nano-based zinc micronutrient for slow release of nutrients to crop. The use efficiency of zinc micronutrients in the soil is only less than 6 percentage. In universal, the deficiency of zinc micronutrients causes malnutrition problems in human beings, especially in children. After considering this problem we planned to prepare zinc nano fertilizer by using the carbon sphere for need-based slow release and increase the use efficiency of zinc micronutrient in soil. In this study we synthesis the carbon sphere nanoparticle after the formation of carbon sphere the zinc sulphate was loaded and characterized by utilizing Scanning Electron Microscopy, Surface Area and Porosity, X-ray diffraction analysis, Fourier Transform Infrared Spectroscopy, Transmission Electron Microscopy. The research result shows that the nano carbon sphere was excellently loaded with zinc sulphate to the tune of 8 percentage and it was confirmed by Energy dispersive X-beam spectroscopy. The zinc loaded carbon sphere release nutrient for a prolonged period of up to 600 h in the case of conventional zinc sulphate zinc release halted after 216 h in percolation reactor studies. The zinc nano fertilizer is recommended in agriculture to increase zinc use efficiency, crop yield without any environmental risk.
The genomic landscape of carcinomas with mucinous differentiation
Authors: Nguyen Bastien , Sanchez-Vega Francisco , Fong Christopher J. , Chatila Walid K. , Boroujeni Amir Momeni , Pareja Fresia , Weigelt Britta , Sotiriou Christos , Larsimont Denis , Reis-Filho Jorge S. , Desmedt Christine , Schultz Nikolaus
Published: May 2021

Mucinous carcinomas can arise in any organ with epithelial cells that produce mucus. While mucinous tumors from different organs are histologically similar, it remains to be elucidated whether they share molecular alterations. Here we analyzed a total of 902 patients across six cancer types by comparing mucinous and non-mucinous samples, integrating text mining of pathology reports, gene expression, methylation, mutational and copy-number profiling. We found that, in addition to genes involved in mucin processing and secretion, MUC2 up-regulation is a multi-cancer biomarker of mucinous histology and is regulated by DNA methylation in colorectal, breast and stomach cancer. The majority of carcinomas with mucinous differentiation had fewer DNA copy-number alterations than non-mucinous tumors. The tumor mutational burden was lower in breast and lung with mucinous differentiation compared to their non-mucinous counterparts. We found several differences in the frequency of oncogenic gene and pathway alterations between mucinous and non-mucinous carcinomas, including a lower frequency of p53 pathway alterations in colorectal and lung cancer, and a lower frequency of PI-3-Kinase/Akt pathway alterations in breast and stomach cancer with mucinous differentiation. This study shows that carcinomas with mucinous differentiation originating from different organs share transcriptomic and genomic similarities. These results might pave the way for a more biologically relevant taxonomy for these rare cancers.
Synergy between a shallow root system with a DRO1 homologue and localized P application improves P uptake of lowland rice
Authors: Oo Aung Zaw , Tsujimoto Yasuhiro , Mukai Mana , Nishigaki Tomohiro , Takai Toshiyuki , Uga Yusaku
Published: May 2021

Improved phosphorus (P) use efficiency for crop production is needed, given the depletion of phosphorus ore deposits, and increasing ecological concerns about its excessive use. Root system architecture (RSA) is important in efficiently capturing immobile P in soils, while agronomically, localized P application near the roots is a potential approach to address this issue. However, the interaction between genetic traits of RSA and localized P application has been little understood. Near-isogenic lines (NILs) and their parent of rice (qsor1-NIL, Dro1-NIL, and IR64, with shallow, deep, and intermediate root growth angles (RGA), respectively) were grown in flooded pots after placing P near the roots at transplanting (P-dipping). The experiment identified that the P-dipping created an available P hotspot at the plant base of the soil surface layer where the qsor1-NIL had the greatest root biomass and root surface area despite no genotyipic differences in total values, whereby the qsor1-NIL had significantly greater biomass and P uptake than the other genotypes in the P-dipping. The superior surface root development of qsor1-NIL could have facilitated P uptakes from the P hotspot, implying that P-use efficiency in crop production can be further increased by combining genetic traits of RSA and localized P application.
Systematic integrated analyses of methylomic and transcriptomic impacts of early combined botanicals on estrogen receptor-negative mammary cancer
Authors: Arora Itika , Li Yuanyuan , Sharma Manvi , Crowley Michael R. , Crossman David K. , Li Shizhao , Tollefsbol Trygve O.
Published: May 2021

Dietary botanicals such as the cruciferous vegetable broccoli sprouts (BSp) as well as green tea polyphenols (GTPs) have shown exciting potential in preventing or delaying breast cancer (BC). However, little is known about their impact on epigenomic aberrations that are centrally involved in the initiation and progression of estrogen receptor-negative [ER(−)] BC. We have investigated the efficacy of combined BSp and GTPs diets on mammary tumor inhibition in transgenic Her2/neu mice that were administered the diets from prepubescence until adulthood. Herein, we present an integrated DNA methylome and transcriptome analyses for defining the early-life epigenetic impacts of combined BSp and GTPs on mammary tumors and our results indicate that a combinatorial administration of BSp and GTPs have a stronger impact at both transcriptome and methylome levels in comparison to BSp or GTPs administered alone. We also demonstrated a streamlined approach by performing an extensive preprocessing, quality assessment and downstream analyses on the genomic dataset. Our identification of differentially methylated regions in response to dietary botanicals administered during early-life will allow us to identify key genes and facilitate implementation of the subsequent downstream functional analyses on a genomic scale and various epigenetic modifications that are crucial in preventing ER(−) mammary cancer. Furthermore, our realtime PCR results were also found to be consistent with our genome-wide analysis results. These results could be exploited as a comprehensive resource for understanding understudied genes and their associated epigenetic modifications in response to these dietary botanicals.