bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective study to define the clinical utility and benefit of Decipher testing in men following prostatectomy
Authors: Marascio Joseph , Spratt Daniel E. , Zhang Jingbin , Trabulsi Edouard J. , Le Tiffany , Sedzorme Worlanyo Sosu , Beeler Whitney H. , Davicioni Elai , Dabbas Bashar , Lin Daniel W. , Gore John L. , Bloom Matthew , Mann Mark , Mark J. Ryan , Calvaresi Anne , Godwin James L. , McCue Peter , Hurwitz Mark D. , Kelly W. Kevin , Lallas Costas D. , Knudsen Karen E. , Gomella Leonard G. , Dicker Adam P. , Den Robert B.
Published: November 2019

Background

Genomic classifiers (GC) have been shown to improve risk stratification post prostatectomy. However, their clinical benefit has not been prospectively demonstrated. We sought to determine the impact of GC testing on postoperative management in men with prostate cancer post prostatectomy.

Methods

Two prospective registries of prostate cancer patients treated between 2014 and 2019 were included. All men underwent Decipher tumor testing for adverse features post prostatectomy (Decipher Biosciences, San Diego, CA). The clinical utility cohort, which measured the change in treatment decision-making, captured pre- and postgenomic treatment recommendations from urologists across diverse practice settings (n = 3455). The clinical benefit cohort, which examined the difference in outcome, was from a single academic institution whose tumor board predefined “best practices” based on GC results (n = 135).

Results

In the clinical utility cohort, providers’ recommendations pregenomic testing were primarily observation (69%). GC testing changed recommendations for 39% of patients, translating to a number needed to test of 3 to change one treatment decision. In the clinical benefit cohort, 61% of patients had genomic high-risk tumors; those who received the recommended adjuvant radiation therapy (ART) had 2-year PSA recurrence of 3 vs. 25% for those who did not (HR 0.1 [95% CI 0.0–0.6], p = 0.013). For the genomic low/intermediate-risk patients, 93% followed recommendations for observation, with similar 2-year PSA recurrence rates compared with those who received ART (p = 0.93).

Conclusions

The use of GC substantially altered treatment decision-making, with a number needed to test of only 3. Implementing best practices to routinely recommend ART for genomic-high patients led to larger than expected improvements in early biochemical endpoints, without jeopardizing outcomes for genomic-low/intermediate-risk patients.
Unlinked rRNA genes are widespread among bacteria and archaea
Authors: Brewer Tess E , Albertsen Mads , Edwards Arwyn , Kirkegaard Rasmus H , Rocha Eduardo P C , Fierer Noah
Published: November 2019

Ribosomes are essential to cellular life and the genes for their RNA components are the most conserved and transcribed genes in bacteria and archaea. Ribosomal RNA genes are typically organized into a single operon, an arrangement thought to facilitate gene regulation. In reality, some bacteria and archaea do not share this canonical rRNA arrangement—their 16S and 23S rRNA genes are separated across the genome and referred to as “unlinked”. This rearrangement has previously been treated as an anomaly or a byproduct of genome degradation in intracellular bacteria. Here, we leverage complete genome and long-read metagenomic data to show that unlinked 16S and 23S rRNA genes are more common than previously thought. Unlinked rRNA genes occur in many phyla, most significantly within Deinococcus-Thermus, Chloroflexi, and Planctomycetes, and occur in differential frequencies across natural environments. We found that up to 41% of rRNA genes in soil were unlinked, in contrast to the human gut, where all sequenced rRNA genes were linked. The frequency of unlinked rRNA genes may reflect meaningful life history traits, as they tend to be associated with a mix of slow-growing free-living species and intracellular species. We speculate that unlinked rRNA genes may confer selective advantages in some environments, though the specific nature of these advantages remains undetermined and worthy of further investigation. More generally, the prevalence of unlinked rRNA genes in poorly-studied taxa serves as a reminder that paradigms derived from model organisms do not necessarily extend to the broader diversity of bacteria and archaea.
Predicting rehospitalization within 2 years of initial patient admission for a major depressive episode: a multimodal machine learning approach
Authors: Cearns Micah , Opel Nils , Clark Scott , Kaehler Claas , Thalamuthu Anbupalam , Heindel Walter , Winter Theresa , Teismann Henning , Minnerup Heike , Dannlowski Udo , Berger Klaus , Baune Bernhard T.
Published: November 2019

Machine learning methods show promise to translate univariate biomarker findings into clinically useful multivariate decision support systems. At current, works in major depressive disorder have predominantly focused on neuroimaging and clinical predictor modalities, with genetic, blood-biomarker, and cardiovascular modalities lacking. In addition, the prediction of rehospitalization after an initial inpatient major depressive episode is yet to be explored, despite its clinical importance. To address this gap in the literature, we have used baseline clinical, structural imaging, blood-biomarker, genetic (polygenic risk scores), bioelectrical impedance and electrocardiography predictors to predict rehospitalization within 2 years of an initial inpatient episode of major depression. Three hundred and eighty patients from the ongoing 12-year Bidirect study were included in the analysis (rehospitalized: yes = 102, no = 278). Inclusion criteria was age ≥35 and <66 years, a current or recent hospitalisation for a major depressive episode and complete structural imaging and genetic data. Optimal performance was achieved with a multimodal panel containing structural imaging, blood-biomarker, clinical, medication type, and sleep quality predictors, attaining a test AUC of 67.74 (p = 9.99−05). This multimodal solution outperformed models based on clinical variables alone, combined biomarkers, and individual data modality prognostication for rehospitalization prediction. This finding points to the potential of predictive models that combine multimodal clinical and biomarker data in the development of clinical decision support systems.
Sex-specific depressive symptoms as markers of pre-Alzheimer dementia: findings from the Three-City cohort study
Authors: Norton Joanna , Carrière Isabelle , Pérès Karine , Gabelle Audrey , Berr Claudine , Ritchie Karen , Ancelin Marie-Laure
Published: November 2019

Late-life depression, as a potential marker of pre-dementia, has seldom been explored by symptom dimension and sex, despite sexual dimorphic differences. This study aimed to examine whether specific depressive dimensions were associated with pre-Alzheimer’s disease dementia (pre-AD), separately for women and men. Data were drawn from 5617 (58% women) community-dwellers aged 65+ recruited in 1999–2000 and followed at 2-year intervals for 12 years. We used Cox proportional hazard models to study associations between time-dependent Centre for Epidemiologic Studies-Depression Scale (CES-D) symptom dimensions (namely somatic, depressed, positive affect, and interpersonal challenge) and pre-AD, defined retrospectively from validated diagnoses established 3.5 (IQR: 3.2–4.0) years onwards. Analyses were performed according to overall depressive symptomatology (DS+: CES-D score ≥ 16) and antidepressant/anxiolytic medication use (AA). Results indicated that in DS+ women only, all four dimensions were significantly associated with pre-AD in the AA- group, in particular somatic item ‘Mind’ and depressed affect items ‘Depressed’ and ‘Blues’. The most depression-specific dimension, depressed affect, was also significantly associated with pre-AD in the DS– AA- women (HR:1.28, 95%CI: 1.12;1.47). In both sexes, in the DS– groups somatic affect was the most robust pre-AD marker, irrespective of treatment (women: HR = 1.22, 95%CI: 1.08;1.38; men: HR = 1.30, 95%CI: 1.14;1.48). Our findings highlight sex-specific associations between depressive symptom dimensions and pre-AD, modulated by depressive symptomatology and treatment. Assessment of specific symptom dimensions taking into account overall symptomatology and treatment could help identify and target high-risk AD-dementia profiles for interventions.
Prefrontal cortex interneurons display dynamic sex-specific stress-induced transcriptomes
Authors: Girgenti Matthew J. , Wohleb Eric S. , Mehta Sameet , Ghosal Sriparna , Fogaca Manoela V. , Duman Ronald S.
Published: November 2019

γ-aminobutyric acid (GABA) inhibitory interneurons play a key role in efferent and afferent control of principle neuron activity in the prefrontal cortex (PFC), thereby regulating signal integrity of cognitive and behavioral processes. Recent evidence suggests that specific subtypes of interneurons in the PFC mediate stress-induced depressive-like behaviors. Abnormalities of GABA interneurons, particularly the somatostatin (human, SST; mouse, Sst) subtype, have been reported in postmortem brains of depressed subjects and include sex differences that could explain the increased incidence of depression in women. Here, we analyze the transcriptional profiles and the effects of chronic stress in males vs. females on GABA interneuron subtypes in the PFC. Using Sst- and Parvalbumin-fluorescence tagged reporter mice and fluorescence-activated cell sorting (FACS) combined with RNA sequencing, we identify distinct transcriptome profiles for these interneuron subtypes in the medial PFC. Based on evidence that SST interneurons are altered in depression, we then determined the effects of chronic stress on this interneuron subtype. Chronic stress causes significant dysregulation of several key pathways, including sex-specific differences in the Sst interneuron profiles. The transcriptional pathways altered by chronic stress in males overlap with enriched pathways in non-stressed females. These changes occurred predominantly in decreased expression of elongation initiation factor 2 (EIF2) signaling, suggesting that dysfunction of the translational machinery of SST interneurons could be critical to the development of depressive-like behaviors in males. In addition, SST interneurons from females exposed to chronic stress show dysregulation of different, growth factor signaling pathways.
Longitudinal neovascular changes on optical coherence tomography angiography in proliferative diabetic retinopathy treated with panretinal photocoagulation alone versus with intravitreal conbercept plus panretinal photocoagulation: a pilot study
Authors: He Feng , Yu Weihong
Published: November 2019

Purpose

To investigate the longitudinal changes in neovascularization of the retinal elsewhere (NVE) size on optical coherence tomography angiography (OCTA) in proliferative diabetic retinopathy (PDR) treated by panretinal photocoagulation (PRP) alone or by single intravitreal conbercept injection plus PRP.

Methods

A prospective pilot study. Forty-four PDR eyes with NVE confirmed by fundus fluorescein angiography (FFA) and OCTA were included. They were assigned to receive PRP alone (PRP group) or intravitreal conbercept injection plus PRP (combination group). Ophthalmic examinations, including BCVA and OCTA to measure the NVE size, were performed at baseline before each PRP session, and at 1, 3, and 6 months.

Results

Twenty-nine eyes were included in the PRP group, and 15 eyes were included in the combination group. There was no significant difference between the two groups with respect to age, BCVA, and NVE area at baseline. In both groups, there was a significant (P < 0.05) NVE size reduction during the majority of study visits, with the reduction observed in the combination group significantly larger than that in the PRP group. No significant BCVA changes were observed in either groups, except that in the PRP group, the BCVA at 3 months was significantly improved (P < 0.05). No deaths or unexpected adverse events (AEs) were reported.

Conclusions

Intravitreal conbercept plus PRP was more effective than PRP monotherapy in NVE regression. Precise quantification of the NVE area by OCTA makes it a useful tool for monitoring the response of retinal neovascular lesions to the therapy.
Higher-order topological solitonic insulators
Authors: Li Zhixiong , Cao Yunshan , Yan Peng , Wang Xiangrong
Published: November 2019

Pursuing topological phase and matter in a variety of systems is one central issue in current physical sciences and engineering. Motivated by the recent experimental observation of corner states in acoustic and photonic structures, we theoretically study the dipolar-coupled gyration motion of magnetic solitons on the two-dimensional breathing kagome lattice. We calculate the phase diagram and predict both the Tamm–Shockley edge modes and the second-order corner states when the ratio between alternate lattice constants is greater than a critical value. We show that the emerging corner states are topologically robust against both structure defects and moderate disorders. Micromagnetic simulations are implemented to verify the theoretical predictions with an excellent agreement. Our results pave the way for investigating higher-order topological insulators based on magnetic solitons.
A calibrated database of kinematics and EMG of the forearm and hand during activities of daily living
Authors: Jarque-Bou Néstor J. , Vergara Margarita , Sancho-Bru Joaquín L. , Gracia-Ibáñez Verónica , Roda-Sales Alba
Published: November 2019

Linking hand kinematics and forearm muscle activity is a challenging and crucial problem for several domains, such as prosthetics, 3D modelling or rehabilitation. To advance in this relationship between hand kinematics and muscle activity, synchronised and well-defined data are needed. However, currently available datasets are scarce, and the presented tasks and data are often limited. This paper presents the KIN-MUS UJI Dataset that contains 572 recordings with anatomical angles and forearm muscle activity of 22 subjects while performing 26 representative activities of daily living. This dataset is, to our knowledge, the biggest currently available hand kinematics and muscle activity dataset to focus on goal-oriented actions. Data were recorded using a CyberGlove instrumented glove and surface EMG electrodes, both properly synchronised. Eighteen hand anatomical angles were obtained from the glove sensors by a validated calibration procedure. Surface EMG activity was recorded from seven representative forearm areas. The statistics verified that data were not affected by the experimental procedures and were similar to the data acquired under real-life conditions.
Efficient travelling-mode quantum key agreement against participant’s attacks
Authors: Huang Wei-cong , Yang Yong-kai , Jiang Dong , Chen Li-jun
Published: November 2019

Quantum key agreement (QKA) is to negotiate a final key among several participants fairly and securely. In this paper, we show that some existing travelling-mode multiparty QKA protocols are vulnerable to internal participant’s attacks. Dishonest participants can exploit a favorable geographical location or collude with other participants to predetermine the final keys without being discovered. To resist such attacks, we propose a new travelling-mode multiparty QKA protocol based on non-orthogonal Bell states. Theoretical analysis shows that the proposed protocol is secure against both external and internal attacks, and can achieve higher efficiency compared with existing travelling-mode multiparty QKA protocols. Finally we design an optical platform for each participant, and show that our proposed protocol is feasible with current technologies.
A detailed investigation of the visual system and visual ecology of the Barrier Reef anemonefish, Amphiprion akindynos
Authors: Stieb Sara M. , de Busserolles Fanny , Carleton Karen L. , Cortesi Fabio , Chung Wen-Sung , Dalton Brian E. , Hammond Luke A. , Marshall N. Justin
Published: November 2019

Vision plays a major role in the life of most teleosts, and is assumingly well adapted to each species ecology and behaviour. Using a multidisciplinary approach, we scrutinised several aspects of the visual system and ecology of the Great Barrier Reef anemonefish,Amphiprion akindynos, including its orange with white patterning, retinal anatomy and molecular biology, its symbiosis with anemones and sequential hermaphroditism.Amphiprion akindynospossesses spectrally distinct visual pigments and opsins: one rod opsin, RH1 (498 nm), and five cone opsins, SWS1 (370 nm), SWS2B (408 nm), RH2B (498 nm), RH2A (520 nm), and LWS (554 nm). Cones were arranged in a regular mosaic with each single cone surrounded by four double cones. Double cones mainly expressedRH2B(53%) in one member andRH2A(46%) in the other, matching the prevailing light. Single cones expressedSWS1(89%), which may serve to detect zooplankton, conspecifics and the host anemone. Moreover, a segregated small fraction of single cones coexpressedSWS1withSWS2B(11%). This novel visual specialisation falls within the region of highest acuity and is suggested to increase the chromatic contrast ofAmphiprion akindynoscolour patterns, which might improve detection of conspecifics.
Prediction of Deleterious Non-synonymous SNPs of Human STK11 Gene by Combining Algorithms, Molecular Docking, and Molecular Dynamics Simulation
Authors: Islam Md. Jahirul , Khan Akib Mahmud , Parves Md. Rimon , Hossain Md Nayeem , Halim Mohammad A.
Published: November 2019

Serine-threonine kinase11 (STK11) is a tumor suppressor gene which plays a key role in regulating cell growth and apoptosis. It is widely known as a multitasking kinase and engaged in cell polarity, cell cycle arrest, chromatin remodeling, energy metabolism, and Wnt signaling. The substitutions of single amino acids in highly conserved regions of the STK11 protein are associated with Peutz–Jeghers syndrome (PJS), which is an autosomal dominant inherited disorder. The abnormal function of the STK11 protein is still not well understood. In this study, we classified disease susceptible single nucleotide polymorphisms (SNPs) in STK11 by using different computational algorithms. We identified the deleterious nsSNPs, constructed mutant protein structures, and evaluated the impact of mutation by employing molecular docking and molecular dynamics analysis. Our results show that W239R and W308C variants are likely to be highly deleterious mutations found in the catalytic kinase domain, which may destabilize structure and disrupt the activation of the STK11 protein as well as reduce its catalytic efficiency. The W239R mutant is likely to have a greater impact on destabilizing the protein structure compared to the W308C mutant. In conclusion, these mutants can help to further realize the large pool of disease susceptibilities linked with catalytic kinase domain activation of STK11 and assist to develop an effective drug for associated diseases.
Phylogenetic surveillance of travel-related Zika virus infections through whole-genome sequencing methods
Authors: Kamelian Kimia , Montoya Vincent , Olmstead Andrea , Dong Winnie , Harrigan Richard , Morshed Muhammad , Joy Jeffrey B.
Published: November 2019

In 2018, the World Health Organization identified the Zika virus (ZIKV) as a pathogen that should be prioritized for public health research due to its epidemic potential. In this study, whole-genome sequencing (WGS) of travel-acquired ZIKV infections was used to examine the limitations of phylogenetic analysis. WGS and phylogenetic analysis were performed to investigate geographic clustering of samples from five Canadians with travel-acquired ZIKV infections and to assess the limitations of phylogenetic analysis of ZIKV sequences using a phylogenetic cluster approach. Genomic variability of ZIKV samples was assessed and for context, compared with hepatitis C virus (HCV) samples. Phylogenetic analysis confirmed the suspected region of ZIKV infection for one of five samples and one sample failed to cluster with sequences from its suspected country of infection. Travel-acquired ZIKV samples depicted low genomic variability relative to HCV samples. A floating patristic distance threshold classified all pre-2000 ZIKV sequences into separate clusters, while only Cambodian, Peruvian, Malaysian, and South Korean sequences were similarly classifiable. While phylogenetic analysis of ZIKV data can identify the broad geographical region of ZIKV infection, ZIKV’s low genomic variability is likely to limit precise interpretations of phylogenetic analysis of the origins of travel-related cases.
Histamine H1 receptor on astrocytes and neurons controls distinct aspects of mouse behaviour
Authors: Kárpáti Anikó , Yoshikawa Takeo , Naganuma Fumito , Matsuzawa Takuro , Kitano Haruna , Yamada Yo , Yokoyama Mariko , Futatsugi Akira , Mikoshiba Katsuhiko , Yanai Kazuhiko
Published: November 2019

Histamine is an important neurotransmitter that contributes to various processes, including the sleep-wake cycle, learning, memory, and stress responses. Its actions are mediated through histamine H1–H4 receptors. Gene knockout and pharmacological studies have revealed the importance of H1 receptors in learning and memory, regulation of aggression, and wakefulness. H1 receptors are abundantly expressed on neurons and astrocytes. However, to date, studies selectively investigating the roles of neuronal and astrocytic H1 receptors in behaviour are lacking. We generated novel astrocyte- and neuron-specific conditional knockout (cKO) mice to address this gap in knowledge. cKO mice showed cell-specific reduction of H1 receptor gene expression. Behavioural assessment revealed significant changes and highlighted the importance of H1 receptors on both astrocytes and neurons. H1 receptors on both cell types played a significant role in anxiety. Astrocytic H1 receptors were involved in regulating aggressive behaviour, circadian rhythms, and quality of wakefulness, but not sleep behaviour. Our results emphasise the roles of neuronal H1 receptors in recognition memory. In conclusion, this study highlights the novel roles of H1 receptors on astrocytes and neurons in various brain functions.
Effects of a stepwise, local patient-specific early oral feeding schedule after gastric cancer surgery: a single-center retrospective study from China
Authors: Chen Ji , Xu Ming , Zhang Yunpeng , Gao Chun , Sun Peng
Published: November 2019

Nowadays, early oral feeding after gastrectomy has been gradually accepted and applied in the clinical practice, but there is still no specific uniform feeding regimen available which works best for patients in different regions with different races and eating habits. Aiming to establish an early oral feeding schedule suitable for local Chinese patients after gastric surgery, from May 2014 to May 2018, 87 gastric cancer patients undergoing various types of gastric resections were enrolled in an early feeding protocol and their clinical course was reviewed retrospectively. A stepwise, local patient-specific, early oral feeding schedule was proposed, implemented within an early recovery after surgery (ERAS) protocol and accessed in terms of its safety and tolerability. The primary surgical outcomes included: a median (interquartile range; IQR) postoperative hospital stay of 6 (3) days; 67 (77%) patients were well tolerant of this schedule from postoperative day (POD) 1 to POD 4; 20 (23%) patients had mild I/II grade complications (Clavien-Dindo classification); 3 (3%) patients had IIIB complications, zero cases of hospital mortality. Compared to similar studies in the past, our early oral feeding program is also safe and beneficial, and it can shorten the postoperative hospital stay without causing any increase in postoperative complications. In summary, our work herein reported the establishment of a detailed early oral feeding schedule embedded within an ERAS protocol which was found to be suitable for local Chinese patients after gastric surgery. Accordingly, this early oral feeding schedule is worth further research and promotion.
Spontaneous Ligand Access Events to Membrane-Bound Cytochrome P450 2D6 Sampled at Atomic Resolution
Authors: Fischer André , Smieško Martin
Published: November 2019

The membrane-anchored enzyme Cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of around 25% of marketed drugs and its metabolic performance shows a high interindividual variation. While it was suggested that ligands access the buried active site of the enzyme from the membrane, no proof from unbiased simulations has been provided to support this hypothesis. Laboratory experiments fail to capture the access process which is suspected to influence binding kinetics. Here, we applied unbiased molecular dynamics (MD) simulations to investigate the access of ligands to wild-type CYP2D6, as well as the allelic variant CYP2D6*53. In multiple simulations, substrates accessed the active site of the enzyme from the protein-membrane interface to ultimately adopt a conformation that would allow a metabolic reaction. We propose the necessary steps for ligand access and the results suggest that the increased metabolic activity of CYP2D6*53 might be caused by a facilitated ligand uptake.
Robust Preimplantation Genetic Testing of Huntington Disease by Combined Triplet-Primed PCR Analysis of the HTT CAG Repeat and Multi-Microsatellite Haplotyping
Authors: Zhao Mingjue , Cheah Felicia Siew Hong , Tan Arnold Sia Chye , Lian Mulias , Phang Gui Ping , Agarwal Anupriya , Chong Samuel S.
Published: November 2019

Huntington disease (HD) is a lethal neurodegenerative disorder caused by expansion of a CAG repeat within the huntingtin (HTT) gene. Disease prevention can be facilitated by preimplantation genetic testing for this monogenic disorder (PGT-M). We developed a strategy for HD PGT-M, involving whole genome amplification (WGA) followed by combined triplet-primed PCR (TP-PCR) for HTT CAG repeat expansion detection and multi-microsatellite marker genotyping for disease haplotype phasing. The strategy was validated and tested pre-clinically in a simulated PGT-M case before clinical application in five cycles of a PGT-M case. The assay reliably and correctly diagnosed all embryos, even where allele dropout (ADO) occurred at the HTT CAG repeat locus or at one or more linked markers. Ten of the 27 embryos analyzed were diagnosed as unaffected. Four embryo transfers were performed, two of which involved fresh cycle double embryo transfers and two were frozen-thawed single embryo transfers. Pregnancies were achieved from each of the frozen-thawed single embryo transfers and confirmed to be unaffected by amniocentesis, culminating in live births at term. This strategy enhances diagnostic confidence for PGT-M of HD and can also be employed in situations where disease haplotype phase cannot be established prior to the start of PGT-M.
A new approach to biomining: Bioengineering surfaces for metal recovery from aqueous solutions
Authors: Urbina Jesica , Patil Advait , Fujishima Kosuke , Paulino-Lima Ivan G. , Saltikov Chad , Rothschild Lynn J.
Published: November 2019

Electronics waste production has been fueled by economic growth and the demand for faster, more efficient consumer electronics. The glass and metals in end-of-life electronics components can be reused or recycled; however, conventional extraction methods rely on energy-intensive processes that are inefficient when applied to recycling e-waste that contains mixed materials and small amounts of metals. To make e-waste recycling economically viable and competitive with obtaining raw materials, recovery methods that lower the cost of metal reclamation and minimize environmental impact need to be developed. Microbial surface adsorption can aid in metal recovery with lower costs and energy requirements than traditional metal-extraction approaches. We introduce a novel method for metal recovery by utilizing metal-binding peptides to functionalize fungal mycelia and enhance metal recovery from aqueous solutions such as those found in bioremediation or biomining processes. Using copper-binding as a proof-of-concept, we compared binding parameters between natural motifs and those derived in silico, and found comparable binding affinity and specificity for Cu. We then combined metal-binding peptides with chitin-binding domains to functionalize a mycelium-based filter to enhance metal recovery from a Cu-rich solution. This finding suggests that engineered peptides could be used to functionalize biological surfaces to recover metals of economic interest and allow for metal recovery from metal-rich effluent with a low environmental footprint, at ambient temperatures, and under circumneutral pH.
Routine Adoption of Urinary [IGFBP7]∙[TIMP-2] to Assess Acute Kidney Injury at Any Stage 12 hours After Intensive Care Unit Admission: a Prospective Cohort Study
Authors: Ferrari Fiorenza , Romero-González Gregorio , Topete Lilia Rizo , Senzolo Mara , Lorenzin Anna , Husain-Syed Faeq , Puci Mariangela Valentina , Ferraro Ottavia Eleonora , Muraro Eva , Serrano-Soto Mara , Triviño Alejandra Molano , Castro Ana Coutinho , Xie Yun , Yang Bo , De Cal Massimo , Corradi Valentina , Brendolan Alessandra , Scarpa Marta , Carta Maria Rosa , Giavarina Davide , Bonato Raffaele , Ronco Claudio
Published: November 2019

The urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 ([TIMP-2]∙[IGFBP7]) have been introduced to improve risk prediction of severe acute kidney injury (AKI) within 12 hours of measurement. We performed a prospective cohort study to evaluate if the predictive value of [TIMP-2]∙[IGFBP7] for AKI might continue after 12 hours. We enrolled 442 critically ill adult patients from June to December 2016. Urine samples were collected at admission for [TIMP-2]∙[IGFBP7] measurement. Baseline patient characteristics were recorded including patients’ demographics, prior health history, and the main reason for admission to build a logistic regression model to predict AKI. AKI occurrence differed between patients with [TIMP-2]∙[IGFBP7] ≤0.3 and >0.3 (ng/ml)2/1000 (31.9% and 68.10% respectively; p < 0.001). Patients with AKI had higher biomarker values compared to those without AKI (0.66 (0.21–2.84) vs 0.22 (0.08–0.63) (ng/ml)2/1000; p < 0.001). [TIMP-2]∙[IGFBP7] at ICU admission had a lower performance in predicting AKI at any stage within 48 hours and 7 days after measurement (area under the receiver operating characteristic curve (AUC) equal to 0.70 (95%CI 0.65–0.76), AUC 0.68 (95%CI 0.63–0.73)). In the logistic regression model, 0.1 (ng/ml)2/1000-unit increment was likely to increase the risk of AKI by 2% (p = 0.002).
Progressive loss of muscle mass could be an adverse prognostic factor of 28-day mortality in septic shock patients
Authors: Seo Dong-Woo , Kim Kyung Won , Sohn Chang Hwan , Ryoo Seung Mok , Kim Youn-Jung , Shin Ahn , Kim Won Young
Published: November 2019

A decrease in skeletal muscle mass has been shown to increase hospital mortality. Nevertheless, little is known about the association between progressive muscle loss over time and clinical outcomes. We aimed to evaluate whether progressive loss of muscle mass in septic shock patients was associated with mortality. We reviewed prospectively enrolled registry of septic shock which had 817 consecutive patients. Of these, 175 patients who had computed tomography (CT) at a time of admission as well as 3–6 months prior to admission were included. Between these two CTs, the change in total abdominal muscle area index (TAMAI) was evaluated for progressive muscle loss. The change in TAMAI was higher in the non-survivors (−7.6 cm2/m2, 19.0% decrease) than the survivors (−4.0 cm2/m2, 10.5% decrease) with statistical significance (p = 0.002). Multiple logistic regression showed that the patients who had more than a 6.4 cm2/m2 (16.7%) reduction of TAMAI had a 4.42-fold higher risk for mortality at 28 days (OR, 4.42; 95% CI, 1.41–13.81, p = 0.011). Our study suggested that progressive loss of muscle mass might be a useful prognostic factor for septic shock patients. This implication will need to be further explored in future prospective studies.
Staphylococcus aureus ClpX localizes at the division septum and impacts transcription of genes involved in cell division, T7-secretion, and SaPI5-excision
Authors: Jensen Camilla , Fosberg Marie J. , Thalsø-Madsen Ida , Bæk Kristoffer T. , Frees Dorte
Published: November 2019

In all living cells, molecular chaperones are essential for facilitating folding and unfolding of proteins. ClpX is a highly conserved ATP-dependent chaperone that besides functioning as a classical chaperone can associate with ClpP to form the ClpXP protease. To investigate the relative impact of the ClpXP protease and the ClpX chaperone in cell physiology of the important pathogenic bacterium Staphylococcus aureus, we assessed the transcriptional changes induced by inactivating only ClpXP, or by completely deleting ClpX. This analysis revealed that ClpX has a profound impact on S. aureus cell physiology that is mediated primarily via ClpXP-dependent pathways. As an example, ClpX impacts expression of virulence genes entirely via ClpXP-dependent mechanisms. Furthermore, ClpX controls a high number of genes and sRNAs via pathways involving both ClpXP protease and ClpX chaperone activities; an interesting example being genes promoting excision and replication of the pathogenicity island SaPI5. Independently of ClpP, ClpX, impacts transcription of only a restricted number of genes involved in peptidoglycan synthesis, cell division, and type seven secretion. Finally, we demonstrate that ClpX localizes in single foci in close proximity to the division septum lending support to the idea that ClpX plays a role in S. aureus cell division.
Differentiation of multiple system atrophy from Parkinson’s disease by structural connectivity derived from probabilistic tractography
Authors: Abos Alexandra , Baggio Hugo C. , Segura Barbara , Campabadal Anna , Uribe Carme , Giraldo Darly Milena , Perez-Soriano Alexandra , Muñoz Esteban , Compta Yaroslau , Junque Carme , Marti Maria Jose
Published: November 2019

Recent studies combining diffusion tensor-derived metrics and machine learning have shown promising results in the discrimination of multiple system atrophy (MSA) and Parkinson’s disease (PD) patients. This approach has not been tested using more complex methodologies such as probabilistic tractography. The aim of this work is assessing whether the strength of structural connectivity between subcortical structures, measured as the number of streamlines (NOS) derived from tractography, can be used to classify MSA and PD patients at the single-patient level. The classification performance of subcortical FA and MD was also evaluated to compare the discriminant ability between diffusion tensor-derived metrics and NOS. Using diffusion-weighted images acquired in a 3 T MRI scanner and probabilistic tractography, we reconstructed the white matter tracts between 18 subcortical structures from a sample of 54 healthy controls, 31 MSA patients and 65 PD patients. NOS between subcortical structures were compared between groups and entered as features into a machine learning algorithm. Reduced NOS in MSA compared with controls and PD were found in connections between the putamen, pallidum, ventral diencephalon, thalamus, and cerebellum, in both right and left hemispheres. The classification procedure achieved an overall accuracy of 78%, with 71% of the MSA subjects and 86% of the PD patients correctly classified. NOS features outperformed the discrimination performance obtained with FA and MD. Our findings suggest that structural connectivity derived from tractography has the potential to correctly distinguish between MSA and PD patients. Furthermore, NOS measures obtained from tractography might be more useful than diffusion tensor-derived metrics for the detection of MSA.
Expansion of LINEs and species-specific DNA repeats drives genome expansion in Asian Gypsy Moths
Authors: Hebert Francois Olivier , Freschi Luca , Blackburn Gwylim , Béliveau Catherine , Dewar Ken , Boyle Brian , Gundersen-Rindal Dawn E. , Sparks Michael E. , Cusson Michel , Hamelin Richard C. , Levesque Roger C.
Published: November 2019

Two subspecies of Asian gypsy moth (AGM), Lymantria dispar asiatica and L. dispar japonica, pose a serious alien invasive threat to North American forests. Despite decades of research on the ecology and biology of this pest, limited AGM-specific genomic resources are currently available. Here, we report on the genome sequences and functional content of these AGM subspecies. The genomes of L.d. asiatica and L.d. japonica are the largest lepidopteran genomes sequenced to date, totaling 921 and 999 megabases, respectively. Large genome size in these subspecies is driven by the accumulation of specific classes of repeats. Genome-wide metabolic pathway reconstructions suggest strong genomic signatures of energy-related pathways in both subspecies, dominated by metabolic functions related to thermogenesis. The genome sequences reported here will provide tools for probing the molecular mechanisms underlying phenotypic traits that are thought to enhance AGM invasiveness.
Increased risk for hypothyroidism associated with carbon monoxide poisoning: a nationwide population-based cohort study
Authors: Huang Chien-Cheng , Ho Chung-Han , Chen Yi-Chen , Hsu Chien-Chin , Lin Hung-Jung , Su Shih-Bin , Wang Jhi-Joung , Guo How-Ran
Published: November 2019

Carbon monoxide poisoning (COP) may cause injuries to the central nervous and endocrine systems, which might increase the risk of developing hypothyroidism. We wanted to evaluate the association between COP and the risk of developing hypothyroidism because epidemiological data on this potential association are limited. We conducted a nationwide population-based cohort study using the Nationwide Poisoning Database and identified 24,328 COP subjects diagnosed between 1999 and 2012. By matching the index date and age, we selected 72,984 non-COP subjects for comparison. Subjects with thyroid diseases and malignancy before 1999 were excluded. We followed up the two groups of subjects until 2013 and compared the risk of developing hypothyroidism. COP subjects had a significantly higher risk for hypothyroidism than non-COP subjects (adjusted hazard ratio [AHR]: 3.8; 95% confidence interval [CI]: 3.2–4.7) after adjusting for age, sex, underlying comorbidities, and monthly income, and the AHR was particular higher in subjects with diabetes mellitus, hyperlipidemia, and mental disorder. The increased risk was highest in the first month after COP (AHR: 41.0; 95% CI: 5.4–310.6), and the impact remained significant even after 4 years. In conclusion, COP was associated with an increased risk for hypothyroidism. Further studies regarding the underlying mechanisms are warranted.
Accurate and precise determination of 90Sr at femtogram level in IAEA proficiency test using Thermal Ionization Mass Spectrometry
Authors: Kavasi Norbert , Sahoo Sarata Kumar , Arae Hideki , Aono Tatsuo , Palacz Zenon
Published: November 2019

A novel method for the determination of ultra-trace level 90Sr has been recently developed applying thermal ionization mass spectrometry (TIMS). The method includes the chemical separation of Zr (isobaric interference of 90Zr) from the samples followed by determination of 90Sr/88Sr abundance  sensitivity (2.1 × 10−10). The analytical performance of this method was assessed in the IAEA-TEL 2017-3 worldwide open proficiency test. For 90Sr determination, tap water and milk powder samples were distributed amongst the participant laboratories with reference values of 11.2 ± 0.3 Bq kg−1 (2.2 ± 0.1 fg g−1) and 99.9 ± 5.0 Bq kg−1 (19.5 ± 1.0 fg g−1), respectively. The stable Sr concentrations were 39.4 ± 0.9 ng g−1 and 2.5 ± 0.1 µg g−1 while the 90Sr/88Sr isotope ratios were 6.47 ± 0.17 × 10−8 and 9.04 ± 0.45 × 10−9 in the tap water and milk powder samples, respectively. For TIMS measurement, 50 mL water and 1 g milk powder samples were taken for analysis. This TIMS method demonstrated an impressive accuracy (relative bias of 4.2% and −2.1%, respectively) and precision (relative combined uncertainty of 4.1% and 7.6%, respectively) when compared with radiometric techniques. For the first time in the history of inorganic mass-spectrometry, 90Sr analysis using a TIMS instrument is confirmed by an independent proficiency test.
Investigation on the pore characteristics of coal specimens with bursting proneness
Authors: Li Yutao , Jiang Yaodong , Zhang Bo , Song Honghua , Dong Wenbo , Wang Pengpeng
Published: November 2019

To achieve further insight into the pore characteristics, the coal specimens with different bursting proneness before and after uniaxial compression failure are tested and compared in this paper. The data of mercury intrusion test is corrected by that of low-temperature nitrogen adsorption and desorption test (LTNAD). The pore size distribution and pore volume of specimens are obtained. The pore compressibility coefficient is determined based on the fractal dimension of pore. Scanning electron microscope (SEM) and computed tomography (CT) are combined to evaluated the pore connectivity. The value of pore compressibility coefficient of specimens with high bursting proneness is larger than that of medium bursting proneness. It means more compressibility and abrupt failure under stress. The researches of both SEM and CT indicate that the pore connectivity of specimens with medium bursting proneness is better. The results show that great differences exist in the pore characteristics of specimens with high and medium bursting proneness, and uniaxial compression failure exacerbates the complexity of pore characteristics.
Neutrophil activation causes tumor regression in Walker 256 tumor-bearing rats
Authors: Kuwabara Wilson Mitsuo Tatagiba , Andrade-Silva Jéssica , Pereira Joice Naiara Bertaglia , Scialfa Julieta Helena , Cipolla-Neto José
Published: November 2019

The role of neutrophils in cancer is still very contradictory. Several studies have demonstrated the cytotoxic capacity of neutrophils against different types of tumors, by releasing inflammatory cytokines, ROS and activating other immune cells. On the other hand, recent papers have claimed the protumorigenic action of neutrophils, mainly by changing their phenotype and producing cytokines that promote tumor growth. In this context, this study aimed to evaluate neutrophil action and function during tumor development. To do so, we used male Wistar rats inoculated with Walker 256 breast carcinoma. Tumor, circulating neutrophils and bone marrow were studied in the following time points after tumor inoculation: 12 h, 24 h, 48 h, 3 d, 5 d, 7 d, 10 d, and 14 d, in order to analyze neutrophil migration kinetics, circulating neutrophil phenotype and bone marrow response to the tumor growth. Herein, our results demonstrated that W256T was unable to trigger an intratumoral inflammatory response after 5 days of tumor development and consequently, from that point on, prevented neutrophil migration to its microenvironment. Also, the tumor changed circulating neutrophil phenotype by up-regulating inflammation-related genes. Even though circulating neutrophils were entirely able to respond to an inflammatory stimulus, they did not recognize and attack the tumor, allowing the tumor to grow without any immune interference. To promote the entry of neutrophils into the tumor microenvironment, LPS was injected intratumorally. Neutrophil migration and activation due to LPS injection resulted in complete tumor regression in all subjects. In conclusion, activating neutrophils, within the tumor, turned the carcinoma into a recognizable immune target and eliminated it.
Effects of Biochar and Straw Application on the Physicochemical and Biological Properties of Paddy Soils in Northeast China
Authors: Zheng Yu , Han Xiaori , Li Yuying , Yang Jinfeng , Li Na , An Ning
Published: November 2019

Applying biochar to soil has been proposed as a strategy to enhance soil quality and crop productivity. To further evaluate the influence of biochar and straw application on soil fertility and crop yield, a five-year fixed site field experiment was conducted in a paddy field in Northeast China. The experimental design included six treatments: control (CK), biochar (C), straw (S), chemical fertilizers (NPK), biochar with chemical fertilizer (CNPK) and straw with chemical fertilizer (SNPK). The results showed that compared with the NPK treatment, CNPK and SNPK significantly increased soil total porosity, soil air permeability coefficient, soil organic carbon (SOC), C/N ratio, soil microbial biomass carbon (SMBC)‚ soil microbial biomass nitrogen (SMBN), invertase activity and rice yield. Furthermore, amendment of biochar had a better effect on SOC, C/N ratio, SMBC, and SMBN than that of straw. In addition, SMBC, SOC, and total nitrogen (TN) had significant correlations with soil enzyme activities. Therefore, amendment of biochar with chemical fertilizer is an effective measure to improve rice production and soil quality in the northeast of China.
Generation of a Comprehensive Transcriptome Atlas and Transcriptome Dynamics in Medicinal Cannabis
Authors: Braich Shivraj , Baillie Rebecca C. , Jewell Larry S. , Spangenberg German C. , Cogan Noel O. I.
Published: November 2019

Cannabinoids are the main medicinal compounds of interest in the plant Cannabis sativa, that are primarily synthesised in the glandular trichomes; found on female floral buds. The content, composition and yield of secondary metabolites (cannabinoids and terpenoids) is influenced by the plant’s genetics and environment. Some initial gene expression experiments have been performed from strains of this plant species that contrasted in cannabinoid production, however the present knowledge about detailed trichome transcriptomics in this species is limited. An extensive transcriptome atlas was generated by RNA sequencing using root, shoot, flower and trichome tissues from a female plant strain (Cannbio-2) and was enhanced with the addition of vegetative and reproductive tissues from a male cannabis plant. Differential gene expression analysis identified genes preferentially expressed in different tissues. Detailed trichomics was performed from extractions specifically from glandular trichomes as well as female floral tissues at varying developmental stages, to identify stage-specific differentially expressed genes. Candidate genes involved in terpene and cannabinoid synthesis were identified and the majority were found to have an abundant expression in trichomes. The comprehensive transcriptome is a significant resource in cannabis for further research of functional genomics to improve the yield of specialised metabolites with high pharmacological value.
Characterization of the dynamics and the conformational entropy in the binding between TAZ1 and CTAD-HIF-1α
Authors: Nyqvist Ida , Dogan Jakob
Published: November 2019

The interaction between the C-terminal transactivation domain of HIF-1α (CTAD-HIF-1α) and the transcriptional adapter zinc binding 1 (TAZ1) domain of CREB binding protein participate in the initiation of gene transcription during hypoxia. Unbound CTAD-HIF-1α is disordered but undergoes a disorder-to-order transition upon binding to TAZ1. We have here performed NMR side chain and backbone relaxation studies on TAZ1 and side chain relaxation measurements on CTAD-HIF-1α in order to investigate the role of picosecond to nanosecond dynamics. We find that the internal motions are significantly affected upon binding, both on the side chain and the backbone level. The dynamic response corresponds to a conformational entropy change that contributes substantially to the binding thermodynamics for both binding partners. Furthermore, the conformational entropy change for the well-folded TAZ1 varies upon binding to different IDP targets. We further identify a cluster consisting of side chains in bound TAZ1 and CTAD-HIF-1α that experience extensive dynamics and are part of the binding region that involves the N-terminal end of the LPQL motif in CTAD-HIF-1α; a feature that might have an important role in the termination of the hypoxic response.