bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical Approaches to the Development of Artificial Transcription Factors Based on Pyrrole‐Imidazole Polyamides
Authors: Hidaka Takuya , Sugiyama Hiroshi
Published: December 2020

To maintain the functions of living organisms, cells have developed complex gene regulatory networks. Transcription factors have a central role in spatiotemporal control of gene expression and this has motivated us to develop artificial transcription factors that mimic their function. We found that three functions could be mimicked by applying our chemical approaches: i) efficient delivery into organelles that contain target DNA, ii) specific DNA binding to the target genomic region, and iii) regulation of gene expression by interaction with other transcription coregulators. We chose pyrrole‐imidazole polyamides (PIPs), sequence‐selective DNA binding molecules, as DNA binding domains, and have achieved each of the required functions by introducing other functional moieties. The developed artificial transcription factors have potential as chemical tools that can be used to artificially modulate gene expression to enable cell fate control and to correct abnormal gene regulation for therapeutic purposes.
Dieckol alleviates dextran sulfate sodium‐induced colitis via inhibition of inflammatory pathway and activation of Nrf2/HO‐1 signaling pathway
Authors: Zhu Xiaoyan , Sun Yuanhua , Zhang Ying , Su Xinyou , Luo Changqin , Alarifi Saud , Yang Hui
Published: December 2020

Ulcerative colitis (UC) is the major type of inflammatory ailment with elevated prevalence worldwide. Dieckol (DEK) is a phlorotannin that is extensively found in marine algae and has been found to have different pharmacological properties. Nevertheless, the impact of DEK in UC has not been investigated earlier. Therefore, we appraised DEK's function in dextran sulfate sodium (DSS)‐induced UC in the mouse. An overall of 30 mice was randomized into 5 equal groups. Control mice treated with a standard diet (group I), colitis mice challenged with 3% of DSS through drinking water for 7 consecutive days (group II), DEK was supplemented via oral gavage from day 1 to 10 at the dosages of 5, 10, and 15 mg/kg b.wt, respectively. All animals were sacrificed on the 11th day. The body weight (bwt), colon length, disease activity index, malondialdehyde (MDA), myeloperoxidase (MPO), and histological features were observed using suitable techniques, and COX‐2 expression was investigated by immunohistochemistry. Moreover, TNF‐α, IL‐1β, p65, IκBα, HO‐1, and Nrf2 expressions were measured using ELISA and RT‐PCR techniques, respectively. DEK treatment to the colitis mice considerably lessened, DSS‐challenged alterations in body weight, DAI, colonic length shortening and histological changes. DEK exhibited potent antioxidant effects due to the reduced MDA and MPO, and Nrf2 expression markers while the HO‐1 marker was augmented. Additionally, DEK also suppressed the expression s of TNF‐α, IL‐1β, and the p‐p65, p‐IκBα, and p65 and augmented the expression of IκBα, which eventually proved the anti‐inflammatory potential of DEK against the DSS‐challenge. Based on these results, DEK has been found effective in mitigating colitis, conceivably alleviating colon inflammation through the NF‐κB inhibition and triggering of Nrf2/HO‐1 signaling cascade.
Nimodipine attenuates dibutyl phthalate‐induced learning and memory impairment in kun ming mice: An in vivo study based on bioinformatics analysis
Authors: Yan Biao , Ma Ping , Chen Shaohui , Cheng Hongguo , Tang Min , Sun Yanling , Yang Xu , Wu Yang , Cheng Menglin
Published: December 2020

Dibutyl phthalate (DBP), a typical representative of phthalate esters (PAEs), is used as a plasticizer in various industrial applications and has been reported to be responsible for neurobehavioral changes. Despite mounting evidence showing that nimodipine (Nim) palys a neuropharmacological and psychopharmacological role in neurons, the attenuating effects of Nim on learning and memory impairment induced by DBP exposure remain unknown. Based on bioinformatics analysis we found that the biological processes affected by both DBP and Nim may involve the calcium signaling pathway, the MAPK signaling pathway and the apoptosis pathway. The results of an in vivo study confirmed that DBP affects the levels of Ca2+‐related proteins, up‐regulates phosphorylated ‐ERK1/2 expression and results in hippocampal neuronal damage and apoptosis, whereas Nim as a Ca2+ antagonist, has a certain neuroprotective role to avoid these adverse effects. Our data suggest that Nim could be used to attenuate the learning and memory impairment in DBP‐exposed mice, to down‐regulate intracellular Ca2+ levels, subordinate the ERK1/2 pathway and attenuate apoptosis in hippocampal tissue.
Ten cases ofMycobacterium aviumsubsp.hominissuisinfections linked to equine abortions in Japan, 2018–2019
Authors: Kinoshita Yuta , Takechi Mari , Uchida‐Fujii Eri , Miyazawa Kunio , Nukada Toshio , Niwa Hidekazu
Published: December 2020

Bacterial placentitis in horses commonly results in abortion, premature birth or compromised neonatal foal health. Although mycobacterial infections are generally uncommon in horses, 10 equine abortion cases caused byMycobacterium aviumsubsp.hominissuis(MAH) infections occurred between 2018 and 2019 in Japan. They occurred on seven Thoroughbred horse farms in the Hidaka district of Hokkaido, but direct contact among the mares on different farms was not recorded. Most cases were characterized by extensive pathological lesions of the placenta, which are not typical in cases of common pathogenic bacteria such asStreptococcus zooepidemicusandEscherichia coli. All abortions featured white–yellow exudates on the surface of the placenta. Mycobacterial granuloma formations were histologically found in the placenta and fetal organs, and acid‐fast bacteria were isolated from the placenta, fetal samples (heart, lung, liver, kidney, spleen and stomach contents) or uterine lavage fluid. The greatest number of bacteria was isolated from necrotic lesions on the placenta, which could be an important site for bacterial isolation in mycobacterial equine abortions. The isolates were identified as MAH based on internal genome sequences. In variable number tandem repeat analysis, all patterns of the strains were identical. Single nucleotide polymorphism analysis of the core genome grouped all strains in the II‐a/SC3 subcluster. Both results reveal that these strains share the same genetic background, suggesting that the horses had been infected by the same unknown contagious source.
A public policy primer on consolidating the water‐energy nexus
Authors: D’Souza Jayesh
Published: December 2020

The purpose of this paper was to study advancing the water‐energy nexus in the context of urban metabolism and to extend past literature reviews to capture water and energy integration policy. The use of water for energy generation and energy for water treatment are a couple of examples of this nexus that have been well‐documented over the years. This paper answers operational and policy questions related to integration while comparing nexus efforts in two countries at the forefront of this discussion: the United States and Australia. Barriers to successful integration include gaps in data collection and lack of a consensus model for integration advancement. The study found that jurisdictions can take advantage of opportunities to consolidate the nexus by adopting new technologies that create efficient and cost‐effective ways for delivering a sustainable output by changing the way inputs are utilized. They could also develop a tracking system to measure the results of their efforts and evaluate if targeted outcomes are being achieved.
Association between coronal caries and malocclusion in an adult population
Authors: Bernhardt Olaf , Krey Karl-Friedrich , Daboul Amro , Völzke Henry , Splieth Christian , Kocher Thomas , Schwahn Christian
Published: December 2020

Purpose

Only a few but conflicting results have been reported on the association between malocclusions and caries. We investigated this association using data from the population-based cross-sectional Study of Health in Pomerania (SHIP).

Methods

Sagittal, vertical and transversal intermaxillary relationship, space conditions and sociodemographic parameters of 1210 dentate subjects (median age 30 years, interquartile range 25–35 years) were collected. Caries was assessed with the Decayed-Missing-Filled Surfaces index but analyzed as ordered outcome (four levels: sound, enamel caries, caries, tooth loss) in ordinal multilevel models, taking into account subject, jaw, and tooth level simultaneously.

Results

Anterior open bite ≤3 mm (odds ratio [OR] = 2.08, 95% confidence interval [CI]: 1.19–3.61), increased sagittal overjet of 4–6 mm (OR = 1.31, CI: 1.05–1.64), distal occlusion of ½ premolar width (OR = 1.27, CI: 1.05–1.53) and distal 1 premolar width (OR = 1.31, CI: 1.06–1.63) were associated with adjusted increased odds for a higher outcome level (caries). Anterior spacing (OR = 0.24, CI: 0.17–0.33), posterior spacing, (OR = 0.69, CI: 0.5–0.95), posterior crowding (OR = 0.57, CI: 0.49–0.66) and buccal nonocclusion (OR = 0.54, CI: 0.33–0.87) were associated with a lower outcome level (caries).

Conclusion

The results from this population-based study suggest that a connection between caries and malocclusion exists to a limited extent in young adults. The associations with caries are contradictory for several malocclusion variables. Distal occlusion (OR = 1.31, CI: 1.06–1.63) and related skeletal anomalies displayed positive associations with caries whereas crowding did not. Orthodontic treatment of anterior crowding would probably not interfere with caries experience. These aspects should be considered for patient information and in treatment decisions.
Abnormalities of synaptic mitochondria in autism spectrum disorder and related neurodevelopmental disorders
Authors: Rojas-Charry Liliana , Nardi Leonardo , Methner Axel , Schmeisser Michael J.
Published: December 2020

Autism spectrum disorder (ASD) is a neurodevelopmental condition primarily characterized by an impairment of social interaction combined with the occurrence of repetitive behaviors. ASD starts in childhood and prevails across the lifespan. The variability of its clinical presentation renders early diagnosis difficult. Mutations in synaptic genes and alterations of mitochondrial functions are considered important underlying pathogenic factors, but it is obvious that we are far from a comprehensive understanding of ASD pathophysiology. At the synapse, mitochondria perform diverse functions, which are clearly not limited to their classical role as energy providers. Here, we review the current knowledge about mitochondria at the synapse and summarize the mitochondrial disturbances found in mouse models of ASD and other ASD-related neurodevelopmental disorders, like DiGeorge syndrome, Rett syndrome, Tuberous sclerosis complex, and Down syndrome.
Schockraum- und Schwerverletztenversorgung als „Verlustgeschäft“
Authors: Gross Thomas , Amsler Felix
Published: December 2020

Hintergrund

Es galt herauszufinden, wie kostendeckend die Versorgung potenziell Schwerverletzter in einem Schweizer Traumazentrum ist, und inwieweit Spitalgewinne bzw. -verluste mit patientenbezogenen Unfall‑, Behandlungs- oder Outcome-Daten korrelieren.

Methodik

Analyse aller 2018 im Schockraum (SR) bzw. mit Verletzungsschwere New Injury Severity Score (NISS) ≥8 notfallmäßig stationär behandelter Patienten eines Schwerverletztenzentrums der Schweiz (uni- und multivariate Analyse; p < 0,05).

Ergebnisse

Für das Studienkollektiv (n = 513; Ø NISS = 18) resultierte gemäß Spitalkostenträgerrechnung ein Defizit von 1,8 Mio. CHF. Bei einem Gesamtdeckungsgrad von 86 % waren 66 % aller Fälle defizitär (71 % der Allgemein- vs. 42 % der Zusatzversicherten; p < 0,001). Im Mittel betrug das Defizit 3493.- pro Patient (allg. Versicherte, Verlust 4545.-, Zusatzversicherte, Gewinn 1318.-; p < 0,001). Auch „in“- und „underlier“ waren in 63 % defizitär. SR-Fälle machten häufiger Verlust als Nicht-SR-Fälle (73 vs. 58 %; p = 0,002) wie auch Traumatologie- vs. Neurochirurgiefälle (72 vs. 55 %; p < 0,001). In der multivariaten Analyse ließen sich 43 % der Varianz erhaltener Erlöse mit den untersuchten Variablen erklären. Hingegen war der ermittelte Deckungsgrad nur zu 11 % (korr. R2) durch die Variablen SR, chirurgisches Fachgebiet, Intensivaufenthalt, Thoraxverletzungsstärke und Spitalletalität zu beschreiben. Case-Mix-Index gemäß aktuellen Diagnosis Related Groups (DRG) und Versicherungsklasse addierten weitere 13 % zu insgesamt 24 % erklärter Varianz.

Diskussion

Die notfallmäßige Versorgung potenziell Schwerverletzter an einem Schweizer Traumazentrum erweist sich nur in einem Drittel der Fälle als zumindest kostendeckend, dies v. a. bei Zusatzversicherten, Patienten mit einem hohen Case-Mix-Index oder einer IPS- bzw. kombinierten Polytrauma- und Schädel-Hirn-Trauma-DRG-Abrechnungsmöglichkeit.
Dynamics of Shadow System of a Singular Gierer–Meinhardt System on an Evolving Domain
Authors: Kavallaris Nikos I. , Barreira Raquel , Madzvamuse Anotida
Published: December 2020

The main purpose of the current paper is to contribute towards the comprehension of the dynamics of the shadow system of a singular Gierer–Meinhardt model on an isotropically evolving domain. In the case where the inhibitor’s response to the activator’s growth is rather weak, then the shadow system of the Gierer–Meinhardt model is reduced to a single though non-local equation whose dynamics is thoroughly investigated throughout the manuscript. The main focus is on the derivation of blow-up results for this non-local equation, which can be interpreted as instability patterns of the shadow system. In particular, a diffusion-driven instability (DDI), or Turing instability, in the neighbourhood of a constant stationary solution, which then is destabilised via diffusion-driven blow-up, is observed. The latter indicates the formation of some unstable patterns, whilst some stability results of global-in-time solutions towards non-constant steady states guarantee the occurrence of some stable patterns. Most of the theoretical results are verified numerically, whilst the numerical approach is also used to exhibit the dynamics of the shadow system when analytical methods fail.
Impact of early vs. delayed initiation of dutasteride/tamsulosin combination therapy on the risk of acute urinary retention or BPH-related surgery in LUTS/BPH patients with moderate-to-severe symptoms at risk of disease progression
Authors: D’Agate Salvatore , Chavan Chandrashekhar , Manyak Michael , Palacios-Moreno Juan Manuel , Oelke Matthias , Michel Martin C. , Roehrborn Claus G. , Della Pasqua Oscar
Published: December 2020

Purpose

To evaluate the effect of delayed start of combination therapy (CT) with dutasteride 0.5 mg and tamsulosin 0.4 mg on the risk of acute urinary retention or benign prostatic hyperplasia (BPH)-related surgery (AUR/S) in patients with moderate-to-severe lower urinary tract symptoms (LUTS) at risk of disease progression.

Methods

Using a time-to-event model based on pooled data from 10,238 patients from Phase III/IV dutasteride trials, clinical trial simulations (CTS) were performed to assess the risk of AUR/S up to 48 months in moderate-to-severe LUTS/BPH patients following immediate and delayed start of CT for those not responding to tamsulosin monotherapy. Simulation scenarios (1300 subjects/arm) were investigated, including immediate start (reference) and alternative delayed start (six scenarios 1–24 months). AUR/S incidence was described by Kaplan–Meier survival curves and analysed using log-rank test. The cumulative incidence of events as well as the relative and attributable risks were summarised stratified by treatment.

Results

Survival curves for patients starting CT at month 1 and 3 did not differ from those who initiated CT immediately. By contrast, significant differences (p < 0.001) were observed when switch to CT occurs ≥ 6 months from the initial treatment. At month 48, AUR/S incidence was 4.6% vs 9.5%, 11.0% and 11.3% in patients receiving immediate CT vs. switchers after 6, 12 and 24 months, respectively.

Conclusions

Start of CT before month 6 appears to significantly reduce the risk of AUR/S compared with delayed start by ≥ 6 months. This has implications for the treatment algorithm for men with LUTS/BPH at risk of disease progression.
Monitoring of the auditory pathway maturation after early intervention during the first year of life in infants with sensorineural hearing loss
Authors: Matin F. , Haumann S. , Roßberg W. , Mitovska D. , Lenarz T. , Lesinski-Schiedat A.
Published: December 2020

Purpose

The objective of this study was to investigate the auditory pathway maturation monitored by auditory brainstem responses (ABR) in infants with hearing loss during the first year of life. ABR were used to estimate hearing thresholds and the effect of early intervention strategies using hearing aids (HA).

Methods

Click-evoked ABRs were measured in 102 infants aged from 0 to 12 months to determine their individual auditory threshold. Early therapy intervention was recommended before 12 months of age and analyzed. To evaluate the effect of hearing amplification on auditory maturation, different subgroups of infants with moderate hearing loss were analyzed and the auditory pathway maturation was determined based on IPL I–V shortening.

Results

Overall, 110 ears (54.0% of 204 ears) with mild to profound HL showed threshold changes of 10 dB up to 60 dB in the follow-up ABR testing. HA were prescribed at the age of 3.8 ± 3.9 months. Cochlear implantation (CI) was performed in cases of repeated profound HL at the age of 9.9 months ± 4.5 months. A significant shortening of IPL I–V in all subgroups of infants (with and without risk factors) who received HA was shown and assumed auditory pathway maturation.

Conclusion

An early intervention using optimally fitted HA influenced auditory pathway maturation and may lead to improvements of hearing thresholds during the first year of life in infants. This study underscores the importance of not only providing HAs to infants, but also controlling for hearing threshold changes ensuring that HAs provide the optimal level of intervention or CI is indicated.
Chiari 1 malformation and exome sequencing in 51 trios: the emerging role of rare missense variants in chromatin-remodeling genes
Authors: Provenzano Aldesia , La Barbera Andrea , Scagnet Mirko , Pagliazzi Angelica , Traficante Giovanna , Pantaleo Marilena , Tiberi Lucia , Vergani Debora , Kurtas Nehir Edibe , Guarducci Silvia , Bargiacchi Sara , Forzano Giulia , Artuso Rosangela , Palazzo Viviana , Kura Ada , Giordano Flavio , di Feo Daniele , Mortilla Marzia , De Filippi Claudio , Mattei Gianluca , Garavelli Livia , Giusti Betti , Genitori Lorenzo , Zuffardi Orsetta , Giglio Sabrina
Published: December 2020

Type 1 Chiari malformation (C1M) is characterized by cerebellar tonsillar herniation of 3–5 mm or more, the frequency of which is presumably much higher than one in 1000 births, as previously believed. Its etiology remains undefined, although a genetic basis is strongly supported by C1M presence in numerous genetic syndromes associated with different genes. Whole-exome sequencing (WES) in 51 between isolated and syndromic pediatric cases and their relatives was performed after confirmation of the defect by brain magnetic resonance image (MRI). Moreover, in all the cases showing an inherited candidate variant, brain MRI was performed in both parents and not only in the carrier one to investigate whether the defect segregated with the variant. More than half of the variants were Missense and belonged to the same chromatin-remodeling genes whose protein truncation variants are associated with severe neurodevelopmental syndromes. In the remaining cases, variants have been detected in genes with a role in cranial bone sutures, microcephaly, neural tube defects, and RASopathy. This study shows that the frequency of C1M is widely underestimated, in fact many of the variants, in particular those in the chromatin-remodeling genes, were inherited from a parent with C1M, either asymptomatic or with mild symptoms. In addition, C1M is a Mendelian trait, in most cases inherited as dominant. Finally, we demonstrate that modifications of the genes that regulate chromatin architecture can cause localized anatomical alterations, with symptoms of varying degrees.
Fast and simple model generation for superjunction power MOSFETs
Authors: Fuchs Michael , Spielberger Lukas , Odreitz Ko , Deutschmann Bernd
Published: December 2020

This paper describes a new way to create a behavioral model for power MOSFETs with highly nonlinear parasitic capacitances like those based on superjunction (SJ) principles. The process ranges from a simple measurement to the final model for SPICE simulations. One of the benefits of the proposed modeling technique is that it does not require any information about the voltage-dependent capacitances of the MOSFET from the data sheet but instead relies on a simple measurement method using a vector network analyzer. The measurement data can be used for modeling all parasitic capacitances and inductances in the SPICE model. Compared to existing simulation models by the manufacturer, the proposed model promises better convergence, more accurate high-frequency behavior and faster simulation time. The advantages and disadvantages of this modeling technique are discussed.
Demographic drivers of Norway rat populations from urban slums in Brazil
Authors: Zeppelini C. G. , Carvalho-Pereira T. , Alves R. Sady , Santiago D. C. C. , Santo V. F. Espirito , Begon M. , Costa F. , Khalil Hussein
Published: December 2020

The Norway rat is a globally distributed pest, known for its resilience to eradication and control programs. Efficient population control, especially in urban settings, is dependent on knowledge of rat demography and population ecology. We analyzed the relationship between four demographic outcomes, estimated by live-trapping data, and fine-scale environmental features measured at the capture site. Wounds, a proxy for agonistic interactions, were associated with mature individuals. Areas with environmental features favorable to rats, such as open sewers and unpaved earth, were associated with more mature individuals with a better body condition index. The control measures (environmental stressors) are likely to be disrupting the social structure of rat colonies, increasing the frequency and distribution of agonistic interactions, which were common in both sexes and maturity states. The relationship between the favorable environmental conditions and the demographic markers analyzed indicate possible targets for infestation control through environmental manipulation, and could be incorporated into current pest management programs to achieve long-term success. Our study indicate that urban interventions focused on removal of potential resources for rats could be potential long-term solutions by reducing the carrying capacity of the environment.
Quantification of different microplastic fibres discharged from textiles in machine wash and tumble drying
Authors: Kärkkäinen Niina , Sillanpää Markus
Published: December 2020

Microplastic fibres released in synthetic cloth washing have been shown to be a source of microplastics into the environment. The annual emission of polyester fibres from household washing machines has earlier been estimated to be 150,000 kg in a country with a population of 5.5 × 106 (Finland). The objectives of this study were (1) to quantify the emissions of synthetic textile fibres discharged from five sequential machine washes (fibre number and length) and tumble dryings (fibre mass) and (2) to determine the collection efficiency of two commercial fibre traps. The synthetic fabrics were five types of polyester textiles, one polyamide and one polyacryl. The number of fibres released from the test fabrics in the first wash varied in the range from 1.0 × 105 to 6.3 × 106 kg−1. The fibre lengths showed that the fleece fabrics released, on average, longer fibres than the technical sports t-shirts. The mass of fibres ranged from 10 to 1700 mg/kg w/w in the first drying. Fibre emissions showed a decreasing trend both in sequential washes and dryings. The ratio of the fibre emissions in machine wash to tumble drying varied between the fabrics: the ratio was larger than one to polyester and polyamide technical t-shirts whereas it was much lower to the other tested textiles. GuppyFriend washing bag and Cora Ball trapped 39% and 10% of the polyester fibres discharged in washings, respectively.
Scale-related governance challenges in the water–energy–food nexus: toward a diagnostic approach
Authors: Pahl-Wostl Claudia , Gorris Philipp , Jager Nicolas , Koch Larissa , Lebel Louis , Stein Christian , Venghaus Sandra , Withanachchi Sisira
Published: December 2020

The notion of a water–energy–food (WEF) nexus was introduced to encourage a more holistic perspective on the sustainable development of natural resources. Most attention has been directed at identifying potential synergies and trade-offs among sectors that could be addressed with improved technologies and management. The governance of the WEF nexus more broadly has received comparatively little attention, and the importance of scale in space and time has been largely ignored. Inspired by scholarship on multi-level governance in individual sectors, this paper identifies four scale-related governance challenges in the WEF nexus, namely: (1)scalar fit, which arises when planning and operating procedures work at different levels along the scales of space and time in different sectors; (2)scalar strategies, wherever the levels at which actors have influence and in which action takes place are contested and negotiated; (3)institutional interplay, where rules and norms in different sectors influence each other at different levels; (4)scalar uncertainty, arising out of the complexity of multi-level and multi-scale interactions. The relevance of these four challenges is illustrated with case studies from developed and developing countries. These examples show the importance of considering multiple levels and scales when assessing the likely effectiveness of WEF nexus governance mechanisms or proposals. The cases underline the need to pay close attention to issues of power, contestation, and negotiation, in addition to the analysis of institutional design. Thus, this paper recommends that nexus governance efforts and proposals be scrutinized for scale assumptions. The four identified challenges offer a suitable starting point for diagnosis.
Prognostic value of skeletal muscle mass during tyrosine kinase inhibitor (TKI) therapy in cancer patients: a systematic review and meta-analysis
Authors: Rinninella Emanuele , Cintoni Marco , Raoul Pauline , Ponziani Francesca Romana , Pompili Maurizio , Pozzo Carmelo , Strippoli Antonia , Bria Emilio , Tortora Giampaolo , Gasbarrini Antonio , Mele Maria Cristina
Published: December 2020

Low muscle mass has been associated with worse clinical outcomes in various cancers. This work investigated whether, during tyrosine kinases inhibitors (TKIs) therapy, low muscle mass was associated with treatment toxicity and survival outcomes. A systematic literature search was performed in Pubmed, Web of Science, and Scopus databases from inception to June 2020, based on fixed inclusion and exclusion criteria. Effect sizes were estimated with hazard ratios (HR) and odds ratios (OR) with 95% confidence interval (CI) and heterogeneity was assessed by measuring inconsistency (I2) based on the Chi squared test. A total of 24 retrospective studies were identified, enrolling patients treated with sorafenib (n = 12), sunitinib (n = 6), lenvatinib (n = 3), regorafenib (n = 2), gefitinib (n = 1), imatinib (n = 1), and pazopanib (n = 1). Thirteen studies were deemed eligible for pooled analyses. Meta-analyses found a significant effect of low muscle mass on dose-limiting toxicity (DLT) (OR 2.40, 95% CI 1.26–4.58, p = 0.008, I2 = 51%) in patients treated with TKI therapy. A subgroup analysis by treatment showed an association between DLT and low muscle during sorafenib or sunitinib, although not significant. A significant association between low skeletal muscle index and poorer overall survival was observed in HCC patients treated with sorafenib (HR 1.45, 95% CI 1.07–1.96, p = 0.02). For other TKIs, although some results showed an association between low muscle mass and worse outcomes, the number of studies for each TKI therapy was too small to reach conclusions. Skeletal muscle mass could influence the prognosis of some TKI-treated patients. This effect is demonstrated in sorafenib-treated HCC patients but remains almost unexplored in other cancer patients undergoing TKI therapy. Further prospective studies with large sample size and sufficient follow-up are needed to clarify the role of muscle mass in the metabolism of TKI-based cancer treatment, and its association with toxicity and survival.
Neurochemical and Behavioral Effects of a New Hallucinogenic Compound 25B-NBOMe in Rats
Authors: Wojtas Adam , Herian Monika , Skawski Mateusz , Sobocińska Małgorzata , González-Marín Alejandro , Noworyta-Sokołowska Karolina , Gołembiowska Krystyna
Published: December 2020

4-Bromo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25B-NBOMe) is a hallucinogen exhibiting high binding affinity for 5-HT2A/C serotonin receptors. In the present work, we investigated its effect on dopamine (DA), serotonin (5-HT), acetylcholine (ACh), and glutamate release in the rat frontal cortex, striatum, and nucleus accumbens. Hallucinogenic activity, impact on cognitive and motor functions, and anxiogenic/anxiolytic properties of this compound were also tested. The release of DA, 5-HT, ACh, and glutamate was studied using microdialysis in freely moving animals. Hallucinogenic activity was investigated using head and body twitch response (WDS), cognitive functions were examined with the novel object recognition test (NOR), locomotor activity was studied in the open field (OF), while anxiogenic/anxiolytic effect was tested using the light/dark box (LDB). Neurotoxicity was evaluated with the comet assay. 25B-NBOMe increased DA, 5-HT, and glutamate release in all studied brain regions, induced hallucinogenic activity, and lowered the recognition index (Ri) vs. control in the NOR test. It also decreased locomotor activity of rats in the OF test. The effect of 25B-NBOMe in the NOR test was inhibited by scopolamine. In the LDB test, the time spent in the dark zone was longer in comparison to control and was dose-dependent. In contrast to MDMA, 25B-NBOMe showed subtle genotoxic effect observed in the comet assay.

Our findings indicate that 25B-NBOMe shows hallucinogenic activity in the wide range of doses. The changes in neurotransmitter levels may be related to 25B-NBOMe affinity for 5-HT2A receptor. Alterations in the NOR, OF, and LDB indicate that 25B-NBOMe impacts short-term memory, locomotion, and may be anxiogenic.
SeSaMe: Metagenome Sequence Classification of Arbuscular Mycorrhizal Fungi-Associated Microorganisms
Authors: Eun Kang Jee , Ciampi Antonio , Hijri Mohamed
Published: December 2020

Arbuscular mycorrhizal fungi (AMF) are plant root symbionts that play key roles in plant growth and soil fertility. They are obligate biotrophic fungi that form coenocytic multinucleated hyphae and spores. Numerous studies have shown that diverse microorganisms live on the surface of and inside their mycelia, resulting in a metagenome when whole-genome sequencing (WGS) data are obtained from sequencing AMF cultivated in vivo. The metagenome contains not only the AMF sequences, but also those from associated microorganisms. In this study, we introduce a novel bioinformatics program, Spore-associated Symbiotic Microbes (SeSaMe), designed for taxonomic classification of short sequences obtained by next-generation DNA sequencing. A genus-specific usage bias database was created based on amino acid usage and codon usage of a three consecutive codon DNA 9-mer encoding an amino acid trimer in a protein secondary structure. The program distinguishes between coding sequence (CDS) and non-CDS, and classifies a query sequence into a genus group out of 54 genera used as reference. The mean percentages of correct predictions of the CDS and the non-CDS test sets at the genus level were 71% and 50% for bacteria, 68% and 73% for fungi (excluding AMF), and 49% and 72% for AMF (Rhizophagus irregularis), respectively. SeSaMe provides not only a means for estimating taxonomic diversity and abundance but also the gene reservoir of the reference taxonomic groups associated with AMF. Therefore, it enables users to study the symbiotic roles of associated microorganisms. It can also be applicable to other microorganisms as well as soil metagenomes. SeSaMe is freely available at www.fungalsesame.org.
SeSaMe PS Function: Functional Analysis of the Whole Metagenome Sequencing Data of the Arbuscular Mycorrhizal Fungi
Authors: Eun Kang Jee , Ciampi Antonio , Hijri Mohamed
Published: December 2020

In this study, we introduce a novel bioinformatics program, Spore-associated Symbiotic Microbes Position-specific Function (SeSaMe PS Function), for position-specific functional analysis of short sequences derived from metagenome sequencing data of the arbuscular mycorrhizal fungi. The unique advantage of the program lies in databases created based on genus-specific sequence properties derived from protein secondary structure, namely amino acid usages, codon usages, and codon contexts of 3-codon DNA 9-mers. SeSaMe PS Function searches a query sequence against reference sequence database, identifies 3-codon DNA 9-mers with structural roles, and creates a comparative dataset containing the codon usage biases of the 3-codon DNA 9-mers from 54 bacterial and fungal genera. The program applies correlation principal component analysis in conjunction with K-means clustering method to the comparative dataset. 3-codon DNA 9-mers clustered as a sole member or with only a few members are often structurally and functionally distinctive sites that provide useful insights into important molecular interactions. The program provides a versatile means for studying functions of short sequences from metagenome sequencing and has a wide spectrum of applications. SeSaMe PS Function is freely accessible at www.fungalsesame.org.
mrMLM v4.0.2: An R Platform for Multi-Locus Genome-Wide Association Studies
Authors: Zhang Ya-Wen , Tamba Cox Lwaka , Wen Yang-Jun , Li Pei , Ren Wen-Long , Ni Yuan-Li , Gao Jun , Zhang Yuan-Ming
Published: December 2020

Previous studies have reported that some important loci are missed in single-locus genome-wide association studies (GWAS), especially because of the large phenotypic error in field experiments. To solve this issue, multi-locus GWAS methods have been recommended. However, only a few software packages for multi-locus GWAS are available. Therefore, we developed an R software named mrMLM v4.0.2. This software integrates mrMLM, FASTmrMLM, FASTmrEMMA, pLARmEB, pKWmEB, and ISIS EM-BLASSO methods developed by our lab. There are four components in mrMLM v4.0.2, including dataset input, parameter setting, software running, and result output. The fread function in data.table is used to quickly read datasets, especially big datasets, and the doParallel package is used to conduct parallel computation using multiple CPUs. In addition, the graphical user interface software mrMLM.GUI v4.0.2, built upon Shiny, is also available. To confirm the correctness of the aforementioned programs, all the methods in mrMLM v4.0.2 and three widely-used methods were used to analyze real and simulated datasets. The results confirm the superior performance of mrMLM v4.0.2 to other methods currently available. False positive rates are effectively controlled, albeit with a less stringent significance threshold. mrMLM v4.0.2 is publicly available at BioCode (https://bigd.big.ac.cn/biocode/tools/BT007077) or R (https://cran.r-project.org/web/packages/mrMLM.GUI/index.html) as an open-source software.
Ethical Dilemmas in Schools
Authors: Simpson Douglas J. , Sacken Donal M.
Published: December 2020

This work investigates the complexity of ethics as a field of inquiry and practice across a principal's career. Fully contextualized, and thus carrying the contradictions and requirements of any school, the issues realistically do not usually lead to a single, beat-all answer, as any solution will likely have positive and negative consequences. Drawn from the authors' experiences and studies of schools over decades, the central figure is a fictional principal of a magnet school, whose dilemmas reflect the questions educators must be prepared for. Each decision takes into account the principal's and staff's identities and values because they are all human and their opinions influence the outcomes. The work injects analytic, virtue, feminist, care, deontological, and critical theory insights as Deweyan ethics provides a lens for examining dilemmas. This accessible work blends reflective theory, the ordinary worlds of schools, and engaging pedagogical practice to guide those planning to enter the education sector.
Defining Crimes in a Global Age: Criminalization as a Transnational Legal Process
Authors: Aaronson Ely , Shaffer Gregory
Published: December 2020

The design of empirical research and theory-building projects in the sociolegal literature on criminalization is often premised on a presumed dichotomy between domestic and international planes of criminal lawmaking. However, in a global era in which domestic processes of criminalization are increasingly shaped by norms, institutions, and actors developed and operating outside national borders, criminalization research should develop a new theoretical frame for studying how international and domestic practices of criminal lawmaking interact with one another. This article builds from the theory of transnational legal orders and the recursivity of law to propose a transnational processual theoretical framework for the study of criminalization. This framework provides tools for investigating how criminal prohibitions are constituted through recursive interactions between actors operating in international, national, and local sites of legal practice. It draws on empirical studies to show how the processes of constructing, applying, and contesting definitions of international and transnational crimes are embedded in broader structures of power. The article demonstrates how a processual theory of transnational criminalization sheds light on important sociolegal questions about the driving forces and consequences of current efforts to harmonize the definitions of criminal activities across national jurisdictions.
Divided government, delegation, and civil service reform
Authors: Ash Elliott , Morelli Massimo , Vannoni Matia
Published: December 2020

This paper sheds new light on the drivers of civil service reform in US states. We first demonstrate theoretically that divided government is a key trigger of civil service reform, providing nuanced predictions for specific configurations of divided government. We then show empirical evidence for these predictions using data from the second half of the 20th century: states tended to introduce these reforms under divided government, and in particular when legislative chambers (rather than legislature and governor) were divided.
(Mis)Calculations, Psychological Mechanisms, and the Future Politics of People of Color
Authors: Pérez Efrén
Published: December 2020

This essay comments on three questions about race, ethnicity, and politics in the contemporary United States—Howdid we get here?Whoare we now? And,whereare we going next? I grapple with these questions as a political psychologist steeped in the study of intergroup politics. In this capacity, I will argue that structural (mis)calculations have paved the road toward present intergroup relations, where identity politics reigns supreme. I then discuss America's current racial landscape, arguing that reality is more complex than before, especially as it concerns political relations between Whites and non-Whites. In this regard, I will claim that political psychology holds special insights to generate new knowledge about how (non-)Whites are navigating this changing racial landscape. Finally, I will advocate, strongly, for a greater sense of wonder about the multiplicity of identities that people of color hold. In particular, I will claim that byrelaxingour assumption that race is the main identity that matters to people of color, we stand to better appreciate just how adaptive non-Whites are to their political surroundings, leading us toward new insights about the origins and nature of mass political engagement and involvement.
Revealing Issue Salience via Costly Protest: How Legislative Behavior Following Protest Advantages Low-Resource Groups
Authors: Gause LaGina
Published: December 2020

Collective action, particularly by low-resource groups, presents an opportunity for re-election-minded legislators to learn about (and subsequently represent) their constituents’ salient interests. In fact, legislators are more likely to support the preferences of protesters than non-protesters. Legislators are also more likely to support the preferences of racial and ethnic minority, low-income and grassroots protesting groups than they are to represent better-resourced protesters. This argument emerges from a formal theory and is empirically tested using legislative roll-call vote data from the 102nd through the 104th US Congresses and data on civil rights, minority issues and civil liberties issue area protests reported in theNew York Times. This counterintuitive result enhances understanding of inequalities in representation. It demonstrates that under certain conditions, political representation favors disadvantaged populations.
New analytical tools and frameworks to understand dementia: what can a human rights lens offer?
Authors: Cahill Suzanne
Published: December 2020

The biomedical model has traditionally informed the dominant discourse on dementia and has significantly shaped practitioners’, policy makers’ and researchers’ responses. This model contextualises dementia as a progressive neuro-degenerative cognitive disorder and focuses on deficits and underlying pathology, often overlooking the fact that the person can and should be an active partner in the treatment process. Beginning in the late 1990s, the exclusive reliance on the bio-medical model has come under increasing scrutiny with a growing awareness that by recasting dementia in broader social and more humanitarian terms, much can be done to promote the individual's quality of life. Different frameworks and analytical tools have been forwarded to help us better understand dementia. These include personhood, citizenship, public health, disability and human rights. This review examines the merits of framing dementia as a disability, a citizenship concern and a human rights issue. It highlights some of the potential gains that can arise for the individual in using a human rights model to enhance practice, inform policy and create a more balanced research agenda. The article concludes by arguing that the complexities and magnitude of dementia are such that it requires multiple responses and a broad range of interpretative frameworks.
Optimal Architecture Planning of Modules for Reconfigurable Manipulators
Authors: Dogra Anubhav , Padhee Srikant Sekhar , Singla Ekta
Published: December 2020

Modules are requisite for the realization of modular reconfigurable manipulators. The design of modules in literature mainly revolves around geometric aspects and features such as lengths, connectivity and adaptivity. Optimizing and designing the modules based on dynamic performance is considered as a challenge here. The present paper introduces an Architecture-Prominent-Sectioning (APS) strategy for the planning of architecture of modules such that a reconfigurable manipulator possesses minimal joint torques during its operations. Proposed here is the transferring of complete structure into an equivalent system, perform optimization and map the resulting arrangement into possible architecture. The strategy has been applied on a set of modular configurations considering three-primitive-paths. The possibility of getting advanced/complex shapes is also discussed to incorporate the idea of a modular library.
Poor vitamin D status and the risk of maternal depression: a dose–response meta-analysis of observational studies
Authors: Tan Quansheng , Liu Shuai , Chen Dajie
Published: December 2020

Objective:

The association between 25-hydroxyvitamin D (25(OH)D) and maternal depression (MD) is deemed to be inconclusive. The current analysis aimed to quantify the relationship between 25(OH)D serum concentrations, the main indicator of vitamin D nutritional status, and MD.

Design:

Dose–response meta-analysis.

Setting:

A systematic search in PubMed, Embase and Web of Science from inception to June 2019.

Participants:

Relevant observational studies reporting risk estimates and 95 % CI of random effects for 25(OH)D concentration on MD were identified.

Results:

Twelve observational studies with thirteen independent reports involving 10 317 pregnant women were included. Compared with the lowest category of 25(OH)D, the pooled OR for the highest category of MD was 0·49 (95 % CI 0·35, 0·63); a high heterogeneity was observed (P= 0·001,I2= 82·1 %). A non-linear association between 25(OH)D and MD was found (Pfor non-linearity = 0·001); the dose–response analysis indicated that the lowest pooled OR was at blood 25(OH)D concentrations of 90–110 nmol/l. Subgroup analyses suggested a stronger association between 25(OH)D and MD in summer time (OR 0·25, 95 % CI 0·08, 0·43) than in other seasons (OR 0·68, 95 % CI 0·52, 0·83) (Pfor interaction = 0·008). A visual inspection of funnel plot and Begg’s and Egger’s tests did not indicate any evidence of publication bias.

Conclusions:

Low circulating 25(OH)D is associated with MD, and our analysis suggests that they influence each other. Further randomised controlled trials would be needed to determine the direction of causation.
Association of sugar-sweetened beverage intake with maternal postpartum weight retention
Authors: Mahabamunuge Jasmin , Simione Meg , Hong Benjamin , Horan Chrissy , Ayala Sujata G , Davison Kirsten , Redline Susan , Taveras Elsie M
Published: December 2020

Objective:

During the perinatal period, modifiable behaviours contributing to excess weight gain, including sugar-sweetened beverage (SSB) intake, are understudied. We examined the extent to which perinatal SSB intake affects postpartum weight retention (PPWR).

Design:

We measured SSB intake frequency in the third trimester and 1-month postpartum using the NHANES Dietary Screener Questionnaire. We assessed the association between SSB intake and PPWR (difference between 6-month postpartum and pregravid weight) using multivariable regression adjusted for socio-demographic and anthropometric variables.

Setting:

Greater Boston area.

Participants:

Three hundred forty-eight mother–infant pairs in the Rise and SHINE prospective birth cohort.

Results:

Mean age was 32·7 (sd 5·0) years; the sample was 47 % white, 32 % Hispanic, 14 % Asian and 7 % Black. Women reported mean daily SSB intake frequencies of 0·9 (sd 1·2) and 0·7 (sd 1·0) times/d in the third trimester and 1-month postpartum, respectively. At 6-month postpartum, average weight retention was 3·4 (sd 5·7) kg; 108 (sd 31 %) women had substantial PPWR, defined as a ≥ 5 kg increase between pregravid and 6-month postpartum weight. Each 1-time/d increment in SSB intake frequency during the third trimester (β = 0·46 kg (95 % CI, 0·07, 0·86)) and 1-month postpartum (β = 0·52 kg (95 % CI 0·03, 1·00)) was associated with higher weight retention at 6 months. Increased SSB intake frequency in the third trimester (OR: 1·37; 95 % CI 1·10, 1·75) and 1-month postpartum (OR: 1·17; 95 % CI 0·92, 1·52) resulted in higher odds of substantial PPWR.

Conclusions:

SSB consumption during the perinatal period is associated with higher weight retention at 6-month postpartum. Avoiding SSB may reduce the risk of excess weight retention.