bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Use of Information Criteria for Model Selection in Phylogenetics
Authors: Susko Edward , Roger Andrew J
Published: October 2019

The information criteria Akaike information criterion (AIC), AICc, and Bayesian information criterion (BIC) are widely used for model selection in phylogenetics, however, their theoretical justification and performance have not been carefully examined in this setting. Here, we investigate these methods under simple and complex phylogenetic models. We show that AIC can give a biased estimate of its intended target, the expected predictive log likelihood (EPLnL) or, equivalently, expected Kullback–Leibler divergence between the estimated model and the true distribution for the data. Reasons for bias include commonly occurring issues such as small edge-lengths or, in mixture models, small weights. The use of partitioned models is another issue that can cause problems with information criteria. We show that for partitioned models, a different BIC correction is required for it to be a valid approximation to a Bayes factor. The commonly used AICc correction is not clearly defined in partitioned models and can actually create a substantial bias when the number of parameters gets large as is the case with larger trees and partitioned models. Bias-corrected cross-validation corrections are shown to provide better approximations to EPLnL than AIC. We also illustrate how EPLnL, the estimation target of AIC, can sometimes favor an incorrect model and give reasons for why selection of incorrectly under-partitioned models might be desirable in partitioned model settings.
Targeted live-cell nuclear delivery of the DNA ‘light-switching’ Ru(II) complex via ion-pairing with chlorophenolate counter-anions: the critical role of binding stability and lipophilicity of the ion-pairing complexes
Authors: Chao Xi-Juan , Tang Miao , Huang Rong , Huang Chun-Hua , Shao Jie , Yan Zhu-Ying , Zhu Ben-Zhan
Published: October 2019

We have found recently that nuclear uptake of the cell-impermeable DNA light-switching Ru(II)-polypyridyl cationic complexes such as [Ru(bpy)2(dppz)]Cl2 was remarkably enhanced by pentachlorophenol (PCP), by forming ion-pairing complexes via a passive diffusion mechanism. However, it is not clear whether the enhanced nuclear uptake of [Ru(bpy)2(dppz)]2+ is only limited to PCP, or it is a general phenomenon for other highly chlorinated phenols (HCPs); and if so, what are the major physicochemical factors in determining nuclear uptake? Here, we found that the nuclear uptake of [Ru(bpy)2(dppz)]2+ can also be facilitated by other two groups of HCPs including three tetrachlorophenol (TeCP) and six trichlorophenol (TCP) isomers. Interestingly and unexpectedly, 2,3,4,5-TeCP was found to be the most effective one for nuclear delivery of [Ru(bpy)2(dppz)]2+, which is even better than the most-highly chlorinated PCP, and much better than its two other TeCP isomers. Further studies showed that the nuclear uptake of [Ru(bpy)2(dppz)]2+ was positively correlated with the binding stability, but to our surprise, inversely correlated with the lipophilicity of the ion-pairing complexes formed between [Ru(bpy)2(dppz)]Cl2 and HCPs. These findings should provide new perspectives for future investigations on using ion-pairing as an effective method for delivering other bio-active metal complexes into their intended cellular targets.
Structure and function of the Toscana virus cap-snatching endonuclease
Authors: Jones Rhian , Lessoued Sana , Meier Kristina , Devignot Stéphanie , Barata-García Sergio , Mate Maria , Bragagnolo Gabriel , Weber Friedemann , Rosenthal Maria , Reguera Juan
Published: October 2019

Toscana virus (TOSV) is an arthropod-borne human pathogen responsible for seasonal outbreaks of fever and meningoencephalitis in the Mediterranean basin. TOSV is a segmented negative-strand RNA virus (sNSV) that belongs to the genus phlebovirus (family Phenuiviridae, order Bunyavirales), encompassing other important human pathogens such as Rift Valley fever virus (RVFV). Here, we carried out a structural and functional characterization of the TOSV cap-snatching endonuclease, an N terminal domain of the viral polymerase (L protein) that provides capped 3′OH primers for transcription. We report TOSV endonuclease crystal structures in the apo form, in complex with a di-ketoacid inhibitor (DPBA) and in an intermediate state of inhibitor release, showing details on substrate binding and active site dynamics. The structure reveals substantial folding rearrangements absent in previously reported cap-snatching endonucleases. These include the relocation of the N terminus and the appearance of new structural motifs important for transcription and replication. The enzyme shows high activity rates comparable to other His+ cap-snatching endonucleases. Moreover, the activity is dependent on conserved residues involved in metal ion and substrate binding. Altogether, these results bring new light on the structure and function of cap-snatching endonucleases and pave the way for the development of specific and broad-spectrum antivirals.
gutMDisorder: a comprehensive database for dysbiosis of the gut microbiota in disorders and interventions
Authors: Cheng Liang , Qi Changlu , Zhuang He , Fu Tongze , Zhang Xue
Published: October 2019

gutMDisorder (http://bio-annotation.cn/gutMDisorder), a manually curated database, aims at providing a comprehensive resource of dysbiosis of the gut microbiota in disorders and interventions. Alterations in the composition of the gut microbial community play crucial roles in the development of chronic disorders. And the beneficial effects of drugs, foods and other intervention measures on disorders could be microbially mediated. The current version of gutMDisorder documents 2263 curated associations between 579 gut microbes and 123 disorders or 77 intervention measures in Human, and 930 curated associations between 273 gut microbes and 33 disorders or 151 intervention measures in Mouse. Each entry in the gutMDisorder contains detailed information on an association, including an intestinal microbe, a disorder name, intervention measures, experimental technology and platform, characteristic of samples, web sites for downloading the sequencing data, a brief description of the association, a literature reference, and so on. gutMDisorder provides a user-friendly interface to browse, retrieve each entry using gut microbes, disorders, and intervention measures. It also offers pages for downloading all the entries and submitting new experimentally validated associations.
High-yield fabrication of DNA and RNA constructs for single molecule force and torque spectroscopy experiments
Authors: Papini Flávia S , Seifert Mona , Dulin David
Published: October 2019

Single molecule biophysics experiments have enabled the observation of biomolecules with a great deal of precision in space and time, e.g. nucleic acids mechanical properties and protein–nucleic acids interactions using force and torque spectroscopy techniques. The success of these experiments strongly depends on the capacity of the researcher to design and fabricate complex nucleic acid structures, as the outcome and the yield of the experiment also strongly depend on the high quality and purity of the final construct. Though the molecular biology techniques involved are well known, the fabrication of nucleic acid constructs for single molecule experiments still remains a difficult task. Here, we present new protocols to generate high quality coilable double-stranded DNA and RNA, as well as DNA and RNA hairpins with ∼500–1000 bp long stems. Importantly, we present a new approach based on single-stranded DNA (ssDNA) annealing and we use magnetic tweezers to show that this approach simplifies the fabrication of complex DNA constructs, such as hairpins, and converts more efficiently the input DNA into construct than the standard PCR-digestion-ligation approach. The protocols we describe here enable the design of a large range of nucleic acid construct for single molecule biophysics experiments.
Animal-ImputeDB: a comprehensive database with multiple animal reference panels for genotype imputation
Authors: Yang Wenqian , Yang Yanbo , Zhao Cecheng , Yang Kun , Wang Dongyang , Yang Jiajun , Niu Xiaohui , Gong Jing
Published: October 2019

Animal-ImputeDB (http://gong_lab.hzau.edu.cn/Animal_ImputeDB/) is a public database with genomic reference panels of 13 animal species for online genotype imputation, genetic variant search, and free download. Genotype imputation is a process of estimating missing genotypes in terms of the haplotypes and genotypes in a reference panel. It can effectively increase the density of single nucleotide polymorphisms (SNPs) and thus can be widely used in large-scale genome-wide association studies (GWASs) using relatively inexpensive and low-density SNP arrays. However, most animals except humans lack high-quality reference panels, which greatly limits the application of genotype imputation in animals. To overcome this limitation, we developed Animal-ImputeDB, which is dedicated to collecting genotype data and whole-genome resequencing data of nonhuman animals from various studies and databases. A computational pipeline was developed to process different types of raw data to construct reference panels. Finally, 13 high-quality reference panels including ∼400 million SNPs from 2265 samples were constructed. In Animal-ImputeDB, an easy-to-use online tool consisting of two popular imputation tools was designed for the purpose of genotype imputation. Collectively, Animal-ImputeDB serves as an important resource for animal genotype imputation and will greatly facilitate research on animal genomic selection and genetic improvement.
Retrons and their applications in genome engineering
Authors: Simon Anna J , Ellington Andrew D , Finkelstein Ilya J
Published: October 2019

Precision genome editing technologies have transformed modern biology. These technologies have arisen from the redirection of natural biological machinery, such as bacteriophage lambda proteins for recombineering and CRISPR nucleases for eliciting site-specific double-strand breaks. Less well-known is a widely distributed class of bacterial retroelements, retrons, that employ specialized reverse transcriptases to produce noncoding intracellular DNAs. Retrons’ natural function and mechanism of genetic transmission have remained enigmatic. However, recent studies have harnessed their ability to produce DNA in situ for genome editing and evolution. This review describes retron biology and function in both natural and synthetic contexts. We also highlight areas that require further study to advance retron-based precision genome editing platforms.
Recruitment of Rec8, Pds5 and Rad61/Wapl to meiotic homolog pairing, recombination, axis formation and S-phase
Authors: Hong Soogil , Joo Jeong H , Yun Hyeseon , Kleckner Nancy , Kim Keun P
Published: October 2019

We have explored the meiotic roles of cohesin modulators Pds5 and Rad61/Wapl, in relation to one another, and to meiotic kleisin Rec8, for homolog pairing, all physically definable steps of recombination, prophase axis length and S-phase progression, in budding yeast. We show that Pds5 promotes early steps of recombination and thus homolog pairing, and also modulates axis length, with both effects independent of a sister chromatid. [Pds5+Rec8] promotes double-strand break formation, maintains homolog bias for crossover formation and promotes S-phase progression. Oppositely, the unique role of Rad61/Wapl is to promote non-crossover recombination by releasing [Pds5+Rec8]. For this effect, Rad61/Wapl probably acts to maintain homolog bias by preventing channeling into sister interactions. Mysteriously, each analyzed molecule has one role that involves neither of the other two. Overall, the presented findings suggest that Pds5’s role in maintenance of sister chromatid cohesion during the mitotic prophase-analogous stage of G2/M is repurposed during meiosis prophase to promote interactions between homologs.
Streamlining effects of extra telomeric repeat on telomeric DNA folding revealed by fluorescence-force spectroscopy
Authors: Mitra Jaba , Ha Taekjip
Published: October 2019

A human telomere ends in a single-stranded 3′ tail, composed of repeats of T2AG3. G-quadruplexes (GQs) formed from four consecutive repeats have been shown to possess high-structural and mechanical diversity. In principle, a GQ can form from any four repeats that are not necessarily consecutive. To understand the dynamics of GQs with positional multiplicity, we studied five and six repeats human telomeric sequence using a combination of single molecule FRET and optical tweezers. Our results suggest preferential formation of GQs at the 3′ end both in K+ and Na+ solutions, with minor populations of 5′-GQ or long-loop GQs. A vectorial folding assay which mimics the directional nature of telomere extension showed that the 3′ preference holds even when folding is allowed to begin from the 5′ side. In 100 mM K+, the unassociated T2AG3 segment has a streamlining effect in that one or two mechanically distinct species was observed at a single position instead of six or more observed without an unassociated repeat. We did not observe such streamlining effect in 100 mM Na+. Location of GQ and reduction in conformational diversity in the presence of extra repeats have implications in telomerase inhibition, T-loop formation and telomere end protection.
CTCF-dependent chromatin boundaries formed by asymmetric nucleosome arrays with decreased linker length
Authors: Clarkson Christopher T , Deeks Emma A , Samarista Ralph , Mamayusupova Hulkar , Zhurkin Victor B , Teif Vladimir B
Published: October 2019

The CCCTC-binding factor (CTCF) organises the genome in 3D through DNA loops and in 1D by setting boundaries isolating different chromatin states, but these processes are not well understood. Here we investigate chromatin boundaries in mouse embryonic stem cells, defined by the regions with decreased Nucleosome Repeat Length (NRL) for ∼20 nucleosomes near CTCF sites, affecting up to 10% of the genome. We found that the nucleosome-depleted region (NDR) near CTCF is asymmetrically located >40 nucleotides 5′-upstream from the centre of CTCF motif. The strength of CTCF binding to DNA and the presence of cohesin is correlated with the decrease of NRL near CTCF, and anti-correlated with the level of asymmetry of the nucleosome array. Individual chromatin remodellers have different contributions, with Snf2h having the strongest effect on the NRL decrease near CTCF and Chd4 playing a major role in the symmetry breaking. Upon differentiation, a subset of preserved, common CTCF sites maintains asymmetric nucleosome pattern and small NRL. The sites which lost CTCF upon differentiation are characterized by nucleosome rearrangement 3′-downstream, with unchanged NDR 5′-upstream of CTCF motifs. Boundaries of topologically associated chromatin domains frequently contain several inward-oriented CTCF motifs whose effects, described above, add up synergistically.
An improved platform for functional assessment of large protein libraries in mammalian cells
Authors: Matreyek Kenneth A , Stephany Jason J , Chiasson Melissa A , Hasle Nicholas , Fowler Douglas M
Published: October 2019

Multiplex genetic assays can simultaneously test thousands of genetic variants for a property of interest. However, limitations of existing multiplex assay methods in cultured mammalian cells hinder the breadth, speed and scale of these experiments. Here, we describe a series of improvements that greatly enhance the capabilities of a Bxb1 recombinase-based landing pad system for conducting different types of multiplex genetic assays in various mammalian cell lines. We incorporate the landing pad into a lentiviral vector, easing the process of generating new landing pad cell lines. We also develop several new landing pad versions, including one where the Bxb1 recombinase is expressed from the landing pad itself, improving recombination efficiency more than 2-fold and permitting rapid prototyping of transgenic constructs. Other versions incorporate positive and negative selection markers that enable drug-based enrichment of recombinant cells, enabling the use of larger libraries and reducing costs. A version with dual convergent promoters allows enrichment of recombinant cells independent of transgene expression, permitting the assessment of libraries of transgenes that perturb cell growth and survival. Lastly, we demonstrate these improvements by assessing the effects of a combinatorial library of oncogenes and tumor suppressors on cell growth. Collectively, these advancements make multiplex genetic assays in diverse cultured cell lines easier, cheaper and more effective, facilitating future studies probing how proteins impact cell function, using transgenic variant libraries tested individually or in combination.
Enhancing Concussion Management in the National Football League: Evolution and Initial Results of the Unaffiliated Neurotrauma Consultants Program, 2012-2017
Authors: Mack Christina , Sendor Rachel R , Solomon Gary , Ellenbogen Richard G , Myers Emily , Berger Mitchel , Sills Allen
Published: October 2019

Background

The real-time detection of concussive injury in professional sports can be challenging for the healthcare provider on the sideline. It can be difficult to monitor all on-field players during active game play and diagnose complex injuries such as concussion during a fast-paced athletic event.

Objective

To enhance the in-game identification of potentially concussed professional athletes, the National Football League (NFL) initiated an Unaffiliated Neurotrauma Consultants (UNC) program in 2013, which, in tandem with other in-arena spotters and live video review systems, is designed to improve the safety of the players through enhanced concussion detection efforts.

Methods

This paper reports on the evolution of the UNC program, describes its participants and training requirements, details the role of UNC involvement, and delineates the systematic revisions and enhancements completed each year in the program.

Results

UNC reporting compliance has increased from 56% in 2014 to 100% in 2017. During the 2016 and 2017 seasons, (1) UNCs submitted an average of 1.9 evaluations per game, and (2) the UNC concussion assessments yielded sensitivity (93.4%-97.4%) and specificity (81.0%-88.3%) values.

Conclusion

The UNC program has enhanced the detection of concussion in NFL players. Directions for research and future program improvements are addressed.
Effects of Cervico-Mandibular Manual Therapy in Patients with Temporomandibular Pain Disorders and Associated Somatic Tinnitus: A Randomized Clinical Trial
Authors: Delgado de la Serna Pablo , Plaza-Manzano Gustavo , Cleland Joshua , Fernández-de-las-Peñas César , Martín-Casas Patricia , Díaz-Arribas María José
Published: October 2019

Objective

This randomized clinical trial investigated the effects of adding cervico-mandibular manual therapies into an exercise and educational program on clinical outcomes in individuals with tinnitus associated with temporomandibular disorders (TMDs).

Methods

Sixty-one patients with tinnitus attributed to TMD were randomized into the physiotherapy and manual therapy group or physiotherapy alone group. All patients received six sessions of physiotherapy treatment including cranio-cervical and temporomandibular joint (TMJ) exercises, self-massage, and patient education for a period of one month. Patients allocated to the manual therapy group also received cervico-mandibular manual therapies targeting the TMJ and cervical and masticatory muscles. Primary outcomes included TMD pain intensity and tinnitus severity. Secondary outcomes included tinnitus-related handicap (Tinnitus Handicap Inventory [THI]), TMD-related disability (Craniofacial Pain and Disability Inventory [CF-PDI]), self-rated quality of life (12-item Short Form Health Survey [SF-12]), depressive symptoms (Beck Depression Inventory [BDI-II]), pressure pain thresholds (PPTs), and mandibular range of motion. Patients were assessed at baseline, one week, three months, and six months after intervention by a blinded assessor.

Results

The adjusted analyses showed better outcomes (all, P < 0.001) in the exercise/education plus manual therapy group (large effect sizes) for TMD pain (η 2 P = 0.153), tinnitus severity (η 2 P = 0.233), THI (η 2 P = 0.501), CF-PDI (η 2 P = 0.395), BDI-II (η 2 P = 0.194), PPTs (0.363 < η 2 P < 0.415), and range of motion (η 2 P = 0.350), but similar changes for the SF-12 (P = 0.622, η 2 P = 0.01) as the exercise/education alone group.

Conclusions

This clinical trial found that application of cervico-mandibular manual therapies in combination with exercise and education resulted in better outcomes than application of exercise/education alone in individuals with tinnitus attributed to TMD.
Physical activity can attenuate, but not eliminate, the negative relationships of high TV viewing with some chronic diseases: findings from a cohort of 60 202 Brazilian adults
Authors: Werneck André O , Oyeyemi Adewale L , Collings Paul J , Cyrino Edilson S , Ronque Enio R V , Szwarcwald Célia L , Sardinha Luís B , Silva Danilo R P
Published: October 2019

Background

This study examined the joint associations of leisure time physical activity and television (TV) viewing time with the prevalence of chronic diseases among Brazilian adults.

Methods

Data from the Brazilian Health Survey, a nationally representative survey conducted in 2013 (n = 60 202; ≥18 years), were used. Time spent in TV viewing and leisure physical activity, physician diagnoses of diabetes, hypertension and heart disease and information on co-variables (chronological age, education, ethnicity, candies/sweets consumption, sodium intake and tobacco smoking) were collected via interview. Descriptive statistics (mean and 95% confidence interval) and logistic regression models were used for etiological analyses.

Results

Physical activity attenuated but did not eliminate the risk associated with high TV viewing for at least one chronic disease in the general population [odds ratio [OR]: 1.29 (1.11–1.50)] and among women [OR: 1.31 (1.09–1.60)], adults [OR: 1.24 (1.05–1.46)] and older adults [OR: 1.63 (1.05–2.53)]. On the other hand, physical activity eliminated the risk associated with high TV viewing for at least one chronic disease among men [OR: 1.24 (0.98–1.58)].

Conclusions

We conclude that physical activity can attenuate but not eliminate the negative effects of high TV viewing on chronic disease among subgroups of Brazilian adults.
Acute renal and splenic infarctions: a review
Authors: Weber E , Grangeon F , Reynaud Q , Hot A , Sève P , Jardel S , Tazarourte K , Fouque D , Juillard L , Salles G , Grange C , Durieu I , Rousset P , Lega J C
Published: October 2019

Background

Renal and splenic infarctions are close entities, with few data concerning their clinical, biological and radiological features.

Aim

The aim of this study was to compare the clinical presentations, etiologies and outcomes of acute renal infarctions (RI) and splenic infarctions (SI).

Design

A retrospective multicentric cohort study included patients of the 6 university hospitals in Lyon with RI, SI, or associated RI-SI infarctions was conducted.

Methods

All consecutive cases diagnosed by CT imaging, between January 2013 and October 2016, were included. The exclusion criteria were causes of infarction that did not require additional investigations.

Results

A total of 161 patients were selected for analysis: 34 patients with RI, 104 patients with SI and 23 patients with both RI-SI. Mean ± SD age of patients was 63.2 ± 16.6 years; 59.6% were male. Only 5/161 (3.1%) were healthy prior to the event. The main symptoms were diffuse abdominal pain (26.4%), followed by nausea/vomiting (18.3%) and fever (16.4%).The causes of RI or SI varied significantly within the three groups. Hypercoagulable state was associated with SI, and embolic disease and arterial injury were associated with RI. Extensive (i.e.>2/3 of organ volume) (OR 6.22, 95%CI 2.0119.22) and bilateral infarctions (OR 15.05, 95%CI 1.79–126.78) were significantly associated with hemodynamic shocks. The survival at 1 month follow-up did not significantly differ between the three groups.

Conclusion

Acute RI and SI are heterogenous entities in regards to their clinical presentation, etiology, associated venous or arterial thrombosis, but prognoses were not different at short term follow-up.
What do we measure with 28-joint DAS in elderly patients? An explorative analysis in the NOR-DMARD study
Authors: van Onna Marloes , Putrik Polina , Lie Elisabeth , Kvien Tore K , Boonen Annelies , Uhlig Till
Published: October 2019

Objective

Insight into the influence of ageing on disease outcomes is limited. The objective of this study was to examine the potential effect of age on disease activity using the 28-joint DAS (DAS28) and its components in patients with RA.

Methods

Baseline data of DMARD-naïve patients with RA from the Norwegian Register of DMARDs were used. Linear regression explored the strength of the association between age (<45, 45–65 and >65 years) and each DAS28 component while accounting for education and gender. Adjusted predicted scores for DAS28 components and total DAS28 score were calculated for each age category.

Results

Baseline data from 2037 patients [mean age 55.2 years (s.d. 14.0), 68% females] were available. Regression models had to be stratified for gender (P for interaction <0.001); education was a significant covariate. Males >65 years of age with an intermediate level of education have a 56% higher ESR and 25% higher 28-joint swollen joint count as compared with their younger counterparts (<45 years). For females, corresponding differences were 51% and 27%, respectively. The age effect on the 28-joint tender joint count and patient global assessment was negligible. In patients with an intermediate education level, DAS28 was 5.0 vs 5.5 (10% increase) in the youngest vs oldest age groups, independent of gender.

Conclusion

The age-related increase in ESR and 28-joint swollen joint count scores without a relevant corresponding increase in 28-joint tender joint count and patient global assessment might imply that age-related processes (e.g. soft tissue changes, physiological ESR increase) contribute to a higher DAS28 in elderly patients.
COMPARISON OF DIFFERENT TECHNIQUES FOR EVALUATION OF DOSE DISTRIBUTIONS IN RADIOTHERAPY USING RADIOCHROMIC EBT3 FILMS
Authors: Dufek V , Horakova I , Koniarova I
Published: October 2019

In radiotherapy, radiochromic films can be used for verification of delivery of dose distributions calculated by treatment planning systems. The main objective of this work was to compare three different techniques for evaluation of dose distributions for prostate cancer treatment plans using radiochromic EBT3 films. These techniques are: red channel evaluation taking into account only a response of irradiated film (R), red channel evaluation taking into account a response of unirradiated and irradiated film (Rcor) and multichannel evaluation in FilmQA software (RGB). Also comparison between film and MatriXX measurement was performed. Comparison showed that gamma analysis passing rates strongly depend on evaluation technique and on a model of scanner for digitizing films. The highest gamma passing rates were obtained with red channel evaluation taking into account a response of unirradiated and irradiated film using Epson V750 scanner (Rcor) and multichannel evaluation in FilmQA using Epson 11000XL scanner.
Investment in innovation for European recovery: A public policy priority
Authors: Archibugi Daniele , Filippetti Andrea , Frenz Marion
Published: October 2019

The 2008 crisis had severe consequences in Europe at many levels. One of them is the significantly lower levels of public and private investments. This article explores to what extent a large plan of public innovation investment could contribute to the overall economic recovery and to opening a new stage of development in the European Union (EU). We argue that key scientific and technological opportunities, currently untapped, exist, which have the potential to accelerate economic growth and to pull in private investments. Decisive instruments, such as the Juncker investment plan and the proposed 2021–7 Framework Programme Horizon Europe, are important steps in that direction. The article concludes by reviving Lundvall’s call for a Council for Innovation and Competence Building that should have the same political weight as the EU Economic and Financial Affairs Council.
Cultivating China’s Cinchona: The Local Developmental State, Global Botanic Networks and Cinchona Cultivation in Yunnan, 1930s–1940s
Authors: Shen Yubin
Published: October 2019

This article reconstructs the history of China’s first successful cinchona cultivation programme in Hekou, Yunnan province from the 1930s to 1940s during the Nationalist era (1928–49). I argue that the Hekou programme was initiated by the Yunnan ‘local developmental state’ to control endemic malaria and achieve quinine self-sufficiency. It was expanded during the Sino-Japanese War (1937–45) as part of the national defence project in order to develop Yunnan’s malaria-ridden southwest frontier to provide more resources for the war, as well as to solve broader wartime epidemic crises in southwest China. A closer examination also indicates that the development of the Hekou programme was closely intertwined with global networks of cinchona cultivation and international politics.
Infamy, infamy, I need an indemnity: the nature and enforcement of the trustee’s right of indemnity
Authors: Sherwin Timothy
Published: October 2019

In this article, I consider the nature and enforcement of the trustee’s right of indemnity. I set out the principles underlying the trustee’s right of indemnity; and I assess the recent decisions Meritus Trust Company Limited v Butterfield Trust (Bermuda) Limited (“Meritus v Butterfield”) and Rawlinson & Hunter Trustees SA v Chiddicks (the “Z Trusts” case), dealing with enforcement of the right of indemnity in light of those principles. Finally, I conclude, in line with the Court of Appeal in Z Trusts that the trustee’s right of indemnity is enforceable by way of a lien or charge, in which lien or charge is an equitable proprietary right that has priority over any subsequent transaction, including over a successor trustee’s rights of indemnity.
Measuring the multiple domains of medication nonadherence: findings from a Delphi survey of adherence experts
Authors: Kronish Ian M , Thorpe Carolyn T , Voils Corrine I
Published: October 2019

Consensus on a gold-standard measure of patient medication nonadherence has been elusive, in part because medication nonadherence involves multiple, distinct behaviors across three phases (initiation, implementation, and persistence). To assess these behaviors, multiple measurement approaches may be needed. The purpose of this study was to identify expert-recommended approaches to measuring nonadherence behaviors. Thirty medication nonadherence experts were e-mailed two consecutive surveys. In both, respondents rated their agreement with definitions of nonadherence behaviors and measurement approaches. In the second survey, respondents rated the suitability of each measurement approach for assessing each behavior and identified the optimal measurement approach for each behavior. Consensus was achieved for eight patient medication nonadherence behaviors: not filling initial prescription and not taking first dose (noninitiation); refilling prescription late, missing doses, taking extra doses, taking doses at wrong time, and improperly administering medication (incorrect implementation); and discontinuing medication early (nonpersistence). Consensus was achieved for seven measurement approaches: self-report, prescription fill data, pill count, drug levels, electronic drug monitoring (EDM), smart technology, and direct observation. Self-report questionnaires were most commonly rated “at least somewhat suitable” for measuring behaviors. EDM was rated as optimal for measuring missing doses, taking extra doses, and taking doses at the wrong time. Prescription fill data were rated as optimal for not filling initial prescription, refilling late, and discontinuing. Direct observation was rated as optimal for measuring improper administration. Suitable and optimal measurement approaches varied across nonadherence behaviors. Researchers should select the measurement approach best suited to assessing the behavior(s) targeted in their research.
A new automated stem CO2 efflux chamber based on industrial ultra-low-cost sensors
Authors: Brändle Johannes , Kunert Norbert
Published: October 2019

Tree autotrophic respiratory processes, especially stem respiration or stem CO2 efflux (Estem), are important components of the forest carbon budget. Despite the efforts to investigate the controlling processes of Estem in the last years a considerable lack in our knowledge remains on the abiotic and biotic drivers affecting Estem dynamics. It has been strongly advocated that long-term measurements would shed light into those processes. The expensive scientific instruments needed to measure gas exchange has prevented from applying Estem measurements on a larger temporal and spatial scale. Here, we present an automated closed dynamic chamber system based on inexpensive and industrially broadly applied CO2 sensors reducing the costs for the sensing system to a minimum. The CO2 sensor was cross-calibrated with a commonly used gas exchange system in the laboratory and in the field, and we found very good accordance of these sensors. We tested the system under harsh tropical climatic conditions, characterized by heavy tropical rainfall events, extreme humidity, and temperatures, in a moist lowland forest in Malaysia. We recorded Estem of three Dyera costulata trees with our prototype over various days. The variation of Estem was large among the three tree individuals and varied by 7.5-fold. However, clear diurnal changes in Estem were present in all three tree individuals. One tree showed high diurnal variation in Estem and the relationship between Estem and temperature was characterized by a strong hysteresis. The large variations found within one single tree species highlights the importance of continuous measurement to quantify ecosystem carbon fluxes.
Forest carbon allocation modelling under climate change
Authors: Merganičová Katarína , Merganič Ján , Lehtonen Aleksi , Vacchiano Giorgio , Sever Maša Zorana Ostrogović , Augustynczik Andrey L D , Grote Rüdiger , Kyselová Ina , Mäkelä Annikki , Yousefpour Rasoul , Krejza Jan , Collalti Alessio , Reyer Christopher P O
Published: October 2019

Carbon allocation plays a key role in ecosystem dynamics and plant adaptation to changing environmental conditions. Hence, proper description of this process in vegetation models is crucial for the simulations of the impact of climate change on carbon cycling in forests. Here we review how carbon allocation modelling is currently implemented in 31 contrasting models to identify the main gaps compared with our theoretical and empirical understanding of carbon allocation. A hybrid approach based on combining several principles and/or types of carbon allocation modelling prevailed in the examined models, while physiologically more sophisticated approaches were used less often than empirical ones. The analysis revealed that, although the number of carbon allocation studies over the past 10 years has substantially increased, some background processes are still insufficiently understood and some issues in models are frequently poorly represented, oversimplified or even omitted. Hence, current challenges for carbon allocation modelling in forest ecosystems are (i) to overcome remaining limits in process understanding, particularly regarding the impact of disturbances on carbon allocation, accumulation and utilization of nonstructural carbohydrates, and carbon use by symbionts, and (ii) to implement existing knowledge of carbon allocation into defence, regeneration and improved resource uptake in order to better account for changing environmental conditions.
Where Cowboys and Indians Meet: A Southern Cheyenne Web of Kinship and the Transnational Cattle Industry, 1877–1885
Authors: Truden John
Published: October 2019

Between 1877 and 1885, a Southern Cheyenne chief named Stone Calf gathered a coalition of Southern Cheyenne women and men, cultural intermediaries, ranchers, missionaries, and U.S. soldiers together in northwestern Indian Territory. Bound by kinship, gendered labor, economic opportunity, and political necessity, this alliance negotiated the transnational cattle industry’s access to the environmental resources of the Southern Great Plains. Using these powerful ties, Stone Calf’s coalition successfully shaped both the cattle industry’s expansion and displaced the Office of Indian Affairs’ influence in the region. By recognizing Stone Calf’s coalition as a powerful transnational force, this article illuminates both the weight of kinship and Indigenous participation in a globally interconnected world.
Imaging inflammation and its resolution in health and disease: current status, clinical needs, challenges, and opportunities
Authors: Liu Christina H. , Abrams Natalie D. , Carrick Danielle M. , Chander Preethi , Dwyer Johanna , Hamlet Michelle R. J. , Kindzelski Andrei L. , PrabhuDas Mercy , Tsai Shang‐Yi Anne , Vedamony Merriline M. , Wang Chiayeng , Tandon Pushpa
Published: October 2019

Inflammation is a normal process in our body; acute inflammation acts to suppress infections and support wound healing. Chronic inflammation likely leads to a wide range of diseases, including cancer. Tools to locate and monitor inflammation are critical for developing effective interventions to arrest inflammation and promote its resolution. To identify current clinical needs, challenges, and opportunities in advancing imaging‐based evaluations of inflammatory status in patients, the U.S. National Institutes of Health convened a workshop on imaging inflammation and its resolution in health and disease. Clinical speakers described their needs for image‐based capabilities that could help determine the extent of inflammatory conditions in patients to guide treatment planning and undertake necessary interventions. The imaging speakers showcased the state‐of‐the‐art in vivo imaging techniques for detecting inflammation in different disease areas. Many imaging capabilities developed for 1 organ or disease can be adapted for other diseases and organs, whereas some have promise for clinical utility within the next 5–10 yr. Several speakers demonstrated that multimodal imaging measurements integrated with serum‐based measures could improve in robustness for clinical utility. All speakers agreed that multiple inflammatory measures should be acquired longitudinally to comprehend the dynamics of unresolved inflammation that leads to disease development. They also agreed that the best strategies for accelerating clinical translation of imaging inflammation capabilities are through integration between new imaging techniques and biofluid‐based biomarkers of inflammation as well as already established imaging measurements.—Liu, C. H., Abrams, N. D., Carrick, D. M., Chander, P., Dwyer, J., Hamlet, M. R. J., Kindzelski, A. L., PrabhuDas, M., Tsai, S.‐Y. A., Vedamony, M. M., Wang, C., Tandon, P. Imaging inflammation and its resolution in health and disease: current status, clinical needs, challenges, and opportunities. FASEB J. 33, 13085–13097 (2019). www.fasebj.org
Evidence-based interventions cause multifold increase of influenza immunization rates in a free clinic
Authors: Falcone Aimee L. , Vess Joy , Johnson Emily
Published: October 2019

Background:

Every year in the United States, influenza-related infection causes thousands of deaths, the complications of which require millions of dollars in hospital-related care. The influenza vaccine is proven to effectively reduce incidence of infection and complications from influenza viruses.

Local problem:

A clinic in southeast Florida for the uninsured offered influenza immunization at no cost to its patients, yet the immunization rate was still low.

Methods:

A quality improvement project was conducted to determine whether the use of evidenced-based bundled interventions would increase the rate of the influenza vaccination at the clinic.

Interventions:

The bundled interventions included mass communication, leadership, improved work flow, and improved access.

Results:

Evidence-based interventions led to a 597% increase in the influenza uptake rate. Trends were analyzed by using data gathered from the electronic medical record regarding patient demographics, influenza immunization uptake rate, type of visit for the immunizations, and reason for declining. Overcoming the access barrier led to great improvements in this clinic. Initially more vaccines were given in nurse visits; as the season progressed, more vaccines were given by providers in the clinic. Common reasons for patient refusal of the vaccine were fear of side effects and fear of contracting the influenza virus. Streamlined documentation could promote continued staff compliance over time.

Conclusions:

To reduce influenza-related costs and improve health outcomes, it is imperative that nurse practitioners use evidence-based interventions in the practice setting to increase influenza uptake rates in the adult uninsured population.
Recovery of malnutrition in a patient with severe brain injury outcomes
Authors: Caliri Santina , Andaloro Adriana , Corallo Francesco , Donato Antonina , Marino Silvia , Mantarro Carmela , Terranova Aurelio , Bramanti Placido , Caminiti Fabrizia , Rifici Carmela
Published: October 2019

Rationale:

Severe brain injury often induces a state of malnutrition due to insufficient caloric and protein input. If left untreated, it will have a negative impact on rehabilitation. Nutritional therapy provides caloric and the nutritional support necessary to cover the daily needs and help contrast hospital infections. Our hypothesis is that integration of natural foods in the daily diet can enhance the recovery of the state of malnutrition and increase rehabilitation outcomes.

Patient concerns:

We present the case of a young man with traumatic brain injury caused by a car accident. Who underwent tracheostomy and percutaneous endoscopic gastrostomy (PEG) procedures, had severe consciousness disorder, was severely malnourished and therefore underweight.

Diagnosis:

He was severely underweight, malnourished, with a severe consciousness disorder that necessitated the tracheostomy and the PEG.

Interventions:

Our approach included caloric implementation of artificial nutrition and the gradual introduction of semi-liquid natural foods administered through PEG.

Outcomes:

The patient was followed for a year during which the metabolic/nutritional pattern and the blood tests improved, normal weight restored, and consciousness regained.

Conclusion:

Nutritional intervention integrated with natural foods, has allowed a gradual increase in weight, a better recovery of the lean mass and the stabilization of the metabolic-nutritional framework.

Nutritional approach used has contributed to the reduction of recovery times, making the therapeutic path more effective.
Hepatocellular carcinoma arising from left accessory liver lobe supplied by the branch of left hepatic artery
Authors: Wang Xiaolong , Zhang Qingqiao , Xu Kai
Published: October 2019

Introduction:

Accessory liver lobe (ALL) is a rare congenital anomaly. ALL combined with hepatocellular carcinoma (HCC) is even rarer. Most ALLs with HCC are often located in the right liver, and are not supplied by the left hepatic artery.

Patient concerns:

A 77-year-old man was referred to our hospital because of the level of serum alpha-fetoprotein (AFP) continually increased for 1 month. He had no history of chronic hepatitis, alcohol abuse, or cirrhosis of the liver.

Diagnoses:

Preoperative computed tomography (CT) scan revealed a 3.0 × 3.0 × 1.0 cm ovaloid-shaped solid mass in the left subphrenic area with isodensity. Magnetic resonance imaging (MRI) showed a mass with a heterogeneous signal on T1- and T2-weighted images. On contrast-enhanced CT and MRI, the mass showed a pattern of early enhancement and washout. Digital subtraction angiography (DSA) confirmed the mass was fed by the branch of left liver artery.

Interventions:

The mass was treated by transatheter arterial embolization (TAE) followed by surgical resection. Histopathologically showed HCC, consistent with a moderately differentiated.

Outcomes:

Follow-up of 3 months after surgery, the level of AFP returned to normal gradually.

Conclusions:

In this report, we describe a rare case of ALL with HCC, located in the left subphrenic area, especially which was supplied by the branch of left hepatic artery has rarely been described. The clinical presentation, radiological features are described in the literature.
Hypoxia with 18F-fluoroerythronitroimidazole integrated positron emission tomography and computed tomography (18F-FETNIM PET/CT) in locoregionally advanced head and neck cancer
Authors: Hu Man , Xie Peng , Lee Nancy Y. , Li Min , Ho Felix , Lian Ming , Zhao Shuqiang , Yang Guoren , Fu Zheng , Zheng Jinsong , Ma Li , Yu Jinming
Published: October 2019

Hypoxia is a well-recognized biological characteristic to therapy resistance and negative prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC). This study aims to investigate the changes of hypoxia measured by 18F-fluoroerythronitroimidazole (FETNIM) uptake on integrated positron emission tomography and computed tomography (PET/CT) during chemoradiotherapy and its prognostic value of clinical outcome in locoregionally advanced HNSCC.

Thirty-two patients with locoregionally advanced HNSCC who received definitive treatment with concurrent chemoradiotherapy underwent FETNIM PET/CT scans before and after 5 weeks of treatment. The intensity of hypoxia using the maximum standardized uptake value (SUVmax) was evaluated both on primary lesion and metastatic lymph node (MLN). The pre-SUVmax and mid-SUVmax were defined as SUVmax on pre- and mid-FETNIM PET/CT. The local control (LC), regional control (RC), distant metastatic-free survival (DMFS), and overall survival (OS) were collected in patient follow-ups.

Mid-SUVmax decreased significantly both in the primary tumor (t = 8.083, P < .001) and MLN (t = 6.808, P < .001) compared to pre-SUVmax. With a median follow-up of 54 months, the 5-year LC, RC, DMFS, and OS rates were 55%, 66.7%, 64.7%, and 55%, respectively, for all of the patients. On univariate analysis, patients with high pre-SUVmax in primary tumor had significantly worse LC (56.3% vs 87.5%, P = .046) and OS (43.8% vs 87.5%, P = .023) than other patients. Patients with high mid-SUVmax had significantly worse DMFS (50% vs 84.6%, P = .049) and OS (33.3% vs 73.1%, P = .028) than other patients. The tumor grade and mid-SUVmax were the significant predictors of OS on multivariate analysis.

In this study, hypoxia in tumor significantly decreased during chemoradiotherapy. The persistent hypoxia predicted poor OS. The data provided evidence that FETNIM PET/CT could be used dynamically for selecting appropriate patients and optimal timing of hypoxia-adapted therapeutic regimens.