bluuebunny/crossref_metadata_2025 huggingface dataset:
Canned Comments in the Hospital Laboratory Information System Can Decrease Microbiology Requests
Authors: Ruff Heather M , Poonawala Husain , Sebastian Christopher , Peaper David R
Published: April 2021

Objectives

Phone calls to the microbiology laboratory can be to clarify culture results and provide education, but those calls also interrupt laboratory workflow. We characterized calls that the laboratory received and developed targeted comments to educate providers.

Methods

Calls were logged and characterized, and we developed comments to address common call subjects. We applied the new comments to cultures and logged calls over the same interval the subsequent year. Data before and after implementation were analyzed.

Results

Call volume decreased from 496 calls to 419 calls after implementation. There was a significant difference in level of training among callers (P < .005), but the nature of the calls did not change. Laboratory response showed an increase in release of previously generated data (eg, suppressed susceptibility results). Comments specifically developed to address intrinsic antibiotic resistance and common susceptibility patterns did not decrease call volume.

Conclusions

Implementation of comments in the laboratory information system decreased call volume, but targeted comments were less effective than anticipated.
1-Ethyl-β-N-acetylglucosaminide increases hyaluronan production in human keratinocytes by being converted to N-acetylglucosamine via β-N-acetylglucosaminidase-dependent manner
Authors: Akazawa Yumiko , Yoshida Hiroyuki , Endo Yoko , Sugita Jun , Yakumaru Masafumi , Sayo Tetsuya
Published: April 2021

Regulation of hyaluronan (HA) is important for the maintenance of epidermal homeostasis. Here, we examined the mechanism by which 1-ethyl-β-N-acetylglucosaminide (β-NAG2), a newly developed N-acetylglucosamine (NAG) derivative, increases HA production in cultured human epidermal keratinocytes. When keratinocytes were treated with β-NAG2, mRNA expression of HA synthase 3, which is responsible for HA production in human keratinocytes, was not influenced, but the intracellular level of UDP-NAG, a substrate used for HA synthesis, was increased. By using a synthetic substrate for β-N-acetylglucosaminidase (β-NAGase), keratinocytes were found to possess β-NAGase activity, and treatment of o-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of β-NAGase, abolished the release of NAG from β-NAG2 in keratinocytes. Furthermore, PUGNAc attenuated the β-NAG2-induced intracellular UDP-NAG and HA production in keratinocytes. These results suggest that β-NAG2 is converted to NAG by endogenous β-NAGase in keratinocytes, and the resulting NAG is further metabolized to UDP-NAG and utilized for HA production.
MMFGRN: a multi-source multi-model fusion method for gene regulatory network reconstruction
Authors: He Wenying , Tang Jijun , Zou Quan , Guo Fei
Published: April 2021

Lots of biological processes are controlled by gene regulatory networks (GRNs), such as growth and differentiation of cells, occurrence and development of the diseases. Therefore, it is important to persistently concentrate on the research of GRN. The determination of the gene–gene relationships from gene expression data is a complex issue. Since it is difficult to efficiently obtain the regularity behind the gene-gene relationship by only relying on biochemical experimental methods, thus various computational methods have been used to construct GRNs, and some achievements have been made. In this paper, we propose a novel method MMFGRN (for “Multi-source Multi-model Fusion for Gene Regulatory Network reconstruction”) to reconstruct the GRN. In order to make full use of the limited datasets and explore the potential regulatory relationships contained in different data types, we construct the MMFGRN model from three perspectives: single time series data model, single steady-data model and time series and steady-data joint model. And, we utilize the weighted fusion strategy to get the final global regulatory link ranking. Finally, MMFGRN model yields the best performance on the DREAM4 InSilico_Size10 data, outperforming other popular inference algorithms, with an overall area under receiver operating characteristic score of 0.909 and area under precision-recall (AUPR) curves score of 0.770 on the 10-gene network. Additionally, as the network scale increases, our method also has certain advantages with an overall AUPR score of 0.335 on the DREAM4 InSilico_Size100 data. These results demonstrate the good robustness of MMFGRN on different scales of networks. At the same time, the integration strategy proposed in this paper provides a new idea for the reconstruction of the biological network model without prior knowledge, which can help researchers to decipher the elusive mechanism of life.
High circulating insulin-like growth factor-1 reduces the risk of renal cell carcinoma: a Mendelian randomization study
Authors: Chen Meng , Tsai Chia-Wen , Chang Wen-Shin , Xiong Grace Y , Xu Yifan , Bau Da-Tian , Gu Jian
Published: April 2021

Insulin and insulin-like growth factors play important roles in carcinogenesis. Circulating insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) have been linked to cancer susceptibility. The associations of circulating IGF-1 and IGFBP-3 with the risk of renal cell carcinoma (RCC) are inconsistent. Recent large genome-wide association studies have identified 413 single nucleotide polymorphisms (SNPs) associated with IGF-1 and 4 SNPs associated with IGFBP-3. In this large case–control study consisting of 2069 RCC patients and 2052 healthy controls of European ancestry, we used a two-sample Mendelian randomization (MR) approach to investigate the associations of genetically predicted circulating IGF-1 and IGFBP-3 with RCC risk. We used an individual level data-based genetic risk score (GRS) and a summary statistics-based inverse-variance weighting (IVW) method in MR analyses. We found that genetically predicted IGF-1 was significantly associated with RCC risk in both the GRS analysis [odds ratio (OR) = 0.43 per SD increase, 95% confidence interval (CI), 0.34–0.53] and the IVW analysis (OR = 0.46 per SD increase, 95% CI, 0.37–0.57). Dichotomized at the median GRS value of IGF-1 in controls, individuals with high GRS had a 45% reduced RCC risk (OR = 0.55, 95% CI, 0.48–0.62) compared with those with low GRS. Genetically predicted circulating IGFBP-3 was not associated with RCC risk. This is the largest RCC study of circulating IGF-1 and IGFBP-3 to date and our data suggest a strong inverse relationship between circulating IGF-1 level and RCC risk.
Outcomes of Multidrug-Resistant Tuberculosis Treated With Bedaquiline or Delamanid
Authors: Hwang Hyeontaek , Kang Hyungseok , Kwon Yong-Soo , Jeon Doosoo , Shim Tae Sun , Yim Jae-Joon
Published: April 2021

Background

Since 1 September 2016, bedaquiline and delamanid have been administered for the treatment of patients with multidrug-resistant/rifampicin-resistant tuberculosis after the official approval in South Korea. This study aimed to assess and compare the final treatment outcomes of patients who received bedaquiline with those of patients who received delamanid.

Methods

This is a nationwide cohort study of patients with multidrug-resistant/rifampicin-resistant tuberculosis in whom bedaquiline or delamanid was administered from 1 September 2016 to 28 February 2018, after receiving the official approval in South Korea. Patients were classified into the bedaquiline and delamanid group according to the first used drug. We evaluated and compared the final treatment outcomes between the groups.

Results

During the study period, 284 patients with multidrug-resistant/rifampicin-resistant tuberculosis were approved to use bedaquiline or delamanid and 260 were included in the final analysis; 119 (45.8%) and 141 patients (54.2%) were classified into bedaquiline and delamanid groups, respectively. Among them, 30 patients (11.5%) exhibited additional resistance to second-line injectable drugs, 94 patients (36.2%) had additional resistance to fluoroquinolones, and 37 patients (14.2%) had resistance to both drugs. The overall treatment success rate was 79.2%. Initiation of bedaquiline rather than delamanid was not associated with treatment success (adjusted odds ratio, .671; 95% confidence interval, .350–1.285). Frequencies of adverse events were not significantly different between the 2 groups.

Conclusions

Initial choice of bedaquiline or delamanid did not make any significant difference in the final treatment outcome or the frequencies of adverse events among patients with multidrug-resistant/rifampicin-resistant tuberculosis.
The safety of speculation …
Authors: Woods J E
Published: April 2021

Doubtless writing tongue-in-cheek to the Estates Committee of King’s College in 1938, Keynes remarked that it was safer to be a speculator than an investor. In the 1920s when first assuming responsibility for the College endowment, he had been a speculator, experiencing a remarkable conversion in the early 1930s to become a genuine long-term investor. Viewing the development of portfolio practice through Keynesian lenses, we demonstrate the essential continuity in conventional practice from Keynes’ time to the present day, the enduring characteristic being the treatment of uncertainty as if it were risk. Current practice is technically sophisticated, manifested in the reliance on benchmarks and risk controls to such an extent that we can refer to the fetish of benchmarking. In contrast, Keynes’ indirect, allusive, indeed elusive, approach embodies a unique insight—one that has been totally obscured by the conventional emphasis on ‘capital appreciation and depreciation generally’.
Optimal Real-Time Scheduling Algorithm for Wireless Sensors with Regenerative Energy
Authors: El Ghor Hussein , Chetto Maryline
Published: April 2021

Dynamic voltage and frequency scaling (DVFS) is a promising and broadly used energy-efficient technique to overcome the main problems arising from using a finite energy reservoir capacity and uncertain energy source in real-time embedded systems. This work investigates an energy management scheme for real-time task scheduling in variable voltage processors located in sensor nodes and powered by ambient energy sources. We use DVFS technique to decrease the energy consumption of sensors at the time when the energy sources are limited. In particular, we develop and prove an optimal real-time scheduling framework with speed stretching, namely energy guarantee DVFS (EG-DVFS), that jointly accounts not only for the timing constraints, but also for the energy state incurred by the properties of the system components. EG-DVFS relies on the well-known earliest deadline-harvesting scheduling algorithm combined with DVFS technique where the sensor processing frequency is fine tuned to further minimize energy consumption and to achieve an energy autonomy of the system. Further, an exact feasibility test for a set of periodic, aperiodic or even sporadic tasks is presented.
Do psychosocial job stressors differentially affect the sleep quality of men and women? A study using the HILDA Survey
Authors: Scovelle A J , King T , Shields M , O’Neil A , Lallukka T , Hewitt B , Milner A
Published: April 2021

The aim of this study was to investigate whether gender was an effect modifier of the relationship between three psychosocial job stressors and sleep quality, in a representative sample of 7280 employed Australians. We conducted linear regressions and effect measure modification analyses. Low job control, high job demands and low job security were associated with poorer sleep quality. There was evidence of effect modification of the relationship between job security and sleep quality by gender on the additive scale, indicating that the combined effect of being male and having low job security is greater than the summed interactive effect.
SIMULATION OF QUANTITATIVE CHARACTERS BY GENES WITH BIOCHEMICALLY DEFINABLE ACTION. VI. MODIFICATIONS OF A SIMPLE MODEL
Authors: Forkmann G , Seyffert W
Published: April 2021

Investigations on metric characters of defined genotypes of Matthiola incana, and application of different linear models for the estimation of genetic parameters, indicate that the use of midparental value as a reference point results in parameter estimates that do not correspond to the actual biological situation. Use of the most recessive genotype as a reference point causes all of the contributions of single loci to be unidirectional and positive, and all the allelic and nonallelic interactions to be unidirectional and negative, in accord with our Model 2.2. The results indicate that the phenotypic response to allelic substitutions follows the characteristics of a saturation curve. The possibility is discussed that the saturation character results from regulating processes, whereas deviations of single measurements from the response curve, or response surface, reflect real interactions between allelic and nonallelic genes.
CYTOPLASMIC MALE STERILITY IN NICOTIANA, RESTORATION OF FERTILITY, AND THE NUCLEOLUS. II. N. DEBNEYI CYTOPLASM
Authors: Burns J A , Gerstel D U , Sand S A
Published: April 2021

Previously, it was shown that a fragment chromosome, apparently derived from the Nicotiana repanda chromosomal complement, restores to normal the morphology and fertility of the abortive and feminized anthers produced by plants that possess the N. tabacum genome in cytoplasm from N. repanda. Furthermore, that restorer chromosome organizes the nucleolus and inhibits the nucleolus-forming activity of the nucleolar organizers of N. tabacum chromosomes present in the same cells, particularly in pollen mother cells. To determine whether these relations are basic or only coincidental, restorer chromosomes for other cytoplasms are now being investigated. The present paper describes a study of a chromosome, presumably derived from N. debneyi, with partial restoring power. Acting in the cytoplasm of N. debneyi, it directs formation of morphologically normal anthers, without, however, restoring pollen fertility. We find that this chromosome also has a functioning nucleolar organizer, but only slightly inhibits the nucleolus-forming capacity of N. tabacum chromosomes. The suggestion of a relationship between the nucleolar apparatus and restoration of normal anthers is thus strengthened by the observation that restorers are found on nucleolus-forming chromosomes from two very distinct Nicotiana species, as well as in several comparable cases cited from the Triticinae. The manner in which the nucleolus, or its organizer, may direct defeminization and restoration of anther morphology is not known; suggestions were offered in the preceding paper in this series (Gerstel, Burns and Burk 1978).
THE ALCOHOL DEHYDROGENASE POLYMORPHISM IN POPULATIONS OF DROSOPHILA MELANOGASTER. I. SELECTION IN DIFFERENT ENVIRONMENTS
Authors: van Delden W , Boerema A C , Kamping A
Published: April 2021

The allozyme polymorphism at the alcohol dehydrogenase locus in Drosophila melanogaster was studied in order to obtain experimental evidence about the maintenance of this polymorphism. Populations started with different initial allele frequencies from homozygous F and S lines showed a convergence of frequencies on regular food at 25°, leading to values equal to those in the base populations. These results were interpreted as due to some kind of balancing selection. In populations kept at 29.8°, a lower equilibrium F frequency was attained. Addition of ethanol and some other alcohols to the food gave a rapid increase in F frequency, and high humidity decreased the F frequency slightly. Combination or alternation of ethanol and high humidity had variable effects in the populations tested. For a further analysis of the allele-frequency changes, estimates were obtained for egg-to-adult survival under different conditions and for adult survival on ethanol-supplemented food. On ethanol food (both at regular and high humidity), egg-to-adult survival of SS homozygotes was considerably lower than that of the FF and FS genotypes. Under regular conditions of food, temperature and humidity, a tendency to heterozygote superiority was observed, while at high humidity a relative high survival of SS was noticed in some tests. Adult survival of SS was lower than that of FF, but FS was generally intermediate, though the degree of dominance differed between populations. The results are consistent with the hypothesis of the occurrence of selection at the Adh locus.
CHROMOSOME FRAGMENTS IN DICTYOSTELIUM DISCOIDEUM OBTAINED FROM PARASEXUAL CROSSES BETWEEN STRAINS OF DIFFERENT GENETIC BACKGROUND
Authors: Williams Keith L , Robson Gillian E , Welker Dennis L
Published: April 2021

The first aneuploid strains of Dictyostelium discoideum have been unambiguously characterized, using cytological and genetic analysis. Three independently isolated, but genetically similar, fragment chromosomes have been observed in segregants from diploids formed between haploid strains derived from the NC4 and VI2 isolates of D. discoideum. Once generated, the fragment chromosomes, all of which have Vl2-derived centromeres, can be maintained in a NC4 genetic background. Genetic evidence is consistent with the view that all three fragment chromosomes studied encompass the region from the centromere to the whiA locus of linkage group II and terminate in the interval between whiA and acrA. From cytological studies, one of the fragment chromosomes consists of approximately half of linkage group II.——We observed no deleterious effect on viability or asexual fruiting-body formation in either haploid or diploid strains carrying an additional incomplete chromosome and hence are disomic or trisomic, respectively, for part of linkage group II. The incomplete chromosome is lost at a frequency of 2 to 3% from disomic and trisomic strains, but surprisingly this loss is not increased in the presence of the haploidizing agent, benlate. A new locus (clyA), whose phenotype is altered colony morphology, is assigned to the region of linkage group II encompassed by the fragment chromosome.
ASSESSMENT OF VARIABILITY WITHIN ELECTROMORPHS OF ALCOHOL DEHYDROGENASE IN DROSOPHILA MELANOGASTER
Authors: Kreitman Martin
Published: April 2021

Ninety-six isochromosomal lines of Drosophila melanogaster from a natural population were screened electrophoretically for unusual mobility variants at the alcohol dehydrogenase locus, using a total of eight conditions of acrylamide electrophoresis. No additional mobility variation was found among the 50 "slow" and 46 "fast" mobility lines beyond that detected by standard methods of electrophoresis. However, two thermostability variants recovered by R. MILKMAN from a natural population, whose electrophoretic mobilities were previously thought to be indistinguishable from those of "standard" alleles, are distinguishable from the standard elcctromorphs by these procedures. These results suggest that the Adhlocus, although polymorphic, does not harbor substantial amounts of "hidden" allelic variability. This study also reports the appearance of substantial mobility variation among isogenic lines that can be induced under specific conditions of sample preparation involving the pretreatment of samples with NAD and acetone. However, genetic analysis demonstrates that this variability cannot be attributed to allelic differences at the structural locus, but instead appears to be dependent upon the concentration of the enzyme in a sample. These results are discussed in relation to the distribution of allelic variation at other enzyme loci.
DNA REARRANGEMENTS ASSOCIATED WITH REVERSION OF BACTERIOPHAGE MU-INDUCED MUTATIONS
Authors: Khatoon Hajra , Bukhari Ahmad I
Published: April 2021

Excision of transposable genetic elements from host DNA is different from the classical prophage lambda type of excision in that it occurs at low frequency and is mostly imprecise; only a minority of excision events restores the wild-type host sequences. In bacteriophage Mu, a highly efficient transposon, imprecise excision is 10–100 times more frequent than precise excision. We have examined a large number of these excision events by starting with Mucts X mutants located in the Z gene of the lac operon of Escherichia coli. Mucts X mutants are defective prophages whose excision occurs at a measurable frequency. Imprecise excision was monitored by selecting for melibiose+ (Mel+) phenotype, which requires only a functioning lacY gene. Mel+ revertants exhibit an array of DNA rearrangements and fall in four main classes, the predominant one being comprised of revertants that have no detectable Mu DNA. Most of these revertants can further revert to Lac+. Perhaps 5 base-pair duplications, originally present at prophage-host junctions, are left in these lacZ  -  Y  + revertants, and they can be further repaired to lacZ  +. Another class has, in addition to the loss of Mu DNA, deletions that extend generally, but not always, to only one side of the prophage. The other two classes of revertants, surprisingly, still have Mu DNA in the lacZ gene. One class has deletions in the Z gene, whereas, no deletions can be detected in the other. Many of the revertants in the last class can further revert to lacZ  +, indicating that the lacY gene must have been turned on by a rearrangement within Mu DNA. Apparently, all of the detectable precise and most of the imprecise excision events require functioning of the Mu A gene. We suggest that a block in large-scale Mu replication allows the excision process to proceed.
CONTROLLING-ELEMENT EVENTS AT THE SHRUNKEN LOCUS IN MAIZE
Authors: Burr B , Burr F A
Published: April 2021

We have examined insertions of the controlling element Ds at the Shrunken locus of maize. A cDNA probe complementary to a portion of the Shrunken locus mRNA was prepared. This probe recognizes a unique sequence in maize DNA. Using lines carrying derivatives of the same short arm of chromosome 9, we have detected modifications at the nucleic acid level caused by Ds. The changes appear to be large insertions, one of which may be more than 20 kilobase pairs in length. These observations provide a basis for the isolation and molecular characterization of one of the maize controlling elements.
GENES IN NEUROSPORA THAT SUPPRESS RECOMBINATION WHEN THEY ARE HETEROZYGOUS
Authors: Catcheside D E A
Published: April 2021

Genes that suppress recombination when heterozygous have been found distributed as a polymorphism in wild and laboratory populations of Neurospora crassa. Three alleles, ssE, ssS and ssC, are associated, respectively, with the three wild types Emerson, St. Lawrence 74A and Costa Rica A. It is proposed that ss (synaptic sequence) genes modulate recombination by determining the pairing closeness of DNA duplexes in the vicinity of the nit-2 locus. When heterozygous, ss suppresses recombination 2- to 20-fold within the nit-2 locus, which it adjoins, but crossing over in intervals flanking nit-2 is not affected. The magnitude of suppression depends upon the ss alleles involved, and ss acts multiplicatively with rec-1; together, these genes modulate recombination within the nit-2 locus over a range exceeding 100-fold. The ss effect is not attributable to gross chromosomal rearrangement, but could be due to small inversions or insertions, such as transposable elements.
A broad read of Ely: Political process theory for fragile democracies
Authors: Cepeda Espinosa Manuel José , Landau David
Published: April 2021

This article, part of a symposium on the fortieth anniversary of John Hart Ely’s Democracy and Distrust, contrasts two reads of Ely’s political process theory. The narrow read, which focuses on keeping clear the channels of political change and protecting discrete and insular minorities, stems from Ely’s focus on the twentieth-century United States. However, when Ely’s work is transplanted into the context of fragile democracies in danger of lapsing into authoritarianism and with serial political dysfunction, a broader read emerges. This article develops a typology of functions that courts play under a broad read, in addition to the traditional focus on protecting discrete and insular minorities: guarding against democratic breakdown, improving the quality of democratic institutions, and responding to failures of political institutions impacting majoritarian groups. The article also shows that although the broad read of Ely raises new problems, it offers a useful guide to theorists and courts.
Veno-venous extra-corporeal membrane oxygenation-assisted right tracheal-sleeve pneumonectomy
Authors: Mazzella Antonio , Bertolaccini Luca , Petrella Francesco , Spaggiari Lorenzo
Published: April 2021

Tracheal sleeve pneumonectomy for lung cancer is an old technique, and it is reserved for exceptional cases with tracheal carina involvement. Intra-operative airways management of this operation is incredibly complex, involving thoracic surgeons, anaesthesiologists and pulmonologists. We report a case of a 38-year-old male with no clinical history, referred to our department for an adenoid-cystic carcinoma involving distal trachea, carina and main right bronchus. Tracheal sleeve pneumonectomy was performed using extra-corporeal membrane oxygenation (ECMO). A veno-venous ECMO circuit was established through a heparin-coated percutaneous cannula in the right femoral vein and a heparin-coated percutaneous cannula in the internal right jugular vein by ultrasound assistance. No major complications occurred, and the patient was discharged after 30-day bronchoscopic control, showing the absence of fistula and negativity of the methylene blue test. ECMO-assisted surgery ensures adequate respiratory support, haemodynamic stability, lower risk of bleeding complications with a clean operating field and better brain and myocardial oxygenation.
Perceptions of event notification following discharge to improve geriatric care: qualitative interviews of care team members from a 2-site cluster randomized trial
Authors: Franzosa Emily , Traylor Morgan , Judon Kimberly M , Guerrero Aquino Vivian , Schwartzkopf Ashley L , Boockvar Kenneth S , Dixon Brian E
Published: April 2021

Objective

To assess primary care teams’ perceptions of a health information exchange (HIE) event notification intervention for geriatric patients in 2 Veterans Health Administration (VHA) medical centers.

Materials and Methods

We conducted a qualitative evaluation of an event notification alerting primary care teams to non-VHA hospital admissions and emergency department visits. Data were collected through semistructured interviews (n = 23) of primary care team physicians, nurses and medical assistants. Study design and analysis were guided by the Consolidated Framework for Implementation Research (CFIR).

Results

Team members found the alerts necessary, helpful for filling information gaps, and effective in supporting timely follow-up care, although some expressed concern over scheduling capacity and distinguishing alerts from other VHA notices. Participants also suggested improvements including additional data on patients’ diagnosis and discharge instructions, timing alerts to patients’ discharge (including clear next steps), including additional team members to ensure alerts were acted upon, and implementing a single sign-on.

Discussion

Primary care team members perceived timely event notification of non-VHA emergency department visits and hospital admissions as potentially improving post-discharge follow-up and patient outcomes. However, they were sometimes unsure of next steps and suggested the alerts and platform could be streamlined for easier use.

Conclusions

Event notifications may be a valuable tool in coordinating care for high-risk older patients. Future intervention research should explore the optimal amount and types of information and delivery method across sites and test the integration of alerts into broader care coordination efforts.
A neuro-symbolic method for understanding free-text medical evidence
Authors: Kang Tian , Turfah Ali , Kim Jaehyun , Perotte Adler , Weng Chunhua
Published: April 2021

Objective

We introduce Medical evidence Dependency (MD)–informed attention, a novel neuro-symbolic model for understanding free-text clinical trial publications with generalizability and interpretability.

Materials and Methods

We trained one head in the multi-head self-attention model to attend to the Medical evidence Ddependency (MD) and to pass linguistic and domain knowledge on to later layers (MD informed). This MD-informed attention model was integrated into BioBERT and tested on 2 public machine reading comprehension benchmarks for clinical trial publications: Evidence Inference 2.0 and PubMedQA. We also curated a small set of recently published articles reporting randomized controlled trials on COVID-19 (coronavirus disease 2019) following the Evidence Inference 2.0 guidelines to evaluate the model’s robustness to unseen data.

Results

The integration of MD-informed attention head improves BioBERT substantially in both benchmark tasks—as large as an increase of +30% in the F1 score—and achieves the new state-of-the-art performance on the Evidence Inference 2.0. It achieves 84% and 82% in overall accuracy and F1 score, respectively, on the unseen COVID-19 data.

Conclusions

MD-informed attention empowers neural reading comprehension models with interpretability and generalizability via reusable domain knowledge. Its compositionality can benefit any transformer-based architecture for machine reading comprehension of free-text medical evidence.
Does foreign investment hurt job creation at home? The geography of outward FDI and employment in the USA
Authors: Crescenzi Riccardo , Ganau , Roberto , Storper Michael
Published: April 2021

Rising political skepticism on the benefits of global economic integration has increased public scrutiny of the foreign activities of domestic firms in virtually all advanced economies. Decisions to invest in new activities abroad are seen by some commentators as potentially detrimental to domestic employment. We contribute to this debate by scrutinizing the relationship between outward ‘greenfield’ Foreign Direct Investments (FDI) and local employment levels. The analysis, at the scale of USA Economic Areas, finds a generally positive link between outward investment and local employment, but with an important range of differences across regions and sectors. Less developed regions benefit the most from the positive returns of outward FDI, and, particularly, from outward FDI if it is undertaken by firms in high-tech manufacturing and services industries. But there is a downside, in the form of increasing intra-regional inequalities between high-skilled and low-skilled workers in these areas.
Regulation of Special Economic Zones Through Regional Trade Agreements: Confronting the Synergy Issue
Authors: Chi Manjiao
Published: April 2021

Special economic zones (SEZs) and regional trade agreements (RTAs) are frequently used by states as policy tools to promote economic development. As SEZs and RTAs overlap in geographical coverage and regulation areas and are implemented in parallel, they could create profound synergies. As there is no specialized international legal framework for SEZ regulation, and national SEZ laws seldom touch upon the synergy issue, SEZ regulation is largely left to RTAs at the international level. Yet, existing SEZ-related provisions in RTAs almost exclusively focus on trade in goods and appear insufficient in addressing the synergy issue—especially ‘new synergies’ created by ‘advanced SEZs’ and ‘deep RTAs’. To properly address the synergy issue, states should treat SEZ policy-making and RTA rule-making in a coordinated way and consider adopting a regional or multilateral approach in SEZ regulation.
Special Economic Zones Facing the Challenges of International Taxation: BEPS Action 5, EU Code of Conduct, and the Future
Authors: Heitmüller Frederik , Mosquera Irma
Published: April 2021

Corporate taxation and particularly corporate tax incentives that jurisdictions introduce in special economic zones have not, until recently, been subject to extensive international regulation. Only in the last decade has a regime of soft law standards and European Union measures with extraterritorial effect been constructed. This article explains how the Base Erosion and Profit Shifting Action Plan developed by the Organisation for Economic Co-operation and Development (OECD) and the European Union Code of Conduct for Business Taxation interact with corporate tax incentives in special economic zones. Empirical evidence from Latin American and Caribbean jurisdictions shows that this emerging international regime began having an impact on special economic zone laws beyond the OECD and European Union Member States. An analysis of ongoing negotiations on the further developments of the international tax regime permits the cautious conclusion that the regulation of SEZs may in the future be affected in a more fundamental manner by international norms. Thereby, the article shows that special economic zones’ unilateralism in corporate taxation may be slowly receding in contrast to other areas of international economic governance.
The Milieu Souterrain Superficiel as hibernation habitat for bats: implications for white-nose syndrome
Authors: Blejwas Karen M , Pendleton Grey W , Kohan Michael L , Beard Laura O
Published: April 2021

Recent studies have revealed that western populations of little brown bats (Myotis lucifugus) in North America exhibit different hibernation behavior than their eastern counterparts. Understanding these differences is essential for assessing the risk white-nose syndrome (WNS) poses to western bat populations. We used acoustic monitoring and radiotelemetry to study the overwintering behavior of little brown bats near Juneau, Alaska during 2011–2014. Our objectives were to identify the structures they use for hibernation, measure the microclimates within those structures, and determine the timing of immergence and emergence and the length of the hibernation season. We radiotracked 10 little brown bats to underground hibernacula dispersed along two ridge systems. All hibernacula were ≤ 24.2 km from where the bats were captured. Eight bats hibernated in the “Milieu Souterrain Superficiel” (MSS), a network of air-filled underground voids between the rock fragments found in scree (talus) deposits. Two bats hibernated in holes in the soil beneath the root system of a tree or stump (rootball). At least two hibernacula in the MSS were reused in subsequent years. Average MSS and rootball temperatures were warmer and more stable than ambient temperature and were well below the optimal growth range of the fungus that causes WNS. Temperatures in the MSS dropped below freezing, but MSS temperatures increased with depth, indicating bats could avoid subfreezing temperatures by moving deeper into the MSS. Relative humidity (RH) approached 100% in the MSS and under rootballs and was more stable than ambient RH, which also was high, but dropped substantially during periods of extreme cold. Acoustic monitoring revealed that bats hibernated by late October and began emerging by the second week of April; estimates of minimum length of the hibernation season ranged from 156 to 190 days. The cold temperatures, dispersed nature of the hibernacula, and close proximity of hibernacula to summering areas may slow the spread and reduce the impacts of WNS on local populations of little brown bats.
Dynamical response of a rotating cantilever pipe conveying fluid based on the absolute nodal coordinate formulation
Authors: Li Yunfeng , Li Yundong , Wen Huabin , Ning Wenbo
Published: April 2021

A dynamical model of a rotating cantilever pipe conveying fluid is derived based on the absolute nodal coordinate formulation. The free vibration and dynamical response of the system are investigated in this paper. Based on the absolute nodal coordinate method and the extended Lagrangian equation proposed by Irschik for the nonmaterial system, the motion equation of the rotating flexible cantilever pipe conveying fluid is built. The influence of the rotational angular velocity and flow velocity on the natural frequency of the system is analyzed. The critical nondimensional circular frequency of in-plane vibration and critical nondimensional flow velocity are investigated. The static deformation is shown under different flow velocities and angular velocities. The nonlinear transient analyses of a rotating flexible cantilever pipe are completed with the variation of parameters. During the rotation, the Coriolis force of fluid acting on the pipe has a great effect on the static deformation.
Nucleotide-sugar metabolism in plants: the legacy of Luis F. Leloir
Authors: Figueroa Carlos M , Lunn John E , Iglesias Alberto A
Published: April 2021

This review commemorates the 50th anniversary of the Nobel Prize in Chemistry awarded to Luis F. Leloir ‘for his discovery of sugar-nucleotides and their role in the biosynthesis of carbohydrates’. He and his co-workers discovered that activated forms of simple sugars, such as UDP-glucose and UDP-galactose, are essential intermediates in the interconversion of sugars. They elucidated the biosynthetic pathways for sucrose and starch, which are the major end-products of photosynthesis, and for trehalose. Trehalose 6-phosphate, the intermediate of trehalose biosynthesis that they discovered, is now a molecule of great interest due to its function as a sugar signalling metabolite that regulates many aspects of plant metabolism and development. The work of the Leloir group also opened the doors to an understanding of the biosynthesis of cellulose and other structural cell wall polysaccharides (hemicelluloses and pectins), and ascorbic acid (vitamin C). Nucleotide-sugars also serve as sugar donors for a myriad of glycosyltransferases that conjugate sugars to other molecules, including lipids, phytohormones, secondary metabolites, and proteins, thereby modifying their biological activity. In this review, we highlight the diversity of nucleotide-sugars and their functions in plants, in recognition of Leloir’s rich and enduring legacy to plant science.
Nanomechanics of G-quadruplexes within the promoter of the KIT oncogene
Authors: Buglione Enrico , Salerno Domenico , Marrano Claudia Adriana , Cassina Valeria , Vesco Guglielmo , Nardo Luca , Dacasto Mauro , Rigo Riccardo , Sissi Claudia , Mantegazza Francesco
Published: April 2021

G-quadruplexes (G4s) are tetrahelical DNA structures stabilized by four guanines paired via Hoogsteen hydrogen bonds into quartets. While their presence within eukaryotic DNA is known to play a key role in regulatory processes, their functional mechanisms are still under investigation. In the present work, we analysed the nanomechanical properties of three G4s present within the promoter of the KIT proto-oncogene from a single-molecule point of view through the use of magnetic tweezers (MTs). The study of DNA extension fluctuations under negative supercoiling allowed us to identify a characteristic fingerprint of G4 folding. We further analysed the energetic contribution of G4 to the double-strand denaturation process in the presence of negative supercoiling, and we observed a reduction in the energy required for strands separation.
Decoupling the bridge helix of Cas12a results in a reduced trimming activity, increased mismatch sensitivity and impaired conformational transitions
Authors: Wörle Elisabeth , Jakob Leonhard , Schmidbauer Andreas , Zinner Gabriel , Grohmann Dina
Published: April 2021

The widespread and versatile prokaryotic CRISPR–Cas systems (clustered regularly interspaced short palindromic repeats and associated Cas proteins) constitute powerful weapons against foreign nucleic acids. Recently, the single-effector nuclease Cas12a that belongs to the type V CRISPR–Cas system was added to the Cas enzymes repertoire employed for gene editing purposes. Cas12a is a bilobal enzyme composed of the REC and Nuc lobe connected by the wedge, REC1 domain and bridge helix (BH). We generated BH variants and integrated biochemical and single-molecule FRET (smFRET) studies to elucidate the role of the BH for the enzymatic activity and conformational flexibility of Francisella novicida Cas12a. We demonstrate that the BH impacts the trimming activity and mismatch sensitivity of Cas12a resulting in Cas12a variants with improved cleavage accuracy. smFRET measurements reveal the hitherto unknown open and closed state of apo Cas12a. BH variants preferentially adopt the open state. Transition to the closed state of the Cas12a-crRNA complex is inefficient in BH variants but the semi-closed state of the ternary complex can be adopted even if the BH is deleted in its entirety. Taken together, these insights reveal that the BH is a structural element that influences the catalytic activity and impacts conformational transitions of FnCas12a.
DDX3 depletion represses translation of mRNAs with complex 5′ UTRs
Authors: Calviello Lorenzo , Venkataramanan Srivats , Rogowski Karol J , Wyler Emanuel , Wilkins Kevin , Tejura Malvika , Thai Bao , Krol Jacek , Filipowicz Witold , Landthaler Markus , Floor Stephen N
Published: April 2021

DDX3 is an RNA chaperone of the DEAD-box family that regulates translation. Ded1, the yeast ortholog of DDX3, is a global regulator of translation, whereas DDX3 is thought to preferentially affect a subset of mRNAs. However, the set of mRNAs that are regulated by DDX3 are unknown, along with the relationship between DDX3 binding and activity. Here, we use ribosome profiling, RNA-seq, and PAR-CLIP to define the set of mRNAs that are regulated by DDX3 in human cells. We find that while DDX3 binds highly expressed mRNAs, depletion of DDX3 particularly affects the translation of a small subset of the transcriptome. We further find that DDX3 binds a site on helix 16 of the human ribosomal rRNA, placing it immediately adjacent to the mRNA entry channel. Translation changes caused by depleting DDX3 levels or expressing an inactive point mutation are different, consistent with different association of these genetic variant types with disease. Taken together, this work defines the subset of the transcriptome that is responsive to DDX3 inhibition, with relevance for basic biology and disease states where DDX3 is altered.
Time-Out and Its Role in Neurosurgery
Authors: LoPresti Melissa A , Du Rebecca Y , Yoshor Daniel
Published: April 2021

BACKGROUND

Safety checklists have improved surgical outcomes; however, much of the literature comes from general surgery.

OBJECTIVE

To identify the role of time-outs in neurosurgery, understand neurosurgeons’ attitudes toward time-out, and highlight areas for improvement.

METHODS

A cross-sectional study using a 15-item survey to evaluate how time-outs were performed across 5 hospitals affiliated with a single neurosurgery training program.

RESULTS

Surveys were sent to 51 neurosurgical faculty, fellows, and residents across 5 hospitals with a 72.5% response rate. At all hospitals, surgeons, anesthesiologists, registered nurses, and circulators were involved in time-outs. Although all required time-out before incision, there was no consensus regarding the precise timing of time-out, in policy or in practice. Overall, respondents believed the existing time-out was adequate for neurosurgical procedures (H1: 17, 65.4%; H2: 19, 86.4%; H3: 14, 70.0%; H4: 20, 80.0%; and H5: 18, 78.3%). Of the respondents, 97.2% believed time-out made surgery safe, 94.6% agreed that time-outs reduce the risk of wrong-side or wrong-level neurosurgery, and 17 (45.9%) saw a role for a neurosurgery-specific safety checklist. Pragmatic challenges (n = 20, 54.1%) and individual beliefs and attitudes (n = 20, 54.1%) were common barriers to implementation of standardized time-outs.

CONCLUSION

Multidisciplinary time-outs have become standard of care in neurosurgery. Despite proximity and overlapping personnel, there is considerable variability between hospitals in the practice of time-outs. This lack of uniformity, allowed for by flexible World Health Organization guidelines, may reflect the origins of surgical time-outs in general surgery, rather than neurosurgery, underscoring the potential for time-out optimization with neurosurgery-specific considerations.
Impact of Smoking Behavior on Survival Following Allogeneic Hematopoietic Stem Cell Transplantation – Smoking Cessation Matters
Authors: Scheidl Stefan , Avian Alexander , Flick Holger , Gaal Sonja , Greinix Hildegard , Olschewski Horst
Published: April 2021

Introduction

There are only a few data on the impact of smoking and smoking cessation on the outcome of patients treated with allogeneic hematopoietic stem cell transplantation, a well-established therapy for hematologic malignancies.

Methods

In a retrospective cohort study design we examined the impact of smoking and smoking cessation on survival among 309 eligible consecutive adults who underwent allogeneic hematopoietic stem cell transplantation using reduced-intensity (n = 179) or myeloablative (n = 130) conditioning between 1999 and 2018.

Results

Smoking and was independently associated with increased mortality with a five-year overall survival of 25% in current smokers versus 53% in never smokers versus 48% in past smokers. Never smokers lived significantly longer (HR: 2.00, 95%CI: 1.19–3.35, p = .008) and had a better event-free survival (HR: 2.11, 95%CI: 1.27–3.49, p = .004) than current smokers. In the long run, never smokers also lived significantly longer than past smokers (HR: 1.45, 95%CI: 1.16–1.81, p = .001). Patients who quit smoking before allogeneic hematopoietic stem cell transplantation showed a tendency towards increased survival compared to those who continued smoking (HR: 1.53, 95%CI: 0.95–2.45, p = .078). In relation to life-time cigarette dose smokers with low-dose (1–10 pack-years) cigarette consumption lived significantly longer (HR: 1.60, 95%CI: 1.03–2.50, p = .037) and had a better event-free survival (HR: 1.66, 95%CI: 1.07–2.58, p = .025) than patients with high-dose (≥10 pack-years) cigarette consumption.

Conclusions

In allogeneic hematopoietic stem cell transplantation for hematologic malignancies, smoking history per se, lifetime cigarette dose, and continued smoking, were significantly associated with increased all-cause mortality and reduced event-free survival.

Implications

Continued and past smoking represent established risk factors for malignant and non-malignant diseases, however, they are also a strong risk factor for a poor outcome after allogeneic hematopoietic stem cell transplantation for hematologic diseases. Our study shows that the hazard ratio for death after such transplantation is doubled if patients continue smoking and even if they have quit smoking, their risk remains significantly elevated. This suggests that the smoking history provides important predictive factors for the outcome of allogeneic hematopoietic stem cell transplantation and that smoking cessation should be implemented in the treatment of hematologic diseases as early as possible.