bluuebunny/crossref_metadata_2025_split huggingface dataset:
Independent Losses of the Hypoxia-Inducible Factor (HIF) Pathway within Crustacea
Authors: Graham Allie M , Barreto Felipe S 
Published: January 2020

AbstractMetazoans respond to hypoxic stress via the hypoxia-inducible factor (HIF) pathway, a mechanism thought to be extremely conserved due to its importance in monitoring cellular oxygen levels and regulating responses to hypoxia. However, recent work revealed that key members of the HIF pathway have been lost in specific lineages (a tardigrade and a copepod), suggesting that this pathway is not as widespread in animals as previously assumed. Using genomic and transcriptomic data from 70 different species across 12 major crustacean groups, we assessed the degree to which the gene HIFα, the master regulator of the HIF pathway, was conserved. Mining of protein domains, followed by phylogenetic analyses of gene families, uncovered group-level losses of HIFα, including one across three orders within Cirripedia, and in three orders within Copepoda. For these groups, additional assessment showed losses of HIF repression machinery (EGLN and VHL). These results suggest the existence of alternative mechanisms for cellular response to low oxygen and highlight these taxa as models useful for probing these evolutionary outcomes.
Understanding the effect of controlling phosphorothioate chirality in the DNA gap on the potency and safety of gapmer antisense oligonucleotides
Authors: Østergaard Michael E , De Hoyos Cheryl L , Wan W Brad , Shen Wen , Low Audrey , Berdeja Andres , Vasquez Guillermo , Murray Susan , Migawa Michael T , Liang Xue-hai , Swayze Eric E , Crooke Stanley T , Seth Punit P 
Published: January 2020

Abstract
Therapeutic oligonucleotides are often modified using the phosphorothioate (PS) backbone modification which enhances stability from nuclease mediated degradation. However, substituting oxygen in the phosphodiester backbone with sulfur introduce chirality into the backbone such that a full PS 16-mer oligonucleotide is comprised of 215 distinct stereoisomers. As a result, the role of PS chirality on the performance of antisense oligonucleotides (ASOs) has been a subject of debate for over two decades. We carried out a systematic analysis to determine if controlling PS chirality in the DNA gap region can enhance the potency and safety of gapmer ASOs modified with high-affinity constrained Ethyl (cEt) nucleotides in the flanks. As part of this effort, we examined the effect of systematically controlling PS chirality on RNase H1 cleavage patterns, protein mislocalization phenotypes, activity and toxicity in cells and in mice. We found that while controlling PS chirality can dramatically modulate interactions with RNase H1 as evidenced by changes in RNA cleavage patterns, these were insufficient to improve the overall therapeutic profile. We also found that controlling PS chirality of only two PS linkages in the DNA gap was sufficient to modulate RNase H1 cleavage patterns and combining these designs with simple modifications such as 2′-OMe to the DNA gap resulted in dramatic improvements in therapeutic index. However, we were unable to demonstrate improved potency relative to the stereorandom parent ASO or improved safety over the 2′-OMe gap-modified stereorandom parent ASO. Overall, our work shows that while controlling PS chirality can modulate RNase H1 cleavage patterns, ASO sequence and design are the primary drivers which determine the pharmacological and toxicological properties of gapmer ASOs.
The Mandate Divide in Policy Representation: The Substantive Representation of Agricultural Interests in the Hungarian Parliament
Authors: Papp Zsófia 
Published: January 2020

AbstractPolicy responsiveness is considered an effective tool for representing the aggregated interests of an electoral district. This article asks the question whether or not legislators in a mixed-member electoral system act on the profile of the constituency in their parliamentary work and, if yes, whether the magnitude of their actions is dependent upon mandate type and electoral security. I answer these questions by using data on Hungarian Members of Parliament (MPs)’ parliamentary questions, and the agricultural profile of the constituencies between 1998 and 2010. It is found that a larger share of the agricultural population correlates with a greater frequency of agriculture questions. Furthermore, as expected, single-member district MPs are more vigilant to the share of the agricultural population than list MPs. Interestingly, MPs remain indifferent to the fierceness of competition: they ask just as any many questions in the case of a safe seat as in the case of stiff competition.
Deadlock on the Board
Authors: Donaldson Jason Roderick , Malenko Nadya , Piacentino Giorgia 
Published: January 2020

AbstractWe develop a dynamic model of board decision-making akin to dynamic voting models in the political economy literature. We show a board could retain a policy all directors agree is worse than an available alternative. Thus, directors may retain a CEO they agree is bad—deadlocked boards lead to entrenched CEOs. We explore how to compose boards and appoint directors to mitigate deadlock. We find board diversity and long director tenure can exacerbate deadlock. We rationalize why CEOs and incumbent directors have power to appoint new directors: to avoid deadlock. Our model speaks to short-termism, staggered boards, and proxy access.
The role of trait empathy in the processing of observed actions in a false-belief task
Authors: Bellebaum Christian , Ghio Marta , Wollmer Marie , Weismüller Benjamin , Thoma Patrizia 
Published: January 2020

Abstract
Empathic brain responses are characterized by overlapping activations between active experience and observation of an emotion in another person, with the pattern for observation being modulated by trait empathy. Also for self-performed and observed errors, similar brain activity has been described, but findings concerning the role of empathy are mixed. We hypothesized that trait empathy modulates the processing of observed responses if expectations concerning the response are based on the beliefs of the observed person. In the present study, we utilized a false-belief task in which observed person’s and observer’s task-related knowledge were dissociated and errors and correct responses could be expected or unexpected. While theta power was generally modulated by the expectancy of the observed response, a negative mediofrontal event-related potential (ERP) component was more pronounced for unexpected observed actions only in participants with higher trait empathy (assessed by the Empathy Quotient), as revealed by linear mixed effects analyses. Cognitive and affective empathy, assessed by the Interpersonal Reactivity Index, were not significantly related to the ERP component. The results suggest that trait empathy can facilitate the generation of predictions and thereby modulate specific aspects of the processing of observed actions, while the contributions of specific empathy components remain unclear.
In Vitro Bioavailability of the Hydrocarbon Fractions of Dimethyl Sulfoxide Extracts of Petroleum Substances
Authors: Luo Yu-Syuan , Ferguson Kyle C , Rusyn Ivan , Chiu Weihsueh A 
Published: January 2020

Abstract
Determining the in vitro bioavailable concentration is a critical, yet unmet need to refine in vitro-to-in vivo extrapolation for unknown or variable composition, complex reaction product or biological material (UVCB) substances. UVCBs such as petroleum substances are commonly subjected to dimethyl sulfoxide (DMSO) extraction in order to retrieve the bioactive polycyclic aromatic compound (PAC) portion for in vitro testing. In addition to DMSO extraction, protein binding in cell culture media and dilution can all influence in vitro bioavailable concentrations of aliphatic and aromatic compounds in petroleum substances. However, these in vitro factors have not been fully characterized. In this study, we aimed to fill in these data gaps by characterizing the effects of these processes using both a defined mixture of analytical standards containing aliphatic and aromatic hydrocarbons, as well as 4 refined petroleum products as prototypical examples of UVCBs. Each substance was extracted with DMSO, and the protein binding in cell culture media was measured by using solid-phase microextraction. Semiquantitative analysis for aliphatic and aromatic compounds was achieved via gas chromatography-mass spectrometry. Our results showed that DMSO selectively extracted PACs from test substances, and that chemical profiles of PACs across molecular classes remained consistent after extraction. With respect to protein binding, chemical profiles were retained at a lower dilution (higher concentration), but a greater dilution factor (ie, lower concentration) resulted in higher protein binding in cell medium, which in turn altered the ultimate chemical profile of bioavailable PACs. Overall, this case study demonstrates that extraction procedures, protein binding in cell culture media, and dilution factors prior to in vitro testing can all contribute to determining the final bioavailable concentrations of bioactive constituents of UVCBs in vitro. Thus, in vitro-to-in vivo extrapolation for UVCBs may require greater attention to the concentration-dependent and compound-specific differences in recovery and bioavailability.
Bioethics: cancelling patient operations
Authors: Denholm Louise , Lal Aashray , Henderson Mark , McConnell Paul 
Published: January 2020

Purpose of review
This review aims to surmise a bioethical approach to the phenomenon of cancelling patient operations. There is increasing public and political interest in the matter with a rise in the frequency of cancellations. Cancellations are emotional for patients and are difficult clinical decisions.

Recent findings
Reasons for cancellation involve patient factors and resource allocation applying to elective and emergency surgery. The four pillars of bioethics are easily applied, (autonomy, beneficence, nonmaleficence and justice), although their failings are becoming more prominent with the rise of more encompassing virtue ethics. These include dignity, solidarity, phronesis and trust. Importantly patient dignity should be preserved, this complimenting solidarity and trust in specialist knowledge more than autonomy does. Beauchamp and Childress have provided a descriptive framework describing futility, which may aid communication and mental clarity when deliberating if it is the right choice to cancel. With regards to resource factors, ideally managerial staff should be involved in these decisions leaving the physician to be the patient's clinical advocate.

Summary
Although cancellations are undesirable, they are inevitable and form part of the duties of a doctor. When they do occur, care must remain patient-centred, asking how we can improve this situation.
Patient Selection for Adjuvant Chemotherapy in High-Risk Stage II Colon Cancer
Authors: Zhang Chao , Yin Songcheng , Tan Yuen , Huang Jinyu , Wang Pengliang , Hou Wenbin , Zhang Zhe , Xu Huimian 
Published: January 2020

Objectives:
Patients with high-risk stage II colon cancer (CC) are recommended to undergo adjuvant chemotherapy (ACT). However, whether such patients can benefit from ACT remains unclear. This meta-analysis aimed to investigate the clinicopathologic parameters that are important for selecting patients for ACT in high-risk stage II CC.

Methods:
We systematically retrieved articles from PubMed, the Cochrane Library, and Embase that were published up to September 13, 2018. We analyzed overall survival (OS) and disease-free survival (DFS) based on hazard ratios (HRs) and 95% confidence intervals (CIs).

Results:
A total of 23 cohort studies and 1 randomized controlled trial were included in our study. Overall analyses showed that ACT improved OS (HR=0.64, 95% CI=0.51-0.80, P<0.001) and DFS (HR=0.46, 95% CI=0.28-0.76, P=0.002) in patients with high-risk stage II CC. Subgroup analyses showed that ACT improved OS in patients with localized intestinal perforation and obstruction and pT4 lesions and improved OS and DFS in patients with <12 sampled lymph nodes. However, ACT had no significant effect on OS in patients with lymphovascular invasion, perineural invasion, or poorly differentiated histology.

Conclusions:
Our study suggests that not all high-risk factors (lymphovascular invasion, perineural invasion, poorly differentiated histology) show a benefit from ACT. Randomized controlled trials selectively targeting high-risk patients will need to be conducted in the future.
Effect of rescue fractional microablative CO2 laser on symptoms and sexual dysfunction in women affected by vulvar lichen sclerosus resistant to long-term use of topic corticosteroid: a prospective longitudinal study
Authors: Pagano Tiziana , Conforti Alessandro , Buonfantino Cira , Schettini Francesco , Vallone Roberta , Gallo Alessandra , Avino Luisa , Alviggi Carlo , De Placido Giuseppe , Sopracordevole Francesco 
Published: January 2020

Abstract

Objective:
The objective of this study was to evaluate the efficacy of rescue fractional microablative CO2 laser treatment in women with severe symptoms and sexual dysfunction related to lichen sclerosus not responsive to long-term ultra-potent topical corticosteroid treatment.

Methods:
Consecutive eligible women with lichen sclerosus referred to our unit who received fractional microablative CO2 laser treatment after failure of ultra-potent topical corticosteroid treatment were enrolled in the study. The diagnosis was confirmed by histological assessment in all cases. Patients underwent two cycles of CO2 laser every 30 to 40 days. The severity of lichen sclerosus-related symptoms, sexual function, and procedure discomfort were evaluated with a visual analog scale in the same individual at baseline, after completion of each treatment cycle. Follow-up visits were scheduled during each treatment cycle and at least 1 month after completion of the treatment. The Friedman ANOVA test was used to evaluate differences in the visual analog scale scores of each symptom during treatment.

Results:
A total of 100 patients with vulvar lichen sclerosus were screened, 40 of whom fulfilled the eligibility criteria. We found a significant improvement in vulvar itching (χ2 [2] = 31,182, P < 0.001), vulvar dryness (χ2 [2] = 40,364, P < 0.001), superficial dyspareunia (χ2 [2] = 37,488, P < 0.001), and sensitivity during intercourse (χ2 [2] = 22,143, P < 0.001) after two CO2 laser cycles. Pain related to probe movement and laser application was low and did not change significantly consequent to treatment. No systemic or local adverse effects occurred during or after laser treatment.

Conclusion:
Fractional microablative CO2 laser treatment is safe and might represent an effective rescue procedure for patients suffering from lichen sclerosus who fail to respond to long-term ultra-potent topical corticosteroid treatment. These preliminary findings require further study with adequately powered randomized controlled trials.
Acute Radiation-induced GI-ARS and H-ARS in a Canine Model of Mixed Neutron/Gamma Relative to Reference Co-60 Gamma Radiation: A Retrospective Study
Authors: MacVittie Thomas J. , Jackson William 
Published: January 2020

Abstract
Studies performed decades ago in the canine and nonhuman primate established the dose response relationships for the hematopoietic acute radiation syndrome in response to mixed neutron/gamma, x-radiation, and 60Co gamma radiation. There were no published studies that determined the dose response relationships for the gastrointestinal acute radiation syndrome in response to either noted radiation quality. This analysis of a retrospective, unpublished study provided the dose response relationships in a canine model for the acute gastrointestinal syndrome relative to the acute hematopoietic syndrome due to mixed neutron/gamma radiation. Canines were exposed to total-body, steady state, bilateral, 0.40 Gy min−1, mixed neutron/gamma (5.4:1) radiation from a TRIGA reactor. The average neutron/gamma energy (MeV) was 0.85/0.9, and exposure was reported as midline tissue dose. Medical management was not administered. The mixed neutron/gamma exposure resulted in an estimated LD50/6 of 2.83 Gy [2.76, 2.94] and LD50/30 of 2.16 Gy [2.01, 2.24] for the GI- and H-ARS respectively. The mean survival times for decedents after mixed neutron/gamma exposure approximate to the LD50/6 were 8.5 d, 10.5 d, and 4 d for 2.75 Gy, 2.80 Gy, 3.00, and 3.12 Gy exposures, respectively. The mean survival times for decedents for mixed neutron/gamma exposure approximate to the LD50/30 were 21.3 d and 15.6 d for 2.00 Gy and 2.25 Gy, respectively. Furthermore, the dose response relationships for the acute hematopoietic syndrome due to mixed neutron/gamma exposure (0.85/0.9 MeV; 5.4:1) resulted in an estimated relative biological effectiveness of 1.2 as compared with reference 60Co gamma radiation.
Reverse hybrid therapy achieves a similar eradication rate as standard hybrid therapy for Helicobacter pylori infection
Authors: Lin Te-Fu , Wu Deng-Chyang , Tsay Feng-Woei , Tsai Kuo-Wang , Tsai Tzung-Jiun , Peng Nan-Jing , Kao Sung-Shuo , Chen Wen-Chi , Chen Yan-Hua , Hsu Ping-I 
Published: January 2020

Background:
Reverse hybrid therapy is a simplified hybrid treatment for Helicobacter pylori infection. It achieves a higher eradication rate than standard triple therapy. This study aimed to compare the efficacies of reverse hybrid and hybrid therapies in the treatment of H. pylori infection.

Methods:
From September 2008 to September 2017, 490 H. pylori-infected patients who received 14 days of reverse hybrid therapy (proton pump inhibitor plus amoxicillin for 14 days and clarithromycin plus metronidazole for the initial 7 days; n = 252) or hybrid therapy (proton pump inhibitor plus amoxicillin for 14 days and clarithromycin plus metronidazole for the final 7 days; n = 238) were included in this retrospective cohort study. Helicobacter pylori status was examined 6–8 weeks after therapy.

Results:
The eradication rates of the reverse hybrid and hybrid therapies by modified intention-to-treat analysis were comparable (96.4% vs 96.6%; p = 0.899). There were no differences in the efficacy of eradication between therapies for clarithromycin-resistant strains (87.0% vs 90.0%) or metronidazole-resistant strains (97.7% vs 100.0%). In addition, there were comparable frequencies of adverse events for both treatments (18.7% vs 13.0%) and treatment adherence (94.4% vs 97.1%).

Conclusion:
Reverse hybrid therapy can achieve a similar eradication rate to hybrid therapy for H. pylori infection.
Comparison of international normalized ratio determined by point-of-care to standard laboratory testing before and after reversal of heparin in cardiac surgery
Authors: Fabbro Michael , Abalo Miguel , Fermin Lilibeth , Andrews David M. , Patel Prakash A. 
Published: January 2020

Study Objective
To compare point-of-care (POC) of international normalized ratio to laboratory-derived values before and after cardiopulmonary bypass, with the primary aim of evaluating for any change in the relationship between the tests.

Methods
This is a prospective observational study with 50 patients undergoing cardiac surgery enrolled. The International normalized ratio measured at two time points, precardiopulmonary bypass and after heparin reversal with protamine using both POC i-STAT and standard laboratory analysis for both time points. A difference of 0.2 between tests at either time point was considered clinically significant based on previous literature. A paired t test was used to test for a changing or statistically significant mean difference between tests. At both time points values were categorized into absolute difference of more than 0.2 or less than 0.2, and a Fisher's exact test was used to determine if an association existed between heparin reversal and a difference more than 0.2. Bland–Altman plots were also evaluated for agreement.

Results
A statistically and clinically significant mean difference [0.09 vs. 0.25, difference −0.163 95% confidence interval (−0.25, −0.08), P = 0.003] was seen between the laboratory and POC tests when pre and postheparin reversal samples were compared. A significantly greater number of patients had a clinically relevant difference between the tests post compared with pre (four patients vs. 18 patients, P = 0.001). Linear regression analysis of the difference compared with the means, showed significant correlation suggesting the presence of a proportional bias (pre r = 0.488, P = <0.01, post r = 0.571, P = <0.01).

Conclusion
Clinically significant differences exist between POC and laboratory testing of international normalized ratio after heparin reversal during cardiac surgery. ClinicalTrials.gov Identifier NCT03267823.
Reconstruction of Congenital Cranial Defect Using Autologous Bone Graft in Aplasia Cutis Congenita
Authors: Seo Du-Heon , Roh Si-Gyun , Koh Eun-Jeong , Shin Jin Yong , Chang Suk Choo , Lee Nae-Ho 
Published: January 2020

Abstract
Many methods have been devised to repair cranial defects. Here, we report the use of a simple technique for the repair of a congenital cranial defect associated with aplasia cutis congenita (ACC).
A newborn baby at 39 weeks of gestation was consulted with a scalp and cranial defect at the vertex measuring 3 × 1.5 cm. A 3-D CT scan of the skull confirmed the presence of a cranial defect at the sagittal suture and a normal brain structure. On the 13th day of life, the newborn was taken to an operating room. An autologous bone graft was harvested from adjacent normal parietal bone and grafted into the debrided congenital cranial defect. The soft tissue defect was then covered by rotation flaps.
The postoperative 3-D CT scan presented a well-positioned autologous bone graft. At 1 month postoperatively, the skull contour was normal and there was no palpable defect.
We report a successful surgical outcome for a congenital cranial and soft tissue defect in ACC treated using an autologous bone graft and rotation flaps. Although conservative therapy may be an alternative option, we recommend appropriate surgical reconstruction in patients at risk of potentially fatal complications.
Impact of the Prevalence of Cognitive Impairment on the Accuracy of the Montreal Cognitive Assessment
Authors: Landsheer Johannes A. 
Published: January 2020

Objectives:
The focus of this study is the classification accuracy of the Montreal Cognitive Assessment (MoCA) for the detection of cognitive impairment (CI). Classification accuracy can be low when the prevalence of CI is either high or low in a clinical sample. A more robust result can be expected when avoiding the range of test scores within which most classification errors are expected, with adequate predictive values for more clinical settings.

Methods:
The classification methods have been applied to the MoCA data of 5019 patients in the Uniform Data Set of the University of Washington’s National Alzheimer’s Coordinating Center, to which 30 Alzheimer Disease Centers (ADCs) contributed.

Results:
The ADCs show sample prevalence of CI varying from 0.22 to 0.87. Applying an optimal cutoff score of 23, the MoCA showed for only 3 of 30 ADCs both a positive predictive value (PPV) and a negative predictive value (NPV) ≥0.8, and in 18 cases, a PPV ≥0.8 and for 13 an NPV ≥0.8. Overall, the test scores between 22 and 25 have low odds of true against false decisions of 1.14 and contains 55.3% of all errors when applying the optimal dichotomous cut-point. Excluding the range 22 to 25 offers higher classification accuracies for the samples of the individual ADCs. Sixteen of 30 ADCs showed both NPV and PPV ≥0.8, 25 show a PPV ≥0.8, and 21 show an NPV ≥0.8.

Conclusion:
In comparison to a dichotomous threshold, considering the most error-prone test scores as uncertain enables a classification that offers adequate classification accuracies in a larger number of clinical settings.