bluuebunny/crossref_metadata_2025 huggingface dataset:
Georg von der Gabelentz
Authors: Elffers Els
Published: January 2020

Hans Georg Conon von der Gabelentz (b. 1840–d. 1893) was a versatile and productive German linguist. He did not belong to the group of historical-comparative linguistics that dominated the field during the 19th century. Instead, from the very beginning of his linguistic career, his descriptive focus was on non-Indo-European languages, which could not be approached by the historical-comparative method. In this respect he followed the example of Wilhelm von Humboldt (b. 1767–d. 1835). Gabelentz developed a strictly synchronic method to describe languages “from within,” also paying attention to language-related cultural characteristics of speakers, in line with the approach of Völkerpsychologie (ethnopsychology) as developed by Heymann Steinthal (b. 1823–d. 1899). Gabelentz was born in Poschwitz (near Altenburg) at the estate of his old aristocratic family. His father, Hans Conon von der Gabelentz (b. 1807–d. 1874), was a renowned government minister, but also a passionate language scholar. His library contained a multitude of documents about languages from all over the world. In this environment, Georg’s interest in “exotic” languages developed very early. Like his father, he studied law and administration, but Georg also studied linguistics in Jena. He entered civil service, but he simultaneously continued his linguistic studies in Leipzig. In 1876 he received a PhD from Dresden for a translation of a philosophical Chinese text. In 1878 Gabelentz acquired a professorship of East Asian languages at the University of Leipzig and resigned his civil service post. His first magnum opus was published in 1881: Chinesische Grammatik (Chinese grammar), which is still regarded as a standard work today. Gabelentz became a professor of sinology and general linguistics at the University of Berlin in 1889. In 1891 his second magnum opus, Die Sprachwissenschaft (The science of language) was published, providing a comprehensive overview of the content and methods of general linguistics, which was a relatively new academic discipline at the time. Alongside these two important books, Gabelentz mainly published numerous articles, some of which became relatively well known, such as his two articles about comparative syntax, published in 1869 and 1875, and his programmatic article about language typology, which appeared posthumously in 1894. Unlike his orientalist work, Gabelentz’s general linguistic work fell into oblivion rather soon after his early death. Its neglect was mainly due to his Humboldtian approach, which included the “evaluation” of languages (Sprachwürderung), a project that was rapidly declining from the turn of the century onward. Gabelentz’s position in earlier linguistic historiography used to be a modest one. However, during the last few decades the importance and surprisingly innovative character of Gabelentz’s work has been more and more recognized. Nowadays, there is an increasing interest in Gabelentz, which has induced a growing number of publications about his work.
Forceful Intervention for Protection of Human Rights in Africa
Authors: Kuwali Dan
Published: January 2020

Article 2(4) of the Charter of the United Nations (UN) obliges States to refrain from the threat or use of force against the territorial integrity or political independence of any State, or in any other manner inconsistent with the purposes of the UN. The formulation of Article 2(4) of the UN Charter gives room to argue that military intervention for purposes of protecting human rights is not covered in the prohibition if it does not threaten the territorial integrity or political independence of a State, especially since promotion of human rights is one of the purposes of the UN under Article 1(3) of the Charter. However, the majority of commentators argue that the Charter prohibits any unilateral use of force and the travaux préparatoires leave no doubt that the terms ‘territorial integrity’ and ‘political independence’ were included not to qualify an absolute prohibition of the use of force but rather as intensifiers to emphasize the protection of States from acts of aggression. The purpose of inserting the phrase ‘or in any other manner inconsistent with’ in Article 2(4) was not to open the door to implicit exceptions from the rule but to make the prohibition watertight. Thus, Article 2(4) constitutes general prohibition of use of force in international law, subject only to the two exceptions outlined in the Charter: self-defense under Article 51 and chapter 7 enforcement action by the Security Council. Thus, except in self-defense, the use of force is the preserve of the Security Council. On this basis, any use of force to protect human rights in another State is subject to authorization of the Security Council.
Balance of Power
Authors: Underwood Erik , Paul T.V.
Published: January 2020

Balance of power is one of the most discussed and contested theoretical and policy concepts in international relations. It is in fact the bedrock of realism of all varieties, in particular classical and structural, and it is the most significant variable in systemic theories of international stability. The idea of balancing power has been popular since 17th-century Europe, although it was around in some fashion in ancient Greek, Indian, and Chinese statecraft. Beginning with the Treaty of Westphalia in 1648, it took a prominent role in legal and political thought, with legal theorists and policymakers seeing the concept as central to considerations of international law and strategy. The fact that balance of power has found enduring relevance to scholars and policymakers throughout the ages suggests that the theory is one whose value should be carefully considered. The theory holds that when power is balanced among competing states, peace is obtained, but disequilibrium in power means a strong state can attack a weaker state and rob the latter of its security and independence. The goal of balance of power is to prevent any power from becoming too strong, first by deterring aggression, but if that fails, by ensuring that the aggressor does not significantly alter the balance of power. For realists, balance of power is born in the crucible of international anarchy. It is either a tool that states manually use to keep the power and aggressive behavior of other states in check, or a state of affairs generated by power competition among states. According to realism, states fear other states, and international anarchy creates a self-help system where one’s own strength and ability to find allies with similar interests are the only means to achieve security.
The Mandate Divide in Policy Representation: The Substantive Representation of Agricultural Interests in the Hungarian Parliament
Authors: Papp Zsófia
Published: January 2020

Policy 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

We 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

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

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.

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.
Successful treatment with brentuximab vedotin for relapsed and refractory adult T cell leukemia
Authors: Oka Satoko , Ono Kazuo , Nohgawa Masaharu
Published: January 2020

Although treatments for adult T-cell leukemia/lymphoma in the past two decades have advanced, the current standard treatment for aggressive adult T-cell leukemia/lymphoma, particularly in patients who are not eligible for stem cell transplantation, remains inadequate; therefore, treatments to prolong the duration of remission and provide relevant benefits in terms of survival and quality of life are needed. Adult T-cell leukemia/lymphoma tumor cells express CD30 in some cases and the increased expression of CD30 is considered to be one of the causes of constitutive NF-κB activation in adult T-cell leukemia/lymphoma cells. Brentuximab vedotin represents a major breakthrough in the treatment of CD30-positive lymphomas. Elderly patients treated with chemotherapy generally have higher rates of grade 3 or 4 adverse events; however a retrospective analysis demonstrated the safety and efficacy of brentuximab vedotin in adults ≥60 years with relapsed and refractory CD30-positive lymphomas. We herein report the clinical effects of brentuximab vedotin and the significance of CD30 expression in an elderly refractory/relapse adult T-cell leukemia/lymphoma patient. CD30 expression is associated with disease progression in adult T-cell leukemia/lymphoma patients and brentuximab vedotin may be a new and promising treatment option for these patients. Further investigations on the use of brentuximab vedotin for adult T-cell leukemia/lymphoma are needed.
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

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

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.
SMARCA4-deficient Sinonasal Carcinoma
Authors: Agaimy Abbas , Jain Deepali , Uddin Nasir , Rooper Lisa M. , Bishop Justin A.
Published: January 2020

The molecular pathogenesis of poorly differentiated sinonasal carcinoma received significant attention in recent years. As a consequence, several unclassified carcinomas in the morphologic spectrum of sinonasal undifferentiated carcinoma have been reclassified as distinctive genetically defined variants or entities. Among the latter are NUT-rearranged carcinoma and SMARCB1-deficient carcinomas. In this study, we further characterize a rare variant of sinonasal undifferentiated carcinoma–like tumors characterized by inactivation of the SWItch/Sucrose Nonfermentable chromatin remodeler SMARCA4 (BRG1) detectable by immunohistochemistry. Patients were 7 males and 3 females aged 20 to 67 years (median, 44). Tumors originated in the nasal cavity (6), nose and sinuses (2), or at unspecified site (2). Six tumors were initially misdiagnosed as small cell neuroendocrine carcinoma (SCNEC) or large cell neuroendocrine carcinoma (LCNEC). Histologically, the tumors were composed of small basaloid (3 cases) or large epithelioid (7) cells disposed into nests and solid sheets with extensive areas of necrosis. No glands or other differentiating features were noted. Abortive rosettes were seen in 1 case. Immunohistochemistry showed consistent expression of pankeratin and absence of CK5, p63, p16, and NUT in all tumors tested. Other tested markers were variably positive: CK7 (2/6), synaptophysin (9/10; mostly focal and weak), chromogranin-A (4/10; focal), and CD56 (3/5; focal). All tumors showed total loss of SMARCA4 and retained expression of SMARCB1/INI1. Co-loss of SMARCA2 was seen in 1 of 8 cases. Limited data were available on treatment and follow-up. Two patients received surgery (1 also radiotherapy) and 3 received chemotherapy. Metastases (cervical nodes, liver, bone, and lung/mediastinal) were detected in 3 patients; 2 were alive under palliative chemotherapy at 8 and 9 months while 1 died of progressive lung disease at 7 months. Three patients (1 with brain invasion) died soon after diagnosis (1 to 3 mo). In total, 4 of 6 patients (66%) with follow-up died of disease (median, 3 mo). This series characterizes SMARCA4-deficient sinonasal carcinoma as a genetically distinct aggressive entity in the spectrum of undifferentiated sinonasal carcinomas. These variants add to the spectrum of SWItch/Sucrose Nonfermentable–deficient sinonasal carcinomas, at the same time expanding the topographic distribution of SMARCA4-related malignancies.
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

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.
What is the role of the thioredoxin antioxidant complex in relation to HAM/TSP?
Authors: Youssefi Masoud , Ghazvini Kiarash , Casseb Jorge , keikha Masoud
Published: January 2020

We have little information about the definite role of the thioredoxin antioxidant complex system during viral infection, particularly during human T-cell lymphotropic virus type 1 (HTLV-1) infection and the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) state. Therefore, we conducted comprehensive next-generation sequencing (NGS) analysis to determine Trx system expression changes in three categories of subjects: sero-negative HTLV-1 individuals, asymptomatic HTLV-1 people and HAM/TSP patients. We found that Trx capacity is reduced in the HAM/TSP state compared to healthy individuals, which indicates increasing inflammation and reduction of apoptosis, which might contribute to the progression of inflammation in the spinal cord, which in turn may develop into the HAM/TSP state.
Alteromonas portus sp. nov., an alginate lyase-excreting marine bacterium
Authors: Huang Huiqin , Mo Kunlian , Li Shuang , Dongmei Sun , Zhu Jun , Zou Xiaoxiao , Hu Yonghua , Bao Shixiang
Published: January 2020

An alginate lyase-excreting bacterium, designated strain HB161718T, was isolated from coastal sand collected from Tanmen Port in Hainan, PR China. Cells were Gram-stain-negative rods and motile with a single polar flagellum. Its major isoprenoid quinone was ubiquinone 8 (Q-8), and its cellular fatty acid profile mainly consisted of C16 : 1 ω7c and/or C16 : 1 ω6c, C18 : 1 ω6c and/or C18 : 1 ω7c, C16 : 0, C17 : 0 10-methyl and C16 : 0 N alcohol. The G+C content of the genomic DNA was 44.1 mol%. 16S rRNA gene sequence analysis suggested that strain HB161718T belonged to the genus

Alteromonas

, sharing 99.5, 99.4, 99.2, 98.9 and 98.5 % sequence similarities to its closest relatives,

Alteromonas macleodii

JCM 20772T,

Alteromonas gracilis

9a2T,

Alteromonas australica

H17T,

Alteromonas marina

SW-47T and

Alteromonas mediterranea

DET, respectively. The low values of DNA–DNA hybridization and average
nucleotide identity showed that it formed a distinct genomic species. The combined phenotypic and molecular features supported the conclusion that strain HB161718T represents a novel species of the genus

Alteromonas

, for which the name Alteromonas portus sp. nov. is proposed. The type strain is HB161718T (=CGMCC 1.13585T=JCM 32687T).
Classification of ‘Streptomyces hyalinum’ Hamada and Yokoyama as Embleya hyalina sp. nov., the second species in the genus Embleya, and emendation of the genus Embleya
Authors: Komaki Hisayuki , Hosoyama Akira , Kimura Akane , Ichikawa Natsuko , Igarashi Yasuhiro , Tamura Tomohiko
Published: January 2020

The 16S rRNA gene sequence of ‘Streptomyces hyalinum’ NBRC 13850T shows 99.7 % similarity to that of

Embleya scabrispora

DSM 41855T; however, it shows <96.1 % similarity to any other type strains, including

Streptomyces

spp. Phylogenetic analysis based on 16S rRNA gene sequences clearly suggests that ‘S. hyalinum’ belongs to the genus

Embleya

rather than to

Streptomyces

. The strain possesses ll-diaminopimelic acid in the cell wall. The major menaquinone observed is MK-9(H6), and MK-9(H4) and MK-9(H8) are minor components. The major polar lipids are diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. In this study, the whole genome of strain NBRC 13850T was sequenced, and digital DNA–DNA hybridisation between ‘S. hyalinum’ NBRC 13850T and

E. scabrispora

DSM 41855T demonstrated 31.2 % of relatedness value between the two genomes. Morphological, chemotaxonomic, biochemical and physiological data also revealed that ‘S. hyalinum’ can be easily differentiated from

E. scabrispora

(the only the valid species of the genus

Embleya

) and that it merits separate species status. This phenotypic and genetic evidence reveals that ‘S. hyalinum’ represents a novel species of the genus

Embleya

; the name Embleya hyalina sp. nov. is proposed for this species. The type strain is NBRC 13850T (=ATCC 29817T=MB 891-A1T). We also emended the description of the genus

Embleya

considering the feature of E. hyalina.
The application of the CRISPR–Cas9 system in Pseudomonas syringae pv. actinidiae
Authors: Ho Joycelyn , Zhao Min , Wojcik Samuel , Taiaroa George , Butler Margi , Poulter Russell
Published: January 2020

Introduction.Pseudomonas syringaepv. actinidiae (Psa) has emerged as a major bacterial pathogen of kiwifruit cultivation throughout the world.

Aim.We aim to introduce a CRISPR–Cas9 system, a commonly used genome editing tool, into Psa. The protocols may also be useful in otherPseudomonasspecies.

Methodology.Using standard molecular biology techniques, we modified plasmid pCas9, which carries the CRISPR–Cas9 sequences fromStreptococcus pyogenes,for use in Psa. The final plasmid, pJH1, was produced in a series of steps and is maintained with selection in bothEscherichia coliand Psa.

Results.We have constructed plasmids carrying a CRISPR–Cas9 system based on that ofS. pyogenes, which can be maintained, under selection, in Psa. We have shown that the gene targeting capacity of the CRISPR–Cas9 system is active and that the Cas9 protein is able to cleave the targeted sites. The Cas9 was directed to several different sites in theP. syringaegenome. Using Cas9 we have generated Psa transformants that no longer carry the native plasmid present in Psa, and other transformants that lack the integrative, conjugative element, Pac_ICE1. Targeting of a specific gene, a chromosomal non-ribosomal peptide synthetase, led to gene knockouts with the transformants having deletions encompassing the target site.

Conclusion.We have constructed shuttle plasmids carrying a CRISPR–Cas9 system that are maintained in bothE. coliandP. syringaepv. actinidiae. We have used this gene editing system to eliminate features of the accessory genome (plasmids or ICEs) from Psa and to target a single chromosomal gene.
Differences in Plasma Metabolites Related to Alzheimer’s Disease, APOE-ε4 status and Ethnicity
Authors: Vardarajan Badri , Kalia Vrinda , Manly Jennifer , Brickman Adam , Reyes-Dumeyer Dolly , Lantigua Rafael , Ionita-Laza Iuliana , Jones Dean P. , Miller Gary W. , Mayeux Richard
Published: January 2020

INTRODUCTION

We investigated metabolites in plasma to capture systemic biochemical changes associated with Alzheimer’s disease (AD).

METHODS

Metabolites in plasma were measured in 59 AD cases and 60 healthy participants of African American (AA), Caribbean Hispanic (CH) and non-Hispanic white (NHW) ancestry using untargeted liquid-chromatography based ultra-high resolution mass spectrometry. Metabolite differences between AD and healthy, ethnic groups and APOEε4 status were analyzed. Untargeted network analysis identified pathways enriched in AD-associated metabolites.

RESULTS

5,929 annotated metabolites were measured. PLS-DA analysis inferred that AD clustered separately from healthy controls (AUC=0.9816); discriminating pathways included glycerophospholipid, sphingolipid and non-essential amino acid (alanine, aspartate, glutamate) metabolism. Metabolic features in AA clustered differently from CH and NHW (AUC=0.9275), and differed betweenAPOEε4-carriers and non-carriers (AUC=0.9972).

DISCUSSION

Metabolites, specifically lipids, were associated with AD,APOEε4 and ethnic group. Metabolite profiling could identify perturbed AD pathways, but genetic and ancestral background need to be considered.
Scaling of information in large neural populations reveals signatures of information-limiting correlations
Authors: Kafashan MohammadMehdi , Jaffe Anna , Chettih Selmaan N. , Nogueira Ramon , Arandia-Romero Iñigo , Harvey Christopher D. , Moreno-Bote Rubén , Drugowitsch Jan
Published: January 2020

How is information distributed across large neuronal populations within a given brain area? One possibility is that information is distributed roughly evenly across neurons, so that total information scales linearly with the number of recorded neurons. Alternatively, the neural code might be highly redundant, meaning that total information saturates. Here we investigated how information about the direction of a moving visual stimulus is distributed across hundreds of simultaneously recorded neurons in mouse primary visual cortex (V1). We found that information scales sublinearly, due to the presence of correlated noise in these populations. Using recent theoretical advances, we compartmentalized noise correlations into information-limiting and nonlimiting components, and then extrapolated to predict how information grows when neural populations are even larger. We predict that tens of thousands of neurons are required to encode 95% of the information about visual stimulus direction, a number much smaller than the number of neurons in V1. Overall, these findings suggest that the brain uses a widely distributed, but nonetheless redundant code that supports recovering most information from smaller subpopulations.
Engram reactivation during memory retrieval predicts long-term memory performance in aged mice
Authors: Karaca Kubra Gulmez , Brito David V.C. , Kupke Janina , Zeuch Benjamin , Oliveira Ana M.M.
Published: January 2020

Age-related cognitive decline preferentially targets long-lasting episodic memories that require intact hippocampal function. Memory traces (or engrams) are believed to be encoded within the neurons activated during learning (neuronal ensembles), and recalled by reactivation of the same population. However, whether engram reactivation dictates memory performance late in life is not known. Here, we labelled neuronal ensembles formed during object location recognition learning in the dentate gyrus, and analyzed the reactivation of this population by long-term memory recall in young adult, cognitively impaired-and unimpaired-aged mice. We found that reactivation of memory-encoding neuronal ensembles at long-term memory recall was disrupted in impaired but not unimpaired-aged mice. Furthermore, we showed that the memory performance in the aged population correlated with the degree of engram reactivation at long-term memory recall. Overall, our data implicates recall-induced engram reactivation as a prediction factor of memory performance in aging. Moreover, our findings suggest impairments in neuronal ensemble stabilization and/or reactivation as an underlying mechanism in age-dependent cognitive decline.
Efficient Calculation of the Genomic Relationship Matrix
Authors: Schlather Martin
Published: January 2020

Since the calculation of a genomic relationship matrix needs a large number of arithmetic operations, fast implementations are of interest. Our fastest algorithm is more accurate and 25× faster than a AVX double precision floating-point implementation.
The evolution of human SIRT1 for multi-specificity is enabled by active-site adaptation
Authors: Hendler Adi , Akiva Eyal , Sandhu Mahakaran , Goldberg Dana , Arbely Eyal , Jackson Colin J. , Aharoni Amir
Published: January 2020

Many enzymes that catalyze protein post-translational modifications (PTM) can specifically modify multiple target proteins. However, little is known regarding the molecular basis and evolution of multi-specificity in these enzymes. Here, we used bioinformatics and experimental approaches to investigate the molecular basis and evolution of multi-specificity in the sirtuin-1 (SIRT1) deacetylase. Guided by bioinformatics analysis of SIRT1 orthologues and substrates, we identified and examined key mutations that have occurred during the evolution of human SIRT1. We found that while these mutants maintain high activity toward conserved histone substrates they exhibit a dramatic loss of activity toward acetylated p53 protein that appeared only in Metazoa. These results demonstrate that active site substitutions in SIRT1 are essential to enable the inclusion of p53 substrate. Our results are consistent with a model in which promiscuous ancestral activity can provide an evolutionary starting point from which multispecificity toward a number of cellular substrates can develop.
Periprotein membrane lipidomics and the role of lipids in transporter function in yeast
Authors: van ‘t Klooster Joury S , Cheng Tan-Yun , Sikkema Hendrik R , Jeucken Aike , Moody D. Branch , Poolman Bert
Published: January 2020

The yeast plasma membrane is segregated into domains: the Micro-Compartment-of-Can1 (MCC) and Pma1 (MCP) have a different protein composition, but their lipid composition is largely unknown. We extracted proteins residing in these microdomains via stoichiometric capture of lipids and proteins in styrene-maleic-acid-lipid-particles (SMALPs). We purified SMALPs by affinity chromatography and quantitatively analyzed the lipids by mass spectrometry and their role in transporter function. We found that phospholipid and sterol concentrations are similar for MCC and MCP, but sphingolipids are enriched in MCP. Ergosterol is depleted from the periprotein lipidome, whereas phosphatidylserine is enriched relative to the bulk of the plasma membrane. Phosphatidylserine, non-bilayer lipids and ergosterol are essential for activity of Lyp1; the transporter also requires a balance of saturated/unsaturated fatty acids. We propose that proteins can function in the yeast plasma membrane by the disordered state of surrounded lipids and diffuse slowly in domains of high lipid order.

Impact statement

Membrane protein-specific lipidomics provides information on the organization of the yeast plasma membrane and the functioning of solute transporters
Cortical source imaging of resting-state MEG with a high resolution atlas: An evaluation of methods
Authors: Tait Luke , Özkan Ayşegül , Szul Maciej J , Zhang Jiaxiang
Published: January 2020

Non-invasive functional neuroimaging of the human brain at rest can give crucial insight into the mechanisms that underpin healthy cognition and neurological disorders. Magnetoencephalography (MEG) measures extracranial magnetic fields originating from neuronal activity with very high temporal resolution, but requires source reconstruction to make neuroanatomical inferences from these signals. Many source reconstruction algorithms for task-based MEG data are available. However, no consensus yet exists on the optimum algorithm for resting-state data.

Here, we evaluated the performance of six commonly-used source reconstruction algorithms based on minimum-norm and beamforming estimates. In the context of human resting-state MEG, we compared the algorithms using quantitative metrics, including resolution properties of inverse solutions and explained variance in sensor-level data. Next, we proposed a data-driven approach to reduce the atlas from the Human Connectome Project’s multimodal parcellation of the human cortex. This procedure produced a reduced cortical atlas with 250 regions, optimized to match the spatial resolution and the rank of MEG data from the current generation of MEG scanners.

For both voxel-wise and parcellated source reconstructions, we showed that the eLORETA inverse algorithm had zero localization error, high spatial resolution, and superior performance in predicting sensor-level activity. Our comprehensive comparisons and recommandations can serve as a guide for choosing appropriate methodologies in future studies of resting-state MEG.
The fate of standing variation and new mutation under climate change
Authors: Lu Cheng-Yueh , Lee Cheng-Ruei
Published: January 2020

Many species face existence threat under anthropogenic climate change, and standing genetic variation was proposed as a way for sessile species to adapt to novel environments. However, it is still unknown whether standing genetic variants, being adaptive to current environmental variability, are sufficient to guarantee future survival. Here we investigate the relative importance of standing variation versus new mutations from the past to infer their future fate in nature. In the wild banana speciesMusa itineranswhere the Taiwanese populations were ancient immigrants from the Chinese populations, new mutations exert larger effect size in precipitation-related variables, where Taiwan contains extreme environments beyond the ancestral climatic range, and new alleles have stronger association with novel environments. For temperature-related variables where Taiwan is within the ancestral climatic range, standing variants are more important than new mutations. The effect sizes of adaptive variants therefore differ under distinct environmental pressures, supporting theoretical predictions that natural selection favors new mutations with larger effect sizes in novel environments where the population is far from the adaptive peak. Despite their importance, large-effect variants also have higher mismatch and may be more vulnerable to future environmental perturbation, leaving minor-effect variants the main source of adaptive response to rapid anthropogenic climate change. Our work provides a support in natural environment to the previous conclusions from theoretical modeling and microbial experiments in well-controlled lab conditions.