bluuebunny/crossref_metadata_2025 huggingface dataset:
Astrocyte DISC1 contributes to cognitive function in a brain region-dependent manner
Authors: Shevelkin Alexey V , Terrillion Chantelle E , Hasegawa Yuto , Mychko Olga A , Jouroukhin Yan , Sawa Akira , Kamiya Atsushi , Pletnikov Mikhail V
Published: August 2020

Our understanding of the contribution of genetic risk factors to neuropsychiatric diseases is limited to abnormal neurodevelopment and neuronal dysfunction. Much less is known about the mechanisms whereby risk variants could affect the physiology of glial cells. Our prior studies have shown that a mutant (dominant-negative) form of a rare but highly penetrant psychiatric risk factor, Disrupted-In-Schizophrenia-1 (DISC1), impairs metabolic functions of astrocytes and leads to cognitive dysfunction. In order to overcome the limitations of the mutant DISC1 model and understand the putative regional properties of astrocyte DISC1, we assessed whether knockdown of Disc1 (Disc1-KD) in mature mouse astrocytes of the prefrontal cortex (PFC) or the hippocampus would produce behavioral abnormalities that could be attributed to astrocyte bioenergetics. We found that Disc1-KD in the hippocampus but not PFC impaired trace fear conditioning in adult mice. Using the innovative deep learning approach and convolutional deep neural networks (cDNNs), ResNet50 or ResNet18, and single cell-based analysis, we found that Disc1-KD decreased the spatial density of astrocytes associated with abnormal levels and distribution of the mitochondrial markers and the glutamate transporter, GLAST. Disc1-KD in astrocytes also led to decreased expression of the glutamatergic and increased expression of the GABA-ergic synaptic markers, possibly via non-apoptotic activation of caspase 3 in neurons located within the individual territories of Disc1-KD astrocytes. Our results indicate that altered expression of DISC1 in astrocytes could impair astrocyte bioenergetics, leading to abnormalities in synaptic neurotransmission and cognitive function in a region-dependent fashion.
Putting a New Spin on the Flight of Jabillo Seeds
Authors: Ribera Jesse , Desai Aman , Whitaker Dwight L
Published: August 2020

Synopsis

Our article describes the explosive seed dispersal of the Hura crepitans fruit. Through high-speed video analysis of an exploding fruit, we observe that the seeds fly with backspin as opposed to topspin, which was previously assumed. Backspin orients seeds to minimize drag during flight and consequently increases dispersal distance. The seeds’ dispersal distance is estimated by using results from the seeds of Ruellia ciliatiflora, which are similarly shaped but ∼10 times smaller than those of H. crepitans. We note that the effects of lowering drag on the dispersal distance are more pronounced at higher speeds. We also see that the effect of launch height on the dispersal distance of the seeds becomes less consequential at higher launch speeds. We conclude that the increased dispersal distance due to flying with backspin should improve fitness in colonizing new habitats or escaping disease or predation and that comparisons of the seed dispersal mechanisms across species within the Euphorbiaceae and Acanthaceae might help reveal the adaptive significance of this behavior.
The Effects of Bi-Anodal tDCS Over the Prefrontal Cortex Regions With Extracephalic Reference Placement on Insight Levels and Cardio-Respiratory and Autonomic Functions in Schizophrenia Patients and Exploratory Biomarker Analyses for Treatment Response
Authors: Chang Chuan-Chia , Kao Yu-Chen , Chao Che-Yi , Tzeng Nian-Sheng , Chang Hsin-An
Published: August 2020

Background

We previously showed the efficacy of bi-anodal transcranial direct current stimulation (tDCS) over the prefrontal cortex (PFC) regions with extracephalic reference placement in improving negative symptoms in schizophrenia. In this ancillary investigation, the effects of this intervention on insight levels, other clinical outcomes, and cardio-respiratory and autonomic functions were examined and the potential of biomarkers for treatment response was explored.

Methods

Schizophrenia patients were randomly allocated to receive 10 sessions of bi-anodal tDCS over the PFC regions with extracephalic reference placement (2 mA, 20 minutes, twice daily for 5 weeks) or sham stimulation. We examined, in 60 patients at baseline, immediately after stimulation and at follow-up visits, the insight levels, other clinical outcomes, blood pressure, respiratory rate, heart rate, and heart rate variability.

Results

Insight levels as assessed by the abbreviated version of the Scale to Assess Unawareness in Mental Disorder in schizophrenia awareness of the disease, positive and negative symptoms dimensions, and beliefs about medication compliance as assessed by Medication Adherence Rating Scale were significantly enhanced by active stimulation relative to sham. No effects were observed on cognitive insight, other clinical outcomes, or cardio-respiratory and autonomic functions. Heart rate variability indices as biomarkers were not associated with the clinical response to the intervention.

Conclusions

Our results provide evidence for bi-anodal tDCS over the PFC regions with extracephalic reference placement in heightening the levels of insight into the disease and symptoms, as well as beliefs about medication compliance in schizophrenia, without impacting other clinical outcomes and cardio-respiratory/autonomic functions.
Orally Administered Bacillus Spores Expressing an Extracellular Vesicle-Derived Tetraspanin Protect Hamsters Against Challenge Infection With Carcinogenic Human Liver Fluke
Authors: Phumrattanaprapin Wuttipong , Chaiyadet Sujittra , Brindley Paul J , Pearson Mark , Smout Michael J , Loukas Alex , Laha Thewarach
Published: August 2020

Background

The human liver fluke Opisthorchis viverrini is a food-borne trematode that causes hepatobiliary disease in humans throughout Southeast Asia. People become infected by consuming raw or undercooked fish containing metacercariae. Development of a vaccine to prevent or minimize pathology would decrease the risk of severe morbidity, including the development of bile duct cancer.

Methods

We produced an oral vaccine based on recombinant Bacillus subtilis spores expressing the large extracellular loop (LEL) of O. viverrini tetraspanin-2 (Ov-TSP-2), a protein that is abundant on the surface of O. viverrini secreted extracellular vesicles (EVs). Recombinant spores expressing Ov-TSP-2-LEL were orally administered to hamsters prior to challenge infection with O. viverrini metacercariae.

Results

Vaccinated hamsters generated serum IgG as well as bile IgG and IgA responses to Ov-TSP-2-LEL, and serum IgG from vaccinated hamsters blocked the uptake of fluke EVs by a human bile duct epithelial cell line. Vaccinated hamsters had 56% reductions in both adult flukes and fecal eggs compared to the control group.

Conclusions

These findings indicate that oral vaccination of hamsters with recombinant B. subtilis spores expressing Ov-TSP-2-LEL is efficacious at reducing infection intensity and could form the basis of a vaccine for control of carcinogenic liver fluke infection in humans.
COVID-19 Vaccines: Should We Fear ADE?
Authors: Halstead Scott B , Katzelnick Leah
Published: August 2020

Might COVID-19 vaccines sensitize humans to antibody-dependent enhanced (ADE) breakthrough infections? This is unlikely because coronavirus diseases in humans lack the clinical, epidemiological, biological, or pathological attributes of ADE disease exemplified by dengue viruses (DENV). In contrast to DENV, SARS and MERS CoVs predominantly infect respiratory epithelium, not macrophages. Severe disease centers on older persons with preexisting conditions and not infants or individuals with previous coronavirus infections. Live virus challenge of animals given SARS or MERS vaccines resulted in vaccine hypersensitivity reactions (VAH), similar to those in humans given inactivated measles or respiratory syncytial virus vaccines. Safe and effective COVID-19 vaccines must avoid VAH.
Ethical frameworks for quality improvement activities: an analysis of international practice
Authors: Naughton Corina , Meehan Elaine , Lehane Elaine , Landers Ciara , Flaherty Sarah Jane , Lane Aoife , Landers Margaret , Kilty Caroline , Saab Mohamad , Goodwin John , Walshe Nuala , Wills Teresa , Mccarthy Vera , Murphy Siobhan , Mccarthy Joan , Cummins Helen , Madden Deirdre , Hegarty Josephine
Published: August 2020

Purpose

To examine international approaches to the ethical oversight and regulation of quality improvement and clinical audit in healthcare systems

Data sources

We searched grey literature including websites of national research and ethics regulatory bodies and health departments of selected countries.

Study selection

National guidance documents were included from six countries: Ireland, England, Australia, New Zealand, the United States of America and Canada.

Data extraction

Data were extracted from 19 documents using an a priori framework developed from the published literature.

Results

We organized data under five themes: ethical frameworks; guidance on ethical review; consent, vulnerable groups and personal health data. Quality improvement activity tended to be outside the scope of the ethics frameworks in most countries. Only New Zealand had integrated national ethics standards for both research and quality improvement. Across countries, there is consensus that this activity should not be automatically exempted from ethical review but requires proportionate review or organizational oversight for minimal risk projects. In the majority of countries, there is a lack of guidance on participant consent, use of personal health information and inclusion of vulnerable groups in routine quality improvement.

Conclusion

Where countries fail to provide specific ethics frameworks for quality improvement, guidance is dispersed across several organizations which may lack legal certainty. Our review demonstrates a need for appropriate oversight and responsive infrastructure for quality improvement underpinned by ethical frameworks that build equivalence with research oversight. It outlines aspects of good practice, especially The New Zealand framework that integrates research and quality improvement ethics.
A self-adaptive population Rao algorithm for optimization of selected bio-energy systems
Authors: Rao R Venkata , Keesari Hameer Singh
Published: August 2020

This work proposes a metaphor-less and algorithm-specific parameter-less algorithm, named as self-adaptive population Rao algorithm, for solving the single-, multi-, and many-objective optimization problems. The proposed algorithm adapts the population size based on the improvement in the fitness value during the search process. The population is randomly divided into four sub-population groups. For each sub-population, a unique perturbation equation is randomly allocated. Each perturbation equation guides the solutions toward different regions of the search space. The performance of the proposed algorithm is examined using standard optimization benchmark problems having different characteristics in the single- and multi-objective optimization scenarios. The results of the application of the proposed algorithm are compared with those obtained by the latest advanced optimization algorithms. It is observed that the results obtained by the proposed method are superior. Furthermore, the proposed algorithm is used to identify optimum design parameters through multi-objective optimization of a fertilizer-assisted microalgae cultivation process and many-objective optimization of a compression ignition biodiesel engine system. From the results of the computational tests, it is observed that the performance of the self-adaptive population Rao algorithm is superior or competitive to the other advanced optimization algorithms. The performances of the considered bio-energy systems are improved by the application of the proposed optimization algorithm. The proposed optimization algorithm is more robust and may be easily extended to solve single-, multi-, and many-objective optimization problems of different science and engineering disciplines.
Capsular thinning on magnetic resonance arthrography is associated with intra-operative hip joint laxity in women
Authors: Packer Jonathan D , Foster Michael J , Riley Geoffrey M , Stewart Russell , Shibata Kotaro R , Richardson Michael L , Boutin Robert D , Safran Marc R
Published: August 2020

Hip microinstability is a recognized cause of hip pain in young patients. Intra-operative evaluation is used to confirm the diagnosis, but limited data exist associating magnetic resonance arthrography (MRA) findings with hip microinstability. To determine if a difference exists in the thickness of the anterior joint capsule and/or the width of the anterior joint recess on MRA in hip arthroscopy patients with and without an intra-operative diagnosis of hip laxity. Sixty-two hip arthroscopy patients were included in the study. Two musculoskeletal radiologists blinded to surgical results reviewed the MRAs for two previously described findings: (i) anterior joint capsule thinning; (ii) widening of the anterior joint recess distal to the zona orbicularis. Operative reports were reviewed for the diagnosis of joint laxity. In all patients with and without intra-operative laxity, there were no significant differences with either MRA measurement. However, twenty-six of 27 patients with intra-operative laxity were women compared with 11 of 35 patients without laxity (P < 0.001). In subgroup analysis of women, the intra-operative laxity group had a higher rate of capsular thinning compared with the non-laxity group (85% versus 45%; P = 0.01). A 82% of women with capsular thinning also had intra-operative laxity, compared with 40% without capsular thinning (P = 0.01). There were no differences regarding the width of the anterior joint recess. In this study, there was an association between capsular thinning and intra-operative laxity in female patients. Measuring anterior capsule thickness on a pre-operative MRA may be useful for the diagnosis of hip microinstability.
The Struggle after the Victory: Non-compliance in the Inter-American Court of Human Rights’ Jurisprudence on Indigenous Territorial Rights
Authors: Navarro Gabriela Cristina Braga
Published: August 2020

This article analyses non-compliance with decisions issued by the Inter-American Court of Human Rights on the matter of indigenous territorial rights. The central objectives of the work are (i) to quantify and to analyse the level of compliance with reparation orders issued by the Court in indigenous territorial decisions and (ii) to understand the elements that fomented and hindered compliance with the cases. Quantitative analyses of the compliance were used, analysing 11 cases decided by the Court. Additionally, a qualitative study was pursued by means of a case analysis, focusing on cases against Paraguay and Suriname. The article concludes that compliance with territorial cases is a complex matter, involving a multiplicity of interconnected elements and actors. Compliance is stimulated by clarity of the orders, existence of domestic institutions in charge of compliance, domestic legal protection of indigenous rights and when the Court exercises an active role as mediator.
Intrahepatic cholangiocarcinoma with gastric infiltration misdiagnosed as gastric submucosal tumor
Authors: Ito Shunichi , Takahashi Yutaka , Yamada Takuji , Kawai Yosuke , Ohira Kei
Published: August 2020

Intrahepatic cholangiocarcinomas (ICC) are rare primary liver tumors. In few cases, they may invade nearby organs and present as extrahepatic growths, leading to poor prognosis. We report a case of a 78-year-old man who presented with fatigue. An upper gastrointestinal endoscopy was performed to find a cause for his anemia, which showed a submucosal tumor with delle at the lesser curvature of the gastric cardia. A computed tomography revealed a low-density tumor of diameter 70 mm at the cardia. It appeared to infiltrate the liver directly. We performed lateral hepatectomy, proximal gastrectomy and lymphadenectomy. The pathological findings revealed an ICC with gastric infiltration. Although adjuvant chemotherapy was administered, 12 months postoperatively, the patient developed pain and multiple bone metastases for which palliative radiation was initiated. The guidelines for lymphadenectomy and adjuvant chemotherapy in such cases are unclear. Appropriate regional lymphadenectomy and adjuvant chemotherapy can improve the prognosis of such patients.
Surgical dilemma of the management of breast cancer in a patient with neurofibromatosis: case report and a review of the literature
Authors: Johnson Miguel , Cook Lorna , Rapisarda Fabio , Bonomi Riccardo , Betal Dibendu
Published: August 2020

Neurofibromatosis type 1 (NF-1)—also commonly known as Von Recklinghausen’s disease—is an autosomal dominant disease that represents a constellation of clinical features. There are well-established links between NF-1 and many tumors; however, the link between NF-1 and breast cancer has more recently been elucidated. While the management of breast cancer is generally well established, there are unique challenges noted in patients with NF-1. There may be delayed presentations due to difficulty in differentiating underlying neurofibroma from a sinister breast mass. Additionally, multiple skin lesions seen in NF-1 create challenges in the interpretation of mammography. Furthermore, a surgical conundrum is created, as these patients appear to have a higher risk of angiosarcoma following radiotherapy. A mastectomy may be the best option as it obviates the need for radiation therapy and ongoing surveillance. A case exemplifying these dilemmas and a review of the literature are presented.
Dwarf and Increased Branching 1 controls plant height and axillary bud outgrowth in Medicago truncatula
Authors: Zhang Xiaojia , He Liangliang , Zhao Baolin , Zhou Shaoli , Li Youhan , He Hua , Bai Quanzi , Zhao Weiyue , Guo Shiqi , Liu Yu , Chen Jianghua
Published: August 2020

Optimizing plant architecture is an efficient approach for breeders to increase crop yields, and phytohormones such as gibberellins (GAs) play an important role in controlling growth. Medicago truncatula is a model legume species, but the molecular mechanisms underlying its architecture are largely unknown. In this study, we examined a tobacco retrotransposon Tnt1-tagged mutant collection of M. truncatula and identified dwarf and increased branching 1 (dib1), which exhibited extreme dwarfism and increased numbers of lateral branches. By analysis of the flanking sequences of Tnt1 insertions in different alleles of the tagged lines, we were able to clone DIB1. Linkage analysis and reverse screening of the flanking-sequence tags identified Medtr2g102570 as the gene corresponding to the DIB1 locus in the dib1 loss-of-function mutants. Phylogenetic analysis indicated that DIB1 was the ortholog of PsGA3ox1/Le in Pisum sativum. Expression analysis using a GUS-staining reporter line showed that DIB1 was expressed in the root apex, pods, and immature seeds. Endogenous GA4 concentrations were markedly decreased whilst some of representative GA biosynthetic enzymes were up-regulated in the dib1 mutant. In addition, exogenous application of GA3 rescued the dib1 mutant phenotypes. Overall, our results suggest that DIB1 controls plant height and axillary bud outgrowth via an influence on the biosynthesis of bioactive GAs. DIB1 could therefore be a good candidate gene for breeders to optimize plant architecture for crop improvement.
What Does Decision Theory Have to Do with Wanting?
Authors: Phillips-Brown Milo
Published: August 2020

Decision theory and folk psychology purport to represent the same phenomena: our belief-like and desire- and preference-like states. They also purport to do the same work with these representations: explain and predict our actions. But they use different concepts. Can we account for the concepts of one with the other’s? If not, we’d have two competing representations and systems of prediction and explanation, a dubious dualism. Many might then reject one of the two pictures, yet neither can be jettisoned lightly. Folk psychology structures daily life, and decision theory pervades various scientific disciplines. I’m interested in accounting for two central folk psychological concepts—believing and wanting—with decision theory. Many have attempted this task for believing. (The Lockean Thesis says that such an account exists.) This paper concerns the parallel task for wanting. I give necessary and sufficient conditions, stated in terms of decision theory, for when you’re truly said to want. I propose an alternative to orthodox accounts that link wanting to preference (e.g. Stalnaker (1984), Lewis (1986)). My account explains the context-sensitivity of want ascriptions, makes sense of conflicting desires, and accommodates phenomena that motivate traditional theses on which ‘want’ has multiple senses (e.g. all-things-considered vs. pro tanto).
Study of the low-order Δν–ρ¯ relation for moderately rotating δ Scuti stars and its impact on their characterization
Authors: Rodríguez-Martín J E , García Hernández A , Suárez J C , Rodón J R
Published: August 2020

The large separation in the low-radial order regime is considered as a highly valuable observable to derive mean densities of δ Scuti stars, due to its independence with rotation. Up to now, theoretical studies of this Δν–${\bar{\rho}}$ relation have been limited to 1D non-rotating models and 2D pseudo-evolutionary models. The present work aims at completing this scenario by investigating quantitatively the impact of rotation in this relation on a large grid of 1D asteroseismic models representative of δ Scuti stars. These include rotation effects on both the stellar evolution and the interaction with pulsation. This allowed us to compute the stellar deformation, get the polar and equatorial radii, and correct the stellar mean densities. We found that the new Δν–${\bar{\rho}}$ relation for rotating models is compatible with previous works. We explained the dispersion of the points around the linear fits as caused mainly by the distribution of the stellar mass, and partially by the evolutionary stage. The new fit is found to be close to the previous theoretical studies for lower masses ($1.3\!-\!1.81\, \mathrm{M}_{\odot }$). However, the opposite holds for the observations: For the higher masses ($1.81\!-\!3\, \mathrm{M}_{\odot }$), the fit is more compatible with the empirical relation. To avoid such discrepancies, we provided new limits to the fit that encompass any possible dependence on mass. We applied these results to characterize the two well-known δ Scuti stars observed by CoRoT, HD 174936 and HD 174966, and compared the physical parameters with those of previous works. The inclusion of rotation in the modelling causes a tendency towards greater masses, radii, and luminosities, and lower density values. Comparison between Δν and Gaia’s luminosities also allowed us to constrain the inclination angles and rotational velocities of both stars. The present results pave the way to systematically constrain the angle of inclination (and thereby the actual surface rotation velocity) of δ Scuti stars.
Ionized outflows in local luminous AGN: what are the real densities and outflow rates?
Authors: Davies R , Baron D , Shimizu T , Netzer H , Burtscher L , de Zeeuw P T , Genzel R , Hicks E K S , Koss M , Lin M-Y , Lutz D , Maciejewski W , Müller-Sánchez F , Orban de Xivry G , Ricci C , Riffel R , Riffel R A , Rosario D , Schartmann M , Schnorr-Müller A , Shangguan J , Sternberg A , Sturm E , Storchi-Bergmann T , Tacconi L , Veilleux S
Published: August 2020

We report on the determination of electron densities, and their impact on the outflow masses and rates, measured in the central few hundred parsecs of 11 local luminous active galaxies. We show that the peak of the integrated line emission in the active galactic nuclei (AGN) is significantly offset from the systemic velocity as traced by the stellar absorption features, indicating that the profiles are dominated by outflow. In contrast, matched inactive galaxies are characterized by a systemic peak and weaker outflow wing. We present three independent estimates of the electron density in these AGN, discussing the merits of the different methods. The electron density derived from the [S ii] doublet is significantly lower than that found with a method developed in the last decade using auroral and transauroral lines, as well as a recently introduced method based on the ionization parameter. The reason is that, for gas photoionized by an AGN, much of the [S ii] emission arises in an extended partially ionized zone where the implicit assumption that the electron density traces the hydrogen density is invalid. We propose ways to deal with this situation and we derive the associated outflow rates for ionized gas, which are in the range 0.001–0.5 M⊙ yr−1 for our AGN sample. We compare these outflow rates to the relation between $\dot{M}_{\rm out}$ and LAGN in the literature, and argue that it may need to be modified and rescaled towards lower mass outflow rates.
Pan-cancer proteogenomic analysis reveals long and circular noncoding RNAs encoding peptides
Authors: Othoum Ghofran , Coonrod Emily , Zhao Sidi , Dang Ha X , Maher Christopher A
Published: August 2020

Recent studies show that annotated long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) encode for stable, functional peptides that contribute to human development and disease. To systematically discover lncRNAs and circRNAs encoding peptides, we performed a comprehensive integrative analysis of mass spectrometry-based proteomic and transcriptomic sequencing data from >900 patients across nine cancer types. This enabled us to identify 19,871 novel peptides derived from 8,903 lncRNAs. Further, we exploited open reading frames overlapping the backspliced region of circRNAs to identify 3,238 peptides that are uniquely derived from 2,834 circRNAs and not their corresponding linear RNAs. Collectively, our pan-cancer proteogenomic analysis will serve as a resource for evaluating the coding potential of lncRNAs and circRNAs that could aid future mechanistic studies exploring their function in cancer.
Targeting acute kidney injury in COVID-19
Authors: Kellum John A , van Till J W Olivier , Mulligan George
Published: August 2020

As of 15 August 2020, Coronavirus disease 2019 (COVID-19) has been reported in >21 million people world-wide and is responsible for more than 750,000 deaths. The occurrence of acute kidney injury (AKI) in patients hospitalized with COVID-19 has been reported to be as high as 43%. This is comparable to AKI in other forms of pneumonia requiring hospitalization, as well as in non-infectious conditions like cardiac surgery. The impact of AKI on COVID-19 outcomes is difficult to assess at present but, similar to other forms of sepsis, AKI is strongly associated with hospital mortality. Indeed, mortality is reported to be very low in COVID-19 patients without AKI. Given that AKI contributes to fluid and acid–base imbalances, compromises immune response and may impair resolution of inflammation, it seems likely that AKI contributes to mortality in these patients. The pathophysiologic mechanisms of AKI in COVID-19 are thought to be multifactorial including systemic immune and inflammatory responses induced by viral infection, systemic tissue hypoxia, reduced renal perfusion, endothelial damage and direct epithelial infection with Severe Acute Respiratory Syndrome Coronavirus 2. Mitochondria play a central role in the metabolic deregulation in the adaptive response to the systemic inflammation and are also found to be vital in response to both direct viral damage and tissue reperfusion. These stress conditions are associated with increased glycolysis and reduced fatty acid oxidation. Thus, there is a strong rationale to target AKI for therapy in COVID-19. Furthermore, many approaches that have been developed for other etiologies of AKI such as sepsis, inflammation and ischemia–reperfusion, have relevance in the treatment of COVID-19 AKI and could be rapidly pivoted to this new disease.
So-called bifocal tumors with diabetes insipidus and negative tumor markers: are they all germinoma?
Authors: Kanamori Masayuki , Takami Hirokazu , Yamaguchi Shigeru , Sasayama Takashi , Yoshimoto Koji , Tominaga Teiji , Inoue Akihiro , Ikeda Naokado , Kambe Atsushi , Kumabe Toshihiro , Matsuda Masahide , Tanaka Shota , Natsumeda Manabu , Matsuda Ken-Ichiro , Nonaka Masahiro , Kurihara Jun , Yamaoka Masayoshi , Kagawa Naoki , Shinojima Naoki , Negoto Tetsuya , Nakahara Yukiko , Arakawa Yoshiki , Hatazaki Seiji , Shimizu Hiroaki , Yoshino Atsuo , Abe Hiroshi , Akimoto Jiro , Kawanishi Yu , Suzuki Tomonari , Natsume Atsushi , Nagane Motoo , Akiyama Yukinori , Keino Dai , Fukami Tadateru , Tomita Takahiro , Kanaya Kohei , Tokuyama Tsutomu , Izumoto Shuichi , Nakada Mitsutoshi , Kuga Daisuke , Yamamoto Shohei , Anei Ryogo , Uzuka Takeo , Fukai Junya , Kijima Noriyuki , Terashima Keita , Ichimura Koichi , Nishikawa Ryo
Published: August 2020

Background

The Delphi consensus statements on the management of germ cell tumors (GCTs) failed to reach agreements on the statement that the cases with (i) pineal and neurohypophyseal bifocal lesion, (ii) with diabetes insipidus, and (iii) with negative tumor markers can be diagnosed as germinoma without histological verification. To answer this, multicenter retrospective analysis was performed.

Methods

A questionnaire on clinical findings, histological diagnosis, and details of surgical procedures was sent to 86 neurosurgical and 35 pediatrics departments in Japan.

Results

Fifty-one institutes reported 132 cases that fulfilled the 3 criteria. Tissue sampling was performed in 91 cases from pineal (n = 44), neurohypophyseal (n = 32), both (n = 6), and distant (n = 9) lesions. Histological diagnosis was established in 89 cases: pure germinoma or germinoma with syncytiotrophoblastic giant cells in 82 (92.1%) cases, germinoma and mature teratoma in 2 cases, and granulomatous inflammation in 2 cases. Histological diagnosis was not established in 2 cases. Although no tumors other than GCTs were identified, 3 (3.4%) patients had non-germinomatous GCTs (NGGCTs). None of the patients developed permanent complications after endoscopic or stereotactic biopsy. Thirty-nine patients underwent simultaneous procedure for acute hydrocephalus without permanent complications, and hydrocephalus was controlled in 94.9% of them.

Conclusion

All patients who fulfilled the 3 criteria had GCTs or granulomatous inflammation, but not other types of tumors. However, no fewer than 3.4% of the patients had NGGCTs. Considering the safety and the effects of simultaneous procedures for acute hydrocephalus, biopsy was recommended in such patients.
Precision radial velocity measurements by the forward-modeling technique in the near-infrared
Authors: Hirano Teruyuki , Kuzuhara Masayuki , Kotani Takayuki , Omiya Masashi , Kudo Tomoyuki , Harakawa Hiroki , Vievard Sébastien , Kurokawa Takashi , Nishikawa Jun , Tamura Motohide , Hodapp Klaus , Ishizuka Masato , Jacobson Shane , Konishi Mihoko , Serizawa Takuma , Ueda Akitoshi , Gaidos Eric , Sato Bun’ei
Published: August 2020

Precision radial velocity (RV) measurements in the near-infrared are a powerful tool to detect and characterize exoplanets around low-mass stars or young stars with higher magnetic activity. However, the presence of strong telluric absorption lines and emission lines in the near-infrared that significantly vary in time can prevent extraction of RV information from these spectra by classical techniques, which ignore or mask the telluric lines. We present a methodology and pipeline to derive precision RVs from near-infrared spectra using a forward-modeling technique. We applied this to spectra with a wide wavelength coverage (Y, J, and H bands, simultaneously), taken by the InfraRed Doppler (IRD) spectrograph on the Subaru 8.2 m telescope. Our pipeline extracts the instantaneous instrumental profile of the spectrograph for each spectral segment, based on a reference spectrum of the laser-frequency comb that is injected into the spectrograph simultaneously with the stellar light. These profiles are used to derive the intrinsic stellar template spectrum, which is free from instrumental broadening and telluric features, as well as model and fit individual observed spectra in the RV analysis. Implementing a series of numerical simulations using theoretical spectra that mimic IRD data, we test the pipeline and show that IRD can achieve <2 m s−1 precision for slowly rotating mid-to-late M dwarfs with a signal-to-noise ratio ≳100 per pixel at 1000 nm. Dependences of RV precision on various stellar parameters (e.g., Teff, vsin i, [Fe/H]) and the impact of telluric-line blendings on the RV accuracy are discussed through the mock spectra analyses. We also apply the RV-analysis pipeline to the observed spectra of GJ 699 and TRAPPIST-1, demonstrating that the spectrograph and the pipeline are capable of an RV accuracy of <3 m s−1 at least on a time-scale of a few months.
Inequality, Media Frames, and Public Support for Welfare
Authors: Epp Derek A , Jennings Jay T
Published: August 2020

The political preferences of those with high and low incomes are highly correlated, and both groups become less supportive of redistributive spending as economic inequality increases. This article looks for a source of these interincome group correlations by examining trends in media coverage. We find that during periods of higher inequality, media coverage is more likely to focus on the personal characteristics of welfare recipients rather than the social consequences and causes of poverty. Observational and experimental data indicate that this shift in media frames can predict declining support for welfare spending, even for those with lower incomes who might benefit from redistribution. These findings help explain the reactions of the American public to rising inequality.
Political Influence and the Renegotiation of Government Contracts
Authors: Brogaard Jonathan , Denes Matthew , Duchin Ran
Published: August 2020

This paper provides novel evidence that corporate political influence operates through renegotiations of existing government contracts. Using detailed data on contractual terms and renegotiations around sudden deaths and resignations of local politicians, the estimates show that politically connected firms initially bid low and successfully renegotiate contract amounts, deadlines, and incentives. The effects hold across different industries and contract types, enhance firm value, and persist around the exogenous increase in contract supply due to the American Recovery and Reinvestment Act. Overall, this paper establishes an unexplored link between political influence, ex post renegotiations, and ex ante bidding of government contracts.
Regulation of entheseal IL-23 expression by IL-4 and IL-13 as an explanation for arthropathy development under dupilumab therapy
Authors: Bridgewood Charlie , Sharif Kassem , Freeston Jane , Saleem Benazir , Russell Tobias , Watad Abdulla , Khan Almas , Loughenbury Peter , Rao Abhay , Wittmann Miriam , McGonagle Dennis
Published: August 2020

Objectives

Dupilumab blocks the IL-4 receptor (IL-4R) and thus signalling of the ‘Th2’ cytokines IL-4 and IL-13. It has a license to treat atopic eczema and was recently linked to emergent enthesitis and psoriasis. We investigated the cellular and functional basis for how IL-4/IL-13 regulates the IL-23–IL-17 axis in entheseal stromal, myeloid and lymphocyte cells.

Methods

Immunohistochemistry was performed on healthy enthesis samples from patients undergoing elective spinal surgery to investigate entheseal tissue IL-4R expression and cytokine expression by intracellular flow cytometry for IL-4 and IL-13. Digested human enthesis samples were stimulated with lipopolysaccharide (LPS) for IL-23 induction, either alone or with IL-4 or IL-13. Enthesis fibroblasts were stimulated with TNF and IL-17 with and without IL-4 or IL-13 to assess the effect on CCL20 secretion. Synovial fluid samples from PsA patients were also analysed by ELISA for levels of IL-4 and IL-13.

Results

The IL-4/IL-13 receptor was present in both the peri-entheseal bone and enthesis soft tissue, and entheseal-derived T cells produced basal levels of IL-4, but not IL-13. Both IL-4 and IL-13 attenuated LPS-induced entheseal IL-23 production. IL-4 also downregulated secretion of TNF/IL-17A-induced CCL20 from entheseal fibroblasts. Both IL-13 and IL-4 were also detectable in the synovial fluid of PsA patients. We also noted a seronegative inflammatory oligoarthritis whilst under dupilumab therapy.

Conclusion

Our findings suggest a previously unknown protective role for IL-4/IL-13 in entheseal induction of the IL-23–IL-17 axis. These findings point towards a novel explanation for IL-13 pathway single nucleotide polymorphisms in PsA and also a molecular explanation for why anti-IL-4/IL-13 therapy may induce musculoskeletal entheseal pathology as recently reported.
ADULT CT EXAMINATIONS IN ALGERIA: TOWARDS UPDATING NATIONAL DIAGNOSTIC REFERENCE LEVELS
Authors: Khelassi-Toutaoui Nadia , Merad Ahmed , Tsapaki Virginia , Meddad Fouzia , Sakhri-Brahimi Zakia , Guedioura Diana , Saadi Samia
Published: August 2020

A pilot study has concerned the most frequent computed tomography examinations (CT). This represents the first results based on actual survey for diagnostic reference levels (DRLs) establishment in Algeria. A total number of 2540 patients underwent this survey that has included the recording of CT parameters, computed tomography dose index (CTDIvol) and dose-length product of the head, thorax, abdomen, abdomen–pelvis (AP), lumbar spine (LS) and thorax–abdomen–pelvis (TAP) performed on standard patients. The proposed DRLs are 71 mGy/1282 mGy.cm for head, 16 mGy/555 mGy.cm for thorax, 18 mGy/671 mGy.cm for abdomen, 21 mGy/950 mGy.cm for AP, 36 mGy/957 mGy.cm for LS and 18 mGy/994 mGy.cm for TAP. The rounded 75th percentile seems to be higher in some examinations compared to the literature. Our findings confirm the need to optimise our practice. These results provide a starting point for institutional evaluation of CT radiation doses.
Entrepreneurial Systems of Syrian Refugees as Stimulators of Host Economy: Case of Ouzaii (Lebanon)
Authors: Yassine Batoul , Al-Harithy Howayda
Published: August 2020

This article investigates the impact of the Syrian displacement on the economic and urban transformation in Ouzaii, a major informal settlement in the southern suburbs of Beirut that is characterised by a complex socio-political structure. It explores the potential of “entrepreneurial systems” that emerge when Syrian refugees become part of the host community and its economy. These systems include Syrian refugees as either part of the lower labour force, business owners, or entrepreneurs. The article locates these entrepreneurial systems within the spatial networks and investigates how Syrian refugees create opportunities for themselves and the host community given the specificity of the market that is subject to legal setups and mediated by the political party of Hezbollah. It uses the construct of “mixed embeddedness” by Kloosterman et al. and the notion of “quiet encroachment” by Asef Bayat to understand how the Syrian refugees were able to infiltrate into Ouzaii’s economy and become part of the “entrepreneurial systems” that stimulate the economic cycle and revitalise the urban space.
The effect of Fennel seed powder on estradiol levels, menopausal symptoms, and sexual desire in postmenopausal women
Authors: Ghaffari Parvin , Hosseininik Maryam , Afrasiabifar Ardashir , Sadeghi Hossein , Hosseininik Amar , Tabatabaei Seyedeh Marzieh , Hosseini Nazafarin
Published: August 2020

Objectives:

The present study was designed to determine the effect of Fennel seed powder on menopausal symptoms, sexual desire, and serum estradiol levels in postmenopausal women.

Methods:

The present study was conducted on 80 eligible women (45-60 y) who were referred to the Mofatteh Gynecology Clinic in Yasuj, Iran. Participants were randomized into equal intervention and control (control) groups. The intervention and control groups received four capsules of Fennel seed powder (2 gr) and starch-containing capsules (2 gr) daily over 8 weeks, respectively. Menopausal symptoms and sexual desire of the participants were evaluated using both the menopausal Kupperman index and Hurlbert index of sexual desire. The questionnaires were completed at baseline, week 4 and week 8 of the study by the participants. The serum estradiol levels were measured at baseline and also at the end of the study. The Chi-square test, independent t test, and repeated-measures analysis of variance were used to analyze the data.

Results:

Menopausal symptoms score significantly decreased from 30.8 ± 6 to 19 ± 5.5 in the intervention group and also from 31.2 ± 6.5 to 26.4 ± 6.2 in the control group (P < 0.05). Treatment with Fennel seed did not significantly enhance the participants sexual desire (P > 0.05). The estradiol levels declined in the intervention (from 60.4 ± 43.4 to 52.6 ± 25.7) and control groups (from 55.1 ± 22.4 to 39.9 ± 26.9). However, this decrease was lower in the intervention group than in the control group. The intergroup differences were not statistically significant (P > 0.05).

Conclusions:

The results of the present study indicated that daily use of Fennel seed significantly improved menopausal symptoms in postmenopausal women over 8 weeks, though its effect on estradiol levels and sexual desire was not significant. Further studies with a larger sample size and longer duration are needed to verify these findings.
Prevalence and risk factors of morphometric vertebral fracture in apparently healthy osteopenic postmenopausal Thai women
Authors: Wattanachanya Lalita , Pongchaiyakul Chatlert
Published: August 2020

Objective:

To determine the prevalence of and risk factors for morphometric vertebral fracture (VF) in apparently healthy postmenopausal women with osteopenia.

Methods:

This cross-sectional study included 490 postmenopausal Thai women with osteopenia. All had no known history of low-trauma fracture, no underlying diseases, or history of taking medications that affect bone metabolism. Morphometric VFs were assessed by thoracolumbar spine x-rays, using the Genant semiquantitative method, and interpreted independently by three radiologists.

Results:

Mean age of participants was 59.9 ± 7.8 years and mean body mass index was 24.3 ± 3.4 kg/m2. Morphometric VFs were present in 29% (142/490) of women (grade 1: 62.0%, grade 2: 19.3%, and grade 3: 18.7%). Of these, 4.9% were aged 50 years or less, 40.1% were aged 50-59 years, 38% were aged 60-69 years, and 16.9% were aged over 70 years. Age and the Fracture Risk Assessment Tool (FRAX) scores for hip and major osteoporotic fracture, with or without bone mineral density, were positively correlated with VF. No differences in fracture prevalence among those with various degrees of osteopenia. Applying the current guidelines for VF screening results in discoveries of less than a half of osteopenic women who have had morphometric VF.

Conclusions:

Almost one third of apparently healthy postmenopausal women with osteopenia had morphometric VF. Advancing age and greater FRAX scores were associated with higher prevalence of morphometric VF.
MEMSID: Results From a Phase 2 Pilot Study on Memantine Treatment for Sickle Cell Disease
Authors: Hegemann Inga , Sasselli Clelia , Valeri Fabio , Makhro Asya , Müller Rouven , Bogdanova Anna , Manz Markus G. , Gassmann Max , Goede Jeroen S.
Published: August 2020

Supplemental Digital Content is available in the text
Systemic AL Amyloidosis: Current Approaches to Diagnosis and Management
Authors: Fotiou Despina , Dimopoulos Meletios Athanasios , Kastritis Efstathios
Published: August 2020

AL amyloidosis is characterized by a low‐level expansion of an indolent, small plasma cell clone that produces amyloidogenic light chains. Amyloid aggregates or preceding intermediaries cause direct cell damage through their proteotoxicity, and amyloid deposits distort tissue architecture, and, eventually, lead to organ impairment. It is a rare, underdiagnosed disease with a diverse clinical presentation depending on the organ tropism of the amyloid fibrils; cardiac and renal involvement is most common, but any organ can be affected, excluding the central nervous system. A high level of awareness and a systematic approach using newly emerging screening biomarkers is required to achieve early diagnosis. Management should be multidisciplinary as supportive management tailored to management of organ dysfunction is paramount to survival and minimization of treatment‐associated toxicity. The initial therapeutic aim is to rapidly eliminate the clonal plasma cell that produces the circulating amyloid precursor and achieve a complete hematologic response, and if possible with undetectable minimal residual disease as assessed by next‐generation methods (flow and sequencing), with minimal toxicity. Treatment is tailored to the initial risk assessment of the patients. Treatments are based on regimens adapted from the expanding options that are available for multiple myeloma patients and hematological response rates have improved. Organ response rates are strongly associated with deeper hematologic response but usually lag behind hematological response and are also dependent on the initial organ function reserve. Agents directed against the amyloid deposits have been explored to aid amyloid clearance and improve organ function, but data are still negative.
Femtosecond laser–assisted cataract surgery compared with phacoemulsification cataract surgery: randomized noninferiority trial with 1-year outcomes
Authors: Day Alexander C. , Burr Jennifer M. , Bennett Kate , Doré Caroline J. , Bunce Catey , Hunter Rachael , Nanavaty Mayank A. , Balaggan Kamaljit S. , Wilkins Mark R. ,   on behalf of the FACT trial group
Published: August 2020

Purpose:

To report the 1-year outcomes of a randomized trial comparing femtosecond laser–assisted cataract surgery (FLACS) and phacoemulsification cataract surgery (PCS).

Setting:

Moorfields Eye Hospital, New Cross Hospital, and Sussex Eye Hospital, United Kingdom.

Design:

Multicenter, randomized controlled noninferiority trial.

Methods:

Patients undergoing cataract surgery were randomized to FLACS or PCS. Postoperative assessments were masked. Outcomes included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), complications, corneal endothelial cell count, and patient-reported outcomes measures.

Results:

The study enrolled 785 participants. A total of 311 of 392 (79%) participants were allocated to FLACS and 292 of 393 (74%) participants were allocated to PCS attended follow-up at 1 year. Mean UDVA was 0.14 (SD = 0.22) for FLACS and 0.17 (0.25) for PCS with difference of −0.03 logarithm of the minimum angle of resolution (logMAR) (95%, −0.06 to 0.01, P = .17). Mean CDVA was 0.003 (0.18) for FLACS and 0.03 (0.23) for PCS with difference of −0.03 logMAR (95% CI, −0.06 to 0.01, P = .11); 75% of both FLACS (230/307) and PCS (218/290) cases were within ±0.5 diopters (D) refractive target, and 292 (95%) of 307 eyes of FLACS and 279 (96%) of 290 eyes of PCS groups were within ±1.0 D. There were no significant differences between arms for all other outcomes with the exception of binocular CDVA mean difference −0.02 (−0.05 to 0.002) logMAR (P = .036) favoring FLACS. Mean cost difference was £167.62 per patient greater for FLACS (95% iterations between −£14.12 and £341.67).

Conclusions:

PCS is not inferior to FLACS regarding vision, patient-reported health, and safety outcomes after 1-year follow-up. A difference was found for binocular CDVA, which, although statistically significant, was not clinically important. FLACS was not cost-effective.