bluuebunny/crossref_metadata_2025 huggingface dataset:
Updated long-term outcomes of salvage surgery after stereotactic body radiotherapy for early-stage non-small-cell lung cancer
Authors: Yamanashi Keiji , Hamaji Masatsugu , Matsuo Yukinori , Kishi Noriko , Chen-Yoshikawa Toyofumi Fengshi , Mizowaki Takashi , Date Hiroshi
Published: August 2020

There is dearth of data regarding the long-term survival outcomes of salvage surgery after stereotactic body radiotherapy for early-stage non-small-cell lung cancer, as previous studies have included a short follow-up period. There is also scarce information on the management of re-relapse in previous studies. This study examined the long-term survival outcomes of patients who underwent salvage surgery for isolated local relapse (LR). We reviewed consecutive patients who underwent salvage surgery for isolated LR after stereotactic body radiotherapy for early-stage non-small-cell lung cancer between 1999 and 2015. All patients were followed up until death or at least 5 years from salvage surgery. Twelve patients were included for analysis. The median follow-up from isolated LR was 62.4 (range: 14.3–152.1) months. The 5-year overall survival rate was 58.3%, updated from 79.5% in our previous report. During the interim, new re-relapses did not occur, whereas there were 5 additional deaths. The median survival after re-relapse was 32.6 months. Our follow-up report confirmed that our patient selection for salvage surgery appeared to be appropriate and that long-term follow-up is required to assess the outcomes of patients undergoing salvage surgery. Long-term follow-up would provide detailed information on late re-relapses, treatment and outcomes of re-relapses and mortality from any causes.
Risperidone and 5-HT2A Receptor Antagonists Attenuate and Reverse Cocaine-Induced Hyperthermia in Rats
Authors: Okada Tsuyoshi , Shioda Katsutoshi , Makiguchi Akiko , Suda Shiro
Published: August 2020

Background

Cocaine (benzoylmethylecgonine) is one of the most widely used illegal psychostimulant drugs worldwide, and mortality from acute intoxication is increasing. Suppressing hyperthermia is effective in reducing cocaine-related mortality, but a definitive therapy has not yet been found. In this study, we assessed the ability of risperidone to attenuate acute cocaine-induced hyperthermia and delineated the mechanism of its action.

Methods

Rats were injected i.p. with saline, risperidone, ketanserin, ritanserin, haloperidol, or SCH 23 390 before and after injection of cocaine (30 mg/kg) or with WAY-00 635, SB 206 553, or sulpiride before cocaine injection; thereafter, the rectal temperature was measured every 30 minutes for up to 4 hours. In vivo microdialysis was used to reveal the effect of risperidone on cocaine-induced elevation of dopamine (DA), serotonin (5-HT), and noradrenaline concentrations in the anterior hypothalamus. For post-administration experiments, saline or risperidone (0.5 mg/kg) were injected into rats, and cocaine (30 mg/kg) was injected 15 minutes later. For every 30 minutes thereafter, DA, 5-HT, and noradrenaline levels were measured for up to 240 minutes after cocaine administration.

Results

Risperidone, 5-HT2A receptor antagonists, and D1 receptor antagonistic drugs prevented and reversed cocaine-induced hyperthermia. In contrast, receptor antagonists for 5-HT1A, 5-HT2B/2C, and D2 did not alter cocaine-induced hyperthermia. Risperidone treatment further attenuated cocaine-induced elevation of DA.

Conclusions

Our results indicate that risperidone attenuates cocaine-induced hyperthermia primarily by blocking the activities of the 5-HT2A and D1 receptors and may be potentially useful for treating cocaine-induced acute hyperthermia in humans.
Case study: international healthcare service quality, building a model for cultivating cultural sensitivity
Authors: Yang Ya-Ting , Hsu Yi-Hsin Elsa , Tang Kung-Pei , Wang Christine , Timmon Stephen , Chiu Wen-Ta , Annavajjula Saileela , Chu Jan-Show
Published: August 2020

Quality problem or issue

In the context of medical tourism, cultural differences and language barriers are unneglectable factors, which compromise the shared decision-making between doctor and patients.

Initial assessment

This study constructs a cultural sensitivity cultivation (CSC) model that could be used to train medical professionals in the sector of medical tourism.

Choice of solution

Since 2016, there have been explorations in new strategies to offer better services. A critical step added is to include clients’ perspectives in the re-examining process as a way to cultivate cultural sensitivity among the service providers. This practice expands to the sector of medical tourism. In our case study, we are able to conclude a new model that could yield quality international healthcare services.

Implementation

The steps of our CSC model include (i) ‘Promote Awareness’ for shifting mindset, (ii) ‘Share Scenarios’ for developing empathy and compassion, (iii) ‘Review Process’ for collecting detail feedback, (iv) ‘Identify Gaps’ for targeting areas for improvement and (v) ‘Improve Systems,’ for changing standard operation procedures (SOPs) based on the strategies through Assmann’s theory with a cultural–anthropological approach.

Evaluation

After Kuang Tien General Hospital (KTGH) implemented the new model for 1 year, the number of international patients has increased by 64%. More research could be done in the future to cover all the important aspects of providing international medical services and could apply the CSC model to different healthcare settings.

Lessons learned

To optimize the shared decision-making between the doctor and medical traveler patients, healthcare providers should not only overcome language and cultural barriers but also should avoid unnecessary gestures in terms of status respect. Inviting patients to be co-investigator for quality improvement is a viable solution.
Anticancer drug synergy prediction in understudied tissues using transfer learning
Authors: Kim Yejin , Zheng Shuyu , Tang Jing , Jim Zheng Wenjin , Li Zhao , Jiang Xiaoqian
Published: August 2020

Objective

Drug combination screening has advantages in identifying cancer treatment options with higher efficacy without degradation in terms of safety. A key challenge is that the accumulated number of observations in in-vitro drug responses varies greatly among different cancer types, where some tissues are more understudied than the others. Thus, we aim to develop a drug synergy prediction model for understudied tissues as a way of overcoming data scarcity problems.

Materials and Methods

We collected a comprehensive set of genetic, molecular, phenotypic features for cancer cell lines. We developed a drug synergy prediction model based on multitask deep neural networks to integrate multimodal input and multiple output. We also utilized transfer learning from data-rich tissues to data-poor tissues.

Results

We showed improved accuracy in predicting synergy in both data-rich tissues and understudied tissues. In data-rich tissue, the prediction model accuracy was 0.9577 AUROC for binarized classification task and 174.3 mean squared error for regression task. We observed that an adequate transfer learning strategy significantly increases accuracy in the understudied tissues.

Conclusions

Our synergy prediction model can be used to rank synergistic drug combinations in understudied tissues and thus help to prioritize future in-vitro experiments. Code is available at https://github.com/yejinjkim/synergy-transfer.
Single Laboratory Validation of UHPLC-MS/MS Assays for Six Milk Thistle Flavonolignans in Human Serum
Authors: Muchiri Ruth N , van Breemen Richard B
Published: August 2020

Background

Extracts of milk thistle, Silybum marianum (L.) Gaertn., are used as dietary supplements for their hepatoprotective, anti-inflammatory, and anti-tumor activities.

Objective

An assay based on UHPLC-MS/MS was developed and validated for the quantitative analysis of six major milk thistle flavonolignans extracted from human serum.

Methods

Ethyl acetate containing 0.1% formic acid was used to extract flavonolignans from human serum. A 10-min UHPLC-MS/MS method using selected reaction ion monitoring was developed for measuring extracts for silybin A, silybin B, isosilybin A, isosilybin B, silychristin, and silydianin.

Results

The quantitative method was validated with respect to selectivity, specificity, accuracy, linearity, precision, LOD, and LLOQ. Extraction efficiency for the quality control standards at LLOQ, low, medium, and high concentrations ranged between 81% and 109%, and the calibration curves were linear (R2 > 0.997) for all flavonolignans. The method precision was determined using coefficients of variation, which were <15%. The method accuracy was assessed using percent relative error which was <15%.

Conclusions

The UHPLC-MS/MS assay is fast, precise, sensitive, selective, accurate, and useful for the analysis of milk thistle flavonolignans in human serum.

Highlights

The UHPLC-MS/MS assay is suitable for rapid quantitative analysis of milk thistle flavonolignans in human serum.
Breast Imaging Fellowship Match: Applicants’ Perspectives of Years Two and Three
Authors: Lee Michelle V , Katzen Janine T , Al-Khalili Rend , Choudhery Sadia , Whitman Gary , Brem Rachel
Published: August 2020

Objective

The purpose of this study is to summarize the results of a survey distributed by the Society of Breast Imaging (SBI) to assess applicants’ experience with the 2018 and 2019 Breast Imaging Fellowship Match process.

Methods

In this institutional review board–exempt study, the SBI issued an anonymous survey to all matched applicants in an attempt to gauge their experience with the 2018 and 2019 Match process.

Results

The survey was sent to all 2018 and 2019 matched applicants and 105/236 (45%) responses were received. The majority (75%, 79/105) of respondents reported a positive experience with the Match, with at least a 4/5 rating, and only 3% (5/105) reported a rating below 3/5. There was some improvement in 2019, with 86% (24/28) of respondents reporting at least a 4/5 rating compared to 71% (55/77) in 2018. No respondent reported a score below a 3/5 rating in 2019. The most commonly cited issues with the Match were the timing of the Match process, the need for a universal application, and the burden of travel. Location and program reputation were the two most important factors contributing to the final rank order of programs.

Conclusion

The great majority of applicants felt that the Match created a positive experience. Planned areas of improvement include the implementation of a universal application, the transition to virtual interviews, and a condensed timeline. These measures are likely to increase applicant satisfaction and provide a fair and efficient experience for future breast radiologists.
Trends in Global Disarmament Treaties
Authors: Casey-Maslen Stuart , Vestner Tobias
Published: August 2020

Since the adoption of the UN Charter, states have concluded numerous international disarmament treaties. What are their core features, and are there any trends in their design? This article discusses the five global disarmament treaties, namely the 1971 Biological Weapons Convention, the 1992 Chemical Weapons Convention, the 1997 Anti-Personnel Mine Ban Convention, the 2008 Convention on Cluster Munitions and the 2017 Treaty on the Prohibition of Nuclear Weapons. It first considers how a broad set of prohibitions of activities with respect to specific weapons has evolved over time. Then, it analyses the treaties’ implementation and compliance support mechanisms as well as their procedural aspects regarding entry into force and withdrawal. This article finds that a pattern has developed over the last two decades to outlaw all and any use of weapons by disarmament treaty, without first instituting a prohibition on their use under international humanitarian law (IHL). It also finds that reporting obligations, meetings of States Parties and treaty-related institutions are generally created, either directly by treaty or by subsequent state party decisions. Finally, there is a tendency to make the treaty’s entry into force easier, and the withdrawal more difficult. It is argued that these trends arise from states’ attempt to establish more easily disarmament treaties, design more robust disarmament treaties and more effectively protect civilians. The article concludes by reflecting whether these trends form the basis of a new branch of international law—international disarmament law—and discusses them in the context of emerging weapons and technologies.
A Review of Black Widow (Araneae: Theridiidae) Envenomation, Epidemiology, and Antivenom Utilization in Canada
Authors: Curran-Sills Gwynn , Wilson Steven M , Bennett Robb
Published: August 2020

Two species of black widow spider (BWS—Latrodectus hesperus Chamberlin & Ivie and Latrodectus variolus Walckenaer) naturally occur in Canada and are capable of causing deleterious envenomation to humans. No Canadian literature exists on the frequency of envenomations by these species or the use of antivenom in the treatment of those patients. A review of primary Canadian arachnology data was undertaken to identify BWS populations. A retrospective review of the Health Canada Special Access Program records generated epidemiology and the utilization of antivenom for BWS envenomations in Canada. The geographical distribution of BWS species is limited to along the southern Canadian border. From January 2009 to December 2015, there were five BWS envenomations that required treatment with antivenom and all cases occurred in British Columbia. An average patient age of 41 yr ± 21 SD (range 7–59) was observed, along with three of the five patients being female. The average number of vials used for treatment was 2 ± 1 SD (range 1–3). BWS Antivenin was also obtained by facilities in Alberta, Ontario, and Nova Scotia, but not used in any of these jurisdictions. Further investigation is necessary to determine the annual incidence of BWS envenomations and if treatment with BWS antivenin is required.
Comparative Phylogeography and Integrative Taxonomy of Ochlerotatus caspius (Dipera: Culicidae) and Ochlerotatus dorsalis
Authors: Francuski Ljubinka , Ludoški Jasmina , Milutinović Aleksandra , Krtinić Bosiljka , Milankov Vesna
Published: August 2020

Given that accurately identifying pathogen vectors is vital for designing efficient mosquito control programs based on the proper surveillance of the epidemiologically important species, it has been suggested the complementary use of independently evolving genes and morphometric traits as a reliable approach for the characterization and delimitation of related species. Hence, we examined the spatial distribution of COI mtDNA and ITS2 rDNA variation from the historical perspective of Ochlerotatus caspius (Pallas, 1771) and O. dorsalis (Meigen, 1830), while simultaneously testing the utility of the two markers in integrative species delimitation when combined with phenotypic character analyses of larvae and adults. Despite the striking difference in haplotype diversity (high in COI mtDNA, low in ITS2 rDNA), no evident phylogeographic structure was apparent in the Palearctic O. caspius. The Holarctic O. dorsalis species was subdivided into two highly distinctive COI mtDNA phylogroups which corresponded to the Nearctic and Palearctic regions. Strong support for the independence of the two allopatric evolutionary lineages suggested that geographical barrier and climatic changes during Pleistocene caused vicariance of the ancestral range. COI mtDNA reliably distinguished O. caspius and O. dorsalis, while ITS2 rDNA yet again lacked the proper resolution for solving this problem. An integrative approach based on the larval and adult morphological traits have varying taxonomic applications due to their differential diagnostic values. Thus, by the implementation of an integrative taxonomic approach, we successfully detected species borders between the two epidemiologically relevant species and uncovered the presence of cryptic diversity within O. dorsalis.
Molecular and Morphological Identification of Dermanyssoid Mites (Parasitiformes: Mesostigmata: Dermanyssoidea) Causatives of a Parasitic Outbreak on Captive Snakes
Authors: Alfonso-Toledo Jorge Alberto , Paredes-León Ricardo
Published: August 2020

A parasitic outbreak caused by dermanyssoid mites in a herpetarium of the Metropolitan area of the Valley of Mexico is revealed. This outbreak was caused by Hemilaelaps triangulus (Ewing), but a second mite species, Ophionyssus natricis (Gervais), was found in low abundance. The parasitic load is analyzed, and the morphological and molecular diagnostic characters to identify each of the two species involved are given. A barcode analysis is presented, and two more molecular markers are presented and analyzed. Hemilaelaps triangulus is recorded for the first time in Mexico, and this is the first record of massive infestation on captive snakes caused by ixodorhynchid mites, and DNA sequences of ixodorhynchid mites are publicly available for the first time.
Nine Tips to Improve Your Everyday Forest Data Analysis
Authors: Russell Matthew B
Published: August 2020

Forestry data are complex—they are collected across long time periods, at different resolutions, and include multiple types and sources. Forestry professionals are increasingly relying on new technologies to make informed decisions using these data. This article describes nine practices that forestry professionals and their organizations can take to improve their everyday forest data analysis. By integrating these practices into their work, forestry professionals can sharpen their data management and analytical skills and contribute to more effective decisions made by their organizations.

Study Implications

Forestry professionals contribute to the collection and analysis of data, but less training is provided to them in managing, organizing, and communicating data. A considerable amount of time is spent organizing and restructuring data in forestry, but these actions do not lead to immediate results that can inform decisions. Creating a workplace culture where data are high-quality and trustworthy can assist forestry professionals in using their analytical skills to address problems in areas such as forestland acquisition, carbon sequestration, and ecosystem services. If data are going to continue to drive forest management and policy decisions at the stand, landscape, or national scale, then data analysis skills need to be valued by foresters and the organizations for which they work.
Prioritizing Research Needs in Natural Resources: Using Q-Methodology as a Focus Group Discussion Tool
Authors: Edgeley Catrin M , Stasiewicz Amanda M , Hammond Darcy H
Published: August 2020

Combining Q-methodology with focus groups offers a novel opportunity to explore how researchers and managers can collectively address natural resource management issues. We explored the potential utility of this pairing for prioritizing long-term vegetation recovery research needs after wildfire at a two-day workshop. The approach entailed individual Q-sort activities, followed by focus group discussion about differences and similarities in Q-sort outcomes between managers and researchers. We found that Q-methodology was a versatile discussion tool that offered opportunities for building shared definitions of management issues and identifying new pathways for collaboration between diverse participants. Group discussion around research needs also fostered opportunities for identifying organizational barriers and fostering partnerships to overcome them. Collecting social data on research needs prior to designing or conducting data collection efforts can help ensure that outputs have practical value and utility for land management.

Study Implications

Establishing shared research priorities between researchers and managers is one way to ensure that scientific advancements have practical applications. Using outputs from Q-sort activities as a prompt to initiate discussion between researchers and managers is an effective technique for understanding divergent prioritizations, identifying organizational and scientific barriers, and establishing feasible next steps for collective action to produce application-oriented research. Employing mixed-method social data collection early in the land management planning process is increasingly valuable; many recent policies for forest and natural resource management require the incorporation of collaborative components.
Endometriosis of the rectus abdominis muscles: a rare case of dual location
Authors: Slaiki Saad , Jamor Jihad
Published: August 2020

Endometriosis of the abdominal wall is a rare entity, the etiopathogenesis remains unclear. It most often occurs after gynecological or obstetric surgery. We report the case of a patient with a dual localization of endometriosis in the abdominal wall, the diagnosis was made by abdominal CT scan. The treatment was surgical. The pathology study confirmed the diagnosis of parietal endometriosis. The postoperative course was uneventful with a favorable outcome for 2 years without recurrence. Through our case, we will discuss the characteristics of this entity in order to understand the interest of an early diagnosis and management to deduce possible means of prevention during each gynecological or obstetric surgery.
Detectability of radio afterglows from binary neutron star mergers and implications for fast radio bursts
Authors: Lin Haoxiang , Totani Tomonori
Published: August 2020

Binary neutron star (BNS) mergers are one of the proposed origins for both repeating and non-repeating fast radio bursts (FRBs), which associates FRBs with gravitational waves and short gamma-ray bursts (GRBs). In this work, we explore detectability of radio afterglows from BNS mergers and compare it to the observed radio limits on FRB afterglow. We calculate the afterglow flux powered by the two components: a relativistic jet and a slower isotropic ejecta, and quantify the detection probability as a function of the source redshift, observing time, and flux sensitivity. The model parameter distributions inferred from short GRB afterglows are adopted, and viewing angle distributions (uniform spherical, gravitational-wave, on-axis biased) are assumed to reflect different searching scenario. Assuming that FRBs are not strongly beamed, we make comparison to FRBs detected with reported radio limits and find the detection probabilities are 1–10 per cent in general, and hence not a strong constraint on the BNS progenitor model considering the small sample number (<10). In particular for some nearby FRBs (e.g. 180916.J0158+65, 190608), we find a high chance of detection (>20 per cent at 10 μJy sensitivity) for the isotropic component that would peak around ∼1–10 yr after the merger. Therefore, a long-term radio monitoring of persistent radio emission for these objects is important.
Multiwavelength study of high-redshift blazars
Authors: Sahakyan N , Israyelyan D , Harutyunyan G , Khachatryan M , Gasparyan S
Published: August 2020

High-redshift blazars are among the most powerful objects in the Universe. The spectral and temporal properties of 33 distant blazars (z > 2.5) detected in the high-energy γ-ray band are investigated by analysing the Fermi-LAT and Swift Ultraviolet and Optical Telescope/X-ray Telescope (UVOT/XRT) data. The considered sources have soft time-averaged γ-ray spectra (Γγ ≥ 2.2) whereas those that have been observed in the X-ray band have hard X-ray spectra (ΓX = 1.01−1.86). The γ-ray flux of high-redshift blazars ranges from 4.84 × 10−10 to 1.50 × 10−7 photon cm−2 s−1 and the luminosity is within (0.10−5.54) × 1048 erg s−1 which during the γ-ray flares increases up to (0.1−1) × 1050 erg s−1. In the X-ray band, only the emission of PKS 0438−43, B2 0743+25, and TXS 0222+185 is found to vary in different Swift XRT observations whereas in the γ-ray band, the emission is variable for fourteen sources: the flux of B3 1343+451 and PKS 0537−286 changes in sub-day scales, that of PKS 0347−211 and PKS 0451−28 in day scales, while the γ-ray variability of the others is in week or month scales. The properties of distant blazar jets are derived by modelling the multiwavelength spectral energy distributions within a one-zone leptonic scenario assuming that the X-ray and γ-ray emissions are produced from inverse Compton scattering of synchrotron and dusty torus photons. From the fitting, the emission region size is found to be ≤0.05 pc and the magnetic field and the Doppler factor are correspondingly within 0.10−1.74 G and 10.0−27.4. By modelling the optical–UV excess, we found that the central black hole masses and accretion disc luminosities are within Ld ≃ (1.09−10.94) × 1046 erg s−1 and (1.69−5.35) × 109 M⊙, respectively.
Inferring efficiency of translation initiation and elongation from ribosome profiling
Authors: Szavits-Nossan Juraj , Ciandrini Luca
Published: August 2020

One of the main goals of ribosome profiling is to quantify the rate of protein synthesis at the level of translation. Here, we develop a method for inferring translation elongation kinetics from ribosome profiling data using recent advances in mathematical modelling of mRNA translation. Our method distinguishes between the elongation rate intrinsic to the ribosome’s stepping cycle and the actual elongation rate that takes into account ribosome interference. This distinction allows us to quantify the extent of ribosomal collisions along the transcript and identify individual codons where ribosomal collisions are likely. When examining ribosome profiling in yeast, we observe that translation initiation and elongation are close to their optima and traffic is minimized at the beginning of the transcript to favour ribosome recruitment. However, we find many individual sites of congestion along the mRNAs where the probability of ribosome interference can reach $50\%$. Our work provides new measures of translation initiation and elongation efficiencies, emphasizing the importance of rating these two stages of translation separately.
Computational Drug Repositioning Identifies Potentially Active Therapies for Chordoma
Authors: Traylor Jeffrey I , Sheppard Hadley E , Ravikumar Visweswaran , Breshears Jonathan , Raza Shaan M , Lin Charles Y , Patel Shreyaskumar R , DeMonte Franco
Published: August 2020

BACKGROUND

Chordomas are aggressive bone tumors that often recur despite maximal resection and adjuvant radiation. To date there are no Food and Drug Administration (FDA)-approved chemotherapies. Computational drug repositioning is an expanding approach to identify pharmacotherapies for clinical trials.

OBJECTIVE

To identify FDA-approved compounds for repurposing in chordoma.

METHODS

Previously identified highly differentially expressed genes from chordoma tissue samples at our institution were compared with pharmacogenomic interactions in the Comparative Toxicogenomics Database (CTD) using ksRepo, a drug-repositioning platform. Compounds selected by ksRepo were then validated in CH22 and UM-Chor1 human chordoma cells in Vitro.

RESULTS

A total of 13 chemical compounds were identified in silico from the CTD, and 6 were selected for preclinical validation in human chordoma cell lines based on their clinical relevance. Of these, 3 identified drugs are FDA-approved chemotherapies for other malignancies (cisplatin, cytarabine, and lucanthone). Cytarabine, a deoxyribonucleic acid polymerase inhibitor approved for the treatment of various leukemias, exhibited a significant concentration-dependent effect against CH22 and UM-Chor1 cells when compared to positive (THZ1) and negative (venetoclax) controls. Tretinoin exhibited a significant concentration-dependent cytotoxic effect in CH22, sacral chordoma-derived cell lines but to a much lesser extent in UM-Chor1, a cell line derived from skull base chordoma.

CONCLUSION

Cytarabine administration reduces the viability of human chordoma cells. The equally effective reduction in viability seen with tretinoin seems to be cell line dependent. Based on our findings, we recommend the evaluation of cytarabine and tretinoin in an expanded set of human chordoma cell lines and animal models.
Multiparameter quantitative histological MRI values in high-grade gliomas: a potential biomarker of tumor progression
Authors: Reuter Gilles , Lommers Emilie , Balteau Evelyne , Simon Jessica , Phillips Christophe , Scholtes Felix , Martin Didier , Lombard Arnaud , Maquet Pierre
Published: August 2020

Background

Conventional MRI poorly distinguishes brain parenchyma microscopically invaded by high-grade gliomas (HGGs) from the normal brain. By contrast, quantitative histological MRI (hMRI) measures brain microstructure in terms of physical MR parameters influenced by histochemical tissue composition. We aimed to determine the relationship between hMRI parameters in the area surrounding the surgical cavity and the presence of HGG recurrence.

Methods

Patients were scanned after surgery with an hMRI multiparameter protocol that allowed for estimations of longitudinal relaxation rate (R1) = 1/T1, effective transverse relaxation rate (R2)*=1/T2*, magnetization transfer saturation (MTsat), and proton density. The initial perioperative zone (IPZ) was segmented on the postoperative MRI. Once recurrence appeared on conventional MRI, the area of relapsing disease was delineated (extension zone, EZ). Conventional MRI showing recurrence and hMRI were coregistered, allowing for the extraction of parameters R1, R2*, MTsat, and PD in 3 areas: the overlap area between the IPZ and EZ (OZ), the peritumoral brain zone, PBZ (PBZ = IPZ – OZ), and the area of recurrence (RZ = EZ – OZ).

Results

Thirty-one patients with HGG who underwent gross-total resection were enrolled. MTsat and R1 were the most strongly associated with tumor progression. MTsat was significantly lower in the OZ and RZ, compared to PBZ. R1 was significantly lower in RZ compared to PBZ. PD was significantly higher in OZ compared to PBZ, and R2* was higher in OZ compared to PBZ or RZ. These changes were detected 4 to 120 weeks before recurrence recognition on conventional MRI.

Conclusions

HGG recurrence was associated with hMRI parameters’ variation after initial surgery, weeks to months before overt recurrence.
Evaluating the Suitability and Potential Efficiency of Cannabis sativa Oil for Patients with Primary Burning Mouth Syndrome: A Prospective, Open-Label, Single-Arm Pilot Study
Authors: Gambino Alessio , Cabras Marco , Panagiotakos Evangelos , Calvo Federico , Macciotta Alessandra , Cafaro Adriana , Suria Marco , Haddad Giorgia El , Broccoletti Roberto , Arduino Paolo Giacomo
Published: August 2020

Objective

To evaluate the use of a Cannabis sativa oil in the management of patients diagnosed with primary burning mouth syndrome (BMS).

Design

Prospective, open-label, single-arm pilot study.

Setting

University hospital.

Subjects

Seventeen patients with diagnosed BMS were included.

Methods

Subjects were treated for 4 weeks with a full cannabis plant extract, which was prepared from standardized plant material (cannabis flos) in specialized pharmacies by means of Romano-Hazekamp extraction and was diluted in oil (1 g of cannabis in 10 g of olive oil). The primary outcome was the change in pain intensity (assessed by the visual analog scale, Present Pain Intensity scale, McGill Pain Questionnaire, and Oral Health Impact Profiles) at the end of the protocol and during the succeeding 24 weeks; the neuropathic pain was also investigated with a specific interview questionnaire (DN4-interview [Douleur Neuropathique en 4 Questions]). Levels of anxiety and depression were considered as secondary outcomes, together with reported adverse events due to the specified treatment.

Results

Subjects showed a statistically significant improvement over time in terms of a clinical remission of the oral symptoms. Levels of anxiety and depression also changed statistically, displaying a favorable improvement. No serious reactions were detailed. None of the patients had to stop the treatment due to adverse events.

Conclusions

In this pilot evaluation, the C. sativa oil provided was effective and well tolerated in patients with primary BMS. Further bigger and properly defined randomized controlled trials, with different therapeutic approaches or placebo control, are needed, however.
What Do Index Options Teach Us About COVID-19?
Authors: Jackwerth Jens
Published: August 2020

Risk-neutral distributions of the S&P 500 are informative about the COVID-19 pandemic beyond what one can learn from index values and the market fear gauge of the VIX alone. We learn that, on February 20, 2020, the index did not yet reflect the impending crisis. Only on March 16, 2020, was the full impact visible, with a pronounced bimodality for longer-maturity options revealing a sizeable crash scenario. The corresponding physical distribution is more symmetric and features a high-volatility crash scenario. Firms bought crash protection ahead of the index crash, whereas retail customers bought it as the index was already recovering.
Screening for Fetal Chromosomal Abnormalities
Authors:   American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics,   Committee on Genetics,   Society for Maternal-Fetal Medicine
Published: August 2020

Prenatal testing for chromosomal abnormalities is designed to provide an accurate assessment of a patient’s risk of carrying a fetus with a chromosomal disorder. A wide variety of prenatal screening and diagnostic tests are available; each offers varying levels of information and performance, and each has relative advantages and limitations. When considering screening test characteristics, no one test is superior in all circumstances, which results in the need for nuanced, patient-centered counseling from the obstetric care professional and complex decision making by the patient. Each patient should be counseled in each pregnancy about options for testing for fetal chromosomal abnormalities. It is important that obstetric care professionals be prepared to discuss not only the risk of fetal chromosomal abnormalities but also the relative benefits and limitations of the available screening and diagnostic tests. Testing for chromosomal abnormalities should be an informed patient choice based on provision of adequate and accurate information, the patient’s clinical context, accessible health care resources, values, interests, and goals. All patients should be offered both screening and diagnostic tests, and all patients have the right to accept or decline testing after counseling.

The purpose of this Practice Bulletin is to provide current information regarding the available screening test options available for fetal chromosomal abnormalities and to review their benefits, performance characteristics, and limitations. For information regarding prenatal diagnostic testing for genetic disorders, refer to Practice Bulletin
No. 162, Prenatal Diagnostic Testing for Genetic Disorders. For additional information regarding counseling about genetic testing and communicating test results, refer to Committee Opinion No. 693, Counseling About Genetic
Testing and Communication of Genetic Test Results. For information regarding carrier screening for genetic conditions, refer to Committee Opinion No. 690, Carrier Screening in the Age of Genomic Medicine and Committee Opinion No. 691, Carrier Screening for Genetic Conditions. This Practice Bulletin has been revised to further clarify methods of screening for fetal chromosomal abnormalities, including expanded information regarding the use of cell-free DNA in all patients regardless of maternal age or baseline risk, and to add guidance related to patient counseling.
Intracranial Pressure Dynamics and Cerebral Vasomotor Reactivity in Coronavirus Disease 2019 Patient With Acute Encephalitis
Authors: Svedung Wettervik Teodor , Kumlien Eva , Rostami Elham , Howells Timothy , von Seth Magnus , Velickaite Vilma , Lewén Anders , Enblad Per
Published: August 2020

Objectives:

We describe the intracranial pressure dynamics and cerebral vasomotor reactivity in a coronavirus disease 2019 patient with acute encephalitis treated with cerebrospinal fluid drainage and therapeutic plasma exchange.

Data Sources:

Coronavirus disease ICU, Uppsala University Hospital, Sweden.

Study Selection:

Case report.

Data Extraction:

Radiology, intracranial pressure, intracranial compliance (correlation between intracranial pressure amplitude and mean intracranial pressure), cerebral vasomotor reactivity (pressure reactivity index), arterial blood pressure, cerebrospinal fluid chemistry, and treatment.

Data Synthesis:

None.

Conclusions:

This is the first reported case of intracranial pressure monitoring in a patient with acute encephalitis following coronavirus disease 2019. Intracranial pressure data exhibited a high incidence of plateau waves with intracranial pressure insults above 40 mm Hg that required cerebrospinal fluid drainage. Intracranial compliance was low, and pressure reactivity was intact. It is probable that the combination of low intracranial compliance and intact pressure autoregulation explain the high degree of plateau intracranial pressure waves and intracranial pressure variability. This case illustrates that it could be of value to consider intracranial pressure monitoring in selected coronavirus disease 2019 patients with suspicion of increased intracranial pressure to be able to confirm and treat intracranial hypertension if needed. In this patient, therapeutic plasma exchange was safe and efficacious as the level of neuroinflammation decreased and the patient regained consciousness.
A single copy of large tumor suppressor 1 or large tumor suppressor 2 is sufficient for normal hematopoiesis
Authors: Li Zhi-Gang , Fu Xue-Mei , Chai Cheng-Yan , Sun Fang-Fang , Xiao Fei-Fei , Huang Yong-Xiu , Yao Kai , Chen Jie-Ping , Hou Yu
Published: August 2020

Background

Hematopoietic stem cells (HSCs) have the ability to differentiate into all subsets of blood cells and self-renew. Large tumor suppressor 1 (LATS1) and large tumor suppressor 2 (LATS2) kinases are essential for cell cycle regulation, organism fitness, genome integrity, and cancer prevention. Here, we investigated whether Lats1 and Lats2 are critical for the maintenance of the self-renewal and quiescence capacities of HSCs in mice.

Methods

Quantitative reverse transcription-polymerase chain reaction was used to determine the expression levels of Lats1 and Lats2 in subsets of progenitor cells and mature bone marrow cells. A clustered regularly interspaced short palindromic repeats system was used to generate Lats1 or Lats2 knockout mice. Complete blood cell counts were used to compare the absolute number of white blood cells, lymphocytes, monocytes, neutrophils, and platelets between Lats1 or Lats2 heterozygotes and littermates. Flow cytometry was used to assess the size of hematopoietic progenitor cells (HPCs) and HSC pools in Lats1 or Lats2 heterozygotes and littermates. The comparison between the two groups was analyzed using Student's t test.

Results

Lats1 and Lats2 were widely expressed in hematopoietic cells with higher expression levels in primitive hematopoietic cells than in mature cells. Lats1 or Lats2 knockout mice were generated, with the homozygotes showing embryonic lethality. The size of the HPC and HSC pools in Lats1 (HPC: wild-type [WT] vs. heterozygote, 220,426.77 ± 54,384.796 vs. 221,149.4 ± 42,688.29, P = 0.988; HSC: WT vs. heterozygote, 2498.932 ± 347.856 vs. 3249.763 ± 370.412, P = 0.105) or Lats2 (HPC: WT vs. heterozygote, 425,540.52 ± 99,721.86 vs. 467,127.8 ± 89,574.48, P = 0.527; HSC: WT vs. heterozygote, 4760.545 ± 1518.01 vs. 5327.437 ± 873.297, P = 0.502) heterozygotes were not impaired. Moreover, the depletion of Lats1 or Lats2 did not affect the overall survival of the heterozygotes (Lats1: P = 0.654; Lats2: P = 0.152).

Conclusion

These results indicate that a single allele of Lats1 or Lats2 may be sufficient for normal hematopoiesis.
Early-life nutrition and metabolic disorders in later life: a new perspective on energy metabolism
Authors: Zhou Li-Yuan , Deng Ming-Qun , Zhang Qian , Xiao Xin-Hua
Published: August 2020

Type 2 diabetes mellitus and metabolic disorders have become an epidemic globally. However, the pathogenesis remains largely unclear and the prevention and treatment are still limited. In addition to environmental factors during adulthood, early life is the critical developmental window with high tissue plasticity, which might be modified by external environmental cues. Substantial evidence has demonstrated the vital role of early-life nutrition in programming the metabolic disorders in later life. In this review, we aim to overview the concepts of fetal programming and investigate the effects of early-life nutrition on energy metabolism in later life and the potential epigenetic mechanism. The related studies published on PubMed database up to March 2020 were included. The results showed that both maternal overnutrition and undernutrition increased the riskes of metabolic disorders in offspring and epigenetic modifications, including DNA methylation, miRNAs, and histone modification, might be the vital mediators. The beneficial effects of early-life lifestyle modifications as well as dietary and nutritional interventions on these deleterious metabolic remolding were initially observed. Overall, characterizing the early-life malnutrition that reshapes metabolic disease trajectories may yield novel targets for early prevention and intervention and provide a new point of view to the energy metabolism.
Pain symptoms and disease extent in deep infiltrating endometriosis (DIE): how to score: rASRM, ENZIAN?
Authors: Montanari Eliana , Keckstein Joerg , Hudelist Gernot
Published: August 2020

Deep infiltrating endometriosis is not fully taken into account by the currently most widely used classification system of endometriosis, the revised American Society for Reproductive Medicine (rASRM) score, and rASRM stages correlate only poorly with presence and severity of different pain symptoms. Therefore, the ENZIAN classification was developed in addition to the rASRM score. Infiltration of certain ENZIAN compartments by endometriotic tissue was found to be associated with the presence of different pain symptoms and lesion size in specific ENZIAN compartments correlated with symptom severity. Accurate staging of endometriosis, especially deep infiltrating endometriosis, appears to be facilitated with the additional use of the revised ENZIAN score.
Peripheral pain mechanisms in osteoarthritis
Authors: Vincent Tonia L.
Published: August 2020

There is a well-established historical observation that structural joint damage by plain X-ray correlates poorly with symptomatic disease in osteoarthritis (OA). This is often attributed to the inability to visualise soft-tissue pathology within the joint and the recognition of heterogeneous patient factors that drive central pain sensitisation. A major issue is the relative paucity of mechanistic studies in which molecular pathogenesis of pain is interrogated in relation to tissue pathology. Nonetheless, in recent years, three broad approaches have been deployed to attempt to address this: correlative clinical studies of peripheral and central pain outcomes using magnetic resonance imaging, where soft-tissue processes can be visualised; molecular studies on tissue from patients with OA; and careful molecular interrogation of preclinical models of OA across the disease time course. Studies have taken advantage of established clinical molecular targets such as nerve growth factor. Not only is the regulation of nerve growth factor within the joint being used to explore the relationship between tissue pathology and the origins of pain in OA, but it also provides a core model on which other molecules present within the joint can modulate the pain response. In this narrative review, how molecular and pathological tissue change relates to joint pain in OA will be discussed. Finally, a model for how tissue damage may lead to pain over the disease course will be proposed.
Dual mini-fragment plate fixation for Neer type-II and -V distal clavicle fractures
Authors: Chen Michael J. , Salazar Brett P. , Bishop Julius A. , Gardner Michael J.
Published: August 2020

Contemporary methods for open reduction and internal fixation of displaced distal clavicle fractures have excellent rates of union and high rates of reoperation for symptomatic implant removal. The authors describe their preferred surgical technique and case series of patients with Neer Type-II and -V distal clavicle fractures treated with lower profile dual mini-fragment plates using interdigitating screws placed into the distal segment to enhance fixation.
Functional SARS-CoV-2-specific immune memory persists after mild COVID-19
Authors: Rodda Lauren B. , Netland Jason , Shehata Laila , Pruner Kurt B. , Morawski Peter A. , Thouvenel Chris , Takehara Kennidy K. , Eggenberger Julie , Hemann Emily A. , Waterman Hayley R. , Fahning Mitchell L. , Chen Yu , Rathe Jennifer , Stokes Caleb , Wrenn Samuel , Fiala Brooke , Carter Lauren , Hamerman Jessica A. , King Neil P. , Gale Michael , Campbell Daniel J. , Rawlings David , Pepper Marion
Published: August 2020

The recently emerged SARS-CoV-2 virus is currently causing a global pandemic and cases continue to rise. The majority of infected individuals experience mildly symptomatic coronavirus disease 2019 (COVID-19), but it is unknown whether this can induce persistent immune memory that might contribute to herd immunity. Thus, we performed a longitudinal assessment of individuals recovered from mildly symptomatic COVID-19 to determine if they develop and sustain immunological memory against the virus. We found that recovered individuals developed SARS-CoV-2-specific IgG antibody and neutralizing plasma, as well as virus-specific memory B and T cells that not only persisted, but in some cases increased numerically over three months following symptom onset. Furthermore, the SARS-CoV-2-specific memory lymphocytes exhibited characteristics associated with potent antiviral immunity: memory T cells secreted IFN-γ and expanded upon antigen re-encounter, while memory B cells expressed receptors capable of neutralizing virus when expressed as antibodies. These findings demonstrate that mild COVID-19 elicits memory lymphocytes that persist and display functional hallmarks associated with antiviral protective immunity.
Disease Spectrum of Breast Cancer Susceptibility Genes
Authors: Wang Jin , Singh Preeti , Yin Kanhua , Zhou Jingan , Bao Yujia , Wu Menghua , Pathak Kush , McKinley Sophia K. , Braun Danielle , Hughes Kevin S.
Published: August 2020

Background

Pathogenic variants in cancer susceptibility genes can increase the risk of a spectrum of diseases. We aim to evaluate the disease spectrum of breast cancer susceptibility genes (BCSGs) to develop a comprehensive resource of gene-disease associations for clinicians.

Methods

Thirteen genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, RECQL, STK11 and TP53), that have been conclusively established as BCSGs by the Clinical Genome Resource (ClinGen) and the NCCN guidelines, were investigated. For these thirteen genes, potential gene-disease associations were identified and evaluated based on six genetic resources (ClinGen, NCCN, OMIM, Genetics Home Reference, GeneCards and Gene-NCBI) and an additional literature review using a semiautomated natural language processing (NLP) abstract classification procedure.

Results

A total of 40 diseases were confirmed as being associated with one or more of the 13 BCSGs by our evaluation. Malignant diseases including prostate cancer, pancreatic cancer, colorectal cancer, brain tumor, gastric cancer, ovarian cancer, and sarcoma were associated with at least 3 BCSGs. Furthermore, a total of 87 gene-disease associations were confirmed by our evaluation, of which 85% (74/87) were confirmed by ClinGen and/or NCCN. Conversely, 9 gene-disease associations absent from both ClinGen and NCCN were confirmed in the other four genetic resources (≥3) and 4 gene-disease associations were confirmed by the NLP-based procedure.

Conclusion

This is the first study to systematically investigate the reported disease spectrum of BCSGs in multiple sources. Our innovative approach provides a general guide for evaluating gene-disease associations, and improves the clinical management for at-risk individuals.