bluuebunny/crossref_metadata_2025 huggingface dataset:
BMAA and MCLR Interact to Modulate Behavior and Exacerbate Molecular Changes Related to Neurodegeneration in Larval Zebrafish
Authors: Martin Rubia M , Bereman Michael S , Marsden Kurt C
Published: November 2020

Exposure to toxins produced by cyanobacteria (ie, cyanotoxins) is an emerging health concern due to their increasing prevalence and previous associations with neurodegenerative diseases including amyotrophic lateral sclerosis. The objective of this study was to evaluate the neurotoxic effects of a mixture of two co-occurring cyanotoxins, β-methylamino-l-alanine (BMAA) and microcystin leucine and arginine (MCLR), using the larval zebrafish model. We combined high-throughput behavior-based toxicity assays with discovery proteomic techniques to identify behavioral and molecular changes following 6 days of exposure. Although neither toxin caused mortality, morphological defects, nor altered general locomotor behavior in zebrafish larvae, both toxins increased acoustic startle sensitivity in a dose-dependent manner by at least 40% (p < .0001). Furthermore, startle sensitivity was enhanced by an additional 40% in larvae exposed to the BMAA/MCLR mixture relative to those exposed to the individual toxins. Supporting these behavioral results, our proteomic analysis revealed a 4-fold increase in the number of differentially expressed proteins in the mixture-exposed group. Additionally, prediction analysis reveals activation and/or inhibition of 8 enriched canonical pathways (enrichment p-value < .01; z-score≥|2|), including ILK, Rho Family GTPase, RhoGDI, and calcium signaling pathways, which have been implicated in neurodegeneration. We also found that expression of TDP-43, of which cytoplasmic aggregates are a hallmark of amyotrophic lateral sclerosis pathology, was significantly upregulated by 5.7-fold following BMAA/MCLR mixture exposure. Together, our results emphasize the importance of including mixtures of cyanotoxins when investigating the link between environmental cyanotoxins and neurodegeneration as we reveal that BMAA and MCLR interact in vivo to enhance neurotoxicity.
Ethical dimensions of neglected tropical disease programming
Authors: Addiss David G , Kienast Yvonne , Lavery James V
Published: November 2020

The global movement to control and eliminate neglected tropical diseases (NTDs) is grounded in an ethic of social justice, solidarity and health equity. NTD programmes deliver significant health benefits in socially complex environments characterized by poverty and economic disparity. We used two ethics frameworks—principlism and Upshur's public health framework—to examine ethical challenges faced by NTD programmes. They include management of serious adverse reactions associated with preventive chemotherapy, centralization of decision-making, ‘opt-out’ policies for school-based deworming, incomplete evidence for ‘pro-poor’ impact and persistent inequities in global partnerships. NTD programmes must actively address ethical challenges while pursuing global health goals.
Two sea anemones (Cnidaria: Anthozoa: Actiniaria) from the Southern Ocean with evidence of a deep-sea, polar lineage of burrowing sea anemones
Authors: Gusmão Luciana C , Rodríguez Estefanía
Published: November 2020

Hexacorals are important components of macrobenthic communities in the Southern Ocean, dominating Antarctic continental shelves. Most of the 119 sea anemones recorded for the Southern Ocean are endemic (81% and 25% endemic species and genera, respectively, one endemic family) with only two species extending beyond the limits of the Southern Ocean. Over 70% of the 83 genera in the Southern Ocean are monotypic, including half of the generic diversity in superfamily Actinostoloidea, which suggests that Antarctica has been isolated long enough for the evolution of new genera but not for many families to evolve. Here, we describe Chitinactis marmara gen. & sp. nov., a new monotypic actinostoloidean genus from Antarctica diagnosed by its unique bi-layered cuticle on column, hexamerous symmetry, unequal development of younger mesenteries and mesogleal tentacle musculature. We also re-describe and extend the geographic distribution of Scytophorus striatus, another endemic Antarctic species. Based on morphological and molecular data, we establish the phylogenetic position of C. marmara and discuss the implications of the phylogenetic position of S. striatus for the resurrection and circumscription of the family Halcampoididae and the evolution of burrowing sea anemones. Finally, we discuss evidence for an actinostoloidean deep-sea, polar lineage of burrowing sea anemones.
Comparison of Nanopore Sequencing Protocols and Real-Time Analysis for Phytopathogen Diagnostics
Authors: Phannareth Tommy , Nunziata Schyler O. , Stulberg Michael J. , Galvez Marco E. , Rivera Yazmín
Published: November 2020

Next-generation sequencing technologies have aided molecular detection and diagnosis of plant pathogens. Short read sequencing technologies can be expensive, time consuming, and lack portability. The Oxford Nanopore Technologies (ONT) MinION sequencer offers plant diagnosticians an alternative for whole-genome and transcriptome sequencing with the advantages of portability, rapid results and access to sequences generated, and relatively low cost. Although this company offers multiple sequencing products, most previous articles focused on comparing this technology with other sequencing technology (Sanger, Illumina) and not comparing ONT product performance. In this project, we explored the potential of using ONT’s kits without modifications for the sequencing of plant pathogens. We compared the performance of DNA library preparation protocols (1D versus 1D2 versus Rapid) and RNA library preparation protocols (cDNA PCR Sequencing versus Direct RNA) on the MinION sequencer and examined different data analysis approaches for two well-characterized plant pathogens of agricultural concern, Ralstonia solanacearum and plum pox virus. For bacterial DNA sequencing, the Rapid Sequencing kit had the lowest throughput but offered the shortest sample-to-sequence turnaround time. The cDNA PCR Sequencing kit was better suited for plant RNA viruses than the Direct RNA. Whole-genome assemblies using all tested kits provided accurate identification of the target pathogen when pure cultures or infected plant material was used. This technology offers a shorter sample-to-sequence timeline than previous technologies for both DNA and RNA samples. Data analysis can still be time- and resource-consuming, but we found that 1 h of data generation was sufficient for accurate identification of the target pathogens, which can alleviate computing resources because a full 48-h run of sequencing data is not required. With the decreasing costs of flow cells, MinION is now an additional tool to be considered by plant diagnosticians for whole-genome and transcriptome-based diagnostics.
First Report and New Hosts of Pseudofabraea citricarpa Causing Citrus Target Spot in China
Authors: Xiao Xiaoe , Zeng Yating , Wang Wen , Cheng Lan , Qiao Xinghua , Hou Xin , Li Hongye
Published: November 2020

Citrus target spot, caused by Pseudofabraea citricarpa (Zhu et al.) Chen, Verkley & Crous, was a recently reported disease on satsuma mandarin and kumquat in Chenggu (Shaanxi province, China). In January 2019, target spot-like disease was also observed on ‘Eureka’ lemon and ‘Beijing’ lemon in Wanzhou (Chongqing province), satsuma in Yichang (Hubei province), and ‘Ponkan’ in Jishou (Hunan province). The identity of the causative agent was conducted and confirmed as P. citricarpa based on symptoms, fungal morphology, and multigene phylogenetic analysis, as well as pathogenicity tests. Investigations revealed that P. citricarpa can also infect ‘Tarocco’ blood orange and ‘Newhall’ navel orange. It can not only infect leaves and shoots but also can infect fruits. These results suggest that P. citricarpa could potentially spread to other citrus-growing regions in China.
Systemic inflammation as a risk factor for portal vein thrombosis in cirrhosis: a prospective longitudinal study
Authors: Nery Filipe , Carneiro Paula , Correia Sofia , Macedo Carlos , Gandara Judit , Lopes Vítor , Valadares Diana , Ferreira Sofia , Oliveira João , Teixeira Gomes Manuel , Miranda Helena Pessegueiro , Rautou Pierre-Emmanuel , Valla Dominique
Published: November 2020

Background and Aims

Various risk factors for portal vein thrombosis (PVT) development in patients with cirrhosis have been identified, but the role of systemic inflammatory reaction is unknown. The study aims to assess the association between markers of systemic inflammation and PVT in cirrhosis.

Methods

Between January 2014 and October 2015, 107 outpatients with cirrhosis and no PVT were recruited, and followed till February 2017. White blood cell count, serum concentrations of high-sensitive C-reactive protein, ferritin, tumor necrosis factor-alpha and interleukin-6 (IL-6) were evaluated at baseline and every 3 or 6 months till PVT diagnosis or end of follow-up.

Results

Median age, model for end-stage liver disease (MELD) score and follow-up period of the studied population was 55 years (IQR 46–62 years), 9.6 points (IQR 7.5–12 points) and 19 months (12–24 months), respectively. PVT developed in 10.3% of the patients. Lymphocyte count below 1.2 ´ 109/L [hazard ratio, 6.04; 95% confidence interval (CI), 1.29–28.2; P = 0.022], IL-6 above 5.5 pg/mL (hazard ratio, 5.64; 95% CI, 1.21–26.33; P  = 0.028) and neutrophil-to-lymphocyte ratio (hazard ratio, 1.46; 95% CI, 1.04–2.04; P = 0.028) were associated with a higher risk of PVT development. IL-6 and lymphopenia remained associated with subsequent PVT development after adjustment for nonselective beta-blockers, spleen size, portosystemic collaterals, oesophageal varices (grade ≥2) and ascites, but also with alcohol as the cause for cirrhosis and MELD ≥13.

Conclusion

In patients with cirrhosis, markers of systemic inflammation IL-6 and lymphopenia are predictive of PVT independently of markers of portal hypertension. These results draw our attention on a factor so far overlooked in the pathogenesis of PVT.
Risk factors for adverse events of colorectal endoscopic submucosal dissection: a systematic review and meta-analysis
Authors: Santos Juliana B. , Nobre Moacyr R.C. , Oliveira Cleyton Z. , Safatle-Ribeiro Adriana V. , Kawaguti Fabio , Martins Bruno , Nahas Sergio C. , Ribeiro Ulysses , Zhang Lanjing , Maluf-Filho Fauze
Published: November 2020

Colorectal endoscopic submucosal dissection (ESD) is already an established treatment for superficial colorectal tumors. However, its technical difficulty and high adverse events rates, compared to endoscopic piecemeal mucosal resection, are a concern to some specialists and have probably contributed to discouragement in its widespread adoption. The debate mentioned above stimulated us to perform a systematic review aiming to identify risk factors for colorectal ESD-related adverse events. We conducted this study following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement and registered in the PROSPERO (University of York) international database (CRD42016042625). We searched MEDLINE, EMBASE, Cochrane Library and LILACS for the publications focused on risk factors for colorectal ESD-related adverse events from inception until April 2020. We included a total of 22 qualified studies in this analysis. We found that fibrosis had an odds ratio (OR) for perforation of 2.90 [95% confidence interval, (1.83–4.59)], right colon location of 2.35 (1.58–3.50), colonic location of 2.20 (1.44–3.35) and larger size of 2.17 (1.47–3.21), as well as one protective factor, the endoscopist experience OR = 0.62 (0.45–0.86). For bleeding, we considered rectal location a risk factor [OR = 3.55 (2.06–6.12)]. Through the several meta-analyses that we performed in this article, we could summarize the main risk factors for perforation and bleeding on colorectal ESD. Therefore, we provide insightful information for clinical judgment on regions where colorectal ESD is already widespread and help in the learning process of this challenging technique.
Associations Between Disability and Breast or Cervical Cancers, Accounting for Screening Disparities
Authors: Iezzoni Lisa I. , Rao Sowmya R. , Agaronnik Nicole D. , El-Jawahri Areej
Published: November 2020

Introduction:

Studies suggest that women with disability experience disparities in routine, high-value screening services, including mammograms and Papanicolaou (Pap) tests. However, few studies have explored whether women with disability have higher risks than other women of developing breast or cervical cancers.

Methods:

The authors analyzed 2010, 2013, 2015, and 2018 National Health Interview Surveys, which involved civilian, noninstitutionalized US residents, and included supplemental surveys on cancer screening. The authors used self-reported functional status limitations to identify women without disability and women with movement difficulties (MDs) or complex activity limitations (CAL) predating breast or cervical cancer diagnoses. Multivariable models evaluated associations of disability status to cancer diagnosis, adjusting for other variables. Analyses used sampling weights, producing national estimates.

Results:

The sample included 66,641 women; 24.4% reported MD and 14.5% reported CAL. Compared with women without disability, women with pre-existing MD or CAL had significantly higher rates of breast cancer (2.2% vs. 3.5% and 3.6%, respectively) and cervical cancer (0.6% vs. 0.8% and 1.0%, respectively). Women with disability had significantly lower recent mammography and Pap test rates than women without disability. After adjusting for all covariates, the values for odds ratio (95% confidence interval) of pre-existing CAL for cancer diagnoses were 1.21 (1.01–1.46; P=0.04) for breast cancer and 1.43 (1.04–1.99; P=0.03) for cervical cancer.

Conclusions:

Pre-existing disability is associated with a higher likelihood of breast and cervical cancer diagnoses, raising the urgency of eliminating disability disparities in mammography and Pap testing. Further research will need to explore the causes of these higher cancer rates.
The optimal timing of supporting patients in health-related behavior change after TIA or ischemic stroke: a prospective cohort study to determinants of health-related intention to change over time
Authors: Brouwer-Goossensen Dorien , Lingsma Hester F. , Koudstaal Peter J. , den Hertog Heleen M.
Published: November 2020

The optimal timing of an intervention to support health-related behavior after transient ischemic attack (TIA) or ischemic stroke is unknown. We aimed to assess determinants of patients’ health-related intention to change over time. We prospectively studied 100 patients with TIA or minor ischemic stroke. Patients completed questionnaires on fear, response-efficacy (belief that lifestyle change reduces risk of recurrent stroke), and self-efficacy (patients’ confidence to carry out lifestyle behavior) for behavior change, at baseline, 6 weeks and at 3 months after their TIA or ischemic stroke. We studied differences between these determinants at each visit by means of Wilcoxon signed-rank tests. Median self-efficacy score at baseline was 4.3 [interquartile range (IQ) 3.9–4.7], median fear 16 (IQ 7–21), and response-efficacy 10 (9–12). Fear was significantly higher at baseline than at 3 months (mean difference 2.0; 95% confidence interval: 0.78–3.9) and started to decrease after 6 weeks. No change in self-efficacy or response-efficacy was found. Since fear significantly decreased over time after TIA or ischemic stroke and self-efficacy and response-efficacy scores remained high, the optimal moment to start an intervention to support patients in health-related behavior change after TIA or ischemic stroke seems directly after the stroke or TIA.
PAX8 Expression in Breast Cancer
Authors: Lu Shaolei , Yakirevich Evgeny , Hart Jesse , Wang Lijuan , Wang Yihong
Published: November 2020

PAX8 expression is frequently detected in renal, thyroidal, and Müllerian carcinomas, and PAX8 immunohistochemistry is often used to confirm the origin of these tumors. Tumors metastatic to the breast may masquerade as primary breast lesions. PAX8 is strongly expressed in tumors of Müllerian origin and largely negative in breast primaries, but an immunohistochemical expression of PAX8 in breast cancer has not been systematically evaluated in a large series. We analyzed 266 cases of invasive carcinoma of the breast on tissue microarrays and whole tissue sections with a PAX8 monoclonal antibody. Both the extent (focal or diffuse) and intensity (weak, moderate, or strong) of nuclear staining were assessed in the tumor cells. In total, 16 cases (6.02%) were positive for PAX8 (12 with weak and 4 with moderate staining). Expression was diffuse in 7 cases and focal in 9 cases. All 16 PAX8-positive tumors were histologic grade III invasive ductal carcinomas, 13 of these were triple-negative, 2 were HER2-positive, only and 1 was progesterone receptor-positive only. Strong PAX8 nuclear expression was not seen in any of the cases. PAX8 was negative in breast tumors with neuroendocrine features. Our study demonstrated a low rate of PAX8 expression in breast cancer. When present, PAX8 expression was only seen in high-grade invasive ductal carcinomas, mostly triple-negative. The presence of PAX8 immunoreactivity alone cannot exclude mammary origin, especially when only weak to moderate staining is observed, so the correlation with available clinical and pathologic data helps to ensure an accurate diagnosis.
Utility and Limitations of Albumin mRNA In Situ Hybridization Detection in the Diagnosis of Hepatobiliary Lesions and Metastatic Carcinoma to the Liver
Authors: Collins Katrina , Newcomb Pamela H. , Cartun Richard W. , Ligato Saverio
Published: November 2020

Albumin messenger RNA (mRNA) in situ hybridization is a sensitive and specific biomarker for hepatocellular carcinoma (HCC). Intrahepatic cholangiocarcinoma (ICC) shows variable sensitivity, whereas extrahepatic cholangiocarcinoma (ECC) and metastatic carcinoma are generally negative. We studied the clinical utility and limitations of albumin mRNA detection in a cohort of HCCs, ICCs, ECCs, bile duct adenomas, bile duct hamartomas, and metastatic carcinomas to the liver; and investigated the variability in sensitivity observed for this biomarker in ICCs. We identified 122 cases of hepatobiliary lesions and metastatic carcinomas. Albumin mRNA detection was performed using RNAscope run on formalin-fixed, paraffin-embedded tissue sections. ICCs were categorized according to the classification proposed by Hayashi and colleagues into the small duct, large duct, and indeterminate subtypes. Albumin mRNA was detected in all 17 HCCs and focally in 6/8 (75%) of bile duct adenomas. All 28 nonhepatic carcinomas, 13 bile duct hamartomas, and 9 ECCs were negative. Albumin mRNA was found in 38/47 (80.9%) of ICC with 35/37 (94.6%) in the small duct subtype, 2/3 (66.7%) in the indeterminate subtype, and 1/7 (14.3%) of the large duct subtype (P<0.003). Albumin mRNA detection is a sensitive and specific biomarker for HCCs. It is highly sensitive and moderately specific in the diagnosis of ICC with small gland morphology, but not ICCs with large duct morphology and in metastatic carcinoma. The variability in the sensitivity of albumin mRNA expression in ICCs may depend on the subtypes of ICC.
Unmet Needs Among Out of Care and Recently Diagnosed Women of Color With HIV: Opportunities for Focused Interventions
Authors: Rajabiun Serena , Childs Ellen , Fortu Karen , Spencer LaShonda Y. , Niles-Carnes Larisa V. , Wahome Rahab , Downes Alicia , Heath Corliss D.
Published: November 2020

Objective:

Women of color (WoC) have lower retention in care and higher HIV/AIDS-related morbidity, compared with other populations. Barriers to care include lack of family support, inadequate HIV/AIDS services, and stigma, and women may face greater unmet needs for services including housing and employment. This descriptive study explores the unmet needs of WoC participating in the Health Resources and Services Administration's Special Projects of National Significance (SPNS) Program, Dissemination of Evidence Informed Interventions (HRSA/SPNS DEII) Initiative.

Setting:

Six urban health clinics across the United States.

Participants:

Eligible participants were cis- or transgender women who were newly diagnosed with HIV/AIDS in the past 12 months, out of care for at least 6 months, or not virally suppressed. Participants enrolled from November 2016 to November 2018.

Main Outcomes:

Our primary outcome of interest was unmet needs at enrollment for 6 core services: housing, transportation, benefits, mental health or substance use treatment, medication assistance, and medical care. We examined differences in unmet needs stratified by participant characteristics and used multivariate regression to identify the social and health risk factors associated with higher unmet needs.

Results:

Among the 529 WoC, the most frequently reported expressed needs were transportation (50.1%), housing (41.2%), benefits (28.2%), medication assistance (24.5%), and substance use or mental health treatment (24.3%). Participants with a significantly higher number of overall unmet needs included those who were older (40 years or older), were unstably housed, had a history of incarceration, identified as a transgender woman, were US born, had no caregiver responsibilities, and did not have a case manager at enrollment.

Conclusions:

Our findings indicate the importance of screening for and developing focused strategies to address the unmet needs for WoC if viral suppression is to be achieved.
Frequent Episodic Utilizers of Veterans Health Administration Homeless Programs Use: Background Characteristics and Health Services Use
Authors: Szymkowiak Dorota , Montgomery Ann Elizabeth , Tsai Jack , O'Toole Thomas P.
Published: November 2020

Objective:

To assess sociodemographic, diagnostic, and services use factors associated with veterans' repeated, episodic use of Veterans Health Administration (VHA) Homeless Programs.

Design:

This retrospective cohort study used stepwise multivariate logistic regression to assess the odds of veterans being frequent episodic utilizers of VHA Homeless Programs (ie, ≥4 services use episodes during the observation period).

Setting:

The study used administrative data from veterans who accessed VHA services across the United States.

Participants:

The sample comprised 31 098 veterans who completed a VHA Homeless Program intake assessment in 2013 and accessed VHA Homeless Programs during 2013-2016.

Main Outcome Measure:

Frequent episodic use of VHA Homeless Programs (ie, ≥4 services use episodes during the observation period).

Results:

Only 2.4% of the study sample had 4 or more episodes of VHA Homeless Program use during the observation period; risk factors included experience of military sexual trauma, history of incarceration, diagnosis of psychosis and substance use disorder, and use of acute care.

Conclusions:

Addressing veterans' needs related to poverty, income, and postincarceration reintegration may reduce the frequent episodic use of VHA Homeless Programs. Interventions embedded in emergency departments and inpatient units may also be considered.
Impact of Accreditation on Health Department Financial Resources
Authors: Heffernan Megan , Kennedy Mallory , Gonick Shannon A. , Siegfried Alexa L.
Published: November 2020

Context:

There is limited data available on the financial benefits of public health accreditation.

Objective:

This study assessed the financial impacts reported by public health departments as a result of participating in the Public Health Accreditation Board (PHAB) national accreditation program.

Design:

Data from an ongoing survey of outcomes among health departments accredited for 1 year were linked to PHAB administrative data on health department characteristics to examine self-reported financial impacts of accreditation as of June 2020.

Setting:

Accredited public health departments in the United States.

Participants:

Leadership from 214 unique state, local, Tribal, and Army installation health departments that had been accredited for 1 year by PHAB.

Main Outcome Measure(s):

Improved utilization of resources, increased competitiveness for funding opportunities, and new funding resulting from accreditation.

Results:

One year following accreditation, 57% of all responding health departments reported improved utilization of resources whereas less than half reported improved competitiveness for funding (39%) and new funding (23%) as a result of accreditation. Health departments reporting new funding as a result of accreditation, compared with those that did not report new funding, were also more likely to report other outcomes from accreditation, including improved staff competencies, increased health department capacity to address health priorities and provide high-quality programs and services, increased use of evidence-based practices, new opportunities for external partnerships and collaboration, improved understanding of the health department's role among governing entities and policy makers, and improved credibility. Accredited local health departments (LHDs) with annual budgets less than $10 million reported new funding more often than LHDs with larger annual budgets.

Conclusions:

Accredited health departments that reported new funding were also more likely to report other outcomes of accreditation, including improved staff competencies, new partnerships, and improved credibility. More research is needed to further understand the relationship between accreditation and financial impacts.
Pulmonary Artery Sarcoma With Low 18F-FDG Uptake
Authors: Rosales Castillo Juan José , García Laura , Bastidas Juan Fernando , Bronte Ángela , García-Velloso María José
Published: November 2020

A 75-year-old man presented with dyspnea for more than 2 months, with blood test showing low platelet count and cardiac ultrasound showing severe pulmonary hypertension (>54 mm Hg). A CT pulmonary angiogram showed a filling defect in the pulmonary trunk, right and left pulmonary arteries, raising the possibilities of pulmonary embolism or artery sarcoma. FDG PET/CT was performed for further evaluation and showed low uptake in the pulmonary wall, which supported the diagnosis of pulmonary embolism. Patient was treated with anticoagulants with no changes on repeated CT pulmonary angiogram. Patient underwent surgery, and histopatological examination revealed a pulmonary artery sarcoma.
Not All Heart Uptakes on 99mTc-DPD Scintigraphy Are Amyloidosis
Authors: Wakfie-Corieh Cristina Gamila , Ramos López Noemí , Saiz-Pardo Sanz Melchor , Pérez Castejón María Jesús , Vilacosta Isidre
Published: November 2020

This was the case of a 61-year-old woman with a medical history significant for hypertension and rheumatoid arthritis treated with chloroquine for the last 10 years. She was admitted to our hospital for heart failure symptoms. Echocardiography revealed severe concentric left ventricular hypertrophy. Serum and urine immunofixation electrophoresis and serum light chain assay were negative. No late gadolinium enhancement was observed on cardiovascular magnetic resonance. 99mTc-99mTc-DPD (3,3-diphosphono-1,2-propanodicarboxylic acid) scintigraphy showed myocardial uptake (Perugini score 2/3). Genetic testing excluded hereditary transthyretin cardiac amyloidosis. Endomyocardial biopsy analysis did not show findings suggestive of amyloidosis but consistent with chloroquine toxicity. Chloroquine-mediated cardiotoxicity is rare, and there are very few reports about bone scintigraphy imaging features.
Duodenal Adenocarcinoma Mimicking Metastasis of Prostate Cancer on 18F–Prostate-Specific Membrane Antigen–1007 PET/CT
Authors: Soeda Fumihiko , Watabe Tadashi , Kato Hiroki , Uemura Motohide , Nonomura Norio
Published: November 2020

A 76-year-old man with dyspnea (initial prostate-specific antigen [PSA]: 216 ng/mL) underwent 18F-FDG PET/CT, with uptake in the prostate, lymph nodes, fifth thoracic vertebra (T5), and cricoid cartilage. A biopsy revealed prostate adenocarcinoma (Gleason score 4 + 5, cT4 N1 M1). On initiation of combined androgen blockade therapy, PSA value decreased. However, 4 years later, in a castration-resistant state (PSA 2.14 ng/mL), CT and bone scintigraphy revealed a duodenal tumor and T5 metastasis. 18F–prostate-specific membrane antigen–1007 PET/CT showed uptake in the already known T5 metastasis (SUVmax, 33.55) and even in the duodenal tumor (16.55). The latter was histologically diagnosed as duodenal adenocarcinoma.
Case Report of 18F-FDG PET/CT Features of Polyacrylamide Hydrogel Mammoplasty
Authors: Maw Aung Min , Sood Samriti , Schembri Geoffrey P.
Published: November 2020

A 57-year-old woman with a history of previous bilateral breast polyacrylamide hydrogel injection presented for 18F-FDG PET/CT imaging to investigate recurrent retroperitoneal liposarcoma. Incidental symmetrical FDG-positive accumulation was noted in the bilateral axillae tracking between the interpectoral planes. The finding is consistent with a chronic inflammatory process secondary to the migration of the polyacrylamide hydrogel injections.
Laparoscopic Port-Site Metastasis From Prostate Cancer on 18F-Fluciclovine PET/CT
Authors: Tran Gary , Parrinello Daniel , Dalal Ishani
Published: November 2020

Laparoscopic port-site metastasis from prostate cancer is a rare complication after radical prostatectomy and pelvic lymph node dissection. We report a case of port-site metastasis from prostate cancer identified on 18F-fluciclovine PET/CT for a patient with evidence of biochemical recurrence. Final pathology after targeted ultrasound and biopsy of the mass in the right abdominal wall revealed prostatic adenocarcinoma.
Liver Transplantation in Acute-on-chronic Liver Failure
Authors: Karvellas Constantine J. , Francoz Claire , Weiss Emmanuel
Published: November 2020

Liver transplantation (LT) has revolutionized outcomes for cirrhotic patients. Current liver allocation policies dictate patients with highest short-term mortality receive the highest priority, thus, several patients become increasingly ill on the waitlist. Given cirrhosis is a progressive disease, it can be complicated by the occurrence of acute-on-chronic liver failure (ACLF), a syndrome defined by an acute deterioration of liver function associated with extrahepatic organ failures requiring intensive care support and a high short-term mortality. Successfully bridging to transplant includes accurate prognostication and prioritization of ACLF patients awaiting LT, optimizing intensive care support pre-LT, and tailoring immunosuppressive and anti-infective therapies post-LT. Furthermore, predicting futility (too sick to undergo LT) in ACLF is challenging. In this review, we summarize the role of LT in ACLF specifically highlighting (a) current prognostic scores in ACLF, (b) critical care management of the ACLF patient awaiting LT, (c) donor issues to consider in transplant in ACLF, and (d) exploring of recent post-LT outcomes in ACLF and potential opportunities to improve outcomes including current care gaps and unmet research needs.
A Comprehensive Overview of the Clinical Relevance and Treatment Options for Antibody-mediated Rejection Associated With Non-HLA Antibodies
Authors: Kardol-Hoefnagel Tineke , Otten Henny G.
Published: November 2020

Although solid organ transplant results have improved significantly in recent decades, a pivotal cause of impaired long-term outcome is the development of antibody-mediated rejection (AMR), a condition characterized by the presence of donor-specific antibodies to HLA or non-HLA antigens. Highly HLA-sensitized recipients are treated with desensitization protocols to rescue the transplantation. These and other therapies are also applied for the treatment of AMR. Therapeutic protocols include removal of antibodies, depletion of plasma and B cells, inhibition of the complement cascade, and suppression of the T-cell–dependent antibody response. As mounting evidence illustrates the importance of non-HLA antibodies in transplant outcome, there is a need to evaluate the efficacy of treatment protocols on non-HLA antibody levels and graft function. Many reviews have been recently published that provide an overview of the literature describing the association of non-HLA antibodies with rejection in transplantation, whereas an overview of the treatment options for non-HLA AMR is still lacking. In this review, we will therefore provide such an overview. Most reports showed positive effects of non-HLA antibody clearance on graft function. However, monitoring non-HLA antibody levels after treatment along with standardization of therapies is needed to optimally treat solid organ transplant recipients.
Functional characterization of the transcription regulator WhiB1 from Gordonia sp. IITR100
Authors: Murarka Pooja , Keshav Aditi , Meena Bintu Kumar , Srivastava Preeti
Published: November 2020

WhiB is a transcription regulator which has been reported to be involved in the regulation of cell morphogenesis, cell division, antibiotic resistance, stress, etc., in several members of the family

Actinomycetes

. The present study describes functional characterization of a WhiB family protein, WhiB1 (protein ID: WP_065632651.1), from

Gordonia

sp. IITR100. We demonstrate that WhiB1 affects chromosome segregation and cell morphology in recombinant

Escherichia coli

,

Gordonia

sp. IITR100 as well as in

Rhodococcus erythropolis

. Multiple sequence alignment suggests that WhiB1 is a conserved protein among members of the family

Actinomycetes

. It has been reported that overexpression of WhiB1 leads to repression of the biodesulfurization operon in recombinant

E. coli

,

Gordonia

sp. IITR100 and

R. erythropolis

. A WhiB1-mut containing a point mutation Q116A in the DNA binding domain of WhiB1 led to partial alleviation of repression of the biodesulfurization operon. We show for the first time that the WhiB family protein WhiB1 is also involved in repression of the biodesulfurization operon by directly binding to the dsz promoter DNA.
Secondary Attack Rate (SAR) in household contacts of expired primary cases of COVID-19: A study from Western India
Authors: Shah Komal , Desai Nupur , Mavalankar Dileep
Published: November 2020

Secondary attack rate (SAR) in household contacts of expired primary COVID-19 cases is not well studied yet. Based on our previous pilot study conducted in Gandhinagar district of Gujarat state, we developed a new research protocol to understand SAR statistics in household contacts of COVID-19 cases that died/expired. The details of expired COVID positive primary cases were obtained from Government records and the details of secondary cases were retrieved using telephonic interviews of the household members. Forty-nine expired cases were registered between March to August, 2020. Out of 49 deaths, 28 families could be reached on phone. Rest were not reachable or refused to give information. These were interviewed after taking verbal consent. The study reported 25% SAR in household contact of expired primary cases with 7.4% of mortality in secondary cases. Though this is representative data only from a single district, it was observed that 75% of the household contacts were still not infected in spite of repeated contact with the sever cases. More such studies in various regions are needed to understand disease transmission.
Rapid and lasting generation of B-cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 disease and convalescence
Authors: Hartley Gemma E. , Edwards Emily S.J. , Aui Pei M. , Varese Nirupama , Stojanovic Stephanie , McMahon James , Peleg Anton Y. , Boo Irene , Drummer Heidi E. , Hogarth P. Mark , O’Hehir Robyn E. , van Zelm Menno C.
Published: November 2020

Background

Lasting immunity to SARS-CoV-2 following infection is questioned because serum antibodies decline in convalescence. However, functional immunity is mediated by long-lived memory T and B (Bmem) cells.

Objective

To determine the longevity and immunophenotype of SARS-CoV-2-specific Bmem cells in COVID-19 patients.

Methods

Recombinant spike receptor binding domain (RBD) and nucleocapsid protein (NCP) were produced for ELISA-based serology, and biotinylated for fluorescent tetramer generation to identify SARS-CoV-2-specific Bmem cells by flow cytometry with a panel of 13 mAbs. 36 blood samples were obtained from 25 COVID-19 patients (11 paired) between 4-242 days post-symptom onset for detection of neutralizing antibodies, IgG serology and flow cytometry.

Results

The recombinant RBD and NCP were specifically recognized by serum IgG in all patients and reactivity declined >20 days post-symptom onset. All patients had detectable RBD- and NCP-specific Bmem cells at 8.23-267.6 cells/ml of blood (0.004-0.13% of B cells) regardless of sampling time. RBD- and NCP-specific Bmem cells predominantly expressed IgM or IgG1, with the latter formed slightly later than the former. RBD-specific IgG+Bmem were predominantly CD27+, and numbers significantly correlated with circulating follicular helper T cell numbers.

Conclusion

RBD- and NCP-specific Bmem cells persisted for 8 months, indicating that the decline in serum antibodies after 1 month does not indicate waning of immunity but a contraction of the immune response. Flowcytometric detection of SARS-CoV-2-specific Bmem cells enables detection of long-term functional immunity following infection or vaccination for COVID-19.
Targeted memory reactivation of a serial reaction time task in SWS, but not REM, preferentially benefits the non-dominant hand
Authors: Koopman Anne C. M. , Abdellahi Mahmoud E. A. , Belal Suliman , Rakowska Martyna , Metcalf Alun , Śledziowska Monika , Hunter Thomas , Lewis Penny
Published: November 2020

Targeted memory reactivation (TMR) is a technique by which sounds paired with learned information can be used to cue neural reactivation of that information during sleep. While TMR in slow-wave sleep (SWS) has been shown to strengthen procedural memories, it is unclear whether TMR in rapid eye movement (REM) sleep, a state strongly associated with motor consolidation, provides equivalent benefit. Furthermore, it is unclear whether this technique influences dominant and non-dominant hands equally. We applied TMR of a two-handed serial reaction time task (SRTT) during either SWS or REM in thirty-two human right handed adults (sixteen female) to examine the impact of stimulation in each sleep stage on right (dominant) and left hands. While TMR in SWS led to strong benefits in reaction times and sequence-specific skill, equivalent cueing in REM led to no benefit at all, suggesting that reactivation in this sleep stage is not important for the SRTT. Event-related potentials elicited by TMR cues for left and right hand movements differed significantly in REM, but not SWS, showing that these cues are at least processed in REM. Interestingly, TMR benefits were apparent only in the non-dominant hand, potentially due to the weaker performance measured in this hand at the outset. Overall, these findings suggest that memory replay in SWS, but not REM, is important for consolidation of the SRTT, and TMR-cued consolidation is stronger in the non-dominant hand.

Significance statement

Targeted memory reactivation (TMR) in sleep leads to memory consolidation, but many aspects of this process remain to be understood. We used TMR of a bimanual serial reaction time task to show that behavioural benefit is only observed after stimulation in SWS, even though electrophysiology shows that the TMR cues are processed in REM. Importantly, TMR selectively benefitted the non-dominant hand. These findings suggest that TMR in REM does not benefit this serial reaction time task, and that TMR in SWS preferentially consolidates weaker memory traces relating to the non-dominant hand.
Potassium Carbonate (K2CO3) – A cheap, non-toxic and high-density floating solution for microplastic isolation from beach sediments
Authors: Gohla Jan , Bračun Sandra , Gretschel Gerwin , Koblmüller Stephan , Maximilian Wagner , Pacher Christian
Published: November 2020

Beaches are good indicators for microplastic distribution and local microplastic pollution. Multiple methods have been developed for extracting microplastics from sediment, mainly through density separation. However, the chemicals applied are often expensive and harmful for the user or to the environment. We briefly review the problems associated with the use of these chemicals and present a new floatation solution, potassium carbonate (K2CO3) that has many advantages over available media. It is non-toxic and cheap, and with a density of 1.54 g/cm3the K2CO3solution yielded a mean recovery rate of around 92% for PVC, one of the densest polymers, that cannot be easily extracted with alternative floatation agents. We propose that the use of K2CO3is particularly promising for long term and large-scale monitoring studies, not least because it allows an increasing involvement of citizen scientists, hopefully leading to an increased public awareness of the plastic problem in the seas.
dsSwissKnife: An R package for federated data analysis
Authors: Dragan Iulian , Sparsø Thomas , Kuznetsov Dmitry , Slieker Roderick , Ibberson Mark
Published: November 2020

dsSwissKnifeis an R package that enables several powerful analyses to be performed on federated datasets. The package works alongside DataSHIELD and extends its functionality. We have developed and implementeddsSwissKnifein a large IMI project on type 2 diabetes, RHAPSODY, where data from 10 observational cohorts have been harmonised and federated in CDISC SDTM format and made available for biomarker discovery.

Availability and implementation

dsSwissKnifeis freely available online athttps://github.com/sib-swiss/dsSwissKnife. The package is distributed under the GNU General Public License version 3.

Contact

mark.ibberson@sib.swiss
Towards personalized auditory models: predicting individual sensorineural-hearing-loss profiles from recorded human auditory physiology
Authors: Keshishzadeh Sarineh , Garrett Markus , Verhulst Sarah
Published: November 2020

Over the past decades, different types of auditory models have been developed to study the functioning of normal and impaired auditory processing. Several models can simulate frequency-dependent sensorineural hearing loss (SNHL), and can in this way be used to develop personalized audio-signal processing for hearing aids. However, to determine individualized SNHL profiles, we rely on indirect and non-invasive markers of cochlear and auditory-nerve (AN) damage. Our progressive knowledge of the functional aspects of different SNHL subtypes stresses the importance of incorporating them into the simulated SNHL profile, but has at the same time complicated the task of accomplishing this on the basis of non-invasive markers. In particular, different auditory evoked potential (AEP) types can show a different sensitivity to outer-hair-cell (OHC), inner-hair-cell (IHC) or AN damage, but it is not clear which AEP-derived metric is best suited to develop personalized auditory models. This study investigates how simulated and recorded AEPs can be used to derive individual AN- or OHC-damage patterns and personalize auditory processing models. First, we individualized the cochlear-model parameters using common methods of frequency-specific OHC-damage quantification, after which we simulated AEPs for different degrees of AN-damage. Using a classification technique, we determined the recorded AEP metric that best predicted the simulated individualized CS profiles. We cross-validated our method using the dataset at hand, but also applied the trained classifier to recorded AEPs from a new cohort to illustrate the generalisability of the method.
Environmental specialization and cryptic genetic divergence in two massive coral species from the Florida Keys Reef Tract
Authors: Rippe John P. , Dixon Groves , Fuller Zachary L. , Liao Yi , Matz Mikhail
Published: November 2020

Broadcast-spawning coral species have wide geographic ranges, spanning strong environmental gradients, but it is unclear how much spatially varying selection these gradients actually impose. Strong divergent selection might present a considerable barrier for demographic exchange between disparate reef habitats. We investigated whether the cross-shelf gradient (nearshore - offshore - deep) is associated with spatially varying selection in two common coral species,Montastraea cavernosaandSiderastrea siderea, in the Florida Keys. Toward this end, we generated ade novogenome assembly forM. cavernosaand used 2bRAD to genotype 20 juveniles and 20 adults of both species from each of the three reef zones to identify signatures of selection occurring within a single generation. Unexpectedly, each species was found to be composed of four genetically distinct lineages, with gene flow between them still ongoing but highly reduced in 13.0-54.7% of the genome. Each species includes two sympatric lineages that are only found in the deep (20 m) habitat, while the other lineages are found almost exclusively on the shallower reefs (3-10 m). The two “shallow” lineages ofM. cavernosaare also specialized for either nearshore or offshore: comparison between adult and juvenile cohorts indicates that cross-shelf migrants are more than twice as likely to die before reaching adulthood than local recruits.Siderastrea sidereaandM. cavernosaare among the most ecologically successful species on the degraded Florida Keys Reef Tract, and this work offers important insight on the genomic background of divergent selection and environmental specialization that may in part explain their resilience and broad environmental range.
Major components in the KARRIKIN INSENSITIVE2-ligand signaling pathway are conserved in the liverwort,Marchantia polymorpha
Authors: Mizuno Yohei , Komatsu Aino , Shimazaki Shota , Xie Xiaonan , Ishizaki Kimitsune , Naramoto Satoshi , Kyozuka Junko
Published: November 2020

KARRIKIN INSENSITIVE2 (KAI2) was first identified inArabidopsis thalianaas a receptor of karrikin, a smoke-derived germination stimulant. KAI2 is also considered a receptor of an unidentified endogenous molecule called the KAI2-ligand (KL). Upon KAI2 activation, signals are transmitted through degradation of D53/SMXL proteins via ubiquitination by a Skp-Cullin-F-box (SCF) E3 ubiquitin ligase complex. All components in the KL signaling pathway exist in the liverwortMarchantia polymorpha, namely MpKAI2Aand MpKAI2B, MpMAX2encoding the F-box protein, and MpSMXL, indicating that the signaling pathway became functional in the common ancestor of bryophytes and seed plants. Genetic analysis using knock-out mutants of these KL signaling genes, produced using the CRISPR system, indicated that MpKAI2A, MpMAX2and MpSMXLact in the same genetic pathway and control early gemma growth. Introduction of MpSMXLd53, in which a domain required for degradation is mutated, into wild-type plants caused phenotypes resembling those of the Mpkai2aand Mpmax2mutants. In addition, Citrine fluorescence was detected in tobacco cells transiently transformed with the35S:MpSMXL-Citrinegene construct and treated with MG132, a proteasome inhibitor. On the other hand, introduction of35S:MpSMXLd53-Citrineconferred Citrine fluorescence without MG132 treatment. These findings imply that MpSMXL is subjected to degradation, and that degradation of MpSMXL is crucial for KL signaling inM. polymorpha. We also showed that MpSMXL is negatively regulated by KL signaling. Taken together, this study demonstrates that basic mechanisms in the KL signaling pathway are conserved inM. polymorpha.