bluuebunny/crossref_metadata_2025 huggingface dataset:
Features of Failed Genomic Testing in Advanced NSCLC Specimens
Authors: Gardner E M , Li W , Cohen M B , Topaloglu U , Ramkissoon S
Published: October 2020

Introduction/Objective

Lung cancer continues to be the leading cause of cancer death in the United States. For individuals with advanced lung cancer, genomic testing has the potential to direct patients and their care teams toward a targeted therapy or a specific clinical trial. In some instances, however, submitted specimens fail to meet test standards or do not survive the analytic process. The implications of a failed genomic test for patients can be grave. In this study, we aim to identify common features among non-small cell lung cancer (NSCLC) samples submitted from our medical center that failed FoundationOne testing (Foundation Medicine Inc. Cambridge, MA).

Methods

From all 366 NSCLC samples listed in the FoundationOne database, we identified 31 (8.5%) unique and accessible accession numbers submitted from our institution that failed processing between 2013-2018. These 31 samples were compared for common features, including NSCLC subtype, tumor location, sampling method, tumor size, submitting team, and reported error type.

Results

From all of our samples, 45% (14/31) were adenocarcinoma, 29% (9/31) were squamous cell carcinoma (SCC), 22% (7/31) were NSCLC otherwise unspecified, and 3% (1/31) was adenoid cystic carcinoma. The majority of samples (20/31) were sampled from primary sites including core biopsies (n=9), FNA (n=5), lobectomy specimens (n=4), and bronchial washings (n=2). The remaining metastatic samples came from sites including lymph node, bone, brain, and adrenal gland. Per FoundationOne: the majority of samples (27, 87%) failed following sequencing, while the remaining four (4, 13%) samples failed in the analytic phase.

Conclusion

At this time, it remains unclear why many of these samples failed sequencing. Our next steps include comparing the degree of necrosis from samples and comparing our failed sample pool to a successful sample pool of equal size to remove potential confounding factors.
Utility of Discordant Mismatch Repair-Deficiency (MMR)/Microsatellite Instability (MSI) Testing in Screening Uterine Leiomyosarcoma Patient for Lynch/Other Familial Cancer Syndromes
Authors: Reddy K S
Published: October 2020

Casestudy

Lynch Syndrome (LS) is primarily linked to colorectal and endometrial cancers. Occasional sarcomas, including leiomyosarcoma, have been recognized within the spectrum of LS demonstrating mismatch repair-deficiency (MMR)/microsatellite instability (MSI) in this context.

Results

A 67-year-old female of bilineal Ashkenazi Jewish descent was recently diagnosed with uterine leiomyosarcoma in addition to metastatic papillary thyroid carcinoma at age 58. She met NCCN criteria for LS and BRCA1/2 (brother with renal cancer at age 64, father with colon cancer at age 60, paternal half-sister with rectal cancer at age 50 and maternal aunt with breast cancer).

Studies have shown that immunohistochemistry (IHC) for MMR proteins and PCR-based MSI have comparable sensitivity and specificity with high concordance, but neither test alone is sufficient to capture all defective MMR tumors. Screening strategies vary depending on the level of clinical suspicion for LS. When high, a normal result by one method warrants testing via a second method or concurrent IHC plus PCR testing to minimize the impact of rare false normal results. Rarely, this strategy can yield discordant results, as in our case wherein MSI by PCR was stable (MSS) but IHC for MLH-1 and PMS-2 showed heterogeneous (patchy/focal) nuclear loss of protein expression. The latter is not always due to artefact but can correspond to MMR status differences within the tumor, requiring recognition to prevent false-positive/false-negative evaluations. Heterogenous MLH1 and/or PMS2 expression, may be suggestive of variable MLH1 methylation/second hit mutations, variable epitope expression or expression related to variable differentiation.

Conclusion

The clinical significance of this pattern was unclear in our patient whose initial genetic screen (including MLH1, PMS2, MSH2, MSH6, EPCAM) was negative. However, as studies have indicated that patients with indeterminate IHC findings can have MLH1 hypermethylation or germline mutations, she had justification to undergo extended genetic screening. A heterozygous pathogenic variant in BLM 2207_2212delinsTAGATTC (p.Tyr736Leufs*5) associated with autosomal recessive Bloom Syndrome (BS) was identified. Carriers of BS do not show symptoms of the disease, but they are at a greater than average risk of developing cancers.
Novel Gene Fusions in Rhabdomyosarcoma
Authors: Montoya-Cerrillo D M , Diaz-Perez J A , Rosenberg A E
Published: October 2020

Introduction/Objective

Rhabdomyosarcoma (RMS) encompasses a heterogeneous group of tumors with striated muscle morphology and/or immunophenotype. Molecular analysis of rhabdomyosarcoma has identified a number of aberrations useful for classification. Initially, fusion associated RMS was restricted to tumors with FOXO1 rearrangements, confirming the diagnosis of alveolar RMS, and identifying patients with poor-outcome. Spindle cell RMS, have been described with VGLL2 fusions, EWSR1/FUS-TFCP2 rearrangements, and myoD1 mutations. In addition, NCOA2-MEIS1 fusion gene was recently described in two primary intraosseous RMSs sharing primitive histology. Herein we report two cases of spindle cell RMS, harboring different novel fusion genes, one presenting EP300-VGLL3, and the second with NCOA2-MEIS1 and CAV1-MET.

Methods

Two cases of RMS were retrieved from the pathology files at the University of Miami Hospital (UMH) and Jackson Memorial Hospital (JMH). Morphology and immunohistochemistry were reviewed. A commercial genomic profiling test for both cases was also analyzed. The study was approved by the Institutional Review Board at UMH.

Results

Case #1 is a 36-year-old man presented with a 1.5 cm submucosal mass in the ventral left tongue. The biopsy revealed a malignant spindle cell neoplasm and immunohistochemistry showed tumor cells positive for desmin, SMA, myogenin and MYOD-1. A partial glossectomy was performed, achieving negative resection margins. Next- generation sequencing (NGS) identified an EP300-VGLL3 fusion. The patient is currently being followed and has been disease-free for 6 months. Case #2 is a 19-years-old male with no medical history admitted with lower extremities weakness and a large expansile pelvic bone lesion and multiple spinal metastases. Biopsy from the pelvic lesion revealed malignant primitive round cells and short spindle cells arranged in fascicles which were positive for desmin, MYOD-1, TLE-1 and CD99 and focally positive for myogenin and WT-1. NGS identified two fusion genes, NCOA2- MEIS1 and CAV1-MET.

Conclusion

Different types of rhabdomyosarcoma are associated with a variety of different gene fusions and some may be of prognostic significance. Our two cases are the first reported with EP300-VGLL3 and CAV1-MET fusion genes. CAV1-MET oncogenic potential has been described only in lung cancer. The prognostic significance of rhabdomyosarcoma with novel gene fusions requires longer follow-up and the identification of additional cases.
Criticality Of Adequate Quality Monitoring Of Pre-Type And Screen Orders For The Operating Room: Role Of The Education, Proactive Communication At VAMC
Authors: Patel V , Petersen J M , Jhala D
Published: October 2020

Introduction/Objective

Ordering pre-operative type and screen specimens before the day of surgery is very important to prevent delays in provision of blood products due to unexpected alloantibody findings, unexpected ABO discrepancies, or need for a repeat ABO-RH testing due to lack of historical testing. However, the important pre- operative type and screen was not always ordered prior to the day of surgery by the clinician. Due to this observation, after discussion and collaboration with the Blood Utilization Committee (BUC), an educational and mentoring intervention for the pre-operative clinicians was undertaken.

Methods

Education and mentoring of clinicians involved in the pre-operative clinics, surgical services, and new incoming physicians on an ongoing basis was undertaken through the BUC since March 2018. As part of quality assurance, to track the results of this widespread educational effort, the daily OR lists from January 2017 to December 2019 were examined with the medical record to determine if a pre-operative type and screen was ordered prior to the day of surgery. The established Maximum Surgery Blood order Schedule (MSBOS) for the facility was used to determine if a pre-operative type and screen would be indicated for the listed procedure.

Results

As we started reinforced pre type and screen should be ordered there has been significant increase in percent of compliance rate average from 76% (2017), 87% (2018), and 95.6% (2019). By the T-test, there was a statistically significant change in the monthly ordering rates (p-value < 0.05). The VAMC’s preferred threshold value of at least 95% with pre-operative type and screen prior to the day of procedure was achieved in the 2019 calendar year with no operating room delays.

Conclusion

Appropriately performing the pre-operative type and screen prior to the day of the elective surgical procedure would reduce the risk of delays due to unexpected findings or lack of a historical ABO-RH type. Educational interventions help tremendously in ensuring this critical patient care practice is followed. The value of collaborating and educating clinicians cannot be understated as it is both cheap, simple, and highly effective.
Utility Of Ebus-Tbna In Diagnosis And Staging Of Lung Nodules In The Setting Of Known Second Malignancy In Veterans - A Quality Assurance Study
Authors: Dalal S , Jhala D
Published: October 2020

Introduction/Objective

Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is minimally invasive procedure for diagnosis/staging/restaging of lung nodules, recommended by the National Comprehensive Cancer Network (NCCN) 2017 Clinical Practice Guidelines. Veteran patients are an elderly patient cohort with multiple comorbidities and many have existing known 2nd malignancy. It will be crucial to diagnose and appropriately stage lung nodules. Our primary aim was to assess the efficacy of EBUS-TBNA in diagnosis/nodal staging in elderly patients with known 2nd malignancy. Our secondary aim was to evaluate the safety of this procedure for veterans.

Methods

A retrospective search for cases of EBUS-TBNA in patients with known second malignancy was carried out in Vista/Fileman at the Corporal Michael J Crescenz VA Medical Center between the period of June 2019 to January 2020. Sites included lung, cervical lymph nodes, mediastinum and hilar region.

Results

Of total 93 EBUS-TBNA procedures performed; EBUS-TBNA targeted both the lung and lymph node (62 cases), lymph nodes alone (28 cases) and only lung (3 cases). Total 53 were diagnosed malignant; with primary being lung (39 cases) and pleura (2 cases); and diagnosis of new metastatic carcinomas to lung was made in (12 cases).

The metastatic neoplasms included 2 urothelial carcinoma, 7 squamous carcinoma, 2 metastatic adenocarcinoma, and 1 prostatic adenocarcinoma. 32/53 (60.3%) had the history of prior extrapulmonary second malignancy.

Immunohistochemical studies was able to be performed in 50/53 (94%) of malignant cases, predictive marker PD-L1 on 50/53 (94%) cases, molecular testing on 23/53(43.3%) cases and Foundation One testing (Cambridge, MA, NGS) on 11/53(20.7%) cases. In all 93 cases, there were no complications (0/93) (0%) of the procedure.

Conclusion

EBUS-TBNA is an efficient, cost effective and minimally invasive modality in elderly veteran patient population with multiple co-morbidities. EBUS-TBNA is successful in procuring adequate material for diagnosis, molecular and predictive marker studies; thus, it can play a crucial role in precision oncology. EBUS-TBNA plays a pivotal role diagnosing and ruling out metastatic nodal disease in veteran patient population which has a high incidence of known 2nd extrapulmonary malignancy. EBUS-TBNA is deemed safe in veterans.
Comparism Of Cryoprecipitate Production Methods Using Fibrinogen And Factor VIII Assay
Authors: Bolarinwa A , Otokiti O E
Published: October 2020

Introduction/Objective

cryopecipiitate is of huge importance in the management of some Bleeding disorders especially in a low resource settings like ours where it is still the mainstay of management of disseminated Intravsacular coagulopathy, Haemophilia and Von willebrand Disease. In this study we aimed to compared the quality of cryoprecipitate produced using the Thaw-siphon method (no centrifugation) and the ones produced using the Slow- thawing (with centrifugation) methods

Methods

Ten units of newly prepared Fresh Frozen plasmas were randomly selected, five of were used to prepare cryoprecipitate using the Thaw-siphon method while cryoprecipitate were prepared using the slow-thawing plus centrifugation method. The Fibrinogen concentration in all the ten units were determined using the modified Claus tehcnique while the Factor Viii assay of each unit was done using the one-stage APTT based Assay method

Results

using the Thaw-siphon method, the mean fibrinogen concentration (152mg/bag) was found to be lower than that of units prepared with slow-thawing plus centrifugation methods (256mg/bag). In a similar manner Factor Viii concentrations were higher in the Slow-thawing with centrifugation methods, Mean Factor Viii concentration was 172Iu/bag when compared with 82 IU/bag in Thaw-siphon methods

Conclusion

We concluded that Cryoprecipiate produced usng the Thaw- centrifugation methods have higher Fibrinogen and factor Viii units and as such, smaller quantity will be required for correction of coagulopathy when compared with the Thaw-siphon methods. Despite this glaring and expected findings, it is worthy of note that the cryoprecipitate units produced by Thaw-siphon methods meets the required criteria for quality cryoprecipitate and will be very useful in a low resource settings.
Sirtuin-1 inhibits endothelin-2 expression in human granulosa-lutein cells via hypoxia inducible factor 1 alpha and epigenetic modifications†
Authors: Szymanska Magdalena , Manthe Sarah , Shrestha Ketan , Girsh Eliezer , Harlev Avi , Kisliouk Tatiana , Meidan Rina
Published: October 2020

Endothelin-2 (EDN2) expression in granulosa cells was previously shown to be highly dependent on the hypoxic mediator, hypoxia inducible factor 1 alpha (HIF1A). Here, we investigated whether sirtuin-1 (SIRT1), by deacetylating HIF1A and class III histones, modulates EDN2 in human granulosa-lutein cells (hGLCs). We found that HIF1A was markedly suppressed in the presence of resveratrol or a specific SIRT1 activator, SRT2104. In turn, hypoxia reduced SIRT1 levels, implying a mutually inhibitory interaction between hypoxia (HIF1A) and SIRT1. Consistent with reduced HIF1A transcriptional activity, SIRT1 activators, resveratrol, SRT2104, and metformin, each acting via different mechanisms, significantly inhibited EDN2. In support, knockdown of SIRT1 with siRNA markedly elevated EDN2, whereas adding SRT2104 to SIRT1-silenced cells abolished the stimulatory effect of siSIRT1 on EDN2 levels further demonstrating that EDN2 is negatively correlated with SIRT1. Next, we investigated whether SIRT1 can also mediate the repression of the EDN2 promoter via histone modification. Chromatin immunoprecipitation (ChIP) analysis revealed that SIRT1 is indeed bound to the EDN2 promoter and that elevated SIRT1 induced a 40% decrease in the acetylation of histone H3, suggesting that SIRT1 inhibits EDN2 promoter activity by inducing a repressive histone configuration. Importantly, SIRT1 activation, using SRT2104 or resveratrol, decreased the viable numbers of hGLC, and silencing SIRT1 enhanced hGLC viability. This effect may be mediated by reducing HIF1A and EDN2 levels, shown to promote cell survival. Taken together, these findings propose novel, physiologically relevant roles for SIRT1 in downregulating EDN2 and survival of hGLCs.
Targeted sequencing of Parkinson’s disease loci genes highlights SYT11, FGF20 and other associations
Authors: Rudakou Uladzislau , Yu Eric , Krohn Lynne , Ruskey Jennifer A , Asayesh Farnaz , Dauvilliers Yves , Spiegelman Dan , Greenbaum Lior , Fahn Stanley , Waters Cheryl H , Dupré Nicolas , Rouleau Guy A , Hassin-Baer Sharon , Fon Edward A , Alcalay Roy N , Gan-Or Ziv
Published: October 2020

Genome-wide association studies (GWAS) have identified numerous loci associated with Parkinson’s disease. The specific genes and variants that drive the associations within the vast majority of these loci are unknown. We aimed to perform a comprehensive analysis of selected genes to determine the potential role of rare and common genetic variants within these loci. We fully sequenced 32 genes from 25 loci previously associated with Parkinson’s disease in 2657 patients and 3647 controls from three cohorts. Capture was done using molecular inversion probes targeting the exons, exon-intron boundaries and untranslated regions (UTRs) of the genes of interest, followed by sequencing. Quality control was performed to include only high-quality variants. We examined the role of rare variants (minor allele frequency < 0.01) using optimized sequence Kernel association tests. The association of common variants was estimated using regression models adjusted for age, sex and ethnicity as required in each cohort, followed by a meta-analysis. After Bonferroni correction, we identified a burden of rare variants in SYT11, FGF20 and GCH1 associated with Parkinson’s disease. Nominal associations were identified in 21 additional genes. Previous reports suggested that the SYT11 GWAS association is driven by variants in the nearby GBA gene. However, the association of SYT11 was mainly driven by a rare 3′ UTR variant (rs945006601) and was independent of GBA variants (P = 5.23 × 10−5 after exclusion of all GBA variant carriers). The association of FGF20 was driven by a rare 5′ UTR variant (rs1034608171) located in the promoter region. The previously reported association of GCH1 with Parkinson’s disease is driven by rare non-synonymous variants, some of which are known to cause dopamine-responsive dystonia. We also identified two LRRK2 variants, p.Arg793Met and p.Gln1353Lys, in 10 and eight controls, respectively, but not in patients. We identified common variants associated with Parkinson’s disease in MAPT, TMEM175, BST1, SNCA and GPNMB, which are all in strong linkage disequilibrium with known GWAS hits in their respective loci. A common coding PM20D1 variant, p.Ile149Val, was nominally associated with reduced risk of Parkinson’s disease (odds ratio 0.73, 95% confidence interval 0.60–0.89, P = 1.161 × 10−3). This variant is not in linkage disequilibrium with the top GWAS hits within this locus and may represent a novel association. These results further demonstrate the importance of fine mapping of GWAS loci, and suggest that SYT11, FGF20, and potentially PM20D1, BST1 and GPNMB should be considered for future studies as possible Parkinson’s disease-related genes.
Clinical Characteristics and Outcomes of Breakthrough Candidemia in 71 Hematologic Malignancy Patients and/or Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Single-center Retrospective Study From China, 2011–2018
Authors: Chen Xiao-Chen , Xu Jie , Wu De-Pei
Published: October 2020

Background

Antifungal prophylaxis may result in breakthrough infections in hematology patients with severe agranulocytosis, with few studies assessing risk factors and clinical outcomes of breakthrough candidemia. We described the distribution of Candida species, assessed risk factors for mortality in such patients, and determined differences in the incidence and mortality of breakthrough candidemia between patients who did or did not receive an allogeneic hematopoietic stem cell transplant.

Methods

We collected clinical and microbiological data of patients with hematologic malignancies and breakthrough candidemia from a single center. Seven-day and 30-day follow-up outcomes were recorded; the incidence and mortality of breakthrough candidemia between patients who did or did not undergo an allogeneic transplant were compared. Kaplan-Meier survival estimates were used to generate survival curves, and predictors were identified using Cox regression analyses.

Results

Of 71 enrolled patients, 17 received allogeneic transplants. Incidences of breakthrough candidemia were 17 of 2924 (0.58%) and 54 of 12 015 (0.45%) in the transplant and nontransplant groups, respectively (P = .35). The most common isolate was Candida tropicalis, and antifungal agent combinations were the most common first-line treatment. Cumulative mortality rates of patients were 21.1% and 31.0% at days 7 and 30, respectively, and they significantly differed between both groups. Septic shock, central venous catheter removal, and granulocyte recovery were significantly associated with 7-day mortality; the latter 2 remained independent predictors of 30-day mortality.

Conclusions

Breakthrough candidemia-related mortality was higher in the allogeneic transplant group, although the incidence was not significantly different between the groups. Prompt and adequate antifungal treatment with catheter removal may reduce mortality.
Using a Composite Maternal–Infant Outcome Measure in Tuberculosis-Prevention Studies Among Pregnant Women
Authors: Montepiedra Grace , Kim Soyeon , Weinberg Adriana , Theron Gerhard , Sterling Timothy R , LaCourse Sylvia M , Bradford Sarah , Chakhtoura Nahida , Jean-Philippe Patrick , Evans Scott , Gupta Amita
Published: October 2020

Background

Tuberculosis (TB-)-preventive therapy (TPT) among pregnant women reduces risk of TB in mothers and infants, but timing of initiation should consider potential adverse effects. We propose an analytical approach to evaluate the risk–benefit of interventions.

Methods

A novel outcome measure that prioritizes maternal and infant events was developed with a 2-stage Delphi survey, where a panel of stakeholders assigned scores from 0 (best) to 100 (worst) based on perceived desirability. Using data from TB APPRISE, a trial among pregnant women living with human immunodeficiency virus (WLWH) that randomized the timing of initiation of isoniazid, antepartum versus postpartum, was evaluated.

Results

The composite outcome scoring/ranking system categorized mother–infant paired outcomes into 8 groups assigned identical median scores by stakeholders. Maternal/infant TB and nonsevere adverse pregnancy outcomes were assigned similar scores. Mean (SD) composite outcome scores were 43.7 (33.0) and 41.2 (33.7) in the antepartum and postpartum TPT initiation arms, respectively. However, a modifying effect of baseline antiretroviral regimen was detected (P = .049). When women received nevirapine, composite scores were higher (worse outcomes) in the antepartum versus postpartum arms (adjusted difference, 14.3; 95% confidence interval [CI], 2.4–26.2; P = .02), whereas when women received efavirenz there was no difference by timing of TPT (adjusted difference, .62; 95% CI, −3.2–6.2; P = .53).

Conclusions

For TPT, when used by otherwise healthy persons, preventing adverse events is paramount from the perspective of stakeholders. Among pregnant WLWH in high-TB-burden regions, it is important to consider the antepartum antiretroviral regimen taken when deciding when to initiate TPT.

Clinical Trials Registration. NCT01494038 (IMPAACT P1078).
Clustering Cases of Chlamydia psittaci Pneumonia in Coronavirus Disease 2019 Screening Ward Staff
Authors: Lei Jian-Hua , Xu Yun , Jiang Yong-Fang , Shi Zhi-Hui , Guo Tao
Published: October 2020

We describe 4 cases of Chlamydia psittaci pneumonia among medical staff in a coronavirus disease 2019 (COVID-19) screening ward, as well as the experience of dealing with this nosocomial infection event. Atypical pneumonia, in addition to COVID-19, should be considered when clustering cases occur, even during a COVID-19 pneumonia pandemic.
Translingual arts-based practices for language learners
Authors: Hirsu Lavinia , Zacharias Sally , Futro Dobrochna
Published: October 2020

In this article, we advocate for the enriching role of arts-based practices in the delivery of a translingual pedagogic approach. With a growing interest in translanguaging, ELT practitioners are searching for models and creative ideas that foster a translingual environment for their learners. We have responded to this call and developed a collaborative project entitled ‘Creative Language Practices: Exploring Translanguaging in Pedagogical Contexts and Beyond’. The project brought together language researchers from the University of Glasgow, creative artists, and school teachers. By sharing our approach and practices, we want to promote the adoption of translingual values and guiding principles through the use of arts as a methodology for language learning and meaning-making. Instead of feeling intimidated by the complexity and difficulty of the concept of translanguaging, teachers and practitioners could adopt an arts-based pedagogy as the catalyst for creative practice that will help learners to explore their creative resources.
CARDIAC RHYTHM MANAGEMENTPredictors and management of cardiac perforation caused by cardiac rhythm device implantation
Authors: Elbatran Ahmed I , Gallagher Mark M , Bajpai Abhay , Grimster Alexander , Li Anthony
Published: October 2020

Background

Cardiac perforation caused by cardiac rhythm device implantation is uncommon but potentially lethal.

Methods

All patients presenting to a single referral centre with cardiac perforation after implantation between December 2017 and July 2019 were identified. Patient demographics, time to diagnosis, the method of lead extraction and 30-day complications were examined.

Results

Thirteen cases of cardiac perforation were identified, 4 of which were implanted at other hospitals. The incidence of perforation for devices implanted at our institution was 9/1031 (0.87%). Median time from implantation to diagnosis was 8 days (IQR = 3–21). Compared with implantations during the same time period, patients with perforation were older (80 ± 10 years vs. 73 ± 15 years, P = 0.005) and predominantly females (9/13 vs. 355/1031, P = 0.009). In all cases, the perforating lead was an active fixation model, an ICD coil in one case. 10 leads were in the right ventricle (3 of which in apical position) and 3 in the right atrium (all in the lateral wall). There was no greater proportion of a particular lead type compared with implantations during the same time period. All had abnormal electrical parameters at device interrogation. Nine patients (69%) had pericardial effusion and four (31%) developed tamponade. Transvenous lead extraction was successfully performed in all 13 patients, with no 30-day mortality.

Conclusion

Older age and female gender were more prevalent in patients with lead perforation. Transvenous lead extraction was safely performed in all patients.
Coseismic changes in the kinetic rotational energy of the Earth from 1976 to 2019
Authors: Xu Changyi
Published: October 2020

The energy changes corresponding to the axis and speed of the Earth’s rotation are the polar motion energy, ΔEpm and the spinning energy, ΔEss. Here we develop an explicit approach to compute the coseismic ΔEpm and ΔEss based on a spherical-Earth elastic dislocation theory. We estimate the cumulative changes induced by global major earthquakes from 1976 to 2019 using the derived expression. The results show that the rate of ΔEpm and ΔEss is 0.45 × 1012 and 0.20 × 1019 J −1, corresponding to 0.01 MW (1 MW = 106 Watt) and 0.06 TW (1 TW = 1012 Watt), respectively. The χ2 test shows that global earthquakes tend to strongly increase the spinning energy rather than the polar motion energy. Comparing the coseismic rotational energy to the coseismic gravitational energy and the radiated seismic-wave energy induced by every single event, we found that coseismic rotational energy is distinctly at least 7.6 times larger than the radiated seismic-wave energy, demonstrating the importance of rotational energy in the energy budget of the faulting.
Surgical management of Ebstein anomaly: impact of the adult congenital heart disease anatomical and physiological classifications
Authors: Homzova Laura , Photiadis Joachim , Sinzobahamvya Nicodème , Ovroutski Stanislav , Cho Mi-Young , Schulz Antonia
Published: October 2020

OBJECTIVES

Our goal was to evaluate the impact of the adult congenital heart disease anatomical and physiological (ACHD AP) classification system on the surgical management of Ebstein anomaly (EA) in adult patients.

METHODS

From February 2000 through August 2017, data of patients aged at least 16 years, who underwent primary EA surgery, were retrospectively evaluated. The cohort was divided in 2 groups according to their ACHD AP classification: the moderate EA group (IIB, IIC) and the severe EA group (IID). Survival, freedom from reoperation and freedom from occurrence of major adverse advents were estimated.

RESULTS

There were 33 patients (21 women, 12 men). Eighteen belonged to the moderate group, 15 to the severe group. There were 12 female patients (80%) in the severe group. Patients in the moderate group were younger than those in the severe group (P = 0.02): 32 ± 12 vs 44 ± 15 years old. Thirty tricuspid valve repairs and 3 replacements were performed. Repair was mainly performed in the moderate group (P = 0.02). Overall survival was 90.1 ± 5.4% at 9 months after the operation and did not change in the later follow-up period. It was 100% for patients in the moderate group and 80.0 ± 10.3% in the severe group (P = 0.07), and 75.0 ± 12.5% for female patients of in the severe group compared to 100% for the remaining patients (P = 0.025). Survival free from major adverse events, including reoperation, at 10 years was 60.0 ± 12.6% in the moderate and 38.1% ± 12.9% in the severe group (P = 0.03). No patient in the moderate group evolved to be in the severe group at late follow-up.

CONCLUSION

Adult EA patients should undergo surgery earlier when they are still in the moderate ACHD AP classification.
Point-of-Care Influenza Testing Impacts Clinical Decision, Patient Flow, and Length of Stay in Hospitalized Adults
Authors: Fjelltveit Elisabeth B , Cox Rebecca J , Østensjø Jørgen , Blomberg Bjørn , Ebbesen Marit H , Langeland Nina , Mohn Kristin G I
Published: October 2020

Background

Influenza is difficult to distinguish clinically from other acute respiratory infections. Rapid laboratory diagnosis can help initiate early effective antiviral treatment and isolation. Implementing a novel point-of-care test (POCT) for influenza in the emergency department (ED) could improve treatment and isolation strategies and reduce the length of stay (LOS).

Methods

In a prospective, controlled observational cohort study, we enrolled patients admitted due to acute respiratory illness to 2 public hospitals in Bergen, Norway, one using a rapid POCT for influenza (n = 400), the other (n = 167) using conventional rapid laboratory-based assay.

Results

Prevalence of influenza was similar in the 2 hospitals (154/400, 38% vs 38%, 63/167; P = .863). Most patients in both hospitals received antiviral (83% vs 81%; P = .703) and antibiotic treatment (72% vs 62%; P = .149). Isolation was more often initiated in ED in the hospital using POCT (91% vs 80%; P = .025). Diagnosis by POCT was associated with shorter hospital stay; old age, diabetes, cancer, and use of antibiotics, particularly broad-spectrum antibiotics, were associated with prolonged stay.

Conclusions

POCT implementation in ED resulted in improved targeted isolation and shorter LOS. Regardless of POCT use, most influenza patients received antivirals (>80%) and antibiotics (>69%).
Improvement of HIV-associated neurocognitive disorders after antiretroviral therapy intensification: the Neuro+3 study
Authors: Force Gilles , Ghout Idir , Ropers Jacques , Carcelain Guislaine , Marigot-Outtandy Dhiba , Hahn Valérie , Darchy Natacha , Defferriere Hélène , Bouaziz-Amar Elodie , Carlier Robert , Dorgham Karim , Callebert Jacques , Peytavin Gilles , Delaugerre Constance , de Truchis Pierre ,   NEURO+3 STUDY GROUP, Cabée Anne-Elisabeth , Lecornu Claire , Aegerter Philippe , Berthe Huguette , Mohand Hocine Ait , Brefort Sandrine , Klement Elise , Le Du Damien , Laplanche Jean-Louis , Labadie-Nere Marie-Laure , Mahjoub Nadia , Zucman David , Khuong Marie-Aude , Genet Philippe , Larroze Maud , Troisvallets Didier , Blum Laurent , Sauvage Myriam
Published: October 2020

Objectives

Despite the effectiveness of antiretroviral (ARV) therapy to control HIV infection, HIV-associated neurocognitive disorders (HAND) remain frequent. The Neuro+3 study assessed the cognitive improvement associated with ARV intensification based on increased CNS penetration effectiveness (CPE) scoring ≥+3 and total CPE score ≥9.

Methods

Thirty-one patients, aged 18–65 years, with confirmed diagnosis of HAND and effective ARV therapy were included. The cognitive improvement was measured using Frascati three-stage classification and global deficit score (GDS) after 48 and 96 weeks of ARV intensification. Ultrasensitive HIV-RNA, neopterin, soluble CD14, CCL2, CXCL10, IL6, IL8 and NF-L were measured in plasma and cerebrospinal fluid at Day 0 (baseline), Week 48 (W48) and W96.

Results

The intensified ARV was associated with a median (IQR) CPE score increase from 6 (4–7) at baseline to 10 (9–11). From baseline to W96, the median (IQR) GDS decreased from 1.4 (0.8–2.2) to 1.0 (0.6–2.0) (P = 0.009); HAND classification improved from 2 to 1 HIV-associated dementia, 22 to 8 mild neurocognitive disorders, 7 to 17 asymptomatic neurocognitive impairment and 0 to 5 patients without any neurocognitive alterations (P = 0.001). In multivariable linear regression analysis, GDS improvement at W96 was significantly associated with CPE score ≥9 after intensification (P = 0.014), CD4 lymphocyte increase at W48 (P < 0.001) and plasma CXCL10 decrease at W96 (P = 0.001).

Conclusions

In patients with HAND, a significant cognitive improvement was observed after the ARV intensification strategy, with a higher CPE score. Cognitive improvement was more often observed in the case of a switch of two drug classes, arguing for better control of CNS HIV immune activation.
Refugee Settlement and Decision-Making Venue: Does Public Concern Instigate Preferences for Local Referendums? Experiences from Norwegian Cities
Authors: Steen Anton
Published: October 2020

Refugee settlement in local communities is often controversial and raises questions of legitimate regulation of access and sustainable integration. This study takes the citizens’ perspective and asks who should determine refugee settlement—the people in a local referendum, political representatives in the local council, or elites in central government—as well as enquiring how immigration scepticism affects preferences for the decision-making venue. The issue speaks to the wealth of literature focusing on ‘the local dimension’ of immigration. The data are from opinion surveys in four Norwegian cities that have experienced extensive refugee settlement during the past few decades. Contrary to expectations, it appears that despite widespread concern about the consequences of newcomers, most trust the decisions made by their local representatives in the city council and prefer the state to enforce refugee settlement at the local level. As expected, those with negative images of refugees, those with a low level of education, and those with rightist party sympathies tend to support a referendum. More surprisingly, a high level of concern for ‘the others’ substantially reduces the general positive effects of social background and political orientation: the worried among the well-educated and left-wingers join forces with the right-wingers and politically alienated in supporting referendums as a channel for influencing the settlement issue. This article suggests that the refugee settlement issue is too controversial to be solved by direct democracy and is also a potential channel for those fearing ‘the others’ across social strata.
The confrontation of the shock-powered synchrotron maser model with the Galactic FRB 200428
Authors: Yu Yun-Wei , Zou Yuan-Chuan , Dai Zi-Gao , Yu Wen-Fei
Published: October 2020

The association of FRB 200428 with an X-ray burst (XRB) from the Galactic magnetar SGR 1935+2154 offers important implications for the physical processes responsible for the fast radio burst (FRB) phenomena. By assuming that the XRB emission is produced in the magnetosphere, we investigate the possibility that the FRB emission is produced by shock-powered synchrotron maser (SM), which is phenomenologically described with a number of free parameters. The observational constraints on the model parameters indicate that the model can in principle be consistent with the FRB 200428 observations, if the ejecta lunched by magnetar activities can have appropriate ingredients and structures and the shock processes occur on the line of sight. To be specific, a complete burst ejecta should consist of an ultra-relativistic and extremely highly collimated e± component and a sub-relativistic and wide-spreading baryonic component. The internal shocks producing the FRB emission arise from a collision between the e± ejecta and the remnant of a previous baryonic ejecta at the same direction. The parameter constraints depend on the uncertain spectrum and efficiency of the SM emission. While the spectrum is tentatively described by a spectral index of −2, we estimate the emission efficiency to be around 10−4 by requiring that the synchrotron emission of the shocked material cannot be much brighter than the magnetosphere XRB emission.
The flaring X-ray corona in the quasar PDS 456
Authors: Reeves J N , Braito V , Porquet D , Lobban A P , Matzeu G A , Nardini E
Published: October 2020

New Swift monitoring observations of the variable, radio-quiet quasar, PDS 456, are presented. A bright X-ray flare was captured in 2018 September, the flux increasing by a factor of 4 and with a doubling time-scale of 2 d. From the light crossing argument, the coronal size is inferred to be ≲30 gravitational radii for a black hole mass of 109 M⊙ and the total flare energy exceeds 1051 erg. A hardening of the X-ray emission accompanied the flare, with the photon index decreasing from Γ = 2.2 to Γ = 1.7 and back again. The flare is produced in the X-ray corona, the lack of any optical or UV variability being consistent with a constant accretion rate. Simultaneous XMM–Newton and NuSTAR observations were performed, 1–3 d after the flare peak and during the decline phase. These caught PDS 456 in a bright, bare state, where no disc wind absorption features are apparent. The hard X-ray spectrum shows a high energy roll-over, with an e-folding energy of $E_{\rm fold}=51^{+11}_{-8}$ keV. The deduced coronal temperature, of kT = 13 keV, is one of the coolest measured in any AGN and PDS 456 lies well below the predicted pair annihilation line in X-ray corona. The spectral variability, becoming softer when fainter following the flare, is consistent with models of cooling X-ray coronae. Alternatively, an increase in a non-thermal component could contribute towards the hard X-ray flare spectrum.
Optical and spectral observations and hydrodynamic modelling of type IIb supernova 2017gpn
Authors: Balakina Elena A , Pruzhinskaya Maria V , Moskvitin Alexander S , Blinnikov Sergei I , Wang Xiaofeng , Xiang Danfeng , Lin Han , Rui Liming , Wang Huijuan
Published: October 2020

In this work we present the photometric and spectroscopic observations of type IIb supernova 2017gpn. This supernova was discovered in the error-box of the LIGO/Virgo G299232 gravitational-wave event. We obtained the light curves in the B and R passbands and modelled them numerically using the one-dimensional radiation hydrocode stella. The best-fitting model has the following parameters: the pre-SN star mass and the radius are M ≈ 3.5 M⊙ and R ≈ 50 R⊙, respectively; the explosion energy is $E_{\rm exp} \approx 1.2\times 10^{51}$ erg; the mass of radioactive nickel is $M_{\rm ^{56}Ni} \approx 0.11$ M⊙, which is completely mixed throughout the ejecta; and the mass of the hydrogen envelope $M_{\rm H\_{env}}$ ≈ 0.06 M⊙. Moreover, SN 2017gpn is a confirmed SN IIb that is located at the farthest distance from the centre of its host galaxy NGC 1343 (i.e. the projected distance is ∼21 kpc). This challenges the scenario of the origin of type IIb supernovae from massive stars.
The large-scale magnetic field of Proxima Centauri near activity maximum
Authors: Klein Baptiste , Donati Jean-François , Hébrard Élodie M , Zaire Bonnie , Folsom Colin P , Morin Julien , Delfosse Xavier , Bonfils Xavier
Published: October 2020

We report the detection of a large-scale magnetic field at the surface of the slowly rotating fully convective (FC) M dwarf Proxima Centauri. 10 circular polarization spectra, collected from 2017 April to July with the HARPS-Pol spectropolarimeter, exhibit rotationally modulated Zeeman signatures suggesting a stellar rotation period of 89.8 ± 4.0 d. Using Zeeman–Doppler Imaging, we invert the circular polarization spectra into a surface distribution of the large-scale magnetic field. We find that Proxima Cen hosts a large-scale magnetic field of typical strength 200 G, whose topology is mainly poloidal, and moderately axisymmetric, featuring, in particular, a dipole component of 135 G tilted at 51° to the rotation axis. The large-scale magnetic flux is roughly 3× smaller than the flux measured from the Zeeman broadening of unpolarized lines, which suggests that the underlying dynamo is efficient at generating a magnetic field at the largest spatial scales. Our observations occur ∼1 yr after the maximum of the reported 7 yr-activity cycle of Proxima Cen, which opens the door for the first long-term study of how the large-scale field evolves with the magnetic cycle in an FC very low mass star. Finally, we find that Proxima Cen’s habitable zone planet, Proxima-b, is likely orbiting outside the Alfvèn surface, where no direct magnetic star–planet interactions occur.
PDCD2 functions as an evolutionarily conserved chaperone dedicated for the 40S ribosomal protein uS5 (RPS2)
Authors: Landry-Voyer Anne-Marie , Bergeron Danny , Yague-Sanz Carlo , Baker Breac , Bachand Francois
Published: October 2020

PDCD2 is an evolutionarily conserved protein with previously characterized homologs in Drosophila (zfrp8) and budding yeast (Tsr4). Although mammalian PDCD2 is essential for cell proliferation and embryonic development, the function of PDCD2 that underlies its fundamental cellular role has remained unclear. Here, we used quantitative proteomics approaches to define the protein-protein interaction network of human PDCD2. Our data revealed that PDCD2 specifically interacts with the 40S ribosomal protein uS5 (RPS2) and that the PDCD2-uS5 complex is assembled co-translationally. Loss of PDCD2 expression leads to defects in the synthesis of the small ribosomal subunit that phenocopy a uS5 deficiency. Notably, we show that PDCD2 is important for the accumulation of soluble uS5 protein as well as its incorporation into 40S ribosomal subunit. Our findings support that the essential molecular function of PDCD2 is to act as a dedicated ribosomal protein chaperone that recognizes uS5 co-translationally in the cytoplasm and accompanies uS5 to ribosome assembly sites in the nucleus. As most dedicated ribosomal protein chaperones have been identified in yeast, our study reveals that similar mechanisms exist in human cells to assist ribosomal proteins coordinate their folding, nuclear import and assembly in pre-ribosomal particles.
Predicting single-cell gene expression profiles of imaging flow cytometry data with machine learning
Authors: Chlis Nikolaos-Kosmas , Rausch Lisa , Brocker Thomas , Kranich Jan , Theis Fabian J
Published: October 2020

High-content imaging and single-cell genomics are two of the most prominent high-throughput technologies for studying cellular properties and functions at scale. Recent studies have demonstrated that information in large imaging datasets can be used to estimate gene mutations and to predict the cell-cycle state and the cellular decision making directly from cellular morphology. Thus, high-throughput imaging methodologies, such as imaging flow cytometry can potentially aim beyond simple sorting of cell-populations. We introduce IFC-seq, a machine learning methodology for predicting the expression profile of every cell in an imaging flow cytometry experiment. Since it is to-date unfeasible to observe single-cell gene expression and morphology in flow, we integrate uncoupled imaging data with an independent transcriptomics dataset by leveraging common surface markers. We demonstrate that IFC-seq successfully models gene expression of a moderate number of key gene-markers for two independent imaging flow cytometry datasets: (i) human blood mononuclear cells and (ii) mouse myeloid progenitor cells. In the case of mouse myeloid progenitor cells IFC-seq can predict gene expression directly from brightfield images in a label-free manner, using a convolutional neural network. The proposed method promises to add gene expression information to existing and new imaging flow cytometry datasets, at no additional cost.
An extracellular vesicle-related gene expression signature identifies high-risk patients in medulloblastoma
Authors: Albert Thomas K , Interlandi Marta , Sill Martin , Graf Monika , Moreno Natalia , Menck Kerstin , Rohlmann Astrid , Melcher Viktoria , Korbanka Sonja , Meyer zu Hörste Gerd , Lautwein Tobias , Frühwald Michael C , Krebs Christian F , Holdhof Dörthe , Schoof Melanie , Bleckmann Annalen , Missler Markus , Dugas Martin , Schüller Ulrich , Jäger Natalie , Pfister Stefan M , Kerl Kornelius
Published: October 2020

Background

Medulloblastoma (MB) is a malignant brain tumor in childhood. It comprises 4 subgroups with different clinical behaviors. The aim of this study was to characterize the transcriptomic landscape of MB, both at the level of individual tumors as well as in large patient cohorts.

Methods

We used a combination of single-cell transcriptomics, cell culture models and biophysical methods such as nanoparticle tracking analysis and electron microscopy to investigate intercellular communication in the MB tumor niche.

Results

Tumor cells of the sonic hedgehog (SHH)–MB subgroup show a differentiation blockade. These cells undergo extensive metabolic reprogramming. The gene expression profiles of individual tumor cells show a partial convergence with those of tumor-associated glial and immune cells. One possible cause is the transfer of extracellular vesicles (EVs) between cells in the tumor niche. We were able to detect EVs in co-culture models of MB tumor cells and oligodendrocytes. We also identified a gene expression signature, EVS, which shows overlap with the proteome profile of large oncosomes from prostate cancer cells. This signature is also present in MB patient samples. A high EVS expression is one common characteristic of tumors that occur in high-risk patients from different MB subgroups or subtypes.

Conclusions

With EVS, our study uncovered a novel gene expression signature that has a high prognostic significance across MB subgroups.