bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of the XBP1s/O-GlcNAcylation Pathway Improves Functional Outcome After Cardiac Arrest and Resuscitation in Young and Aged Mice
Authors: Li Ran , Shen Yuntian , Li Xuan , Lu Liping , Wang Zhuoran , Sheng Huaxin , Hoffmann Ulrike , Yang Wei
Published: January 2021

After cardiac arrest (CA) and resuscitation, the unfolded protein response (UPR) is activated in various organs including the brain. However, the role of the UPR in CA outcome remains largely unknown. One UPR branch involves spliced X-box-binding protein-1 (XBP1s). Notably, XBP1s, a transcriptional factor, can upregulate expression of specific enzymes related to glucose metabolism, and subsequently boost O-linked β-N-acetylglucosamine modification (O-GlcNAcylation). The current study is focused on effects of the XBP1 UPR branch and its downstream O-GlcNAcylation on CA outcome. Using both loss-of-function and gain-of-function mouse genetic tools, we provide the first evidence that activation of the XBP1 UPR branch in the post-CA brain is neuroprotective. Specifically, neuron-specific Xbp1 knockout mice had worse CA outcome, while mice with neuron-specific expression of Xbp1s in the brain had better CA outcome. Since it has been shown that the protective role of the XBP1s signaling pathway under ischemic conditions is mediated by increasing O-GlcNAcylation, we then treated young mice with glucosamine, and found that functional deficits were mitigated on day 3 post CA. Finally, after confirming that glucosamine can boost O-GlcNAcylation in the aged brain, we subjected aged mice to 8 min CA, and then treated them with glucosamine. We found that glucosamine-treated aged mice performed significantly better in behavioral tests. Together, our data indicate that the XBP1s/O-GlcNAc pathway is a promising target for CA therapy.
Outcomes of Pediatric Liver Transplantation in Japan: A Report from the Registry of the Japanese Liver Transplantation Society
Authors: Kasahara Mureo , Umeshita Koji , Eguchi Susumu , Eguchi Hidetoshi , Sakamoto Seisuke , Fukuda Akinari , Egawa Hiroto , Haga Hironori , Kokudo Norihiro , Sakisaka Shotaro , Takada Yasutsugu , Tanaka Eiji , Uemoto Shinji , Ohdan Hideki
Published: January 2021

Background.

The Japanese Liver Transplantation Society (JLTS), a cooperative research consortium, was established in 1980 to characterize and follow trends in patient characteristics and graft survival among all liver transplant patients in Japan. This study analyzed factors that may affect the current outcomes of pediatric patients who undergo liver transplantation (LT) by evaluating one of the largest pediatric LT cohorts in the world.

Methods.

Between November 1989 and December 2018, 3347 pediatric patients underwent LT in Japan. The survival outcomes of each donor and recipient variant were evaluated.

Results.

The procedures performed during the study period included living donor LT (LDLT; n = 3271), deceased donor LT (DDLT; n = 69), and domino LT (n = 7). There were 1510 male (45.1%) and 1837 female (54.9%) recipients with a median age of 1.7 y (range: 9 d to 17.9 y). The graft survival rates at 1, 10, 20, and 30 y were 88.9%, 82.2%, 77.1%, and 75.4%, respectively. Donor age, donor BMI, blood type incompatibility, recipient age, etiology of liver disease, transplant type, center experience, and transplant era were found to be significant predictors of overall graft survival. LDLT is a major treatment modality for the end-stage liver disease in children; DDLT and domino LT were applied as alternative treatments for LDLT in patients with specific pediatric liver diseases that are considered to have a poor prognosis following LDLT.

Conclusions.

Satisfactory long-term pediatric patient survival outcomes were achieved in the JLTS series, and we should continue to promote the deceased donor organ transplantation program in Japan.
Portal Vein Thrombosis May Be More Strongly Associated With Islet Infusion Than Extreme Thrombocytosis After Total Pancreatectomy With Islet Autotransplantation
Authors: Boucher Alexander A. , Wastvedt Solvejg , Hodges James S. , Beilman Gregory J. , Kirchner Varvara A. , Pruett Timothy L. , Hering Bernhard J. , Schwarzenberg Sarah J. , Downs Elissa , Freeman Martin , Trikudanathan Guru , Chinnakotla Srinath , Bellin Melena D.
Published: January 2021

Background.

Total pancreatectomy with islet autotransplantation (TPIAT) involves pancreatectomy, splenectomy, and reinjection of the patient’s pancreatic islets into the portal vein. This process triggers a local inflammatory reaction and increase in portal pressure, threatening islet survival and potentially causing portal vein thrombosis. Recent research has highlighted a high frequency of extreme thrombocytosis (platelets ≥1000 × 109/L) after TPIAT, but its cause and association with thrombotic risk remain unclear.

Methods.

This retrospective single-site study of a contemporary cohort of 409 pediatric and adult patients analyzed the frequency of thrombocytosis, risk factors for thrombosis, and antiplatelet and anticoagulation strategies.

Results.

Of 409 patients, 67% developed extreme thrombocytosis, peaking around postoperative day 16. Extreme thrombocytosis was significantly associated with infused islet volumes. Thromboembolic events occurred in 12.2% of patients, with portal vein thromboses occurring significantly earlier than peripheral thromboses. Portal vein thromboses were associated with infused islet volumes and portal pressures but not platelet counts or other measures. Most thromboembolic events (82.7%) occurred before the postoperative day of maximum platelet count. Only 4 of 27 (14.8%) of portal vein thromboses occurred at platelet counts ≥500 × 109/L. Perioperative heparin was given to all patients. Treatment of reactive thrombocytosis using aspirin in adults and hydroxyurea in children was not associated with significantly decreased thromboembolic risk.

Conclusions.

These results suggest that post-TPIAT thrombocytosis and portal vein thromboses may be linked to the islet infusion inflammation, not directly to each other, and further reducing this inflammation may reduce thrombosis and thrombocytosis frequencies simultaneously.
Treating Type 1 Diabetes by Pancreas Transplant Alone: A Cohort Study on Actual Long-term (10 Years) Efficacy and Safety
Authors: Boggi Ugo , Baronti Walter , Amorese Gabriella , Pilotti Silvia , Occhipinti Margherita , Perrone Vittorio , Marselli Lorella , Barsotti Massimiliano , Campani Daniela , Gianetti Elena , Insilla Andrea Cacciato , Bosi Emanuele , Kaufmann Emanuele , Terrenzio Chiara , Vistoli Fabio , Marchetti Piero
Published: January 2021

Background.

Physiologically regulated insulin secretion and euglycemia are achievable in type 1 diabetes (T1D) by islet or pancreas transplantation. However, pancreas transplant alone (PTA) remains a debated approach, with uncertainties on its relative benefits and risks. We determined the actual long-term (10 y) efficacy and safety of PTA in carefully characterized T1D subjects.

Methods.

This is a single-center, cohort study in 66 consecutive T1D subjects who received a PTA between April 2001 and December 2007, and were then all followed until 10 y since transplant. Main features evaluated were patient survival, pancreas graft function, C-peptide levels, glycemic parameters, and the function of the native kidneys.

Results.

Ten-year actual patient survival was 92.4%. Optimal (insulin independence) or good (minimal insulin requirement) graft function was observed in 57.4% and 3.2% of patients, respectively. Six (9.0%) patients developed stage 5 or 4 chronic kidney disease. In the remaining individuals bearing a successful PTA, estimated glomerular filtration rate (eGFR) decline per year was −2.29 ± 2.69 mL/min/1.73 m2. Reduction of eGFR at 1 y post-PTA was higher in those with pre-PTA hyperfiltration and higher HbA1c concentrations; eGFR changes afterward significantly correlated with diabetes duration. In recipients with normoglycemia at 10 y, 74% of normoalbuminuric or microalbuminuric subjects pre-PTA remained stable, and 26% progressed toward a worse stage; conversely, in 62.5% of the macroalbuminuric individuals albuminuria severity regressed.

Conclusions.

These long-term effects of PTA on patient survival, graft function, and the native kidneys support PTA as a suitable approach to treat diabetes in selected T1D patients.
Influence of Cold Ischemia Time on the Outcome of Kidney Transplants from Donors Aged 70 Years and Above—A Collaborative Transplant Study Report
Authors: Echterdiek Fabian , Latus Joerg , Döhler Bernd , Schwenger Vedat , Süsal Caner
Published: January 2021

Background.

The use of kidney allografts from ≥70-y-old donors has increased persistently over the last 20 y. Prolonged cold ischemia time (CIT) is well known to increase graft failure risk. However, despite their growing importance, no data are available on the impact of CIT, specifically on survival of allografts from ≥70-y-old donors.

Methods.

In total, 47 585 kidney transplantations from expanded criteria donors (ECDs) performed during 2000–2017 and reported to the Collaborative Transplant Study were analyzed. The impact of CIT on 5-y death-censored graft and patient survival was studied for transplantations from <70-y (n = 33 305) and ≥70-y-old ECDs (n = 14 280).

Results.

Compared with the reference of ≤12 h CIT, a CIT of 13–18 h did not increase the risk of graft failure significantly, either for recipients of kidneys from <70-y or from ≥70-y-old ECDs. In contrast, graft failure risk increased significantly when CIT exceeded 18 h, both in recipients of kidneys from <70-y and, more pronounced, from ≥70-y-old ECDs (CIT 19–24 h: hazard ratio [HR] = 1.19 and 1.24; P < 0.001; CIT ≥24 h: HR = 1.28 and 1.32, P < 0.001 and P =0.003, respectively). Within the 18-h CIT interval, additional HLA matching further improved survival of ECD transplants significantly, whereas the negative impact of a prolonged CIT >18 h was stronger in ≥65-y-old recipients and for transplants with multiple HLA mismatches. The influence of CIT on patient survival was less pronounced.

Conclusions.

CIT, as long it is kept ≤18 h, has no significant impact on survival of kidney transplants, even from ≥70-y-old ECDs.
Identification of Crp as a novel regulator of the Std fimbrial expression in Salmonella
Authors: Dufresne Karine , Daigle France
Published: January 2021

The

Salmonella enterica

serovar Typhi genome contains 14 putative fimbrial systems. The Std fimbriae belong to the chaperone-usher family and its regulation has not been investigated in S. Typhi. Several regulators of Std were previously identified in the closely related serovar Typhimurium. We hypothesize that regulators of S. Typhimurium may be shared with S. Typhi, but that several other regulators remain to be discovered. Here, we describe the role of more than 50 different candidate regulators on std expression. Three types of regulators were investigated: known regulators in S. Typhimurium, in silico predicted regulators and virulence/metabolic regulators. Expression of std was determined in the regulator mutants and compared with the wild-type strain. Overall, 21 regulator mutations affect std promoter expression. The role of Crp, a newly identified factor for std expression, was further investigated. Crp acted as an activator of std expression on a distal region of the std promoter region. Together, our results demonstrate the major influence of Crp as a novel transcriptional factor on std promoter expression and later production of Std fimbriae in

Salmonella

.
The N501Y mutation in SARS-CoV-2 spike leads to morbidity in obese and aged mice and is neutralized by convalescent and post-vaccination human sera
Authors: Rathnasinghe Raveen , Jangra Sonia , Cupic Anastasija , Martínez-Romero Carles , Mulder Lubbertus C.F. , Kehrer Thomas , Yildiz Soner , Choi Angela , Mena Ignacio , De Vrieze Jana , Aslam Sadaf , Stadlbauer Daniel , Meekins David A. , McDowell Chester D. , Balaraman Velmurugan , Richt Juergen A. , De Geest Bruno G. , Miorin Lisa ,   PVI study group, Krammer Florian , Simon Viviana , García-Sastre Adolfo , Schotsaert Michael
Published: January 2021

The current COVID-19 (coronavirus disease 19) pandemic, caused by SARS-CoV-2, disproportionally affects the elderly and people with comorbidities like obesity and associated type 2 diabetes mellitus. Small animal models are crucial for the successful development and validation of antiviral vaccines, therapies and to study the role that comorbidities have on the outcome of viral infections. The initially available SARS-CoV-2 isolates require adaptation in order to use the mouse angiotensin converting enzyme 2 (mACE-2) entry receptor and to productively infect the cells of the murine respiratory tract. We have “mouse-adapted” SARS-CoV-2 by serial passaging a clinical virus isolate in the lungs of mice. We then used low doses of this virus in mouse models for advanced age, diabetes and obesity. Similar to SARS-CoV-2 infection in humans, the outcome of infection with mouse-adapted SARS-CoV-2 resulted in enhanced morbidity in aged and diabetic obese mice. Mutations associated with mouse adaptation occurred in the S, M, N and ORF8 genes. Interestingly, one mutation in the receptor binding domain of the S protein results in the change of an asparagine to tyrosine residue at position 501 (N501Y). This mutation is also present in the newly emerging SARS-CoV-2 variant viruses reported in the U.K. (20B/501Y.V1, B1.1.7 lineage) that is epidemiologically associated with high human to human transmission. We show that human convalescent and post vaccination sera can neutralize the newly emerging N501Y virus variant with similar efficiency as that of the reference USA-WA1/2020 virus, suggesting that current SARS-CoV-2 vaccines will protect against the 20B/501Y.V1 strain.
Overcrowding and Exposure to Secondhand Smoke Increase Risk for COVID-19 Infection Among Latinx Families in Greater San Francisco Bay Area
Authors: Mendez Andrea DeCastro , Escobar Milagro , Romero Maria , Wojcicki Janet M.
Published: January 2021

Background

The novel coronavirus (COVID-19) has disproportionately impacted the Latinx community in the United States. Environmental risk factors, including community level pollution burden and exposure to smoking and secondhand smoke, have not been evaluated in relation to risk for infection with COVID-19.

Methods

We evaluated self-reported infection rates of COVID-19 in three, preexisting, longitudinal, Latinx family cohorts in the San Francisco Bay Area from May through September 2020 (N=383 households, 1,875 people). All households were previously recruited during pregnancy and postpartum at Zuckerberg San Francisco General Hospital (ZSFG) and UCSF Benioff before the pandemic. For the COVID-19 sub-study, participants responded to a 15-minute telephonic interview where we assessed food consumption patterns, housing and employment status, and history of COVID-19 infection based on community and hospital-based testing. We also evaluated secondhand smoke exposure based on previously collected self-reported data. Environmental pollution exposure was determined from census tract residence using California’s EnviroScreen 2.0 data. Non-parametric tests and multiple logistic regression were used to assess possible associations and independent predictors of COVID-19 infection.

Results

In the combined Latinx, Eating and Diabetes Cohort (LEAD) and Hispanic, Eating and Nutrition (HEN) cohorts there was a 7.6% household infection rate (14/183) with a lower rate of 3.5% (7/200) in the Telomeres at Birth (TAB) cohort. Larger household size increased risk for infection (OR, 1.43 (95%CI 1.10-1.87)) in the combined LEAD/HEN cohorts and increasing number of children trended towards significance in the TAB cohort (OR 1.82, 95% CI 0.98-3.37). Any exposure to secondhand smoke in the household also trended towards increasing risk after adjusting for household size and other exposures (OR 3.20, 95%CI 0.80-12.73) and (OR 4.37, 95% CI 0.80-23.70). We did not find any associations between neighborhood pollution level based on census track location and risk of infection. Furthermore, we found weak evidence between dietary exposure and risk of COVID-19 infection after adjusting for possible confounders.

Conclusion

Crowding as indicated by household size increases risk for COVID-19 infection in Latinx families. Exposure to secondhand smoke may also increase risk for COVID-19 through increased coughing, respiratory impairment and increased travel of virus on smoke particles. Public policy and health interventions need to ensure that multiunit residential complexes prevent any exposure to secondhand smoke.
Helarchaeota and Co-occurring Sulfate-Reducing Bacteria in Subseafloor Sediments from the Costa Rica Margin
Authors: Zhao Rui , Biddle Jennifer F.
Published: January 2021

Deep sediments host many archaeal lineages, including those of the Asgard superphylum that may depend on/require syntrophic partnerships. Our knowledge about sedimentary archaeal diversity and their metabolic pathways and syntrophic partners is still very limited. We present here new genomes of Helarchaeota and co-occurring sulfate-reducing bacteria (SRB) recovered from organic-rich sediments off Costa Rica Margin. Our molecular analyses revealed three new metagenome-assembled genomes (MAGs) affiliating with Helarchaeota, each of which has three variants of the methyl-CoM reductase-like (MCR-like) complex that may enable them to oxidize short-chain alkanes anaerobically. These Helarchaeota have no multi-heme cytochromes (MHCs) but have Group 3b and Group 3c [NiFe] hydrogenases, and formate dehydrogenase, and therefore could transfer the reducing equivalents generated from alkane oxidation to external partners via the transfer of these substances. We also recovered five MAGs of SRB affiliated with the class of Desulfobacteria, two of which showed relative abundances (represented by genome coverages) positively correlated with those of the three Helarchaeota. Genome analysis suggested that these SRB bacteria have the capacity of H2and formate utilizations and may facilitate electron transfers from other organisms by means of these reduced substances. Our findings suggest that Helarchaeota may metabolize synergistically with SRB in marine anoxic sediments, and exert an important influence on the carbon cycle by mitigating the hydrocarbon emission from sediments to the overlying ocean.
Exploring overcrowding trends in an inner city emergence department in the UK before and during COVID-19 epidemic
Authors: Panovska-Griffiths J , Ross J , Elkhodair S , Baxter-Derrington C , Laing C , Raine R
Published: January 2021

Background

We compared impact of three pre-COVID-19 interventions and of the COVID-19 UK-epidemic and the first UK national lockdown on overcrowding within University College London Hospital Emergency Department (UCLH ED). The three interventions: target the influx of patients at ED (A), reduce the pressure on in-patients’ beds (B) and improve ED processes to improve the flow of patents out from ED (C).

Methods

We analysed the change in overcrowding metrics (daily attendances, the proportion of people leaving within four hours of arrival (four-hours target) and the reduction in overall waiting time) across three analysis. The first analysis used data 01/04/2017-31/12-2019 to calculate changes over a period of six months before and after the start of interventions A-C. The second and third analyses focused on evaluating the impact of the COVID-19 epidemic, comparing the first 10 months in 2020 and 2019, and of the first national lockdown (23/03/2020-31/05/2020).

Results

Pre-COVID-19 all interventions led to small reductions in waiting time (17%, p<0.001 for A and C;9%, p=0.322 for B) but also to a small decrease in the number of patients leaving within four hours of arrival (6.6%,7.4%,6.2% respectively A-C,p<0.001).

In presence of the COVID-19 pandemic, attendance and waiting time were reduced (40% and 8%;p<0.001), and the number of people leaving within four hours of arrival was increased (6%,p<0.001). During the first lockdown, there was 65% reduction in attendance, 22% reduction in waiting time and 8% increase in number of people leaving within 4 hours of arrival (p<0.001). Crucially, when the lockdown was lifted, there was an increase (6.5%,p<0.001) in the percentage of people leaving within four hours, together with a larger (12.5%,p<0.001) decrease in waiting time. This occurred despite the increase of 49.6%(p<0.001) in attendance after lockdown ended.

Conclusions

The mixed results pre-COVID-19 (significant improvements in waiting time with some interventions but not improvement in the four-hours target), may be due to a ‘spill-over effect’ where clogging up one part of the ED system affects other parts. Hence multifaceted interventions and a system-wide approach to improve the pathway of flow through the ED system is necessary.

During 2020 and in presence of the COVID-19 epidemic, a shift in public behaviour with anxiety over attending hospitals and higher use of virtual consultations, led to notable drop in UCLH ED attendance and consequential curbing of overcrowding.

Importantly, once the lockdown was lifted, although there was an increase in arrivals at UCLH ED, overcrowding metrics were reduced. Thus, the combination of shifted public behaviour and the restructuring changes during COVID-19 epidemic, maybe be able to curb future ED overcrowding, but longer timeframe analysis is required to confirm this.
Spatio-temporal analysis identifies hotspots of marine mammal strandings along the Indian coastline: implications for developing a National Marine Mammal Stranding Response and Management policy
Authors: Dudhat Sohini , Pande Anant , Nair Aditi , Mondal Indranil , Sivakumar Kuppusamy
Published: January 2021

Marine mammal strandings provide vital information on their life histories, population health and status of marine ecosystems. Opportunistic reporting of strandings serve as a potent low-cost tool for conservation monitoring of these highly mobile species. We present the results of spatio-temporal analyses of marine mammal stranding events to identify hotpots along Indian coastline. We collated data over a long-time frame (~270 years) available from various open access databases, reports and publications. Given the inadequacy in data collection over these years, we grouped data into four major groups viz. baleen whales, toothed whales, small cetaceans and dugongs. Further, we described the trends in data for marine mammal sightings, incidental mortalities, induced mortalities and stranding events using the last group for spatio-temporal analysis. Annual strandings along the Indian coast has increased considerably in the recent years (11.25 ± 9.10 strandings/ year), peaking in the last two years (2015-17, mean = 27.66±12.03 strandings /year). We found that number of strandings spiked in June- September along the west coast and December- January along the east coast. We identified several sections of coastline which have consistently received comparatively higher number of stranded animals (0.38 - 1.82 strandings/km) throughout the study period. Use of novel geospatial tool ‘Emerging Hotspot Analysis’ revealed new and consecutive hotspots along the north-west coast, and sporadic hotspots along the south-east coast. Despite the challenges of working with an opportunistic database, this study highlights critical areas to be prioritized for monitoring marine mammal strandings in the country. We recommend establishing regional marine mammal stranding response centres at the identified hotspots coordinated by a National Stranding Monitoring Centre with adequate funding support. Regular conduct of stranding response programs for field veterinarians, frontline personnel focused around identified stranding hotspots would help develop a comprehensive picture of marine mammal populations in Indian waters.
Recombination facilitates adaptive evolution in rhizobial soil bacteria
Authors: Cavassim Maria Izabel A. , Andersen Stig U. , Bataillon Thomas , Schierup Mikkel Heide
Published: January 2021

Homologous recombination is expected to increase natural selection efficacy by decoupling the fate of beneficial and deleterious mutations and by readily creating new combinations of beneficial alleles. Here, we investigate how the proportion of amino acid substitutions fixed by adaptive evolution (α) depends on the recombination rate in bacteria. We analyze 3086 core protein-coding sequences from 196 genomes belonging to five closely-related species of the genusRhizobium. These genes are found in all species and do not display any signs of introgression between species. We estimateαusing the site frequency spectrum (SFS) and divergence data for all pairs of species. We evaluate the impact of recombination within each species by dividing genes into three equally sized recombination classes based on their average level of intragenic linkage disequilibrium. We find thatαvaries from 0.07 to 0.39 across species and is positively correlated with the level of recombination. This is both due to a higher estimated rate of adaptive evolution and a lower estimated rate of non-adaptive evolution, suggesting that recombination both increases the fixation probability of advantageous variants and decreases the probability of fixation of deleterious variants. Our results demonstrate that homologous recombination facilitates adaptive evolution measured byαin the core genome of prokaryote species in agreement with studies in eukaryotes.

Significance statement

Whether intraspecific homologous recombination has a net beneficial or detrimental effect on adaptive evolution is largely unexplored in natural bacterial populations. We address this question by evaluating polymorphism and divergence data across the core genomes of 196 bacterial sequences––belonging to five closely related species of the genusRhizobium. We show that the proportion of amino acid changes fixed due to adaptive evolution (α) increases with an increased recombination rate. This correlation is observed both in the interspecies and intraspecific comparisons. By using a population genetics approach our results demonstrate that homologous recombination directly impacts the efficacy of natural selection in the core genome of prokaryotes, as previously reported in eukaryotes.
A bidirectional scanning method for scanning transmission X-ray microscopy
Authors: Sun Tianxiao , Zhang Xiangzhi , Xu Zijian , Wang Yong , Guo Zhi , Wang Jian , Tai Renzhong
Published: January 2021

Scanning mode is a key factor for the comprehensive performance, including imaging efficiency, of scanning transmission X-ray microscopy (STXM). Herein is presented a bidirectional scanning method designed for STXM with an S-shaped moving track. In this method, artificially designed ramp waves are generated by a piezo-stage controller to control the two-dimensional scanning of the sample. The sample position information is measured using laser interferometric sensors and sent to a field-programmable gate array (FPGA) board which also acquires the X-ray signals simultaneously from the detector. Since the data recorded by the FPGA contain the real position of each scanned point, the influence of the backlash caused by the back-turning movement on the STXM image can be eliminated. By employing an adapted post-processing program, a re-meshed high-resolution STXM image can be obtained. This S-track bidirectional scanning method in fly-scan mode has been implemented on the STXM endstation at the Shanghai Synchrotron Radiation Facility (SSRF), and successfully resolved the ∼30 nm interval between the innermost strips of a Siemens star. This work removes the limitation on bidirectional scanning caused by motor backlash and vibration, and significantly improves the efficiency of STXM experiments.
Tumor‐educated platelet SNORD55 as a potential biomarker for the early diagnosis of non‐small cell lung cancer
Authors: Dong Xiaohan , Song Xingguo , Ding Shanshan , Yu Miao , Shang Xiaoling , Wang Kangyu , Chang Minghui , Xie Li , Song Xianrang
Published: January 2021

Background

Despite the emerging insights into many snoRNAs (small nucleolar RNAs) which are detectable in body fluids and serve as noninvasive biomarkers, few studies have previously discussed the role of snoRNAs in tumor‐educated platelets (TEPs). Herein, we systematically estimated dysregulation of snoRNAs in non‐small cell lung cancer (NSCLC) and clarified the biomarker potential of SNORD55 in platelets.

Methods

We compared expression of snoRNAs between NSCLC and normal tissues using SNORic datasets. Platelets were isolated from plasma using low‐speed centrifugation and subjected to quantitative polymerase chain reaction (qPCR) for SNORD55 detection.

Results

SNORD55 was significantly decreased in TEPs from NSCLC patients especially in early‐stage patients compared with healthy controls. Importantly, we validated that TEP SNORD55 was capable of acting as a promising biomarker for NSCLC. It exerted diagnostic performance for NSCLC diagnosis, possessing an AUC of 0.803, as well as for early NSCLC diagnosis, possessing an AUC of 0.784. Moreover, the combination of TEP SNORD55 and carcinoembryonic antigen (CEA) improved the diagnostic efficiency of cancer progression. In addition, TEP SNORD55 also potentially acts as a noninvasive early biomarker for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) with favorable diagnostic efficiencies.

Conclusions

In summary, TEP SNORD55 could potentially serve as a noninvasive biomarker for NSCLC diagnosis and early diagnosis.

Key points

SNORD55 was significantly decreased in TEPs from NSCLC patients compared to healthy controls and acted as a novel biomarker for early NSCLC.
Preserving transcriptional stress responses as an anti‐aging strategy
Authors: Cheng Yang , Pitoniak Andrew , Wang Julia , Bohmann Dirk
Published: January 2021

The progressively increasing frailty, morbidity and mortality of aging organisms coincides with, and may be causally related to, their waning ability to adapt to environmental perturbations. Transcriptional responses to challenges, such as oxidative stress or pathogens, diminish with age. This effect is manifest in the declining function of the stress responsive transcription factor Nrf2. Protective gene expression programs that are controlled by the Drosophila Nrf2 homolog, CncC, support homeostasis and longevity. Age‐associated chromatin changes make these genes inaccessible to CncC binding and render them inert to signal‐dependent transcriptional activation in old animals. In a previous paper, we have reported that overexpression of the CncC dimerization partner Maf‐S counteracts this degenerative effect and preserves organism fitness. Building on this work, we show here that Maf‐S overexpression prevents loss of chromatin accessibility and maintains gene responsiveness. Moreover, the same outcome, along with an extension of lifespan, can be achieved by inducing CncC target gene expression pharmacologically throughout adult life. Thus, pharmacological or dietary interventions that can preserve stress responsive gene expression may be feasible anti‐aging strategies.
Basophil activation test: Mechanisms and considerations for use in clinical trials and clinical practice
Authors: Santos Alexandra F. , Alpan Oral , Hoffmann Hans‐Jürgen
Published: January 2021

The basophil activation test (BAT) is a functional assay that measures the degree of degranulation following stimulation with allergen or controls by flow cytometry. It correlates directly with histamine release. From the dose‐response curve resulting from BAT in allergic patients, basophil reactivity (%CD63+ basophils) and basophil sensitivity (EC50 or similar) are the main outcomes of the test. BAT takes into account all characteristics of IgE and allergen and thus can be more specific than sensitization tests in the diagnosis of allergic disease. BAT reduces the need for in vivo procedures, such as intradermal tests and allergen challenges, which can cause allergic reactions of unpredictable severity. As it closely reflects the patients' phenotype in most cases, it may be used to support the diagnosis of food, venom and drug allergies and chronic urticaria, to monitor the natural resolution of food allergies and to predict and monitor clinical the response to immunomodulatory treatments, such as allergen‐specific immunotherapy and biologicals. Clinical application of BAT requires analytical validation, clinical validation, standardization of procedures and quality assurance to ensure reproducibility and reliability of results. Currently, efforts are ongoing to establish a platform that could be used by laboratories in Europe and in the USA for quality assurance and certification.
Chilean and Transnational Performances of Disobedience: LasTesis and the Phenomenon of Un violador en tu camino
Authors: Martin Deborah , Shaw Deborah
Published: January 2021

This article analyses the performance Un violador en tu camino created by Chilean feminist theatre collective LasTesis, shared by millions and re‐staged across the globe. It explores the relationship between the original piece and theorist Rita Segato's insights on rape culture, and how it counters aspects of this culture. It examines how the transnational spread of Un violador counters tendencies of MeToo, and examines four cases of the performance's re‐staging in Latin America and beyond, showing how they make manifest the pervasiveness of rape culture as well as how groups have adapted them to speak to local issues.
Harmine alleviates atherogenesis by inhibiting disturbed flow‐mediated endothelial activation via protein tyrosine phosphatase PTPN14 and YAP
Authors: Yang Yujie , Ma Qiannan , Li Zhiyu , Wang Hui , Zhang Chenghu , Liu Yajin , Li Bochuan , Wang Yingmei , Cui Qinghua , Xue Fengxia , Ai Ding , Zhu Yi , He Jinlong
Published: January 2021

Background and Purpose

Disturbed flow induces endothelial dysfunction and contributes to uneven distribution of atherosclerotic plaque. Emerging evidence suggests that harmine, a natural constituent of extracts of Peganum harmala, has potent beneficial activities. Here, we investigated if harmine has an atheroprotective role under disturbed flow and the underlying mechanism.

Experimental Approach

Mice of ApoE−/−, LDLR−/−, and endothelial cell (EC)‐specific overexpression of yes‐associated protein (YAP) in ApoE−/− background were fed with a Western diet and given harmine for 4 weeks. Atherosclerotic lesion size, cellular composition, and expression of inflammatory genes in the aortic roots were assessed. HUVECs were treated with oscillatory shear stress (OSS) and harmine and also used for proteomic analysis.

Key Results

Harmine retarded atherogenesis in both ApoE−/− and LDLR−/− mice by inhibiting the endothelial inflammatory response. Mechanistically, harmine blocked OSS‐induced YAP nuclear translocation and EC activation by reducing phosphorylation of YAP at Y357. Overexpression of endothelial YAP blunted the beneficial effects of harmine in mice. Proteomic study revealed that protein tyrosine phosphatase non‐receptor type 14 (PTPN14) could bind to YAP. Moreover, harmine increased PTPN14 expression by stabilizing its protein level and inhibiting its degradation in proteasomes. PTPN14 knockdown blocked the effects of harmine on YAPY357 and EC activation. Finally, overexpression of PTPN14 mimicked the effects of harmine and ameliorated atherosclerosis, and knockdown of PTPN14 blunted the atheroprotective effects of harmine and accelerated atherosclerosis, in a partial ligation mouse model.

Conclusion and Implications

Harmine alleviated OSS‐induced EC activation via a PTPN14/YAPY357 pathway and had a potent atheroprotective role.
“Dancing” Together: Infant–Mother Locomotor Synchrony
Authors: Hoch Justine E. , Ossmy Ori , Cole Whitney G. , Hasan Shohan , Adolph Karen E.
Published: January 2021

Pre‐mobile infants and caregivers spontaneously engage in a sequence of contingent facial expressions and vocalizations that researchers have referred to as a social “dance.” Does this dance continue when both partners are free to move across the floor? Locomotor synchrony was assessed in 13‐ to 19‐month‐old infant–mother dyads (N = 30) by tracking each partner’s step‐to‐step location during free play. Although infants moved more than mothers, dyads spontaneously synchronized their locomotor activity. For 27 dyads, the spatiotemporal path of one partner uniquely identified the path of the other. Clustering analyses revealed two patterns of synchrony (mother‐follow and yo‐yo), and infants were more likely than mothers to lead the dance. Like face‐to‐face synchrony, locomotor synchrony scaffolds infants’ interactions with the outside world.
The diagnosis and management of subclinical hypothyroidism is assay‐dependent– Implications for clinical practice
Authors: Kalaria Tejas , Sanders Anna , Fenn Jonathan , Ashby Helen L. , Mohammed Pervaz , Buch Harit N. , Ford Clare , Gama Rousseau
Published: January 2021

Objective

We assessed the commutativity of Roche and Abbott thyroid assays in the diagnosis and management of subclinical hypothyroidism (SCH). The Roche and Abbott thyroid assays are used by approximately 75% of clinical laboratories in the UK.

Method

Consecutive samples received from primary care on patients with SCH who had a raised thyroid‐stimulating hormone (TSH) <10 mIU/L and a normal free thyroxine (fT4) from two laboratories using either Roche or Abbott thyroid assays were identified over 10 working days. Following identification, samples were analysed at the other site within 24 hours. Diagnostic and management discordance were studied using the relevant manufacturer‐provided reference ranges.

Results

We identified 93 patients with SCH (53 using the Roche assay). Roche TSH and fT4 results were respectively 40% ± 15% and 16% ± 7% higher (P < .001) compared to Abbott results. Of the 93 patients, 41 (44%) were concordant for SCH on both methods. Of the 53 patients with SCH on the Roche assays, 40 (75.5%) had normal thyroid function and 13 (24.5%) had SCH when analysed using the Abbott assays. Of the 40 patients with SCH on the Abbott assays, 28 (70%) had SCH and 12 (30%) had results indicative for levothyroxine replacement when analysed on the Roche assays. Of these 12 patients, four had TSH > 10 mIU/L, five had low fT4 and three had both.

Conclusion

The diagnosis and management of SCH is strikingly different when using TSH and fT4 assays provided by Abbott Laboratories and Roche Diagnostics. Clinicians and laboratorians should be aware that between‐assay differences and variations in reference ranges will directly impact the diagnosis and management of subclinical hypothyroidism.
The founder chief executive officer: A review of current insights and directions for future research
Authors: Abebe Michael A. , Li Pingshu , Acharya Keshab , Daspit Joshua J.
Published: January 2021

Research Question/Issue

From its inception in the late 1980s and early 1990s, founder‐chief executive officer (CEO) research has garnered significant scholarly attention in the strategy and entrepreneurship disciplines, although other fields—such as economics, finance, and family business—have also generated substantial research insight on this topic. Despite this progress, a limited consensus exists on the influence of the founder CEO owing to the fragmented nature of extant research. In this review, we address this fragmentation by reviewing current literature, synthesizing the discipline‐specific findings into an integrated framework, and highlighting promising directions for future founder‐CEO research.

Research Findings/Insights

Using a cross‐disciplinary review of founder‐CEO research based on 221 articles from 24 academic journals, we synthesize current research and provide directions for future research. Our framework organizes current research on the founder CEO into three broad themes. First, we review and synthesize scholarly work on factors related to the founder CEO during the nascent years of the firm. In the second theme, we review research that explores the impact of the founder CEO on strategic choices and firm configurations. In the third theme, we review the performance consequences of the founder CEO.

Theoretical/Academic Implications

This review advances research on the founder CEO by taking stock of insights from various disciplines, highlighting advancements made, and suggesting promising directions for future research on founder CEOs. Additionally, a critical evaluation of current methodological approaches provides opportunities for strengthening the rigor of scholarly inquiry in this area.

Practitioner/Policy Implications

This review provides corporate governance scholars and policymakers with a current, multidisciplinary summary of research findings on founder CEOs and their impact on the firm across various stages of the organizational life cycle.
Mtor inhibitors associated with higher cardiovascular adverse events—A large population database analysis
Authors: Nguyen Vi N. , Abagyan Ruben , Tsunoda Shirley M.
Published: January 2021

There are limited real‐world data available regarding adverse events (AEs) of immunosuppressants. We utilized the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2018 to perform a retrospective database analysis. We analyzed AE reports due to the individual agents tacrolimus, sirolimus, or everolimus and compared reporting odds ratios of the mTOR inhibitors to tacrolimus. The mTOR inhibitors arm had 1282 reports with 4176 AEs, while the tacrolimus arm had a total of 7587 reports with 20 940 individual AEs. mTOR inhibitors had significantly higher incidences of cardiovascular (ROR 1.95, 95% CI 1.70, 2.23), dermatologic (ROR 1.34, 95% CI 1.04, 1.73), endocrine (ROR 1.52, 95% CI 1.26, 1.82), gastrointestinal (ROR 1.15, 95% CI 1.01, 1.30), infectious disease (ROR 1.35, 95% 1.20, 1.52), musculoskeletal (ROR 1.39, 95% CI 1.13, 1.70), pulmonary (ROR 3.46, 95% 2.97, 4.03), renal (ROR 1.27, 95% CI 1.10, 1.46), and vascular AEs (ROR 3.10, 95% CI 2.14, 4.49). Across every organ type, mTOR inhibitors had greater cardiovascular AEs compared to tacrolimus, specifically in arteriosclerosis, heart failure, hypotension, tachycardia, chest pain, edema, and pericardial disorders. mTOR inhibitors may be associated with higher cardiovascular AEs. Further investigation is required to determine the potential mechanism of this effect.
Post‐transplant primary cutaneous peripheral T‐cell lymphoma not otherwise specified in a pediatric patient
Authors: Cardwell Leah A. , Majerowski Jacquelyn , Chiu Yvonne E. , Harrington Alexandra M. , Sokumbi Olayemi
Published: January 2021

Solid organ and hematopoietic stem cell transplantation may be complicated by the development of post‐transplant lymphoproliferative disorders (PTLDs). The World Health Organization categorizes PTLDs into four entities including non‐destructive, monomorphic, polymorphic, and classical Hodgkin lymphoma types. The most common PTLDs are B‐cell lymphomas, with T‐cell lymphomas accounting for only a few cases. Cutaneous T‐cell lymphomas are rarer still in post‐transplant patients with primary cutaneous peripheral T‐cell lymphoma being an extraordinarily rare subtype in this population. PTLDs may be aggressive and are often associated with high morbidity and mortality. Advances in medicine have led to increased awareness of PTLDs and improved diagnostic tools which assist in the diagnosis of these conditions. However, the clinical and histopathologic heterogeneity of PTLDs may make diagnosis a challenge. In the transplant patient population, the cutaneous manifestations of the lymphoproliferative disease may mimic other conditions, such as eczematous dermatitis and graft‐vs‐host disease. Herein, we report a case of post‐transplant primary cutaneous peripheral T‐cell lymphoma not otherwise specified (PTCL‐NOS) in a pediatric heart transplant patient and describe the clinical presentation and diagnostic histopathologic features.
Defining criteria for the reintroduction of locally extinct populations based on contemporary and ancient genetic diversity: The case of the Adriatic Beluga sturgeon (Huso huso)
Authors: Boscari Elisa , Marino Ilaria A. M. , Caruso Chiara , Gessner Jörn , Lari Martina , Mugue Nikolai , Barmintseva Anna , Suciu Radu , Onara Dalia , Zane Lorenzo , Congiu Leonardo
Published: January 2021

Aim

The restoration of the extinct Adriatic population of Beluga sturgeon, an iconic species with economic and traditional relevance, is a priority in upcoming conservation strategies but it must not occur without deep prior knowledge on the current diversity distribution. We defined informed criteria for the reintroduction of Beluga in Italian rivers by analysing its contemporary and ancient diversity based on a multi‐markers approach.

Location

Ponto–Caspian and Adriatic basins.

Methods

We examined the distribution pattern of genetic diversity of the extant beluga populations by conducting genetic analysis on the mitochondrial dLoop and 27 nuclear microsatellites in 119 individuals from 3 geographical basins (Azov, Black and Caspian seas) and genomic analysis on 893 SNPs isolated through the 2bRAD approach in a subgroup of 92 samples. Mitochondrial information was also used to evaluate the variability of the extinct Adriatic population by analysing a few available museum samples.

Results

The historical Adriatic sample cannot be traced back to any of the contemporary ones laying to hypothesize the presence of a past isolated population. Instead, mitochondrial data did not reveal any geographically based clustering possibly reflecting the deep paleogeographical changes experienced by those areas. The genomic approach allowed us to depict for the first time a clear and supported genetic differentiation between two areas (the Black–Azov and the Caspian basins) but microsatellites also revealed a signal of differentiation of the Azov sample, possibly related to historical management activities in that area.

Main conclusions

The outcomes of the study revealed an unprecedented amount of information that can provide great benefits to the establishment of ex situ Beluga broodstocks and support any future translocations. The provided guidelines should be taken as a reference for the upcoming restoring of the Italian extinct Beluga population and also for any future management activity of this species in its entire distribution range.
Rousseau's theory of value and the case of women
Authors: Rousselière Geneviève
Published: January 2021

In Emile, Rousseau claims that the value of women ought to be determined by the opinion that men have of them. Women, contrary to commodities and men, escape what I call Rousseau's “dual theory of value.” According to the latter, the apparent value of commodities and men is determined by opinion and either unrelated or inverse to “real value,” which is assessed through objective criteria. The dual theory of value is the basis of Rousseau's critique of commercial society. However, women warrant an exception to this theory. As women's apparent worth is their real worth, women are the unique object in the world that ought to be subjected to the rule of opinion, which is the rule of commercial market that Rousseau so violently rejects. This article investigates why this is the case and locates three functions to the unique position of women in Rousseau's theory of value.