bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer-testis non-coding RNA LEF1-AS1 regulates the nuclear translocation of PDCD5 and suppresses its interaction with p53 signaling: a novel target for immunotherapy in esophageal squamous cell carcinoma
Authors: Xiao Zhihan , Si Mingxuan , Cao Jing , Chen Xiru , Wang Zichen , Zhang Tongyu , Zhou Yichan , Li Hai , Dai Juncheng , Wang Cheng , Chen Liang , Xu Jing
Published: February 2023

Despite the improvement of current classical treatment, the prognosis of esophageal squamous cell carcinoma (ESCC) remains poor. Immunotherapy, as a new treatment method, has revolutionized the therapy of various cancer types and created more attractive for ESCC. Cancer-testis genes (CTGs), because of its characteristic expression and immunomodulation property, are considered as the ideal targets for tumor immunotherapy. However, the ESCC-specific CTGs, especially long non-coding RNA (lncRNA), has not been elucidated. In the present study, a systematic strategy was adopted to screen ESCC-specific cancer-testis lncRNA (CT-lncRNA). Collectively, 447 genes were recognized as ESCC-specific CT-lncRNAs, in particularly LEF1-AS1 showed the most aberrantly expression and clinically associated with poor outcome. Functional assays revealed that H3K27 acetylation in LEF1-AS1 promoter might give rise to the activation of LEF1-AS1 during ESCC tumorigenesis. The activated LEF1-AS1 was predominantly localized in the cytoplasm implicated in regulation of apoptosis and proliferation capacities of ESCC cells in vitro and in vivo. Further mechanistic studies unveiled that LEF1-AS1 participated in ESCC by interacting with RNA binding protein PDCD5 through weakened its nuclear translocation binding to TP53, leading to p53 degradation and disruption the transcription of downstream genes. Taken together, our findings suggest that LEF1-AS1 acts as a CT-lncRNA and might be an ideal immunotherapeutic target for clinical intervention for ESCC.
Genomic coevolution of papillomavirus and immune system in placental mammals indicates the role of IFN-γ in the emergence of new variants
Authors: Karamveer  , Tiwary Basant K
Published: February 2023

Papillomaviruses (PVs) are causative agents for warts and cancers in different parts of the body in the mammalian lineage. Therefore, these viruses are proposed as model organisms to study host immune responses to pathogens causing chronic infections. The virus-associated cancer progression depends on two integral processes namely angiogenesis and immune response (AIR). The angiogenesis process aids in tumour progression through vessel formation and maturation but the host immune response, in contrast, makes every attempt to eliminate pathogens and thereby maintain healthy tissues. However, the evolutionary contribution of individual viral genes and host AIR genes in carcinogenesis is yet to be explored. Here, we applied the evolutionary genomics approach to find correlated evolution between six PV genes and 23 host AIR-related genes. We estimated that interferon (IFN)-γ is the only host gene evolving in a correlated manner with all six PV genes under study. Furthermore, three PV genes, such as L2, E6 and E7, are found to interact with two thirds of host AIR-related genes. Moreover, a combined differential gene expression analysis and network analysis showed that inflammatory cytokine IFN-γ is the key regulator of hub genes in the protein–protein interaction network of the differentially expressed genes. Functional enrichment of these hub genes is consistent with their established role in different cancers and viral infections. Overall, we conclude that IFN-γ maintains selective pressure on mammalian PV genes and seems to be a potential biomarker for PV-related cancers. This study demonstrates the evolutionary importance of IFN-γ in deciding the fate of carcinogenic PV variants.
Research on cooling-temperature control strategy of fuel-cell engine test bench
Authors: Du Chang , Ma Tiancai , Lin Weikang , Song Kaihang , Liang Yonghao
Published: February 2023

As one of the important ways to utilize hydrogen energy, fuel cells are receiving more and more attention and research from countries and institutions. To meet the practical needs of testing the performance of high-power fuel-cell systems and simulate the actual application environment as much as possible, a fuel-cell system test bench is usually used to test the system performance, in which the cooling-temperature control of the test bench has a great impact on the results of the performance of the fuel-cell system. This paper studies the cooling-temperature control strategy of a 150-kW-class fuel-cell engine test platform, proposes a new test-bench cooling-system structure with a thermostat and heat exchanger as the main heat-dissipation components, and compares and analyzes the impact of coordinated thermostat and heat-exchanger control on the fuel-cell system test performance. The test results show that the control strategy of the coordinated operation of a thermostat and heat exchanger can maintain the steady-state error to within ±0.3℃ and maintain the temperature variation to within ±1.5℃ during the loading-condition test, so as to avoid the limitation of system output performance due to excessive cooling-temperature fluctuation and ensure that the fuel-cell engine performance-test process is carried out smoothly and efficiently.
CRISPR-gene-engineered CYBB knock-out PLB-985 cells, a useful model to study functional impact of X-linked chronic granulomatous disease mutations: application to the G412E X91+-CGD mutation
Authors: Beaumel Sylvain , Verbrugge Lucile , Fieschi Franck , Stasia Marie José
Published: February 2023

Chronic granulomatous disease (CGD) is a rare primary immune disorder caused by mutations in one of the five subunits of the NADPH oxidase complex expressed in phagocytes. Two-thirds of CGD cases are caused by mutations in CYBB that encodes NOX2 or gp91phox. Some rare X91+-CGD point mutations lead to a loss of function but with a normal expression of the mutated NOX2 protein. It is therefore necessary to ensure that this mutation is indeed responsible for the loss of activity in order to make a safe diagnosis for genetic counselling. We previously used the X-CGD PLB-985 cell model of M.C. Dinauer obtained by homologous recombination in the original PLB-985 human myeloid cell line, in order to study the functional impact of such mutations. Although the PLB-985 cell line was originally described by K.A. Tucker et al. in1987 as a distinct cell line isolated from a patient with acute nonlymphocytic leukemia, it is actually identified as a subclone of the HL-60 cells. In order to use a cellular model that meets the quality standard for the functional study of X91+-CGD mutations in CGD diagnosis, we developed our own model using the CRISPR-Cas9 technology in a certified PLB-985 cell line from DSMZ-German Collection of Microorganisms and Cell Cultures. Thanks to this new X-CGD model, we demonstrated that the G412E mutation in NOX2 found in a X91+-CGD patient prohibits access of the electron donor NADPH to its binding site explaining the absence of superoxide production in his neutrophils.
Crohn’s Disease Patient Experiences and Preferences With Disease Monitoring: An International Qualitative Study
Authors: Rohatinsky Noelle , Zelinsky Sandra , Dolinger Michael , Christensen Britt , Wilkens Rune , Radford Shellie , Dubinsky Marla , Novak Kerri
Published: February 2023

Background

Strategies incorporating objective disease monitoring in Crohn’s disease (CD), beyond clinical symptoms are important to improve patient outcomes. Little evidence exists to explore patient understanding of CD treatment goals, nor preferences and experiences with monitoring options. This qualitative study aimed to explore patient experiences and preferences of CD monitoring to inform monitoring strategies, improve patient engagement, and optimize a patient-centered approach to care.

Methods

This study used a patient-oriented, qualitative descriptive design. Convenience and snowball sampling were used to recruit adult participants diagnosed with CD who had experience with at least 2 types of disease monitoring. Online focus groups were conducted and data were analyzed using thematic analysis.

Results

This international study included 37 participants from Australia, Canada, United Kingdom, and the United States. Overall, participants preferred more noninvasive types of monitoring [eg, intestinal ultrasound (IUS)] but were willing to undergo more invasive monitoring (eg, colonoscopy) if required. To improve disease monitoring, participants wanted increased access to IUS, establishment of a patient-centered interdisciplinary team and access to information and self-testing. Participants identified challenges with communication between patients and providers and stressed the importance of participating in shared decision making and being equal team members in their care.

Conclusions

It is imperative to incorporate patient-driven preferences into how we can best structure monitoring strategies, to ensure equitable access to those preferred modalities and embrace a shared decision-making approach to disease management in CD.
Percutaneous large-bore aspiration embolectomy with veno-arterial extracorporal membrane oxygenation support or standby in patients with high-risk pulmonary embolism and contraindications to thrombolysis: a preliminary single centre experience
Authors: Kucher Nils , Ouda Ahmed , Voci Davide , Barco Stefano , Micieli Evy , Münger Mario , Pleming William , Grigorean Alexandru , Sromicki Juri , Schmiady Martin Oliver , Holy Erik W
Published: February 2023

Aims

Large-bore catheter aspiration embolectomy reduces thrombus burden and right ventricle strain and improves haemodynamics after pulmonary embolism (PE). Sparse data are available for patients with high-risk PE and contraindications to thrombolysis or thrombolysis failure, particularly if veno-arterial extracorporal membrane oxygenation (VA-ECMO) is required.

Methods and results

All patients with acute high-risk PE and contraindications to thrombolysis undergoing FlowTriever® percutaneous embolectomy and VA-ECMO circulatory support (or standby) at the University Hospital Zurich between April 2021 and August 2022 were retrospectively analysed. The primary outcome was the combination of recurrent PE, heart failure hospitalization, and all-cause death at 30 days. The analysis included 15 patients: mean age was 63.1 years and 14 (93%) were men. Overall, four (27%) patients presented with cardiac arrest, eight (53%) with ongoing obstructive shock, and three (20%) with persistent arterial hypotension. Veno-arterial extracorporal membrane oxygenation was implanted prior to aspiration embolectomy in eight (53%) patients. Three of seven patients without initial VA-ECMO support experienced periprocedural cardiac arrest, of whom two received ECMO support before completion of embolectomy. Veno-arterial extracorporal membrane oxygenation weaning was successful in all patients after a mean of 5.4 days. There was one periprocedural death in a patient who did not receive VA-ECMO support following a periprocedural cardiac arrest. The primary outcome at 30 days occurred in five (33.3%; 95% confidence interval 13.0–61.3%) patients.

Conclusion

This study provides preliminary evidence for the feasibility of percutaneous large-bore aspiration embolectomy in combination with VA-ECMO support (or standby) in patients with high-risk PE and contraindications to thrombolysis.
Differences between cardiac troponin I vs. T according to the duration of myocardial ischaemia
Authors: Espinosa Aaron Shekka , Hussain Shafaat , Al-Awar Amin , Jha Sandeep , Elmahdy Ahmed , Kalani Mana , Kakei Yalda , Zulfaj Ermir , Aune Emma , Poller Angela , Bobbio Emanuele , Thoirleifsson Sigurdur , Zeijlon Rickard , Gudmundursson Thorstein , Wernbom Mathias , Lindahl Bertil , Polte Christian L , Omerovic Elmir , Hammarsten Ola , Redfors Björn
Published: February 2023

Aims

Cardiac troponin T (cTnT) and troponin I (cTnI) are expressed as an obligate 1:1 complex in the myocardium. However, blood levels of cTnI often rise much higher than that of cTnT in myocardial infarction (MI), whereas cTnT is often higher in patients with stable conditions such as atrial fibrillation. Here we examine high-sensitive (hs) cTnI and hs-cTnT after different durations of experimental cardiac ischaemia.

Methods and results

hs-cTnI, hs-cTnT, and the hs-cTnT/hs-cTnI ratio were measured in plasma samples from rats before and at 30 and 120 min after 5, 10, 15, and 30 min of myocardial ischaemia. The animals were killed after 120 min of reperfusion, and the infarct volume and volume at risk were measured. hs-cTnI, hs-cTnT, and the hs-cTnT/hs-cTnI ratio were also measured in plasma samples collected from patients with ST-elevation myocardial infarction (STEMI). hs-cTnT and hs-cTnI increased over 10-fold in all rats subjected to ischaemia. The increase of hs-cTnI and hs-cTnT after 30 min was similar, resulting in a hs-cTnI/hs-cTnT ratio around 1. The hs-cTnI/hs-cTnT ratio was also around 1 in blood samples collected at 120 min in rats subjected to 5 or 10 min of ischaemia where no localized necrosis was observed. In contrast, the hs-cTnI/hs-cTnT ratio at 2 h was 3.6–5.5 after longer ischaemia that induced cardiac necrosis. The large hs-cTnI/hs-cTnT ratio was confirmed in patients with anterior STEMI.

Conclusion

Both hs-cTnI and hs-cTnT increased similarly after brief periods of ischaemia that did not cause overt necrosis, whereas the hs-cTnI/hs-cTnT ratio tended to increase following longer ischaemia that induced substantial necrosis. A low hs-cTnI/hs-cTnT ratio around 1 may signify non-necrotic cTn release.
Number of calcified aortic valve leaflets: natural history and prognostic value in patients undergoing haemodialysis
Authors: Kurasawa Shimon , Okazaki Masaki , Imaizumi Takahiro , Kondo Toru , Hishida Manabu , Nishibori Nobuhiro , Takeda Yuki , Kasuga Hirotake , Maruyama Shoichi
Published: February 2023

Aims

Aortic valve calcification in aortic sclerosis, a precursor of aortic stenosis (AS), is not always present in all three leaflets; how calcification develops in each leaflet is unknown. We aimed to investigate the natural history of calcification development in each aortic valve leaflet and the prognostic value of the number of calcified leaflets.

Methods and results

In a retrospective multicentre cohort study of patients undergoing haemodialysis without AS, we observed calcification development in each aortic valve leaflet using echocardiography. We investigated the association between the number of calcified leaflets and AS development and mortality using time-to-event analysis. Among the 1507 patients (mean age, 66 years; 66% male) included in the longitudinal echocardiography analysis, 709 (47%) had aortic sclerosis at baseline: one-leaflet calcified, 370 (52%); two-leaflet calcified, 215 (30%); and three-leaflet calcified, 124 (17%). The median time for one calcified leaflet increase was 3–4 years, and 251 (17%) patients developed AS during a median 3.2-year follow-up. The increased number of calcified aortic valve leaflets was associated with developing AS; compared with that of one-leaflet calcified, the adjusted hazard ratios (aHRs) [95% confidence intervals (CIs)] of two- and three-leaflet calcified were 2.12 (1.49–3.00) and 4.43 (3.01–6.52), respectively; the aHR (95% CI) per one calcified leaflet increase was 2.24 (1.96–2.55). It was also associated with all-cause mortality; the aHR (95% CI) per one calcified leaflet increase was 1.18 (1.08–1.27).

Conclusion

The number of calcified aortic valve leaflets strongly predicted AS development and even mortality in patients undergoing haemodialysis, suggesting the usefulness of assessing calcification for each valve leaflet separately using echocardiography.
Ventilator-assisted transcatheter edge-to-edge mitral valve repair for severe atrial functional mitral regurgitation: a case report
Authors: Masumoto Akiko , Yamamoto Hiroyuki , Takahashi Nobuyuki , Onishi Tetsuari , Takaya Tomofumi
Published: February 2023

Background

Atrial functional mitral regurgitation (AFMR) is an entity of mitral regurgitation (MR) in atrial fibrillation (AF) with dilated left atrium (LA) and/or normal left ventricular function. Transcatheter edge-to-edge mitral valve repair with MitraClip is reportedly an effective therapy for AFMR. However, performing MitraClip for patients with such condition is challenging because of its characteristic morphology.

Case summary

An 80-year-old man with permanent AF and severe MR was hospitalized for heart failure with preserved ejection fraction. On echocardiography, a marked dilation of the LA caused the anterior mitral leaflet to flatten along the mitral annulus (MA) plane. The posterior mitral leaflet was tethered towards the posterior left ventricle, thus producing a coaptation gap of 6.5 mm between the leaflets. Given his high surgical risk, MitraClip therapy was performed, but leaflet grasping was difficult because of the notable coaptation gap. When positive end-expiratory pressure (PEEP) was applied by mechanical ventilation, the MA gradually decreased in diameter. Under 20 cm H2O of PEEP, the coaptation gap decreased to 0 mm, which finally enabled the grasping of the leaflets. The clip was deployed, thus leaving only mild MR. Thereafter, the patient had an uneventful clinical course.

Discussion

In patients with AFMR, the sagittal dilation of the MA and asymmetry in the tethering angles of the leaflets often produce a marked coaptation gap, which poses a challenge in MitraClip therapy. In our patient, the ventilator-assisted technique effectively reduced the coaptation gap between the leaflets, thus leading to successful results.
Chest pain and Raynaud’s phenomenon after COVID-19 vaccination in a patient previously diagnosed with systemic lupus erythematosus: a case report
Authors: Kawano Hiroaki , Umeda Masataka , Okano Shinji , Kudo Takashi
Published: February 2023

Background

Cardiovascular events, including pericarditis, myocarditis, and myocardial ischaemia, have been reported as complications following COVID-19 vaccination.

Case summary

A 28-year-old Japanese woman diagnosed 10 years earlier with systemic lupus erythematosus and antiphospholipid syndrome was admitted to our hospital because of chest pain and Raynaud’s phenomenon. She had received a second dose of the COVID-19 BNT162b2 mRNA vaccine 28 days earlier. 123I-β-methyl iodophenyl pentadecanoic acid (BMIPP) and 201thallium dual myocardial single-photon emission computed tomography demonstrated mildly reduced perfusion of BMIPP in the mid-anterior wall of the left ventricle. Coronary angiography revealed normal coronary arteries; additionally, an endomyocardial biopsy was performed. Histopathological evaluation revealed a normal myocardium without cell infiltration. However, immunostaining for the severe acute respiratory coronavirus (SARS-CoV)/severe acute respiratory coronavirus 2 (SARS-CoV-2) spike protein was positive in the small intramural coronary arteries. The administration of azathioprine (50 mg/day) and amlodipine (5 mg/day) and increases in her prednisolone (10 mg/day) and aspirin doses led to improvements in the symptoms of the patient.

Discussion

Our data lead us to speculate that two events in the timeline of the patient, namely, receiving COVID-19 vaccination and the presence of SARS-CoV/SARS-CoV-2 spike protein in small intramural coronary arteries, may be related to the myocardial microangiopathy observed in this patient.
Bleeding and thrombotic events in post-cardiotomy extracorporeal life support
Authors: Schaefer Anne-Kristin , Latus Michaela , Riebandt Julia , Goliasch Georg , Bernardi Martin H , Laufer Günther , Zimpfer Daniel , Wiedemann Dominik
Published: February 2023

OBJECTIVES

Haemorrhagic and thrombotic complications are known obstacles in extracorporeal life support (ECLS), and patients requiring post-cardiotomy (PC)-ECLS are particularly prone. The objective of this study was to characterize the incidence, type and clinical relevance of bleeding and thrombotic events in patients on PC-ECLS.

METHODS

A total of 504 patients receiving PC-ECLS between 2000 and 2021 at a single centre were included in a retrospective analysis. Incidence and type of haemorrhagic and thrombotic complications in patients on PC-ECLS were assessed. Overall survival was compared, and perioperative risk factors for bleeding and thrombotic events were assessed by binary logistic regression.

RESULTS

Of the 504 patients requiring PC-ECLS, 196 patients (38.9%) had 235 bleeding events [surgical site: n = 135 (26.8%); cannulation site: n = 68(13.4%); requiring surgical revision: n = 39 (7.7%); cannulation site change: n = 17 (3.4%); fatal cannulation site bleeding: n = 4(0.8%); intracranial haemorrhage: n = 11 (2.1%); gastrointestinal haemorrhage: n = 8 (1.6%); pulmonary haemorrhage: n = 8 (1.6%); and intra-abdominal/retroperitoneal haemorrhage: n = 5 (1%)]. Overall mortality was higher in patients with major bleeding complications than in patients without bleeding complications (P < 0.0001).

A total of 74 patients (14.7%) had 84 thrombotic events [ischaemic stroke, n = 39 (7.7%); cannula/circuit thrombosis, n = 26 (5.2%); peripheral embolism, n = 11 (2.2%); device exchange for haemolysis, n = 8 (1.6%)]. Another 246 patients (48.8%) had at least 1 haemocompatibility-related adverse event. Preoperative dual antiplatelet therapy [adjusted odds ratio (OR): 1.83, 95% confidence interval (CI): 1.063–3.137] and ECLS duration (adjusted OR: 1.14, 95% CI: 1.086–1.197) were identified as independent risk factors for haemorrhage. Prior stroke/transient ischaemic attack (adjusted OR: 1.91, 95% CI: 1.08–3.83) and ECLS duration (adjusted OR: 1.09, 95% CI: 1.04–1.15) were identified as risk factors for thrombotic events.

CONCLUSIONS

Bleeding complications in patients on ECLS are common and significantly impair survival. Nearly half of the patients were affected by any haemocompatibility-related event.
Childhood adversity and risk of later labor market marginalization in young employees in Sweden
Authors: Björkenstam Emma , Helgesson Magnus , Mittendorfer-Rutz Ellenor
Published: February 2023

Background

The present study examined the independent and combined effects of childhood adversity (CA) and occupational class on the risk of future labor market marginalization (LMM) in young employees in Sweden. Occupational class (non-manual/manual workers) was also explored as a potential mediator.

Methods

This population-based longitudinal cohort study included 556 793 employees, 19–29 years, residing in Sweden in 2009. CAs included parental death, parental mental and somatic disorders, parental separation, household public assistance, single-parent household and residential instability. Measures of LMM included long-term unemployment (LTU), long-term sickness absence (LTSA) and disability pension. Estimates of risk of each LMM measure, between 2010 and 2016 were calculated as hazard ratios (HRs) with 95% confidence intervals (CIs), using a Cox regression analysis.

Results

Those exposed to CA had an elevated risk for all measures of LMM. Manual workers with a history of household public assistance had the highest risk estimates compared to non-manual workers with no CAs [adjusted HR spanning from 1.59 (LTSA) to 2.50 (LTU)]. Regardless of occupational class, the risk of LMM grew higher with increasing number of CAs (e.g. adjusted HR of LMM in manual workers with 3+ CAs: 1.87, 95% CI: 1.81–1.94). These patterns persisted after adjustments for a range of confounders, including psychiatric and somatic morbidity. Last, we found a small but significant mediating effect of occupational class in the association between CA and LMM.

Conclusions

Information on CAs are important determinants of LMM in young adults, and especially in manual workers.
The first consultation for low mood in general practice: what do patients find helpful?
Authors: Morgan Ian , Dowrick Chris , Macdonald Sara , Wilkes Scott , Watson Stuart
Published: February 2023

Background

Recent evidence suggests that the first consultation with a general practitioner (GP) for symptoms of depression may be more than just a vehicle for assessment and management planning (as current guidelines imply).

Objectives

To identify what patients find helpful, or otherwise, in their first consultation for low mood with a GP.

Methods

A cross-sectional questionnaire and interview study of patients with low mood who had recently consulted their GP, in the North of England. Patients were asked to complete a questionnaire regarding the consultation, and a Patient Health Questionnaire-9 (PHQ-9), within 2 weeks. They were also invited to take part in a face–face interview with a researcher. Both sources of data were subjected to qualitative thematic analysis.

Results

Thirty-seven questionnaires were returned; 5 interviews took place. The majority of participants felt better after consulting a GP for the first time for low mood. The factors most commonly cited as helpful were “being listened to” and “understanding or empathy from the GP.” Others included “admitting the problem,” “being reassured of normality,” and “being provided with optimism or hope for change.” The most commonly reported difficulty was the patients’ struggle to express themselves. Patients often felt that GP follow-up was inadequate.

Conclusions

These results suggest that the therapeutic benefit of the GP consultation is under-recognized in current guidelines. The results of our study will provide crucial information as to how such consultations can be tailored to improve patient satisfaction.
Quasi-2-D Bayesian inversion of central loop transient electromagnetic data using an adaptive Voronoi parametrization
Authors: Peng Ronghua , Yogeshwar Pritam , Liu Yajun , Hu Xiangyun
Published: February 2023

Central loop transient electromagnetic (TEM) data are often interpreted by conventional 1-D or quasi-2-D inversion techniques. For example, the lateral constrained inversion (LCI) is a powerful technique for quick interpretation of central loop TEM data, and can produce spatially consistent resistivity images for profile data by assuming spatial correlation between adjacent model parameters. Such quasi-2-D techniques are very powerful in cases multidimensional effects are small or negligible. However, the inverse solution of conventional LCI methods strongly depends on subjective interpreter choices such as the model regularization and the imposed lateral constraints. Due to inherent non-linearity and nonuniqueness of the TEM inverse problems, this can result in biased model parameters and their estimated model uncertainties. We present a transdimensional Markov chain Monte Carlo method for the quasi-2-D inversion of TEM data using a Bayesian inference framework. We term the approach quasi-2-D, since the model is parametrized in 2-D with unstructured Voronoi cells, whereas the TEM response at each station is predicted using a 1-D forward solution to make the problem computationally affordable. During the inversion, the number of Voronoi cells as well as their positions and resistivities are variable. Accordingly, the level of model complexity is automatically determined by the framework and adapted to the spatial resolution of the data, thus avoiding the need for subjective model regularization or spatial constraints. The approach is validated using synthetic data and compared to 1-D Bayesian and conventional Gauss Newton inversion techniques. The application to dense field data from a floating TEM survey leads to a consistent subsurface image with unbiased uncertainty estimates and a plausible depth of investigation. The quantitative uncertainty information provided by the Bayesian framework is beneficial in identifying resolution.
MUC5AC Genetic Variation Is Associated With Tuberculous Meningitis Cerebral Spinal Fluid Cytokine Responses and Mortality
Authors: Sabo Michelle C , Thuong Nguyen T T , Chang Xuling , Ardiansyah Edwin , Tram Trinh T B , Hai Hoang T , Nghia Ho D T , Bang Nguyen D , Dian Sofiati , Ganiem A Rizal , Shaporifar Shima , Kumar Vinod , Li Zheng , Hibberd Martin , Khor Chiea Chuen , Thwaites Guy E , Heemskerk Dorothee , van Laarhoven Arjan , van Crevel Reinout , Dunstan Sarah J , Shah Javeed A
Published: February 2023

Background

The purpose of this study was to assess if single nucleotide polymorphisms (SNPs) in lung mucins MUC5B and MUC5AC are associated with Mycobacterium tuberculosis outcomes.

Methods

Independent SNPs in MUC5B and MUC5AC (genotyped by Illumina HumanOmniExpress array) were assessed for associations with tumor necrosis factor (TNF) concentrations (measured by immunoassay) in cerebral spinal fluid (CSF) from tuberculous meningitis (TBM) patients. SNPs associated with CSF TNF concentrations were carried forward for analyses of pulmonary and meningeal tuberculosis susceptibility and TBM mortality.

Results

MUC5AC SNP rs28737416 T allele was associated with lower CSF concentrations of TNF (P = 1.8 × 10−8) and IFN-γ (P = 2.3 × 10−6). In an additive genetic model, rs28737416 T/T genotype was associated with higher susceptibility to TBM (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.03–1.49; P = .02), but not pulmonary tuberculosis (OR, 1.11, 95% CI, .98–1.25; P = .10). TBM mortality was higher among participants with the rs28737416 T/T and T/C genotypes (35/119, 30.4%) versus the C/C genotype (11/89, 12.4%; log-rank P = .005) in a Vietnam discovery cohort (n = 210), an independent Vietnam validation cohort (n = 87; 9/87, 19.1% vs 1/20, 2.5%; log-rank P = .02), and an Indonesia validation cohort (n = 468, 127/287, 44.3% vs 65/181, 35.9%; log-rank P = .06).

Conclusions

MUC5AC variants may contribute to immune changes that influence TBM outcomes.
Passenger vehicle interior decontamination by low concentration hydrogen peroxide vapor following a wide area biological contamination incident
Authors: Oudejans Lukas , Richter William , Sunderman Michelle , Calfee M Worth , Mickelsen R Leroy , Hofacre Kent , Keyes Patrick , Lee Sang Don
Published: February 2023

Aims

To assess low concentration hydrogen peroxide (LCHP) (H2O2) vapor dispersed with a home humidifier for its ability to decontaminate vehicle interiors contaminated with Bacillus anthracis surrogate Bacillus atrophaeus spores.

Methods and results

Efficacy of a vaporized 3% H2O2 solution was evaluated for liquid volumes, on/off vehicle heating, ventilation, and air conditioning (HVAC) system operations, and temperatures that ranged from 5 to 27°C. Survival of the spores was assessed by quantification of remaining viable spores with efficacy quantified in terms of mean log10 reduction. Decontamination efficacy after the 6-day dwell time increased when the 3% H2O2 liquid volume was doubled, increasing from 4-of-10 to 10-of-10 nondetects (zero colonies counted using standard dilution and filter plating) inside the vehicle cabin. Recirculating cabin air through the HVAC system during decontamination decreased efficacy to 6-of-10 non-detects. While no 6-log10 reduction in viable spores was observed on the cabin filter with the cabin filter kept in place, a 6-log10 reduction was achieved after its removal and placement in the cabin during treatment.

Conclusions

Results from this study allow for informed decisions on the use of LCHP vapor as an effective decontamination approach for vehicle interiors.
Multi-attention-based soft partition network for vehicle re-identification
Authors: Lee Sangrok , Woo Taekang , Lee Sang Hun
Published: February 2023

Vehicle re-identification helps in distinguishing between images of the same and other vehicles. It is a challenging process because of significant intra-instance differences between identical vehicles from different views and subtle inter-instance differences between similar vehicles. To solve this issue, researchers have extracted view-aware or part-specific features via spatial attention mechanisms, which usually result in noisy attention maps or otherwise require expensive additional annotation for metadata, such as key points, to improve the quality. Meanwhile, based on the researchers’ insights, various handcrafted multi-attention architectures for specific viewpoints or vehicle parts have been proposed. However, this approach does not guarantee that the number and nature of attention branches will be optimal for real-world re-identification tasks. To address these problems, we proposed a new vehicle re-identification network based on a multiple soft attention mechanism for capturing various discriminative regions from different viewpoints more efficiently. Furthermore, this model can significantly reduce the noise in spatial attention maps by devising a new method for creating an attention map for insignificant regions and then excluding it from generating the final result. We also combined a channel-wise attention mechanism with a spatial attention mechanism for the efficient selection of important semantic attributes for vehicle re-identification. Our experiments showed that our proposed model achieved a state-of-the-art performance among the attention-based methods without metadata and was comparable to the approaches using metadata for the VehicleID and VERI-Wild datasets.
Loan Amount versus Monthly Payments: The Effect of Loan Application Formats on Consumer Borrowing Decisions
Authors: Johnson Alicia M , Villanova Daniel , Smith Ronn J
Published: February 2023

Do different loan application formats affect consumer loan requests? Six studies show that when consumers are asked to provide a preferred monthly payment (MP) (vs. loan amount [LA]), they request different principal amounts. This is because these loan application formats differ in the scale-compatible information they bring to consumers’ mind. When LAs are elicited, consumers think of and request the cost of the expenditure they seek to finance. When MPs are elicited, however, consumers think of their monthly budget slack to construct and then request MPs they perceive to be affordable. For lower cost loans with a given term and interest rate, the MP (vs. LA) format results in larger principal requests. This effect reverses for higher cost acquisitions because individuals’ budget slack caps out around $500 per month. These studies provide insight into how consumer loan application formats can affect consumer borrowing, as well as the psychological underpinnings responsible for the effect. Theoretical, managerial, and consumer welfare implications of the findings are discussed.
Degradation of helicase-like transcription factor (HLTF) by β-TrCP promotes hepatocarcinogenesis via activation of the p62/mTOR axis
Authors: Tan Ye , Wu Di , Liu Ze-Yu , Yu Hong-Qiang , Zheng Xiang-Ru , Lin Xiao-Tong , Bie Ping , Zhang Lei-Da , Xie Chuan-Ming
Published: February 2023

Helicase-like transcription factor (HLTF) has been found to be involved in the maintenance of genome stability and tumour suppression, but whether its downregulation in cancers is associated with posttranslational regulation remains unclear. Here, we observed that HLTF was significantly downregulated in hepatocellular carcinoma (HCC) tissues and positively associated with the survival of HCC patients. Mechanistically, the decreased expression of HLTF in HCC was attributed to elevated β-TrCP-mediated ubiquitination and degradation. Knockdown of HLTF enhanced p62 transcriptional activity and mammalian target of rapamycin (mTOR) activation, leading to HCC tumourigenesis. Inhibition of mTOR effectively blocked β-TrCP overexpression- or HLTF knockdown-mediated HCC tumourigenesis and metastasis. Furthermore, in clinical tissues, decreased HLTF expression was positively correlated with elevated expression of β-TrCP, p62, or p-mTOR in HCC patients. Overall, our data not only uncover new roles of HLTF in HCC cell proliferation and metastasis, but also reveal a novel posttranslational modification of HLTF by β-TrCP, indicating that the β-TrCP/HLTF/p62/mTOR axis may be a new oncogenic driver involved in HCC development. This finding provides a potential therapeutic strategy for HCC patients by targeting the β-TrCP/HLTF/p62/mTOR axis.
Double vision approach applied by two teams for retrosternal gastric conduit for gastric tube cancer
Authors: Machino Ryusuke , Kobayashi Shinichiro , Tagawa Tsutomu , Taniguchi Ken , Kanetaka Kengo , Eguchi Susumu , Nagayasu Takeshi
Published: February 2023

Gastric tube cancer is classically treated with resection through a midline sternal incision. However, because of its invasiveness and limited reconstructive potential, transdiaphragmatic laparoscopic or thoracoscopic dissection of the gastric tube has been investigated. As resection from only the abdominal or thoracic cavity is difficult, we performed surgery with a thoracic surgeon approaching from the thoracic cavity and an abdominal surgeon simultaneously approaching from the cervical and abdominal regions. The gastric tube may be tightly adhered to the back of the sternum, cervicothoracic transition or thoracoabdominal transition. Dissection can be safely performed by operating from two directions simultaneously, the neck and chest or chest and abdomen, to successfully withdraw the gastric tube from the abdominal cavity. We performed this surgery in four cases. This collaborative operation provided a good surgical view and allowed for safe dissection of the gastric tube without requiring sternotomy.
Ossification of ligamentum flavum related to progressive thoracic myelopathy and acute paraplegia in a Central-European male with a thoracic kyphoscoliosis
Authors: Erdani Danijel , Topolovec Matevž , Hero Nikša , Brumat Peter
Published: February 2023

The ossification of the ligamentum flavum (OLF) presents a significant risk factor in the development of spinal cord compression in the (lower) thoracic spine, particularly in eastern Asian elderly males. The definite causes for OLF have not yet been fully uncovered, whereby age, genetics, metabolic disorders and mechanical stress are deemed among the most plausible pathophysiological factors in OLF. Spinal deformities (mostly kyphotic) are associated with an excess in tensile forces, which may lead to hypertrophy and OLF. This unique case of OLF-related acute paraplegia and progressive thoracic myelopathy in a Central-European male patient may indicate the role of a (kyphoscoliotic) spinal deformity in the initiation and progression of the OLF-related (thoracic) myelopathy. Promptly initiated surgical decompression and (partial) deformity correction may, along with proper subsequent intradisciplinary rehabilitation process, greatly improve the clinical outcome post-treatment, especially in terms of quality of life and residual pain.
Spontaneous periduodenal hematoma: a rare surgical and radiological conundrum
Authors: Padar Maria , Rieseberg Amie , Hendahewa Rasika
Published: February 2023

This is a case of a 68-year-old female with spontaneous and rare periduodenal hematoma of unknown origin without any signs or symptoms of duodenal stenosis. All causes of known precipitating factors, such as trauma, intervention, anticoagulation, pancreatitis or malignant processes, were ruled out. She was managed conservatively, with a series of radiological investigations performed throughout her 7-day admission to further define stability and investigate the possible cause for the periduodenal hemorrhage. A repeat magnetic resonance imaging 4 weeks later showed near resolution of the hematoma. The underlying cause in this case remains unclear.
Discovery of optical emission associated with the supernova remnant G107.5−1.5
Authors: Bakış H , Bulut G , Bakış V , Sano H , Sezer A
Published: February 2023

We present the first results from an imaging and a spectroscopic survey of the optical emission associated with supernova remnant (SNR) G107.5−1.5. We discovered optical diffuse and filamentary emission from G107.5−1.5 using the 1.5- and 1-m telescopes. The optical emissions from the North-East (NE) and North-West (NW) regions show the diffuse structure, while the South-East (SE) and East (E) regions show filamentary structure. From long-slit spectra, we found [S ii]/H α > 0.5 for the SE and E regions, which supports the origin of the emission being from shock-heated gas. The average [S ii]/H α ratio is found to be ∼0.4 and ∼0.3 for the NW and NE regions, respectively, indicating that the optical emission is coming from ionized gas in an H ii region. From the ratios of [S ii]λλ 6716/6731, we estimate an average electron density of ∼2400 cm−3 for the NW region, which can be attributed to the dense ionized gas. The average [S ii]λλ 6716/6731 ratios are ∼1.25 and ∼1.15 for the SE and E regions, respectively, which are indicative of low-electron density.
Varying alpha, blinding, and bias in existing measurements
Authors: Lee Chung-Chi , Webb John K , Carswell Robert F , Dzuba Vladimir A , Flambaum Victor V , Milaković Dinko
Published: February 2023

The high resolution spectrograph ESPRESSO on the VLT allows measurements of fundamental constants at unprecedented precision and hence enables tests for space–time variations predicted by some theories. In a series of recent papers, we developed optimal analysis procedures that expose and eliminate the subjectivity and bias in previous quasar absorption system measurements. In this paper, we analyse the ESPRESSO spectrum of the absorption system at zabs = 1.15 towards the quasar HE 0515-4414. Our goal here is not to provide a new unbiased measurement of Δα/α in this system (that will be done separately). Rather, it is to carefully examine the impact of blinding procedures applied in many previous measurements of the fine structure constant in quasar absorption systems. To do this, we emulate previous procedures, using supercomputer Monte Carlo AI calculations to generate a large number of independently constructed models of the absorption complex. Each model is obtained using ai-vpfit, with Δα/α fixed until a ‘final’ model for the absorption system is obtained, at which point Δα/α is then released as a free parameter for one final optimization. The results show that the value of Δα/α obtained in this way is systematically biased towards the initially fixed value i.e. this process produces measurements that are unrelated to the true value of Δα/α. The implication is straightforward: to avoid bias, all future measurements must include Δα/α as a free parameter from the beginning of the modelling process.
3D radiative transfer kilonova modelling for binary neutron star merger simulations
Authors: Collins Christine E , Bauswein Andreas , Sim Stuart A , Vijayan Vimal , Martínez-Pinedo Gabriel , Just Oliver , Shingles Luke J , Kromer Markus
Published: February 2023

The detection of GW170817 and the accompanying electromagnetic counterpart, AT2017gfo, have provided an important set of observational constraints for theoretical models of neutron star mergers, nucleosynthesis, and radiative transfer for kilonovae. We apply the three-dimensional (3D) Monte Carlo radiative transfer code artis to produce synthetic light curves of the dynamical ejecta from a neutron star merger, which has been modelled with 3D smooth particle hydrodynamics and included neutrino interactions. Nucleosynthesis calculations provide the energy released from radioactive decays of r-process nuclei, and radiation transport is performed using grey opacities given as functions of the electron fraction. We present line-of-sight-dependent bolometric light curves, and find the emission along polar lines of sight to be up to a factor of ∼2 brighter than that along equatorial lines of sight. Instead of a distinct emission peak, our bolometric light curve exhibits a monotonic decline, characterized by a shoulder at the time when the bulk ejecta becomes optically thin. We show approximate band light curves based on radiation temperatures and compare these to the observations of AT2017gfo. We find that the rapidly declining temperatures lead to a blue to red colour evolution similar to that shown by AT2017gfo. We also investigate the impact of an additional, spherically symmetric secular ejecta component, and we find that the early light curve remains nearly unaffected, while after about $1\,$ d the emission is strongly enhanced and dominated by the secular ejecta, leading to the shift of the shoulder from ∼1–2 to 6–10 d.
Excess Mortality Associated With Loiasis: Confirmation by a New Retrospective Cohort Study Conducted in the Republic of Congo
Authors: Hemilembolo Marlhand C , Niama Ange Clauvel , Campillo Jérémy T , Pion Sébastien D , Missamou François , Whittaker Charles , Kankou Jean-Médard , Ndziessi Gilbert , Bileckot Richard R , Boussinesq Michel , Chesnais Cédric B
Published: February 2023

Background

Loiasis (Loa loa filariasis) is considered a benign disease and is currently not included in the World Health Organization’s (WHO's) list of Neglected Tropical Diseases, despite mounting evidence suggesting significant disease burden in endemic areas. We conducted a retrospective cohort study to assess the mortality associated with L. loa microfilaremia in the Southwestern Republic of Congo.

Methods

The cohort included 3329 individuals from 53 villages screened for loiasis in 2004. We compared mortality rates in 2021 for individuals initially diagnosed as with or without L. loa microfilariae 17 years earlier. Data were analyzed at the community level to calculate crude mortality rates. Survival models were used to estimate the effect of L. loa microfilaremia on mortality in the population.

Results

At baseline, prevalence of microfilaremia was 16.2%. During 17.62 years of cohort follow-up, 751 deaths were recorded, representing a crude mortality rate of 15.36 (95% CI, 14.28–16.50) per 1000 person-years. Median survival time was 58.5 (95% CI, 49.7–67.3) years and 39.2 (95% CI, 32.6–45.8) years for amicrofilaremic and microfilaremic indiviudals, respectively.

Conclusions

A significant reduction in life expectancy was associated with L. loa microfilaremia, confirming previous observations from Cameroon. This adds to the evidence that loiasis is not a benign disease and deserves to be included in the WHO's list of Neglected Tropical Diseases.
PP2C.D phosphatase SAL1 positively regulates aluminum resistance via restriction of aluminum uptake in rice
Authors: Xie Wenxiang , Liu Shuo , Gao Huiling , Wu Jun , Liu Dilin , Kinoshita Toshinori , Huang Chao-Feng
Published: February 2023

Aluminum (Al) toxicity represents a primary constraint for crop production in acidic soils. Rice (Oryza sativa) is a highly Al-resistant species; however, the molecular mechanisms underlying its high Al resistance are still not fully understood. Here, we identified SAL1 (SENSITIVE TO ALUMINUM 1), which encodes a plasma membrane (PM)-localized PP2C.D phosphatase, as a crucial regulator of Al resistance using a forward genetic screen. SAL1 was found to interact with and inhibit the activity of PM H+-ATPases, and mutation of SAL1 increased PM H+-ATPase activity and Al uptake, causing hypersensitivity to internal Al toxicity. Furthermore, knockout of NRAT1 (NRAMP ALUMINUM TRANSPORTER 1) encoding an Al uptake transporter in a sal1 background rescued the Al-sensitive phenotype of sal1, revealing that coordination of Al accumulation in the cell, wall and symplasm is critical for Al resistance in rice. By contrast, we found that mutations of PP2C.D phosphatase-encoding genes in Arabidopsis (Arabidopsis thaliana) enhanced Al resistance, which was attributed to increased malate secretion. Our results reveal the importance of PP2C.D phosphatases in Al resistance and the different strategies used by rice and Arabidopsis to defend against Al toxicity.
Are Executives in Short Supply? Evidence from Death Events
Authors: Sauvagnat Julien , Schivardi Fabiano
Published: February 2023

Using exhaustive administrative data on Italian social security records, we construct measures of local labour market thickness for executives that vary by industry and location. We show that firm performance is strongly and persistently affected by executive death, but only in thin local labour markets. The new executives hired after death events in thin local labour markets have lower education levels and are more likely to be replaced. These predictions are consistent with a simple model of executive search in which market thickness determines the arrival rate of applications for executive positions.