bluuebunny/crossref_metadata_2025 huggingface dataset:
CoDNaS-RNA: a database of conformational diversity in the native state of RNA
Authors: González Buitrón Martín , Tunque Cahui Ronaldo Romario , García Ríos Emilio , Hirsh Layla , Parisi Gustavo , Fornasari María Silvina , Palopoli Nicolas
Published: December 2021

Conformational changes in RNA native ensembles are central to fulfill many of their biological roles. Systematic knowledge of the extent and possible modulators of this conformational diversity is desirable to better understand the relationship between RNA dynamics and function. We have developed CoDNaS-RNA as the first database of conformational diversity in RNA molecules. Known RNA structures are retrieved and clustered to identify alternative conformers of each molecule. Pairwise structural comparisons between all conformers within each cluster allows to measure the variability of the molecule. Additional annotations about structural features, molecular interactions and biological function are provided. All data in CoDNaS-RNA is free to download and available as a public website that can be of interest for researchers in computational biology and other life science disciplines.

Availability and implementation

The data underlying this article are available at http://ufq.unq.edu.ar/codnasrna or https://codnas-rna.bioinformatica.org/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Safety and economic analysis of selective histopathology following cholecystectomy: multicentre, prospective, cross-sectional FANCY study
Authors: Bastiaenen Vivian P. , van Vliet Jaap L. P. , de Savornin Lohman Elise A. J. , Corten Bartholomeus J. G. A. , de Jonge Joske , Kraima Anne C. , Swank Hilko A. , van Acker Gijs J. D. , van Geloven Anna A. W. , in ‘t Hof Klaas H. , Koens Lianne , de Reuver Philip R. , van Rossem Charles C. , Slooter Gerrit D. , Tanis Pieter J. , Terpstra Valeska , Dijkgraaf Marcel G. W. , Bemelman Willem A. ,   for the Dutch Snapshot Research Group
Published: December 2021

Background

There is ongoing debate concerning the necessity of routine histopathological examination following cholecystectomy. In order to reduce the pathology workload and save costs, a selective approach has been suggested, but evidence regarding its oncological safety is lacking.

Methods

In this multicentre, prospective, cross-sectional study, all gallbladders removed for gallstone disease or cholecystitis were systematically examined by the surgeon for macroscopic abnormalities indicative of malignancy. Before sending all specimens to the pathologist, the surgeon judged whether histopathological examination was indicated. The main outcomes were the number of patients with hypothetically missed malignancy with clinical consequences (upper limit two-sided 95 per cent c.i. below 3:1000 considered oncologically safe) and potential cost savings of selective histopathological examination.

Results

Twenty-two (2.19:1000) of 10 041 specimens exhibited malignancy with clinical consequences. In case of a selective policy, surgeons would have held back 7846 of 10041 (78.1 per cent) gallbladders from histopathological examination. Malignancy with clinical consequences would have been missed in seven of 7846 patients (0.89:1000, upper limit 95% c.i. 1.40:1000). No patient benefitted from the clinical consequences, while two were harmed (futile additional surgery). Of 15 patients in whom malignancy with clinical consequences would have been diagnosed, one benefitted (residual disease radically removed), two potentially benefitted (palliative systemic therapy), and four experienced harm (futile additional surgery). Estimated cost savings established by replacing routine for selective histopathological examination were €703 500 per 10 000 patients.

Conclusion

Selective histopathological examination following cholecystectomy is oncologically safe and could reduce pathology workload, costs, and futile re-resections.
Long-term oncological prognosis after curative-intent liver resection for hepatocellular carcinoma in the youngversusthe elderly: multicentre propensity score-matching study
Authors: Pu Jia-Le , Chen Zhong , Yao Lan-Qing , Feng Ji-Ye , Diao Yong-Kang , Guan Ming-Cheng , Li Ju-Dong , Chen Zheng-Liang , Zhou Ya-Hao , Wang Hong , Gu Wei-Min , Li Jie , Li Chao , Wang Ming-Da , Zhu Hong , Liang Ying-Jian , Shen Feng , Pawlik Timothy M. , Lau Wan Yee , Yang Tian
Published: December 2021

Background

Hepatocellular carcinoma (HCC) is the most common malignancy in the elderly worldwide, but it is also common among younger individuals in areas with endemic hepatitis B virus infection. The differences in long-term oncological prognosis of young versus elderly patients after R0 liver resection for HCC were explored in this study.

Methods

Using a Chinese multicentre database, consecutive patients who underwent R0 liver resection for HCC between 2007 and 2019 were analysed retrospectively. After excluding middle-aged (36–69 years old) patients, overall survival (OS), cancer-specific survival (CSS), and recurrence were compared between young (35 years or younger) and elderly (70 years or older) patients using propensity score matching (PSM).

Results

Among 531 enrolled patients, there were 192 (36.2 per cent) and 339 (63.8 per cent) patients categorized as young and elderly respectively. PSM created 140 pairs of matched patients. In the PSM cohort, 5-year OS was comparable for young versus elderly patients (51.7 versus 52.3 per cent, P = 0.533). Young patients, however, had a higher 5-year cumulative recurrence rate (62.1 versus 51.6 per cent, P = 0.011) and a worse 5-year CSS rate (54.0 versus 64.3 per cent, P = 0.034) than elderly patients. On multivariable Cox regression analyses, young patient age remained independently associated with an increased recurrence rate (hazard ratio 1.62, P = 0.016) and a decreased CSS rate (hazard ratio 1.69, P = 0.021) compared with older age.

Conclusion

Following R0 liver resection for HCC, younger patients were at a higher risk of recurrence, and elderly patients had a better CSS rate. Thus, enhanced surveillance for HCC recurrence should be implemented for young patients.
Exploring Reproductive Health Decision Experiences and Preferences of Women With Pediatric-Onset Inflammatory Bowel Diseases
Authors: Picciarelli Zach , Stransky Olivia M , Leech Mary M , Michel Hilary K , Schwartz Marc , Kim Sandra C , Gray Whitney M , Kazmerski Traci M
Published: December 2021

Background

Women with inflammatory bowel diseases (IBDs), such as Crohn’s disease or ulcerative colitis, face several disease-specific concerns related to their reproductive health decisions. This study explored the reproductive health decision-making experiences and preferences of women with IBD to discover ways to improve this aspect of comprehensive care.

Methods

We recruited women ages 18–44 years with IBD to participate in individual, semistructured interviews exploring their experiences and attitudes toward parenthood, pregnancy, contraception, and family planning care. Two independent coders performed analysis using an inductive and deductive coding approach and identified key themes.

Results

Twenty-one women with IBD participated in interviews (average age 24.7 ± 5.9 years, range 18–43 years; average age of diagnosis 14.1 ± 2.0 years). We identified 4 key themes: (1) Nulliparous women who do not currently desire pregnancy appear to lack reproductive health knowledge; (2) Women with IBD lack clarity regarding the role IBD plays in contraceptive choice; (3) Related to pregnancy, women are concerned about the heredity of IBD, antepartum disease activity, and the safety of their current medications; (4) Women with IBD typically default to their reproductive health provider for reproductive health care and counseling, but they expect their gastroenterologist to initiate relevant reproductive health discussions with them and to provide information in the context of their disease.

Conclusions

Women have concerns about the effects of IBD on pregnancy, parenthood, and contraceptive choice; however, many have had limited or no discussion with their gastroenterologist about the topic.
Recombinant Adjuvanted Zoster Vaccine and Reduced Risk of Coronavirus Disease 2019 Diagnosis and Hospitalization in Older Adults
Authors: Bruxvoort Katia J , Ackerson Bradley , Sy Lina S , Bhavsar Amit , Tseng Hung Fu , Florea Ana , Luo Yi , Tian Yun , Solano Zendi , Widenmaier Robyn , Shi Meng , Van Der Most Robbert , Schmidt Johannes Eberhard , Danier Jasur , Breuer Thomas , Qian Lei
Published: December 2021

Background

Some vaccines elicit nonspecific immune responses that may protect against heterologous infections. We evaluated the association between recombinant adjuvanted zoster vaccine (RZV) and coronavirus disease 2019 (COVID-19) outcomes at Kaiser Permanente Southern California.

Methods

In a cohort design, adults aged ≥50 years who received ≥1 RZV dose before 1 March 2020 were matched 1:2 to unvaccinated individuals and followed until 31 December 2020. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for COVID-19 outcomes were estimated using Cox proportional hazards regression. In a test-negative design, cases had a positive severe acute respiratory syndrome coronavirus 2 test and controls had only negative tests, during 1 March–31 December 2020. Adjusted odds ratios (aORs) and 95% CIs for RZV receipt were estimated using logistic regression.

Results

In the cohort design, 149 244 RZV recipients were matched to 298 488 unvaccinated individuals. The aHRs for COVID-19 diagnosis and hospitalization were 0.84 (95% CI, .81–.87) and 0.68 (95% CI, .64–.74), respectively. In the test-negative design, 8.4% of 75 726 test-positive cases and 13.1% of 340 898 test-negative controls had received ≥1 RZV dose (aOR, 0.84 [95% CI, .81–.86]).

Conclusions

RZV vaccination was associated with a 16% lower risk of COVID-19 diagnosis and 32% lower risk of hospitalization. Further study of vaccine-induced nonspecific immunity for potential attenuation of future pandemics is warranted.
Comparative analysis of in vitro dynamics and mechanisms of ceftolozane/tazobactam and imipenem/relebactam resistance development in Pseudomonas aeruginosa XDR high-risk clones
Authors: Gomis-Font María A. , Cabot Gabriel , López-Argüello Silvia , Zamorano Laura , Juan Carlos , Moyá Bartolomé , Oliver Antonio
Published: December 2021

Objectives

To analyse the dynamics and mechanisms of stepwise resistance development to ceftolozane/tazobactam and imipenem/relebactam in XDR Pseudomonas aeruginosa clinical strains.

Methods

XDR clinical isolates belonging to ST111 (main resistance mechanisms: oprD−, dacB−, CARB-2), ST175 (oprD−, ampR-G154R) and ST235 (oprD−, OXA-2) high-risk clones were incubated for 24 h in Müeller-Hinton Broth with 0.125–64 mg/L of ceftolozane + tazobactam 4 mg/L or imipenem + relebactam 4 mg/L. Tubes from the highest antibiotic concentration showing growth were reinoculated into fresh medium containing concentrations up to 64 mg/L for 7 consecutive days. Two colonies per strain from each of the triplicate experiments were characterized by determining the susceptibility profiles, whole genome sequencing (WGS), and in vitro fitness through competitive growth assays.

Results

Resistance development occurred more slowly and reached a lower level for imipenem/relebactam than for ceftolozane/tazobactam in all tested XDR strains. Moreover, resistance development to imipenem/relebactam remained low even for ST175 isolates that had developed ceftolozane/tazobactam resistance during therapy. Lineages evolved in the presence of ceftolozane/tazobactam showed high-level resistance, imipenem/relebactam hypersusceptibility and low fitness cost, whereas lineages evolved in the presence of imipenem/relebactam showed moderate (borderline) resistance, no cross-resistance to ceftolozane/tazobactam and high fitness cost. WGS evidenced that ceftolozane/tazobactam resistance was mainly caused by mutations in the catalytic centres of intrinsic (AmpC) or acquired (OXA) β-lactamases, whereas lineages evolved in imipenem/relebactam frequently showed structural mutations in MexB or in ParS, along with some strain-specific mutations.

Conclusions

Imipenem/relebactam could be a useful alternative for the treatment of XDR P. aeruginosa infections, potentially reducing resistance development during therapy.
Continuous seasonal monitoring of nitrogen and water content in lettuce using a dual phenomics system
Authors: Weksler Shahar , Rozenstein Offer , Ben Dor Eyal
Published: December 2021

The collection and analysis of large amounts of information on a plant-by-plant basis contributes to the development of precision fertigation and may be achieved by combining remote-sensing technology with high-throughput phenotyping methods. Here, lettuce plants (Lactuca sativa) were grown under optimal and suboptimal nitrogen and irrigation treatments from seedlings to harvest. A Plantarray system was used to calculate and log weights, daily transpiration, and momentary transpiration rates throughout the experiment. From 15 d after planting until experiment termination, the entire array of plants was imaged hourly (from 09.00 h to 14.00 h) using a hyperspectral moving camera. Three vegetation indices were calculated from the plants’ reflectance signal: red-edge chlorophyll index (RECI), photochemical reflectance index (PRI), and water index (WI), and combined treatments, physiological measurements, and vegetation indices were compared. RECI values differed significantly between nitrogen treatments from the first day of imaging, and WI values distinguished well-irrigated from drought-treated groups before detecting significant differences in daily transpiration rate. The PRI, calculated hourly during the drought-treatment phase, changed with the momentary transpiration rate. Thus, hyperspectral imaging might be used in growing facilities to detect nitrogen or water shortages in plants before their physiological response affects yields.
Phytolectin nanoconjugates in combination with standard antifungals curb multi-species biofilms and virulence of vulvovaginal candidiasis (VVC) causing Candida albicans and non-albicans Candida
Authors: Senthilganesh Jayasankari , Kuppusamy Shruthi , Durairajan Rubini , Subramaniyan Siva Bala , Veerappan Anbazhagan , Paramasivam Nithyanand
Published: December 2021

Vulvovaginal candidiasis (VVC) is a commonly occurring yeast infection caused by Candida species in women. Among Candida species, C. albicans is the predominant member that causes vaginal candidiasis followed by Candida glabrata. Biofilm formation by Candida albicans on the vaginal mucosal tissue leads to VVC infection and is one of the factors for a commensal organism to get into virulent form leading to disease. In addition to that, morphological switching from yeast to hyphal form increases the risk of pathogenesis as it aids in tissue invasion. In this study, jacalin, a phytolectin complexed copper sulfide nanoparticles (NPs) have been explored to eradicate the mono and mixed species biofilms formed by fluconazole-resistant C. albicans and C. glabrata isolated from VVC patients. NPs along with standard antifungals like micafungin and amphotericin B have been evaluated to explore interaction behavior and we observed synergistic interactions between them. Microscopic techniques like light microscopy, phase contrast microscopy, scanning electron microscopy, confocal laser scanning microscopy were used to visualize the inhibition of biofilm by NPs and in synergistic combinations with standard antifungals. Real-time PCR analysis was carried out to study the expression pattern of the highly virulent genes which are responsible for yeast to hyphal switch, drug resistance and biofilm formation upon treatment with NPs in combination with standard antifungals. The current study shows that lectin-conjugated NPs with standard antifungals might be a different means to disrupt the mixed species population of Candida spp. that causes VVC.

Lay Summary

The present study focuses on exploiting the high biding affinity between the cell surface glycans present in Candida cells and the plant lectin, Jacalin. Jacalin serves as a ‘Trojan Horse’ wherein the lectin-coupled nanoparticles show a high efficacy when compared with the unconjugated nanoparticles. The present approach also improves the anti-biofilm activity of the antifungal drugs against drug-resistant Candida strains.
Gravitational wave signals from 2D core–collapse supernova models with rotation and magnetic fields
Authors: Jardine Rylan , Powell Jade , Müller Bernhard
Published: December 2021

We investigate the impact of rotation and magnetic fields on the dynamics and gravitational wave emission in 2D core–collapse supernova simulations with neutrino transport. We simulate 17 different models of $15\, {\rm M}_\odot$ and $39\, {\rm M}_\odot$ progenitor stars with various initial rotation profiles and initial magnetic fields strengths up to $10^{12}\, \mathrm{G}$, assuming a dipolar field geometry in the progenitor. Strong magnetic fields generally prove conducive to shock revival, though this trend is not without exceptions. The impact of rotation on the post-bounce dynamics is more variegated, in line with previous studies. A significant impact on the time-frequency structure of the gravitational wave signal is found only for rapid rotation or strong initial fields. For rapid rotation, the angular momentum gradient at the proto-neutron star surface can appreciably affect the frequency of the dominant mode, so that known analytic relations for the high-frequency emission band no longer hold. In case of two magnetorotational explosion models, the deviation from these analytic relations is even more pronounced. One of the magnetorotational explosions has been evolved to more than half a second after the onset of the explosion and shows a subsidence of high-frequency emission at late times. Its most conspicuous gravitational wave signature is a high-amplitude tail signal. We also estimate the maximum detection distances for our waveforms. The magnetorotational models do not stick out for higher detectability during the post-bounce and explosion phase.
Radiographic factors associated with painful callosities after forefoot surgery in patients with rheumatoid arthritis
Authors: Tobimatsu Haruki , Ikari Katsunori , Yano Koichiro , Okazaki Ken
Published: December 2021

Objectives

Operative procedures for rheumatoid forefoot deformities have gradually changed from arthrodesis or resection arthroplasty to joint-preserving surgery. Although joint-preserving arthroplasty has yielded good outcomes, painful plantar callosities may occur post-operatively. This study aimed to reveal the radiographic factors associated with painful callosities after joint-preserving surgery for forefoot deformities in patients with rheumatoid arthritis (RA).

Methods

We retrospectively evaluated 166 feet in 133 patients with RA who underwent forefoot joint-preserving arthroplasty, including proximal rotational closing-wedge osteotomies of the first metatarsal, between January 2012 and December 2015. Logistic regression analysis was performed with the objective variable set as the presence/absence of painful plantar callosities at the final observation and the explanatory variables set as several radiographic factors, including post-operative relative first metatarsal length (RML), amount of dorsal dislocation of the fifth metatarsal (5DD), and arc failure of the lesser toes.

Results

At the final follow-up, 42 of the 166 feet (25.3%) had painful callosities under the metatarsal heads post-operatively. Logistic regression analysis showed that the RML, 5DD, and lesser toes’ arc failure were significantly associated with painful callosities.

Conclusions

We identified that RML, 5DD, and arc failure of the lesser toes were associated with painful plantar callosities after the surgery.
Associations of Smokeless Tobacco Use With Cardiovascular Disease Risk: Insights From the Population Assessment of Tobacco and Health Study
Authors: Rezk-Hanna Mary , Warda Umme Shefa , Stokes Andrew C , Fetterman Jessica , Li Jian , Macey Paul M , Darawad Muhammad , Song Yeonsu , Ben Taleb Ziyad , Brecht Mary-Lynn , Benowitz Neal L
Published: December 2021

Introduction

Cigarette smoking is strongly associated with the development of cardiovascular disease (CVD). However, evidence is limited as to whether smokeless tobacco (ST) use is associated with CVD.

Aims and Methods

Using data from 4347 adults in the Population Assessment of Tobacco and Health Study (2013–2014), we compared geometric mean concentrations of CVD-related harm biomarkers and biomarkers of exposure among exclusive ST users and exclusive cigarette smokers—in relation to recent nicotine exposure—and never tobacco users, adjusting for age, sex, race/ethnicity, income, body mass index, and CVD. Biomarker levels among exclusive ST users who were former established cigarette smokers were compared with exclusive cigarette smokers.

Results

Compared with cigarette smokers, ST users had significantly higher concentrations of total nicotine equivalents (TNE) but lower concentrations of inflammatory (high-sensitivity C-reactive protein, interleukin-6, intercellular adhesion molecule, fibrinogen) and oxidative stress (8-isoprostane) biomarkers (all p < .05). Biomarker levels among ST users were similar to never smokers. ST users who were former cigarette smokers had lower levels of inflammatory and oxidative stress biomarkers and biomarkers of exposure (cadmium, lead, 1-hydroxypyrene, acrylonitrile, and acrolein), compared with cigarettes smokers (p < .05), despite having higher TNE levels (p < .05). Among cigarette smokers, but not among ST users, inflammatory biomarkers and TNE were highly correlated.

Conclusions

ST use is not associated with increases in biomarkers of CVD-related harm and exposure, compared with never smokers, despite exposure to nicotine at levels higher than those observed among cigarette smokers. These findings support the concept that increases in CVD risk among cigarette smokers is caused primarily by constituents of tobacco smoke other than nicotine.

Implications

Despite having higher levels of nicotine and compared with exclusive cigarette smokers, exclusive ST users (including those who were former cigarette smokers) had significantly lower concentrations of inflammatory and oxidative stress biomarkers, comparable to levels observed among never tobacco users. These findings suggest that increases in CVD risk among cigarette smokers is caused primarily by tobacco constituents other than nicotine and that switching to ST is likely associated with lower CVD risk.
Price and Income Elasticities of Cigarette Smoking Demand in Bangladesh: Evidence from Urban Adolescents and Young Adults
Authors: Ahmed Moin Uddin , Pulok Mohammad Habibullah , Hashmi Rubayyat , Hajizadeh Mohammad , Nargis Nigar
Published: December 2021

Introduction

Understanding the elasticities of cigarette smoking demand among the youth could help improve the effectiveness of tobacco control interventions. The objective of this study is to measure the price and income elasticities of cigarette smoking demand among urban Bangladeshi male adolescents and young adults aged 10-24 years.

Method

Using data from a cross-sectional survey conducted in seven urban districts of Bangladesh, we applied probit and ordinary least square (OLS) models to examine the effect of price and income on smoking participation (decision to smoke) and intensity (number of cigarettes smoked).

Results

Our results showed that price was not significantly associated with the decision to smoke, while income was a significant determinant of smoking participation. Both price and income determined the smoking intensity. The positive income elasticity (0.39) indicated that participants with greater access to money were more likely to participate in cigarette smoking and smoked more cigarettes. Negative price elasticity (-0.62) implied that increasing prices could lead to a reduction in smoking intensity among adolescents and young adults in urban Bangladesh.

Conclusion

The inelastic price demand for cigarette smoking suggests that there is scope for increasing tax on cigarettes without compromising the tax revenue.

Implications

This is the first study to investigate price and income elasticities among urban adolescents and young adults in Bangladesh. The study found no evidence that increasing the price of cigarettes discourages smoking participation but did show that increasing the price reduces the intensity of smoking among existing smokers. The results also suggest that economic measures such as taxation that increase the price of cigarettes could be a useful policy tool to limit smoking intensity without compromising government tax revenue.
Safety and Efficacy of Antibiotic De-escalation and Discontinuation in High-Risk Hematological Patients With Febrile Neutropenia: A Single-Center Experience
Authors: Verlinden Anke , Jansens Hilde , Goossens Herman , Anguille Sébastien , Berneman Zwi N , Schroyens Wilfried A , Gadisseur Alain P
Published: December 2021

Background

There is currently no consensus on optimal duration of antibiotic treatment in febrile neutropenia. We report on the clinical impact of implementation of antibiotic de-escalation and discontinuation strategies based on the Fourth European Conference on Infections in Leukaemia (ECIL-4) recommendations in high-risk hematological patients.

Methods

We studied 446 admissions after introduction of an ECIL-4–based protocol (hereafter “ECIL-4 group”) in comparison to a historic cohort of 512 admissions. Primary clinical endpoints were the incidence of infectious complications including septic shock, infection-related intensive care unit (ICU) admission, and overall mortality. Secondary endpoints included the incidence of recurrent fever, bacteremia, and antibiotic consumption.

Results

Bacteremia occurred more frequently in the ECIL-4 group (46.9% [209/446] vs 30.5% [156/512]; P < .001), without an associated increase in septic shock (4.7% [21/446] vs 4.5% [23/512]; P = .878) or infection-related ICU admission (4.9% [22/446] vs 4.1% [21/512]; P = .424). Overall mortality was significantly lower in the ECIL-4 group (0.7% [3/446] vs 2.7% [14/512]; P = .016), resulting mainly from a decrease in infection-related mortality (0.4% [2/446] vs 1.8% [9/512]; P = .058). Antibiotic consumption was significantly reduced by a median of 2 days on antibiotic therapy (12 vs 14; P = .001) and 7 daily antibiotic doses (17 vs 24; P < .001) per admission period.

Conclusions

Our results support implementation of ECIL-4 recommendations to be both safe and effective based on real-world data in a large high-risk patient population. We found no increase in infectious complications and total antibiotic exposure was significantly reduced.
Cofactor-independent RNA editing by a synthetic S-type PPR protein
Authors: Bernath-Levin Kalia , Schmidberger Jason , Honkanen Suvi , Gutmann Bernard , Sun Yueming Kelly , Pullakhandam Anuradha , Colas des Francs-Small Catherine , Bond Charles S , Small Ian
Published: December 2021

Pentatricopeptide repeat (PPR) proteins are RNA-binding proteins that are attractive tools for RNA processing in synthetic biology applications given their modular structure and ease of design. Several distinct types of motifs have been described from natural PPR proteins, but almost all work so far with synthetic PPR proteins has focused on the most widespread P-type motifs. We have investigated synthetic PPR proteins based on tandem repeats of the more compact S-type PPR motif found in plant organellar RNA editing factors and particularly prevalent in the lycophyte Selaginella. With the aid of a novel plate-based screening method, we show that synthetic S-type PPR proteins are easy to design and bind with high affinity and specificity and are functional in a wide range of pH, salt and temperature conditions. We find that they outperform a synthetic P-type PPR scaffold in many situations. We designed an S-type editing factor to edit an RNA target in E. coli and demonstrate that it edits effectively without requiring any additional cofactors to be added to the system. These qualities make S-type PPR scaffolds ideal for developing new RNA processing tools.
High recombination rate of hepatitis C virus revealed by a green fluorescent protein reconstitution cell system
Authors: Galli Andrea , Fahnøe Ulrik , Bukh Jens
Published: December 2021

Genetic recombination is an important evolutionary mechanism for RNA viruses and can facilitate escape from immune and drug pressure. Recombinant hepatitis C virus (HCV) variants have rarely been detected in patients, suggesting that HCV has intrinsic low recombination rate. Recombination of HCV has been demonstrated in vitro between non-functional genomes, but its frequency and relevance for viral evolution and life cycle has not been clarified. We developed a cell-based assay to detect and quantify recombination between fully viable HCV genomes, using the reconstitution of green fluorescent protein (GFP) as a surrogate marker for recombination. Here, two GFP-expressing HCV genomes carrying different inactivating GFP mutations can produce a virus carrying a functional GFP by recombining within the GFP region. Generated constructs allowed quantification of recombination rates between markers spaced 603 and 553 nucleotides apart by flow cytometry and next-generation sequencing (NGS). Viral constructs showed comparable spread kinetics and reached similar infectivity titers in Huh7.5 cells, allowing their use in co-transfections and co-infections. Single-cycle co-transfection experiments, performed in CD81-deficient S29 cells, showed GFP expression in double-infected cells, demonstrating genome mixing and occurrence of recombination. Quantification of recombinant genomes by NGS revealed an average rate of 6.1 per cent, corresponding to 49 per cent of maximum detectable recombination (MDR). Experiments examining recombination during the full replication cycle of HCV, performed in Huh7.5 cells, demonstrated average recombination rates of 5.0 per cent (40.0 per cent MDR) and 3.6 per cent (28.8 per cent MDR) for markers spaced by 603 and 553 nucleotides, respectively, supporting a linear relationship between marker distance and recombination rates. First passage infections using recombinant virus supernatant resulted in comparable recombination rates of 5.9 per cent (47.2 per cent MDR) and 3.5 per cent (28.0 per cent MDR), respectively, for markers spaced by 603 and 553 nucleotides. We developed a functional cell-based assay that, to the best of our knowledge, allows for the first time detailed quantification of recombination rates using fully viable HCV constructs. Our data indicate that HCV recombines at high frequency between highly similar genomes and that the frequency of recombination increases with the distance between marker sites. These results have implication for our understanding of HCV evolution and emphasize the importance of recombination in the reassortment of mutations in the HCV genome.
Lymphadenopathy secondary to tattoo ink in a patient with a history of Hodgkin lymphoma
Authors: Melnick Natalie , Pierce Bradley
Published: December 2021

The finding of lymphadenopathy on physical examination and radiographically can suggest a wide range of differential diagnoses for patients, including a benign inflammatory process, infection, or malignancy. This article describes a patient with a history of Hodgkin lymphoma who developed postremission left axillary lymphadenopathy caused by deposits of tattoo ink in the node.
Clinical considerations for the evaluation of patients with left ventricular assist devices
Authors: McMullen Leah , Barker Kelly , Fried Justin , Wagener Gebhard
Published: December 2021

A left ventricular assist device (LVAD) provides mechanical circulatory support for patients with end-stage heart failure. As these devices become more prevalent, clinicians must be familiar with the device's function, common complications, and management strategies when evaluating this patient population.
Comparison of the mean of the first two blood pressure readings with the overall mean of three readings on a single occasion
Authors: Xu Shao-Kun , Chen Xin , Sheng Chang-Sheng , Cheng Yi-Bang , Wang Hong-Yu , Yu Wei , Li Yan , Wang Ji-Guang
Published: December 2021

Objective:

Guidelines differed on the required number of blood pressure (BP) readings for accurate BP assessment. We, therefore, compared the mean of the first two BP readings with the overall mean of three readings in the diagnosis of hypertension.

Methods:

BP was measured three times consecutively with a 1 min interval using a validated automated electronic BP monitor in volunteers aged at least 18 years. The mean of the first and second BP readings was compared with the mean of the three blood pressure readings for the diagnostic accuracy of hypertension.

Results:

Of the 77 520 study participants, 65.2 and 25.2% had a SBP or DBP difference at least 5 mmHg and at least 10 mmHg between the first and second BP readings, respectively. Regardless whether the BP difference between the first two BP readings was at least 5 mmHg or at least 10 mmHg for systolic and diastolic alone or both, significant (P < 0.0001) SBP/DBP differences between the mean of the first two BP readings and the overall mean of three readings were observed with an absolute value up to 1.28/1.11 mmHg. However, the mean of the first two BP readings exhibited good reliability and sufficient agreement in the diagnosis of hypertension with a kappa statistic at least 0.88, except that the difference between the first and second BP readings was at least 10 mmHg for both systolic and diastolic (κ=0.79). The diagnostic accuracy was similar across age quartile, sex, and BP category.

Conclusion:

Two BP readings may be sufficient, unless the BP difference between the two readings was at least 10 mmHg for both systolic and diastolic.
The association of uric acid with mortality modifies at old age: data from the uric acid right for heart health (URRAH) study
Authors: Ungar Andrea , Rivasi Giulia , Di Bari Mauro , Virdis Agostino , Casiglia Edoardo , Masi Stefano , Mengozzi Alessandro , Barbagallo Carlo M. , Bombelli Michele , Bruno Bernardino , Cicero Arrigo F.G. , Cirillo Massimo , Cirillo Pietro , Desideri Giovambattista , D’elia Lanfranco , Ferri Claudio , Galletti Ferruccio , Gesualdo Loreto , Giannattasio Cristina , Iaccarino Guido , Ciccarelli Michele , Lippa Luciano , Mallamaci Francesca , Maloberti Alessandro , Mazza Alberto , Muiesan Maria Lorenza , Nazzaro Pietro , Palatini Paolo , Parati Gianfranco , Pontremoli Roberto , Quarti-Trevano Fosca , Rattazzi Marcello , Salvetti Massimo , Tikhonoff Valérie , Tocci Giuliano , Cianci Rosario , Verdecchia Paolo , Viazzi Francesca , Volpe Massimo , Grassi Guido , Borghi Claudio
Published: December 2021

Objectives:

In older individuals, the role of serum uric acid (SUA) as risk factor for mortality is debated. This study investigated the association of SUA with all-cause and cardiovascular (CV) mortality in older adults participating in the large multicentre observational uric acid right for heart health (URRAH) study.

Methods:

Eight thousand URRAH participants aged 65+ were included in the analysis. The predictive role of SUA was assessed using Cox regression models stratified according to the cut-off age of 75. SUA was tested as continuous and categorical variable (age-specific quartiles). The prognostic threshold of SUA for mortality was analysed using receiver operating characteristic curves.

Results:

Among participants aged 65–74, multivariate Cox regression analysis adjusted for CV risk factors and comorbidities identified an independent association of SUA with both all-cause mortality (hazard ratio [HR] 1.169, 95% confidence interval [CI] 1.107–1.235) and CV mortality (HR 1.146, 95% CI 1.064–1.235). The cut-off value of 4.8 mg/dl discriminated mortality status. In participants aged 75+, we observed a J-shaped relationship of SUA with all-cause and CV mortality, with risk increasing at extreme SUA levels.

Conclusions:

These results confirmed the predictive role of SUA for all-cause and CV mortality in older adults, while revealing considerable age-related differences. Mortality risk increased at higher SUA levels in participants aged 65–74, with a prognostic threshold of 4.8 mg/dl. The relationship between SUA and mortality was J-shaped in oldest participants. Large interventional studies are needed to clarify the benefits and possible risks of urate-lowering treatments in older adults.
The effects of lung involvement, clinical and laboratory parameters on outcome in elderly patients with coronavirus disease 2019
Authors: Bilgir Ferda , Çalik Şebnem , Demir Ismail , Akan Özden Y.i.ldirim , Bilgir Oktay
Published: December 2021

We aimed to investigate the association of lung involvement and biochemical parameters with patients’ demographic characteristics, and how this association effects the disease course and mortality in elderly patients diagnosed with coronavirus disease 2019 (COVID-19). Age, degree of pulmonary involvement, comorbidities, and biochemical parameters of 211 patients who were 60 years or older, diagnosed with COVID-19, and had lung involvement were analyzed. The effects of these parameters on ICU admission and mortality were investigated. Advanced age, severity of lung involvement, elevated D-dimer, ferritin, and fibrinogen levels, and a previous history ofchronic obstructive pulmonary disease (COPD)were significant for predicting ICU admission and mortality. Along with advanced age, both the severity of lung involvement and a history of COPD had major impact on mortality in the course of COVID-19.
HMB and leucine supplementation during critical illness and recovery
Authors: Bear Danielle E. , Rooyackers Olav
Published: December 2021

Purpose of review

Skeletal muscle wasting is a serious consequence of critical illness, which may impact on long term physical and functional disability. To date, no intervention has been proven to reduce skeletal muscle wasting. Leucine and it's metabolite β-hydroxy-β-methylbutyrate (HMB) have been proposed as interventions. This review details the mechanism of action of both leucine and HMB, discusses the most recent research for both leucine and HMB and lastly discusses considerations for future research.

Recent findings

Only one study of leucine in critical illness has recently been published. This was a feasibility study where the physiological and muscle related outcomes were not reported to be feasible. Three studies on HMB have been reported recently with no effect seen on either muscle mass or strength. The main limitation in our understanding of the potential use of leucine or HMB on skeletal muscle wasting is the lack of mechanistic studies available in this population.

Mechanistic studies should be a priority before embarking on further randomized controlled trials related to this topic.
Case report of pure single-port robotic left lateral sectionectomy using the da Vinci SP system
Authors: Kim Wan-Joon , Park Pyoung-Jae , Choi Sae-Byeol , Kim Wan-Bae
Published: December 2021

Introduction:

Since its first appearance in the early 1990s, laparoscopic hepatic resection has become increasingly accepted and recognized as safe as laparotomy. The recent introduction of robotic surgery systems has brought new innovations to the field of minimally invasive surgery, such as laparoscopic surgery. The da Vinci line of surgical systems has recently released a true single-port platform called the da Vinci SP system, which has 3 fully wristed and elbowed instruments and a flexible camera in a single 2.5 cm cannula. We present the first case of robotic liver resection using the da Vinci SP system and demonstrate the technical feasibility of this platform.

Patient concerns and diagnosis:

A 63-year-old woman presented with elevated liver function test results and abdominal pain. Computed tomography (CT) and magnetic resonance cholangiopancreatography showed multiple intrahepatic duct stones in the left lateral section and distal common bile duct stones near the ampulla of Vater.

Interventions:

The docking time was 8 minute. The patient underwent successful da Vinci SP with a total operation time of 135 minute. The estimated blood loss was 50.0 ml. No significant intraoperative events were observed.

Outcomes:

The numerical pain intensity score was 3/10 in the immediate postoperative period and 1/10 on postoperative day 2. The patient was discharged on postoperative day 5 after verifying that the CT scan did not show any surgical complications.

Conclusion:

We report a technique of left lateral sectionectomy, without the use of an additional port, via the da Vinci SP system. The present case suggests that minor hepatic resection is technically feasible and safe with the new da Vinci SP system in select patients. For the active application of the da Vinci SP system in hepatobiliary surgery, further device development and research are needed.
Pre-operative angle of trunk rotation in prone position estimates postoperative correction results
Authors: Uehara Masashi , Ikegami Shota , Kuraishi Shugo , Oba Hiroki , Takizawa Takashi , Munakata Ryo , Hatakenaka Terue , Koseki Michihiko , Takahashi Jun
Published: December 2021

This study investigated whether postoperative rotational deformity in adolescent idiopathic scoliosis patients could be predicted by prone-position pre-operative angle of trunk rotation (ATR).

Surgical rib hump correction is performed with the patient in a prone position. However, the association between pre-operative ATR in the prone position and postoperative ATR results is unknown.

Thirty-four consecutive patients who underwent skip pedicle screw fixation for Lenke type 1 or 2 adolescent idiopathic scoliosis were retrospectively reviewed. All subjects were followed for a minimum of 1 year. ATR measurements were taken for the standing-flexion position with a scoliometer before surgery and at 1 year afterward. Pre-operative measurements were also taken for the prone position. Correlations between pre- and postoperative ATR were calculated by means of Pearson correlation coefficient. Associations between the correction angle from the standing-flexion position to prone position and postoperative standing-flexion correction angle were determined by linear regression analysis.

Pre- and postoperative ATR for the standing-flexion position showed a moderate association (r = 0.64, P < .01). A similar correlation was seen for pre-operative prone-position ATR and postoperative standing-flexion ATR (r = 0.56, P < .01). In linear regression analysis, there was significant proportional error between the correction angle from the standing-flexion position to prone position and postoperative standing-flexion correction angle (β = 0.40, P < .01).

In conclusion, pre-operative ATR in either standing-flexion or prone position and postoperative standing-flexion ATR displayed moderate associations. Linear regression analysis revealed that ATR correction angle could be estimated by calculating the correction gains of 0.4° per 1° of correction angle in the prone position.
Triaging urological surgeries to cope with the coronavirus-19 pandemic
Authors: Spooner Jesse , Lawen Tarek , Ory Jesse
Published: December 2021

Purpose of review

The coronavirus-19 (COVID-19) pandemic has led to strains on hospital resources and difficulties in safely and effectively triaging surgical procedures. In this article, we discuss the important considerations for triaging urologic surgeries during a global pandemic, mitigating factors on how to perform surgeries safely, and general guidelines for specific surgeries.

Recent findings

Many urological procedures have been cut back due to the pandemic, with benign disease states being most affected whereas oncology cases affected least. Current recommendations in urology triage life-threatening conditions, or conditions that may lead to life-threatening ailments as a priority for treatment during the pandemic. Additionally, published recommendations have been put forth recommending all surgical patients be screened for COVID-19 to protect staff, prevent disease dissemination, and to educate patients on worse outcomes that can occur if infected with COVID-19 in the postoperative period.

COVID-19 has caused worldwide shortages of healthcare resources and increased the need to ethically triage resources to adequately treat the urologic community. These resource limitations have led to increased wait times and cancellations of many urology surgeries that are considered ’elective’.
Medicolegal Implications of Fatalities Because of Entanglement in the Augers of Feed Mixer Wagons
Authors: Moreschi Carlo , Da Broi Ugo , Tse Rexson , Garland Jack , Ondruschka Benjamin , Cividino Sirio Rossano , Vello Michela , Gubiani Rino
Published: December 2021

Feed mixer or total mixed ration mixer wagons are powerful agricultural machines used to shred and mix silage with other ingredients and deliver it direct to the feeding troughs on livestock farms. Fatalities involving these feed mixers may occur when operators become trapped in the augers or, less frequently, are crushed by moving wagons. Death can occur very rapidly because of dismemberment, multiple lesions, or crushing. The aim of this review is to focus on the diagnostic evaluations that need to be performed to confirm that the death was accidental and to exclude a hypothesis of murder or suicide. Forensic investigations in such cases must involve the detailed analysis of the death scene and the mechanical characteristics of the machinery with an accurate postmortem and toxicological examination.
Drowning Accidents in a Spanish Pediatric Intensive Care Unit
Authors: Salas Ballestín Alberto , Frontera Juan Guillem , Sharluyan Petrosyan Artur , Chocano González Eva , Figuerola Mulet Joan , De Carlos Vicente Juan Carlos
Published: December 2021

Introduction

Drowning is one of the most frequent accidents in children. We aimed to describe demographic and epidemiological characteristics of drowned children who required admission to a pediatric intensive care unit (PICU) to identify risk factors to guide possible preventive measures to avoid severe drowning.

Methods

We conducted an observational study for 29 years (retrospective between 1991 and 2004; prospective between 2005 and 2019) that included all children (0–15 years old) requiring PICU admission after drowning. Data regarding patient characteristics, accident circumstances, and neurological outcomes at PICU discharge were analyzed.

Results

A total of 160 patients were included, with no significant decrease over the study period. There was a predominance of males (75%), young age (60%; 1–5 years), summer months (91.1%; May–September), tourists (14.12 [95% confidence interval, 9.2–21.7] times higher risk of drowning than residents), swimming pool accidents (88.8%), and inadequate supervision (77.9%). The mortality was 18.7%, and 7.5% of admitted children had severe neurological sequelae. The initial resuscitation maneuvers by accident witnesses were incorrect in nearly half of the patients in whom these could be analyzed.

Conclusions

Emphasis should be placed on implementing preventive measures, focused on the described risk groups, and insisting on adequate supervision, swimming training programs, and training of the general population in safe rescue and cardiopulmonary resuscitation.