bluuebunny/crossref_metadata_2025 huggingface dataset:
Proportion of Incident Genital Human Papillomavirus Detections not Attributable to Transmission and Potentially Attributable to Latent Infections: Implications for Cervical Cancer Screening
Authors: Malagón Talía , MacCosham Aaron , Burchell Ann N , El-Zein Mariam , Tellier Pierre Paul , Coutlée François , Franco Eduardo L ,   HITCH Study Group, Kelsall Gail , Dumais Suzanne , Drew Melanie , Kelsall Gail , Dumais Suzanne , Morykon Natalia , Rocamora Amela , Slavtcheva Nathalie , Rodrigues Allita , D’Anjou-Pomerleau Vicky , Selinger Jennifer , Montpetit-Dubrule Elizabeth , Sammut Jessica , Lapointe Emilie , Bleecker Johanna , Rahayel Shady , Voyer Hélène , Legault Véronique , Guénoun Julie , Comète Emilie
Published: November 2021

Background

Infections with human papillomaviruses (HPVs) may enter a latent state, and eventually become reactivated following loss of immune control. It is unclear what proportion of incident HPV detections are reactivations of previous latent infections vs new transmissions.

Methods

The HPV Infection and Transmission among Couples through Heterosexual activity (HITCH) cohort study prospectively followed young newly formed heterosexual partners recruited between 2005 and 2011 in Montréal, Canada. We calculated the fraction of incident HPV detections nonattributable to sexual transmission risk factors with a Bayesian Markov model. Results are the median (2.5th-97.5th percentiles) of the estimated posterior distribution.

Results

A total of 544 type-specific incident HPV detection events occurred in 849 participants; 33% of incident HPV detections occurred in participants whose HITCH partners were negative for that HPV type and who reported no other sex partners over follow-up. We estimate that 43% (38%–48%) of all incident HPV detections in this population were not attributable to recent sexual transmission and might be potentially reactivation of latent infections.

Conclusions

A positive HPV test result in many cases may be a reactivated past infection, rather than a new infection from recent sexual behaviors or partner infidelity. The potential for reactivation of latent infections in previously HPV-negative women should be considered in the context of cervical cancer screening.
Quality assuring early dialysis care: evaluating rates of death and recovery within 90 days of first dialysis using the UK Renal Registry
Authors: Hole Barnaby D , Casula Anna , Caskey Fergus J
Published: November 2021

Background

Kidney disease registries typically report populations incident to kidney replacement therapy (KRT) after excluding reversible disease. Registry-based audit and quality assurance is thus based on populations depleted of those with the highest early mortality. It is now mandatory for UK kidney units to report all recipients of dialysis, both acute and chronic. This work presents 90-day survival and recovery outcomes for all reported adults.

Methods

Seventy adult centres reporting to the UK Renal Registry were included. Those assessed as underreporting death and recovery were excluded. Survival was evaluated using a Kaplan–Meier estimator. Cox regression was used to describe hazard ratios (HRs) for age, sex and acute/chronic dialysis coding on day 1. Analysis of all-cause 90-day mortality with recovery as a competing risk is presented.

Results

Twenty-four centres were assessed as underreporting, with rates of death/recovery below the 99.7th centile. Of 5784 dialysis starters in the remaining 46 centres, 2163 (37.4%) were coded as receiving acute dialysis on day 1. Ninety days after starting, 3860 (66.7%) of all starters were receiving KRT, 1157 (20.0%) were alive having stopped, 716 (12.4%) were dead and 51 (0.9%) were lost to follow-up. Mortality was higher among those coded as receiving acute dialysis on day 1 (HR 4.88, P < 0.001). The sub-HR for recovery among those coded as receiving acute compared with chronic dialysis was 56.14 (P < 0.001).

Conclusions

Death and recovery rates are substantially higher than reported in conventional incident populations. This work highlights a vulnerable subgroup of patients largely overlooked by most national quality assurance systems.
Hyperglycaemic disorders associated with PCSK9 inhibitors: a real-world, pharmacovigilance study
Authors: Goldman Adam , Raschi Emanuel , Cukierman-Yaffe Tali , Dankner Rachel , Shouval Roni , Shechter Michael , Ben-Zvi Ilan , Gerstein Hertzel C , Maor Elad
Published: November 2021

Aims

While genetic and biological studies indicated a potential association between proprotein-convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and hyperglycaemia, real-world data are limited. Therefore, we sought to investigate this association using the FDA adverse event reporting system (FAERS).

Methods and results

The FAERS database (2015–2020) was retrospectively queried to characterize reporting of hyperglycaemic adverse events (AEs) with PCSK9i. Disproportionality analyses were performed using the adjusted reporting odds ratio (adj.ROR), and the lower bound of the information component (IC) 95% credibility interval (IC025 > 0 is deemed significant). Among 7 295 624 eligible patients, 71 748 reports of evolocumab and 15 976 of alirocumab were identified. Compared to the full database, PCSK9i treatment was associated with increased reporting of hyperglycaemic AEs [n = 1841, adj.ROR = 1.14 (1.07–1.22), IC025 = 0.13]. Hyperglycaemic AEs were primarily mild hyperglycaemia [n = 1469, adj. ROR = 1.48 (1.36–1.62), IC025 = 0.51] rather than diabetes [n = 372, adj. ROR = 0.67 (0.60–0.74), IC025 = −0.90]. Among PCSK9i agents, evolocumab, but not alirocumab, was associated with hyperglycaemic AEs [n = 1587, adj. ROR = 1.24 (1.15–1.32), IC025 = 0.20; n = 254, adj. ROR = 0.73 (0.60–0.88), IC025 = −0.38, respectively]. Hyperglycaemic AEs were reported more often with PCSK9i compared to ezetimibe [adj.ROR = 1.99 (1.35–2.94)], and less often compared to statins [adj.ROR = 0.26 (0.25–0.28)]. Notably, hyperglycaemic AEs were reported more frequently by diabetic than by non-diabetic patients (P < 0.001), mostly occurred within 6 months of treatment and were reversible upon drug discontinuation.

Conclusion

In a real-world setting, PCSK9i treatment was associated with increased reporting of mild hyperglycaemia, but not diabetes. While initial monitoring is warranted, the favourable glycaemic safety profile compared to statins supports their essential role in the management of lipid disorders.
Temperature dependence of nitrate-reducing Fe(II) oxidation by Acidovorax strain BoFeN1 – evaluating the role of enzymatic vs. abiotic Fe(II) oxidation by nitrite
Authors: Dopffel Nicole , Jamieson James , Bryce Casey , Joshi Prachi , Mansor Muammar , Siade Adam , Prommer Henning , Kappler Andreas
Published: November 2021

Fe(II) oxidation coupled to nitrate reduction is a widely observed metabolism. However, to what extent the observed Fe(II) oxidation is driven enzymatically or abiotically by metabolically produced nitrite remains puzzling. To distinguish between biotic and abiotic reactions, we cultivated the mixotrophic nitrate-reducing Fe(II)-oxidizing Acidovorax strain BoFeN1 over a wide range of temperatures and compared it to abiotic Fe(II) oxidation by nitrite at temperatures up to 60°C. The collected experimental data were subsequently analyzed through biogeochemical modeling. At 5°C, BoFeN1 cultures consumed acetate and reduced nitrate but did not significantly oxidize Fe(II). Abiotic Fe(II) oxidation by nitrite at different temperatures showed an Arrhenius-type behavior with an activation energy of 80±7 kJ/mol. Above 40°C, the kinetics of Fe(II) oxidation were abiotically driven, whereas at 30°C, where BoFeN1 can actively metabolize, the model-based interpretation strongly suggested that an enzymatic pathway was responsible for a large fraction (ca. 62%) of the oxidation. This result was reproduced even when no additional carbon source was present. Our results show that at below 30°C, i.e. at temperatures representing most natural environments, biological Fe(II) oxidation was largely responsible for overall Fe(II) oxidation, while abiotic Fe(II) oxidation by nitrite played a less important role.
Microbial fermentation of Fossence™, a short-chain fructo-oligosaccharide, under simulated human proximal colonic condition and assessment of its prebiotic effects- A pilot study
Authors: Tiwari Deepika P , Shah Priyali , Van den Abbeele Pieter , Marzorati Massimo , Calatayud Marta , Ghyselinck Jonas , Dubey Ashok Kumar , Narayanan S , Jain Manish
Published: November 2021

A short-chain fructo-oligosaccharide (sc-FOS) was tested in a simulator of the human gut microbial ecosystem (SHIME) in-vitro model to quantify its prebiotic effects according to Prebiotic index (PI) and Measure of prebiotic effect (MPE) equations. FossenceTM, (sc-FOS, 0.5%) was fermented in a simulated human proximal colonic condition, using a fecal inoculum from a healthy individual. We analyzed the pH reduction, substrate utilization, lactate and short-chain fatty acid (SCFA) production and microbial community modulation. Microbial fermentation of sc-FOS strongly reduced the media pH indicating the production of lactate and SCFA with accumulation of lactate and enhanced levels of acetate (34.38 ± 0.38mM), propionate (20.93 ± 0.56mM), and butyrate (4.93 ± 0.03mM) compared to 18.46 ± 0.20mM, 6.24 ± 0.10mM, and 3.3 ± 0.06mM in the blank, respectively. Total SCFA production in test media was 61.91 ± 0.87mM compared to 33.65 ± 0.36mM in blank and the contribution of free-sugars present in sc-FOS to SCFAs was negligible. Modulation of the microbial community was analyzed through 16S rRNA sequencing and we found that sc-FOS greatly stimulated the beneficial bacteria such as Bifidobacteria and Lactobacillus. We report the PI and MPE values for FossenceTM, as 14.9 and 0.01 respectively at the end of 24h, which is an indicator of a strong prebiotic effect.
Effect of attenuation on amplitude distribution andbvalue in rock acoustic emission tests
Authors: Chen Daolong , Liu Xiling , He Wei , Xia Changgen , Gong Fengqiang , Li Xibing , Cao Xinya
Published: November 2021

The b value is a critical parameter that has been used to describe spatial and temporal size distribution characteristics in data from both natural seismicity and laboratory rock acoustic emission (AE) tests. However, unlike the magnitude used for b value estimation in earthquakes which corrects for hypocentral distance, the apparent amplitude of the AE, is most commonly used for b value estimation in the rock AE test. This ignores the effect of attenuation, which may modify the frequency–amplitude distribution and affect the b value results. Here, we investigate the attenuation effect on the estimate of b value from synthetic data generated by random sampling of a doubly truncated frequency–amplitude distribution and a known underlying b value from a statistical perspective. We generated AE source amplitudes that obey an exponential distribution with different theoretical b values and applied an attenuation operator to obtain apparent frequency–amplitude data for comparison with the true underlying distribution. The results show that the b value is unchanged within a specific interval of amplitude distribution after accounting for attenuation under the conditions examined here, and that data truncation is the primary cause of modification of the frequency–amplitude distribution in the presence of attenuation, rather than attenuation alone. In addition, we employed the same synthetic data simulation scheme to estimate the minimum data volume for accurate estimation of the underlying b value from the apparent amplitude distribution. We found that the determination of the minimum data volume is influenced by the theoretical b value of the underlying distribution: the higher the theoretical b value, the larger the minimum data volume required, varying from 200 events from b < 1.5 to 300 for b > 1.5.
Evaluating the implementation and use of patient-reported outcome measures in a mental health hospital in Denmark: a qualitative study
Authors: Kristensen Solvejg , Holmskov Jens , Baandrup Lone , Videbech Poul , Bonde Maria , Mainz Jan
Published: November 2021

Background

Reporting of barriers and successes associated with the implementation and use of patient-reported outcomes (PROs) is limited as a means to ensure enhanced patient involvement, shared decision-making and improved treatment and care. We set out to evaluate the implementation and use of the PRO-Psychiatry initiative on patient-reported outcome measures in Danish mental health care. We aimed to described four specific areas: the quality of the clinical consultations before and after the implementation of PRO-Psychiatry as perceived by the patients (objective A), the motivation for participating in PRO-Psychiatry as perceived by patients and clinicians (objective B), the implementation process as perceived by patients, clinicians and managers (objective C) and suggestions for improvement (objective D).

Methods

The PRO-Psychiatry initiative was evaluated through a participatory approach, including patients, clinicians and managers. A repeated cross-sectional interview-based survey explored the quality of the clinical consultation before and after the implementation of PRO-Psychiatry. A three-step semi-structured group interview, inspired by the modified mini-Delphi method, was used to establish consensus on the evaluation of the implementation and use of the initiative.

Results

The evaluation pointed at PRO-Psychiatry as a meaningful initiative, which motivated patients and supported clinicians. The patients emphasised the importance of PROs, but they also found that PROs were not used enough. Clinically relevant improvements were detected after the implementation of the initiative; more patients felt heard and experienced that clinicians took a greater interest in their problems. The clinicians valued the easily accessible real-time graphical display of the PRO responses in the electronic health record (EHR). Clinicians and managers agreed that clinical PRO practices, patient compliance and use of PROs in treatment and care should be supported during implementation.

Conclusion

The evaluation was overall positive. Patients and clinicians were willing to participate, found the online reporting easy and valued the direct access to PRO responses in the EHR. An essential feature was the integration of well-defined and functional PRO practices into the existing clinical workflow. Using PROs in the clinical sessions in a way that was palpable to the patient was found to be a significant improvement need. At the individual level, PRO-Psychiatry can use patient outcome information to support dialogue, encourage shared decision-making and promote self-management during recovery. At the aggregated patient level, the PROs can be used for monitoring the patient-perceived quality of care and for research.
Exploring temporal trends and risk factors for resistance in Escherichia coli-causing bacteraemia in England between 2013 and 2018: an ecological study
Authors: Aliabadi Shirin , Jauneikaite Elita , Müller-Pebody Berit , Hope Russell , Vihta Karina-Doris , Horner Carolyne , Costelloe Céire E
Published: November 2021

Background

Escherichia coli are Gram-negative bacteria associated with an increasing burden of antimicrobial resistance (AMR) in England.

Objectives

To create a comprehensive epidemiological picture of E. coli bacteraemia resistance trends and risk factors in England by linking national microbiology data sources and performing a longitudinal analysis of rates.

Methods

A retrospective observational study was conducted on all national records for antimicrobial susceptibility testing on E. coli bacteraemia in England from 1 January 2013 to 31 December 2018 from the UK Health Security Agency (UKHSA) and the BSAC Resistance Surveillance Programme (BSAC-RSP). Trends in AMR and MDR were estimated using iterative sequential regression. Logistic regression analyses were performed on UKHSA data to estimate the relationship between risk factors and AMR or MDR in E. coli bacteraemia isolates.

Results

An increase in resistance rates was observed in community- and hospital-onset bacteraemia for third-generation cephalosporins, co-amoxiclav, gentamicin and ciprofloxacin. Among community-acquired cases, and after adjustment for other factors, patients aged >65 years were more likely to be infected by E. coli isolates resistant to at least one of 11 antibiotics than those aged 18–64 years (OR: 1.21, 95% CI: 1.18–1.25; P < 0.05). In hospital-onset cases, E. coli isolates from those aged 1–17 years were more likely to be resistant than those aged 18–64 years (OR: 1.33, 95% CI: 1.02–1.73; P < 0.05).

Conclusions

Antibiotic resistance rates in E. coli-causing bacteraemia increased between 2013 and 2018 in England for key antimicrobial agents. Findings of this study have implications for guiding future policies on a prescribing of antimicrobial agents, for specific patient populations in particular.
Next Step for Global Adolescent and Young Adult Oncology: A Core Patient-Centered Outcome Set
Authors: Husson Olga , Reeve Bryce B , Darlington Anne-Sophie , Cheung Christabel K , Sodergren Samantha , van der Graaf Winette T A , Salsman John M
Published: November 2021

The relatively small number of cancers in the adolescent and young adult (AYA) age group, those aged 15-39 years, does not appropriately reflect the personal and societal costs of cancer in this population, as reflected in the potential years of life lost or saved, the decreased productivity and health-related quality of life due to the impact of the disease during formative years, and long-term complications or disabilities. Improvements in care and outcomes for AYAs with cancer require collaboration among different stakeholders at different levels (patients, caregivers, health-care professionals, researchers, industry, and policymakers). Development of a Core Outcome Set (COS), an agreed minimum set of outcomes that should be measured globally in research and routine clinical practice—specifically for AYAs with cancer—with outcomes that are well defined based on the perspective of those who are affected and assessed with validated measures, is urgently required. A globally implemented COS for AYAs with cancer will facilitate better pooling of research data and the implementation of high-quality health-care registries, which by benchmarking not only nationally but also internationally, may ultimately improve the value of the care given to these underserved young cancer patients. We reflect on the need to develop a COS for AYAs with cancer, the arenas of application, and the challenges of implementing an age-specific COS in research and clinical practice.
A National Survey of Outpatient Parenteral Antibiotic Therapy Practices
Authors: Vaz Louise E , Felder Kimberly K , Newland Jason G , Hersh Adam L , Rajapakse Nipunie S , Willis Zachary I , Banerjee Ritu , Gerber Jeffrey S , Schwenk Hayden T , Wang Marie E
Published: November 2021

We conducted a national survey of pediatric infectious diseases (ID) clinicians on outpatient parenteral antibiotic therapy (OPAT) practices and post-discharge ID follow-up. Only 15% of sites required ID consultation for all OPAT. ID division resources for post-discharge care varied. Opportunities exist to increase ID involvement in post-discharge management of serious infections.
A comparative study between curcumin and curcumin nanoemulsion on high-fat, high-fructose diet-induced impaired spermatogenesis in rats
Authors: Nasr Maha , Abd-Allah Hend , Ahmed-Farid Omar A H , Bakeer Rofanda M , Hassan Nabila S , Ahmed Rania F
Published: November 2021

Objectives

Curcumin is a promising nutraceutical with reported diverse therapeutic properties, but of limited oral bioavailability. The current manuscript investigates the role of encapsulation of curcumin in nanoemulsion form in counteracting the adverse effect of chronic ingestion of a high-fat high-fructose diet (HFHF) by juvenile male rats regarding testicular abnormalities and declined spermatogenesis.

Methods

Curcumin nanoemulsion was administered orally to Wistar rats at a dose of 5 or 10 mg/kg and compared with curcumin powder, followed by a pharmacological and histological assessment.

Key findings

Results demonstrated that curcumin nanoemulsion was superior to curcumin powder, particularly in enhancing the percentage progressive motility of spermatozoa, normalization of essential and non-essential amino acids in semen, normalization of serum leptin and testosterone levels, as well as normalization of oxidative and nitrosative parameters. It was also proven to reduce testicular DNA fragmentation, while elevating testicular cellular energy. In addition, curcumin nanoemulsion administered at a dose of 10 mg/kg induced the highest level of spermatogenesis, delineated by histological examination of the seminiferous tubules.

Conclusions

It can be concluded that curcumin nanoemulsion administered at a dose of 10 mg/kg successfully ameliorates the adverse effects of a HFHF on spermatogenesis.
Immunity-associated volatile emissions of β-ionone and nonanal propagate defence responses in neighbouring barley plants
Authors: Brambilla Alessandro , Sommer Anna , Ghirardo Andrea , Wenig Marion , Knappe Claudia , Weber Baris , Amesmaier Melissa , Lenk Miriam , Schnitzler Jörg-Peter , Vlot A Corina
Published: November 2021

Plants activate biochemical responses to combat stress. (Hemi-)biotrophic pathogens are fended off by systemic acquired resistance (SAR), a primed state allowing plants to respond faster and more strongly upon subsequent infection. Here, we show that SAR-like defences in barley (Hordeum vulgare) are propagated between neighbouring plants, which respond with enhanced resistance to the volatile cues from infected senders. The emissions of the sender plants contained 15 volatile organic compounds (VOCs) associated with infection. Two of these, β-ionone and nonanal, elicited resistance upon plant exposure. Whole-genome transcriptomics analysis confirmed that interplant propagation of defence in barley is established as a form of priming. Although gene expression changes were more pronounced after challenge infection of the receiver plants with Blumeria graminis f. sp. hordei, differential gene expression in response to the volatile cues of the sender plants included an induction of HISTONE DEACETYLASE 2 (HvHDA2) and priming of TETRATRICOPEPTIDE REPEAT-LIKE superfamily protein (HvTPL). Because HvHDA2 and HvTPL transcript accumulation was also enhanced by exposure of barley to β-ionone and nonanal, our data identify both genes as possible defence/priming markers in barley. Our results suggest that VOCs and plant–plant interactions are relevant for possible crop protection strategies priming defence responses in barley.
Loop restricted existential rules and first-order rewritability for query answering
Authors: Asuncion Vernon , Zhang Yan , Zhang Heng , Bai Yun
Published: November 2021

In ontology-based data access (OBDA), the classical database is enhanced with an ontology in the form of logical assertions generating new intensional knowledge. A powerful form of such logical assertions is the tuple-generating dependencies (TGDs), also called existential rules, where Horn rules are extended by allowing existential quantifiers to appear in the rule heads. In this paper, we introduce a new language called loop restricted (LR) TGDs (existential rules), which are TGDs with certain restrictions on the loops embedded in the underlying rule set. We study the complexity of this new language. We show that the conjunctive query answering (CQA) under the LR TGDs is decidable. In particular, we prove that this language satisfies the so-called bounded derivation-depth property (BDDP), which implies that the CQA is first-order rewritable, and its data complexity is in Ac$^{0}$. We also prove that the combined complexity of the CQA is 2-ExpTime complete, while the language membership is Pspace complete. Then we extend the LR TGDs language to the generalized loop restricted (GLR) TGDs language and prove that this class of TGDs still remains to be first-order rewritable and properly contains most of other first-order rewritable TGDs classes discovered in the literature so far.
The survival of multiphase dusty clouds in hot winds
Authors: Farber Ryan J , Gronke Max
Published: November 2021

Much progress has been made recently in the acceleration of ∼104 K clouds to explain absorption line measurements of the circumgalactic medium and the warm, atomic phase of galactic winds. However, the origin of the cold, molecular phase in galactic winds has received relatively little theoretical attention. Studies of the survival of ∼104 K clouds suggest efficient radiative cooling may enable the survival of expelled material from galactic discs. Alternatively, gas colder than 104 K may form within the outflow, including molecules if dust survives the acceleration process. We explore the survival of dusty clouds in a hot wind with three-dimensional hydrodynamic simulations including radiative cooling and dust modelled as tracer particles. We find that cold ∼103 K gas can be destroyed, survive, or transformed entirely to ${\sim}10^4\,$ K gas. We establish analytic criteria distinguishing these three outcomes that compare characteristic cooling times to the system’s ‘cloud crushing’ time. In contrast to typically studied ∼104 K clouds, colder clouds are entrained faster than the drag time as a result of efficient mixing. We find that while dust can in principle survive embedded in the accelerated clouds, the survival fraction depends critically on the time dust spends in the hot phase and on the effective threshold temperature for destruction. We discuss our results in the context of polluting the circumgalactic medium with dust and metals, as well as understanding observations suggesting rapid acceleration of molecular galactic winds and ram-pressure-stripped tails of jellyfish galaxies.
Internally driven warps in disc galaxies
Authors: Sellwood J A , Debattista Victor P
Published: November 2021

Any perturbation to a disc galaxy that creates a misalignment between the planes of the inner and outer disc, will excite a slowly evolving bending wave in the outer disc. The torque from the stiff inner disc drives a retrograde, leading spiral bending wave that grows in amplitude as it propagates outwards over a period of several Gyr. The part of the disc left behind by the outwardly propagating wave is brought into alignment with the inner disc. This behaviour creates warps that obey the rules established from observations, and operates no matter what the original cause of the misalignment between the inner and outer disc. Here, we confirm that mild warps in simulations of disc galaxies can be excited by shot noise in the halo, as was recently reported. We show that the quadrupole component of the noise creates disc distortions most effectively. Bending waves caused by shot noise in carefully constructed equilibrium simulations of isolated galaxies are far too mild to be observable, but perturbations from halo substructure and galaxy assembly must excite larger amplitude bending waves in real galaxies.
Removal and replacement of interference in tied-array radio pulsar observations using the spectral kurtosis estimator
Authors: Purver M , Bassa C G , Cognard I , Janssen G H , Karuppusamy R , Kramer M , Lee K J , Liu K , McKee J W , Perrodin D , Sanidas S , Smits R , Stappers B W
Published: November 2021

We describe how to implement the spectral kurtosis method of interference removal (zapping) on a digitized signal of averaged power values. Spectral kurtosis is a hypothesis test, analogous to the t-test, with a null hypothesis that the amplitudes from which power is formed belong to a ‘good’ distribution – typically Gaussian with zero mean – where power values are zapped if the hypothesis is rejected at a specified confidence level. We derive signal-to-noise ratios (SNRs) as a function of amount of zapping for folded radio pulsar observations consisting of a sum of signals from multiple telescopes in independent radio-frequency interference environments, comparing four methods to compensate for lost data with coherent (tied-array) and incoherent summation. For coherently summed amplitudes, scaling amplitudes from non-zapped telescopes achieves a higher SNR than replacing zapped amplitudes with artificial noise. For incoherently summed power values, the highest SNR is given by scaling power from non-zapped telescopes to maintain a constant mean. We use spectral kurtosis to clean a tied-array radio pulsar observation by the Large European Array for Pulsars: the signal from one telescope is zapped with time and frequency resolutions of $6.25\, \mathrm{ms}$ and $0.16\, \mathrm{MHz}$, removing interference, along with 0.27 per cent of ‘good’ data, giving an uncertainty of $0.25\, \mathrm{\mu \mathrm{ s}}$ in pulse time of arrival (TOA) for PSR J1022+1001. We use a single-telescope observation to demonstrate recovery of the pulse profile shape, with 0.6 per cent of data zapped and a reduction from 1.22 to $0.70\, \mathrm{\mu \mathrm{ s}}$ in TOA uncertainty.
Identification and targeting of G-quadruplex structures in MALAT1 long non-coding RNA
Authors: Mou Xi , Liew Shiau Wei , Kwok Chun Kit
Published: November 2021

RNA G-quadruplexes (rG4s) have functional roles in many cellular processes in diverse organisms. While a number of rG4 examples have been reported in coding messenger RNAs (mRNA), so far only limited works have studied rG4s in non-coding RNAs (ncRNAs), especially in long non-coding RNAs (lncRNAs) that are of emerging interest and significance in biology. Herein, we report that MALAT1 lncRNA contains conserved rG4 motifs, forming thermostable rG4 structures with parallel topology. We also show that rG4s in MALAT1 lncRNA can interact with NONO protein with high specificity and affinity in vitro and in nuclear cell lysate, and we provide cellular data to support that NONO protein recognizes MALAT1 lncRNA via rG4 motifs. Notably, we demonstrate that rG4s in MALAT1 lncRNA can be targeted by the rG4-specific small molecule, peptide, and L-aptamer, leading to the dissociation of MALAT1 rG4-NONO protein interaction. Altogether, this study uncovers new and important rG4s in MALAT1 lncRNAs, reveals their specific interactions with NONO protein, offers multiple strategies for targeting MALAT1 and its RNA–protein complex via its rG4 structure and illustrates the prevalence and significance of rG4s in ncRNAs.
Pathways to de novo domestication of crop wild relatives
Authors: Curtin Shaun , Qi Yiping , Peres Lázaro E P , Fernie Alisdair R , Zsögön Agustin
Published: November 2021

Growing knowledge about crop domestication, combined with increasingly powerful gene-editing toolkits, sets the stage for the continual domestication of crop wild relatives and other lesser-known plant species.
Atherosclerosis progression in antiphospholipid syndrome is comparable to diabetes mellitus: a 3 year prospective study
Authors: Evangelatos Gerasimos , Kravvariti Evrydiki , Konstantonis George , Tentolouris Nikolaos , Sfikakis Petros P , Tektonidou Maria G
Published: November 2021

Background

Antiphospholipid syndrome (APS) is an autoimmune thrombophilia leading to life-threatening cardiovascular events. Cross-sectional data support that APS is associated with accelerated atherosclerosis, but this has not been confirmed in prospective studies. We aimed to compare the rate of atherosclerosis progression over a 3 year period between patients with APS, diabetes mellitus (DM) and healthy controls (HCs).

Methods

Eighty-six patients with APS [43 with primary APS (PAPS), 43 with SLE-related APS (SLE-APS)] and an equal number of age- and sex-matched patients with DM and HCs who underwent a baseline US of the carotid and femoral arteries were invited for a 3 year follow-up evaluation for atherosclerotic plaque progression. Multivariate analysis was performed for the assessment of determinants of plaque progression after adjustment for disease-related and traditional cardiovascular risk factors.

Results

Seventy-four APS patients (74.3% female, 38 with PAPS), 58 DM patients and 73 HCs were included. APS patients exhibited a 3.3-fold higher risk of new atherosclerotic plaque formation compared with HCs (P = 0.031), similar to that in DM [odds ratio (OR) 3.45, P = 0.028]. In APS patients, plaque development risk was higher in SLE-APS vs PAPS (OR 7.75, P = 0.038) and was independently associated with the presence of traditional cardiovascular risk factors as expressed by the Systematic Coronary Risk Evaluation risk (OR 2.31, P = 0.008).

Conclusion

APS is characterized by accelerated rates of subclinical atherosclerosis to a degree comparable to DM, which is more pronounced in SLE-APS patients. Traditional cardiovascular risk factors are major determinants of this risk, warranting aggressive management as in other disorders with high cardiovascular risk.
Competency-Based Medical Education: Considering Its Past, Present, and a Post–COVID-19 Era
Authors: Ryan Michael S. , Holmboe Eric S. , Chandra Subani
Published: November 2021

Advancement toward competency-based medical education (CBME) has been hindered by inertia and a myriad of implementation challenges, including those associated with assessment of competency, accreditation/regulation, and logistical considerations. The COVID-19 pandemic disrupted medical education at every level. Time-in-training sometimes was shortened or significantly altered and there were reductions in the number and variety of clinical exposures. These and other unanticipated changes to existing models highlighted the need to advance the core principles of CBME. This manuscript describes the impact of COVID-19 on the ongoing transition to CBME, including the effects on training, curricular, and assessment processes for medical school and graduate medical education programs. The authors outline consequences of the COVID-19 disruption on learner training and assessment of competency, such as conversion to virtual learning modalities in medical school, redeployment of residents within health systems, and early graduation of trainees based on achievement of competency. Finally, the authors reflect on what the COVID-19 pandemic taught them about realization of CBME as the medical education community looks forward to a postpandemic future.
Ethical Dilemmas, Moral Distress, and the Risk of Moral Injury: Experiences of Residents and Fellows During the COVID-19 Pandemic in the United States
Authors: Farrell Colleen M. , Hayward Bradley J.
Published: November 2021

The ongoing COVID-19 pandemic has brought numerous ethical dilemmas to the forefront of clinical care, including for resident and fellow physician trainees. In this paper, the authors draw on their own experiences providing frontline COVID-19 clinical care in New York City in their respective roles as an internal medicine resident and later a pulmonary and critical care fellow, and as an associate program director for a pulmonary and critical care fellowship, along with published literature on trainees’ experiences in the pandemic, to describe common ethical dilemmas confronted by residents and fellows during the pandemic. These dilemmas are related to personal health risk, resource allocation, health care inequities, and media relations. The authors use a framework of microethics to underscore how these dilemmas are highly contextualized within trainees’ institutions, their specific roles, and the patient populations to which they provide care. They argue that frequent ethical dilemmas, compounded by the intense physical and emotional stress of medical training and the pandemic itself, increase the potential for trainees to experience moral distress. Recurrent moral distress may, in turn, put trainees at risk for moral injury with consequences for their mental health and overall well-being. It is imperative to gain a clear understanding of this issue, not only for those trainees who have experienced or are at risk for experiencing personal consequences but also because it may help identify ways to better support the well-being of providers and the care of patients going forward.
Social Determinants, Risk Factors, and Needs: A New Paradigm for Medical Education
Authors: Muller David , Hurtado Alicia , Cunningham Tara , Soriano Rainier P. , Palermo Ann-Gel S. , Hess Leona , Willis Michelle Sainté , Linkowski Lauren , Forsyth Beverly , Parkas Valerie
Published: November 2021

COVID-19 and the escalation of racism and bias that has come in its wake have had a devastating impact on health professions students. In addition to academic challenges and personal health risks, aspects of students’ lives that have often gone unnoticed or inadequately addressed have come to light. Financial constraints that impact access to housing and food, neighborhood safety in light of the spike in hate crimes, and the bias inherent in the continuum from premedical education to undergraduate and graduate medical education are some examples. The authors believe that to better understand students’ lived experiences and determine how to best support them, the social determinants of health framework should be applied. This framework, the social determinants of education, encompasses concepts such as social risk factors and social needs in an effort to focus more intentionally on what can be done at a policy, institutional, and individual level. In response to the pandemic, the authors expanded their appreciation of students’ risk factors and needs by advancing the scope and refining the definitions of 3 key determinants: from well-being to the power of individual and communal resilience, from equity to centering racial justice, and from student health to public health and infection prevention. The authors propose applying this same paradigm to the lived experiences of staff in medical education, whose needs are often neglected in favor of students and faculty, and who, in many cases, were the most negatively impacted by COVID-19 of all the constituents in an academic health center.
Lumbar Spinal Stenosis with Degenerative Spondylolisthesis Treated with Decompression Alone. A Cohort of 346 Patients at a Large Spine Unit. Clinical Outcome, Complications and Subsequent Surgery
Authors: Pazarlis Konstantinos , Frost Anders , Försth Peter
Published: November 2021

Study Design.

Cohort study.

Objective.

To study the clinical outcome, complications and subsequent surgery rate of DA for lumbar spinal stenosis (LSS) with DS.

Summary of Background Data.

There is still no consensus regarding the treatment approach for LSS with DS.

Methods.

We performed a retrospectively designed cohort study on prospectively collected data from a single high productive spine surgical center. Results from the Swedish Spine Registry and a local register for complications were used for the analyses. Patients with LSS and DS (>3 mm) who underwent DA during January 2012 to August 2017 were included. Patient reported outcome measures at baseline and 2 years after surgery were analyzed. Complications within 30 days of surgery and all subsequent surgery in the lumbar spine were registered.

Results.

We identified and included 346 patients with completed 2-year follow-up registration. At 2-year follow-up there was a significant improvement in all outcome measures. The global assessment success rate for back and leg pain was 68.3% and 67.6% respectively. Forty-one patients had at least 1 intra- or postoperative complication (11.9%). Nine patients (2.6%), underwent subsequent surgery within 2 years of the primary surgery whereof 2 underwent fusion. During the whole period of data collection, that is, as of June 2020, 28 patients had undergone subsequent surgery (8.1%) whereas 8 of them had had 2 surgeries. Fifteen patients underwent fusion.

Conclusion.

DA provides good clinical outcome at 2-year follow-up in patients with LSS and DS with low rate of intra- and postoperative complications and subsequent surgery. Our data supports the evidence that DA is effective and safe for LSS with DS.

Level of Evidence: 3
Heparin-Induced Thrombocytopenia
Authors: Smith Raymond , Bullard Zackery
Published: November 2021

Heparin-induced thrombocytopenia (HIT) is a life-threatening adverse drug reaction that relies on quick assessment and treatment by the health care team to prevent poor outcomes. Nurses can play a critical role in recognizing disease, advocating for patients, and facilitating treatment by being familiar with current guideline recommendations and risk stratification approaches. The purpose of this article is to review management of HIT including pathogenesis, clinical presentation, current guideline recommendations for risk assessment, laboratory testing, and treatment, as well as discuss nonheparin anticoagulation options that may be ordered when HIT is suspected.
Factors Affecting Inpatient Mortality and Length of Stay in Nonmetastatic Colorectal Cancer
Authors: Ulanja Mark B. , Beutler Bryce D. , Antwi-Amoabeng Daniel , Moody Alastair E. , Chang Phoebe T. , Rahman Ganiyu A. , Apanga Paschal A. , Alese Olatunji B.
Published: November 2021

Objective:

The objective of this study was to assess the effect of opioid use and other factors on inpatient length of stay (LOS) and mortality among patients hospitalized with nonmetastatic colorectal cancer (NMCRC).

Materials and Methods:

We analyzed discharge encounters collected from the 2016 to 2017 National Inpatient Sample (NIS) to evaluate the effect of long-term opioid use (90 d or longer) and cancer-related complications on LOS and mortality among hospitalized patients with NMCRC.

Results:

A total of 94,535 patients with NMCRC were included in the analysis. Long-term opioid users had a shorter average LOS and reduced inpatient mortality as compared with nonopioid users (5.97±5.75 vs. 6.66±6.92 d, P<0.01; and adjusted odds ratio=0.72, 95% confidence interval: 0.56-0.93, respectively). Factors that significantly increased both LOS and mortality included infection, venous thromboembolism, and chemotherapy-induced neutropenia; the average LOS was 2.7, 2.6, and 0.7 days longer, and the adjusted odds ratio for risk of inpatient mortality was 3.7, 1.2, and 1.2, respectively (P<0.05), for patients admitted with these cancer-related complications.

Conclusions:

Long-term opioid use is associated with decreased LOS and inpatient mortality among patients with NMCRC. Individuals admitted for cancer-related complications face a longer LOS and increased mortality as compared with those admitted without these morbidities.
Health Service Utilization Among Children and Adolescents with Posttraumatic Stress Disorder: A Case-Control Study
Authors: Goger Pauline , Zerr Argero A. , Weersing V. Robin , Dickerson John F. , Crawford Phillip M. , Sterling Stacy A. , Waitzfelder Beth , Daida Yihe G. , Ahmedani Brian K. , Penfold Robert B. , Lynch Frances L.
Published: November 2021

Objective:

Trauma exposure is widely prevalent, with more than 60% of adolescents having experienced at least 1 traumatic event and a third of those at high risk to develop posttraumatic stress disorder (PTSD). Data are scarce and out of date on the services children and adolescents with PTSD receive, impeding efforts to improve care and outcomes. This study examines health service use for a large and diverse sample of children and adolescents with and without a diagnosis of PTSD.

Method:

Using a matched case-control study, we gathered information from 4 large health care systems participating in the Mental Health Research Network. Data from each site's electronic medical records on diagnoses, health care encounters, and demographics were analyzed. Nine hundred fifty-five 4- to 18-year-olds with a diagnosis of PTSD were identified and matched on a 1:5 ratio to 4770 controls. We compared cases with controls on frequency of service use in outpatient primary care, medical specialty care, acute care, and mental health care. We also assessed psychotropic medication use.

Results:

Children and adolescents diagnosed with PTSD used nearly all physical and mental health service categories at a higher rate than controls. However, one-third of children and adolescents did not receive even 1 outpatient mental health visit (36.86%) during the year-long sampling window.

Conclusion:

Our findings suggest that children and adolescents diagnosed with PTSD may have unmet mental health needs. They are high utilizers of health services overall, but lower utilizers of the sectors that may be most helpful in resolving their symptoms.
Use of Social Media to Exchange Critical Care Practice Evidence During the Pandemic
Authors: Bourgault Annette M. , Davis Jean W. , Peach Brian C. , Ahmed Rohina , Wheeler Megan
Published: November 2021

Background

The evidence-based practice (EBP) process was challenged during the early phase of the COVID-19 pandemic by factors such as a novel disease, rapidly changing guidelines, shortage of personal protective equipment, and other health care supplies.

Objectives

Our aims were to (1) explore sources of evidence sought by critical care nurses during a pandemic and (2) explore nurses' perceptions of EBP.

Methods

A qualitative exploratory study was conducted using deidentified data from the American Association of Critical-Care Nurses (ACCN) open-access Facebook page, January 28 to April 30, 2020.

Results

Two major themes were identified: (1) “sharing and seeking evidence,” that is, nurses used both formal and informal sources to explore evidence supporting evolving clinical practices, and (2) “concerns about evidence,” that is, nurses expressed concerns about lack of evidence and mistrust of evolving evidence.

Discussion

Initially, there was a mismatch in nurses' expectations of the American Association of Critical-Care Nurses Facebook page. A major limitation of Facebook is the lack of a repository for quick retrieval of information. Despite these limitations, and fear and mistrust of changing guidelines, social media was used to communicate, collaborate, and share evidence to support clinical practice. Critical care nurses seemed to value evidence to support patient management and their personal safety during this evolving health crisis.

Conclusions

Social media played a large role in dissemination of timely evidence-based information during the early pandemic. Our results show that current EBP models should be revised to prepare for future crises and include direction for dealing with limited health care resources, and lack of and/or rapidly changing evidence.
Integration Process With a Donated Heart
Authors: Bahramnezhad Fatemeh , Dehghan Nayeri Nahid , Asgari Parvaneh
Published: November 2021

Background

In the posttransplant period, recipients face a complex phenomenon called the new heart, which is a symbol of physical and emotional life. They use different methods to get used to the new heart.

Objective

The aim of this study was to explore the integration process with a donated heart in heart transplant patients.

Methods

A qualitative study design with a grounded theory approach following Corbin and Strauss was used. Purposive and then theoretical sampling led to the inclusion of 15 heart transplant patients with diverse characteristics. Observations and semistructured interviews were conducted during a 1-year period in 2019 to 2020. Data collection and analysis occurred simultaneously.

Results

The process of integration with the new heart in the transplant patients or the core category in this study was “rebirth.” The process involved thre3 sequential and overlapping phases, which over time led to toleration and management of the situation. Religious issues, emotional chaos, additional worries, and sense of duality in the early stages after transplantation form a cycle, and the person is moving in this cycle.

Discussion

The results of this study indicated that the patients experienced several emotional and psychological changes after heart transplantation. It was also shown that the participants experienced a change in the emotions and feelings over time. On the basis of the findings of this study, it can be suggested that health care providers need to improve their knowledge about posttransplant changes, recipients' feelings, and adaptation strategies.