bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypertension: a cardiovascular risk factor
Authors: Salmon Thomas , Hatherley James , Sankaranarayanan Rajiv
Published: October 2022

Hypertension is a major risk factor for cardiovascular disease, with cardiovascular disease being the leading cause of hypertension-related mortality. Systolic blood pressure is superior to diastolic blood pressure when predicting cardiovascular risk. Despite this, diastolic blood pressure still plays a significant role in calculating risk, particularly of ischaemic heart disease in older populations and stroke in younger populations. Hypertension frequently occurs in the presence of other cardiovascular risk factors, including dyslipidaemias, hyperglycaemia, and raised body mass index. Scoring tools, such as QRISK3 and SCORE, can be used to calculate cardiovascular risk in the context of a patient’s age, lifestyle, and comorbidities. Reducing elevated blood pressure can lead to a reduction in cardiovascular risk, with recent studies advocating for a target systolic blood pressure of less than 130 mmHg.
Atrial fibrillation and hypertension
Authors: Najeeb Al-Rawahi Mohammed
Published: October 2022

Hypertension is one of the most common cardiovascular disorders, affecting around half of the adult population worldwide. On a population basis, hypertension is considered to be a major independent risk factor for atrial fibrillation (AF) development. The incidence of both diseases has increased significantly in the past decades and is expected to continuously rise in the coming years. Despite the well-known association between hypertension and AF, several pathogenic mechanisms underlying the higher risk of AF in hypertensive patients, as well as the best medical approach to prevent AF in this population, are still not clear. This chapter summarizes the main mechanisms through which hypertension is believed to promote AF. It also explores the latest therapies that favour intensive blood pressure control and the use of renin–angiotensin–aldosterone system (RAAS) inhibitors to reduce AF development and recurrence. Finally, an outline of AF detection strategies in hypertensive patients and anticoagulation approaches will be discussed.
The brain in hypertension
Authors: Gujjar Arunodaya R.
Published: October 2022

Hypertension is known to cause ‘end-organ damage’ in multiple systems, with significant involvement of the brain. Hypertension is a risk factor for conditions such as stroke, dementia, large artery atherosclerosis, and aneurysmal subarachnoid haemorrhage, as well as cerebral small vessel disease. Evidence now confirms the association of hypertension with dementia—both vascular dementia and Alzheimer’s disease. Early recognition and prompt and adequate treatment of hypertension are recognized to be of importance in the prevention of stroke and dementia. Such interventions may require to be nuanced to adapt to specific situations. This article reviews the pathophysiology, clinical and radiological manifestations, and reasons, as well as recommendations, for treatment of hypertension in the context of these conditions.
The kidneys in hypertension
Authors: Ahmad Sarah , Cohen Jordana B.
Published: October 2022

Similar to other organs, the kidney is susceptible to microvascular and macrovascular damage as a result of both acutely elevated blood pressures and inadequate control of chronic hypertension. The autoregulatory mechanisms within the kidney help to mitigate microvascular injury from elevations in blood pressure in healthy individuals, but can become impaired or overwhelmed, leaving the kidney unprotected when constantly exposed to high blood pressures. Whilst the causal relationship of hypertension with incident chronic kidney disease is controversial, ample evidence supports the relationship of inadequate blood pressure control with progression of chronic kidney disease. This chapter provides an overview of the physiological and epidemiological evidence related to kidney target organ injury in hypertension, as well as clinical approaches to try to minimize adverse renal effects from elevated blood pressure.
Hypertension and cardiovascular risk management
Authors: Sheppard James P. , Nadar Sunil K.
Published: October 2022

Hypertension is an important risk factor for the development of cardiovascular disease. Both systolic and diastolic blood pressures bear a relationship to cardiovascular morbidity and mortality. The main objective in the treatment of hypertension is to reduce the risk of cardiovascular disease and its complications. This ensures patients have increased life expectancy and improved quality of life. In those at high risk of cardiovascular disease, treatment should be focused on addressing all risk factors, and not blood pressure alone. Reducing cardiovascular risk in these patients involves treating associated risk factors such as diabetes and hyperlipidemia, by medications and by encouraging healthier lifestyle choices. Medications such as antiplatelet agents and lipid lowering drugs may be beneficial in those at high risk for cardiovascular events.
Diuretics in hypertension
Authors: Goel Harsh , Kumar Ashish
Published: October 2022

Diuretics are effective as sole agents for early-stage hypertension or in combination with other antihypertensive drugs for more severe hypertension. Although grouped together in one class as diuretics, they vary greatly in terms of mode of action, efficacy, indications and tolerability. The choice of diuretic depends on various factors, including age, ethnicity, and comorbidities. Loop diuretics are more effective than thiazide diuretics in advanced renal failure. Aldosterone antagonists like spironolactone are preferred in patients with difficult to control or resistant hypertension. Rigorous monitoring of electrolyte balance and renal function is essential during treatment. Combination of thiazide or loop diuretics with a potassium-sparing agent may further improve blood pressure control and aid maintenance of normokalaemia. Aldosterone antagonists are especially effective in management of resistant hypertension.
Calcium channel blockers in hypertension
Authors: Lip Stefanie , Padmanabhan Sandosh
Published: October 2022

Calcium channel blockers are a diverse group of drugs that are very effective in lowering blood pressure. Although all CCBs share the common property of inhibiting cellular calcium influx, they possess differing effects on vascular smooth muscle, cardiac myocytes, and cardiac conductive tissue. A majority of randomized controlled trials (RCTs) demonstrating the benefits of CCBs on outcomes have used dihydropyridines (especially amlodipine), and a minority have studied non-dihydropyridines (verapamil and diltiazem). There is however, no significant difference in effectiveness between dihydropyridines and non-dihydropyridines, compared to other antihypertensive drug classes in improving, cardiovascular outcomes in patients with hypertension at high cardiovascular risk. Current guidelines recommend that these agents be used as first-line drugs in the treatment of hypertension. They are generally well tolerated.
Hypertensive emergencies
Authors: Shantsila Alena
Published: October 2022

Hypertensive emergencies can manifest with a range of acute hypertension-mediated organ damage. This chapter reviews the epidemiology and common pathophysiological mechanisms causing the development of such emergencies. It discusses differences in clinical presentations of specific organ-specific damage such as hypertensive encephalopathy, malignant hypertension with retinal lesions, pre-eclampsia and eclampsia, acute left ventricular failure with pulmonary oedema, coronary ischaemia, acute aortic dissection, and renal failure. The chapter also reviews the evidence and current recommendations on appropriate management of these acute states and justification of preferable strategies for blood pressure reduction. Overall, the chapter aims to encourage a holistic approach to the management of these potentially life-threatening and often underdiagnosed forms of clinical emergency.
Treatment of the older adult
Authors: Akpan Asangaedem
Published: October 2022

Hypertension, especially isolated systolic hypertension, is common in older people. White coat hypertension is also very common in older individuals making ambulatory blood pressure monitoring (ABPM) essential to confirm the diagnosis of hypertension. Hypertension is a major risk factor for cerebrovascular accidents, coronary artery disease, heart failure, retinopathy, chronic renal disease, and cognitive impairment. The benefits of treating hypertension including isolated systolic hypertension in the elderly has been demonstrated conclusively. Overtreatment can be harmful and caution is advocated in the very old. Non-pharmacological approaches are an integral part of management. Management can be challenging because of side effects especially postural hypotension, polypharmacy, frailty, and coexisting multiple chronic conditions.
RM2Target: a comprehensive database for targets of writers, erasers and readers of RNA modifications
Authors: Bao Xiaoqiong , Zhang Yin , Li Huiqin , Teng Yuyan , Ma Lixia , Chen Zhihang , Luo Xiaotong , Zheng Jian , Zhao An , Ren Jian , Zuo Zhixiang
Published: October 2022

RNA modification is a dynamic and reversible process regulated by a series of writers, erasers and readers (WERs). Abnormal changes of WERs will disrupt the RNA modification homeostasis of their target genes, leading to the dysregulation of RNA metabolisms such as RNA stability and translation, and consequently to diseases such as cancer. A public repository hosting the regulatory relationships between WERs and their target genes will help in understanding the roles of RNA modifications in various physiological and pathological conditions. Previously, we developed a database named ‘m6A2Target’ to host targets of WERs in m6A, one of the most prevalent RNA modifications in eukaryotic cells. To host all RNA modification (RM)-related WER–target associations, we hereby present an updated database, named ‘RM2Target’ (http://rm2target.canceromics.org/). In this update, RM2Target encompasses 1 619 653 WER–target associations for nine RNA modifications in human and mouse, including m6A, m6Am, m5C, m5U, m1A, m7G, pseudouridine, 2′-O-Me and A-to-I. Extensive annotations of target genes are available in RM2Target, including but not limited to basic gene information, RNA modifications, RNA–RNA/RNA–protein interactions and related diseases. Altogether, we expect that RM2Target will facilitate further downstream functional and mechanistic studies in the field of RNA modification research.
Brood parasitism of Hooded Warblers by Brown-headed Cowbirds: Severe impact on individual nests but modest consequences for seasonal fecundity and conservation
Authors: Lignac Claire , Mumme Ronald L
Published: October 2022

Brood parasitism by Brown-headed Cowbirds (Molothrus ater) often has pronounced negative effects on host nests. However, the extent to which parasitism reduces annual reproduction and presents conservation challenges for host species is unclear. We address this issue with data from a color-banded population of Hooded Warblers (Setophaga citrina) in Pennsylvania, where Hooded Warblers have increased dramatically despite frequent nest parasitism. Our analysis is based on both an extensive dataset (8 years, 847 nests) on the per-nest impacts of cowbird parasitism and female-based stochastic simulations that accurately reflect the reproductive biology and parasitism rate (30%) of our study population. Cowbird parasitism has multiple negative consequences for Hooded Warbler nests, including (1) reduced host clutch size; (2) increased nest abandonment; (3) increased risk of complete failure due to predation; and (4) in surviving nests increased egg loss, hatching failure, and nestling mortality. We estimate that parasitism reduces success of Hooded Warbler nests 68%, from 1.29 to 0.41 fledglings per nest. For females and populations, however, the consequences of nest parasitism are considerably less extreme; female annual fecundity decreases 25% for each nesting attempt parasitized, and population-level fecundity drops 5.6% for each 10% increase in the frequency of parasitism. These more modest impacts are attributable to (1) steep declines in rates of cowbird parasitism as the nesting season progresses, (2) rapid renesting following abandonment or failure of parasitized nests, and (3) regular double brooding, with second broods initiated in late June and July when the incidence of cowbird parasitism is low. Our results help resolve the paradox of how cowbird parasitism can have both severe consequences for individual host nests but more modest and sustainable conservation impacts on the seasonal fecundity of females and populations. They further underscore the importance of determining population-level effects of brood parasites before investing in costly management efforts.
Social workers in integrated care beyond primary care: a scoping review
Authors: Milano Nicole , Petruzzi Liana , Covington Elle , Jones Barbara , Findley Patricia A
Published: October 2022

Social workers are key members of integrated care (IC) teams, yet there is limited research on the presence and roles of social workers on IC teams. Research literature from 2014 to 2021 was identified using the following search engines: Academic Search Complete, PsycINFO, CINAHL Plus, SocINDEX and MEDLINE. An exploratory search was conducted in January 2021 and an updated search was conducted in August 2021. This search resulted in 802 references, 50 of which met criteria for full-text review. Nine articles were identified through supplemental searching. 20 articles were included in the final review. Of the 20 studies included, most were randomized control trials (45%; n = 9). Studies varied across settings including specialty care (40%; n = 8), community-based practices (35%; n = 7), and primary care (25%; n = 5). Social workers engaged in a variety of roles including behavioral interventions, care coordination, and intake assessment. Social workers are engaged in IC in a variety of roles across healthcare settings. Findings suggest that patients’ mental health outcomes improve in IC settings which include social workers. Future research is needed to isolate the impact that social workers have in IC.

Social workers are key members of integrated care teams, yet there is a need to explore their roles on these teams. Using a methodological approach, research literature from 2014 to 2021 was explored to establish the roles, responsibilities, and settings of social workers on integrated care teams. Of the 20 articles included in the review, social workers held various roles including intake assessment, care coordination, and behavioral interventions, such as psychotherapy or cognitive behavioral therapy. Findings suggest that social workers are on integrated care teams in a variety of roles across various healthcare settings and that patients’ mental health outcomes improve in integrated care settings that include social workers.
Dissecting the below- and aboveground specific responses of two waterlogging-tolerant arbor species to nutrient supply under waterlogging conditions
Authors: Li Dadong , Miao Lingfeng , Cisse El-Hadji Malick , Li Lijun , Chen Boshen , Yang Fan
Published: October 2022

Although environmental factors affecting adventitious root (AR) formation have been examined, how nutrient status affects ARs under waterlogging conditions remains unclear. In this study, plants’ performance in responding to AR regulation based on nutrient supply was investigated in terms of plant morphology, physiology and AR traits. Results indicated that Cleistocalyx operculatus possesses higher waterlogging tolerance than Syzygium cumini according to the waterlogging tolerance coefficient, mainly because of the higher fresh weight, porosity and length of AR in C. operculatus. Nutrient supply treatment under a waterlogging condition significantly decreased the fresh weight, length, number, porosity, cortex area of AR and the ratio of cortex-to-stele area in both species relative to those in the waterlogging treatment, but significantly increased the activities and stele areas of AR, and leaf nutrient content. This result showed that nutrient supply caused variations in the morphological and anatomical structures of AR that were more beneficial to improve nutrient transportation than oxygen absorption under waterlogging conditions, supporting the nutrient-priority hypothesis. Moreover, nutrient supply under waterlogging conditions induced greater increase in stele area of ARs, fresh weight of the whole plant, total leaf area, leaf nitrogen level, total chlorophyll content, net photosynthesis rate and maximum photochemical quantum yield of PSII in S. cumini than in C. operculatus, suggesting that S. cumini can transport more nutrients and easily adapts to increase in nutrient supply under waterlogging conditions. Thus, S. cumini have better performance in extracting and utilizing nutrients in the water for plant growth. The findings showed that terrestrial arbor plants have physiological and microstructural mechanisms that respond to nutrient supply under waterlogging conditions and provide novel insights into the phytoremediation of eutrophic water bodies in wetland systems.
Checklists and cognitive aids: underutilized and under-researched tools to promote patient safety and optimize clinician performance
Authors: Daly Guris Rodrigo J. , Lane-Fall Meghan B.
Published: October 2022

Purpose of review

Checklists and other cognitive aids serve multiple purposes in the peri-operative setting and have become nearly ubiquitous in healthcare. This review lays out the evidence for their use, shortcomings and pitfalls to be aware of, and how technology and innovation may improve checklist and cognitive aid relevance and usability.

Recent findings

It has been difficult to show a direct link between the use of checklists alone and patient outcomes, but simulation studies have repeatedly demonstrated an association between checklist or cognitive aid use and improved performance. When implemented as part of a bundle of interventions, checklists likely have a positive impact, but the benefit of checklists and other cognitive aids may be both context- and user dependent. Advances in technology and automation demonstrate promise, but usability, design, and implementation research in this area are necessary to maximize effectiveness.

Cognitive aids like checklists are powerful tools in the perioperative and critical care setting. Further research and innovation may elevate what is possible by improving the usability and relevance of these tools, possibly translating into improved patient outcomes.
Development and implementation of databases to track patient and safety outcomes
Authors: Mukasa Christopher D.M. , Kovacheva Vesela P.
Published: October 2022

Purpose of review

Recent advancements in big data analytical tools and large patient databases have expanded tremendously the opportunities to track patient and safety outcomes.

We discuss the strengths and limitations of large databases and implementation in practice with a focus on the current opportunities to use technological advancements to improve patient safety.

Recent findings

The most used sources of data for large patient safety observational studies are administrative databases, clinical registries, and electronic health records. These data sources have enabled research on patient safety topics ranging from rare adverse outcomes to large cohort studies of the modalities for pain control and safety of medications. Implementing the insights from big perioperative data research is augmented by automating data collection and tracking the safety outcomes on a provider, institutional, national, and global level. In the near future, big data from wearable devices, physiological waveforms, and genomics may lead to the development of personalized outcome measures.

Patient safety research using large databases can provide actionable insights to improve outcomes in the perioperative setting. As datasets and methods to gain insights from those continue to grow, adopting novel technologies to implement personalized quality assurance initiatives can significantly improve patient care.
Immunosuppressant Monitoring—Performance of the First Mass Spectrometry–Based Automated Clinical Analyzer Cascadion
Authors: Grote-Koska Denis , Czajkowski Stefan , Staaden Antje , Brand Korbinian
Published: October 2022

Background:

Automatic analyzers simplify processes and may help improve standardization. The first automated analyzer based on mass spectrometry is available and offers a panel for monitoring cyclosporin A, tacrolimus, sirolimus, and everolimus. Method comparisons and evaluation tests are presented to verify the capability of the Cascadion system for use in a clinical laboratory.

Methods:

Sample preparation and measurements were performed using the Cascadion clinical analyzer. More than 1000 measurement values of patient samples were compared with an in vitro diagnostic–certified assay run on a liquid chromatography tandem mass spectrometry instrument. Precision and accuracy were determined using commercial quality control and external quality assessment (EQA) samples.

Results:

A good correlation between the 2 instruments was observed (Pearson correlation r = 0.956–0.996). Deming regression revealed 95% confidence intervals of slopes and intercepts covering the values 1 and 0, for sirolimus and everolimus, respectively, indicating equivalence of both measuring systems. However, for cyclosporin A, a bias was observed and confirmed using a Bland–Altman plot (−9.1%). Measurement repeatability and intermediate measurement precision were appropriate showing coefficients of variation of 0.9%–6.1% and 2.0%–5.3%, respectively. Accuracy according to internal quality controls was 85%–111% and 81%–100% in the EQA samples of Reference Institute of Bioanalytics and Laboratory of the Government Chemist, respectively. High robustness was found with regard to the linearity of the calibration lines (linear regression coefficient r
2 > 0.99). Carryover was negligible (0.1%).

Conclusions:

The Cascadion automatic analyzer produced convincing results in the measurement of patient, control, and EQA samples. The throughput was sufficient for routine use. Overall, it can be used as an alternative to open liquid chromatography tandem mass spectrometry instruments for immunosuppressant monitoring, simplifying processes without the need for specially trained personnel.
The Use of Extracorporeal Membrane Oxygenation for Burns: A Systematic Review and Meta-Analysis
Authors: Ng Emily Shu Ting , Ling Ryan Ruiyang , Mitra Saikat , Tan Chuen Seng , MacLaren Graeme , Ramanathan Kollengode
Published: October 2022

Burns are among the leading causes of trauma worldwide, and acute respiratory distress syndrome (ARDS) is a common cause of death in burn patients. Some patients develop hypoxemia refractory to conventional therapies and may be initiated on extracorporeal membrane oxygenation (ECMO) as rescue therapy. We conducted a meta-analysis for studies reporting on survival rates of patients receiving ECMO for burns or inhalation injuries, which was the primary outcome. Secondary outcomes included the hospital and intensive care unit length of stay and duration of ECMO. Random-effects (DerSimonian and Laird) were conducted. The pooled survival from 10 studies was 53.6% (95% confidence interval [CI]: 37.6–69.2%, high certainty). Survival was significantly associated with age (regression coefficient [B]: −0.0088, 95% CI: −0.0155 to −0.0021, p = 0.011) and the proportion of male patients (B: −1.0137 95% CI: −1.9695 to −0.0580, p = 0.038). Patients were cannulated on ECMO for a mean of 8.4 days (95% CI: 6.1–10.7) and remained in the ICU for a mean of 40.4 days (95% CI: 11.4–69.3). Mean hospital length of stay was 45.4 days (95% CI: 31.7–59.0). In conclusion, patients with burn and inhalation injuries who develop ARDS refractory to conservative management have a survival rate of 54% when placed on ECMO.
Social determinants of health screening in pediatric healthcare settings
Authors: Nerlinger Abby L. , Kopsombut Gift
Published: October 2022

Purpose of review

This article outlines updates in social determinants of health (SDOH) screening practices in pediatric healthcare and community settings. The transition to value-based care and the COVID-19 pandemic have both had significant impacts on screening practices, with implications for providers, communities, and policymakers.

Recent findings

The COVID-19 pandemic has exacerbated social needs for vulnerable patients and families, resulting in increased recognition by healthcare teams through screening. Policy frameworks like value-based care that aim to deliver whole-child care in the community are reorienting the logistics of screening, including screening in acute-care settings and community settings. Recent studies on family and provider perspectives should be integrated into screening practices.

Despite significant advances in and expansion of SDOH screening in the pediatric healthcare setting, there remain limitations and future research needs. More data is needed to evaluate social need screeners and interventions, and determine how healthcare systems, communities, and states can spread and scale such interventions based on outcomes and value measurements. Population-based social indices have the potential to augment individual patient screening, but this remains a future research need.
Food Addiction
Authors: Florio Ligia , Lassi Dângela L.S. , de Azevedo-Marques Perico Cintia , Vignoli Natalia G. , Torales Julio , Ventriglio Antonio , Castaldelli-Maia João M.
Published: October 2022

Food addiction is associated with dysfunctions in the reward circuit, such as hyperresponsiveness during the exposure to high-calorie flavors in overweight and obese individuals. Similar to drug addiction, there is also impaired self-regulatory control supported by deregulation of the frontostriatal circuit. The inclusion of validated measures of food addiction in clinical research, such as the Yale Food Addiction Scale, has increased the understanding of the clinical utility of this concept. Furthermore, food addiction, eating disorders, and obesity are interrelated. Thus, it is important to recognize food addiction among individuals affected by obesity and candidates for bariatric surgery (ie, preoperative and postoperative assessment). In this context, it has been reported that food addiction may impede weight loss and increase the likelihood of regaining weight when associated with personality traits such as neuroticism and impulsiveness, which are also related to mood disorders, anxiety, and addictive behaviors.
Rekindling a Passion for Nursing
Authors: Lal M. Maureen
Published: October 2022

Daily, I see another story about a nurse who has decided to leave the profession. The constant stress of caring for desperately ill COVID-19 patients, staffing issues, and other challenges have combined to push nurses out of our profession at an alarming rate. What we don't hear about are stories of nurses who leave the profession temporarily and then opt to return. I recently read an editorial written by a nurse who resigned at the height of the COVID pandemic. After a year off, she realized how much being a nurse was a part of her identity and she returned to bedside care. Her story is my story, too. Reading it inspired me to depart from the usual format of the Magnet® Perspectives column to share my nursing story in hopes it will inspire others.
Upper Eyelid Skin Laxity in Elderly Patients
Authors: Guo Fangfang , Song Jialin , Wang Lu , Yu Xinyang
Published: October 2022

Background

Laxity of the upper eyelid skin in the elderly usually leads to an aged appearance and visual field defect, which affects their quality of life. However, there are very few reports on the evaluation and treatment strategy for upper eyelid skin redundancy in elderly Asians. Hence, this article describes an upper eyelid skin laxity correction surgery using an innovative parallel palpebral margin incision to improve ptosis and enlarge the visual field.

Methods

From August 2012 to March 2021, 87 patients with severe eyelid laxity and ptosis presented to the Plastic Surgery Department of the Zhongda Hospital Affiliated to Southeast University. Upper eyelid skin laxity correction surgery with eyelid marginal incision was performed to correct the excessive tissue between the eyebrow and the upper eyelid and improve patients' vision field. Thereafter, a postoperative follow-up was conducted to observe the results in terms of skin laxity, eyelid shape changes, visual field improvement, postoperative scars, and patients' satisfaction.

Results

During the follow-up, information was collected between 3 months and 1 year after surgery. No visible scars were seen in patients after the operation, and the sagging skin of the upper eyelid was corrected. In addition, the effect of correcting visual field defect is stable, with no recurrence within 1 year. The operation was effective, and patients were satisfied.

Conclusion

This surgical strategy significantly improved severe upper eyelid skin laxity with inconspicuous postoperative scars. After the operation, patients felt satisfied, and their quality of life was notably improved.
A retrospective cross-sectional observational study of SARS-CoV-2 reinfection in La Ribera Health Department, Valencia, Spain
Authors: Belloch García Sebastián Luis
Published: October 2022

Introduction. The possibility of reinfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a widely proven fact and may have clinical implications.

Hypothesis /Gap Statement. It is not known whether there have been cases of reinfection by SARS-CoV-2 in La Ribera Health Department.

Aim. To determine whether there have been cases of reinfection by SARS-CoV-2 in La Ribera Health Department and to identify their characteristics.

Methodology. Retrospective cross-sectional observational study of cases of reinfection by SARS-CoV-2 in the population of La Ribera Department between March 2020 and February 2021. The positive baseline cohort includes all cases positive by RT-PCR for SARS-CoV-2, with reinfection cases being those that, after resolution of the first episode according to the World Health Organization (WHO) criteria, presented a new positive RT-PCR result.

Results. Out of a total of 15 687 cases with positive RT-PCR, 40 were considered to be reinfections, which meant a cumulative incidence of 0.255 % and an incidence density of 5.05 cases per 100 000 person-days. Most of the cases occurred during the highest incidence peaks of the pandemic in the department. Seventy-five per cent of the patients in these cases were older than 40 years, 42.5 % were healthcare professionals or nursing home residents and 12.5 % had an immunosuppressive comorbidity. There were no severe, critical or death cases. In the reinfection episodes, with respect to the first episode, there was a tendency to be milder, they required fewer days of hospitalization, their RT-PCR became negative earlier, they developed a greater humoral response and the sick leave period was shorter. The median period between the RT-PCR in the first episode and the RT-PCR in the second episode was 127.5 days (range: 48–301; IQR: 89.5–256.25)

Conclusions. SARS-CoV-2 reinfection cases are rare, tend to be mild and can occur within a median period of 127.5 days.
Epidemiological links and antimicrobial resistance of clinical Salmonella enterica ST198 isolates: a nationwide microbial population genomic study in Switzerland
Authors: Biggel Michael , Horlbog Jule , Nüesch-Inderbinen Magdalena , Chattaway Marie Anne , Stephan Roger
Published: October 2022

Salmonella

is a leading cause of foodborne outbreaks and systemic infections worldwide. Emerging multi-drug resistant

Salmonella

lineages such as a ciprofloxacin-resistant subclade (CIPR) within

Salmonella enterica

serovar Kentucky ST198 threaten the effective prevention and treatment of infections. To understand the genomic diversity and antimicrobial resistance gene content associated with S. Kentucky in Switzerland, we whole-genome sequenced 70 human clinical isolates obtained between 2010 and 2020. Most isolates belonged to ST198-CIPR. High- and low-level ciprofloxacin resistance among CIPR isolates was associated with variable mutations in ramR and acrB in combination with stable mutations in quinolone-resistance determining regions (QRDRs). Analysis of isolates from patients with prolonged ST198 colonization indicated subclonal adaptions with the ramR locus as a mutational hotspot. SNP analyses identified multiple clusters of near-identical isolates, which were often associated with travel but included spatiotemporally linked isolates from Switzerland. The largest SNP cluster was associated with travellers returning from Indonesia, and investigation of global data linked >60 additional ST198 salmonellosis isolates to this cluster. Our results emphasize the urgent need for implementing whole-genome sequencing as a routine tool for

Salmonella

surveillance and outbreak detection.
Dissemination of metaldehyde catabolic pathways is driven by mobile genetic elements in Proteobacteria
Authors: Castro-Gutierrez Víctor , Fuller Edward , Garcillán-Barcia María Pilar , Helgason Thorunn , Hassard Francis , Moir James
Published: October 2022

Bioremediation of metaldehyde from drinking water using metaldehyde-degrading strains has recently emerged as a promising alternative. Whole-genome sequencing was used to obtain full genomes for metaldehyde degraders

Acinetobacter calcoaceticus

E1 and

Sphingobium

CMET-H. For the former, the genetic context of the metaldehyde-degrading genes had not been explored, while for the latter, none of the degrading genes themselves had been identified. In

A. calcoaceticus

E1, IS91 and IS6-family insertion sequences (ISs) were found surrounding the metaldehyde-degrading gene cluster located in plasmid pAME76. This cluster was located in closely-related plasmids and associated to identical ISs in most metaldehyde-degrading β- and γ-Proteobacteria, indicating horizontal gene transfer (HGT). For

Sphingobium

CMET-H, sequence analysis suggested a phytanoyl-CoA family oxygenase as a metaldehyde-degrading gene candidate due to its close homology to a previously identified metaldehyde-degrading gene known as mahX. Heterologous gene expression in

Escherichia coli

alongside degradation tests verified its functional significance and the degrading gene homolog was henceforth called mahS. It was found that mahS is hosted within the conjugative plasmid pSM1 and its genetic context suggested a crossover between the metaldehyde and acetoin degradation pathways. Here, specific replicons and ISs responsible for maintaining and dispersing metaldehyde-degrading genes in α, β and γ-Proteobacteria through HGT were identified and described. In addition, a homologous gene implicated in the first step of metaldehyde utilisation in an α-Proteobacteria was uncovered. Insights into specific steps of this possible degradation pathway are provided.
An operationally implementable model for predicting the effects of an infectious disease on a comprehensive regional healthcare system
Authors: Chertok Daniel L. , Konchak Chad , Shah Nirav , Singh Kamaljit , Au Loretta , Hammernik Jared , Murray Brian , Solomonides Anthony , Wang Ernest , Halasyamani Lakshmi
Published: October 2022

An operationally implementable predictive model has been developed to forecast the number of COVID-19 infections in the patient population, hospital floor and ICU censuses, ventilator and related supply chain demand. The model is intended for clinical, operational, financial and supply chain leaders and executives of a comprehensive healthcare system responsible for making decisions that depend on epidemiological contingencies. This paper describes the model that was implemented at NorthShore University HealthSystem and is applicable to any communicable disease whose risk of reinfection for the duration of the pandemic is negligible.
Adhesion to VCAM1 and P-selectin Predict Time-to-Resolution (TTR) of Vaso-Occlusive Crisis
Authors: Tarasev Michael , Gao Xiufeng , Ferranti Marta , White Jennell , Hines Patrick C.
Published: October 2022

Sickle cell disease (SCD) is characterized by frequent and unpredictable vaso-occlusive crises (VOCs) resulting in increased morbidity and mortality. Reliable biomarkers that predict the onset and progression of VOCs in SCD are unavailable, thus the existing standard of care is more focused on VOC intervention as opposed to VOC prevention. Sickle blood cells contribute to VOCs by adhering to the endothelium and aggregating to other blood cells in the circulation through pathologic adhesive interactions. In our previously described ELIPSIS study, blood samples were collected from 35 study subjects with SCD every 3 weeks during self-reported baseline and during self-reported VOCs (at home or in a healthcare setting). An electronic, patient-reported outcomes (ePRO) tool captured daily pain, VOC, and VOC resolution. Flow adhesion of whole blood to VCAM-1 (FA-WB-VCAM) and P-selectin (FA-WB-Psel) were assessed during each visit. Time-To-Resolution was established as the duration between the onset and subject self-reported resolution of VOC resolution and varied between 2 and 48 days. For the subset of TTR limited to ≤ 7 day, TTR was negatively correlated with FA-WB-PSel measured at the onset of VOC (R2=0.45; r=-0.67;p<0.05). Coefficient of determination increased to 0.62 when baseline FA-WB-VCAM levels were used as a second predictor in the multi-parametric model. In such a model, baseline FA-WB-VCAM was positively correlated with TTR at ≤ 7 day, with the difference in the sign of P-selectin and VCAM-1 effect on the reduction of pain (TTR duration) likely reflecting different mechanisms driving VOCs. Supplementation of FA-WB-VCAM and FA-WB-Psel multiparametric model with select blood chemistry biomarkers including several inflammatory mediators, further enhanced models ability to predict TTR. This study indicates that functional biomarkers obtained both at baseline and at the time of VOC can give insight into the time it may take for that specific VOC to resolve. These could assist providers in predicting which VOCs may require more intensive intervention. These data may also identify specific VOC phenotypes, allowing providers to intervene with a more patient-specific approach. Future studies are required to determine if FA-WB-VCAM and FA-WB-Psel can be used clinically to enable a more precision medicine-based approach to manage VOCs and if such an approach could result in improved outcomes and reduced healthcare costs by predicting VOCs for early intervention.
The genomic landscape of recurrent ovarian high grade serous carcinoma: the BriTROC-1 study
Authors: Smith P-S. , Bradley T. , Gavarró L. Morrill , Goranova T. , Ennis D. , Mirza H. , De Silva D. , Piskorz A.M. , Al-Khalidi S. , Sauer C. , Funingana I-G. , Reinius M. , Giannone G. , Lewsley L-A. , Stobo J. , McQueen J. , Bryson G. , Eldridge M. ,   The BriTROC Investigators, Macintyre G. , Markowetz F. , Brenton J.D. , McNeish I.A.
Published: October 2022

The drivers of recurrence and resistance in ovarian high grade serous carcinoma (HGSC) remain unclear. We established BriTROC-1 to investigate the acquisition of resistance by collecting tumour biopsies from women with recurrent ovarian HGSC that had relapsed following at least one line of platinum-based chemotherapy. Patients underwent biopsy or secondary debulking surgery, with tumour samples fixed in methanol-based fixative. Normal and tumour DNA samples underwent tagged-amplicon panel sequencing. Tumour DNA underwent shallow whole genome sequencing (sWGS). Tissue microarrays (TMA), created from diagnosis samples, were stained for CD3, CD8, CD20 and FoxP3. 276 patients were recruited (209 platinum-sensitive, 67 platinum-resistant). Panel sequencing showed close concordance between diagnosis and relapse, with only 4 discordant cases, and no revertant mutations inBRCA1orBRCA2were identified in relapse samples. CN signatures were strongly correlated with immune cell infiltration. There was very strong concordance in copy number (CN) between diagnosis and relapse, with no significant difference in purity, ploidy or focal somatic CN alterations, even when stratified by platinum sensitivity or prior chemotherapy lines. Small increases in CN signature 3 and 7 exposure were observed between diagnosis and relapse across the whole cohort but were not present in matched sample pairs. Diagnosis samples from patients with primary platinum resistance had increased rates ofCCNE1andKRASamplification and CN signature 6 exposure. The HGSC genome is remarkably stable between diagnosis and relapse and acquired chemotherapy resistance does not select for common copy number drivers. We have identified new genomic events at diagnosis, includingKRASamplification and CN signature 6 exposure, that are associated with primary platinum resistance.
Genomic epidemiology of Human Adenovirus F40 and F41 in Coastal Kenya: A retrospective hospital-based surveillance study (2013-2022)
Authors: Lambisia Arnold W. , Makori Timothy O. , Mutunga Martin , Cheruiyot Robinson , Murunga Nickson , Quick Joshua , Githinji George , Nokes D. James , Houldcroft Charlotte J. , Agoti Charles N.
Published: October 2022

Introduction

Human adenoviruses type F (HAdV-F) are leading cause of childhood diarrhoeal deaths. Genomic analysis would be key for understanding their potential drivers of disease severity, transmission dynamics, and for vaccine development. However, currently there is only limited data on HAdV-F genomes globally.

Methods

Here, we sequenced and analysed HAdV-F from stool samples collected in coastal Kenya between 2013 and 2022. The samples were collected at Kilifi County Hospital in Kilifi, Kenya, from children < 13 years of age who reported a history of ≥ 3 loose stools in the previous 24hrs. The genomes were compared with data from the rest of the world by phylogenetic analysis and mutational profiling. Genotypes and lineages were assigned based on clustering on the global phylogenetic tree and from previously described nomenclature. Participant clinical and demographic data were linked to genotypic data.

Results

Of 91 cases identified using real-time PCR, 83 near-complete genomes were assembled, and these classified into HAdV-F40 and F41. These genotypes cocirculated throughout the study period. Three and four distinct lineages were observed for HAdV-F40 (Lineage 1-3) and F41 (Lineage 1, 2A, 3A, 3C and 3D). Genotype F40 and F41 coinfections were observed in five samples, and F41 and B7 in one sample. Two children with F40 and 41 coinfections were also infected with rotavirus and had moderate and severe disease, respectively. Intratypic recombination was found in 4 HAdV-F40 sequences occurring between lineages 1 and 3. None of the HAdV-F41 cases had jaundice.

Interpretation

This study provides evidence of extensive genetic diversity, coinfections and recombination within HAdV-F40 in a high adenovirus transmission setting that will inform public health policy, vaccine development that includes the locally circulating lineages, and molecular diagnostic assay development. We recommend future comprehensive studies elucidating on HAdV-F genetic diversity and immunity for rational vaccine development.
Evidence for an Intricate Relationship Between Express Visuomotor Responses, Postural Control and Rapid Step Initiation in the Lower Limbs
Authors: Billen Lucas S. , Corneil Brian D. , Weerdesteyn Vivian
Published: October 2022

Recent work has described express visuomotor responses (EVRs) on the upper limb. EVRs are directionally-tuned bursts of muscle activity that occur within 100 ms of visual stimulus appearance, facilitating rapid reaching. Rapid stepping responses are also important in daily life, and while there is evidence of EVR expression on lower limbs, it is unknown whether lower-limb EVRs are influenced by increased postural demands. Here, we investigate the interaction between stepping-related EVRs and anticipatory postural adjustments (APAs) that typically precede step initiation.

16 healthy young subjects rapidly stepped towards visual targets presented in front of the left or right foot. We recorded bilateral surface EMG of gluteus medius (GM), a muscle involved in both APAs and stepping, and bilateral ground reaction forces. Two conditions were introduced: an anterolateral or anteromedial stepping condition with reduced or increased postural demands, respectively. In the anterolateral stepping condition, EVRs were robustly and strongly present in stance-side GM, and ground reaction forces revealed strongly decreased expression of APAs. Larger EVRs preceded shorter RTs, consistent with EVRs facilitating step initiation. In contrast, in the anteromedial stepping condition, EVRs were largely absent, and ground reaction forces revealed the consistent expression of APAs. When occasionally present, EVRs in the anteromedial stepping condition preceded larger APAs and longer RTs. Thus, while EVRs in lower limbs can facilitate rapid stepping, their expression is normally suppressed when postural stability is low. Failing to appropriately suppress EVRs in such situations disrupts postural stability, necessitating larger compensatory APAs and leading to longer stepping RTs.

Key Points

Express visuomotor responses (EVRs) are directionally tuned bursts of muscle activity that aid the rapid initiation of a goal-directed movement. They are thought to be relayed to the motor periphery along a rapid subcortical pathway involving the superior colliculus.

While EVRs have predominantly been studied in reaching, it is unclear whether EVRs extend to the lower extremities and if so, whether increasing the postural demands of a stepping task interfere with lower-limb EVR expression.

We found that when postural demands were low, strong EVRs in the hip abductor muscle gluteus medius facilitated a rapid stepping response. Conversely, when postural demands were high, EVRs hindered a fast stepping response, as they necessitated larger, compensatory postural adjustments prior to step onset.

These results help us better understand the interaction between ultra-rapid visuomotor transformations in the EVR network, the postural demands of a given stepping task, and subsequent step initiation.
Selective memory retrieval revealed by electroencephalographic (EEG) neural pattern reinstatement
Authors: Moccia Arianna , Plummer Matthew , Simpson Ivor , Morcom Alexa M.
Published: October 2022

1.

For past experiences to guide our actions we need to retrieve the relevant memories. Here, we used electroencephalography (EEG) to investigate how memories are selected for retrieval from a large store of mnemonic traces, and to test how current goals and external retrieval cues drive selection during the retrieval cascade. We analysed data from two studies in which people studied objects in picture or auditory word formats, and later recalled them using either written words (Experiment 1, N=28) or line drawings (Experiment 2, N=28) as retrieval cues. We used multivariate decoding to quantify the reinstatement of study phase neural patterns when people successfully identified items that had been studied in the format currently designated as targets, versus non-targeted items. Neural reinstatement emerged at around 500 ms post-stimulus, as did the established left parietal event-related potential (ERP) signature of recollection. Reinstatement was also target-selective (greater for targets than non-targets) when test cues overlapped more with targets, a pattern previously shown for the left parietal ERP (Moccia & Morcom, 2021). In contrast, when cues overlapped more with non-targets, neural reinstatement was reversed – greater for non-targets – unlike the left parietal ERP. We also tested for goal-directed mental reinstatement proposed to guide selection prior to retrieval cues. When words were cues there was strong evidence of this proactive reinstatement, but it was not detected when pictures were cues. Together, the data suggest that selection can act at multiple stages of memory retrieval and depends on both external cues and goal-directed control.