bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic review with meta‐analysis: volatile organic compound analysis to improve faecal immunochemical testing in the detection of colorectal cancer
Authors: Chandrapalan Subashini , Bosch Sofie , Cubiella Joaquín , Guardiola Jordi , Kimani Peter , Mulder Chris , Persaud Krishna , de Meij Tim G. J. , Altomare Donato F. , Brenner Herman , de Boer Nanne K. H. , Ricciardiello Luigi , Arasaradnam Ramesh P.
Published: May 2021

Background

Faecal immunochemical test (FIT) is emerging as a valid test to rule‐out the presence of colorectal cancer (CRC). However, the accuracy of FIT is dependent on the cut‐off applied. An additional low‐cost test could improve further detection of CRC.

Aims

To evaluate the efficacy of combined FIT and volatile organic compounds (VOC) in the detection of CRC within symptomatic populations.

Methods

Systematic reviews on the diagnostic accuracy of FIT and VOC, for the detection of CRC, were updated. Meta‐analyses were performed adopting a bivariate model for sensitivity and specificity. Clinical utility of combined FIT and VOC was estimated using Fagan's nomogram. Post‐test probability of FIT negatives was used as a pre‐test probability for VOC.

Results

The pooled sensitivity and specificity of FIT at 10 µg/g faeces, for the detection of CRC, were 0.914 (95% confidence interval [CI] = 0.894‐0.936) and 0.783 (CI = 0.850‐0.696), respectively. For VOC, the sensitivity was 0.837 (CI = 0.781‐0.881) and the specificity was 0.803 (CI = 0.870‐0.712). The area under the curve for FIT and VOC were 0.926 and 0.885, respectively. In a population with 5% CRC prevalence, the estimated probability of having CRC following a negative FIT was 0.5% and following both negative FIT and VOC was 0.1%.

Conclusions

In a FIT‐negative symptomatic population, VOC can be a good test to rule‐out the presence of CRC. The estimated probability reduction by 0.4% when both tests being negative offers adequate safety netting in primary care for the exclusion of CRC. The number needed to colonoscope to identify one CRC is eight if either FIT or VOC positive. Cost‐effectiveness and clinical accuracy of this approach will need further evaluation.
How decision‐making about euthanasia for animals is taught to Australasian veterinary students
Authors: Littlewood KE , Beausoleil NJ , Stafford KJ , Stephens C , Collins T , Quain A , Hazel S , Lloyd JK.F , Mallia C , Richards L , Wedler NK , Zito S
Published: May 2021

This study set out to explore how euthanasia decision‐making for animals was taught to students in eight Australasian veterinary schools. A questionnaire‐style interview guide was used by a representative at each university to interview educators. Educators were interviewed about their teaching of euthanasia decision‐making for four categories of animals: livestock, equine, companion and avian/wildlife. Using thematic analysis, the terms provided by participants to describe how (mode of teaching) and what (specific content) they taught to students were categorised. Information about content was categorised into human‐centredfactorsthat influence decision‐making, and animal‐basedindicatorsused to directly inform decision‐making. All eight representatives reported some teaching relevant to euthanasia decision‐making at their university for livestock, companion animal and avian/wildlife. One representative reported no such teaching for equid animals at their university. Observation of a euthanasia case was rarely reported as a teaching method. Five universities reported multiple modes of teaching relevant information, while two universities made use of modalities that could be described as opportunistic teaching (e.g., 'Discussion of clinical cases'). Factors taught at most universities included financial considerations, and that it is the owner's decision to make, while animal‐based indicators taught included QoL/animal welfare, prognosis and behaviour change. Overall, most universities used a variety of methods to cover relevant material, usually including lectures and several other approaches for all animal types. However, because two universities relied on presentation of clinical cases, not all students at these veterinary schools will be exposed to make, or assist in making, euthanasia decisions.
Novel therapies in β‐thalassaemia
Authors: Grech Laura , Borg Karen , Borg Joseph
Published: May 2021

Beta‐thalassaemia is one of the most significant haemoglobinopathies worldwide resulting in the synthesis of little or no β‐globin chains. Without treatment, β‐thalassaemia major is lethal within the first decade of life due to the complex pathophysiology, which leads to wide clinical manifestations. Current clinical management for these patients depends on repeated transfusions followed by iron‐chelating therapy. Several novel approaches to correct the resulting α/β‐globin chain imbalance, treat ineffective erythropoiesis and improve iron overload are currently being developed. Up to now, the only curative treatment for β‐thalassemia is haematopoietic stem‐cell transplantation, but this is a risky and costly procedure. Gene therapy, gene editing and base editing are emerging as a powerful approach to treat this disease. In β‐thalassaemia, gene therapy involves the insertion of a vector containing the normal β‐globin or γ‐globin gene into haematopoietic stem cells to permanently produce normal red blood cells. Gene editing and base editing involves the use of zinc finger nucleases, transcription activator‐like nucleases and clustered regularly interspaced short palindromic repeats/Cas9 to either correct the causative mutation or else insert a single nucleotide variant that will increase foetal haemoglobin. In this review, we will examine the current management strategies used to treat β‐thalassaemia and focus on the novel therapies targeting ineffective erythropoiesis, improving iron overload and correction of the globin chain imbalance.
Familial aggregation of early‐onset haematological malignancies
Authors: Rönkkö Rosa , Hirvonen Elli , Malila Nea , Kilpivaara Outi , Wartiovaara‐Kautto Ulla , Pitkäniemi Janne
Published: May 2021

Population‐based studies on familial aggregation of haematological malignancies (HM) have rarely focused specifically on early‐onset HMs. We estimated standardized incidence ratios (SIR) and cumulative risks of relatives with Hodgkin lymphoma (HL), non‐Hodgkin lymphomas (NHL), acute lymphoblastic leukaemia/lymphoma (ALL/LBL) and acute myeloid leukaemia (AML) when index persons and relatives were diagnosed with early‐onset HM. A total of 8791 patients aged ≤40 years and diagnosed with primary HM in Finland from 1970 to 2012 were identified from the Finnish Cancer Registry and their 75 774 family members were retrieved from the population registry. SIRs for concordant HMs were elevated among first‐degree relatives in all of the most common HMs of children and adolescents and young adults (AYA). The risk was highest among siblings with HL (SIR 9·09, 95% confidence interval 5·55–14·04) and AML (8·29, 1·00–29·96). HL also had the highest cumulative risk for siblings at ≤40 years of age (0·92% vs. 0·11% in the population). In conclusion, significantly elevated SIRs indicate a role of shared aetiological factors in some families, which should be noted in the clinical setting when caring for patients with early‐onset HMs.
Using DNA metabarcoding to detect burrowing seabirds in a remote landscape
Authors: McInnes Julie C. , Bird Jeremy P. , Deagle Bruce E. , Polanowski Andrea M. , Shaw Justine D.
Published: May 2021

Species inventories and biodiversity assessments are critical to conservation. Yet cryptic species or recolonizing species can be challenging to detect. DNA metabarcoding provides an alternative tool to identify species that can be difficult to observe during field surveys. We test the efficacy of DNA analysis to identify burrowing petrel species in a rapidly changing landscape, on a remote sub‐Antarctic island following pest eradication. Discarded feathers and scats provided high quality DNA for species identification, assisting in detection of new species arrivals and new breeding sites across Macquarie Island. We highlight how DNA metabarcoding informs species inventories and is a valuable tool to complement seabird field surveys.
Prehospital troponin as a predictor of early clinical deterioration
Authors: Martín‐Rodríguez Francisco , Sanz‐García Ancor , Castro‐Portillo Enrique , Delgado‐Benito Juan F. , del Pozo Vegas Carlos , Ortega Rabbione Guillermo , Martín‐Herrero Francisco , Martín‐Conty José Luis , López‐Izquierdo Raúl
Published: May 2021

Background and Objectives

Elevated troponin T (cTnT) values are associated with comorbidities and early mortality, in both cardiovascular and noncardiovascular diseases. The objective of this study is to evaluate the prognostic accuracy of the sole utilization of prehospital point‐of‐care cardiac troponin T to identify the risk of early in‐hospital deterioration, including mortality within 28 days.

Methods

We conducted a prospective, multicentric, controlled, ambulance‐based, observational study in adults with acute diseases transferred with high priority by ambulance to emergency departments, between 1 January and 30 September 2020. Patients with hospital diagnosis of acute coronary syndrome were excluded. The discriminative power of the predictive cTnT was assessed through a discrimination model trained using a derivation cohort and evaluated by the area under the curve of the receiver operating characteristic on a validation cohort.

Results

A total of 848 patients were included in our study. The median age was 68 years (25th‐75th percentiles: 50‐81 years), and 385 (45.4%) were women. The mortality rate within 28 days was 12.4% (156 cases). The predictive ability of cTnT to predict mortality presented an area under the curve of 0.903 (95% CI: 0.85‐0.954; P < .001). Risk stratification was performed, resulting in three categories with the following optimal cTnT cut‐off points: high risk greater than or equal to 100, intermediate risk 40‐100 and low risk less than 40 ng/L. In the high‐risk group, the mortality rate was 61.7%, and on the contrary, the low‐risk group presented a mortality of 2.3%.

Conclusions

The implementation of a routine determination of cTnT on the ambulance in patients transferred with high priority to the emergency department can help to stratify the risk of these patients and to detect unknown early clinical deterioration.
Native fish losses due to water extraction in Australian rivers: Evidence, impacts and a solution in modern fish‐ and farm‐friendly screens
Authors: Boys Craig A. , Rayner Thomas S. , Baumgartner Lee J. , Doyle Katherine E.
Published: May 2021

The diversion of water from rivers removes millions of fish from Australian waterways each year. Modern diversion screens are available that can reduce fish losses by 90% and stop debris entering irrigation systems. Uptake of this technology in the United States has protected fish and infrastructure. However, application in Australia has been poor and both the problem and its solution continue to be overlooked. To address this, we summarise multiple lines of evidence of fish losses in Australia and propose a way forward. Large losses of fish at diversions have been reported for close to a century, providing compelling evidence of population‐scale impacts on native fish. We discuss the solution, outlining the progress being made to bring modern screening technology to Australia, including a social learning framework to improve how water is diverted and focussing on collaboration between the fisheries, agriculture and engineering sectors, and underpinned by science. We conclude that uptake of modern screens will rely on dialogue moving past whether a problem or solution exists, to the following: how screening can be better integrated with water and environmental management; where investment should be prioritised; and how screening could be funded. If Australia gets this right, substantial benefits can be realised, saving millions of native fish every year, bolstering native fish recovery programmes, reducing ongoing costs for water users and enhancing the economic and social value in regional areas by boosting manufacturing, service industries, tourism and recreational fisheries.
Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations
Authors: Stevelink Remi , Luykx Jurjen J. , Lin Bochao D. , Leu Costin , Lal Dennis , Smith Alexander W. , Schijven Dick , Carpay Johannes A. , Rademaker Koen , Rodrigues Baldez Roiza A. , Devinsky Orrin , Braun Kees P. J. , Jansen Floor E. , Smit Dirk J. A. , Koeleman Bobby P. C. ,   International League Against Epilepsy Consortium on Complex Epilepsies,   Epi25 Collaborative
Published: May 2021

Objective

Paroxysmal epileptiform abnormalities on electroencephalography (EEG) are the hallmark of epilepsies, but it is uncertain to what extent epilepsy and background EEG oscillations share neurobiological underpinnings. Here, we aimed to assess the genetic correlation between epilepsy and background EEG oscillations.

Methods

Confounding factors, including the heterogeneous etiology of epilepsies and medication effects, hamper studies on background brain activity in people with epilepsy. To overcome this limitation, we compared genetic data from a genome‐wide association study (GWAS) on epilepsy (n = 12 803 people with epilepsy and 24 218 controls) with that from a GWAS on background EEG (n = 8425 subjects without epilepsy), in which background EEG oscillation power was quantified in four different frequency bands: alpha, beta, delta, and theta. We replicated our findings in an independent epilepsy replication dataset (n = 4851 people with epilepsy and 20 428 controls). To assess the genetic overlap between these phenotypes, we performed genetic correlation analyses using linkage disequilibrium score regression, polygenic risk scores, and Mendelian randomization analyses.

Results

Our analyses show strong genetic correlations of genetic generalized epilepsy (GGE) with background EEG oscillations, primarily in the beta frequency band. Furthermore, we show that subjects with higher beta and theta polygenic risk scores have a significantly higher risk of having generalized epilepsy. Mendelian randomization analyses suggest a causal effect of GGE genetic liability on beta oscillations.

Significance

Our results point to shared biological mechanisms underlying background EEG oscillations and the susceptibility for GGE, opening avenues to investigate the clinical utility of background EEG oscillations in the diagnostic workup of epilepsy.
Development of an antiseizure drug screening platform for Dravet syndrome at the NINDS contract site for the Epilepsy Therapy Screening Program
Authors: Pernici Chelsea D. , Mensah Jeffrey A. , Dahle E. Jill , Johnson Kristina J. , Handy Laura , Buxton Lauren , Smith Misty D. , West Peter J. , Metcalf Cameron S. , Wilcox Karen S.
Published: May 2021

Objective

Dravet syndrome (DS) is a rare but catastrophic genetic epilepsy, with 80% of patients carrying a mutation in the SCN1A gene. Currently, no antiseizure drug (ASD) exists that adequately controls seizures. In the clinic, individuals with DS often present first with a febrile seizure and, subsequently, generalized tonic‐clonic seizures that can continue throughout life. To facilitate the development of ASDs for DS, the contract site of the National Institute of Neurological Disorders and Stroke (NINDS) Epilepsy Therapy Screening Program (ETSP) has evaluated a mouse model of DS using the conditional knock‐in Scn1aA1783V/WT mouse.

Methods

Survival rates and temperature thresholds for Scn1aA1783V/WT were determined. Prototype ASDs were administered via intraperitoneal injections at the time‐to‐peak effect, which was previously determined, prior to the induction of hyperthermia‐induced seizures. ASDs were considered effective if they significantly increased the temperature at which Scn1aA1783V/WT mice had seizures.

Results

Approximately 50% of Scn1aA1783V/WT survive to adulthood and all have hyperthermia‐induced seizures. The results suggest that hyperthermia‐induced seizures in this model of DS are highly refractory to a battery of ASDs. Exceptions were clobazam, tiagabine, levetiracetam, and the combination of clobazam and valproic acid with add‐on stiripentol, which elevated seizure thresholds.

Significance

Overall, the data demonstrate that the proposed model for DS is suitable for screening novel compounds for the ability to block hyperthermia‐induced seizures and that heterozygous mice can be evaluated repeatedly over the course of several weeks, allowing for higher throughput screening.
Effects of early life seizures on coordination of hippocampal–prefrontal networks: Influence of sex and dynamic brain states
Authors: Niedecker Rhys W. , Kloc Michelle L. , Holmes Gregory L. , Barry Jeremy M.
Published: May 2021

Objective

Early life seizures (ELSs) alter activity‐dependent maturation of neuronal circuits underlying learning and memory. The pathophysiological mechanisms underpinning seizure‐induced cognitive impairment are not fully understood, and critical variables such as sex and dynamic brain states with regard to cognitive outcomes have not been explored. We hypothesized that in comparison to control (CTL) rats, ELS rats would exhibit deficits in spatial cognition correlating with impaired dynamic neural signal coordination between the hippocampus and medial prefrontal cortex (mPFC).

Methods

Male and female rat pups were given 50 flurothyl‐induced seizures over 10 days starting at postnatal Day 15. As adults, spatial cognition was tested through active avoidance on a rotating arena. Microwire tetrodes were implanted in the mPFC and CA1 subfield. Single cells and local field potentials were recorded and analyzed in each region during active avoidance and sleep.

Results

ELS males exhibited avoidance impairments, whereas female rats were unaffected. During avoidance, hippocampus–mPFC coherence was higher in CTL females than CTL males across bandwidths. In comparison to CTL males, ELS male learners exhibit increased coherence within theta bandwidth as well as altered burst‐timing in mPFC cell activity. Hippocampus–mPFC coherence levels are predictive of cognitive outcome in the active avoidance spatial task.

Significance

Spatial cognitive outcome post‐ELS is sex‐dependent, as females fare better than males. ELS males that learn the task exhibit increased mPFC coherence levels at low‐theta frequency, which may compensate for ELS effects on mPFC cell timing. These results suggest that coherence may serve as a biomarker for spatial cognitive outcome post‐ELS and emphasize the significance of analyzing sex and dynamic cognition as variables in understanding seizure effects on the developing brain.
Insights into adult atopic dermatitis heterogeneity derived from circulating biomarker profiling in patients with moderate‐to‐severe disease
Authors: Sims Jonathan T. , Chang Ching‐Yun , Higgs Richard E. , Engle Sarah M. , Liu Yushi , Sissons Sean E. , Rodgers George H. , Simpson Eric L. , Silverberg Jonathan I. , Forman Seth B. , Janes Jonathan M. , Colvin Stephanie C. , Guttman‐Yassky Emma
Published: May 2021

Atopic dermatitis (AD) is a heterogeneous systemic inflammatory skin disease associated with dysregulated immune responses, barrier dysfunction and activated sensory nerves. To characterize circulating inflammatory profiles and underlying systemic disease heterogeneity within AD patients, blood samples from adult patients (N = 123) with moderate‐to‐severe AD in a phase 2 study of baricitinib (JAHG) were analysed. Baseline levels of 131 markers were evaluated using high‐throughput and ultrasensitive proteomic platforms, patient clusters were generated based on these peripheral markers. We implemented a novel cluster reproducibility method to validate cluster outcomes within our study and used publicly available AD biomarker data set (73 markers,N = 58 patients) to validate our findings. Cluster reproducibility analysis demonstrated best consistency for 2 clusters byk‐means, reproducibility of this clustering outcome was validated in an independent patient cohort. These unique JAHG patient subgroups either possessed elevated pro‐inflammatory mediators, notably TNFβ, MCP‐3 and IL‐13, among a variety of immune responses (high inflammatory) or lower levels of inflammatory biomarkers (low inflammatory). The high inflammatory subgroup was associated with greater baseline disease severity, demonstrated by greater EASI, SCORAD Index, Itch NRS and DLQI scores, compared with low inflammatory subgroup. African‐American patients were predominantly associated with the high inflammatory subgroup and increased baseline disease severity. In patients with moderate‐to‐severe AD, heterogeneity was identified by the detection of 2 disease subgroups, differential clustering amongst ethnic groups and elevated pro‐inflammatory mediators extending beyond traditional polarized immune responses. Therapeutic strategies targeting multiple pro‐inflammatory cytokines may be needed to address this heterogeneity.
Long‐term nitrogen addition does not sustain host tree stem radial growth but doubles the abundance of high‐biomass ectomycorrhizal fungi
Authors: Karst Justine , Wasyliw Joshua , Birch Joseph D. , Franklin James , Chang Scott X. , Erbilgin Nadir
Published: May 2021

Global change has altered nitrogen availability in boreal forest soils. As ectomycorrhizal fungi play critical ecological functions, shifts in their abundance and community composition must be considered in the response of forests to changes in nitrogen availability. Furthermore, ectomycorrhizas are symbiotic, so the response of ectomycorrhizal fungi to nitrogen cannot be understood in isolation of their plant partners. Most previous studies, however, neglect to measure the response of host trees to nitrogen addition simultaneously with that of fungal communities. In addition to being one‐sided, most of these studies have also been conducted in coniferous forests. Deciduous and “dual‐mycorrhizal” tree species, namely those that form ecto‐ and arbuscular mycorrhizas, have received little attention despite being widespread in the boreal forest. We applied nitrogen (30 kg ha−1 year−1) for 13 years to stands dominated by aspen (Populus tremuloides Michx.) and hypothesized that tree stem radial growth would increase, ectomycorrhizal fungal biomass would decrease, ectomycorrhizal fungal community composition would shift, and the abundance of arbuscular mycorrhizal (AM) fungi would increase. Nitrogen addition initially increased stem radial growth of aspen, but it was not sustained at the time we characterized their mycorrhizas. After 13 years, the abundance of fungi possessing extramatrical hyphae, or “high‐biomass” ectomycorrhizas, doubled. No changes occurred in ectomycorrhizal and AM fungal community composition, or in ecto‐ and AM abundance measured as root colonization. This dual‐mycorrhizal tree species did not shift away from ectomycorrhizal fungal dominance with long‐term nitrogen input. The unexpected increase in high‐biomass ectomycorrhizal fungi with nitrogen addition may be due to increased carbon allocation to their fungal partners by growth‐limited trees. Given the focus on conifers in past studies, reconciling results of plant–mycorrhizal fungal relationships in stands of deciduous trees may demand a broader view on the impacts of nitrogen addition on the structure and function of boreal forests.
PPI‐amoxicillin dual therapy four times daily is superior to guidelines recommended regimens in the Helicobacter pylori eradication therapy within Asia: A systematic review and meta‐analysis
Authors: Li Cailing , Shi Yanyan , Suo Baojun , Tian Xueli , Zhou Liya , Song Zhiqiang
Published: May 2021

Background

Systematic reviews suggested that the eradication efficacy of PPI‐amoxicillin dual therapy is similar to that of other commonly used regimens. However, it might be affected by the medication frequency. Basic and clinical studies have shown that dual therapy administered four‐times daily has a reliable pathophysiological basis and could achieve satisfactory efficacy. Therefore, a systematic review of RCTs of dual therapy and other regimens was conducted to clarify whether dual therapy is superior to guidelines recommended regimens.

Materials and Methods

The RCTs comparing dual therapy with other regimens were subjected to meta‐analysis to evaluate the eradication rate, adverse reactions, and compliance using a random‐effects model.

Results

Dual therapy administered four‐times daily had a higher eradication rate than other regimens (intention‐to‐treat analysis: 89.7% vs 84.6%, OR: 1.52, 95%CI 1.08–2.14, p = 0.02; per‐protocol analysis: 92.6% vs 88.2%, OR: 1.54, 95%CI 1.01–2.34, p = 0.04). In first‐line therapy, according to intention‐to‐treat analysis, the eradication rate of dual therapy was higher than other regimens (89.8% vs 84.2%, OR: 1.63, 95%CI 1.02–2.61, p = 0.04). In per‐protocol analysis, dual therapy showed better efficacy than others (92.9% vs 88.3%, OR: 1.68, 95% CI 0.98–2.89, p = 0.06), but not significantly. In salvage treatment, no significant difference was detected. The safety of dual therapy was significantly better than other regimens (19.6% vs 36.7%, p < 0.01), but no difference was observed in compliance (p = 0.58).

Conclusion

PPI‐amoxicillin dual therapy administered four‐times daily has better efficacy and safety in H. pylori eradication than current guidelines recommended regimens, especially in first‐line therapy, and mainly in Asia.
Gestational diabetes in women living with HIV in Botswana: lower rates with dolutegravir‐ than with efavirenz‐based antiretroviral therapy
Authors: Mmasa KN , Powis K , Sun S , Makhema J , Mmalane M , Kgole S , Masasa G , Moyo S , Gerschenson M , Mohammed T , Legbedze J , Abrams EJ , Kurland IJ , Geffner ME , Jao J
Published: May 2021

Background

There are few data on the prevalence of gestational diabetes (GDM) in pregnant women living with HIV (WLHIV) in sub‐Saharan Africa, particularly those using integrase strand transfer inhibitors such as dolutegravir (DTG).

Methods

We prospectively enrolled pregnant WLHIV and pregnant women without HIV ≥18 years old in Gaborone, Botswana, excluding those with pre‐existing diabetes. We screened for GDM using a 75 g oral glucose tolerance test (OGTT) performed at 24–28 weeks’ gestation or at the earliest prenatal visit for those presenting after 28 weeks. Logistic regression models were fitted to assess the association between maternal HIV infection and GDM. Subgroup analyses were performed among WLHIV to assess the association between maternal antiretroviral therapy (ART) in pregnancy [DTG vs. efavirenz (EFV) with tenofovir/emtricitabine] and GDM.

Results

Of 486 pregnant women, 66.5% were WLHIV, and they were older than women without HIV (median age 30 vs. 25 years, P < 0.01). Among WLHIV, 97.8% had an HIV‐1 RNA level < 400 copies/mL at enrolment. Overall, 8.4% had GDM with similar rates between WLHIV and those without HIV (9.0% vs. 7.4%). The WLHIV receiving DTG‐based ART had a 60% lower risk for GDM compared with those on EFV‐based ART (adjusted odds ratio = 0.40, 95% CI: 0.18–0.92) after adjusting for confounders.

Conclusions

Pregnant WLHIV on ART in Botswana were not at increased risk of GDM compared with women without HIV. Among WLHIV, the risk of GDM was lower with DTG‐ than with EFV‐based ART. Further studies with larger cohorts are warranted to confirm these findings.
Revitalizing previously treated teeth with open apices: A case report and a literature review
Authors: Nosrat Ali , Bolhari Behnam , Saber Tahan Shima , Dianat Omid , Dummer Paul Michael Howell
Published: May 2021

Revitalizing the root canals of previously treated teeth with open apices is appealing to clinicians and patients. However, there are fundamental differences in the microbiome and the microenvironment between a canal with a primary endodontic infection and a canal with a persistent endodontic infection. The aims of this report are to report a case where a previously treated tooth with an open apex and a large apical radiolucency was treated successfully using regenerative endodontic treatment (RET) and to review and critically appraise the literature on procedures and outcomes of RET that result in revitalization of canal(s) in previously treated teeth with open apices. A maxillary central incisor with poor‐quality root filling, a large apical radiolucency and an open apex was retreated using RET using platelet‐rich fibrin as the scaffold. After 24 months, there was complete healing of the periapical lesion and obvious radiographic signs of apical root closure. Electronic searches were performed in MEDLINE, Scopus and Embase, and the baseline, procedural and outcome data of qualified articles were collected. An assessment tool was developed to rate the quality of evidence reported in these case report/series. Nine articles, three case series and six case reports, with a total of 17 teeth of all types, were included in the reports identified. The age of patients ranged from 7 to 48 years (mean: 19.4 years). The recall period ranged from 12 to 72 months (mean: 29 months). All 17 teeth survived and were functional with healing/healed outcomes. “Apical closure” was the most common radiographic finding regarding root development. The quality of evidence using the new assessment tool was rated “Excellent” in three case reports but only “Fair” in the other six articles. The present case report, as well as the review of the literature, suggests that revitalizing the root canal system of teeth with open apices and post‐treatment disease using RET is a potentially valid treatment option. However, more clinical studies with higher levels of evidence and higher quality of evidence are required to confirm the viability of this treatment approach.
Nursing care factors influencing patients' outcomes in the intensive care unit: Findings from a rapid review
Authors: Danielis Matteo , Destrebecq Anne Lucia Leona , Terzoni Stefano , Palese Alvisa
Published: May 2021

Aims

To examine the nursing care factors investigated regarding their influence on outcomes of critically ill patients.

Background

A large number of studies have considered patients' outcomes as sensitive to nursing practice in intensive care unit environments. However, no summary of nursing factors influencing these outcomes has been provided.

Design

Rapid review, following the seven‐stage process outlined by Tricco and colleagues.

Data Sources

Articles published up to March 2020 were identified in MEDLINE (via PubMed), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Scopus databases.

Review Methods

Eligibility of studies was first assessed at the title and abstracts level. Study inclusion was then established by two researchers by analysing the full texts.

Results

A total of 93 studies were included, with a total of 21 nursing care factors documented. At the structural level, nursing factors have been investigated at the organizational and at the personnel level. At the process level, nurse‐led programmes, independent nursing interventions and nurse behaviours have been investigated to date.

Conclusion

The set of nursing factors that emerged can be used in future research to improve poorly developed areas and to accumulate further evidence through additional studies, both at managerial and practice levels.
Optimal CD8+ T‐cell memory formation following subcutaneous cytomegalovirus infection requires virus replication but not early dendritic cell responses
Authors: Dimonte Sandra , Gimeno‐Brias Silvia , Marsden Morgan , Chapman Lucy , Sabberwal Pragati , Clement Mathew , Humphreys Ian R
Published: May 2021

Cytomegalovirus (CMV) induction of large frequencies of highly functional memory T cells has attracted much interest in the utility of CMV‐based vaccine vectors, with exciting preclinical data obtained in models of infectious diseases and cancer. However, pathogenesis of human CMV (HCMV) remains a concern. Attenuated CMV‐based vectors, such as replication‐ or spread‐deficient viruses, potentially offer an alternative to fully replicating vectors. However, it is not well understood how CMV attenuation impacts vector immunogenicity, particularly when administered via relevant routes of immunization such as the skin. Herein, we used the murine cytomegalovirus (MCMV) model to investigate the impact of vector attenuation on T‐cell memory formation following subcutaneous administration. We found that the spread‐deficient virus (ΔgL‐MCMV) was impaired in its ability to induce memory CD8+ T cells reactive to some (M38, IE1) but not all (IE3) viral antigens. Impaired‐memory T‐cell development was associated with a preferential and pronounced loss of polyfunctional (IFN‐γ+ TNF‐α+) T cells and also reduced accumulation of TCF1+ T cells, and was not rescued by increasing the dose of replication‐defective MCMV. Finally, whilst vector attenuation reduced dendritic cell (DC) recruitment to skin‐draining lymph nodes, systematic depletion of multiple DC subsets during acute subcutaneous MCMV infection had a negligible impact on T‐cell memory formation, implying that attenuated responses induced by replication‐deficient vectors were likely not a consequence of impaired initial DC activation. Thus, overall, these data imply that the choice of antigen and/or cloning strategy of exogenous antigen in combination with the route of immunization may influence the ability of attenuated CMV vectors to induce robust functional T‐cell memory.
Reimagining laboratory‐based immunology education in the time of COVID‐19
Authors: Wilkinson Thomas S. , Nibbs Rob , Francis Nigel J.
Published: May 2021

The pandemic has brought challenges to teaching lab and research skills. Here Nigel Francis and colleagues explore the diverse approaches taken to replace lab‐based immunology teaching, explain how networks of educators have driven this innovation and discuss the importance of retaining best practice into the future.
Safeners improve early‐stage chilling‐stress tolerance in sorghum
Authors: Vennapusa Amaranatha R. , Assefa Yared , Sebela David , Somayanda Impa , Perumal Ramasamy , Riechers Dean E. , Vara Prasad P. V. , Jagadish S. V. Krishna
Published: May 2021

Sorghum [Sorghum bicolor (L.) Moench] is highly sensitive to chilling temperatures (<15°C soil temperatures) during germination and early seedling establishment. Hence, the main objectives of this research were to (a) validate the potential level of chilling tolerance in selected sorghum genotypes, (b) determine effective concentrations of selected safeners for improving chilling tolerance and (c) determine if safener combinations further enhance chilling tolerance compared to individual safener treatments. Four experiments were conducted with five sorghum genotypes, four safeners (oxabetrinil, fluxofenim, naphthalic anhydride and benoxacor), nine safener concentrations (0–25 μM) and two temperatures. The chilling‐tolerant genotypes recorded higher germination percentage (98% vs. 63%) and root (3.0 vs. 0.8 cm) and shoot lengths (0.7 vs. 0.1 cm) compared to sensitive genotypes under continuous 15℃. Each of the four safeners applied at the highest concentrations tested (20 and 25 μM) significantly enhanced seed germination and seedling growth at 15℃. The combination of four safeners was more effective in reducing chilling stress‐induced injury compared to individual, two‐ or three‐way combinations. Enhanced chilling tolerance may be extended to other cereal crops after optimizing the genetic background and effects of agro‐climatic conditions on safener chemistry, concentration, and proper combination of seed‐applied safeners.
Middle portion of the wheat culm remobilizes more carbon reserve to grains under drought
Authors: Thapa Sushil , Rudd Jackie C. , Jessup Kirk E. , Liu Shuyu , Baker Jason A. , Devkota Ravindra N. , Xue Qingwu
Published: May 2021

In a semi‐arid climate, heat and drought stress can significantly reduce photosynthesis during grain filling hence, the remobilization of stored carbon reserves from stems becomes important to wheat (Triticum aestivum L.) yield. A 2‐year field study was conducted to better understand the contributions of different internodes to grain yield. We measured remobilization of stored carbon reserves in eight wheat genotypes under irrigated and dryland conditions. For each genotype, plant samples consisting of ten culms were collected between anthesis and physiological maturity. There was no difference in single stem weight loss between two water levels, but the stem loss contribution to yield was higher in dryland wheat (54.4%) than that in irrigated wheat (38.5%). Among the genotypes, the stem loss contribution to yield ranged 38.9%–58.1% in the relatively wet season of 2017 and 36.5%–62.5% in the dry season of 2018. The amount of stem loss showed a strong relationship with grain yield, especially under the dryland condition. At each sampling date, length as well as the dry weight of peduncle (first internode from the top) was greater than the other internodes; however, more stem loss (in weight and percentage weight) occurred in the third internode, followed by second and fourth internodes. Results suggest that the stem loss contribution to yield is greater under dryland than irrigated condition and occurs mainly in the middle portion of the culm.
Artificial intelligence in nursing: Priorities and opportunities from an international invitational think‐tank of the Nursing and Artificial Intelligence Leadership Collaborative
Authors: Ronquillo Charlene Esteban , Peltonen Laura‐Maria , Pruinelli Lisiane , Chu Charlene H. , Bakken Suzanne , Beduschi Ana , Cato Kenrick , Hardiker Nicholas , Junger Alain , Michalowski Martin , Nyrup Rune , Rahimi Samira , Reed Donald Nigel , Salakoski Tapio , Salanterä Sanna , Walton Nancy , Weber Patrick , Wiegand Thomas , Topaz Maxim
Published: May 2021

Aim

To develop a consensus paper on the central points of an international invitational think‐tank on nursing and artificial intelligence (AI).

Methods

We established the Nursing and Artificial Intelligence Leadership (NAIL) Collaborative, comprising interdisciplinary experts in AI development, biomedical ethics, AI in primary care, AI legal aspects, philosophy of AI in health, nursing practice, implementation science, leaders in health informatics practice and international health informatics groups, a representative of patients and the public, and the Chair of the ITU/WHO Focus Group on Artificial Intelligence for Health. The NAIL Collaborative convened at a 3‐day invitational think tank in autumn 2019. Activities included a pre‐event survey, expert presentations and working sessions to identify priority areas for action, opportunities and recommendations to address these. In this paper, we summarize the key discussion points and notes from the aforementioned activities.

Implications for nursing

Nursing's limited current engagement with discourses on AI and health posts a risk that the profession is not part of the conversations that have potentially significant impacts on nursing practice.

Conclusion

There are numerous gaps and a timely need for the nursing profession to be among the leaders and drivers of conversations around AI in health systems.

Impact

We outline crucial gaps where focused effort is required for nursing to take a leadership role in shaping AI use in health systems. Three priorities were identified that need to be addressed in the near future: (a) Nurses must understand the relationship between the data they collect and AI technologies they use; (b) Nurses need to be meaningfully involved in all stages of AI: from development to implementation; and (c) There is a substantial untapped and an unexplored potential for nursing to contribute to the development of AI technologies for global health and humanitarian efforts.
Interplay between long‐term vulnerability and new risk: Young adolescent and maternal mental health immediately before and during the COVID‐19 pandemic
Authors: Wright Nicola , Hill Jonathan , Sharp Helen , Pickles Andrew
Published: May 2021

Background

We examine whether there has been an increase in young adolescent and maternal mental health problems from pre‐ to post‐onset of the COVID‐19 pandemic.

Methods

Children aged 11–12 years and their mothers participating in a UK population‐based birth cohort (Wirral Child Health and Development Study) provided mental health data between December 2019 and March 2020, and again 3 months after lockdown, 89% (N = 202) of 226 assessed pre‐COVID‐19. Emotional and behavioural problems were assessed by self‐ and maternal reports, and long‐term vulnerability by maternal report of prior child adjustment, and maternal prenatal depression.

Results

The young adolescents reported a 44% (95% confidence interval [CI: 23%–65%]) increase in symptoms of depression and 26% (95% CI [12%–40%]) for post‐traumatic stress disorder, with corresponding maternal reports of child symptoms of 71% (95% CI [44%–99%]) and 43% (95% CI 29%–86%). Disruptive behaviour problem symptoms increased by 76% (95% CI [43%–109%]) particularly in children without previous externalising symptoms. Both female gender and having had high internalising symptoms earlier in childhood were associated with elevated rates of depression pre‐pandemic, and with greater absolute increases during COVID‐19. Mothers' own depression symptoms increased by 42% (95% CI [20%–65%]), and this change was greater among mothers who had prenatal depression. No change in anxiety was observed among children or mothers. None of these increases were moderated by COVID‐19‐related experiences such as frontline worker status of a parent. Prior to the pandemic, rates of maternal and child depression were greater in families experiencing higher deprivation, but changed only in less deprived families, raising their rates to those of the high deprivation group.

Conclusions

COVID‐19 has led to a marked increase in mental health problems in young adolescents and their mothers with concomitant requirements for mental health services to have the resources to adapt to meet the level and nature of the needs.
Elevated serum pentosidine is independently associated with the high prevalence of sarcopenia in Chinese middle‐aged and elderly men with type 2 diabetes mellitus
Authors: Zhang Xiaofan , Liu Juan , Zhang Qing , Lu Aijiao , Du Yunfeng , Ye Xinhua
Published: May 2021

Aims/Introduction

Sarcopenia has recently been recognized as another complication associated with diabetes, but its early screening still lacks clinical markers. Here, we aimed to investigate the relationship between serum levels of pentosidine, which is an advanced glycation end‐product, and sarcopenia in Chinese middle‐aged and elderly men with type 2 diabetes mellitus and evaluate whether pentosidine could be used as a kind of screening maker.

Materials and Methods

A total of 182 male type 2 diabetes mellitus patients aged ≥50 years were selected in the cross‐sectional study for whole‐body dual‐energy X‐ray measurement and calculating the appendicular skeletal muscle mass index. At the same time, handgrip strength and gait speed were assessed. According to the updated consensus on Asian sarcopenia in 2019, the patients were divided into the sarcopenia group (n = 83) and non‐sarcopenia group (n = 99). Serum pentosidine levels in the two groups were detected using enzyme‐linked immunosorbent assay.

Results

Serum pentosidine was significantly higher in the sarcopenia group (191.27 pmol/mL) than in the non‐sarcopenia group (34.93 pmol/mL). Serum pentosidine was negatively correlated with appendicular skeletal muscle mass index and handgrip strength (r = −0.30 and −0.25, respectively; P < 0.05), but not gait speed. The prevalence of sarcopenia increased as the quartile of serum pentosidine increased (P < 0.05). The association between pentosidine and the prevalence of sarcopenia was still significant after additional adjustments (odds ratio 1.01, P < 0.05).

Conclusions

Pentosidine is an independent risk factor for sarcopenia in Chinese middle‐aged and elderly men with type 2 diabetes mellitus. The detection of serum pentosidine levels in clinics might be helpful for the monitoring of type 2 diabetes mellitus complicated with sarcopenia.
Insulin resistance limits corneal nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control
Authors: Ponirakis Georgios , Abdul‐Ghani Muhammad A , Jayyousi Amin , Zirie Mahmoud A , Al‐Mohannadi Salma , Almuhannadi Hamad , Petropoulos Ioannis N , Khan Adnan , Gad Hoda , Migahid Osama , Megahed Ayman , Qazi Murtaza , AlMarri Fatema , Al‐Khayat Fatima , Mahfoud Ziyad , DeFronzo Ralph , Malik Rayaz A
Published: May 2021

Aims/Introduction

This study aimed to investigate whether insulin resistance (IR) in individuals with type 2 diabetes undergoing intensive glycemic control determines the extent of improvement in neuropathy.

Materials and Methods

This was an exploratory substudy of an open‐label, randomized controlled trial of individuals with poorly controlled type 2 diabetes treated with exenatide and pioglitazone or insulin to achieve a glycated hemoglobin <7.0% (<53 mmol/mol). Baseline IR was defined using homeostasis model assessment of IR, and change in neuropathy was assessed using corneal confocal microscopy.

Results

A total of 38 individuals with type 2 diabetes aged 50.2 ± 8.5 years with (n = 25, 66%) and without (n = 13, 34%) IR were studied. There was a significant decrease in glycated hemoglobin (P < 0.0001), diastolic blood pressure (P < 0.0001), total cholesterol (P < 0.01) and low‐density lipoprotein (P = 0.05), and an increase in bodyweight (P < 0.0001) with treatment. Individuals with homeostasis model assessment of IR <1.9 showed a significant increase in corneal nerve fiber density (P ≤ 0.01), length (P ≤ 0.01) and branch density (P ≤ 0.01), whereas individuals with homeostasis model assessment of IR ≥1.9 showed no change. IR was negatively associated with change in corneal nerve fiber density after adjusting for change in bodyweight (P < 0.05).

Conclusions

Nerve regeneration might be limited in individuals with type 2 diabetes and IR undergoing treatment with pioglitazone plus exenatide or insulin to improve glycemic control.
S2k guidelines (consensus statement) for diagnosis and therapy of dermatitis herpetiformis initiated by the European Academy of Dermatology and Venereology (EADV)
Authors: Görög A. , Antiga E. , Caproni M. , Cianchini G. , De D. , Dmochowski M. , Dolinsek J. , Drenovska K. , Feliciani C. , Hervonen K. , Lakos Jukic I. , Kinyó Á. , Koltai T. , Korponay‐Szabó I. , Marzano A.V. , Patsatsi A. , Rose C. , Salmi T. , Schmidt E. , Setterfield J. , Shahid M. , Sitaru C. , Uzun S. , Valitutti F. , Vassileva S. , Yayli S. , Sárdy M.
Published: May 2021

Introduction

Dermatitis herpetiformis (DH) is a chronic, pruritic, gluten‐induced skin disorder characterized by subepidermal granular IgA deposition and a variable degree of enteropathy identical to that seen in coeliac disease. So far, there has been no European consensus about the management of DH.

Methods

The guidelines were created by small subgroups of a guideline committee consisting of 26 specialists from various medical fields and one patients’ representative. The members of the committee then discussed the guidelines and voted for the final version at two consensus meetings. The guidelines were developed under the support of the European Academy of Dermatology and Venereology (EADV) and in collaboration with the European Dermatology Forum (EDF).

Results

The guidelines summarize evidence‐based and expert‐based recommendations (S2 level) for the management of DH (see Appendix).

Conclusion

These guidelines will improve the quality of management of DH and support dermatologists in their diagnostic and therapeutic decisions.