bluuebunny/crossref_metadata_2025 huggingface dataset:
P185 Does BASDAI score correlate to MRI changes in ankylosing spondylarthritis?
Authors: Jain Nibha , Byravan Swetha Byravan , Stairs Jenna , Rennie Winston , Arumugam Moorthy
Published: April 2021

Background/Aims 

The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is routinely used subjective outcome measurement of disease activity in Ankylosing Spondylitis (AS). BASDAI > 4 is used as a criterion for commencing anti-TNF therapy. Previous studies shown BASDAI correlation with MRI has been proven to be weak. We did this study to systemically compare clinical and radiological data of patients with AS and to look for the degree of correlation between BASDAI score and MRI changes positive for spondyloarthritis in our cohort of patients.

Methods 

A retrospective analysis of AS patients attending Leicester spondylarthritis service at University Hospitals Leicester Trust (UHL) was carried out. Clinical characteristics such as HLA-B27 status, extra-articular features, family history of AS and CRP measurement were obtained from online systems and clinic letters. Online records were reviewed to see if patients had a MRI of the sacroiliac joints along with a BASDAI score at the time of MRI. Medcalc calculator was used for statistical analysis.

Results 

A total of 106 patients were analysed with a mean age of 45.6 +/- 11.6 years (M = 62, F = 44) with mean BASDAI of 5.0 +/- 2.5. Mean CRP was 17.01+/- 30.4 (median CRP 6.5). 61% (n = 65) were HLA-B27 positive. 70 of 106 patients had a sacroiliac MRI scan which could be reviewed to a satisfactory level to determine whether disease is present or not. Two results were statistically significant when comparing active versus no active lesions on MRI: inflammatory back pain and anti-TNF therapy (Table 1). P185 Table 1:Comparison of clinical features in patients with active versus inactive lesions on MRI sacroiliac joint.Active lesions on MRI N = 45No active lesions on MRI N = 25P valueMean BASDAI (SD)5.0 (2.6)5.4(2.6)0.5Mean ASDAS CRP (SD)2.14(1.1)2.04(0.6)0.73Mean CRP (SD) mg/l14.7(21)17.8(33)0.645.5HLA-B2731180.Uveitis1190.3Inflammatory back pain40170.03Enthesitis820.3Peripheral Arthritis670.1Dactylitis010.2Psoriasis211Inflammatory bowel disease710.1Ethnicity: Caucasian37230.2Ethnicity: Asian820.3Age45.5 (10.2)50.5(11.3)0.06M: F26:1916:90.7Anti-TNF therapy1840.03BASDAI >428150.8BASDAI <417100.8BASDAI= Bath ankylosing spondylitis disease activity index, ASDAS= Ankylosing Spondylitis disease. CRP=C-reactive protein, HLA= human leucocyte antigen.

Conclusion 

BASDAI score did not statistically correlate with the severity of inflammation as objectively observed on MRI. Only inflammatory back pain and anti-TNF therapy correlated with MRI disease activity. There was no difference in clinical features including HLA-B27 between patients with active and inactive MRI. Thus, BASDAI as a criterion for biologic therapy may need re-considering.

Disclosure 

N. Jain: None. S. Byravan: None. J. Stairs: None. W. Rennie: None. M. Arumugam: Other; Speaker and Conference Fee MSD, Novartis, Abbvie.
Prevalence and predictors of adverse events with methotrexate mono- and combination-therapy for rheumatoid arthritis: a systematic review
Authors: Sherbini Ahmad A , Sharma Seema D , Gwinnutt James M , Hyrich Kimme L , Verstappen Suzanne M M
Published: April 2021

Objectives

This systematic review aims to summarize rates of adverse events (AEs) in patients with RA or inflammatory arthritis starting MTX as monotherapy or in combination with other csDMARDs, and to identify reported predictors of AEs.

Methods

Three databases were searched for studies reporting AEs in MTX-naïve patients with RA. Randomized controlled trials (RCTs) and observational cohort studies were included. Prevalence rates of AEs were pooled using random effects meta-analysis, stratified by study design.

Results

Forty-six articles (34 RCTs and 12 observational studies) were identified. The pooled prevalence of total AEs was 80.1% in RCTs (95% CI: 73.5, 85.9), compared with 23.1% in observational studies (95% CI: 12.3, 36.0). The pooled prevalence of serious AEs was 9.5% in RCTs (95% CI: 7.4, 11.7), and 2.1% in observational studies (95% CI: 1.0, 3.4). MTX discontinuation due to AEs was higher in observational studies (15.5%, 95% CI: 9.6, 22.3) compared with RCTs (6.7%, 95% CI: 4.7, 8.9). Gastrointestinal events were the most commonly reported AEs (pooled prevalence: 32.7%, 95% CI: 18.5, 48.7). Five studies examined predictors of AEs. RF status, BMI and HAQ score were associated with MTX discontinuation due to AEs; ACPA negativity, smoking and elevated creatinine were associated with increased risk of elevated liver enzymes.

Conclusion

The review provides an up-to-date overview of the prevalence of AEs associated with MTX in patients with RA. The findings should be communicated to patients to help them make informed choices prior to commencing MTX.
The association between increased body mass index and response to conventional synthetic disease-modifying anti-rheumatic drug treatment in rheumatoid arthritis: results from the METEOR database
Authors: Dey Mrinalini , Zhao Sizheng S , Moots Robert J , Bergstra Sytske Anne , Landewe Robert B , Goodson Nicola J
Published: April 2021

Background

Few data exist on the association between increased BMI and response to conventional synthetic DMARDs (csDMARDs) in RA. We aimed to explore the association between increased (overweight or obese) BMI on csDMARD prescribing, MTX dose and disease activity over 12 months.

Methods

Participants in an international RA database were stratified into early (<1 year post-diagnosis) and established RA. EULAR response, 28-joint DAS (DAS28) remission and treatments were recorded at baseline, 6 months and 12 months. Increased BMI was explored in early and established RA as predictors of good EULAR response, DAS28 remission, number of csDMARDs and MTX dose, using logistic and linear regression.

Results

Data from 1313 patients, 44.3% with early RA, were examined. In early RA, increased BMI was not significantly associated with remission. In established RA, obese patients on monotherapy were significantly less likely to achieve good EULAR response or DAS28 remission at 6 months and more likely to be treated with combination csDMARDs compared with normal BMI. In patients taking MTX, overweight and obese patients with early and established RA were exposed to higher MTX doses (mono- and combination therapy), with a mean dose of 20 mg/week, compared with 15 mg/week in those of normal BMI.

Conclusion

We observed that compared with patients with normal BMI, overweight and obese individuals experienced more intensive csDMARD exposures. Similar response rates were observed in early RA but increased BMI was associated with reduced response in established RA. Optimization of targeted RA treatment remains important, particularly in those with increased BMI where response in established disease may be attenuated.
Decoupling in science and education: A collateral damage beyond deteriorating US–China relations
Authors: Tang Li , Cao Cong , Wang Zheng , Zhou Zhuo
Published: April 2021

Deteriorating relations between the USA and China since 2018 have extended to education and scientific research arenas. We put the US–China science and education in a historical perspective and describe the win–win situation when both countries collaborated. We discuss an ongoing loss–loss scenario of the decoupling and speculate its far-reaching adverse impacts beyond bilateral territories. We call for actions to be taken for a brighter future by the leaderships in both countries.
12Theatre and Performance
Authors: Simpson Hannah
Published: April 2021

There is a sad irony in writing about theatre and performance scholarship at a time when most US and UK theatre are still closed as a result of the Covid-19 pandemic. However, for all its challenges, 2020 saw the publication of several noteworthy books that significantly advanced the field of theatre and performance studies, and which offer some cause for celebration. This review focuses on three major subject areas: 1. Performing Women, Women in Performance, 2. Tackling the Body, and 3. Social and National Borders. Several larger ideas unite the texts reviewed here, in varying constellations across these three sections: questions about representing identity, about failure and impossibility, and about unity, division, and the porous boundaries between the two. The term ‘encounter’ recurred with startling frequency across these eight texts, signalling a shared central concern with how far the performance space might offer a site of communion—or, at least, communication—in our fractious historical moment.
Patient educational needs and challenges in psoriatic arthritis
Authors: Adebajo Adewale O. , Akintayo Richard O.
Published: April 2021

Purpose of review

To provide an overview of the recent research publications on educational needs of patients with psoriatic arthritis (PsA) and the associated challenges.

Recent findings

The rate of good treatment adherence in PsA can be as low as 57.7% and successful patient education can help improve treatment adherence. Also, 78.7% of patients who stopped their disease modifying anti-rheumatic drugs during the first wave of the COVID-19 pandemic did so without the advice of their clinician. In delivering educational needs, the aspects of disease process, treatment, self-help measures, managing pain, movement, psychological and social needs should all be addressed, whilst at the same time, recognising that PsA patients with multidomain disease, are likely to be dealing with more than just pain. Arthritis self-care management education is potentially beneficial, but up to 11% of educational YouTube videos may contain misleading patient opinion and many existing apps do not meet the needs of the patients with PsA.

Significant room for improvement exists in treatment adherence in PsA and patient education addressing the relevant educational needs could assist with this issue. However, patients should be advised to be wary of internet videos and other educational aids that were not created by health professionals.
A Pilot Study of Short-course Nivolumab and Low-dose Ipilimumab for Adjuvant Treatment of Melanoma
Authors: Constantinou Maria , Miner Thomas J. , Vatkevitch John M. , Naboush Ali , Dionson Sopha , Anderson Jasmine , Kolvek Taylor , Medeiros Maria , MacKinnon Kelsey , Wood Roxanne , Safran Howard
Published: April 2021

Background:

Combined cytotoxic T-lymphocyte-associated antigen 4 and programmed death 1 inhibitor blockade is a promising strategy in advanced melanoma and other solid tumors. This pilot study assessed the safety and toxicity of nivolumab plus low-dose ipilimumab in patients with high-risk completely resected melanoma.

Patients and Methods:

Patients received ipilimumab, 1 mg/kg every 6 weeks, and nivolumab, 3 mg/kg every 2 weeks, for a total of 24 weeks (4 cycles). The primary objective was to assess the toxicity of the combined regimen.

Results:

Twenty-one patients with resected melanoma were enrolled. One patient was stage IIC, 16 patients were stage III and 4 patients had resected stage 4 disease. Ten of 21 (48%) had grade 3 treatment-related toxicities but there was no grade 4 or grade 5 toxicities. The rate of grade 3 nonhematologic toxicities exceeded the toxicity limits defined by the study. Fifteen of 21 patients (71%) completed all 4 cycles of therapy. The median follow-up is 41 months. The 2-year recurrence-free survival is 85.7% and the 2-year overall survival is 90.5%.

Conclusion:

A 6-month course of nivolumab and low-dose ipilimumab may be a promising adjuvant treatment for patients with resected melanoma. Further studies of this regimen are indicated.
Desmoplastic Trichoepithelioma With Pseudocarcinomatous Hyperplasia: A Folliculosebaceous Neoplasm in Young Persons
Authors: Wang Michael Z. , McNiff Jennifer M. , McCalmont Timothy H. , LeBoit Philip E.
Published: April 2021

Pseudocarcinomatous desmoplastic trichoepithelioma (PDTE) features verrucous squamous epidermal hyperplasia with a jagged undersurface overlying cords of follicular germinative cells in a fibrotic stroma. To date, only 5 cases have been reported. We identified 7 new PDTEs from 2 institutions and reviewed their clinical manifestations and immunohistochemical profile. The median age was 14 years (range 8–34 years). New findings included vacuolization of the basal layer of the pseudocarcinomatous surface epithelium, and the frequent presence of singly distributed sebocytes within the cords of basaloid cells. The immunohistochemical profile resembles desmoplastic trichoepithelioma, with expression of TDAG51, CK15, and Ber-Ep4. Colonizing CK20+ Merkel cells were present in all cases. PDTE needs to be differentiated from malignant neoplasms such as squamous cell carcinoma, morphoeic basal cell carcinoma, and microcystic adnexal carcinoma. Recognizing the features of this sclerosing folliculosebaceous neoplasm facilitates accurate diagnosis and avoids overtreatment.
Correlation of FISH and PRAME Immunohistochemistry in Ambiguous Superficial Cutaneous Melanocytic Proliferations
Authors: Harvey Nathan T. , Peverall Joanne , Acott Nathan , Mesbah Ardakani Nima , Leecy Tamazin N. , Iacobelli Jean , McCallum Dugald , Van Vliet Chris , Wood Benjamin A.
Published: April 2021

Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated repressor of retinoic acid signaling which is expressed in melanoma and has emerged as a potential biomarker for malignant behavior in melanocytic neoplasms. Although ancillary molecular techniques such as fluorescence in situ hybridization (FISH) are established techniques in the diagnosis of problematic cutaneous melanocytic proliferations, they are expensive, time-consuming, and require appropriate infrastructure, which places them out of reach of some laboratories. The advent of readily available commercial antibodies to PRAME has the potential to provide a more accessible alternative. The aim of this study was to determine whether immunohistochemistry for PRAME could serve as a surrogate for FISH analysis in a subgroup of challenging superficial melanocytic proliferations. Cases which had previously been submitted for FISH analysis were stained for PRAME and interpreted by a panel of at least 3 dermatopathologists is a blinded fashion. Of a study set of 55 cases, 42 (76%) showed a pattern of PRAME immunostaining which was concordant with the cytogenetic interpretation, with an unweighted kappa of 0.42 (representing mild-to-moderate agreement). Thus, although there was a correlation between positive immunohistochemistry for PRAME and abnormal findings on FISH analysis, in our view, the concordance was not sufficient to enable PRAME immunohistochemistry to act as a surrogate for FISH testing. Our findings reiterate the principle that interpretation of problematic superficial melanocytic proliferations requires a synthesis of all the available data, including clinical scenario, morphological features, immunohistochemistry, and ancillary molecular investigations.
Verrucous Venous Malformation—Subcutaneous Variant
Authors: Schmidt Birgitta A.R. , El Zein Sophie , Cuoto Javier , Al-Ibraheemi Alyaa , Liang Marilyn G. , Paltiel Harriet J. , Anderson Megan E. , Labow Brian I. , Upton Joseph , Fishman Steven J. , Mulliken John B. , Greene Arin K. , Warman Mathew L. , Kozakewich Harry
Published: April 2021

Background:

Verrucous venous malformation (VVM), previously called “verrucous hemangioma,” typically involves the dermis and the subcutaneous fat. We have encountered patients with VVM confined to the hypodermis.

Materials and Methods:

During a nearly 20-year period, 13 patients, aged 2–17 years, presented with a subcutaneous mass in the limb without clinically obvious epidermal alterations. Consequently, operative excisions did not include the skin.

Results:

Histopathologically, the specimens were composed of blood-filled channels with morphologic characteristics of capillaries and veins that infiltrated adipose tissue. Aggregates often formed nodules with variable fibrosis and a component of large and radially oriented vessels. A diagnosis of VVM was supported by endothelial immunopositivity for GLUT-1 (25%–75% immunopositive channels in 16/16 specimens); D2-40 (1%–25% channels in 14/15 specimens); and Prox-1 (1%–50% of channels in 14/16 specimens). A MAP3K3 mutation was identified by droplet digital PCR in 3 of the 6 specimens.

Conclusions:

Diagnosis of VVM in this uncommon location is challenging because of absence of epidermal changes and lack of dermal involvement. Imaging is not pathognomonic, and mimickers are many. Appropriate immunohistochemical stains and molecular analysis contribute to the correct diagnosis.
Hemodynamic clinical phenotyping in septic shock
Authors: Daulasim Anousone , Vieillard-Baron Antoine , Geri Guillaume
Published: April 2021

Purpose of review

Recent studies have failed to show significant benefit from a uniform strategy, suggesting that hemodynamic management must be individually adapted in septic shock depending on different phenotypes. Different approaches that may be used to this end will be discussed.

Recent findings

Fluid management is a cornerstone of resuscitation, as the positive fluid balance has been associated with higher mortality and right ventricular failure. Myocardial evaluation is mandatory, as sepsis patients may present with a hyperkinetic state, left ventricular (systolic and diastolic) and/or right ventricular dysfunction, the latter being associated with higher mortality. Statistical approaches with the identification of hemodynamic clusters based on echocardiographic and clinical parameters might be integrated into daily practice to develop precision medicine. Such approaches may also predict the progression of septic shock.

Different hemodynamic phenotypes can occur at any stage of sepsis and be associated with one another. The clinician must regularly assess dynamic changes in phenotypes in septic shock patients. Statistical approaches based on machine learning need to be validated by prospective studies.
Esophageal afferent innervation and its role in gastro-esophageal reflux disease symptoms
Authors: Ustaoglu Ahsen , Woodland Philip
Published: April 2021

Purpose of review

Despite the wide prevalence of gastro-esophageal reflux disease (GERD), the neurophysiological mechanisms underlying heartburn perception in the esophagus of patients with GERD remains incompletely understood. Recent studies have highlighted the potential influence sensory afferent nerves innervating the oesophageal epithelium may have on heartburn pathogenesis. The purpose of this review is to consider the current understanding of esophageal afferent neuronal innervation, including the nociceptive role of acid-sensing receptors expressed on these sensory nerves, in relation to pain perception in the esophagus of GERD patients.

Recent findings

Central and peripheral pathways of sensitization following noxious stimulation of nociceptive receptors expressed on afferent nerves can regulate the strength of sensory nerve activation in the esophagus, which can result in the amplification or suppression of afferent signal transmission. The localization and characterization of mucosal sensory afferent nerves vary between GERD phenotypes and may explain the heterogeneity of symptom perception in patients with apparently similar levels of reflux.

In this review, we discuss the relevance of afferent esophageal innervation in heartburn perception, with a particular focus on the pathways of reflux-induced activation of nociceptive nerves.
Moral Injury and Burnout in Health Care Professionals During the COVID-19 Pandemic
Authors: Mantri Sneha , Song Ye Kyung , Lawson Jennifer M. , Berger Elizabeth J. , Koenig Harold G.
Published: April 2021

The coronavirus pandemic (COVID-19) is predicted to increase burnout in health professionals (HPs), but little is known about moral injury (MI) in this context. We administered the Moral Injury Symptoms Scale for Health Professionals (MISS-HP) and the abbreviated Maslach Burnout Inventory via online survey to a global sample of 1831 HPs in April and October 2020. Mean MISS-HP increased from 27.4 (SD, 11.6) in April to 36.4 (SD, 13.8) in October (p < 0.001), with an accompanying increase in personal accomplishment (April: 4.7; SD, 3.1; October: 9.3; SD, 3.1; p < 0.001) and no change in other burnout subscales. In April, 26.7% of respondents reported at least moderate functional impairment from MI, increasing to 45.7% in October (p < 0.001). Predictors of MISS-HP included younger age and being a nurse. Odds of functional impairment were higher in respondents who were widowed, divorced, never married, or had direct experience caring for patients with COVID-19. COVID-19 has increased MI but not burnout in HPs; younger or unmarried individuals, nurses, and frontline workers may benefit from targeted outreach to reduce downstream effects of MI, depression, and/or posttraumatic stress disorder.
Cytoplasmic Pattern p53 Immunoexpression in Pelvic and Endometrial Carcinomas With TP53 Mutation Involving Nuclear Localization Domains
Authors: Rabban Joseph T. , Garg Karuna , Ladwig Nicholas R. , Zaloudek Charles J. , Devine W. Patrick
Published: April 2021

A cytoplasmic pattern of p53 immunohistochemical expression has recently been reported in a rare subset of pelvic and endometrial cancers with a TP53 mutation involving domains affecting nuclear localization. This study reports the clinicopathologic features of 31 cases with a TP53 mutation involving nuclear localization, the largest study to date, emphasizing practical strategies for recognizing this uncommon variant and distinguishing it from the p53 wild-type pattern. The study also evaluates the prognostic significance of TP53 mutation involving nuclear localization in the ovarian high-grade serous carcinoma (HGSC) cohort of The Cancer Genome Atlas database. Most of the 31 tumors were advanced stage pelvic or endometrial HGSC. All TP53 mutations were predicted to result in loss of function. The p53 overexpression pattern was present in 6 tumors; the p53 null pattern in 3 and the p53 cytoplasmic pattern in 22 tumors. The p53 cytoplasmic pattern predominantly consisted of weak to moderate cytoplasmic staining in >95% of tumor cells as well as variable intensity nuclear staining involving a range of just a few cells to just under 80% of tumor cells. The p53 cytoplasmic pattern was observed in 100% of tumors with TP53 mutation in the nuclear localization domain and in 33% to 44% of tumors with a mutation in the adjacent tetramerization domain or nuclear exclusion sequence (P<0.01). p16 immunoexpression was present in 74% of tumors. In The Cancer Genome Atlas ovarian HGSC cohort, 9% of 471 nonredundant TP53-mutant cases had a nuclear localization domain, tetramerization domain, or nuclear exclusion sequence mutation but there was no significant difference in survival when compared to cases with TP53 mutation outside those domains (P>0.05). p53 cytoplasmic staining merits classification as an aberrant result despite coexisting nuclear staining that in some cases may resemble the p53 wild-type pattern. While positive p16 immunostaining may be of value to confirm diagnostically challenging cases of p53 cytoplasmic staining, a negative result is noninformative and molecular testing for TP53 mutation should be considered, if available.
Towards a More Standardized Approach to Pathologic Reporting of Pancreatoduodenectomy Specimens for Pancreatic Ductal Adenocarcinoma
Authors: Dhall Deepti , Shi Jiaqi , Allende Daniela S. , Jang Kee-Taek , Basturk Olca , Adsay Volkan , Kim Grace E.
Published: April 2021

In recent literature and international meetings held, it has become clear that there are significant differences regarding the definition of what constitutes as margins and how best to document the pathologic findings in pancreatic ductal adenocarcinoma. To capture the current practice, Pancreatobiliary Pathology Society (PBPS) Grossing Working Group conducted an international multispecialty survey encompassing 25 statements, regarding pathologic examination and reporting of pancreatic ductal adenocarcinoma, particularly in pancreatoduodenectomy specimens. The survey results highlighted several discordances; however, consensus/high concordance was reached for the following: (1) the pancreatic neck margin should be entirely submitted en face, and if tumor on the slide, then it is considered equivalent to R1; (2) uncinate margin should be submitted entirely and perpendicularly sectioned, and tumor distance from the uncinate margin should be reported; (3) all other surfaces (including vascular groove, posterior surface, and anterior surface) should be examined and documented; (4) carcinoma involving separately submitted celiac axis specimen should be staged as pT4. Although no consensus was achieved regarding what constitutes R1 versus R0, most participants agreed that ink on tumor or at and within 1 mm to the tumor is equivalent to R1 only in areas designated as a margin, not surface. In conclusion, this survey raises the awareness of the discordances and serves as a starting point towards further standardization of the pancreatoduodenectomy grossing and reporting protocols.
Transmission characteristics of SARS-CoV-2 variants of concern Rapid Scoping Review
Authors: Curran Janet , Dol Justine , Boulos Leah , Somerville Mari , McCulloch Holly , MacDonald Marilyn , LeBlanc Jason , Barrett Lisa , Hatchette Todd , Comeau Jeannette , Reynolds Bearach , Shin Danielle , Gallant Allyson , Wong Helen , Crowther Daniel , Yu Ziwa
Published: April 2021

Background

As of March 2021, three SARS-CoV-2 variants of concern (VOC) have been identified (B.1.1.7, B.1.351 and P.1) and been detected in over 111 countries. Despite their widespread circulation, little is known about their transmission characteristics. There is a need to understand current evidence on VOCs before practice and policy decisions can be made. This study aimed to map the evidence related to the transmission characteristics of three VOCs.

Methods

A rapid scoping review approach was used. Seven databases were searched on February 21, 2021 for terms related to VOCs, transmission, public health and health systems. A grey literature search was conducted on February 26, 2021. Title/abstracts were screened independently by one reviewer, while full texts were screened in duplicate. Data were extracted using a standardized form which was co-developed with infectious disease experts. A second data extractor verified the results. Studies were included if they reported on at least one of the VOCs and transmissibility. Animal studies and modeling studies were excluded. The final report was reviewed by content experts.

Results

Of the 1796 articles and 67 grey literature sources retrieved, 16 papers and 7 grey sources were included. Included studies used a wide range of designs and methods. The majority (n=20) reported on B.1.1.7. Risk of transmission, reported in 15 studies, was 45-71% higher for B.1.1.7 compared to non-VOCs, while R0 was 75-78% higher and the reported Rt ranged from 1.1-2.8. There was insufficient evidence on the transmission risk of B.1.35.1 and P.1. Twelve studies discussed the mechanism of transmission of VOCs. Evidence suggests an increase in viral load among VOCs based on cycle threshold values, and possible immune evasion due to increased ACE2 binding capacity of VOCs. However, findings should be interpreted with caution due to the variability in study designs and methods.

Conclusion

VOCs appear to be more transmissible than non-VOCs, however the mechanism of transmission is unclear. With majority of studies focusing on the B.1.1.7 VOC, more research is needed to build upon these preliminary findings. It is recommended that decision-makers continue to monitor VOCs and emerging evidence on this topic to inform public health policy.
Shifted dynamics of glucose metabolism in the hippocampus during aging
Authors: Ge Ivan , Kirschen Gregory W. , Wang Xinxing
Published: April 2021

Aging is a process that adversely affects brain functions such as cognitive behaviors. Brain activity is a high-energy consumption process. Glucose serves as the main energy source under normal circumstances. Whether the dynamics of glucose metabolism during aging remains unchanged is not well understood. This study sought to investigate the activity-dependent changes in glucose metabolism of the mouse hippocampus during aging. In brief, after one hour of contextual exploration in an enriched environmental condition or one hour in a familiar home cage condition, metabolites were measured from the hippocampus of both adult and aged mice with metabolomic profiling. Compared to the home cage context, the enriched contextual exploration condition resulted in changes in the concentration of 11 glucose metabolism-related metabolites in the adult hippocampus. In contrast, glucose metabolism-related metabolite changes were more apparent in the aged group during contextual exploration when compared to those in the home cage condition. Importantly, in the aged groups, several key metabolites involved in glycolysis, the TCA cycle, and ketone body metabolism accumulated, suggesting the less efficient metabolization of glucose-based energy resources. Altogether, the analyses revealed that in the aged mice during enriched contextual exploration, the glucose resource seems to be unable to provide enough energy for hippocampal function.

Highlights

Glycolysis becomes less efficient in the aged hippocampus during contextual exploration.

TCA cycle is altered in the aged hippocampus during contextual exploration.

Ketone body metabolism is elevated in the aged hippocampus during contextual exploration.
Fat storage influences fasting endurance more than body size in an ungulate
Authors: Trondrud L. Monica , Pigeon Gabriel , Król Elżbieta , Albon Steve , Evans Alina L. , Arnold Walter , Hambly Catherine , Irvine R. Justin , Ropstad Erik , Stien Audun , Veiberg Vebjørn , Speakman John R. , Loe Leif Egil
Published: April 2021

The fasting endurance hypothesis (FEH) predicts strong selection for large body size in mammals living in environments where food supply is interrupted over prolonged periods of time. The Arctic is a highly seasonal and food‐restricted environment, but contrary to predictions from the FEH, empirical evidence shows that Arctic mammals are often smaller than their temperate conspecifics. Intraspecific studies integrating physiology and behaviour of different‐sized individuals may shed light on this paradox.

We tested the FEH in free‐living Svalbard reindeer Rangifer tarandus platyrhynchus. We measured daily energy expenditure (DEE), subcutaneous body temperature (Tsc) and activity levels during the late winter in 14 adult females with body masses ranging from 46.3 to 57.8 kg. Winter energy expenditure (WEE) and fasting endurance (FE) were modelled dynamically by combining these data with body composition measurements of culled individuals at the onset of winter (14 years, n = 140) and variation in activity level throughout winter (10 years, n = 70).

Mean DEE was 6.3 ± 0.7 MJ/day. Lean mass, Tsc and activity had significantly positive effects on DEE. Across all 140 individuals, mean FE was 85 ± 17 days (range 48–137 days). In contrast to the predictions of the FEH, the dominant factor affecting FE was initial fat mass, while body mass and FE were not correlated. Furthermore, lean mass and fat mass were not correlated. FE was on average 80% (45 days) longer in fat than lean individuals of the same size. Reducing activity levels by ~16% or Tsc by ~5% increased FE by 7% and 4% respectively.

Our results fail to support the FEH. Rather, we demonstrate that (a) the size of fat reserves can be independent of lean mass and body size within a species, (b) ecological and environmental variation influence FE via their effects on body composition and (c) physiological and behavioural adjustments can improve FE within individuals. Altogether, our results suggest that there is a selection in Svalbard reindeer to accumulate body fat, rather than to grow structurally large.

A free Plain Language Summary can be found within the Supporting Information of this article.
Land‐use intensity affects the potential for apparent competition within and between habitats
Authors: Miller Kirsten E. , Aguilera Guillermo , Bommarco Riccardo , Roslin Tomas
Published: April 2021

Arthropod communities dwelling in adjacent habitats are able to impact one another via shared natural enemies. In agricultural landscapes, drastic differences in resource availability between crop and non‐crop habitats cause variation in insect herbivore densities over short distances, potentially driving inter‐habitat effects. Moreover, the composition of the landscape in which the habitats are embedded likely affects realised attack rates from natural enemies via impacts on local arthropod community structure.

Here, we examine indirect effects between herbivore species within and between habitat types by calculating the potential for apparent competition between multiple populations. Firstly, we aim to determine how disparities in resource availability impact the strength of the potential for apparent competition occurring between habitats, secondly to examine the impact of landscape composition upon these effects, and finally to couch these observations in reality by investigating the link between the potential for apparent competition and realised attack rates.

We used DNA metabarcoding to characterise host–parasitoid interactions within two habitat types (with divergent nutrient inputs) at 11 locations with variable landscape composition within an agroecosystem context. We then used these interaction networks to estimate the potential for apparent competition between each host pair and to compare expected versus realised attack rates across the system.

Shared natural enemies were found to structure host herbivore communities within and across habitat boundaries. The size of this effect was related to the resource availability of habitats, such that the habitat with high nutrient input exerted a stronger effect. The overall potential for apparent competition declined with increasing land‐use intensity in the surrounding landscape and exhibited a discernible impact on realised attack rates upon herbivore species.

Thus, our results suggest that increasing the proportion of perennial habitat in agroecosystems could increase the prevalence of indirect effects such as apparent competition among insect herbivore communities, potentially leading to enhanced population regulation via increased attack rates from natural enemies like parasitoid wasps.
Talk Less, Learn More: Strategic Disclosure in Response to Managerial Learning from the Options Market
Authors: CHEN YANGYANG , NG JEFFREY , YANG XIN
Published: April 2021

We examine how options trading affects voluntary corporate disclosure, so that we can shed light on whether managers’ potential learning from the options market induces them to withhold disclosure. We find that options trading reduces the likelihood and frequency of management earnings forecasts, suggesting that firms that have active options trading on their stock make fewer voluntary disclosures. This finding is in accordance with the theoretical prediction that managers strategically reduce disclosure to avoid crowding out informed trading, which can give them informative feedback for their decision making. In support of the managerial learning channel, we document a real effect of reduced disclosure: When managers disclose less, options trading has a stronger positive effect on firm investment efficiency. The more pronounced effect of options trading on management earnings forecasts when the need for managerial learning is higher further supports the learning channel.
Introduction to the Special Issue: ‘Governing Climate‐altering Approaches’
Authors: Pasztor Janos , Harrison Nicholas
Published: April 2021

While awareness of the global climate emergency is growing, so too are greenhouse gas emissions and a persistent gap remains between international commitments and the 1.5–2°C goal of the Paris Agreement. Additional climate‐altering approaches are being considered to reduce atmospheric concentrations of carbon dioxide (carbon dioxide removal) or the amount of absorbed solar energy in the climate system (solar radiation modification) but they face multiple uncertainties and knowledge gaps relating to their feasibility, acceptability, sustainability and governance. This special issue presents new insights relating to the governance of climate‐altering approaches together with possible ways to address knowledge and governance gaps in future.
Steroids to reduce the impact on delirium (STRIDE): a double‐blind, randomised, placebo‐controlled feasibility trial of pre‐operative dexamethasone in people with hip fracture
Authors: Kluger M. T. , Skarin M. , Collier J. , Rice D. A. , McNair P. J. , Seow M.Y. , Connolly M. J.
Published: April 2021

Neuro‐inflammation may be important in the pathogenesis of postoperative delirium following hip fracture surgery. Studies have suggested a potential role for steroids in reducing postoperative delirium; however, the potential efficacy and safety of pre‐operative high‐dose dexamethasone in this specific population is largely unknown. Conducting such a study could be challenging, considering the multidisciplinary team involvement and the emergency nature of the surgery. The aim of this study was to assess feasibility and effectiveness of dexamethasone given as early as possible following hospital admission for hip fracture, to inform whether a full‐scale trial is warranted. This single‐centre, randomised, double‐blind, placebo‐controlled study randomly allocated 79 participants undergoing hip fracture surgery to dexamethasone 20 mg or placebo pre‐operatively. Eligibility and recruitment rates, timing of the intervention and adverse events were recorded. Incidence and severity of postoperative delirium were assessed using the 4AT delirium screening tool and the Memorial Delirium Assessment Scale. Postoperative pain, length of stay and mortality were also assessed. The eligibility rate for inclusion was 178/527 (34%), and 57/178 (32%) of eligible patients presented to hospital when no researcher was available (e.g. after‐hours, weekends, public holidays). Recruitment was limited mainly by ethical limitations (not including patients with impaired cognition) and lack of weekend staffing. Median (IQR [range]) time from emergency department admission to drug administration was 13.3 (5.9–17.6 [1.8–139.6]) hours. There was a significant difference in delirium severity scores, favouring the dexamethasone group: median (IQR [range]) 5 (3–6 [3–7]) vs. 9 (6–13 [5–14]) in the placebo group, with the probability of superiority effect size being 0.89, p = 0.010. Delirium incidence did not differ between groups: 6/40 (15%) in the dexamethasone group vs. 9/39 (23%) in the placebo group, relative risk (95%CI) 0.65 (0.22–1.65), p = 0.360). A larger randomised controlled trial is feasible and ideally this should include people with existing cognitive impairment, seven days‐a‐week cover and a multicentre design.
Astragalus polysaccharide supplementation improves production performance, egg quality, serum biochemical index and gut microbiota in Chongren hens
Authors: Lv Hongwei , Tang Yanqiang , Zhang Haihan , Li Siming , Fan Zhiyong
Published: April 2021

This research aimed to determine whether the astragalus polysaccharide (AP) can improve the production performance and gut microbiota in Chongren hens.120 Chongren hens (240‐d old) were randomly allocated into 4 treatments with 30 hens and fed with a control basal diet (CON) or CON supplemented with the different levels of AP (100, 200, and 400 mg/kg) for 56 d. The egg production and feed conversion ratio were decreased (p < .05) with the levels of AP. The yolk weight, yolk color, eggshell thickness, eggshell redness index and egg shell yellowness were increased (p < .05). AP supplementation increased CAT and T‐AOC and SOD, and decreased MDA (p < .05). Supplementation of AP decreased IL‐2, IL‐6 and TNF‐α levels (p < .05), but increased the IL‐4 level in the liver (p < .05). The villus heights of duodenum, jejunum ileum, the crypt depth and V/C in the jejunum were increased (p < .05). Dietary supplementation of 200 mg/kg AP increased (P relative abundances of Firmicutes and Lactobacteriaceae in the cecum of Chongren hens. In conclusion, addition of AP improved the production performance, egg quality, antioxidant function, and intestinal morphology in hens, which might be associated with the gut microbiota.
Carbohydrates effects on nutrition and health functions in pigs
Authors: Zhou Hua , Yu Bing , Chen Hong , Chen Daiwen
Published: April 2021

The greatest improvement in carbohydrates studies on pig nutrition and health is that carbohydrates are classified more clearly, which is based not only on their chemical structure but also on their physiological characteristics. Besides its primary energy source, different types and structures of carbohydrates are a benefit for nutrition and health functions in pigs, which are involved in promoting growth performance and intestinal functions, regulating the community of gut microbiota, and modulating the lipids and glucose metabolism. The underlying mechanism of carbohydrates regulates the lipids and glucose metabolism through their metabolites (short‐chain fatty acids [SCFAs]) and mainly via the SCFAs‐GPR43/41‐PYY/GLP1, SCFAs‐AMP/ATP‐AMPK, and SCFAs‐AMPK‐G6Pase/PEPCK pathways. Emerging research had evaluated an optimal combination in different types and structures of carbohydrates, which could enhance growth performance and nutrient digestibility, promote intestinal functions, and increase the abundances of butyrate‐producing bacteria in pigs. Overall, compelling evidence supports the notion that carbohydrates play important roles in both nutrition and health functions in pigs. Moreover, identifying the carbohydrates combinations will be of both theoretical and practical values for developing the technology of carbohydrates balance in pigs.
Tacrolimus variability score outperforms coefficient of variation in predicting clinical outcomes of living kidney transplantation
Authors: Yin Saifu , Wang Xianding , Huang Zhongli , Fan Yu , Song Turun , Lin Tao
Published: April 2021

Aims

Intrapatient variability (IPV) was previously defined as coefficient of variation (CV) or standard deviation of tacrolimus (Tac) exposure while none of them was easily being interpreted and translated into clinical practice after kidney transplantation.

Methods

We developed a novel Tac variability score (TVS) to evaluate IPV by calculating the frequency of clinically significant changes of Tac trough levels after kidney transplantation. Multivariate Cox proportional analyses were conducted to compare the impact of TVS and CV on transplant outcomes.

Results

A total of 1343 patients were divided into high TVS (>0.30) and low TVS (<0.30) groups, and low CV (<0.30) and high CV (>0.30) groups. Univariate analyses showed that high TVS (hazard ratio [HR]: 2.323, 95% confidence interval [CI]: 1.455–3.709) and high CV (HR: 1.606, 95%CI: 1.044–2.471) were associated with inferior graft survival. However, only TVS was an independent predictor for graft failure in multivariate analyses (HR: 1.972, 95%CI: 1.2–3.24), and the correlation maintained in high CV (P = .020) and low CV (P = .037) subgroups, while CV failed to predict graft loss in neither low (P = .387) nor high TVS (P = .600) subgroups. In addition, TVS had a higher correlation with graft survival in patients with Tac exposure within the therapeutic range and the correlation was less influenced by mean Tac trough levels.

Conclusion

TVS is a novel measure of Tac IPV with higher correlation with graft survival and more convenience in clinical use than CV after kidney transplantation.
Improving oral health in nursing home residents: A cluster randomized trial of a shared oral care intervention
Authors: Overgaard Charlotte , Bøggild Henrik , Hede Børge , Bagger Maiken , Hartmann Line Gøtz , Aagaard Karin
Published: April 2021

Objectives

To compare a designated shared oral care intervention in a group of public nursing home residents with a standard oral care programme, focusing on levels of oral plaque and oral inflammation.

Methods

A cluster randomized field trial was undertaken in 14 Danish public nursing homes. There were 145 participants included in the intervention group and 98 in the control group. We undertook a six‐month intervention based on the principle of situated interprofessional learning. The primary outcomes were plaque and inflammation levels measured with the mucosal plaque index (MPS); this was assessed at baseline, after three and six months (end of intervention), and at follow‐up (six months postintervention). The odds ratios (OR) and 95% confidence intervals (CI) were estimated with ordinal regression.

Results

Socio‐demographic characteristics and oral health status at baseline were comparable between the two groups, with the exception of age: the intervention group were significantly younger than controls (median 82 vs 87 years). After three and six months, those receiving the shared oral care intervention had significantly lower plaque and inflammation than the control group. The adjusted ORs for a reduction in MPS were 11.8 (CI: 6.5‐21.3) and 11.0 (CI: 5.8‐20.9), respectively. At follow‐up, plaque levels and oral inflammation had approached the pre‐intervention level, with no remaining statistically significant group differences.

Conclusions

The shared oral care intervention based on a situated learning perspective was effective in improving oral health among care home residents. However, after termination of the intervention, the effect quickly decreased. This confirms the challenges of achieving long‐term improvement in oral health in nursing home residents. An implementation strategy focusing on achieving changes at both organizational and individual levels with persistent attention to oral health care seem required for long‐term improvement.
Associations between T cell infiltration, T cell receptor clonality, histology and recurrence in renal cell carcinoma
Authors: Gadot Moran , Gal Mordechay , Dobosz Paula , Dotan Zohar , Ramon Jacob , Berger Raanan , Avni Dror , Fridman Eduard , Leibowitz Raya
Published: April 2021

Renal cell carcinoma (RCC) is comprised of clear-cell (ccRCC) and non-clear-cell (nccRCC) tumors. Despite definitive surgical resection in localized disease, recurrence often occurs. A commercial method based on a multiplex polymerase chain reaction (PCR) assay exclusively targets rearranged T cell receptor (TCR) genes to generate high-throughput sequencing-based data, allowing characterization of the immune repertoire within tumors. In this study we performed a retrospective analysis on archived tumor samples from patients with recurring versus non-recurring T3 ccRCC and on samples from early nccRCC versus ccRCC. Following genomic DNA extraction and multiplex PCR, the fraction of T cells within tumors, the number of unique receptors (‘richness’) and their relative abundances (‘clonality’) were calculated. Statistical significance and correlations were calculated using Student's t-test and Spearman's rho, respectively. Average fraction and clonality of T cells in tumors from non-recurring patients was 2.5- and 4.3-fold higher than in recurring patients (P = 0.025 and P = 0.043, respectively). A significant positive correlation was found between T cell fraction and clonality (Spearman's rho = 0.78, P = 0.008). The average fraction of T cells in ccRCC tumors was 2.8-fold higher than in nccRCC tumors (P = 0.015). Clonality and estimated richness were similar between ccRCC and nccRCC tumors. In summary, recurrence of ccRCC is associated with a lower fraction and clonality of T cells within tumors; nccRCC tumors are more ‘deserted’ than ccRCC, but similar in their ability to generate a clonal T cell repertoire. Our work suggests associations between the characteristics of T cell infiltrate, histology and tumor recurrence.