bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstructing Sovereignty on Ancient Mesoamerica's Southern Pacific Coast
Authors: Rosenswig Robert M.
Published: April 2021

The internal control and external sovereignty that define nation‐states today has a long (pre)history. Many archaeologists undertheorize sovereignty by only implicitly inferring the sovereign status of the polities they study. Sovereignty also remains insufficiently operationalized in terms of its material remains, especially for those ancient societies without written accounts. During the final centuries before the Common Era, a network of kingdoms existed along the Pacific coast of Mexico, Guatemala, and El Salvador. Large earthen mounds that formed plazas lined with stelae, elaborately carved in a shared art style, defined each kingdom's capital city. Izapa was the largest of these kingdoms, and recent lidar (light detection and ranging) and pedestrian surveys document the entire territory encompassing dozens of political centers. These data reveal an integrated three‐tiered political hierarchy within the kingdom with the largest centers arranged defensively around the perimeter of Izapa's territory. Further, the “30 km rule” is defined as a cross‐cultural pattern for the spacing of sovereign polities and confirmed based on the location of Izapa and neighboring Pacific coast kingdoms. The record of millennia of hierarchically organized human pluralities generates a more complete, comparative understanding of how sovereignty was established and how it functions. [sovereignty, territoriality, political organization, Mesoamerica]
Cervical cancer prevention among older women – challenges in screening, diagnostic workup and treatment
Authors: Gustafson Line W. , Petersen Lone Kjeld , Bor Pinar , Andersen Berit , Hammer Anne
Published: April 2021

Cervical cancer incidence and mortality have declined dramatically after screening for cervical cancer was implemented. Yet, studies have reported high cervical cancer incidence and mortality rates at older age despite low HPV prevalence and incidence of precursor lesions. The underlying reason for these findings remains unclear. However, it is well known that the impact of screening depends not only on the uptake and effectiveness of screening but also on the uptake and effectiveness of diagnostic workup (ie colposcopy), treatment and follow‐up. In older women, sensitivity of screening and performance of colposcopy are impaired due to age‐dependent changes to the cervix. In this commentary, we aimed to discuss challenges in screening and clinical management of older women, and to identify crucial areas of particular interest for future research.
Health screening among children newly granted asylum in Denmark
Authors: Frederiksen Nicoline Willum , Christoffersen Nanna Marie , Haugaard Anna Karen , Ahmadi Afsaneh , Poulsen Anja , Norredam Marie , Kruse Alexandra
Published: April 2021

Aim

To describe the findings and recommendations of the general health assessment (GHA) of newly resettled refugee children in Denmark.

Methods

This cross‐sectional study included children (aged <18 years) undergoing GHA from 2017 to 2019 at a university hospital Section of Immigrant Medicine. GHA was offered to all refugees newly resettled in the Municipality of Copenhagen. It comprised of a structured questionnaire, clinical examination, blood test and recommendations.

Results

In the study period, 107 children were eligible, 100 children had a GHA performed and of whom all were included in the study. Trauma was reported in 61% (n = 61/100) of children. The median duration of the asylum‐seeking process was 18 months (IQR: 8‐24), and the highest number of relocations was nine. Latent tuberculosis (n = 2/100 [2%]) was the only infectious disease diagnosed. Specific recommendations for follow‐up were frequent and included referral to specialist departments (n = 26/100 [26%]), suggestions for family doctor (n = 96/100 [96%]) and for municipality (n = 62/100 [62%]).

Conclusion

Self‐reported trauma was frequent among 100 newly resettled refugee children. For most children, the asylum process was protracted and included several relocations. Specific follow‐up recommendations were given to the vast majority. GHA may contribute to improving health, which could possibly support integration for the child and family.
Dietary influences on the Dahl SS rat gut microbiota and its effects on salt‐sensitive hypertension and renal damage
Authors: Abais‐Battad Justine M. , Saravia Fatima L. , Lund Hayley , Dasinger John Henry , Fehrenbach Daniel J. , Alsheikh Ammar J. , Zemaj Jeylan , Kirby John R. , Mattson David L.
Published: April 2021

Aim

Our previous studies have demonstrated the importance of dietary factors in the determination of hypertension in Dahl salt‐sensitive (SS) rats. Since the gut microbiota has been implicated in chronic diseases like hypertension, we hypothesized that dietary alterations shift the microbiota to mediate the development of salt‐sensitive hypertension and renal disease.

Methods

This study utilized SS rats from the Medical College of Wisconsin (SS/MCW) maintained on a purified, casein‐based diet (0.4% NaCl AIN‐76A, Dyets) and from Charles River Laboratories (SS/CRL) fed a whole grain diet (0.75% NaCl 5L79, LabDiet). Faecal 16S rDNA sequencing was used to phenotype the gut microbiota. Directly examining the contribution of the gut microbiota, SS/CRL rats were administered faecal microbiota transfer (FMT) experiments with either SS/MCW stool or vehicle (Vehl) in conjunction with the HS AIN‐76A diet.

Results

SS/MCW rats exhibit renal damage and inflammation when fed high salt (HS, 4.0% NaCl AIN‐76A), which is significantly attenuated in SS/CRL. Gut microbiota phenotyping revealed distinct profiles that correlate with disease severity. SS/MCW FMT worsened the SS/CRL response to HS, evidenced by increased albuminuria (67.4 ± 6.9 vs 113.7 ± 25.0 mg/day, Vehl vs FMT, P = .007), systolic arterial pressure (158.6 ± 5.8 vs 177.8 ± 8.9 mmHg, Vehl vs FMT, P = .09) and renal T‐cell infiltration (1.9‐fold). Amplicon sequence variant (ASV)‐based analysis of faecal 16S rDNA sequencing data revealed taxa that significantly shifted with FMT: Erysipelotrichaceae_2, Parabacteroides gordonii, Streptococcus alactolyticus, Bacteroidales_1, Desulfovibrionaceae_2, Ruminococcus albus.

Conclusions

These data demonstrate that dietary modulation of the gut microbiota directly contributes to the development of Dahl SS hypertension and renal injury.
Regression with interval‐censored covariates: Application to cross‐sectional incidence estimation
Authors: Morrison Doug , Laeyendecker Oliver , Brookmeyer Ron
Published: April 2021

A method for generalized linear regression with interval‐censored covariates is described, extending previous approaches. A scenario is considered in which an interval‐censored covariate of interest is defined as a function of other variables. Instead of directly modeling the distribution of the interval‐censored covariate of interest, the distributions of the variables which determine that covariate are modeled, and the distribution of the covariate of interest is inferred indirectly. This approach leads to an estimation procedure using the Expectation‐Maximization (EM) algorithm. The performance of this approach is compared to two alternative approaches, one in which the censoring interval midpoints are used as estimates of the censored covariate values, and another in which the censored values are multiply imputed using uniform distributions over the censoring intervals. A simulation framework is constructed to assess these methods’ accuracies across a range of scenarios. The proposed approach is found to have less bias than midpoint analysis and uniform imputation, at the cost of small increases in standard error.
Personalising digital learning for young children: Leveraging psychosocial identities and Techne for literacy development
Authors: Rice Mary Frances , Cun Aijuan
Published: April 2021

Children learn literacies as social practices in context. Increasingly, these contexts include technological tools. Moreover, children engage with psychosocial identity tasks that involve more than cognitive growth. With the rapid rise in digital personalisation, there is a need to consider ways to ensure that digital technologies attend to literacies using understandings about psychosocial development. In this paper, we share ideas from Erik Erikson about the psychosocial tasks children must achieve in their communities from infancy and we relate these to literacy. The psychosocial tasks are trust, autonomy, initiative and industry. We explain how digital personalisation efforts might contribute to holistic psychosocial development that are also supportive of expansive literacies. Then, we make three recommendations for enhancing the digital personalisation efforts. These include attending to identity tasks, considering multiple types of growth simultaneously and involving multiple systems (eg, parents, caregivers and community) in planning, implementing and evaluating personalised instructional materials for young children.

Practitioner notes

What is already known

Personalisation is a concept centred on meeting learners' individual needs.

Digital personalisation tools and practices for young children have not fully leveraged unique aspects of childhood versus other phases of life.

What this paper adds

Digital personalisation processes for young children can be enhanced through psychosocial considerations within social contexts, particularly for literacy learning.

Psychosocial developmental theories offer new ways to think about how to involve parents and other caregivers in digital personalisation processes.

Implications for practice

Planners, implementers and evaluators of digital personalised instructional materials should tether their efforts to psychosocial identity tasks.

Planners, implementers and evaluators should also consider ways to layer multiple types of learning (cognitive, social and psychological) within identity tasks.

Planners, implementers and evaluators should work to include multiple support systems (parents, educators and communities) in their efforts to personalise digital activities and materials.
Union Membership Peaks in Midlife
Authors: Blanchflower David G. , Bryson Alex
Published: April 2021

Using data from 68 countries on over eight million respondents over 40 years we show union membership peaks in midlife — usually around workers’ late 40s or early 50s. In doing so we extend Blanchflower's earlier study, incorporating a further 39 countries and another decade or so of data. We show the age peak in union membership is apparent across birth cohorts, and that the introduction of cohort dummies makes little difference to the age at which membership peaks. In Europe we show the peak coincides with the age point at which exit rates from union membership rise. We show that, among those aged 50 and over, retirement rates are higher among ex‐members than among those who have never been union members, suggesting the increased prevalence of non‐membership among workers later in life is due to union members retiring earlier, as one might expect given their pension entitlements. The age at which union membership peaks increases only very slightly over time in the United States but rises markedly in the United Kingdom. Since unions are democratic organizations, the implication is that unions in the United Kingdom may shift what they do to maximize the utility of an ageing membership.
Real‐world Omalizumab and Mepolizumab treated difficult asthma phenotypes and their clinical outcomes
Authors: Fong Wei Chern Gavin , Azim Adnan , Knight Deborah , Mistry Heena , Freeman Anna , Felongco Mae , Kyyaly Aref , Harvey Matthew , Dennison Patrick , Zhang Hongmei , Howarth Peter , Arshad Syed Hasan , Kurukulaaratchy Ramesh J.
Published: April 2021

Background

Omalizumab and Mepolizumab are biologic drugs with proven efficacy in clinical trials. However, a better understanding of their real‐world effectiveness in severe asthma management is needed.

Objectives

To better understand the real‐world effectiveness of Omalizumab and Mepolizumab, elucidate the clinical phenotypes of patients treated with these drugs, identify baseline characteristics associated with biologic response and assess the spectrum of responses to these medications.

Methods

Using real‐world clinical data, we retrospectively phenotyped biologic naïve patients from the Wessex AsThma CoHort of difficult asthma (N = 478) commenced on Omalizumab (N = 105) or Mepolizumab (N = 62) compared to severe asthma patients not receiving biologics (SNB, N = 178). We also assessed multiple clinical endpoints and identified features associated with response.

Results

Compared to SNB, Omalizumab patients were younger, diagnosed with asthma earlier, and more likely to have rhinitis. Conversely, compared to SNB, Mepolizumab patients were predominantly older males, diagnosed with asthma later, and more likely to have nasal polyposis but less dysfunctional breathing. Both treatments reduced exacerbations, Acute Healthcare Encounters [AHE] (emergency department or hospital admissions), maintenance oral corticosteroid dose, and improved Asthma Control Questionnaire 6 (ACQ6) scores. Omalizumab response was independently associated with more baseline exacerbations (p = .024) but fewer AHE (p = .050) and absence of anxiety (p = .008). Lower baseline ACQ6 was independently associated with Mepolizumab response (p = .007). A composite group of non‐responders demonstrated significantly more psychopathologies and worse baseline subjective disease compared to responder groups.

Conclusions and Clinical Relevance

In a difficult asthma cohort, Omalizumab and Mepolizumab were used in distinct clinical phenotypes but were both multidimensionally efficacious. Certain baseline clinical characteristics were associated with poorer biologic responses, such as psychological co‐morbidity, which may assist clinicians in biologic selection. These characteristics also emphasize the need for comprehensive approaches to support these patients.
Functional variants in the chromosome 4q21 locus contribute to allergic rhinitis risk by modulating the expression of N‐acylethanolamine acid amidase
Authors: Sio Yang Yie , Shi Ping , Say Yee‐How , Chew Fook Tim
Published: April 2021

Background

Previous haplotype‐based association studies identified chromosome 4q21 as an allergic rhinitis (AR) susceptibility locus; however, the functional role of 4q21 single nucleotide polymorphisms (SNPs) on AR risk remains unclear.

Objective

To investigate the functional effect of 4q21 SNPs on AR risk by conducting cohort‐based functional genomics and genetic association analyses.

Methods

The associations between 4q21 SNPs and mRNA expression levels of three 4q21‐associated genes (SDAD1, NAAA and CXCL9) in peripheral blood mononuclear cells (PBMCs) were assessed in a Singapore/Malaysia Chinese cohort (n = 291). Exon expression levels of these genes in PBMCs were tested against the tag‐SNP genotypes in a Singapore Chinese cohort (n = 30). Serum protein levels of these genes were assessed with tag‐SNP genotypes in a Singapore Chinese cohort (n = 193). SNP functions were characterized through luciferase assay. In a Singapore Chinese cohort (n = 1794), we confirmed the associations between functional SNPs and AR.

Results

Forty SNPs in 4q21 showed significant associations with NAAA (but not SDAD1 or CXCL9) mRNA expression in PBMCs, of which were tagged by two tag‐SNPs, rs17001237 and rs2242470. Both tag‐SNPs rs2242470 and rs12648687 (a proxy for rs17001237) were also significantly associated with the expression level of NAAA exon 1. Tag‐SNP rs12648687 was correlated with serum NAAA level. A four promoter SNPs‐haplotype tagged by rs17001237 influenced the NAAA promoter activity in HEK293T cells. Lastly, individuals carrying the risk allele A of rs12648687 exhibited significantly higher AR risk in the Singapore Chinese population.

Conclusions & Clinical Relevance

The rs17001237 linkage set SNPs in the 4q21 locus are associated with NAAA expression at both gene and protein levels ex vivo, have functional consequences in vitro and contribute to AR susceptibility in our study population. Our findings provided a better understanding of the genetic mechanism that contributes to AR pathogenesis.
Intracellular expression of granzymes A, B, K and M in blood lymphocyte subsets of critically ill patients with or without sepsis
Authors: García-Laorden M Isabel , Hoogendijk Arie J , Wiewel Maryse A , van Vught Lonneke A , Schultz Marcus J , Bovenschen Niels , de Vos Alex F , van der Poll Tom
Published: April 2021

Sepsis is a complex syndrome related to an infection-induced exaggerated inflammatory response, which is associated with a high mortality. Granzymes (Gzm) are proteases mainly found in cytotoxic lymphocytes that not only have a role in target cell death, but also as mediators of infection and inflammation. In this study we sought to analyse the intracellular expression of GzmA, B, M and K by flow cytometry in diverse blood lymphocyte populations from 22 sepsis patients, 12 non-infected intensive care unit (ICU) patients and 32 healthy controls. Additionally, we measured GzmA and B plasma levels. Both groups of patients presented decreased percentage of natural killer (NK) cells expressing GzmA, B and M relative to healthy controls, while sepsis patients showed an increased proportion of CD8+ T cells expressing GzmB compared to controls. Expression of GzmK remained relatively unaltered between groups. Extracellular levels of GzmB were increased in non-infected ICU patients relative to sepsis patients and healthy controls. Our results show differential alterations in intracellular expression of Gzm in sepsis patients and non-infected critically ill patients compared to healthy individuals depending on the lymphocyte population and on the Gzm.
16α-Bromoepiandrosterone as a new candidate for experimental diabetes–tuberculosis co-morbidity treatment
Authors: López-Torres Manuel Othoniel , Marquina-Castillo Brenda , Ramos-Espinosa Octavio , Mata-Espinosa Dulce , Barrios-Payan Jorge A , Baay-Guzman Guillermina , Yepez Sara Huerta , Bini Estela , Torre-Villalvazo Ivan , Torres Nimbe , Tovar Armando , Chamberlin William , Ge Yu , Carranza Andrea , Hernández-Pando Rogelio
Published: April 2021

Tuberculosis (TB) is the leading cause of death from a single bacterial infectious agent and is one of the most relevant issues of public health. Another pandemic disease is type II diabetes mellitus (T2D) that is estimated to affect half a billion people in the world. T2D is directly associated with obesity and a sedentary lifestyle and is frequently associated with immunosuppression. Immune dysfunction induced by hyperglycemia increases infection frequency and severity. Thus, in developing countries the T2D/TB co-morbidity is frequent and represents one of the most significant challenges for the health-care systems. Several immunoendocrine abnormalities are occurring during the chronic phase of both diseases, such as high extra-adrenal production of active glucocorticoids (GCs) by the activity of 11-β-hydroxysteroid dehydrogenase type 1 (11-βHSD1). 11-βHSD1 catalyzes the conversion of inactive cortisone to active cortisol or corticosterone in lungs and liver, while 11-β-hydroxysteroid dehydrogenase type 2 (11-βHSD2) has the opposite effect. Active GCs have been related to insulin resistance and suppression of Th1 responses, which are deleterious factors in both T2D and TB. The anabolic adrenal hormone dehydroepiandrosterone (DHEA) exerts antagonistic effects on GC signaling in immune cells and metabolic tissues; however, its anabolic effects prohibit its use to treat immunoendocrine diseases. 16α-bromoepiandrosterone (BEA) is a water miscible synthetic sterol related to DHEA that lacks an anabolic effect while amplifying the immune and metabolic properties with important potential therapeutic uses. In this work, we compared the expression of 11-βHSD1 and the therapeutic efficacy of BEA in diabetic mice infected with tuberculosis (TB) (T2D/TB) with respect to non-diabetic TB-infected mice (TB). T2D was induced by feeding mice with a high-fat diet and administering a single low-dose of streptozotocin. After 4 weeks of T2D establishment, mice were infected intratracheally with a high-dose of Mycobacterium tuberculosis strain H37Rv. Then, mice were treated with BEA three times a week by subcutaneous and intratracheal routes. Infection with TB increased the expression of 11-βHSD1 and corticosterone in the lungs and liver of both T2D/TB and TB mice; however, T2D/TB mice developed a more severe lung disease than TB mice. In comparison with untreated animals, BEA decreased GC and 11-βHSD1 expression while increasing 11-βHSD2 expression. These molecular effects of BEA were associated with a reduction in hyperglycemia and liver steatosis, lower lung bacillary loads and pneumonia. These results uphold BEA as a promising effective therapy for the T2D/TB co-morbidity.
Scleral necrosis after brachytherapy for uveal melanoma: Analysis of risk factors
Authors: Jabbarli Leyla , Guberina Maja , Biewald Eva , Flühs Dirk , Guberina Nika , Le Guin Claudia H. D. , Sauerwein Wolfgang , Bornfeld Norbert , Stuschke Martin , Bechrakis Nikolaos E.
Published: April 2021

Background

Radiation‐induced scleral necrosis (RISN) is a rare, but a serious complication of brachytherapy for uveal melanoma. We aimed at analysing the incidence, timing and risk factors associated with development of RISN in a large institutional series.

Methods

All consecutive cases with brachytherapy for uveal melanoma treated by the Departments of Ophthalmology and Radiotherapy at University Hospital Essen between 1999 and 2016 were eligible. Development of RISN during the post‐treatment follow‐up was recorded. A 1:2 propensity score matched case–control study was performed for the evaluation of the prognostic value of different tumour‐ and treatment‐associated parameters.

Results

RISN was documented in 115 (2.9%) of 3960 patients with uveal melanoma included in the final analysis, and occurred at the mean 30.3 months (range: 1.26–226 months) after brachytherapy. In the whole cohort, younger age (p = 0.042), plaque type (p = 0.001) and ciliary body involvement (p < 0.0001) were independently associated with the RISN occurrence. In the case–control study, multivariable weighted proportional hazard analysis discovered the association of the following additional tumour‐ and treatment‐associated characteristics with RISN: posterior tumour margin anterior to equatorial region (p = 0.0003), extraocular tumour extension (p = <0.0001), scleral contact dose (p = <0.0001), conjunctival dehiscence after therapy (p = 0.0001), disinsertion of the superior rectus muscle (p = 0.001) and the glaucoma medication (p = 0.014).

Conclusions

Our study confirms RISN as a rare complication, which might occur even years later after the brachytherapy for uveal melanoma. Alongside with scleral dose five other tumour and therapy related factors predict the risk of RISN after brachytherapy for uveal melanoma were established.
Severe congenital cutis laxa: Identification of novel homozygous LOX gene variants in two families
Authors: McKenzie Fiona , Mina Kym , Callewaert Bert , Beyens Aude , Dickinson Jan E. , Jevon Gareth , Papadimitriou John , Diness Birgitte Rode , Steensberg Jesper Norman , Ek Jakob , Baynam Gareth
Published: April 2021

We report three babies from two families with a severe lethal form of congenital cutis laxa. All three had redundant and doughy‐textured skin and two siblings from one family had facial dysmorphism. Echocardiograms showed thickened and poorly contractile hearts, arterial dilatation and tortuosity. Post‐mortem examination in two of the babies further revealed widespread ectasia and tortuosity of medium and large sized arteries, myocardial hypertrophy, rib and skull fractures. The presence of fractures initially suggested a diagnosis of osteogenesis imperfecta. Under light microscopy bony matrices were abnormal and arterial wall architecture was grossly abnormal showing fragmented elastic fibres. Molecular analysis of known cutis laxa genes did not yield any pathogenic defects. Whole exome sequencing of DNA following informed consent identified two separate homozygous variants in the LOX (Lysyl Oxidase) gene. LOX belongs to the 5‐lysyl oxidase gene family involved in initiation of cross‐linking of elastin and collagen. A mouse model of a different variant in this gene recapitulates the phenotype seen in the three babies. Our findings suggest that the LOX gene is a novel cause of severe congenital cutis laxa with arterial tortuosity, bone fragility and respiratory failure.
Single‐use device endoscopy for the diagnosis of acute bacterial rhinosinusitis in primary care: A pilot and feasibility study
Authors: Glinz Dominik , Georg Hansen Jens , Trutmann Caroline , Schaller Bernhard , Vogt Jürg , Diermayr Claus , Marti Andreas , Leitmeyer Katharina , Doerig Patrick , Zeller Andreas , Welge‐Luessen Lemcke Antje , Bucher Heiner C.
Published: April 2021

Objective

Antibiotics are largely overprescribed for acute rhinosinusitis in primary care, mainly due to the lack of diagnostic tests to confirm or rule out bacterial infection. The study objective was to assess the on‐site applicability and safety of the newly developed JGG endoscope® for the diagnosis of acute bacterial rhinosinusitis in primary care.

Design

Five Swiss primary care centres and one university‐affiliated ENT unit participated in this single‐arm pilot study.

Participants

Adults with acute suspected bacterial rhinosinusitis. The newly developed JGG endoscope®, which is attached to a pocket otoscope, was used to inspect after local anaesthesia the nasal cavity and middle meatus and to gain material for bacterial culture from paranasal sinuses draining ostium.

Main outcome measures

Applicability and safety.

Results

The visualisation of the middle meatus was successful in 16 of 21 patients (13 in both sides and three in one side), and unclear or unsuccessful in five patients. Sample collection from the middle meatus was successful in 10 patients (six on both and four on one side) and unclear or unsuccessful in the remaining patients. Only one culture‐confirmed bacterial rhinosinusitis and 11 PCR‐confirmed viral infections were identified from collected samples. After a 2‐week follow‐up, no serious adverse events were observed.

Conclusions

The on‐site use of the JGG endoscope® in daily primary care routine is feasible and safe and was well accepted by the trial physicians and patients (assessed with structured questionnaires). The JGG endoscope® may support general practitioners to differentiate between bacterial and viral rhinosinusitis.
CT‐guided microcoil localization for pulmonary nodules in the scapula‐shadowed area before Video‐Assisted Thoracic Surgery
Authors: Xu Yanyan , Ma Lingchuan , Lin Jie , Sun Hongliang , Huang Zhenguo , Zhang Zhenrong , Xiao Fei , Ma Qianli
Published: April 2021

Purpose

To evaluate the feasibility and safety of CT‐guided microcoil localization for pulmonary nodules in the scapula‐shadowed area before video‐assisted thoracic surgery (VATS).

Materials and Methods

Forty‐seven patients (18 males, 19 females; mean age 57.5 years) with 48 pulmonary nodules covered by the scapulae were consecutively enrolled in this study. Successful targeting, localization, and VATS were defined as implantation of microcoil at the target site on CT image obtained immediately after the marking procedure, visualization of nodule location during VATS, and complete resection of the target nodule with adequate margin, respectively. Meanwhile, the procedure‐related complication rate was also recorded.

Results

The rates of successful targeting and localization were 95.8% (46/48) and 89.6% (43/48), respectively. Of all nodules, 47 were successfully resected with VATS (30 wedge resections; 17 anatomic resections) and 1 nodule was converted to open thoracotomy for diffuse pleural adhesion, thus the successful VATS rate was 97.9% (47/48).

With respect to procedure‐related complications, only minor complications (including localized pneumothorax and intrapulmonary hemorrhage) were developed and the rate of overall procedure‐related complications was 37.5% (18/48), including minor pneumothorax developed in 15 of 48 nodules (31.3%) and intrapulmonary hemorrhage in 6 of 48 nodules (12.5%).

Conclusions

CT‐guided microcoil technique is a safe and effective localization method prior to VATS for the nodules in the scapula‐shadowed area.
Obesity is a risk factor for progression to kidney transplant waitlisting after liver transplantation
Authors: Locke Jayme E. , Shelton Brittany , Orandi Babak , Olthoff Kim , Pomfret Elizabeth , Forde Kimberly A. , Sawinski Deirdre , Gray Meagan , Ascher Nancy
Published: April 2021

Background

Non‐alcoholic steatohepatitis has emerged as a leading cause of cirrhosis, and obesity‐associated comorbidities, including renal disease, have increased in prevalence. Obesity predisposes the kidney to hyperfiltration injury, potentially impairing acute kidney injury recovery. Identification of patients at risk for renal dysfunction is impeded by poor performance of renal function estimating equations among cirrhotics. To better understand obesity among cirrhotics and renal disease progression, we examined likelihood of kidney transplantation (KT) waitlisting after liver transplant alone (LTA) by obesity class.

Methods

68 607 LTA recipients were identified in SRTR (2005–2018). Fine and Gray competing risks models were used to analyze likelihood of KT waitlisting.

Results

27.4% of recipients were obese (BMI ≥ 30 kg/m2) and were 10% more likely to require KT waitlisting (aHR: 1.10, 95%CI: 1.01–1.20). Risk was highest among recipients with Classes II and III obesity (BMI: ≥35 kg/m2) (aHR: 1.37, 95%CI: 1.17–1.56). Moreover, recipients with Classes II and III obesity were 57% more likely to require KT waitlisting within one year post‐LTA (aHR: 1.57, 95%CI: 1.18–2.10) compared to non‐obese recipients.

Discussion

These findings suggest obesity was a risk factor for renal recovery failure and/or renal disease progression post‐LTA and may confound identification of renal dysfunction and/or prediction of renal recovery among cirrhotics.
Ecology of Oobius rudnevi, egg parasitoid of Cerambyx cerdo and Cerambyx welensii in oak forests
Authors: Torres‐Vila Luis M. , López‐Calvo Rafael , Sánchez‐González Álvaro , Mendiola‐Díaz F. Javier
Published: April 2021

Oobius rudnevi (Nowicki) (Hymenoptera: Encyrtidae) is a gregarious egg parasitoid of Cerambyx cerdo L. and Cerambyx welensii (Küster) (Coleoptera: Cerambycidae), two well‐known large oak‐living saproxylic beetles with different pest/legal status: whereas C. cerdo is a protected species, C. welensii is considered an emerging pest. Despite the potential interest of O. rudnevi as a native parasitoid, the knowledge of its biology remains very limited. We used sentinel eggs to assess the distribution of O. rudnevi in Extremadura (southwest Spain) and to explore its ecology, phenology, behavior, parasitism rates, and host preference. More than 13 500 sentinel eggs, housed in 1 030 wood disks, were field‐exposed during 2016–2018 in 147 oak stands over an array of oak forests. Oobius rudnevi was the only egg parasitoid detected, being widespread and relatively abundant over the studied area (90/147 stands, 61.2%) with adults flying in May–July. Parasitoids were detected in both host species, but net parasitism (PN) was significantly higher in C. cerdo (22.4%) than in C. welensii (9.5%). Net parasitism was affected by altitude (it was higher at 600–800 m) and tended to increase in colder aspects; PN was poorly related to host egg density (no. eggs per disk) and unrelated to host population size (no. adults per trap). Most parasitoids overwintered and emerged in the following spring (synchronously with their hosts) but some phenotypes/lineages did not undergo obligate diapause and were bivoltine. Bivoltine wasps were spatially widespread (27/90 stands, 30%), even if their actual prevalence was rather low (60/1641 parasitized eggs, 3.7%). We also found that O. rudnevi was slightly protogynous, the sex ratio was female‐biased, and the mean (± SEM) number of wasps emerging per parasitized egg was 9.3 ± 0.1 (range 1–29). We discuss the potential role of O. rudnevi as a biological control agent from an evolutionary perspective.
Effect of adult feeding on the δ15N signatures of different tissues for Popillia japonica
Authors: Henden Jacob , Guédot Christelle
Published: April 2021

As insects feed, stable isotopes from their diets are assimilated into their tissues. Stable isotopes provide a method to determine what insects are feeding on, and in some cases, where the insects have been feeding. One method for evaluating what adult holometabolous insects fed on as larvae, is to sample tissues from the integument of the adult. The integument should have isotopic signatures that reflect the diet of the larvae, and these inert tissues should be less influenced by adult feeding compared to other tissues. The objective of our research was to examine how isotopic signatures of nitrogen in various tissues of adult Popillia japonica (Newman) (Coleoptera: Scarabaeidae) beetles would be influenced by adults feeding on 15N‐enriched plant material. We collected adults from emergences cages at unenriched grasses and fed them for 0, 2, 5, or 10 days with grape plants fertilized with isotopically enriched or unenriched potassium nitrate. The δ15N signature of elytra and soft tissues both increased over time when fed enriched plant material. The δ15N signatures of soft tissues were higher than that of the elytra over time. Adult beetles fed highly enriched plant material displayed increased δ15N signatures over time of tissues generally considered metabolically inactive, which suggests that adult feeding does contribute to the isotopic signatures of elytra tissue. The difference between the δ15N signatures of soft tissues and elytra demonstrates a lower turnover rate in the elytra and highlights the fact that diet does contribute to the signature of elytra.
Subfield‐specific effects of chronic mild unpredictable stress on hippocampal astrocytes
Authors: Virmani Garima , D'almeida Priyal , Nandi Arnab , Marathe Swananda
Published: April 2021

Major depressive disorder (MDD) is a debilitating neuropsychiatric illness affecting over 20% of the population worldwide. Despite its prevalence, our understanding of its pathophysiology is severely limited, thus hampering the development of novel therapeutic strategies. Recent advances have clearly established astrocytes as major players in the pathophysiology, and plausibly pathogenesis, of major depression. In particular, astrocyte density in the hippocampus is severely diminished in MDD patients and correlates strongly with the disease outcome. Moreover, astrocyte densities from different subfields of the hippocampus show varying trends in terms of their correlation to the disease outcome. Given the central role that hippocampus plays in the pathophysiology of depression and in the action of antidepressant drugs, changes in hippocampal astrocyte density and physiology may have a significant effect on behavioral symptoms of MDD. In this study, we used chronic mild unpredictable stress (CMUS) in mice, which induces a depressive‐like state, and examined its effects on astrocytes from different subfields of the hippocampus. We used SOX9 and S100β immunostaining to estimate the number of astrocytes per square millimeter from various hippocampal subfields. Furthermore, using confocal images of fluorescently labeled glial fibrillary acidic protein (GFAP)‐immunopositive hippocampal astrocytes, we quantified various morphology‐related parameters and performed Sholl analysis. We found that CMUS exerts differential effects on astrocyte cell numbers, ramification, cell radius, surface area, and process width of hippocampal astrocytes from different hippocampal subfields. Taken together, our study reveals that chronic stress does not uniformly affect all hippocampal astrocytes; but exerts its effects differentially on different astrocytic subpopulations within the hippocampus.
Intracerebral electrical stimulation to understand the neural basis of human face identity recognition
Authors: Jonas Jacques , Rossion Bruno
Published: April 2021

Recognizing people's identity by their faces is a key function in the human species, supported by regions of the ventral occipito‐temporal cortex (VOTC). In the last decade, there have been several reports of perceptual face distortion during direct electrical stimulation (DES) with subdural electrodes positioned over a well‐known face‐selective VOTC region of the right lateral middle fusiform gyrus (LatMidFG; i.e., the “Fusiform Face Area”, FFA). However, transient impairments of face identity recognition (FIR) have been extremely rare and only behaviorally quantified during DES with intracerebral (i.e., depth) electrodes in stereo‐electroencephalography (SEEG). The three detailed cases reported so far, summarized here, were specifically impaired at FIR during DES inside different anatomical VOTC regions of the right hemisphere: the inferior occipital gyrus (IOG) and the LatMidFG, as well as a region that lies at the heart of a large magnetic susceptibility artifact in functional magnetic resonance imaging (fMRI): the anterior fusiform gyrus (AntFG). In the first two regions, the eloquent electrode contacts were systematically associated with the highest face‐selective and (unfamiliar) face individuation responses as measured with intracerebral electrophysiology. Stimulation in the right AntFG did not lead to perceptual changes but also caused an inability to remember having been presented face pictures, as if the episode was never recorded in memory. These observations support the view of an extensive network of face‐selective VOTC regions subtending human FIR, with at least three critical nodes in the right hemisphere associated with differential intrinsic and extrinsic patterns of reentrant connectivity.
Priority knowledge needs for management of migratory fish species in Cambodia
Authors: Loury Erin K. , Elliott Vittoria L. , Ainsley Shaara M. , Baird Ian G. , Baumgartner Lee J. , Chhuoy Samol , Lee Dana J. , Ngor Peng Bun , Touch Bunthang , Vu An V. , Hogan Zeb S.
Published: April 2021

Despite their economic and ecological importance, migratory fishes of the Lower Mekong Basin (LMB) remain understudied, which hampers effective management to sustain valuable fisheries and address serious threats such as habitat degradation, development and overharvest. From a list of potential knowledge needs, a group of fisheries professionals most frequently identified six top priorities for managing migratory fishes in Cambodia: (1) population abundances and trends, (2) life cycles and life history, (3) migration timing and triggers, (4) migration routes and distances, (5) locations of key habitats and spawning areas, and (6) environmental and habitat requirements. These needs are discussed along with nine relevant methodologies for addressing them, including fisheries‐dependent and fisheries‐independent sampling, reproductive techniques and captive studies, otolith and genetic analysis tools, and tagging and imaging techniques. A suggested research framework is also presented to inform adaptive management of migratory fishes. While emphasis is given to Cambodia, the analysis is also applicable to other LMB countries, given that migratory fishes occur throughout the basin and migrate across borders. It is suggested that a robust research and monitoring agenda is required to prioritise knowledge needs and select appropriate methodologies to answer questions vital to inform sustainable migratory fish management in Cambodia.
Evaluating Lower Computational Burden Approaches for Calibration of Large Environmental Models
Authors: Hunt Randall J. , White Jeremy T. , Duncan Leslie L. , Haugh Connor J. , Doherty John
Published: April 2021

Realistic environmental models used for decision making typically require a highly parameterized approach. Calibration of such models is computationally intensive because widely used parameter estimation approaches require individual forward runs for each parameter adjusted. These runs construct a parameter‐to‐observation sensitivity, or Jacobian, matrix used to develop candidate parameter upgrades. Parameter estimation algorithms are also commonly adversely affected by numerical noise in the calculated sensitivities within the Jacobian matrix, which can result in unnecessary parameter estimation iterations and less model‐to‐measurement fit. Ideally, approaches to reduce the computational burden of parameter estimation will also increase the signal‐to‐noise ratio related to observations influential to the parameter estimation even as the number of forward runs decrease. In this work a simultaneous increments, an iterative ensemble smoother (IES), and a randomized Jacobian approach were compared to a traditional approach that uses a full Jacobian matrix. All approaches were applied to the same model developed for decision making in the Mississippi Alluvial Plain, USA. Both the IES and randomized Jacobian approach achieved a desirable fit and similar parameter fields in many fewer forward runs than the traditional approach; in both cases the fit was obtained in fewer runs than the number of adjustable parameters. The simultaneous increments approach did not perform as well as the other methods due to inability to overcome suboptimal dropping of parameter sensitivities. This work indicates that use of highly efficient algorithms can greatly speed parameter estimation, which in turn increases calibration vetting and utility of realistic models used for decision making.
Validation of factor VIII activity for monitoring standard and extended half‐life products and correlation to thrombin generation assays
Authors: Augustsson Cecilia , Norström Eva , Lind Vivian , Martin Myriam , Astermark Jan , Strandberg Karin
Published: April 2021

Introduction

Monitoring replacement therapy with standard and extended half‐life (EHL) products is challenging, since one‐stage assay (OSA) and chromogenic substrate assay (CSA) results may differ significantly. Recent recommendations include local validation of each new product with recovery within 20–30%, depending on activity level.

Aim

To validate factor VIII (FVIII) activity for monitoring products in clinical use on Atellica Coag and to correlate it with thrombin generation.

Methods

Plasma samples spiked with Advate®, Elocta®, Adynovi®, Nuwiq®, NovoEight® and Afstyla® (0.05, 0.20, 0.50 and 0.80 IU/ml) were analysed using Atellica Coag 360 with CSA‐1 (Coatest SP) and CSA‐2 (FVIII chromogenic), and OSA (Actin FS). Thrombin generation was performed using two thrombin generation assays (TGA‐1 (Thrombinoscope) and TGA‐2 (Technothrombin).

Results

All products at levels above 0.05 IU/ml, except Adynovi, showed acceptable recovery using CSA‐1, whereas measurements using CSA‐2 gave more results outside the target level. All products, except Afstyla, showed acceptable recovery using OSA. Correlation between CSA‐1 and OSA was excellent (r2=1.0) with biases of 6–3​2%, depending on FVIII product. A clear dose‐response was seen for all thrombin generation parameters and products using both methods, except at low levels for lag time using TGA‐1. With CSA‐1 as an independent variable, the correlations to thrombin peak (measured with TGA‐2) were good (r2 = .8–.9).

Conclusion

Our data revealed good correlation and acceptable bias between CSA and OSA using our sets of reagents, methods and analyser in spiked samples. Thrombin generation gave good correlation to CSA‐1 factor activity and is a possible complement to factor activity assays.
An evaluation of PROMIS health domains in adults with haemophilia: A cross‐sectional study
Authors: Barry Vaughn , Buckner Tyler W. , Lynch Mary Ellen , Figueroa Janet , Mattis Shanna , Stout Mary E. , Kempton Christine L.
Published: April 2021

Introduction

The Patient‐Reported Outcomes Measurement Information System (PROMIS) provides measures of health status that assess physical, mental and social well‐being from the patient perspective. PROMIS measures are used in clinical practice and research across various patient populations but are not yet validated among patients with haemophilia.

Aim

Evaluate the sensitivity of PROMIS to indicators of haemophilia clinical severity and compare PROMIS measures to those from other PRO instruments.

Methods

Male adults with haemophilia (n = 115) completed the PROMIS‐29 short form which includes 4 questions for each of 7 domains: depression, anxiety, ability to participate in social roles and activities, physical function, pain interference, fatigue and sleep disturbance. Participant responses for each domain were scored on a T‐score metric with a mean of 50 and a standard deviation of 10 based on the original PROMIS reference sample of US adults. Participants also completed other generic and haemophilia‐specific health‐related quality of life questionnaires.

Results

Participants who experienced higher pain and depression levels reported significantly worse health in every PROMIS domain compared with their peers. Those who had recently needed to use crutches, visit an emergency department or were currently unemployed or disabled also reported poor PROMIS scores on most domains. Construct validity was supported by correlations between PROMIS domain scores and domain scores reported using the EQ‐5D‐5L and Haem‐A‐QoL.

Conclusion

The PROMIS instrument provides a potentially valuable tool to evaluate the impact of haemophilia and suggests usefulness in research and clinical practice.
The significance of focally enhanced gastritis in haematopoietic stem cell transplant recipients
Authors: Johncilla Melanie , Elsoukkary Sarah , Jessurun Jose
Published: April 2021

Aims

The histological diagnosis of acute gastric graft‐versus‐host‐disease (aGVHD) in patients with a history of haematopoietic stem cell transplant (HSCT) is based on the presence of epithelial cell apoptosis and karyorrhectic debris. There is, however, limited information on the histological findings in patients who develop symptoms several months after transplant. Focally enhanced gastritis (FEG), defined by the presence of focal periglandular lymphohistiocytic inflammation with neutrophilic or lymphocytic intra‐epithelial infiltration of gastric glands, has been described in patients with inflammatory bowel disease and in HSCT patients. The pattern closely resembles the focal periductal inflammation and lymphocytic exocytosis seen in chronic GVHD of the salivary gland. We sought to evaluate the significance of FEG in HSCT patients.

Methods and results

Gastric biopsies from 151 HSCT patients who underwent endoscopies for GVHD‐like symptoms were identified. Time from transplant to biopsy, presence of extra‐gastric GVHD, medications and outcome were noted. Thirty‐five biopsies showed FEG and 21 showed aGVHD; the remainder were either normal or showed non‐specific changes. Twenty‐one (60%) FEG patients had concurrent histologically proven extra‐gastric GVHD. The time to biopsy in FEG patients was significantly longer than in aGVHD patients (162 versus 57 days, P < 0.01). Prior or subsequent gastric biopsies of 14 patients in the FEG cohort were also evaluated and, of these, six showed aGVHD while one showed persistent FEG.

Conclusions

These findings suggest that FEG probably represents a form of late‐occurring GVHD. This histological pattern should not be overlooked when identified in gastric biopsies from HSCT patients.