bluuebunny/crossref_metadata_2025 huggingface dataset:
A single-center pilot study in Malaysia on the clinical utility of whole-exome sequencing for inborn errors of immunity
Authors: Ripen Adiratna Mat , Chear Chai Teng , Baharin Mohd Farid , Nallusamy Revathy , Chan Kwai Cheng , Kassim Asiah , Choo Chong Ming , Wong Ke Juin , Fong Siew Moy , Tan Kah Kee , Nachiappan Jeyaseelan P , Teo Kai Ru , Chiow Mei Yee , Hishamshah Munirah , Ghani Hamidah , Muralitharan Rikeish R , Mohamad Saharuddin Bin
Published: June 2021

Primary immunodeficiency diseases refer to inborn errors of immunity (IEI) that affect the normal development and function of the immune system. The phenotypical and genetic heterogeneity of IEI have made their diagnosis challenging. Hence, whole-exome sequencing (WES) was employed in this pilot study to identify the genetic etiology of 30 pediatric patients clinically diagnosed with IEI. The potential causative variants identified by WES were validated using Sanger sequencing. Genetic diagnosis was attained in 46.7% (14 of 30) of the patients and categorized into autoinflammatory disorders (n = 3), diseases of immune dysregulation (n = 3), defects in intrinsic and innate immunity (n = 3), predominantly antibody deficiencies (n = 2), combined immunodeficiencies with associated and syndromic features (n = 2) and immunodeficiencies affecting cellular and humoral immunity (n = 1). Of the 15 genetic variants identified, two were novel variants. Genetic findings differed from the provisional clinical diagnoses in seven cases (50.0%). This study showed that WES enhances the capacity to diagnose IEI, allowing more patients to receive appropriate therapy and disease management.
Impact of cocoa agricultural intensification on bird diversity and community composition
Authors: Bennett Ruth E. , Sillett T. Scott , Rice Robert A. , Marra Peter P.
Published: June 2021

To meet the growing demand for chocolate, cocoa (Theobroma cacao) agriculture is expanding and intensifying. Although this threatens tropical forests, cocoa sustainability initiatives largely overlook biodiversity conservation. To inform these initiatives, we analyzed how cocoa agriculture affects bird diversity at farm and landscape scales with a meta‐analysis of 23 studies. We extracted 214 Hedges' g* comparisons of bird diversity and 14 comparisons of community similarity between a forest baseline and 4 farming systems that cover an intensification gradient in landscapes with high and low forest cover, and we summarized 119 correlations between cocoa farm features and bird diversity. Bird diversity declined sharply in low shade cocoa. Cocoa with >30% canopy cover from diverse trees retained bird diversity similar to nearby primary or mature secondary forest but held a different community of birds. Diversity of endemic species, frugivores, and insectivores (agriculture avoiders) declined, whereas diversity of habitat generalists, migrants, nectarivores, and granivores (agriculture associates) increased. As forest decreased on the landscape, the difference in bird community composition between forest and cocoa also decreased, indicating agriculture associates replaced agriculture avoiders in forest patches. Our results emphasize the need to conserve forested landscapes (land sparing) and invest in mixed‐shade agroforestry (land sharing) because each strategy benefits a diverse and distinct biological community.
REG3α is a novel biomarker that potentially correlates with acute allograft rejection after intestinal transplantation
Authors: Smullin Carolyn P. , Venick Robert S. , Marcus Elizabeth A. , Naini Bita V. , Farmer Douglas G.
Published: June 2021

Monitoring of intestinal allograft function remains a challenge. While frequent endoscopies and biopsies are the gold standard, no single biomarker exists to screen for intestinal transplant rejection. The novel REG3α, an antimicrobial peptide secreted by intestinal enterocytes and Paneth cells, has been associated with inflammatory bowel disease as well as intestinal graft versus host disease. Our aim was to identify and describe a role of REG3α in monitoring or predicting acute allograft rejection after intestinal transplantation (ITx). Since 2019, we have incorporated REG3α into the standard monitoring of patients after ITx. We conducted a retrospective analysis of a prospectively maintained IRB‐approved database and present, herein, the results of 2 adults with irreversible intestinal failure who underwent isolated ITx under this monitoring protocol. Increases in REG3α corresponded with acute allograft rejection in both cases and preceded acute allograft rejection by 1 week in one of the cases. We describe REG3α as a non‐invasive marker of acute allograft rejection after adult isolated ITx which not only corresponded with acute allograft rejection but also preceded histopathological changes by 1 week.
Health‐related quality of life in youth with type 1 diabetes: Associations with multiple comorbidities and mental health conditions
Authors: Shapira Amit , Harrington Kara R. , Goethals Eveline R. , Volkening Lisa K. , Laffel Lori M.
Published: June 2021

Aim

This cross‐sectional study examined the associations of comorbid conditions on health‐related quality of life (HRQOL) in 601 youth with type 1 diabetes. We evaluated associations between number of comorbid conditions (0, 1, ≥2) and particular comorbid conditions and youth HRQOL by self‐report and parent proxy‐report.

Research design and methods

Youth with type 1 diabetes, aged 5–18 years, and their parents completed the PedsQL 4.0 Generic Core Scales self‐report and parent proxy‐report, respectively; they also reported youths' comorbid medical and mental health conditions. Separate linear regression models tested the relationship between number of comorbid conditions and specific comorbid conditions with youth‐reported and parent proxy‐reported HRQOL.

Results

Youth with ≥2 comorbid conditions had significantly lower HRQOL by both self‐ and parent proxy‐reports compared with youth with 0 or 1 comorbid condition (youth self‐report: 0: 85 ± 12, 1: 85 ± 13, 2+: 78 ± 16, p = <0.0001; parent proxy‐report: 0: 83 ± 12, 1: 81 ± 13, 2+: 74 ± 15, p = <0.0001). Amongst the comorbid conditions, only a mental health comorbidity was associated with lower HRQOL. For youth and parent proxy‐reports, both the number of comorbidities (≥2) and the presence of a mental health comorbidity were significantly associated with lower HRQOL.

Conclusions

Health‐related quality of life seems to be preserved in youth with type 1 diabetes unless confronted by multiple comorbidities as reported by youth and their parents. Our findings highlight the importance of tracking the presence of multiple comorbid conditions, possibly by reviewing problem and medication lists in the medical record, as well as screening for and addressing mental health conditions in routine diabetes care.
Sporadic Creutzfeldt–Jakob disease with extremely long 14‐year survival period
Authors: Kortazar‐Zubizarreta Izaro , Ruiz‐Onandi Rebeca , Pereda Arrate , Vado Yerai , González‐Chinchon Gonzalo , Eraña Hasier , Perez de Nanclares Guiomar , Castilla Joaquín
Published: June 2021

Background and purpose

Sporadic Creutzfeldt–Jakob disease is a rapidly progressing and highly variable neurodegenerative disease with heterogeneous clinical presentation and a median survival time from diagnosis to death of 4–6 months.

Methods

We report a rare case of a 61‐year‐old woman with a history of initially rapidly progressive dementia, with subsequent development of pyramidal and extrapyramidal signs and with an unusually long survival period of 14 years. Initial magnetic resonance imaging evaluation, single‐photon emission computed tomography, and electroencephalogram did not show relevant alterations.

Results

The postmortem examination of the brain showed diffuse spongiform change, gliosis, and neuronal loss along with abnormal immunostaining of prion protein in the grey matter, especially in the cerebellum. Indirect PRNP genetic analysis was negative.

Conclusions

This case is, to our knowledge, the sporadic Creutzfeldt–Jakob disease patient with the longest survival period ever documented. This surprisingly long duration highlights the importance of histopathological confirmation with brain autopsies for suspected cases, as the disease can easily be misdiagnosed in such slowly progressing cases.
Genotype–phenotype correlation in French patients with myelin protein zero gene‐related inherited neuropathy
Authors: Subréville Marie , Bonello‐Palot Nathalie , Yahiaoui Douniazed , Beloribi‐Djefaflia Sadia , Fernandes Sara , Stojkovic Tanya , Cassereau Julien , Péréon Yann , Echaniz‐Laguna Andoni , Violleau Marie‐Hélène , Soulages Antoine , Louis Sarah Léonard , Masingue Marion , Magot Armelle , Delmont Emilien , Sacconi Sabrina , Adams David , Labeyrie Céline , Genestet Steeve , Noury Jean‐Baptiste , Chanson Jean‐Baptiste , Lévy Nicolas , Juntas‐Morales Raul , Tard Céline , Sole Guilhem , Attarian Shahram
Published: June 2021

Background and purpose

Preparations for clinical trials of unfolded protein response (UPR) inhibitors (such as Sephin1) that target the upregulated UPR in patients with Charcot–Marie–Tooth disease (CMT) carrying MPZ mutations are currently underway. The inclusion criteria for these trials are still being formulated. Our objective was to characterize the relation between genotypes and phenotypes in patients with CMT caused by MPZ mutations, and to refine the inclusion criteria for future trials.

Methods

Clinical and neurophysiological data of CMT patients with MPZ mutations were retrospectively collected at 11 French reference centers.

Results

Forty‐four mutations in MPZ were identified in 91 patients from 61 families. There was considerable heterogeneity. The same mutation was found to cause either axonal or demyelinating neuropathy. Three groups were identified according to the age at disease onset. CMT Examination Score (CMTES) tended to be higher in the early (≤22 years) and adult (23–47 years) onset groups (mean CMTESv2 = 10.4 and 10.0, respectively) than in the late onset group (>47 years, mean CMTESv2 = 8.6, p = 0.47). There was a significant positive correlation between CMTESv2 and the age of patients in Groups I (p = 0.027) and II (p = 0.023), indicating that clinical severity progressed with age in these patients.

Conclusions

To optimize the selection of CMT patients carrying MPZ mutations for the upcoming trials, inclusion criteria should take into account the pathophysiology of the disease (upregulated UPR). Recruited patients should have a mild to moderate disease severity and a disease onset at between 18 and 50 years, as these patients exhibit significant disease progression over time.
A computed tomographic study of endodontic and apical changes in 81 equine cheek teeth with sagittal fractures
Authors: Rowley Kieran J. , Townsend Neil B. , Chang Yu‐Mei R. , Fiske‐Jackson Andrew R.
Published: June 2021

Background

Sagittal fractures of equine cheek teeth are commonly observed during oral examination. There are few reports on the apical and endodontic pathology associated with such fractures seen during computed tomographic (CT) examination.

Objectives

This study aimed to document the prevalence of CT changes indicative of apical disease in equine cheek teeth, which have suffered a sagittal fracture involving the clinical ± reserve crown.

Study design

This study is a retrospective case series.

Methods

CT examinations of equine heads with sagittal fractures of cheek teeth present were reviewed: 81 teeth from 49 horses were identified to have a sagittal cheek tooth fracture. The images were evaluated for apical pathology including gas (in the endodontic system and periapically), widened periodontal space, periapical sclerosis, apical clubbing, cementoma/hypercementosis, lamina dura loss, associated sinusitis and sinus mucosal swelling. An apical infection grading system was created to give each tooth a score. Hounsfield units were used to measure the density of the endodontic, apical and periapical regions. The fracture length ratio was recorded. Statistical analysis was performed using a generalised estimating equation to evaluate predictors of apical infection and associations between clinical signs and CT abnormalities.

Results

Eighty‐seven sagittal fractures (56 buccal, 17 palatal/lingual and 14 midline) from 81 teeth were recorded (74 maxillary and 7 mandibular). Apical infection was diagnosed in 73% (37/51, P = .05) of buccal, 55% (6/11, P = .07) of palatal/lingual, 100% (13/13) of midline, 100% (6/6) of multiple fractures and 96% (23/24, P = .008) of fractures involving infundibula. There was no significant relationship between apical infection and the presence of clinical signs associated with dental pathology (P = .4). There was no significant association between fracture length ratio and apical infection (P = 1.0). Midline sagittal fractures were significantly associated with sinusitis when compared with all other maxillary fractures (odds ratio [OR] 5.92, 95% confidence interval [CI] 1.67‐20.83, P = .006). Loss of the lamina dura was not significantly associated with apical infection (P = .5).

Main limitations

There is a maxillary cheek tooth bias in the data set and the subjective grading system.

Conclusions

A large proportion of fractured cheek teeth have evidence of apical infection on CT examination and therefore warrant treatment.
A review and tests of validation and sensitivity of geolocation models for marine fish tracking
Authors: Gatti Paul , Fisher Jonathan A. D. , Cyr Frédéric , Galbraith Peter S. , Robert Dominique , Le Bris Arnault
Published: June 2021

Uncertainties in fish tracking studies limit their integration into conservation and fisheries management plans. This is especially true for archival tagging studies that rely on geolocation models to infer fish tracks from recorded environmental variables. Hidden Markov Models (HMMs) are increasingly popular to geolocate marine fish equipped with archival tags; however, true errors and sensitivity of geolocation HMMs are seldom evaluated. In this study, we first review validation methods and implementations of geolocation HMMs to adapt to regional oceanography, fish species and tag data. We then use a case‐study to evaluate strengths and limitations of each validation approach and to illustrate the sensitivity of geolocation HMMs to implementation assumptions. Simulated and fixed tag locations are the most widely implemented methods, but less common methods relying on true fish tracking, that is double‐tagging or distance from recapture experiments, provide more informative estimates of model accuracy and precision. Results showed that model performance can be improved using simple assumptions when pre‐processing tag data rather than using a complex movement behaviour model. In addition, accelerometer show potential to further parameterise geolocation models. Overall, results from our case‐study and previous studies showed that current geolocation HMMs have average errors of ca. 30–50 and 120 km for demersal and large pelagic fish, respectively. We suggest that these errors are acceptable for investigations at the scale of fisheries management units.
Influence of load ratio on torsion very high cycle fatigue of high‐strength spring steel in the presence of detrimental defects
Authors: Karr Ulrike , Schönbauer Bernd M. , Sandaiji Yusuke , Mayer Herwig
Published: June 2021

The influence of mean shear stress on torsion very high cycle fatigue (VHCF) for internal inclusion‐initiated fracture is investigated. Ultrasonic torsion fatigue tests are performed at load ratios R = −1, 0.1, and 0.35 with high‐strength spring steel SWOSC‐V featuring an increased number of nonmetallic inclusions. Based on Murakami and Endo's
parameter model, an equation predicting the torsion fatigue limit in the presence of detrimental defects is rendered. Stress biaxiality is considered using a ratio of torsion to axial fatigue strength of τa/σa = 0.86. Considering the load ratio sensitivity according to ([1 − R]/2)α, the value for α is experimentally determined to be 0.550. A fine granular area (FGA) is generated at an artificial surface defect in a fully reversed cyclic torsion test in vacuum. Measured growth rates in the FGA were 10−14–10−12 m/cycle, and the formation of the FGA consumed 98% of the VHCF lifetime.
Brine chemistry matters: Isolation by environment and by distance explain population genetic structure ofArtemia franciscanain saline lakes
Authors: Frisch Dagmar , Lejeusne Christophe , Hayashi Masaki , Bidwell Mark T. , Sánchez‐Fontenla Javier , Green Andy J.
Published: June 2021

The American brine shrimpArtemia franciscanais important in aquaculture and has become invasive in other continents, aided by dispersal via waterbirds. However, little is known about processes underlying its genetic diversity and population structure in its natural habitat in North America. These processes, including dispersal and local adaptation, are pivotal drivers of species distribution and community structure, and therefore central to aquatic biodiversity.

We studied 15 populations in natural saline lakes of Saskatchewan, Canada to determine the influence of variation in geological history, water chemistry, lake size, and location. We aimed to determine the relative importance of isolation by distance and isolation by environment using the cytochromecoxidase subunit 1 gene (CO1) as a mitochondrial marker and five nuclear microsatellite markers.

Geographic patterns for CO1 and microsatellites differed, with lakes clustering in different groups based on genetic distances according to the marker used. CO1 better indicated historical colonisation processes, suggesting potential routes of initial colonisation when lakes were formed after deglaciation 11,000–15,000 years ago.

Differentiation between lakes based on nuclear markers was strongly related to variation in hydrochemistry, suggested by distance‐based redundancy analysis, but there was no indication of isolation by distance. The ratio between alkalinity and the sum of Ca and Mg concentrations was particularly important, although a lake with a high Cl concentration caused by potash mining also had a uniqueArtemiapopulation.

Geochemistry is important in the adaptive radiation of anostracan crustaceans. Our study suggests that it also underlies intraspecific genetic variation between populations, promoting isolation by environment, and making dispersal ineffective when cysts are moved by birds between lakes with different hydrochemistry.

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Differential effects of the formin inhibitor SMIFH2 on contractility and Ca2+ handling in frog and mouse cardiomyocytes
Authors: Sakata Koji , Matsuyama Sho , Kurebayashi Nagomi , Hayamizu Kengo , Murayama Takashi , Nakamura Kunihide , Kitamura Kazuo , Morimoto Sachio , Takeya Ryu
Published: June 2021

Genetic mutations in actin regulators have been emerging as a cause of cardiomyopathy, although the functional link between actin dynamics and cardiac contraction remains largely unknown. To obtain insight into this issue, we examined the effects of pharmacological inhibition of formins, a major class of actin‐assembling proteins. The formin inhibitor SMIFH2 significantly enhanced the cardiac contractility of isolated frog hearts, thereby augmenting cardiac performance. SMIFH2 treatment had no significant effects on the Ca2+ sensitivity of frog muscle fibers. Instead, it unexpectedly increased Ca2+ concentrations of isolated frog cardiomyocytes, suggesting that the inotropic effect is due to enhanced Ca2+ transients. In contrast to frog hearts, the contractility of mouse cardiomyocytes was attenuated by SMIFH2 treatment with decreasing Ca2+ transients. Thus, SMIFH2 has opposing effects on the Ca2+ transient and contractility between frog and mouse cardiomyocytes. We further found that SMIFH2 suppressed Ca2+‐release via type 2 ryanodine receptor (RyR2); this inhibitory effect may explain the species differences, since RyR2 is critical for Ca2+ transients in mouse myocardium but absent in frog myocardium. Although the mechanisms underlying the enhancement of Ca2+ transients in frog cardiomyocytes remain unclear, SMIFH2 differentially affects the cardiac contraction of amphibian and mammalian by differentially modulating their Ca2+ handling.
Late thrombotic complications after SARS‐CoV‐2 infection in hemodialysis patients
Authors: Shabaka Amir , Gruss Enrique , Landaluce‐Triska Eugenia , Gallego‐Valcarce Eduardo , Cases‐Corona Clara , Ocaña Javier , Tato‐Ribera Ana , Lopez‐Revuelta Katia , Furaz‐Czerpak Karina R. , Fernández‐Juárez Gema
Published: June 2021

Introduction

There is an increased risk of thrombotic complications in patients with COVID‐19. Hemodialysis patients are already at an increased risk for thromboembolic events such as stroke and pulmonary embolism. The aim of our study was to determine the incidence of late thrombotic complications (deep vein thrombosis, pulmonary embolism, stroke, new‐onset vascular access thrombosis) in maintenance hemodialysis patients after recovery from COVID‐19.

Methods

We performed a retrospective cohort study of 200 prevalent hemodialysis patients in our center at the start of the pandemic. We excluded incident patients after the cohort entry date and those who required hemodialysis for acute kidney injury, and excluded patients with less than 1 month follow‐up due to kidney transplantation or death from non‐thrombotic causes.

Findings

One‐hundred and eighty five prevalent hemodialysis patients finally met the inclusion criteria; 37 patients (17.6%) had SARS‐CoV‐2 infection, out of which 10 (27%) died during the acute phase of disease without evidence of thrombotic events. There was an increased risk of thrombotic events in COVID‐19 survivors compared to the non‐infected cohort (18.5% vs. 1.9%, p = 0.002) after a median follow‐up of 7 months. Multivariate regression analysis showed that COVID‐19 infection increased risk for late thrombotic events adjusted for age, sex, hypertension, diabetes, antithrombotic treatment, and previous thrombotic events (Odds Ratio (OR) 26.4, 95% confidence interval 2.5–280.6, p = 0.01). Clinical and laboratory markers did not predict thrombotic events.

Conclusions

There is an increased risk of late thrombotic complications in hemodialysis patients after infection with COVID‐19. Further studies should evaluate the benefit of prolonged prophylactic anticoagulation in hemodialysis patients after recovery from COVID‐19.
Conceptualizing patient participation in psychiatry: A survey describing the voice of patients in outpatient care
Authors: Wärdig Rikard , Olofsson Fredrik , Eldh Ann Catrine
Published: June 2021

Background

While increasingly discussed in somatic care, the concept of patient participation remains unsettled in psychiatric care, potentially impeding person‐centred experiences.

Objective

To describe outpatient psychiatric care patients’ conceptualization of patient participation.

Design

An exploratory survey.

Setting and participants

Patients in four psychiatric outpatient care units.

Variables

Patients conceptualized patient participation by completing a semi‐structured questionnaire, including optional attributes and free text. Data were analysed using statistics for ordinal data and content analysis for free text.

Results

In total, 137 patients (69% of potential respondents) completed the questionnaire. The discrete items were favoured for conceptualizing patient participation, indicating a primary connotation that participation means being listened to, being in a reciprocal dialogue, learning about one's health care and managing one's symptoms. Additional free‐text responses acknowledged the attributes previously recognized, and provided supplementary notions, including that patient participation is about mutual respect and shared trust.

Discussion

What patient participation is and how it can be facilitated needs to be agreed in order to enable preference‐based patient participation. Patients in outpatient psychiatric care conceptualize participation in terms of both sharing of and sharing in, including taking part in joint and solo activities, such as a reciprocal dialogue and managing symptoms by yourself.

Conclusion

While being a patient in psychiatric care has been associated with a lack of voice, an increased understanding of patient participation enables person‐centred care, with the benefits of collaboration, co‐production and enhanced quality of care.

Patient contribution

Patients provided their conceptualization of patient participation in accordance with their lived experience.
Does patient empowerment matter in building loyalty?
Authors: Mohd‐Any Amrul Asraf , Sundramohana Meenatharisni , Sarker Moniruzzaman
Published: June 2021

Patient empowerment is becoming an essential tool for improving patient–doctor relationships in the healthcare sector. Past research on empowerment within this sector has focused primarily on hospital staff such as nurses and practitioners, whereas very few studies have focused on patients. Moreover, even less attention has been paid to exploring the effect of patient empowerment on patients' trust in doctors, patient–doctor relationship commitment and patient loyalty. Hence, we investigate the relationships between patient empowerment components (patient education, patient perceived control, doctor support and patient participation), patients' trust in doctors and patient–doctor relationship commitment, which leads to the desired state of patient loyalty. Using hospital‐intercept surveys, 234 responses were obtained from patients at a private healthcare facility in Kuala Lumpur, Malaysia. Using partial least‐squares structural equation modelling (PLS‐SEM) techniques, the results demonstrated that patients who were empowered through education and doctor support were more trusting and that such empowerment also fostered relationship commitment towards their doctor. Patient participation and patients' perceived control did not produce similar outcomes. Consequently, relationship commitment was found to be the dominant predictor in building patient loyalty. This study broadens the dimension of patient empowerment by adding patient education, which is shown to have a positive impact on patient–doctor relationships and to promote patient loyalty. In an increasingly competitive healthcare market where patient loyalty is highly sought after, these findings suggest that empowering patients during healthcare consultation is conducive to the building of long‐term relationships between patients and their doctors.
Comparing the effectiveness of three pain relief methods for inserting a needle into the implanted venous access chemoport: A randomized controlled trial
Authors: Shin Jinhee , Kim Gwang Suk , Sim Hyebeen
Published: June 2021

Aims

Effective methods for relieving pain in inserting a needle for chemotherapy in cancer patients have been studied. This study examined the pain relief effects during needle insertion into the implanted venous access chemoport by comparing three methods.

Methods

This randomized controlled trial included 120 cancer patients who were randomly assigned. The experimental groups received applications of lidocaine cream (n = 30), cryotherapy (n = 30) and cutaneous stimulation therapy (n = 30); the control group (n = 30) received routine care. Premeasurements and postmeasurements were evaluated using a visual analogue pain scale and nurses' careful observations of patients' pain behaviour checklists during needle insertion.

Results

Pain levels were reduced by all three interventions, with the level of relief depending on the type of application. All experimental groups showed significant reduction in pain compared with the control group. Lidocaine cream had the strongest effect, followed by cryotherapy and then cutaneous stimulation.

Conclusion

Lidocaine cream, cryotherapy and cutaneous stimulation therapy all reduced cancer patients' pain levels during insertion of an implanted central venous access chemoport needle. Nurses can apply cryotherapy and cutaneous stimulation therapy independently to reduce the pain associated with this procedure. Future studies should consider using these methods to control for any individual differences that may exist.
B cell/stromal cell crosstalk in health, disease, and treatment: Follicular lymphoma as a paradigm
Authors: Lamaison Claire , Tarte Karin
Published: June 2021

Stromal cells organize specific anatomic compartments within bone marrow (BM) and secondary lymphoid organs where they finely regulate the behavior of mature normal B cells. In particular, lymphoid stromal cells (LSCs) form a phenotypically heterogeneous compartment including various cell subsets variably supporting B‐cell survival, activation, proliferation, and differentiation. In turn, activated B cells trigger in‐depth remodeling of LSC networks within lymph nodes (LN) and BM. Follicular lymphoma (FL) is one of the best paradigms of a B‐cell neoplasia depending on a specific tumor microenvironment (TME), including cancer‐associated fibroblasts (CAFs) emerging from the reprogramming of LN LSCs or poorly characterized local BM precursors. FL‐CAFs support directly malignant B‐cell growth and orchestrate FL permissive cell niche by contributing, through a bidirectional crosstalk, to the recruitment and polarization of immune TME subsets. Recent studies have highlighted a previously unexpected level of heterogeneity of both FL B cells and FL TME, underlined by FL‐CAF plasticity. A better understanding of the signaling pathways, molecular mechanisms, and kinetic of stromal cell remodeling in FL would be useful to delineate new predictive markers and new therapeutic approaches in this still fatal malignancy.
Consensus on a conversation aid for shared decision making with people with intellectual disabilities in the palliative phase
Authors: Noorlandt Hanna W. , Korfage Ida J. , Tuffrey‐Wijne Irene , Festen Dederieke , Vrijmoeth Cis , van der Heide Agnes , Echteld Michael
Published: June 2021

Background

Little is known about how to involve people with intellectual disabilities in making decisions about treatment and care in their palliative phase. We aimed to reach a consensus about a shared decision‐making (SDM) conversation aid for people with intellectual disabilities, relatives, and healthcare professionals.

Methods

In a Delphi process, an expert panel of 11 people with intellectual disabilities, 14 relatives, and 65 healthcare professionals completed online questionnaires about the relevance and feasibility of a draft conversation aid.

Results

In Round 1, components were rated as (very) relevant by 70–98% of participants (M = 87%). In Round 2, after amending the aid in response to feedback, relevance ratings were 67–97% (M = 90%) and feasibility ratings 66–86% (M = 77%). The final version consists of four themes: who are you; illness/end‐of‐life; making decisions; and evaluating the decision.

Conclusion

The consensus‐based conversation aid is considered sufficiently relevant and feasible to be implemented in practice.
Pathogen‐mediated selection favours the maintenance of innate immunity gene polymorphism in a widespread wild ungulate
Authors: Quéméré Erwan , Hessenauer Pauline , Galan Maxime , Fernandez Marie , Merlet Joël , Chaval Yannick , Morellet Nicolas , Verheyden Hélène , Gilot‐Fromont Emmanuelle , Charbonnel Nathalie
Published: June 2021

Toll‐like receptors (TLR) play a central role in recognition and host frontline defence against a wide range of pathogens. A number of recent studies have shown that TLR genes (Tlrs) often exhibit large polymorphism in natural populations. Yet, there is little knowledge on how this polymorphism is maintained and how it influences disease susceptibility in the wild. In previous work, we showed that some Tlrs exhibit similarly high levels of genetic diversity as genes of the Major Histocompatibility Complex (MHC), and signatures of contemporary balancing selection in roe deer (Capreolus capreolus), the most abundant cervid species in Europe. Here, we investigated the evolutionary mechanisms by which pathogen‐mediated selection could shape this innate immunity genetic diversity by examining the relationships between Tlr (Tlr2, Tlr4 and Tlr5) genotypes (heterozygosity status and presence of specific alleles) and infections with Toxoplasma and Chlamydia, two widespread intracellular pathogens known to cause reproductive failure in ungulates. We showed that Toxoplasma and Chlamydia exposures vary significantly across years and landscape features with few co‐infection events detected and that the two pathogens exert antagonistic selection on Tlr2 polymorphism. By contrast, we found limited support for Tlr heterozygote advantage. Our study confirmed the importance of looking beyond Mhc genes in wildlife immunogenetic studies. It also emphasized the necessity to consider multiple pathogen challenges and their spatiotemporal variation to improve our understanding of vertebrate defence evolution against pathogens.
A systematic review of food waste audit methods in hospital foodservices: development of a consensus pathway food waste audit tool
Authors: Cook Nathan , Collins Jorja , Goodwin Denise , Porter Judi
Published: June 2021

Background

To understand, monitor and compare the scope of food waste in hospital foodservices, it is essential to measure food waste using a standardised method. The aims of this systematic review were to: (i) describe and critique the methodological features of waste audits used in hospital foodservice settings that measure aggregate food and food‐related waste and (ii) develop a consensus tool for conducting a food waste audit in a hospital foodservice setting.

Methods

Seven electronic databases were searched for peer reviewed literature, and 17 Google Advanced searches located grey literature that described food waste audit methods previously used or developed for hospital foodservices. Study selection and quality assessment occurred in duplicate. Data describing the audit method, its feasibility, and strengths and limitations were extracted and synthesised to develop a consensus tool.

Results

Eight peer reviewed and nine grey literature documents describing a variety of food waste audit methods were found. The most common practices were 2‐week data collection (n = 5), foodservice staff collecting data (n = 6), measuring food waste only (n = 11), measuring food waste at main meals (n = 5) and using electronic scales to measure waste (n = 12). A consensus tool was developed that proposes a method for preparing, conducting and analysing data from a food waste audit.

Conclusions

This review used published evidence to develop the first ever food waste audit consensus tool for hospital foodservices to use and measure food and food‐related waste. Future research is needed to apply and test this tool in practice.
Association of occupational stress, period circadian regulator 3 (PER3) gene polymorphism and their interaction with poor sleep quality
Authors: Peng Xiaoli , Li Ju , Han Bin , Zhu Yanfeng , Cheng Daomei , Li Qiyu , Du Jingchang
Published: June 2021

Occupational stress is associated with sleep quality among workers and the human variable number tandem repeat (VNTR) polymorphism of the period circadian regulator 3 (PER3) gene relates to sleep–wake regulation. The main aims of the present study were to examine the effects ofPER3VNTR genotypes, occupational stress, and their interactions on sleep quality. A cross‐sectional study was conducted and 729 workers were recruited in Sichuan. Sleep quality were assessed using the Pittsburgh Sleep Quality Index. Occupational stress was measured using the Generic Job Stress Questionnaire.PER3genotypes were determined with polymerase chain reaction. High and medium occupational stress were linked to a higher risk of poor sleep quality than low levels. Unconditional logistic regression indicated thatPER3genotype was significantly associated with sleep quality, and an increased risk of poor sleep of >1.5‐times was observed in those with the allele 5 compared to allele 4. The 5/5 genotype was associated with both sleep latency and sleep duration. Crossover analysis showed an occupational stress × PER3interaction. Compared to subjects with both low and medium occupational stress and 4/4 + 4/5 genotype, those with both high occupational stress and 5/5 genotype had a higher risk of poor sleep quality. Stratified logistic analyses found that compared with low and medium occupational stress, high occupational stress increased the risk of poor sleep by more than five‐times in 5/5 genotype carriers. Occupational stress andPER3genotype had both separate and combined effects on poor sleep quality of workers. The results suggest that occupational stress may increase the risk of poor sleep quality through interaction with thePER3gene polymorphism.
Notes on the accumulation and utilization of capital: Some empirical issues
Authors: Nikiforos Michalis
Published: June 2021

The paper makes three contributions. First, it provides an in‐depth examination of the Federal Reserve measure of capacity utilization and shows that it is closer to a cyclical indicator than a measure of long‐run variations of normal utilization. Other measures, such as the Average Workweek of Capital or the National Emergency Utilization Rate are more appropriate for examining long‐run changes in utilization. Second, and related to that, it argues that a relatively stationary measure of utilization is not consistent with any theory of the determination of utilization. Third, based on data on the lifetime of fixed assets it shows that for the issues around the “utilization controversy” the long run is a period after thirty years or more. This makes it a platonic idea for some economic problems.
Medical educators’ views and experiences of trigger warnings in teaching sensitive content
Authors: Nolan Helen Anne , Roberts Lesley
Published: June 2021

Background

Trigger warnings—prior notification of topics so recipients may prepare for ensuing distress—are encountered widely in contemporary culture. Students at some universities have expressed expectations for trigger warnings. Medical education routinely exposes students to numerous potentially distressing topics. However, this topic remains understudied in medical education. Little is understood about educators’ views or practice relating to warnings in the context of medical education.

Methods

Twenty medical educators from a medical degree programme in the UK participated in a semi‐structured qualitative interview study, exploring medical educators’ views and experiences of managing distressing situations and, specifically, their use of warnings. We analysed interview transcripts by thematic coding and identified themes.

Results

Analysis identified themes relating to educators’ conceptualisation of trigger warnings and rationale for use, concerns about the use of warnings and the critical purpose of medical school in ensuring preparedness for clinical practice.

Participants shared that warnings were given to empower students in approaching distressing topics and to enable engagement with learning. Warnings acknowledged that some experiences would be distressing and normalised and signalled acceptability of emotional responses. Decisions to use warnings were influenced by the nature of content and, reactively, in response to experiences of student distress. Terminology regarding trigger warnings was interpreted varyingly by participants. A broad variety of topics were identified as potentially sensitive. A number of concerns were noted regarding the use of warnings.

Discussion

Warnings alone did not fulfil educators’ responsibility in supporting students’ professional development, but may be a useful adjunct, signalling that self‐care is valued and should be prioritised. Despite frequent use of warnings, individual educator practice was shaped by varying rationale. A framework that addresses competing tensions of preventing distress and supporting professional development is needed as part of a trauma‐informed approach to medical education.
Funding of health professional education: China’s 20‐year process and a global comparison
Authors: Wu Hongbin , Li Wenzhuo , Xie A’na , Kang Le , Ke Yang , Wang Weimin
Published: June 2021

Context

Funding is an essential requirement for ensuring the quality of health professional education worldwide. Adequate funding is of immense significance in training health professionals. Due to the difficulty of accessing relevant data, quantitative research of the kind is scarce.

Objectives

This study aims at analysing the trends of funding levels and funding sources for health professional institutions in China spanning the past 20 years and making a global comparison.

Methods

We used data from Ministry of Education (MOE) of the People's Republic of China to analyse its funding level and structure of funding sources of health professional education in China during 1998‐2017. When analysing funding level, we used two indicators: total funding and funding per student. We chose the United States, and analysed its funding level and structure to allow easy comparison to the situation in China. The data from a Lancet report (Lancet, 376, 2010, 1923) were also used to analyse global funding status to make an international comparison.

Results

Funding levels of health professional institutions in China has increased significantly in the past 20 years, while the average annual growth rate of funding per student (4.5%) is lower than that of total funding (19.9%). In terms of the structure of funding sources, fiscal appropriation accounts for 51.1% on average, and tuition, fees and scientific research income explains 37.0%.

Conclusion

From 1998 to 2017, the total funding and funding per student of HPE in China increased continuously, and the total funding increased at a faster rate. The increase in funding of HPE in China is closely related to the efforts of the Chinese government and the implementation of relevant policies. Even so, funding of HPE in China is likely to remain relatively low compared to other countries.
Unraveling the antitrypanosomal mechanism of benznidazole and related 2‐nitroimidazoles: From prodrug activation to DNA damage
Authors: Dattani Ambika , Drammeh Isatou , Mahmood Aishah , Rahman Mahbubur , Szular Joanna , Wilkinson Shane R.
Published: June 2021

Nitroheterocycles represent an important class of compound used to treat trypanosomiasis. They often function as prodrugs and can undergo type I nitroreductase (NTR1)‐mediated activation before promoting their antiparasitic activities although the nature of these downstream effects has yet to be determined. Here, we show that in an NTR1‐dependent process, benznidazole promotes DNA damage in the nuclear genome of Trypanosoma brucei, providing the first direct link between activation of this prodrug and a downstream trypanocidal mechanism. Phenotypic and protein expression studies revealed that components of the trypanosome’s homologous recombination (HR) repair pathway (TbMRE11, γH2A, TbRAD51) cooperate to resolve the benznidazole‐induced damage, indicating that the prodrug‐induced lesions are most likely double stand DNA breaks, while the sequence/recruitment kinetics of these factors parallels that in other eukaryotes HR systems. When extended to other NTR1‐activated 2‐nitroimidazoles, some were shown to promote DNA damage. Intriguingly, the lesions induced by these required TbMRE11 and TbCSB activities to fix leading us to postulate that TbCSB may operate in systems other than the transcription‐coupled nucleotide excision repair pathway. Understanding how existing trypanosomal drugs work will aid future drug design and help unlock novel reactions/pathways that could be exploited as targets for therapeutic intervention.
Seeing dew deposition from satellites: leveraging microwave remote sensing for the study of water dynamics in and on plants
Authors: Gerlein‐Safdi Cynthia
Published: June 2021

This article is a Commentary on Xu et al. (2021), 231: 122–136.
Immuno‐genetic importance of Th17 in susceptibility to TB
Authors: Rapolu Bhagya Laxmi , Pullagurla Ashwini , Ganta Soujanya , Komaravalli Prasanna Latha , Gaddam Suman Latha
Published: June 2021

Tuberculosis is a highly infectious disease caused by Mycobacterium tuberculosis (M. tb) which is infecting around one‐third of the world population. The majority of individuals develop latent tuberculosis infection (LTBI), but only 10% of LTBI individuals develop active TB. Household contacts (HHC) of TB patients are 10‐60 times more likely to develop the disease than non exposed individuals. Dendritic cells strengthen the immune response against M. tb through the stimulation of CD4+T cells, which differentiate into different types of T helper cells (Th) such as Th1, Th2 and Th17 lineages. Th17 cells play an important role in coordinating pulmonary immune defence and enhance the expression of cytokines (IL‐17A, IL‐17F, IL‐21 and IL‐22), chemokines and antimicrobial peptides that lead to phagocytosis of M. tb. Previous studies have reported that Th17 polymorphisms are associated with TB susceptibility. In this review, we focused on the immuno‐genetic importance of Th17 in TB and screening the HHC

for Th17 genetic variants may help for the early detection of TB infection in individuals who are at risk.
Archaeological Digital Archiving in Heritage Management in Slovakia
Authors: Bisták Peter , Zachar Ján , Rášová Alexandra , Lieskovský Tibor , Kravjanská Ivica , Orosová Martina , Kročková Kristína , Felcan Michal
Published: June 2021

The Monuments Board of the Slovak Republic (MB SR) and the Regional Monuments Boards have been the state administrators of the cultural heritage, including archaeology, since 2002. This article aims to map the current state of archaeological digital archives within MB SR and eight Regional Monuments Boards, as well as present the usage and management of digital datasets within ongoing projects. The central archive of the MB SR maintains historical plans and cultural heritage documentation, created since the 1920s and continuously digitised (the collections of negatives, diapositives, projects, plans, schematic maps, and fieldwork documentation). Since 2012, MB SR has taken part in the Digital Monuments Fund project. Within this project, 2D and 3D documentation of a great number of cultural monuments has been created. In 2019 the implementation phase of the Monuments information system (PAMIS) project started. Its basic modules are the presentation layer, the knowledge agenda and state administration. There are several features in preparation within these modules, such as: updating; collection, consolidation and GIS processing of archaeological site data that belong to the monuments fund, including data from aerial laser scanning; the archaeological excavation registry and the archive of fieldwork reports; the registry of finds in the administration of MB SR; the electronic processing of the state administration activity within the protection of the archaeological cultural heritage. The PAMIS project will provide processed data and make them accessible to the state and public administration, owners of monuments, as well as to professionals and the general public, using online solutions (web GIS) with various approaches according to defined user roles.
Archiving Archaeological Data in the United Kingdom
Authors: Richards Julian D.
Published: June 2021

Owing to its early lead in the world of digital preservation, fostered by the creation of the Archaeology Data Service in 1996, the UK is often considered to be in an advanced position for digital archiving of archaeological data. In some ways it is, but the situation is also complex, due to a highly fragmented landscape, spread across four nations, and multiple sectors. This overview article describes the organisation and structure of archaeology across the UK, and the provision for digital preservation and access. Digital archiving is still far from standard, but the situation is improving, and rests on firm foundations.