bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and characterisation of mitochondrial sequences integrated into the ovine nuclear genome
Authors: Féménia M. , Charles M. , Boulling A. , Rocha D. 
Published: June 2021

SummaryMitochondrial DNA sequences are frequently transferred into the nuclear genome, generating nuclear mitochondrial DNA sequences (NUMTs). Here, we analysed, for the first time, NUMTs in the ovine genome. We obtained 760 alignment matches covering 513.8 kbp of the sheep nuclear genome. After a merging step, we identified 390 NUMT regions with a total length of ~720 kbp, representing 0.02% of the nuclear genome. We discovered copies of all mitochondrial regions and found that most NUMT regions are intergenic or intronic. Ovine NUMTs are mostly not transcribed. However, we identified within some of the NUMTs, potential new genes encoding nuclear humanin isoforms. To rule out the possibility that the identified NUMTs could be artifacts of the Oar Rambouillet v1.0 genome assembly, we validated experimentally nine NUMT regions by PCR amplification. As we found several NUMT regions showing high similarity to the mitochondrial genome that potentially could pose a risk to ovine DNA mitochondrial studies, special care must be taken for the selection of primers for PCR amplification of mitochondrial DNA sequences.
Treatment with assisted reproduction technologies in women with acute hepatic porphyria
Authors: Vassiliou Daphne , Lindén Hirschberg Angelica , Sardh Eliane 
Published: June 2021

AbstractIntroductionAcute porphyrias are rare disorders of the heme biosynthetic pathway and present with acute neurovisceral symptoms that can be induced by hormonal changes and medications. Women are far more likely to present with clinical symptoms than men, particularly during parts of their lifetime with changes in the level of female sex hormones such as ovulation, menstruation, and pregnancy. Treatment of ovulatory dysfunction and controlled ovarian hyperstimulation require the administration of hormones, which are considered porphyrinogenic. Women with acute hepatic porphyria have therefore been considered unsuitable for such treatments in the past.Material and methodsWe report on nine women with acute hepatic porphyria who underwent in vitro fertilization (IVF), preceded by ovarian stimulation. Their mean age at the start of IVF was 33.2 years (range 27–38 years). Two women had been diagnosed with polycystic ovarian syndrome, two were treated for hyperprolactinemia, two had hypothyroidism, of which one also had type 1 diabetes, one had a uterus malformation, one had anovulatory cycles, and one used a sperm donor.ResultsAll patients were able to undergo fertility treatment without experiencing severe porphyria attacks.ConclusionsWomen with acute hepatic porphyria considering fertility treatments should be assessed individually for potential risks, treatment should be planned in close collaboration with a porphyria specialist, and biochemical activity should be monitored regularly during ovarian stimulation. As we gather more knowledge, we hope that the porphyrinogenicity of the stimulation agents is re‐assessed and that more studies will shed light on the reproductive health of women living with acute hepatic porphyria.
Intermediate‐ and long‐term oncological outcomes of active surveillance for localized renal masses: a systematic review and quantitative analysis
Authors: Klatte Tobias , Berni Alessandro , Serni Sergio , Campi Riccardo 
Published: June 2021

ObjectiveTo evaluate intermediate‐ and long‐term oncological outcomes of active surveillance (AS) for localized renal masses (LRMs).MethodsThis systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement and registered on PROSPERO (CRD42021230416). Studies on AS for LRMs with at least 3 years' follow‐up were eligible. Two review authors independently screened the literature, extracted data, and assessed risk of bias. The primary outcomes were metastasis rate, renal cell carcinoma (RCC)‐specific mortality (RCC‐SM) and all‐cause mortality (ACM). Pooled estimates were obtained from random‐effects models. Subgroup analyses were performed for small renal masses (SRMs; ≤4 cm) and non‐SRMs (>4 cm).ResultsWe analysed 18 unique cohorts comprising 2066 patients. The pooled initial maximum tumour size was 2.8 cm (95% confidence interval [CI] 2.7–3.0) and the percutaneous biopsy rate was 28%. The pooled mean annual growth rate was 2.8 mm (95% CI 2.1–3.4). Within a pooled mean follow‐up of 53 months, 2.1% (95% CI 1.0–3.6) of patients developed metastatic disease, 1.0% (95% CI 0.3–2.1) died from RCC and 22.6% (95% CI 15.8–30.2) died from any cause. For patients with SRMs (nine studies, n = 987), the pooled metastasis rate was 1.8% (95% CI 0.5–3.7), RCC‐SM was 0.6% (95% CI 0–2.1), and ACM was 28.5% (95% CI 17.4–41.4). Across five studies reporting on outcomes of 239 patients with non‐SRMs, the pooled metastasis rate was 5.1% (95% CI 0–17.3), RCC‐SM was 2.1% (95% CI 0–8.9) and ACM was 29.1% (95% CI 13.6–47.3). This review is limited by non‐standardized inclusion criteria, definitions and follow‐up, data heterogeneity, limited patient numbers in sub‐analyses and absence of high‐quality studies.ConclusionsActive surveillance is a safe intermediate‐ and long‐term management option for well‐selected patients with LRMs, especially those with SRMs. Limited data are available for non‐SRMs, but current evidence would support further evaluation of this approach in selected patients. It is not possible to draw definitive conclusions until more high‐quality data become available.
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

Abstract
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

AbstractTo 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

AbstractMonitoring 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

AbstractAimThis 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 methodsYouth 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.ResultsYouth 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.ConclusionsHealth‐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

AbstractBackground and purposeSporadic 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.MethodsWe 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.ResultsThe 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.ConclusionsThis 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

AbstractBackground and purposePreparations 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.MethodsClinical and neurophysiological data of CMT patients with MPZ mutations were retrospectively collected at 11 French reference centers.ResultsForty‐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.ConclusionsTo 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

AbstractBackgroundSagittal 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.ObjectivesThis 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 designThis study is a retrospective case series.MethodsCT 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.ResultsEighty‐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 limitationsThere is a maxillary cheek tooth bias in the data set and the subjective grading system.ConclusionsA 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

AbstractUncertainties 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

AbstractThe 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

AbstractThe 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.​