bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum biomarkers in primary mitochondrial disorders
Authors: Varhaug Kristin N , Hikmat Omar , Nakkestad Hanne Linda , Vedeler Christian A , Bindoff Laurence A 
Published: January 2021

Abstract
The aim of this study was to explore the utility of the serum biomarkers neurofilament light chain, fibroblast growth factor 21 and growth and differentiation factor 15 in diagnosing primary mitochondrial disorders. We measured serum neurofilament light chain, fibroblast growth factor 21 and growth and differentiation factor 15 in 26 patients with a genetically proven mitochondrial disease. Fibroblast growth factor 21 and growth and differentiation factor 15 were measured by enzyme-linked immunosorbent assay and neurofilament light chain with the Simoa assay. Neurofilament light chain was highest in patients with multi-systemic involvement that included the central nervous system such as those with the m.3242A&gt;G mutation. Mean neurofilament light chain was also highest in patients with epilepsy versus those without [49.74 pg/ml versus 19.7 pg/ml (P = 0.015)], whereas fibroblast growth factor 21 and growth and differentiation factor 15 levels were highest in patients with prominent myopathy, such as those with single-mitochondrial DNA deletion. Our results suggest that the combination of neurofilament light chain, fibroblast growth factor 21 and growth and differentiation factor 15 is useful in the diagnostic evaluation of mitochondrial disease. Growth and differentiation factor 15 and fibroblast growth factor 21 identify those with muscle involvement, whereas neurofilament light chain is a clear marker for central nervous system involvement independent of underlying mitochondrial pathology. Levels of neurofilament light chain appear to correlate with the degree of ongoing damage suggesting, therefore, that monitoring neurofilament light chain levels may provide prognostic information and a way of monitoring disease activity.
An update on the rod microglia variant in experimental and clinical brain injury and disease
Authors: Giordano Katherine R , Denman Charlotte R , Dubisch Phoebe S , Akhter Murtaza , Lifshitz Jonathan 
Published: January 2021

Abstract
Contemporary microglia morphologies include ramified, activated and amoeboid, with the morphology of microglia considered highly coupled to the cellular function. Rod microglia are an additional activated microglia variant observed in the ageing, injured and diseased brain. Rod microglia were reported frequently in the early 1900s by neuropathologists in post-mortem cases of general paresis, Alzheimer’s disease and encephalitis, and then remained largely ignored for almost 100 years. Recent reports have renewed interest in rod microglia, most notably after experimental traumatic brain injury. Rod microglia are formed by the narrowing of the soma and retraction of planar processes, which results in the appearance of an elongated, rod-shaped cell. Rod microglia are most commonly observed in the cortex, aligned perpendicular to the dural surface and adjacent to neuronal processes; in the hippocampus, they are aligned perpendicular to hippocampal layers. Furthermore, rod microglia form trains with one another, apical end to basal end. By replicating the process of sketching microscopic observation, rod microglia are re-defined by circumnutation around the long axis. In this update, we summarize the rod microglia variant in clinical and experimental literature and advocate for investigation into mechanisms of rod microglia origin and function.
Fumaric acid ester-induced renal Fanconi syndrome: evidence of mitochondrial toxicity
Authors: Wan Elizabeth R , Siew Keith , Heptinstall Lauren , Walsh Stephen B 
Published: January 2021

Abstract

Background
Fumaric acid esters (FAEs) are used to treat chronic plaque psoriasis. Fumarate is a crucial component of the Krebs cycle and mitochondrial function. Proximal tubule cells have high energy demands and rely on aerobic respiration. Proximal tubular dysfunction can cause renal Fanconi syndrome and acute kidney injury. We sought to better understand the mechanism for this in the context of FAE therapy.

Methods
We describe a case series of 10 patients with FAE-associated Fanconi syndrome. Patients were diagnosed and managed at a tertiary renal tubular disorder clinic, with examination of serum and urine biochemistry. Five patients had a renal biopsy with examination of the specimens by electron microscopy.

Results
The median age was 36.5 years [interquartile range (IQR) 32.25–54.25]. The median dose of FAE was 720 mg/day (IQR 390–720). There was low molecular weight proteinuria: the median urinary retinol-binding protein (RBP) at presentation was 8385 μg/mL (IQR 2793–14 600) and the RBP:creatinine ratio was 710 (IQR 390–2415). All patients had hyperphosphaturia [median fractional excretion of phosphate 24.2% (IQR 20.8–26.9), normal range &lt;20%] as well as relative hypophosphataemia, with a median serum phosphate concentration of 0.93 mmol/L (IQR 0.83–0.97). Renal histology showed proximal tubular damage and abnormal mitochondrial morphology. Two patients had a favourable biochemical response to treatment with probenecid.

Conclusions
We document for the first time that FAE-associated renal Fanconi syndrome is associated with mitochondrial damage visible on electron microscopy. This effect may be ameliorated by antagonism of the organic anion transporter with probenecid.
Serum Prostate-Specific Antigen Testing for Early Detection of Prostate Cancer: Managing the Gap between Clinical and Laboratory Practice
Authors: Ferraro Simona , Bussetti Marco , Panteghini Mauro 
Published: January 2021

Abstract

Background
Current clinical practice guidelines (CPGs) for early detection of prostate cancer recommend for clinical decision-making a personalized prostate-specific antigen (PSA)-based management to improve the risk-benefit ratio of the screening strategy. Some important critical issues regarding the PSA determination in the clinical framework are, however, still neglected in current guidelines and a major focus of recommendations on those aspects would be needed to improve their effectiveness.

Content
Evidence sources in the available literature concerning the interchangeability of total PSA results measured with different commercial methods were critically appraised. We discuss how the heterogeneity of the measurand, the intermethod bias, and the design and selectivity of immunoassays may affect the diagnostic accuracy of selected PSA thresholds, and how knowledge of the analytical characteristics of assays in service, such as the recognized PSA circulating forms and the cross-reactivity with PSA homologs, is basic for improving both clinical decision-making in cancer screening and the reliability of the clinical interpretation of results at the individual level.

Summary
Current CPGs ignore the poor interchangeability of PSA results obtained from different assays and the substantial role of laboratory issues in clinical performance of PSA testing. Involved stakeholders should contribute to fill the existing gap by: (a) preparing commutable reference materials for immunoassay calibration; (b) providing analytical characteristics that may explain the different performance of assays; (c) deriving outcome-based analytical performance specifications for PSA measurement; and (d) giving more focus on laboratory items when CPGs are prepared.
Added-value of molecular imaging in myocardial metastasis of an ileal neuroendocrine tumour treated with peptide receptor radionuclide therapy: a case report
Authors: Mallón Araujo María Del Carmen , Abou Jokh Casas Estephany , Abou Jokh Casas Charigan , Pubul Núñez Virginia 
Published: January 2021

Abstract

Background
Neuroendocrine tumours (NET) conform a rare type of neoplasm, mostly located in the gastrointestinal tract. They are slow-growing tumours, so at the time of the diagnosis, most patients present with metastatic lesions, mainly in the liver. The myocardium is a rare and important organ for metastasis, in which 68Ga-Dotatate positron emission tomography-computed tomography (PET/CT) shows a high diagnostic sensitivity for its detection, contrary to carcinoid valve disease, where anatomic imaging plays a key role, especially the echocardiogram.

Case summary
A 60-year-old man diagnosed with metastatic progressive ileal NET, who underwent a 68Ga-Dotatate PET/CT prior 177Lu-Dotatate therapy, showed a metastatic lesion in the left ventricle that was undetected in previous studies, such as an Octreoscan® and CT. A transthoracic echocardiogram was performed revealing the existence of a second cardiac lesion, a tricuspid valve carcinoid disease. A cardiac magnetic resonance showed no late gadolinium enhancement.

Discussion
The 68Ga-Dotatate PET/CT is currently considered the gold standard for assessment and follow-up of NET, including those with rare sites of metastasis such as cardiac infiltration. In this case, it stimulated the persue of possible cardiac involvement, detecting the coexistence of two types of lesions (cardiac metastasis and carcinoid valve disease). Of these, carcinoid valvulopathy develops in 50% of NET cases, while cardiac metastasis (CM) is less frequent (only 5%).
STOP-sexual violence: evaluation of a community-based nightlife worker awareness raising bystander training programme
Authors: Quigg Zara , Bellis Mark A , Hughes Karen , Kulhanek Adam , Brito Irma , Ross-Houle Kim , Bigland Charlotte , Calafat Amador , Duch Mariàngels ,   the STOP-SV group
Published: January 2021

Abstract

Background
Preventing sexual violence in nightlife environments is a pervasive issue across many countries. This study explored the associated impact of a nightlife worker sexual violence awareness raising/bystander training programme (STOP-SV) on trainees’ sexual violence myth acceptance and readiness and confidence to intervene.

Methods
: Pre- and post-test (n = 118), and 3-month follow-up (n = 38) trainee surveys were implemented across three countries (Czech Republic, Portugal and Spain). Paired-sample tests examined changes across time-periods in participants’ myth acceptance (e.g. unwanted sexual advances are a normal part of a night out), and readiness and confidence to intervene. Multi-nominal regression was used to examine the relationship between the change in pre-to-post-training scores and trainee characteristics.

Results
Compared to pre-training, post-training participants were significantly (P &lt; 0.01) less likely to agree with sexual violence myths, and more likely to be ready and confident to intervene. In bi-variate and multi-variate analyses, we found no significant associations between the change in pre-to-post-training scores and trainee characteristics. Analyses of the small follow-up sub-sample illustrated some positive changes at the post-training and follow-up time-periods (i.e. reduction in sexual violence myth acceptance).

Conclusion
This exploratory study suggests that the STOP-SV training programme was associated with a decrease in trainees’ acceptance of sexual violence myths, and an increase in their readiness and confidence to intervene. Our findings support the case for further implementation and evaluation of awareness raising/bystander programmes for nightlife workers that aim to prevent and respond to sexual violence.
Independent evolution toward larger body size in the distinctive Faroe Island mice
Authors: Wilches Ricardo , Beluch William H , McConnell Ellen , Tautz Diethard , Chan Yingguang Frank 
Published: January 2021

Abstract
Most phenotypic traits in nature involve the collective action of many genes. Traits that evolve repeatedly are particularly useful for understanding how selection may act on changing trait values. In mice, large body size has evolved repeatedly on islands and under artificial selection in the laboratory. Identifying the loci and genes involved in this process may shed light on the evolution of complex, polygenic traits. Here, we have mapped the genetic basis of body size variation by making a genetic cross between mice from the Faroe Islands, which are among the largest and most distinctive natural populations of mice in the world, and a laboratory mouse strain selected for small body size, SM/J. Using this F2 intercross of 841 animals, we have identified 111 loci controlling various aspects of body size, weight and growth hormone levels. By comparing against other studies, including the use of a joint meta-analysis, we found that the loci involved in the evolution of large size in the Faroese mice were largely independent from those of a different island population or other laboratory strains. We hypothesize that colonization bottleneck, historical hybridization, or the redundancy between multiple loci have resulted in the Faroese mice achieving an outwardly similar phenotype through a distinct evolutionary path.
Molecular Evolution of Antigen-Processing Genes in Salamanders: Do They Coevolve withMHCClass I Genes?
Authors: Palomar Gemma , Dudek Katarzyna , Wielstra Ben , Jockusch Elizabeth L , Vinkler Michal , Arntzen Jan W , Ficetola Gentile F , Matsunami Masatoshi , Waldman Bruce , Těšický Martin , Zieliński Piotr , Babik Wiesław 
Published: January 2021

AbstractProteins encoded by antigen-processing genes (APGs) prepare antigens for presentation by the major histocompatibility complex class I (MHC I) molecules. Coevolution between APGs and MHC I genes has been proposed as the ancestral gnathostome condition. The hypothesis predicts a single highly expressed MHC I gene and tight linkage between APGs and MHC I. In addition, APGs should evolve under positive selection, a consequence of the adaptive evolution in MHC I. The presence of multiple highly expressed MHC I genes in some teleosts, birds, and urodeles appears incompatible with the coevolution hypothesis. Here, we use urodele amphibians to test two key expectations derived from the coevolution hypothesis: 1) the linkage between APGs and MHC I was studied in Lissotriton newts and 2) the evidence for adaptive evolution in APGs was assessed using 42 urodele species comprising 21 genera from seven families. We demonstrated that five APGs (PSMB8, PSMB9, TAP1, TAP2, and TAPBP) are tightly linked (&lt;0.5 cM) to MHC I. Although all APGs showed some codons under episodic positive selection, we did not find a pervasive signal of positive selection expected under the coevolution hypothesis. Gene duplications, putative gene losses, and divergent allelic lineages detected in some APGs demonstrate considerable evolutionary dynamics of APGs in salamanders. Overall, our results indicate that if coevolution between APGs and MHC I occurred in urodeles, it would be more complex than envisaged in the original formulation of the hypothesis.
The Relationship Between Symptoms of Depression and Anxiety and Disease Activity in IBD Over Time
Authors: Marrie Ruth Ann , Graff Lesley A , Fisk John D , Patten Scott B , Bernstein Charles N 
Published: January 2021

Abstract

Brackground
We aimed to examine associations between elevated symptoms of depression and anxiety and disease activity in inflammatory bowel disease (IBD). Previous findings have been inconsistent and have not accounted for variability in the courses of these conditions over time.

Methods
We followed 247 participants with IBD (153 Crohn’s disease [CD], 94 ulcerative colitis [UC]) for 3 years. Annually, participants underwent an abdominal examination, reported therapies used for IBD, and completed the Hospital Anxiety and Depression Scale (HADS) questionnaire. We evaluated associations of elevated symptoms (scores ≥11) of anxiety (HADS-A) and depression (HADS-D) with the presence of active IBD as measured using the Powell Tuck Index for UC and the Harvey-Bradshaw Disease Activity Index for CD. We employed logistic regression with generalized estimating equations, simultaneously estimating between-person and within-person effects.

Results
Of 247 participants, 15 (6.1%) had elevated symptoms of depression (HADS-D ≥11) at enrollment, 41 (16.6%) had elevated symptoms of anxiety (HADS-A ≥11), and 101 (40.9%) had active IBD. On average, individuals with elevated symptoms of depression (odds ratio [OR], 6.27; 95% CI, 1.39–28.2) and anxiety (OR, 2.17; 95% CI, 1.01–4.66) had increased odds of active IBD. Within individuals, elevations in symptoms of depression over time were associated with increased odds of active IBD (OR, 2.70; 95% CI, 1.15–6.34), but elevated symptoms of anxiety were not. After adjustment for covariates (including disease activity), elevated symptoms of depression were also associated with increased odds of biologic therapy use (OR, 2.02; 95% CI, 1.02–4.00).

Conclusion
Symptoms of depression and anxiety are associated with disease activity in IBD over time. Reducing these symptoms should be incorporated into the management of IBD.
Prevention of Respiratory Syncytial Virus Infection in Healthy Adults by a Single Immunization of Ad26.RSV.preF in a Human Challenge Study
Authors: Sadoff Jerald , De Paepe Els , DeVincenzo John , Gymnopoulou Efi , Menten Joris , Murray Bryan , Rosemary Bastian Arangassery , Vandebosch An , Haazen Wouter , Noulin Nicolas , Comeaux Christy , Heijnen Esther , Eze Kingsley , Gilbert Anthony , Lambkin-Williams Rob , Schuitemaker Hanneke , Callendret Benoit 
Published: January 2021

Abstract

Background
Respiratory syncytial virus (RSV) is a significant cause of severe lower respiratory tract disease in children and older adults, but has no approved vaccine. This study assessed the potential of Ad26.RSV.preF to protect against RSV infection and disease in an RSV human challenge model.

Methods
In this double-blind, placebo-controlled study, healthy adults aged 18–50 years were randomized 1:1 to receive 1 × 1011 vp Ad26.RSV.preF or placebo intramuscularly. Twenty-eight days postimmunization, volunteers were challenged intranasally with RSV-A (Memphis 37b). Assessments included viral load (VL), RSV infections, clinical symptom score (CSS), safety, and immunogenicity.

Results
Postchallenge, VL, RSV infections, and disease severity were lower in Ad26.RSV.preF (n = 27) vs placebo (n = 26) recipients: median VL area under the curve (AUC) quantitative real-time polymerase chain reaction: 0.0 vs 236.0 (P = .012; predefined primary endpoint); median VL-AUC quantitative culture: 0.0 vs 109; RSV infections 11 (40.7%) vs 17 (65.4%); median RSV AUC-CSS 35 vs 167, respectively. From baseline to 28 days postimmunization, geometric mean fold increases in RSV A2 neutralizing antibody titers of 5.8 and 0.9 were observed in Ad26.RSV.preF and placebo, respectively. Ad26.RSV.preF was well tolerated.

Conclusions
Ad26.RSV.preF demonstrated protection from RSV infection through immunization in a human challenge model, and therefore could potentially protect against natural RSV infection and disease.

Clinical Trials Registration
NCT03334695; CR108398, 2017-003194-33 (EudraCT); VAC18193RSV2002.
Nutritional approaches to slow late finishing pig growth: implications on carcass composition and pork quality
Authors: Helm Emma T , Ross Jason W , Patience John F , Lonergan Steven M , Huff-Lonergan Elisabeth , Greiner Laura L , Reever Leah M , Hastad Chad W , Arkfeld Emily K , Gabler Nicholas K 
Published: January 2021

AbstractAlthough pork producers typically aim to optimize growth rates, occasionally it is necessary to slow growth, such as when harvest facility capacity is limited. In finishing pigs, numerous dietary strategies can be used to slow growth so pigs are at optimal slaughter body weights when harvest facility capacity and/or access is restored. However, the impact of these diets on pork carcass quality is largely unknown. Thus, this study aimed to evaluate the efficacy of dietary strategies to slow growth in late finishing pigs and evaluate their effects on carcass composition and pork quality. Mixed-sex pigs (n = 897; 125 ± 2 kg BW) were randomly allotted across 48 pens and assigned to 1 of 6 dietary treatments (n = 8 pens/treatment): (1) Control diet representative of a typical finisher diet (CON); (2) diet containing 3% calcium chloride (CaCl2); (3) diet containing 97% corn and no soybean meal (Corn); (4) diet deficient in isoleucine (LowIle); (5) diet containing 15% neutral detergent fiber (NDF) from soybean hulls (15% NDF); and (6) diet containing 20% NDF from soybean hulls (20% NDF). Over 42 d, pen body weights and feed disappearance were collected. Pigs were harvested in 3 groups (14, 28, and 42 d on feed) and carcass data collected. From the harvest group, 1 loin was collected from 120 randomly selected carcasses (20 loins/treatment) to evaluate pork quality traits. Overall, ADG was reduced in CaCl2, Corn, and 20% NDF pigs compared with CON pigs (P &lt; 0.001). However, ADFI was only reduced in CaCl2 and 20% NDF pigs compared with CON (P &lt; 0.001). Feed efficiency was reduced in CaCl2 and Corn pigs compared with CON (P &lt; 0.001). Hot carcass weights were reduced in CaCl2 pigs at all harvest dates (P &lt; 0.001) and were reduced in Corn and 20% NDF pigs at days 28 and 42 compared with CON pigs (P &lt; 0.001). In general, CaCl2 and 20% NDF diets resulted in leaner carcasses, whereas the Corn diet increased backfat by 42 d on test (P &lt; 0.05). Loin pH was reduced and star probe increased in CaCl2 pigs compared with CON pigs (P &lt; 0.05); no treatments differed from CON pigs regarding drip loss, cook loss, color, firmness, or marbling (P ≥ 0.117). Overall, these data indicate that several dietary strategies can slow finishing pig growth without evidence of behavioral vices. However, changes to carcass composition and quality were also observed, indicating quality should be taken into consideration when choosing diets to slow growth.
Worldwide distribution and depth limits of decapod crustaceans (Penaeoidea, Oplophoroidea) across the abyssal-hadal transition zone of eleven subduction trenches and five additional deep-sea features
Authors: Swan Jackson A , Jamieson Alan J , Linley Thomas D , Yancey Paul H 
Published: January 2021

Abstract
Decapod crustaceans are conspicuous members of marine benthic communities to at least 7,700 m deep. To assess the bathymetric extent of this taxonomic group, baited landers were deployed to across the abyssal-hadal transition zone of 11 subduction trenches spanning the Pacific, Atlantic, Southern, and Indian oceans and additional sites. Decapods were dominated by penaeid shrimps (superfamily Penaeoidea), in particular Benthesicymus Spence Bate, 1881 and Cerataspis Gray, 1828, with the former being found deeper. Benthesicymus cf. crenatus Spence Bate, 1881 was observed in the Kermadec, Mariana, New Hebrides, Puerto Rico, Peru-Chile, Tonga, San Cristobal, and Santa Cruz trenches, plus the South Fiji Basin and the Wallaby-Zenith Fracture Zone. They were not recorded in the Abaco Canyon, Agulhas Fracture Zone, Java Trench, or any of the polar locations. Cerataspis cf. monstrosus Gray, 1828 was present in the Kermadec, Mariana, New Hebrides, Puerto Rico, and Java trenches, the Abaco Canyon, Agulhas Fracture Zone, Wallaby-Zenith Fracture Zone and the South Fiji Basin, but absent from the Tonga, San Cristobal and Santa Cruz trenches. Hymenopenaeus nereus (Faxon, 1893) was only recorded in the Peru-Chile Trench. Unidentified species belonging to superfamily Oplophoroidea were observed to a maximum depth of 6,931 m. Decapods are thus are primarily represented at hadal depths by penaeoid shrimps, consistently present at tropical and temperate latitudes to ~7,700 m, while absent from equivalent depths in polar regions. Their maximum depth may be limited due to hydrostatic pressure, while potentially affected by temperature and oxygen in some instances. Muscle samples of three specimens from 6,000 m (Mariana and Kermadec trenches) were found to have high levels of trimethylamine N-oxide (TMAO; 260 mmol kg–1), the major piezolyte, a protectant against hydrostatic pressure, in other deep-sea organisms. We speculate that physiological limits to TMAO concentration may prevent them from inhabiting the greatest hadal depths.