bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol use and brain morphology in adolescence: A longitudinal study in three different cohorts
Authors: El Marroun Hanan , Klapwijk Eduard T. , Koevoets Martijn , Brouwer Rachel M. , Peters Sabine , van't Ent Dennis , Boomsma Dorret I. , Muetzel Ryan L. , Crone Eveline A. , Hulshoff Pol Hilleke E. , Franken Ingmar H. A.
Published: August 2021

Alcohol consumption is commonly initiated during adolescence, but the effects on human brain development remain unknown. In this multisite study, we investigated the longitudinal associations of adolescent alcohol use and brain morphology. Three longitudinal cohorts in the Netherlands (BrainScale n = 200, BrainTime n = 239 and a subsample of the Generation R study n = 318) of typically developing participants aged between 8 and 29 years were included. Adolescent alcohol use was self‐reported. Longitudinal neuroimaging data were collected for at least two time points. Processing pipelines and statistical analyses were harmonized across cohorts. Main outcomes were global and regional brain volumes, which were a priori selected. Linear mixed effect models were used to test main effects of alcohol use and interaction effects of alcohol use with age in each cohort separately. Alcohol use was associated with adolescent's brain morphology showing accelerated decrease in grey matter volumes, in particular in the frontal and cingulate cortex volumes, and decelerated increase in white matter volumes. No dose–response association was observed. The findings were most prominent and consistent in the older cohorts (BrainScale and BrainTime). In summary, this longitudinal study demonstrated differences in neurodevelopmental trajectories of grey and white matter volume in adolescents who consume alcohol compared with non‐users. These findings highlight the importance to further understand underlying neurobiological mechanisms when adolescents initiate alcohol consumption. Therefore, further studies need to determine to what extent this reflects the causal nature of this association, as this longitudinal observational study does not allow for causal inference.
Ultrahigh field in vivo characterization of microstructural abnormalities in the orbitofrontal cortex and amygdala in autism
Authors: Fischi‐Gomez Elda , Bonnier Guillaume , Ward Noreen , Granziera Cristina , Hadjikhani Nouchine
Published: August 2021

There are currently no biomarkers for autism spectrum disorder (ASD). This neurodevelopmental condition has previously been associated with histopathological findings, including increased neuronal packing density in the amygdala, abnormal laminar cytoarchitecture and increased average neuronal density in the prefrontal cortex. The present study examined whether new brain imaging technologies could reveal in vivo, in adults with ASD, the manifestation of previously described histopathological changes. Using quantitative mapping at ultrahigh field (7 Tesla), we show that we can observe microstructural alterations in the right lateral orbitofrontal cortex and the bilateral amygdala in adult individuals with ASD in vivo. These imaging alterations point to an abnormal laminar cytoarchitecture and to an increased neuronal density, similar to what has been previously described in post‐mortem data in ASD. Our data demonstrate that it is possible to visualize, in vivo and at the individual level, alterations of cortical and subcortical microstructure in ASD. Future studies will be needed to extend these findings to a larger group of individuals and evaluate their association with symptomatology as well as their specificity among the different neurodevelopmental disorders.
Riluzole does not ameliorate disease caused by cytoplasmic TDP‐43 in a mouse model of amyotrophic lateral sclerosis
Authors: Wright Amanda L. , Della Gatta Paul A. , Le Sheng , Berning Britt A. , Mehta Prachi , Jacobs Kelly R. , Gul Hossai , San Gil Rebecca , Hedl Thomas J. , Riddell Winonah R. , Watson Owen , Keating Sean S. , Venturato Juliana , Chung Roger S. , Atkin Julie D. , Lee Albert , Shi Bingyang , Blizzard Catherine A. , Morsch Marco , Walker Adam K.
Published: August 2021

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease commonly treated with riluzole, a small molecule that may act via modulation of glutamatergic neurotransmission. However, riluzole only modestly extends lifespan for people living with ALS, and its precise mechanisms of action remain unclear. Most ALS cases are characterised by accumulation of cytoplasmic TAR DNA binding protein of 43 kDa (TDP‐43), and understanding the effects of riluzole in models that closely recapitulate TDP‐43 pathology may provide insights for development of improved therapeutics. We therefore investigated the effects of riluzole in female transgenic mice that inducibly express nuclear localisation sequence (NLS)‐deficient human TDP‐43 in neurons (NEFH‐tTA/tetO‐hTDP‐43ΔNLS, ‘rNLS8’, mice). Riluzole treatment from the first day of hTDP‐43ΔNLS expression did not alter disease onset, weight loss or performance on multiple motor behavioural tasks. Riluzole treatment also did not alter TDP‐43 protein levels, solubility or phosphorylation. Although we identified a significant decrease in GluA2 and GluA3 proteins in the cortex of rNLS8 mice, riluzole did not ameliorate this disease‐associated molecular phenotype. Likewise, riluzole did not alter the disease‐associated atrophy of hindlimb muscle in rNLS8 mice. Finally, riluzole treatment beginning after disease onset in rNLS8 mice similarly had no effect on progression of late‐stage disease or animal survival. Together, we demonstrate specific glutamatergic receptor alterations and muscle fibre‐type changes reminiscent of ALS in female rNLS8 mice, but riluzole had no effect on these or any other disease phenotypes. Future targeting of pathways related to accumulation of TDP‐43 pathology may be needed to develop better treatments for ALS.
A novel morphometric signature of brain alterations in type 2 diabetes: Patterns of changed cortical gyrification
Authors: Crisóstomo Joana , Duarte João V. , Moreno Carolina , Gomes Leonor , Castelo‐Branco Miguel
Published: August 2021

Type 2 diabetes is a chronic disease that creates atrophic signatures in the brain, including decreases of total and regional volume of grey matter, white matter and cortical thickness. However, there is a lack of studies assessing cortical gyrification in type 2 diabetes. Changes in this emerging feature have been associated mainly with genetic legacy, but environmental factors may also play a role. Here, we investigated alterations of the gyrification index and classical morphometric measures in type 2 diabetes, a late acquired disease with complex aetiology with both underlying genetic and more preponderant environmental factors. In this cross‐sectional study, we analysed brain anatomical magnetic resonance images of 86 participants with type 2 diabetes and 40 healthy control participants, to investigate structural alterations in type 2 diabetes, including whole‐brain volumetric measures, local alterations of grey matter volume, cortical thickness and the gyrification index. We found concordant significant decrements in total and regional grey matter volume, and cortical thickness. Surprisingly, the cortical gyrification index was found to be mainly increased and mainly located in cortical sensory areas in type 2 diabetes. Moreover, alterations in gyrification correlated with clinical data, suggesting an influence of metabolic profile in alterations of gyrification in type 2 diabetes. Further studies should address causal influences of genetic and/or environmental factors in patterns of cortical gyrification in type 2 diabetes.
Magnetic resonance imaging findings in focal‐onset status epilepticus
Authors: Sarria‐Estrada Silvana , Santamarina Estevo , Quintana Manuel , Pareto Deborah , Sueiras Maria , Auger Cristina , Toledo Manuel , Rovira Alex
Published: August 2021

Background and purpose

Magnetic resonance imaging (MRI) is commonly used in the diagnostic work‐up for status epilepticus (SE). The purpose of this study was to characterize MRI features in SE patients and determine their association with clinical and electroencephalography (EEG) findings. The mid‐term consequences of baseline MRI features were also analysed.

Methods

This is a prospective study including consecutive patients with SE who underwent brain MRI within 240 h after SE onset. The MRI protocol included T1‐weighted (T1WI), T2‐weighted (T2W), fluid‐attenuated inversion recovery (FLAIR) and diffusion‐weighted imaging (DWI) sequences. Follow‐up MRI was performed after SE resolution in some patients.

Results

Sixty patients (56.7% men, mean age 58.3 years) were included. SE‐related MRI abnormalities were seen in 31 (51.7%), manifesting as hyperintensities on T2W/FLAIR imaging (58.1%) and DWI (74.2%) sequences. Hippocampal and pulvinar involvement was seen in 58.0% and 25.8% of patients, respectively. MRI abnormalities were associated with a longer SE duration (p = 0.013) and the presence of lateralized periodic discharges (LPDs) on EEG (p < 0.001). Amongst the 33 follow‐up MRIs, nine (27.3%) showed mesial temporal sclerosis (MTS), which was associated with severe clinical status (p = 0.031), hippocampal oedema (p = 0.001) and LPDs (p = 0.001) at baseline. A poorer clinical outcome was associated with baseline T2W/FLAIR imaging hyperintensities (p = 0.003).

Conclusion

MRI showed abnormalities in more than half of SE patients. A longer SE duration and LPDs on EEG were associated with SE‐related MRI abnormalities and the development of MTS.
Phosphorus rather than nitrogen regulates ecosystem carbon dynamics after permafrost thaw
Authors: Yang Guibiao , Peng Yunfeng , Abbott Benjamin W. , Biasi Christina , Wei Bin , Zhang Dianye , Wang Jun , Yu Jianchun , Li Fei , Wang Guanqin , Kou Dan , Liu Futing , Yang Yuanhe
Published: August 2021

Ecosystem carbon (C) dynamics after permafrost thaw depends on more than just climate change since soil nutrient status may also impact ecosystem C balance. It has been advocated that nitrogen (N) release upon permafrost thaw could promote plant growth and thus offset soil C loss. However, compared with the widely accepted C‐N interactions, little is known about the potential role of soil phosphorus (P) availability. We combined 3‐year field observations along a thaw sequence (constituted by four thaw stages, i.e., non‐collapse and 5, 14, and 22 years since collapse) with an in‐situ fertilization experiment (included N and P additions at the level of 10 g N m−2 year−1 and 10 g P m−2 year−1) to evaluate ecosystem C‐nutrient interactions upon permafrost thaw. We found that changes in soil P availability rather than N availability played an important role in regulating gross primary productivity and net ecosystem productivity along the thaw sequence. The fertilization experiment confirmed that P addition had stronger effects on plant growth than N addition in this permafrost ecosystem. These two lines of evidence highlight the crucial role of soil P availability in altering the trajectory of permafrost C cycle under climate warming.
Land‐use change and biodiversity: Challenges for assembling evidence on the greatest threat to nature
Authors: Davison Charles W. , Rahbek Carsten , Morueta‐Holme Naia
Published: August 2021

Land‐use change is considered the greatest threat to nature, having caused worldwide declines in the abundance, diversity, and health of species and ecosystems. Despite increasing research on this global change driver, there are still challenges to forming an effective synthesis. The estimated impact of land‐use change on biodiversity can depend on location, research methods, and taxonomic focus, with recent global meta‐analyses reaching disparate conclusions. Here, we critically appraise this research body and our ability to reach a reliable consensus. We employ named entity recognition to analyze more than 4000 abstracts, alongside full reading of 100 randomly selected papers. We highlight the broad range of study designs and methodologies used; the most common being local space‐for‐time comparisons that classify land use in situ. Species metrics including abundance, distribution, and diversity were measured more frequently than complex responses such as demography, vital rates, and behavior. We identified taxonomic biases, with vertebrates well represented while detritivores were largely missing. Omitting this group may hinder our understanding of how land‐use change affects ecosystem feedback. Research was heavily biased toward temperate forested biomes in North America and Europe, with warmer regions being acutely underrepresented despite offering potential insights into the future effects of land‐use change under novel climates. Various land‐use histories were covered, although more research in understudied regions including Africa and the Middle East is required to capture regional differences in the form of current and historical land‐use practices. Failure to address these challenges will impede our global understanding of land‐use change impacts on biodiversity, limit the reliability of future projections and have repercussions for the conservation of threatened species. Beyond identifying literature biases, we highlight the research priorities and data gaps that need urgent attention and offer perspectives on how to move forward.
Impact of physical frailty on the clinical outcomes of older patients hospitalized for pneumonia
Authors: Yamada Kanji , Iwata Kentaro , Tachikawa Ryo , Yoshimura Yoshihiro , Kanejima Yuji , Yamamoto Akio , Ono Kumiko , Honda Akihiro , Kohara Nobuo , Tomii Keisuke , Ishikawa Akira , Kitai Takeshi
Published: August 2021

Aim

This study aimed to assess the association between physical frailty and clinical outcomes among older patients hospitalized for pneumonia.

Methods

This study examined 852 consecutive patients hospitalized for pneumonia between October 2018 and September 2020. Patients who were <65 years old, scheduled for admission, did not receive inpatient rehabilitation, or died during admission were excluded. A short physical performance battery (SPPB) test was performed by physical therapists upon discharge. The primary outcome measure was a composite endpoint of readmission or mortality due to any cause within 6 months of discharge.

Results

In total, 521 patients (median age, 80 years; interquartile range, 74–86 years) were included in the analyses, and were divided into the following two groups: robust group with SPPB scores >9 (n = 150), and physical frailty group with SPPB scores ≤9 (n = 371). Of these, 346 (66.4%) patients were men; and the median SPPB score was 6 (interquartile range, 1–10). During the median follow‐up period of 53 days (interquartile range, 4–180 days), 92 (17.6%) patients were readmitted and 25 (4.8%) patients died. Patients with physical frailty were at an increased risk for the primary endpoint (hazard ratio, 2.21; 95% confidence interval, 1.44–3.41; P < 0.001); the risk remained significant after adjusting for multiple variables (adjusted hazard ratio, 1.70; 95% confidence interval, 1.05–2.74; P = 0.028).

Conclusions

Among older patients with pneumonia, physical frailty status at discharge was an independent risk factor for readmission and mortality within 6 months after initial discharge. Geriatr Gerontol Int 2021; 21: 926–931.
Changes in pain profile of patients with haemophilia during 1‐year follow‐up
Authors: Krüger Steffen , Herzig Marie , Hilberg Thomas
Published: August 2021

Introduction

Patients with haemophilia (PwH) may experience increased sensitivity to pain. Based on the assessment of the somatosensory system, a recent study showed a specific pain profile in PwH when compared to controls by using Quantitative Sensory Testing (QST).

Aim

This study aimed to evaluate the pain profile of affected joints (knee or ankle joints) and a non‐affected site (dominant hand) in adult PwH over a 1‐year period.

Methods

Twenty‐four PwH (severe haemophilia A = 19, B = 3; moderate haemophilia A = 1, B = 1; age: 52±8 years) and 21 healthy controls (age: 52±12 years) were examined by QST. Both knee or ankle joints and the hand as reference were examined twice with an interval of 1 year in order to assess several detection (DT) and pain thresholds (PT).

Results

Statistically significant altered mechanical (P < .001) and pressure (P < .05) PT were found at affected joints and at a non‐affected site in PwH when compared to controls. Mechanical DT showed a significant increase at all assessed sites (e.g., at ankle joints PwH vs. controls at baseline/follow up in mN: 13.9±9.8 vs. 12.0±8.2/19.4±12.4 vs. 13.7±11.1; P < .01) in both cohorts. Nevertheless, changes in most parameters within 1 year occurred similarly in both groups.

Conclusion

The statistically significant different QST profile between PwH and controls does not seem to deteriorate further over the course of the year. Thus, under prophylactic treatment, the existing difference in the pain profile between PwH and controls at baseline does not appear to be a progressive process within 1 year.
Toxicity of ivermectin residues in aged farmyard manure to terrestrial and freshwater invertebrates
Authors: Sands Bryony , Noll Madeleine
Published: August 2021

Farmyard manure is often stored, aged and spread on fields as fertiliser; however, dung may be contaminated with residues of veterinary endectocides used to treat livestock for parasites. The persistence of these chemicals during storage and impact on invertebrate biodiversity after spreading are not well understood.

This study considered whether residues in aged cattle manure could have impacts on terrestrial and freshwater invertebrate biodiversity and ecosystem function.

Fresh cattle dung was spiked with known concentrations of the endectocide ivermectin or an excipient only (control) and aged in the field for 4 months between February and May 2020. Each month rainwater run‐off was collected and used to examine toxicity using the freshwater invertebrate Daphnia magna. In June 2020, manure was spread on mesocosms containing topsoil, and above‐ground insect emergence, soil fauna feeding rate, earthworm abundance and pasture productivity (perennial ryegrass growth), were measured over 10 weeks.

Rainwater‐runoff from manure contaminated with ivermectin was highly toxic (60–100% mortality) to D. magna for the entire 4 months of storage. Coleoptera and Diptera emergence was lower from mesocosms spread with ivermectin‐contaminated manure compared with control manure. Pasture productivity was significantly lower (18–20%) in mesocosms spread with ivermectin‐contaminated manure.

The results indicate that ivermectin residues aged manure have the potential to retain toxic effects on terrestrial and freshwater invertebrates for at least 4 months of storage, could reduce pasture productivity, and may have pervasive impacts on invertebrate biodiversity in agricultural systems.
COVID‐19 impact, knowledge and preparedness among dental hygienists in Saudi Arabia: A cross‐sectional study
Authors: Alkhalifah Futun N. , Tobbal Ayoub Y. , Fried Jacquelyn L.
Published: August 2021

Objectives

The study investigates the impact of COVID‐19 on dental hygiene professionals practising in Saudi Arabia, and measuring the knowledge and preparedness of dental hygienists to provide care during the pandemic.

Methods

A non‐experimental, cross‐sectional study was conducted targeting dental hygiene professionals in Saudi Arabia. The online survey consisted of 31 close‐ended questions: 9‐items related to demographics, and 22‐items that are COVID‐19 related. Data were tested at two levels; descriptive and preliminary using Chi‐square test, and significance was set at the 0.05 level.

Results

One hundred and thirty‐one responses were received and the final sample included one hundred and eighteen responses as it excluded unemployed dental hygienists with estimated 39.6% response rate. The stress level to return to practice was considered moderate among 65.3% of participants. Over two‐thirds (73.7%) of dental hygienists were not providing any kind of care/treatment during quarantine. Generally, a moderate level of knowledge (57.8%) was demonstrated by participants. For preparedness level to practice during the pandemic, sixty‐four dental hygienists (54.2%) were adequately prepared to provide care. Significant correlations were found between impact and knowledge (p = 0.045), impact and preparedness (p = 0.053), and knowledge and preparedness (p = 0.024).

Conclusions

Dissemination of COVID‐19 protocols, guidelines and scientific literature increased the respondents’ level of knowledge and preparedness to an adequate level. This study indicated that knowledgeable dental hygienists were significantly more prepared to treat patients during the pandemic and that stress positively influenced the COVID‐19 knowledge acquisition. Non‐practising dental hygienists during quarantine were more knowledgeable and more prepared to practice during the pandemic.
Level of patient comfort and measurement reproducibility of three different probes: A cross‐sectional study
Authors: Flores‐Rodrigo Daisy , Meza‐Mauricio Jonathan , Retamal‐Valdes Belen , Mayta‐Tovalino Frank , Mendoza‐Azpur Gerardo
Published: August 2021

Objective

To determine the comfort level and reproducibility assessment of the probing pocket depth obtained with three different probes.

Methods

A cross‐sectional clinical study was conducted in accordance with the STROBE standards. Three different types of periodontal probes were selected: (1) University of North Carolina (UNC) probe, (2) World health organization (WHO) probe and (3) UNC12 COLORVUE probe. Three experienced and calibrated periodontists performed periodontal clinical assessments (probing depth) and pain assessment with the visual analogue scale (VAS).

Results

The clinical evaluations were carried out in 13 volunteers who attended the dental clinic of the Universidad Científica del Sur (Lima, Peru). A total of 2106 periodontal clinical measurements were obtained (702 measurements per examiner). Each examiner evaluated 234 sites for each type of probe. When patient comfort values during the periodontal evaluation performed with the 3 types of probes were compared, the patients evaluated with the UNC12 COLORVUE probe perceived less pain with a mean value of 0.61, followed by the WHO probe and the UNC probe. When evaluating the clinical measurements, the UNC probe was observed to obtain the greatest mean depth on probing 1.4 + 0.5 mm, while with the UNC12 Colorvue probe, the values obtained were 1.1 + 0.3 mm, and with the WHO probe, 1.2 + 0.4 mm.

Conclusions

Based on the periodontal probe used, experience of the examiner and the patient, we can conclude that the UNC12 Colorvue probe was the instrument that promoted the greatest comfort or the slightest response to pain, followed by the WHO probe. However, the use of the WHO probe resulted in obtaining the lowest reproducibility among depths on probing. The UNC probe produced the highest response to pain in the patients.
Fabrication and characterization of Nb2O5‐doped 3Y‐TZP materials sintered by microwave technology
Authors: Guillén Pineda René M. , Salvador María D. , Gutiérrez‐González Carlos F. , Catalá‐Civera Jose M. , Borrell Amparo
Published: August 2021

The purpose of this research is focused on the manufacture and characterization of a partially stabilized zirconia ceramic with 3 mol% of Yttria and doped with .5 and 1.5 mol% of Nb2O5 to analyze the influence of doping, with the purpose of improving the properties before hydrothermal degradation. In the first instance, the microwave sintering process was used for the consolidation of this material, then the physical and mechanical properties were characterized. Together, the results obtained by the conventional sintering process were compared. A low hydrothermal degradation study (LTD) is presented at low temperatures in which possible changes in the mechanical properties of the ceramic materials are analyzed and its influence on the phase transformation that zirconia may present is observed. The mechanical properties were evaluated through hardness, fracture toughness, and Young's modulus tests. Likewise, their density was analyzed, and microstructure was characterized by FESEM. It was found that the microwave‐sintered samples at 1200°C exhibited superior properties of toughness than even samples sintered by conventional methods at higher temperatures (1400°C). The sample of 3Y‐TZP with 1.5 mol% Nb2O5 sintered by microwave with <.2% of porosity achieved a maximum fracture toughness value around 40% higher than the dense monolithic 3Y‐TZP material.
Dose‐effect relationship between brisk walking and blood pressure in Chinese occupational population with sedentary lifestyles
Authors: YU Yingxiang , CHANG Cuiqing , WU Yifan , GUO Chengcheng , XIE Lan
Published: August 2021

The purpose of this study was to explore the effects of brisk walking on blood pressure (BP) in Chinese Han occupational populations to identify the appropriate volume of exercise needed for BP management. Eight‐hundred and two office staff with sedentary lifestyles were recruited to receive a prescription pedometer‐assisted brisk walking intervention for 3 months. To evaluate exercise intervention efficiency using statistical methods, the effective steps was divided as follows: 4000‐ < 8000 (Level 1), 8000‐ < 10 000 (Level 2), 10 000–12 000 (Level 3), and > 12 000 (Level 4) steps/day. The data of 688 participants who completed the study were analyzed. After intervention, Systolic BP (SBP) and Diastolic BP (DBP) at Levels 1–3 were significantly decreased (p < .05). For participants with hypertension at baseline, all four levels demonstrated a significantly reduced SBP and DBP. In addition, there was a significant dose‐effect relationship between the effective steps and the SBP. Compared with the maximum effective steps level (Level 4), the average change of SBP between level 1–3 and level 4 were statistically significant, with ‐3.24 mm Hg (95%CI: ‐5.74 to ‐0.74, p = .011), ‐2.58 mm Hg (95%CI: ‐4.73 to ‐0.43, p = .019), and ‐2.19 mm Hg (95%CI: ‐4.20 to ‐0.18, p = .033), respectively. For the hypertensive cohort, only the difference between Level 1 and 4 was statistically significant (Level 1 vs. Level 4: difference in means = ‐6.22 mm Hg, 95%CI: ‐12.68 to ‐0.24, p = .036). No significant dose‐effect relationship of DBP was observed. Our findings showed brisk walking can effectively control BP in Chinese populations and a significant dose‐effect relationship was found between exercise and SBP.
Gonadal morphology and difference in reproductive development of two isolated populations of Astyanax rivularis (Teleostei, Characidae)
Authors: Quirino Patricia Postingel , de Siqueira‐Silva Diógenes Henrique , da Silva Rodrigues Maira , dos Santos‐Silva Amanda Pereira , Delgado Maria Luiza Ribeiro , Senhorini José Augusto , Ninhaus‐Silveira Alexandre , Veríssimo‐Silveira Rosicleire
Published: August 2021

Individuals of the same species may present different reproductive tactics depending on the environment in which they develop and mature. The present study aimed to define the gonadal development phases of males and females of Astyanax rivularis and to carry out a comparative analysis of the reproductive development of specimens captured in two isolated environments of the São Francisco River basin in Serra da Canastra, Brazil (Point 1: low vegetation and river showing calm and crystalline waters with small well formations; Point 2: current waters, and well‐established areas of arboreal vegetation). Thus, the gonads of A. rivularis specimens were collected, fixed and processed with techniques for light microscopy. Five maturation phases of the females' reproductive cycle were established: immature, developing, spawning capable, regressing and regenerating. Three maturation phases of the males' reproductive cycle were observed: spawning capable, regressing, and regenerating. There are differences in the phases of gonadal development of A. rivularis between the two sampling points so that, possibly, animals upstream of the waterfall demonstrate a delay in the reproductive cycle in relation to animals downstream.
Immersion vaccines against Yersinia ruckeri infection in rainbow trout: Comparative effects of strain differences
Authors: Yang He , Zhujin Ding , Marana Moonika H. , Dalsgaard Inger , Rzgar Jaafar , Heidi Mathiessen , Asma Karami M. , Per Kania W. , Kurt Buchmann
Published: August 2021

The protective effects of autogenous and commercial ERM immersion vaccines (bacterins based on Yersinia ruckeri, serotype O1, biotypes 1 and 2) for rainbow trout (Oncorhynchus mykiss) were compared in order to evaluate whether the use of local pathogen strains for immunization can improve protection. In addition, the effect of the bacterin concentration was established for the commercial product. Following sublethal challenge of vaccinated and non‐vaccinated control fish with live bacteria, we followed the bacterial count in the fish (gills, liver and spleen). The expression of genes encoding immune factors (IL‐1β, IL‐6, IL‐8, IL‐10, IFN‐γ, MHCI, MHCII, CD4, CD8, TCRβ, IgM, IgT, IgD, cathelicidins 1 and 2, SAA and C3) and densities of immune cells in organs were recorded. Both vaccines conferred protection as judged from the reduced bacterial load in exposed fish. Innate immune genes were upregulated in all groups following bacterial challenge but significantly more in non‐vaccinated naive fish in which densities of SAA‐positive immune cells increased. Immunoglobulin genes were upregulated on day 5 post‐challenge, and fish vaccinated with the high commercial bacterin dosage showed increased IgM levels by ELISA on day 14 post‐challenge, reflecting that the vaccine dosage was correlated to protection. In conclusion, both vaccine types offered protection to rainbow trout when exposed to live Y. ruckeri and no significant difference between commercial and autogenous vaccines was established.
Finding a way to live with the past: ‘self‐repair’, ‘informal repair’, and reparations in transitional justice
Authors: GILMORE SUNNEVA , MOFFETT LUKE
Published: August 2021

Reparations are widely regarded as a key element of dealing with the past in transitional justice. Over the past three decades, there has been a plethora of state practice, jurisprudence, and international norms requiring states and other responsible actors to redress victims’ harm. Yet in practice there remain significant deficiencies in delivering reparations on the ground to those affected. This article explores what victims and their civil society allies do to manage their suffering in the absence of or delay to reparations. Drawing upon fieldwork in seven societies transitioning from conflict, we suggest that victims find their own way to live with the past as they await reparations, through ‘self‐repair’ measures or through ‘informal repair’ provided by non‐governmental organizations. This alternative perspective aims to shed light on victims’ agency and resilience, as well as to critique notions of state dependence that a needs and rights discourse often encourages with victims. We also argue that victims’ self‐repair strategies and informal pathways can complement more formal measures, and be conducive to victims making the most of state‐based reparation programmes.
Identification and characterization ofColletotrichum brevisporumandC. truncatumcausing papaya anthracnose in the Philippines
Authors: Laurel Niño R. , Magdalita Pablito M. , Dela Cueva Fe M.
Published: August 2021

Papaya (Carica papayaL.) fruits showing typical anthracnose lesions were collected from Los Baños, Laguna, Philippines. Infected fruits showed brown to black, sunken water‐soaked lesions with salmon‐ and black‐coloured acervuli. Fungal pathogens were isolated from the fruit samples, plated on potato dextrose agar (PDA) and purified for subsequent analyses. A total of sixColletotrichumisolates were subjected to morphological assessment and were divided into two morphotypes (I and II). Morphotype I produced conidia which were hyaline, fusiform with obtuse ends, while Morphotype II produced conidia which were hyaline, falcate with pointy ends. For phylogenetic analysis, sequence analysis of the internal transcribed spacer (ITS) region, glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), actin (ACT) and chitin synthase‐1 (CHS‐1) was performed and resulted in two well‐supported and distinct clades. All test isolates were pathogenic in the detached fruit assay, and the same isolates were successfully re‐isolated from the symptomatic fruit samples, thereby fulfilling Koch's postulate. The results of the phylogenetic analysis, morphological assessment and pathogenicity testing confirmed the identity of the isolates asC. brevisporumandC. truncatum. To our knowledge, this is the first confirmed report of the two new species associated with papaya anthracnose in the Philippines.
Melatonin reduces nanoplastic uptake, translocation, and toxicity in wheat
Authors: Li Shuxin , Guo Junhong , Wang Tianya , Gong Lei , Liu Fulai , Brestic Marian , Liu Shengqun , Song Fengbin , Li Xiangnan
Published: August 2021

With increasing plastic production and consumption, large amounts of polystyrene nanoplastics are accumulated in soil due to improper disposal causing pollution and deleterious effects to environment. However, little information is available about how to alleviate the adverse impacts of nanoplastics on crops. In this study, the involvement of melatonin in modulating nanoplastic uptake, translocation, and toxicity in wheat plant was investigated. The results demonstrated that exogenous melatonin application reduced the nanoplastic uptake by roots and their translocation to shoots via regulating the expression of genes associated with aquaporin, including the upregulation of the TIP2‐9, PIP2, PIP3, and PIP1.2 in leaves and TIP2‐9, PIP1‐5, PIP2, and PIP1.2 in roots. Melatonin activated the ROS scavenging system to maintain a better redox homeostasis and ameliorated the negative effects of nanoplastics on carbohydrate metabolism, hence ameliorated the plant growth and enhanced the tolerance to nanoplastics toxicity. This process was closely related to the exogenous melatonin application induced melatonin accumulation in leave. These results suggest that melatonin could alleviate the adverse effects of nanoplastics on wheat, and exogenous melatonin application might be used as a promising management strategy to sustain crop production in the nanoplastic‐polluted soils.
Hepatocellular carcinoma risk in hepatitis C stage‐3 fibrosis after sustained virological response with direct‐acting antivirals
Authors: Sánchez‐Azofra María , Fernández Inmaculada , García‐Buey María L. , Domínguez‐Domínguez Lourdes , Fernández‐Rodríguez Conrado M. , Mancebo Antonio , Bonet Lucía , Ryan Pablo , Gea Francisco , Díaz‐Sánchez Antonio , García‐Mayor Marian , Martín‐Carbonero Luz , Castillo Pilar , Manzano María L. , González‐Moreno Leticia , Pulido Federico , Gutiérrez María L. , Moreno José M. , García‐Amengual Irene M. , Cuevas Guillermo , Guerrero Antonio , Rivero‐Fernández Miguel , Portales María E. , Montes María L. , Olveira Antonio
Published: August 2021

Background & Aims

Patients with chronic hepatitis C and stage 3 fibrosis are thought to remain at risk of hepatocellular carcinoma after sustained virological response. We investigated this risk in a large cohort of patients with well‐defined stage 3 fibrosis.

Methods

We performed a multicentre, ambispective, observational study of chronic hepatitis C patients with sustained virological response after treatment with direct‐acting antivirals started between January and December 2015. Baseline stage 3 was defined in a two‐step procedure: we selected patients with transient elastography values of 9.5‐14.5 kPa and subsequently excluded those with nodular liver surface, splenomegaly, ascites or collaterals on imaging, thrombopenia or esophago‐gastric varices. Patients were screened twice‐yearly using ultrasound.

Results

The final sample comprised 506 patients (median age, 57.4 years; males, 59.9%; diabetes, 17.2%; overweight, 44.1%; genotype 3, 8.9%; HIV coinfection, 18.4%; altered liver values, 15.2%). Median follow‐up was 33.7 (22.1‐39.1) months. Five hepatocellular carcinomas and 1 cholangiocarcinoma were detected after a median of 29.4 months (95% CI: 26.8‐39.3), with an incidence of 0.47/100 patients/year (95% CI: 0.17‐1.01). In the multivariate analysis, only males older than 55 years had a significant higher risk (hazard ratio 7.2 [95% CI: 1.2‐41.7; P = .029]) with an incidence of 1.1/100 patients/year (95% CI: 0.3‐2.8).

Conclusions

In a large, well‐defined cohort of patients with baseline hepatitis C stage‐3 fibrosis, the incidence of primary liver tumours was low after sustained virological response and far from the threshold for cost‐effectiveness of screening, except in males older than 55 years.
Management, outcomes and survival of an Australian IgG4‐SC cohort: The MOSAIC study
Authors: Kemp William , Majeed Ammar , Mitchell Joanne , Majumdar Avik , Tse Edmund , Skoien Richard , Croagh Daniel , Dev Anouk , Gao Hugh , Weltman Martin , Craig Philip , Stuart Katherine , Cheng Wendy , Edmunds Simon , Lee Eric , Sood Siddharth , Metz Andrew , Thompson Alexander , Sinclair Marie , Beswick Lauren , Nicoll Amanda , Riordan Stephen , Braund Alicia , Muller Kate , MacQuillan Gerry , Sandanayake Neomal , Shackel Nicholas , Roberts Stuart Keith
Published: August 2021

Background and Aims

IgG4 sclerosing cholangitis (IgG4‐SC) is the biliary component of the multisystem IgG4‐related disease. We aimed to investigate the clinical features, demographics, treatment response and outcomes of IgG4‐SC in a large Australian cohort.

Methods

We conducted nationwide retrospective cohort via the Australian Liver Association Clinical Trials Network (ALA‐CRN). 39 sites were invited to participate. IgG4‐SC was defined by the clinical diagnostic criteria established by the Japanese Biliary Association in 2012. Data were collected on patient demographic, clinical and laboratory information, presenting features, response to therapy and clinical outcomes.

Results

67 patients meet inclusion criteria from 22 sites. 76% were male with mean age of 63.3 ± 14.5 years and a median IgG4 level of 3.6 g/L [0.09‐67.1]. The most frequent presenting symptom was jaundice (62%) and abdominal pain (42%) and Type 1 biliary stricturing (52%) at the distal common bile duct was the most frequent biliary tract finding. Prednisolone was used as a primary treatment in 61 (91%) and partial or complete response occurred in 95% of subjects. Relapse was common (42%) in those who ceased medical therapy. After a median follow up of 3.9 years there was one hepatocellular carcinoma and no cholangiocarcinomas.

Conclusions

Our study confirms the preponderance of IgG4‐SC in males and highlights the steroid response nature of this condition although relapse is common after steroid cessation. Progression to malignancy was uncommon.
Population structure, genomic diversity and demographic history of Komodo dragons inferred from whole‐genome sequencing
Authors: Iannucci Alessio , Benazzo Andrea , Natali Chiara , Arida Evy Ayu , Zein Moch Samsul Arifin , Jessop Tim S. , Bertorelle Giorgio , Ciofi Claudio
Published: August 2021

Population and conservation genetics studies have greatly benefited from the development of new techniques and bioinformatic tools associated with next‐generation sequencing. Analysis of extensive data sets from whole‐genome sequencing of even a few individuals allows the detection of patterns of fine‐scale population structure and detailed reconstruction of demographic dynamics through time. In this study, we investigated the population structure, genomic diversity and demographic history of the Komodo dragon (Varanus komodoensis), the world's largest lizard, by sequencing the whole genomes of 24 individuals from the five main Indonesian islands comprising the entire range of the species. Three main genomic groups were observed. The populations of the Island of Komodo and the northern coast of Flores, in particular, were identified as two distinct conservation units. Degrees of genomic divergence among island populations were interpreted as a result of changes in sea level affecting connectivity across islands. Demographic inference suggested that Komodo dragons probably experienced a relatively steep population decline over the last million years, reaching a relatively stable Ne during the Saalian glacial cycle (400–150 thousand years ago) followed by a rapid Ne decrease. Genomic diversity of Komodo dragons was similar to that found in endangered or already extinct reptile species. Overall, this study provides an example of how whole‐genome analysis of a few individuals per population can help define population structure and intraspecific demographic dynamics. This is particularly important when applying population genomics data to conservation of rare or elusive endangered species.
Circadian and circatidal rhythms of protein abundance in the California mussel (Mytilus californianus)
Authors: Elowe Cory , Tomanek Lars
Published: August 2021

Coastal habitats fluctuate with the 12.4 h tidal and 24 h light/dark cycle to predictably alter conditions such as air exposure, temperature, and food availability. Intertidal sessile bivalves exhibit behavioural and physiological adjustments to minimize the challenges of this environment. We investigated a high‐resolution time course of the changes in protein abundance in the gill tissue of the intertidal mussel Mytilus californianus in a simulated tidal environment of 12:12 h light:dark cycles and a matching 6:6 h high:low tide cycle within each 12 h period. Approximately 38% of detected proteins showed significant rhythms in their abundances, with diversity in the phases of rhythmic isoforms. The circadian rhythm was dominant in protein abundance changes, particularly with oxidative metabolism. A tidal cycle elicited changes within functional groups, including in cytoskeletal proteins, chaperones, and oxidative stress proteins. In addition to protein abundance changes, we found the possibility for post‐translational modifications driving rhythms, including methylation, mitochondrial peptide processing (proteolysis), and acylation. Dynamic changes in the proteome across functional categories demonstrate the importance of the tidal environment in entraining cellular processes, confirming that differential expression studies should not assume a static baseline of cellular conditions in intertidal organisms.
Hydroxybenzoate hydroxylase genes underlying protocatechuic acid production in Valsa mali are required for full pathogenicity in apple trees
Authors: Meng Lulu , Sun Cuicui , Gao Liyong , Saleem Muhammad , Li Baohua , Wang Caixia
Published: August 2021

Valsa mali is the causative agent of apple tree valsa canker, which causes significant losses in apple production. It produces various toxic compounds that kill plant cells, facilitating infection. Among these, protocatechuic acid exhibits the highest phytotoxic activity. However, those genes involved in toxin production have not been studied. In this study we identified four hydroxybenzoate hydroxylase genes (VmHbh1, VmHbh2, VmHbh3, and VmHbh4) from the transcriptome of V. mali. The VmHbh protein had high enzymatic activities of hydroxybenzoate hydroxylase, which could convert 4‐hydroxybenzoate to protocatechuic acid. These four VmHbh genes all had highly elevated transcript levels during the V. mali infection process, especially VmHbh1 and VmHbh4, with 26.0‐ and 53.4‐fold increases, respectively. Mutants of the four genes were generated to study whether VmHbhs are required for V. mali pathogenicity. Of the four genes, the VmHbh1 and VmHbh4 deletion mutants considerably attenuated V. mali virulence in apple leaves and in twigs, coupled with much reduced toxin levels. The VmHbh2 and VmHbh3 deletion mutants promoted the transcript levels of the other VmHbhs, suggesting functional redundancies of VmHbhs in V. mali virulence. The results provide insights into the functions of VmHbhs in the production of protocatechuic acid by V. mali during its infection of apple trees.
Treatment preferences for primary membranous nephropathy: Results of a multinational survey among nephrologists in the South Asia Pacific region
Authors: Bose Bhadran , Badve Sunil V. , Johnson David W. , Hawley Carmel , Jha Vivekanand , Reidlinger Donna , Peh Chen Au
Published: August 2021

Aim

There is no clear consensus on how best to treat primary membranous nephropathy (PMN). This study aimed to ascertain prevailing views among nephrologists on their choice of immunosuppressive agents to treat this disease.

Methods

The Australasian Kidney Trials Network conducted a multinational online survey among nephrologists from the South Asia‐Pacific region to identify prescribing practices to treat PMN. Survey questions focused on the types of immunosuppressive therapies used, preferred first‐line and second‐line therapies, indications for starting immunosuppressive therapy, the preferred mode of combining corticosteroid and cyclophosphamide, the use of serum phospholipase A2 receptor antibody testing in clinical practice, indications for anticoagulation, and interest in participating in future clinical trials in PMN.

Results

One hundered fifty‐five nephrologists from eight countries responded to the online survey. The majority of them were senior nephrologists from Australia and India with significant experience managing patients with PMN. The combination of cyclophosphamide and corticosteroid was the preferred first‐line therapy. Of those who used this combination, only 34.8% followed the Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines by adding intravenous methylprednisolone. The combination of calcineurin inhibitor with corticosteroid was the most common second‐line therapy. Most respondents considered prophylactic anticoagulation if serum albumin was less than 25 g/L. Most nephrologists were keen to participate in a clinical trial with a control arm consisting of cyclophosphamide and corticosteroids.

Conclusion

The combination of corticosteroid with cyclophosphamide (without intravenous methylprednisolone) is the most commonly reported first‐line immunosuppressive therapy for the management of PMN.
Oral/oesophageal candidiasis is a risk factor for severe infection after kidney transplantation
Authors: Abe Tetsuya , Futamura Kenta , Goto Norihiko , Ohara Kiyomi , Ogasa Taiki , Tomosugi Toshihide , Okada Manabu , Hiramitsu Takahisa , Narumi Shunji , Watarai Yoshihiko
Published: August 2021

Aim

Bacterial and fungal infections are serious, life‐threatening conditions after kidney transplantation. The development of oral/oesophageal candidiasis after kidney transplantation is not a reported risk factor for subsequent severe infection. This study was performed to investigate the relationship between oral/oesophageal candidiasis after kidney transplantation and the development of subsequent infection requiring hospitalization.

Methods

This retrospective study included 522 consecutive patients who underwent kidney transplantation at Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital from 1 January 2010 to 1 February 2019. Ninety‐five percentage of patients were living donor transplant recipients. Visual examination was performed to detect oral candidiasis, beginning immediately after kidney transplantation; upper gastrointestinal endoscopy was performed 8–10 months after kidney transplantation. Twenty‐five patients developed candidiasis (Candida‐onset group) and 497 did not (non‐Candida‐onset group). The follow‐up periods were 67 (37–86) months in the Candida‐onset group and 55 (34–89) months in the non‐Candida‐onset group. Severe infection was defined as bacterial or fungal infection requiring hospitalization; viral infections were excluded.

Results

Severe infection developed in 9/25 (36%) patients in the Candida‐onset group and in 77/497 (15%) patients in the non‐Candida‐onset group (p = .006). Binomial logistic analysis revealed that Candida infection (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.06–6.06; p = .037) and use of rituximab (OR 1.81, 95% CI 1.12–2.93; p = .016) were significant predictors of subsequent severe infection.

Conclusion

Oral/oesophageal candidiasis is a risk factor for severe infection after kidney transplantation and suggests an over‐immunosuppressive state, which should prompt evaluation of immunosuppression.