bluuebunny/crossref_metadata_2025 huggingface dataset:
Puerarin prevents cadmium‐induced disorder of testicular lactic acid metabolism in rats by activating 5′AMP‐activated protein kinase (AMPK)/sirtuin 1 (SIRT1) signaling pathway
Authors: Dong Wenxuan , Zhang Kanglei , Liu Gang , Tan Yun , Zou Hui , Yuan Yan , Gu Jianhong , Song Ruilong , Zhu Jiaqiao , Liu Zongping
Published: January 2021

Cadmium (Cd) interferes with the function of the male reproductive system; however, the molecular mechanism is poorly understood. This study aimed to evaluate the effect of puerarin (PU) on Cd‐induced testicular lactic acid metabolism disorder. Weaning male Sprague–Dawley rats were pre‐fed for 7 days, weighed, and randomly divided into four groups: Control group, CdAc2group, CdAc2 + PU group, PU group. The results showed that Cd accumulated in the testis, the testicles became congested and shrank, and the testis index decreased in the rats treated in the CdAc2group. Cadmium exposure reduced the serum concentration of testosterone, and the concentration of lactic acid and pyruvate in the testis. Cd decreased testicular superoxide dismutase activity and total antioxidant capacity, and increased testicular malondialdehyde levels. Cd reduced the level of ATP, glycolytic gene expression, and lactate production‐related proteins in the testis. Cd also decreased the expression of 5′ AMP‐activated protein kinase (AMPK)/sirtuin 1 (SIRT1) signaling pathway‐related proteins in the testis. However, these negative effects were attenuated by PU administration. In summary, Cd reduces the production of lactic acid in the testis of rats, while PU administration restores the production of lactic acid and reduces the toxicity of Cd to the testis of rats.
Erratum to: Asymptotic flux compactifications and the swampland
Authors: Grimm Thomas W. , Li Chongchuo , Valenzuela Irene
Published: January 2021

In the original paper a wrong affiliation has been assigned to author Chongchuo Li during the typesetting.
Movements of green turtles from foraging areas of the United Arab Emirates: regional habitat connectivity and use of marine protected areas
Authors: Pilcher Nicolas James , Antonopoulou Marina A. , Rodriguez-Zarate Clara Jimena , Mateos-Molina Daniel , Das Himansu Sekhar , Bugla Ibrahim , Al Ghais Saif Mohammed
Published: January 2021

Adult sea turtles migrate between foraging areas and nesting sites that may be 100 s–1000 s of km away. Little is known of the connectivity between these sites in the Arabian region for green sea turtles. We document linkages between two foraging areas in the United Arab Emirates (UAE) with key nesting sites and provide insights on effectiveness of marine protected areas for green sea turtles. Tracking 45 adult green sea turtlesChelonia mydasfrom foraging areas in the UAE, we show that the primary nesting destination for turtles foraging in Bu Tinah in the UAE is Ras al Hadd in Oman. The turtles use the waters of the UAE, Iran and Oman during breeding migrations and generally stay ~ 20 km off the coast, in waters 10–20 m deep except when crossing the Sea of Oman. Turtles display substantial fidelity to the original foraging sites, often traversing other known foraging sites when returning from the breeding migration. A small proportion of turtles also utilise more than one foraging site. Our data indicate that the Marawah Marine Biosphere Reserve in Abu Dhabi is broadly coincident with the foraging areas of turtles offering substantial protection from fishery activities and that the marine protected area in Ras Al Khaimah would be more effective in protecting green sea turtles if it extended offshore and along the coast. These data may contribute to targeted and effective national and international management and conservation initiatives in the Arabian region.
Impact of changes in controlled drugs legislation on benzodiazepine receptor agonist prescribing in Ireland: a repeated cross-sectional study
Authors: Cadogan Cathal A. , Bradley Colin P. , Bennett Kathleen
Published: January 2021

Purpose

To examine the impact of new controlled drugs legislation introduced in May 2017 on benzodiazepine receptor agonist (BZRA) prescribing in Ireland.

Methods

A repeated cross-sectional analysis was conducted using publically available monthly pharmacy claims data from the General Medical Services (GMS) database. The study population comprised all GMS-eligible individuals aged ≥ 16 years from January 2016 to September 2019. Monthly prevalence rates of individuals receiving BZRA prescriptions per 10,000 eligible population were calculated and trends examined over time. Segmented linear regression of prevalence rates was used to examine changes before and after introduction of the legislation stratified by gender and age groups. Regression coefficients (β) and 95% confidence intervals (CIs) for monthly change were calculated.

Results

Pre-legislation (January 2016 to April 2017), there was a significant monthly decline in benzodiazepine prevalence rate (β = − 1.18; 95% CI − 1.84, − 0.51; p < 0.001) but no significant change in Z-drug prescribing. Post-legislation (May 2017 to September 2019), increases in prevalence rates were observed for benzodiazepines (β = 1.04; 95% CI 0.17, 1.92; p = 0.021) and Z-drugs (β = 1.04; 95% CI 0.26, 1.83; p = 0.010). Post-legislation trends showed increases in BZRA prevalence rates among the youngest subgroup (16–44 years), with variable changes in the middle-aged subgroup (45–64 years) and no changes in the oldest subgroup (≥ 65 years).

Conclusions

This study indicates that introduction of new legislation had limited impact on BZRA prescribing on the main public health scheme in Ireland. Interventions targeting specific population subgroups may be required to achieve sustained reductions in prescribing.
Safety and efficacy of tolcapone in Parkinson’s disease: systematic review
Authors: Artusi Carlo Alberto , Sarro Lidia , Imbalzano Gabriele , Fabbri Margherita , Lopiano Leonardo
Published: January 2021

Purpose

Tolcapone is an efficacious catechol-O-methyltransferase inhibitor for Parkinson’s disease (PD). However, safety issues hampered its use in clinical practice. We aimed to provide evidence of safety and efficacy of tolcapone by a systematic literature review to support clinicians’ choices in the use of an enlarging PD therapeutic armamentarium.

Methods

We searched PubMed for studies on PD patients treated with tolcapone, documenting the following outcomes: liver enzyme, adverse events (AEs), daily Off-time, levodopa daily dose, unified Parkinson’s disease rating scale (UPDRS) part-III, quality of life (QoL), and non-motor symptoms. FAERS and EudraVigilance databases for suspected AEs were interrogated for potential additional cases of hepatotoxicity.

Results

Thirty-two studies were included, for a total of 4780 patients treated with tolcapone. Pertaining safety, 0.9% of patients showed liver enzyme elevation > 2. Over 23 years, we found 7 cases of severe liver injury related to tolcapone, 3 of which were fatal. All fatal cases did not follow the guidelines for liver function monitoring. FAERS and EudraVigilance database search yielded 61 reports of suspected liver AEs possibly related to tolcapone.

Pertaining efficacy, the median reduction of hours/day spent in Off was 2.1 (range 1–3.2), of levodopa was 108.9 mg (1–251.5), of “On” UPDRS-III was 3.6 points (1.1–6.5). Most studies reported a significant improvement of QoL and non-motor symptoms.

Conclusion

Literature data showed the absence of relevant safety concerns of tolcapone when strict adherence to hepatic function monitoring is respected. Given its high efficacy on motor fluctuations, tolcapone is probably an underutilized tool in the therapeutic PD armamentarium.
Feasibility of generalised diffusion kurtosis imaging approach for brain glioma grading
Authors: Pogosbekian E. L. , Pronin I. N. , Zakharova N. E. , Batalov A. I. , Turkin A. M. , Konakova T. A. , Maximov I. I.
Published: January 2021

Purpose

An accurate differentiation of brain glioma grade constitutes an important clinical issue. Powerful non-invasive approach based on diffusion MRI has already demonstrated its feasibility in glioma grade stratification. However, the conventional diffusion tensor (DTI) and kurtosis imaging (DKI) demonstrated moderate sensitivity and performance in glioma grading. In the present work, we apply generalised DKI (gDKI) approach in order to assess its diagnostic accuracy and potential application in glioma grading.

Methods

Diffusion scalar metrics were obtained from 50 patients with different glioma grades confirmed by histological tests following biopsy or surgery. All patients were divided into two groups with low- and high-grade gliomas as grade II versus grades III and IV, respectively. For a comparison, trained radiologists segmented the brain tissue into three regions with solid tumour, oedema, and normal appearing white matter. For each region, we estimated the conventional and gDKI metrics including DTI maps.

Results

We found high correlations between DKI and gDKI metrics in high-grade glioma. Further, gDKI metrics enabled introduction of a complementary measure for glioma differentiation based on correlations between the conventional and generalised approaches. Both conventional and generalised DKI metrics showed quantitative maps of tumour heterogeneity and oedema behaviour. gDKI approach demonstrated largely similar sensitivity and specificity in low-high glioma differentiation as in the case of conventional DKI method.

Conclusion

The generalised diffusion kurtosis imaging enables differentiation of low- and high-grade gliomas at the same level as the conventional DKI. Additionally, gDKI exhibited higher sensitivity to tumour heterogeneity and tissue contrast between tumour and healthy tissue and, thus, may contribute as a complementary source of information on tumour differentiation.
Improved amyloid burden quantification with nonspecific estimates using deep learning
Authors: Liu Haohui , Nai Ying-Hwey , Saridin Francis , Tanaka Tomotaka , O’ Doherty Jim , Hilal Saima , Gyanwali Bibek , Chen Christopher P. , Robins Edward G. , Reilhac Anthonin
Published: January 2021

Purpose

Standardized uptake value ratio (SUVr) used to quantify amyloid-β burden from amyloid-PET scans can be biased by variations in the tracer’s nonspecific (NS) binding caused by the presence of cerebrovascular disease (CeVD). In this work, we propose a novel amyloid-PET quantification approach that harnesses the intermodal image translation capability of convolutional networks to remove this undesirable source of variability.

Methods

Paired MR and PET images exhibiting very low specific uptake were selected from a Singaporean amyloid-PET study involving 172 participants with different severities of CeVD. Two convolutional neural networks (CNN), ScaleNet and HighRes3DNet, and one conditional generative adversarial network (cGAN) were trained to map structural MR to NS PET images. NS estimates generated for all subjects using the most promising network were then subtracted from SUVr images to determine specific amyloid load only (SAβL). Associations of SAβL with various cognitive and functional test scores were then computed and compared to results using conventional SUVr.

Results

Multimodal ScaleNet outperformed other networks in predicting the NS content in cortical gray matter with a mean relative error below 2%. Compared to SUVr, SAβL showed increased association with cognitive and functional test scores by up to 67%.

Conclusion

Removing the undesirable NS uptake from the amyloid load measurement is possible using deep learning and substantially improves its accuracy. This novel analysis approach opens a new window of opportunity for improved data modeling in Alzheimer’s disease and for other neurodegenerative diseases that utilize PET imaging.
Does the appearance of the cutaneous scar after cesarean section reflect the residual myometrial thickness?
Authors: Al Naimi Ammar , Mouzakiti Niki , Eißmann Carmen , Louwen Frank , Bahlmann Franz
Published: January 2021

Purpose

The aim of this study is to utilize the Manchester scar scale (MSS) and ultrasound in investigating the association between uterine wall defects and cutaneous scar characteristics after cesarean section (CS).

Methods

This is a prospective cohort study. The degree of myometrial loss was quantified by calculating a residual myometrial thickness (RMT) ratio as a percentage of RMT to the pre-cesarean anterior uterine wall thickness. Cutaneous scar assessment was performed according to the MSS. Spearman’s correlation and the Kruskal–Wallis test with a cut-off value of p < 0.05 were used for statistical analysis.

Results

Two hundred forty seven women, of which 2.4% had an Asian, 3.6% an Afro-American, 82% a Caucasian and 12% a Mediterranean background, were recruited. The RMT ratio ranged between 11.9 and 100% with a median of 55.8% and an average of 56%. MSS scores ranged from 4 to 13 with a median of 5 and an average of 6. Spearman’s correlation between MSS and RMT ratio show a rho of − 0.01 with a p value of 0.8. The correlation between MSS and RMT ratio within the four ethnical groups showed a p value between 0.3 and 0.8 and a rho between 0.8 and − 0.8. The Kruskal–Wallis test showed an eta2 of 0.13 and a p value of 0.0002 for the effect of ethnicity on MSS and an eta2 of 0.009 and a p value of 0.68 for the effect of ethnicity on the RMT ratio.

Conclusion

CS laparotomy scars heal differently between ethnical groups, but generally with satisfying results. Ethnicity does not affect myometrial healing and scar appearance does not reflect myometrial healing after CS. Thus, separate uterine sonographic assessment is recommended.
Systematic identification and characterization of circular RNAs involved in flag leaf senescence of rice
Authors: Huang Xiaoping , Zhang Hongyu , Guo Rong , Wang Qiang , Liu Xuanzhi , Kuang Weigang , Song Haiyan , Liao Jianglin , Huang Yingjin , Wang Zhaohai
Published: January 2021

Main conclusion

Circular RNAs (circRNAs) identification, expression profiles, and construction of circRNA-parental gene relationships and circRNA-miRNA-mRNA ceRNA networks indicate that circRNAs are involved in flag leaf senescence of rice.

Circular RNAs (circRNAs) are a class of 3′-5′ head-to-tail covalently closed non-coding RNAs which have been proved to play important roles in various biological processes. However, no systematic identification of circRNAs associated with leaf senescence in rice has been studied. In this study, a genome-wide high-throughput sequencing analysis was performed using rice flag leaves developing from normal to senescence. Here, a total of 6612 circRNAs were identified, among which, 113 circRNAs were differentially expressed (DE) during the leaf senescence process. Moreover, 4601 (69.59%) circRNAs were derived from the exons or introns of their parental genes, while 2110 (71%) of the parental genes produced only one circRNA. The sequence alignment analysis showed that hundreds of rice circRNAs were conserved among different plant species. Gene Ontology (GO) enrichment analysis revealed that parental genes of DE circRNAs were enriched in many biological processes closely related to leaf senescence. Through weighted gene co-expression network analysis (WGCNA), six continuously down-expressed circRNAs, 18 continuously up-expressed circRNAs and 15 turn-point high-expressed circRNAs were considered to be highly associated with leaf senescence. Additionally, a total of 17 senescence-associated circRNAs were predicted to have parental genes, in which, regulations of three circRNAs to their parental genes were validated by qRT-PCR. The competing endogenous RNA (ceRNA) networks were also constructed. And a total of 11 senescence-associated circRNAs were predicted to act as miRNA sponges to regulate mRNAs, in which, regulation of two circRNAs to eight mRNAs was validated by qRT-PCR. It is discussed that senescence-associated circRNAs were involved in flag leaf senescence probably through mediating their parental genes and ceRNA networks, to participate in several well-studied senescence-associated processes, mainly including the processes of transcription, translation, and posttranslational modification (especially protein glycosylation), oxidation–reduction process, involvement of senescence-associated genes, hormone signaling pathway, proteolysis, and DNA damage repair. This study not only showed the systematic identification of circRNAs involved in leaf senescence of rice, but also laid a foundation for functional research on candidate circRNAs.
Surgical and oncological efficacy of laparoscopic-assisted total gastrectomy versus open total gastrectomy for gastric cancer by propensity score matching: a retrospective comparative study
Authors: Fan Yingcong , Liu Maoxing , Li Shijie , Yu Jianhong , Qi Xinyu , Tan Fei , Xu Kai , Zhang Nan , Yao Zhendan , Yang Hong , Zhang Chenghai , Xing Jiadi , Wang Zaozao , Cui Ming , Su Xiangqian
Published: January 2021

Purpose

The application of laparoscopic-assisted total gastrectomy (LATG) for resectable gastric cancer (GC) remains controversial compared with open total gastrectomy (OTG), especially for advanced gastric cancer (AGC) patients according to the inconsistent results demonstrated in the previous studies. The aim of this study was to evaluate the short-term and long-term outcomes between LATG and OTG in a population with more than 80% AGC patients by applying propensity score matching (PSM) method.

Methods

The data of 365 clinical stage I–III GC cases who underwent total gastrectomy with D2 lymphadenectomy were retrospectively collected from January 2011 to April 2018 in the Department of Gastrointestinal Surgery IV of Peking University Cancer Hospital. Propensity scores were generated through taking all covariates into consideration and 131 pairs of patients receiving either LATG or OTG were matched. Intraoperative, postoperative, and survival parameters were compared in the matched groups accordingly. Risk factors for postoperative complications and overall survival were further analyzed.

Results

Patient characteristics in the LATG and OTG groups were well balanced after PSM. LATG showed advantages with respect to shorter time to ambulation, first flatus, and first whole liquid diet intake. No significant differences were found between the two groups with regard to postoperative complications as well as overall survival in terms of different pathological stage. Older age was found as an independent risk factor for postoperative complications, and pathological stage for overall survival as well.

Conclusion

LATG appears to have comparable surgical and oncological safety with OTG by experienced surgeons.
Climate change affects seed aging? Initiation mechanism and consequences of loss of forest tree seed viability
Authors: Kijowska-Oberc Joanna , Staszak Aleksandra M. , Ratajczak Ewelina
Published: January 2021

Key message

Environmental stress resulting from rapid climate changes leads to the initiation of the seed aging process in mitochondria and peroxisomes. Seed storage methods limiting germinability loss are fundamental for forest future.

Seed aging is a natural process. It decreases the seed germination rate, i.e. the process is essential for the plant’s life cycle. Aging involves a progressive accumulation of oxidative damage over time. One of the main plant responses to stress is an excessive production of reactive oxygen species (ROS), such as O
2
−•
, H2O2 and •OH. If the concentration of ROS is too high, it causes damage of the structure of lipid membranes, proteins, carbohydrates, and DNA. Climate changes affect tree reproduction and may have long-term consequences in the form of reduced species dispersal and acquisition of new habitats. High temperatures accelerate the aging of seeds and decrease their viability. There is, therefore, an indisputable need to store forest reproductive material to maintain continuity of regeneration in farm forests. The quality of seeds subjected to long-term storage correlates negatively with ROS concentration, as ROS accumulation typically occurs in tissues experiencing oxidative stress. Therefore, to preserve forest genetic resources, it is particularly important to know the causes and sites of initiation of the aging process in seed cells, as well as to prevent the germination rate decrease by developing appropriate storage methods. The main organelles responsible for intracellular ROS production are mitochondria and peroxisomes. This article aims at verifying the causes of seed aging and determining its consequences for future forest regeneration due to climate changes. We review the literature on oxidative stress, as well as the sites where the tree seed aging process originates, such as mitochondria and peroxisomes.
Tutorial on systems with antifragility to downtime
Authors: Hole Kjell Jørgen
Published: January 2021

An antifragile system of software and stakeholders, including designers, developers, and operators, learn from incidents how to avoid outages and maintain high uptime. This tutorial article reviews how to design and operate such socio-technical systems with antifragility to downtime. It documents the importance of four design principles and two operational principles by exploring the polar opposite anti-principles and the interplay between the principles and the anti-principles. The design principles mandate a software design of separate and isolatable processes with sufficient diversity and redundancy. The processes should communicate asynchronously over an external network. The operational principles imply that the software development teams should repeatedly inject artificial failures into the production system to understand its behavior and detect and mitigate vulnerabilities as the system and its environment change.
Facial emotion recognition impairment predicts social and emotional problems in children with (subthreshold) ADHD
Authors: Staff Anouck I. , Luman Marjolein , van der Oord Saskia , Bergwerff Catharina E. , van den Hoofdakker Barbara J. , Oosterlaan Jaap
Published: January 2021

Children with attention-deficit/hyperactivity disorder (ADHD) symptoms often experience social and emotional problems. Impaired facial emotion recognition has been suggested as a possible underlying mechanism, although impairments may depend on the type and intensity of emotions. We investigated facial emotion recognition in children with (subthreshold) ADHD and controls using a novel task with children’s faces of emotional expressions varying in type and intensity. We further investigated associations between emotion recognition accuracy and social and emotional problems in the ADHD group. 83 children displaying ADHD symptoms and 30 controls (6–12 years) completed the Morphed Facial Emotion Recognition Task (MFERT). The MFERT assesses emotion recognition accuracy on four emotions using five expression intensity levels. Teachers and parents rated social and emotional problems on the Strengths and Difficulties Questionnaire. Repeated measures analysis of variance revealed that the ADHD group showed poorer emotion recognition accuracy compared to controls across emotions (small effect). The significant group by expression intensity interaction (small effect) showed that the increase in accuracy with increasing expression intensity was smaller in the ADHD group compared to controls. Multiple regression analyses within the ADHD group showed that emotion recognition accuracy was inversely related to social and emotional problems, but not prosocial behavior. Not only children with an ADHD diagnosis, but also children with subthreshold ADHD experience impairments in facial emotion recognition. This impairment is predictive for social and emotional problems, which may suggest that emotion recognition may contribute to the development of social and emotional problems in these children.
Runoff and focused groundwater-recharge response to flooding rains in the arid zone of Australia
Authors: Acworth R. Ian , Rau Gabriel C. , Cuthbert Mark O. , Leggett Keith , Andersen Martin S.
Published: January 2021

A groundwater recharge investigation in the arid zone of Australia is presented. The investigation used a wide range of hydrogeological techniques including geological mapping, surface and borehole geophysics, groundwater hydraulics, streambed temperature and pressure monitoring, and hydrogeochemical and environmental tracer sampling, and it was complemented by analysis of rainfall intensity from 18 tipping-bucked rain gauges, climate data and stream runoff measurements. Run-off and recharge from a 200-mm rainfall event in January 2015, the largest daily rainfall in the local 50-year record, were investigated in detail. While this major storm provided substantial run-off as a potential source for focused, indirect recharge, it only produced enough actual recharge to the shallow aquifer to temporarily halt a long-term groundwater recession. A series of smaller rainfall-runoff events in 2016 produced a similar recharge response. The results suggest that the total magnitude of a flood event is not the main control on indirect groundwater recharge at this location. A deeper aquifer shows no hydraulic response to surface-water flow events and is isolated from the shallow system, consistent with its Pleistocene groundwater age. This supports a growing body of evidence indicating that attributing or predicting generalised changes in recharge to changes in climate in dryland environments should not be attempted without first unravelling the dynamic processes governing groundwater recharge in the locality of interest. The results should prompt more detailed and long-term field investigation in other arid zone locations to further understand the episodic and nonlinear nature of recharge in such environments.
Factors that influence biological survival in rheumatoid arthritis: results of a real-world academic cohort from the Netherlands
Authors: van Mulligen Elise , Ahmed Saad , Weel Angelique E. A. M. , Hazes Johanna M. W. , van der Helm- van Mil Annette H. M. , de Jong Pascal H. P.
Published: January 2021

We aim to explore real-world biological survival stratified for discontinuation reason and determine its influenceability in rheumatoid arthritis (RA) patients. Data from the local pharmacy database and patient records of a university hospital in the Netherlands were used. RA patients who started a biological between 2000 and 2020 were included. Data on age, anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) status, presence of erosions, gender, body mass index, time to first biological, biological survival time, use of csDMARDs, and discontinuation reasons were collected. Of the included 318 patients, 12% started their first biological within 6 months after diagnosis. The median time to first biological was 3.6 years (95% CI, 1.0–7.2). The median survival of the first- and second-line biological was respectively 1.7 years (95% CI, 1.3–2.2) and 0.8 years (95% CI, 0.5–1.0) (p = 0.0001). Discontinuation reasons for the first-line biological were ineffectiveness (47%), adverse events (17%), remission (16%), pregnancy (30%), or patient preference (10%). Multivariable Cox regression analyses for discontinuation due to inefficacy or adverse events showed that concomitant use of csDMARDs (HR = 1.32, p < 0.001) positively while RF positivity negatively (HR = 0.82, p = 0.03) influenced biological survival. ACPA positivity was associated with the inability to discontinue biologicals after achieving remission (HR = 1.43, p = 0.023). Second-line TNF inhibitor survival was similar between patients with a primary and secondary non-response on the first-line TNF inhibitor (HR = 1.28, p = 0.34). Biological survival diminishes with the number of biologicals used. Biological survival is prolonged if patients use csDMARDs. RF was negatively associated with biological survival. ACPA was negatively associated with the inability to discontinue biologicals after achieving remission. Therefore, tailoring treatment based upon autoantibody status might be the first step towards personalized medicine in RA.

Key Points• Prolonged biological survival is a surrogate for treatment effectiveness; however, an increasing amount of patients will taper treatment due to remission, and factors influencing biological survival based on separate reasons for discontinuation have not been explored.• We found that combining a biological DMARD with a conventional synthetic DMARD increases biological DMARD survival. Rheumatoid factor is negatively associated with biological survival. Anti-citrullinated protein antibody is negatively associated with the inability to discontinue the biological when remission was reached.• The first step towards personalized medicine might be tailoring of treatment based upon autoantibody status.
Serodiagnosis of Lyme borreliosis—is IgM in serum more harmful than helpful?
Authors: Hillerdal Henrik , Henningsson Anna J.
Published: January 2021

Interpretation of serological findings in suspected Lyme borreliosis (LB) may be challenging and IgM reactivities in serum are often unspecific (false positive). There is a risk for overdiagnosis of LB, inadequate use of antibiotics, and potential delay of proper diagnosis. In this study, we evaluated the diagnostic value of IgM analysis in serum and IgM antibody index (AI) in LB diagnosis. This was a retrospective observational study regarding Borrelia-specific antibodies in serum and Borrelia-specific AI in LB investigations being made during 2017 in Jönköping County, Sweden. Medical records of 610 patients with detectable anti-Borrelia antibodies in serum (IgM and/or IgG) and 15 patients with elevated Borrelia-specific AI were retrospectively scrutinized, and the compliance to current European recommendations was assessed. Among the 610 patients, only 30% were tested according to the European recommendations. Within this group of tests taken correctly, 50% of the LB diagnoses in patients with isolated IgM reactivity in serum were retrospectively assessed as incorrect (LB unlikely). Three pediatric patients with clinical and laboratory findings suggestive of Lyme neuroborreliosis (LNB) had elevated IgM AI alone. Serological testing without distinct clinical signs/symptoms consistent with LB contributes to most misdiagnoses. Isolated IgM positivity in serum shows limited clinical value and needs further assessment before being reported by the laboratory. Detection of IgM in combination with IgG antibodies in serum shows no clinical enhancement for correct LB diagnosis compared to isolated IgG positivity. However, Borrelia-specific IgM AI may be important for sensitivity in early LNB.
Serious adverse events with novel beta-lactam/beta-lactamase inhibitor combinations: a large-scale pharmacovigilance analysis
Authors: Gatti Milo , Raschi Emanuel , De Ponti Fabrizio
Published: January 2021

The purpose of this study is to characterize adverse events (AEs) of clinical interest reported with ceftolozane-tazobactam and ceftazidime-avibactam, as an aid in monitoring patients affected by severe multidrug-resistant Gram-negative infections. We queried the worldwide FDA Adverse Event Reporting System (FAERS) and performed disproportionality analysis, selecting only designated medical events (DMEs) where ceftolozane-tazobactam and ceftazidime-avibactam were reported as suspect. Serious neurological AEs were further investigated. The reporting odds ratios were calculated, deemed significant by the lower limit of the 95% confidence interval (LL95% CI) > 1. All other drugs/events recorded in FAERS and cephalosporins showing clinical evidence of neurological AEs were respectively selected as comparator for analysis of DMEs and neurotoxicity. Qualitative analysis including case-by-case assessment and deduplication was also performed. Overall, 654 and 506 reports mentioning respectively ceftolozane-tazobactam and ceftazidime-avibactam were found, with DMEs accounting respectively for 13.1% and 10.9% of cases. Agranulocytosis (N = 12; LL95% CI = 12.40) and pancytopenia (14; 6.18) emerged as unexpected AEs with ceftolozane-tazobactam, while acute pancreatitis (7; 8.63) was an over-reported unexpected DME with ceftazidime-avibactam. After deduplication, four unequivocally different cases of agranulocytosis with ceftolozane-tazobactam were retained, occurring on average after 8.8 days. Causality was probable and possible respectively in three and one case. Among neurological AEs exhibiting significant disproportionality, encephalopathy with both antibiotics and mental status changes with ceftazidime-avibactam were retained in at least three cases after deduplication. Although rare, clinicians should monitor high-risk patients (i.e. individuals affected by haematological malignances, HIV infection, or treated with concomitant myelotoxic agents) for early unexpected occurrence of agranulocytosis with ceftolozane-tazobactam.
Geo-referenced simulation of pharmaceuticals in whole watersheds: application of GREAT-ER 4.1 in Germany
Authors: Lämmchen Volker , Niebaum Gunnar , Berlekamp Jürgen , Klasmeier Jörg
Published: January 2021

The geo-referenced regional exposure assessment tool for European rivers (GREAT-ER) is designed to support river basin management or the implementation process within the EU Water Framework Directive by predicting spatially resolved exposure concentrations in whole watersheds. The usefulness of the complimentary application of targeted monitoring and GREAT-ER simulations is demonstrated with case studies for three pharmaceuticals in selected German watersheds. Comparison with monitoring data corroborates the capability of the probabilistic model approach to predict the expected range of spatial surface water concentrations. Explicit consideration of local pharmaceutical emissions from hospitals or private doctor’s offices (e.g., for X-ray contrast agents) can improve predictions on the local scale without compromising regional exposure assessment. Pharmaceuticals exhibiting low concentrations hardly detectable with established analytical methods (e.g., EE2) can be evaluated with model simulations. Management scenarios allow for a priori assessment of risk reduction measures. In combination with targeted monitoring approaches, the GREAT-ER model can serve as valuable support tool for exposure and risk assessment of pharmaceuticals in whole watersheds.
Decreased parenchymal arteriolar tone uncouples vessel-to-neuronal communication in a mouse model of vascular cognitive impairment
Authors: Kim Ki Jung , Diaz Juan Ramiro , Presa Jessica L. , Muller P. Robinson , Brands Michael W. , Khan Mohammad B. , Hess David C. , Althammer Ferdinand , Stern Javier E. , Filosa Jessica A.
Published: January 2021

Chronic hypoperfusion is a key contributor to cognitive decline and neurodegenerative conditions, but the cellular mechanisms remain ill-defined. Using a multidisciplinary approach, we sought to elucidate chronic hypoperfusion-evoked functional changes at the neurovascular unit. We used bilateral common carotid artery stenosis (BCAS), a well-established model of vascular cognitive impairment, combined with an ex vivo preparation that allows pressurization of parenchymal arterioles in a brain slice. Our results demonstrate that mild (~ 30%), chronic hypoperfusion significantly altered the functional integrity of the cortical neurovascular unit. Although pial cerebral perfusion recovered over time, parenchymal arterioles progressively lost tone, exhibiting significant reductions by day 28 post-surgery. We provide supportive evidence for reduced adenosine 1 receptor-mediated vasoconstriction as a potential mechanism in the adaptive response underlying the reduced baseline tone in parenchymal arterioles. In addition, we show that in response to the neuromodulator adenosine, the action potential frequency of cortical pyramidal neurons was significantly reduced in all groups. However, a significant decrease in adenosine-induced hyperpolarization was observed in BCAS 14 days. At the microvascular level, constriction-induced inhibition of pyramidal neurons was significantly compromised in BCAS mice. Collectively, these results suggest that BCAS uncouples vessel-to-neuron communication—vasculo-neuronal coupling—a potential early event in cognitive decline.
Diagnostic approach in patients with angina and no obstructive coronary artery disease: emphasising the role of the coronary function test
Authors: Konst R. E. , Damman P. , Pellegrini D. , van Royen N. , Maas A. H. E. M. , Elias-Smale S. E.
Published: January 2021

Background

Many patients with angina do not have obstructive coronary artery disease (CAD), also referred to as “Ischaemia with No Obstructive Coronary Arteries“ (INOCA). Coronary vascular dysfunction is the underlying cause of this ischaemic heart disease in as much as 59–89% of these patients, including the endotypes of coronary microvascular dysfunction and epicardial coronary vasospasm. Currently, a coronary function test (CFT) is the only comprehensive diagnostic modality to evaluate all endotypes of coronary vascular dysfunction in patients with INOCA.

Objective

In this paper we discuss the relevance of performing a CFT, provide considerations for patient selection, and present an overview of the procedure and its safety.

Methods

We reviewed the latest published data, guidelines and consensus documents, combined with a discussion of novel original data, to present this point of view.

Results

The use of a CFT could lead to a more accurate and timely diagnosis of vascular dysfunction, identifies patients at risk for cardiovascular events, and enables stratified treatment which improves symptoms and quality of life. Current guidelines recommend considering a CFT in patients with INOCA and persistent symptoms. The safety of the procedure is comparable to that of a regular coronary angiography with physiological measurements. Non-invasive alternatives have limited diagnostic accuracy for the identification of coronary vascular dysfunction in patients with INOCA, and a regular coronary angiography and/or coronary computed tomography scan cannot establish the diagnosis.

Conclusions

A complete CFT, including acetylcholine and adenosine tests, should be considered in patients with INOCA.
From tree to architecture: how functional morphology of arborescence connects plant biology, evolution and physics
Authors: Roth-Nebelsick Anita , Miranda Tatiana , Ebner Martin , Konrad Wilfried , Traiser Christopher
Published: January 2021

Trees are the fundamental element of forest ecosystems, made possible by their mechanical qualities and their highly sophisticated conductive tissues. The evolution of trees, and thereby the evolution of forests, were ecologically transformative and affected climate and biogeochemical cycles fundamentally. Trees also offer a substantial amount of ecological niches for other organisms, such as epiphytes, creating a vast amount of habitats. During land plant evolution, a variety of different tree constructions evolved and their constructional principles are a subject of ongoing research. Understanding the “natural construction” of trees benefits strongly from methods and approaches from physics and engineering. Plant water transport is a good example for the ongoing demand for interdisciplinary efforts to unravel form-function relationships on vastly differing scales. Identification of the unique mechanism of water long-distance transport requires a solid basis of interfacial physics and thermodynamics. Studying tree functions by using theoretical approaches is, however, not a one-sided affair: The complex interrelationships between traits, functionality, trade-offs and phylogeny inspire engineers, physicists and architects until today.
Genetic mapping of pollen fertility restoration QTLs in rye (Secale cereale L.) with CMS Pampa
Authors: Niedziela Agnieszka , Brukwiński Waldemar , Bednarek Piotr Tomasz
Published: January 2021

Cytoplasmic male sterility (CMS) is a widely applied plant breeding tool for hybrid seed production. The phenomenon is often caused by chimeric genes with altered open reading frames (ORFs) located in the mitochondrial genomes and expressed as novel genotoxic products that induce pollen abortion. The fertility of CMS plants can be restored by nuclear-encoded genes that inhibit the action of ORFs responsible for pollen sterility. A recombinant inbred line (RIL) mapping population S64/04/01, encompassing 175 individuals, was used for genetic map construction and identification of quantitative trait loci (QTLs) responsible for fertility restoration in rye (Secale cereale L.) with CMS Pampa. The genetic map of all seven rye chromosomes included 15,516 SNP and silicoDArT markers and covered 1070.5 cm. Individual QTLs explaining 60% and 5.5% of the fertility trait’s phenotypic variance were mapped to chromosomes 4R (QRft-4R) and 5R (QRft-5R), respectively. Association mapping identified markers with the highest R2 value of 0.58 (p value = 2.21E-28). Markers showing the highest associations with the trait were also mapped to the 4R chromosome within the QRft-4R region. Based on marker sequence homology, putative genes involved in pollen fertility restoration were suggested. Five silicoDArTs were converted into PCR-based markers for further breeding purposes.
On semilocal convergence of three-step Kurchatov method under weak condition
Authors: Kumar Himanshu
Published: January 2021

The purpose of this paper to establish the semilocal convergence analysis of three-step Kurchatov method under weaker conditions in Banach spaces. We construct the recurrence relations under the assumption that involved first-order divided difference operators satisfy the $$\omega $$
ω
condition. Theorems are given for the existence-uniqueness balls enclosing the unique solution. The application of the iterative method is shown by solving nonlinear system of equations and nonlinear Hammerstein-type integral equations. It illustrates the theoretical development of this study.
Fast laser surface texturing of spherical samples to improve the frictional performance of elasto-hydrodynamic lubricated contacts
Authors: Boidi G. , Grützmacher P. G. , Kadiric A. , Profito F. J. , Machado I. F. , Gachot C. , Dini D.
Published: January 2021

Textured surfaces offer the potential to promote friction and wear reduction by increasing the hydrodynamic pressure, fluid uptake, or acting as oil or debris reservoirs. However, texturing techniques often require additional manufacturing steps and costs, thus frequently being not economically feasible for real engineering applications. This experimental study aims at applying a fast laser texturing technique on curved surfaces for obtaining superior tribological performances. A femtosecond pulsed laser (Ti:Sapphire) and direct laser interference patterning (with a solid-state Nd:YAG laser) were used for manufacturing dimple and groove patterns on curved steel surfaces (ball samples). Tribological tests were carried out under elasto-hydrodynamic lubricated contact conditions varying slide-roll ratio using a ball-on-disk configuration. Furthermore, a specific interferometry technique for rough surfaces was used to measure the film thickness of smooth and textured surfaces. Smooth steel samples were used to obtain data for the reference surface. The results showed that dimples promoted friction reduction (up to 20%) compared to the reference smooth specimens, whereas grooves generally caused less beneficial or detrimental effects. In addition, dimples promoted the formation of full film lubrication conditions at lower speeds. This study demonstrates how fast texturing techniques could potentially be used for improving the tribological performance of bearings as well as other mechanical components utilised in several engineering applications.
Impact of chosen force fields and applied load on thin film lubrication
Authors: Ta Thi D. , Ta Hien D. , Tieu Kiet A. , Tran Bach H.
Published: January 2021

The rapid development of molecular dynamics (MD) simulations, as well as classical and reactive atomic potentials, has enabled tribologists to gain new insights into lubrication performance at the fundamental level. However, the impact of adopted potentials on the rheological properties and tribological performance of hydrocarbons has not been researched adequately. This extensive study analyzed the effects of surface structure, applied load, and force field (FF) on the thin film lubrication of hexadecane. The lubricant film became more solid-like as the applied load increased. In particular, with increasing applied load, there was an increase in the velocity slip, shear viscosity, and friction. The degree of ordering structure also changed with the applied load but rather insignificantly. It was also significantly dependent on the surface structure. The chosen FFs significantly influenced the lubrication performance, rheological properties, and molecular structure. The adaptive intermolecular reactive empirical bond order (AIREBO) potential resulted in more significant liquid-like behaviors, and the smallest velocity slip, degree of ordering structure, and shear stress were compared using the optimized potential for liquid simulations of united atoms (OPLS-UAs), condensed-phase optimized molecular potential for atomic simulation studies (COMPASS), and ReaxFF. Generally, classical potentials, such as OPLS-UA and COMPASS, exhibit more solid-like behavior than reactive potentials do. Furthermore, owing to the solid-like behavior, the lubricant temperatures obtained from OPLS-UA and COMPASS were much lower than those obtained from AIREBO and ReaxFF. The increase in shear stress, as well as the decrease in velocity slip with an increase in the surface potential parameter ζ, remained conserved for all chosen FFs, thus indicating that the proposed surface potential parameter ζ for the COMPASS FF can be verified for a wide range of atomic models.
Employment Uncertainty and Mental Health During the COVID-19 Pandemic Initial Social Distancing Implementation: a Cross-national Study
Authors: Ruffolo Mary , Price Daicia , Schoultz Mariyana , Leung Janni , Bonsaksen Tore , Thygesen Hilde , Geirdal Amy Østertun
Published: January 2021

Background

Social distancing during the COVID-19 pandemic has resulted in changes in the work environment and employment uncertainty. This paper reports on a cross-national comparison of four countries (Norway, UK, USA and Australia) and examines the differences in mental health between those individuals employed and those not employed during the social distancing implementation.

Methods

Participants (N = 3,810) were recruited through social media in April/May 2020 and were invited to complete a self-administered electronic survey over a 3-week period. Differences between those employed and those not employed with regard to their sociodemographic characteristics and mental health were investigated with chi-square tests, independent t tests, and one-way analysis of variances (ANOVAs).

Results

Compared with their counterparts, participants who were employed reported lower levels of mental health distress (p < 0.001), higher levels of psychosocial well-being (p < 0.001), better overall quality of life (p < 0.001), and lower levels of overall loneliness, social loneliness, and emotional loneliness (p < 0.001). Small to medium but consistent differences (Cohen’s d = 0.23–0.67) in mental health favor those with employment or those who were retired.

Conclusion

Further study is needed to assess mental health over time as the COVID-19 pandemic and employment uncertainty continues.