bluuebunny/crossref_metadata_2025 huggingface dataset:
Peri‐implantation cytokine profile differs between singleton and twin IVF pregnancies
Authors: Simpson Samantha , Kaislasuo Janina , Peng Gang , Aldo Paulomi , Paidas Michael , Guller Seth , Mor Gil , Pal Lubna
Published: September 2020

Problem

It is unknown whether maternal cytokine production differs between twin and singleton gestations in the implantation phase. A difference in maternal serum cytokine concentrations in twins would imply a dose‐response to the invading embryos, as opposed to a general immune reaction.

Method of study

A prospective longitudinal cohort of women aged 18‐45 at an academic fertility center undergoing in vitro fertilization and embryo transfer (IVF‐ET) underwent routine collection of serial serum samples starting 9 days after ET and then approximately every 48 hours thereafter. Cryopreserved aliquots of these samples were assayed for interleukin‐10 (IL‐10), tumor necrosis factor‐alpha (TNF‐α), and C‐X‐C motif chemokine ligand 10 (CXCL10) using the SimplePlex immunoassay platform. Pregnancies were followed until delivery. Serial measures of serum concentrations of IL‐10, CXCL10, and TNF‐α in singleton or di‐di twin pregnancies from 9 to 15 days after IVF‐ET were compared.

Results

Maternal serum levels of CXCL10 are significantly lower in women with di‐di twin pregnancies in early implantation compared to those with singleton gestation (day 9‐11, P = .02). Serum levels of TNF‐α and IL‐10 were comparable at all studied time points (P > .05).

Conclusion

Maternal serum levels of CXCL10 are significantly lower in the earliest implantation phase in di‐di twins compared to singleton conceptions. Given the known anti‐angiogenic role of CXCL10, we hypothesize that lower CXCL10 levels in twin implantations allow an environment that is conducive for the greater vascularization required for the establishment of dual placentation in di‐di twins.
Getting Creative with Data: Managing Relationships and Quantitative Proof in an Indian NGO
Authors: Goodman Rachael
Published: September 2020

While many scholars have documented how the pursuit of objective data reshapes relationships, I show how relationships can also affect how people interact with data. The donors and managers of a nongovernmental organization (NGO) in the foothills of the Indian Himalayas were most invested in their relationships with one another. These ties required quantitative data to act as proof that development was happening and money was well spent in the absence of direct observation. In order for numbers to serve this communicative function, the NGO's leaders treated the data produced by development projects as if they were objective representations of reality. However, the NGO's fieldworkers, who produced the data, were invested in ties outside the development community. They relied on their relationships with the NGO's beneficiaries—who were also their friends, neighbors, and kin—to help them survive (socially, emotionally, physically, and financially) in ways that NGO employment could not replace. Far from needing numbers to be objective proof, these relationships required fieldworkers to treat data as flexible and open to interpretation. Beneficiaries used projects in ways that the NGO's leaders did not anticipate or value, and fieldworkers were creative with data production to maintain their ties to both leaders and beneficiaries. [development, data, relationships, NGOs, South Asia]
Results of surgical correction of upper eyelid retraction in Graves’ Orbitopathy
Authors: Pinas Dianta , O.B. De Keizer Ronald , Wubbels Rene J. , van den Bosch Willem A. , Paridaens Dion
Published: September 2020

Introduction

Anterior levator disinsertion/reinsertion and Müllerectomy (ALDM) is generally performed to correct upper eyelid retraction in patients with Graves’ orbitopathy (GO). We studied the outcome of this procedure and its correlation with clinical parameters.

Patients and Methods

Retrospective analysis of results of ALDM in 305 consecutive euthyroid patients with burnt‐out GO treated in our hospital between 1 January 2000 and 1 January 2016. From the patient files, we recorded data on age, gender, laterality of surgery, smoking history and previous interventions. For outcome analysis, we used a qualitative scoring system with subdivision into three categories (good (MRD‐1 of 4–5 mm, smooth upper eyelid contour and left‐right difference of < 1 mm); acceptable (MRD‐1 of 3–<4 or> 5–6 mm), smooth upper eyelid contour and left‐right difference of < 2 mm; poor: if none of the above criteria was met). We analysed the outcome per eyelid as well as per patient.

Results

Of the 305 patients (471 eyelids), 166 underwent bilateral and 139 unilateral surgery. Regarding eyelids, the outcome of surgery was good in 71.6% (337/471) acceptable in 15.7% (74/471) and poor in 12.7% (60/471). Regarding patients, the outcome was good in 64.3% (196/305), acceptable in 15.7% (48/305) and poor in 20% (61/305). Concerning bilateral and unilateral surgery, the outcome was good in 60.8% (101/166) and acceptable in 16.9% (28/166) of patients after bilateral surgery, and good in 68.3% (95/139) and acceptable in 14.4% (20/139) of the patients after unilateral surgery (p = 0.17). Reoperation was performed in 16% (75 of 471) of eyelids and in 22 % (66 of 305) of patients. After secondary surgery, the cumulative success percentage was good in 78.6% (370/471) of eyelids and in 79% (241/305) of patients. We found no relation between surgical outcome and any other studied parameter, such as age, gender, smoking history and previous intervention such as extraocular muscle surgery and/or orbital decompression.

Conclusion

Correction of upper eyelid retraction yields a good result in 64.3% of patients and 71.6% of eyelids. With one additional procedure, the procedure proved was successful in 79% of patients and eyelids. We found no relation between the outcome of surgery and any other parameter, such as previous disease severity, previous interventions or smoking history. For comparative analysis, we recommend to report the outcome per patient rather than per eyelid.
Reed bed vegetation structure and plant species diversity depend on management type and the time period since last management
Authors: Andersen Line Holm , Nummi Petri , Bahrndorff Simon , Pertoldi Cino , Trøjelsgaard Kristian , Lauridsen Torben Linding , Rafn Jeppe , Frederiksen Cecilie Majgaard Skak , Kristjansen Mads Prengel , Bruhn Dan
Published: September 2020

Question

Reed beds, dominated by common reed (Phragmites australis), have high ecological value. Several studies have examined the differences between managed and unmanaged reed beds without taking into account the time passed since the last management. In this paper, we seek to answer the question: how does the time passed since last management and the management method itself affect the plant community and the habitat structure of reed beds?

Location

“De Østlige Vejler,” Northern Jutland, Denmark.

Methods

We examined four reed bed treatments — beds either cut or harvested during the year of the study (0‐year‐old reed beds) and reed beds harvested 3 and 25 years ago, respectively. The reed bed plant communities and the reed bed habitat structure were determined in May and August. We tested the data for overall between‐treatment differences (multivariate analysis of variance [MANOVA] and principal components analysis [PCA]) and specific differences in the plant community and habitat structure (Kruskal–Wallis).

Results

The plant community differed significantly between the four reed beds according to treatment, and each reed bed exhibited unique species. Species richness was significantly higher in the recently harvested reed beds (0 and 3 years since harvest) compared with the 25‐year‐old reed beds. Harvest sparked reed rejuvenation and increased the growth of new reeds. The 3‐year‐old reed bed had a habitat structure that equally resembled that of the newly harvested (e.g., similar green reed shoot density) and the 25‐year‐old reed beds (e.g., similar height). Cutting, as opposed to harvesting, created a plant community adapted to less light availability.

Conclusions

To secure most plant species and most variation in habitat structure, reed beds should contain a mosaic of differently aged and differently managed patches. Previous studies have disagreed on the effect of management on plant species diversity, which could be explained either by different reed bed age or different sampling periods.
Trends in cesarean birth rates in Iceland over a 19‐year period
Authors: Haggar Fatima , Einarsdóttir Kristjana
Published: September 2020

Background

Cesarean birth (CB) rates have increased in high‐resource countries during the past two decades, yet it is not known whether CB rates have changed according to maternal age and/or gestational age.

Methods

All singleton live births in Iceland between 1997 and 2015 were identified from the Icelandic Medical Birth Registry (80 130). Rates of cesarean births (intrapartum and prelabor) were calculated overall and separately for maternal age groups and gestational age groups and by parity. Logit binomial regression was used to calculate odds ratios (ORs) and confidence intervals (CIs) for annual change in cesarean birth rates adjusted for maternal characteristics and clinical indication groups.

Results

The overall CB rate was 15.7% in 1997 and 15.8% in 2015; the CB rate did not change significantly during the study period. The overall CB rate for early‐term deliveries (37‐38 weeks) decreased for multiparas (annual aOR = 0.99 [95% CI = 0.98‐0.99]), and the preterm (<37 weeks) prelabor cesarean rate increased significantly (1.11 [1.09‐1.14]) for both primiparas and multiparas. For multiparas only, the intrapartum CB rate decreased (0.97 [0.97‐0.98]), whereas the prelabor CB rate increased, predominantly for women aged over 35 years (1.03 [1.02‐1.04]). Adjustment for clinical indication groups did not change these results.

Conclusions

Findings indicate a rise in prelabor cesarean for preterm births and women aged over 35 years (multiparas only). As adjustment for clinical indications did not affect these results, changes in obstetric practice are more likely to have affected these rate changes rather than changes in clinical indications.
The rise of complement in ANCA-associated vasculitis: from marginal player to target of modern therapy
Authors: Trivioli G , Vaglio A
Published: September 2020

The complement system plays a central role in autoimmune diseases, including anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Although complement deposition is scarce in AAV pathological samples, complement activation is required for the development of necrotizing crescentic glomerulonephritis (NCGN) in mouse models of AAV and occurs via the alternative pathway. The anaphylatoxin C5a, produced by the final complement pathway, is determinant to drive the disease in animal models. C5a primes human neutrophils and enhances their activation induced by ANCA; activated neutrophils, in turn, release factors that lead to C5a generation, establishing a self-amplifying loop. C5a is also significantly increased in the serum of AAV patients with active disease compared to those in remission or healthy controls. Inhibition of the C5a receptor with avacopan is an emerging therapy that will probably allow AAV treatment with glucocorticoid-free regimens.
Protease inhibitors elicit anti-inflammatory effects in CF mice with Pseudomonas aeruginosa acute lung infection
Authors: Sandri A , Lleo M M , Signoretto C , Boaretti M , Boschi F
Published: September 2020

Pseudomonas aeruginosa is the major respiratory pathogen in patients with cystic fibrosis (CF). P. aeruginosa-secreted proteases, in addition to host proteases, degrade lung tissue and interfere with immune processes. In this study, we aimed at evaluating the possible anti-inflammatory effects of protease inhibitors Marimastat and Ilomastat in the treatment of P. aeruginosa infection. Lung infection with the P. aeruginosa PAO1 strain was established in wild-type and cystic fibrosis transmembrane conductance regulator (CFTR) knock-out C57BL/6 mice expressing a luciferase gene under control of bovine interleukin (IL)-8 promoter. After intratracheal instillation with 150 µM Marimastat and Ilomastat, lung inflammation was monitored by in-vivo bioluminescence imaging and bacterial load in the lungs was assessed. In vitro, the effects of protease inhibitors on PAO1 growth and viability were evaluated. Acute lung infection was established in both wild-type and CFTR knock-out mice. After 24 h, the infection induced IL-8-dependent bioluminescence emission, indicating lung inflammation. In infected mice with ongoing inflammation, intratracheal treatment with 150 µM Marimastat and Ilomastat reduced the bioluminescence signal in comparison to untreated, infected animals. Bacterial load in the lungs was not affected by the treatment, and in vitro the same dose of Marimastat and Ilomastat did not affect PAO1 growth and viability, confirming that these molecules have no additional anti-bacterial activity. Our results show that inhibition of protease activity elicits anti-inflammatory effects in cystic fibrosis (CF) mice with acute P. aeruginosa lung infection. Thus, Marimastat and Ilomastat represent candidate molecules for the treatment of CF patients, encouraging further studies on protease inhibitors and their application in inflammatory diseases.
Conjunctival thickness as a predictive imaging biomarker for the glaucoma filtration surgery outcome: An optical coherence tomography study
Authors: Mastropasqua Leonardo , Brescia Lorenza , Oddone Francesco , Sacchi Matteo , Aloia Raffaella , Totta Michele , Scatena Barbara , Mastropasqua Rodolfo , Agnifili Luca
Published: September 2020

Importance

To analyse the preoperative conjunctival thickness in glaucomatous patients undergoing filtration surgery (FS), using optical coherence tomography (OCT).

Background

The conjunctival status represents one of the most critical determinants of the FS outcome.

Design

Retrospective study.

Participants

Sixty‐seven patients candidate to FS for uncontrolled glaucoma were enrolled.

Methods

OCT was performed at the superior bulbar conjunctiva before FS, and at bleb site at the last follow‐up (LF‐up) after surgery.

Main Outcome Measures

Preoperative full, epithelial, and stromal conjunctival thickness (FCT, CET, CST) and reflectivity (CR), and LF‐up bleb‐wall thickness (BT), reflectivity (BR) and intraocular pressure (IOP), were the major outcomes. The relations between preoperative parameters and LF‐up‐IOP, BT and BR were calculated.

Results

FS was completely successful in 23 patients (group 1), successful with medications in 22 (group 2), and failed in 22 (group 3). FCT, CET and CST were lower, whereas CR higher, in group 3 compared to groups 1 and 2 (P < .05); BT was lower (P < .001), whereas BR higher (P < .05) in group 3 compared to group 1. FCT and CST were predictors of FS outcome with lower thickness associated with increased odds of failure (odds ratio 0.922, P = .08; 0.941, P = .025). LF‐up‐IOP inversely correlated with FCT and CST (r = −0.447, P = .003; r = −0.408, P = .007), whereas positively correlated with CR (r = 0.789, P < .001).

Conclusions and Relevance

Preoperative conjunctival thickness and reflectivity show significant correlations with the FS outcome, both in terms of IOP and bleb‐wall features. Therefore, they may be proposed as predictive imaging biomarkers to estimate the risk of filtration failure.
Two questions may be enough – screening for depression in patients with psoriasis: a multicenter study
Authors: Gerdes Sascha , Wilsmann‐Theis Dagmar , Celis Daniel , Kromer Christian , Mössner Rotraut
Published: September 2020

Background

Depression is frequently underdiagnosed and insufficiently treated in psoriatic patients in their daily routine. The aim of this study was to screen and analyze the impact of patient and disease characteristics on depression scores.

Patients and Methods

In this cross‐sectional multicenter cohort study, adult psoriasis patients were screened for depression with two validated tools: the Whooley questions and the revised Beck Depression Inventory (BDI‐II).

Results

Overall, 538 patients (median PASI 3.0, mean DLQI 5.3) were screened for depressive symptoms (mean BDI‐II score 8.3). 24.2 % of all participants reached a BDI‐II score ≥ 13, suggesting a depression that was at least mild. The results of the Whooley questions were positive for 28.2 % of the patients. There was a strong correlation between the two tools (p < 0.001). In the subgroup with a BDI‐II score ≥ 13, disease activity (median PASI 3.8 vs. 2.8, p = 0.06) and DLQI scores (mean 10.1 vs. 3.7, p < 0.0001) were higher, and psoriatic arthritis and diabetes were more prevalent (52.6 % vs. 37.8 %, p = 0.002, and 16.2 % vs. 10.0 %, p = 0.04, respectively) than in the subgroup with a BDI‐II score < 13.

Conclusions

In specialized psoriatic outpatient clinics, a BDI‐II score ≥ 13 was present in almost every fourth patient despite a low median PASI. The Whooley questions might be easy to use as a screening tool for depression in psoriasis patients.
The Christology of Veli‐Matti Kärkkäinen re‐visited from the perspective of Scandinavian Creation Theology
Authors: Kristensson Uggla Bengt
Published: September 2020

This article is a response to Veli‐Matti Kärkkäinen's Christology from the perspective of Scandinavian creation theology. Starting from the identification of a common post‐liberal horizon, together with similar challenges from anti‐liberal theology, the author enters into a critical examination of Kärkkäinen's systematic theology elaborating on the possible contributions from Gustaf Wingren. First, the significance of creation as horizon of understanding for Christology is discussed. Second, the relationship between anthropology and Christology is investigated, with a special focus on theological resources to transcend the dichotomies and the zero‐sum game that places God and humans in opposition as competitors.
A look to the future in non‐alcoholic fatty liver disease: Are glucagon‐like peptide‐1 analogues or sodium‐glucose co‐transporter‐2 inhibitors the answer?
Authors: Vincent Rebecca K. , Williams David M. , Evans Marc
Published: September 2020

The increasing prevalence of diabetes and non‐alcoholic fatty liver disease (NAFLD) is a growing public health concern associated with significant morbidity, mortality and economic cost, particularly in those who progress to cirrhosis. Medical treatment is frequently limited, with no specific licensed treatments currently available for people with NAFLD. Its association with diabetes raises the possibility of shared mechanisms of disease progression and treatment. With the ever‐growing interest in the non‐glycaemic effects of diabetes medications, studies and clinical trials have investigated hepatic outcomes associated with the use of drug classes used for people with type 2 diabetes (T2D), such as glucagon‐like peptide‐1 (GLP‐1) analogues or sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors. Studies exploring the use of GLP‐1 analogues or SGLT2 inhibitors in people with NAFLD have observed improved measures of hepatic inflammation, liver enzymes and radiological features over short periods. However, these studies tend to have variable study populations and inconsistent reported outcomes, limiting comparison between drugs and drug classes. As these drugs appear to improve biomarkers of NAFLD, clinicians should consider their use in patients with NAFLD and T2D. However, further evidence with greater participant numbers and longer trial durations is required to support specific licensing for people with NAFLD. Larger trials would allow reporting of major adverse hepatic events, akin to cardiovascular and renal outcome trials, to be determined. This would provide a more meaningful evaluation of the impact of these drugs in NAFLD. Nevertheless, these drugs represent a future potential therapeutic avenue in this difficult‐to‐treat population and may beget significant health and economic impacts.
The impact of thermal seasonality on terrestrial endotherm food web dynamics: a revision of the Exploitation Ecosystem Hypothesis
Authors: Oksanen Tarja , Oksanen Lauri , Vuorinen Katariina E. M. , Wolf Christopher , Mäkynen Aurelia , Olofsson Johan , Ripple William J. , Virtanen Risto , Utsi Tove Aa.
Published: September 2020

Many terrestrial endotherm food webs constitute three trophic level cascades. Others have two trophic level dynamics (food limited herbivores; plants adapted to tackle intense herbivory) or one trophic level dynamic (herbivorous endotherms absent, thus plants compete for the few places where they can survive and grow). According to the Exploitation Ecosystems Hypothesis (EEH), these contrasting dynamics are consequences of differences in primary productivity. The productivity thresholds for changing food web dynamics were assumed to be global constants. We challenged this assumption and found that several model parameters are sensitive to the contrast between persistently warm and seasonally cold climates. In persistently warm environments, three trophic level dynamics can be expected to prevail almost everywhere, save the most extreme deserts. We revised EEH accordingly and tested it by compiling direct evidence of three and two trophic level dynamics and by studying the global distribution of felids. In seasonally cold environments, we found evidence for three trophic level dynamics only in productive ecosystems, while evidence for two trophic level dynamics appeared in ecosystems with low primary productivity. In persistently warm environments, we found evidence for three trophic level dynamics in all types of ecosystems. The distribution of felids corroborated these results. The empirical evidence thus indicates that two trophic level dynamics, as defined by EEH, are restricted to seasonally cold biomes with low primary productivity, such as the artic–alpine tundra and the temperate steppe.
Impact of mandibular third molars on angle fractures: A retrospective study
Authors: Kandel Laxmi , Mishra Ravish , Yadav Deepak , Tripathi Shashank , Shubham Snigdha , Chhetri Pradip
Published: September 2020

Background

Previous studies have shown that the position and presence of mandibular third molars is associated with a high risk of mandibular angle fractures. The aim of this study was to assess the relationship between the position and presence of mandibular third molars and mandibular angle fractures.

Material and Methods

A retrospective study consisting of 256 patients who were admitted for treatment of mandibular fractures between January 2016 and January 2018 was undertaken. Patients' data and orthopantomogram radiographs were obtained from their medical record. The predictor variable was the presence and position of mandibular third molars. The position of the third molars was grouped based on the Pell and Gregory classification. The outcome variable was the presence of an angle fracture. Other study variables included age, gender, mechanism of injury, and fracture location.

Results

Patients with mandibular third molars had a 2.7 times greater chance of an angle fracture than patients without third molars. Patients with their third molars present at occlusal position C and ramus position level 3 had a higher risk of angle fracture in comparison with other groups. There was a statistically significant variation in the risk of an angle fracture, depending on mandibular third molar position (P < .001).

Conclusion

Patients with mandibular third molars have an increased risk of angle fractures. The risk for an angle fracture varied depending on the third molar position.
Shifting limitation of primary production: experimental support for a new model in lake ecosystems
Authors: Olson Carly R. , Solomon Christopher T. , Jones Stuart E.
Published: September 2020

The limits on primary production vary in complex ways across space and time. Strong tests of clear conceptual models have been instrumental in understanding these patterns in both terrestrial and aquatic ecosystems. Here we present the first experimental test of a new model describing how shifts from nutrient to light limitation control primary productivity in lake ecosystems as hydrological inputs of nutrients and organic matter vary. We found support for two key predictions of the model: that gross primary production (GPP) follows a hump‐shaped relationship with increasing dissolved organic carbon (DOC) concentrations; and that the maximum GPP, and the critical DOC concentration at which the hump occurs, are determined by the stoichiometry and chromophoricity of the hydrological inputs. Our results advance fundamental understanding of the limits on aquatic primary production, and have important applications given ongoing anthropogenic alterations of the nutrient and organic matter inputs to surface waters.
Changes in caregiver depression, anxiety, and satisfaction with family relationships in families of children who did and did not undergo resective epilepsy surgery
Authors: Phillips Natalie L. , Widjaja Elysa , Smith Mary Lou
Published: September 2020

Objective

To evaluate longitudinal changes in caregiver depression, anxiety, and family relationships following resective surgery for pediatric drug‐resistant epilepsy (DRE).

Methods

This multicenter cohort study involved 177 caregivers of children with DRE aged 4‐18 years (63 surgical and 114 nonsurgical). Caregivers completed measures of depression (Quick Inventory of Depressive Symptomatology), anxiety (Generalized Anxiety Disorder 7‐item scale), and satisfaction with family relationships (Family Adaptability, Partnership, Growth, Affective, and Resolve scale) at baseline, 6 months, and 1 year. Additional data collected at baseline included child, caregiver, and family sociodemographic and clinical factors as well as family environment (demands and resources).

Results

At 1 year, 64% and 27% of surgical and nonsurgical patients were seizure‐free, respectively. Linear mixed‐effects models found a reduction in caregiver depression (b = −0.85, P = .004) and anxiety (b = −1.09, P = .003), but not family satisfaction (b = 0.18, P = .31) over time. There was no effect of treatment. When seizure outcome was added to the model, seizure freedom was associated with fewer depressive symptoms (b = −1.15, P = .005) and greater family satisfaction (b = 0.65, P = .006), but not anxiety (b = −0.41, P = .42). A greater proportion of caregivers of patients who achieved seizure freedom (32%) versus continued seizures (18%) reported clinically meaningful improvement in depression at 1 year (P = .03). Lower baseline depression (β = 0.42, P < .001), greater family resources (β = −0.18, P = .04), and male caregiver (β = 0.15, P = .02) predicted lower caregiver depression, and lower baseline anxiety (β = 0.47, P < .001), greater family resources (β = −0.24, P = .01), and higher education (β = −0.13, P = .04) predicted lower caregiver anxiety at 1 year. Baseline functioning was the only predictor of family relationships at 1 year (β = 0.49, P < .001).

Significance

Caregivers of children who achieved seizure freedom, irrespective of surgical treatment, report fewer depressive symptoms and greater satisfaction with family relationships. Baseline functioning is the strongest predictor of outcome; however, caregivers of families with fewer resources and supports are also at risk of poor psychosocial outcomes.
Preictal variability of high‐frequency oscillation rates in refractory epilepsy
Authors: Scott Jared M. , Ren Sijin , Gliske Stephen V. , Stacey William C.
Published: September 2020

Objective

High‐frequency oscillations (HFOs) have shown promising utility in the spatial localization of the seizure onset zone for patients with focal refractory epilepsy. Comparatively few studies have addressed potential temporal variations in HFOs, or their role in the preictal period. Here, we introduce a novel evaluation of the instantaneous HFO rate through interictal and peri‐ictal epochs to assess their usefulness in identifying imminent seizure onset.

Methods

Utilizing an automated HFO detector, we analyzed intracranial electroencephalographic data from 30 patients with refractory epilepsy undergoing long‐term presurgical evaluation. We evaluated HFO rates both as a 30‐minute average and as a continuous function of time and used nonparametric statistical methods to compare individual and population‐level differences in rate during peri‐ictal and interictal periods.

Results

Mean HFO rate was significantly higher for all epochs in seizure onset zone channels versus other channels. Across the 30 patients of our cohort, we found no statistically significant differences in mean HFO rate during preictal and interictal epochs. For continuous HFO rates in seizure onset zone channels, however, we found significant population‐wide increases in preictal trends relative to interictal periods. Using a data‐driven analysis, we identified a subset of 11 patients in whom either preictal HFO rates or their continuous trends were significantly increased relative to those of interictal baseline and the rest of the population.

Significance

These results corroborate existing findings that HFO rates within epileptic tissue are higher during interictal periods. We show this finding is also present in preictal, ictal, and postictal data, and identify a novel biomarker of preictal state: an upward trend in HFO rate leading into seizures in some patients. Overall, our findings provide preliminary evidence that HFOs can function as a temporal biomarker of seizure onset.
Temperature does matter—an additional dimension in kinase inhibitor development
Authors: Strauch Miriam , Heyd Florian
Published: September 2020

Kinase inhibitors are a major focus in drug development. Recent work shows that subtle temperature changes in the physiologically relevant temperature range can dramatically alter kinase activity and specificity. We argue that temperature is an essential factor that should be considered in inhibitor screening campaigns. In many cases, high‐throughput screening is performed at room temperature or 30 °C, which may lead to many false positives and false negatives when evaluating potential inhibitors in the physiological temperature range. As one example, we discuss a new antimalaria compound that inhibits the highly temperature‐sensitive kinase CLK3 (CDC2‐like kinase 3) from Plasmodium falciparum.
Review: Epidemiology of Helicobacter pylori
Authors: Mezmale Linda , Coelho Luiz Gonzaga , Bordin Dmitry , Leja Marcis
Published: September 2020

This review summarizes the recent knowledge on the epidemiology of Helicobacter pylori and the potential modes of transmission. In addition to English language publications, the authors have included original full‐text publications from Russia and Latin America published in the original languages. High H pylori prevalence has been reported in Russia, Jordan, Iran, China, and Latin American countries as well as in Arctic populations in Canada. Indigenous inhabitants in the Arctic were found to be infected substantially more frequently than non‐indigenous inhabitants. In Amsterdam, the Netherlands, the ethnic minority groups were at a significantly higher risk of being H pylori seropositive compared to the Dutch population. For the first time, data on the prevalence from Armenia have been published indicating 41.5% H pylori prevalence. Convincing evidence on the decline of H pylori prevalence in Southeast Hungary and Taiwan was published. A study from Chile suggested high infection rates in newborns during the first month after birth. Two meta‐analyses covered the potential correlation between H pylori and periodontal diseases, therefore addressing the potential oro‐oral transmission rates. Periodontal disease was found to be more prevalent in H pylori‐infected subjects. Other studies addressed the potential role of drinking water and food products as well as socioeconomic factors in transmitting the infection. Several studies in Asia addressed annual reinfection rates of H pylori, ranging from 1.5% in China to 3.1% in Korea. Finally, a review was published on the current evidence and future perspective of analysing H pylori in ancient human remains by a metagenomic approach.
Progression to fibrosing diffuse alveolar damage in a series of 30 minimally invasive autopsies with COVID‐19 pneumonia in Wuhan, China
Authors: Li Yan , Wu Junhua , Wang Sihua , Li Xiang , Zhou Junjie , Huang Bo , Luo Danju , Cao Qin , Chen Yajun , Chen Shuo , Ma Lin , Peng Li , Pan Huaxiong , Travis William D. , Nie Xiu
Published: September 2020

Aims

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), infection has been deemed as a global pandemic by the World Health Organisation. While diffuse alveolar damage (DAD) is recognised to be the primary manifestation of COVID‐19 pneumonia, there has been little emphasis on the progression to the fibrosing phase of DAD. This topic is of great interest, due to growing concerns regarding the potential long‐term complications in prolonged survivors.

Methods and results

Here we report a detailed histopathological study of 30 autopsy cases with COVID‐19 virus infection, based on minimally invasive autopsies performed between February and March, 2020. The mean age was 69 years, with 20 (67%) males and 10 (33%) females and frequent (70.0%) underlying comorbidities. The duration of illness ranged from 16 to 82 (median = 42) days. Histologically, the most common manifestation was diffuse alveolar damage (DAD) in 28 (93.3%) cases which showed predominantly acute (32%), organising (25%) and/or fibrosing (43%) patterns. Patients with fibrosing DAD were one decade younger (P = 0.034) and they had a longer duration of illness (P = 0.033), hospitalisation (P = 0.037) and mechanical ventilation (P = 0.014) compared to those with acute DAD. Patients with organising DAD had a longer duration of illness (P = 0.032) and hospitalisation (P = 0.023) compared to those with acute DAD.

Conclusions

COVID‐19 pneumonia patients who develop DAD can progress to the fibrosing pattern. While we observed fibrosing DAD in fatal cases, whether or not surviving patients are at risk for developing pulmonary fibrosis and the frequency of this complication will require further clinical and radiological follow‐up studies.
Demonstrating the value of community pharmacists in New Zealand educating a targeted group of people to temporarily discontinue medicines when they are unwell to reduce the risk of acute kidney injury
Authors: Vicary Dianne , Hutchison Colin , Aspden Trudi
Published: September 2020

Objective

Acute kidney injury (AKI) prevention strategies for community-acquired AKI associated with severe acute illness have received attention in recent years. The objective of this study was to evaluate a community pharmacist AKI education programme aimed at patient self-management during acute dehydrating illnesses.

Methods

This was a multimethod study. Potential participants were identified by community pharmacists when they presented a prescription containing a study medicine. The intervention consisted of completion of a short demographic questionnaire and a pharmacist providing verbal AKI information and advice on self-management during acute dehydrating illness, including medicine withholding. This information was supported with take-home information. Participants were telephoned between 4 and 11 months later and invited to participate in a structured telephone interview. Descriptive statistics were generated from questionnaire responses, and interview data were analysed using manifest content analysis.

Key findings

One hundred and thirteen adults were recruited and 93 (82%) interviewed. Fifty-four (58%) interviewees remembered the pharmacist’s education, and 51 (55%) had retained the information sheet. Fifty-eight (62%) would temporarily withhold medicines during acute dehydrating illnesses. Thirty-nine were comfortable they knew when to restart their medicines; 15 (38%) indicated this was once symptom-free for 48 h. Forty-six interviewees were comfortable about contacting their general practice; 16 (35%) would do this after 24 h of illness. Participants found the educational content and pharmacist approach acceptable.

Conclusion

A majority of participants accepted and remembered the information provided by their community pharmacist and felt comfortable to self-manage during acute dehydrating illness. A caveat is participant actions in practice may not be consistent with stated intentions.
Decreased long non‐coding RNA lincFOXF1 indicates poor progression and promotes cell migration and metastasis in osteosarcoma
Authors: Yang Shengquan , Chen Jian , Lv Bin , Zhang Jun , Li Deli , Huang Mengyuan , Yuan Li , Yin Guoyong
Published: September 2020

Long non‐coding RNAs have been demonstrated to be important regulators of various cancers, though the precise mechanisms remain unclear. Although lincFOXF1 has been reported to act as a tumour suppressor, its function and underlying mechanisms in osteosarcoma have not yet been explored. We employed quantitative real‐time polymerase chain reaction (qRT‐PCR) to evaluate the expression of lincFOXF1 and GAPDH in osteosarcoma tissues and cell lines, and colony‐formation, CCK8, wound‐healing, and transwell assays were conducted to analyse the proliferation, migration, and invasion capacity of osteosarcoma cells. Subcellular localization analysis by fractionation and RNA immunoprecipitation assays were performed to elucidate the mechanism responsible for lincFOXF1‐mediated phenotypes of osteosarcoma cells. The results revealed that lincFOXF1 expression is significantly decreased and strongly related to Enneking stage as well as metastasis in osteosarcoma patients. Further experiments showed that lincFOXF1 inhibits the migration, invasion and metastasis of cells in vitro and vivo. Mechanistic investigation demonstrated that lincFOXF1 physically binds to EZH2, a polycomb repressive complex 2 (PRC2) component, and a search for downstream targets suggested that G‐protein‐coupled receptor kinase‐interacting protein 1 (GIT1) is involved in the lincFOXF1‐mediated repression of osteosarcoma cells migration and invasion. Moreover, GIT1 expression is inversely correlated with lincFOXF1 in osteosarcoma. The present findings indicate that lincFOXF1 is involved in the progression of osteosarcoma through binding with EZH2, further regulating GIT1 expression. Our results suggest that lincFOXF1 may serve as a biomarker and therapeutic target for osteosarcoma patients.
Biological functions and clinical applications of exosomal long non‐coding RNAs in cancer
Authors: Wang Yali , Zhang Mengdi , Zhou Fangfang
Published: September 2020

Exosomes are extracellular vesicles secreted by donor cells, and one of the important roles of exosomes is intercellular communication. Exosomes contain proteins, lipids, DNA and RNA. The components exert their functions by modulating the cellular processes of recipient cells. Exosomal long non‐coding RNAs (lncRNAs) are important components and play multiple roles in tumorigenesis and tumour development. In this review, we summarize the biological functions and clinical applications of exosomal lncRNAs in cancer. Exosomal lncRNAs regulate cell proliferation, metastasis, drug resistance and angiogenesis in human cancers. Since exosomal lncRNAs are associated with clinicopathological characteristics of cancer, these might be potentially useful biomarkers for diagnosis and prognosis of cancer. Exosomal lncRNAs participate in multiple processes of cancer progression, which makes them promising therapeutic targets for cancer treatment.
Association of the nasolabial angle and lip length with the gingival and interdental smile line—A gender based evaluation
Authors: Kolte Abhay P. , Kolte Rajashri A. , Samarth Gopal K.
Published: September 2020

Objective

Proportionate existence of the lip framework and gingival scaffold have a critical role in smile esthetics. So, the present study was conducted to assess and correlate the nasolabial angle (NLA) and lip length (LL) with gingival smile line (GSL) and interdental smile line (ISL).

Materials and methods

One hundred and twenty periodontally healthy patients with an age group 20 to 40 years were equally divided based on gender into two groups. The parameters of NLA, LL, GSL, ISL, amount of midfacial gingiva, and interdental papilla display were recorded in the maxillary anterior sextant.

Results

The mean values of NLA and LL at rest and on smiling were found to be higher in males. Majority of study population exhibited Low GSL (LGSL) and High ISL (HISL). On correlation of LL with GSL, the difference in the mean values between males and females for LGSL were highly significant, for HGSL and Cupid's bow the values were significant. The mean values of midfacial gingiva and interdental papilla visible in females was greater than males.

Conclusion

The NLA and LL influence the quantum of gingival exhibit in maxillary anterior teeth with a definitive sexual dimorphism and this can be considered a valuable reference point in smile designing procedures.

Clinical significance

The quantum of gingival exhibit on smiling is an important feature in periodontal, implant, restorative, and smile designing procedures in patients possessing HGSL and HISL category of GSL and ISL. It is indicated that the lip length is correlated with the amount of gingival tissue display both in midfacial as well as interdental region and which needs to be considered by the clinician.
Does Mealtime Communication Improve Happiness? Considering the Trait of Shyness1
Authors: Kimura Shunsuke , Yano Kosuke , Oishi Kazuo
Published: September 2020

Shared mealtimes have been found to be important daily rituals with positive effects on behavior and mental health, such as increasing subjective well‐being. However, most previous studies have not considered possible barriers to these positive effects, specifically shyness. We investigated the relationships among shared mealtime quality, shyness, and subjective well‐being, and the moderating role of shyness in the relationship between the other two variables by surveying a sample of college students (n = 305). Correlational analyses revealed that shared mealtime quality was negatively associated with shyness and positively associated with subjective well‐being. Hierarchical regression analyses revealed that shared mealtime quality was significantly associated with subjective well‐being, as was the interaction between the friend factor of shared mealtime quality and shyness. Therefore, shared mealtime quality might help improve happiness, but shyness should be considered a possible barrier to this beneficial effect when meals are shared with friends.
Physical maturity in common bottlenose dolphins (Tursiops truncatus) from Sarasota Bay, Florida
Authors: Hazelkorn Rebeccah A. , Wells Randall S. , Siders Zachary A. , DeLynn Ruth , Lovewell Gretchen N.
Published: September 2020

Cetacean physical maturity is defined by growth cessation and complete fusion of epiphyses to vertebral bodies indicated by invisible sutures. Many studies have shown epiphyseal fusion is highly variable among individuals. In‐depth examinations into fusion variability are lacking. We analyzed vertebrae of 37 (n= 21female,n= 16male) stranded common bottlenose dolphins (Tursiops truncatus) from the well‐studied Gulf of Mexico, Sarasota Bay community. For each specimen, vertebrae were examined by vertebral region for degree of fusion anteriorly and posteriorly of each centrum and categorized from unfused to fused in five degrees. An ordinal logistic regression was used to estimate degree of fusion probability for each epiphysis. The model had fixed effects for age, number of offspring, sex, sexual maturity, and a random effect for epiphysis. Results show that age/reproductive status significantly explains an individual's degree of fusion. Adult females with fewer calves had more fusion than those with more reproductive experience across multiple ages. Access to long‐term observational and sample data on the dolphins residing in the area served by Mote Marine Laboratory's Stranding Investigations Program offers a unique opportunity to examine the relationship between energetic demands of reproduction (calcium production/reproductive output) versus preconceived definitions of physical maturity (skeletal fusion) more closely.
Changes in fecal short‐chain fatty acids following fecal microbiota transplantation in patients with irritable bowel syndrome
Authors: El‐Salhy Magdy , Valeur Jørgen , Hausken Trygve , Gunnar Hatlebakk Jan
Published: September 2020

Background

Short‐chain fatty acids (SCFAs) may play a role in the pathophysiology of irritable bowel syndrome (IBS). This study analyzed fecal SCFAs after performing fecal microbiota transplantation (FMT) in the IBS patients who were included in our previous study of the efficacy of FMT.

Methods

This study included 142 of the 164 IBS patients who participated in our previous study. They were belonging to three groups: placebo (own feces), 30‐g (superdonor feces), and 60‐g (superdonor feces) FMT. The patients completed the IBS Severity Scoring System (IBS‐SSS) Birmingham IBS Symptom, Fatigue Assessment Scale (FAS), the IBS Quality of Life (IBS‐QoL) and Short‐Form Nepean Dyspepsia Index (SF‐NDI) questionnaires and delivered fecal samples at the baseline and 1 month after FMT. The SCFA levels were determined by vacuum distillation followed by gas chromatography.

Key Results

The fecal butyric acid level was significantly increased after FMT in both the 30‐g and 60‐g groups (both P ≤ 0.001). In the 60‐g group, the levels of total SCFAs and isobutyric, isovaleric, and valeric acids increased after FMT. Butyric acid levels in the responders in both the 30‐g and 60‐g FMT groups were significantly inversely correlated with IBS‐SSS and FAS scores (P = 0.001, r = −0.3 and P = 0.0001. r=‐ 0.3, respectively). There were no differences in the SCFA levels in the placebo group after FMT.

Conclusion and Inferences

FMT increases the fecal SCFA levels in IBS patients. The increase in the butyric acid level is inversely correlated with symptoms in IBS patients following FMT, suggesting that SCFAs might play a role in the pathophysiology of IBS. www.clini​caltr​ials.gov (NCT03822299).
Wittgenstein on Aspect‐Recognition in Philosophy and Mathematics
Authors: Hymers Michael
Published: September 2020

Although Wittgenstein’s most extensive discussion of aspect‐recognition appears in Part II of the Philosophical Investigations, aspect‐recognition was of interest to Wittgenstein almost from the beginning of his engagement with philosophy at Cambridge in 1912. However, the nature of that interest changes upon his return to Cambridge in 1929, and that change in turn is connected with the inter‐related ideas that philosophical clarity rests on recognising aspects of our grammar and that mathematical proof leads us to recognise new aspects of mathematical expressions.