bluuebunny/crossref_metadata_2025 huggingface dataset:
Triggers of breathlessness in inducible laryngeal obstruction and asthma
Authors: Haines Jemma , Chua Sarah H. K. , Smith Jacky , Slinger Claire , Simpson Andrew J. , Fowler Stephen J.
Published: July 2020

Background

Inducible laryngeal obstruction (ILO) is often misdiagnosed as, or may coexist with, asthma. Identifying differences in triggering factors may assist clinicians to differentiate between the two conditions and could give mechanistic insights.

Objective

To identify and compare patient‐reported triggers in ILO and asthma.

Methods

This was a two‐part study. Initially, we conducted a retrospective case note review of the triggers of ILO from endoscopically confirmed ILO patients to generate a Breathlessness Triggers Survey (BrTS). Triggers were categorized as scents, environmental factors, temperature, emotions, mechanical factors and daily activities. Secondly, ILO and/or asthma patients completed the BrTS prospectively, rating the likelihood of each item triggering their symptoms using a five‐point Likert scale (strongly disagree to strongly agree). Chi‐square testing was performed to compare responses by cohort.

Results

Data from 202 patients with ILO [73% female, mean (SD) age 53(16) years] were included in the case note review. For the prospective study, 38 patients with ILO only [63% females, age 57(16) years], 39 patients with asthma only [(56% female, age 53(13) years] and 12 patients with both ILO and asthma [83% female, mean age, 57 (14) years)] completed the BrTS. The triggers identified in the case note review were confirmed in the independent sample of patients with ILO and/or asthma and identified several difference in prevalence of the triggers between disease types. Mechanical factors (talking [P < .001], shouting [P = .007] and swallowing [P = .002]) were more common in the ILO cohort compared to patients with asthma. Environmental factors (pollen/flowers [P = .005] and damp air [P = .012]) were more common in asthma. There were no differences between groups in frequency of reporting scents as triggers (except for vinegar, more common in ILO, P = .019), temperature, emotions or daily activities.

Conclusion

There were notable differences between patient‐reported triggers of ILO and asthma, which may support clinician differential diagnosis.
The relationship between maternal vitamin D deficiency and glycolipid metabolism and adverse pregnancy outcome
Authors: Chen Hai‐Ying , Zhang Hong‐Ping , Yang Jie , Huang Zhi‐Qiong , Xu Hai‐Xia , Jin Jiang , Xu Kai , Tong Yu , Dong Qian‐Qian , Zheng Jian‐Qiong
Published: July 2020

Objective

Maternal vitamin D deficiency is associated with glucose and lipid metabolism in the mother and offspring. Meanwhile, it can also lead to adverse pregnancy outcomes. The aim of this case‐control study was to document maternal, umbilical arterial glucose and lipid metabolic levels and correlations in pregnancies with or without vitamin D deficiency, while also investigating adverse pregnancy outcomes.

Design/Participants/Measurements

A total of 425 pregnant women who received antenatal care and delivered at Wenzhou People's Hospital were enrolled. According to their serum 25‐hydroxyvitamin D [25(OH)D] level, the pregnant women were divided into the vitamin D deficiency group [25(OH)D < 20 ng/mL, 185 participants] and the control group [25(OH)D ≥ 20 ng/mL, 240 participants]. Maternal blood samples were collected at 24‐28 weeks of gestation and delivery for 75‐g oral glucose tolerance test (OGTT), and measurements of glucose and lipid metabolite levels and 25(OH)D levels. Umbilical arterial samples were collected during delivery (33.57‐41.43 gestational weeks).

Results

Compared with control participants, vitamin D deficiency women had significantly higher concentrations of fasting blood‐glucose (P < .01), 1‐h OGTT plasma glucose (P < .01), 2‐h OGTT plasma glucose (P < .01), insulin (P < .01), HOMA‐IR (P < .01), LDL (P < .01) and triglycerides (P = .02) and lower concentrations of HOMA‐S (P < .01). Compared with the control group, vitamin D deficiency women had higher concentrations of triglycerides (P < .01) and lower concentrations of HDL‐C (P < .01) and HOMA‐β (P = .01) in infant umbilical arterial blood. Pearson's correlation analysis demonstrated that the maternal 25(OH)D level was negatively correlated with maternal plasma glucose, insulin, LDL‐C, cholesterol, triglyceride and HOMA‐IR (r = −.38, −.27, −.2, −.11, −.11, −.33 and .11; P < .01, <.01, <.01, <.05, <.05 and <.01, respectively), while there was a positive correlation between maternal serum 25(OH)D and HOMA‐S (r = .11, P < .05). The triglyceride level in the umbilical artery was negatively correlated with maternal serum 25(OH)D concentration (r = −.286, P < .01), while the HDL‐C and HOMA‐β in umbilical artery were positively related (r = .154, .103, P < .01). Compared with the control group, the incidences of pre‐eclampsia [4.8% (9/185) vs 1.25% (3/240), P = .03], gestational diabetes mellitus [19.45% (36/185) vs 12.08% (29/240), P = .04] and premature rupture of membranes [15.68% (29/185) vs 5.42% (13/240), P < .01] were higher in the vitamin D deficiency group.

Conclusion

Vitamin D deficiency during pregnancy is associated with maternal glucose and lipid metabolism and pregnancy outcomes. Therefore, it is worth recommending to maintain vitamin D status at an optimal level in pregnant women to prevent metabolic disorders and pregnancy complications.
Elevated level of uric acid in aqueous humour is associated with posterior subcapsular cataract in human lens
Authors: Qin Yong Jie , Chan Sun On , Lin Hong Liang , Zhang Yu Qiao , Chen Yan Lei , Niu Yong Yi , Xie Wen Juan , Chu Wai Kit , Pang Chi Pui , Zhang Hong Yang
Published: July 2020

Importance

Age‐related cataract is the leading cause of blindness worldwide. The pathological mechanisms causing this disease remain elusive.

Background

To examine the involvement of uric acid (UA) in the pathogenesis of posterior subcapsular cataract (PSC).

Design

Retrospective study and experimental investigation.

Participants

A total of 180 patients with PSC or non‐PSC were included.

Methods

Samples obtained from the patients were used to analyse content of UA and for histochemical examinations. The effects of UA on human lens epithelial cells were also investigated.

Main Outcome Measures

Aqueous humour UA and urate deposits.

Results

The results showed a significant increase of aqueous humour UA in patients with PSC. After adjustment for potential confounders, elevated aqueous humour UA (odds ratio [OR] = 1.45) showed a stronger association with PSC than serum UA (OR = 1.10). Gomori methenamine silver staining revealed in PSC an intense deposit of urates in the lens fibres in equatorial regions, and in subcapsular fibres in posterior regions of the lens. Such staining was not detected in the lens with non‐PSC. Treatment with UA‐induced senescence and apoptosis in human lens epithelial cells in a dose dependent manner. Our results suggest that the elevated level of UA in aqueous humour causes a deposition of urates in human lens epithelium, which could possibly lead to dysfunction of these cells that generates opacification in PSC.

Conclusions and Relevance

These findings indicate the local action of excessive UA in the pathogenesis of PSC. Control of serum UA level could delay the progression of PSC.
Clinical features and underlying genetic causes in neonatal encephalopathy: A large cohort study
Authors: Yang Lin , Chen Xiang , Liu Xu , Dong Xinran , Ye Chang , Deng Dongli , Lu Yulan , Lin Yifeng , Zhou Wenhao
Published: July 2020

This study aimed to investigate the potential genetic causes of neonatal encephalopathy (NE) in a large cohort of Chinese patients. We included 366 neonates with encephalopathy. Whole exome sequencing was performed to assess the potential molecular defects. In this study, 43 patients (11.7%) were identified with pathogenic or likely pathogenic variants and 10 patients (2.7%) carried variants with unknown significance. Compared with patients without genetic findings (28.9%), patients with genetic findings (96.2%) displayed a significant higher incidence of seizure (P = .0009); however, a lower frequency of abnormal magnetic resonance imaging (MRI) results (P < .0001). Epileptic encephalopathy related genes account for nearly half (46.4%) of all genetic defects of NE with seizures. Follow‐up results revealed genetic diagnosis, seizure and severe abnormal electroencephalograph results were significantly associated with high risk of developmental delay (P < .05). This study increases the understanding of genetic contribution to NE. Our findings suggest that the full‐term NE patients with seizure, the greater the possibility of genetic diseases. However, for newborns especially the preterm babies with abnormal MRI findings, there is smaller possibility of genetic diseases. NE caused from genetic diseases have poor prognosis, and intensive intervention and follow‐up is necessary for these newborns.
Intracerebral transplantation of HLA‐homozygous human iPSC‐derived neural precursors ameliorates the behavioural and pathological deficits in a rodent model of ischaemic stroke
Authors: Noh Jeong‐Eun , Oh Seung‐Hun , Lee Suji , Lee Soohyeon , Kim Young Hoon , Park Hyun Jung , Ju Ji Hyeon , Kim Hyun Sook , Huh Ji Young , Song Jihwan
Published: July 2020

Objectives

Human‐induced pluripotent stem cells (hiPSCs) are a promising cell source for treating ischaemic stroke. Although autologous hiPSCs provide the advantage of avoiding immune rejection, their practical limitations, such as substantial amount of time and costs to generate individual iPSC lines, have hampered their widespread application in clinical settings. In this study, we investigated the therapeutic potential of neural precursor cells derived from human HLA‐homozygous induced pluripotent stem cells (hiPSC‐NPCs) following intracerebral transplantation into a rodent model of middle cerebral artery occlusion (MCAo).

Materials and Methods

We differentiated a GMP‐grade HLA‐homozygous hiPSC line (CMC‐hiPSC‐004) into neural precursor cells for transplantation into rats at the subacute stage of ischaemic stroke (ie at 7 days after the induction of MCAo). To investigate functional recovery, the transplanted animals were subjected to five behavioural tests, namely the rotarod, stepping, mNSS, staircase and apomorphine‐induced rotation tests, for up to 12 weeks, followed by histological analyses.

Results

We observed that the hiPSC‐NPC transplantation produced significant behavioural improvements. At 12 weeks post‐transplantation, a high proportion of transplanted cells survived and had differentiated into MAP2+ mature neurons, GABAergic neurons and DARPP32+ medium spiny neurons. The transplanted cells formed neuronal connections with striatal neurons in the host brain. In addition, hiPSC‐NPC transplantation gave rise to enhanced endogenous repair processes, including decreases of post‐stroke neuroinflammation and glial scar formation and an increase of proliferating endogenous neural stem cells in the subventricular zone as well as the perilesional capillary networks.

Conclusions

These results strongly suggest that HLA‐homozygous hiPSC‐NPCs may be useful for treating ischaemic stroke patients.
Thyroid dysfunctions in adult patients after allogeneic hematopoietic stem cell transplantation
Authors: Ataca Atilla Pinar , Akkus Erman , Atilla Erden , Gokmen Neslihan , Civriz Bozdag Sinem , Kurt Yuksel Meltem , Toprak Selami Kocak , Baskal Nilgun , Akan Hamdi , Demirer Taner , Topcuoglu Pervin , Arslan Onder , Ilhan Osman , Ozcan Muhit , Beksac Meral , Gurman Gunhan
Published: July 2020

Introduction

Thyroid dysfunction (TD) is one of the major endocrinopathies shown after allogeneic hematopoietic stem cell transplantation over the long term. The incidence and the risk factors for TD have varied widely.

Patients and Methods

Two hundred and fifty‐nine patients with pre‐transplant normal thyroid function tests who survived at least 1 year after allo‐HSCT between 2006‐2016 were included in the study.

Results

Sixty‐four patients (25%) developed TD at median of 34 months (range, 1‐112 months). Hypothyroidism was detected in 32 patients (12%): 5 patients had primary hypothyroidism, and subclinical hypothyroidism occurred in 27 patients. 18 patients (7%) were diagnosed with hyperthyroidism: 2 patients (0.07%) were treated for primary hyperthyroidism, and 16 patients (6%) were followed for subclinical hyperthyroidism. Euthyroid sick syndrome occurred in 14 cases. None of the patients with thyroid dysfunction developed secondary thyroid malignancy. Receiving high‐dose TBI (P = .001) was found to be significant risk for hypothyroidism; older age than median (P = .01) and pre‐transplant active disease (P < .0001) were related to hyperthyroidism.

Conclusions

Thyroid dysfunction, mostly hypothyroidism, is a long‐term complication after allo‐HSCT in 25% of patients. Older age, pre‐transplant active disease, and receiving TBI are among the risk factors. Sustained long‐term monitoring of thyroid function test should be considered post allo‐HSCT.
Lang bestehende Morphea und das Risiko für Plattenepithelkarzinome der Haut
Authors: Heck Johannes , Olk Joanna , Kneitz Hermann , Hamm Henning , Goebeler Matthias
Published: July 2020

Der Begriff Sklerodermie umfasst eine heterogene Gruppe fibrosierender Bindegewebserkrankungen unbekannter Ätiologie. Die Morphea (Syn.: zirkumskripte Sklerodermie) ist eine umschriebene Form der Sklerodermie, die in einigen Fällen zu (chronischen) Erosionen und Ulzerationen betroffener Hautareale führen kann. Fibrosierung, Entzündung und chronische Ulzerationen können die Entwicklung von Hauttumoren begünstigen; die Morphea stellt daher einen seltenen, aber etablierten Risikofaktor für kutane Plattenepithelkarzinome (kPEK) dar. In der vorliegenden Arbeit präsentieren wir eine Übersicht von 16 Patienten mit Morphea (15 Fallberichte, die mittels systematischer Literaturrecherche in der Datenbank PubMed identifiziert wurden; einen Fall aus unserer Klinik), die ein kPEK entwickelt hatten, und wir diskutieren mögliche zugrunde liegende Mechanismen. Die statistische Analyse ergab, dass sich kPEK auf dem Boden einer Morphea am häufigsten an der unteren Extremität manifestieren. Im Durchschnitt vergingen zehn bis zwanzig Jahre zwischen dem Beginn der Morphea und der Entstehung eines kPEK. Bei Patienten mit Morphea sollte bei Nachuntersuchungen auf Hauttumoren geachtet werden. Vor dem Einsatz von Immunsuppressiva oder Phototherapien ist angesichts des karzinogenen Potenzials dieser Therapieformen eine sorgfältige Risiko‐Nutzen‐Abwägung angezeigt.
Die Dermatofluoroskopie als Diagnoseverfahren bei verschiedenen pigmentierten Hautläsionen: Stärken und Schwächen
Authors: Hofmann Maja Ann , Keim Ulrike , Jagoda Agata , Forschner Andrea , Fink Christine , Spänkuch Iris , Tampouri Ioanna , Eigentler Thomas , Weide Benjamin , Haenssle Holger A. , Garbe Claus
Published: July 2020

Hintergrund

Die Melaninfluoreszenz von Hautläsionen kann mittels Zwei‐Photonen‐Anregung gemessen werden. Dieses als Dermatofluoroskopie bezeichnete Verfahren führt zu einer Verschiebung vom grünen Spektrum bei gutartigen melanozytären Läsionen zum roten Spektrum bei Melanomen. Diese Studie widmete sich der Frage, welche Art von pigmentierten Läsionen korrekt als melaninhaltige maligne Tumoren erkannt werden können.

Methoden

Es wurden 476 pigmentierte Läsionen, darunter 101 kutane Melanome, dermatofluoroskopisch untersucht. Dazu wurde die Melaninfluoreszenz Punkt für Punkt mit einem Abstand der Messpunkte von 0,2 mm gemessen. Die Ergebnisse der Dermatofluoroskopie wurden als diagnostischer Score mit einem Cut‐off‐Wert von ≥ 28 für die Diagnose melaninhaltiger maligner Tumor angegeben und mit dem Goldstandard der Histopathologie verglichen.

Ergebnisse

Die Differenz zwischen den diagnostischen Scores verschiedener Hauttumoren war hochsignifikant (p < 0.0001). Der dermatofluoroskopisch ermittelte Score zeigte bei den Melanomen die höchste Sensitivität (92,1 %). Bemerkenswert ist, dass die meisten pigmentierten Basalzellkarzinome (BZK, 88,9 %) als melaninhaltige maligne Tumoren erkannt wurden. Eine höhere Sensitivität für die richtige Diagnose wurde bei älteren Patienten (≥ 53 Jahre, p = 0,003), Patienten mit gebräunter Haut (p = 0,025) und bei Patienten mit Sommersprossen in der Kindheit (p = 0,046) beobachtet.

Schlussfolgerungen

Die Zwei‐Photonen‐Fluoreszenz ist ein innovatives Verfahren für die Diagnose pigmentierter Hautläsionen mit einer hohen Sensitivität beim Nachweis von Melanomen und pigmentierten BZK.
Relationships between the distribution of wildlife and livestock diversity
Authors: Velado‐Alonso Elena , Morales‐Castilla Ignacio , Rebollo Salvador , Gómez‐Sal Antonio
Published: July 2020

Aim

Wild biodiversity and agrobiodiversity are affected by challenges such as agricultural intensification. However, it is unknown whether or not both components of biodiversity respond similarly to environmental factors and to these challenges. Here, we examine the spatial relationships between the distributions of wild biodiversity and agrobiodiversity, to quantify how and where they covary across the geography.

Location

Mainland Spain, a European region that harbours high values of both wild and agro‐ biodiversity.

Methods

We used geographically weighted regression models to analyse the spatial variation in the relationships between the distribution of wild vertebrates and environmental and agrobiodiversity variables. We modelled the spatial gradients in species richness of native terrestrial vertebrates—that is, specific groups of amphibians, reptiles, birds and mammals—as a function of local livestock breed richness—that is, bovine, ovine, caprine, asinine, equine and porcine—climate variables and human footprint.

Results

We found significant covariation between the distribution of native vertebrate species richness and climate, human footprint and livestock diversity. Overall, the association between species richness of the four wild terrestrial vertebrate groups and local livestock breed richness is positive across most of the studied area. However, local breed richness of cattle and sheep breed displays contrasting patterns, where cattle breeds associate positively to most wildlife vertebrates and sheep breeds show negative associations.

Main conclusion

Wildlife diversity distributions are significantly associated with livestock agrobiodiversity. These spatial relationships are mediated by large‐scale environmental gradients. Since both, wildlife and livestock agrobiodiversity, tend to co‐occur spatially, future strategies for conservation in agricultural landscapes could benefit from integrated approaches.
Climate–diversity relationships underlying cross‐taxon diversity of the African fauna and their implications for conservation
Authors: Pinkert Stefan , Zeuss Dirk , Dijkstra Klaas‐Douwe B. , Kipping Jens , Clausnitzer Viola , Brunzel Stefan , Brandl Roland
Published: July 2020

Aim

Many taxa show remarkable similarities in their diversity patterns, and these similarities are commonly used to define large‐scale conservation priorities. Here, we investigated the relative importance of contemporary climate and climate change since the Last Glacial Maximum for determining the species richness and rarity patterns of four animal taxa. We assessed the extent to which diversity patterns are congruent across taxa because of similar responses to these climatic aspects, and we identify regions that are disproportionately diverse due to their palaeoclimatic stability.

Location

Sub‐Saharan Africa.

Time period

LGM–contemporary.

Major taxa studied

Mammal, bird, amphibian and dragonfly species.

Methods

Diversity patterns were predicted based on their relationships with contemporary climate and Quaternary climate change, respectively. Climate–diversity relationships were modelled with and without accounting for spatial autocorrelation. For raw and predicted diversity patterns, cross‐taxon congruence and the coverage of diversity hotspots by protected areas were determined.

Results

Species richness and rarity of all taxa increased with increasing temperature and precipitation, but also with increasing palaeoclimatic stability. Cross‐taxon congruence was higher for predictions based on contemporary climate than for predictions based on Quaternary climate change. Protected areas covered 17%–37% of the species richness and rarity hotspots and approximately 6% fewer hotspots of the underlying signatures of Quaternary climate change (i.e. biodiversity refugia).

Main conclusions

Both contemporary climate and past climatic changes strongly affect species richness and rarity patterns. However, whereas contemporary climate–diversity relationships are largely congruent across taxa, signatures of Quaternary climate change differ among taxa. Furthermore, protected areas emphasize regions with high species richness and rarity but fewer biodiversity refugia—even less than expected by random placement (<21%). Our results highlight the importance of historical factors for shaping large‐scale diversity patterns and the potential of using palaeoclimatic stability‐diversity relationships for identifying important conservation areas at the global scale.
Chronic use of statins and acetylsalicylic acid and incidence of post‐endoscopic retrograde cholangiopancreatography acute pancreatitis: A multicenter, prospective, cohort study
Authors: Cárdenas‐Jaén Karina , Archibugi Livia , Poropat Goran , Korpela Taija , Maisonneuve Patrick , Aparicio Jose R. , Udd Marianne , Stimac Davor , Arcidiacono Paolo G. , De Pretis Niccolò , Valente Roberto , Di Giulio Emilio , Casellas Juan A. , Kylänpää Leena , Hauser Goran , Mariani Alberto , Gabbrielli Armando , Löhr Matthias , Vanella Giuseppe , Rainio Mia , Brozzi Lorenzo , Arnelo Urban , Fagerström Niklas , Capurso Gabriele , de‐Madaria Enrique
Published: July 2020

Objectives

Post‐endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis (PEP) is a frequent complication of this endoscopic procedure. Chronic statin intake has been linked to lower incidence and severity of acute pancreatitis (AP). Periprocedural rectal administration of non‐steroidal anti‐inflammatory drugs is protective against PEP, but the role of chronic acetylsalicylic acid (ASA) treatment is unclear. We aimed to investigate whether statins and chronic ASA intake are associated with lower risk of PEP.

Methods

An international, multicenter, prospective cohort study. Consecutive patients undergoing ERCP in seven European centers were included. Patients were followed‐up to detect those with PEP. Multivariate analysis by means of binary logistic regression was performed, and adjusted odds ratios (aORs) were calculated.

Results

A total of 1150 patients were included, and 70 (6.1%) patients developed PEP. Among statins users, 8.1% developed PEP vs. 5.4% among non‐users (P = 0.09). Multivariate analysis showed no association between statin use and PEP incidence (aOR 1.68 (95% CI 0.94–2.99, P = 0.08)). Statin use had no effect on severity of PEP, being mild in 92.0% of statin users vs. 82.2% in non‐statin users (P = 0.31). Chronic ASA use was not associated with PEP either (aOR 1.02 (95% CI 0.49–2.13), P = 0.96). Abuse of alcohol and previous endoscopic biliary sphincterotomy were protective factors against PEP, while >1 pancreatic guidewire passage, normal bilirubin values, and duration of the procedure >20 minutes, were risk factors.

Conclusions

The use of statins or ASA is not associated with a lower risk or a milder course of PEP.
Mechanistic insights into the evolution of the differential expression of tandemly arrayed cone opsin genes in zebrafish
Authors: Tsujimura Taro
Published: July 2020

The genome of many organisms contains several loci consisting of duplicated genes that are arrayed in tandem. The daughter genes produced by duplication typically exhibit differential expression patterns with each other or otherwise experience pseudogenization. Remarkably, opsin genes in fish are preserved after many duplications in different lineages. This fact indicates that fish opsin genes are characterized by a regulatory mechanism that could intrinsically facilitate the differentiation of the expression patterns. However, little is known about the mechanisms that underlie the differential expression patterns or how they were established during evolution. The loci of green (RH2)‐ and red (LWS)‐sensitive cone opsin genes in zebrafish have been used as model systems to study the differential regulation of tandemly arrayed opsin genes. Over a decade of studies have uncovered several mechanistic features that might have assisted the differentiation and preservation of duplicated genes. Furthermore, recent progress in the understanding of the transcriptional process in general has added essential insights. In this article, the current understanding of the transcriptional regulation of differentially expressed tandemly arrayed cone opsin genes in zebrafish is summarized and a possible evolutionary scenario that could achieve this differentiation is discussed.
A pseudoaneurysm of the left atrium as a rare source of coronary artery embolization
Authors: Mohseni Badalabadi Reza , Sahebjam Mohammad , Poorhosseini Hamidreza , Jenab Yaser , Haddadi Marjan , Hedayat Behnam
Published: July 2020

A 67 years old woman with history of surgical Mitral valve replacement underwent transoesophageal echocardiography for evaluation of mild dyspnoea. It revealed a large narrow‐necked outpouching from medial portion of the inferior wall of the left atrium (LA) that was extended to the interatrial septum. A diagnosis of the LA pseudoaneurysm was made. It contained a fresh clot. Five days later, the patient presented with an acute inferior ST‐elevation myocardial infarction. Coronary angiography revealed an occluded right coronary artery at its distal part by a large thrombus. Thromboaspiration was done and resulted in restoration of a Thrombolysis in Myocardial Infarction Score (TIMI) flow 3 without underlying stenosis.
Relation of microvascular dysfunction and exercise tolerance in patients with heart failure with preserved ejection fraction
Authors: Mahfouz Ragab A. , Gouda Mohammad , Abdelhamid Mohamed
Published: July 2020

Purpose

We aimed to investigate the association of coronary flow reserve (CFR) with exercise tolerance (ET) in subjects with heart failure with preserved ejection fraction (HFpEF).

Materials and Methods

Seventy‐seven patients with HFpEF were recruited for the study and compared with 30 healthy matched age and sex controls. All subjects underwent comprehensive echocardiographic evaluation. Exercise tolerance was assessed using 6‐minute walking test (6 MWT). CFR was calculated with adenosine stress transthoracic Doppler echocardiography.

Results

Out of 77 patients with HFpEF, 51 (66%) had CFR < 2.0. Patients with CFR < 2.0 had lower 6 MWT distance (P < .001), increased E/e' ratio (P < .001), when compared to HFpEF patients with CFR ≥ 2.0 and controls. In subjects with HFpEF, CFR was significantly correlated with 6 MWTD (P < .001) and inversely correlated with E/e" (P < .01). With univariate analysis, the results showed that left ventricular mass index, left atrial volume index, E/e', and CFR were independent predictors for reduced exercise tolerance, whereas at multivariate analysis, reduced CFR was the only independent predictor (P < .001) for both reduced exercise tolerance in patients with HFpEF.

Conclusion

The current study demonstrated that reduced CFR was an independent predictor for reduced exercise tolerance in patients with HFpEF. We supposed that microvascular dysfunction has an important role in pathogenesis and clinical course in subjects with HFpEF.
House prices in the Ottoman Empire: evidence from eighteenth‐century Edirne†
Authors: Karagedikli Gürer , Tunçer Ali Coşkun
Published: July 2020

This study uses a new dataset of 2,246 notarial deeds of house sales from one of the major cities of the Ottoman Empire, Edirne, covering the period from 1720 to 1814. It estimates real hedonic house prices and urban wealth inequality for the housing market. It shows that house size, proximity to the commercial centre, access to fresh water, and family ties were important determinants of relative house prices. These findings also apply to the different quartiles of the market, indicating limited market segmentation. It demonstrates that there was an increase in housing wealth inequality during the eighteenth century as house prices became more dispersed. The hedonic house price index provides evidence that inflation‐adjusted house prices declined substantially following the Russo‐Turkish war of 1768–74. The decline is mainly explained through demographic shocks induced by plague epidemics, natural disasters, and other population movements driven by wars, army mobilization, and political upheavals.
An evaluation of soil phytoliths for reconstructing plant communities and palaeoclimate in the northern temperate region
Authors: Liu Lidan , Jie Dongmei , Liu Hongyan , Gao Guizai , Li Dehui , Li Nannan
Published: July 2020

Phytoliths can act as efficient carriers of information about palaeovegetation and palaeoclimatic conditions, but the representativeness of soil phytoliths from palaeoecological sediments has not been fully understood. In this study, phytolith assemblages in topsoils and associated plant communities at 55 sites in Northeast China were compared. The results indicate that samples from herbaceous and woody communities could be reliably differentiated by topsoil phytoliths. Notably, different phytolith types exhibit varying degrees of representational bias in terms of the aboveground plant community. Some morphotypes (e.g., bilobate, rondel and lanceolate) over‐represent the richness of the corresponding plant; some morphotypes, including microhair, conical epidermal, silicified stomata and epidermal phytoliths, under‐represent the parent plant abundance; additional morphotypes (e.g., elongate, saddle and trapeziform sinuate) are consistent with the changes of associated plants. Based on the representational bias, we calibrated the percentages of topsoil phytoliths and established a phytolith‐based transfer function for precipitation in Northeast China. A palaeoclimate reconstruction in the Changbai Mountains (in the eastern part of Northeast China) based on the above phytolith‐based transfer function for precipitation shows that the region has gone through continuous climatic changes since the late glacial period: from cold and dry conditions to warm and dry conditions, then to warm and wet conditions, and finally to cool and dry conditions. The phytolith‐based reconstructed climate changes since the late glacial period correspond well to those reconstructed by other records from the same stratigraphic profile, and our phytolith‐based climatic reconstruction also confirms the reliability of abrupt cold climatic shifts at 8.2, 6.8, 5.6, 4.6 and 4.2 ka. In conclusion, our results provide the basis for the reliability of phytoliths for reconstructing climatic changes in the northern temperate region.

Highlights

Calibrating soil phytolith assemblages for any quantitative palaeovegetation reconstruction using phytoliths is necessary.

Phytolith morphotypes in topsoils may over‐ or under‐represent or agree with the abundance of modern plant taxa.

Phytolith‐based climatic reconstruction corresponds well with the abrupt climate changes evident since the Late Glacial period and other proxy records.
Seizure forecasting and cyclic control of seizures
Authors: Stirling Rachel E. , Cook Mark J. , Grayden David B. , Karoly Philippa J.
Published: July 2020

Epilepsy is a unique neurologic condition characterized by recurrent seizures, where causes, underlying biomarkers, triggers, and patterns differ across individuals. The unpredictability of seizures can heighten fear and anxiety in people with epilepsy, making it difficult to take part in day‐to‐day activities. Epilepsy researchers have prioritized developing seizure prediction algorithms to combat episodic seizures for decades, but the utility and effectiveness of prediction algorithms has not been investigated thoroughly in clinical settings. In contrast, seizure forecasts, which theoretically provide the probability of a seizure at any time (as opposed to predicting the next seizure occurrence), may be more feasible. Many advances have been made over the past decade in the field of seizure forecasting, including improvements in algorithms as a result of machine learning and exploration of non–EEG‐based measures of seizure susceptibility, such as physiological biomarkers, behavioral changes, environmental drivers, and cyclic seizure patterns. For example, recent work investigating periodicities in individual seizure patterns has determined that more than 90% of people have circadian rhythms in their seizures, and many also experience multiday, weekly, or longer cycles. Other potential indicators of seizure susceptibility include stress levels, heart rate, and sleep quality, all of which have the potential to be captured noninvasively over long time scales. There are many possible applications of a seizure‐forecasting device, including improving quality of life for people with epilepsy, guiding treatment plans and medication titration, optimizing presurgical monitoring, and focusing scientific research. To realize this potential, it is vital to better understand the user requirements of a seizure‐forecasting device, continue to advance forecasting algorithms, and design clear guidelines for prospective clinical trials of seizure forecasting.
Machine learning and wearable devices of the future
Authors: Beniczky Sándor , Karoly Philippa , Nurse Ewan , Ryvlin Philippe , Cook Mark
Published: July 2020

Machine learning (ML) is increasingly recognized as a useful tool in healthcare applications, including epilepsy. One of the most important applications of ML in epilepsy is seizure detection and prediction, using wearable devices (WDs). However, not all currently available algorithms implemented in WDs are using ML. In this review, we summarize the state of the art of using WDs and ML in epilepsy, and we outline future development in these domains. There is published evidence for reliable detection of epileptic seizures using implanted electroencephalography (EEG) electrodes and wearable, non‐EEG devices. Application of ML using the data recorded with WDs from a large number of patients could change radically the way we diagnose and manage patients with epilepsy.
A novel dynamometer for the standardisation of the force applied during distal forelimb flexion tests in horses
Authors: Nocera I. , Sgorbini M. , Gracia‐Calvo L. A. , Cacini M. , Vitale V. , Citi S.
Published: July 2020

Variability in the technique employed for flexion tests may produce different responses and veterinary assessments. We propose a novel custom‐designed dynamometer and compare the results with the literature. Ten horses were enrolled in the present study, with a total of 20 forelimbs. The horses were found to be healthy based on orthopaedic and radiographic examination of the distal forelimb region, performed on both limbs. Lower forelimb flexion tests were performed by applying three different forces (75, 100 and 120 N), measured with a dynamometer, for one minute, with a time interval of 48 h between each test. Each horse was trotted before and after the flexion test. The experiment was videotaped, and the responses were assessed randomly and blindly by three experienced equine veterinarians. None of the horses responded with a lameness grade exceeding 1/5 on a numerical 6‐point scale. Two out of three veterinarians detected a increased degree of lameness between the minimum and the maximum force applied, while one veterinarian showed no change in the interpretation of the flexion test for all three applied forces. A mild agreement was detected between veterinarian A and B, applying a force of 100 N, and between A and C, with 120 N; a moderate agreement was found between veterinarian A and B, with 120 N. The chi‐square test showed that the results observed were only like the expected ones for 100 N. With a force of 100 N, there is no relationship between intensity and the evaluation of lameness; consequently, 100 N could be used to achieve a real standardisation of the lameness score. The use of the dynamometer was found to be easy and practical. It also enabled the applied force and the manipulation technique to be objectified.
Vulnerability of global coral reef habitat suitability to ocean warming, acidification and eutrophication
Authors: Guan Yi , Hohn Sönke , Wild Christian , Merico Agostino
Published: July 2020

Coral reefs are threatened by global and local stressors. Yet, reefs appear to respond differently to different environmental stressors. Using a global dataset of coral reef occurrence as a proxy for the long‐term adaptation of corals to environmental conditions in combination with global environmental data, we show here how global (warming: sea surface temperature; acidification: aragonite saturation state, Ωarag) and local (eutrophication: nitrate concentration, and phosphate concentration) stressors influence coral reef habitat suitability. We analyse the relative distance of coral communities to their regional environmental optima. In addition, we calculate the expected change of coral reef habitat suitability across the tropics in relation to an increase of 0.1°C in temperature, an increase of 0.02 μmol/L in nitrate, an increase of 0.01 μmol/L in phosphate and a decrease of 0.04 in Ωarag. Our findings reveal that only 6% of the reefs worldwide will be unaffected by local and global stressors and can thus act as temporary refugia. Local stressors, driven by nutrient increase, will affect 22% of the reefs worldwide, whereas global stressors will affect 11% of these reefs. The remaining 61% of the reefs will be simultaneously affected by local and global stressors. Appropriate wastewater treatments can mitigate local eutrophication and could increase areas of temporary refugia to 28%, allowing us to ‘buy time’, while international agreements are found to abate global stressors.
Field Demonstration of the Horizontal Treatment Well (HRX Well®) for Passive In Situ Remediation
Authors: Divine Craig E. , Wright Jesse , Crimi Michelle , Devlin J.F. , Lubrecht Michael , Wang Jack , McDonough Jeff , Kladias Michael , Hinkle Jesse , Cormican Allison , Osorno Trevor , Nzeribe Blossom N. , Laramay Fiona , Ombalski Daniel , Gerber Kathleen , Anderson Hunter
Published: July 2020

The horizontal reactive media treatment well (HRX Well®) uses directionally drilled horizontal wells filled with a treatment media to induce flow‐focusing behavior created by the well‐to‐aquifer permeability contrast to passively capture proportionally large volumes of groundwater. Groundwater is treated in situ as it flows through the HRX Well and downgradient portions of the aquifer are cleaned via elution as these zones are flushed with clean water discharging from the HRX Well. The HRX Well concept is particularly well suited for sites where long‐term mass discharge control is a primary performance objective. This concept is appropriate for recalcitrant and difficult‐to‐treat constituents, including chlorinated solvents, per‐ and polyfluoroalkyl substances (PFAS), 1,4‐dioxane, and metals. A full‐scale HRX Well was installed and operated to treat trichloroethene (TCE) with zero valent iron (ZVI). The model‐predicted enhanced flow through the HRX Well (compared to the flow in and equivalent cross‐sectional area orthogonal to flow in the natural formation before HRX Well installation) and treatment zone width was consistent with flows and widths estimated independently by point velocity probe (PVP) testing, HRX Well tracer testing, and observed treatment in downgradient monitoring wells. The actual average capture zone width was estimated to be between 45 and 69 feet. Total TCE mass discharge reduction was maintained through the duration of the performance monitoring period and exceeded 99.99% (%). Decreases in TCE concentrations were observed at all four downgradient monitoring wells within the treatment zone (ranging from 50 to 74% at day 436), and the first arrival of treated water was consistent with model predictions. The field demonstration confirmed the HRX Well technology is best suited for long‐term mass discharge control, can be installed under active infrastructure, requires limited ongoing operation and maintenance, and has low life cycle energy and water requirements.
The one‐stage assay or chromogenic assay to monitor baseline factor VIII levels and desmopressin effect in non‐severe haemophilia A: Superiority or non‐inferiority?
Authors: Schütte Lisette M. , Hodes Luca S. , van Moort Iris , Stoof Sara C. M. , Leebeek Frank W. G. , Cnossen Marjon H. , de Maat Moniek P. M. , Kruip Marieke J. H. A.
Published: July 2020

Introduction

Diagnosis, treatment monitoring and assessment of desmopressin effect in haemophilia A patients are performed by measurement of factor VIII activity (FVIII). The two assays commonly applied are the one‐stage assay and the chromogenic assay. Especially in non‐severe haemophilia A, discrepancies between these assays are common. It is still unestablished which assay corresponds best with bleeding phenotype and desmopressin effect.

Aim

To correlate FVIII levels measured by the one‐stage assay and by the chromogenic assay with bleeding phenotype and, additionally, to compare FVIII assay discrepancies before and after desmopressin administration.

Method

Factor VIII was measured in 130 non‐severe haemophilia A patients during routine visits to the outpatient clinic and/or during desmopressin testing. FVIII was measured by both the one‐stage assay and the chromogenic assay. Discrepancies between assays were defined as at least a twofold difference of FVIII or an absolute FVIII difference between measurements of ≥0.10 IU/mL. Bleeding phenotype was defined as annual number of treated bleedings (adjusted ABR).

Results

Hundred and thirty non‐severe haemophilia A patients were included. In 31/130 patients, assay results were discrepant. However, FVIII measurements with both assays correlated adequately with adjusted ABR. In addition, in 27/130 patients FVIII measurements at baseline and after desmopressin administration were analysed. In 13/27 patients, all measurements were either equivalent or discrepant when results were compared. In 14/27 patients, this was not the case as both equivalent measurements and discrepant measurements at different time points within one patient were observed.

Conclusion

Neither the one‐stage assay nor the chromogenic assay is superior in predicting bleeding phenotype. In addition, equivalent or discrepant FVIII results measured before desmopressin do not always predict FVIII assay results after desmopressin administration.
Patients With Vestibular Migraine are More Likely to Have Occipital Headaches than those With Migraine Without Vestibular Symptoms
Authors: Wattiez Anne‐Sophie , O’Shea Sarah A. , Ten Eyck Patrick , Sowers Levi P. , Recober Ana , Russo Andrew F. , Fattal Deema
Published: July 2020

Objective

To determine whether patients with vestibular migraine are more likely to suffer from an occipital headache than patients with migraine without vestibular symptoms.

Background

Vestibular migraine is an underdiagnosed disorder in which migraine is associated with vestibular symptoms. Anatomical evidence and symptomatology hint at the involvement of brain structures in the posterior fossa (back of the head location). We hypothesized that vestibular migraine patients are more likely than migraineurs without vestibular symptoms to experience headaches located in the back of the head, that is, occipital headaches.

Methods

A retrospective cross‐sectional study was conducted at the University of Iowa Hospital and Clinics. Chart analysis of 169 patients was performed. The primary outcome was the location of the headache in vestibular migraine patients and migraineurs without vestibular symptoms. The secondary outcomes included the association of vestibular migraine with gender, age at onset of headache, age at onset of vestibular symptoms (such as vertigo, head motion‐induced dizziness), aura, motion sickness, other associated symptoms, family history of headaches, and family history of motion sickness.

Results

In vestibular migraine group, 45/103 (44%) had occipital location for their headaches vs 12/66 (18%) in migraine patients without vestibular symptoms, for an odd’s ratio of 3.5 (95% CI = 1.7‐7.2, P < .001). Additionally, the age at onset of headache was greater in the vestibular migraine group (28 ± 12 vs 18 ± 9 years, P < .001) and motion sickness was more common (41/98 (42%) in the vestibular migraine group, 1/64 (2%) in the migraine without vestibular symptoms group, P < .001).

Conclusions

This study suggests that patients with vestibular migraine are more likely to have occipital headaches than patients with migraine without vestibular symptoms. Our data support the initiation of a prospective study to determine whether a patient presenting with occipital headaches, with late onset of age of headache, and with a history of motion sickness is at an increased risk for the possible development of vestibular migraine.
Helicobacter pylori infection modulates endogenous hydrogen sulfide production in gastric cancer AGS cells
Authors: Kawahara Yoshinari , Hirashita Yuka , Tamura Chikako , Kudo Yoko , Sakai Kumiko , Togo Kazumi , Fukuda Kensuke , Matsunari Osamu , Okamoto Kazuhisa , Ogawa Ryo , Mizukami Kazuhiro , Okimoto Tadayoshi , Kodama Masaaki , Murakami Kazunari
Published: July 2020

Background

Persistent Helicobacter pylori infection induces gastric mucosal atrophy, which is a precancerous condition. Hydrogen sulfide (H2S), a gaseous biological transmitter, has been implicated in both the physiological functions of the gastrointestinal tract and its diseases. To understand gastric epithelial cell response against H pylori infection, we investigated the metabolic changes of gastric cancer cells co‐cultured with H pylori and observed the modulation of endogenous H2S production.

Materials and Methods

Gastric cancer AGS cells were co‐cultured with an H pylori standard strain possessing bacterial virulence factor CagA (ATCC 43504) and a strain without CagA (ATCC 51932). Three hours after inoculation, the cells were subjected to metabolomics analysis using gas chromatography‐tandem mass spectrometry (GC‐MS/MS). Orthogonal projections to latent structures discriminant analysis (OPLS‐DA) and pathway analysis were performed. In addition, intracellular H2S levels were measured by using HSip‐1 fluorescent probe.

Results

Results of OPLS‐DA showed a significant difference between the metabolism of untreated control cells and cells inoculated with the H pylori strains ATCC 51932 or ATCC 43504, mainly due to 45 metabolites. Pathway analysis with the selected metabolites indicated that methionine metabolism, which is related to H2S production, was the most frequently altered pathway. H pylori‐inoculated cells produced more endogenous H2S than control cells. Moreover, ATCC 43504‐inoculated cells produced less H2S than ATCC 51932‐inoculated cells.

Conclusions

H pylori infection modulates endogenous H2S production in AGS cells, suggesting that H2S might be one of the bioactive molecules involved in the biological mechanisms of gastric mucosal disease including mucosal atrophy.