bluuebunny/crossref_metadata_2025 huggingface dataset:
Offspring birthweight and placental weight—does the type of maternal diabetes matter? A population‐based study of 319 076 pregnancies
Authors: Strøm‐Roum Ellen M. , Jukic Anne M. , Eskild Anne
Published: June 2021

Introduction

Our aim was to estimate the difference in birthweight and in placental weight in pregnancies with type 1 diabetes, type 2 diabetes, and gestational diabetes compared with pregnancies without diabetes.

Material and methods

By using data from the Medical Birth Registry of Norway during the years 2009–2017, we included 319 076 singleton pregnancies with delivery after the 21st week of pregnancy. We used linear regression analyses to estimate the difference in birthweight and in placental weight in grams (g) in pregnancies with type 1 diabetes, type 2 diabetes, and gestational diabetes, using pregnancies without diabetes as the reference. Adjustments were made for pregnancy duration and pre‐pregnancy body mass index.

Results

In pregnancies without diabetes, mean crude birthweight was 3527 g (SD 552 g). The adjusted mean birthweight was 525 g (95% CI 502–548 g) higher in pregnancies with type 1 diabetes compared with pregnancies without diabetes. In pregnancies with type 2 diabetes, and pregnancies with gestational diabetes, birthweights were 192 g (95% CI 160–223 g) and 102 g (95% CI 93–110 g) higher, respectively. Mean crude placental weight was 664 g (SD 147 g) in pregnancies without diabetes. Compared with pregnancies without diabetes, the adjusted mean placental weight was 109 g (95% CI 101–116 g) higher in pregnancies with type 1 diabetes, 50 g (95% CI 39–60 g) higher in pregnancies with type 2 diabetes, and 31 g (95% CI 28–34 g) higher in pregnancies with gestational diabetes.

Conclusions

The increase in birthweight and in placental weight associated with maternal diabetes was most pronounced for type 1 diabetes, followed by type 2 diabetes, and gestational diabetes.
Soluble fms‐like tyrosine kinase 1 (sFlt‐1): A novel biochemical marker for acute fatty liver of pregnancy
Authors: Trottmann Fabienne , Raio Luigi , Amylidi‐Mohr Sofia , Mosimann Beatrice , Jarquin Campos Araceli , Messerli Franz H. , Risch Lorenz , Baumann Marc U.
Published: June 2021

Introduction

Acute fatty liver of pregnancy (AFLP) substantially contributes to maternal and neonatal morbidity and mortality. Other liver‐associated pregnancy complications such as preeclampsia‐associated HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome may be difficult to differentiate from AFLP as these diseases overlap with regard to multiple clinical and laboratory features. The aim of this study was to investigate angiogenic profiles by measuring soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF) in pregnancies compromised by AFLP and to compare them with those complicated by HELLP syndrome.

Material and methods

Pregnant women affected by AFLP or HELLP syndrome were enrolled. The study population of women with HELLP syndrome was part of a larger data collection obtained in our clinic that has been used for previous work. Patients’ angiogenic profiles were assessed by measuring sFlt‐1 and PlGF serum levels. To assess the diagnostic potential of these angiogenic markers in AFLP, as well as discriminating it from HELLP syndrome, non‐parametric tests were used and receiver operating curves were calculated.

Results

Six women with AFLP and 48 women with HELLP syndrome were included in the study. Patients with AFLP showed significantly higher sFlt‐1 levels (median: 57 570 pg/mL; range 31 609–147 170 pg/mL) than patients with HELLP syndrome (9713 pg/mL; 1348–30 781 pg/mL; p < 0.001). PlGF serum levels were higher in patients with AFLP compared with those with HELLP syndrome (197 pg/mL; 127–487 pg/mL vs. 40 pg/mL; 9–644 pg/mL, respectively; p < 0.01). sFlt‐1/PlGF ratios were not significantly different between AFLP and HELLP syndrome patients (192; 157–1159 vs. 232; 3–948, respectively; NS). In our study population, an sFlt‐1 cut‐off value of 31 100 pg/mL allowed differentiation between these two diseases with a sensitivity and specificity of 100%. A linear correlation was found between the cumulative numbers of Swansea criteria and sFlt‐1 serum levels (r = 0.97; p < 0.01).

Conclusions

AFLP is associated with very high sFlt‐1 serum levels in particular in women fulfilling eight or more Swansea criteria. Besides the suggested Swansea criteria to diagnose AFLP, an sFlt‐1 value above 31 100 pg/mL may be an additional biochemical feature improving discrimination between AFLP and HELLP syndrome. However, because of the small number of pregnancies affected by AFLP included in this work further studies are needed to corroborate our findings.
The CredibleMeds® list: Usage of QT interval prolonging drugs in Germany and discordances with prescribing information
Authors: Then Melanie I. , Andrikyan Wahram , Maas Renke , Fromm Martin F.
Published: June 2021

Aims

A substantial number of Summaries of Product Characteristics (SmPCs)/Prescribing Information (PI) have warnings or contraindications on QT interval prolongation. The goal of this work was to quantify usage of QT interval prolonging drugs according to the CredibleMeds® database of the German outpatient drug prescription market and to evaluate discrepancies between German SmPCs/US PI and CredibleMeds®.

Methods

Drugs listed on CredibleMeds® with known, possible or conditional risk for torsade de pointes were evaluated from 2000 to 2020. The German drug prescription report was used as source for defined daily dose‐ (DDD‐) based prescriptions of the German outpatient drug prescription market of the public health insurance system. German SmPCs and US PI of 253 CredibleMeds®‐listed drugs were evaluated for contents regarding QT interval prolongation.

Results

Of the drugs currently listed on CredibleMeds®, 59.7% (95% confidence interval [CI] 53.5–65.5%) were listed after 2012. Due to newly listed drugs, the proportion of DDDs of CredibleMeds® drugs among all prescriptions increased from 4.6% in 2013 to 21.1% in 2019. DDD‐based usage of the CredibleMeds® drugs already listed in 2013 was similar in 2019. Among the drugs with known QT risk according to CredibleMeds®, 7.5% (95% CI 2.6–19.9%) of German SmPCs and 21.1% (95% CI 11.1–36.3%) of US PI had no mention of QT issues whatsoever.

Conclusion

A significant proportion of all drugs prescribed in the outpatient sector is associated with QT risks according to CredibleMeds®. SmPCs and PI should systematically be evaluated for concordance with the widely used CredibleMeds® database to increase medication safety.
Professional perspectives on applying the NICE and British Psychological Society Guidelines for the management of Behaviours that Challenge in dementia care: an e‐survey
Authors: Gray Kristina Lily , Moniz‐Cook Esme , Reichelt Katharina , Duffy Frances , James Ian Andrew
Published: June 2021

Objectives

Behaviours that challenge (BtC) reflect the most costly and burdensome aspects of dementia where non‐pharmacological interventions rather than antipsychotic medication have been recommended as first‐line approaches for over a decade (NICE 2006). This paper outlines professionals’ views about their application of the Dementia NICE Guideline 97 (2018) and a British Psychological Society, Division of Clinical Psychology (BPS‐DCP) Briefing paper (2013) on alternatives to antipsychotics.

Methods

A mixed‐methods 34‐item e‐survey, with five items about the use of the NICE Guideline 97 (2018) and the BPS‐DCP Briefing paper (2013) for the management of BtC, was conducted. Participants were recruited through multidisciplinary professional dementia networks across the United Kingdom. Quantitative data were descriptively summarized and thematic analysis of open‐ended questions undertaken.

Results

Two hundred and forty‐seven participants completed the questions relating to guidelines. Mean ratings of ‘moderately useful’ for both the NICE and BPS‐DCP guidance were obtained across professions and geographical locations, with the exception of psychiatrists who rated the NICE guidance as ‘slightly useful’. The qualitative themes identified were a mix of positive and cautionary perspectives, relating to ‘evidence base’, the ‘accessibility of the guides’, ‘problems with implementation’, and ‘lack of detail and clarity’.

Conclusion

Professionals were cautiously positive regarding the guidance for BtC management, but highlighted a need for improved clarity about the use of non‐pharmacological approaches, and more specificity about how these can be implemented in clinical settings. Tailored ‘setting‐specific’ toolkits are required to update and refine the BPS‐DCP (2013) if the aspirations of the NICE Dementia Guideline 97 (2018) are to inform professional practice.

Practitioner Points

Owing to major concerns about the problematic side effects of using psychotropics in the treatment of behaviours that challenge (BtC), there is a need for national guidance on the use on non‐drug alternatives.

The NICE (2018) guidance was seen by participants as accessible and clear but lacking in detail in the use of non‐pharmacological interventions, which are the first‐line treatments for BtC.

The BPS Guidelines on ‘Alternatives to antipsychotics’ (2013) were seen as having good structured advice for allocating non‐pharmacological resources but were lacking in flexibility for meeting individual needs or what might be an acceptable fit for clinical services.

The findings suggest that we need to develop UK‐wide bespoke specific advice for practitioners and services for both the use and the delivery of non‐pharmacological evidence‐based interventions for BtC.
Two cases of DCDC2‐related neonatal sclerosing cholangitis with developmental delay and literature review
Authors: Syryn Hannes , Hoorens Anne , Grammatikopoulos Tassos , Deheragoda Maesha , Symoens Sofie , Vande Velde Saskia , Van Biervliet Stephanie , Van Winckel Myriam , Verloo Patrick , Callewaert Bert , De Bruyne Ruth
Published: June 2021

Ciliopathies are a group of clinical and molecular heterogeneous conditions with pleiotropic manifestations affecting the central nervous system, renal, liver, skeletal, and ocular systems. Biallelic pathogenic variants in DCDC2 cause a ciliopathy primarily presenting with neonatal sclerosing cholangitis (NSC). Pathogenic variants in DCDC2 have further been reported in the context of nephronophthisis and non‐syndromic recessive deafness. Polymorphisms in DCDC2 have also been associated with dyslexia and DCDC2 has a role in neuronal development. We report on two unrelated patients with DCDC2‐related NSC with additional central nervous system impairment manifesting as microcephaly, global developmental delay, and axial hypotonia. Histological findings of our patients can mimic biliary atresia or congenital hepatic fibrosis. We further show that transmission electron microscopy in patients with NSC does not always show absence of primary cilia. Hence patients with DCDC2 pathogenic variants should also undergo an evaluation of neuromotor development. Review of all reported patients further reveals a risk for supra‐aortic arterial aneurysms.
Prognostic value of cardiopulmonary exercise test after heart transplantation
Authors: Iglesias Diego , Masson Walter , Barbagelata Leandro , Rossi Emiliano , Mora Mishel , Cornejo Guillermo , Lagoria Juan , Belziti Cesar , Vulcano Norberto , Marenchino Ricardo , Pizarro Rodolfo , Ventura Hector
Published: June 2021

Background

The clinical utility of cardiopulmonary exercise testing (CPET) has not been extensively studied yet in heart transplantation (HTX) patients.

Objective

To analyze the predictive value of the CPET on hospitalizations and mortality in HTX recipients.

Methods

A retrospective cohort was performed from a secondary database. Patients > 18 years with HTX who underwent a CPET between 3 and 12 months after transplantation were included. Time to the first primary endpoint (HTX‐related hospitalization) was analyzed and adjusted using Cox proportional hazards regression model.

Results

A total of 122 patients (mean age 50.1 years, 77.0% men) were included. Fifty‐seven patients (46.7%) had the primary endpoint. Peak VO2(HR .95; CI 95% .90–.99,P = .03), oxygen pulse (HR .57; CI 95% .34–.96,P = .03) and predicted VO2(HR .97; CI 95% .96–.99,P = .002) were associated with the endpoint. We did not find a significant association between the other variables and the outcome.

Conclusion

In HTX recipients, peak VO2, oxygen pulse, and predicted VO2were independently associated with hospitalizations at follow up.
Lower‐level associations in Gilles de la Tourette syndrome: Convergence between hyperbinding of stimulus and response features and procedural hyperfunctioning theories
Authors: Takacs Adam , Münchau Alexander , Nemeth Dezso , Roessner Veit , Beste Christian
Published: June 2021

Gilles de la Tourette syndrome (GTS) can be characterized by enhanced cognitive functions related to creating, modifying and maintaining connections between stimuli and responses (S‐R links). Specifically, two areas, procedural sequence learning and, as a novel finding, also event file binding, show converging evidence of hyperfunctioning in GTS. In this review, we describe how these two enhanced functions can be considered as cognitive mechanisms behind habitual behaviour, such as tics in GTS. Moreover, the presence of both procedural sequence learning and event file binding hyperfunctioning in the same disorder can be treated as evidence for their functional connections, even beyond GTS. Importantly though, we argue that hyperfunctioning of event file binding and procedural learning are not interchangeable: they have different time scales, different sensitivities to potential impairment in action sequencing and distinguishable contributions to the cognitive profile of GTS. An integrated theoretical account of hyperbinding and hyperlearning in GTS allows to formulate predictions for the emergence, activation and long‐term persistence of tics in GTS.
Long‐term survival after primary intracerebral hemorrhage: A population‐based case–control study spanning a quarter of a century
Authors: Lahti Anna‐Maija , Nätynki Mirva , Huhtakangas Juha , Bode Michaela , Juvela Seppo , Ohtonen Pasi , Tetri Sami
Published: June 2021

Background and purpose

The aim of this study was to determine the differences in life expectancy and causes of death after primary intracerebral hemorrhage (ICH) relative to general population controls.

Methods

In a population‐based setting, 963 patients from Northern Ostrobothnia who had their first‐ever ICH between 1993 and 2008 were compared with a cohort of 2884 sex‐ and age‐matched controls in terms of dates and causes of death as extracted from the Causes of Death Register kept by Statistics Finland and valid up to the end of 2017.

Results

Of our 963 patients, 781 died during the follow‐up time (mortality 81.1%). Cerebrovascular disease was the most common cause of death for these patients, 37.3% compared with 8.2% amongst the controls. The most common reasons for cerebrovascular mortality in the ICH patients were late sequelae of ICH in 12.8% (controls 0%) and new bleeding in 10.6% (controls 1.0%). The long‐term survivors had a smaller ICH volume (median 12 ml) than those patients who died within 3 months (median 39 ml). The mortality rate of ICH patients during a follow‐up between 12 and 24 years was still higher than that of their controls (hazard ratio 2.08, 95% confidence interval 1.58–2.74, p < 0.001).

Conclusions

Very long‐term ICH survivors have a constant excess mortality relative to controls even 10 years after the index event. A significantly larger proportion of patients died of cerebrovascular causes and fewer because of cancer relative to the controls.
Facilitating technology‐based character learning in emergency remote teaching
Authors: Xu Yi , Jin Li , Deifell Elizabeth , Angus Katie
Published: June 2021

The study reports pedagogical adaptations that Chinese language instructors made to support students' character learning during emergency remote teaching in 2020. Data from an online questionnaire and follow‐up interviews show that the handwriting requirement in the language curriculum was modified to give way to technology‐based instruction, making the conventionally isolated and solitary task of character learning more integrative and interactive. Beginning‐level instructors' use of technology in character instruction was correlated with their self‐confidence, perceived time sufficiency, technology access, and support received. Meanwhile, intermediate‐ and upper‐level instructors' self‐confidence and perceived values of online teaching were factors associated with their technology use. The crucial role of teacher communities in offering language‐specific training and peer support is emphasized, and implications to the broader field of foreign language teaching are discussed.
Response of the peatland carbon dioxide sink function to future climate change scenarios and water level management
Authors: Salimi Shokoufeh , Berggren Martin , Scholz Miklas
Published: June 2021

Stress factors such as climate change and drought may switch the role of temperate peatlands from carbon dioxide (CO2) sinks to sources, leading to positive feedback to global climate change. Water level management has been regarded as an important climate change mitigation strategy as it can sustain the natural net CO2 sink function of a peatland. Little is known about how resilient peatlands are in the face of future climate change scenarios, as well as how effectively water level management can sustain the CO2 sink function to mitigate global warming. The authors assess the effect of climate change on CO2 exchange of south Swedish temperate peatlands, which were either unmanaged or subject to water level regulation. Climate chamber simulations were conducted using experimental peatland mesocosms exposed to current and future representative concentration pathway (RCP) climate scenarios (RCP 2.6, 4.5 and 8.5). The results showed that all managed and unmanaged systems under future climate scenarios could serve as CO2 sinks throughout the experimental period. However, the 2018 extreme drought caused the unmanaged mesocosms under the RCP 4.5 and RCP 8.5 switch from a net CO2 sink to a source during summer. Surprisingly, the unmanaged mesocosms under RCP 2.6 benefited from the warmer climate, and served as the best sink among the other unmanaged systems. Water level management had the greatest effect on the CO2 sink function under RCP 8.5 and RCP 4.5, which improved their CO2 sink capability up to six and two times, respectively. Under the current climate scenario, water level management had a negative effect on the CO2 sink function, and it had almost no effect under RCP 2.6. Therefore, the researchers conclude that water level management is necessary for RCP 8.5, beneficial for RCP 4.5 and unimportant for RCP 2.6 and the current climate.
Occupational safety and health challenges for maritime key workers in the global COVID‐19 pandemic
Authors: SHAN Desai
Published: June 2021

The COVID‐19 pandemic has changed the world of work. But global trade is still recognized as an essential area of business, and maritime transport, being an engine of globalization, cannot be paused. Since the onset of the pandemic, few governments have allowed seafarers – who transport more than 90 per cent of global commodities – to leave their ships and return home. The travel restrictions related to COVID‐19 have led to a crisis of occupational safety and health (OSH) at sea. Drawing on 29 interviews, this article explores the OSH challenges faced by international seafarers during the pandemic.
Medical Oncology Group of Australia position statement: COVID‐19 vaccination in patients with solid tumours
Authors: Kanjanapan Yada , Blinman Prunella , Underhill Craig , Karikios Deme , Segelov Eva , Yip Desmond
Published: June 2021

People with cancer are vulnerable to increased morbidity and mortality from the coronavirus disease 2019 (COVID‐19). COVID‐19 vaccination is key to protecting the population of people with cancer from adverse outcomes of SARS‐CoV‐2 infection. The Medical Oncology Group of Australia aimed to address the considerations around COVID‐19 vaccination in people with cancer, in particular, safety and efficacy of vaccination. The assessment of patients with generalised allergic reaction to anti‐cancer therapy containing vaccine components and practical implementation of vaccination of people on active anti‐cancer therapy are also discussed.
Sentiments expressed inYouTubepublic awareness campaigns: stroke
Authors: Phan Thanh G. , Beare Richard , Srikanth Velandai , Ma Henry
Published: June 2021

Social media (YouTube) has been used to educate the public on stroke signs and the need to contact emergency hotline. We perform sentiment analysis to explore the emotional response to the 2006 North American and contrast this with the five Australian campaigns (2009–2015). The positive sentiment in the North American campaign provides insights for developing material for public health campaigns.
Source pool diversity and proximity shape the compositional uniqueness of insular mammal assemblages worldwide
Authors: Hébert Katherine , Millien Virginie , Lessard Jean‐Philippe
Published: June 2021

Aim

Islands have been the test bed of several theories in community ecology, biogeography, and evolutionary biology. Progress within these disciplines has given a more comprehensive and mechanistic understanding of the processes governing variation in species richness among islands. However, it remains unclear whether these same processes also explain variation in species and phylogenetic composition among islands. Integrating theory from ecology and biogeography, we infer the roles of dispersal, selection, and stochasticity on the composition of insular assemblages within archipelagos. We further assess the influence of source pool diversity and connectivity on the compositional uniqueness of insular assemblages.

Location

Island systems worldwide.

Taxon

Mammals.

Methods

We compiled data on species composition of nonvolant mammals on ~200 islands in nine archipelagos distributed worldwide from the literature. We used variation partitioning to quantify the relative influence of the environment (selection) and geographic distance (dispersal) relative to a null model (stochasticity, randomness) on taxonomic and phylogenetic compositional turnover within archipelagos. We then used a linear mixed model to gain further insight into the underlying mechanisms shaping variation in assemblage composition among islands at a global scale. Specifically, we assessed the influence of source pool diversity, isolation from the source pool, and island characteristics on compositional uniqueness.

Results

Our results suggest that within‐archipelago variation in the composition of insular mammal assemblages is associated with stochastic or unmeasured processes rather than abiotic selection or dispersal limitation. The diversity and proximity of the source pool, as well as some island characteristics, explained variation in phylogenetic, but not taxonomic, compositional uniqueness globally. Globally, isolated islands associated with phylogenetically diverse source pools exhibit high phylogenetic uniqueness whereas well‐connected islands associated with phylogenetically clustered source pools show the opposite trend. Phylogenetically unique assemblages also tend occur on islands with a small elevational span and low annual temperature variation.

Main conclusions

Taken together, our results suggest that source pool diversity, along with the potential for colonization from those pools, has a strong influence on the composition of insular mammal assemblages worldwide.
Geranylgeranylacetone promotes human osteosarcoma cell apoptosis by inducing the degradation of PRMT1 through the E3 ubiquitin ligase CHIP
Authors: Jiang Lucen , Liao Jia , Liu Jianghuan , Wei Qingzhu , Wang Yiyang
Published: June 2021

Geranylgeranylacetone (GGA), an inducer of heat shock proteins, exerts anticancer activity in some tumours. However, the effect of GGA on human osteosarcoma (OS) has not been reported. This work is designed to evaluate the effect of GGA on the proliferation and apoptosis of human OS cells and to explore the underlying mechanisms. It was found that GGA markedly inhibited the proliferation and induced apoptosis of U‐2 OS cells in a dose‐dependent manner and also up‐regulated the expression of heat shock protein 70 (Hsp70). The degradation and ubiquitination of protein arginine N‐methyltransferase 1 (PRMT1) were obviously enhanced in U‐2 OS cells with CHIP overexpression and GGA treatment. The expression of PRMT1 was reversed in GGA‐treated cell after CHIP knockdown. The turnover of PRMT1 was obviously faster in cells overexpressing CHIP than that in control cells. The methylation and activity of STAT3 were induced by PRMT1, resulting in the inhibition of FAS transcription. Overexpression of PRMT1 reversed the effect of GGA on activation of apoptosis‐related proteins and U‐2 OS cell apoptosis. The expressions of PRMT1 were significantly up‐regulated in OS tissues compared with the adjacent normal tissues and benign bone tumours. In conclusion, GGA promotes the degradation of PRMT1 through the Hsp70‐CHIP‐mediated proteasome pathway, thereby inducing the FAS‐triggered cell apoptosis. Inhibition of PRMT1 may be a potential therapeutic strategy for OS patients.
The combined effects of innovation and corporate social responsibility on firm financial risk
Authors: Liu Bai , Ju Tao , Gao Simon S.S.
Published: June 2021

Prior literature has largely dealt with the effect of either corporate social responsibility (CSR) or innovation on firm financial risk. No earlier research has examined the combined effect of a firm's simultaneous pursuit of CSR and innovation on firm financial risk. This study investigates the combined effects with a view to fostering our understanding of relationships of CSR and innovation with financial risk. Using the patent application and CSR data of 2,174 Chinese listed firms over the period 2010–2016, this study finds that firms with higher levels of imitative innovation and good CSR performance exhibit higher financial risk. The results remain after a series of robustness tests including the use of an alternative measure of firm financial risk and CSR. The results indicate that firms with a higher level of imitative innovation exhibit greater financial risk; however, the risk cannot be mitigated by firms' good CSR performance. CSR performance helps firms boost the positive image of a “good citizen” and reduce firm financial risk; however, the combined effects of CSR and imitative innovation trigger higher financial risk. The results of this study support the umbrella theory of CSR that exacerbates the moral hazard for those firms that rely on imitative innovation.
The contribution of elastic geothermobarometry to the debate on HP versus UHP metamorphism
Authors: Gilio Mattia , Scambelluri Marco , Angel Ross J. , Alvaro Matteo
Published: June 2021

Characterizing the pressure and temperature (P–T) histories of eclogite facies rocks is of key importance for unravelling subduction zone processes at all scales. Accurate P–T estimates provide constraints on tectonic and geochemical processes affecting subduction dynamics and help in interpreting the geophysical images of present‐day converging plates. Conventional equilibrium geothermobarometers are challenged in ultra high pressure (UHP) metamorphic terranes, as minerals may undergo re‐equilibration along their exhumation path. Elastic geobarometry applied to host‐inclusion systems is a complementary method to determine P–T conditions of metamorphism independent from chemical equilibrium. Because only a single measurement, the inclusion strain, is made, only a line in P–T space of possible entrapment conditions, the entrapment isomeke, can be determined. Thus, the entrapment pressure along an isomeke can only be determined if the entrapment temperature is known. An alternative is to calculate entrapment conditions for two types of inclusions that are believed, from petrological evidence such as being in the same garnet growth zone, to have been entrapped at the same time. The intersection between the two sets of isomeke calculated on multiple quartz and zircon inclusions demonstrates that measuring different inclusion phases trapped inside a single host allows unique P–T conditions for the host rock to be determined. Here, we combine Zr‐in‐Rutile thermometry and thermodynamic modelling with micro‐Raman measurements on quartz and zircon inclusions trapped in garnet to obtain pressures and temperatures of equilibration of a quartz–garnet vein from the Proterozoic Ulla gneiss basement and of garnet–kyanite gneiss from the Caledonian Blåhø nappe, both in the Fjørtoft UHP terrane, Norway. We find that the quartz–garnet vein formed at high pressure (1.5–2.5 GPa and 750–800°C) and recrystallized at ~1.2 GPa and 880°C. In contrast, the garnet–kyanite gneiss followed an anticlockwise path with peak P–T at 1.2 GPa and 880°C: these estimates are consistent with previous thermodynamic modelling and suggest that the Ulla gneiss and the Blåhø nappe came into contact at these last conditions. We also discuss a new method to detect hydrostatic versus Non‐hydrostatic stresses near quartz and zircon inclusions in garnet.
Characteristics of ovarian endometrioma during pregnancy
Authors: Takami Mio , Kajiyama Ryoko , Miyagi Etsuko , Aoki Shigeru
Published: June 2021

Aim

During pregnancy, the ovarian endometrioma generally decreases in size and occasionally ruptures. We evaluated (1) whether and how ovarian‐endometrioma size changes from the first trimester to the postdelivery period, and (2) the type of endometrioma more likely to rupture during pregnancy.

Methods

During an 18‐year period (2000–2018), ultrasound in the first trimester revealed ovarian endometrioma in 149 pregnant women at our tertiary institute. Among these, we subjected 138 endometriomas in 145 patients to expectant management (wait‐and‐watch approach during pregnancy). We compared the cyst sizes in the first trimester and the postdelivery period, and defined a >1 cm diameter size‐change as a significant increase/decrease. We analyzed four patients with rupture and characterized the predictors of rupture.

Results

A comparison of cyst sizes in the first trimester and the postdelivery period revealed that the size of 94 (68%), 37 (27%), and 7 ovaries (5.0%), respectively, decreased, remained unchanged, and increased; in 56 ovaries (40%), apparent cysts were no longer present. Of the 145 patients, four (2.8%) required emergency surgery for cyst rupture. Adhesion to the surroundings, an increase in cyst size, large size (diameter of ≥6 cm), and compression due to the enlarged uterus in late pregnancy were factors clinically related to rupture.

Conclusions

Approximately two‐thirds of ovarian endometriomas decreased in size during pregnancy (40% disappeared), 27% remained unchanged, and only 5% increased in size. However, 2.8% of pregnant women with endometrial cysts experienced rupture. We characterized risk factors for rupture; however, clinical application requires further evaluation.
Proposal for developing treatment algorithms of women with symptomatic adenomyosis: A single‐center experience
Authors: Kobayashi Hiroshi , Imanaka Shogo
Published: June 2021

Aims

The most common symptoms of adenomyosis include heavy menstrual bleeding and dysmenorrhea. A variety of medical or surgical techniques are utilized for the treatment of adenomyosis, but there are currently no specific treatment guidelines and best practice recommendations for management. The aim of this study is to summarize current treatment strategies for women with symptomatic adenomyosis in a single‐center university hospital in order to provide reliable information for developing treatment algorithms.

Methods

We conducted an observational cross‐sectional study using data from the adenomyosis cohort study from January 2008 to December 2020. Detailed information, including demographic, clinicopathological, and imaging data, were collected from 220 pathologically confirmed patients with adenomyosis.

Results

First, we identified clinical and imaging characteristics in women who underwent surgery or hormone therapy, especially dienogest (DNG) treatment, as first‐line treatment. Surgery was generally recommended for multiparous women over the age of 43, especially for patients with intrinsic adenomyosis. Next, we identified the parameters that allowed the continuation of DNG treatment. Oral DNG was given to certain patients with a myometrium thickness of 35 mm or greater and coexisting with endometriosis and/or uterine fibroids. To prevent serious bleeding, DNG treatment can be limited to women with extrinsic adenomyosis with a uterine length of 125 mm or less.

Discussion

Our findings may provide useful information in developing an evidence‐based treatment guideline for patients with symptomatic adenomyosis, nevertheless, further investigation is needed for the validation of treatment algorithms.
Pregnancy outcomes in children, adolescents, and young adults that survived cancer: A nationwide survey in Japan
Authors: Yasuoka Toshiaki , Iwama Noriyuki , Ota Kuniaki , Harada Miyuki , Hasegawa Junichi , Yaegashi Nobuo , Sugiyama Takashi , Suzuki Nao , Osuga Yutaka
Published: June 2021

Aim

Recent advances in cancer treatment have improved the prognosis of child, adolescent, and young adult (CAYA) cancer survivors. This study aimed to examine the current status of pregnancy outcomes among female cancer survivors in Japan.

Methods

The first questionnaire was sent to 633 major tertiary institutions certified by the Japan Society of Obstetrics and Gynecology to identify institutions managing cases of pregnant cancer survivors between January 2011 and December 2015. The second questionnaire was sent only to institutions with pregnant cancer survivors during the study period.

Results

We analyzed 2242 singleton deliveries of cancer survivors based on the responses received in the second questionnaire (199/255 responses; 78.0%). The three most frequent types of malignant tumors were uterine cervical (23.4%), breast (17.6%), and thyroid cancers (17.5%). Conception was aided by the use of assisted reproductive technology in 17.0% of the patients. The proportions of mothers aged 35–39.9 and ≥ 40 years were 36.5% and 11.8%, respectively. The prevalence of preterm birth (PTB) at <37, <34, and < 32 weeks' gestation were 16.7%, 6.8%, and 4.3%, respectively. The proportion of infants with low birth weight (LBW) was 18.9%.

Conclusion

The present study findings suggest that advanced maternal age was common among pregnant cancer survivors and these survivors often gave birth to PTB and LBW infants in Japan. The likelihood of adverse pregnancy outcomes should be considered by healthcare providers when planning counseling and perinatal care for cancer survivors.
Need to warm up! Ambient coldness increases vice inclinations
Authors: Yu Yining , Wang Lei
Published: June 2021

While researchers have begun to investigate how ambient elements affect people's vice inclinations, the effect of ambient temperature on vice inclinations is relatively unknown. Through three experiments, the present study reveals that ambient coldness (vs. hotness) increases vice inclinations, including both vice consumptions and vice activities. This phenomenon is induced by the automatically activated affective decision‐making mode, which helps people acquire emotional warmth to complement their physical coldness. Driven by the affective decision‐making mode, people are more inclined to vice behaviors. The present study is among the first to explore the effect of ambient temperature on vice inclinations (i.e., vice consumption and vice activity) which extends the literature regarding the downstream consequences of thermoregulation.

Practical Applications

Our study provides practical insights for the sake of activity organizers, policymakers, educators, and employers. First, we suggest that changing the temperature inside lower than the outside could trigger vice inclinations, which offers an easy and cheap method for activity organizers to enliven the atmosphere and increase participant's involvement. Also, it might be less effective for policymakers to promote vice‐resisting campaigns on cold days since people are more inclined to temptations in the cold atmosphere. Moreover, our findings are instructive for educators and employers. A colder‐than‐average atmosphere might hamper students' and employees' academic or work performances, respectively.
Computerised decision support in veterinary medicine, exemplified in a canine idiopathic epilepsy care pathway
Authors: Fox K. , Fox J. , Bexfield N. , Freeman P.
Published: June 2021

Computerised decision support is of emerging and increasing importance in human medicine, but as yet has not been thoroughly applied or evaluated in veterinary medicine. In this essay, the authors report on the first example of a veterinary care pathway, a specific form of computerised decision support, which guides clinicians through a clinical workflow and incorporates individual patient data to inform patient‐specific decision recommendations. The veterinary care pathway was designed using consensus statements and specialist neurologist opinion to create a decision support tool concerning canine idiopathic epilepsy. The authors evaluated the care pathway by comparing 35 clinical decisions made by referral clinicians in historical cases of idiopathic epilepsy to decisions recommended by the care pathway when presented with the same clinical case. Their results show that in 77.1% (95% confidence interval [59.9, 89.6]) of cases the care pathway recommended a decision that was the same or similar to a specialist neurologist's decision. Whilst further studies are needed to explore the potential use of such technology in clinical practice, the authors believe this first application provides great promise of a new and alternative method of clinical decision support.
Is elimination of HCV in 2030 realistic in Central Europe
Authors: Flisiak Robert , Zarębska‐Michaluk Dorota , Frankova Sona , Grgurevic Ivica , Hunyady Bela , Jarcuska Peter , Kupčinskas Limas , Makara Michael , Simonova Marieta , Sperl Jan , Tolmane Ieva , Vince Adriana
Published: June 2021

According to the recent data presented by Central‐European HCV experts, the estimated prevalence of HCV is between 0.2% and 1.7% in certain countries in this region. There are no financial limitations to access to treatment in most countries. Patients in these countries have access to at least one pangenotypic regimen. The most common barriers to the elimination of HCV in Central Europe are a lack of established national screening programmes and limited political commitment to the elimination of HCV. Covid‐19 has significantly affected the number of patients who have been diagnosed and treated, thus, delaying the potential elimination of HCV. These data suggest that the elimination of HCV elimination projected by WHO before 2030 will not be possible in the Central Europe.
Hepatitis B cure: How and when
Authors: Dusheiko Geoffrey
Published: June 2021

Background

First‐ and second‐ generation new treatments are being evaluated to provide a cure for hepatitis B. The life cycle of HBV includes several well‐ categorized steps that are targets for new treatments. A cure remains a major challenge even if it is measured by HBsAg seroclearance alone. The notion of a functional cure of hepatitis B has been accepted, while a partial functional cure has been more tentatively defined as a decline in HBsAg concentrations to lower levels after finite treatment.

Methods

More profound suppression of hepatitis B replication through the addition of capsid inhibitors with nucleoside analogues could improve patient prognosis and a sustained treatment response. Several strategies are being evaluated to achieve a cure: (a) deepening inhibition of HBV replication or (b) a reduction in HBsAg presentation for HBsAg seroclearance.

Results

Fortunately, there are signs of important progress in the treatment of hepatitis B including improved on‐ treatment reductions or seroclearance of HBsAg in phase 2 studies that was not achieved with chain terminators and inhibitors of initiation of DNA synthesis. Progress in immunomodulatory therapy has lagged behind that of antiviral therapy.

Conclusions

Increasing the multilayered impaired and dysfunctional immune response in hepatitis B is perhaps more likely and feasible after a reduction in host antigen burden. Other potential experimental strategies include CRISPR‐ Cas9 genome‐ editing nucleases to specifically target and cleave cccDNA or novel monoclonal antibodies.
COVID‐19 and the liver – Lessons learned
Authors: Herta Toni , Berg Thomas
Published: June 2021

Liver involvement, indicated by elevated liver function test results, is common in hospitalized patients with coronavirus disease 2019 (COVID‐19) and has been linked to disease severity and outcome. A dual pattern of elevated liver function tests can be observed especially in patients with severe or critical COVID‐19, characterized by an increase in aminotransferases early in the course of this disease, followed by an increase in cholestasis‐associated biochemistry markers at later stages. This dual pattern is associated with inflammatory response markers and poor outcome. Current notions on the mechanisms of liver injury in COVID‐19 include direct cytopathic effects of the virus on hepatocytes and cholangiocytes, ischemic and hypoxic liver damage, drug‐induced liver injury, activation of hepatic immune cells by excess cytokine production and exacerbation of pre‐existing liver disease. Patients with obesity‐related non‐alcoholic fatty liver disease and, in particular, patients with cirrhosis are at high risk of liver injury and a fatal outcome from COVID‐19. In contrast, individuals receiving stable immunosuppressive medication for autoimmune liver diseases or during long‐term follow‐up after liver transplantation do not have a higher case‐to‐infection ratio and have a fairly favourable outcome. The present review describes the epidemiology, characteristics and potential pathological mechanisms of COVID‐19‐related liver injury. Moreover, the influence of pre‐existing liver disease on the susceptibility and severity of liver injury in COVID‐19 are discussed.
Acute‐on‐chronic liver failure: Where do we stand?
Authors: Durand François , Roux Olivier , Weiss Emmanuel , Francoz Claire
Published: June 2021

Acute‐on‐chronic liver failure (ACLF) is defined by the rapid development of organ(s) failure(s) associated with high rates of early (28‐day) mortality in patients with cirrhosis. ACLF has been categorized into three grades of increasing severity according to the nature and number of organ failures. In patients with grade 3 ACLF, 28‐day mortality is >70%. While the definition of ACLF has been endorsed by European scientific societies, North American and Asian Pacific associations have proposed alternative definitions. A prognostic score called the CLIF‐C ACLF score provides a more precise assessment of the prognosis of patients with ACLF. Although bacterial infections and variceal bleeding are common precipitating factors, no precipitating factor can be identified in almost 60% of patients with ACLF. There is increasing evidence that cirrhosis is a condition characterized by a systemic inflammatory state and occult infections or translocation of bacteria or bacterial products from the lumen of the GUT to the systemic circulation which could play a role in the development of ACLF. Simple and readily available variables to predict the occurrence of ACLF in patients with cirrhosis have been identified and high‐risk patients need careful management. Whether prolonged administration of statins, rifaximin or albumin can prevent ACLF requires further study. Patients with organ(s) failure(s) may needed to be admitted to the ICU and there should be no hesitation in admitting patients with cirrhosis to the ICU. No benefit to survival was observed with albumin dialysis and rescue transplantation is the best option in the most severe patients. One‐year post‐transplant survival rates exceeding 70%‐75% have been reported, including in patients with grade 3 ACLF but these patients were highly selected. Criteria have been proposed to define futile transplantation (too ill to be transplanted), but these criteria need to be refined to include age, comorbidities and frailty in addition to markers of disease severity.
Hepatocellular adenoma in men: A nationwide assessment of pathology and correlation with clinical course
Authors: van Rosmalen Belle V. , Furumaya Alicia , Klompenhouwer Anne J. , Tushuizen Maarten E. , Braat Andries E. , Reinten Roy J. , Ligthart Marjolein A. P. , Haring Martijn P. D. , de Meijer Vincent E. , van Voorthuizen Theo , Takkenberg R. Bart , Dejong Cornelis H. C. , de Man Robert A. , IJzermans Jan N. M. , Doukas Michail , van Gulik Thomas M. , Verheij Joanne ,   the Dutch Benign Liver Tumor Group and the PALGA group
Published: June 2021

Background & Aims

Hepatocellular adenomas (HCA) rarely occur in males, and if so, are frequently associated with malignant transformation. Guidelines are based on small numbers of patients and advise resection of HCA in male patients, irrespective of size or subtype. This nationwide retrospective cohort study is the largest series of HCA in men correlating (immuno)histopathological and molecular findings with the clinical course.

Methods

Dutch male patients with available histological slides with a (differential) diagnosis of HCA between 2000 and 2017 were identified through the Dutch Pathology Registry (PALGA). Histopathology and immunohistochemistry according to international guidelines were revised by two expert hepatopathologists. Next generation sequencing (NGS) was performed to confirm hepatocellular carcinoma (HCC) and/or subtype HCA. Final pathological diagnosis was correlated with recurrence, metastasis and death.

Results

A total of 66 patients from 26 centres fulfilling the inclusion criteria with a mean (±SD) age of 45.0 ± 21.6 years were included. The diagnosis was changed after expert revision and NGS in 33 of the 66 patients (50%). After a median follow‐up of 9.6 years, tumour‐related mortality of patients with accessible clinical data was 1/18 (5.6%) in HCA, 5/14 (35.7%) in uncertain HCA/HCC and 4/9 (44.4%) in the HCC groups (P = .031). Four B‐catenin mutated HCA were identified using NGS, which were not yet identified by immunohistochemistry and expert revision.

Conclusions

Expert revision with relevant immunohistochemistry may help the challenging but prognostically relevant distinction between HCA and well‐differentiated HCC in male patients. NGS may be more important to subtype HCA than indicated in present guidelines.