bluuebunny/crossref_metadata_2025 huggingface dataset:
IgD+age‐associated B cells are the progenitors of the main T‐independent B cell response to infection that generates protective Ab and can be induced by an inactivated vaccine in the aged
Authors: Kugler‐Umana Olivia , Zhang Wenliang , Kuang Yi , Liang Jialing , Castonguay Catherine H. , Tonkonogy Susan L. , Marshak‐Rothstein Ann , Devarajan Priyadharshini , Swain Susan L.
Published: September 2022

Age‐associated B cells (ABC) accumulate with age and are associated with autoimmunity and chronic infection. However, their contributions to acute infection in the aged and their developmental pathways are unclear. We find that the response against influenza A virus infection in aged mice is dominated by a Fas+GL7− effector B cell population we call infection‐induced ABC (iABC). Most iABC express IgM and include antibody‐secreting cells in the spleen, lung, and bone marrow. We find that in response to influenza, IgD+CD21−CD23−ABC are the precursors of iABC and become memory B cells. These IgD+ABC develop in germ‐free mice, so are independent of foreign antigen recognition. The response of ABC to influenza infection, resulting in iABC, is T cell independent and requires both extrinsic TLR7 and TLR9 signals. In response to influenza infection, IgD+ABC can induce a faster recovery of weight and higher total anti‐influenza IgG and IgM titers that can neutralize virus. Immunization with whole inactivated virus also generates iABC in aged mice. Thus, in unimmunized aged mice, whose other B and T cell responses have waned, IgD+ABC are likely the naive B cells with the potential to become Ab‐secreting cells and to provide protection from infection in the aged.
Feeding behaviour in Australian gregarious Lophyrotoma sawflies (Hymenoptera: Pergidae)
Authors: Takeuchi Masatoshi , Zalucki Myron P.
Published: September 2022

Details of feeding behaviour of Australian sawfly species on eucalypt hosts are not well known. In this study, we report new findings on two pergid sawflies, Lophyrotoma interrupta and an unidentified species of Lophyrotoma, after observing larvae feed. We confirmed both daily and nightly feeding regimes, with L. interrupta and Lophyrotoma sp. engaged in feeding‐related activities 92.2% and 67.0% of the time, respectively. A colony sometimes splits into subcolonies as a leaf depletes; individuals leave singly and explore surrounding leaves before joining the rest of the colony feeding on the new leaf. As a specific feeding behaviour, the larvae of both species cut midveins on surrounding leaves in one of several ways before and during feeding. Larvae used pre‐processed cut leaves at a ratio ranging from 0.64 to 0.88 of the whole leaves eaten. Of the leaves cut prior to feeding, approximately half were not consumed, whereas the remaining were consumed 2 days after cutting (median time). We observed a decreasing trend of further cuttings when the proportion of damaged leaves in the surrounding area was increased. Feeding of Lophyrotoma sp. followed a clear pattern: Usually, the last individual remaining on the leaf severed the leaf petiole as it left. This petiole snipping occurred in over half the leaves that larvae had used; however, this behaviour was not observed in L. interrupta.
Experimental validation of seminal miR‐31‐5p as biomarker for azoospermia and evaluation of the effect of preanalytical variables
Authors: Plata‐Peña Laura , López‐Rodrigo Olga , Bassas Lluís , Larriba Sara
Published: September 2022

Background and objectives

Predicting the origin of azoospermia with non‐invasive biomarkers is clinically relevant for determining the chance of successful sperm retrieval from the testes before attempting assisted reproduction treatment. Here, the semen small extracellular vesicle microRNA miR‐31‐5p‐based biomarker test to distinguish obstructive azoospermia from secretory azoospermia (previously described by our group) is validated for clinical use, and additionally, the sample source (seminal small extracellular vesicles vs. total seminal plasma) as a preanalytical variable is considered to optimize the procedure.

Results and Discussion

Our results provide evidence that altered miR‐31‐5p expression can be determined both from extracellular vesicles and from the whole seminal plasma to discriminate obstructive from secretory azoospermic samples. Not only have we validated this microRNA‐based molecular model as a clinically useful test for predicting the origin of azoospermia in a sample from azoospermic individuals, but additionally, and more interestingly for the clinicians, we have evidenced its usefulness for predicting the presence of spermatogenic failure in azoospermic patients with follicle‐stimulating hormone values <10 IU/L as a sensitive and specific biomarker (area under the receiver operating characteristic curve >0.88; p‐value < 0.006).

The use of total seminal plasma as an analytical sample would facilitate the use of a simplified technical procedure for miR‐31‐5p quantification and would represent a great improvement in reproductive treatment decision protocols for azoospermia in clinical practice.
National register data are of value in studies on miscarriage—Validation of the healthcare register data in Finland
Authors: Helle Nea , Niinimäki Maarit , Linnakaari Reetta , But Anna , Gissler Mika , Heikinheimo Oskari , Mentula Maarit
Published: September 2022

Introduction

Despite the high prevalence of miscarriages, they are not systematically registered and few epidemiological studies have been done. As Finnish health registries are comprehensive and widely used in research, we validated the Finnish register data concerning diagnostics and treatment of miscarriage, and treatment‐related adverse events.

Material and methods

We conducted a validation study regarding miscarriage‐related codes of diagnoses and surgical procedures in a Finnish National Hospital Discharge Registry (NHDR) by comparing the information from the NHDR with that of the hospital records. We selected a random sample of 4 months during 1998–2016 from three hospitals, comprising 687 women aged 15–49 experiencing a first miscarriage during follow‐up. Women with diagnoses unrelated to miscarriage, or proven to be other than miscarriage, were excluded. The final sample consisted of 643 women with confirmed miscarriage, which was used for analyses regarding the diagnosis, treatment and adverse events of miscarriage treatment.

Results

The majority of miscarriages registered in the NHDR were confirmed by the hospital records (positive predictive value [PPV] = 93.6% [95% confidence interval [CI] 91.8%–95.4%]). Different types of miscarriage were also reliably identified; spontaneous abortion with PPV = 85.6% (95% CI 80.9%–89.2%), missed abortion with PPV = 92.7% (95% CI 88.8%–95.3%) and blighted ovum with PPV = 91.1% (95% CI 84.3%–95.1%). The PPV of surgical treatment (62.2% [95% CI 55.7%–68.3%]) was lower than the PPV of non‐surgical treatment (93.3% [95% CI 90.5%–95.3%]). The diagnoses regarding adverse events of miscarriage treatment could be reliably identified. The PPV for clinical infections was 76.0% (95% CI 56.6%–88.5%) and for retained products of conception or/and vaginal bleeding 96.8% (95% CI 83.8%–99.4%).

Conclusions

The coverage of the NHDR was good concerning identification of miscarriages, different types of miscarriages and non‐surgical treatment. Nevertheless, there is a need for clearly defined procedural codes concerning to medical treatment of miscarriage. The register‐based data are reliable and practicable for both clinical evaluation and research concerning miscarriage.
The impact of macronutrient composition on metabolic regulation: An Islet‐Centric view
Authors: dos Santos Klinsmann Carolo , Olofsson Camilla , Cunha João Paulo M. C. M. , Roberts Fiona , Catrina Sergiu‐Bogdan , Fex Malin , Ekberg Neda Rajamand , Spégel Peter
Published: September 2022

Aim

The influence of dietary carbohydrates and fats on weight gain is inconclusively understood. We studied the acute impact of these nutrients on the overall metabolic state utilizing the insulin:glucagon ratio (IGR).

Methods

Following in vitro glucose and palmitate treatment, insulin and glucagon secretion from islets isolated from C57Bl/6J mice was measured. Our human in vivo study included 21 normoglycaemia (mean age 51.9 ± 16.5 years, BMI 23.9 ± 3.5 kg/m2, and HbA1c 36.9 ± 3.3 mmol/mol) and 20 type 2 diabetes (T2D) diagnosed individuals (duration 12 ± 7 years, mean age 63.6 ± 4.5 years, BMI 29.1 ± 2.4 kg/m2, and HbA1c 52.3 ± 9.5 mmol/mol). Individuals consumed a carbohydrate‐rich or fat‐rich meal (600 kcal) in a cross‐over design. Plasma insulin and glucagon levels were measured at −30, −5, and 0 min, and every 30 min until 240 min after meal ingestion.

Results

The IGR measured from mouse islets was determined solely by glucose levels. The palmitate‐stimulated hormone secretion was largely glucose independent in the analysed mouse islets. The acute meal tolerance test demonstrated that insulin and glucagon secretion is dependent on glycaemic status and meal composition, whereas the IGR was dependent upon meal composition. The relative reduction in IGR elicited by the fat‐rich meal was more pronounced in obese individuals. This effect was blunted in T2D individuals with elevated HbA1c levels.

Conclusion

The metabolic state in normoglycaemic individuals and T2D‐diagnosed individuals is regulated by glucose. We demonstrate that consumption of a low carbohydrate diet, eliciting a catabolic state, may be beneficial for weight loss, particularly in obese individuals.
CDCA7 promotes TGF‐β‐induced epithelial–mesenchymal transition via transcriptionally regulating Smad4/Smad7 in ESCC
Authors: Li Hongyi , Wang Shaojie , Li Xiubo , Weng Yongjia , Guo Dinghe , Kong Pengzhou , Cheng Caixia , Wang Yanqiang , Zhang Ling , Cheng Xiaolong , Cui Yongping
Published: September 2022

Cell division cycle associated 7 (CDCA7) is a copy number amplification gene that contributes to the metastasis and invasion of tumors, including esophageal squamous cell carcinoma (ESCC). This present study aimed at clarifying whether high expression of CDCA7 promotes the metastasis and invasion of ESCC cell lines and exploring the underlying mechanisms implicated in epithelial–mesenchymal transition (EMT) of ESCC. The role of CDCA7 in the regulation of ESCC metastasis and invasion was evaluated using ESCC cell lines. Expression of EMT‐related markers including E‐cadherin, N‐cadherin, Vimentin, Snail, and Slug, transforming growth factor β (TGF‐β) signaling pathway including Smad2/3, p‐Smad2/3, Smad4, and Smad7 were detected in CDCA7 knockdown and overexpressed cell lines. Dual‐luciferase reporter assay and rescue assay were used to explore the underlying mechanisms that CDCA7 contributed to the metastasis and invasion of ESCC. High CDCA7 expression significantly promoted the metastasis and invasion of ESCC cell lines both in vivo and in vitro. Additionally, the expression of CDCA7 positively correlated with the expression of N‐cadherin, Vimentin, Snail, Slug, TGF‐β signaling pathway and negatively correlated with the expression of E‐cadherin. Furthermore, CDCA7 transcriptionally regulated the expression of Smad4 and Smad7. Knockdown of CDCA7 inhibited the TGF‐β signaling pathway and therefore inhibited EMT. Our data indicated that CDCA7 was heavily involved in EMT by regulating the expression of Smad4 and Smad7 in TGF‐β signaling pathway. CDCA7 might be a new therapeutic target in the suppression of metastasis and invasion of ESCC.
CT and CEA‐based machine learning model for predicting malignant pulmonary nodules
Authors: Liu Man , Zhou Zhigang , Liu Fenghui , Wang Meng , Wang Yulin , Gao Mengyu , Sun Huifang , Zhang Xue , Yang Ting , Ji Longtao , Li Jiaqi , Si Qiufang , Dai Liping , Ouyang Songyun
Published: September 2022

Computed tomography (CT), an efficient radiological technology, is used to detect lung cancer in the clinic. Carcinoembryonic antigen (CEA), a common tumor biomarker, is applied in the detection of various tumors. To highlight the advantages of two‐dimensional techniques and assist clinicians in optimizing lung cancer diagnostic schemes, we established a favorable model combining CT and CEA. In the study, univariate analysis was performed to screen independent predictors in a training cohort of 271 patients with malignant pulmonary nodules (MPNs) and 92 with benign pulmonary nodules (BPNs). Six machine learning–based models involving five CT predictors (mediastinal lymph node enlargement, lobulation, vascular notch sign, spiculation, and nodule number) and lnCEA were constructed and validated in an independent cohort of 129 participants (92 MPNs and 37 BPNs) by SPSS Modeler. A nomogram and the Delong test were generated by R software. Finally, the model established by logistic regression had highest diagnostic efficiency (area under the curve [AUC] = 0.912). Moreover, the diagnostic ability of the logistic model in the validation cohort (AUC = 0.882, 80.4% sensitivity, 75.7% specificity) was higher than that of the Peking University model (AUC = 0.712, 68.5% sensitivity, 70.3% specificity) and the Mayo model (AUC = 0.745, 62.0% sensitivity, 75.7% specificity). Interestingly, for the participants with intermediate (10‐30 mm) and CEA‐negative nodule, the model reached an AUC of 0.835 (72.3% sensitivity, 83.3% specificity). The AUC for the early lung cancer was as high as 0.822 with 67.3% sensitivity and 78.9% specificity. As a conclusion, this promising model presents a new diagnostic strategy for the clinic to distinguish MPNs from BPNs.
Are mobile phone ownership and age of acquisition associated with child adjustment? A 5‐year prospective study among low‐income Latinx children
Authors: Sun Xiaoran , Haydel K. Farish , Matheson Donna , Desai Manisha , Robinson Thomas N.
Published: September 2022

This prospective, longitudinal study examined associations between whether and when children first acquire a mobile phone and their adjustment measures, among low‐income Latinx children. Children (N = 263; 55% female; baseline Mage = 9.5) and their parents were assessed annually for 5 years from 2012. Children first acquired a mobile phone at a mean (SD) age of 11.62 (1.41) years. Pre‐registered multilevel models tested associations linking phone ownership, phone acquisition age, and the interaction between ownership and acquisition age to levels and changing trends of depressive symptoms, school grades, and reported and objectively assessed sleep. Results showed no statistically significant associations, controlling the False Discovery Rate. Findings suggest an absence of meaningful links from mobile phone ownership and acquisition age to child adjustment.
Evaluating dermatology education and training
Authors: Byrne-Davis Lucie , Cohen Stuart N. , Turner Rebecca R.
Published: September 2022

The purpose of education and training in dermatology ranges from increasing knowledge and skills to improving confidence or enhancing patient outcomes. Specification of the purpose of the education and training is vital so that evaluation can be aligned to purpose, and thus provide evidence on effectiveness. Further, the quality and quality improvement of education and training can be enhanced by a careful specification of how they are expected to achieve their purpose. Multiple theories and methods can be used to evaluate both the process and the outcome of education and training. In this paper, we summarize some of these and focus particularly on the use of behavioural science to evaluate education and training. We illustrate these theories and methods with an example in dermatology.
Myelin oligodendrocyte glycoprotein antibody‐associated disease presenting as recurrent acute disseminated encephalomyelitis: Case report of the youngest Mexican patient in the literature
Authors: García‐Estrada Christian , Gómez‐Figueroa Enrique , Morelos‐Cisneros Juan Pablo , Deras‐Martinez Alondra
Published: September 2022

Background

Myelin oligodendrocyte glycoprotein antibody‐associated disease myelin oligodendrocyte glycoprotein antibody‐associated disease is an emerging demyelinating condition distinct from neuromyelitis optica spectrum disorder and multiple sclerosis affecting both children and adults with a spectrum of clinical manifestations ranging from optic neuritis, myelitis and acute disseminated encephalomyelitis.

Case report

We describe the case of a 2 year‐old girl diagnosed with myelin oligodendrocyte glycoprotein antibody‐associated disease presenting as recurrent acute disseminated encephalomyelitis who showed suppression of disease activity after treatment with rituximab. This case represents the youngest Mexican patient with myelin oligodendrocyte glycoprotein antibody‐associated disease reported to date.

Conclusions

Information regarding the clinical presentation and evolution among different population could help to a better understanding of the presentation of this entity.
Headway and the remaining hurdles of mesenchymal stem cells therapy for bronchopulmonary dysplasia
Authors: Tang Eireen , Zaidi Mariam , Lim Wen‐Huey , Govindasamy Vijayendran , Then Kong‐Yong , Then Khong‐Lek , Das Anjan Kumar , Cheong Soon‐Keng
Published: September 2022

Objective

Preterm infants are at a high risk of developing BPD. Although progression in neonatal care has improved, BPD still causes significant morbidity and mortality, which can be attributed to the limited therapeutic choices for BPD. This review discusses the potential of MSC in treating BPD as well as their hurdles and possible solutions.

Data Sources

The search for data was not limited to any sites but was mostly performed on all clinical trials available in ClinicalTrials.gov as well as on PubMed by applying the following keywords: lung injury, preterm, inflammation, neonatal, bronchopulmonary dysplasia and mesenchymal stem cells.

Study Selections

The articles chosen for this review were collectively determined to be relevant and appropriate in discussing MSC not only as a potential treatment strategy for curbing the incidence of BPD but also including insights on problems regarding MSC treatment for BPD.

Results

Clinical trials regarding the use of MSC for BPD had good results but also illustrated insights on problems to be addressed in the future regarding the treatment strategy. Despite that, the clinical trials had mostly favourable reviews.

Conclusion

With BPD existing as a constant threat and there being no permanent solutions, the idea of regenerative medicine such as MSC may prove to be a breakthrough strategy when it comes to treating BPD. The success in clinical trials led to the formulation of prospective MSC‐derived products such as PNEUMOSTEM®, and there is the possibility of a stem cell medication and permanent treatment for BPD in the near future.
State‐of‐the‐art therapies for Rett syndrome
Authors: Panayotis Nicolas , Ehinger Yann , Felix Marie Solenne , Roux Jean‐Christophe
Published: September 2022

Rett syndrome (RTT) is an X‐linked neurogenetic disorder caused by mutations of the MECP2 (methyl‐CpG‐binding protein 2) gene. Over two decades of work established MeCP2 as a protein with pivotal roles in the regulation of the epigenome, neuronal physiology, synaptic maintenance, and behaviour. Given the genetic aetiology of RTT and the proof of concept of its reversal in a mouse model, considerable efforts have been made to design therapeutic approaches to re‐express MeCP2. By being at the forefront of the development of innovative gene therapies, research on RTT is of paramount importance for the treatment of monogenic neurological diseases. Here we discuss the recent advances and challenges of promising genetic strategies for the treatment of RTT including gene replacement therapies, gene/RNA editing strategies, and reactivation of the silenced X chromosome.

What this paper adds

Recent advances shed light on the promises of gene replacement therapy with new vectors designed to control the levels of MeCP2 expression.

New developments in DNA/RNA editing approaches or reactivation of the silenced X chromosome open the possibility to re‐express the native MeCP2 locus at endogenous levels.

Current strategies still face limitations in transduction efficiency and future work is needed to improve brain delivery.
All‐cause and cardiorenal mortality in 6 million adults with and without type 2 diabetes: A comparative, trend analysis in Canada, Spain, and the UK
Authors: Ling Suping , Zaccardi Francesco , Vlacho Bogdan , Li Ping , Real Gatius Jordi , Mata‐Cases Manel , Franch‐Nadal Josep , Kosiborod Mikhail N. , Gillies Clare , Fenici Peter , Mauricio Dídac , Shah Baiju R. , Khunti Kamlesh
Published: September 2022

Aims

To understand geographical and temporal patterns in the diabetes gap, the excess mortality risk associated with type 2 diabetes (T2D), in three high‐income countries.

Methods

Using databases from Canada (Ontario), Spain (Catalonia) and the UK (England), we harmonized the study design and the analytical strategy to extract information on subjects aged over 35 years with incident T2D between 1998 and 2018 matched to up to five subjects without diabetes. We used Poisson models to estimate age‐specific mortality trends by diabetes status and rate ratios and rate differences associated with T2D.

Results

In more than 6 million people, 694 454 deaths occurred during a follow‐up of 52 million person‐years. Trends in all‐cause mortality rates differed between Ontario and England; yet, the diabetes gaps were very similar in recent years: in 2018, we estimated 1.3 (95% confidence interval: 0.8, 1.8) and 0.8 (0.2, 1.5) more deaths per 1000 person‐years in 50‐year‐old men with diabetes in Ontario and England, respectively, and 8.9 (6.1, 11.7) and 12.1 (9.1, 15.1) in 80‐year‐old men; between‐country differences were small also in women. In Catalonia, rate ratios comparing T2D with no diabetes in men in 2018 were 1.53 (1.11, 2.11) at 50 years old, 0.88 (0.72, 1.06) at 60 years old, 0.74 (0.60, 0.90) at 70 years old and 0.81 (0.66, 1.00) at 80 years old, indicating lower mortality rates in men with T2D from the age of 60 years; rates were similar in women with and without diabetes at all ages. The diabetes gaps in cardiorenal mortality mirrored those of all‐cause mortality: we observed consistent reductions in the proportions of cardiorenal deaths in subjects aged 80 years but variations in subjects aged ≤70 years, regardless of the presence of diabetes.

Conclusions

By reducing the confounding impact of epidemiological and analytical differences, this study showed geographical similarities and differences in the diabetes gap: an excess risk of all‐cause and cardiorenal mortality in subjects with T2D is still present in Ontario and England in recent years, particularly in elderly subjects. Conversely, there were very small gaps in young men with T2D or even lower mortality rates in older subjects with T2D in Catalonia.
Sodium‐glucose cotransporter‐2 inhibitors and the risk of gout in patients with type 2 diabetes mellitus: A propensity‐score‐matched, new‐user design study with an active comparator using the IQVIA Medical Research Data UK database
Authors: Subramanian Anuradhaa , Gokhale Krishna , Sainsbury Christopher , Nirantharakumar Krishnarajah , Toulis Konstantinos A.
Published: September 2022

Aim

To conduct a pharmacoepidemiological study to explore the association between sodium‐glucose cotransporter‐2 (SGLT2) inhibitors and gout in patients with type 2 diabetes mellitus (T2DM).

Materials and Methods

A retrospective open cohort study using the IQVIA Medical Research Data UK database was performed between November 1, 2012 and December 31, 2018, estimating the risk of gout in patients with T2DM who were new users of SGLT2 inhibitors, compared to propensity‐score‐matched new users of dipeptidyl peptidase‐4 (DPP‐4) inhibitors.

Results

A total of 85 incident cases of gout were recorded over 30 389 person‐years of observation in 13 617 new users of SGLT2 inhibitors and 29 426 new users of DPP‐4 inhibitors. Crude incidence rates (IRs) per 1000 person‐years were 2.90 and 2.47 for new users of SGLT2 inhibitors and DPP‐4 inhibitors, respectively. The unadjusted hazard ratio (HR) was 1.18 (95% confidence interval [CI] 0.76‐1.83). The adjusted HR was 1.20 (95% CI 0.77‐1.86). In the at‐treatment analysis, crude IRs per 1000 person‐years were found to be 2.68 and 2.53 for SGLT2 inhibitor and DPP‐4 inhibitor users, respectively. In the adjusted model, the adjusted HR was 1.3 (95% CI 0.90‐2.29). Sensitivity analyses did not change the findings.

Conclusions

In this nationwide study, no difference in the incidence of gout was documented in patients treated with SGLT2 inhibitors compared to DPP‐4 inhibitor users. This neutral finding remained consistent in sensitivity analyses.
Comparison of imaging characteristics for mortality risk analysis between young and older acute aortic dissection patients
Authors: Zhou Ling , Chen Chen , Zheng Minjuan , Liu Lu , Xu Pan , Niu Yicui
Published: September 2022

Background

There are differences between young and older patients diagnosed with acute aortic dissection. We aimed to explore the differences in echocardiographic and computed tomography angiography (CTA) characteristics between the young and the older patients diagnosed with acute aortic dissection.

Methods

The data from 1220 patients with aortic dissection were collected. They were divided into the young and the older groups with the age threshold set at 45 years old. The basic information and imaging data were collected and compared between the two groups. Univariate regression was used to find the risk factors for mortality in each group.

Results

Echocardiographic results showed the proportion of left ventricular enlargement (young vs older, 39.9% vs 26.9%, p‐value <.001) and left ventricular dysfunction (22.3% vs 14.1%, p‐value ​​smaller than .001) in the young group was significantly higher. Although there is no statistically significant difference in mortality within 60 days after admission (12.0% vs 15.1%, p‐value equals to .164), the involvements of aortic branches were the risk factor for the mortality in the young group. For the older patients, the left ventricular remodeling detected by echocardiography (left atrial enlargement, ascending aortic dilation, aortic regurgitation) and decreased heart function were the risk factors for mortality.

Conclusions

The mortality of the young and the older groups with acute aortic dissection are comparable. The involvements of aortic branches were the mortality risk factors in the young patients while the structural and functional change of the left ventricle detected by echocardiography was the mortality risk factor for the older patients.
Allele PaLAR3B in root rot resistance locus does not influence the infection pressure by Heterobasidion parviporum through root contacts
Authors: Terhonen Eeva , Kashif Muhammad , Piri Tuula , Haapanen Matti , Hantula Jarkko
Published: September 2022

The most destructive root rot pathogen of Norway spruce (Picea abies) in Finland is Heterobasidion parviporum. After primary infection, this pathogen spreads from tree to tree through root contacts and eventually causes high levels of root and stem rot. Locus PaLAR3 has been associated with root rot resistance of Norway spruce, and higher resistance in Norway spruce against H. parviporum has been noted when trees have allele PaLAR3B instead of the more common PaLAR3A. In this study we tested if trees with homo‐ or heterozygous PaLAR3B allele can better resist the infection through root contacts. The study was established in 2018 in a site where spruce trees had grown at a dense spacing for 10 years. The 72 trees were cut down and a mixture of four H. parviporum strains was inoculated on the stumps. After 3 years, 459 trees surrounding the inoculated stumps were harvested and analysed. Based on the presence of conidiospores, forty percent (40%) of the trees were infected by H. parviporum. The homozygous PaLAR3B genotype was found only in 1% of the trees. There were no differences in infection rates between the genotypes AA and AB (or BB). Similarly, the distance from inoculated stump or the diameter of the tree did not influence the infection rate.
Not an ordinary bank but a great engine of state: The Bank of England and the British economy, 1694–1844
Authors: O'Brien Patrick K. , Palma Nuno
Published: September 2022

From its foundation as a private corporation in 1694, the Bank of England extended large amounts of credit to support the British private economy and to support an increasingly centralised British state. The Bank helped the British state reach a position of geopolitical and economic hegemony in the international economic order. In this paper, we deploy recalibrated financial data to analyse an evolving trajectory of connections between the British economy, the state, and the Bank of England. We show how these connections contributed to form an effective and efficient fiscal–naval state and promote the development of a system of financial intermediation for the economy. This symbiotic relationship became stronger after 1793. The evidence that we consider here shows that although the Bank was nominally a private institution and profits were paid to its shareholders, it was playing a public role well before Bagehot's doctrine.
Third space workers in higher education in times of dislocated complexity
Authors: Livingston Kay , Ling Lorraine
Published: September 2022

In this article we examine the changing nature of the higher education workforce with specific reference to the increasing influence and importance of third space workers (e.g., blended learning designers, e‐learning developers, partnerships managers, associate tutors, learning technology specialists and communication and engagement officers). Discussing the contextual framework, we contend that the higher education context is uncertain and has taken on a disrupted character, generating a social condition that we term dislocated complexity. Through the lens of Giddens' Theory of Structuration, we analyse empirical data from two studies—one in Scotland and one in Australia—to shed light on how the workforce in higher education is changing. We illuminate the need for greater recognition of third‐space workers as part of a team alongside academic discipline experts in these times of dislocated complexity. We propose the term dislocated complexity as a means to describe the heightened state of complexity that exists in higher education systems in times of crisis, such as the COVID‐19 pandemic, and highlight the need for structural and policy changes.
JAK inhibition with ruxolitinib in relapsed or refractory classical Hodgkin lymphoma: Final results of a phase II, open label, multicentre clinical trial (JeRiCHO)
Authors: Gillessen Sarah , Pluetschow Annette , Vucinic Vladan , Ostermann Helmut , Kobe Carsten , Bröckelmann Paul J. , Böll Boris , Eichenauer Dennis A. , Heger Jan‐Michel , Borchmann Sven , Fuchs Michael , Borchmann Peter , Engert Andreas , von Tresckow Bastian
Published: September 2022

Objectives

Patients with classical Hodgkin lymphoma (cHL) relapsing after second‐line therapy have a dismal prognosis and novel approaches are required for this patient group. Based on promising (pre‐)clinical data and the favourable toxicity profile, we performed a phase II clinical trial with the JAK inhibitor ruxolitinib in patients with relapsed or refractory cHL (r/r cHL).

Methods

Patients ≥18 years with histologically confirmed r/r cHL who failed second‐line treatment were included. Ruxolitinib was given orally at a dose of 25 mg twice daily in continuous 28‐day cycles until progression or unacceptable toxicity. Primary endpoint was the PET/CT‐based overall response rate (ORR; complete response (CR) or partial response (PR)) after 2 cycles; secondary endpoints included progression‐free (PFS) and overall survival (OS) as well as feasibility. The Jericho Trial adopted a 2‐stage phase 2 design (Simon 1989).

Results

Among the 12 included patients in stage 1, 2 had a PR, 3 had a stable disease (SD) and 6 had progressive disease (PD) after two treatment cycles (ORR: 2/12 evaluable patients, 16.7%). Median PFS was 3.6 months, the 1‐year OS estimate was 50.6% (median not reached). The toxicity profile was favourable with only one grade IV adverse event (7.1%) reported.

Conclusion

Ruxolitinib exhibited a favourable side effect profile but modest activity in r/r cHL. Although the formal stopping criterion after stage 1 was not met, the trial did not continue to stage 2 due to the low response and PFS rates observed in stage 1.
Clinical autonomic nervous system laboratories in Europe
Authors: Habek Mario , Leys Fabian , Krbot Skorić Magdalena , Reis Carneiro Diogo , Calandra‐Buonaura Giovanna , Camaradou Jennifer , Chiaro Giacomo , Cortelli Pietro , Falup‐Pecurariu Cristian , Granata Roberta , Guaraldi Pietro , Helbok Raimund , Hilz Max J. , Iodice Valeria , Jordan Jens , Kaal Evert C. A. , Kamondi Anita , Pavy Le Traon Anne , Rocha Isabel , Sellner Johann , Senard Jean Michel , Terkelsen Astrid , Wenning Gregor K. , Berger Thomas , Thijs Roland D. , Struhal Walter , Fanciulli Alessandra ,   the Collaborators of the European Network of Clinical ANS laboratories
Published: September 2022

Background and purpose

Disorders of the autonomic nervous system (ANS) are common conditions, but it is unclear whether access to ANS healthcare provision is homogeneous across European countries. The aim of this study was to identify neurology‐driven or interdisciplinary clinical ANS laboratories in Europe, describe their characteristics and explore regional differences.

Methods

We contacted the European national ANS and neurological societies, as well as members of our professional network, to identify clinical ANS laboratories in each country and invite them to answer a web‐based survey.

Results

We identified 84 laboratories in 22 countries and 46 (55%) answered the survey. All laboratories perform cardiovascular autonomic function tests, and 83% also perform sweat tests. Testing for catecholamines and autoantibodies are performed in 63% and 56% of laboratories, and epidermal nerve fiber density analysis in 63%. Each laboratory is staffed by a median of two consultants, one resident, one technician and one nurse. The median (interquartile range [IQR]) number of head‐up tilt tests/laboratory/year is 105 (49–251). Reflex syncope and neurogenic orthostatic hypotension are the most frequently diagnosed cardiovascular ANS disorders. Thirty‐five centers (76%) have an ANS outpatient clinic, with a median (IQR) of 200 (100–360) outpatient visits/year; 42 centers (91%) also offer inpatient care (median 20 [IQR 4–110] inpatient stays/year). Forty‐one laboratories (89%) are involved in research activities. We observed a significant difference in the geographical distribution of ANS services among European regions: 11 out of 12 countries from North/West Europe have at least one ANS laboratory versus 11 out of 21 from South/East/Greater Europe (p = 0.021).

Conclusions

This survey highlights disparities in the availability of healthcare services for people with ANS disorders across European countries, stressing the need for improved access to specialized care in South, East and Greater Europe.
Subtle vascular and astrocytic changes in the brain of coronavirus disease 2019 (COVID‐19) patients
Authors: Rosu Gabriela Camelia , Mateescu Valentin Octavian , Simionescu Alexandra , Istrate‐Ofiteru Anca‐Maria , Curcă George Cristian , Pirici Ionica , Mogoanta Laurentiu , Mindrila Ion , Kumar‐Singh Samir , Hostiuc Sorin , Pirici Daniel
Published: September 2022

Background and purpose

In the central nervous system, a multitude of changes have been described associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, such as microglial activation, perivascular lymphocyte cuffing, hypoxic‐ischaemic changes, microthrombosis, infarcts or haemorrhages. It was sought here to assess the vascular basement membranes (vBMs) and surrounding perivascular astrocytes for any morphological changes in acute respiratory syndrome (coronavirus disease 2019, COVID‐19) patients.

Methods

The light microscopy morphology of the vBMs and perivascular astrocytes from brains of 14 patients with confirmed SARS‐CoV‐2 infection was analysed and compared to four control patients utilizing fluorescent immunohistochemistry for collagen IV and astrocytes (GFAP), endothelia (CD31), tight junction 1 (TJ1) adhesion protein, as well as the aquaporin 4 (AQP4) water channel. On 2D and 3D deconvoluted images from the cortex and white matter, vessel densities, diameters, degree of gliosis, collagen IV/GFAP and GFAP/AQP4 colocalizations were calculated, as well as the fractal dimension of astrocytes and vBMs viewed in tangential planes.

Results

Fractal dimension analysis of the GFAP‐stained astrocytes revealed lower branching complexities and decreased GFAP/collagen IV colocalization for COVID‐19 patients. Interestingly, vBMs showed significantly increased irregularities (fractal dimension values) compared to controls. Vessel diameters were increased in COVID‐19 cases, especially for the white matter, TJ1 protein decreased its colocalization with the endothelia, and AQP4 reduced its co‐expression in astrocytes.

Conclusions

Our data on the irregularity of the basement membranes, loss of endothelial tight junction, reduction of the astrocyte end‐feet and decrease of AQP4 suggest subtle morphological changes of the blood–brain barrier in COVID‐19 brains that could be linked with indirect inflammatory signalling or hypoxia/hypercapnia.
Vestibular syndromes after COVID‐19 vaccination: A prospective cohort study
Authors: Gerb Johannes , Becker‐Bense Sandra , Zwergal Andreas , Huppert Doreen
Published: September 2022

Background and purpose

Dizziness and vertigo are common symptoms after COVID‐19‐vaccination. We aimed to prospectively evaluate objective central or peripheral vestibular function in patients with dizziness, vertigo, and postural symptoms that started or worsened after COVID‐19‐vaccination.

Methods

Of 4137 patients who presented between January 2021 and April 2022 at the German Center for Vertigo and Balance Disorders, Ludwig Maximilian University of Munich, we identified 72 patients (mean age = 47 years) with enduring vestibular symptoms following COVID‐19 vaccination. All underwent medical history‐taking, and neurological and neuro‐otological workup with bithermal caloric test, video head‐impulse test, orthoptics, and audiometry. Diagnoses were based on international criteria. The distribution of diagnoses was compared to a cohort of 39,964 patients seen before the COVID‐19 pandemic.

Results

Symptom onset was within the first 4 weeks postvaccination. The most prevalent diagnoses were somatoform vestibular disorders (34.7%), vestibular migraine (19.4%), and overlap syndromes of both (18.1%). These disorders were significantly overrepresented compared to the prepandemic control cohort. Thirty‐six percent of patients with somatoform complaints reported a positive history of depressive or anxiety disorders. Nine patients presented with benign paroxysmal positional vertigo, three with acute unilateral vestibulopathy, and seven with different entities (vestibular paroxysmia, Ménière disease, polyneuropathy, ocular muscular paresis). Causally related central vestibular deficits were lacking. Novel peripheral vestibular deficits were found in four patients.

Conclusions

Newly induced persistent vestibular deficits following COVID‐19 vaccination were rare. The predominant causes of prolonged vestibular complaints were somatoform vestibular disorders and vestibular migraine, possibly triggered or aggravated by stress‐related circumstances due to the COVID‐19 pandemic or vaccination. An increase of other central or peripheral vestibular syndromes after COVID‐19 vaccination was not observed.
Revisiting the Happy Jack Uraninite Reference Material: A Combined Electron Beam and Laser Ablation In Situ Study
Authors: Zhou Lingli , Riegler Thomas , Bonnetti Christophe , McClenaghan Sean , Kamber Balz
Published: September 2022

This new comprehensive in situ mineral‐chemical characterisation of the Happy Jack uraninite has discovered additional information regarding matrix effects and trace element homogeneity, relevant to proposals that it could serve as a reference material (RM). On the LA‐ICP‐MS instrumentation used, there was an absence of discernible matrix effects relative to the silicate glass NIST SRM 610. Lanthanides and Y are found to be very homogeneously distributed in Happy Jack uraninite, Zr, Nb and Ti mass fractions reproducible but only within individual fragments, and other elements still generally heterogeneous. This means that the Happy Jack uraninite can serve as a secondary RM for quality control in studies of natural uraninites. In terms of absolute accuracy and intermediate measurement precision, the Happy Jack uraninite can be used for the homogeneous elements. For elements that are homogeneous within individual fragments only, intermediate measurement precision can still be evaluated, while information values will be obtained for the generally heterogeneous elements. Two distinct groups (high vs. low Zr) were distinguished to exist among different Happy Jack fragments in association with minor variation of REE mass fractions, which possibly explains the observed (heavy) REE discrepancy between in situ laser ablation and bulk solution ICP‐MS analyses.
A qualitative formative evaluation of a patient facing intervention to improve care transitions for older people moving from hospital to home
Authors: Shannon Rosie , Baxter Ruth , Hardicre Natasha , Mills Thomas , Murray Jenni , Lawton Rebecca , O'Hara Jane K.
Published: September 2022

Background

The Partners at Care Transitions (PACTs) intervention was developed to support older people's involvement in hospital to improve outcomes at home. A booklet, question card, record sheet, induction leaflet, and patient‐friendly discharge letter support patients to be more involved in their health and wellbeing, medications, activities of daily living and post‐discharge care. We aimed to assess intervention acceptability, identify implementation tools, and further develop the intervention.

Methods

This was a qualitative formative evaluation involving three wards from one hospital. We recruited 25 patients aged 75 years and older. Ward staff supported intervention delivery. Data were collected in wards and patients' homes, through semi‐structured interviews, observation, and documentary analysis. Data were analysed inductively and iteratively with findings sorted according to the research aims.

Results

Patients and staff felt there was a need for, and understood the purpose of, the PACT intervention. Most patients read the booklet but other components were variably used. Implementation challenges included time, awareness, and balancing intervention benefits against risks. Changes to the intervention and implementation included clarifying the booklet's messages, simplifying the discharge letter to reduce staff burden, and using prompts and handouts to promote awareness.

Conclusion

The PACT intervention offers a promising new way to improve care transitions for older people by supporting patient involvement in their care. After further development of the intervention and implementation package, it will undergo further testing.

Patient or Public Contribution

This study regularly consulted a panel representing the local patient community, who supported the development of this intervention and its implementation.
Thermal conductivity of several geopolymer composites and discussion of their formulation
Authors: Samuel Devon M. , Inumerable Nathaniel , Stumpf Andrew , Kriven Waltraud M.
Published: September 2022

We fabricated 50.8‐mm cube‐shaped samples of metakaolin geopolymer (GP) composites with various additives chosen to increase or decrease the thermal conductivity of the composite. Sodium‐based GP (NaGP) and GP composites were more conductive than potassium‐based GP (KGP) composites for a given phase fraction of filler, but the maximum amount of filler phase was higher with KGP due to the lower viscosity of the KGP mixture. The highest thermal conductivity achieved was about 8 W/m K by KGP + 44‐vol% graphite flakes, whereas NaGP + 27 vol% graphite flakes reached 4.7 W/m K. The thermal conductivity was strongly affected by the moisture remaining in the composite, which appeared to have a greater effect at higher filler content. On the other hand, the size of alumina particles (6, 40, or 120 μm) did not have any apparent effect on thermal conductivity for the same filler content. Larger particles caused less change in mixture viscosity, though, thus permitting incorporation of higher filler phase fractions and therefore higher thermal conductivity.
Study on chemical compositions, antioxidants and intracellular anti‐melanogenic activities of varieties of Ganoderma lucidum in Vietnam
Authors: Ha Hue Thi , Tran‐Van Hieu , Van Tran Thuan , Nguyen Hanh Thi Ngoc , Phan Dao Thi Anh
Published: September 2022

Here, five selected Vietnam Ganoderma lucidum varieties were first prepared and examined for total polyphenol content (TPC) and antioxidant activities (including DPPH, FRAP and tyrosinase inhibition). All the selected extracts exhibited significant bioactivities, which could be attributed to their large TPC values with Pearson statistical coefficients r ~ 0.8 (P < 0.10). Ethanol extract of Korean lingzhi (E‐KR), the largest bioactive one, was identified with 16 bioactive compounds using FT‐IR and HPLC‐MS, including proteins, glucosides, triterpenoids, alkaloids, phenolic compounds, flavonoids and polysaccharides, which could prove the excellent bioactivities of the extract. The E‐KR (40 μg mL−1) examined on B16 melanoma cells did not cause any significant toxicity to cell viability and exhibited significant inhibition towards melanin formation (29.34%) and reduction of intracellular tyrosinase activity (21.93%), which was not a significant difference to the positive control of arbutin (P > 0.05). These results promise a great potential of G. lucidum in skincare cosmetics for therapy treatment of skin pigmentation.
UK NEQAS Haematology pilot scheme: Reticulocyte haemoglobin content quantitation
Authors: Mordue Kathryn E. , Hector Yvonne , Thomas D. Wayne , De La Salle Barbara J.
Published: September 2022

Introduction

Established parameters for the investigation of suspected iron deficiency have recognized limitations that affect their sensitivity and specificity. Reticulocyte haemoglobin content (RHC) is an early biomarker of iron deficiency or restriction, which also demonstrates response to iron therapy. RHC parameters are offered on all major automated haematology analysers. There is no external quality assessment (EQA) for RHC in the UK, restricting its wider clinical application. The UK National External Quality Assessment Scheme (UKNEQAS) for Haematology has completed a pilot study on the use of stabilized blood for RHC EQA.

Methods

Blood was obtained from two JAK2 V617F mutation‐positive, polycythaemia vera patients undergoing regular venesection, and from a healthy volunteer donor. Aliquots of each donation were distributed to users of Abbott, Horiba, Siemens and Sysmex automated analysers for RHC analysis on days 1, 3, 5 and 7.

Results

Results were received from 20 laboratories using four different platforms. The daily mean and standard deviation (SD) were calculated for each aliquot, by day of analysis and platform. With RHC there was no significant within‐platform difference (p > 0.5) between testing days, although there were statistically significant differences (p < 0.001) between different platforms. The greatest difference was seen between Abbott MCHr and Horiba RhCc (−6.14 ± 1.25 pg). Despite inter‐platform differences, it was possible to define iron deficient, borderline, and normal cut‐offs to classify 95% of results correctly.

Conclusions

The results demonstrate that it is possible to provide RHC EQA material using UKNEQAS standard procedures. The results are clinically relevant but indicate a requirement for inter‐user comparison.