bluuebunny/crossref_metadata_2025 huggingface dataset:
Age estimation based on blood DNA methylation levels in brown bears
Authors: Nakamura Shiori , Yamazaki Jumpei , Matsumoto Naoya , Inoue‐Murayama Miho , Qi Huiyuan , Yamanaka Masami , Nakanishi Masanao , Yanagawa Yojiro , Sashika Mariko , Tsubota Toshio , Ito Hideyuki , Shimozuru Michito
Published: March 2023

Age is an essential trait for understanding the ecology and management of wildlife. A conventional method of estimating age in wild animals is counting annuli formed in the cementum of teeth. This method has been used in bears despite some disadvantages, such as high invasiveness and the requirement for experienced observers. In this study, we established a novel age estimation method based on DNA methylation levels using blood collected from 49 brown bears of known ages living in both captivity and the wild. We performed bisulfite pyrosequencing and obtained methylation levels at 39 cytosine‐phosphate‐guanine (CpG) sites adjacent to 12 genes. The methylation levels of CpGs adjacent to four genes showed a significant correlation with age. The best model was based on DNA methylation levels at just four CpG sites adjacent to a single gene, SLC12A5, and it had high accuracy with a mean absolute error of 1.3 years and median absolute error of 1.0 year after leave‐one‐out cross‐validation. This model represents the first epigenetic method of age estimation in brown bears, which provides benefits over tooth‐based methods, including high accuracy, less invasiveness, and a simple procedure. Our model has the potential for application to other bear species, which will greatly improve ecological research, conservation, and management.
Anti‐CD3 inhibits circulatory and tissue‐resident memory CD4 T cells that drive asthma exacerbations in mice
Authors: Sethi Gurupreet S. , Gracias Donald T. , Gupta Rinkesh K. , Carr Daniel , Miki Haruka , Da Silva Antunes Ricardo , Croft Michael
Published: March 2023

Background

Exacerbations of asthma are thought to be strongly dependent on reactivation of allergen‐induced lung tissue‐resident and circulatory memory CD4 T cells. Strategies that broadly inhibit multiple T cell populations might then be useful to limit asthma. Accordingly, we tested whether targeting CD3 during exposure to inhaled allergen could prevent the accumulation of lung‐localized effector memory CD4 T cells and block exacerbations of asthmatic inflammation.

Methods

House dust mite‐sensitized and repetitively challenged BL/6 mice were transiently treated therapeutically with F(ab′)2 anti‐CD3ε and memory T cell responses and lung inflammation were assessed. PBMCs from HDM‐allergic donors were examined for the effect of anti‐CD3 on expansion of allergen‐reactive T cells.

Results

Allergen‐sensitized mice undergoing exacerbations of asthma were protected from lung inflammation by transient therapeutic treatment with F(ab′)2 anti‐CD3. Regardless of whether sensitized mice underwent a secondary or tertiary recall response to inhaled allergen, anti‐CD3 inhibited all phenotypes of effector memory CD4 T cells in the lung tissue and lung vasculature by 80%–90%, including those derived from tissue‐resident and circulatory memory T cells. This did not depend on Treg cells suggesting it was primarily a blocking effect on memory T cell signaling. Correspondingly, anti‐CD3 also strongly inhibited proliferation of human allergen‐reactive memory CD4 T cells from allergic individuals. In contrast, the number of surviving tissue‐resident memory CD4 T cells that were maintained in the lungs at later times was not robustly reduced by anti‐CD3.

Conclusion

Anti‐CD3 F(ab′)2 administration at the time of allergen exposure represents a viable strategy for limiting the immediate activity of allergen‐responding memory T cells and asthma exacerbations.
Postoperative mortality and complications in patients with and without pre‐operative SARS‐CoV‐2 infection: a service evaluation of 24 million linked records using OpenSAFELY
Authors: McInerney C. D. , Kotzé A. , Bacon S. , Cutting J. E. , Fisher L. , Goldacre B. , Johnson O. A. , Kua J. , McGuckin D. , Mehrkar A. ,   the OpenSAFELY Collaborative, Moonesinghe S. R.
Published: March 2023

Surgical decision‐making after SARS‐CoV‐2 infection is influenced by the presence of comorbidity, infection severity and whether the surgical problem is time‐sensitive. Contemporary surgical policy to delay surgery is informed by highly heterogeneous country‐specific guidance. We evaluated surgical provision in England during the COVID‐19 pandemic to assess real‐world practice and whether deferral remains necessary. Using the OpenSAFELY platform, we adapted the COVIDSurg protocol for a service evaluation of surgical procedures that took place within the English NHS from 17 March 2018 to 17 March 2022. We assessed whether hospitals adhered to guidance not to operate on patients within 7 weeks of an indication of SARS‐CoV‐2 infection. Additional outcomes were postoperative all‐cause mortality (30 days, 6 months) and complications (pulmonary, cardiac, cerebrovascular). The exposure was the interval between the most recent indication of SARS‐CoV‐2 infection and subsequent surgery. In any 6‐month window, < 3% of surgical procedures were conducted within 7 weeks of an indication of SARS‐CoV‐2 infection. Mortality for surgery conducted within 2 weeks of a positive test in the era since widespread SARS‐CoV‐2 vaccine availability was 1.1%, declining to 0.3% by 4 weeks. Compared with the COVIDSurg study cohort, outcomes for patients in the English NHS cohort were better during the COVIDSurg data collection period and the pandemic era before vaccines became available. Clinicians within the English NHS followed national guidance by operating on very few patients within 7 weeks of a positive indication of SARS‐CoV‐2 infection. In England, surgical patients' overall risk following an indication of SARS‐CoV‐2 infection is lower than previously thought.
The changing pattern of COVID‐19 infection in hemodialysis and peritoneal dialysis patients
Authors: Goodlad Cate , Davenport Andrew
Published: March 2023

Introduction

Following the first wave of COVID‐19 there have been several variants. We wished to review the number and severity of infections with the different variants in a population of hemodialysis (HD) and peritoneal dialysis (PD) patients.

Methods

We reviewed the outcomes and results in HD and PD patients testing positive for COVID‐19 between March 2020 and August 2022.

Results

Seven hundred and ninety‐five cases of COVID‐19 were recorded in 710 dialysis patients. More HD patients than PD contracted wild type (21.4% vs. 6.8%), delta (23.3% vs 6.3%), and omicron (27.7% vs. 14.7%), all p < 0.01, but no difference with alpha (4.6% vs. 6.3%) or beta variants (5.7% vs. 6.85%). Hospitalization and death were greatest for alpha followed by wild type, beta, delta, and omicron (60.6% vs. 57% vs. 47.5% vs. 21.2% vs. 19.3%), respectively, p < 0.001. C reactive protein progressively increased from outpatient management to hospitalization to hospitalization with critical care or death (14 (4–30) vs. 41 (18–101) vs. 94 (47–168) mg/L, p < 0.001. Despite previous infection and vaccination 85 (12%) patients had two or more infections with COVID‐19.

Conclusion

Disease severity declined and survival improved as the virus mutated from wild‐type and alpha to beta, delta, and omicron variants. Whether this related to reduction in viral virulence, vaccination, natural acquired immunity, or introduction of pharmacological treatments remains to be determined. Government lockdowns and enhanced infection control measures reduced the percentage of HD patients contracting alpha and beta variants to that of PD. Vaccination and prior infection did not prevent reinfection.
Editorial: risankizumab – ready to break ceilings?
Authors: Ferrante Marc
Published: March 2023

LINKED CONTENT

This article is linked to Fumery et al papers. To view these articles, visit https://doi.org/10.1111/apt.17358 and https://doi.org/10.1111/apt.17435
Editorial: risankizumab – ready to break ceilings? author's reply
Authors: Fumery Mathurin , Peyrin‐Biroulet Laurent
Published: March 2023

LINKED CONTENT

This article is linked to Fumery et al papers. To view these articles, visit https://doi.org/10.1111/apt.17358 and https://doi.org/10.1111/apt.17401
Effect of Korean trade union on wage discrimination between regular and irregular workers
Authors: Kim Myounghwan , Kim Giseung
Published: March 2023

Whether the dual labor market structure implied by employment type and unionization causes wage discrimination is an intriguing and relevant policy question in the context of South Korea. This study examines the effect of trade unions on wage discrimination against irregular workers by extracting and comparing the ratios of the discriminatory wage gap by employment type between unionized and non‐unionized workplaces. As per the analysis, all generalized decomposition frameworks show that the presence of trade unions expands discrimination regardless of the employment type. In addition, the effects of unionization on the degree of discrimination differ by factors characterized by the dual labor market. The effects are statistically significantly greater for women, youth, service industries, and white‐collar jobs.
Child and adolescent anxiety as a risk factor for bipolar disorder: A systematic review of longitudinal studies
Authors: Buckley Vanessa , Young Allan H. , Smith Patrick
Published: March 2023

Objectives

Several studies have suggested that anxiety disorders in childhood and adolescence often precede the onset of bipolar disorder. We therefore systematically reviewed the relationship between child and adolescent anxiety and later bipolar disorder.

Methods

Online databases (Medline [for Ovid], EMBASE and PsychINFO) were searched for original, peer‐reviewed studies examining the relationship between child and adolescent anxiety and later bipolar disorder. Studies in both community samples and bipolar offspring samples were included.

Results

A total of 16 studies were included in the review. The results were broadly consistent and revealed that child and adolescent anxiety disorders are associated with later bipolar disorder in community samples. In bipolar offspring, child and adolescent anxiety disorders are a marker of increased risk and predict the onset of bipolar disorder and other major mood disorders.

Conclusions

There is evidence that anxiety disorders in childhood and adolescence increase the risk of later bipolar disorder. Anxiety disorders may be a useful target for early intervention in those at high‐risk of bipolar disorder.
Visual attention to own‐ versus other‐race faces: Perspectives from learning mechanisms and task demands
Authors: Hsiao Janet H. , Chan Antoni B.
Published: March 2023

Multiple factors have been proposed to contribute to the other‐race effect in face recognition, including perceptual expertise and social‐cognitive accounts. Here, we propose to understand the effect and its contributing factors from the perspectives of learning mechanisms that involve joint learning of visual attention strategies and internal representations for faces, which can be modulated by quality of contact with other‐race individuals including emotional and motivational factors. Computational simulations of this process will enhance our understanding of interactions among factors and help resolve inconsistent results in the literature. In particular, since learning is driven by task demands, visual attention effects observed in different face‐processing tasks, such as passive viewing or recognition, are likely to be task specific (although may be associated) and should be examined and compared separately. When examining visual attention strategies, the use of more data‐driven and comprehensive eye movement measures, taking both spatial–temporal pattern and consistency of eye movements into account, can lead to novel discoveries in other‐race face processing. The proposed framework and analysis methods may be applied to other tasks of real‐life significance such as face emotion recognition, further enhancing our understanding of the relationship between learning and visual cognition.
Body satisfaction and self‐perception profile: Reliability and validity analyses of the Children's body image scale for Turkish children
Authors: Akliman Çiğdem Keven , Avcı Mehmet , Avcı İlknur Kiraz
Published: March 2023

In recent years, appearance, and body image in particular, has become a very important concern not only for adults but also for children. Children's self‐evaluation of their bodies is critical in the occurrence of eating disorders. This study aims to conduct (1) a validity and reliability analysis of the Children's Body Image Scale (CBIS) adapted to the Turkish culture and (2) the relationship between body satisfaction, self‐worth and physical appearance. The psychometric properties of the CBIS were examined on a sample of 473 (211 girls and 262 boys) children aged 8–11 (mean 9.38). The data obtained from boys and girls were divided into two groups according to grade and analysed using descriptive and inferential statistics. The reliability level of the scale was at an acceptable level, and a statistically significant relationship was found between the scale's Body Mass Index and the dimensions of Self‐Perception Profile. The results revealed that there is a significant relationship between body satisfaction and general self‐worth and physical appearance. In addition, the scores obtained on the CBIS after a 3‐week period showed significant internal consistency and test–retest reliability. The analyses revealed that the CBIS is a valid and reliable measurement tool for Turkish children. The results of the study can be a useful tool for education and health professionals that they need screening tools to help them detect body dissatisfaction. The study also showed some correlates of high body dissatisfaction in children that can be used before the rise in eating disorders in adolescence.
Bornean orangutanPongo pygmaeus pygmaeuspopulation estimate within and around Danau Sentarum National Park, Kapuas Hulu, West Kalimantan
Authors: Yuliani Elizabeth Linda , Bakara Denny O. , Ilyas Mohammad , Russon Anne E. , Salim Agus , Sammy Jim , Sunderland‐Groves J. L. , Sunderland T. C. H.
Published: March 2023

Of the three subspecies of Critically Endangered Bornean orangutans,Pongo pygmaeus pygmaeushas the smallest population size. One of its most important habitats is the tropical forest within and around Danau Sentarum National Park (DSNP). Research in the late 1990s estimated that ca. 1025 orangutans inhabited DSNP, while ca. 1717 orangutans inhabited the forest beyond DSNP's boundaries. However, concerns were later raised that incorrectly estimated nest decay rates (tvalues) may have led to the overestimation of the population size. Furthermore, the area experienced forest degradation and land use change between 2000 and 2013. Given these changing landscapes, updated population estimates were needed to inform policy makers and land‐use planners on the implications of habitat loss for resident orangutans. We conducted this study to recalculate nest decay rates based on current recommended methods, and to update our knowledge on the orangutan population in the region. Our average nest decay rate was 288.3 days; applying this to the study in the late 1990s generated estimates of 807 individuals within DSNP and 1578 beyond DNSP's boundaries. New surveys of the transects undertaken between 2010 and 2014 revealed that the population size had declined substantially in these two areas, to 202 and 71 individuals respectively. Both declines are considerable, but larger losses occurred in logged‐over and cleared forests outside the park. We discuss factors potentially driving these declines, emphasizing the need to improve habitat protection both inside and outside of DSNP, and make recommendations for improving the prospects for future orangutan conservation.
Preliminary evidence for selective cortical responses to music in one‐month‐old infants
Authors: Kosakowski Heather L. , Norman‐Haignere Samuel , Mynick Anna , Takahashi Atsushi , Saxe Rebecca , Kanwisher Nancy
Published: March 2023

Prior studies have observed selective neural responses in the adult human auditory cortex to music and speech that cannot be explained by the differing lower‐level acoustic properties of these stimuli. Does infant cortex exhibit similarly selective responses to music and speech shortly after birth? To answer this question, we attempted to collect functional magnetic resonance imaging (fMRI) data from 45 sleeping infants (2.0‐ to 11.9‐weeks‐old) while they listened to monophonic instrumental lullabies and infant‐directed speech produced by a mother. To match acoustic variation between music and speech sounds we (1) recorded music from instruments that had a similar spectral range as female infant‐directed speech, (2) used a novel excitation‐matching algorithm to match the cochleagrams of music and speech stimuli, and (3) synthesized “model‐matched” stimuli that were matched in spectrotemporal modulation statistics to (yet perceptually distinct from) music or speech. Of the 36 infants we collected usable data from, 19 had significant activations to sounds overall compared to scanner noise. From these infants, we observed a set of voxels in non‐primary auditory cortex (NPAC) but not in Heschl's Gyrus that responded significantly more to music than to each of the other three stimulus types (but not significantly more strongly than to the background scanner noise). In contrast, our planned analyses did not reveal voxels in NPAC that responded more to speech than to model‐matched speech, although other unplanned analyses did. These preliminary findings suggest that music selectivity arises within the first month of life. A video abstract of this article can be viewed at https://youtu.be/c8IGFvzxudk.

Research Highlights

Responses to music, speech, and control sounds matched for the spectrotemporal modulation‐statistics of each sound were measured from 2‐ to 11‐week‐old sleeping infants using fMRI.

Auditory cortex was significantly activated by these stimuli in 19 out of 36 sleeping infants.

Selective responses to music compared to the three other stimulus classes were found in non‐primary auditory cortex but not in nearby Heschl's Gyrus.

Selective responses to speech were not observed in planned analyses but were observed in unplanned, exploratory analyses.
G6 continuous glucose monitoring system feature use and its associations with glycaemia in Europe
Authors: Acciaroli Giada , Parkin Christopher G. , Thomas Roy , Layne Jennifer , Norman Gregory J. , Leone Keri
Published: March 2023

Aims

Current continuous glucose monitoring (CGM) devices provide features that alert individuals with diabetes about their current and impending adverse glycaemic events. The use of these features has been associated with glycaemic improvements. However, how these features are utilised under real‐world conditions has not been well studied. We queried a large database to quantify utilisation of the Dexcom G6 system features and how utilisation impacted glycaemic outcomes within a cohort of European users.

Methods

This 6‐month retrospective, observational, large database analysis utilised anonymised data from a sample of 47,784 Europe‐based G6 users. Primary outcome measures were associations between utilisation and customisation of High/Low threshold alerts, ‘urgent low soon’ (ULS) alert, and established CGM metrics.

Results

Users in the Germany, Austria, Switzerland region (n = 20,257), the Nordic countries (n = 10,314), United Kingdom (n = 9006), Italy (n = 4747), France (n = 2130) and Spain (1330) were included. All alert features were utilised by >75% of the cohort across all regions/countries and age groups. Enabling the Low alert and ULS alert was associated with lower percentage of time below range compared to disabling the Low alert (p < 0.001). Enabling the High alert was associated with higher percentage of time in range (%TIR) and lower percentage of time above range (%TAR) %TAR compared to disabling the High alert (p < 0.001). Paediatric patients and older adults tended to set a higher threshold for High/Low alerts, while younger adults tended to use lower threshold values for High/Low alerts.

Conclusions

Individuals who utilised the Dexcom G6 features showed better glycaemic control, particularly among those who utilised more sensitive High alert and Low alert settings, than users who did not utilise the system features.
Clinical outcomes of patients referred for asymptomatic neutropenia: A focus on racial disparities in hematology
Authors: Oyogoa Emmanuella , Mathews Rick , Olson Sven , DeLoughery Thomas , Shatzel Joseph J. , Martens Kylee L.
Published: March 2023

Background

Asymptomatic neutropenia is a common hematology referral, though standardized reference ranges and published clinical outcomes are lacking.

Methods

In our retrospective analysis, we evaluated demographics, laboratory, and clinical outcomes of adult patients referred to an academic hematology practice for evaluation of neutropenia from 2010 to 2018. Primary and secondary outcomes included incidence of hematologic disorders and rates of Duffy‐null positivity by race, respectively. In a separate analysis, we reviewed absolute neutrophil count (ANC) reference ranges from publicly available Association of American Medical Colleges Medical School Member laboratory directories to assess institutional variations.

Results

In total, 163 patients were included, with disproportionate number of Black patients referred compared to local demographics. Twenty‐three percent of patients (n = 38) were found to have a clinically relevant hematologic outcome (mean ANC of 0.59 × 109/L), and only six were identified with ANC ≥1.0 × 109/L. Incidence of hematologic outcomes was lowest among Black patients (p = .05), and nearly all Blacks who underwent Duffy‐null phenotype testing were positive (93%), compared to 50% of Whites (p = .04). In separate review of laboratory directories, we confirmed wide variation in ANC lower limit of normal (0.91–2.40 × 109/L).

Conclusion

Hematologic disorders were rare in patients with mild neutropenia and among Blacks, highlighting the need to standardize hematological ranges representative of non‐White communities.
Traditional echoes, contemporary shifts: Chinese college students' views of the “good mother”
Authors: Nie Tana Xiaoguang , Zhang Qianqian , Bowcher Wendy L.
Published: March 2023

Objective

The objective of this research was to investigate contemporary Chinese college students' perceptions of the “good mother.”

Background

Increased lifestyle and self‐fulfillment choices have recently become available for college‐age students in China. However, there is government, societal, and family pressure for women to be married, ideally by 25 years of age, and to bear children as a patriotic and socially stabilizing duty.

Method

A qualitative study using thematic analysis to code data from semistructured interviews with 20 male and female college students.

Results

Five attributes of a good mother were identified: “is a guide,” “is loving,” “communicates with her child as with a friend,” “is not overcontrolling,” and “balances paid work and time with her child.”

Conclusion

This study contributes to ongoing research across cultures and societies, which aims to understand what young adults believe to be a “good mother” and how this may affect their future parenting practices. Within the Chinese context, perceptions of a “good mother” include traditional echoes—for example, mother as primary caregiver—mixed with contemporary ideas—for example, pursuing the right to seek personal fulfillment and financial autonomy and a move away from a top‐down authoritarian style of parenting. Gendered perceptions of physical punishment, childrearing anxiety, and parental sacrifice were identified.

Implications

Future policymakers should provide greater social and workplace options and implement support services to alleviate the anxiety women experience in their dual aspirations to succeed in paid work and to be good mothers. Educating men regarding their contribution to caregiving and the fostering of family harmony should also be prioritized.
The Adoption and Safe Families Act is not worth saving: The case for repeal
Authors: Trivedi Shanta
Published: March 2023

The controlling federal family regulation law, the Adoption and Safe Families Act of 1997 (“ASFA”), has long been criticized for unnecessarily terminating the rights of parents and leaving thousands of children in its wake without legal parents or any prospect for adoption. Critics highlight the irreparable destruction ASFA has caused the Black community, and many suggest that this result is by design, not disproportionate impact. As a result, a growing movement of impacted parents, advocates, and scholars have called for ASFA's total repeal. This article draws on the work of these parents, advocates, and scholars to argue that a law whose foundation is built on inherently prejudicial policies cannot be repaired; it must be dismantled in its entirety. Dismantling is necessary not only for practical legal reasons, but also because of the symbolic importance of repeal to those most impacted by the law and its attendant policies. Laws have expressive value, and as such, the repeal of harmful laws demonstrates our priorities, our beliefs and who we are as a society. This article examines previous attempts at reform to demonstrate that any attempt to amend ASFA would be insufficient to address its fundamental flaws. Finally, the article concludes by proposing a path forward that is led by impacted families, respects the right to family integrity and recognizes the importance of supporting and investing in communities.
The extreme 2016 wheat yield failure in France
Authors: Nóia Júnior Rogério de S. , Deswarte Jean‐Charles , Cohan Jean‐Pierre , Martre Pierre , van der Velde Marijn , Lecerf Remi , Webber Heidi , Ewert Frank , Ruane Alex C. , Slafer Gustavo A. , Asseng Senthold
Published: March 2023

France suffered, in 2016, the most extreme wheat yield decline in recent history, with some districts losing 55% yield. To attribute causes, we combined the largest coherent detailed wheat field experimental dataset with statistical and crop model techniques, climate information, and yield physiology. The 2016 yield was composed of up to 40% fewer grains that were up to 30% lighter than expected across eight research stations in France. The flowering stage was affected by prolonged cloud cover and heavy rainfall when 31% of the loss in grain yield was incurred from reduced solar radiation and 19% from floret damage. Grain filling was also affected as 26% of grain yield loss was caused by soil anoxia, 11% by fungal foliar diseases, and 10% by ear blight. Compounding climate effects caused the extreme yield decline. The likelihood of these compound factors recurring under future climate change is estimated to change with a higher frequency of extremely low wheat yields.
Characterisation of Three Sri Lankan Zircon Megacrysts as Potential Reference Materials for Microbeam U‐Pb Geochronology and Hf‐O‐Zr Isotope Measurements
Authors: Hu Pan , Luo Tao , Crowley James , Wu Yuanbao , Zhang Chenxi , Xia Xiaoping , Long Tao , Zhang Shaobing , Bao Zhian , Xu Lei , Feng Lanping , Zhang Wen , Hu Zhaochu
Published: March 2023

In situ U‐Pb geochronology and hafnium, oxygen and zirconium isotope measurements in zircons using laser ablation‐inductively coupled plasma‐mass spectrometry (LA‐ICP‐MS) and ion microprobe techniques can provide essential isotopic data to constrain geological evolutionary histories. Developing reliable zircon reference materials is the cornerstone for in situ zircon chronology and isotopic studies. In this study, the homogeneity of U‐Pb ages and Hf‐O‐Zr isotope ratios in three Sri Lankan zircon megacrysts (SLZA, SLZB and SLZC) were investigated using multiple analytical methods. The obtained U, Th, Pb and Hf mass fractions of the SLZA zircon were 839 ± 56 μg g‐1 (1s), 151 ± 15 μg g‐1 (1s), 198 ± 28 μg g‐1 (1s) and 8635 ± 286 μg g‐1 (1s), respectively. The mass fractions of U, Th, Pb and Hf in the SLZB zircon were 1106 ± 106 μg g‐1 (1s), 331 ± 61 μg g‐1 (1s), 376 ± 57 μg g‐1 (1s) and 9673 ± 976 μg g‐1 (1s), respectively. The U, Th, Pb and Hf mass fractions determined in the SLZC zircon were 551 ± 35 μg g‐1 (1s), 111 ± 8 μg g‐1 (1s), 129 ± 18 μg g‐1 (1s) and 7881 ± 393 μg g‐1 (1s), respectively. The chemical abrasion isotope dilution thermal ionisation mass‐spectrometry (CA‐ID‐TIMS) method yielded a Th‐corrected weighted mean 206Pb/238U age of 556.94 ± 1.29 Ma (95% conf., n = 5) for the SLZA zircon, 552.90 ± 1.29 Ma (95% conf., n = 7) for the SLZB zircon and 560.83 ± 1.29 Ma (95% conf., n = 7) for the SLZC zircon. The obtained Hf isotopic compositions of the SLZA, SLZB and SLZC zircons determined with the solution MC‐ICP‐MS method were 0.281651 ± 0.000014 (2s, n = 10), 0.281704 ± 0.000008 (2s, n = 10) and 0.281676 ± 0.000006 (2s, n = 10), respectively. The obtained O isotopes of the SLZA and SLZB zircons measured with the laser fluorination method were 12.14 ± 0.56‰ (2s, n = 4) and 11.91 ± 0.30‰ (2s, n = 4), respectively. The Zr isotopes of the SLZA, SLZB and SLZC zircons determined with double spike TIMS analysis yielded mean δ94/90ZrSRM3169 values of ‐0.03 ± 0.06‰ (2s, n = 10), ‐0.03 ± 0.04‰ (2s, n = 10) and 0.00 ± 0.07‰ (2s, n = 8), respectively. The SLZA zircon can be used as a primary reference or quality control material for microbeam U‐Pb, Hf and Zr isotope measurements because of its slight heterogeneity. The U‐Pb, Hf and Zr isotopic compositions of the SLZB and SLZC megacrysts were homogeneous. The O isotopic compositions in the SLZA and SLZB zircon were slightly dispersed, indicating that these two megacrysts can only serve as secondary reference materials for microbeam O isotope measurements.
THE SINS OF THE FATHERS: LEONARD FORSTER'S REPLY TO AN EARLY CRITIC OF THE PENGUIN BOOK OF GERMAN VERSE1
Authors: Mason Catherine
Published: March 2023

This essay follows‐up on a reminiscence written by Leonard Forster for GLL in 1988. Forster was the editor of The Penguin Book of German Verse, first published in 1957. The anthology was intended for a post‐war British readership, particularly in schools, that seemed, despite everything, to have preserved an affectionate admiration for German poetry. Forster's selections often appear to have served as deliberate correctives to the ideological preferences of the previous generation's National Socialist critics, some of which had also resonated with several British Germanists. Shortly after publication, Forster received a letter from ‘Bernward Michaelsen’, who objected at great (though courteous) length to many of the anthology's inclusions. Forster and fellow German scholar S. H. Steinberg judged the writer to be an elderly German schoolteacher whose conservative literary taste had been formed after World War I. Forster's equally courteous and detailed response to Michaelsen's criticisms received no answer. What they did not know (although Steinberg came close to guessing) was that Michaelsen was actually Bernward Vesper, the eighteen‐year‐old son of Will Vesper, a notorious National Socialist editor and poet. Bernward's political trajectory from extreme right to left after his father's death was not unique for his generation but, unknown to Forster in 1988, had long since ended in tragedy.
A systematic review of adeno‐associated virus gene therapy clinical trials for HIV – A potential solution for patients with haemophilia and HIV?
Authors: Levy‐Mendelovich Sarina , Walsh Christopher E. , Schapiro Jonathan M. , Soffer Shelly , Klang Eyal , Kenet Gili
Published: March 2023

Introduction

In the past HIV infection was a common complication of haemophilia therapy. Gene therapy trials in Haemophilia patients using rAAV have shown promising results; Unfortunately, the majority of gene therapy trials studies have excluded HIV positive patients. We decided to systematically review the published clinical trials using rAAV for HIV prevention.

Methods

A comprehensive literature search was performed to identify studies evaluating clinical trials using rAAV for HIV. The search was conducted using the MEDLINE/PubMed databases. Search keywords included ‘gene therapy’, ‘adeno‐associated virus’, ‘HIV’ and ‘clinical trial’.

Results

Three studies met our inclusion criteria. Two were phase 1 studies and one was a phase 2 study. One study examined an AAV coding for human monoclonal IgG1 antibody whereas the other two studies delivered a vector coding for viral protease and part of reverse transcriptase. All studies administered the vaccine intramuscularly and showed a response as well a good safety profile.

Discussion

The concept of using a viral vector to prevent a viral infection is revolutionary. Due to the paucity of information regarding application of any gene therapy in HIV patients and the potential use of gene therapy in haemophilia patients with HIV in the future warrants attention.
Necessity of prophylactic drainage tube in retroperitoneal laparoscopic nephroureterectomy with open distal ureterectomy: A matched‐pair analysis
Authors: Hagimoto Hiroki , Kambe Takanari , Mine Yuta , Kokubun Hidetoshi , Hattori Yuto , Abe Yohei , Kubota Masashi , Tsutsumi Naofumi , Yamasaki Toshinari , Kawakita Mutsushi
Published: March 2023

Objectives

To assess the necessity of prophylactic drain placement in retroperitoneal laparoscopic nephroureterectomy with open distal ureterectomy for upper tract urothelial cancer.

Methods

Between July 2011 and March 2021, 200 patients with localized clinical Tis‐T3 upper urinary tract urothelial carcinoma underwent laparoscopic nephroureterectomy with open distal ureterectomy. After removing the specimen, drainage tubes were placed on the renal beds and/or in the retrovesical spaces. Drain tubes were omitted for most patients after 2017. We compared the postoperative outcomes between the patients with drain placement (D+ group) and without drain placement (D− group) using propensity score matching.

Results

A total of 164 patients (90 in the D+ group and 74 in the D− group) were enrolled, and matched pairs of 108 patients were analyzed. There was no significant difference in the incidence of complications according to Clavien–Dindo grade in the two groups after the propensity score matching. There was no significant difference in the incidence of postoperative lymphocele (n = 5 vs. 9, p = 0.395) and symptomatic lymphocele (n = 1 vs. 1, p = 1) between the two groups. The length of hospital stay was significantly shorter in the D− group (11 vs. 8 days, p < 0.0001).

Conclusions

We found that omitting the drainage tube after laparoscopic radical nephroureterectomy did not increase postoperative complications or lymphocele and shortened the post‐hospital stay.
Intersection of social determinants of symptomatic breast cancer presentation in a rural setting: A critical ethnographic study
Authors: Kailemia Peter Ntoiti , Lee Elaine Carole , Renfrew Mary Josephine
Published: March 2023

Aim

The aim of the study was to explore the determinants of time to presentation of women with breast cancer symptoms within a rural setting in Kenya.

Design

A critical ethnographic study.

Methods

Data were collected between July 2019 and April 2020 using semi‐structured interviews and focus groups with 12 women and 23 disclosure recipients, respectively. Interviews and focus group discussions were audio recorded, transcribed verbatim, translated into English and thematically analysed. Further analysis using an intersectional lens added new insights into the data. Ethics approval was obtained in both Kenya and United Kingdom.

Results

Participants narrated their experiences from the time they self‐discovered breast cancer symptoms to the time they first came into contact with a healthcare professional. The core themes identified included local cancer knowledge, embodied experience, women's responses, social networks, cultural cancer schemas, gendered social structures and healthcare system experiences.

Conclusion

The findings revealed that symptomatic women predominantly faced multiple intersecting barriers to timely presentation. The key drivers of timeliness to presentation of women with breast cancer symptoms were identified. Several proximal and distal determinants, including economic, social, psychological and cultural determinants intersected to shape women's timeliness to symptomatic presentation.

Impact

This study identified intersectional structural determinants to timely symptomatic presentation of women with breast cancer symptoms. The findings have global health implications for social inequalities in female breast cancer and may inform the development of intersectional interventions to promote timely symptomatic presentation. Furthermore, this study identified an additional interval, precursory interval and revision of the Model of pathway to treatment may be needed should this interval be validated by future studies.

Patient or public contribution

To ensure the interview guides were culturally sensitive, they were co‐designed with a female breast cancer survivor, nurses providing reproductive health care to women and a bilingual expert. Both women and disclosure recipients participated in scheduling for the interviews, including the mutually agreeable days and time. Participants were frequently contacted during data analysis and report writing to clarify meaning of certain words or pieces of data.
A longitudinal study of free leptin index in pre‐eclamptic pregnancies
Authors: Garcés María Fernanda , Buell‐Acosta Julieth Daniela , Rodríguez‐Navarro Haiver Antonio , Páez‐Leal María Carolina , Maldonado‐Acosta Luis Miguel , Peralta‐Franco Jhon Jairo , Burgos‐Cardenas Álvaro Javier , Ángel‐Müller Edith , Parada‐Baños Arturo José , Parra‐Pineda Mario Orlando , Eslava‐Schmalbach Javier , Escobar‐Sarmiento Camilo Andrés , Lacunza Ezequiel , Caminos‐Cepeda Sofia Alexandra , Castaño Justo P. , Nogueiras Rubén , Dieguez Carlos , Ruiz‐Parra Ariel Iván , Caminos Jorge Eduardo
Published: March 2023

The ratio between circulating levels of leptin and soluble leptin receptor (sOB‐R), the free leptin index (FLI), is used as a marker of leptin resistance. Therefore, the aim of our study was to investigate the FLI in mild pre‐eclamptic pregnancies in a nested case–control study within a prospective observational study. Circulating levels of leptin and sOB‐R levels rise significantly during pregnancy in healthy (p < 0.05) (n = 46) and pre‐eclamptic pregnancies (p < 0.05) (n = 20). Serum levels of leptin were significantly higher in pre‐eclamptic compared to healthy pregnancies at second and third trimesters of pregnancy (p < 0.05). Additionally, serum levels of sOB‐R were significantly lower in pre‐eclamptic pregnancies during the second and third trimesters of pregnancy compared to healthy pregnancies (p < 0.05). Moreover, we found that FLI did not vary significantly during pregnancy in healthy women (p > 0.05), while it increases in pre‐eclamptic pregnancies (p < 0.05). Indeed, FLI was significantly higher at second and third trimesters of pregnancy in pre‐eclamptic compared to healthy pregnancies (p < 0.05). In addition, FLI was significantly higher in the luteal phase compared with the follicular phase of the menstrual cycle in eumenorrheic women (p < 0.05). Receiver operating characteristic (ROC) curve analysis revealed the ability of leptin (AUC = 0.72) and FLI (AUC = 0.67) as a reliable predictor for mild pre‐eclampsia during the second trimester of pregnancy. In conclusion, our findings show that FLI were significantly increased in mild pre‐eclamptic pregnancies and allowed us to hypothesize that this rise might alter leptin bioavailability and bioactivity which might lead to the sympathetic hyperactivity and the hypertensive disorders during pregnancy.
Development and validation of a model to predict complex Mohs micrographic surgery in clinical practice: REGESMOSH scale
Authors: Montero‐Vilchez Trinidad , Garcés Joan R. , Rodríguez‐Prieto Manuel A. , Ruiz‐Salas Verónica , de Eusebio‐Murillo Esther , Miñano‐Medrano Román , Escutia‐Muñoz Begoña , González‐Sixto Beatriz , Artola‐Igarza Juan L. , Alfaro‐Rubio Alberto , Redondo Pedro , Delgado‐Jiménez Yolanda , Sánchez‐Schmidt Julia M. , Allende‐Markixana Irati , Alonso‐Pacheco María L. , García‐Bracamonte Beatriz , de la Cueva‐Dobao Pablo , Navarro‐Tejedor Raquel , Ciudad‐Blanco Cristina , Carnero‐González Lucía , Vázquez‐Veiga Hugo , Cano‐Martínez Natividad , Vilarrasa Eva , Sánchez‐Sambucety Pedro , López‐Estebaranz José L. , Botella‐Estrada Rafael , Feal‐Cortizas Juan Carlos , Martorell‐Calatayud Antonio , Gil Pilar , Morales‐Gordillo Victoriano , Toll‐Abelló Agustí , Ocerin‐Guerra Izascun , Mayor‐Arenal Matías , Suárez‐Fernández Ricardo , Sainz‐Gaspar Laura , Descalzo Miguel A. , Garcia‐Doval Ignacio , Sanmartin‐Jiménez Onofre ,   REGESMOHS (Registro Español de Cirugía de Mohs)
Published: March 2023

Introduction

There is still a need to develop a simple algorithm to identify patients likely to need complex Mohs micrographic surgery (MMS) and optimize MMS schedule. The main objectives of this study are to identify factors associated with a complex MMS and develop a predictor model of the number of stages needed in surgery and the need for a complex closure.

Materials and Methods

A nationwide prospective cohort study (REGESMOHS, the Spanish Mohs surgery registry) was conducted including all patients with a histological diagnosis of basal cell carcinoma (BCC). Factors related to three or more stages and a complex closure (that needing a flap and/or a graft) were explored and predictive models were constructed and validated to construct the REGESMOSH scale.

Results

A total of 5226 patients that underwent MMS were included in the REGESMOHS registry, with 4402 (84%) having a histological diagnosis of BCC. A total of 3689 (88.9%) surgeries only needed one or two stages and 460 (11.1%) required three or more stages. A model to predict the need for three or more stages included tumour dimension, immunosuppression, recurrence, location in risk areas, histological aggressiveness and previous surgery. Regarding the closure type, 1616 (38.8%) surgeries were closed using a non‐complex closure technique and 2552 (61.2%) needed a complex closure. A model to predict the need for a complex closure included histological aggressiveness, evolution time, patient age, maximum tumour dimension and location.

Conclusion

We present a model to predict MMS needing ≥3 stages and a complex closure based on epidemiological and clinical data validated in a large population (with real practice variability) including different centres that could be easily implemented in clinical practice. This model could be used to optimize surgery schedule and properly inform patients about the surgery duration.
SEC1A and SEC6 synergistically regulate pollen tube polar growth
Authors: Fan Tingting , Fan Yuemin , Yang Yang , Qian Dong , Niu Yue , An Lizhe , Xiang Yun
Published: March 2023

Pollen tube polar growth is a key physiological activity for angiosperms to complete double fertilization, which is highly dependent on the transport of polar substances mediated by secretory vesicles. The exocyst and Sec1/Munc18 (SM) proteins are involved in the regulation of the tethering and fusion of vesicles and plasma membranes, but the molecular mechanism by which they regulate pollen tube polar growth is still unclear. In this study, we found that loss of function of SEC1A, a member of the SM protein family inArabidopsis thaliana, resulted in reducing pollen tube growth and a significant increase in pollen tube width. SEC1A was diffusely distributed in the pollen tube cytoplasm, and was more concentrated at the tip of the pollen tube. Through co‐immunoprecipitation‐mass spectrometry screening, protein interaction analysis andin vivomicroscopy, we found that SEC1A interacted with the exocyst subunit SEC6, and they mutually affected the distribution and secretion rate at the tip of the pollen tube. Meanwhile, the functional loss of SEC1A and SEC6 significantly affected the distribution of the SNARE (soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor) complex member SYP125 at the tip of the pollen tube, and led to the disorder of pollen tube cell wall components. Genetic analysis revealed that the pollen tube‐related phenotype of thesec1a sec6double mutant was significantly enhanced compared with their respective single mutants. Therefore, we speculated that SEC1A and SEC6 cooperatively regulate the fusion of secretory vesicles and plasma membranes in pollen tubes, thereby affecting the length and the width of pollen tubes.
In Search of a Risk‐Free Asset: Search Costs and Sticky Deposit Rates
Authors: YANKOV VLADIMIR
Published: March 2023

I examine the role of costly consumer search for the pricing of deposits. Estimates of a model of heterogeneous search cost households reveal a large fraction of high‐search‐cost depositors composed of elderly and less financially sophisticated households. Those households grant banks significant monopoly power that results in low and asymmetric interest rate pass‐through. The predictions of the estimated model are consistent with responses in the Survey of Consumer Finances to questions related to financial sophistication, search for investment return, and deposit allocations across multiple bank accounts. The estimated model also reveals a nonmonotone relationship between bank entry, deposit rates, and consumer surplus.
Relationships and dynamics in families with a child with a kidney transplant—A study of parents' everyday life experiences
Authors: Agerskov Hanne , Thiesson Helle C. , Schultz Helen , Pedersen Birthe D.
Published: March 2023

Background

Paediatric kidney transplantation is often the best choice of treatment for kidney failure with replacement therapy and represents an important change in the child's well‐being. There are, however, still a number of challenges in addition to the parental role. The magnitude of intensive parental caregiving and support required by children with a kidney transplant could be disruptive to family relationships and dynamics.

Objective

To explore the experiences of family relationships and dynamics among parents of a child with a kidney transplant.

Design

An explorative study using a qualitative method.

Participants

Twelve parents (seven mothers and five fathers) of seven children with a kidney transplant were included.

Approach

A phenomenological–hermeneutic approach was applied.

Method

Semistructured, individual interviews were conducted. The data were analysed using Ricoeur's theory of interpretation on three levels: naïve reading, structural analysis and critical interpretation and discussion.

Findings

Three themes were generated: Emotions during ups and downs in everyday life; Balancing different needs among children; and Opportunities and having consideration in the family.

Conclusion

Relationships between parents that are based on mutual emotional support are significant and essential during periods of severe illness in a child. Parents who are alone or emotionally marked by their child's disease history feel vulnerable and struggle to overcome challenges. Different health situations among siblings lead to challenges in bringing up the children and emotional dilemmas among parents that impact family dynamics. Resilience in parents is a shifting phenomenon that can influence how they deal with family relationships and dynamics.