bluuebunny/crossref_metadata_2025 huggingface dataset:
Birth cohort‐specific consideration in an Emergency Department Hepatitis C Testing Programme: A description of age‐related characteristics and outcomes
Authors: Walter Lauren A. , Prados Myles , Lloyd Audrey , Sontheimer Sylvie , Heimann Matthew , Rodgers Joel B. , Hand Delissa T. , Franco Ricardo
Published: February 2024

The emergency department (ED) has increasingly become an important public health partner in non‐targeted hepatitis C virus (HCV) testing and referral to care efforts. HCV has traditionally been an infection associated with the Baby Boomer generation; however, recent exacerbation of the opioid epidemic has resulted in a growing number of younger cohorts, namely Millennials, also impacted by HCV. Examination of this age‐related demographic shift, including subsequent linkage success and linkage barriers, from the perspective of an ED‐based testing and linkage programme may have implications for future population and health systems interventions. A retrospective descriptive chart review was performed, inclusive of data from August 2015 through December 2020. We compared the quantity of positive HCV screening antibody (Ab) and confirmatory (RNA) tests and further considered linkage rates and correlative demographics (e.g. gender, race). Patient barriers to HCV care linkage (e.g. substance misuse, lack of health insurance, homelessness) were also evaluated. The data set was disaggregated by birth cohort to include Silent Generation (SG) (1928–45), Baby Boomer (BB) (1946–64), Generation X (Gen X) (1965–80), Millennial (1981–96) and Generation Z (1997–2012). Descriptive statistics and chi‐square analysis were performed. Overall, 83,817 patients were tested for HCV (50.6% of eligible); 6187 (7.4%) were HCV Ab positive, and 2665 were HCV RNA positive (3.2%). RNA‐positive individuals were more likely to be white (70.4%) and male (67.7%); generational distribution was similar (BB 33.3%, Gen X 32.0% and Millennials 32.7%). Amongst Ab‐positive patients, white (45.5%), male (47.2%) and Millennial (49.7%) individuals were most likely to be RNA‐positive. Overall, 28.1% of the RNA‐positive cohort successfully linked to care; linkage to care rates were significantly higher in older generations (38.1% in BB vs. 17.8% in Millennials) (p < .00001). Over 90% were identified as having at least one linkage to care barrier. Younger generations (Gen X and Millennials) were disproportionately impacted by linkage barriers, including incarceration, lack of health insurance, history of mental health and substance use disorders, as well as history of or active injection drug use (IDU) (p < .00001). Older generations (SG and BB) were more likely to be impacted by competing medical comorbidities (p < .00001). The ED population represents a particularly vulnerable, at‐risk cohort with a high prevalence of HCV and linkage to care barriers. While past HCV‐specific recommendations and interventions have focused on Baby Boomers, this data suggests that younger generations, including Gen X and Millennials, are increasingly affected by HCV and face disparate social risk and social need factors which impede definitive care linkage and treatment.
Experimental Evaluation of the Impact of Lived Experience and Personal Story on Neuroscience Knowledge Translation Effectiveness: Sharing the Neuroscience of ADHD with Pre‐Service Teachers
Authors: Barker Conor , Yorke Kathryn Isenor , Mak Emily , Draper Ethan C. , Mazerolle Erin L.
Published: February 2024

Previous work suggested that sharing personal stories is effective for knowledge translation (KT) of the neuroscience of attention deficit hyperactivity disorder (ADHD) for a teacher audience. In the current study, we experimentally evaluated the impact of personal story and lived experience on a similar KT activity. We measured knowledge and attitudes about ADHD before and after our KT activity and used a factorial design to evaluate the impact of personal story (personalized versus depersonalized) and lived experience (presenter with versus without an ADHD diagnosis) with N = 14 to 24 per group. The presenter without an ADHD diagnosis was a neuroscience expert. All conditions were associated with increased attribution of ADHD symptoms to the brain. Speaker quality ratings were high, especially in the personalized + ADHD diagnosis condition and the depersonalized + no ADHD diagnosis condition. While incorporating lived experience is important for authentic KT, we demonstrated that the KT presenter themselves need not have lived experience to change pre‐service teacher attitudes and beliefs. More work is needed to address the potential impacts of neuroscience expertise and other aspects of the presenters in our study.
Underwater vocalizations in foraging female Antarctic fur seals (Arctocephalus gazella) in the Kerguelen Islands
Authors: Chevallay Mathilde , Guinet Christophe , Jeanniard du Dot Tiphaine
Published: February 2024

In the marine environment, many animals use sound to interact and communicate with their conspecifics or other species. Over the last decades, the development of sound recording systems has allowed a significant advance in our knowledge of sound production in marine animals. We deployed miniature sound and movement tags on Antarctic fur seals (AFS), a small otariid foraging on mesopelagic fish, to uncover potential underwater vocalizations in this species. Tags recorded underwater sounds synchronously with high‐resolution AFS movements and diving behavior, allowing us to investigate the behavioral context of vocalizations in the natural environment. We provide evidence of underwater vocalizations in foraging female AFS in a context of foraging at sea. AFS produced stereotyped calls made of low‐frequency pulses produced in series, exclusively during foraging dives. We hypothesized that these acoustic pulse series could be used as an acoustic lure to confuse or attract fish prey, however, a larger sample size is needed to study the adaptive significance of these underwater vocalizations.
Suberin deficiency and its effect on the transport physiology of young poplar roots
Authors: Grünhofer Paul , Heimerich Ines , Pohl Svenja , Oertel Marlene , Meng Hongjun , Zi Lin , Lucignano Kevin , Bokhari Syed Nadeem Hussain , Guo Yayu , Li Ruili , Lin Jinxing , Fladung Matthias , Kreszies Tino , Stöcker Tyll , Schoof Heiko , Schreiber Lukas
Published: February 2024

The precise functions of suberized apoplastic barriers in root water and nutrient transport physiology have not fully been elucidated. While lots of research has been performed with mutants of Arabidopsis, little to no data are available for mutants of agricultural crop or tree species.

By employing a combined set of physiological, histochemical, analytical, and transport physiological methods as well as RNA‐sequencing, this study investigated the implications of remarkable CRISPR/Cas9‐induced suberization defects in young roots of the economically important gray poplar.

While barely affecting overall plant development, contrary to literature‐based expectations significant root suberin reductions of up to 80–95% in four independent mutants were shown to not evidently affect the root hydraulic conductivity during non‐stress conditions. In addition, subliminal iron deficiency symptoms and increased translocation of a photosynthesis inhibitor as well as NaCl highlight the involvement of suberin in nutrient transport physiology.

The multifaceted nature of the root hydraulic conductivity does not allow drawing simplified conclusions such as that the suberin amount must always be correlated with the water transport properties of roots. However, the decreased masking of plasma membrane surface area could facilitate the uptake but also leakage of beneficial and harmful solutes.
Lipid transfer protein StLTPa enhances potato disease resistance against different pathogens by binding and disturbing the integrity of pathogens plasma membrane
Authors: Chen Xiaokang , Feng Jiashu , Li Zhenzhen , Feng Hui , Song Chunxu , Cai Lin , Joosten Matthieu H. A. J. , Du Yu
Published: February 2024

Potato is the third most important food crop worldwide. Potato production suffers from severe diseases caused by multiple detrimental plant pathogens, and broad‐spectrum disease resistance genes are rarely identified in potato. Here we identified the potato non‐specific lipid transfer protein StLTPa, which enhances species none‐specific disease resistance against various pathogens, such as the oomycete pathogen Phytophthora infestans, the fungal pathogens Botrytis cinerea and Verticillium dahliae, and the bacterial pathogens Pectobacterium carotovorum and Ralstonia solanacearum. The StLTPa overexpression potato lines do not show growth penalty. Furthermore, we provide evidence that StLTPa binds to lipids present in the plasma membrane (PM) of the hyphal cells of P. infestans, leading to an increased permeability of the PM. Adding of PI(3,5)P2 and PI(3)P could compete the binding of StLTPa to pathogen PM and reduce the inhibition effect of StLTPa. The lipid‐binding activity of StLTPa is essential for its role in pathogen inhibition and promotion of potato disease resistance. We propose that StLTPa enhances potato broad‐spectrum disease resistance by binding to, and thereby promoting the permeability of the PM of the cells of various pathogens. Overall, our discovery illustrates that increasing the expression of a single gene in potato enhances potato disease resistance against different pathogens without growth penalty.
CRISPR‐targeted mutagenesis of mitogen‐activated protein kinase phosphatase 1 improves both immunity and yield in wheat
Authors: Liu Saifei , Zhang Fengfeng , Su Jiaxuan , Fang Anfei , Tian Binnian , Yu Yang , Bi Chaowei , Ma Dongfang , Xiao Shunyuan , Yang Yuheng
Published: February 2024

Plants have evolved a sophisticated immunity system for specific detection of pathogens and rapid induction of measured defences. Over‐ or constitutive activation of defences would negatively affect plant growth and development. Hence, the plant immune system is under tight positive and negative regulation. MAP kinase phosphatase1 (MKP1) has been identified as a negative regulator of plant immunity in model plant Arabidopsis. However, the molecular mechanisms by which MKP1 regulates immune signalling in wheat (Triticum aestivum) are poorly understood. In this study, we investigated the role of TaMKP1 in wheat defence against two devastating fungal pathogens and determined its subcellular localization. We demonstrated that knock‐down of TaMKP1 by CRISPR/Cas9 in wheat resulted in enhanced resistance to rust caused by Puccinia striiformis f. sp. tritici (Pst) and powdery mildew caused by Blumeria graminis f. sp. tritici (Bgt), indicating that TaMKP1 negatively regulates disease resistance in wheat. Unexpectedly, while Tamkp1 mutant plants showed increased resistance to the two tested fungal pathogens they also had higher yield compared with wild‐type control plants without infection. Our results suggested that TaMKP1 interacts directly with dephosphorylated and activated TaMPK3/4/6, and TaMPK4 interacts directly with TaPAL. Taken together, we demonstrated TaMKP1 exert negative modulating roles in the activation of TaMPK3/4/6, which are required for MAPK‐mediated defence signalling. This facilitates our understanding of the important roles of MAP kinase phosphatases and MAPK cascades in plant immunity and production, and provides germplasm resources for breeding for high resistance and high yield.
Bilateral accessory axillary breast tissue in a premenarchal female
Authors: Class Madelyn M. , McCoy Kelly , Melin Alyson A. , Hafeez Farhaan , Abidi Nadia , Krakowski Andrew C.
Published: February 2024

A 9‐year‐old premenarchal female presented to pediatric dermatology with a 6‐month history of periodically tender, bilateral and symmetric axillary masses. Magnetic resonance imaging and subsequent surgical excision confirmed the diagnosis of bilateral accessory axillary breast tissue. Accessory axillary breast tissue is a rare condition seen most in pubertal, pregnant and breastfeeding women. However, it can arise in pre‐adolescent patients and should be added to the differential diagnosis of an axillary mass.
Diversity of Colletotrichum causing anthracnose on Psidium guajava in varied Brazilian physiographic regions
Authors: Soares William R. O. , Vieira Willie A. S. , Reis Ailton , Miller Robert N. G. , Santos Maria D. M. , de Castro Costa Érica , Câmara Marcos P. S. , Café‐Filho Adalberto C.
Published: February 2024

Anthracnose, caused by several Colletotrichum species, is a major restricting factor for guava production, but no comprehensive study of the causal agent has been conducted from the plant host centre of diversity. This work characterizes isolates from guava, mainly from the fruit, but also leaves and flowers, representing most Brazilian physiographies according to the partial sequences of the rDNA‐ITS, ApMAT, TUB2, HIS3 and GAPDH gene regions. In addition, the pathogenicity and aggressiveness to fruits of two widely planted guava varieties (SLG and RM) are described. Guava‐derived Colletotrichum isolates were found in five complexes: gloeosporioides, acutatum, boninense, gigasporum and orchidearum. The gloeosporioides complex was the most prevalent (81%), followed by the acutatum complex (14%). A total of 16 Colletotrichum species were naturally associated with guava anthracnose: C. aeschynomenes, C. asianum, C. chrysophilum, C. fructicola, C. gigasporum, C. gloeosporioides, C. karsti, C. melonis, C. musae, C. nymphaeae, C. paranaense, C. siamense, C. sojae, C. syzygicola, C. theobromicola and C. tropicale. Apart from C. nymphaeae and C. gloeosporioides, all the remaining 14 taxa are reported for the first time in P. guajava. The most aggressive species belonged to the C. gloeosporioides complex. C. siamense was the most prevalent, especially in warmer regions, followed by C. chrysophilum, mostly in temperate environments. The most aggressive species were C. siamense, C. chrysophilum, C. fructicola and C. tropicale. Fruits of the variety SLG were consistently more resistant to anthracnose than the fruits of RM.
Temporal changes in pre‐existing health conditions five years prior to pregnancy in British Columbia, Canada, 2000–2019
Authors: Lundborg Louise , Joseph K. S. , Lisonkova Sarka , Chan Wee‐Shian , Wen Qi , Ananth Cande V. , Razaz Neda
Published: February 2024

Background

Pre‐existing health conditions increase the risk of obstetric complications during pregnancy and birth. However, the prevalence and recent changes in the frequency of pre‐existing health conditions in the childbearing population remain unknown.

Objectives

To estimate the temporal changes in the prevalence of pre‐existing health conditions among pregnant women in British Columbia, Canada.

Methods

We carried out a population‐based cross‐sectional study of 825,203 deliveries in BC between 2000 and 2019 and examined 17 categories of physical and psychiatric health conditions recorded within 5 years before childbirth. We also undertook age‐period‐cohort analyses to evaluate temporal changes in pre‐existing health conditions.

Results

The prevalence of any pre‐existing health condition was 26.2% (n = 216,214) with overall trends remaining stable during the study period. Between 2000 and 2019, the prevalence rates of anxiety (5.6%–9.6%), bipolar (1.6%–3.4%), psychosis (0.7%–0.8%), and eating disorders (0.2%–0.3%) increased. The prevalence of hypertension increased sharply from 0.06% in 2000 to 0.3% in 2019. Diabetes mellitus and stroke rates increased, as did the prevalence of systemic lupus, multiple sclerosis, and chronic kidney disease. Advanced maternal age was strongly associated with both psychiatric and circulatory/metabolic conditions. A strong birth cohort effect was evident, with rates of psychiatric conditions increasing among women born after 1985.

Conclusions

In British Columbia, Canada, 1 in 4 mothers had a pre‐existing health condition 5 years prior to pregnancy. These findings underscore the need for multi‐disciplinary care for women with pre‐existing health conditions to improve maternal, foetal, and infant health.
Effects of simulated radioulnar synostosis on supination and pronation in cats. A cadaveric study
Authors: Senn Markus , Paulick Lutz , Brunnberg Leo , Slunsky Pavel
Published: February 2024

Objective

To evaluate the effect of an induced synostosis with a screw on pronation and supination in cats.

Study design

Ex vivo biomechanical study.

Sample population

A total of 58 feline forelimbs.

Methods

A total of 58 cadaveric feline thoracic limbs were mounted on a custom‐built jig with the elbow and carpus flexed at a 90° angle. To exclude any orthopedic disease, radiographs of the forelimbs were performed prior to the mechanical tests. Radioulnar synostosis was imitated with a 2 mm cortical screw through the radius into the ulna in the proximal (Group P; n = 54), middle (Group M; n = 52), and distal (Group D; n = 53) radial diaphysis. The angles of pronation and supination were recorded after manually applying a two‐finger tight rotational force to the metacarpus. Rotational tests were performed without a screw (Group N) and with a screw in each of the aforementioned positions. Pairwise comparisons between the groups were performed based on their angles of rotation with a paired t‐test with the Benjamini‐Hochberg procedure and a mixed model ANOVA.

Results

Mean angles of rotation decreased between Group N (129.5 ± 15.9°) and all groups with imitated radioulnar synostosis to a mean angle of 37.5 ± 14.5° (p < .0001). Mean angles of rotation did not differ between the groups with imitated radioulnar synostosis.

Conclusion

Induced radioulnar synostosis decreases antebrachial rotation by more than two‐thirds, regardless of location.

Clinical significance

Implants fixating the radius to the ulna should be avoided in cats, regardless where they are located along the radial diaphysis.
Actualization of evidence‐based nursing in primary, specialized, and social care settings—A cross‐sectional survey
Authors: Hamari Lotta , Holopainen Arja , Nyman Johanna , Pukkila Heidi , Siltanen Hannele , Parisod Heidi
Published: February 2024

Background

Basing practice on evidence is a widely acknowledged requirement for nursing, but shortcomings still exist. An increased understanding of the actualization of evidence‐based nursing (EBN) across different nursing contexts is needed to develop better support for EBN and promote uniform high‐quality nursing.

Aims

The aim of this study was to compare the actualization of EBN in different organizational contexts in Finland.

Methods

Data for this survey were collected in 2021. The actualization of EBN in primary, specialized, and social care organizations was evaluated with the Actualization of Evidence‐Based Nursing instrument, nurses' version, which focuses on individual and organizational‐level EBN support structures. Differences between (1) specialized and primary healthcare, and (2) different nursing practice settings were tested with Welch's two sample t‐test, the Kruskal–Wallis rank sum test, and the Wilcoxon rank sum test.

Results

Based on nurse (n = 1020) evaluations, those working in specialized healthcare hold more positive attitudes toward EBN (p = .021) and evaluated their organization's methods for monitoring and evaluating nursing practices (p = .004) more positively than those working in primary healthcare. Regarding different nursing practice settings (n = 1241), the most positive results were observed within preventive healthcare where nurses evaluated their attitudes toward EBN, EBN competence, and personal evidence‐based practices more positively compared to other nursing practice settings. The results were parallel regarding several organizational structures for EBN. Positive results were also observed within somatic units at university hospitals, and most negative results were within institutional care settings, health centers, and home care settings.

Linking Evidence to Action

There is a need for targeted support to strengthen EBN across different organizational contexts, with special attention to those contexts where nursing professionals with lower education levels work. Future research needs to focus on further analyzing the organizational differences and what can be learned, especially from preventive healthcare but also somatic units at university hospitals.
Frieze patterns over algebraic numbers
Authors: Cuntz Michael , Holm Thorsten , Pagano Carlo
Published: February 2024

Conway and Coxeter have shown that frieze patterns over positive rational integers are in bijection with triangulations of polygons. An investigation of frieze patterns over other subsets of the complex numbers has recently been initiated by Jørgensen and the first two authors. In this paper, we first show that a ring of algebraic numbers has finitely many units if and only if it is an order in a quadratic number field where . We conclude that these are exactly the rings of algebraic numbers over which there are finitely many non‐zero frieze patterns for any given height. We then show that apart from the cases all non‐zero frieze patterns over the rings of integers for have only integral entries and hence are known as (twisted) Conway–Coxeter frieze patterns.
Cognition is selectively impaired in males with spinal pain: A retrospective analysis of data from the Longitudinal Study of Ageing Danish Twins
Authors: Byfield David C. , Stacey Benjamin S. , Bailey Damian M.
Published: February 2024

Cognitive decline and spinal pain (back pain [BP] and neck pain [NP]) represent a major public health challenge, yet the potential relationship between them remains elusive. A retrospective analysis of the Longitudinal Study of Ageing Danish Twins was performed to determine any potential relationships between BP/NP and cognitive function adjusting for age, sex, educational and socioeconomic status. A total of 4731 adults (2788 females/1943 males) aged 78 ± 6 (SD) years were included in the analysis. We observed a 1‐month prevalence of 25% with BP, 21% with NP and 11% for combined BP/NP. While there were no differences in cognition scores for males and females reporting combined BP/NP, compared to those without combined BP/NP (34.38 points [95% confidence interval (CI) = 31.88, 36.88] vs. 35.72 points [95% CI = 35.19, 36.26]; P = 0.180; and 35.72 points [95% CI = 35.19, 36.26] vs. 35.85 points [95% CI = 35.39, 36.31]; P = 0.327; for male and females, respectively), an adjusted analysis revealed that males with combined BP/NP presented with lower cognitive scores compared to males without combined BP/NP (81.26 points [95% CI = 73.80, 88.72] vs. 79.48 points [95% CI = 70.31, 88.66]; P = 0.043). The findings of this hypothesis‐generating study may highlight a potential sex‐specific association between spinal pain and later‐life neurodegeneration.
In vivo treatment with calcilytic of CaSR knock‐in mice ameliorates renal phenotype reversing downregulation of the vasopressin‐AQP2 pathway
Authors: Ranieri Marianna , Angelini Ines , D'Agostino Mariagrazia , Di Mise Annarita , Centrone Mariangela , Venneri Maria , Ferrulli Angela , Mastrodonato Maria , Tamma Grazia , Endo Itsuro , Fukumoto Seiji , Matsumoto Toshio , Valenti Giovanna
Published: February 2024

High concentrations of urinary calcium counteract vasopressin action via the activation of the Calcium‐Sensing Receptor (CaSR) expressed in the luminal membrane of the collecting duct cells, which impairs the trafficking of aquaporin‐2 (AQP2). In line with these findings, we provide evidence that, with respect to wild‐type mice, CaSR knock‐in (KI) mice mimicking autosomal dominant hypocalcaemia, display a significant decrease in the total content of AQP2 associated with significantly higher levels of AQP2 phosphorylation at Ser261, a phosphorylation site involved in AQP2 degradation. Interestingly, KI mice also had significantly higher levels of phosphorylated p38MAPK, a downstream effector of CaSR and known to phosphorylate AQP2 at Ser261. Moreover, ATF1 phosphorylated at Ser63, a transcription factor downstream of p38MAPK, was significantly higher in KI. In addition, KI mice had significantly higher levels of AQP2‐targeting miRNA137 consistent with a post‐transcriptional downregulation of AQP2. In vivo treatment of KI mice with the calcilytic JTT‐305, a CaSR antagonist, increased AQP2 expression and reduced AQP2‐targeting miRNA137 levels in KI mice. Together, these results provide direct evidence for a critical role of CaSR in impairing both short‐term vasopressin response by increasing AQP2‐pS261, as well as AQP2 abundance, via the p38MAPK‐ATF1‐miR137 pathway.

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Key points

Calcium‐Sensing Receptor (CaSR) activating mutations are the main cause of autosomal dominant hypocalcaemia (ADH) characterized by inappropriate renal calcium excretion leading to hypocalcaemia and hypercalciuria. Current treatments of ADH patients with parathyroid hormone, although improving hypocalcaemia, do not improve hypercalciuria or nephrocalcinosis.

In vivo treatment with calcilytic JTT‐305/MK‐5442 ameliorates most of the ADH phenotypes of the CaSR knock‐in mice including hypercalciuria or nephrocalcinosis and reverses the downregulation of the vasopressin‐sensitive aquaporin‐2 (AQP2) expression, providing direct evidence for a critical role of CaSR in impairing vasopressin response.

The beneficial effect of calcilytic in reducing the risk of renal calcification may occur in a parathyroid hormone‐independent action through vasopressin‐dependent inhibition of cAMP synthesis in the thick ascending limb and in the collecting duct.

The amelioration of most of the abnormalities in calcium metabolism including hypercalciuria, renal calcification, and AQP2‐mediated osmotic water reabsorption makes calcilytic a good candidate as a novel therapeutic agent for ADH.
Hormonal intrauterine devices and heat exchange during exercise
Authors: Kirby Nathalie V. , Meade Robert D. , Richards Brodie J. , Notley Sean R. , Kenny Glen P.
Published: February 2024

Synthetic progestins in oral contraceptives are thought to blunt heat dissipation by reducing skin blood flow and sweating. However, whether progestin‐releasing intrauterine devices (IUDs) modulate heat loss during exercise‐heat stress is unknown. We used direct calorimetry to measure whole‐body total (dry + evaporative) heat loss in young, physically active women (mean (SD); aged 24 (4) years, 39.3 (5.3) ml/kg/min) with (IUD; n = 19) and without (Control; n = 17) IUDs in the follicular and luteal phases of the menstrual cycle during light‐ and moderate‐intensity exercise at fixed rates of heat production (∼175 and ∼275 W/m2) in 30°C, ∼21% relative humidity. Between‐group and ‐phase differences were evaluated using traditional hypothesis testing and statistical equivalence testing within pre‐determined bounds (±11 W/m2; difference required to elicit a ±0.3°C difference in core temperature over 1 h) in each exercise bout. Whole‐body total heat loss was statistically equivalent between groups within ±11 W m−2 (IUD–Control [90% CIs]; Light: −2 [−8, 5] W/m2, P = 0.007; Moderate: 0 [−6, 6] W/m2, P = 0.002), as were dry and evaporative heat loss (P ≤ 0.023), except for evaporative heat loss during moderate‐intensity exercise (equivalence: P = 0.063, difference: P = 0.647). Whole‐body total and evaporative heat loss were not different between phases (P ≥ 0.267), but dry heat loss was 3 [95% CIs: 1, 5] W/m2 greater in the luteal phase (P ≤ 0.022). Despite this, all whole‐body heat loss outcomes were equivalent between phases (P ≤ 0.003). These findings expand our understanding of the factors that modulate heat exchange in women and provide valuable mechanistic insight of the role of endogenous and exogenous female sex hormones in thermoregulation.

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Key points

Progestin released by hormonal intrauterine devices (IUDs) may negatively impact heat dissipation during exercise by blunting skin blood flow and sweating. However, the influence of IUDs on thermoregulation has not previously been assessed.

We used direct calorimetry to show that IUD users and non‐users display statistically equivalent whole‐body dry and evaporative heat loss, body heat storage and oesophageal temperature during moderate‐ and high‐intensity exercise in a warm, dry environment, indicating that IUDs do not appear to compromise exercise thermoregulation.

However, within IUD users and non‐users, dry heat loss was increased and body heat storage and oesophageal temperature were reduced in the luteal compared to the follicular phase of the menstrual cycle, though these effects were small and unlikely to be practically meaningful.

Together, these findings expand our understanding of the factors that modulate heat exchange in women and have important practical implications for the design of future studies of exercise thermoregulation.
Usefulness of skills in point of care ultrasound and simulation-based training as essential competencies in acute management of neonatal cardiac tamponade
Authors: Jain Ankit , Patra Saikat , Chetan Chinmay , Gupta Girish
Published: February 2024

Peripherally inserted central catheter (PICC) insertion is a routine procedure in the neonatal intensive care unit required for prolonged intravenous fluid, nutrition and medication support. Neonatal cardiac tamponade is a serious and rare complication of PICC line insertion. Early detection by point of care ultrasound (POCUS) and management by pericardiocentesis improves the chances of survival. Regular simulation-based training sessions on a mannequin, along with knowledge of POCUS, can assist neonatologists and paediatricians for a quick and appropriate response in this emergency condition.
Cardiovascular collapse and McConnell’s sign as early manifestations of leucostasis
Authors: Rozenbaum Daniel , Lebold Katie M , Lee Dasom , Salmi Darren , Htet Natalie N
Published: February 2024

A man in his late 70s with chronic myelomonocytic leukaemia presented for evaluation of acute leukaemic transformation and initiation of cytoreductive therapy after being found to have asymptomatic hyperleucocytosis. Within 24 hours, the patient developed vasopressor-refractory shock, severe lactic acidosis and multiorgan failure. Serial echocardiographic assessments revealed interval enlargement of the right ventricle with development of the McConnell’s sign, and abdominal CT showed diffuse bowel wall thickening, likely due to ischaemia. CT angiography excluded pulmonary embolism or occlusion of intra-abdominal arteries. Despite aggressive care, the patient died from cardiovascular collapse within 8 hours of the onset of hypotension. An autopsy revealed extensive infiltration of early myeloid cells in pulmonary, myocardial, hepatic and intestinal microvasculature. This case illustrates different mechanisms by which leucostasis causes acute cardiovascular collapse and stresses the emergent nature of this diagnosis.
Recurrent ectopic primary breast adenocarcinoma of the vulva with a 19-year follow-up period
Authors: Barrios Mirelys , Perez Nathalie E , Briski Laurence M , Pluguez-Turull Cedric
Published: February 2024

We present a case of an ectopic breast adenocarcinoma of the vulva with metastatic local recurrence and a total follow-up period of 19 years, the longest documented in the literature to our knowledge. Following surgical excision, radiation therapy and hormonal treatment after the recurrence, the patient has remained disease free. This case demonstrates the potential for malignant transformation in accessory breast tissue and highlights the importance of close surveillance and regular physical examinations in patients with a history of ectopic breast malignancy.
Long-term nivolumab treatment possibly associated with aseptic meningitis.
Authors: Al-Khateeb Wasef , Jarad John , Kim Yuri , Battisti Robert
Published: February 2024

Nivolumab is a programmed death-1 receptor blocker within the family of medications called immune checkpoint inhibitors (ICIs). Although generally well tolerated, cases of immune‐related adverse events (irAEs) have been reported. We present a case of a man being treated with nivolumab for renal cell carcinoma who presented to the emergency department with problems of headache, fever and disorientation. After extensive evaluation, a diagnosis of immunotherapy-induced aseptic meningitis was considered more probable than infectious. Due to stable clinical status, no treatment was initiated, and the patient’s condition improved spontaneously. The patient was discharged home. To date, only a handful of prior cases of nivolumab-induced meningitis have been reported. Our case demonstrates that irAEs can occur years after the initiation of ICIs. This was a milder presentation of a neurological irAE that resolved spontaneously with watchful waiting, showing that irAEs are likely an evolving spectrum of disease for which clinicians should be aware.
Follow up of a rare case of adrenal insufficiency due toNNTmutation
Authors: Khadse Savita , Bhade Karishma , Shah Nikhil , Ghildiyal Radha
Published: February 2024

Hypoglycaemia is one of the most common causes of convulsions in neonatal period. Repeated hypoglycaemic convulsions have to be addressed with utmost urgency to prevent its morbid sequelae. Repeated ketotic hypoglycaemia in the infantile period needs detailed endocrine evaluation. Our patient is a boy in the third year of his life, had presented in infancy with hypoglycaemic convulsions and hyperpigmentation of skin and mucous membrane. Investigations revealed ketotic hypoglycaemia, hypocortisolaemia with high adrenocorticotropic hormone (ACTH) and normal aldosterone, 17-hydroxyprogesterone (17-OHP) and testosterone levels. This suggested isolated glucocorticoid deficiency without mineralocorticoid deficiency. He responded well to hydrocortisone therapy with resolution of symptoms and normalisation of lab parameters. Genetic study confirmed the diagnosis of familial glucocorticoid deficiency (FGD) with homozygous mutation inNNT(nicotinamide nucleotide transhydrogenase) gene with a novel p.Thr578lle variant. This is the first case of FGD withNNTmutation to be reported from the Indian subcontinent.
ADNEX risk prediction model for diagnosis of ovarian cancer: systematic review and meta-analysis of external validation studies
Authors: Barreñada Lasai , Ledger Ashleigh , Dhiman Paula , Collins Gary , Wynants Laure , Verbakel Jan Y , Timmerman Dirk , Valentin Lil , Van Calster Ben
Published: February 2024

Objectives

To conduct a systematic review of studies externally validating the ADNEX (Assessment of Different Neoplasias in the adnexa) model for diagnosis of ovarian cancer and to present a meta-analysis of its performance.

Design

Systematic review and meta-analysis of external validation studies

Data sources

Medline, Embase, Web of Science, Scopus, and Europe PMC, from 15 October 2014 to 15 May 2023.

Eligibility criteria for selecting studies

All external validation studies of the performance of ADNEX, with any study design and any study population of patients with an adnexal mass. Two independent reviewers extracted the data. Disagreements were resolved by discussion. Reporting quality of the studies was scored with the TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) reporting guideline, and methodological conduct and risk of bias with PROBAST (Prediction model Risk Of Bias Assessment Tool). Random effects meta-analysis of the area under the receiver operating characteristic curve (AUC), sensitivity and specificity at the 10% risk of malignancy threshold, and net benefit and relative utility at the 10% risk of malignancy threshold were performed.

Results

47 studies (17 007 tumours) were included, with a median study sample size of 261 (range 24-4905). On average, 61% of TRIPOD items were reported. Handling of missing data, justification of sample size, and model calibration were rarely described. 91% of validations were at high risk of bias, mainly because of the unexplained exclusion of incomplete cases, small sample size, or no assessment of calibration. The summary AUC to distinguish benign from malignant tumours in patients who underwent surgery was 0.93 (95% confidence interval 0.92 to 0.94, 95% prediction interval 0.85 to 0.98) for ADNEX with the serum biomarker, cancer antigen 125 (CA125), as a predictor (9202 tumours, 43 centres, 18 countries, and 21 studies) and 0.93 (95% confidence interval 0.91 to 0.94, 95% prediction interval 0.85 to 0.98) for ADNEX without CA125 (6309 tumours, 31 centres, 13 countries, and 12 studies). The estimated probability that the model has use clinically in a new centre was 95% (with CA125) and 91% (without CA125). When restricting analysis to studies with a low risk of bias, summary AUC values were 0.93 (with CA125) and 0.91 (without CA125), and estimated probabilities that the model has use clinically were 89% (with CA125) and 87% (without CA125).

Conclusions

The results of the meta-analysis indicated that ADNEX performed well in distinguishing between benign and malignant tumours in populations from different countries and settings, regardless of whether the serum biomarker, CA125, was used as a predictor. A key limitation was that calibration was rarely assessed.

Systematic review registration

PROSPERO CRD42022373182.
All-cause and suicide mortalities among adolescents and young adults who contacted specialised gender identity services in Finland in 1996–2019: a register study
Authors: Ruuska Sami-Matti , Tuisku Katinka , Holttinen Timo , Kaltiala Riittakerttu
Published: February 2024

Background

All-cause and suicide mortalities of gender-referred adolescents compared with matched controls have not been studied, and particularly the role of psychiatric morbidity in mortality is unknown.

Objective

To examine all-cause and suicide mortalities in gender-referred adolescents and the impact of psychiatric morbidity on mortality.

Methods

Finnish nationwide cohort of all <23 year-old gender-referred adolescents in 1996–2019 (n=2083) and 16 643 matched controls. Cox regression models with HRs and 95% CIs were used to analyse all-cause and suicide mortalities.

Findings

Of the 55 deaths in the study population, 20 (36%) were suicides. In bivariate analyses, all-cause mortality did not statistically significantly differ between gender-referred adolescents and controls (0.5% vs 0.3%); however, the proportion of suicides was higher in the gender-referred group (0.3% vs 0.1%). The all-cause mortality rate among gender-referred adolescents (controls) was 0.81 per 1000 person-years (0.40 per 1000 person-years), and the suicide mortality rate was 0.51 per 1000 person-years (0.12 per 1000 person-years). However, when specialist-level psychiatric treatment was controlled for, neither all-cause nor suicide mortality differed between the two groups: HR for all-cause mortality among gender-referred adolescents was 1.0 (95% CI 0.5 to 2.0) and for suicide mortality was 1.8 (95% CI 0.6 to 4.8).

Conclusions

Clinical gender dysphoria does not appear to be predictive of all-cause nor suicide mortality when psychiatric treatment history is accounted for.

Clinical implications

It is of utmost importance to identify and appropriately treat mental disorders in adolescents experiencing gender dysphoria to prevent suicide.
Cost-effectiveness of the ONCORAL multidisciplinary programme for the management of outpatients taking oral anticancer agents at risk of drug-related event: protocol for a pragmatic randomised controlled study
Authors: Huot Laure , Guerre Pascale , Descotes Guillaume , Caffin Anne-Gaëlle , Herledan Chloé , Ranchon Florence , Rioufol Catherine
Published: February 2024

Introduction

The development of oral anticancer agents (OAA) has profoundly changed cancer care, leading patients to manage their chemotherapy treatment on an outpatient basis. The prevention of iatrogenic effects of OAA remains a major concern, especially since their side effects are not less serious than those of intravenous chemotherapy. The ONCORAL programme was set up to secure the management of OAA in cancer patients followed at the Lyon University Hospital. This multidisciplinary programme involves hospital pharmacists, nurses, oncologists, and haematologists, as well as community health professionals. Given the economic stakes that this programme entails for the health system, a medico-economic study was designed.

Methods and analysis

This is a prospective controlled study, with individual open-label randomisation. A total of 216 outpatients treated with OAA and at risk of developing a drug-related iatrogenic event, will be randomised (2:1) to undergo follow-up in the ONCORAL programme or usual care. The primary outcome will be the estimation of the incremental cost-effectiveness ratio (difference in total costs per quality adjusted life years gained) at 12 months between the two groups. The secondary outcomes will be evaluation of OAA management consequences (relative-dose intensity, adherence, adverse drug events, drug–drug interactions, and proven medication errors), evaluation of overall survival and cancer-related quality of life, and patient-reported outcomes in relation to the treatment. A budget impact analysis will be implemented. Patient and health professional satisfaction regarding the ONCORAL programme will be measured.

Ethics and dissemination

Approval to conduct this study was obtained from an Ethics Committee (Comité de Protection des Personnes Ile-de-France VI) in October 2019, and from the French data protection agency (Commission Nationale de l’Informatique et des Libertés), according to the French Law. Trial results will be disseminated at clinical conferences and published in peer-reviewed journals.

Trial registration

NCT03660670.
Nudging towards COVID-19 and influenza vaccination uptake in medically at-risk children: EPIC study protocol of randomised controlled trials in Australian paediatric outpatient clinics
Authors: Wang Bing , Andraweera Prabha , Danchin Margaret , Blyth Christopher C , Vlaev Ivo , Ong Jason , Dodd Jodie M , Couper Jennifer , Sullivan Thomas R , Karnon Jonathan , Spurrier Nicola , Cusack Michael , Mordaunt Dylan , Simatos Dimi , Dekker Gustaaf , Carlson Samantha , Tuckerman Jane , Wood Nicholas , Whop Lisa J , Marshall Helen
Published: February 2024

Introduction

Children with chronic medical diseases are at an unacceptable risk of hospitalisation and death from influenza and SARS-CoV-2 infections. Over the past two decades, behavioural scientists have learnt how to design non-coercive ‘nudge’ interventions to encourage positive health behaviours. Our study aims to evaluate the impact of multicomponent nudge interventions on the uptake of COVID-19 and influenza vaccines in medically at-risk children.

Methods and analyses

Two separate randomised controlled trials (RCTs), each with 1038 children, will enrol a total of approximately 2076 children with chronic medical conditions who are attending tertiary hospitals in South Australia, Western Australia and Victoria. Participants will be randomly assigned (1:1) to the standard care or intervention group. The nudge intervention in each RCT will consist of three text message reminders with four behavioural nudges including (1) social norm messages, (2) different messengers through links to short educational videos from a paediatrician, medically at-risk child and parent and nurse, (3) a pledge to have their child or themselves vaccinated and (4) information salience through links to the current guidelines and vaccine safety information. The primary outcome is the proportion of medically at-risk children who receive at least one dose of vaccine within 3 months of randomisation. Logistic regression analysis will be performed to determine the effect of the intervention on the probability of vaccination uptake.

Ethics and dissemination

The protocol and study documents have been reviewed and approved by the Women’s and Children’s Health Network Human Research Ethics Committee (HREC/22/WCHN/2022/00082). The results will be published via peer-reviewed journals and presented at scientific meetings and public forums.

Trial registration number

NCT05613751.
Weight stigma and allostatic load in adults: protocol for a scoping review
Authors: Cassiani-Miranda Carlos Arturo , Díaz Rincón Maritza , Arroyo-Gamero Leonar Antonio , Giraldo-Barrios Luis Gabriel , Carmona-Meza Zenen
Published: February 2024

Introduction

Weight-related stigma (WS) has been associated with adverse psychosocial and physical health effects. Despite the relationship between WS and allostatic load, there are no integrative reviews of this association. This scoping review aims to provide a comprehensive overview of the relationship between allostatic load biomarkers associated with WS by identifying gaps in this topic and proposing recommendations for future research.

Methods and analysis

This protocol was guided by the methodological framework of Arksey and O'Malley and the Joanna Briggs Institute (JBI). The research questions were based on the population–concept–context framework. Studies in adults diagnosed as overweight or obese, exposed to WS and assessing the association between WS and biomarkers of allostatic load will be included. A search will be conducted in Medline (Ovid), PsycINFO (Ovid), Scopus (Elsevier), Cochrane Library (Wiley) and Google Scholar. The search strategy will be conducted in three stages, based on the JBI recommendation with the MESH terms “Social Stigma,” “Weight Prejudice,” “Biomarkers,” “Allostasis,” “Adults” and related terms. Data extraction will be done with a template adapted from JBI. The search strategy and selection process results will be presented in a flow chart and summarised in the text. The main results will be presented in a descriptive synthesis.

Ethics and dissemination

Ethics review and approval are not required. The results will be disseminated through peer-reviewed publications, conferences, congresses or symposia.