bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin‐like growth factor‐1 promotes the testicular sperm production by improving germ cell survival and proliferation in high‐fat diet‐treated male mice
Authors: Liu Guoqiang , Liu Di , Zhu Minggang , Zhang Mingrui , Li Chunyang , Xu Xiaohong , Pan Feng 
Published: April 2024

AbstractBackgroundA decrease in semen volume among men is comparable to the rising prevalence of obesity worldwide. The anabolic hormone insulin‐like growth factor‐1 (IGF‐1) can promote proliferation and differentiation in cultured mouse spermatogonial stem cells and alleviate abnormal in vitro spermatogenesis. Additionally, serum IGF‐1 level is negatively correlated with body mass index. Whereas the role of IGF‐1 in the sperm production in obese men remains unclear.ObjectiveTo investigate the therapeutic effect and potential mechanism of IGF‐1 on spermatogenesis of high‐fat diet (HFD)‐induced obesity mice.MethodsAn HFD‐induced obesity mouse model was established. Alterations in testicular morphology, sperm count, proliferation, and apoptosis were observed by H&E staining,immunohistochemistry, immunofluorescence, and Western blotting. Exogenous recombinant IGF‐1 was administered to obese mice to investigate the correlations between altered testicular IGF‐1 levels and sperm production.ResultsThe sperm count was reduced, the testicular structure was disordered, and sex hormone levels were abnormal in HFD‐fed mice compared with normal diet‐fed mice. The expression of proliferation‐related antigens such as proliferating cell nuclear antigen (PCNA) and Ki‐67 was decreased, while that of proapoptotic proteins such as c‐caspase3 was increased in testes from HFD‐fed mice. Most importantly, the phosphorylation of insulin‐like growth factor‐1 receptor (IGF‐1R) in testes was decreased due to reductions in IGF‐1 from hepatocytes and Sertoli cells. Recombinant IGF‐1 alleviated these functional impairments by promoting IGF‐1R, Akt, and Erk1/2 phosphorylation in the testes.ConclusionsInsufficient IGF‐1/IGF‐1R signaling is intimately linked to damaged sperm production in obese male mice. Exogenous IGF‐1 can improve survival and proliferation as well as sperm production. This study provides a novel theoretical basis and a target for the treatment of obese men with oligozoospermia.
Shared risk and shared responsibility: the ethics of male contraceptives
Authors: Campelia Georgina D. , Adashi Eli Y. , Amory John K. 
Published: April 2024

AbstractIntroductionEfforts to develop reversible male contraceptives analogous to female oral contraceptives are underway and may be introduced in the next decade. The advent of novel male contraceptives provides an opportunity for an ethical reformulation of the contraceptive paradigm given the relational, rather than individual, nature of sexual relationships, and family planning. For individuals in any sexual relationship that could result in pregnancy, issues of reproductive autonomy, freedom, equality in reproductive decision‐making and risks—both of side effects and of unintended pregnancies—are significant. Historically, however, women have been attributed the greatest responsibilities simultaneously with the most restrictions on their freedom of choice and access to reproductive care.ObjectivesIn this paper, we extend our prior “shared risk” model of male contraception to one of “shared risk and responsibility” to ethically inform this discourse.ConclusionsThis updated framework more fully captures the complexity of this novel technology and may be of use to regulatory and legal agencies grappling with an intervention that poses medical risks to the member of the relationship who does not face risks of becoming pregnant.
Early warning signals observed in motor activity preceding mood state change in bipolar disorder
Authors: Jakobsen Petter , Côté‐Allard Ulysse , Riegler Michael Alexander , Stabell Lena Antonsen , Stautland Andrea , Nordgreen Tine , Torresen Jim , Fasmer Ole Bernt , Oedegaard Ketil Joachim 
Published: April 2024

AbstractIntroductionAlterations in motor activity are well‐established symptoms of bipolar disorder, and time series of motor activity can be considered complex dynamical systems. In such systems, early warning signals (EWS) occur in a critical transition period preceding a sudden shift (tipping point) in the system. EWS are statistical observations occurring due to a system's declining ability to maintain homeostasis when approaching a tipping point. The aim was to identify critical transition periods preceding bipolar mood state changes.MethodsParticipants with a validated bipolar diagnosis were included to a one‐year follow‐up study, with repeated assessments of the participants' mood. Motor activity was recorded continuously by a wrist‐worn actigraph. Participants assessed to have relapsed during follow‐up were analyzed. Recognized EWS features were extracted from the motor activity data and analyzed by an unsupervised change point detection algorithm, capable of processing multi‐dimensional data and developed to identify when the statistical property of a time series changes.ResultsOf 49 participants, four depressive and four hypomanic/manic relapses among six individuals occurred, recording actigraphy for 23.8 ± 0.2 h/day, for 39.8 ± 4.6 days. The algorithm detected change points in the time series and identified critical transition periods spanning 13.5 ± 7.2 days. For depressions 11.4 ± 1.8, and hypomania/mania 15.6 ± 10.2 days.ConclusionThe change point detection algorithm seems capable of recognizing impending mood episodes in continuous flowing data streams. Hence, we present an innovative method for forecasting approaching relapses to improve the clinical management of bipolar disorder.
Real‐world effectiveness and safety of insulin glargine 100 U/mL plus lixisenatide in adults with type 2 diabetes: An international, multicentre, 12‐month, prospective observational study
Authors: Malik Rayaz A. , Hwu Chii‐Min , Jammah Anwar A. , Arteaga‐Díaz Juan M. , Djaballah Khier , Pilorget Valerie , Alvarez Agustina , Vera Carine , Vikulova Olga 
Published: April 2024

AbstractAimTo assess the impact of insulin glargine (100 U/mL) and lixisenatide (iGlarLixi) fixed‐ratio combination therapy on the overall management of glycaemia in patients with type 2 diabetes (T2D), previously inadequately controlled with oral antidiabetic drugs ± basal insulin or glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs).Materials and MethodsThis 12‐month, international, multicentre, prospective, observational study included patients (age ≥ 18 years) with T2D who had initiated iGlarLixi within 1 month prior to study inclusion. Data were collected at study inclusion, month 3, month 6 and month 12 from patient diaries, self‐measured plasma glucose, and questionnaires. The primary endpoint was change in HbA1c from baseline to month 6.ResultsOf the 737 eligible participants (mean age: 57.8 [standard deviation: 11.2] years; male: 49%), 685 had baseline and post‐baseline HbA1c data available. The least squares mean change in HbA1c from baseline to month 6 was −1.4% (standard error [95% confidence interval (CI)]: 0.05 [−1.5, −1.3]). The absolute change from baseline at month 12 was −1.7% ± 1.9% (95% CI: −1.9, −1.5). There were 72 hypoglycaemia events reported during the study period, with a very low incidence of severe hypoglycaemia (two participants [rate: 0.003 events per patient‐year]).ConclusionsThis real‐world observational study shows that initiation of iGlarLixi in people with T2D inadequately controlled on oral antidiabetic drugs ± basal insulin or GLP‐1 RAs improves glycaemic control with a low incidence of hypoglycaemia.
Life‐giving Flesh: Deity, Humanity, and the Efficacy of the Atonement – Part One
Authors: Duby Steven J. 
Published: April 2024

AbstractThe life‐giving power of Christ's flesh and the unique efficacy of his atoning death are grounded in the fact that the flesh belongs to a divine person, the eternal Word. Though some theologians have argued that this should be explained by a divine sort of suffering taking place on the cross, this essay briefly critiques the idea of divine suffering in the atonement and proceeds to offer constructive discussion of other ways in which the life‐giving power of Christ's flesh and the efficacy of his atoning death are grounded in his deity. This first requires a consideration of the way in which Christ's humanity is empowered and supported by his deity in his suffering and atoning death, which will be articulated in dialogue with several patristic, medieval, and early modern theologians. A second essay will then elaborate further on the relationship between the efficacy of the atonement and the deity of Christ by discussing the way in which the ransom that Christ pays on the cross derives its infinite worth from his deity.
Trends and determinants of mental illness in humanitarian migrants resettled in Australia: Analysis of longitudinal data
Authors: Handiso Demelash Woldeyohannes , Paul Eldho , Boyle Jacqueline A. , Shawyer Frances , Meadows Graham , Enticott Joanne C. 
Published: April 2024

AbstractGiven the frequent exposure of humanitarian migrants to traumatic or stressful circumstances, there exists a potential predisposition to mental illness. Our objective was to pinpoint the trends and determinants of mental illness among humanitarian migrants resettled in Australia. This study considered five waves of longitudinal data involving humanitarian migrants resettled in Australia. Post‐traumatic stress disorder (PTSD) and psychological distress were assessed using PTSD‐8 and Kessler‐6 screening tools. Through a Generalised Linear Mixed model (GLMM), variables displaying a 95% CI that excluded the value of 1.0 for the odds ratio were identified as associated factors for both PTSD and elevated psychological distress. The selection of multivariable covariates was guided by causal loop diagrams and least absolute shrinkage and selection operators methods. At baseline, there were 2399 humanitarian migrants with 1881 retained and at the fifth yearly wave; the response rate was 78.4%. PTSD prevalence decreased from 33.3% (95% CI: 31.4–35.3) at baseline to 28.3% (95% CI: 26.2–30.5) at year 5. Elevated psychological distress persisted across all waves: 17.1% (95% CI: 15.5–18.6) at baseline and 17.1% (95% CI: 15.3–18.9) at year 5. Across the five waves, 34.0% of humanitarian migrants met screening criteria for mental illness, either PTSD or elevated psychological distress. In the multivariate model, factors associated with PTSD were loneliness (AOR 1.5, 95% CI: 1.3–1.8), discrimination (AOR 1.6: 1.2–2.1), temporary housing contract (AOR 3.7: 2.1–6.7), financial hardship (AOR 2.2:1.4–3.6) and chronic health conditions (AOR 1.3: 1.1–1.5), whereas the associated factors for elevated psychological distress were loneliness (AOR 1.8: 1.5–2.2), discrimination (AOR 1.7: 1.3–2.2) and short‐term lease housing (AOR 1.6: 1.0–1.7). The prevalence, persistence and consequential burden of mental illness within this demographic underscore the urgent need for targeted social and healthcare policies. These policies should aim to mitigate modifiable risk factors, thereby alleviating the significant impact of mental health challenges on this population.
Working effectively with consumers: Perspectives from students, teachers, nurses, and consumers
Authors: Hall Karen , Skues Jason , Kiegaldie Debra 
Published: April 2024

AbstractPreparing enrolled nurses (ENs) to effectively work with mental health consumers is crucial to meeting Australia's healthcare demands. This qualitative study aimed to explore various stakeholders’ perceptions regarding the mental health knowledge, skills, and attributes (KSAs) required by ENs to engage with individuals experiencing mental health issues, thus guiding future training priorities. The sample comprised 44 participants including 18 students, 3 graduate ENs, 5 experienced ENs, 5 registered nurses (RNs), 4 nurse unit managers (NUMs), 5 teachers, and 5 consumers of mental health services. Focus groups were used to collect data from the students, whilst individual interviews were conducted with all other participants. A thematic analysis revealed communication was the most vital skill for effectively working with mental health consumers. Skills such as critical thinking and clinical reasoning were also deemed crucial, given the volatile nature of the mental health inpatient environment, necessitating effective responses to acute escalations to prevent adverse outcomes for both staff and consumers. Essential knowledge components included understanding mental health disorders, symptoms, and treatments, particularly medications used for mental health issues. Participants also emphasised the importance of attributes like confidence and empathy in supporting and caring for consumers, who often experienced trauma and vulnerability. These findings provide valuable insights into the content that should be incorporated into the diploma of nursing (DN) training to produce competent graduate ENs.
Impact of omitting the intravenous heparin bolus on outcomes of leadless pacemaker implantation
Authors: Huang Jingwen , Bhatia Neal K. , Lloyd Michael S. , Westerman Stacy , Shah Anand , Delurgio David , Patel Anshul M. , Tompkins Christine , El‐Chami Mikhael F. , Merchant Faisal M. 
Published: April 2024

AbstractBackgroundEarly guidance recommended a bolus of intravenous heparin at the beginning of leadless pacemaker (LP) implantation procedures. However, due to concern about bleeding complications, more recent practice has tended toward omitting the bolus and only running a continuous heparin infusion through the introducer sheath. The impact of omitting the heparin bolus on procedural outcomes is not clear.MethodsWe reviewed all Medtronic Micra LP implants at our institution from 9/2014 to 9/2022. The decision to bolus with heparin was at operator discretion.ResultsAmong 621 LP implants, 326 received an intravenous heparin bolus, 243 did not, and 52 patients were excluded because heparin bolus status could not be confirmed. There was a trend toward more frequent omission of the heparin bolus with more recent implants. Median follow‐up after LP implant was 14.3 (interquartile range [IQR]: 8.4–27.9) months. There was no difference between heparin bolus and no bolus groups in the number of device deployments/recaptures (1.42 ± 0.81 vs. 1.31 ± 0.66, p = .15). Implant‐related adverse events were also similar between heparin bolus and no bolus groups: access‐site hematoma requiring intervention (7 vs. 5, p = .99), pseudoaneurysm (1 vs. 1, p = .99), cardiac perforation (1 vs. 1, p = .99), intraprocedural device thrombus formation (2 vs. 4, p = .41), 30‐day rehospitalization (21 vs. 15, p = .98), and 30‐day all‐cause mortality (16 vs. 14, p = .70). There was one additional nonfatal cardiac perforation in a patient who was excluded due to unknown heparin bolus status. Regarding device electrical parameters between heparin bolus and no bolus groups, there were no significant differences at the time of implant: pacing capture threshold 0.5 ± 0.4 vs. 0.5 ± 0.3, p = .10; pacing impedance 739.9 ± 226.4 vs. 719.1 ± 215.4, p = .52; R wave sensing 11.7 ± 5.7 vs. 12.0 ± 5.4, p = .34). Long‐term device performance was also similar between groups.ConclusionOmission of the systemic heparin bolus at the time of LP implantation appears safe in appropriately selected patients. Heparin bolus may still be considered in long cases requiring multiple device deployments or in patients at high risk for thrombotic complications.
The β3‐AR agonist BRL37344 ameliorates the main symptoms of X‐linked nephrogenic diabetes insipidus in the mouse model of the disease
Authors: Milano Serena , Saponara Ilenia , Gerbino Andrea , Carmosino Monica , Svelto Maria , Procino Giuseppe 
Published: April 2024

AbstractX‐linked nephrogenic diabetes insipidus (X‐NDI) is a rare congenital disease caused by inactivating mutations of the vasopressin type‐2 receptor (AVPR2), characterized by impaired renal concentrating ability, dramatic polyuria, polydipsia and risk of dehydration. The disease, which still lacks a cure, could benefit from the pharmacologic stimulation of other GPCRs, activating the cAMP‐intracellular pathway in the kidney cells expressing the AVPR2. On the basis of our previous studies, we here hypothesized that the β3‐adrenergic receptor could be such an ideal candidate. We evaluated the effect of continuous 24 h stimulation of the β3‐AR with the agonist BRL37344 and assessed the effects on urine output, urine osmolarity, water intake and the abundance and activation of the key renal water and electrolyte transporters, in the mouse model of X‐NDI. Here we demonstrate that the β3‐AR agonism exhibits a potent antidiuretic effect. The strong improvement in symptoms of X‐NDI produced by a single i.p. injection of BRL37344 (1 mg/kg) was limited to 3 h but repeated administrations in the 24 h, mimicking the effect of a slow‐release preparation, promoted a sustained antidiuretic effect, reducing the 24 h urine output by 27%, increasing urine osmolarity by 25% and reducing the water intake by 20%. At the molecular level, we show that BRL37344 acted by increasing the phosphorylation of NKCC2, NCC and AQP2 in the renal cell membrane, thereby increasing electrolytes and water reabsorption in the kidney tubule of X‐NDI mice. Taken together, these data suggest that human β3‐AR agonists might represent an effective possible treatment strategy for X‐NDI.
Should gestational weight gain charts exclude individuals with excess postpartum weight retention?
Authors: Socha Peter M. , Johansson Kari , Bodnar Lisa M. , Hutcheon Jennifer A. 
Published: April 2024

AbstractBackgroundHigh gestational weight gain is associated with excess postpartum weight retention, yet excess postpartum weight retention is not an exclusion criterion for current gestational weight gain charts. We aimed to assess the impact of excluding individuals with high interpregnancy weight change (a proxy for excess postpartum weight retention) on gestational weight gain distributions.MethodsWe included individuals with an index birth from 2008 to 2014 and a subsequent birth before 2019, in the population‐based Stockholm‐Gotland Perinatal Cohort. We estimated gestational weight gain (kg) at 25 and 37 weeks, using weight at first prenatal visit (<14 weeks) as the reference. We calculated high interpregnancy weight change (≥10 kg and ≥5 kg) using the difference between weight at the start of an index and subsequent pregnancy. We compared gestational weight gain distributions and percentiles (stratified by early‐pregnancy body mass index) before and after excluding participants with high interpregnancy weight change.ResultsAmong 55,723 participants, 17% had ≥10 kg and 34% had ≥5 kg interpregnancy weight change. The third, tenth, 50th, 90th and 97th percentiles of gestational weight gain were similar (largely within 1 kg) before versus after excluding participants with high interpregnancy weight change, at both 25 and 37 weeks. For example, among normal weight participants at 37 weeks, the 50th and 97th percentiles were 14 kg and 23 kg including versus 13 kg and 23 kg excluding participants with ≥5 kg interpregnancy weight change.ConclusionsExcluding individuals with excess postpartum weight retention from normative gestational weight gain charts may not meaningfully impact the charts' percentiles.
The road less taken: Dihydroflavonol 4‐reductase inactivation and delphinidin anthocyanin loss underpins a natural intraspecific flower colour variation
Authors: Wong Darren C. J. , Wang Zemin , Perkins James , Jin Xin , Marsh Grace Emma , John Emma Grace , Peakall Rod 
Published: April 2024

AbstractVisual cues are of critical importance for the attraction of animal pollinators, however, little is known about the molecular mechanisms underpinning intraspecific floral colour variation. Here, we combined comparative spectral analysis, targeted metabolite profiling, multi‐tissue transcriptomics, differential gene expression, sequence analysis and functional analysis to investigate a bee‐pollinated orchid species, Glossodia major with common purple‐ and infrequent white‐flowered morphs. We found uncommon and previously unreported delphinidin‐based anthocyanins responsible for the conspicuous and pollinator‐perceivable colour of the purple morph and three genetic changes underpinning the loss of colour in the white morph – (1) a loss‐of‐function (LOF; frameshift) mutation affecting dihydroflavonol 4‐reductase (DFR1) coding sequence due to a unique 4‐bp insertion, (2) specific downregulation of functional DFR1 expression and (3) the unexpected discovery of chimeric Gypsy transposable element (TE)‐gene (DFR) transcripts with potential consequences to the genomic stability and post‐transcriptional or epigenetic regulation of DFR. This is one of few known cases where regulatory changes and LOF mutation in an anthocyanin structural gene, rather than transcription factors, are important. Furthermore, if TEs prove to be a frequent source of mutation, the interplay between environmental stress‐induced TE evolution and pollinator‐mediated selection for adaptive colour variation may be an overlooked mechanism maintaining floral colour polymorphism in nature.
Motor dysfunction of the gut in Duchenne muscular dystrophy: A review
Authors: Subhan Fazal , Zizzo Maria Grazia , Serio Rosa 
Published: April 2024

AbstractBackgroundDuchenne's muscular dystrophy (DMD) is a severe type of hereditary, neuromuscular disorder caused by a mutation in the dystrophin gene resulting in the absence or production of truncated dystrophin protein. Conventionally, clinical descriptions of the disorder focus principally on striated muscle defects; however, DMD manifestations involving gastrointestinal (GI) smooth muscle have been reported, even if not rigorously studied.PurposeThe objective of the present review is to offer a comprehensive perspective on the existing knowledge concerning GI manifestations in DMD, focusing the attention on evidence in DMD patients and mdx mice. This includes an assessment of symptomatology, etiological pathways, and potential corrective approaches. This paper could provide helpful information about DMD gastrointestinal implications that could serve as a valuable orientation for prospective research endeavors in this field. This manuscript emphasizes the effectiveness of mdx mice, a DMD animal model, in unraveling mechanistic insights and exploring the pathological alterations in the GI tract. The gastrointestinal consequences evident in patients with DMD and the mdx mice models are a significant area of focus for researchers. The exploration of this area in depth could facilitate the development of more efficient therapeutic approaches and improve the well‐being of individuals impacted by the condition.