bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial neural network risk prediction of chronic obstructive pulmonary disease (COPD) exacerbations using urine biomarkers
Authors: Yousuf Ahmed J. , Parekh Gita , Farrow Malcolm , Ball Graham , Graziadio Sara , Wilson Kevin , Lendrem Clare , Carr Liesl , Watson Lynne , Parker Sarah , Finch Joanne , Glover Sarah , Mistry Vijay , Porter Kate , Duvoix Annelyse , O'Brien Linda , Rees Sarah , Lewis Keir E. , Davis Paul , Brightling Christopher E.
Published: November 2024

Background

Chronic obstructive pulmonary disease (COPD) exacerbations cause considerable morbidity and mortality. We sought to identify a panel of urine biomarkers that can distinguish between stable and exacerbation states and predict risk of future exacerbations.

Methods

A retrospective discovery study was done measuring 35 biomarkers implicated in COPD pathogenesis in paired urine samples from 55 COPD subjects during stable and exacerbation states. A logistic regression model combining the 10 most discriminatory biomarkers in distinguishing between stable and exacerbation states was developed as a near-patient dipstick test with an opto-electronic reader. This biomarker panel was tested in a prospective study of 105 COPD subjects who undertook daily home urine testing over 6 months. The regression model was validated in paired samples from 26 individuals out of 105. An artificial neural network (ANN) using the urine biomarkers from 85 out of 105 subjects was developed and tested as a clinical decision tool to predict risk of an exacerbation.

Results

The 10-biomarker panel (NGAL, TIMP1, CRP, fibrinogen, CC16, fMLP, TIMP2, A1AT, B2M, and MMP8) was able to distinguish exacerbationversusstable state in the discovery study (ROC with an AUC 0.84 [95% CI, 0.76 to 0.92; p <0.01]), and validation study (AUC 0.81 [95% CI; 0.70 to 0.92, p<0.01]). The ANN model predicted an exacerbation within a 13-day window frame with an AUC 0.89 (95% CI 0.89–0.90) and identified an exacerbation median (interquartile range) 7 (5 to 9) days prior to clinical diagnosis.

Conclusion

We identified a panel of biomarkers that can distinguish between stable and exacerbation state and using an artificial neural network model, it can predict exacerbations before symptoms occur.
A double knockout for zinc transporter 8 and somatostatin in mice reveals their distinct roles in regulation of insulin secretion and obesity
Authors: Yang Zhongyue , Kirschke Catherine P. , Cai Yimeng , Huang Liping
Published: November 2024

Background

Both zinc transporter 8 (ZnT8) and somatostatin (Sst) play crucial roles in the regulation of insulin and glucagon secretion. However, the interaction between them in controlling glucose metabolism was not well understood. The aim of this study was to explore the interactive effects of a double knockout of Znt8 and Sst on insulin and glucose metabolism in mice.

Methods

Co-expression of ZnT8 with hormones secreted from gastrointestinal endocrine cells of mice was determined using immunofluorescence. Male Znt8 knockout (Znt8KO), Sst knockout (SstKO), double knockout for Sst and Znt8 (DKO), and the wild-type (WT) mice were fed a regular chow diet (CD) or a high-fat diet (HFD) at 3 weeks old for 15 weeks. Weights and fasting or fed glucose levels were determined. Glucose and insulin tolerance tests were performed; metabolic-relevant hormone levels including insulin, glucagon, glucagon-like peptide 1, Pyy, and leptin were determined.

Results

ZnT8 is co-expressed with Sst in a subpopulation of endocrine D cells in the gastrointestinal tract. The absence of ZnT8 expression resulted in an increased density of the dense cores in the secretory granules of the D cell. DKO mice had reduced weight compared to WT when maintained on the CD. Compared to Znt8KO and SstKO, DKO mice did not show significant differences in fed or fasting blood glucose level regardless of dietary conditions. However, the CD-fed DKO mice had impaired insulin secretion without alterations in islet morphology or numbers. Moreover, DKO mice displayed diet-induced insulin resistance and disrupted secretion of metabolic-related hormones.

Conclusions

Somatostatin as well as a normal insulin sensitivity are required for normalizing glucose metabolism in Znt8KO mice. ZnT8 may play a role in regulating fat mass and leptin secretion. These findings shed light on the multifaceted nature of Znt8 and Sst interactions, opening new avenues to understand their roles in controlling glucose metabolism and fat mass.
Comparison of heart rate variability, hemodynamic, metabolic and inflammatory parameters in various phases of decompansatory hemorrhagic shock of normal and vagotomized conscious male rats
Authors: Khodadadi Fateme , Punait Sujata , Ketabchi Farzaneh , Khodabandeh Zahra , Bahaoddini Aminollah , Lewis Gregory F.
Published: November 2024

Background

Heart rate variability (HRV) analysis has shown promise as a valuable complementary tool for clinical assessment in trauma cases. This study aims to evaluate the utility of HRV in monitoring different severities of hemorrhagic shock (HS) and its correlation with traditional hemodynamic and metabolic parameters.

Methods

Male Sprague–Dawley rats were divided into different experimental groups, including those with and without vagotomy, and were exposed to different classes of decompensatory HS. To induce varying severities of HS, volume resuscitation was delayed by gradually returning 0%, 20%, or 50% of the shed blood volume at the end of the compensation phase, referred to as 0% DFR, 20% DFR, and 50% DFR class, respectively. Hemodynamic parameters were monitored, and HRV was calculated. Levels of TNF-α and IL-10 were determined in lung tissue at the end of the experiments. Correlations between HRV, hemodynamic parameters, inflammatory gene expression and arterial blood gas variables were evaluated.

Results

HRV showed increased power of the low-frequency (LF) and respiratory sinus arrhythmia (RSA) in all groups during the hypotension phase of HS (Nadir 1). Subdiaphragmatic vagotomy blunted the increase in the LF component in the Nadir 1. After volume resuscitation, systolic blood pressure (SBP), RSA and LF returned to baseline in the 0% DFR and 20% DFR classes. However, animals in 50% DFR class exhibited a reduced SBP and LF and lower pH. Notably, strong correlations were found between LF and SBP as well as tissue hypoperfusion markers. The expression of TNF-α in the lung was increased in all HS groups, while this gene expression was significantly higher in the vagotomized animals.

Conclusion

The alterations in HRV components were found to be significantly correlated with the hemodynamic and metabolic status of the animals, while showing no association with inflammatory responses. Additionally, the intervention of subdiaphragmatic vagotomy significantly impacted both HRV components and inflammatory responses. Collectively, these findings suggest the potential of HRV components for the assessment of the presence and severity of HS.
Family events and child behavior in late childhood: a cross-sectional study
Authors: Hosokawa Rikuya , Tomozawa Riho , Fujimoto Megumi , Katsura Toshiki
Published: November 2024

Background

Children’s social behavior develops through diverse experiences. However, the relationship between children’s experiences of celebratory events and their behavioral development has not been previously quantified. Therefore, this study aimed to quantitatively explore this relationship.

Methods

In 2020, a self-reported questionnaire was completed by 653 sixth-grade students (aged 11–12 years) and/or their caregivers in Nagoya, Aichi, a major metropolitan area in Japan. The main items surveyed were children’s experiences with events celebrated by their family and their behavioral development. The Strengths and Difficulties Questionnaire was used to assess children’s behavior. This questionnaire identifies behavioral and emotional problems and prosocial behavior. Multiple regression analysis was conducted with the number of family events experienced by children as the explanatory variable and their emotional and prosocial behavior as the objective variables.

Results

Children from families who participated in fewer family events tended to have higher problematic behavior risk scores and lower prosociality scores compared with their counterparts. Compared with children who participated in more than 20 family events, those who participated in fewer than 10 family events had more than three times the risk for exhibiting problem behaviors (odds: 3.558, 95% CI: 1.252–10.111, p = .017) and prosocial problems (odds: 3.184, 95% CI: 1.726–5.876, p < .001). Conversely, children from families who participated in more family events tended to have lower problematic behavior risk scores and higher prosociality scores.

Conclusions

A higher number of family events may reduce the risk of behavioral problems in children and increase their prosociality. Enjoying family events may be beneficial for social adjustment.
Improvement of persistent impairments in executive functions and attention following electroconvulsive therapy in a case control longitudinal follow up study
Authors: Hammar Åsa , Ronold Eivind Haga , Spurkeland Malene Alden , Ueland Rita , Kessler Ute , Oedegaard Ketil J. , Oltedal Leif
Published: November 2024

Background

How cognition is influenced by electroconvulsive treatment (ECT) and major depressive disorder (MDD) is still debated. The development and etiology of neurocognitive impairment in MDD were examined by investigating the cognitive profile following ECT related to the state, scar, and trait perspectives, with the former predicting improvements parallel with depressive symptoms, while the two latter expected persisting impairments. Executive functions (EF) and attention are central to cognition and alterations in these functions could influence other domains like memory. The main aims of the present study were to examine the short and long-term effects of ECT on EF and attention in patients with major depressive disorder by exploiting the rapid antidepressant effect of this treatment.

Methods

A case-control longitudinal follow-up design was used to investigate the effects of unilateral brief-pulse ECT on EF and attention in patients with depression (n = 36) compared to untreated healthy controls (n = 16). EF and attention were measured pre-treatment, approximately two weeks, and six months post-treatment.

Results

The patient group showed significantly worse performance on most tests compared to healthy controls pre-treatment, and no short- or long-term worsening of EF and attention following ECT was found. Significant improvement was identified in patients’ attention, processing speed and inhibition after ECT.

Conclusions

The present study showed that there was no cognitive worsening after ECT treatment. An improvement in several of the tests measuring inhibition, attention, and processing speed was parallel to symptom reduction, with the former showing associations to symptom change, suggesting state-related effects from improved mood. Still, the patient group performed significantly worse on most measures both pre-treatment and at the short and long-term follow-ups, indicating prevailing trait or scar effects on cognitive functions and potential lack of practice effects.

Clinical trial number

NCT04348825 (14.04.20).
Parenteral prostacyclin utilization in patients with pulmonary arterial hypertension in the intermediate-risk strata: a retrospective chart review and cross-sectional survey
Authors: Vaidya Anjali , Sketch Margaret R. , Broderick Meredith , Shlobin Oksana A.
Published: November 2024

Background

Current clinical guidelines support use of parenteral prostacyclin therapy for patients with pulmonary arterial hypertension (PAH) at intermediate risk. The objective of this study was to assess parenteral prostacyclin therapy use among patients at intermediate risk according to the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) 2.0 four-strata risk assessment model.

Methods

This was a retrospective chart review and cross-sectional online survey of healthcare professionals (HCPs). Included patients were classified as intermediate-low or intermediate-high risk per COMPERA 2.0 between 2016 and 2020 (index visit), initiated on a parenteral prostacyclin any time following intermediate risk assessment, and had World Health Organization (WHO) Functional Class (FC), 6-minute walk distance (6MWD), and B-type natriuretic peptide/N-terminal pro B-type natriuretic peptide (BNP/NT-proBNP) assessments at index and first comprehensive follow-up visits (follow-up).

Results

A total of 139 HCPs (53% community-based, 47% Pulmonary Hypertension Care Center-based) participated in the survey and provided 350 patient records; among these, mean age (SD) was 54.1 (15.3) years and 52% were female. Median (IQR) time from parenteral prostacyclin initiation to follow-up was 3.0 months (2.0, 7.0). At parenteral prostacyclin initiation for the 280 patient records with available COMPERA 2.0 assessments, 62% of patients were intermediate-high risk, 33% were intermediate-low risk and 3% were low risk, improving to 38%, 53%, and 8%, respectively, at follow-up.

Conclusions

Improvements were seen for the individual COMPERA 2.0 risk calculator parameters and for several other clinical parameters. Findings from this study substantiate recent guidelines suggesting earlier use of this treatment in intermediate-risk patients with PAH.

Clinical trial number

Not applicable.
Global collaborative research in metabolic and bariatric surgery (GCRMBS): current status and directions for the future
Authors: Pouwels Sjaak , Thaher Omar , Vladimirov Miljana , Felsenreich Daniel Moritz , Pascotto Beniamino , Taha Safwan , Bausch Dirk , Oviedo Rodolfo J.
Published: November 2024

Obesity has been recognized as a chronic disorder by the World Health Organisation (WHO) and was first reported in the Paleolithic age. In the recent years there has not been an international collaborative that facilitates professional cooperation on a worldwide level to increase the output of high-level evidence in the fields of obesity treatment and metabolic and bariatric surgery (MBS). In other surgical and medical fields, international collaborative research networks have shown to increase the quality and amount of treatment-changing evidence. In general, Global Collaborative Research in MBS (GCRMBS) should have the following goals: (1) clinical specialty–based research in obesity and MBS, (2) designing research protocols and studies to generate long-term data in obesity and MBS, (3) understanding the uncommon/rare complications and events associated with obesity and MBS, (4) increasing the number of participants in research and (5) investigating ethical and racial disparities in bariatric research. This review gives an overview of the current status and the future of international collaborative research in MBS.
Eurasian spruce bark beetle detects lanierone using a highly expressed specialist odorant receptor, present in several functional sensillum types
Authors: Yuvaraj Jothi Kumar , Kandasamy Dineshkumar , Roberts Rebecca E. , Hansson Bill S. , Gershenzon Jonathan , Andersson Martin N.
Published: November 2024

Background

Insects detect odours using odorant receptors (ORs) expressed in olfactory sensory neurons (OSNs) in the antennae. Ecologically important odours are often detected by selective and abundant OSNs; hence, ORs with high antennal expression. However, little is known about the function of highly expressed ORs in beetles, since few ORs have been functionally characterized. Here, we functionally characterized the most highly expressed OR (ItypOR36) in the bark beetle Ips typographus L. (Coleoptera, Curculionidae, Scolytinae), a major pest of spruce. We hypothesized that this OR would detect a compound important to beetle fitness, such as a pheromone component. We next investigated the antennal distribution of this OR using single sensillum recordings (SSR) and in situ hybridization, followed by field- and laboratory experiments to evaluate the behavioural effects of the discovered ligand.

Results

We expressed ItypOR36 in HEK293 cells and challenged it with 64 ecologically relevant odours. The OR responded exclusively to the monoterpene-derived ketone lanierone with high sensitivity. Lanierone is used in chemical communication in North American Ips species, but it has never been shown to be produced by I. typographus, nor has it been studied in relation to this species’ sensory physiology. Single sensillum recordings revealed a novel and abundant lanierone-responsive OSN class with the same specific response as ItypOR36. Strikingly, these OSNs were co-localized in sensilla together with seven different previously described OSN classes. Field experiments revealed that low release rates of lanierone inhibited beetle attraction to traps baited with aggregation pheromone, with strongest effects on males. Female beetles were attracted to lanierone in laboratory walking bioassays.

Conclusions

Our study highlights the importance of the so-called ‘reverse chemical ecology’ approach to identify novel semiochemicals for ecologically important insect species. Our discovery of the co-localization pattern involving the lanierone OSN class suggests organizational differences in the peripheral olfactory sense between insect orders. Our behavioural experiments show that lanierone elicits different responses in the two sexes, which also depend on whether beetles are walking in the laboratory or flying in the field. Unravelling the source of lanierone in the natural environment of I. typographus is required to understand these context-dependent behaviours.
Layers of inequality: gender, medicalisation and obstetric violence in Ghana
Authors: Yalley Abena Asefuaba
Published: November 2024

Background

This study explored how gender inequalities in health systems influence women’s experiences of obstetric violence in Ghana. Obstetric violence is recognised as a major public health concern and human rights violation. In particular, it reduces women’s trust and use of health facilities for childbirth, thereby increasing the risks of maternal and neonatal mortality. In Ghana, obstetric violence is pervasive and normalised; yet, little is known about the gendered dynamics of this phenomenon.

Methodology

A qualitative study was conducted in eight public health facilities in Ghana. Specifically, semi-structured interviews were conducted with 30 midwives who work in the maternity units and 35 women who have utilised the obstetric services of the hospitals for childbirth. The midwives and women were selected using the purposive sampling technique. The transcripts of the interviews were coded using NVivo qualitative data analysis software and were thematically analysed. Secondary materials such as existing data on the medical profession in Ghana were utilised to complement the primary data.

Results

The study revealed that there are huge structural inequalities that keep women at the lower cadres of the health system. Five major themes depicting how gender inequalities contribute to women’s experiences of obstetric violence emerged: gender inequality in the medical profession, unequally and heavily tasked, feminisation of midwifery, patriarchal pressures and ideologies, and gender insensitivity in resource provision. These inequalities impact the kind of care midwives provide, which is often characterised by mistreatment and abuse of women during childbirth. The study also discovered that patriarchal ideologies about women and their bodies lead to power and control in the delivery room and violence has become a major instrument of domination and control.

Conclusion

The hierarchical structure of the healthcare profession puts the midwifery profession in a vulnerable position, with negative consequences for maternity care (obstetric violence). The study recommends that gender-responsive approaches that address structural inequalities in health systems, women’s empowerment over their bodies and male involvement in women’s reproductive care are crucial in dealing with obstetric violence in Ghana.
Resistance intensity test (RIT): a novel bioassay for quantifying the level of acaricide resistance in Rhipicephalus microplus ticks
Authors: Jongejan Frans , Berger Laura , Homminga Laura , Hulsebos Iris , Petersen Alita , Ferreira Priscila Teixeira , Reck José , Klafke Guilherme
Published: November 2024

Background

One bioassay for detecting acaricide resistance in livestock ticks is the adult immersion test (AIT), wherein engorged ticks are briefly immersed into a solution of a particular acaricidal compound and examined for mortality, their egg-laying capacity and offspring hatchability in vitro. Usually, the recommended label dose or an established discriminating dose of an acaricide is used to determine high mortality (≥ 95%) of susceptible tick strains. Such a test intends to detect the presence of resistance in a tick population. However, the adult immersion test does not directly translate the bioassay results to the predicted efficacy in the field. In this paper, we used the AIT as an initial screening bioassay supplemented with the resistance intensity test (RIT), a novel larval-based bioassay, wherein the resistance level can be determined and translated to the expected field efficacy. This was done by adopting World Health Organisation (WHO) guidelines for resistance detection in mosquitoes, which combines a 1 × recommended dose with 5 × and 10 × concentrated doses to reveal low, moderate and high resistance intensity, respectively.

Methods

Engorged Rhipicephalus microplus ticks were collected from cattle at six different ranches across Rio Grande do Sul, Brazil, as part of the state’s acaricide resistance surveillance program. Groups of adult ticks from each field collection were subjected to the AIT from each field sample. Additionally, engorged female ticks from each ranch were allowed to lay eggs, and their larval progeny aged 14 to 28 days were then used in the RIT. Deltamethrin and a combination of cypermethrin, chlorpyrifos and piperonyl butoxide were used in both tests, and the results were statistically analysed.

Results

The in vitro efficacy of deltamethrin against adult ticks in the AIT ranged between 8.74% and 25.38%. The corresponding RIT results on their larval progeny indicated a high resistance level. In the immersion test, the in vitro efficacy of the combination of cypermethrin, chlorpyrifos, and piperonyl butoxide against adult ticks ranged between 49.31% and 100%. The corresponding RIT results on their larval progeny indicated a similar response ranging from fully susceptible to low or moderate resistance. The Pearson correlation coefficient (r = 0.883) showed a high correlation between tick mortality at the 1 × recommended concentrations of acaricides in both tests.

Conclusions

The resistance intensity test is a valuable addition to the range of bioassays currently available for detecting acaricide resistance by determining the level of acaricide resistance. This is relevant to whether or not to continue using a particular acaricidal class for controlling cattle ticks.

Graphical Abstract
Breaking down the laughter: an exploration into the linguistic dimensions in stand-up comedy ratings
Authors: Cela Herald , Veit Sarah-Vanessa , Wood Guilherme
Published: November 2024

Despite the pervasive influence of humor in society, comprehensive quantitative studies exploring its dimensions and societal reception are scarce. This study advances the field by analyzing stand-up comedy specials, linking linguistic elements to humor theories and audience ratings, using the Linguistic Inquiry and Word Count (LIWC-22). The analysis explored the presence and association of Affect, Social, and Cognitive dimensions with ratings of standup comedy shows. Statistical analyses entailed using linear mixed models, incorporating comedians as random effects. Female comedians consistently received lower ratings than males, reflecting historical gender biases, while recent shows received lower ratings than older ones, suggesting the challenge of surpassing pioneering works. Negative emotion positively influenced ratings, while negative mood words had a detrimental effect, highlighting the delicate balance in comedic narratives. Social markers significantly predicted ratings, with moralization negatively impacting them, while the use of social referents, particularly female pronouns, improved ratings. These findings offer valuable insights into the linguistic dynamics of stand-up comedy, informing future research and practice in the comedy industry.
Macrophage depletion in inflamed rat knees prevents the activation of synovial mesenchymal stem cells by weakening Nampt and Spp1 signaling
Authors: Kodama Hayato , Endo Kentaro , Sekiya Ichiro
Published: November 2024

Background

Macrophages and mesenchymal stem cells (MSCs) engage in crucial interplay during inflammation and have significant roles in tissue regeneration. Synovial MSCs, as key players in joint regeneration, are known to proliferate together with macrophages in synovitis. However, the crosstalk between synovial MSCs and macrophages remains unclear. In this study, we investigated changes in the activation of synovial MSCs in inflamed rat knees following selective depletion of macrophages with clodronate liposomes.

Methods

Acute inflammation was induced in rat knee joints by injection of carrageenan (day 0). Clodronate liposomes were administered intra-articularly on days 1 and 4 to deplete macrophages, with empty liposomes as a control. Knee joints were collected on day 7 for evaluation by histology, flow cytometry, and colony-forming assays. Concurrently, synovial MSCs were cultured and subjected to proliferation assays, flow cytometry, and chondrogenesis assessments. We also analyzed their crosstalk using single-cell RNA sequencing (scRNA-seq).

Results

Clodronate liposome treatment significantly reduced CD68-positive macrophage numbers and suppressed synovitis. Immunohistochemistry and flow cytometry showed decreased expression of CD68 (a macrophage marker) and CD44 and CD271 (MSC markers) in the clodronate group, while CD73 expression remained unchanged. The number of colony-forming cells per 1000 nucleated cells and per gram of synovium was significantly lower in the clodronate group than in the control group. Cultured synovial MSCs from both groups showed comparable proliferation, surface antigen expression, and chondrogenic capacity. scRNA-seq identified seven distinct synovial fibroblast (SF) subsets, with a notable decrease in the Mki67+ SF subset, corresponding to synovial MSCs, in the clodronate group. Clodronate treatment downregulated genes related to extracellular matrix organization and anabolic pathways in Mki67+ SF. Cell–cell communication analysis revealed diminished Nampt and Spp1 signaling interaction between macrophages and Mki67+ SF and diminished Ccl7, Spp1, and Csf1 signaling interaction between Mki67+ SF and macrophages in the clodronate group. Spp1 and Nampt promoted the proliferation and/or chondrogenesis of synovial MSCs.

Conclusions

Macrophage depletion with clodronate liposomes suppressed synovitis and reduced the number and activity of synovial MSCs, highlighting the significance of macrophage-derived Nampt and Spp1 signals in synovial MSC activation. These findings offer potential therapeutic strategies to promote joint tissue regeneration by enhancing beneficial signals between macrophages and synovial MSCs.
Evaluation of pulmonary artery pressure, blood indices, and myocardial microcirculation in rats returning from high altitude to moderate altitude
Authors: Yan Chunlong , Ma Jinfeng , Tian Dengfeng , Yan Tingjun , Zhang Chenhong , Zhang Fengjuan , Zhao Yuchun , Fu Shihan , Zhang Qiang , Xia Mengxue , Li Yue , Sun Yanqiu
Published: November 2024

Background

To investigate changes in pulmonary artery pressure (PAP), blood indices, and myocardial microcirculation in rats returning from high altitude (HA) to moderate altitude (MA).

Methods

Forty 4-week-old male Sprague-Dawley rats were randomly divided into four groups with ten rats in each group. One group was transported to the MA area (MA-group), and the other three groups were transported to HA (HA-group-A, HA-group-B, and HA-group-C). After 28 weeks of age, the rats from the HA area were transported to the MA area for 0 days, 10 days, and 20 days, respectively. PAP, routine blood tests, and computed tomography myocardial perfusion indices were measured.

Results

Compared with the MA-group, the body weight of HA-groups decreased (p < 0.05), and PAP in HA-group-A and HA-group-B increased (p < 0.05). In the HA groups, PAP initially increased and then decreased. Compared with the MA-group, red blood cells (RBC), hemoglobin (HGB), and hematocrit (HCT) of rats in HA-group-A increased (p < 0.05). Compared with the HA-group-A, RBC, HGB, and HCT of HA-group-B gradually decreased (p < 0.05) while MCV decreased (p < 0.05), and PLT of HA-group-C increased (p < 0.05). Compared with the MA group, blood flow (BF) and blood volume (BV) of the HA-group-A decreased (p < 0.05). Compared with the HA-group-A, TTP increased first and then decreased (p < 0.05), and BF and BV increased gradually (p < 0.05). Pathological results showed that myocardial fiber arrangement was disordered, and cell space widened in the HA group.

Conclusion

PAP, blood parameters, and myocardial microcirculation in rats returning from high to MA exhibited significant changes.

Relevance statement

This study provides an experimental basis for understanding the physiological and pathological mechanisms during the process of deacclimatization to HA and offers new insights for the prevention and treatment of deacclimatization to HA syndrome.

Key Points

Forty rats were raised in a real plateau environment.

Myocardial microcirculation was detected by CT myocardial perfusion imaging.

The PAP of the unacclimated rats increased first and then decreased.

The myocardial microcirculation of the deacclimated rats showed hyperperfusion changes.

Graphical Abstract
The inverse correlation between serum zinc levels and depression severity in Egyptian adolescent students: a case–control study
Authors: Abdelmoneam Amany H. , Khafagy Ghada M. , Elbeh Khaled A. , Hasan Marwa D. A.
Published: November 2024

Background

Depression significantly impacts adolescents’ quality of life, with zinc deficiency suggested as a contributing factor. This study aimed to explore the relationship between serum zinc levels and depression among Egyptian adolescent students, hypothesizing an inverse correlation between zinc levels and depression severity. In a case–control study, 358 students from two randomly selected secondary schools in (blind to peer review) Governorate, Egypt, were screened for depression using the Arabic version of the Beck Depression Inventory. Based on the screening, 86 cases with depression and 86 matched controls were identified. Serum zinc levels were measured, and socio-economic status (SES) was assessed using the Gilany SES questionnaire. Statistical analysis was conducted using SPSS 26.0, employing t-tests, ANOVA, and Chi-square tests, with significance set at p < 0.05.

Results

The study found a statistically significant difference in serum zinc levels between depressed and non-depressed groups, with depressed participants exhibiting lower zinc levels. Furthermore, a significant negative correlation was observed between depression severity and zinc levels, even after adjusting for age, sex, and SES. The predictive value of zinc levels in diagnosing depression demonstrated a sensitivity of 64% and specificity of 60.5%.

Conclusions

The findings confirm the hypothesis of an inverse relationship between serum zinc levels and depression among adolescents, underscoring the potential role of zinc in depression's pathophysiology and its relevance in preventive and therapeutic strategies. Future research should investigate the mechanisms underlying this association and evaluate zinc supplementation's efficacy in depression management.
Association between estrogen receptor-1 gene polymorphisms (rs1801132, rs2228480, rs2234693) and migraine susceptibility: an unveiling association through a comprehensive meta-analysis
Authors: Stephen Sharon Benita , Saravanan Jayakanthan , Chandrashekar Gurudeva , Subbaraj Gowtham Kumar
Published: November 2024

Introduction

This meta-analysis aims to find the relationship of ESR-1 gene polymorphisms (rs1801132, rs2228480, and rs2234693) with migraine risk among Caucasian and Asian populations.

Methods

To perform the present meta-analysis a search was carried out across several databases. The data obtained from the databases were analysed statistically using Review Manager 5.4 and MetaGenyo software. A total of 20 case–control studies were selected among them 12 articles were consisting of seven articles belonging to rs1801132, five articles belonging to rs2228480, and six articles belonging to rs2234693 for revealing the relationship between ESR-1 gene polymorphisms (rs1801132, rs2228480, and rs2234693) and migraine risk. The protocol for the present meta-analysis was registered (PROSPERO ID Number: 441920).

Results

A total of 20 articles were included in this meta-analysis. According to the findings of this study, people with ESR-1 (rs1801132, rs2228480, and rs2234693 did not show an association with migraine risk in the allelic, recessive, dominant, and over-dominant models.

Conclusion

However, the results from the present meta-analysis are conflicting from the previously meta-analysis reports. Further research is needed to unravel the complex genetic basis of this debilitating condition.
Increased atrial, ventricular, and total epicardial fat volumes in non-valvular atrial fibrillation: a CMR DIXON study
Authors: Mohammad Abdelaziz Hanaa Mahmoud , Salem Salem Reham Shaaban , Fathy Waly Hesham Mohammed , Abdul Lateef Maaty Abdul Razek , Fouda Nehad Samy , Abu-El Fadl Hend Gamal
Published: November 2024

Background

Atrial fibrillation (AF) is the most prevalent persistent arrhythmia in the heart. Several clinical conditions are known to predispose AF development including obesity. Impressive data suggests that local epicardial fat depots play an important role in AF development. When determining total body fat, magnetic resonance imaging (MRI) is often regarded as the gold standard. It is also a viable option for identifying and measuring epicardial fat. We aimed to evaluate the relation between epicardial fat volume measured by cardiac MRI and the presence of non-valvular atrial fibrillation.

Subjects and methods

The study is an observational comparative case–control study conducted on 31 patients with AF and a comparative group of 31 individuals with matched age, sex, and other risk factors who had never experienced AF. Each participant was subjected to full history taking, a detailed history of AF, and cardiac MRI. CMR Dixon sequence was used and manually processed for epicardial fat volume quantification, then atrial, ventricular and total epicardial fat volumes were compared in the 2 groups.

Results

There is a statistically significant difference between AF case group vs control group with higher atrial, ventricular, and total epicardial fat volume in AF case group (193.9 ± 68.0 ml, 248.2 ± 55.5 ml, 442.1 ± 94.6 ml) vs control (91.4 ± 34.0 ml, 134.5 ± 44.4 ml, 225.9 ± 69.7 ml), respectively.

Conclusion

Our study reveals a higher epicardial fat volume in AF patients compared to healthy controls, suggesting epicardial fat as a potential risk factor for non-valvular AF.
Breast metastasis from primary renal cell carcinoma, ten years after nephrectomy
Authors: Fares Nevien Ragae , Hosny Ghada Ezzat
Published: November 2024

Background

Metastasis to the breast from non-breast tumors is uncommon, and breast metastasis from renal cell carcinoma (RCC) is extremely rare. Despite the high incidence of primary breast cancer, it is important to consider metastasis from other cancers in patients with a history of malignancies.

Case presentation

A 60-year-old female with a history of right nephrectomy for RCC 10 years prior, who had missed follow-up for 7 years, presented with hepatic metastases that had been under treatment for the past 2 years. During routine follow-up, a small lesion in her right breast was incidentally found on chest-computed tomography. She was referred for further imaging, and mammography and ultrasound revealed a BI-RADS 3 lesion. Six months later, the lesion had grown rapidly, and a follow-up CT showed a tripling in size along with an increase in the size and number of hepatic metastases. A biopsy of the breast lesion confirmed it as metastatic RCC.

Conclusions

This case is unusual due to the rare site of metastatic spread. Physicians should be aware of considering metastasis when new breast lesions appear in patients with a history of RCC. A biopsy should be considered essential in such cases to ensure accurate diagnosis.
Multifunctional approach with LHRH-mediated PLGA nanoconjugate for site-specific codelivery of curcumin and BCL2 siRNA in mice lung cancer
Authors: Lahan Madhuchandra , Saikia Trideep , Dutta Kalpajit , Baishya Rinku , Bharali Alakesh , Baruah Sunayana , Bharadwaj Rituraj , Medhi Subhash , Sahu Bhanu P.
Published: November 2024

Background

Lung cancer remains a leading cancer type, but current chemotherapy is limited by issues including poor drug delivery, toxicity, and resistance. To address these challenges, we developed a novel PLGA-PEG-LHRH (PPL) nanoconjugate system for improved drug delivery. Curcumin, known for its anticancer and P-gp inhibition properties, was co-loaded with bcl2siRNA (bclsR) to inhibit the bcl2 protein, thus overcoming both resistance mechanisms.

Results

The PPL conjugate was successfully synthesized and characterized using FTIR, 1H NMR, XRD, XPS and BCA assay. Curcumin and bclsR-loaded PLGA nanoemulsions were prepared by double emulsion solvent evaporation method and characterized. The optimized nanoconjugate had size of 179 ± 16 nm, favorable zeta potential, high drug entrapment, and was confirmed via TEM. Controlled release studies indicated 83% drug release within 24 h. In vitro studies revealed significant cytotoxicity against A549 lung cancer cells, with the nanoconjugate showing IC50 of 8.24 µg/mL compared to 21.26 µg/mL for plain curcumin. Enhanced cellular uptake and effective targeting of A549 cells were observed. Molecular analyses demonstrated significant downregulation of MDR1 and Bcl2 RNA and protein expression, highlighting the nanoconjugates' ability to suppress resistance mechanisms. Pharmacokinetic studies in Wistar rats showed superior plasma drug concentrations, half-life, and AUC for the nanoconjugate versus pure drug suspension. Biodistribution studies showed increased drug accumulation in the lungs. In vivo efficacy studies in Balb/c mice demonstrated higher tumor inhibition ratios for CUR-siRNA PPL NPs (66.89%) and CUR-PPL NPs (59.84%) which was further confirmed with TNFα and p53 levels in blood. Histopathological studies showed good healing in the CUR-siRNA PPL NP- and CUR-PPL NP-treated mice compared to suspension.

Conclusion

From the study, it may be concluded that the PPL nanoconjugate system, loaded with curcumin and bcsR, can be potentially effective, multifunctional targeted approach for lung cancer therapy.

Graphical Abstract
Familial Glucocorticoid Deficiency in Twins: A Novel Mutation and Impact on Social Determinants of Health Outcome
Authors: Wei Wei , Shaibi Gabriel Q , Cooper-Hastings Laura , Newbern Dorothee
Published: November 2024

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder that causes isolated glucocorticoid deficiency. Here, we report on 22-month-old twin females of Native American ancestry who presented within 1 week of each other in adrenal crisis and were ultimately diagnosed with FGD because of a novel pathogenic variant, c1924G>T (p. Gly642*), in the nicotinamide nucleotide transhydrogenase (NNT) gene. This is the first report of FGD in a Native American population. The process of reaching the final diagnosis was complicated by several social determinants including geographic rurality, access to subspecialists, financial constraints, and challenges obtaining approval for genetic testing despite having insurance. Concerted efforts by the family, the local pediatrician, the Indian Health Service, and our tertiary care pediatric health system were required to reach the final diagnosis and develop an appropriate plan of care for the patients.
ImmunoCellCycle-ID – a high-precision immunofluorescence-based method for cell cycle identification
Authors: Chen Yu-Lin , Chen Yu-Chia , Suzuki Aussie
Published: November 2024

The cell cycle is a fundamental process essential for cell proliferation, differentiation and development. It consists of four major phases: G1, S, G2 and M. These phases collectively drive the reproductive cycle and are meticulously regulated by various proteins that play crucial roles in both the prevention and progression of cancer. Traditional methods for studying these functions, such as flow cytometry, require a substantial number of cells to ensure accuracy. In this study, we have developed a user-friendly immunofluorescence-based method for identifying cell cycle stages, providing single-cell resolution and precise identification of G1, early/mid S, late S, early/mid G2, late G2, and each sub-stage of the M phase using fluorescence microscopy called ImmunoCellCycle-ID. This method provides high-precision cell cycle identification and can serve as an alternative to, or in combination with, traditional flow cytometry to dissect detailed sub-stages of the cell cycle in a variety of cell lines.
Efficacy of combined tympanostomy tube insertion and adenoidectomy in the treatment of otitis media with effusion in children
Authors: Weng Yongcai , Wu Yong , Hao Chunhua , Chu Yanjun , Qian Xiong
Published: November 2024

Objective: To assess the efficacy of combined tympanostomy tube insertion (TTI) and adenoidectomy (Ad) versus Ad alone in the treatment of otitis media with effusion (OME) in children.
Methods: Clinical data of 145 children with OME who underwent surgical treatment in Jiaxing University Affiliated TCM Hospital from January 2022 to November 2023, were retrospectively analyzed. Patients were grouped based on whether or not Ad was performed with TTI: children who underwent Ad alone were grouped as Ad group (n=71), and children who underwent a combined TTI and Ad were grouped as TTI+Ad group (n=74). Clinical efficacy, clinical indicators (recovery of hearing, disappearance of tinnitus, eardrum healing, and disappearance time of middle ear effusion), serum levels of inflammatory factors, recurrence, and incidence of complications were compared between the two groups.
Results: Combined TTI+Ad resulted in a significantly better therapeutic effect three months after the surgery compared Ad alone (P<0.05). Combined treatment was associated with significantly shorter time needed for hearing recovery, disappearance of tinnitus, eardrum healing, and disappearance of middle ear effusion (P<0.05). Combined procedure significantly lowered levels of inflammatory factors (P<0.05), and was associated with lower postoperative recurrence rate (P<0.05) compared to Ad alone. There was no significant difference in the incidence of complications between the two methods of surgical OME treatment (P>0.05).
Conclusions: Compared to Ad alone, combined TTI+Ad treatment is equally safe and more effective in the treatment of OME in children. This surgical approach is associated with reduced local inflammatory reactions and lower recurrence rate.
doi: https://doi.org/10.12669/pjms.40.11.10713
How to cite this: Weng Y, Wu Y, Hao C, Chu Y, Qian X. Efficacy of combined tympanostomy tube insertion and adenoidectomy in the treatment of otitis media with effusion in children. Pak J Med Sci. 2024;40(11):2577-2582. doi: https://doi.org/10.12669/pjms.40.11.10713
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Efficacy of Risk Prevention Management Based on Heinrich’s Law in Nursing Care of Elderly Patients Undergoing Digestive Endoscopy
Authors: Huang Li , Zhu Sujuan , Chu Jing , Zhong Suqin
Published: November 2024

Objective: To study the efficacy of risk prevention management based on Heinrich’s Law in nursing care of elderly patients undergoing digestive endoscopy (DE).
Methods: In this retrospective study clinical data of 182 elderly patients who underwent DE in Hai’an Traditional Chinese Medicine Hospital from April 2021 to September 2023 were collected. A total of 89 patients received routine nursing care (Control-group), and 93 patients received risk prevention management based on Heinrich’s Law in addition to the routine nursing (Observation-group). Vital signs indicators, stress response levels, Boston bowel preparation score, State-Trait Anxiety Inventory-State (STAI-S), State-Trait Anxiety Inventory-Trait (STAI-T) score, incidence of adverse events, and nursing satisfaction were assessed and compared between the two groups.
Results: Vital signs of the patients in the Observation-group were more stable than those of the Control-group 15 minutes and 30 minutes after the endoscopic inspection (P<0.05). After the procedure, stress response of the Observation-group was significantly milder than that of the Control-group (P<0.05). The Boston bowel preparation score in the Observation-group was significantly higher (P<0.05), while STAI-S and STAI-T scores were significantly lower than those in the Control-group (P<0.05). Implementing risk prevention management based on Heinrich’s Law was associated with significantly lower incidence of adverse events (P<0.05), and markedly higher nursing satisfaction (P<0.05).
Conclusions: Adopting a risk prevention management model based on Heinrich’s Law for elderly patients undergoing DE can stabilize vital signs, alleviate anxiety, reduce the risk of adverse events, and increase patient satisfaction in this vulnerable group.
doi: https://doi.org/10.12669/pjms.40.11.10744
How to cite this: Huang L, Zhu S, Chu J, Zhong S. Efficacy of Risk Prevention Management Based on Heinrich’s Law in Nursing Care of Elderly Patients Undergoing Digestive Endoscopy. Pak J Med Sci. 2024;40(11):2502-2507.  doi: https://doi.org/10.12669/pjms.40.11.10744
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.