bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers to proper maternal referral system in selected health facilities in Eastern Ethiopia: a qualitative study
Authors: Mengist Betelhem , Semahegn Agumasie , Yibabie Shegaye , Amsalu Bezabih , Tura Abera Kenay
Published: March 2024

Background

Appropriate maternal referral system plays an essential role in curbing maternal mortality. Although the occurrence of obstetric complications is often unpredictable, addressing bottlenecks of the referral system is crucial to facilitate the women to have access to timely lifesaving interventions. Nonetheless, little is known about the barriers to maternal referral system in the eastern Ethiopia. Therefore, this study aimed to explore the barriers to maternal referral system at selected referral hospitals in eastern Ethiopia.

Methods

Key informant interviews and in-depth interviews were conducted among purposively selected respondents who had a role in maternal referral processes. A total of 12 key informants that comprised of liaison officers, healthcare providers and three in-depth interviews with referred women were conducted. Semi-structured interview guide was developed and used to facilitate the interviews. All the interviews were tape recorded, complemented by note taking. Then audio recorded interviews were transcribed as per verbatim and imported to NVivo for coding and merging. The data were thematically synthesized.

Results

The study identified a range of barriers that affect the maternal referral system in Eastern Ethiopia. The main barriers are grouped into three domains, such as: communication, transportation, and healthcare system. The most commonly reported barriers were lack of pre-referral communication and feedback, using informal communication, incomplete referral forms, poor ambulance service including misuse of ambulances, lack of skilled healthcare escort and lack of medical equipment at emergency, unnecessary self-referrals, poor referral skills and limited number of health professions.

Conclusions

The maternal referral system is overwhelmingly affected by lack of skill, logistics (referral form), misuse of available ambulance, poor communication, and limited seeking of feedback. Regular consultative meeting with relevant stakeholders and uptake of feedback are crucial to improve referral communication, proper use of ambulance and building capacity of health workforce about referral are essential to improve maternal referral system.
Green fabrication of ZnO nanoparticles via spirulina platensis and its efficiency against biofilm forming pathogens
Authors: Ahmed Nashwa A. , Othman Amal S.
Published: March 2024

Excessive consumption of antibiotics is considered one of the top public health threats, this necessitates the development of new compounds that can hamper the spread of infections. A facile green technology for the biosynthesis of Zinc oxide nanoparticles (ZnO NPs) using the methanol extract of Spirulina platensis as a reducing and stabilizing agent has been developed. A bunch of spectroscopic and microscopic investigations confirmed the biogenic generation of nano-scaled ZnO with a mean size of 19.103 ± 5.66 nm. The prepared ZnO NPs were scrutinized for their antibacterial and antibiofilm potentiality, the inhibition zone diameters ranged from 12.57 ± 0.006 mm to 17.33 ± 0.006 mm (at 20 µg/mL) for a variety of Gram-positive and Gram-negative pathogens, also significant eradication of the biofilms formed by Staphylococcus aureus and Klebsiella pneumoniae by 96.7% and 94.8% respectively was detected. The free radical scavenging test showed a promising antioxidant capacity of the biogenic ZnO NPs (IC50=78.35 µg/mL). Furthermore, the anti-inflammatory role detected using the HRBCs-MSM technique revealed an efficient stabilization of red blood cells in a concentration-dependent manner. In addition, the biogenic ZnO NPs have significant anticoagulant and antitumor activities as well as minimal cytotoxicity against Vero cells. Thus, this study offered green ZnO NPs that can act as a secure substitute for synthetic antimicrobials and could be applied in numerous biomedical applications.
Non-ribosomal peptide synthetase (NRPS)-encoding products and their biosynthetic logics in Fusarium
Authors: Huang Ziwei , Zhu Wangjie , Bai Yifan , Bai Xuelian , Zhang Huawei
Published: March 2024

Fungal non-ribosomal peptide synthetase (NRPS)-encoding products play a paramount role in new drug discovery. Fusarium, one of the most common filamentous fungi, is well-known for its biosynthetic potential of NRPS-type compounds with diverse structural motifs and various biological properties. With the continuous improvement and extensive application of bioinformatic tools (e.g., anti-SMASH, NCBI, UniProt), more and more biosynthetic gene clusters (BGCs) of secondary metabolites (SMs) have been identified in Fusarium strains. However, the biosynthetic logics of these SMs have not yet been well investigated till now. With the aim to increase our knowledge of the biosynthetic logics of NPRS-encoding products in Fusarium, this review firstly provides an overview of research advances in elucidating their biosynthetic pathways.
Characterization of the biological and transcriptomic landscapes of bone marrow-derived mesenchymal stem cells in patients with multiple myeloma
Authors: Lu Yu , Zheng Chaohui , Zhang Wenxia , Liu Xuan , Zhou Ziwei , Wang Zhenzhen , Hua Huan , Song Zhengrong , Zhang Xuejun , Liu Shuyi , Zhang Leisheng , Wang Fuxu
Published: March 2024

Background

Mesenchymal stem/stromal cells (MSCs) have been acknowledged as the most important stromal cells in the bone marrow (BM) microenvironment for physiologic hematopoiesis and the concomitant hematologic malignancies. However, the systematic and detailed dissection of the biological and transcriptomic signatures of BM-MSCs in multiple myeloma (MM) are largely unknown.

Methods

In this study, we isolated and identified BM-MSCs from 10 primary MM patients and 10 healthy donors (HD). On the one hand, we compared the multifaceted biological characteristics of the indicated two BM-MSCs, including biomarker expression pattern, multilineage differentiation potential, stemness and karyotyping, together with the cellular vitality and immunosuppressive property. On the other hand, we took advantage of RNA-SEQ and bioinformatics analysis to verify the similarities and differences at the transcriptomic level between MM-MSCs and HD-MSCs.

Results

As to biological phenotypes and biofunctions, MM-MSCs revealed conservation in immunophenotype, stemness and differentiation towards adipocytes and chondrocytes with HD-MSCs, whereas with impaired osteogenic differentiation potential, cellular vitality and immunosuppressive property. As to transcriptomic properties, MM-MSCs revealed multidimensional alterations in gene expression profiling and genetic variations.

Conclusions

Overall, our date systematic and detailed reflected the multifaceted similarities and variations between MM-MSCs and HD-MSCs both at the cellular and molecular levels, and in particular, the alterations of immunomodulation and cellular viability of MM-MSCs, which wound benefit the further exploration of the pathogenesis and new drug application (NDA) of multiple myeloma from the view of BM-MSCs.
An evaluation of LLIN physical integrity and population attitudes towards net use, care and handling during the Magude project in southern Mozambique
Authors: Alafo Celso , Montoya Lucia Fernandez , Martí-Soler Helena , Máquina Mara , Malheia Arlindo , Sacoor Charfudin , Abílio Ana Paula , Marrenjo Dulcisaria , Cuamba Nelson , Galatas Beatriz , Aide Pedro , Saúte Francisco , Paaijmans Krijn P.
Published: March 2024

Background

The Magude Project assessed the feasibility of eliminating malaria in Magude district, a low transmission setting in southern Mozambique, using a package of interventions, including long-lasting insecticidal nets (LLINs). As the efficacy of LLINs depends in part on their physical integrity, this metric was quantified for Olyset® Nets post mass-distribution, in addition to net use, care and handling practices and other risk factors associated with net physical integrity.

Methods

Nets were collected during a cross-sectional net evaluation, nine months after the Magude project commenced, which was 2 years after the nets were distributed by the National Malaria Control Programme (NMCP). The physical integrity of the nets was assessed by counting and sizing the holes at different positions on each net. A structured questionnaire was administered to assess how the selected net was used and treated (care, wash and repair). Net bio-efficacy was assessed following the standard World Health Organization (WHO) cone bioassay procedures.

Results

Out of the 170 Olyset® Nets included in the analysis, 63.5% had been used the night before. The main reason for not using a net was the notion that there were no mosquitoes present. The average number of people using each net was 1.79. Two thirds of the nets had only been washed once or twice since distribution. Most nets (80.9%) were holed and 18% were torn, but none of the risk factors were significantly associated with net integrity, except for presence of mice in the household. Less than half of the participants noticed holes in holed nets, and of those only 38.6% attempted to repair those. None of the six nets that were tested for bio-efficacy passed the WHO threshold of 80% mosquito mortality.

Conclusion

Overall the majority of Olyset® Nets were in serviceable condition two years post-distribution, but their insecticidal effect may have been lost. This study—together with previous evidence on suboptimal access to and use of LLINs in Magude district—highlights that LLINs as an intervention could have been optimized during the Magude project to achieve maximum intervention impact.
Characterizing and forecasting neoantigens-resulting from MUC mutations in COAD
Authors: Chen Min , Zhang Xin , Ming Zihe , Lingyu  , Feng Xiaorong , Han Zhenguo , An Han-Xiang
Published: March 2024

Background

The treatment for colon adenocarcinoma (COAD) faces challenges in terms of immunotherapy effectiveness due to multiple factors. Because of the high tumor specificity and immunogenicity, neoantigen has been considered a pivotal target for cancer immunotherapy. Therefore, this study aims to identify and predict the potential tumor antigens of MUC somatic mutations (MUCmut) in COAD.

Methods

Three databases of TCGA, TIMER2.0, and cBioPortal were used for a detailed evaluation of the association between MUCmut and multi-factors like tumor mutation burden (TMB), microsatellite instability (MSI), prognosis, and the tumor microenvironment within the context of total 2242 COAD patients. Next, TSNAdb and the differential agretopicity index (DAI) were utilized to predict high-confidence neopeptides for MUCmut based on 531 COAD patients’ genomic information. DAI was calculated by subtraction of its predicted HLA binding affinity of the MUCmut peptide from the corresponding wild-type peptide.

Results

The top six mutation frequencies (14 to 2.9%) were from MUC16, MUC17, MUC5B, MUC2, MUC4 and MUC6. COAD patients with MUC16 and MUC4 mutations had longer DFS and PFS. However, patients with MUC13 and MUC20 mutations had shorter OS. Patients with the mutation of MUC16, MUC5B, MUC2, MUC4, and MUC6 exhibited higher TMB and MSI. Moreover, these mutations from the MUC family were associated with the infiltration of diverse lymphocyte cells and the expression of immune checkpoint genes. Through TSNAdb 1.0/NetMHCpan v2.8, 452 single nucleotide variants (SNVs) of MUCmut peptides were identified. Moreover, through TSNAdb2.0/NetMHCpan v4.0, 57 SNVs, 1 Q-frame shift (TS), and 157 short insertions/deletions (INDELs) of MUCmut were identified. Finally, 10 high-confidence neopeptides of MUCmut were predicted by DAI.

Conclusions

Together, our findings establish the immunogenicity and therapeutic potential of mutant MUC family-derived neoantigens. Through combining the tools of TSNAdb and DAI, a group of novel MUCmut neoantigens were identified as potential targets for immunotherapy.
Cognitive decline, Aβ pathology, and blood–brain barrier function in aged 5xFAD mice
Authors: Nehra Geetika , Promsan Sasivimon , Yubolphan Ruedeemars , Chumboatong Wijitra , Vivithanaporn Pornpun , Maloney Bryan J. , Lungkaphin Anusorn , Bauer Bjoern , Hartz Anika M. S.
Published: March 2024

Background

Patients with Alzheimer's disease (AD) develop blood–brain barrier dysfunction to varying degrees. How aging impacts Aβ pathology, blood–brain barrier function, and cognitive decline in AD remains largely unknown. In this study, we used 5xFAD mice to investigate changes in Aβ levels, barrier function, and cognitive decline over time.

Methods

5xFAD and wild-type (WT) mice were aged between 9.5 and 15.5 months and tested for spatial learning and reference memory with the Morris Water Maze (MWM). After behavior testing, mice were implanted with acute cranial windows and intravenously injected with fluorescent-labeled dextrans to assess their in vivo distribution in the brain by two-photon microscopy. Images were processed and segmented to obtain intravascular intensity, extravascular intensity, and vessel diameters as a measure of barrier integrity. Mice were sacrificed after in vivo imaging to isolate brain and plasma for measuring Aβ levels. The effect of age and genotype were evaluated for each assay using generalized or cumulative-linked logistic mixed-level modeling and model selection by Akaike Information Criterion (AICc). Pairwise comparisons were used to identify outcome differences between the two groups.

Results

5xFAD mice displayed spatial memory deficits compared to age-matched WT mice in the MWM assay, which worsened with age. Memory impairment was evident in 5xFAD mice by 2–threefold higher escape latencies, twofold greater cumulative distances until they reach the platform, and twice as frequent use of repetitive search strategies in the pool when compared with age-matched WT mice. Presence of therd1allele worsened MWM performance in 5xFAD mice at all ages but did not alter the rate of learning or probe trial outcomes. 9.5-month-old 15.5-month-old 5xFAD mice had twofold higher brain Aβ40and Aβ42levels (p < 0.001) and 2.5-fold higher (p = 0.007) plasma Aβ40levels compared to 9.5-month-old 5xFAD mice. Image analysis showed that vessel diameters and intra- and extravascular dextran intensities were not significantly different in 9.5- and 15.5-month-old 5xFAD mice compared to age-matched WT mice.

Conclusion

5xFAD mice continue to develop spatial memory deficits and increased Aβ brain levels while aging. Given in vivo MP imaging limitations, further investigation with smaller molecular weight markers combined with advanced imaging techniques would be needed to reliably assess subtle differences in barrier integrity in aged mice.
Impact of sitting at work on musculoskeletal complaints of German workers - results from the study on mental health at work (S-MGA)
Authors: Dang T. H. An , Starke Karla Romero , Liebers Falk , Burr Hermann , Seidler Andreas , Hegewald Janice
Published: March 2024

Introduction

Sedentary behavior (including prolonged sitting) is a form of physical inactivity that has a negative impact on health, possibly including musculoskeletal complaints (MSCs). The purpose of this study was to determine the extent to which time spent sitting at work is associated with the one-year prevalence of MSCs in the neck, shoulder, upper back/thoracic spine, and lower back among workers from the Study of Mental Health in the Workplace (S-MGA). In addition, the study also examined whether leisure time, physical activity, and sex modify the relationship between occupational sitting and MSCs.

Methods

For this analysis, we used the S-MGA, a 5-year prospective study in Germany. The S-MGA is a nationwide representative employee cohort study with a baseline survey in 2012 and a follow-up survey in 2017. Sitting at work was measured using a question asked at baseline. The Nordic Musculoskeletal Questionnaire was used to determine the one-year prevalence of MSCs in the neck, shoulder, upper back, and lower back pain (yes/no). The assessment of MSCs was only conducted at the 2017 follow-up. Adjusted Poisson regression models were used to determine the association of baseline level of weekly hours spent sitting at work with MSCs during follow-up. In addition to unadjusted models, models were adjusted for demographic (age, sex, body mass index and occupational skill level), occupational (heavy lifting at work), psychological disorders and lifestyle factors (smoking status and leisure time physical activity), as well as preexisting musculoskeletal conditions reported at baseline. To examine whether the relationship between sitting time and pain was modified by sex and leisure time physical activity, the models were stratified for both these variables.

Results

Among the participants analyzed (n = 2,082), 49.8% were male, while 50.2% were female, and more than 60% of the study population spent over half of their working hours in a sitting position. Exposure to increased sitting at work reported at baseline was not consistently associated with 12-month prevalence of MSCs in the upper body at follow-up. However, differences in the association between occupational sitting and MSCs were dependent on the intensity of leisure time physical activity. Prevalence ratios (PRs) indicated an increased prevalence of MSC in the neck (PR = 1.46; 95% CI = 1.18–1.80) and shoulder (PR = 1.30; 95% CI = 1.03–1.64) in workers without leisure time physical activity who spent 25 to < 35 weekly working hours sitting.

Discussion

These findings suggest that leisure time physical activity interacts with the relationship between sitting at work and MSCs. The relationship between sitting at work and musculoskeletal pain needs further investigation, but we found indications that leisure time physical activity may counter the effects of sitting at work.
HDGFL2 cryptic proteins report presence of TDP-43 pathology in neurodegenerative diseases
Authors: Calliari Anna , Daughrity Lillian M. , Albagli Ellen A. , Castellanos Otero Paula , Yue Mei , Jansen-West Karen , Islam Naeyma N. , Caulfield Thomas , Rawlinson Bailey , DeTure Michael , Cook Casey , Graff-Radford Neill R. , Day Gregory S. , Boeve Bradley F. , Knopman David S. , Petersen Ronald C. , Josephs Keith A. , Oskarsson Björn , Gitler Aaron D. , Dickson Dennis W. , Gendron Tania F. , Prudencio Mercedes , Ward Michael E. , Zhang Yong-Jie , Petrucelli Leonard
Published: March 2024

This letter demonstrates the potential of novel cryptic proteins resulting from TAR DNA-binding protein 43 (TDP-43) dysfunction as markers of TDP-43 pathology in neurodegenerative diseases.
Role of polyphenols in remodeling the host gut microbiota in polycystic ovary syndrome
Authors: Zhou Ping , Feng Penghui , Liao Baoying , Fu Lin , Shan Hongying , Cao Canhui , Luo Renxin , Peng Tianliu , Liu Fenting , Li Rong
Published: March 2024

Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic condition in women of childbearing age and a major cause of anovulatory infertility. The pathophysiology of PCOS is complex. Recent studies have reported that apart from hyperandrogenism, insulin resistance, systemic chronic inflammation, and ovarian dysfunction, gut microbiota dysbiosis is also involved in PCOS development and may aggravate inflammation and metabolic dysfunction, forming a vicious cycle. As naturally occurring plant secondary metabolites, polyphenols have been demonstrated to have anticancer, antibacterial, vasodilator, and analgesic properties, mechanistically creating putative bioactive, low-molecular-weight metabolites in the human gut. Here, we summarize the role of gut microbiota dysbiosis in the development of PCOS and demonstrate the ability of different polyphenols - including anthocyanin, catechins, and resveratrol - to regulate gut microbes and alleviate chronic inflammation, thus providing new insights that may assist in the development of novel therapeutic strategies to treat women with PCOS.
Unraveling the role of HIF-1α in sepsis: from pathophysiology to potential therapeutics—a narrative review
Authors: Ruan Hang , Zhang Qin , Zhang You-ping , Li Shu-sheng , Ran Xiao
Published: March 2024

Sepsis is characterized by organ dysfunction resulting from a dysregulated inflammatory response triggered by infection, involving multifactorial and intricate molecular mechanisms. Hypoxia-inducible factor-1α (HIF-1α), a notable transcription factor, assumes a pivotal role in the onset and progression of sepsis. This review aims to furnish a comprehensive overview of HIF-1α's mechanism of action in sepsis, scrutinizing its involvement in inflammatory regulation, hypoxia adaptation, immune response, and organ dysfunction. The review encompasses an analysis of the structural features, regulatory activation, and downstream signaling pathways of HIF-1α, alongside its mechanism of action in the pathophysiological processes of sepsis. Furthermore, it will delve into the roles of HIF-1α in modulating the inflammatory response, including its association with inflammatory mediators, immune cell activation, and vasodilation. Additionally, attention will be directed toward the regulatory function of HIF-1α in hypoxic environments and its linkage with intracellular signaling, oxidative stress, and mitochondrial damage. Finally, the potential therapeutic value of HIF-1α as a targeted therapy and its significance in the clinical management of sepsis will be discussed, aiming to serve as a significant reference for an in-depth understanding of sepsis pathogenesis and potential therapeutic targets, as well as to establish a theoretical foundation for clinical applications.

Graphical Abstract
Systematic immune cell dysregulation and molecular subtypes revealed by single-cell RNA-seq of subjects with type 1 diabetes
Authors: Honardoost Mohammad Amin , Adinatha Andreas , Schmidt Florian , Ranjan Bobby , Ghaeidamini Maryam , Arul Rayan Nirmala , Gek Liang Lim Michelle , Joanito Ignasius , Xiao Xuan Lin Quy , Rajagopalan Deepa , Qi Mok Shi , Hwang You Yi , Larbi Anis , Khor Chiea Chuen , Foo Roger , Boehm Bernhard Otto , Prabhakar Shyam
Published: March 2024

Background

Type 1 diabetes mellitus (T1DM) is a prototypic endocrine autoimmune disease resulting from an immune-mediated destruction of pancreatic insulin-secreting $$\beta$$
β
 cells. A comprehensive immune cell phenotype evaluation in T1DM has not been performed thus far at the single-cell level.

Methods

In this cross-sectional analysis, we generated a single-cell transcriptomic dataset of peripheral blood mononuclear cells (PBMCs) from 46 manifest T1DM (stage 3) cases and 31 matched controls.

Results

We surprisingly detected profound alterations in circulatory immune cells (1784 dysregulated genes in 13 immune cell types), far exceeding the count in the comparator systemic autoimmune disease SLE. Genes upregulated in T1DM were involved in WNT signaling, interferon signaling and migration of T/NK cells, antigen presentation by B cells, and monocyte activation. A significant fraction of these differentially expressed genes were also altered in T1DM pancreatic islets. We used the single-cell data to construct a T1DM metagene z-score (TMZ score) that distinguished cases and controls and classified patients into molecular subtypes. This score correlated with known prognostic immune markers of T1DM, as well as with drug response in clinical trials.

Conclusions

Our study reveals a surprisingly strong systemic dimension at the level of immune cell network in T1DM, defines disease-relevant molecular subtypes, and has the potential to guide non-invasive test development and patient stratification.
Donepezil-induced bradycardia in a schizophrenic patient with comorbid neurocognitive disorder: a case report and review of the literature
Authors: Odenigbo Nkolika , Nkemjika Stanley , Atolagbe Ayodele , Nwabueze Christian , Olwit Connie , Lawrence Jeffery , Olupona Tolulope
Published: March 2024

Background

Trials of cholinergic and glutamatergic agents have improved cognition and memory for the geriatric schizophrenic population. Donepezil is an acetylcholinesterase inhibitor that improves cognition by preventing postsynaptic degradation of hippocampal acetylcholine in patients with mild-to-moderate dementia. Donepezil has been attributed to some adverse effects, especially gastrointestinal symptoms. However, cardiovascular adverse effects are not common as there remains a dearth of literature regarding donepezil-induced bradycardia.

Case report

Hence, we present the case of a 70-year-old Hispanic female with past psychiatry history of schizophrenia who developed bradycardia and syncope following the commencement of low-dose donepezil in the inpatient unit and subsequent resolution with cessation. She had no prior cardiovascular symptoms or diagnosis.

Discussion

Considering there is no baseline cardiac monitoring requirement guideline for patients on Donepezil treatment, pre-assessment electrocardiogram is advised before the commencement of acetylcholinesterase inhibitors. Finally, routine monitoring of vital signs for at least the first 72 hours following the start of donepezil might be good proactive practice for all psychiatrists. Extending this practice to inpatient and outpatient service settings will be worthwhile.
Gut barrier dysfunction and the risk of ICU-acquired bacteremia- a case–control study
Authors: Varkila Meri R. J. , Verboom Diana M. , Derde Lennie P. G. , van der Poll Tom , Bonten Marc J. M. , Cremer Olaf L. ,   the MARS consortium, de Beer Friso M. , Bos Lieuwe D. J. , Glas Gerie J. , Hoogendijk Arie J. , van Hooijdonk Roosmarijn T. M. , Horn Janneke , Huson Mischa A. , Juffermans Nicole P. , Schouten Laura R. A. , Scicluna Brendon , Schultz Marcus J. , Straat Marleen , van Vught Lonneke A. , Wieske Luuk , Wiewel Maryse A. , Witteveen Esther , Bonten Marc J. M. , Cremer Olaf L. , Frencken Jos F. , van de Groep Kirsten , Klouwenberg Peter M. C. Klein , Koster-Brouwer Maria E. , Ong David S. Y. , Varkila Meri R. J. , Verboom Diana M.
Published: March 2024

Background

Impaired intestinal barrier function can enable passage of enteric microorganisms into the bloodstream and lead to nosocomial bloodstream infections during critical illness. We aimed to determine the relative importance of gut translocation as a source for ICU-acquired enterococcal bacteremia of unknown origin.

Methods

We conducted a nested case–control study in two mixed medical-surgical tertiary ICUs in the Netherlands among patients enrolled between 2011 and 2018. We selected 72 cases with ICU-acquired bacteremia due to enterococci (which are known gastrointestinal tract commensals) and 137 matched controls with bacteremia due to coagulase-negative staphylococci (CoNS) (which are of non-intestinal origin). We measured intestinal fatty acid-binding protein, trefoil factor-3, and citrulline 48 h before bacteremia onset. A composite measure for Gut Barrier Injury (GBI) was calculated as the sum of standardized z-scores for each biomarker plus a clinical gastrointestinal failure score.

Results

No single biomarker yielded statistically significant differences between cases and controls. Median composite GBI was higher in cases than in controls (0.58, IQR − 0.36–1.69 vs. 0.32, IQR − 0.53–1.57, p = 0.33) and higher composite measures of GBI correlated with higher disease severity and ICU mortality (p < 0.001). In multivariable analysis, higher composite GBI was not significantly associated with increased occurrence of enterococcal bacteremia relative to CoNS bacteremia (adjusted OR 1.12 95% CI 0.93–1.34, p = 0.22).

Conclusions

We could not demonstrate an association between biomarkers of gastrointestinal barrier dysfunction and an increased occurrence of bacteremia due to gut compared to skin flora during critical illness, suggesting against bacterial translocation as a major vector for acquisition of nosocomial bloodstream infections in the ICU.
An end-to-end approach for blindly rendering a virtual sound source in an audio augmented reality environment
Authors: Saini Shivam , Engel Isaac , Peissig Jürgen
Published: March 2024

Audio augmented reality (AAR), a prominent topic in the field of audio, requires understanding the listening environment of the user for rendering an authentic virtual auditory object. Reverberation time ($$RT_{60}$$

R

T
60

) is a predominant metric for the characterization of room acoustics and numerous approaches have been proposed to estimate it blindly from a reverberant speech signal. However, a single $$RT_{60}$$

R

T
60

value may not be sufficient to correctly describe and render the acoustics of a room. This contribution presents a method for the estimation of multiple room acoustic parameters required to render close-to-accurate room acoustics in an unknown environment. It is shown how these parameters can be estimated blindly using an audio transformer that can be deployed on a mobile device. Furthermore, the paper also discusses the use of the estimated room acoustic parameters to find a similar room from a dataset of real BRIRs that can be further used for rendering the virtual audio source. Additionally, a novel binaural room impulse response (BRIR) augmentation technique to overcome the limitation of inadequate data is proposed. Finally, the proposed method is validated perceptually by means of a listening test.
Neuropathological changes associated with aberrant cerebrospinal fluid p-tau181 and Aβ42 in Alzheimer’s disease and other neurodegenerative diseases
Authors: Kurihara Masanori , Matsubara Tomoyasu , Morimoto Satoru , Arakawa Akira , Ohse Kensuke , Kanemaru Kazutomi , Iwata Atsushi , Murayama Shigeo , Saito Yuko
Published: March 2024

Recent studies suggest that increased cerebrospinal fluid (CSF) phospho-tau is associated with brain amyloid pathology rather than the tau pathology. However, confirmation using gold standard neuropathological assessments remains limited. This study aimed to determine background pathologies associated with aberrant CSF p-tau181 and amyloid-beta 1–42 (Aβ42) in Alzheimer’s disease (AD) and other neurodegenerative diseases. We retrospectively studied all patients with antemortem CSF and postmortem neuropathologic data at our institution. Comprehensive neuropathologic assessments were conducted for all patients, including Thal phase, Braak NFT stage, and CERAD score for AD. CSF concentrations of p-tau181 and Aβ42 were compared between AD neuropathological scores at autopsy by one-way ANOVA stratified by other pathologies. A total of 127 patients with AD (n = 22), Lewy body disease (n = 26), primary tauopathies (n = 30), TDP-43 proteinopathy (n = 16), and other diseases (n = 33) were included. The age at lumbar puncture was 76.3 ± 9.1 years, 40.8% were female, and median time from lumbar puncture to autopsy was 637 (175–1625) days. While Braak NFT 0–II was prevalent without amyloid pathology, Braak NFT ≥IV was observed exclusively in patients with amyloid pathology. Stratified analyses showed that CSF p-tau181 was slightly but significantly higher in patients with high Thal phase or CERAD score even in those with Braak NFT 0–II at autopsy. In patients with amyloid pathology, CSF p-tau181 was significantly and more profoundly elevated in those with Braak NFT ≥III at autopsy. CSF Aβ42 was lower in patients with high amyloid pathological scores. However, 34% with Thal ≤ 2 and 38% with CERAD ≤ sparse also showed decreased Aβ42. Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) were overrepresented in this group. These results neuropathologically confirmed previous studies that CSF p-tau181 levels were slightly elevated with amyloid pathology alone and were even higher with tau pathology, and that CSFAβ42 can be decreased in PSP/CBD.
A multi-level quantitative analysis method on the scale, shape and quantity of rockeries in Chinese classical gardens: taking Wanfang Anhe rockery in the Old Summer Palace as an example
Authors: Li Xinchen , He Xiaoxiao , Xiao Yuqing , Jia Shizhen , Qin Ke
Published: March 2024

Currently, the use of digital technology for the protection and research of cultural heritage has become a trend in this field. Rockeries in Chinese classical gardens have become an important cultural heritage type because of their unique shape, ingenious skills and rich connotations. Based on relevant historical information and 3D digital technology, this paper puts forward a multi-level quantitative analysis method on the scale, shape and quantity of rockeries in Chinese classical gardens, aiming at exploring the objective description and quantitative analysis path of rockeries at different levels. This method develops four levels: overall, regional, hierarchical, and individual and their corresponding quantitative contents, which in turn enable data extraction and analysis of the rockery through the different levels. The proposed method was applied to seven different Chinese classical garden rockeries, and taking Wanfang Anhe Rockery in the Old Summer Palace as an example for objective and comprehensive quantitative analysis and verification. The results show that this method is feasible and effective for quantitative analysis of the scale, shape and quantity of rockeries, which can help understand the basic background of stone rockeries and enhance a refined understanding of stone rockery construction, thereby providing data for preventive protection and informatization management of stone rockeries. The 3D rockery model database based on the overall, regional, hierarchical and individual quantitative analysis and numbering method brings a good application prospect for preventive protection and informatization management of the rockery.
The role of classifiers and data complexity in learned Bloom filters: insights and recommendations
Authors: Malchiodi Dario , Raimondi Davide , Fumagalli Giacomo , Giancarlo Raffaele , Frasca Marco
Published: March 2024

Bloom filters, since their introduction over 50 years ago, have become a pillar to handle membership queries in small space, with relevant application in Big Data Mining and Stream Processing. Further improvements have been recently proposed with the use of Machine Learning techniques: learned Bloom filters. Those latter make considerably more complicated the proper parameter setting of this multi-criteria data structure, in particular in regard to the choice of one of its key components (the classifier) and accounting for the classification complexity of the input dataset. Given this State of the Art, our contributions are as follows. (1) A novel methodology, supported by software, for designing, analyzing and implementing learned Bloom filters that account for their own multi-criteria nature, in particular concerning classifier type choice and data classification complexity. Extensive experiments show the validity of the proposed methodology and, being our software public, we offer a valid tool to the practitioners interested in using learned Bloom filters. (2) Further contributions to the advancement of the State of the Art that are of great practical relevance are the following: (a) the classifier inference time should not be taken as a proxy for the filter reject time; (b) of the many classifiers we have considered, only two offer good performance; this result is in agreement with and further strengthens early findings in the literature; (c) Sandwiched Bloom filter, which is already known as being one of the references of this area, is further shown here to have the remarkable property of robustness to data complexity and classifier performance variability.
Metabolic Consequences of Anabolic Steroids, Insulin, and Growth Hormone Abuse in Recreational Bodybuilders: Implications for the World Anti-Doping Agency Passport
Authors: Di Girolamo Filippo Giorgio , Biasinutto Chiara , Mangogna Alessandro , Fiotti Nicola , Vinci Pierandrea , Pisot Rado , Mearelli Filippo , Simunic Bostjan , Roni Chiara , Biolo Gianni
Published: March 2024

Background

Hormonal doping in recreational sports is a public-health concern. The World Anti-Doping Agency (WADA) promoted the creation of the Athlete Biological Passport, aiming to monitor athlete’s biological variables over time to facilitate indirect detection of doping. Detection tests for anabolic androgenic steroids (AAS) and growth hormone (GH) are available while insulin abuse cannot be revealed. We have determined in recreational bodybuilders the metabolic effects associated with different patterns of hormone abuse. All analyses were conducted using Statistical Package for Social Sciences (SPSS) 21.0 software (SPSS Chicago, IL).

Results

We have assessed plasma concentrations of selected metabolic markers and fatty acid content in erythrocyte membranes of 92 male bodybuilders and in 45 healthy controls. Hormonal abuse was identified by anonymous questionnaires. 43% (%) of recruited bodybuilders regularly abused hormones, i.e., anabolic androgenic steroids (95%) often associated with GH (30%) and/or insulin (38%). HDL-cholesterol was lower in insulin and/or GH abusers. Alanine (ALT) and aspartic (AST) transaminases were greater in hormone abusing bodybuilders than in non-doping bodybuilders and controls. Insulin doping was selectively associated with increased plasma ALT-to-AST ratio. In erythrocyte membranes, elongase activity (i.e., stearic-to-palmitic ratio) was lower in insulin and/or growth hormone doping, whereas increased Δ-9 desaturase activity (i.e., palmitoleic-to-palmitic ratio) was selectively associated with insulin doping.

Conclusions

In conclusion, our study demonstrates that insulin and GH abuse are characterized by multiple alterations of specific metabolic markers. Although further studies are needed to test whether longitudinal monitoring of selected metabolic marker such as muscle contraction time, HDL levels, ALT-AST ratio as well as the activities of selected enzymes (e.g. Δ-9 desaturase and elongase), could contribute to the detection of insulin and GH abuse in sport.
Different outcomes between downward and lateral peritoneal dialysis catheter exit-site directions
Authors: Treamtrakanpon Worapot , Phutrakool Phanupong , Pongpirul Krit
Published: March 2024

Background

The International Society for Peritoneal Dialysis guidelines suggest lateral or downward exit positions for peritoneal dialysis (PD) catheter. In cases with straight inter-cuff design (used in Thailand), downward exit may lead to more complications due to catheter memory force. We compared lateral (lateral group) and downward (downward group) exits in PD patients.

Methods

We retrospectively studied end-stage kidney disease patients with PD catheters from 2011 to 2021 at Chao Phraya Abhaibhubejhr Hospital, Thailand. We analysed catheter malfunction, exit-site infection (ESI) and patient survival.

Results

A total of 425 patients, aged 11–87 years (57% female and 59% with diabetes mellitus). 326 had downward exits, and 99 had lateral exits. Both groups had similar 2-years patient survival (p = 0.592), 1-year survival catheter dysfunction requiring removal (p = 0.146) and First-year ESI (p = 0.432). In the lateral exit group, the percent of catheter dysfunction requiring removal was slightly lower (1.01 vs. 3.99, p = 0.204) while the percent of patient with ESI at first year was slightly higher (8.08 vs. 6.13, p = 0.494) compared to downward exit group.

Conclusions

Lateral exit and downward exit with a straight inter-cuff design have similar outcome of catheter survival/function, exit site infection and patient survival. Lateral exit site is a good option in context of a straight inter-cuff design.
Integrating agency and resource dependency theories: the moderating effect of board size on the relationship between dividends and firm value in Malaysia
Authors: Bakri Mohd Ashari , Ayub Nurjeehan , Gazali Haneffa Muchlis
Published: March 2024

Purpose

This paper aims to examine the moderating effects of board size on the relationship between dividends and firm value in Malaysian settings. The theoretical foundations of this research were the integration between agency and resources dependency theories.

Design/methodology/approach

Panel data are extracted from DataStream and the annual report for the period of 2012 to 2021, and pooled OLS, random effects, and fixed effects analyses were employed to examine the relationship. Breusch–Pagan Lagrange multiplier (LM) test and the Hausman test used to determine the most appropriate between these three analyses (OLS, random effects, and fixed effects). The results are valid even after calculating the robust standard error to mitigate the potential heteroskedasticity and serial correlation.

Findings

The empirical results show that board size positively moderates the relationship between dividends and firm value in all the models tested. The results indicate that a larger board of size can minimize the agency problem (agency theory) because a larger board size can more effectively monitor and control management's opportunistic behavior due to more set of skilled and talented individuals included in the boardroom (resources dependency theory). Additionally, effective monitoring can also lead to the increase in dividend payout to maintain a good reputation among investors and simultaneously increase firm value.

Practical implication

This study contributes to helping the regulators and industry players in Malaysia to improve existing guidelines for determining dividend and board size to increase firm value. The findings may also provide inputs to the policymakers in recommending the optimum dividend and board size that resulting an increase in valuation.

Originality/value

By incorporating agency and resources dependency theory, authors investigate the moderating effect of board size on dividend and firm value relationships in Malaysian markets.
Development and Characterization of Transdermal Patches Using Novel Thymoquinone-L-Arginine-Based Polyamide Nanocapsules for Potential Use in the Management of Psoriasis
Authors: Dahmash Eman Zmaily , Attiany Lama Murad , Ali Dalia , Assaf Shereen M. , Alkrad Jamal , Alyami Hamad
Published: March 2024

Thymoquinone (TQ) is a phytochemical compound present in Nigella sativa and has potential benefits for treating dermatological conditions such as psoriasis. However, its clinical use is limited due to its restricted bioavailability, caused mainly by its low solubility and permeability. To overcome this, a new transdermal drug delivery system is required. Nanoparticles are known to enhance material solubility and permeability, and hence, this study aimed to synthesize TQ-loaded L-arginine-based polyamide (TQ/Arg PA) nanocapsules incorporated into transdermal patches for prolonged delivery of TQ. To achieve this, Eudragit E polymer, plasticizers, and aloe vera as penetration enhancer were used to develop the transdermal patch. Furthermore, novel TQ/Arg-PA was synthesized via interfacial polymerization, and the resultant nanocapsules (NCs) were incorporated into the matrix transdermal patch. The Arg-PA NCs’ structure was confirmed via NMR and FTIR, and optimal TQ/Arg-PA NCs containing formulation showed high entrapment efficiency of TQ (99.60%). Molecular and thermal profiling of TQ/Arg-PA and the transdermal patch revealed the effective development of spherical NCs with an average particle size of 129.23 ± 18.22 nm. Using Franz diffusion cells and synthetic membrane (STRAT M®), the in vitro permeation profile of the prepared patches demonstrated an extended release of TQ over 24 h, with enhanced permeation by 42.64% when aloe vera was employed. In conclusion, the produced formulation has a potential substitute for corticosteroids and other drugs commonly used to treat psoriasis due to its effectiveness, safety, and lack of the side effects typically associated with other drugs.

Graphical Abstract
Energetics of a pulsed quantum battery
Authors: Downing Charles Andrew , Ukhtary Muhammad Shoufie
Published: March 2024

The challenge of storing energy efficiently and sustainably is highly prominent within modern scientific investigations. Due to the ongoing trend of miniaturization, the design of expressly quantum storage devices is itself a crucial task within current quantum technological research. Here we provide a transparent analytic model of a two-component quantum battery, composed of a charger and an energy holder, which is driven by a short laser pulse. We provide simple expressions for the energy stored in the battery, the maximum amount of work which can be extracted, both the instantaneous and the average powers, and the relevant charging times. This allows us to discuss explicitly the optimal design of the battery in terms of the driving strength of the pulse, the coupling between the charger and the holder, and the inevitable energy loss into the environment. We anticipate that our theory can act as a helpful guide for the nascent experimental work building and characterizing the first generation of truly quantum batteries.
Assessing the Interaction Effects of Mitochondrial DNA Polymorphisms and Lifestyle on Heel Bone Mineral Density
Authors: He Dan , Liu Huan , Zhao Yijing , Wei Wenming , Cai Qingqing , Shi Sirong , Chu Xiaoge , Zhang Na , Qin Xiaoyue , Jia Yumeng , Wen Yan , Cheng Bolun , Zhang Feng
Published: March 2024

Background

Bone mineral density (BMD) is a major predictor of osteoporotic fractures, and previous studies have reported the effects of mitochondrial dysfunction and lifestyle on BMD, respectively. However, their interaction effects on BMD are still unclear.

Objective

We aimed to investigate the possible interaction of mitochondrial DNA (mtDNA) and common lifestyles contributing to osteoporosis.

Methods

Our analysis included 119 120 white participants (Nfemale = 65 949 and Nmale = 53 171) from the UK Biobank with heel BMD phenotype data. A generalized linear regression model of PLINK was performed to assess the interaction effects of mtDNA and 5 life environmental factors on heel BMD, including smoking, drinking, physical activity, dietary diversity score, and vitamin D. In addition, we also performed linear regression analysis for total body BMD. Finally, we assessed the potential causal relationships between mtDNA copy number (mtDNA-CN) and life environmental factors using Mendelian randomization (MR) analysis.

Results

Our study identified 4 mtDNA loci showing suggestive evidence of heel BMD, such as m.16356T>C (MT-DLOOP; P = 1.50 × 10−3) in total samples. Multiple candidate mtDNA × lifestyle interactions were also detected for heel BMD, such as MT-ND2 × physical activity (P = 2.88 × 10−3) in total samples and MT-ND1 × smoking (P = 8.54 × 10−4) in males. Notably, MT-CYB was a common candidate mtDNA loci for heel BMD to interact with 5 life environmental factors. Multivariable MR analysis indicated a causal effect of physical activity on heel BMD when mtDNA-CN was considered (P = 1.13 × 10−3).

Conclusion

Our study suggests the candidate interaction between mtDNA and lifestyles on heel BMD, providing novel clues for exploring the pathogenesis of osteoporosis.