bluuebunny/crossref_metadata_2025 huggingface dataset:
Using digital technology as a platform to strengthen the continuum of care at community level for maternal, child and adolescent health in Tanzania: introducing the Afya-Tek program
Authors: Dillip Angel , Kahamba Gloria , Sambaiga Richard , Shekalaghe Elizabeth , Kapologwe Ntuli , Kitali Erick , Kengia James Tumaini , Haonga Tumaini , Nzilibili Simon , Tanda Mark , Haroun Yasini , Hofmann Rachel , Litner Rebecca , Lampariello Riccardo , Kimatta Suleiman , Ketende Sosthenes , James Johanitha , Fumbwe Khadija , Mahmoud Fatma , Lugumamu Oscar , Gabunda Christina , Salim Ally , Allen Megan , Mathew Eden , Nkaka Melania , Liana Jafary , Norman Toby , Mbwasi Romuald , Sarkar Nandini
Published: July 2024

Inadequate care within Tanzania’s primary health system contributes to thousands of preventable maternal and child deaths, and unwanted pregnancies each year. A key contributor is lack of coordination between three primary healthcare actors: public sector Community Health Workers (CHWs) and health facilities, and private sector Accredited Drug Dispensing Outlets (ADDOs). The Afya-Tek program aims to improve the continuity of care amongst these actors in Kibaha district, through a mobile-application based digital referral system that focuses on improving maternal, child and adolescent health. The digital system called Afya-Tek was co-created with users and beneficiaries, and utilises open-source technology in-line with existing government systems. The system guides healthcare actors with individualised decision support during client visits and recommends accurate next steps (education, treatment, or referral). From July 2020 to June 2023, a total of 241,000 individuals were enrolled in the Afya-Tek program covering 7,557 pregnant women, 6,582 postpartum women, 45,900 children, and 25,700 adolescents. CHWs have conducted a total of 626,000 home visits to provide health services, including screening clients for danger signs. This has resulted in 38,100 referrals to health facilities and 24,300 linkages to ADDOs. At the ADDO level, 48,552 clients self-presented; 33% of children with pneumonia symptoms received Amoxicillin; 34% of children with diarrhoea symptoms received ORS and zinc; and 4,203 referrals were made to nearest health facilities. Adolescents preferred services at ADDOs as a result of increased perceived privacy and confidentiality. In total, 89% of all referrals were attended by health facilities. As the first digital health program in Tanzania to demonstrate the linkage among public and private sector primary healthcare actors, Afya-Tek holds promise to improve maternal, child and adolescent health as well as for scale-up and sustainability, through incorporation of other disease conditions and integration with government’s Unified Community System (UCS).
Multi-omic signatures of sarcoidosis and progression in bronchoalveolar lavage cells
Authors: Konigsberg Iain R. , Lin Nancy W. , Liao Shu-Yi , Liu Cuining , MacPhail Kristyn , Mroz Margaret M. , Davidson Elizabeth , Restrepo Clara I. , Sharma Sunita , Li Li , Maier Lisa A. , Yang Ivana V.
Published: July 2024

Background

Sarcoidosis is a heterogeneous granulomatous disease with no accurate biomarkers of disease progression. Therefore, we profiled and integrated the DNA methylome, mRNAs, and microRNAs to identify molecular changes associated with sarcoidosis and disease progression that might illuminate underlying mechanisms of disease and potential biomarkers.

Methods

Bronchoalveolar lavage cells from 64 sarcoidosis subjects and 16 healthy controls were used. DNA methylation was profiled on Illumina HumanMethylationEPIC arrays, mRNA by RNA-sequencing, and miRNAs by small RNA-sequencing. Linear models were fit to test for effect of sarcoidosis diagnosis and progression phenotype, adjusting for age, sex, smoking, and principal components of the data. We built a supervised multi-omics model using a subset of features from each dataset.

Results

We identified 1,459 CpGs, 64 mRNAs, and five miRNAs associated with sarcoidosis versus controls and four mRNAs associated with disease progression. Our integrated model emphasized the prominence of the PI3K/AKT1 pathway, which is important in T cell and mTOR function. Novel immune related genes and miRNAs including LYST, RGS14, SLFN12L, and hsa-miR-199b-5p, distinguished sarcoidosis from controls. Our integrated model also demonstrated differential expression/methylation of IL20RB, ABCC11, SFSWAP, AGBL4, miR-146a-3p, and miR-378b between non-progressive and progressive sarcoidosis.

Conclusions

Leveraging the DNA methylome, transcriptome, and miRNA-sequencing in sarcoidosis BAL cells, we detected widespread molecular changes associated with disease, many which are involved in immune response. These molecules may serve as diagnostic/prognostic biomarkers and/or drug targets, although future testing is required for confirmation.
Assessing receptivity to malaria using case surveillance and forest data in a near-elimination setting in northeast Thailand
Authors: Walshe Rebecca , Pongsoipetch Kulchada , Mukem Suwanna , Kamsri Tanong , Singkham Navarat , Sudathip Prayuth , Kitchakarn Suravadee , Maude Rapeephan Rattanawongnara , Maude Richard James
Published: July 2024

Background

Thailand aimed to eliminate malaria by 2024, and as such is planning for future prevention of re-establishment in malaria free provinces. Understanding the receptivity of local areas to malaria allows the appropriate targeting of interventions. Current approaches to assessing receptivity involve collecting entomological data. Forest coverage is known to be associated with malaria risk, as an environment conducive to both vector breeding and high-risk human behaviours.

Methods

Geolocated, anonymized, individual-level surveillance data from 2011 to 2021 from the Thai Division of Vector-Borne Disease (DVBD) was used to calculate incidence and estimated Rc at village level. Forest cover was calculated using raster maps of tree crown cover density and year of forest loss from the publicly available Hansen dataset. Incidence and forest cover were compared graphically and using Spearman’s rho. The current foci classification system was applied to data from the last 5 years (2017–2021) and forest cover for 2021 compared between the classifications. A simple risk score was developed to identify villages with high receptivity.

Results

There was a non-linear decrease in annual cases by 96.6% (1061 to 36) across the two provinces from 2011 to 2021. Indigenous Annual Parasite Index (API) and approximated Rc were higher in villages in highly forested subdistricts, and with higher forest cover within 5 km. Forest cover was also higher in malaria foci which consistently reported malaria cases each year than those which did not. An Rc > 1 was only reported in villages in subdistricts with > 25% forest cover. When applying a simple risk score using forest cover and recent case history, the classifications were comparable to those of the risk stratification system currently used by the DVBD.

Conclusions

There was a positive association between forest coverage around a village and indigenous malaria cases. Most local transmission was observed in the heavily forested subdistricts on the international borders with Laos and Cambodia, which are where the most receptive villages are located. These areas are at greater risk of importation of malaria due to population mobility and forest-going activities. Combining forest cover and recent case surveillance data with measures of vulnerability may be useful for prediction of malaria recurrence risk.
Infection microenvironment-triggered nanoparticles eradicate MRSA by thermally amplified chemodynamic therapy and M1 macrophage
Authors: Hong Qimin , Zhang Wei , Liu Zhen , Li Bo , Liu Xi , Wang Zhinan , Wang Rui , Yang Jianping , Nie Bin’en , Yue Bing
Published: July 2024

It is of great significance to develop a novel approach to treat bacterial infections, as the frequent misuse of antibiotics leads to the serious problem of bacterial resistance. This study proposed antibiotic-free antibacterial nanoparticles for eliminating methicillin-resistant Staphylococcus aureus (MRSA) based on a multi-model synergistic antibacterial ability of chemodynamic therapy (CDT), photothermal effect, and innate immunomodulation. Specifically, a polydopamine (PDA) layer coated and Ag nanoparticles loaded core-shell structure Fe3O4 nanoparticles (Fe3O4@PDA-Ag) is prepared. The Fe3O4 catalyzes H2O2 present in acidic microenvironment of bacterial infection into more toxic reactive oxygen species (ROS) and synergizes with the released Ag ions to exert a stronger bactericidal capacity, which can be augmented by photothermal action of PDA triggered by near-infrared light and loosen the biofilm by photothermal action to promote the penetration of ROS and Ag ion into the biofilm, result in disrupting biofilm structure along with killing encapsulated bacteria. Furthermore, Fe3O4@PDA-Ag exerts indirect antibacterial effects by promoting M1 macrophage polarizing. Animal models demonstrated that Fe3O4@PDA-Ag effectively controlled MRSA-induced infections through photothermal enhanced CDT, Ag+ releasing, and macrophage-mediated bactericidal properties. The acid-triggered antibacterial nanoparticles are expected to combat drug-resistant bacteria infection.

Graphical abstract
Magnetothermal-activated gene editing strategy for enhanced tumor cell apoptosis
Authors: Li Mingyuan , Li Siqian , Guo YueDong , Hu Ping , Shi Jianlin
Published: July 2024

Precise and effective initiation of the apoptotic mechanism in tumor cells is one of the most promising approaches for the treatment of solid tumors. However, current techniques such as high-temperature ablation or gene editing suffer from the risk of damage to adjacent normal tissues. This study proposes a magnetothermal-induced CRISPR-Cas9 gene editing system for the targeted knockout of HSP70 and BCL2 genes, thereby enhancing tumor cell apoptosis. The magnetothermal nanoparticulate platform is composed of superparamagnetic ZnCoFe2O4@ZnMnFe2O4 nanoparticles and the modified polyethyleneimine (PEI) and hyaluronic acid (HA) on the surface, on which plasmid DNA can be effectively loaded. Under the induction of a controllable alternating magnetic field, the mild magnetothermal effect (42℃) not only triggers dual-genome editing to disrupt the apoptosis resistance mechanism of tumor cells but also sensitizes tumor cells to apoptosis through the heat effect itself, achieving a synergistic therapeutic effect. This strategy can precisely regulate the activation of the CRISPR-Cas9 system for tumor cell apoptosis without inducing significant damage to healthy tissues, thus providing a new avenue for cancer treatment.
Comparing patient- and proxy-reported health-related quality of life of frail older patients at the emergency department
Authors: Ha Joey Wei Yee , Pereira Michelle Jessica , Chong Edward Kah Chun , Molina Joseph Antonio De Castro , Lim Wee Shiong
Published: July 2024

Purpose

To examine agreement between patient- and proxy-reported Health-Related Quality of Life (HRQoL) scores, and their associations with clinical measures and patient demographics.

Methods

We examined the patient-proxy agreement in HRQoL within a cohort of community-dwelling frail older patients (Clinical Frailty Scale [CFS] score 4–6) planned for discharge from the Emergency Department (ED) of a 1700-bed tertiary hospital in Singapore. Patients were recruited as part of the Emergency Department Interventions for Frailty (EDIFY) program, a quasi-experimental study evaluating the effectiveness of a multicomponent frailty intervention (MFI) in maintaining or improving functional outcomes. HRQoL was measured using the EuroQoL five-dimensional questionnaire (EQ-5D-5L) for patients and proxies. We analysed a sample of dyadic-reported HRQoL to explore the inter-rater agreement using intraclass correlation coefficients (ICC), and the influencing factors of concordance.

Results

We recruited 140 participants with 23 pairs of patient-proxy dyads having concurrent EQ-5D reported. There was poor inter-rater agreement between patient- and proxy-reported EQ-5D (ICC 0.18) with proxies perceiving poorer average HRQoL than patients. On the domain level, there was poor agreement in self-care and pain domains (ICC − 0.07 and 0.20), where proxies perceived more problems than patients. In multivariate regressions, lower frailty scores were associated with poorer agreement in EQ-5D scores (p < 0.05).

Conclusion

In conclusion, our findings demonstrate differences between patient- and proxy-reported HRQoL outcomes among frail older patients, with significant discordance observed among patients who are “less frail”. Hence, proxy-reported responses should be interpreted with care especially when the abovementioned characteristics are present in an older patient.
Comparison of data fusion strategies for automated prostate lesion detection using mpMRI correlated with whole mount histology
Authors: Gunashekar Deepa Darshini , Bielak Lars , Oerther Benedict , Benndorf Matthias , Nedelcu Andrea , Hickey Samantha , Zamboglou Constantinos , Grosu Anca-Ligia , Bock Michael
Published: July 2024

Background

In this work, we compare input level, feature level and decision level data fusion techniques for automatic detection of clinically significant prostate lesions (csPCa).

Methods

Multiple deep learning CNN architectures were developed using the Unet as the baseline. The CNNs use both multiparametric MRI images (T2W, ADC, and High b-value) and quantitative clinical data (prostate specific antigen (PSA), PSA density (PSAD), prostate gland volume & gross tumor volume (GTV)), and only mp-MRI images (n = 118), as input. In addition, co-registered ground truth data from whole mount histopathology images (n = 22) were used as a test set for evaluation.

Results

The CNNs achieved for early/intermediate / late level fusion a precision of 0.41/0.51/0.61, recall value of 0.18/0.22/0.25, an average precision of 0.13 / 0.19 / 0.27, and F scores of 0.55/0.67/ 0.76. Dice Sorensen Coefficient (DSC) was used to evaluate the influence of combining mpMRI with parametric clinical data for the detection of csPCa. We compared the DSC between the predictions of CNN’s trained with mpMRI and parametric clinical and the CNN’s trained with only mpMRI images as input with the ground truth. We obtained a DSC of data 0.30/0.34/0.36 and 0.26/0.33/0.34 respectively. Additionally, we evaluated the influence of each mpMRI input channel for the task of csPCa detection and obtained a DSC of 0.14 / 0.25 / 0.28.

Conclusion

The results show that the decision level fusion network performs better for the task of prostate lesion detection. Combining mpMRI data with quantitative clinical data does not show significant differences between these networks (p = 0.26/0.62/0.85). The results show that CNNs trained with all mpMRI data outperform CNNs with less input channels which is consistent with current clinical protocols where the same input is used for PI-RADS lesion scoring.

Trial registration

The trial was registered retrospectively at the German Register for Clinical Studies (DRKS) under proposal number Nr. 476/14 & 476/19.
CTSG may inhibit disease progression in HIV-related lung cancer patients by affecting immunosuppression
Authors: Yan Xuan , Wei Shuoyan , Yang Yuexiang , Zhao Zhangyan , Wu Qingguo , Tang Haicheng
Published: July 2024

Objectives

Lung cancer is an independent risk factor for pulmonary complications following HIV infection. This study aimed to examine the expression and clinical significance of Cathepsin G (CTSG) protein in both non-HIV and HIV-related lung cancers.

Methods

The data related to lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) in the TCGA dataset and the data related to healthy individuals in the GTEx dataset, the GEPIA2 database was used to excavate the distinction in the expression of CTSG protein in non-small cell lung cancer (NSCLC) tissues versus normal non-cancerous tissues. The Ualcan database was used to compare the differences in CTSG expression at different stages of LUAD and LUSC. Immunohistochemistry (IHC) was used to detect the expression of CTSG proteins in the pathological tissues of patients with HIV-related lung cancer and patients with lung cancer without co-infection, the Kaplan-Meier method was used for survival analysis.

Results

We observed that CTSG expression in NSCLC is lower compared to adjacent non-tumor tissues and correlates with NSCLC clinical stage. CTSG protein expression in HIV-related lung cancer tissues was lower than in adjacent tissues and lower than in lung cancer tissues without HIV infection, with a statistically significant difference (P < 0.05). It correlated with CD4 + T cell count and CD4+/CD8 + T cell ratio, as well as with the pathological type, distant metastasis, and clinical stage of HIV-related lung cancer, all with statistical significance (P < 0.05).

Conclusions

CTSG could potentially mitigate disease advancement in HIV-related lung cancer patients by inhibiting immune depletion, serving as a prospective immunotherapeutic target for both non-HIV and HIV-associated lung cancers.
Sharenting: characteristics and awareness of parents publishing sensitive content of their children on online platforms
Authors: Conti Maria Giulia , Del Parco Fabiola , Pulcinelli Francesca Maria , Mancino Enrica , Petrarca Laura , Nenna Raffaella , Di Mattia Greta , Matera Luigi , La Regina Domenico Paolo , Bonci Enea , Caruso Cinthia , Midulla Fabio
Published: July 2024

Background

The term “sharenting” describes the increasingly popular habit of parents to share photos, videos, or other information regarding their children on their social profiles, through online platforms. It is highly likely that many parents are posting content about their underage children online with little knowledge of the risks associated with this practice. This study aims to investigate whether variables such as parents’ age, gender, marital status, occupation and educational level influence the practice of sharing child-related content and the degree of awareness.

Methods

We performed a pilot cross-sectional study, based on an anonymous questionnaire. The questionnaire was administered to parents of underage children attending the pediatric outpatient clinic of the Umberto I Hospital, Sapienza University, in Rome, Italy, by researchers, through the google forms platform; qualitative variables were generated on excel sheets and a statistical analysis was performed on SPSS Ibm-statistics using the chi-square test.

Results

Two hundred twenty-eight parents of children under 18 years of age completed the questionnaire (82% mothers, 18% fathers); 98% of the respondents used social media and 75% of them published their children’s related content online. Thirty-one percent of the compilers started their practice of sharenting in the first 6 months of life of their child. Our analysis showed that compared to parents who do not post online, parents who usually post online their children are significantly more likely to be partial employees or unemployed (p = 0,002), with lower educational level (p = 0,05), younger (less than 35 years of age (p = 0,01)) and have a higher number of followers (p < 0,001). Finally, 93% of the compilers were not aware of the current legislation and of the risks related to the practice of sharenting.

Conclusions

Pediatricians, healthcare assistants and preventive healthcare professionals should play a central role in alerting parents and families to the risks of sharenting; the results of our study could draw their attention to the increasing practice of sharenting and make healthcare professionals active part in the protection of children.
Strain and model development for auto- and heterotrophic 2,3-butanediol production using Cupriavidus necator H16
Authors: Weiler Janek R. , Jürgensen Nikolai , Cornejo Infante Monica , Knoll Melanie T. , Gescher Johannes
Published: July 2024

The production of platform chemicals from renewable energy sources is a crucial step towards a post-fossil economy. This study reports on the production of acetoin and 2,3-butanediol heterotrophically with fructose as substrate and autotrophically from CO2 as carbon source, H2 as electron donor and O2 as electron acceptor with Cupriavidus necator. In a previous study, the strain was developed for the production of acetoin with high carbon efficiency. Acetoin can serve as a precursor for the synthesis of 2,3-butanediol by the integration of a butanediol dehydrogenase. In this study, different plasmid backbones and butanediol dehydrogenases were evaluated regarding efficiency for CO2-based 2,3-butanediol production. The developed strain utilizes the pBBR1 plasmid bearing a 2,3-butanediol dehydrogenase from Enterobacter cloacae and is characterized by 2,3-butanediol as the main product and a heterotrophic total product yield of 88.11%, an autotrophic volumetric productivity of 39.45 mg L−1 h−1, a total product carbon yield of 81.6%, an H2 efficiency of 33.46%, and a specific productivity of 0.016 g product per gram of biomass per hour. In addition, a mathematical model was developed to simulate the processes under these conditions. With this model, it was possible to calculate productivities and substrate usage at distinct time points of the production processes and calculate productivities and substrate usage with high resolution which will be useful in future applications.
Rapid and reliable detection of Leishmania antibodies in canine serum with double-antigen sandwich homogeneous chemical luminescence
Authors: Zhao Xiangjun , Ma Licai , Jin Yipeng , Barkema Herman W. , Kastelic John P. , Wang Lu , Wen Kai , Liu Gang
Published: July 2024

Background

Leishmaniasis, caused byLeishmaniaspp. parasites, is an important zoonotic disease globally, posing severe threats to humans and animals. In the absence of effective vaccines, reliable serological diagnostic methods are critical for disease control. However, the enzyme-linked immunosorbent assay (ELISA) and immunochromatographic assay have limitations due to complexity, time required and/or sensitivity. Therefore, our objective was to develop an accurate, rapid and user-friendly detection method of canine leishmania antibody based on double-antigen sandwich homogeneous chemical luminescence.

Methods

Homogeneous chemiluminescent technology was employed, and expressed recombinant fusion proteins containing full-length K9, K39 and K26 repeat sequences were used as diagnostic antigens. To establish a dual-antigen sandwich serological assay capable of detecting various antibody types, a factorial design was used to optimize concentrations of diagnostic antigen-receptor microspheres and of biotinylated diagnostic antigens, as well as of reaction solution composition and reaction duration. To evaluate and validate this newly developed method, we collected 41Leishmania-positive serum samples, 30Leishmania-negative control serum samples and 78 clinical serum samples for which no diagnostic information was available. Comparative analyses were performed using parasitological testing and an indirect ELISA as reference methods, focusing on diagnostic sensitivity and specificity.

Results

Sodium dodecyl sulfate–polyacrylamide gel electrophoresis confirmed the purification of the diagnostic antigens, which exhibited clear bands without impurities. Based on results from the 41Leishmania-positive samples and 30Leishmania-negative samples, there was sufficient sensitivity to detect samples diluted up to 256-fold, with analytical specificity of 100%. Overall diagnostic sensitivity was 100% and diagnostic specificity was 93.3%. Diagnostic performance was highly consistent between the newly developed method and the indirect ELISA (Kappa = 0.82,P < 0.01). Testing could be completed within 35 min with the new method

Conclusions

We have developed a novel double-antigen sandwich homogeneous chemical luminescence method to detect canineLeishmaniaantibodies, with high sensitively and specificity, a short incubation interval and a simple protocol. This streamlined approach not only offers a sensitive and efficient method for clinical diagnosis but also has great potential for use in automated testing.

Graphical Abstract
Expression of CD163 and major histocompatibility complex class I as diagnostic markers for idiopathic inflammatory myopathies
Authors: Ghang Byeongzu , Nam So Hye , Choi Wonho , Kim Hwa Jung , Lee Jungsun , Lim Doo-Ho , Ahn Soo Min , Oh Ji Seon , Hong Seokchan , Kim Yong-Gil , Lee Chang-Keun , Kim Jinseok , Yoo Bin , Nam Soo Jeong
Published: July 2024

Background

To develop an inflammation-related immunohistochemistry marker-based algorithm that confers higher diagnostic ability for idiopathic inflammatory myopathies (IIMs) than IIM-related histopathologic features.

Methods

Muscle biopsy tissues from 129 IIM patients who met the 2017 EULAR/ACR criteria and 73 control tissues from patients with non-inflammatory myopathies or healthy muscle specimens were evaluated for histological features and immunostaining results of CD3, CD4, CD8, CD20, CD68, CD163, MX1, MHC class I, MHC class II, and HLA-DR. Diagnostic algorithms for IIM were developed based on the results of the classification and regression tree (CART) analysis, which used immunostaining results as predictor variables for classifying patients with IIMs.

Results

In the analysis set (IIM, n = 129; control, n = 73), IIM-related histopathologic features had a diagnostic accuracy of 87.6% (sensitivity 80.6%; specificity 100.0%) for IIMs. Notably, muscular expression of CD163 (99.2% vs. 20.8%, p < 0.001) and MHC class I (87.6% vs. 23.1%, p < 0.001) was significantly higher in the IIM group than in controls. Based on the CART analysis results, we developed an algorithm combining CD163 and MHC class I expression that conferred a diagnostic accuracy of 95.5% (sensitivity 96.1%; specificity 94.5%). In addition, our algorithm was able to correctly diagnose IIM in 94.1% (16/17) of patients who did not meet the 2017 EUALR/ACR criteria but were diagnosed as having IIMs by an expert physician.

Conclusions

Combination of CD163 and MHC class I muscular expression may be useful in diagnosing IIMs.
No unfavorable effects on the menstruation recovery of early postoperative hypoprolactinemia after transsphenoidal surgery in patients with lactotroph pituitary neuroendocrine tumor
Authors: Ishida Tomohisa , Kawaguchi Tomohiro , Ogawa Yoshikazu , Tominaga Teiji , Endo Hidenori
Published: July 2024

Objective

Transsphenoidal surgery for lactotroph pituitary neuroendocrine tumor (PitNET) lowers serum prolactin concentrations, occasionally below the normal range. However, the clinical significance of postoperative hypoprolactinemia is still unclear. In this study, we retrospectively reviewed the female patients with lactotroph PitNET who were treated with transsphenoidal surgery to elucidate the influence of postoperative hypoprolactinemia on regular menstruation restoration and endocrinological remission.

Results

The serum prolactin levels in all thirty three participating females had decreased following surgery. Serum prolactin levels in seven patients had decreased below the lower limit of normal ranges (hypoproactinemia group) and in the remaining twenty six patients, it was within the normal range (non-hypoproractinemia group). In hypoprolactinemia group, regular menstruation was restored in all patients with only lactotroph axis deficiency. Nine patients from the non-hypoprolactinemia group experienced re-elevation of serum prolactin concentration (27%). No patient in hypoprolactinemia group experienced the relapse of hyperprolactinemia. These data suggest that early postoperative hypoprolactinemia after transsphenoidal surgery for lactotroph PitNET is not only a good predictive factor for endocrinological remission but also no unfavorable effects on regular menstruation restoration.
A descriptive study of the single-nucleotide polymorphisms known to affect the Tacrolimus trough concentration per dose, among a population of kidney failure patients in a tertiary hospital in Ghana
Authors: Kwakyi Edward , Nartey Edmund Tetteh , Otabil Michael Kobina , Asiedu-Gyekye Isaac , Ahorhorlu Samuel Yao , Bioma Vincent , Kudzi William
Published: July 2024

Background

The burden of chronic kidney disease (CKD) and kidney failure in Ghana is on the ascendency, with the prevalence of CKD estimated at 13.3%. Patients with CKD who progress to kidney failure require life sustaining kidney replacement therapy (KRT) which is almost exclusively available in Ghana as haemodialysis. Kidney transplantation is considered the best KRT option for patients with irreversible kidney failure due to its relative cost efficiency as well as its superiority in terms of survival and quality of life. However, because transplants may trigger an immune response with potential organ rejection, immunosuppressants such as tacrolimus dosing are required.

Objective

This study sought to determine single nucleotide polymorphisms in CYP3A5, CYP3A4 and MDR1 genes that affect the pharmacokinetics of Tacrolimus in a population of Ghanaian patients with kidney failure.

Method

This cross-sectional study comprised of 82 kidney failure patients undergoing maintenance haemodialysis at the Renal and Dialysis unit of Korle-Bu Teaching Hospital (KBTH). Clinical and demographic data were collected and genomic DNA isolated. Samples were genotyped for specific SNPs using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).

Results

Participants, 58/82 (70.73%) harbored the wildtype CYP3A5*1/*1 AA genotype, 20/82 (24.39%) carried the heterozygous CYP3A5*1/*3 AG genotype, and 4/82 (4.88%) had the homozygous mutant CYP3A5*3/*3 GG genotype. Also, 6/82 (7.32%) carried the wildtype AA genotype, 11/82 (13.41%) had the heterozygous AG genotype, and 65/82 (79.27%) harbored the homozygous mutant GG genotype of CYP3A4*1B (-290 A>G). For MDR1_Ex21 (2677 G>T), 81/82 (98.78%) carried the wildtype GG genotype, while 1/82 (1.22%) had the heterozygous GT genotype. For MDR1_Ex26 (3435 C>T), 63/82 (76.83%) had the wildtype CC genotype, while 18/82 (21.95%) carried the heterozygous CT genotype, and 1/82 (1.22%) harbored the mutant TT genotype.

Conclusion

SNPs in CYP3A4, CYP3A5, and MDR1 genes in a population of Ghanaian kidney failure patients were described. The varying SNPs of the featured genes suggest the need to consider the genetic status of Ghanaians kidney failure patients prior to transplantation and tacrolimus therapy.
Association of oxidative stress and inflammatory metabolites with Alzheimer’s disease cerebrospinal fluid biomarkers in mild cognitive impairment
Authors: Ahmad Shahzad , Yang Wei , Orellana Adelina , Frölich Lutz , de Rojas Itziar , Cano Amanda , Boada Mercè , Hernández Isabel , Hausner Lucrezia , Harms Amy C. , Bakker Margot H. M. , Cabrera-Socorro Alfredo , Amin Najaf , Ramírez Alfredo , Ruiz Agustín , Van Duijn Cornelia M. , Hankemeier Thomas
Published: July 2024

Background

Isoprostanes and prostaglandins are biomarkers for oxidative stress and inflammation. Their role in Alzheimer's disease (AD) pathophysiology is yet unknown. In the current study, we aim to identify the association of isoprostanes and prostaglandins with the Amyloid, Tau, Neurodegeneration (ATN) biomarkers (Aβ-42, p-tau, and t-tau) of AD pathophysiology in mild cognitive impairment (MCI) subjects.

Methods

Targeted metabolomics profiling was performed using liquid chromatography-mass spectrometry (LCMS) in 147 paired plasma-CSF samples from the Ace Alzheimer Center Barcelona and 58 CSF samples of MCI patients from the Mannheim/Heidelberg cohort. Linear regression was used to evaluate the association of metabolites with CSF levels of ATN biomarkers in the overall sample and stratified by Aβ-42 pathology and APOE genotype. We further evaluated the role of metabolites in MCI to AD dementia progression.

Results

Increased CSF levels of PGF2α, 8,12-iso-iPF2α VI, and 5-iPF2α VI were significantly associated (False discovery rate (FDR) < 0.05) with higher p-tau levels. Additionally, 8,12-iso-iPF2α VI was associated with increased total tau levels in CSF. In MCI due to AD, PGF2α was associated with both p-tau and total tau, whereases 8,12-iso-iPF2α VI was specifically associated with p-tau levels. In APOE stratified analysis, association of PGF2α with p-tau and t-tau was observed in only APOE ε4 carriers while 5-iPF2α VI showed association with both p-tau and t-tau in APOE ε33 carriers. CSF levels of 8,12- iso-iPF2α VI showed association with p-tau and t-tau in APOE ε33/APOE ε4 carriers and with t-tau in APOE ε3 carriers. None of the metabolites showed evidence of association with MCI to AD progression.

Conclusions

Oxidative stress (8,12-iso-iPF2α VI) and inflammatory (PGF2α) biomarkers are correlated with biomarkers of AD pathology during the prodromal stage of AD and relation of PGF2α with tau pathology markers may be influenced by APOE genotype.
Chemical entity normalization for successful translational development of Alzheimer’s disease and dementia therapeutics
Authors: Mullin Sarah , McDougal Robert , Cheung Kei-Hoi , Kilicoglu Halil , Beck Amanda , Zeiss Caroline J.
Published: July 2024

Background

Identifying chemical mentions within the Alzheimer’s and dementia literature can provide a powerful tool to further therapeutic research. Leveraging the Chemical Entities of Biological Interest (ChEBI) ontology, which is rich in hierarchical and other relationship types, for entity normalization can provide an advantage for future downstream applications. We provide a reproducible hybrid approach that combines an ontology-enhanced PubMedBERT model for disambiguation with a dictionary-based method for candidate selection.

Results

There were 56,553 chemical mentions in the titles of 44,812 unique PubMed article abstracts. Based on our gold standard, our method of disambiguation improved entity normalization by 25.3 percentage points compared to using only the dictionary-based approach with fuzzy-string matching for disambiguation. For the CRAFT corpus, our method outperformed baselines (maximum 78.4%) with a 91.17% accuracy. For our Alzheimer’s and dementia cohort, we were able to add 47.1% more potential mappings between MeSH and ChEBI when compared to BioPortal.

Conclusion

Use of natural language models like PubMedBERT and resources such as ChEBI and PubChem provide a beneficial way to link entity mentions to ontology terms, while further supporting downstream tasks like filtering ChEBI mentions based on roles and assertions to find beneficial therapies for Alzheimer’s and dementia.
Testing dental microwear as a proxy for characterising trophic ecology in fossil elasmobranchs (chondrichthyans)
Authors: Paredes-Aliaga María Victoria , Botella Héctor , Romero Alejandro
Published: July 2024

Dental microwear analysis is a well-established technique that provides valuable information about the diets of extant and extinct taxa. It has been used effectively in most major groups of vertebrates. However, in chondrichthyans, these methods have been implemented only recently in the form of dental microwear texture analysis, with conflicting results. Causes intrinsic to chondrichthyan biology, such as limited food-to-tooth contact, low diversity in terms of trophic categories or fast tooth replacement, have been suggested to reduce diet-related wear on individual teeth, hindering the use of this approach for reliable dietary reconstruction. Here, we explored the relationship between diet and dental microwear in chondrichthyans by using 2D analysis, which can provide finer-scale identification and accurate definition of scratch morphology from tooth surfaces a priori. Scratches were counted and measured on the teeth of 34 extant elasmobranchs grouped into three categories (piscivorous, durophagous and generalist) according to dietary preferences. Our results revealed specific patterns of tooth microwear as a function of dietary abrasiveness, enabling the discrimination of trophic groups and thus establishing a useful comparative framework for inferring aspects of trophic ecology in fossils. We then used this information to study dental microwear in six fossil species from the same locality and stratigraphic levels. First, analyses of the enameloid surfaces of the fossil show that post-mortem alterations are distinguishable, allowing reliable quantification of diet-related ante-mortem microwear signatures. Discriminant analysis allowed the recognition of microwear patterns comparable to those of living sharks and linked them to specific trophic groups with high probability levels (> 90%). Thus, microwear features developing on chondrichthyan teeth during feeding are intense enough to retain information regarding diet preferences. 2D microwear analysis can track this information, proving to be a useful tool for providing significant information not only about diet but also about oral processing mechanisms in extinct chondrichthyans.
Exploring the relationship between social activities and financial risk aversion in adults aged 50 + with depression caseness
Authors: Musbat Shay , Reuveni Inbal , Magnezi Racheli
Published: July 2024

Background

Risk aversion due to depression is common among older adults, and social participation is associated with improved mental health and a lower risk of late-life depression. However, little is known about the connection between participation in social activities and risky financial decisions among adults with depression. Thus, we aim to examine the connection between participation in social activities and taking financial risks and investing in risky financial assets (with high-return potential) in such individuals, differentiated by age and gender. The study also focuses on analyzing the percentage of investors within each social activity, their attendance frequency, and motivation.

Methods

The data was obtained from the Survey of Health, Ageing and Retirement in Europe (SHARE) database Wave 2 (2006–2010). The study included 8,769 individuals aged 50 + with depression caseness, from 15 European countries and Israel who answered the question on participation in social activities and reported financial risk-taking intentions or behaviors (investing in stocks or shares, mutual funds or managed investment accounts, and both). The study utilized Pearson chi-square, odds ratios, Z, and hierarchical logistic regression tests.

Results

The odds for taking financial risks and investing in risky financial assets were higher for those participating in social activities compared to those who did not, on both intentional (by 173%) and behavioral (by 240–397%) levels. Such social activities (attended at least once a week, without financial motivation) have been shown to be primarily represented by educational or training courses — where 33% of participants invested in risky financial assets. The connection persisted after controlling for gender, age, marital status, children, income.

Conclusions

By overcoming the subjects’ financial risk aversion, participation in social activities may help improve mental health in individuals aged 50 + with depression caseness. This has important implications for policymakers in healthcare, who by updating healthcare policies can fund and facilitate participation in social activities. As a result, the national healthcare system may benefit from lower hospitalization-related expenses, and generate higher cash flows into the country’s economy using the population’s renewed interest in investing available funds. These results are relevant in the wake of COVID-19 that increased loneliness and depression rates.
Analysis of Gaussian phase noise effects in DFT-s-OFDM systems for sub-THz transmissions
Authors: Bello Yaya , Doré Jean-Baptiste , Demmer David
Published: July 2024

The future generations of communication technologies envision the transmission of signals across the millimeter wave and sub-THz spectrums. However, the characteristics of the propagation channel at such high frequencies differ from what is observed in the conventional low-frequency spectrum with for instance, the apparition of stronger phase noise (PN) induced by the Radio Frequency (RF) transceivers and more especially by the oscillators. That is why there is growing interest in evaluating and adapting the 5G new radio (5G-NR) physical layer to the presence of PN. This article is dedicated to the study of discrete Fourier transform-spread-Orthogonal Frequency Division Multiplexing (DFT-s-OFDM) under uncorrelated Gaussian PN (GPN) impairments. We show that the presence of GPN induces two distortions: (i) a frequency-dependent random rotation of data, namely the subcarrier phase error (SPE) and (ii) a frequency-dependent intercarrier interference (ICI) that are analytically expressed. Then, we investigate the design of the adapted and optimal detection criterion according to the baseband model we derived in this paper. We demonstrate that (i) the proposed polar detector outperforms the conventional Euclidean detector and (ii) contrary to legacy OFDM, DFT-s-OFDM is a promising solution when strong GPN is involved.
Effect of anesthesia on the success rate of external cephalic version: GRADE- assessed systematic review and meta-analysis of randomized controlled trials
Authors: Lei Liming , Fang Zhiyong , Xu Chenyang , Wang Zhaohui , Li Hui , Ma Li
Published: July 2024

Background

External cephalic version (ECV) is a medical procedure in which an extracorporeal manipulation is performed to render the breech presentation (BP) fetus in the cephalic position. The use of anesthesia to facilitate repositioning has been evaluated in various randomized clinical trials (RCTs), but its potential effectiveness remains controversial.

Methods

A systematic literature search was carried out in 8 electronic databases. In the meta-analysis, a random effects model was used to calculate the pooled relative risk (RR) and its 95% confidence interval (CI), and the pooled standardized mean difference (SMD) and its 95% CI, in order to systematically assess the effect of anesthesia on the success rates of ECV, vaginal delivery, cesarean delivery as well as other outcomes. Relevant subgroup analyses, publication bias test and sensitivity analyses were also conducted.

Results

This review included 17 RCTs. Women who received anesthesia had a significantly higher incidence of successful ECV (RR: 1.37, 95% CIs: 1.19-1.58) and vaginal delivery (RR: 1.23, 95% CIs: 1.03-1.47), and a significantly lower incidence of cesarean delivery (RR: 0.69, 95% CIs: 0.53-0.91), compared with those who did not.

Conclusion

The administration of anesthesia not only significantly reduces maternal pain but also significantly increases the success rate of ECV in women with malpresentation at term, leading to a significant rise in the incidence of vaginal delivery. However, it may increase the incidence of maternal hypotension.

Systematic review registration

The protocol was prospectively registered with PROSPERO, registration CRD42022381552.
Investigating composite electrode materials of metal oxides for advanced energy storage applications
Authors: Pazhamalai Parthiban , Krishnan Vignesh , Mohamed Saleem Mohamed Sadiq , Kim Sang-Jae , Seo Hye-Won
Published: July 2024

Electrochemical energy systems mark a pivotal advancement in the energy sector, delivering substantial improvements over conventional systems. Yet, a major challenge remains the deficiency in storage technology to effectively retain the energy produced. Amongst these are batteries and supercapacitors, renowned for their versatility and efficiency, which depend heavily on the quality of their electrode materials. Metal oxide composites, in particular, have emerged as highly promising due to the synergistic effects that significantly enhance their functionality and efficiency beyond individual components. This review explores the application of metal oxide composites in the electrodes of batteries and SCs, focusing on various material perspectives and synthesis methodologies, including exfoliation and hydrothermal/solvothermal processes. It also examines how these methods influence device performance. Furthermore, the review confronts the challenges and charts future directions for metal oxide composite-based energy storage systems, critically evaluating aspects such as scalability of synthesis, cost-effectiveness, environmental sustainability, and integration with advanced nanomaterials and electrolytes. These factors are crucial for advancing next-generation energy storage technologies, striving to enhance performance while upholding sustainability and economic viability.
Scaffolded team-based computational modeling and simulation projects for promoting representational competence and regulatory skills
Authors: Magana Alejandra J. , Arigye Joreen , Udosen Abasiafak , Lyon Joseph A. , Joshi Parth , Pienaar Elsje
Published: July 2024

Background

This study posits that scaffolded team-based computational modeling and simulation projects can support model-based learning that can result in evidence of representational competence and regulatory skills. The study involved 116 students from a second-year thermodynamics undergraduate course organized into 24 teams, who worked on three two-week-long team-based computational modeling and simulation projects and reflected upon their experience.

Results

Results characterized different levels of engagement with computational model-based learning in the form of problem formulation and model planning, implementation and use of the computational model, evaluation, and interpretation of the outputs of the model, as well as reflection on the process. Results report on students’ levels of representational competence as related to the computational model, meaning-making of the underlying code of the computational model, graphical representations generated by the model, and explanations and interpretations of the output representations. Results also described regulatory skills as challenges and strategies related to programming skills, challenges and strategies related to meaning-making skills for understanding and connecting the science to the code and the results, and challenges and strategies related to process management mainly focused on project management skills.

Conclusion

Characterizing dimensions of computational model-based reasoning provides insights that showcase students’ learning, benefits, and challenges when engaging in team-based computational modeling and simulation projects. This study also contributes to evidence-based scaffolding strategies that can support undergraduate students' engagement in the context of computational modeling and simulation.