bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient perspectives of using reproductive autonomy to measure quality of care: a qualitative study
Authors: Manze Meredith G. , Srinivasulu Silpa , Jones Heidi E.
Published: December 2023

Background

Current measures of reproductive health care quality, such as rates of “unintended” pregnancies, neglect to incorporate patients’ desires and center their reproductive autonomy. This study explores patients’ perspectives on and receptivity to alternative metrics for measuring quality of such care.

Methods

An online research recruitment firm identified eligible participants living in New York, ages 18–45, self-identifying as women, and having visited a primary care provider in the last year. We conducted five virtual focus groups and eight in-depth interviews with participants (N = 30) in 2021. Semi-structured guides queried on ideal clinic interactions when preventing or attempting pregnancy and their perspectives on how to measure the quality of such encounters, including receptivity to using our definition of reproductive autonomy to develop one such metric: “whether the patient got the reproductive health service or counseling that they wanted to get, while having all the information about and access to their options, and not feeling forced into anything.” We employed an inductive thematic analysis.

Results

Participants wanted care that was non-judgmental, respectful, and responsive to their needs and preferences. For pregnancy prevention, many preferred unbiased information about contraceptive options to help make their own decisions. For pregnancy, many desired comprehensive information and more provider support. There was considerable support for using reproductive autonomy to measure quality of care.

Conclusions

Patients had distinct desires in their preferred approach to discussions about preventing versus attempting pregnancy. Quality of reproductive health care should be measured from the patient’s perspective. Given participants’ demonstrated support, future research is needed to develop and test a new metric that assesses patients’ perceptions of reproductive autonomy during clinical encounters.
Evaluation of online educational curriculum on HPV vaccination practices among adult primary care providers
Authors: Zhang Christiana , Greengold Judy , Tackett Sean , Lentz Caroline , Bennett Wendy , McGuire Maura
Published: December 2023

Background

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. While HPV is a vaccine-preventable illness, vaccine utilization rates in the United States remain low, particularly among adults.

Methods

The objective of this study was to assess the impact of an online, asynchronous educational module on HPV vaccination for adult primary care providers. We designed and implemented the module for family medicine, internal medicine, medicine/pediatrics, and obstetrics/gynecology providers in a community practice network affiliated with a large academic health system. We evaluated the effect of the module on provider knowledge, attitudes, and self-reported behaviors with pre-, post-, and delayed post-tests, using Likert-scales for measurement. We summarized data with descriptive statistics and compared changes in individuals using paired t-tests.

Results

One hundred forty-four out of 223 providers completed the module (response rate of 65%). At baseline, internists had the lowest knowledge scores compared to other specialties (pre-test mean of 3.6, out of 5, SD 1.2). Internists were also the least likely to counsel patients on HPV vaccination (mean 1.6, SD 0.9). There was a statistically significant improvement in knowledge from pre-test to post-test (from mean of 3.8 to 4.6, out of 5, p < .001) across all specialties. There was also statistically significant improvement in mean confidence for all providers from pre-test to post-test to identify patients aged 19–26 (3.3 to 3.7, p < .001) and patients aged 27–45 (2.7 to 3.5, p < .001) who needed vaccination. There was a statistically significant improvement in likelihood to counsel eligible patients on the risks of HPV infection (mean 2.3 to 2.8, p-value 0.002). The delayed post-test demonstrated retention of improved knowledge, confidence, and self-reported behavior.

Conclusions

This study demonstrated that an asynchronous online module was effective at improving confidence, knowledge, and self-reported behavior of adult primary care providers in recommending HPV immunization. Given the important role that healthcare providers play in vaccine uptake, this study suggests that an online educational intervention can be a powerful tool to encourage increased utilization and delivery of the HPV vaccine. Further efforts are needed to educate internists and providers who take care of the adult population on HPV vaccination.
Mapping and identifying service models for community-based services for children with intellectual disabilities and behaviours that challenge in England
Authors: Taylor Emma L. , Thompson Paul A. , Manktelow Nicholas , Flynn Samantha , Gillespie David , Bradshaw Jill , Gore Nick , Liew Ashley , Lovell Mark , Sutton Kate , Richards Caroline , Petrou Stavros , Langdon Peter E. , Grant Gemma , Cooper Vivien , Seers Kate , Hastings Richard P.
Published: December 2023

Background

One in five children with an intellectual disability in the UK display behaviours that challenge. Despite associated impacts on the children themselves, their families, and services, little research has been published about how best to design, organise, and deliver health and care services to these children. The purpose of this study was to describe how services are structured and organised (“service models”) in England for community-based health and care services for children with intellectual disability who display behaviours that challenge.

Methods

Survey data about services were collected from 161 eligible community-based services in England. Staff from 60 of these services were also interviewed. A combination of latent class and descriptive analysis, coupled with consultation with family carers and professionals was used to identify and describe groupings of similar services (i.e., “service models”).

Results

The latent class analysis, completed as a first step in the process, supported a distinction between specialist services and non-specialist services for children who display behaviours that challenge. Planned descriptive analyses incorporating additional study variables were undertaken to further refine the service models.

Five service models were identified: Child and Adolescent Mental Health Services (CAMHS) (n = 69 services), Intellectual Disability CAMHS (n = 28 services), Children and Young People Disability services (n = 25 services), Specialist services for children who display behaviours that challenge (n = 27 services), and broader age range services for children and/or adolescents and adults (n= 12 services).

Conclusions

Our analysis led to a typology of five service models for community health and care services for children with intellectual disabilities and behaviours that challenge in England. Identification of a typology of service models is a first step in building evidence about the best provision of services for children with intellectual disabilities who display behaviours that challenge. The methods used in the current study may be useful in research developing service typologies in other specialist fields of health and care.

Study registration

Trial Registration: Current Controlled Trials ISRCTN88920546, Date assigned 05/07/2022.
Plasmodium yoelii iron transporter PyDMT1 interacts with host ferritin and is required in full activity for malarial pathogenesis
Authors: Zhong Mengjiao , Zhou Bing
Published: December 2023

Background

The rapid reproduction of malaria parasites requires proper iron uptake. However, the process of iron absorption by parasites is rarely studied. Divalent metal transporter (DMT1) is a critical iron transporter responsible for uptaking iron. A homolog of human DMT1 exists in the malaria parasite genome, which in Plasmodium yoelii is hereafter named PyDMT1.

Results

PyDMT1 knockout appears to be lethal. Surprisingly, despite dwelling in an iron-rich environment, the parasite cannot afford to lose even partial expression of PyDMT1; PyDMT1 hypomorphs were associated with severe growth defects and quick loss of pathogenicity. Iron supplementation could completely suppress the defect of the PyDMT1 hypomorph during in vitro culturing. Genetic manipulation through host ferritin (Fth1) knockout to increase intracellular iron levels enforced significant growth inhibition in vivo on the normal parasites but not the mutant. In vitro culturing with isolated ferritin knockout mouse erythrocytes completely rescued PyDMT1-hypomorph parasites.

Conclusion

A critical iron requirement of malaria parasites at the blood stage as mediated by this newly identified iron importer PyDMT1, and the iron homeostasis in malarial parasites is finely tuned. Tipping the iron balance between the parasite and host will efficiently kill the pathogenicity of the parasite. Lastly, PyDMT1 hypomorph parasites were less sensitive to the action of artemisinin.
Noninvasive urinary protein signatures combined clinical information associated with microvascular invasion risk in HCC patients
Authors: Wang Yaru , Meng Bo , Wang Xijun , Wu Anke , Li Xiaoyu , Qian Xiaohong , Wu Jianxiong , Ying Wantao , Xiao Ting , Rong Weiqi
Published: December 2023

Background

Microvascular invasion (MVI) is the main factor affecting the prognosis of patients with hepatocellular carcinoma (HCC). The aim of this study was to identify accurate diagnostic biomarkers from urinary protein signatures for preoperative prediction.

Methods

We conducted label-free quantitative proteomic studies on urine samples of 91 HCC patients and 22 healthy controls. We identified candidate biomarkers capable of predicting MVI status and combined them with patient clinical information to perform a preoperative nomogram for predicting MVI status in the training cohort. Then, the nomogram was validated in the testing cohort (n = 23). Expression levels of biomarkers were further confirmed by enzyme-linked immunosorbent assay (ELISA) in an independent validation HCC cohort (n = 57).

Results

Urinary proteomic features of healthy controls are mainly characterized by active metabolic processes. Cell adhesion and cell proliferation-related pathways were highly defined in the HCC group, such as extracellular matrix organization, cell–cell adhesion, and cell–cell junction organization, which confirms the malignant phenotype of HCC patients. Based on the expression levels of four proteins: CETP, HGFL, L1CAM, and LAIR2, combined with tumor diameter, serum AFP, and GGT concentrations to establish a preoperative MVI status prediction model for HCC patients. The nomogram achieved good concordance indexes of 0.809 and 0.783 in predicting MVI in the training and testing cohorts.

Conclusions

The four-protein-related nomogram in urine samples is a promising preoperative prediction model for the MVI status of HCC patients. Using the model, the risk for an individual patient to harbor MVI can be determined.
Enhancement of phycocyanin productivity and thermostability from Arthrospira platensis using organic acids
Authors: Gomaa Mohamed , Ali Shimaa Abdelmohsen , Hifney Awatief F.
Published: December 2023

Intracellular hyperaccumulation of phycocyanin (PC) and its high susceptibility to degradation at higher temperatures are major challenging problems associated with its production from cyanobacteria. The present study evaluated different concentrations of organic acids (1, 2, and 3 mM) (citric acid, acetic acid, succinic acid, fumaric acid, and oxalic acid) under fed-batch mode on the biomass and phycobiliproteins’ production from Arthrospira platensis. Besides they were evaluated at 2.5–7.5 mM as preservative to stabilize PC at high temperatures. The incorporation of 3 mM of succinic acid into the cultivation medium enhanced the biomass and PC productivity to 164.05 and 26.70 mg L−1 day−1, which was ~ 2- and threefold higher than control, respectively. The produced PC in this treatment was food-grade with a 2.2 purity ratio. The use of organic acids also enhanced the thermal stability of PC. Citric acid (7.5 mM) markedly promoted the half-life values of PC to 189.44 min compared to 71.84 min in the control. The thermodynamic analysis confirmed higher thermostability of PC in the presence of organic acids and indicated the endothermic and non-spontaneity of the thermal denaturation process. The findings of the present study confirmed that organic acids could be utilized as cost effective and sustainable compounds for promoting not only phycobiliproteins’ production but also the thermostability of PC for potential application in food industry.
Polysaccharides from Spirulina platensis (PSP): promising biostimulants for the green synthesis of silver nanoparticles and their potential application in the treatment of cancer tumors
Authors: Al-Badwy Asmaa H. , Khalil Ahmed M. , Bashal Ali H. , Kebeish Rashad
Published: December 2023

Photosynthetic cyanobacterial components are gaining great economic importance as prospective low-cost biostimulants for the green synthesis of metal nanoparticles with valuable medical and industrial applications. The current study comprises the biological synthesis of silver nanoparticles (Ag-NPs) using soluble polysaccharides isolated from Spirulina platensis (PSP) as reducing and capping agents. FTIR spectra showed major functional groups of PSP and biogenic silver nanoparticles including O–H, C–H (CH2), C–H (CH3), C=O, amide, and COO– groups. The UV/Vis spectroscopy scan analyses of the extracted PSP showed absorption spectra in the range of 200–400 nm, whereas the biogenic Ag-NPs showed a maximum spectrum at 285 nm. Transmission electron microscopy (TEM) analysis of the synthesized Ag-NPs showed spherical nanoparticles with mean size between 12 and 15.3 nm. The extracted PSP and Ag-NPs exhibited effective cytotoxic activity against Hep-G2 (human hepatocellular carcinoma). The IC50 for PSP and Ag-NPs were 65.4 and 24.5 µg/mL, respectively. Moreover, cell apoptosis assays for PSP and Ag-NPs against the growth of Hep-G2 cells revealed superior growth inhibitory effects of the green synthesized Ag-NPs that encouraged tracing the apoptotic signalling pathway. In conclusion, the current study demonstrated an unprecedented approach for the green synthesis of silver nanoparticles (NPs), using the polysaccharide of Spirulina platensis as reducing and capping agents, with superior anticancer activity against a hepatocellular carcinoma cell line.
The function and mechanism of PSMD14 in promoting progression and resistance to anlotinib in osteosarcoma
Authors: Liu Zhiyong , Wang Xin , Li Chao , Zhao Ruina
Published: December 2023

Background

Osteosarcoma is a rare bone malignancy that frequently affects adolescents and poses formidable obstacles in its advanced stages. Studies revealed that PSMD14 may be a viable osteosarcoma treatment target. However, PSMD14’s function and mechanism in osteosarcoma remain unknown. This study aimed to examine the function and mechanism of PSMD14 in the biological behavior of osteosarcoma and its role in anlotinib resistance.

Methods

Western blotting, qRT-PCR, and immunohistochemistry (IHC) studies were used to examine PSMD14 levels. The role of PSMD14 in the malignant phenotype of osteosarcoma and its molecular pathway was explored by a series of studies, including Western blotting, cell amplification assay, transwell assay, and tumor growth. Furthermore, a series of in vitro investigations were done to determine the effect of PSMD14 on anlotinib-resistant osteosarcoma cell lines.

Results

PSMD14 expression was elevated in osteosarcoma tissues compared to normal tissues. Overexpression of PSMD14 was associated with osteosarcoma patients’ pathological grade and clinical stage, and PSMD14 was an independent poor prognostic factor. PSMD14 knockdown inhibits in vitro cell proliferation, migration, invasion, and in vivo tumor growth. PSMD14 knockdown has the potential to downregulate the PI3K/Akt/mTOR pathway, which was regarded as one of the key mechanisms promoting tumor growth. PSMD14 was likewise overexpressed in anlotinib-resistant OS cell lines, and its knockdown not only reduced the proliferation, migration, and invasion of subline cells and triggered cell apoptosis. Importantly, combination therapy with anlotinib enhanced these effects.

Conclusions

PSMD14 is substantially expressed in osteosarcoma and may be an independent risk factor associated with poor prognosis. It can promote tumor progression and anlotinib resistance in osteosarcoma and may promote osteosarcoma progression by modulating PI3K/AKT/mTOR signaling pathway.
25(OH)D3 improves granulosa cell proliferation and IVF pregnancy outcomes in patients with endometriosis by increasing G2M+S phase cells
Authors: Hu Rui , Li Leilei , Liang Lanlan , Qi YuXin , Ma Xiaoling , Yang Yuan
Published: December 2023

Background

The 25-hydroxyvitamin D3 (25 (OH) D3) is crucial for follicular development. This study aimed to investigate the relationship between the level of 25 (OH) D3 in endometriosis patients, pregnancy outcomes of in vitro fertilization (IVF), and the underlying mechanism.

Methods

The 25 (OH) D3 levels in serum and follicular Fluid (FF) samples were detected using enzyme-linked immunosorbent assay (ELISA). Clinical features and pregnancy outcomes of endometriosis patients were also compared between the deficient group (< 20 ug/ml) and the adequate group (≥ 20 ug/ml). The effects of 25 (OH) D3 on the proliferation and cell cycle of human ovarian granulosa cells were respectively detected by CCK-8 assay and flow cytometry (FCM). The differentially expressed genes (DEGs) in granulosa cells of endometriosis and tubal infertility patients were screened from GEO database. The effects of 25 (OH) D3 on the expressions of CDKN2D, PPARA, TGFB2 and THBD were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot.

Results

The levels of 25 (OH) D3 in serum and FF samples were decreased in endometriosis patients. The deficient group had fewer embryos that can be transferred, lower quality embryos and lower clinical pregnancy rates. Adequate 25 (OH) D3 levels in FF samples was a protective factor for live birth outcome in endometriosis patients. 25 (OH) D3 enhanced the proliferation capacity of granulosa cells (the concentration of 10 nM was the most significant) and increased the proportion of G2M + S phase cells. The expression of CDKN2D was decreased and TGFB2 and THBD were significantly upregulated.

Conclusions

25 (OH) D3 deficiency may be associated with poor IVF pregnancy outcomes in endometriosis patients. 25 (OH) D3 promotes ovarian granulosa cell proliferation by promoting the ability of cells to divide, and may accelerate cell cycle progression by up-regulating THBD and down-regulating CDKN2D expression.
Senescence-associated secretory phenotypes in mesenchymal cells contribute to cytotoxic immune response in oral lichen planus
Authors: Ijima Shogo , Saito Yuki , Yamamoto Sena , Nagaoka Kentaro , Iwamoto Taiki , Kita Arisa , Miyajima Maki , Sato Tsukasa , Miyazaki Akihiro , Chikenji Takako S.
Published: December 2023

Oral lichen planus is a chronic inflammatory condition that adversely affects the oral mucosa; however, its etiology remains elusive. Consequently, therapeutic interventions for oral lichen planus are limited to symptomatic management. This study provides evidence of the accumulation of senescent mesenchymal cells, CD8 + T cells, and natural killer cells in patients with oral lichen planus. We profiled the patients’ tissues using the National Center for Biotechnology Information Gene Expression Omnibus database and found that senescence-related genes were upregulated in these tissues by gene set enrichment analysis. Immunohistochemical analysis showed increased senescent mesenchymal cells in the subepithelial layer of patients with oral lichen planus. Single-cell RNA-seq data retrieved from the Gene Expression Omnibus database of patients with oral lichen planus revealed that mesenchymal cells were marked by the upregulation of senescence-related genes. Cell-cell communication analysis using CellChat showed that senescent mesenchymal cells significantly influenced CD8 + T cells and natural killer cells via CXCL12-CXCR4 signaling, which is known to activate and recruit CD8 + T cells and NK cells. Finally, in vitro assays demonstrated that the secretion of senescence-associated factors from mesenchymal cells stimulated the activation of T cells and natural killer cells and promoted epithelial cell senescence and cytotoxicity. These findings suggest that the accumulation of mesenchymal cells with senescence-associated secretory phenotype may be a key driver of oral lichen planus pathogenesis.
Challenges in international health financing and implications for the new pandemic fund
Authors: Brown Garrett Wallace , Rhodes Natalie , Tacheva Blagovesta , Loewenson Rene , Shahid Minahil , Poitier Francis
Published: December 2023

Background

The failures of the international COVID-19 response highlighted key gaps in pandemic preparedness and response (PPR). The G20 and WHO have called for additional funding of $10.5 billion per year to adequately strengthen the global PPR architecture. In response to these calls, in 2022 the World Bank announced the launch of a new Financial Intermediary Fund (The Pandemic Fund) to catalyse this additional funding. However, there is considerable unclarity regarding the governance makeup and financial modalities of the Pandemic Fund, and divergence of opinion about whether the Fund has been successfully designed to respond to key challenges in global health financing.

Methods/Results

The article outlines eight challenges associated with global health financing instruments and development aid for health within the global health literature. These include misaligned aid allocation; accountability; multistakeholder representation and participation; country ownership; donor coherency and fragmentation; transparency; power dynamics, and; anti-corruption. Using available information about the Pandemic Fund, the article positions the Pandemic Fund against these challenges to determine in what ways the financing instrument recognizes, addresses, partially addresses, or ignores them. The assessment argues that although the Pandemic Fund has adopted a few measures to recognise and address some of the challenges, overall, the Pandemic Fund has unclear policies in response to most of the challenges while leaving many unaddressed.

Conclusion

It remains unclear how the Pandemic Fund is explicitly addressing challenges widely recognized in the global health financing literature. Moreover, there is evidence that the Pandemic Fund might be exacerbating these global financing challenges, thus raising questions about its potential efficacy, suitability, and chances of success. In response, this article offers four sets of policy recommendations for how the Pandemic Fund and the PPR financing architecture might respond more effectively to the identified challenges.
Alarm with care—a de-implementation strategy to reduce fall prevention alarm use in US hospitals: a study protocol for a hybrid 2 effectiveness-implementation trial
Authors: Turner Kea , McNett Molly , Potter Catima , Cramer Emily , Al Taweel Mona , Shorr Ronald I. , Mion Lorraine C.
Published: December 2023

Background

Fall prevention alarms are commonly used among US hospitals as a fall prevention strategy despite limited evidence of effectiveness. Further, fall prevention alarms are harmful to healthcare staff (e.g., alarm fatigue) and patients (e.g., sleep disturbance, mobility restriction). There is a need for research to develop and test strategies for reducing use of fall prevention alarms in US hospitals.

Methods

To address this gap, we propose testing the effectiveness and implementation of Alarm with Care, a de-implementation strategy to reduce fall prevention alarm use using a stepped-wedge randomized controlled trial among 30 adult medical or medical surgical units from nonfederal US acute care hospitals. Guided by the Choosing Wisely De-Implementation Framework, we will (1) identify barriers to fall prevention alarm de-implementation and develop tailored de-implementation strategies for each unit and (2) compare the implementation and effectiveness of high- versus low-intensity coaching to support site-specific de-implementation of fall prevention alarms. We will evaluate effectiveness and implementation outcomes and examine the effect of multi-level (e.g., hospital, unit, and patient) factors on effectiveness and implementation. Rate of fall prevention alarm use is the primary outcome. Balancing measures will include fall rates and fall-related injuries. Implementation outcomes will include feasibility, acceptability, appropriateness, and fidelity.

Discussion

Findings from this line of research could be used to support scale-up of fall prevention alarm de-implementation in other healthcare settings. Further, research generated from this proposal will advance the field of de-implementation science by determining the extent to which low-intensity coaching is an effective and feasible de-implementation strategy.

Trial registration

ClinicalTrials.gov identifier: NCT06089239. Date of registration: October 17, 2023.
Association of autoimmune diseases with the occurrence and 28-day mortality of sepsis: an observational and Mendelian randomization study
Authors: Li Hui , Pan Xiaojun , Zhang Sheng , Shen Xuan , Li Wan , Shang Weifeng , Wen Zhenliang , Huang Sisi , Chen Limin , Zhang Xu , Chen Dechang , Liu Jiao
Published: December 2023

Background

Observational studies have indicated a potential association between autoimmune diseases and the occurrence of sepsis, with an increased risk of mortality among affected patients. However, whether a causal relationship exists between the two remains unknown.

Methods

In the Mendelian randomization (MR) study, we accessed exposure Genome-wide association study (GWAS) data from both the MRC Integrative Epidemiology Unit (MRC-IEU) and the FinnGen consortium. GWAS data for sepsis and its 28-day mortality were obtained from MRC-IEU. We employed univariable, multivariable, and reverse MR analyses to explore potential associations between autoimmune disorders and sepsis and its 28-day mortality. Additionally, a two-step mediation MR analysis was performed to investigate indirect factors possibly influencing the relationship between autoimmune disorders and sepsis. Afterward, we conducted an observational analysis to further explore the relationship between autoimmune disease and occurrence as well as 28-day mortality of sepsis using a real-world database (the MIMIC-IV database). A cohort of 2537 patients diagnosed with autoimmune disease were extracted from the database for analysis. Multivariable logistic regression models were used to confirm the association between autoimmune diseases and the occurrence of sepsis, as well as the 28-day mortality associated with sepsis.

Results

In univariable MR analysis, there appeared to be causal relationships between genetically predicted type 1 diabetes (OR = 1.036, 95% CI = 1.023–1.048, p = 9.130E-09), rheumatoid arthritis (OR = 1.077, 95% CI = 1.058–1.097, p = 1.00E-15) and sepsis, while a potential causal link was observed between celiac disease and sepsis (OR = 1.013, 95% CI = 1.002–1.024, p = 0.026). In a subsequent multivariable MR analysis, only rheumatoid arthritis was found to be independently associated with the risk of sepsis (OR = 1.138, 95% CI = 1.044–1.240, p = 3.36E-03). Furthermore, there was no causal link between autoimmune disorders and 28-day mortality from sepsis. In reverse MR analysis, sepsis was suggested to potentially trigger the onset of psoriasis (OR = 1.084, 95% CI = 1.040–1.131, p = 1.488E-04). In the real-world observational study, adjusting for multiple confounders, rheumatoid arthritis (OR = 1.34, 95% CI = 1.11–1.64, p = 0.003) and multiple sclerosis (OR = 1.31, 95% CI = 1.03–1.68, p = 0.02) were associated with a higher risk of sepsis. In addition, we did not find that autoimmune diseases were associated with 28-day mortality from sepsis.

Conclusion

Both in observational and MR analysis, only rheumatoid arthritis is highly correlated with occurrence of sepsis. However, autoimmune disease was not associated with an increased 28-day mortality in patient with sepsis. Sepsis may increase the risk of developing psoriasis.
A large-scale genomically predicted protein mass database enables rapid and broad-spectrum identification of bacterial and archaeal isolates by mass spectrometry
Authors: Sekiguchi Yuji , Teramoto Kanae , Tourlousse Dieter M. , Ohashi Akiko , Hamajima Mayu , Miura Daisuke , Yamada Yoshihiro , Iwamoto Shinichi , Tanaka Koichi
Published: December 2023

MALDI-TOF MS-based microbial identification relies on reference spectral libraries, which limits the screening of diverse isolates, including uncultured lineages. We present a new strategy for broad-spectrum identification of bacterial and archaeal isolates by MALDI-TOF MS using a large-scale database of protein masses predicted from nearly 200,000 publicly available genomes. We verify the ability of the database to identify microorganisms at the species level and below, achieving correct identification for > 90% of measured spectra. We further demonstrate its utility by identifying uncultured strains from mouse feces with metagenomics, allowing the identification of new strains by customizing the database with metagenome-assembled genomes.
Integration of datasets for individual prediction of DNA methylation-based biomarkers
Authors: Merzbacher Charlotte , Ryan Barry , Goldsborough Thibaut , Hillary Robert F. , Campbell Archie , Murphy Lee , McIntosh Andrew M. , Liewald David , Harris Sarah E. , McRae Allan F. , Cox Simon R. , Cannings Timothy I. , Vallejos Catalina A. , McCartney Daniel L. , Marioni Riccardo E.
Published: December 2023

Background

Epigenetic scores (EpiScores) can provide biomarkers of lifestyle and disease risk. Projecting new datasets onto a reference panel is challenging due to separation of technical and biological variation with array data. Normalisation can standardise data distributions but may also remove population-level biological variation.

Results

We compare two birth cohorts (Lothian Birth Cohorts of 1921 and 1936 — nLBC1921 = 387 and nLBC1936 = 498) with blood-based DNA methylation assessed at the same chronological age (79 years) and processed in the same lab but in different years and experimental batches. We examine the effect of 16 normalisation methods on a novel BMI EpiScore (trained in an external cohort, n = 18,413), and Horvath’s pan-tissue DNA methylation age, when the cohorts are normalised separately and together. The BMI EpiScore explains a maximum variance of R2=24.5% in BMI in LBC1936 (SWAN normalisation). Although there are cross-cohort R2 differences, the normalisation method makes a minimal difference to within-cohort estimates. Conversely, a range of absolute differences are seen for individual-level EpiScore estimates for BMI and age when cohorts are normalised separately versus together. While within-array methods result in identical EpiScores whether a cohort is normalised on its own or together with the second dataset, a range of differences is observed for between-array methods.

Conclusions

Normalisation methods returning similar EpiScores, whether cohorts are analysed separately or together, will minimise technical variation when projecting new data onto a reference panel. These methods are important for cases where raw data is unavailable and joint normalisation of cohorts is computationally expensive.
The effect of a helmet type, home-use low-level light therapy device for chemotherapy-induced alopecia: study protocol for a randomized controlled trial
Authors: Wu Cong-Xian , Li Cheng-Hsin , Shiao Yi-Hsien , Cheng Huan-Yu , Wu Tsung-Han , Lee Chun-Hui , Chang Zi-Yu , Yeh Yuan-Chieh
Published: December 2023

Background

Alopecia is one of the most common adverse effects of chemotherapy. It reduces the patient’s self-esteem and quality of life and the effect of therapy. Scalp cooling is the only verified current method for prevention but success is not guaranteed, particularly after receiving anthracycline-based combinations.

Low-level light therapy has been clinically proven to inhibit the progress of androgenic alopecia. A previous study using human subjects shows limited benefits for low-level light therapy for patients who suffer chemotherapy-induced alopecia but an increase in the number of probes and the optimization of light sources may improve the efficacy. This study determines the efficacy of low-level light therapy for the prevention of chemotherapy-induced hair loss for patients with breast cancer using a randomized controlled trial.

Methods

One hundred six eligible breast cancer patients were randomly distributed into a low-level light therapy group and a control group, after receiving chemotherapy. Subjects in the low-level light therapy group received 12 courses of intervention within 4 weeks. Subjects in the control group received no intervention but were closely monitored.

The primary outcome is measured as the difference in the hair count in a target area between the baseline and at the end of week 4, as measured using a phototrichogram (Sentra scalp analyzer). The secondary outcomes include the change in hair count at the end of week 1, week 2, and week 3 and hair width at the end of week 1, week 2, week 3, and week 4, as measured using a phototrichogram, and the change in distress, the quality of life, and self-esteem due to chemotherapy-induced alopecia, at the end of week 4, as measured using a questionnaire.

Discussion

This study improves cancer patients’ quality of life and provides clinical evidence.

Trial registration

Registered at ClinicalTrials.gov—NCT05397457 on 1 June 2022.
Whole-brain modeling of the differential influences of amyloid-beta and tau in Alzheimer’s disease
Authors: Patow Gustavo , Stefanovski Leon , Ritter Petra , Deco Gustavo , Kobeleva Xenia ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: December 2023

Background

Alzheimer’s disease is a neurodegenerative condition associated with the accumulation of two misfolded proteins, amyloid-beta (A$$\beta$$
β
) and tau. We study their effect on neuronal activity, with the aim of assessing their individual and combined impact.

Methods

We use a whole-brain dynamic model to find the optimal parameters that best describe the effects of A$$\beta$$
β
and tau on the excitation-inhibition balance of the local nodes.

Results

We found a clear dominance of A$$\beta$$
β
over tau in the early disease stages (MCI), while tau dominates over A$$\beta$$
β
in the latest stages (AD). We identify crucial roles for A$$\beta$$
β
and tau in complex neuronal dynamics and demonstrate the viability of using regional distributions to define models of large-scale brain function in AD.

Conclusions

Our study provides further insight into the dynamics and complex interplay between these two proteins, opening the path for further investigations on biomarkers and candidate therapeutic targets in-silico.
Neural cell engraftment therapy for sporadic Creutzfeldt-Jakob disease restores neuroelectrophysiological parameters in a cerebral organoid model
Authors: Williams Katie , Foliaki Simote T. , Race Brent , Smith Anna , Thomas Tina , Groveman Bradley R. , Haigh Cathryn L.
Published: December 2023

Background

Sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, is a fatal neurodegenerative disease with currently no treatment options. Stem cell therapy for neurodegenerative diseases is emerging as a possible treatment option. However, while there are a few clinical trials for other neurodegenerative disorders such as Parkinson’s disease, prion disease cell therapy research has so far been confined to animal models.

Methods

Here, we use a novel approach to study cell therapies in sCJD using a human cerebral organoid model. Cerebral organoids can be infected with sCJD prions allowing us to assess how neural precursor cell (NPC) therapy impacts the progression of sCJD. After 90 days of sCJD or mock infection, organoids were either seeded with NPCs or left unseeded and monitored for cellular composition changes, prion infection parameters and neuroelectrophysiological function at 180 days post-infection.

Results

Our results showed NPCs integrated into organoids leading to an increase in neuronal markers and changes in cell signaling irrespective of sCJD infection. Although a small, but significant, decrease in protease-resistant PrP deposition was observed in the CJD-infected organoids that received the NPCs, other disease-associated parameters showed minimal changes. However, the NPCs had a beneficial impact on organoid function following infection. sCJD infection caused reduction in neuronal spike rate and mean burst spike rate, indicative of reduced action potentials. NPC seeding restored these electrophysiological parameters to the uninfected control level.

Conclusions

Together with the previous animal studies, our results support that cell therapy may have some functional benefit for the treatment of human prion diseases.
Assessing resolvability, parsability, and consistency of RDF resources: a use case in rare diseases
Authors: Zhang Shuxin , Benis Nirupama , Cornet Ronald
Published: December 2023

Introduction

Healthcare data and the knowledge gleaned from it play a key role in improving the health of current and future patients. These knowledge sources are regularly represented as ‘linked’ resources based on the Resource Description Framework (RDF). Making resources ‘linkable’ to facilitate their interoperability is especially important in the rare-disease domain, where health resources are scattered and scarce. However, to benefit from using RDF, resources need to be of good quality. Based on existing metrics, we aim to assess the quality of RDF resources related to rare diseases and provide recommendations for their improvement.

Methods

Sixteen resources of relevance for the rare-disease domain were selected: two schemas, three metadatasets, and eleven ontologies. These resources were tested on six objective metrics regarding resolvability, parsability, and consistency. Any URI that failed the test based on any of the six metrics was recorded as an error. The error count and percentage of each tested resource were recorded. The assessment results were represented in RDF, using the Data Quality Vocabulary schema.

Results

For three out of the six metrics, the assessment revealed quality issues. Eleven resources have non-resolvable URIs with proportion to all URIs ranging from 0.1% (6/6,712) in the Anatomical Therapeutic Chemical Classification to 13.7% (17/124) in the WikiPathways Ontology; seven resources have undefined URIs; and two resources have incorrectly used properties of the ‘owl:ObjectProperty’ type. Individual errors were examined to generate suggestions for the development of high-quality RDF resources, including the tested resources.

Conclusion

We assessed the resolvability, parsability, and consistency of RDF resources in the rare-disease domain, and determined the extent of these types of errors that potentially affect interoperability. The qualitative investigation on these errors reveals how they can be avoided. All findings serve as valuable input for the development of a guideline for creating high-quality RDF resources, thereby enhancing the interoperability of biomedical resources.
The early fossil record of Caturoidea (Halecomorphi: Amiiformes): biogeographic implications
Authors: López-Arbarello Adriana , Concheyro Andrea , Palma Ricardo M. , Aguirre-Urreta Beatriz
Published: December 2023

Caturoidea is a clade of Mesozoic predatory ray-finned fishes which lived mainly in the Jurassic. The clade has a few records in the earliest Cretaceous and only two in the Triassic. Among the latter, specimen MPCA 632 Caturus sp. doubtfully from continental Early Triassic of Argentina, i.e., outside Europe, was particularly problematic in the light of the known fossil record of the group, which suggested their origin in the Western Tethys. The micropaleontological and geochemical analysis of bulk-rock samples of MPCA 632 allowed us to correct the provenance of the specimen which corresponds to Tithonian marine outcrops of the Vaca Muerta Formation, Neuquén, Argentina. Specimen MPCA 632 is excluded from Caturus and reclassified as Caturoidea sp. MPCA 632 might be a specimen of Catutoichthys olsacheri, the only caturoid known from the Vaca Muerta Formation (Los Catutos Member), but the fossils are not comparable and, thus, this hypothesis needs further study. Additionally, the first-hand study of the type material of the only other alleged Triassic caturoid, Furo insignis, in the Norian of Seefeld, Austria, led to the exclusion of this taxon from the Caturoidea. Consequently, the clade Caturoidea is restricted to the Jurassic–Lowest Cretaceous. After a modest evolution during the Early Jurassic, the group had its initial radiation and westward dispersion across the Hispanic Corridor during the Middle Jurassic and reached its maximal diversity during the Kimmeridgian and Tithonian.
Prolonged vs intermittent intravenous infusion of β-lactam antibiotics for patients with sepsis: a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis
Authors: Li Xiaoming , Long Yi , Wu Guixin , Li Rui , Zhou Mingming , He Aiting , Jiang Zhengying
Published: December 2023

Background

The prolonged β-lactam antibiotics infusion has been an attractive strategy in severe infections, because it provides a more stable free drug concentration and a longer duration of free drug concentration above the minimum inhibitory concentration (MIC). We conducted this systematic review of randomized clinical trials (RCTs) with meta-analysis and trial sequential analysis (TSA) to compare the effects of prolonged vs intermittent intravenous infusion of β-lactam antibiotics for patients with sepsis.

Methods

This study was prospectively registered on PROSPERO database (CRD42023447692). We searched EMBASE, PubMed, and Cochrane Library to identify eligible studies (up to July 6, 2023). Any study meeting the inclusion and exclusion criteria would be included. The primary outcome was all-cause mortality within 30 days. Two authors independently screened studies and extracted data. When the I2 values < 50%, we used fixed-effect mode. Otherwise, the random effects model was used. TSA was also performed to search for the possibility of false-positive (type I error) or false-negative (type II error) results.

Results

A total of 4355 studies were identified in our search, and nine studies with 1762 patients were finally included. The pooled results showed that, compared with intermittent intravenous infusion, prolonged intravenous infusion of beta-lactam antibiotics resulted in a significant reduction in all-cause mortality within 30 days in patients with sepsis (RR 0.82; 95%CI 0.70–0.96; P = 0.01; TSA-adjusted CI 0.62–1.07). However, the certainty of the evidence was rated as low, and the TSA results suggested that more studies were needed to further confirm our conclusion. In addition, it is associated with lower hospital mortality, ICU mortality, and higher clinical cure. No significant reduction in 90-day mortality or the emergence of resistance bacteria was detected between the two groups.

Conclusions

Prolonged intravenous infusion of beta-lactam antibiotics in patients with sepsis was associated with short-term survival benefits and higher clinical cure. However, the TSA results suggested that more studies are needed to reach a definitive conclusion. In terms of long-term survival benefits, we could not show an improvement.
Comprehensive analysis of immune cell landscapes revealed that immune cell ratio eosinophil/B.cell.memory is predictive of survival in sepsis
Authors: Wang Lei , Zhang Guoan , Sun Wenjie , Zhang Yan , Tian Yi , Yang Xiaohui , Liu Yingfu
Published: December 2023

Background

Immune dysregulation is a feature of sepsis. However, a comprehensive analysis of the immune landscapes in septic patients has not been conducted.

Objectives

This study aims to explore the abundance ratios of immune cells in sepsis and investigate their clinical value.

Methods

Sepsis transcriptome data sets were downloaded from the NCBI GEO database. The immunedeconv R package was employed to analyze the abundance of immune cells in sepsis patients and calculate the ratios of different immune cell types. Differential analysis of immune cell ratios was performed using the t test. The Spearman rank correlation coefficient was utilized to find the relationships between immune cell abundance and pathways. The prognostic significance of immune cell ratios for patient survival probability was assessed using the log-rank test. In addition, differential gene expression was performed using the limma package, and gene co-expression analysis was executed using the WGCNA package.

Results

We found significant changes in immune cell ratios between sepsis patients and healthy controls. Some of these ratios were associated with 28-day survival. Certain pathways showed significant correlations with immune cell ratios. Notably, six immune cell ratios demonstrated discriminative ability for patients with systemic inflammatory response syndrome (SIRS), bacterial sepsis, and viral sepsis, with an Area Under the Curve (AUC) larger than 0.84. Patients with a high eosinophil/B.cell.memory ratio exhibited poor survival outcomes. A total of 774 differential genes were identified in sepsis patients with a high eosinophil/B.cell.memory ratio compared to those with a low ratio. These genes were organized into seven co-expression modules associated with relevant pathways, including interferon signaling, T-cell receptor signaling, and specific granule pathways.

Conclusions

Immune cell ratios eosinophil/B.cell.memory and NK.cell.activated/NK.cell.resting in sepsis patients can be utilized for disease subtyping, prognosis, and diagnosis. The proposed cell ratios may have higher prognostic values than the neutrophil-to-lymphocyte ratio (NLR).
Nanotechnology in leukemia: diagnosis, efficient-targeted drug delivery, and clinical trials
Authors: Salama Maha M. , Aborehab Nora M. , El Mahdy Nihal M. , Zayed Ahmed , Ezzat Shahira M.
Published: December 2023

Leukemia is a group of malignant disorders which affect the blood and blood-forming tissues in the bone marrow, lymphatic system, and spleen. Many types of leukemia exist; thus, their diagnosis and treatment are somewhat complicated. The use of conventional strategies for treatment such as chemotherapy and radiotherapy may develop many side effects and toxicity. Hence, modern research is concerned with the development of specific nano-formulations for targeted delivery of anti-leukemic drugs avoiding toxic effects on normal cells. Nanostructures can be applied not only in treatment but also in diagnosis. In this article, types of leukemia, its causes, diagnosis as well as conventional treatment of leukemia shall be reviewed. Then, the use of nanoparticles in diagnosis of leukemia and synthesis of nanocarriers for efficient delivery of anti-leukemia drugs being investigated in in vivo and clinical studies. Therefore, it may contribute to the discovery of novel and emerging nanoparticles for targeted treatment of leukemia with less side effects and toxicities.