bluuebunny/crossref_metadata_2025 huggingface dataset:
SGLT2i relieve proteinuria in diabetic nephropathy patients potentially by inhibiting renal oxidative stress rather than through AGEs pathway
Authors: Zeng Xiao-chun , Tian Yuan , Liang Xian-ming , Wu Xiao-bin , Yao Chun-meng , Chen Xiao-min
Published: February 2024

Aims

To estimate the effects of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) on proteinuria and oxidative stress expression in type 2 diabetes patients.

Materials and methods

68 patients with type 2 diabetes mellitus (T2DM) were divided into three groups according urinary albumin-to-creatinine ratio (UACR), including T2DM with non-albuminuria group (UACR < 30 mg/g), T2DM with microalbuminuria group (30 ≤ UACR ≤ 300 mg/g), T2DM with macroalbuminuria group (UACR>300 mg/g). They all received SGLT2 inhibitors (SGLT2i) treatment for 12 weeks. The expression of advanced glycation end products (AGEs) in plasma and 8-hydroxy-2-deoxyguanosine (8-OHdG) in urine were measured as indications of oxidative stress. The 24-hour urine samples were collected to measure the concentration of proteinuria and 8-OHdG before and after 12 weeks SGLT2i treatment. Plasma renin activity (PRA), angiotensin II (Ang II) and Aldosterone (ALD) were measured to evaluate renin angiotensin aldosterone system (RASS) levels.

Results

After 12 weeks SGLT2 inhibitors treatment, the median values of 24-hour proteinuria decreased in macroalbuminuria compared to baseline (970 vs. 821 mg/d, P = 0.006). The median values of AGEs and 8-OHdG decreased in microalbuminuria and macroalbuminuria groups when compared to baseline, AGEs (777 vs. 136 ug/ml, P = 0.003) and (755 vs. 210 ug/ml, P = 0.001), 8-OHdG (8.00 vs. 1.88 ng/ml, P = 0.001) and (11.18 vs. 1.90 ng/ml, P < 0.001), respectively. Partial correlations showed that 8-OHdG were relevant to the baseline 24-h proteinuria (r = 0.389, p = 0.001), the reduction of OHdG (Δ8-OHdG) were positively correlated with the decrease of 24-h proteinuria (Δ24-h proteinuria) after 12 weeks of SGLT2i treatment (r = 0.283, P = 0.031). There was no significant correlation between 24-h proteinuria and AGEs in baseline (r = −0.059, p = 0.640) as well as between ΔAGEs and Δ24-h proteinuria (r = 0.022, p = 0.872) after12 weeks of SGLT2i treatment in T2DM patients.

Conclusions

SGLT2i may reduce proteinuria in diabetic nephropathy patients, potentially by inhibiting renal oxidative stress, but not through the AGEs pathway and does not induce RAAS activation.

Trial registration

This clinical trial was registered on 15/10/2019, in ClinicalTrials.gov, and the registry number is NCT04127084.
Genome-wide association study and polygenic risk scores of retinal thickness across the cognitive continuum: data from the NORFACE cohort
Authors: Sáez María Eugenia , García-Sánchez Ainhoa , de Rojas Itziar , Alarcón-Martín Emilio , Martínez Joan , Cano Amanda , García-González Pablo , Puerta Raquel , Olivé Clàudia , Capdevila Maria , García-Gutiérrez Fernando , Castilla-Martí Miguel , Castilla-Martí Luis , Espinosa Ana , Alegret Montserrat , Ricciardi Mario , Pytel Vanesa , Valero Sergi , Tárraga Lluís , Boada Mercè , Ruiz Agustín , Marquié Marta
Published: February 2024

Background

Several studies have reported a relationship between retinal thickness and dementia. Therefore, optical coherence tomography (OCT) has been proposed as an early diagnosis method for Alzheimer’s disease (AD). In this study, we performed a genome-wide association study (GWAS) aimed at identifying genes associated with retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thickness assessed by OCT and exploring the relationships between the spectrum of cognitive decline (including AD and non-AD cases) and retinal thickness.

Methods

RNFL and GCIPL thickness at the macula were determined using two different OCT devices (Triton and Maestro). These determinations were tested for association with common single nucleotide polymorphism (SNPs) using adjusted linear regression models and combined using meta-analysis methods. Polygenic risk scores (PRSs) for retinal thickness and AD were generated.

Results

Several genetic loci affecting retinal thickness were identified across the genome in accordance with previous reports. The genetic overlap between retinal thickness and dementia, however, was weak and limited to the GCIPL layer; only those observable with all-type dementia cases were considered.

Conclusions

Our study does not support the existence of a genetic link between dementia and retinal thickness.
The search for clarity regarding “clinically meaningful outcomes” in Alzheimer disease clinical trials: CLARITY-AD and Beyond
Authors: Tarawneh Rawan , Pankratz Vernon S.
Published: February 2024

CLARITY-AD is an 18-month, double-blinded, placebo-controlled, phase 3 trial which examined the safety and efficacy of the anti-amyloid agent, lecanemab, in mild cognitive impairment and mild dementia due to Alzheimer disease (AD). Lecanemab effectively reduced mean brain amyloid burden and was associated with statistically significant favorable effects, reflected by moderately less decline in the primary and secondary clinical outcomes, at 18 months compared to placebo. However, there is controversy within the AD community regarding the clinical significance of these results and whether they translate into clinically meaningful and tangible benefits on cognition or daily functions.

We here review the primary and secondary clinical outcomes of CLARITY-AD and present our interpretation of the potential clinical meaningfulness of the group-level differences in study outcomes in the context of the 18-month study duration. We propose that the validation of stage-appropriate group-level thresholds for clinical meaningfulness of AD trial outcomes in biologically confirmed cohorts will allow objective interpretation of trial results and guide clinical decision-making. Further, in accordance with FDA guidance which emphasizes patient-focused drug development, the contextualization of AD clinical trial outcomes can be facilitated by supplementary individual-level data analyses which measure the risk of disease progression or summarize intraindividual change, using prespecified thresholds of clinically meaningful change, in each of the study groups over the trial period. The concepts of “time-saved” and “time-based” slowing in disease progression can be used to communicate clinical outcomes associated with emerging disease-modifying AD therapies to various stakeholders. We also describe several factors that need to be considered when evaluating outcomes of emerging AD therapies, including disease stage, the neuropathologic complexity of AD, time-based effects of disease-modifying therapies, and the possible influence of individual factors on treatment response and/or risk for adverse events. The consideration of these factors in the design and reporting of future trials of emerging AD therapies will guide clinicians regarding their appropriateness for use in various patient populations.

Finally, we emphasize that data from clinical cohorts with longer durations of treatment and follow-up, including extension studies and patient registries, is needed to evaluate the long-term safety and efficacy of lecanemab in early symptomatic AD.
Intravoxel incoherent motion diffusion-weighted imaging for predicting kidney allograft function decline: comparison with clinical parameters
Authors: Wang Wei , Yu Yuanmeng , Chen Jinsong , Zhang Longjiang , Li Xue
Published: February 2024

Objective

To evaluate the added benefit of diffusion-weighted imaging (DWI) over clinical parameters in predicting kidney allograft function decline.

Methods

Data from 97 patients with DWI of the kidney allograft were retrospectively analyzed. The DWI signals were analyzed with both the mono-exponential and bi-exponential models, yielding total apparent diffusion coefficient (ADCT), true diffusion (D), pseudo-diffusion (D*), and perfusion fraction (fp). Three predictive models were constructed: Model 1 with clinical parameters, Model 2 with DWI parameters, and Model 3 with both clinical and DWI parameters. The predictive capability of each model was compared by calculating the area under the receiver-operating characteristic curve (AUROC).

Results

Forty-five patients experienced kidney allograft function decline during a median follow-up of 98 months. The AUROC for Model 1 gradually decreased with follow-up time > 40 months, whereas Model 2 and Model 3 maintained relatively stable AUROCs. The AUROCs of Model 1 and Model 2 were not statistically significant. Multivariable analysis showed that the Model 3 included cortical D (HR = 3.93, p = 0.001) and cortical fp (HR = 2.85, p = 0.006), in addition to baseline estimated glomerular filtration rate (eGFR) and proteinuria. The AUROCs for Model 3 were significantly higher than those for Model 1 at 60-month (0.91 vs 0.86, p = 0.02) and 84-month (0.90 vs 0.83, p = 0.007) follow-up.

Conclusions

DWI parameters were comparable to clinical parameters in predicting kidney allograft function decline. Integrating cortical D and fp into the clinical model with baseline eGFR and proteinuria may add prognostic value for long-term allograft function decline.

Critical relevance statement

Our findings suggested that cortical D and fp derived from IVIM-DWI increased the performance to predict long-term kidney allograft function decline. This preliminary study provided basis for the utility of multi-b DWI for managing patients with a kidney transplant.

Key points

• Both clinical and multi-b DWI parameters could predict kidney allograft function decline.

• The ability to predict kidney allograft function decline was similar between DWI and clinical parameters.

• Cortical D and fp derived from IVIM-DWI increased the performance to predict long-term kidney allograft function decline.

Graphical Abstract
Imaging-based deep learning in kidney diseases: recent progress and future prospects
Authors: Zhang Meng , Ye Zheng , Yuan Enyu , Lv Xinyang , Zhang Yiteng , Tan Yuqi , Xia Chunchao , Tang Jing , Huang Jin , Li Zhenlin
Published: February 2024

Kidney diseases result from various causes, which can generally be divided into neoplastic and non-neoplastic diseases. Deep learning based on medical imaging is an established methodology for further data mining and an evolving field of expertise, which provides the possibility for precise management of kidney diseases. Recently, imaging-based deep learning has been widely applied to many clinical scenarios of kidney diseases including organ segmentation, lesion detection, differential diagnosis, surgical planning, and prognosis prediction, which can provide support for disease diagnosis and management. In this review, we will introduce the basic methodology of imaging-based deep learning and its recent clinical applications in neoplastic and non-neoplastic kidney diseases. Additionally, we further discuss its current challenges and future prospects and conclude that achieving data balance, addressing heterogeneity, and managing data size remain challenges for imaging-based deep learning. Meanwhile, the interpretability of algorithms, ethical risks, and barriers of bias assessment are also issues that require consideration in future development. We hope to provide urologists, nephrologists, and radiologists with clear ideas about imaging-based deep learning and reveal its great potential in clinical practice.

Critical relevance statement The wide clinical applications of imaging-based deep learning in kidney diseases can help doctors to diagnose, treat, and manage patients with neoplastic or non-neoplastic renal diseases.

Key points

• Imaging-based deep learning is widely applied to neoplastic and non-neoplastic renal diseases.

• Imaging-based deep learning improves the accuracy of the delineation, diagnosis, and evaluation of kidney diseases.

• The small dataset, various lesion sizes, and so on are still challenges for deep learning.

Graphical Abstract
Bruns Garland Syndrome as the first presentation of type 2 diabetes: two case reports and a practical approach to diagnosis
Authors: Ambawatte Sathyajith , Wijewickrama Piyumi , Gunarathne Kamal , Somasundaram Noel
Published: February 2024

Background

Diabetes is a global health problem causing a significant burden on the healthcare systems both due to the disease itself and associated complications. Diabetic radiculoplexus neuropathies or Bruns–Garland syndrome constitutes a rare form of microvascular complications, more commonly affecting the lumbosacral plexus and, very rarely, the cervical plexus. We describe two Sri Lankan males who presented with diabetic lumbosacral radiculoplexus neuropathy and diabetic cervical radiculoplexus neuropathy as the initial manifestation of diabetes.

Case description

Case 1: a 49-year-old Sri Lankan hotel chef presented with subacute painful weakness and wasting of the left upper arm for 3 months and weight loss. Left upper limb proximal muscles were wasted with diminished power and reflexes. A nerve conduction study showed comparative amplitude reduction. An electromyogram revealed positive sharp waves, frequent fibrillations, and high amplitude polyphasic motor unit potentials with reduced recruitment in proximal muscles of left upper limb. Case-2: a 47-year-old Sri Lankan carpenter presented with subacute progressive asymmetrical painful weakness and wasting of bilateral thighs for 5 months and weight loss. Lower limb proximal muscles were wasted with reduced power and knee jerks. The nerve conduction study was normal. The electromyogram was similar to case 1 involving both quadratus femoris muscles, which was more prominent on the left side. The work up for an underlying etiology revealed only elevated fasting blood glucose and HbA1c, suggesting a new diagnosis of diabetes associated with neurological symptoms. Patient 1 was diagnosed with diabetic cervical radiculoplexus neuropathy and patient 2 with diabetic lumbosacral radiculoplexus neuropathy. Both showed significant improvement following optimization of glycemic control together with symptomatic treatment and physiotherapy.

Conclusion

Diagnosis of diabetic radiculoplexus neuropathy requires a comprehensive workup to rule out other sinister pathologies. This case report has a dual importance; it describes diabetic radiculoplexus neuropathy as the very first manifestation of two previously healthy people, giving rise to a new diagnosis of diabetes and, at the same time, reporting on diabetic cervical radiculoplexus neuropathy, which is extremely rare and has never been previously reported in Sri Lanka.
Gingival-derived mesenchymal stem cell therapy regenerated the radiated salivary glands: functional and histological evidence in murine model
Authors: Zayed Hagar M. , Kheir El Din Nevine H. , Abu-Seida Ashraf M. , Abo Zeid Asmaa A. , Ezzatt Ola M.
Published: February 2024

Background

Radiotherapy in head and neck cancer management causes degeneration of the salivary glands (SG). This study was designed to determine the potential of gingival mesenchymal stem cells (GMSCs) as a cell-based therapy to regenerate irradiated parotid SG tissues and restore their function using a murine model.

Methods

Cultured isolated cells from gingival tissues of 4 healthy guinea pigs at passage 3 were characterized as GMSCSs using flow cytometry for surface markers and multilineage differentiation capacity. Twenty-one Guinea pigs were equally divided into three groups: Group I/Test, received single local irradiation of 15 Gy to the head and neck field followed by intravenous injection of labeled GMSCs, Group II/Positive control, which received the same irradiation dose followed by injection of phosphate buffer solution (PBS), and Group III/Negative control, received (PBS) injection only. Body weight and salivary flow rate (SFR) were measured at baseline, 11 days, 8-, 13- and 16-weeks post-irradiation. At 16 weeks, parotid glands were harvested for assessment of gland weight and histological and immunohistochemical analysis.

Results

The injected GMSCs homed to degenerated glands, with subsequent restoration of the normal gland histological acinar and tubular structure associated with a significant increase in cell proliferation and reduction in apoptotic activity. Subsequently, a significant increase in body weight and SFR, as well as an increase in gland weight at 16 weeks in comparison with the irradiated non-treated group were observed.

Conclusion

The study provided a new potential therapeutic strategy for the treatment of xerostomia by re-engineering radiated SG using GMSCs.
POSEIDON: Peptidic Objects SEquence-based Interaction with cellular DOmaiNs: a new database and predictor
Authors: Preto António J. , Caniceiro Ana B. , Duarte Francisco , Fernandes Hugo , Ferreira Lino , Mourão Joana , Moreira Irina S.
Published: February 2024

Cell-penetrating peptides (CPPs) are short chains of amino acids that have shown remarkable potential to cross the cell membrane and deliver coupled therapeutic cargoes into cells. Designing and testing different CPPs to target specific cells or tissues is crucial to ensure high delivery efficiency and reduced toxicity. However, in vivo/in vitro testing of various CPPs can be both time-consuming and costly, which has led to interest in computational methodologies, such as Machine Learning (ML) approaches, as faster and cheaper methods for CPP design and uptake prediction. However, most ML models developed to date focus on classification rather than regression techniques, because of the lack of informative quantitative uptake values. To address these challenges, we developed POSEIDON, an open-access and up-to-date curated database that provides experimental quantitative uptake values for over 2,300 entries and physicochemical properties of 1,315 peptides. POSEIDON also offers physicochemical properties, such as cell line, cargo, and sequence, among others. By leveraging this database along with cell line genomic features, we processed a dataset of over 1,200 entries to develop an ML regression CPP uptake predictor. Our results demonstrated that POSEIDON accurately predicted peptide cell line uptake, achieving a Pearson correlation of 0.87, Spearman correlation of 0.88, and r2 score of 0.76, on an independent test set. With its comprehensive and novel dataset, along with its potent predictive capabilities, the POSEIDON database and its associated ML predictor signify a significant leap forward in CPP research and development. The POSEIDON database and ML Predictor are available for free and with a user-friendly interface at https://moreiralab.com/resources/poseidon/, making them valuable resources for advancing research on CPP-related topics. Scientific Contribution Statement: Our research addresses the critical need for more efficient and cost-effective methodologies in Cell-Penetrating Peptide (CPP) research. We introduced POSEIDON, a comprehensive and freely accessible database that delivers quantitative uptake values for over 2,300 entries, along with detailed physicochemical profiles for 1,315 peptides. Recognizing the limitations of current Machine Learning (ML) models for CPP design, our work leveraged the rich dataset provided by POSEIDON to develop a highly accurate ML regression model for predicting CPP uptake.

Graphical Abstract
Effects of topical application of resveratrol on tight junction barrier and antimicrobial compound production in lactating goat mammary glands
Authors: Tsugami Yusaku , Nii Takahiro , Isobe Naoki
Published: February 2024

In mammary glands, the formation of less-permeable tight junctions (TJs) and the production of antimicrobial compounds like lactoferrin and defensins are important for preventing mastitis. Resveratrol, a polyphenol contained in red grapes, is known to protect mammary epithelial cells (MECs) from oxidative stress; however, oral administration of resveratrol causes a decrease in certain biological processes through conjugation and metabolic conversion. In this study, we determined the beneficial effects of resveratrol on TJs and antimicrobial compounds in cultured goat MECs by adding it to the medium, and in lactating goat mammary glands by topical application for percutaneous absorption. TJ barrier function was evaluated by transepithelial resistance and expression or localization pattern of claudins for culture model in vitro and by somatic cell count, Na+, albumin, and IgG in milk for topical application in vivo. Concentrations of antimicrobial compounds and cytokines were measured using ELISA. Activation of STAT3 was evaluated by Western blotting. Resveratrol strengthened TJ barrier function by upregulating claudin-3 in cultured MECs and topical application to udders reduced somatic cell count, Na+, albumin, and IgG in milk. Resveratrol increased β-defensin and S100A7 levels in cultured MECs and milk. In addition, resveratrol down-regulated cytokine production and STAT3 pathway. These findings suggest that the topical application of resveratrol to udders may be effective in preventing mastitis.
Genomic characteristics of cfr and fexA carrying Staphylococcus aureus isolated from pig carcasses in Korea
Authors: Kim Eiseul , Yang Seung-Min , Kwak Hyo-Sun , Moon Bo-Youn , Lim Suk-Kyung , Kim Hae-Yeong
Published: February 2024

The emergence of transferable linezolid resistance genes poses significant challenges to public health, as it does not only confer linezolid resistance but also reduces susceptibility to florfenicol, which is widely used in the veterinary field. This study evaluated the genetic characteristics of linezolid-resistant Staphylococcus aureus strains isolated from pig carcasses and further clarified potential resistance and virulence mechanisms in a newly identified sequence type. Of more than 2500 strains isolated in a prior study, 15 isolated from pig carcasses exhibited linezolid resistance (minimum inhibitory concentration ≥ 8 mg/L). The strains were characterized in detail by genomic analysis. Linezolid-resistant S. aureus strains exhibited a high degree of genetic lineage diversity, with one strain (LNZ_R_SAU_64) belonging to ST8004, which has not been reported previously. The 15 strains carried a total of 21 antibiotic resistance genes, and five carried mecA associated with methicillin resistance. All strains harbored cfr and fexA, which mediate resistance to linezolid, phenicol, and other antibiotics. Moreover, the strains carried enterotoxin gene clusters, including the hemolysin, leukotoxin, and protease genes, which are associated with humans or livestock. Some genes were predicted to be carried in plasmids or flanked by ISSau9 and the transposon Tn554, thus being transmittable between staphylococci. Strains carrying the plasmid replicon repUS5 displayed high sequence similarity (99%) to the previously reported strain pSA737 in human clinical samples in the United States. The results illustrate the need for continuous monitoring of the prevalence and transmission of linezolid-resistant S. aureus isolated from animals and their products.
Automatic classification of the physical surface in sound uroflowmetry using machine learning methods
Authors: Alvarez Marcos Lazaro , Arjona Laura , Iglesias Martínez Miguel E. , Bahillo Alfonso
Published: February 2024

This work constitutes the first approach for automatically classifying the surface that the voiding flow impacts in non-invasive sound uroflowmetry tests using machine learning. Often, the voiding flow impacts the toilet walls (traditionally made of ceramic) instead of the water in the toilet. This may cause a reduction in the strength of the recorded audio signal, leading to a decrease in the amplitude of the extracted envelope. As a result, just from analysing the envelope, it is impossible to tell if that reduction in the envelope amplitude is due to a reduction in the voiding flow or an impact on the toilet wall. In this work, we study the classification of sound uroflowmetry data in male subjects depending on the surface that the urine impacts within the toilet: the three classes are water, ceramic and silence (where silence refers to an interruption of the voiding flow). We explore three frequency bands to study the feasibility of removing the human-speech band (below 8 kHz) to preserve user privacy. Regarding the classification task, three machine learning algorithms were evaluated: the support vector machine, random forest and k-nearest neighbours. These algorithms obtained accuracies of 96%, 99.46% and 99.05%, respectively. The algorithms were trained on a novel dataset consisting of audio signals recorded in four standard Spanish toilets. The dataset consists of 6481 1-s audio signals labelled as silence, voiding on ceramics and voiding on water. The obtained results represent a step forward in evaluating sound uroflowmetry tests without requiring patients to always aim the voiding flow at the water. We open the door for future studies that attempt to estimate the flow parameters and reconstruct the signal envelope based on the surface that the urine hits in the toilet.
The global economic burden of COVID-19 disease: a comprehensive systematic review and meta-analysis
Authors: Faramarzi Ahmad , Norouzi Soheila , Dehdarirad Hossein , Aghlmand Siamak , Yusefzadeh Hasan , Javan-Noughabi Javad
Published: February 2024

Background

The COVID-19 pandemic has caused a considerable threat to the economics of patients, health systems, and society.

Objectives

This meta-analysis aims to quantitatively assess the global economic burden of COVID-19.

Methods

A comprehensive search was performed in the PubMed, Scopus, and Web of Science databases to identify studies examining the economic impact of COVID-19. The selected studies were classified into two categories based on the cost-of-illness (COI) study approach: top-down and bottom-up studies. The results of top-down COI studies were presented by calculating the average costs as a percentage of gross domestic product (GDP) and health expenditures. Conversely, the findings of bottom-up studies were analyzed through meta-analysis using the standardized mean difference.

Results

The implemented search strategy yielded 3271 records, of which 27 studies met the inclusion criteria, consisting of 7 top-down and 20 bottom-up studies. The included studies were conducted in various countries, including the USA (5), China (5), Spain (2), Brazil (2), South Korea (2), India (2), and one study each in Italy, South Africa, the Philippines, Greece, Iran, Kenya, Nigeria, and the Kingdom of Saudi Arabia. The results of the top-down studies indicated that indirect costs represent 10.53% of GDP, while the total estimated cost accounts for 85.91% of healthcare expenditures and 9.13% of GDP. In contrast, the bottom-up studies revealed that the average direct medical costs ranged from US $1264 to US $79,315. The meta-analysis demonstrated that the medical costs for COVID-19 patients in the intensive care unit (ICU) were approximately twice as high as those for patients in general wards, with a range from 0.05 to 3.48 times higher.

Conclusions

Our study indicates that the COVID-19 pandemic has imposed a significant economic burden worldwide, with varying degrees of impact across countries. The findings of our study, along with those of other research, underscore the vital role of economic consequences in the post-COVID-19 era for communities and families. Therefore, policymakers and health administrators should prioritize economic programs and accord them heightened attention.
Judgment, shame, and coercion: the criminal legal system and reproductive autonomy
Authors: Garcia-Alexander Ginny , Thompson Melissa
Published: February 2024

Background

A growing body of research has called attention to limitations to reproductive autonomy in both women who are socially disadvantaged and in those who have had contact with the criminal legal (CL) system. However, it is unclear whether CL system contact influences contraceptive use patterns and how these processes unfold. We utilize a mixed-methods approach to investigate whether history of arrest is associated with receipt of contraceptive counseling, use of long-term contraception, sterilization, and subsequent desire for reversal of sterilization. We further consider how agents in and around the CL system may influence women’s reproductive decisions and outcomes (856 survey respondents; 10 interviewees).

Results

We observe that women who have been arrested more commonly report receipt of contraceptive counseling and sterilization. They are also significantly more likely to want their sterilization reversed. Our in-depth interviews suggest that women with CL contact experience considerable shame, and in some cases, coercion to limit fertility from various agents in and outside the criminal legal system including medical providers, Parole/Probation Officers (POs), guards, and family members.

Conclusions

Our findings suggest the need for ongoing attention to how exposure to this system may promote uneven use of certain forms of contraception and dissatisfaction, i.e., desire for reversal of sterilization, among these women. Findings further suggest that de-emphasizing the CL system as a means through which to address reproductive needs should be considered.
Novel plasma-polymerized coating facilitates HeLa cell spheroid formation, exerting necroptosis via β-cyclodextrin-encapsulated resveratrol
Authors: Jang Sujeong , Baek Namwuk , Seo Youngsik , Lim Hyuna , Jung Donggeun , Park Heonyong
Published: February 2024

Beta-cyclodextrins (β-CDs) comprise a pore for accommodating resveratrol (Res), thereby boosting its bioavailability. Res-incorporated β -CD (Res/CD) may be cytotoxic against both normal and cancer cells. Herein, we examined whether Res/CD exhibits anticancer activity against tumor spheroids, similar to in vivo tumor mass. To prepare three-dimensional spheroids, 1,1,1,3,5,7,7,7 octamethyl-3,5-bis(trimethylsiloxyl) tetrasiloxane (OMBTSTS) was deposited to the surface of the culture dish via plasma polymerization. We observed that HeLa cells grew as spheroids on the OMBTSTS-deposited surface at 20 W plasma power. Res/CD was delivered to the hypoxic core of the spheroid, inducing necrosis, whereas Res was not. Consistently, 10 μM Res alone was not cytotoxic to two-dimensional HeLa cells grown on a culture dish and three-dimensional spheroids. However, Res/CD promoted the necroptosis of spheroids, which were split into small fragments, ultimately inducing cell spheroid death. Collectively, our data suggest that nontoxic levels of Res/CD were efficiently delivered to the hypoxic core of tumor spheroids, promoting cell death. Therefore, Res/CD can be used as an effective anticancer drug. Moreover, the plasma-polymerized OMBTSTS modification technique provides insights into the efficient formation of spheroids in various cancer cell lines.
Students’ perspectives on the ‘STEM belonging’ concept at A-level, undergraduate, and postgraduate levels: an examination of gender and ethnicity in student descriptions
Authors: Dost Gulsah
Published: February 2024

Background

Women and ethnic minorities have historically been underrepresented in some STEM fields. It is therefore important to understand the factors influencing students’ persistence in STEM fields, and what STEM belonging means from the voices of socio-demographically diverse students, in order to ensure equity among students in STEM fields and to increase their belonging to this field, which has not been clearly defined in the literature, and there is a lack of agreement about the definition of belonging itself. For this purpose, the perspectives of students in England are brought together in this study in an attempt to better understand the concept of STEM belonging within a broader context of integration.

Result

The inductive thematic analysis with the voices of socio-demographically diverse 313 A-level, undergraduate and postgraduate Mathematics, Physics, and Chemistry students showed that compared to male students, it was mostly female, non-binary, non-White, and first-generation students who defined STEM belonging as ‘Feeling safe and comfortable in the STEM community and settings’. This theme was defined by the participants as the group/community/learning environment in which the individual belongs, the interaction with the people in the field, and the comfort that this participation/interaction creates. Students stressed the importance of creating a supportive and welcoming STEM environment so that individuals can feel at home, as well as a safe and comfortable STEM environment for people of all identities, genders, ethnicities, and backgrounds. Based on the participants’ responses, this study also conceptualised the concept of STEM belonging as having four phases: the ‘adaptation phase’, the ‘integration phase’, the ‘continuum phase’, and the ‘transition phase’. These four phases which comprise the STEM belonging concept are consecutive and interconnected.

Conclusion

The study concluded that all human beings are connected in a relational way (either strong or weak) and that the concept of STEM belonging develops as a result of interactions with ‘self’ and ‘others’ who have a shared passion and an interest in STEM fields. Although individuals have intrinsic motivation and individual prompts in STEM fields (i.e. resilience, beliefs in their capacity/ability and curiosity, etc.), social determinants (i.e. receiving adequate support from members of the STEM community, social capital and social cohesion, etc.) also play a significant role in influencing individual’s sense of STEM belonging.
Ultraviolet resistance on weft knitted fabric coated by benzotriazoles
Authors: Nguyen Tuan Anh , Nguyen Nu Nhu Tram
Published: February 2024

Ultraviolet resistance upon four different types of weft knitted fabrics including Lacoste, Single Jersey, Rib and Interlock were experimentally measured and evaluated by ultraviolet–visible spectroscopy under effects of gauge, specific weight, fiber composition and finishing agent as benzotriazole derivatives. The results showed that ultraviolet protection factor (UPF) of Interlock sample reached the highest value at 42.7. Simultaneously, the higher gauge of Single Jersey knitted fabrics was, the better its ultraviolet protection exhibited. Also, insertion of polyester fibers or spandex fibers into cotton knitted fabrics with a certain ratio strongly increased UPF values. Notably, all UPFs of coated fabrics with a given content of benzotriazole were significantly improved and almost coated samples could undergo several washing cycles and still retain their inherent breathability. This work demonstrated that cotton knitted fabrics coated with benzotriazoles were excellently enhanced ultraviolet protection. Especially, the UPF values on Interlock or Rib specimens as well as Single Jersey samples blended with polyester/spandex fibers were found to be higher than 15.
Chinese social value change and its relevant factors: an age-period-cohort effect analysis
Authors: Haiyan Gao , Peng Wang , Tam Tony
Published: February 2024

Using data from the World Values Survey (1990–2012), this article attempts to describe and analyze the changing trends in public values during social transformations in China. It is found that public attitudes toward authority tend to be increasingly favorable over time, values in the private sphere tend to be more open, while postmaterialist values show a trend of first rising and then falling. The most salient feature of the cohort effect is that the generations born after the reform and opening-up in 1978 identify more closely with the value of respect for authority, while their recognition of postmaterialist values tends to decline. The change in values is related to China's modernization process, global cultural diffusion, and important historical events and is also deeply influenced by the two-way interaction between tradition and modernity.
Exploring the potential role of decentralised biogas plants in meeting energy needs in sub-Saharan African countries: a techno-economic systems analysis
Authors: Robin Thomas , Ehimen Ehiaze
Published: February 2024

To achieve the Sustainable Development Goals by 2030, low-income sub-Saharan African countries urgently need to electrify. Biogas production from anaerobic digestion could make a contribution to a solution to improved electricity generation and access in these regions. This study evaluates its feasibility using Malawi as a case study. The aim is to provide households with a continuous supply of gas for cooking and electricity. The study examines different sizes of fixed dome reactors (3, 6, 12 m3) and assumes individual household ownership of 2, 4, and 6 cows. Several feedstocks and conditions are considered, such as cow dung alone, co-generation of cow dung with human faeces, cow dung with grass, and cow dung with maize residue. The economic benefits of selling biogas and fertilisers are calculated, and the cost of construction for different sizes of reactors is determined. Results show that co-generation of cow dung and grass silage in the reactor of 12 m3 with six cows has a positive net present value (NPV) of $8962, while for a small farm with a 6 m3 reactor capacity, co-digestion of cow dung with maize residue is preferable. The feasibility of the technology depends heavily on current national economic conditions, such as inflation, electricity prices, and construction material costs. A sensitivity analysis estimated that a 25% increase in the cost of electricity could increase the net present value (NPV) from − $3345 to $1526 for the generation of biogas from cow dung alone. Overall, this technology could have a significant impact on the lives of low-income households in sub-Saharan Africa by improving their access to electricity and providing a source of income through the sale of biogas and digestate.
Large litters have a detrimental impact on litter performance and postpartum maternal behaviour in primiparous sows
Authors: Lee Juho , Shin Hyeonwook , Kim Junsik , Lee Geonil , Yun Jinhyeon
Published: February 2024

Background

Our previous study confirmed that large litter size adversely affects prepartum maternal hormones and behaviour, concurrently with heightened oxidative stress in primiparous sows. The purpose of this study was to examine the effect of large litter size on litter performance, postpartum maternal behaviour, salivary cortisol levels, and colostral immunoglobulin levels in sows, as well as investigate their correlations with the levels of oxidative stress parameters.

Results

A total of 24 primiparous sows (Landrace$$ \times $$Large white) and their offspring were categorised into two groups based on litter size: NORMAL (n = 8) with litter size ranging from 7 to 14 (mean 11.5$$ \pm $$2.7), and LARGE (n=16) with litter size ranging from 15 to 20 (mean 15.9$$ \pm $$1.4). All sows were housed in a group housing system during gestation and transitioned to an adaptable loose housing system (2.4$$ \times $$2.3 m) during the farrowing and lactation periods. The nursing and carefulness behaviour of the sows was monitored over a 24-h period between 72 and 96 h after parturition. Saliva samples were collected for cortisol assay on 35, 21, and 7 days before parturition (D-35, D-21, and D-7, respectively), as well as on days 1, 7, and 28 after parturition (D1, D7, and D28, respectively). On D1, higher piglet mortality rates were observed among the LARGE group compared to the NORMAL group (p<0.01). The total and successful nursing behaviours of the sows were less frequent in the LARGE group than in the NORMAL group (p<0.05, for both), and the carefulness score of the LARGE group was also lower than that of the NORMAL group (p< 0.01). On D1, cortisol levels in LARGE sows were higher than those in NORMAL sows (p< 0.05), and for other time points (D-21, D-7, D7, and D28), cortisol levels in LARGE sows tended to be higher than those in NORMAL sows (p < 0.10, for all). Successful nursing behaviour displayed negative correlations with levels of salivary cortisol and certain oxidative stress parameters measured on D1.

Conclusions

These findings suggest that the strategy for alleviating physiological and oxidative stress during the peripartum periods could benefit potential postpartum maternal behaviour and litter performance in the sows with large litters.
Preclinical evaluation of new GRPR-antagonists with improved metabolic stability for radiotheranostic use in oncology
Authors: Kanellopoulos Panagiotis , Mattsson Adam , Abouzayed Ayman , Obeid Karim , Nock Berthold A. , Tolmachev Vladimir , Maina Theodosia , Orlova Anna
Published: February 2024

Background

The gastrin-releasing peptide receptor (GRPR) has been extensively studied as a biomolecular target for peptide-based radiotheranostics. However, the lack of metabolic stability and the rapid clearance of peptide radioligands, including radiolabeled GRPR-antagonists, often impede clinical application. Aiming at circumventing these drawbacks, we have designed three new GRPR-antagonist radioligands using [99mTc]Tc-DB15 ([99mTc]Tc-N4-AMA-DIG-DPhe-Gln-Trp-Ala-Val-Sar-His-Leu-NHEt; AMA: p-aminomethylaniline; DIG: diglycolate) as a motif, due to its high GRPR-affinity and stability to neprilysin (NEP). The new analogues carry the DOTAGA-chelator (1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid) through different linkers at the N-terminus to allow for labeling with the theranostic radionuclide pair In-111/Lu-177. After labeling with In-111 the following radioligands were evaluated: (i) [111In]In-AU-SAR-M1 ([111In]In-DOTAGA-AMA-DIG-DPhe-Gln-Trp-Ala-Val-Sar-His-Leu-NHEt), (ii) [111In]In-AU-SAR-M2 ([111In]In-[DOTAGA-Arg]AU-SAR-M1) and (iii) [111In]In-AU-SAR-M3 ([111In]In-[DOTAGA-DArg]AU-SAR-M1).

Results

These radioligands were compared in a series of in vitro assays using prostate adenocarcinoma PC-3 cells and in murine models. They all displayed high and GRPR-specific uptake in PC-3 cells. Analysis of mice blood collected 5 min post-injection (pi) revealed similar or even higher metabolic stability of the new radioligands compared with [99mTc]Tc-DB15. The stability could be further increased when the mice were treated with Entresto® to in situ induce NEP-inhibition. In PC-3 xenograft-bearing mice, [111In]In-AU-SAR-M1 displayed the most favourable biodistribution profile, combining a good tumor retention with the highest tumor-to-organ ratios, with the kidneys as the dose-limiting organ.

Conclusions

These findings strongly point at AU-SAR-M1 as a promising radiotherapeutic candidate when labeled with Lu-177, or other medically appealing therapeutic radiometals, especially when combined with in situ NEP-inhibition. To this goal further investigations are currently pursued.
Glioma grading using an optimized T1-weighted dynamic contrast-enhanced magnetic resonance imaging paradigm
Authors: Abdi Aza Ismail
Published: February 2024

Background

Glioma grading is a critical procedure for selecting the most effective treatment policy. Biopsy result is the gold standard method for glioma grading, but inherent sampling errors in the biopsy procedure could lead to tumor misclassification.

Aim

This study evaluated grading performances of a more comprehensive collection of the physiological indices quantified using an optimized dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) paradigm for glioma grading.

Methods

Thirty-five patients with glioma underwent DCE-MR imaging to evaluate the grading performances of DCE-MRI-derived physiological indices. The statistical differences in the physiological indices between the different grades of gliomas were studied, and the grading performances of these parameters were evaluated using the leave-one-out cross-validation method.

Results

There were significant statistical differences in DCE-MRI-derived physiological indices between the different grades of gliomas. The mean rCBVs for grade II (low-grade glioma, LGG), grade III, grade IV, and high-grade (HGG) gliomas were 2.03 ± 0.78, 3.61 ± 1.64, 7.14 ± 3.19, and 5.28 ± 3.02, respectively. The mean rCBFs of 1.94 ± 0.97, 2.67 ± 0.96, 4.57 ± 1.77, and 3.57 ± 1.68 were, respectively, quantified for grade II (LGG), grade III, grade IV, and high-grade gliomas. The leave-one-out cross-validation method indicates that the grades of glioma tumors could be determined based on a specific threshold for each physiological index; for example, the optimal cutoff values for rCBF, rCBV, Ktrans, Kep, and Vp indices to distinguish between HGGs and LGGs were 2.11, 2.80, 0.025 mL/g min, 0.29 min−1, and 0.065 mL/g, respectively.

Conclusions

From the results, it could be concluded that glioma grades could be determined using DCE-MRI-derived physiological indices with an acceptable agreement with histopathological results.
Multilevel approaches to address disparities in lung cancer screening: a study protocol
Authors: Williams Randi M. , Whealan Julia , Taylor Kathryn L. , Adams-Campbell Lucile , Miller Kristen E. , Foley Kristie , Luta George , Brandt Heather , Glassmeyer Katharine , Sangraula Anu , Yee Peyton , Camidge Kaylin , Blumenthal Joseph , Modi Saumil , Kratz Heather
Published: February 2024

Background

Low-dose computed tomography (lung cancer screening) can reduce lung cancer-specific mortality by 20–24%. Based on this evidence, the United States Preventive Services Task Force recommends annual lung cancer screening for asymptomatic high-risk individuals. Despite this recommendation, utilization is low (3–20%). Lung cancer screening may be particularly beneficial for African American patients because they are more likely to have advanced disease, lower survival, and lower screening rates compared to White individuals. Evidence points to multilevel approaches that simultaneously address multiple determinants to increase screening rates and decrease lung cancer burden in minoritized populations. This study will test the effects of provider- and patient-level strategies for promoting equitable lung cancer screening utilization.

Methods

Guided by the Health Disparities Research Framework and the Practical, Robust Implementation and Sustainability Model, we will conduct a quasi-experimental study with four primary care clinics within a large health system (MedStar Health). Individuals eligible for lung cancer screening, defined as 50–80 years old, ≥ 20 pack-years, currently smoking, or quit < 15 years, no history of lung cancer, who have an appointment scheduled with their provider, and who are non-adherent to screening will be identified via the EHR, contacted, and enrolled (N = 184 for implementation clinics, N = 184 for comparison clinics; total N = 368). Provider participants will include those practicing at the partner clinics (N = 26). To increase provider-prompted discussions about lung screening, an electronic health record (EHR) clinician reminder will be sent to providers prior to scheduled visits with the screening-eligible participants. To increase patient-level knowledge and patient activation about screening, an inreach specialist will conduct a pre-visit phone-based educational session with participants. Patient participants will be assessed at baseline and 1-week post-visit to measure provider-patient discussion, screening intentions, and knowledge. Screening referrals and screening completion rates will be assessed via the EHR at 6 months. We will use mixed methods and multilevel assessments of patients and providers to evaluate the implementation outcomes (adoption, feasibility, acceptability, and fidelity).

Discussion

The study will inform future work designed to measure the independent and overlapping contributions of the multilevel implementation strategies to advance equity in lung screening rates.

Trial registration

ClinicalTrials.gov, NCT04675476. Registered December 19, 2020.