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Cost-utility of aripiprazole once-monthly versus paliperidone palmitate once-monthly injectable for schizophrenia in China

Objectives From the perspective of Chinese healthcare system, this study compared the cost-utility of aripiprazole once-monthly (AOM) and paliperidone palmitate once-monthly injectable (PP1M) in the treatment of adult patients with schizophrenia in China. Methods A 5-state Markov model was developed to evaluate the cost-utility of 10 years of long-acting injections (LAI) treatment for schizophrenia. The long-term costs and quality-adjusted life years (QALYs) were estimated, with the incremental cost-effectiveness ratio (ICER) as the primary outcome. The annual discount rate was set at 5%. A cost-effectiveness threshold (CET) of 0.51 times China’s 2023 gross domestic product (GDP) (US$ 6,394.536) was used to judge the economics of intervention. Results The current price of AOM in China is relatively high (US$418.140). To assess its cost-effectiveness in the context of potential price negotiations with China Healthcare Security Administration (CHS) for inclusion in the National Reimbursement Drug List (NRDL), we simulated a 40% price reduction (US$257.619). At a CET of 0.51 times GDP per capita (US$6,394.536), the base-case analysis showed that the incremental costs of AOM relative to PP1M after 10 years of treatment were US$1,926.373 with an incremental gain of 0.306 QALYs. The ICER for AOM was US$6,285.303 per QALY, which is below the CET, indicating that AOM is cost-effective. One-way sensitivity analysis identified AOM’s drug cost as the parameter with the greatest impact on results. Probabilistic sensitivity analysis revealed that with a 40% price reduction, the probability of AOM being cost-effective is only 41.70%. However, with a 60% price reduction, AOM became dominantly cost-effective, with the probability increasing to 100%. When the CET was relaxed to 0.90 times GDP per capita (US$11,284.476), the probability of cost-effectiveness for AOM after a 40% price reduction rose to 85.10%. Scenario analyses conducted over a time horizon extending from 10 to 30 years showed that the ICER decreased significantly with longer follow-up, gradually approaching the 0.51GDP threshold and remaining below the 0.90 GDP threshold throughout the analysis. Conclusions The cost-effectiveness of AOM relative to PP1M is highly influenced by its price and the CET. Healthcare decision makers or clinical users need to balance innovation incentives and accessibility.

Nebulized and intravenous enzyme replacement therapy in mice with mucopolysaccharidosis type II

Mucopolysaccharidosis Type II is a hereditary lysosomal storage disease characterized by deficiency in the enzyme iduronate 2-sulfatase (IDS). IDS is critical in the breakdown of sulfated glycosaminoglycans and its deficiency leads to an accumulation of these compounds across various tissue types resulting in multisystemic dysfunction. Intravenous administration of recombinant IDS (idursulfase) substantially improves patients’ quality and length of life. However, recombinant IDS delivered intravenously is sequestered in the liver and respiratory failure remains as the leading cause of death for patients independent of idursulfase treatment, which suggests insufficient delivery to the lungs. This study aimed to assess a novel method of idursulfase administration using a nebulizer in combination with intravenous treatment and determine if this combination may improve lung delivery of idursulfase and overall pathology. Whole body IDS knockout mice underwent twelve weeks of intravenous, combination treatment, or vehicle injection and we harvested liver and lungs seven days after the last treatment for assessment of IDS activity, histological markers, and global proteomics for comparison with wild-type mice. Combination treatment increased IDS enzyme activity in the liver but not lungs Proteomics data demonstrated attenuation of key features of the disease in liver (metabolic pathways) and lungs (glycosaminoglycan pathways) with both treatments. Overall, adding nebulized administration of IDS did not lead to sustained increase in enzyme activity in the lungs but caused persistent modifications in glycosaminoglycan degradation pathway suggesting additional benefits to intravenous administration alone.

Concerned about freedom of science and truth

Lightweight dynamic model for fusion of three-dimensional surface–stratum underground structures

Three-dimensional visual modeling of surface-stratum-structure is an inevitable requirement for intelligent geotechnical engineering. However, the heterogeneity of surface, stratigraphic and structural data sources and modeling methods leads to incompatibility of model attributes. Only a few studies have directly realized the three-dimensional (3D) modeling of surface-strata-structure. In order to solve this problem, this study uses the Kriging interpolation method based on relative elevation to realize the fusion of borehole data and surface data, and establishes a 3D surface-strata model. The Boolean difference set operation based on the bounding box method is used to propose a geometric fusion method for the 3D surface-strata-underground structure model. In addition, an attribute fusion method of 3D surface-stratum-underground structure model is introduced by using variable storage method. Finally, this study established a comprehensive 3D model of surface-strata-underground structure. Considering the characteristics of the fusion model, the dynamic expression of the 3D settlement model is realized, and a lightweight processing method using layered rendering technology is proposed, which is helpful to establish a lightweight 3D dynamic model of surface-strata-underground structure. The feasibility and reliability of the above method are verified by engineering application analysis. The main contributions of this method include simplifying the integration process of surface, stratum and structure models, which may enhance the modeling of integrated engineering information.

Who marries whom and intentions for second child: Using family decision-making power as mediator

Interest in exploring fertility intentions, decisions, or the actual number of children through the perspective of assortative mating has been increasing; however, the mechanisms linking these variables remain unclear. Existing studies have shown that gaps in socio-economic resources between spouses shape intra-household decision-making patterns. Individuals who have the final-say power over homemaking exhibit more bargaining power in family fertility decisions. Based on the 2014 China Family Panel Studies, this research used latent class analysis to obtain the intra-household decision-making variable. A generalized structural equation model was built to examine this potential mediator. The findings reveal that family decision-making power helps to elucidate the relationship between the patterns of assortative mating and fertility intentions. Differences in couples’ educational attainment are a key aspect in assessing “who” is in charge of the household. The desire for a second child was greater if husbands had the final say. Participants in marriages where wives held decision-making power reported a lower willingness to have a second child. The mediation effects of “husband-dominated” or “wife-dominated” decision-making were confirmed in hypergamous marriage. Indirect-only mediating effects were found in mid-educated homogamous partnerships and hypogamous marriages. Suppression effects were present in educational homogamy among highly educated individuals.

A study on the development of data technology taxonomy for data economy

As the data economy era is in full swing, the impact of data is accelerating across the economy and society. In particular, as digital transformation accelerates, data technology is becoming more important, and new products and services are being created based on data. However, despite the increasing importance of data, the lack of a comprehensive taxonomy for data technology has resulted in inadequate systematic policy development and execution. Therefore, this study proposes a data technology taxonomy that can be used for data technology-related policy making, business planning, and national R&D investment direction setting. To this end, the study defines the concept of data technology that has not been officially announced, and develops a classification system while establishing the validity of the classification system through the derivation of the limitations of similar taxonomy and the collection of expert opinions. In addition, an expert adequacy assessment will be conducted to verify whether the proposed taxonomy can be used in the field, and the current status will be analyzed by classifying the data technology-related national R&D projects based on the taxonomy. The results of this study are meaningful in helping to understand data technology and improving the system in the future when formulating data policies and conducting research and development.

Retrospective evaluation of Facial nerve monitoring to prevent nerve damage during robotic drilling in the largest series of patients undergoing the HEARO-procedure

Introduction Robot-assisted cochlear implantation surgery (RACIS) involves the drilling of a keyhole access to the inner ear for cochlear implant placement to treat patients with severe-to-profound sensorineural hearing loss. RACIS with the HEARO-procedure does not require the drilling of a mastoidectomy and posterior tympanotomy to pass through the facial recess. Instead, it directly drills through it guarding a safe distance from both the facial nerve and chorda tympani. Cochlear implantation surgery involves a well described risk for facial nerve injury when passing through the facial recess. Neuromonitoring as a safety protocol gained great importance in conventional CI surgery and is proving its benefits in RACIS. RACIS in the HEARO-procedure involves a customized facial nerve monitoring (FNM) device that was designed and tested in an animal model study. Here, this device was retrospectively assessed in the largest series of patients undergoing the HEARO-procedure. Materials and methods The safety protocol in the HEARO-procedure involves FNM and intra-operative cone-beam CT (CBCT) imaging with a 0.1 mm spatial resolution. The customized FNM device was employed, using both active mono- and bipolar stimulation to estimate the distance to the facial nerve in RACIS. Linear regression was used to determine if the minimum stimulation thresholds (FNM) could significantly predict the intra-operative distance (CBCT) between the drilled trajectory and the facial nerve. Logistic regression was used to calculate if FNM can distinguish distances smaller and greater than 0.4 mm to the facial nerve. Results The minimum stimulation thresholds significantly predicted the distances between the drilling trajectory and the facial nerve for both the monopolar (p = 0.001) and bipolar 3 (p = 0.008) stimulation configuration. Both the monopolar (β = -0.189, S.E. = 0.063, p = 0.003) and bipolar 3 (β = -0.187, S.E. = 0.080, p = 0.019) stimulation configuration are negative and significant predictors of the probability of the distance being smaller than 0.4 mm. Conclusion FNM will alert the surgeon when the drilling trajectory comes closer than 0.4 mm to the facial nerve in RACIS. A linear relationship was observed between the minimum stimulation thresholds and the intra-operative distance towards the facial nerve.

One dose of gene therapy gives years of relief from blood disorder

1-methylnicotinamide attenuated inflammation and regulated flora in Necrotizing enterocolitis

Background Necrotizing enterocolitis(NEC) is a prevalent and destructive illness in neonates. Nicotinamide N-methyltransferase (NNMT) and its derivative, 1-methylnicotinamide (1-MNA), are known to be significant in conditions such as cardiovascular inflammation and renal tubular damage, and 1-MNA has been recognized for its anti-inflammatory effects in various diseases. However, the involvement of NNMT and 1-MNA in the development of NEC remains unclear. Methods We collected intestinal tissues and blood samples from children with NEC and control subjects for biochemical analysis. The NEC rats were induced by hypoxic cold stimulation and lipopolysaccharide, and control, NEC and NEC + 1-MNA groups were established. Neonatal rats were executed on the fourth day and blood, intestinal and fecal specimens were taken for subsequent testing. Results Elevated NNMT and 1-MNA were found in NEC children and NEC rats. Exogenous supplementation of 1-MNA to NEC rats reduced mortality, pathological and inflammatory damage, and inhibited activation of the TLR4-NF-κB pathway in neonatal rats. In addition, 1-MNA improved intestinal barrier function and modulated intestinal flora in NEC rats. Conclusion 1-MNA attenuated NEC injury by seemingly inhibiting the TLR4-NF-κB pathway, improving intestinal barrier function and modulating intestinal flora. These findings suggest a potential therapeutic role for 1-MNA in NEC management.

Efficacy and safety of cisplatin + docetaxel + 5-FU + leucovorin + methotrexate and epirubicin combination chemotherapy for advanced esophageal cancer

Abstraction Esophageal cancer is a devastating disease. The cisplatin and 5-FU regimen is the most widely used concurrent chemoradiotherapy protocol for metastatic, unresectable advanced esophageal cancer in Asia. However, its effectiveness remains limited due to unsatisfactory outcomes. Therefore, we conducted a retrospective study to evaluate the efficacy and toxicity of Cisplatin + 5-FU combined with docetaxel, leucovorin, methotrexate, and epirubicin (CDFLME), a first-line multi-agent chemotherapy regimen used for the treatment of advanced esophageal cancer in Taiwan. We enrolled 94 patients in our study from January 2018 to June 2022. All patients were diagnosed with metastatic or unresectable advanced esophageal cancer. Among them, 81 patients received fluorouracil + cisplatin regimen serving as the control group, while 13 patients received the CDFLME combination regimen. Significant improvements were observed in the CDFLME group compared to the fluorouracil + cisplatin group in overall survival time, complete response rate, and disease control rate. No significant differences were noted in treatment-related deaths or grade 3–4 adverse events, except for grade 1–2 mucositis. Based on these findings, we conclude that the CDFLME regimen is a promising alternative treatment with relatively minor adverse events and is an effective protocol for patients with advanced esophageal cancer.

Parental hesitancy on COVID-19 vaccination of children under the age of 16: A cross-sectional mixed-methods study among factory workers

Background Thanks to the development of COVID-19 vaccines, now they can be safely and effectively used to guard COVID-19 patients against severe illness, hospitalization, and even mortality. However, parents’ unwillingness to vaccinate their children depends on a large extent on factors beyond the availability of vaccines, and understanding the factors associated with parental vaccine hesitancy has become increasingly important to the development of the COVID-19 vaccine program. Therefore, this study aimed to determine the parental COVID-19 vaccine hesitancy to their children and its associated factors among factory workers in Myanmar. Methods A cross-sectional mixed-methods study was conducted as an explanatory sequential design, at Tri Star tyre factory (Ywar Ma), Yangon, Myanmar from August 2022 to February 2023. A total of 170 factory workers with children under the age of 16 participated in this study. The quantitative data were collected by the face-to-face interviews using a pretested structured questionnaire that included the Oxford COVID-19 vaccine hesitancy scale. Data were analyzed by using binary logistic regression to identify associated factors of parental hesitancy. Adjusted odds ratio (AOR) with a 95% confidence interval (CI) was computed to determine the level of significance with a p value ≤ 0.05. A subsample of 6 participants from each “hesitant group” and “non-hesitant group” towards COVID-19 vaccination was interviewed by the individual in-depth-interview guide to provide the reasons for their willingness or unwillingness to vaccinate to their children. The thematic analysis was undertaken for the qualitative data. Results Among the total, 18.2% (95% CI: 12.7–24.9%) of the parents were hesitant to vaccinate their children against COVID-19 while 25.9% (95% CI: 19.5–33.1%) responded as unsure and 55.9% (95% CI: 48.1–63.5%) were non-hesitant for vaccination to their children. Male (AOR: 3.04, 95% CI: 1.35–6.84) and those who were not infected with SARS-CoV-2 (AOR: 2.66, 95% CI: 1.06–6.70) were significantly associated with parental COVID-19 vaccine hesitancy. The most common reasons for the unwillingness to receive the COVID-19 vaccination to their children were too young for vaccination, concerns about the safety of the vaccines, uncertainty about the effectiveness of the vaccines, and lack of trust in the origin of the vaccines. Conclusions In this study, nearly one-fifth of the parents were hesitant to vaccinate their children against COVID-19. The findings of this study suggested that the government and healthcare professionals should provide health education about the importance of COVID-19 vaccination and the safety and efficacy of currently providing COVID-19 vaccines using mainstream media to improve the proportion of children getting vaccinated against COVID-19.

Judge rules against NIH grant cuts — and calls them discriminatory

Drivers and effects of fish-for-sex related single parenthood in a fishing coastal community in Ghana

The migration of fishers from one community to another is often associated with fish-for-sex (FFS) exchanges. FFS can lead to social issues such as absentee parenting and the generational cycle of FFS relationships. This study examined the perception of the frequency of FFS-related female single parenthood and the drivers and effects of single parenthood arising from FFS relationships in Elmina, Ghana. This study used a convergent parallel mixed-methods design to examine the views of 385 fishers, 30 key informants, and 20 focus group participants on FFS-related single parenthood. Descriptive statistics was used to analyze the quantitative data, while the transcript of participants were analyzed thematically. The findings show that most fishers (63.1%) indicated the occurrence of FFS female single parenthood in Elmina. The driver of FFS female single parenthood included uncertain paternity resulting from multiple sexual partners and male partners denial of paternity due to suspicions of promiscuity. Also, the adverse effects of FFS female single parenthood included paternal absence, child developmental challenges, maternal burden, and the intergenerational cycle of FFS relationships. This study demonstrated that FFS female single parenthood is a common phenomenon in Elmina. There is an urgent need for policymakers to design interventions to address the phenomenon of FFS female single parenthood to enhance the well-being of children and mothers with children from FFS relationships.

Scholarly publishing’s hidden diversity: How exclusive databases sustain the oligopoly of academic publishers

Global scholarly publishing has been dominated by a small number of publishers for several decades. This paper revisits the data on corporate control of scholarly publishing by analyzing the relative shares of scholarly journals and articles published by the major publishers and the “long tail” of smaller, independent publishers, using Dimensions and Web of Science (WoS). The reduction of expenses for printing and distribution and the availability of open-source journal management tools may have contributed to the emergence of small publishers, while recently developed inclusive databases may allow for the study of these. Dimensions’ inclusive indexing revealed the number of scholarly journals and articles published by smaller publishers has been growing rapidly, especially since the onset of large-scale online publishing around 2000, resulting in a higher share of articles from smaller publishers. In parallel, WoS shows increasing concentration within a few corporate publishers. For the 1980–2021 period, we retrieved 32% more articles from Dimensions compared to the more selective WoS. Dimensions’ data showed the expansion of small publishers was most pronounced in the Social Sciences and the Arts and Humanities, but a similar trend is observed in the Natural Sciences and Engineering, and the Health Sciences. A major geographical divergence is also revealed, with English-speaking countries and/or those located in northwestern Europe relying heavily on major publishers for the dissemination of their research, while the rest of the world being relatively independent of the oligopoly. Finally, independent journals publish more often in open access in general, and in Diamond open access in particular. We conclude that enhanced indexing and visibility of recently created, independent journals may favour their growth and stimulate global scholarly bibliodiversity.

Comparative investigation of bagging enhanced machine learning for early detection of HCV infections using class imbalance technique with feature selection

Around 1.5 million new cases of Hepatitis C Virus (HCV) are diagnosed globally each year (World Health Organization, 2023). Consequently, there is a pressing need for early diagnostic methods for HCV. This study investigates the prognostic accuracy of several ensemble machine learning (ML) models for diagnosing HCV infection. The study utilizes a dataset comprising demographic information of 615 individuals suspected of having HCV infection. Additionally, the research employs oversampling and undersampling techniques to address class imbalances in the dataset and conducts feature reduction using the F-test in one-way analysis of variance. Ensemble ML methods, including Support Vector Machine (SVM), k-Nearest Neighbors (k-NN), Logistic Regression (LR), Random Forest (RF), Naïve Bayes (NB), and Decision Tree (DT), are used to predict HCV infection. The performance of these ensemble methods is evaluated using metrics such as accuracy, recall, precision, F1 score, G-mean, balanced accuracy, cross-validation (CV), area under the curve (AUC), standard deviation, and error rate. Compared with previous studies, the Bagging k-NN model demonstrated superior performance under oversampling conditions, achieving 98.37% accuracy, 98.23% CV score, 97.67% precision, 97.93% recall, 98.18% selectivity, 97.79% F1 score, 98.06% balanced accuracy, 98.05% G-mean, a 1.63% error rate, 0.98 AUC, and a standard deviation of 0.192. This study highlights the potential of ensemble ML approaches in improving the diagnosis of HCV. The findings provide a foundation for developing accurate predictive methods for HCV diagnosis.

Evaluating real-world performance of an automated offline glaucoma AI on a smartphone fundus camera across glaucoma severity stages

Purpose Leveraging an artificial intelligence system (AI) for glaucoma screening can mitigate the current challenges and provide prompt detection and management crucial in averting irreversible blindness. The study reports the real-world performance of a glaucoma AI system deployed on a smartphone-based fundus camera across various severities of glaucoma. Methods In this prospective comparative study at a tertiary care glaucoma clinic, consecutive patients were evaluated by a glaucoma specialist using clinical assessment, visual field tests, and SD-OCT, and categorized as definite glaucoma, glaucoma suspect, or no glaucoma. For glaucoma patients, severity was determined using Hoddap-Parrish-Anderson criteria based on visual field mean deviation (MD). A disc-centered image per eye was captured using a validated portable non-mydriatic fundus camera. The AI tool’s ability to detect referral-warranted glaucoma (glaucoma and glaucoma suspects) versus no glaucoma was compared to the specialist’s diagnosis. Results We included 213 participants with a mean age of 55 ± 14.7 years (18, 88). The glaucoma specialist diagnosed 129 subjects as definite glaucoma (early-23, moderate-31, severe-75), 33-disc suspects and 51 as no-glaucoma. The automated AI system based on fundus images achieved an overall diagnostic accuracy of 92.02%, sensitivity of 91.36% (95%CI 85.93% to 95.19%) and specificity of 94.12% (83.76% to 98.77%) for referral warranted glaucoma. The 14 false negatives included 5-disc suspects and 9 definite glaucoma (3-early, 3-moderate and 3-advanced glaucoma). The sensitivity of AI for detecting early, moderate and advanced glaucoma was 86.9% (95%CI 66.4–97.2), 90.3% (95%CI 74.3–97.96), and 96% (88.75% to 99.17%) respectively. Conclusion In a real-world setting, the AI-based offline tool integrated on a smartphone fundus camera showed a promising performance in detecting referral-warranted glaucoma compared to a glaucoma specialist’s diagnosis. The AI showed higher accuracy in detecting advanced glaucoma followed by moderate and early glaucoma.

Metal coordination and enzymatic reaction of the glioma-target R132H isocitrate dehydrogenase 1: Insights by molecular simulations

R132H IDH1 is an important therapeutic target for a variety of brain cancers, yet drug leads and radiotracers which selectively bind only to the mutant over the wild type are so far lacking. Here we have predicted the structural determinants of the Michaelis complex of this mutant using a QM/MM MD-based protocol. It shows some important differences with the X-ray structure, from the metal coordination to the positioning of key residues at the active site. In particular, one lysine residue (K212) emerges as a mostly likely proton donor in the key proton-transfer step of the R132H IDH1 catalytic reaction. Intriguingly, the same residue in its deprotonated state is likely to be involved in the reaction catalyzed by the wild-type enzyme (though the mechanisms are different). Our QM/MM protocol could also be used for other metal-based enzymes, which cannot be modelled easily by force field-based MD, like in this case.

Developing a predictive model for anticipating technology convergence: A transformer-based model and supervised learning approach

This study proposes a novel approach to anticipating technology convergence in the bio-healthcare sector by integrating text mining based on transformer models and supervised learning methodologies. The overarching goal is to develop a robust method for predicting technology convergence, leveraging the interrelationships between technology topics extracted from patents and research articles. Through the application of advanced techniques and by leveraging the strengths of transformer-based models such as BERTopic with KeyBERT and OpenAI integration to generate technology topics, we identified potential convergence opportunities and explored emerging trends within the dataset. The proposed method seeks to predict technology convergence effectively by employing various machine learning and deep learning techniques to train prediction models by integrating technological similarity, link prediction measures, and causal relationships between technology topics as input features, offering a more accurate and comprehensive understanding of the intricate relationships within the technological landscape. This study contributes to the literature on technology convergence by offering a novel methodology for anticipating future trends and identifying opportunities for interdisciplinary collaboration in the bio-healthcare sector. Overall, the outcomes of this study hold significant implications for businesses seeking to capitalize on emerging convergence opportunities for sustainable growth.

Deep origin of eukaryotes outside Heimdallarchaeia within Asgardarchaeota

“I don’t know if it makes a difference to safety?” perception vs actuality: A mixed-methods study on older adults’ experiences of home stair falls revealed during COVID-19 lockdown

In the United Kingdom (UK), stair falls in older adults’ homes cause up to 575 deaths and 350,000 injuries annually, costing the NHS £435 million. The stair falls may be related to hazards such as poorly designed/absent handrails, too steep/narrow stairs, poor step surface (e.g., loose carpets), and poor lighting. Our study aimed to understand older adults’ experiences of independent living and home stair falls during the first COVID-19 lockdown, and shed light on older adults’ physical staircase dimensions that influence stair fall risks in relation to UK government guidelines. A mixed-methods approach was employed, conducting semi-structured interviews alongside quantitative home stair assessments with 22 participants aged ≥ 60 years. The stair assessments captured the physical dimensions (i.e., measurements of pitch, rise and goings) of their home stairs, and if they perceived their stairs safe to negotiate. We identified four overarching themes common across older people living independently: effects of lockdown on daily living during the COVID-19 pandemic; stair-related accidents and perceived causes; fall preventative measures and safety awareness; and attitudes towards ageing and care services. Although all of the participants perceived their stairs to be safe, nearly half of participants’ staircases (40%) did not meeting the UK government guidelines for pitch, rise and going. While the COVID-19 lockdown provided a unique context for exploring fall risk and stair safety, our findings highlight broader, ongoing issues. Despite emotional attachment to their homes, many lacked staircases that meet current UK government guidelines, highlighting a need for targeted interventions to mitigate environmental hazards. Additionally, financial constraints and education further complicate efforts to enhance home safety. Discrepancies between perceived and objective safety assessments highlight the need for comprehensive care approaches and evidence-based home design guidelines, allowing for collaborative support for ageing in place. Bridging this gap is essential for reducing home stair falls.