bluuebunny/crossref_metadata_2025 huggingface dataset:
Ventilation shutdown and the breath-taking violence of infectious disease emergency management in industrial livestock production
Authors: Sinel Martin , Weis Tony
Published: February 2024

Powerful ventilation systems are a crucial technology in industrial livestock production, mitigating the unhealthy ambient conditions that result from great densities of animal bodies, biowastes, and chemical agents, and enabling the rapid production of massive quantities of flesh and eggs in such crowded indoor spaces. But bad air is just one of many biophysical and technoscientific challenges managed in these spaces, chief among them the ever-present risks of infectious disease transmission and evolution that threaten animal health and productivity and pose untold risks for humans. This article examines the intersection of these two central problems, where ventilation systems that are normally used to manage bad air within enclosures have been repurposed in the context of disease outbreaks to quickly and cheaply kill infected populations by hyperthermia. An analysis of this nascent practice, euphemistically termed “ventilation shutdown,” shows how governments and publicly funded scientific institutions have worked with private industry to develop and systematize the use of this and other technologies of mass death to respond to infectious disease emergencies, a dynamic that, we argue, sheds new light on both the precarity and the violence of industrial livestock production.
Adjuvants in COVID-19 vaccines: innocent bystanders or culpable abettors for stirring up COVID-heart syndrome
Authors: Kanuri Sri Harsha , Sirrkay Prapthi Jayesh
Published: February 2024

COVID-19 infection is a multi-system clinical disorder that was associated with increased morbidity and mortality. Even though antiviral therapies such as Remdesvir offered modest efficacy in reducing the mortality and morbidity, they were not efficacious in reducing the risk of future infections. So, FDA approved COVID-19 vaccines which are widely administered in the general population worldwide. These COVID-19 vaccines offered a safety net against future infections and re-infections. Most of these vaccines contain inactivated virus or spike protein mRNA that are primarily responsible for inducing innate and adaptive immunity. These vaccines were also formulated to contain supplementary adjuvants that are beneficial in boosting the immune response. During the pandemic, clinicians all over the world witnessed an uprise in the incidence and prevalence of cardiovascular diseases (COVID-Heart Syndrome) in patients with and without cardiovascular risk factors. Clinical researchers were not certain about the underlying reason for the upsurge of cardiovascular disorders with some blaming them on COVID-19 infections while others blaming them on COVID-19 vaccines. Based on the literature review, we hypothesize that adjuvants included in the COVID-19 vaccines are the real culprits for causation of cardiovascular disorders. Operation of various pathological signaling events under the influence of these adjuvants including autoimmunity, bystander effect, direct toxicity, anti-phospholipid syndrome (APS), anaphylaxis, hypersensitivity, genetic susceptibility, epitope spreading, and anti-idiotypic antibodies were partially responsible for stirring up the onset of cardiovascular disorders. With these mechanisms in place, a minor contribution from COVID-19 virus itself cannot be ruled out. With that being said, we strongly advocate for careful selection of vaccine adjuvants included in COVID-19 vaccines so that future adverse cardiac disorders can be averted.
Usability of home use medical technology: The patient perspective
Authors: Tase Arkeliana , Buckle Peter , Ni Melody Z. , Hanna George B.
Published: February 2024

Introduction

Technological advancements have increased the scope and range of home-use medical devices. These have allowed development of care at home. This requires appropriate understanding of patient's needs with regards to such devices for safe use of medical technology at home and minimise usability errors. This study sought to investigate patient experiences of usability and to identify future requirements for such devices

Methods

A qualitative mixed methods study was chosen. The participants were asked to complete a survey which included both multiple-choice and free-text entry questions. Participant recruitment was through purposive and snowball sampling approaches. All participants were required to have direct experience in using a medical device. Data were thematically analysed.

Results

There were 360 responses by patients, parents and carers. 503 devices were used by these participants. 99.4% used their device(s) on a daily basis. The largest group of responders were from type 1 diabetic patients. Multiple usability challenges were reported with respect to training, device interoperability, development of workarounds and the device-user interfaces. Device acceptance and their costs were also raised as issues for concern. A list of usability challenges was compiled.

Conclusions

Patients and other end users continue to experience multiple usability challenges in the use of medical devices at home despite guidance from regulatory bodies. Better post market studies are required to generate evidence to enable the improved design and safety of the device. This should be accompanied with an evaluation of improvements in patient satisfaction and their compliance with monitoring and treatment.
Tuberous Xanthoma: A Clue to the Diagnosis of Familial Hypercholesterolemia
Authors: Matthias Anne Thushara , Fernandopulle Anthony Nilesh Ranjeev
Published: February 2024

A 35-year-old patient found to have tuberous xanthomas was diagnosed to have familial hypercholesterolemia (FH). Dermatological manifestations can trigger the diagnosis of FH.
Between monitoring and surveillance: Geographies of emerging drone technologies in contemporary conservation
Authors: Millner Naomi , Newport Ben , Sandbrook Chris , Simlai Trishant
Published: February 2024

Conservation has employed technologies for monitoring and visual capture since its inception in the nineteenth century. Since then, the capacities of conservation technologies have developed considerably, affording a wide range of data relating to ecological change and biodiversity loss. However, new technologies introduce fresh ethical and political issues into environmental protection, especially as they can be used – deliberately or accidentally – to collect information about human activities. This potential is important, given that many areas of biodiversity protection are also areas of longstanding conflict. We focus here on the political and ethical implications surrounding drones, which collect photographic and video footage that can include images of humans. We review approaches to technology, visuality, and surveillance across and beyond environmental geography over the last two decades, teasing out conceptual approaches that support a nuanced and critical analysis of conservation drones. Our analysis focuses on the ways that conservation drones alter (i) processes of decision-making, (ii) dynamics of fearmongering and control, (iii) processes of securitisation in protected areas, (iv) the production and circulation of (racial) stereotypes, and (v) the practices and outcomes of data justice. We unpack these themes through three case studies from our own fieldwork, clarifying the range of intentional and non-intentional political outcomes that emerge, and ethical themes that will be vital to explore further in the future.
The direct binding of bioactive peptide Andersonin-W1 to TLR4 expedites the healing of diabetic skin wounds
Authors: Li Chao , Xiong Yuxin , Fu Zhe , Ji Yuxin , Yan Jiayi , Kong Yan , Peng Ying , Ru Zeqiong , Huang Yubing , Li Yilin , Yang Ying , He Li , Tang Jing , Wang Ying , Yang Xinwang
Published: February 2024

Background

Chronic nonhealing wounds remain a considerable challenge in clinical treatment due to excessive inflammation and impeded reepithelialization and angiogenesis. Therefore, the discovery of novel prohealing agents for chronic skin wounds are urgent and important. Amphibian-derived prohealing peptides, especially immunomodulatory peptides, provide a promising strategy for the treatment of chronic skin trauma. However, the mechanism of immunomodulatory peptides accelerating the skin wound healing remains poorly understood.

Methods

The prohealing ability of peptide Andersonin-W1 (AW1) was assessed by cell scratch, cell proliferation, transwell, and tube formation. Next, full-thickness, deep second-degree burns and diabetic full-thickness skin wounds in mice were performed to detect the therapeutic effects of AW1. Moreover, the tissue regeneration and expression of inflammatory cytokines were evaluated by hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry staining. Molecular docking, colocalization, and western blotting were used to explore the mechanism of AW1 in promoting wound healing.

Results

We provide solid evidence to display excellent prohealing effects of AW1, identified as a short antimicrobial peptide in our previous report. At relative low concentration of nM, AW1 promoted the proliferation, migration, and scratch repair of keratinocyte, macrophage proliferation, and tube formation of HUVEC. AW1 also facilitated reepithelialization, granulation regeneration, and angiogenesis, thus significantly boosting the healing of full-thickness, deep second-degree burns and diabetic skin wounds in mice. Mechanistically, in macrophages, AW1 directly bound to Toll-like receptor 4 (TLR4) in the extracellular region and regulated the downstream nuclear factor‐κB (NF-κB) signaling pathway to facilitate the inflammatory factor secretion and suppress excessive inflammation induced by lipopolysaccharide (LPS). Moreover, AW1 regulated macrophage polarization to promote the transition from the inflammatory to the proliferative phase and then facilitated reepithelialization, granulation regeneration, and angiogenesis, thus exhibiting excellent therapeutic effects on diabetic skin wounds.

Conclusions

AW1 modulates inflammation and the wound healing process by the TLR4/NF-κB molecular axis, thus facilitating reepithelialization, granulation regeneration, and angiogenesis. These findings not only provided a promising multifunctional prohealing drug candidate for chronic nonhealing skin wounds but also highlighted the unique roles of “small” peptides in the elucidation of “big” human disease mechanisms.

Graphical Abstract
Modifying the false discovery rate procedure based on the information theory under arbitrary correlation structure and its performance in high-dimensional genomic data
Authors: Rastaghi Sedighe , Saki Azadeh , Tabesh Hamed
Published: February 2024

Background

Controlling the False Discovery Rate (FDR) in Multiple Comparison Procedures (MCPs) has widespread applications in many scientific fields. Previous studies show that the correlation structure between test statistics increases the variance and bias of FDR. The objective of this study is to modify the effect of correlation in MCPs based on the information theory. We proposed three modified procedures (M1, M2, and M3) under strong, moderate, and mild assumptions based on the conditional Fisher Information of the consecutive sorted test statistics for controlling the false discovery rate under arbitrary correlation structure. The performance of the proposed procedures was compared with the Benjamini–Hochberg (BH) and Benjamini–Yekutieli (BY) procedures in simulation study and real high-dimensional data of colorectal cancer gene expressions. In the simulation study, we generated 1000 differential multivariate Gaussian features with different levels of the correlation structure and screened the significance features by the FDR controlling procedures, with strong control on the Family Wise Error Rates.

Results

When there was no correlation between 1000 simulated features, the performance of the BH procedure was similar to the three proposed procedures. In low to medium correlation structures the BY procedure is too conservative. The BH procedure is too liberal, and the mean number of screened features was constant at the different levels of the correlation between features. The mean number of screened features by proposed procedures was between BY and BH procedures and reduced when the correlations increased. Where the features are highly correlated the number of screened features by proposed procedures reached the Bonferroni (BF) procedure, as expected. In real data analysis the BY, BH, M1, M2, and M3 procedures were done to screen gene expressions of colorectal cancer. To fit a predictive model based on the screened features the Efficient Bayesian Logistic Regression (EBLR) model was used. The fitted EBLR models based on the screened features by M1 and M2 procedures have minimum entropies and are more efficient than BY and BH procedures.

Conclusion

The modified proposed procedures based on information theory, are much more flexible than BH and BY procedures for the amount of correlation between test statistics. The modified procedures avoided screening the non-informative features and so the number of screened features reduced with the increase in the level of correlation.
Integration analysis of ATAC-seq and RNA-seq provides insight into fatty acid biosynthesis in Schizochytrium limacinum under nitrogen limitation stress
Authors: Chen Duo , Chen Jing , Dai Rongchun , Zheng Xuehai , Han Yuying , Chen Youqiang , Xue Ting
Published: February 2024

Background

Schizochytrium limacinum holds significant value utilized in the industrial-scale synthesis of natural DHA. Nitrogen-limited treatment can effectively increase the content of fatty acids and DHA, but there is currently no research on chromatin accessibility during the process of transcript regulation. The objective of this research was to delve into the workings of fatty acid production in S. limacinum by examining the accessibility of promoters and profiling gene expressions.

Results

Results showed that differentially accessible chromatin regions (DARs)-associated genes were enriched in fatty acid metabolism, signal transduction mechanisms, and energy production. By identifying and annotating DARs-associated motifs, the study obtained 54 target transcription factor classes, including BPC, RAMOSA1, SPI1, MYC, and MYB families. Transcriptomics results revealed that several differentially expressed genes (DEGs), including SlFAD2, SlALDH, SlCAS1, SlNSDHL, and SlDGKI, are directly related to the biosynthesis of fatty acids, meanwhile, SlRPS6KA, SlCAMK1, SlMYB3R1, and SlMYB3R5 serve as transcription factors that could potentially influence the regulation of fatty acid production. In the integration analysis of DARs and ATAC-seq, 13 genes were identified, which were shared by both DEGs and DARs-associated genes, including SlCAKM, SlRP2, SlSHOC2, SlTN, SlSGK2, SlHMP, SlOGT, SlclpB, and SlDNAAF3.

Conclusions

SlCAKM may act as a negative regulator of fatty acid and DHA synthesis, while SlSGK2 may act as a positive regulator, which requires further study in the future. These insights enhance our comprehension of the processes underlying fatty acid and DHA production in S. limacinum. They also supply a foundational theoretical framework and practical assistance for the development of strains rich in fatty acids and DHA.
Increased resected lymph node stations improved survival of esophageal squamous cell carcinoma
Authors: Lu Run-Da , Wei Zheng-Dao , Liu Yi-Xin , Tian Dong , Zhang Han-Lu , Shang Qi-Xin , Hu Wei-Peng , Yang Lin , Yang Yu-Shang , Chen Long-Qi
Published: February 2024

Background

Neoadjuvant chemoradiotherapy (nCRT) and surgery have been recommended as the standard treatments for locally advanced esophageal squamous cell carcinoma (ESCC). In addition, nodal metastases decreased in frequency and changed in distribution after neoadjuvant therapy. This study aimed to examine the optimal strategy for lymph node dissection (LND) in patients with ESCC who underwent nCRT.

Methods

The hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were calculated using the Cox proportional hazard model. To determine the minimal number of LNDs (n-LNS) or least station of LNDs (e-LNS), the Chow test was used.

Results

In total, 333 patients were included. The estimated cut-off values for e-LNS and n-LNS were 9 and 15, respectively. A higher number of e-LNS was significantly associated with improved OS (HR: 0.90; 95% CI 0.84–0.97, P = 0.0075) and DFS (HR: 0.012; 95% CI: 0.84–0.98, P = 0.0074). The e-LNS was a significant prognostic factor in multivariate analyses. The local recurrence rate of 23.1% in high e-LNS is much lower than the results of low e-LNS (13.3%). Comparable morbidity was found in both the e-LNS and n-LND subgroups.

Conclusion

This cohort study revealed an association between the extent of LND and overall survival, suggesting the therapeutic value of extended lymphadenectomy during esophagectomy. Therefore, more lymph node stations being sampled leads to higher survival rates among patients who receive nCRT, and standard lymphadenectomy of at least 9 stations is strongly recommended.
Interaction between Wnt/β-catenin signaling pathway and EMT pathway mediates the mechanism of sunitinib resistance in renal cell carcinoma
Authors: Cai Fangzhen , Li Jianwei , Zhang Yanmei , Huang Sihuai , Liu Wenbin , Zhuo Weifeng , Qiu Chengzhi
Published: February 2024

Background

Targeted drugs are the main methods of RCC treatment. However, drug resistance is common in RCC patients, in-depth study of the drug-resistant mechanism is essential.

Methods

We constructed sunitinib resistant and Twist overexpressed A498 cells, and studied its mechanisms in vitro and in vivo.

Results

In cell research, we found that either sunitinib resistance or Twist overexpression can activate Wnt/β-catenin and EMT signaling pathway, and the sunitinib resistance may work through β-catenin/TWIST/TCF4 trimer. In zebrafish research, we confirmed the similarity of Twist overexpression and sunitinib resistance, and the promoting effect of Twist overexpression on drug resistance.

Conclusions

Sunitinib resistance and Twist overexpression can activate Wnt/β-catenin signaling pathway and EMT to promote the growth and metastasis of RCC cells.
‘Fear, uncertain, tired…...’ psychological distress among pulmonary hypertension patients: a qualitative interview study
Authors: Zhang Juxia , Zhang Yiyin , Yin Yuhuan , Feng Yuping , Zhang Rong , Meng Hongyan , Wang Jing
Published: February 2024

Background

Patient-centered health care for patients with pulmonary hypertension (PH) is important and requires an understanding of patient experiences. However, there is a lack of approaches to examine what's the effects and how the disease impact patients’ psychological well-beings.

Methods

We conducted qualitative interviews with PH patient representatives to understand patient psychological experiences and inform patient-centered research and care. Participants were chosen from a tertiary hospital located in northwest China. 20 patients with PH who be treated at the hospital (13 participants were women, aged 18-74 years) were strategically selected and individually interviewed. We used qualitative analysis to identify themes relating to existential psychological distress that would clarify the nature of such concerns.

Results

We found that patients experience tremendous psychological distress throughout the treatment process. Four categories that describe patients' psychological experiences emerged: burden of PH treatment, fear and uncertainty about the disease, frustration in social and family role, and lack of recognition of the condition.

Conclusions

Existential concerns are salient in PH and involve the experience of loss and disruptions to the sense of self and relationships. Healthcare practitioners must work more in collaboration to detect patients' need for support and to develop the patient's own skills to manage daily life. The PH teams should tailor interventions to provide emotional, informational and instrumental support and guidance to patients.
Associations between ADHD and risk of six psychiatric disorders: a Mendelian randomization study
Authors: Guo Yanwei , Li Junyao , Hu Renqin , Luo Huirong , Zhang Zheng , Tan Jinglan , Luo Qinghua
Published: February 2024

Background

Observational studies and diagnostic criteria have indicated that Attention Deficit Hyperactivity Disorder (ADHD) frequently comorbid with various psychiatric disorders. Therefore, we conducted a Mendelian randomization (MR) study to explore this potential genetic association between ADHD and six psychiatric disorders.

Methods

Using a two-sample Mendelian randomization (MR) design, this study systematically screened genetic instrumental variables (IVs) based on the genome-wide association studies (GWAS) of ADHD and six psychiatric disorders, with the inverse variance weighted (IVW) method as the primary approach.

Results

The study revealed a positive and causal association between ADHD and the risk of ASD, with an odds ratio (OR) of 2.328 (95%CI: 1.241–4.368) in the IVW MR analysis. Additionally, ADHD showed a positive causal effect on an increased risk of schizophrenia, with an OR of 1.867 (95%CI: 1.260–2.767) in the IVW MR analysis. However, no causal effect of Tic disorder, Mental retardation, Mood disorders and Anxiety disorder with ADHD was found in the analysis mentioned above.

Conclusion

Our MR analysis provides robust evidence of the causal role of ADHD in increasing the risk of ASD and schizophrenia. However, ADHD is not associated with the risk of Tic Disorder, Mental Retardation, Mood Disorders and Anxiety Disorder. This suggests the need for increased attention to the co-occurrence of ADHD-ASD or ADHD-schizophrenia and the implementation of timely intervention and treatment.
Monthly engagement with EIP keyworkers was associated with a five-fold increase in the odds of engagement with psychosocial interventions
Authors: Darker C. D. , Nicolson G. , Reddon H. , O’Connor K. , Jennings R. , O’Connell N.
Published: February 2024

Background

Early intervention in psychosis (EIP) supports people who are experiencing their first episode of psychosis (FEP). A new Model of Care (MoC) for EIP services was launched in Ireland in 2019. Three EIP demonstration sites were chosen to test this MoC through a ‘hub and spoke’ approach. These services were a new way of organising care for people experiencing FEP, based upon a recovery model of care, and which sought to standardise care, improve access by clinically led multidisciplinary teams. This included newly created EIP keyworker roles whereby keyworkers assumed responsibilities regarding assessment, comprehensive individual care planning and coordination of care.

Methods

A mixed methods design utilising the UK Medical Research Council’s process evaluation framework. Purposive sampling techniques were utilised. Descriptive analyses and logistic regression were performed to examine how increased keyworker engagement influenced the use of other psychosocial interventions within the EIP demonstration sites. Thematic analyses was used for qualitative data.

Results

There was a strong positive relationship between keyworker contacts and psychosocial interventions offered. Specifically, the odds of achieving at least monthly engagement with cognitive behavioural therapy for psychosis (CBTp; (5.76 (2.43–13.64), p < 0.001), and behavioural family therapy (BFT; (5.52(1.63–18.69, p < 0.006)) increased by fivefold with each additional monthly keyworker contact. For individual placement support (IPS) each additional monthly keyworker contact was associated with a three-fold increase in the odds of achieving monthly attendance with IPS (3.73 (1.64–8.48), p < 0.002). Qualitative results found that the EIP keyworker role as viewed by both service users and staff as a valuable nodal point, with a particular emphasis on care coordination and effective communication.

Conclusions

This study advances the understanding of keyworker effects through qualitative evidence of keyworkers functioning as a “linchpin” to the service, while the positive response association between keyworker contacts and engagement with other services provides quantitative support for keyworkers reducing the organisational or structural barriers to service access. Given the importance of these positions, health systems should ensure that EIP programmes identify qualified and experienced staff to fill these roles, as well as allocate the appropriate funding and protected time to support keyworker engagement and impact.
Pornography, sexual orientation and ambivalent sexism in young adults in Spain
Authors: Sanz-Barbero Belén , Estévez-García J. Francisco , Madrona-Bonastre Raquel , Vicens Gemma Renart , Serra Laura , Vives-Cases Carmen
Published: February 2024

Background

On line platforms offer access to an almost unlimited variety of pornographic material that shows high levels of sexism. Despite this fact, there are still few studies that assess the effect of pornography on sexism in young adults The aim of this study is to analyze the association of pornography consumption and sexual orientation with benevolent sexism (BS) and hostile sexism (HS) in young men and women.

Methods

We surveyed 2,346 people aged 18–35 years old. Multiple regression models were carried out for BS and HS. The independent variables: current pornography consumption and sexual orientation. Covariates: socio-demographic variables -age, sex, level of education and place of birth-.

Results

A) HS: Men who consumed pornography had higher median values of HS than those who did not [β(95%CI):2.39(0.67;4.10)]. Homosexual/ bisexual men displayed lower values of HS than heterosexual men [β(95%CI):-2.98(-4.52;-1.45)]. The increase in HS levels associated with pornography consumption was notably greater in homosexual and bisexual women relative to heterosexual women, where that pattern was not observed [β(95%CI for interaction): 2.27(0.11; 4.43)]. B) BS: Mean values of BS were observed to be lower for both women [β(95%CI):-2.16(-2.99;-1.32)] and men [β(95%CI):-4.30(-5.75;-2.86)] who consumed pornography compared to those who did not. Homosexual/bisexual men recorded mean values of BS lower than heterosexual men [β(95%CI):-3.10(-4.21;-1.99)].

Conclusions

Pornography consumption is related to sexism and differs according to sex and sexual orientation. As sexism is the substratum of inequality between men and women, it is urgent to launch affective-sexual education programs for young people that take into account the determinants of sexism.
Comparison of performances of SIREN or MFSRS in stroke risk prediction in an African environment
Authors: Onwuakagba Ifeoma Uchenna , Okoye Emmanuel Chiebuka , Kanu Favour Chidera , Kalu Chukwuemeka Michael , Akosile Christopher Olusanjo
Published: February 2024

Background

The Modified Framingham Stroke Risk Score (MFSRS) is a widely utilized stroke risk assessment algorithm usually applied in international comparison. The Stroke Investigative Research and Educational Network (SIREN) is the only known African-specific stroke risk assessment algorithm.

Aims and objectives

To compare stroke risk estimates from the SIREN and the MFSRS in an African community.

Methods

This was a population-based cross-sectional survey involving consecutively recruited 310 consenting adult residents (mean age = 37.21 ± 15.84 years) of a Nigerian community. Risk factors of stroke were assessed among the participants and were utilized in calculating stroke risk estimates on the MFSRS and the SIREN. The obtained data were analyzed using descriptive statistics and the Spearman-rank order correlation test at an alpha level of 0.05.

Results

The percentage stroke risk scores estimated by the SIREN and the MFSRS were 34.5% and 6.79% respectively. The most prevalent risk factors among the participants were hypertriglyceridemia (100.0%), raised waist-hip ratio (50.6%), hypercholesterolemia (45.5), physical inactivity (43.2%), psychological stress (41.3%), and hypertension (37.7%). Only two (hypertriglyceridemia and high blood pressure) out of the six factors considered in the MFSRS were rated among the first 10 most impactful risks by the SIREN. There was a weak correlation between the total scores on the MFSRS and the SIREN (rho = 0.39; p < 0.01) suggesting that the two ratings were discordant.

Conclusion

There were disagreements between the risk estimates on the SIREN and MFSRS with SIREN having a higher estimate that corresponded with the literature; this may be suggesting a poorer estimation of stroke risks by the MFSRS in an African environment. There is a need for large African-based quality control studies to determine and address these lapses.
Success rates of single-thread and double-thread orthodontic miniscrews in the maxillary arch
Authors: Merati Mohsen , Ghaffari Hassanali , Javid Fatemeh , Ahrari Farzaneh
Published: February 2024

Aim

There is limited research on the clinical performance of double-thread orthodontic miniscrews. This study aimed to compare the stability of double-thread and single-thread orthodontic miniscrews and identify the potential associations between patient-related and location-related factors with miniscrew stability.

Methods

This retrospective cohort study involved 90 orthodontic miniscrews (45 single-thread, 45 double-thread) with identical dimensions (8 mm length, 1.6 mm diameter). The screws were inserted in various locations within the upper jaw of 83 patients (54 females, 29 males; mean age = 15.1 ± 2.4 years). Failure was defined as excessive mobility or loss of miniscrew after placement. The data recorded were patient age, gender, insertion site, side of insertion (buccal or lingual), duration of force application, and failure occurrence.

Results

The overall success rate within the sample was 92.2%. Double-thread miniscrews exhibited a significantly higher success rate than single-thread miniscrews (P = 0.049), with 97.8% and 86.7% success rates, respectively. Gender, age, insertion location, and side of insertion did not show significant associations with failure (P > 0.05). Log-rank analysis revealed a significant difference between the two groups (P = 0.046), indicating a higher probability of survival for the double-thread design.

Conclusions

The overall success rate of orthodontic miniscrews was high in the present sample. Double-thread miniscrews placed in various locations within the maxillary arch demonstrated superior stability and survival rates compared to their single-thread counterparts. Therefore, double-thread miniscrews may be preferred when bone quality is inadequate, such as in young patients.
Prenatal incidence of cleft lip/palate and cocaine abuse in parents: a systematic review and meta-analysis
Authors: Alayyash Afnan , Alam Mohammad Khursheed , Rashid Mohammed Enamur , Mathew Asok , Di Blasio Marco , Ronsivalle Vincenzo , Cicciù Marco , Minervini Giuseppe
Published: February 2024

Background

The study aimed to investigate the association between maternal cocaine abuse during pregnancy and the prevalence of cleft lip/palate (CL/P) in offspring, synthesizing existing evidence through a systematic review and meta-analysis. CL/P is a congenital craniofacial anomaly with complex etiology, and prior research has suggested potential links between maternal cocaine use and CL/P. However, these associations remain inconclusive.

Methods

A comprehensive literature search was conducted to identify relevant studies published up to the study’s cutoff date in September 2021. Several databases were systematically searched using predefined search terms. Inclusion criteria were set to encompass studies reporting on the prevalence of CL/P in infants born to mothers with a history of cocaine use during pregnancy, with a comparison group of non-cocaine-using mothers. Data were extracted, and a meta-analysis was performed using a random-effects model to calculate pooled odds ratios (OR) and relative risks (RR) with their respective 95% confidence intervals (CI).

Results

The review included data from 4 studies that met the inclusion criteria. The combined OR from two studies was 0.05 (95% CI: 0.00, 4.41), which does not suggest a statistically significant association between prenatal cocaine exposure and the incidence of CL/P due to the confidence interval crossing the null value. Additionally, the combined RR was 0.17 (95% CI: 0.04, 0.66), indicating a statistically significant decrease in the risk of CL/P associated with prenatal cocaine exposure. These results, with an OR that is not statistically significant and an RR suggesting decreased risk, should be interpreted with caution due to considerable heterogeneity and variability among the included studies’ findings. Further research is needed to clarify these associations.

Conclusion

The findings from this systematic review and meta-analysis suggest that maternal cocaine use during pregnancy is not a statistically significant independent risk factor for the development of CL/P in offspring. These results underscore the multifactorial nature of CL/P etiology and emphasize the importance of considering other genetic, environmental, and nutritional factors in understanding the condition’s origins. While the study provides important insights, limitations such as data heterogeneity and potential confounders should be acknowledged. Future research should adopt rigorous study designs and explore a broader range of potential risk factors to comprehensively elucidate CL/P development.
E-portfolio as an effective tool for improvement of practitioner nurses’ clinical competence
Authors: Najaffard Nastaran , Mohammadi Aeen , Mojtahedzadeh Rita , Zarei Afagh
Published: February 2024

Background

Clinical competence is essential for providing effective patient care. Clinical Governance (CG) is a framework for learning and assessing clinical competence. A portfolio is a work-placed-based tool for monitoring and reflecting on clinical practice. This study aimed to investigate the effect of using an e-portfolio on the practitioner nurses’ competence improvement through the CG framework.

Methods

This was a quasi-experimental study with 30 nurses in each intervention and control group. After taking the pretests of knowledge and performance, the participants attended the in-person classes and received the educational materials around CG standards for four weeks. In addition, nurses in the intervention group received the links to their e-portfolios individually and filled them out. They reflected on their clinical practice and received feedback. Finally, nurses in both groups were taken the post-tests.

Results

Comparing the pre-and post-test scores in each group indicated a significant increase in knowledge and performance scores. The post-test scores for knowledge and performance were significantly higher in the intervention group than in the control one, except for the initial patient assessment.

Conclusion

This study showed that the e-portfolio is an effective tool for the improvement of the nurses’ awareness and performance in CG standards. Since the CG standards are closely related to clinical competencies, it is concluded that using portfolios effectively improves clinical competence in practitioner nurses.
An LQT2-related mutation in the voltage-sensing domain is involved in switching the gating polarity of hERG
Authors: Liu Zhipei , Wang Feng , Yuan Hui , Tian Fuyun , Yang Chuanyan , Hu Fei , Liu Yiyao , Tang Meiqin , Ping Meixuan , Kang Chunlan , Luo Ting , Yang Guimei , Hu Mei , Gao Zhaobing , Li Ping
Published: February 2024

Background

Cyclic Nucleotide-Binding Domain (CNBD)-family channels display distinct voltage-sensing properties despite sharing sequence and structural similarity. For example, the human Ether-a-go-go Related Gene (hERG) channel and the Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channel share high amino acid sequence similarity and identical domain structures. hERG conducts outward current and is activated by positive membrane potentials (depolarization), whereas HCN conducts inward current and is activated by negative membrane potentials (hyperpolarization). The structural basis for the “opposite” voltage-sensing properties of hERG and HCN remains unknown.

Results

We found the voltage-sensing domain (VSD) involves in modulating the gating polarity of hERG. We identified that a long-QT syndrome type 2-related mutation within the VSD, K525N, mediated an inwardly rectifying non-deactivating current, perturbing the channel closure, but sparing the open state and inactivated state. K525N rescued the current of a non-functional mutation in the pore helix region (F627Y) of hERG. K525N&F627Y switched hERG into a hyperpolarization-activated channel. The reactivated inward current induced by hyperpolarization mediated by K525N&F627Y can be inhibited by E-4031 and dofetilide quite well. Moreover, we report an extracellular interaction between the S1 helix and the S5-P region is crucial for modulating the gating polarity. The alanine substitution of several residues in this region (F431A, C566A, I607A, and Y611A) impaired the inward current of K525N&F627Y.

Conclusions

Our data provide evidence that a potential cooperation mechanism in the extracellular vestibule of the VSD and the PD would determine the gating polarity in hERG.
Th1 cells contribute to retinal ganglion cell loss in glaucoma in a VCAM-1-dependent manner
Authors: He Chong , Peng Kun , Zhu Xiong , Wang Zuo , Xiu Wenbo , Zhang Gao , Chen Yang , Sun Chaonan , Xiao Xiao , Liu Donghua , Li An , Gao Yanping , Wang Jinxia , Shuai Ping , Chen Yilian , Yu Ling , Lu Fang
Published: February 2024

Glaucoma is a complex neurodegenerative disorder characterized by the progressive loss of retinal ganglion cells (RGC) and optic nerve axons, leading to irreversible visual impairment. Despite its clinical significance, the underlying mechanisms of glaucoma pathogenesis remain poorly understood. In this study, we aimed to unravel the multifaceted nature of glaucoma by investigating the interaction between T cells and retinas. By utilizing clinical samples, murine glaucoma models, and T cell transfer models, we made several key findings. Firstly, we observed that CD4+ T cells from glaucoma patients displayed enhanced activation and a bias towards T helper (Th) 1 responses, which correlated with visual impairment. Secondly, we identified the infiltration of Th1 cells into the retina, where they targeted RGC and integrated into the pro-inflammatory glial network, contributing to progressive RGC loss. Thirdly, we discovered that circulating Th1 cells upregulated vascular cell adhesion protein 1 (VCAM-1) on retinal microvessels, facilitating their entry into the neural retina. Lastly, we found that Th1 cells underwent functional reprogramming before reaching the retina, acquiring a phenotype associated with lymphocyte migration and neurodegenerative diseases. Our study provides novel insights into the role of peripheral CD4+ T cells in glaucoma pathogenesis, shedding light on the mechanisms underlying their infiltration into the retina and offering potential avenues for innovative therapeutic interventions in this sight-threatening disease.

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The role of NLRP3 inflammasome in aging and age-related diseases
Authors: Liang Ruikai , Qi Xinrui , Cai Qi , Niu Liyan , Huang Xi , Zhang Deju , Ling Jitao , Wu Yuting , Chen Yixuan , Yang Pingping , Liu Jianping , Zhang Jing , Yu Peng
Published: February 2024

The gradual aging of the global population has led to a surge in age-related diseases, which seriously threaten human health. Researchers are dedicated to understanding and coping with the complexities of aging, constantly uncovering the substances and mechanism related to aging like chronic low-grade inflammation. The NOD-like receptor protein 3 (NLRP3), a key regulator of the innate immune response, recognizes molecular patterns associated with pathogens and injury, initiating an intrinsic inflammatory immune response. Dysfunctional NLRP3 is linked to the onset of related diseases, particularly in the context of aging. Therefore, a profound comprehension of the regulatory mechanisms of the NLRP3 inflammasome in aging-related diseases holds the potential to enhance treatment strategies for these conditions. In this article, we review the significance of the NLRP3 inflammasome in the initiation and progression of diverse aging-related diseases. Furthermore, we explore preventive and therapeutic strategies for aging and related diseases by manipulating the NLRP3 inflammasome, along with its upstream and downstream mechanisms.
Design of a novel lateral mass screw–plate system for the treatment of unstable atlas fractures: a finite element analysis
Authors: Niu He-Gang , Zhang Jing-Jing , Yan Yi-Zhu , Zhao Cheng-Kun , Yang Kun , Zhang Yin-Shun
Published: February 2024

Background

Osteosynthesis of unstable atlas fractures preserves joint motion and therefore has a distinct advantage over a range of treatment procedures. To prevent the potential disadvantages associated with osteosynthesis, a new atlas lateral mass screw–plate (LMSP) system has been designed. However, the biomechanical role of using the LMSP system in atlas internal fixation is not known. The aim of this study was to compare the biomechanical stability of a new LMSP with traditional posterior screw and rod (PSR) fixation techniques on the occipitocervical junction (C0–C2) through finite element analysis.

Methods

A nonlinear C0–C2 finite element model of the intact upper cervical spine was developed and validated. The unstable model using the PSR system was then compared with the model using the LMSP system for fixation. A vertical load of 40 N was applied to the C0 to simulate head weight, while a torque of 1.5 Nm was applied to the C0 to simulate flexion, extension, lateral bending, and axial rotation.

Results

The range of motion of both systems was close to the intact model. Compared with the LMSP system model, the PSR system model increased flexion, extension, lateral bending, and axial rotation by 4.9%, 3.0%, 5.0%, and 29.5% in the C0–C1 segments, and 4.9%, 2.7%, 2.4%, and 22.6% in the C1–C2, respectively. In flexion, extension, and lateral bending motion, the LMSP system model exhibited similar stress to the PSR system model, while in axial rotation, the PSR system model exhibited higher stress.

Conclusions

The findings of our study indicate that the two tested system models provide comparable stability. However, better stability was achieved during axial rotation with the LMSP system, and in this system, the maximum von Mises stress was less than that of the PSR one. As the atlantoaxial joint functions primarily as a rotational joint, the use of the LMSP system may provide a more stable environment for the joint that has become unstable due to fracture.
Discontinuation and nonpublication of clinical trials in orthopaedic oncology
Authors: Singh Gurbinder , Wague Aboubacar , Arora Ayush , Rao Varun , Ward Derek , Barry Jeffrey
Published: February 2024

Background

Despite the pivotal role of clinical trials in advancing orthopaedic oncology knowledge and treatment strategies, the persistent issues of trial discontinuation and nonpublication are significant problems. This study conducted an analysis examining clinical trial discontinuation rates, associations between intervention types and discontinuation/nonpublication, and the role of funding, enrollment size, and their implications for trial success and completion.

Methods

This study, conducted on May 1, 2023, utilized a cross-sectional design to comprehensively analyze phase 3 and 4 randomized controlled trials within the realm of orthopaedic oncology. We specifically incorporated Phase 3 and 4 trials as they are designed to evaluate prolonged outcomes in human subjects and are more likely to reach publication. Study characteristics of interest included the intervention utilized in the clinical trial, presence of funding, whether the trial was published, completed, and trial enrollment size. The investigation involved an examination of ClinicalTrials.gov, a prominent online repository of clinical trial data managed by the National Library of Medicine of the USA. Descriptive statistics and multivariate logistic regressions were used to determine statistical significance.

Results

Among the cohort of 130 trials, 19.2% were prematurely discontinued. Completion rates varied based on intervention type; 111 pharmaceutical trials demonstrated a completion rate of 83.8%, whereas 19 non-pharmaceutical trials exhibited a completion rate of 8.0% (P < .001). Surgical trials, totaling 10, showed a completion rate of 90%. The overall trial publication rate was 86.15%, with pharmaceutical interventions achieving a publication rate of 91.96%. Larger-scale trials (≥ 261 participants) emerged as a protective factor against both discontinuation (Adjusted Odds Ratio [AOR]: 0.85, 95% Confidence Interval [CI] 0.42–0.95) and nonpublication (AOR: 0.19, 95% CI 0.13–.47), compared to smaller-scale trials.

Conclusion

This study accentuates the heightened vulnerability of non-pharmaceutical interventions and trials exhibiting lower rates of enrollment to the issues of discontinuation and nonpublication. Moving forward, the advancement of clinical trials necessitates a concerted effort to enhance trial methodologies, especially concerning nonpharmaceutical interventions, along with a meticulous refinement of participant enrollment criteria.
Microglial ferroptotic stress causes non-cell autonomous neuronal death
Authors: Liddell Jeffrey R. , Hilton James B. W. , Kysenius Kai , Billings Jessica L. , Nikseresht Sara , McInnes Lachlan E. , Hare Dominic J. , Paul Bence , Mercer Stephen W. , Belaidi Abdel A. , Ayton Scott , Roberts Blaine R. , Beckman Joseph S. , McLean Catriona A. , White Anthony R. , Donnelly Paul S. , Bush Ashley I. , Crouch Peter J.
Published: February 2024

Background

Ferroptosis is a form of regulated cell death characterised by lipid peroxidation as the terminal endpoint and a requirement for iron. Although it protects against cancer and infection, ferroptosis is also implicated in causing neuronal death in degenerative diseases of the central nervous system (CNS). The precise role for ferroptosis in causing neuronal death is yet to be fully resolved.

Methods

To elucidate the role of ferroptosis in neuronal death we utilised co-culture and conditioned medium transfer experiments involving microglia, astrocytes and neurones. We ratified clinical significance of our cell culture findings via assessment of human CNS tissue from cases of the fatal, paralysing neurodegenerative condition of amyotrophic lateral sclerosis (ALS). We utilised the SOD1G37R mouse model of ALS and a CNS-permeant ferroptosis inhibitor to verify pharmacological significance in vivo.

Results

We found that sublethal ferroptotic stress selectively affecting microglia triggers an inflammatory cascade that results in non-cell autonomous neuronal death. Central to this cascade is the conversion of astrocytes to a neurotoxic state. We show that spinal cord tissue from human cases of ALS exhibits a signature of ferroptosis that encompasses atomic, molecular and biochemical features. Further, we show the molecular correlation between ferroptosis and neurotoxic astrocytes evident in human ALS-affected spinal cord is recapitulated in the SOD1G37R mouse model where treatment with a CNS-permeant ferroptosis inhibitor, CuII(atsm), ameliorated these markers and was neuroprotective.

Conclusions

By showing that microglia responding to sublethal ferroptotic stress culminates in non-cell autonomous neuronal death, our results implicate microglial ferroptotic stress as a rectifiable cause of neuronal death in neurodegenerative disease. As ferroptosis is currently primarily regarded as an intrinsic cell death phenomenon, these results introduce an entirely new pathophysiological role for ferroptosis in disease.

Graphical Abstract