bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of neurofibromatosis type 1 with plexiform neurofibromas on the health-related quality of life and work productivity of adult patients and caregivers in the UK: a cross-sectional survey
Authors: Yoo Hyun Kyoo , Porteous Alex , Ng Alvin , Haria Keval , Griffiths Annabel , Lloyd Andrew , Yang Xiaoqin , Kazeem Gbenga , Barut Volkan
Published: November 2023

Background

Plexiform neurofibromas (PN) are complex, benign nerve-sheath tumours that occur in 30–50% of patients with neurofibromatosis type 1 (NF1), a rare, genetic disorder. PN are associated with substantial, heterogeneous morbidities that impact health-related quality of life (HRQoL), including affecting motor function and causing pain, though HRQoL and work productivity data are scarce. This UK cross-sectional study explored HRQoL and work productivity in adult patients with NF1 PN and caregivers of paediatric patients.

Methods

Adult patients and caregivers of paediatric patients self-enrolled in an online survey (March–April 2021). Outcomes included EQ-5D-5L, PROMIS® GH and INF1-QOL (adult patients only), and EQ-5D-5L, CarerQol and WPAI (caregivers only). Utilities were estimated from EQ-5D-5L responses using the UK crosswalk value set. Linear regression models explored univariable associations between adult patient characteristics and HRQoL.

Results

Mean (± standard deviation) EQ-5D utility in adult patients with NF1 PN was 0.65 (± 0.29; n = 35; age-/sex-matched norm: 0.89 [± 0.04]). Moderate–extreme pain/discomfort and anxiety/depression were reported by 14/35 (40.0%) and 18/35 (51.4%) patients, respectively. Mean PROMIS® GH physical and mental health scores were 43.6 (± 9.19) and 41.7 (± 11.5; n = 35; matched norm: 50.0 [± 10.0]). Mean INF1-QOL score was 11.03 (± 6.02; n = 33). Chronic itching, at least one symptom, at least one comorbidity, PN location at extremities (arms/legs) and pain were associated with worse HRQoL scores.

Mean caregiver EQ-5D utility was 0.72 (± 0.24; n = 8; age-/sex-matched norm: 0.88 [± 0.03]). Moderate pain/discomfort and moderate–severe anxiety/depression were reported by 4/8 (50.0%) and 2/8 (25.0%) caregivers, respectively. Mean CarerQol score was 69.3 (± 13.9; n = 8). Mean WPAI regular activity productivity loss was 36.3% (± 31.6%; n = 8).

Conclusions

NF1 PN worsens adult patient and caregiver HRQoL compared to the general population, notably affecting pain and discomfort, anxiety and depression and caregiver productivity.
Risk factors associated with preterm birth among mothers delivered at Lira Regional Referral Hospital
Authors: Etil Tom , Opio Bosco , Odur Bernard , Lwanga Charles , Atuhaire Leonard
Published: November 2023

Background

The World Health Organization (WHO) defines Preterm Birth (PTB) as “a live birth taking place before the expected 37 weeks of gestation”. Annually, approximately 15 million infants are born prematurely, constituting significantly to infant mortality during the initial four weeks of life, responsible for 40% of deaths among children under the age of five. Evidently, preterm deliveries have contributed to 46% of admissions to the neonatal intensive care unit (NICU) at Lira Regional Referral Hospital (LRRH) over the past three years. Paradoxically, while the prevalence of preterm births remains high, there is a lack of documented information regarding the underlying risk factors. Consequently, the primary objective of this study was to assess the potential risk factors associated with preterm birth at LRRH.

Methods

An analytical cross-sectional research was undertaken at LRRH, employing a quantitative methodology. The study utilized secondary data obtained from a total of 590 comprehensive maternal medical records, of deliveries that occurred at the facility between April 2020 and July 2021. The collected data underwent analysis using STATA version 17 software. To identify predictors of preterm birth, a Logistic regression model was applied, yielding adjusted odds ratios (AOR) alongside 95% confidence intervals (CI). The significance level was set at p < 0.05 to establish statistical significance. Furthermore, assessments for multicollinearity and model fitness were conducted using the Variance Inflation Factor (VIF) and linktest, respectively.

Results

The prevalence of preterm delivery among mothers who gave birth at LRRH stood at 35.8%. The outcomes of logistic regression analysis revealed that maternal employment status had a statistically significant association with preterm birth (AOR = 0.657, p = 0.037, 95%CI: 0.443–0.975); having a baby with low birth weight (AOR = 0.228, p < 0.001, 95% CI: 0.099–0.527) and experiencing preeclampsia (AOR = 0.142, p < 0.001, 95% CI: 0.088–0.229) were also identified as significant predictors of preterm birth in the study.

Conclusions and recommendations

The occurrence of preterm delivery is significantly higher (35.8%) among mothers who gave birth at LRRH when compared to the national average (13.6%). The prevalence of preterm birth among mothers was linked to factors such as employment status, delivery of low birth weight infants, and the presence of preeclampsia. Consequently, the research proposes a set of recommendations. Firstly, the Ministry of Health (MoH) should evaluate the present state of readiness within the healthcare system to effectively handle cases of preterm birth both within medical facilities and the community. Secondly, the Ministry of Gender, Labour, and Social Development should leverage Labor Officers to implement and uphold the regulations stipulated in the Employment Act and Labor Laws.
Factors associated with the prevalence of depression and anxiety among parents of children with neurodevelopmental disorders in Saudi Arabia
Authors: Alsaad Ali J. , Al Khamees Mujtaba M. , Alkadi Abdulelah N. , Alsaleh Majd A. , Alshairdah Aeshah S. , Alessa Zahra’a A.
Published: November 2023

Background

Neurodevelopmental disorders (NDDs) are a group of conditions that include attention-deficit/hyperactivity disorders, specific learning disorders, autism spectrum disorder, intellectual disability, and other disorders. Raising a child with an NDD can be difficult because it affects the social lives of the parents and their relationships. It also requires the parents to develop another set of skills to deal with their child. These factors increase their risk of depression and anxiety.

Aim

To measure the prevalence rates of depression and anxiety among parents of children with different NDDs, compare the rates between mothers and fathers, and measure the relevant associated factors.

Methodology

This study was a prospective, qualitative, cross-sectional, anonymous questionnaire-based study. The participants were 416 parents of children with NDDs in Saudi Arabia. The sample size was determined using the Richard Geiger equation with a 5% margin of error, a 95% confidence level, and a 50% response distribution. The screening was performed using a validated Arabic version of the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7). These are short and understandable screening tools that assist in identifying and grading the severity of depression and anxiety symptoms. The participants were reached by distributing the questionnaire to parents who followed up with Saudi NDD-related associations, clinics, and psychiatric clinics from November 20 to May 8, 2022. The data were collected, reviewed, and then entered into SPSS 21.

Results

In total, 416 parents of children with NDDs in Saudi Arabia participated in the study. We demonstrated that 85.1% of parents of children with NDDs had depression and that 85.8% had anxiety. Mothers and fathers had similar rates of depression and anxiety. No significant difference was found between the type of NDD and rates of depression and anxiety in parents.

Conclusion

Children with NDDs affect their parents’ mental health in terms of increased rates of depression and anxiety. This increase is not correlated with a specific etiology. Healthcare professionals who care for children with NDDs should also assess parental mental health and seek an early diagnosis of mental illness to ensure that the appropriate interventions are provided for parents.
Difficulties in using simulation to assess abdominal palpation skills
Authors: Xu Xiaowei , Wang Haoyu , Luo Jingfang , Zhang Changhua , Konge Lars , Tang Lina
Published: November 2023

Objectives

Abdominal palpation is an essential examination to diagnose various digestive system diseases. This study aimed to develop an objective and standardized test based on abdominal palpation simulators, and establish a credible pass/fail standard of basic competency.

Methods

Two tests were designed using the newly developed Jucheng abdominal palpation simulator (test 1) and the AbSim simulator (test 2), respectively. Validity evidence for both tests was gathered according to Messick’s contemporary framework by using experts to define test content and then administering the tests in a highly standardized way to participants of different experience. Different simulator setups modified by the built-in software were selected from hepatomegaly, splenomegaly, positive McBurney’s sign plus rebound tenderness, gallbladder tenderness (Murphy’s sign), pancreas tenderness, and a normal setup without pathologies, with six sets used in test 1 and five sets used in test 2. Different novices and experienced were included in the tests, and test 1 was also administered to an intermediate group. Scores and test time were collected and analyzed statistically.

Results

The internal consistency reliability of test 1 and test 2 showed low Cronbach’s alphas of 0.35 and -0.41, respectively. Cronbach’s alpha for palpation time across cases were 0.65 for test 1 and 0.76 for test 2. There was no statistical difference in total time spent and total scores among the three groups in test 1 (P-values (ANOVA) were 0.53 and 0.35 respectively), nor between novices and experienced groups in test 2 (P-values (t-test) were 0.13 and 1.0 respectively). It was not relevant to try to establish pass/fail standards due to the low reliability and lack of discriminatory ability of the tests.

Conclusions

It was not possible to measure abdominal palpation skills in a valid way using either of the two standardized, simulation-based tests in our study. Assessment of the patient’s abdomen using palpation is a challenging clinical skill that is difficult to simulate as it highly relies on tactile sensations and adequate responsiveness from the patients.
Why should stakeholders consider the effect of tensions in collaborative innovation in healthcare—lessons learned from surveying integrated care projects in Germany
Authors: Haring Malte , Schiller Juliane , Gersch Martin , Amelung Volker
Published: November 2023

Introduction

The German Innovation Fund supports projects that aim to improve healthcare through integration and intersectoral collaboration. As is typical for collaborative innovation projects, partners often pursue different objectives, which can create tensions and affect outcomes. The study aims to explore the causes and effects of tensions in integrated care projects and how frameworks, processes, and management should be designed to deal with tensions and achieve their productive effects.

Methods

In an online survey we asked participants about the causes, effects, and management of tensions and their implications for integrated care projects (n = 58 completed questionnaires). We applied bivariate descriptive statistics to analyse the quantitative data.

Results

Tensions between stakeholders, caused by deep-seated differences and the design of the project frameworks, often affect the course and outcome of innovative integrated care projects. However, through appropriate conflict management and negotiation processes such tensions can be managed constructively and lead to better outcomes.

Discussion

Tension is usually seen as something unpleasant to be avoided and/or overcome. In fact, tensions can have positive effects, the importance of which remains little understood. Developing appropriate frameworks for managing and integrating different perspectives are key factors in unlocking the positive potential of tensions in integrated care projects.
Safety, tolerability, pharmacokinetics and effects of diet on AD16, a novel neuroinflammatory inhibitor for Alzheimer’s disease: a randomized phase 1 study
Authors: Peng Daizhuang , Xu Sumei , Zou Ting , Wang Yahui , Ouyang Wenjuan , Zhang Yalan , Dong Chengmei , Li Dai , Guo Jie , Shen Qiuying , Hu Xiaolei , Zhou Wenzhi , Li Xiaomin , Qin Qun
Published: November 2023

Background

AD16 is a Class 1.1 new drug candidate for Alzheimer’s disease (AD), which has demonstrated potential benefits in AD by reducing neuroinflammation in preclinical studies. Herein, the pharmacokinetics (PK), safety, and tolerability of single and multiple-dose AD16 and the effect of food were assessed in healthy Chinese adults.

Methods

Single-center, randomized, placebo-controlled, double-blind studies were conducted for single and multiple ascending doses. A total of 62 subjects were enrolled in single-dose groups; 10 each in 5, 10, 20, 30, and 40 mg groups, and 6 each in 60 and 80 mg dose groups. Twenty subjects were divided equally into 30 and 40 mg groups for the multiple-dose study. To determine the effect of a high-fat diet on AD16, 16 subjects were administered a single 20 mg dose of AD16 under the fasted and fed condition in a single-center, randomized, open-label, two-cycle, two-crossover study. Moreover, safety and PK parameters were also assessed.

Results

Plasma exposure to a single oral dose of AD16 increased at an approximate dose-increasing rate. The pharmacodynamic dose of the AD16 can be maintained through the accumulation effect of the drug within the safety window. Compared to fasting, ingesting a high-fat meal decelerated the rate of AD16 absorption, albeit without effect on its overall absorption. No dose-related toxicities were seen in any of the studies, all treatment-emergent adverse events were grade I/II, and no serious adverse event occurred.

Conclusions

The present study exhibited favorable safety, tolerability, and PK profile of AD16, supporting its further research as a potential drug treatment for AD.

Trial registration

ClinicalTrials.gov; NCT05787028, NCT05787041, NCT05806177. The SAD and FE studies were retrospectively registered on 28 March 2023. The MAD study was retrospectively registered on 10 April 2023.
Metabolic dynamics and prediction of sFGR and adverse fetal outcomes: a prospective longitudinal cohort study
Authors: Huang Nana , Chen Wei , Jiang Hai , Yang Jing , Zhang Youzhen , Shi Huifeng , Wang Ying , Yuan Pengbo , Qiao Jie , Wei Yuan , Zhao Yangyu
Published: November 2023

Background

Selective fetal growth restriction (sFGR) is an extreme complication that significantly increases the risk of perinatal mortality and long-term adverse neurological outcomes in offspring, affecting approximately 15% of monochorionic diamniotic (MCDA) twin pregnancies. The lack of longitudinal cohort studies hinders the early prediction and intervention of sFGR.

Methods

We constructed a prospective longitudinal cohort study of sFGR, and quantified 25 key metabolites in 337 samples from maternal plasma in the first, second, and third trimester and from cord plasma. In particular, our study examined fetal growth and brain injury data from ultrasonography and used the Ages and Stages Questionnaire-third edition subscale (ASQ-3) to evaluate the long-term neurocognitive behavioral development of infants aged 2–3 years. Furthermore, we correlated metabolite levels with ultrasound data, including physical development and brain injury indicators, and ASQ-3 data using Spearman’s-based correlation tests. In addition, special combinations of differential metabolites were used to construct predictive models for the occurrence of sFGR and fetal brain injury.

Results

Our findings revealed various dynamic patterns for these metabolites during pregnancy and a maximum of differential metabolites between sFGR and MCDA in the second trimester (n = 8). The combination of l-phenylalanine, l-leucine, and l-isoleucine in the second trimester, which were closely related to fetal growth indicators, was highly predictive of sFGR occurrence (area under the curve [AUC]: 0.878). The combination of l-serine, l-histidine, and l-arginine in the first trimester and creatinine in the second trimester was correlated with long-term neurocognitive behavioral development and showed the capacity to identify fetal brain injury with high accuracy (AUC: 0.94).

Conclusions

The performance of maternal plasma metabolites from the first and second trimester is superior to those from the third trimester and cord plasma in discerning sFGR and fetal brain injury. These metabolites may serve as useful biomarkers for early prediction and promising targets for early intervention in clinical settings.
Male- and female-specific reproductive risk factors across the lifespan for dementia or cognitive decline: a systematic review and meta-analysis
Authors: Han Shuang-Ling , Liu De-Chun , Tan Chen-Chen , Tan Lan , Xu Wei
Published: November 2023

Background

Sex difference exists in the prevalence of dementia and cognitive decline. The impacts of sex-specific reproductive risk factors across the lifespan on the risk of dementia or cognitive decline are still unclear. Herein, we conducted this systemic review and meta-analysis to finely depict the longitudinal associations between sex-specific reproductive factors and dementia or cognitive decline.

Methods

PubMed, EMBASE, and Cochrane Library were searched up to January 2023. Studies focused on the associations of female- and male-specific reproductive factors with dementia or cognitive decline were included. Multivariable-adjusted effects were pooled via the random effect models. Evidence credibility was scored by the GRADE system. The study protocol was pre-registered in PROSPERO and the registration number is CRD42021278732.

Results

A total of 94 studies were identified for evidence synthesis, comprising 9,839,964 females and 3,436,520 males. Among the identified studies, 63 of them were included in the meta-analysis. According to the results, seven female-specific reproductive factors including late menarche (risk increase by 15%), nulliparous (11%), grand parity (32%), bilateral oophorectomy (8%), short reproductive period (14%), early menopause (22%), increased estradiol level (46%), and two male-specific reproductive factors, androgen deprivation therapy (18%), and serum sex hormone–binding globulin (22%) were associated with an elevated risk of dementia or cognitive decline.

Conclusions

These findings potentially reflect sex hormone-driven discrepancy in the occurrence of dementia and could help build sex-based precise strategies for preventing dementia.
S100A alarmins and thymic stromal lymphopoietin (TSLP) regulation in severe asthma following bronchial thermoplasty
Authors: Gagnon Pierre-Alexandre , Klein Martin , De Vos John , Biardel Sabrina , Côté Andréanne , Godbout Krystelle , Laviolette Michel , Laprise Catherine , Assou Said , Chakir Jamila
Published: November 2023

Rationale

Severe asthma affects a small proportion of asthmatics but represents a significant healthcare challenge. Bronchial thermoplasty (BT) is an interventional treatment approach preconized for uncontrolled severe asthma after considering biologics therapy. It was showed that BT long-lastingly improves asthma control. These improvements seem to be related to the ability of BT to reduce airway smooth muscle remodeling, reduce the number of nerve fibers and to modulate bronchial epithelium integrity and behavior. Current evidence suggest that BT downregulates epithelial mucins expression, cytokine production and metabolic profile. Despite these observations, biological mechanisms explaining asthma control improvement post-BT are still not well understood.

Objectives

To assess whether BT affects gene signatures in bronchial epithelial cells (BECs).

Methods

In this study we evaluated the transcriptome of cultured bronchial epithelial cells (BECs) of severe asthmatics obtained pre- and post-BT treatment using microarrays. We further validated gene and protein expressions in BECs and in bronchial biopsies with immunohistochemistry pre- and post-BT treatment.

Measurements and main results

Transcriptomics analysis revealed that a large portion of differentially expressed genes (DEG) was involved in anti-viral response, anti-microbial response and pathogen induced cytokine storm signaling pathway. S100A gene family stood out as five members of this family where consistently downregulated post-BT. Further validation revealed that S100A7, S100A8, S100A9 and their receptor (RAGE, TLR4, CD36) expressions were highly enriched in severe asthmatic BECs. Further, these S100A family members were downregulated at the gene and protein levels in BECs and in bronchial biopsies of severe asthmatics post-BT. TLR4 and CD36 protein expression were also reduced in BECs post-BT. Thymic stromal lymphopoietin (TSLP) and human β-defensin 2 (hBD2) were significantly decreased while no significant change was observed in IL-25 and IL-33.

Conclusions

These data suggest that BT might improve asthma control by downregulating epithelial derived S100A family expression and related downstream signaling pathways.
Relationship between the colours of the rivers in the Amazon and the incidence of malaria
Authors: Fonseca Fernanda , Martinez Jean-Michel , Balieiro Antônio , Orellana Jesem , Santos James D. , Filizola Naziano
Published: November 2023

Background

Malaria is transmitted by different Anopheles species. In Brazil, the disease is concentrated in the Amazon region. Rivers play an important role in the life cycle of malaria since the vector reproduces in aquatic environments. The waters of the rivers in the Amazon have distinct chemical characteristics, which affect the colour of the water and therefore, the study analysed whether the colour of the waters of the rivers have an on influence the distribution of malaria. The goal of the study was to correlate the different colourations of the water (black, white and mixed water) and the malaria incidence in 50 municipalities of the Amazonas state, Brazil, and then test hypotheses about the characteristics of the colour of the rivers and disease incidence.

Methods

This study was conducted for a period of seventeen years (2003–2019) in 50 municipalities in the state of Amazonas, Brazil. A conditionally Gaussian dynamic linear model was developed to analyse the association of malaria incidence and three types of river colour: white, black and mixed.

Results

The analyses indicate that the distribution of malaria is related to the colouration of the rivers. The results showed that places located near black-water rivers have a higher malaria incidence when compared to places on the banks of white-water rivers.

Conclusions

Historically, the hydrological regime has played an important role in the dynamics of malaria in the Amazon, but little is known about the relationship between river colours and the incidence of the disease. This research was carried out in a region with hydrographic characteristics that were heterogeneous enough to allow an analysis that contrasted different colours of the rivers and covered almost the whole of the state of Amazonas. The results help to identify the places with the highest risk of malaria transmission and it is believed that they will be able to contribute to more precise planning of actions aimed at controlling the disease in the region.
The impact of urban–rural medical insurance integration on medical impoverishment: evidence from China
Authors: Huo Jinkang , Hu Mingzheng , Li Shaojie
Published: November 2023

Background

Financial protection is a key dimension of Universal Health Coverage (UHC), and social medical insurance is an effective measure to provide financial protection. The aim of this study is to examine the impact of urban–rural medical insurance integration on medical impoverishment in China.

Methods

We collected the time of integration policy in 337 prefecture-level cities across China, combined with the longitudinal database of China Labor-force Dynamics Survey (CLDS) from 2012–2016, and used a difference-in-differences (DID) method with multiple time periods at the city level to study the effect of urban–rural medical insurance integration on the medical impoverishment. Besides, to explore the heterogeneity of policy effects across populations, we conducted subgroup analyses based on respondents' age, household registration, and whether they were rural–urban migrants.

Findings

A total of 8,397 samples were included in the study. The integration policy has significantly reduced the incidence of medical impoverishment (average treatment effect on the treated (ATT) =  − 0.055,p < 0.05). Subgroup analysis showed that the impacts on medical impoverishment varied by age group, and the integration policy has more effect on older people than on younger people (ATT for age 15–34 =  − 0.018,p > 0.05; ATT for age 35–54 =  − 0.042,p < 0.05; ATT for age 55–64 =  − 0.163,p < 0.01). Moreover, the impacts also varied by household registration. The integration policy has a more significant impact on rural residents (ATT for rural =  − 0.067,p < 0.05) compared to urban residents (ATT for urban =  − 0.007,p > 0.05). Additionally, the policy has a bigger influence on rural–urban migrants (ATT for rural–urban migrated =  − 0.086,p < 0.05) than on those who have not migrated (ATT for rural–urban unmigrated =  − 0.071,p < 0.05).

Conclusion

China's policy of integrating urban–rural medical insurance has been successful in reducing medical impoverishment, especially for older age, rural, and rural–urban migrated people. It can be speculated that the integrating policy may be adapted to other similar settings in developing countries to reduce medical impoverishment.
A review of nitric oxide and oxidative stress in typical ovulatory women and in the pathogenesis of ovulatory dysfunction in PCOS
Authors: Awonuga Awoniyi O. , Camp Olivia G , Abu-Soud Husam M
Published: November 2023

Polycystic ovary syndrome (PCOS) is a heterogeneous functional endocrine disorder associated with a low-grade, chronic inflammatory state. Patients with PCOS present an increased risk of metabolic comorbidities and often menstrual dysregulation and infertility due to anovulation and/or poor oocyte quality. Multiple mechanisms including oxidative stress and low-grade inflammation are believed to be responsible for oocyte deterioration; however, the influence of nitric oxide (NO) insufficiency in oocyte quality and ovulatory dysfunction in PCOS is still a matter for debate. Higher production of superoxide (O2•−) mediated DNA damage and impaired antioxidant defense have been implicated as contributory factors for the development of PCOS, with reported alteration in superoxide dismutase (SOD) function, an imbalanced zinc/copper ratio, and increased catalase activity. These events may result in decreased hydrogen peroxide (H2O2) accumulation with increased lipid peroxidation events. A decrease in NO, potentially due to increased activity of NO synthase (NOS) inhibitors such as asymmetric dimethylarginine (ADMA), and imbalance in the distribution of reactive oxygen species (ROS), such as decreased H2O2 and increased O2•−, may offset the physiological processes surrounding follicular development, oocyte maturation, and ovulation contributing to the reproductive dysfunction in patients with PCOS. Thus, this proposal aims to evaluate the specific roles of NO, oxidative stress, ROS, and enzymatic and nonenzymatic elements in the pathogenesis of PCOS ovarian dysfunction, including oligo- anovulation and oocyte quality, with the intent to inspire better application of therapeutic options. The authors believe more consideration into the specific roles of oxidative stress, ROS, and enzymatic and nonenzymatic elements may allow for a more thorough understanding of PCOS. Future efforts elaborating on the role of NO in the preoptic nucleus to determine its influence on GnRH firing and follicle-stimulating hormone/Luteinizing hormone (FSH/LH) production with ovulation would be of benefit in PCOS. Consequently, treatment with an ADMA inhibitor or NO donor may prove beneficial to PCOS patients experiencing reproductive dysfunction and infertility.
New insights into the regulation of METTL3 and its role in tumors
Authors: Jin Qiu , Qu Huinan , Quan Chengshi
Published: November 2023

As one of the most abundant epigenetic modifications in RNA, N6-methyladenosine (m6A) affects RNA transcription, splicing, stability, and posttranscriptional translation. Methyltransferase-like 3 (METTL3), a key component of the m6A methyltransferase complex, dynamically regulates target genes expression through m6A modification. METTL3 has been found to play a critical role in tumorigenesis, tumor growth, metastasis, metabolic reprogramming, immune cell infiltration, and tumor drug resistance. As a result, the development of targeted drugs against METTL3 is becoming increasingly popular. This review systematically summarizes the factors that regulate METTL3 expression and explores the specific mechanisms by which METTL3 affects multiple tumor biological behaviors. We aim to provide fundamental support for tumor diagnosis and treatment, at the same time, to offer new ideas for the development of tumor-targeting drugs.
Association of diet and lifestyle factors with semen quality in male partners of Chinese couples preparing for pregnancy
Authors: Mai Hanran , Ke Junyi , Zheng Zilin , Luo Jieyi , Li Miaomiao , Qu Yanxia , Jiang Fan , Cai Simian , Zuo Liandong
Published: November 2023

Background

Semen quality significantly influences conception, and its preservation is crucial for couples seeking pregnancy. We investigated dietary and lifestyle risk factors impacting semen quality.

Methods

A total of 466 males from the Guangzhou Women and Children’s Medical Center’s pre-pregnancy consultation clinic were recruited between January 2021 and March 2023 for inclusion. Semen analysis was performed, and diet and lifestyle data were gathered via questionnaire. Logistic regression was utilized to examine the link between diet, lifestyle variables, and semen quality.

Results

Smoking worsened progressive sperm motility (38.0% vs. 36.0%, t = 2.262; P = 0.049). Alcohol consumption impaired progressive motility (40.5 ± 17.8% vs. 34.7 ± 16.1%, t = 3.396; P < 0.001) and total motility (56.0% vs. 64.0%; P = 0.001). Using plastic beverage bottles for oil or seasonings lowered sperm concentrations (40.4% vs. 59.0% vs. 65.5%; P = 0.032). A sweet diet correlated with higher total sperm motility (55.0% vs. 60.0%, 62.0% vs. 63.2%; P = 0.017). Higher milk product intake improved sperm concentration (41.6106vs. 63.7106 vs. 66.1*106; P = 0.021) and motility (54.5% vs. 56.0% vs. 63.0%; P = 0.033). More frequent egg consumption increased semen volume (3.1 mL vs. 3.8 mL vs. 4.0 mL; P = 0.038). Roughage intake enhanced sperm concentration (160.8106 vs. 224.6106; P = 0.027), and adequate sleep improved progressive sperm motility rate (35.4% ± 18.2% vs. 40.2 ± 16.3%, F = 3.747; P = 0.024) and total motility (52.7% vs. 61.5%; P = 0.013). The regression model showed that using plastic containers for condiments was a protective factor for semen volume (OR: 0.12; CI 0.03–0.55; P = 0.006), sperm concentration (OR: 0.001, CI 0.00–0.30; P = 0.012), and count (OR: 0.12, CI 0.03–0.48; P = 0.003). Milk and egg consumption were also protective for semen volume (OR: 0.18, CI 0.06–0.51; P = 0.001 and OR: 0.11, CI 0.03–0.55; P = 0.006, respectively), while sufficient sleep benefitted total sperm motility (OR: 0.47, CI 0.24–0.95; P = 0.034).

Conclusions

Smoking and drinking, type of condiment container, diet preference, sleep duration, and milk, roughage, and egg consumption may reduce semen quality.
Evaluation of ARK5 and SIRT3 expression in renal cell carcinoma and their clinical significance
Authors: Elkady Noha , Aldesoky Amira I. , Dawoud Marwa Mohammed
Published: November 2023

Background

Globally Renal Cell Carcinoma (RCC) represents 3% of malignant tumours in adults and 1.78% in Egypt. AMPK-related protein kinase 5 (ARK5) is mainly associated with a hypoxic microenvironment which is a feature of the major RCC subtypes. Additionally, it displays decreased mitochondrial respiration. SIRT3 is a mitochondrial deacetylase that modifies multiple mitochondrial proteins.

Material and methods

Fifty eight cases of RCC, and 30 non-neoplastic cases (of End-Stage Kidney Disease (ESKD) were subjected to immunohistochemistry by ARK5 and SIRT3. The results of IHC were correlated together and correlated with the available clinicopathologic and survival data.

Results

Although no significant difference was detected between RCC and ESKD groups regarding ARK5 expression, there was a significant association with RCC regarding H-score and nucleocytoplasmic expression (both P = 0.001). Also, SIRT3 was highly expressed in RCC in comparison to the ESKD group (H-score: P = 0.001). There were significant associations between nucleocytoplasmic ARK5 expression and higher tumour grade, low apoptotic and high mitotic indices, tumour extent, advanced tumour stage, and impaired response of tumours to chemotherapeutic drugs (P = 0.039, P = 0.001, P = 0.027, P = 0.011, P = 0.009, and P = 0.014 respectively). Moreover, the H score of ARK5 expression showed significant associations with tumour grade, apoptotic and mitotic indices, tumour extension, tumour stage, and response to therapy (P = 0.01, 0.035, 0.001, 0.004. 0.003 and 0.013). Regarding SIRT3 expression, it showed significant associations with apoptotic and mitotic indices, tumour extent, tumour stage and response to therapy (P = 0.022, 0.02, 0.042, 0.039 and 0.027). Interestingly, there was a highly significant correlation between the expression of ARK5 and SIRT3 (P = 0.009). Univariate survival analysis revealed a significant association between short survival duration and both nucleocytoplasmic expression of ARK5 and positive SIRT3 expression (P = 0.014 and 0.035).

Conclusion

ARK5 and SIRT3 are overexpressed in RCC and associated with parameters of poor prognosis as well as short survival. Both seem to influence response to therapy in RCC. So, they could be new targets for therapy that may improve tumour response and patients’ survival. There is a postulated relationship that needs more extensive investigation.
Design of a dual randomized trial in a type 2 hybrid effectiveness—implementation study
Authors: Stevens June , Mills Sarah Denton , Millett Mary-Louise , Lin Feng-Chang , Leeman Jennifer
Published: November 2023

Background

Dual randomized controlled trials (DRCT) are type 2 hybrid studies that include two randomized trials: one testing implementation strategies and one testing an intervention. We argue that this study design offers efficiency by providing rigorous investigation of both implementation and intervention in one study and has potential to accelerate generation of the evidence needed to translate interventions that work into real-world practice. Nevertheless, studies using this design are rare in the literature.

Main text

We construct a paradigm that breaks down the components of the DRCT and provide a step-by-step explanation of features of the design and recommendations for use. A clear distinction is made between the dual strands that test the implementation versus the intervention, and a minimum of three randomized arms is advocated. We suggest an active treatment arm that includes both the implementation strategy and intervention that are hypothesized to be superior. We suggest two comparison/control arms: one to test the implementation strategy and the second to test the intervention. Further, we recommend selection criteria for the two control arms that place emphasis on maximizing the utility of the study design to advance public health practice.

Conclusions

On the surface, the design of a DRCT can appear simple, but actual application is complex. We believe it is that complexity that has limited its use in the literature. We hope that this paper will give both implementation scientists and trialists who are not familiar with implementation science a better understanding of the DRCT design and encouragement to use it.
Prospective evaluation of clinical and radiographic 10-year results of Fitmore short-stem total hip arthroplasty
Authors: Schader Jana F. , Thalmann Caroline , Maier Katharina S. , Schiener Tom , Stoffel Karl , Frigg Arno
Published: November 2023

Background

Short stems were introduced into total hip arthroplasty (THA) to preserve bone stock, to transmit more load to the proximal femur, and to enable minimal invasive approaches. This study is the first long-term study (with a follow-up of 10 years) of the survival as well as the clinical and radiographic outcomes of the Fitmore hip stem, a short curved uncemented stem.

Methods

In total, 123 Fitmore hip stems were prospectively evaluated. At the final 10-year follow-up, 80 Fitmore stems (78 patients: 30 female, 48 male) were eligible for evaluation. Clinical parameters were thigh pain, EQ-5D, Harris Hip Score (HHS) and Oxford Hip Score. Radiographic parameters were cortical hypertrophy (CH), bone condensation, cortical thinning, radiolucency, reactive lines, calcar rounding, calcar resorption, subsidence and varus/valgus position.

Results

After 10 years, there was a survival rate of 99% (1 revision because of aseptic stem loosening). HHS had improved from 59 to 94 and Oxford Hip Score from 22 to 43. CH rate after 1 year was 69% and after 10 years 74%. In the first year, radiolucency was found in 58% and in 17.5% after 10 years. Subsidence after 1 year was 1.6 ± 1.6 mm and 5.0 ± 3.1 mm after 10 years.

Conclusions

The Fitmore hip stem showed a survival rate of 99% as well as good clinical and radiographic outcomes in the long-term follow-up of 10 years.
Prioritization of research engaged with rare disease stakeholders: a systematic review and thematic analysis
Authors: Yoon Soho , Lee Minjee , Jung Hoi-In , Khan M. Mahmud , Kim So-Yoon , Kim Hannah , Wasti Sophia
Published: November 2023

Background

Although rare diseases (RD) are increasingly becoming a priority for healthcare activities and services around the world, developing research policy for investigating RD in public settings proves challenging due to the limited nature of existing evidence. Rare conditions require the involvement of a wide range of stakeholders in order to promote general awareness and garner political support. Consequently, it is critically important to identify trends in the various types of research focusing on rare disease stakeholders, including the specific topics or issues to be included in surveys and studies focused on RD stakeholders. This systematic review and thematic analysis analyses the existing literature based on RD surveys, including the stakeholders involved, and proposes potential research priorities and initiatives for policy-making related to RD.

Methods

Articles were downloaded and analyzed from across five electronic databases (PubMed, EMBASE, Cochrane Central, Web of Science, and CINHAL) and 115 studies were included.

Results

Across 115 studies, the main research participants were patients and/or caregivers (n = 77, 67.0%), health professionals (n = 18, 15.7%), and the public (n = 7, 6.1%). The studies discussed RDs in general (n = 46, 40.0%), endocrine, nutritional, and metabolic diseases (n = 20, 17.4%) and other RDs. Experiences with RD were examined by more than half of the selected studies (n = 74, 64.3%), followed by the opinions of stakeholders (n = 24, 20.9%). Most of the studies used surveys in order to collect relevant data (n = 114, 99.1%). Additionally, the majority of the studies were conducted in high-income countries (n = 92, 80.0%) and rarely in middle and low-income countries (n = 12, 13.8%).

Conclusion

Stakeholder research on RD reveals that there are significant instances of unmet needs and various challenges faced by the medical system in dealing with RDs.

Furthermore, public awareness and support is critical to ensuring political feasibility of increasing national-level investments for RDs and development of medical products and treatment.
Multi-omics analysis reveals the molecular response to heat stress in a “red tide” dinoflagellate
Authors: Dougan Katherine E. , Deng Zhi-Luo , Wöhlbrand Lars , Reuse Carsten , Bunk Boyke , Chen Yibi , Hartlich Juliane , Hiller Karsten , John Uwe , Kalvelage Jana , Mansky Johannes , Neumann-Schaal Meina , Overmann Jörg , Petersen Jörn , Sanchez-Garcia Selene , Schmidt-Hohagen Kerstin , Shah Sarah , Spröer Cathrin , Sztajer Helena , Wang Hui , Bhattacharya Debashish , Rabus Ralf , Jahn Dieter , Chan Cheong Xin , Wagner-Döbler Irene
Published: November 2023

Background

“Red tides” are harmful algal blooms caused by dinoflagellate microalgae that accumulate toxins lethal to other organisms, including humans via consumption of contaminated seafood. These algal blooms are driven by a combination of environmental factors including nutrient enrichment, particularly in warm waters, and are increasingly frequent. The molecular, regulatory, and evolutionary mechanisms that underlie the heat stress response in these harmful bloom-forming algal species remain little understood, due in part to the limited genomic resources from dinoflagellates, complicated by the large sizes of genomes, exhibiting features atypical of eukaryotes.

Results

We present the de novo assembled genome (~ 4.75 Gbp with 85,849 protein-coding genes), transcriptome, proteome, and metabolome from Prorocentrum cordatum, a globally abundant, bloom-forming dinoflagellate. Using axenic algal cultures, we study the molecular mechanisms that underpin the algal response to heat stress, which is relevant to current ocean warming trends. We present the first evidence of a complementary interplay between RNA editing and exon usage that regulates the expression and functional diversity of biomolecules, reflected by reduction in photosynthesis, central metabolism, and protein synthesis. These results reveal genomic signatures and post-transcriptional regulation for the first time in a pelagic dinoflagellate.

Conclusions

Our multi-omics analyses uncover the molecular response to heat stress in an important bloom-forming algal species, which is driven by complex gene structures in a large, high-G+C genome, combined with multi-level transcriptional regulation. The dynamics and interplay of molecular regulatory mechanisms may explain in part how dinoflagellates diversified to become some of the most ecologically successful organisms on Earth.
Use of continuous glucose monitoring in insulin-treated older adults with type 2 diabetes
Authors: Leite Silmara A O , Silva Michael P , Lavalle Ana C R , Bertogy Maria C V , Bastos Murilo , Kuklik Suelen C Vieira , Umpierrez Guillermo
Published: November 2023

Background

Few studies have reported the adherence to and efficacy of continuous glucose monitoring (CGM) for improving diabetes management in insulin-treated older adults with type 2 diabetes mellitus (T2DM).

Methods

Prospective observational cohort study using FreeStyle Libre Flash CGM in insulin-treated adults > 65 years with T2DM and HbA1c between 7% and 9%. The participants wore the CGM during the 6-weeks study period. The primary outcome was time in range (TIR) between 70 and 180 mg/dL. Secondary outcomes included time below range (TBR), glycemic variability (GV), adherence, and use of glucose data for self-insulin adjustment. Linear regressions with random effects verified the changes in TBR, TIR, time above range (TAR), GV, and GMI across the three visits using CGM (baseline, 4 weeks and 6 weeks), controlled for sex, age, educational level, and health system (private or public).

Results

A total of 66 participants completed the six weeks of CGM (age 72·8 ± 5·3 years; BMI 27·8 ± 3·6 kg/m2), HbA1c: 8·0 ± 0·6%, with an overall sensor utilization of 93·1 ± 6·0%. We observed a stability in TIR (baseline: 63.5 ± 18.9% vs. endpoint: 65.5 ± 18.8%; β = 1,0, p = 0.190). Despite the low TBR at the baseline, we observed statistically significant reduction over the study period (baseline: 5.8 ± 7.0% vs. endpoint: 3.8 ± 4.7%; (β=-1.00, p = 0.008). Glucose variability also reduced from the baseline (34.9 ± 7.2%) to the endpoint (33.0 ± 6.8%) (β=-0.99, p = < 0.001).

Conclusion

FreeStyle Libre Flash CGM is well accepted by older adults with T2DM and allows participants to make therapeutic decisions to reduce TBR and glycemic variability.
Reversible acute blindness in suspected metformin-associated lactic acidosis: a case report
Authors: Huang Rui , Sun Wentao
Published: November 2023

Background

Metformin is commonly used for the treatment of type 2 diabetes mellitus. Its multiple advantages include low risk of hypoglycemia, weight neutrality, low cost, and cardioprotective and anti-inflammatory effects. Renal insufficiency is one of the contraindications for its use. Inadvertent prescription in patients with renal insufficiency may lead to metformin-associated lactic acidosis, which brings a high risk of mortality. The early recognition and management of metformin-associated lactic acidosis are essential.

Case report

We present the case of a 58-year-old Hui woman with a history of type 2 diabetes mellitus with nephropathy and heart disease for which she was treated with metformin, insulin, and heart medications. She developed nausea, vomiting, anion gap metabolic acidosis due to hyperlactatemia, and acute kidney injury. She was hospitalized to receive intravenous hydration and correction of metabolic acidosis after she suddenly developed blindness. The diagnostic workup ruled out central causes and her symptoms resolved briefly after continuous venovenous hemodialysis was initiated, confirming the diagnosis of metformin-associated lactic acidosis.

Conclusions

Metabolic disruption can cause acute blindness. Metabolic acidosis in a patient with a history of metformin intake should suggest the possibility of metformin-associated lactic acidosis, which must be treated immediately, without waiting for the results of other examinations, especially in patients with sudden blindness. Further study of reversible blindness-associated severe metabolic acidosis is needed.
An explainability framework for deep learning on chemical reactions exemplified by enzyme-catalysed reaction classification
Authors: Probst Daniel
Published: November 2023

Assigning or proposing a catalysing enzyme given a chemical or biochemical reaction is of great interest to life sciences and chemistry alike. The exploration and design of metabolic pathways and the challenge of finding more sustainable enzyme-catalysed alternatives to traditional organic reactions are just two examples of tasks that require an association between reaction and enzyme. However, given the lack of large and balanced annotated data sets of enzyme-catalysed reactions, assigning an enzyme to a reaction still relies on expert-curated rules and databases. Here, we present a data-driven explainable human-in-the-loop machine learning approach to support and ultimately automate the association of a catalysing enzyme with a given biochemical reaction. In addition, the proposed method is capable of predicting enzymes as candidate catalysts for organic reactions amendable to biocatalysis. Finally, the introduced explainability and visualisation methods can easily be generalised to support other machine-learning approaches involving chemical and biochemical reactions.