Search Results (694)

Background: HPV vaccination is the key measure to prevent cervical cancer, but uptake in China lags behind global targets. Understanding Chinese guardians’ preferences is key to improving vaccine acceptance and coverage. Methods: A nationwide online discrete choice experiment survey was conducted among 4933 Chinese guardians across seven provinces in 2022 to quantify preferences and willingness to pay. Attributes included effectiveness, safety, duration, valency, location, and out-of-pocket cost. Results: Out of the 4933 guardians who participated in the study, 4179 (84.72%) were mothers. More than 60% of the guardians belonged to the age group of 35–44 years. Additionally, over half of the respondents (53.15%) had daughters between the ages of 9 and 14 years. Respondents were open to accepting the HPV vaccine with 95% efficacy and exceptional safety. Guardians expressed a preference for longer protection duration (specifically 15 years (βa = 0.340, 95% CI: 0.31, 0.37)) and higher vaccine valency. As for willingness to pay, the respondents placed the highest value on vaccine efficacy, being willing to shell out more than USD 1100 for 95% protection as compared to 50%. Furthermore, very good safety commanded a premium of over USD 800 when compared to average safety. When it comes to willingness to uptake, a vaccine with 95% efficacy led to a more than 35% increase in acceptance as compared to one with 50% efficacy. Similarly, exceptional safety resulted in an increased willingness to uptake of over 25% when compared to average safety. Conclusions: The DCE highlighted effectiveness, safety, and durability as critical drivers of HPV vaccine acceptance, but substantial barriers persist regarding adolescent female coverage in China. Full article

Background and Objectives: Dovitinib (DVB) is a pan-tyrosine kinase inhibitor (TKI) that can be administered orally. In September 2023, the FDA granted Oncoheroes approval to proceed with an Investigational New Drug (IND) application for dovitinib. This application is intended for the treatment of relapsed or advanced juvenile solid tumors, namely, osteosarcoma. Materials and Methods: The target of the present study was to develop a rapid, green, accurate, and sensitive UHPLC-MS/MS method for measuring DVB levels in human liver microsomes (HLMs). The validations of the HLMs were performed via the established UHPLC-MS/MS approach, as stated in the US FDA reported guidelines for the standards of bioanalytical method validation protocol. The StarDrop in silico software package (version 6.6), which involves the DEREK and WhichP450 in silico modules, was used to check the DVB structure for hazardous alerts and metabolic instability. The DVB and encorafenib (EFB), internal standard, and chromatographic peaks were successfully separated using a reversed phase column (an Eclipse Plus Agilent C8 column) and an isocratic mobile phase. The production of DVB parent ions was accomplished by utilizing the positive ionization mode of an ESI source. The identification and measurement of DVB daughter ions were conducted using the MRM mode. Results: The inter-day accuracy and precision exhibited a spectrum of values in the range of −0.56% to 9.33%, while the intra-day accuracy and precision showcased a range of scores between 0.28% and 7.28%. The DVB calibration curve showed a linear relationship that ranged from 1 to 3000 ng/mL. The usefulness of the currently validated UHPLC-MS/MS method was approved by the lower limit of quantification (LLOQ) of 1 ng/mL. The AGREE findings demonstrate that the UHPLC-MS/MS method had a noteworthy degree of ecological greenness. The in vitro half-life (t_1/2) and intrinsic clearance (Cl_int) of DVB were calculated to be 15.48 min and 52.39 mL/min/kg, respectively, which aligned with the findings from the WhichP450 software (version 6.6). Conclusions: Via the usage of in silico software, it has been observed that making small changes to the structure of the aryl piperazine ring and quinolinone moieties, or replacing these groups in the drug design process, shows potential for enhancing the metabolic safety and stability of newly developed derivatives compared to DVB. Full article

The objective of this study was to determine whether the parity and age of dams affect the longevity of their offspring in dairy cows in pasture-based systems. A total of 12,792 dairy cows born between 2000 and 2017 across five farms were evaluated using records from the Dairy Herd Improvement Database at Instituto Nacional para el Control y Mejoramiento Lechero (Uruguay). Dams were classified as primiparous or multiparous, and parity number and age were considered. The effect of parity status on herd life (HL), the length of productive life (LPL), and the productive life index (PLI) was evaluated using a generalized mixed model. Associations between parity number and dam age with HL, LPL, and PLI were evaluated using regression models. HL, LPL, and PLI were significantly higher for daughters of multiparous cows. Dams with more parities gave birth to longer-living daughters, with an average HL difference of 4.4 months between the first and seventh parity of the dams. The parity number and age of the dam showed a significant association with HL, LPL, and PLI. In conclusion, the parity and age of the dam influence the longevity of dairy cows in pasture-based systems, with older dams and higher parity yielding daughters with greater longevity. Full article

Eukaryotic cells must accurately transfer their genetic material and cellular components to their daughter cells. Initially, cells duplicate their chromosomes and subsequently segregate them toward the poles. The actomyosin ring, a crucial molecular machinery normally located in the middle of the cells and underneath the plasma membrane, then physically divides the cytoplasm and all components into two daughter cells, each ready to start a new cell cycle. This process, known as cytokinesis, is conserved throughout evolution. Defects in cytokinesis can lead to the generation of genetically unstable tetraploid cells, potentially initiating uncontrolled proliferation and cancer. This review focuses on the molecular mechanisms by which budding yeast cells build the actomyosin ring and the preceding steps involved in forming a scaffolding structure that supports the challenging structural changes throughout cytokinesis. Additionally, we describe how cells coordinate actomyosin ring contraction, plasma membrane ingression, and extracellular matrix deposition to successfully complete cytokinesis. Furthermore, the review discusses the regulatory roles of Cyclin-Dependent Kinase (Cdk1) and the Mitotic Exit Network (MEN) in ensuring the precise timing and execution of cytokinesis. Understanding these processes in yeast provides insights into the fundamental aspects of cell division and its implications for human health. Full article

Background: In 2020, the WHO proposed the global strategic goal of accelerating the elimination of cervical cancer (CC). One of the key strategies is that, by 2030, 90% of girls will complete HPV vaccination by age 15. In 2017, HPV vaccines were first marketed in China. Objectives: This study aimed to explore the changes in parents’ knowledge about CC, HPV, HPV vaccines, and acceptance of HPV vaccination 5 years after the introduction of HPV vaccines into China. Associated factors and reasons for refusal by parents were also explored. Methods: A school-based follow-up study was conducted among parents in China from May 2018 to May 2023. Comparison using Chi-square tests was performed to measure the changes. Univariate and multivariate analyses were used to explore factors associated with HPV vaccination among teenage girls. Results: The overall cognitive level in terms of CC- and HPV-related knowledge among parents increased, and they expressed more willingness to vaccinate their daughter (35.4% in 2018 vs. 56.6% in 2023). The HPV vaccination rate among teenage girls remained at a low level (4.4% in 2018, 9.8% in 2023). The main obstacles reported by parents were limited knowledge (42.0%), scarcity of the HPV vaccine (29.2%), waiting until their daughter was older (27.5%), safety concerns (14.7%), high cost (9.0%), and effectiveness concerns (4.6%). Parents who are elderly, local residents, have received HPV vaccines themselves, have had experience of vaccinating their children with influenza vaccines, and have a higher knowledge level of CC, HPV and HPV vaccines are more likely to vaccinate their children with HPV vaccines. Conclusions: Although we observed an increment in parents’ knowledge level in terms of CC, HPV, HPV vaccines, and HPV vaccine uptake over the past 5 years, the HPV vaccine coverage among girls still falls short of the WHO’s 2030 target. Comprehensive intervention strategies, including tailored health education among adolescents and their parents, doctor recommendations, and providing financial subsidies or free HPV vaccines are needed in China. Full article

Cytokinesis, the process by which the cytoplasm divides to generate two daughter cells after mitosis, is a crucial stage of the cell cycle. Successful cytokinesis must be coordinated with chromosome segregation and requires the fine orchestration of several processes, such as constriction of the actomyosin ring, membrane reorganization, and, in fungi, cell wall deposition. In Saccharomyces cerevisiae, commonly known as budding yeast, septins play a pivotal role in the control of cytokinesis by assisting the assembly of the cytokinetic machinery at the division site and controlling its activity. Yeast septins form a collar at the division site that undergoes major dynamic transitions during the cell cycle. This review discusses the functions of septins in yeast cytokinesis, their regulation and the implications of their dynamic remodelling for cell division. Full article

Cell division is crucial for the survival of living organisms. Human cells undergo three types of cell division: mitosis, meiosis, and amitosis. The former two types occur in somatic cells and germ cells, respectively. Amitosis involves nuclear budding and occurs in cells that exhibit abnormal nuclear morphology (e.g., polyploidy) with increased cell size. In the early 2000s, Kirsten Walen and Rengaswami Rajaraman and his associates independently reported that polyploid human cells are capable of producing progeny via amitotic cell division, and that a subset of emerging daughter cells proliferate rapidly, exhibit stem cell-like properties, and can contribute to tumorigenesis. Polyploid cells that arise in solid tumors/tumor-derived cell lines are referred to as polyploid giant cancer cells (PGCCs) and are known to contribute to therapy resistance and disease recurrence following anticancer treatment. This commentary provides an update on some of these intriguing discoveries as a tribute to Drs. Walen and Rajaraman. Full article

Wagner syndrome is a rare autosomal dominant vitreoretinopathy caused by mutations in chondroitin sulphate proteoglycan 2 (CSPG2)/Versican (VCAN). Here, we present a retrospective case series of a family pedigree with genetically confirmed Wagner syndrome (heterozygous VCAN exon 8 deletion), as follows: a 34-year-old mother (P1), 12-year-old daughter (P2), and a 2-year-old son (P3). The phenotype included early-onset cataract (P1), optically empty vitreous with avascular membranes (P1, 2), nasal dragging of optic nerve heads associated with foveal hypoplasia (P1, 2), tractional retinoschisis on optical coherence tomography (P2), and peripheral circumferential vitreo-retinal interface abnormality resembling white-without-pressure (P3) progressing to pigmented chorio-retinal atrophy (P1, 2). P2 developed a macula-off retinal detachment, which was treated initially with encircling band + vitrectomy + gas, followed by vitrectomy + heavy silicone oil tamponade for re-detachment from new inferior breaks. Strong vitreo-retinal adhesion was noted intraoperatively, which prevented the separation of posterior hyaloid beyond the equator. Electroretinograms from P1&2 demonstrated attenuated b-waves, a-waves, and flicker responses in light- and dark-adapted conditions, suggestive of generalised retinal dysfunction. Our patients demonstrated the clinical spectrum of Wagner syndrome, highlighting nasal dragging with foveal disruption as a distinguishing feature from other inherited vitreoretinopathies. Surgical outcomes demonstrate significant challenges in managing vitreo-retinal traction and need for further research into strategies to prevent sight loss. Full article

Cervical cancer (CC) is the second most common cancer in Western Africa, accounting for 12,000 cases and 6000 deaths annually. While vaccination against human papilloma virus (HPV) and CC screenings reduce the incidence and mortality of CC in many developed countries, 90% of CC deaths are in low-income countries. Lack of knowledge about the connection between HPV and CC, lack of access to vaccines and screenings, weak healthcare infrastructure, and stigma related to sexually transmitted diseases are among the factors that contribute to this disparity. Previously, we evaluated the knowledge of HPV and CC in Bamako, Mali, showing that knowledge of the link between HPV and CC was very low (less than 8% of participants) and that less than 3% of women were screened for CC. Subsequent implementation of a community-based education program and support for local clinics resulted in a five-fold increase in CC screening at the five participating clinics in 2015. In this study, we paired CC screenings of mothers with HPV vaccination of their daughters to target out-of-school (OOS) girls whom school-based vaccination campaigns would not reach. Our campaign resulted in a 10.7% increase in HPV vaccination. Full article

Turbulence implies nonlinear wave–wave coupling, and determining cause and effect of either is important to understand mixing responsible for enhanced number, momentum, or energy (NME) transport. To explain the identification of parent and daughter modes via a look-up table, we sketch the framework of bispectral analysis without repeating the mathematical formalism of earlier bispectrum researchers. We then apply this technique to a test signal and plasma fluctuation data from the WVU-Q machine, where the inhomogeneous energy density-driven spectrum exhibited a degree of coupling to lower frequencies that was absent in the case of the related, single-eigenmode, current-driven spectrum. Full article

As the capacity of individual offshore wind turbines increases, prolonged downtime (due to maintenance or faults) will result in significant economic losses. This necessitates enhancing the efficiency of vessel operation and maintenance (O&M) to reduce O&M costs. Existing research mostly focuses on planning O&M schemes for individual vessels. However, there exists a research gap in the scientific scheduling for state-of-the-art O&M vessels. To bridge this gap, this paper considers the use of an advanced O&M vessel in the O&M process, taking into account the downtime costs associated with wind turbine maintenance and repair incidents. A mathematical model is constructed with the objective of minimizing overall O&M expenditure. Building upon this formulation, this paper introduces a novel restructuring particle swarm optimization which is tailed with a bespoke encoding and decoding strategy, designed to yield an optimized solution that aligns with the intricate demands of the problem at hand. The simulation results indicate that the proposed method can achieve significant savings of 28.85% in O&M costs. The outcomes demonstrate the algorithm’s proficiency in tackling the model efficiently and effectively. Full article

In 2023, the genetics scientific community celebrated two special anniversaries: the discovery of the double helix structure of DNA was published in 1953 and in 2003 the Human Genome Project was declared completed and made publicly available. To this day, genetics and genomics research is continuing to evolve at high pace and is identifying a steadily increasing number of genes as causal for distinct genetic diseases. The success story of genetics and genomics would not be complete without taking due account of the role of patient advocacy organizations in this process. This paper is based on the personal narrative (oral history) of a father whose daughter was born with a rare genetic disease (RGD) in the 1960s. The first-hand experience of living as a family with an RGD in those days made him a leading pioneer not only in the foundation of patient organizations at national, pan-European, and international levels but also in the development of multi-stakeholder co-operation and networking. Today, patient advocacy organizations play an active role in shaping health and research policies at national, EU, and international levels to ensure that their needs in regard to advancing RGD diagnostics, care, and treatment are addressed. Full article

In Indonesia, knowledge of parents’ experiences of their daughters’ HPV vaccination in school settings is limited. As Indonesia seeks to scale up its HPV vaccination program nationwide, parents’ perspectives hold important insights into how elements of the vaccination model can be sustained and improved. This study explored mothers’ experiences of their daughters’ HPV vaccination experiences, their knowledge of HPV risks and prevention, and factors associated with willingness to recommend HPV vaccination for girls. A cross-sectional online survey was conducted with 143 mothers of schoolgirls who had received HPV vaccination at schools in Yogyakarta and Jakarta. Multivariate logistic regression was used to assess factors associated with willingness to recommend HPV vaccination. Chi-square and independent t-tests were performed to assess relationships between variables. One-way ANOVA was used to test mean differences in knowledge scores among mothers with different education levels. Many respondents (62.4%) received key health information before their daughters’ HPV vaccination. Mothers’ average knowledge score was 6.07/10 (SD 2.35). Receiving satisfactory information was significantly associated with willingness to recommend HPV vaccination for girls to others. A significant association was found between mothers’ willingness to recommend HPV vaccination and having ever participated in cervical cancer screening themselves. Providing consistent health information that addresses the knowledge gaps and affirms the benefits and safety of HPV vaccines can improve the likelihood of mothers recommending HPV vaccination to others. The benefit of a synchronized approach to promoting primary and secondary prevention was supported by the findings. Full article

Trichomonas vaginalis (Tvag) is a sexually transmitted human pathogen that is commonly infected with strains of one or more of five known species of Trichomonas vaginalis viruses (TVVs), members of genus Trichomonasvirus. TVVs are thought not to have an extracellular phase to their lifecycle and instead to be transmitted vertically from mother to daughter cells. As a result, generation of isogenic virus-positive and virus-negative sets of Tvag clones has been a major barrier to studying interactions between TVVs and their host. Nucleoside analog 2′-C-methylcytidine (2CMC) has been recently reported to clear trichomonads of infections with TVV1, TVV2, and TVV3. We used 2CMC to treat a panel of Tvag isolates that collectively harbor at least one representative strain of each TVV species and thereby provided evidence that infections with TVV4 and TVV5 can also be cleared by 2CMC. Furthermore, our results suggest a newly identified difference in drug susceptibility between TVV species. We took advantage of these susceptibility difference to generate isogenic sets of Tvag clones harboring different combinations of the five TVV species. These results provide both new insight into differences between these species and new avenues for generating tools to study the potential roles of TVVs in Tvag biology. Full article

PRKAG2 cardiomyopathy is a rare genetic disorder that manifests early in life with an autosomal dominant inheritance pattern. It harbors left ventricular hypertrophy (LVH), ventricular pre-excitation and progressively worsening conduction system defects. Its estimated prevalence among patients with LVH ranges from 0.23 to about 1%, but it is likely an underdiagnosed condition. We report the association of the PRKAG2 missense variant c.1006G>A p. (Val336Ile) with LVH, conduction abnormalities (short PR interval and incomplete right bundle branch bock) and early-onset arterial hypertension (AH) in a 44-year-old Caucasian patient. While cardiac magnetic resonance (CMR) showed a mild hypertrophic phenotype with maximal wall thickness of 17 mm in absence of tissue alterations, the electric phenotype was relevant including brady–tachy syndrome and recurrent syncope. The same variant has been detected in the patient’s sister and daughter, with LVH + early-onset AH and electrocardiographic (ECG) alterations + lipothymic episodes, respectively. Paying close attention to the coexistence of LVH and ECG alterations in the proband has been helpful in directing genetic tests to exclude primary cardiomyopathy. Hence, identifying the genetic basis in the patient allowed for familial screening as well as a proper follow-up and therapeutic management of the affected members. A review of the PRKAG2 cardiomyopathy literature is provided alongside the case report. Full article