Autism spectrum: parents' perspectives reflecting the different needs of different families.

BACKGROUND: Parents of children on the autism spectrum often face great challenges in the care of their child. Early support tailored to families' individual needs is therefore crucial for the development and quality of life of both children on the autism spectrum and their families. However, to date it is unclear whether the support available meets the parents' needs. STUDY AIM: To investigate how the system of care, support, and therapies for children on the autism spectrum is perceived by their parents. METHOD: A total of 57 parents of Swiss children on the autism spectrum participated in an online survey, and 20 of them participated in additional semi-structured interviews. RESULTS: We found that parents of children on the autism spectrum may face substantial challenges and that social support is essential. Two thirds of the participating parents reported a long and difficult diagnostic process as challenging, and 60% expressed their need for closer follow-up after diagnosis and more support. Only one third of the parents stated that they manage their everyday lives well, whereas 17.5% felt exhausted, and more than half of the parents responded that they felt challenged. One fifth indicated that they had poor family support, and half reported substantial financial challenges. At the same time, most families also emphasize how important their neurodivergent children are to the family`s life together. CONCLUSION: It is important that primary pediatricians not only initiate the diagnostic process, but also assess the different needs of the different family independent of the diagnosis and, if necessary, initiate adequate measures or guide parents to institutions in charge. Parents who do not actively express their individual needs should nevertheless be advised about support services, including financial counseling. The positive aspects mentioned by families can be emphasized and used as resources to improve their quality of life.

Plakophilin 4 controls the spatio-temporal activity of RhoA at adherens junctions to promote cortical actin ring formation and tissue tension.

Plakophilin 4 (PKP4) is a component of cell-cell junctions that regulates intercellular adhesion and Rho-signaling during cytokinesis with an unknown function during epidermal differentiation. Here we show that keratinocytes lacking PKP4 fail to develop a cortical actin ring, preventing adherens junction maturation and generation of tissue tension. Instead, PKP4-depleted cells display increased stress fibers. PKP4-dependent RhoA localization at AJs was required to activate a RhoA-ROCK2-MLCK-MLC2 axis and organize actin into a cortical ring. AJ-associated PKP4 provided a scaffold for the Rho activator ARHGEF2 and the RhoA effectors MLCK and MLC2, facilitating the spatio-temporal activation of RhoA signaling at cell junctions to allow cortical ring formation and actomyosin contraction. In contrast, association of PKP4 with the Rho suppressor ARHGAP23 reduced ARHGAP23 binding to RhoA which prevented RhoA activation in the cytoplasm and stress fiber formation. These data identify PKP4 as an AJ component that transduces mechanical signals into cytoskeletal organization.

Exploring auditory temporal resolution and dichotic listening skills among individuals with type 2 diabetes mellitus.

The study aimed to explore the auditory temporal resolution and dichotic listening skills in patients with type 2 diabetes mellitus (T2DM) and identify associated health-related factors. Using a cross-sectional design, 87 adults with T2DM and 48 non-diabetic controls, all with normal hearing, participated. The two central auditory processing (CAP) skills were assessed through the Gaps-In-Noise (GIN) and Dichotic-Digits Listening (DDL) tests. T2DM participants underwent blood tests to measure various health-related factors. In the GIN test, the shortest gap threshold (GapTh) obtained across both ears was significantly higher in the diabetic group (9.1 ± 2.4 ms) compared to the non-diabetic group (7.5 ± 1.5 ms), and the score of correctly identified gaps (GapSc) in the diabetic group (45±11 %) was significantly lower than GapSc in the non-diabetic group (52±9 %), p < 0.001. In the DDL test, the free-recall score (73.8 ± 18.5 %) across both ears and the right-ear advantage (-1.3 ± 20.6 %) in the diabetic group were significantly lower than the free-recall score (85.8 ± 11.9 %) and right-ear advantage (6.9 ± 11.9 %) in the non-diabetic group, p < 0.005. Furthermore, the duration of diabetes, eGFR level, retinopathy, carotid plaque, fasting blood glucose level, and HDL-C (good cholesterol) level were factors significantly associated with performances in the GIN and/or DDL tests for T2DM participants. In conclusion, individuals with T2DM are at risk of reduced auditory processing skills in temporal resolution and dichotic listening, impacting their speech understanding. Six health-related factors were identified as significantly associated with CAP skills in T2DM patients.

Familial hypercholesterolemia care by Dutch pediatricians-mind the gaps.

PURPOSE: Familial hypercholesterolemia (FH) leads to elevated low-density lipoprotein cholesterol levels, which increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). Since the first functional and morphologic changes of the arterial wall occur in childhood, treatment should start early in childhood to mitigate the elevated risk of ASCVD. Pediatricians play an important role in the detection and care of children with FH. In this study, we aim to explore potential gaps in FH care amongst Dutch pediatricians, in order to enhance their knowledge and awareness of detecting and treating children with FH. METHODS: An anonymous online survey, deployed using Google Forms, including 26 closed and semi-closed questions on FH care in children was distributed by the Dutch Association of Pediatrics via a newsletter to which the majority of the practicing Dutch pediatricians subscribe. In addition, we requested that the pediatric departments of all Dutch hospitals in the Netherlands distribute this survey personally among their employed pediatricians. Respondents were instructed to answer the questions without any help or use of online resources. RESULTS: Between September 1st, 2023 and November 1st, 2023, 158 (an estimated 11% response rate) Dutch pediatricians completed the survey. They reported a median (IQR) of 15.0 (6.0-22.0) years of experience as a pediatrician, and 34 (21.5%) were working in academic hospitals. The majority (76.6%) of pediatricians correctly identified a typical FH lipid profile but 68 (43.0%) underestimated the true prevalence of FH (1:300). Underestimation and unawareness of the increased risk of FH patients for ASCVD were reported by 37.3% and 25.9% of pediatricians, respectively. Although 70.9% of the pediatricians correctly defined FH, only 67 (42.4%) selected statins and ezetimibe to treat severe hypercholesterolemia. CONCLUSIONS: The results of this study suggest significant gaps in knowledge and awareness of FH in children among Dutch pediatricians. FH care in children needs improvement through educational and training initiatives to mitigate the life-long risk of ASCVD from early life. WHAT IS KNOWN: • Familial hypercholesterolemia (FH) leads to elevated LDL-cholesterol levels, which increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). • The process of atherosclerosis starts in childhood • Pediatricians play an important role in the detection and treatment of children with FH. WHAT IS NEW: • Our results highlight significant gaps in care for children with FH amongst pediatricians and this may lead to suboptimal detection and treatment. • FH care in children needs improvement by educational initiatives to ultimately prevent ASCVD in adulthood.

Macro and microplastic pollution in Romania: addressing knowledge gaps and potential solutions under the circular economy framework.

Background: This review reveals the role of linear economy prevalence and mismanagement practices in plastic pollution of aquatic and terrestrial environments and related knowledge gaps in Romania while outlining downstream and upstream solutions to reduce plastic pollution and adopt circular economy strategies. Thus, the major aim of this study is the investigation of the stage of scientific knowledge concerning all these demands in the Romanian context. Methodology: This work integrates two main approaches: (i) a bibliometric analysis fed by Web of Science and Scopus databases to reveal the current coverage of peer-reviewed literature related to plastic waste in Romania and (ii) a subject-based review to underline the main themes related to plastic waste management, plastic pollution, and mitigating options in Romania in line with circular economy principles. Results: Reducing plastic pollution requires scientific knowledge, multi-sectoral cooperation, and societal awareness. Following this, the topics of plastic waste and plastic pollution appeared to be under-investigated in the literature considering Romania as a case study and concentrated around the 2020 year, emphasizing, in this way, the trendiness of plastic waste concerns and their management in the current research landscape. Our analysis points out that: (i) Romania is facing massive plastic pollution requiring solid improvements in waste management performances; (ii) few peer-reviewed research studies are performed in Romania for both macro and microplastic concerns with unknown pollution levels in most of its geographical regions; (iii) the plastic waste management is still understudied here, while waste statistics are poorly available at local levels; (iv) the perspectives of circular economy transition are still limited, feeding the plastic pollution in the coming years. Conclusions: Several knowledge gaps are identified and must be covered by future research such as (i) adjusting mismanaged plastic waste levels to regional waste management performances and determining littering rates in urban and rural areas to improve the plastic pollution modeling inputs; (ii) examining plastic pollution associated with landfill sites and waste imports; (iii) assessing the sectoral contributions to macro and microplastic pollution of aquatic environments related to municipalities, tourist destinations, agriculture, etc.; (iv) determining retention levels of plastic in river basins and role of riparian vegetation; (v) analyzing microplastics presence in all types of freshwater environments and interlinkage between macroplastic fragmentation and microplastic; (vi) assessing the plastic loads of transboundary rivers related to mismanagement practices; (vii) determining concentrations of microplastics in air, soil, and other land use ecosystems.

Trends and Missing Links in (De)Hydration Research: A Narrative Review.

Despite decades of literature on (de)hydration in healthy individuals, many unanswered questions remain. To outline research and policy priorities, it is fundamental to recognize the literature trends on (de)hydration and identify current research gaps, which herein we aimed to pinpoint. From a representative sample of 180 (de)hydration studies with 4350 individuals, we found that research is mainly limited to small-scale laboratory-based sample sizes, with high variability in demographics (sex, age, and level of competition); to non-ecological (highly simulated and controlled) conditions; and with a focus on recreationally active male adults (e.g., Tier 1, non-athletes). The laboratory-simulated environments are limiting factors underpinning the need to better translate scientific research into field studies. Although, consistently, dehydration is defined as the loss of 2% of body weight, the hydration status is estimated using a very heterogeneous range of parameters. Water is the most researched hydration fluid, followed by alcoholic beverages with added carbohydrates (CHO). The current research still overlooks beverages supplemented with proteins, amino acids (AA), and glycerol. Future research should invest more effort in "real-world" studies with larger and more heterogeneous cohorts, exploring the entire available spectrum of fluids while addressing hydration outcomes more harmoniously.

Lesion durability found during mandated percutaneous catheter ablation after surgical cryo-ablation for treatment of non-paroxysmal atrial fibrillation.

OBJECTIVES: Current recommendations support surgical treatment of atrial fibrillation (AF) in patients indicated for cardiac surgery. These procedures are referred to as concomitant and may be carried out using radiofrequency energy or cryo-ablation. This study aimed to assess the electrophysiological findings in patients undergoing concomitant cryo-ablation. METHODS: Patients with non-paroxysmal AF undergoing coronary artery bypass grafting and/or valve repair/replacement were included in the trial if concomitant cryo-ablation was part of the treatment plan according to current guidelines. The patients reported in this study were assigned to undergo staged percutaneous radiofrequency catheter ablation (PRFCA), i.e., hybrid treatment, as a part of the SURHYB trial protocol. RESULTS: We analyzed 103 patients who underwent PRFCA 105 ± 35 days after surgery. Left and right pulmonary veins (PVs) were found isolated in 65 (63.1%) and 63 (61.2%) patients, respectively. The LA posterior wall isolation and mitral isthmus conduction block were found in 38 (36.9%) and 18 (20.0%) patients, respectively. Electrical reconnections (gaps) in the left PVs were more often localized superiorly than inferiorly (57.9% vs. 26.3%, P = 0.005) and anteriorly than posteriorly (65.8% vs. 31.6%, P = 0.003). Gaps in the right PVs were more equally distributed anteroposteriorly but dominated in superior segments (72.5% vs. 40.0%, P = 0.003). There was a higher number of gaps on the roof line compared to the inferior line (131 (67.2%) vs. 67 (42.2%), P < 0.001). Compared to epicardial cryo-ablation, endocardial was more effective in creating PVs and LA posterior wall isolation (P < 0.05). Cryo-ablation using nitrous oxide (N20) or argon (Ar) gas as cooling agents was similarly effective (P = NS). CONCLUSIONS: The effectiveness of surgical cryo-ablation in achieving transmural and durable lesions in the left atrium is surprisingly low. Gaps are located predominantly in the superior and anterior portions of the PVs and on the roof line. Endocardial cryo-ablation is more effective than epicardial ablation, irrespective of the cooling agent used.

Effects of canopy gaps on microclimate, soil biological activity and their relationship in a European mixed floodplain forest.

Forest canopy gaps can influence understorey microclimate and ecosystem functions such as decomposition. Gaps can arise from silviculture or tree mortality, increasingly influenced by climate change. However, to what degree canopy gaps affect the buffered microclimate in the understorey under macroclimatic changes is unclear. We, therefore, investigated the effect of forest gaps differing in structure and size (25 gaps: single tree gaps up to 0.67 ha cuttings) on microclimate and soil biological activity compared to closed forest in a European mixed floodplain forest. During the investigation period in the drought year 2022 between May and October, mean soil moisture and temperature as well as soil and air temperature fluctuations increased with increasing openness. In summer, the highest difference of monthly means between cuttings and closed forest in the topsoil was 3.98 ± 9.43 % volumetric moisture and 2.05 ± 0.89 °C temperature, and in the air at 30 cm height 0.61 ± 0.35 °C temperature. For buffering, both the over- and understorey tree layers appeared as relevant with a particularly strong influence of understorey density on soil temperature. Three experiments, investigating soil biological activity by quantifying decomposition rates of tea and wooden spatulas as well as mesofauna feeding activity with bait-lamina stripes, revealed no significant differences between gaps and closed forest. However, we found a positive significant effect of mean soil temperature on feeding activity throughout the season. Although soil moisture decreased during this period, it showed no counteracting effect on feeding activity. Generally, very few significant relationships were observed between microclimate and soil biological activity in single experiments. Despite the dry growing season, decomposition rates remained high, suggesting temperature had a stronger influence than soil moisture. We conclude that the microclimatic differences within the gap gradient of our experiment were not strong enough to affect soil biological activity considerably.

Adult obesity treatment and prevention: A trans-agency commentary on the research landscape, gaps, and future opportunities.

Given the high and growing prevalence of obesity among adults in the United States, obesity treatment and prevention are important topics in biomedical and public health research. Although researchers recognize the significance of this problem, much remains unknown about safe and effective prevention and treatment of obesity in adults. In response to the worsening obesity epidemic and the many unknowns regarding the disease, a group of key scientific and program staff members of the National Institutes of Health (NIH) and other federal and non-government agencies gathered virtually in September 2021 to discuss the current state of obesity research, research gaps, and opportunities for future research in adult obesity prevention and treatment. The current article synthesizes presentations given by attendees and shares their organizations' current initiatives and identified gaps and opportunities. By integrating the information discussed in the meeting and current initiatives, we identify potential targets and overlapping priorities for future research, including health equity and disparities in obesity, the heterogeneity of obesity, and the use of technological and innovative approaches in interventions.

Groundwater systems under siege: The silent invasion of microplastics and cock-tails worldwide.

Microplastics (MPs) contamination is one of the significant escalating environmental concerns worldwide, and this stems from the increasing production and unlawful disposal of plastic materials. Regretfully, the synthesis of plastic materials is expected to triple in the upcoming years. Nevertheless, MPs pollution in marine, aquatic, and terrestrial settings has received much attention, unlike in groundwater systems. This study exhaustively reviewed varying degrees of recent publications in various search engines and provided a detailed state of current knowledge and research progress vis-à-vis MPs and cock-tail pollution in groundwater systems. Evidently, groundwater sources are severely contaminated as a result of growing anthropogenic activities and vertical movement of MPs and cock-tails from the atmospheric, terrestrial, and aquatic environments, however, fewer researchers have fixated their attention on estimating the occurrence of MPs in groundwater resources, while sufficient information regarding their sources, sampling methods, abundance, transport pathways, fate, modeling techniques, appropriate and adequate data, sorption properties, separation from other environmental media, toxicity, and remedial measures are extensively lacking. In addition, MPs may combine with other toxic emerging contaminants to improve migration and toxicity; however, no research has been conducted to fully understand cock-tail migration mechanisms and impacts in groundwater systems. Over time, groundwater may be regarded as the primary sink for MPs, if effective actions are neglected. Overall, this study detected a lack of concern and innumerable voids in this field; hence, vital and nascent research gaps were identified for immediate, advanced, and interdisciplinary research investigations.

Weather Extremes Shock Maize Production: Current Approaches and Future Research Directions in Africa.

Extreme weather events have led to widespread yield losses and significant global economic damage in recent decades. African agriculture is particularly vulnerable due to its harsh environments and limited adaptation capacity. This systematic review analyzes 96 articles from Web of Science, Science Direct, and Google Scholar, focusing on biophysical studies related to maize in Africa and worldwide. We investigated the observed and projected extreme weather events in Africa, their impacts on maize production, and the approaches used to assess these effects. Our analysis reveals that drought, heatwaves, and floods are major threats to African maize production, impacting yields, suitable cultivation areas, and farmers' livelihoods. While studies have employed various methods, including field experiments, statistical models, and process-based modeling, African research is often limited by data gaps and technological constraints. We identify three main gaps: (i) lack of reliable long-term experimental and empirical data, (ii) limited access to advanced climate change adaptation technologies, and (iii) insufficient knowledge about specific extreme weather patterns and their interactions with management regimes. This review highlights the urgent need for targeted research in Africa to improve understanding of extreme weather impacts and formulate effective adaptation strategies. We advocate for focused research on data collection, technology transfer, and integration of local knowledge with new technologies to bolster maize resilience and food security in Africa.

Understanding the research and practical needs required to control toxocariasis in Iran.

Human toxocariasis (HT) is a widespread zoonotic infection globally, notably prevalent in tropical areas. Enhancing our understanding of toxocariasis can lead to increased attention towards the socioeconomic impact and control of this neglected zoonosis. We conducted a comprehensive review of all available articles and official documents on toxocariasis in Iran to identify research gaps and critical needs for its control. This review highlights that despite numerous studies exploring various aspects of toxocariasis in definitive and paratenic hosts, as well as humans and environmental contamination, significant data deficiencies and gaps persist across different regions in the country. These gaps involve investigating the worm burden and reinfection rates in definitive hosts, developing more sensitive methods to detect and differentiate of Toxocara species, and understanding the behavior of definitive host animals. Additionally, identifying potential paratenic hosts for HT and exploring the organ-specific affinity and survival duration of Toxocara larvae within these hosts are essential areas for exploration. It's also imperative to comprehend the sylvatic and domestic cycles of the parasite in paratenic hosts. Furthermore, assessing egg density in the environment, exploring potential new sources such as water, and identifying regions with optimal climatic conditions for the survival and development of Toxocara eggs are crucial for the formulation of effective prevention and control strategies. Identifying at-risk groups, developing early diagnosis techniques, employing imaging methods, and identifying long-term complications in humans are also crucial. Community health organizations should prioritize health education for the public and professionals. Furthermore, accurately estimating definitive host populations, monitoring and preventing their movements in public places, implementing regular deworming practices for pets and stray hosts, and recognizing the infection's significance as a health priority are critical. This comprehensive understanding advocates for a holistic "one health" approach to control of HT.

Real-Time Use of SGLT2i Verified in Pre-dialysis: The RSVP Cross-sectional Study.

BACKGROUND: The use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in nephrology practice is increasingly becoming standard of care in patients with diabetes or those with proteinuria. OBJECTIVES: The primary outcome was to identify the proportion of pre-dialysis patients with chronic kidney disease (CKD) G3a, G3b, or G4 prescribed an SGLT2i and describe their characteristics. METHODS: This was a retrospective, multicentric, cross-sectional study of patients with CKD followed at 4 pre-dialysis clinics in the province of Quebec, Canada. We collected data of multiple covariates associated with prescribing SGLT2i in patients over 18 years of age with CKD G3a, G3b, or G4. We then performed a multivariate logistic regression to assess their associations. RESULTS: Of the 874 patients included, 22.7% were prescribed an SGLT2i. Factors most strongly associated included male sex (odds ratio [OR] = 4.88, 95% CI = 2.38-10.03), being prescribed metformin (OR = 4.30, 95% CI = 2.23-8.31), having type 2 diabetes (OR = 4.00, 95% CI = 1.86-8.62), or having an albumin-to-creatinine ratio greater than 300 mg/g (OR = 1.84, 95% CI = 1.08-3.14). The majority of patients (60.4%) had their SGLT2i initiated by the pre-dialysis clinic and the most frequent adverse event was an initial increase in serum creatinine 1 week after starting treatment (33.9%). CONCLUSION AND RELEVANCE: An increasing number of patients with CKD are being prescribed SGLT2i. Nonetheless, significant disparities in sex, severity of disease, and comorbidities remain. We suggest that specific strategies be put in place to promote prescribing of SGLT2i in women and other at-risk populations, in particular among nephrology teams, to improve patient care.

Environmental diseases, recognition for care: A qualitative study of nurses' perceptions.

OBJECTIVES: This study aims to investigate hospital nurses' perceptions of illness due to environmental exposures. DESIGN: A qualitative exploratory study, designed in accordance with the specified reporting guidelines for qualitative research. SAMPLE: Nurses working in Italian hospitals. METHODS: Semi-structured interviews were used to collect data, then evaluated using the framework analysis methodology. Data collection was from January to June 2022 and analysed from July to September 2022. RESULTS: Forty-two nurses were interviewed. Data analysis revealed three themes: 1) the concept of disease in relation to environmental exposure; 2) the dangers of chemical and physical substances; 3) environmental changes cause concern and a sense of helplessness for the future. CONCLUSIONS: The results suggest the need for specific training on topics related to environmental disease types, environmental exposure, preventive measures, health promotion, and environmental impact to support professional development and support nurses in the management of this important aspect of health care.

Frailty evidence-practice gaps in acute care hospitals.

OBJECTIVES: Frailty is common in hospitalised older people. Clinical practice guidelines for the management of frailty provide recommendations for identification and management; however, adoption into practice in hospitals is limited. This study identified and quantified the evidence-practice gap between frailty guidelines and clinical practice in two hospitals using an audit tool. METHODS: A cross-sectional audit of medical records of frail older patients admitted to two hospitals was conducted. Data were collected using an audit tool based on the Asia Pacific Clinical Practice Guidelines for frailty management. Data were analysed using descriptive statistics and inter-rater reliability of the tool was assessed. RESULTS: Auditing of n = 70 electronic medical records showed that assessment of frailty in the acute setting did not regularly occur (17%). Few participants received guideline-recommended interventions. Physiotherapy treatment was limited, with 23% of participants receiving progressive resistance strength training. Gaps exist in provision of nutritional supplementation (26%) with limited recordings of weight during the admission for 10% of participants. Pharmacy review of medications was consistently documented on admission (84%) and discharge (93%). Vitamin D was prescribed for 57% of participants. Inter-rater reliability showed a high level of agreement using the audit tool. CONCLUSIONS: An audit tool was feasible to assess frailty evidence-practice gaps in the hospital setting. Further understanding of the contextual barriers is needed to inform implementation strategies (dedicated staffing, education and training and ongoing audit of practice cycles) for the uptake of frailty guidelines in hospital settings.

The Arf-GAPs, AoAge1 and AoAge2, regulate diverse cellular processes, conidiation, trap formation, and secondary metabolism in Arthrobotrys oligospora.

Guanine nucleotide-binding proteins of the ADP ribosylation factor (Arf) family and their activating proteins (Arf-GAPs) are essential for diverse biological processes. Here, two homologous Arf-GAPs, Age1 (AoAge1) and Age2 (AoAge2), were identified in the widespread nematode-trapping fungus Arthrobotrys oligospora. Our results demonstrated that AoAge1, especially AoAge2, played crucial roles in mycelial growth, sporulation, trap production, stress response, mitochondrial activity, DNA damage, endocytosis, reactive oxygen species production, and autophagy. Notably, transcriptome data revealed that approximately 62.7% of the genes were directly or indirectly regulated by AoAge2, and dysregulated genes in Aoage2 deletion were enriched in metabolism, ribosome biogenesis, secondary metabolite biosynthesis, and autophagy. Furthermore, Aoage2 inactivation caused a substantial reduction in several compounds compared to the wild-type strain. Based on these results, a regulatory network for AoAge1 and AoAge2 was proposed and verified using a yeast two-hybrid assay. Based on our findings, AoAge1 and AoAge2 are essential for vegetative growth and mycelial development. Specifically, AoAge2 is required for sporulation and trapping morphogenesis. Our results demonstrated the critical functions of AoAge1 and AoAge2 in mycelial growth, diverse cellular processes, and pathogenicity, offering deep insights into the functions and regulatory mechanisms of Arf-GAPs in nematode-trapping fungi.

Exploration of poly (ADP-ribose) polymerase inhibitor resistance in the treatment of BRCA1/2-mutated cancer.

Breast cancer susceptibility 1/2 (BRCA1/2) genes play a crucial role in DNA damage repair, yet mutations in these genes increase the susceptibility to tumorigenesis. Exploiting the synthetic lethality mechanism between BRCA1/2 mutations and poly(ADP-ribose) polymerase (PARP) inhibition has led to the development and clinical approval of PARP inhibitor (PARPi), representing a milestone in targeted therapy for BRCA1/2 mutant tumors. This approach has paved the way for leveraging synthetic lethality in tumor treatment strategies. Despite the initial success of PARPis, resistance to these agents diminishes their efficacy in BRCA1/2-mutant tumors. Investigations into PARPi resistance have identified replication fork stability and homologous recombination repair as key factors sensitive to PARPis. Additionally, studies suggest that replication gaps may also confer sensitivity to PARPis. Moreover, emerging evidence indicates a correlation between PARPi resistance and cisplatin resistance, suggesting a potential overlap in the mechanisms underlying resistance to both agents. Given these findings, it is imperative to explore the interplay between replication gaps and PARPi resistance, particularly in the context of platinum resistance. Understanding the impact of replication gaps on PARPi resistance may offer insights into novel therapeutic strategies to overcome resistance mechanisms and enhance the efficacy of targeted therapies in BRCA1/2-mutant tumors.

Five aspects of research waste in biomedicine: A scoping review.

BACKGROUND: The number of published journal articles has grown exponentially during the last 30 years, which may have led to some wasteful research. However, the terminology associated with research waste remains unclear. To address this, we aimed to identify, define, and categorize the aspects of research waste in published biomedical reports. METHODS: In this scoping review, we systematically searched for biomedical literature reports from 1993 to 2023 in two databases, focusing on those addressing and defining research waste. Through data charting, we analyzed and categorized the aspects of research waste. RESULTS: Based on 4285 initial records in the searches, a total of 832 reports were included in the analysis. The included reports were primarily narrative reviews (26%) and original reports (21%). We categorized research waste into five aspects: methodological, invisible, negligible, underreported, and structural (MINUS) research waste. More than half of the reports (56%) covered methodological research waste concerning flaws in study design, study conduct, or analysis. Invisible research waste covered nonpublication, discontinuation, and lack of data-sharing. Negligible research waste primarily concerned unnecessary repetition, for example, stemming from the absence of preceding a trial with a systematic review of the literature. Underreported research waste mainly included poor reporting, resulting in a lack of transparency. Structural research waste comprised inadequate management, collaboration, prioritization, implementation, and dissemination. CONCLUSION: MINUS encapsulates the five main aspects of research waste. Recognizing these aspects of research waste is important for addressing and preventing further research waste and thereby ensuring efficient resource allocation and scientific integrity.

Modelling techniques in cholera epidemiology: A systematic and critical review.

Diverse modelling techniques in cholera epidemiology have been developed and used to (1) study its transmission dynamics, (2) predict and manage cholera outbreaks, and (3) assess the impact of various control and mitigation measures. In this study, we carry out a critical and systematic review of various approaches used for modelling the dynamics of cholera. Also, we discuss the strengths and weaknesses of each modelling approach. A systematic search of articles was conducted in Google Scholar, PubMed, Science Direct, and Taylor & Francis. Eligible studies were those concerned with the dynamics of cholera excluding studies focused on models for cholera transmission in animals, socio-economic factors, and genetic & molecular related studies. A total of 476 peer-reviewed articles met the inclusion criteria, with about 40% (32%) of the studies carried out in Asia (Africa). About 52%, 21%, and 9%, of the studies, were based on compartmental (e.g., SIRB), statistical (time series and regression), and spatial (spatiotemporal clustering) models, respectively, while the rest of the analysed studies used other modelling approaches such as network, machine learning and artificial intelligence, Bayesian, and agent-based approaches. Cholera modelling studies that incorporate vector/housefly transmission of the pathogen are scarce and a small portion of researchers (3.99%) considers the estimation of key epidemiological parameters. Vaccination only platform was utilized as a control measure in more than half (58%) of the studies. Research productivity in cholera epidemiological modelling studies have increased in recent years, but authors used diverse range of models. Future models should consider incorporating vector/housefly transmission of the pathogen and on the estimation of key epidemiological parameters for the transmission of cholera dynamics.