Unresolved Concern Research Articles

Ischaemic cardiotoxicity of aromatase inhibitors in postmenopausal patients with early breast cancer in Denmark: a cohort study of real-world data

For aromatase inhibitor treatment (AIT) in breast cancer, there is an unresolved concern about ischaemic cardiotoxicity. We investigated the association between AIT and ischaemic cardiotoxicity in a prospective cohort of female patients with early breast cancer who received contemporary treatment in Denmark. In this prospective cohort study in Denmark, we identified postmenopausal patients of any age diagnosed with breast cancer as recorded in the nationwide Danish Breast Cancer Cooperative Group (DBCG) clinical database between Jan 1, 2009, and Dec 31, 2020, and linked them to other nationwide registries. Exclusion criteria included having a history of other primary cancer, less than 2 years of residency in Denmark, and no inclusion in a treatment protocol according to the DBCG database, including for metastatic or locally advanced breast cancer. Information on demography, hospital diagnoses, filled prescriptions, laboratory testing, and socioeconomic status were recorded. We stratified the patient cohort according to history (yes vs no) of selected cardiovascular disease defined as ischaemic heart disease, ischaemic stroke, and heart failure, and defined the primary outcome as two-point major adverse cardiovascular events (MACE; acute myocardial infarction or ischaemic stroke). We estimated cause-specific hazard ratios (HRs) according to allocation to AIT versus not in an intention-to-treat analysis using a Cox proportional hazards regression model with age as the underlying time scale, adjusting for demographic characteristics, tumour characteristics, and other anti-cancer treatments. 43 440 postmenopausal patients diagnosed with breast cancer were identified, of whom 32 635 were followed up and included in analyses. Of 29 118 postmenopausal patients with no history of selected cardiovascular disease, we observed 510 two-point MACEs among 22 135 patients allocated to AIT (incidence rate 4·3/1000 person-years of follow-up) and 170 two-point MACEs among 6983 patients not allocated to AIT (4·1/1000 person-years). The adjusted HR was 0·91 (95% CI 0·73-1·14) for patients allocated to AIT versus patients not allocated to AIT. Among 3517 patients with a history of selected cardiovascular disease, we observed 158 two-point MACEs among 2661 patients allocated to AIT (incidence rate 12·4/1000 person-years) and 50 two-point MACEs (12·1/1000 person-years) among 856 patients not allocated to AIT (adjusted HR 0·81 [95% CI 0·58-1·15]). Our findings do not support a clinically relevant ischaemic cardiotoxic potential of AIT in patients with early breast cancer and do not support avoiding AIT prescription in patients with early breast cancer. Bispebjerg and Frederiksberg Hospital, Kræftens Bekæmpelse, Fonden til Lægevidenskabens Fremme, Aase og Ejnar Danielsens Fond, Helsefonden, and Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis' Legat.

Comparison of predictive models in postoperative nausea and vomiting in patients undergoing breast cancer surgery

BackgroundPost-operative nausea and vomiting remain an unresolved concern in Türkiye and some parts of the world, impacting the quality of the patient's recovery process and diminishing overall satisfaction.ObjectiveThis study was conducted as a descriptive investigation to compare the incidence of nausea and vomiting following breast cancer surgery with the nausea and vomiting risk scores proposed by Apfel and Koivuranta.MethodsThis study was conducted with 100 patients admitted to the General Surgery service of a university hospital between 31 August 2019 and 31 May 2021 for breast cancer surgery. The patient information form developed by the researchers, Apfel Nausea and Vomiting Risk Score, and Koivuranta Nausea and Vomiting Risk Score were used as data collection tools.ResultsIt was identified that 61% of the patients experienced nausea and vomiting within the initial 24 h following surgery. A significant correlation was found between age, post-operative opioid use, motion sickness or history of PONV, and nausea and vomiting (p < 0,05). The sensitivity of the Apfel score obtained was 80%, the specificity was 46%, and the AUC value was 0.686. The sensitivity of the Koivuranta score was 80%, the specificity was 35%, and the AUC value was 0.675 (p < 0.05).ConclusionIt has been observed that patients experience high rates of nausea and vomiting after breast cancer surgery and that the Apfel and Koivuranta Risk Scores are equally applicable in predicting post-operative nausea and vomiting.

Test Panel of Hidden Allergens for “Idiopathic Anaphylaxis” Reveals Wheat Allergy Dependent on Augmentation Factors as Common Final Diagnosis

Idiopathic anaphylaxis (IA) is an unresolved concern. Hidden allergens may be relevant in IA and in nonsteroidal anti-inflammatory drug hypersensitivity (NSAID-HS). To identify hidden elicitors for IA and NSAID-HS by a skin prick test (SPT) (13 allergens) and allergen-specific IgE (sIgE) panel (12 allergens) and to determine the value of each tested allergen. We retrospectively included all patients from 2018 to 2021 referred with a suspicion of IA or NSAID-HS by history in whom SPT and/or sIgE to allergens of the IA panel were performed. Patient characteristics from patients' records included comorbidities, history and symptoms of anaphylaxis, serum baseline tryptase level, total IgE level, SPT, sIgE, challenge results, and final diagnoses. A total of 134 patients (77 female, mean age 39.7 ± 14.6 years) were included. Median serum baseline tryptase and total IgE levels were 4.23 μg/L and 133.5 kU/L, respectively. Allergologic workup with the IA panel resulted in positive SPT and sIgE in 61 (47%) and 66 (60%) patients, respectively. In those, confirmation or exclusion of allergy, mostly by challenge, led to a definitive diagnosis in 61 of 134 patients (46%). Skin prick test was most frequently positive to gluten (22.4%) and sIgE to ω5-gliadin (21.6%), which correlated with the history (r= 0.310, P < .001; and r= 0.407, P < .001, respectively). In 28 of 134 patients (21%) with initially suspected IA or NSAID-HS, challenges confirmed occult food allergy in which wheat allergy dependent on augmentation factors was the most frequent cause of anaphylaxis (19%). Wheat allergy dependent on augmentation factors should be considered in all patients with anaphylaxis of unknown cause or after NSAID intake.

A Reworking on the Cow Dung Waste Concern into Design

Globally, environmental pollution stemming from livestock waste remains a widespread and unresolved concern. The contamination resulting from such waste can have adverse effects on both air and water quality, impacting not only livestock owners but also neighboring non-farming communities. This paper focuses specifically on the case study of cow dung waste accumulation in the local ditches of a Cattle Farmers' village in West Java called Bukatanah Village to discuss socio-environmental concerns. Our ongoing research closely aligns with exploring the potential of residents in Bukatanah Village to address the environmental issues prevalent in their living areas. Moreover, this paper is dedicated to illustrating the significance of co-designing the concept in collaboration with the local community rather than imposing a top-down approach in the village. The process is shaped by a series of design ethnography observations, participatory design workshops, material exploration, and project evaluation stages. This paper illustrates a rethinking of solving environmental problems by engaging the locals in "design-making" activities. As a method, the concept of participatory design conducted by the PP-PBL ITB team becomes crucial to be implemented for gaining mutual ideas together with the locals. The research-initiated collaborative system empowers Bukatanah Village residents, fostering creativity and creating home-based business opportunities. This is a continued focus in multidisciplinary community development research, encompassing participatory design and ethnography methods in the process.

Microplastics in aquatic environments: a growing, unresolved concern

The global rise in plastic demand and production, combined with the significant amount of plastics found in municipal solid waste, has led to the ubiquitous occurrence of microplastics (MPs) in the aquatic environment. This review examines the existing information on the origin, behaviour, fate, and effects of MPs on living organisms and the environment. In aquatic ecosystems, the reported high concentrations of MPs potential threat to the exposed organisms, causing blockage of the intestinal tract, alterations in feeding and digestive habits, injury, and death. Both fresh and aged MPs interact with different components of the aquatic ecosystem, leading to changes in their behaviour and bioavailability. Additionally, MPs often serve as vectors for sorbed pollutants and the chemicals leaching from their polymeric chains, enhancing the transportation of contaminants within the aquatic environment and to predators. With the current rate of plastic production and use coupled with the lack of proper waste management policies in many countries, the worries about environmental MPs have increased in recent years. Hence, a better understanding, continuous monitoring, and plastics management methods and waste control plans are crucial to address the issue of MPs in the environment.

Acute kidney injury due to bilateral malignant ureteral obstruction: Is there an optimal mode of drainage?

There is a well-known relationship between malignancy and impairment of kidney functions, either in the form of acute kidney injury or chronic kidney disease. In the former, however, bilateral malignant ureteral obstruction is a surgically correctable factor of this complex pathology. It warrants urgent drainage of the kidneys in emergency settings. However, there are multiple controversies and debates about the optimal mode of drainage of the bilaterally obstructed kidneys in these patients. This review addressed most of the concerns and provided a comprehensive presentation of this topic from the recent literature. Also, we provided different perspectives on the management of the bilateral obstructed kidneys due to malignancy. Despite the frequent trials for improving the success rates and functions of ureteral stents, placement of a percutaneous nephrostomy tube remains the most recommended tool of drainage due to bilateral ureteral obstruction, especially in patients with advanced malignancy. However, the disturbance of the quality of life of those patients remains a major unresolved concern. Beside the unfavorable prognostic potential of the underlying malignancy and the various risk stratification models that have been proposed, the response of the kidney to initial drainage can be anticipated and evaluated by multiple renal prognostic factors, including increased urine output, serum creatinine trajectory, and time-to-nadir serum creatinine after drainage.

Lightweight Secure Key Distribution Protocol (LSKDP) for Wireless Sensor Networks

Because of the enormous technological revolution, the most difficult tasks that humans cannot perform are now easily addressed by small digital gadgets. An example of this technological revolution is Wireless Sensor Networks (WSN). In the WSN, numerous heterogeneous types of sensors work together to sense, monitor, capture, process, and control the physical condition of a specific region or object. The WSN has been used extensively in a number of key areas, particularly in the medical, agricultural, military, and traffic management sectors. The little electronic gadget that forms the WSN is composed of three major components: a sensing component, a power storage component, and a wireless transmission component. Despite the numerous benefits of this modern technology, security remains an unresolved concern. The goal of this work is to develop an efficient Lightweight Secure Key Distribution Protocol (LSKDP) for enhancing the process's safety in heterogeneous medical WSNs. Additionally, security and performance analyses were conducted to demonstrate the suggested methodology's efficacy. The security analysis is performed to ascertain the proposed method's vulnerability to network threats. Additionally, performance analysis is used to determine the CPU utilization, memory consumption, processing power, and computational overhead of the suggested methodology. The experimental results indicate that the suggested strategy detects attacks more accurately and with a lower computational overhead.

Experimental-simulation methodology for estimation of thermal parameters of adaptive facades in mild climate conditions: A water-flow glazing case study

Adaptive glazings facades have the potential to play a significant role in new buildings with high energy performance, since they enable the envelope to adapt its properties dynamically to transient ambient thermal conditions. In particular, Water-Flow Glazings (WFG) are a type of dynamic glazing able to enhance energy efficiency of buildings. However, WFG simulation in Building Energy Modelling (BEM) software is still an unresolved concern because simulation software is mainly designed to use glazings as passive solar elements. The lack of such a thermal simulation tool limits the use of WFG for building designers and constructors. A hybrid experimental-simulation methodology using TRNSYS is presented to face this issue. This work proposes a novel procedure to determine thermal specific U-value and SHGC of adaptive WFG facades in mild climates. The proposed methodology makes possible to reach a rapid empirical estimation of these two thermal parameters of WFG facades. This heuristic approach proved to be helpful to reproduce the experimental results in mild climate conditions and is proposed to evaluate the thermal performance and energy contribution of adaptive facades.

A Study on Encryption and Decryption System

The presented document aims to review the methodologies used for cryptography. Cryptography, a Greek word meaning 'protected data with an unreadable format' has become the need of the hour. In the world of digitalization, cyber attacks, data leaks have become prominent. In order to prevent the same, data cryptography is highly in demand. Various techniques have been applied for the same. One such algorithm, RSA algorithm is another most significant method. However, its computation time has remained an unresolved concern. This paper discusses one such method to modify the following algorithm to reduce its space-time complexity.

Assessment of the possible risk factors for primary common bile duct stone recurrence after cholecystectomy.

Common bile duct (CBD) stone recurrence is considered an unresolved concern after cholecystectomy and complete extraction of previous CBD stones. This study aimed to investigate the potential risk factors for primary CBD stone recurrence after cholecystectomy and endoscopic treatment. The endoscopic retrograde cholangiopancreatography (ERCP) database of our medical center was retrospectively reviewed between February 2008 and May 2018. A total of 45 patients with CBD stone recurrence with a history of previous cholecystectomy were recruited in the study. Moreover, 104 patients who underwent cholecystectomy at our medical center and who were followed up for more than 1 year without CBD stone recurrence were assigned to the control group. The characteristics of the patients, surgical records during cholecystectomy, and ERCP records obtained immediately before cholecystectomy were analyzed. Univariate analysis, based on the binary logistic regression method, indicated that age (p = 0.01) and the presence of the periampullary diverticulum (PAD; p = 0.006) were significantly different between the non-recurrence and recurrence groups. However, the surgical records during cholecystectomy were not significantly different between the two groups. The CBD stone number (p = 0.039), CBD stone diameter (≥ 10mm; p = 0.05), and CBD diameter (≥ 15 mm; p < 0.001), based on the ERCP findings were significantly different between the two groups. Multivariate analysis revealed that CBD diameter (≥ 15mm; OR, 3.878; 95% CI, 1.406-10.697; p = 0.008) was the independent risk factors for CBD stone recurrence after cholecystectomy. CBD diameter (≥ 15mm) at the time of the initial ERCP is associated with CBD stone recurrence after cholecystectomy.

Anthropogenic contaminants of high concern: Existence in water resources and their adverse effects.

Existence of anthropogenic contaminants (ACs) in different environmental matrices is a serious and unresolved concern. For instance, ACs from different sectors, such as industrial, agricultural, and pharmaceutical, are found in water bodies with considerable endocrine disruptors potency and can damage the biotic components of the environment. The continuous ACs exposure can cause cellular toxicity, apoptosis, genotoxicity, and alterations in sex ratios in human beings. Whereas, aquatic organisms show bioaccumulation, trophic chains, and biomagnification of ACs through different entry route. These problems have been found in many countries around the globe, making them a worldwide concern. ACs have been found in different environmental matrices, such as water reservoirs for human consumption, wastewater treatment plants (WWTPs), drinking water treatment plants (DWTPs), groundwaters, surface waters, rivers, and seas, which demonstrate their free movement within the environment in an uncontrolled manner. This work provides a detailed overview of ACs occurrence in water bodies along with their toxicological effect on living organisms. The literature data reported between 2017 and 2018 is compiled following inclusion-exclusion criteria, and the obtained information was mapped as per type and source of ACs. The most important ACs are pharmaceuticals (diclofenac, ibuprofen, naproxen, ofloxacin, acetaminophen, progesterone ranitidine, and testosterone), agricultural products or pesticides (atrazine, carbendazim, fipronil), narcotics and illegal drugs (amphetamines, cocaine, and benzoylecgonine), food industry derivatives (bisphenol A, and caffeine), and personal care products (triclosan, and other related surfactants). Considering this threatening issue, robust detection and removal strategies must be considered in the design of WWTPs and DWTPs.

Habitus and reflexivity in tandem? Insights from postcolonial Sri Lanka

This article contributes to the unresolved concern about the relationship between habitus and reflexivity. Using Sri Lanka, a postcolonial social context, as the research ground, the article provides a contemporary interpretation of individuals’ reflexive and habitual behaviour that displaces Bourdieu’s concept of habitus as inappropriate for the representation of 21st-century social dynamics. While Sri Lanka is often labelled a traditional society, where habitual, routine, pre-reflexive action is thought to be more common, studies that question this generalised view appear to be largely absent. Therefore, based on a critical realist morphogenetic perspective that offers the analytical possibility of both routine and conscious action, this article investigates the role of habitus and reflexivity through 75 work and life histories gathered from Sri Lanka. The findings suggest that even the reproduction of traditional practices has increasingly become a reflexive task; thus, this work supports the position that habitus fails to provide reliable guidance to understand social action, even within a society labelled as traditional.

Role of Family Planning in Women With Multiple Sclerosis in Switzerland: Results of the Women With Multiple Sclerosis Patient Survey.

Background: Women of child bearing age with multiple sclerosis (MS) must carefully consider treatments when planning a family, since disease modifying drugs (DMDs) are contraindicated during pregnancy.Objectives: This questionnaire-based study aimed to improve understanding of the effect of family planning on treatment decisions in female, Swiss MS patients.Methods: Female patients with MS (aged 18–55 years) participated in the 26-question survey between September 2014 and August 2015. Information captured included patient background, family planning status, treatment course, and previous pregnancies.Results: In total, 271 questionnaires distributed from 15 MS centres were returned for analysis. Of these, 250 (92.3%) participants received DMD therapy and 106 (39.1%) wanted children or were pregnant. Significantly more patients with a short-term plan to conceive within 2 years were treated with injectables (19/54) compared with those without a plan to conceive (19/108; p = 0.013). A proportionally greater number of women not planning to conceive took oral (34/108) or infusion therapies (41/108) compared with those with a short- (13/54 and 16/54, respectively) or medium-term (after 2 years or more; infusion therapy only, 14/44) plan to conceive.Conclusion: The study highlights that pregnancy remains an important yet unresolved concern in the treatment of MS patients. Nearly all women received DMD treatment, and type of DMD treatment was influenced by family planning, with significantly more women with a short-term plan to conceive using injectables.

Study of Coronal Rotation using X-ray images observed by Hinode

AbstractSolar rotation is still one of the unresolved concern of solar physics. We performed time series analysis on the bins formed on equally separated latitude regions on the soft X-ray images. These images are observed with the X-ray telescope (XRT) on board the Hinode satellite. The flux modulation method traces the passage of X-ray feature over the solar disc and statistical analysis of the time series data of the SXR images (one per day) for the period extends from year 2015 to 2017 gives the coronal rotation period as a function of latitude. The investigation provided quite systematic information of the solar rotation and its variability.

The October 2014 United States Treasury bond flash crash and the contributory effect of mini flash crashes.

We investigate the causal uncertainty surrounding the flash crash in the U.S. Treasury bond market on October 15, 2014, and the unresolved concern that no clear link has been identified between the start of the flash crash at 9:33 and the opening of the U.S. equity market at 9:30. We consider the contributory effect of mini flash crashes in equity markets, and find that the number of equity mini flash crashes in the three-minute window between market open and the Treasury Flash Crash was 2.6 times larger than the number experienced in any other three-minute window in the prior ten weekdays. We argue that (a) this statistically significant finding suggests that mini flash crashes in equity markets both predicted and contributed to the October 2014 U.S. Treasury Bond Flash Crash, and (b) mini-flash crashes are important phenomena with negative externalities that deserve much greater scholarly attention.

Cellular and Molecular Dynamics of Th17 Differentiation and its Developmental Plasticity in the Intestinal Immune Response.

After emerging from the thymus, naive CD4 T cells circulate through secondary lymphoid tissues, including gut-associated lymphoid tissue of the intestine. The activation of naïve CD4 T cells by antigen-presenting cells offering cognate antigen initiate differentiation programs that lead to the development of highly specialized T helper (Th) cell lineages. Although initially believed that developmental programing of effector T cells such as T helper 1 (Th1) or T helper 2 (Th2) resulted in irreversible commitment to a fixed fate, subsequent studies have demonstrated greater flexibility, or plasticity, in effector T cell stability than originally conceived. This is particularly so for the Th17 subset, differentiation of which is a highly dynamic process with overlapping developmental axes with inducible regulatory T (iTreg), T helper 22 (Th22), and Th1 cells. Accordingly, intermediary stages of Th17 cells are found in various tissues, which co-express lineage-specific transcription factor(s) or cytokine(s) of developmentally related CD4 T cell subsets. A highly specialized tissue like that of the intestine, which harbors the largest immune compartment of the body, adds several layers of complexity to the intricate process of Th differentiation. Due to constant exposure to millions of commensal microbes and periodic exposure to pathogens, the intestinal mucosa maintains a delicate balance between regulatory and effector T cells. It is becoming increasingly clear that equilibrium between tolerogenic and inflammatory axes is maintained in the intestine by shuttling the flexible genetic programming of a developing CD4 T cell along the developmental axis of iTreg, Th17, Th22, and Th1 subsets. Currently, Th17 plasticity remains an unresolved concern in the field of clinical research as targeting Th17 cells to cure immune-mediated disease might also target its related subsets. In this review, we discuss the expanding sphere of Th17 plasticity through its shared developmental axes with related cellular subsets such as Th22, Th1, and iTreg in the context of intestinal inflammation and also examine the molecular and epigenetic features of Th17 cells that mediate these overlapping developmental programs.

Community Families: Bridging the gap between mental health services and civil society - A qualitative study from users' perspective.

Social interventions to support people with severe mental illness are important to improving the quality of life. The perspectives of users are essential in this process. This article explores users' experiences, investments and concerns of a befriending programme. Focus group and individual qualitative interviews with service users. Overall, the experiences with the programme were positive, and the social interaction was highly valued. However, that the relationships were arranged and facilitated by mental health workers remained an unresolved concern even after several years. People with severe mental illness benefit from relationships despite the need of professional assistant.

Does a rifamycin-containing preventive regimen increase rifampicin resistance? An unresolved concern

Does a rifamycin-containing preventive regimen increase rifampicin resistance? An unresolved concern

Comparison of short-term mortality and morbidity between parenteral and enteral nutrition for adults without cancer: a propensity-matched analysis using a national inpatient database

Proper artificial nutrition for patients who are unable to eat normally is an ongoing, unresolved concern in geriatric medicine and home medical care. Controversy surrounds prognostic differences between parenteral and enteral nutrition, 2 methods for artificial nutrition. Short-term outcomes of parenteral and enteral nutrition for patients who are unable to eat normally were compared and analyzed. Data were acquired from patients selected from a national inpatient database covering 1057 hospitals in Japan. Participants had received artificial nutrition between April 2012 and March 2013, were aged ≥20 y, and did not have cancer. They were separated into 2 groups: those who received parenteral nutrition and those who received enteral nutrition. We performed one-to-one propensity score matching between the groups. The primary outcome measurements were mortality rates at 30 and 90 d after the start of the procedure. The secondary outcomes were postprocedural complications, pneumonia, and sepsis. We analyzed survival length of stay after the procedure with the use of a Cox proportional hazards model. There were 3750 patients in the parenteral group and 22,166 patients in the enteral group. Propensity score matching created 2912 pairs in the 2 groups. Patients with a similar propensity score (probability of being assigned to the enteral group) calculated from the baseline condition were matched. Mortality rates at 30 and 90 d after start of treatment were 7.6% and 5.7% (P = 0.003) and 12.3% and 9.9% (P = 0.002) in the parenteral and enteral groups, respectively. In Cox regression analysis, the HR for the enteral group relative to the parenteral group was 0.62 (95% CI: 0.54, 0.71; P < 0.001). The incidences of postprocedural pneumonia and sepsis were 11.9% and 15.5% (P < 0.001) and 4.4% and 3.7% (P = 0.164) for the parenteral and enteral groups, respectively. The present analysis showed the better survival rate with enteral compared with parenteral nutrition for adults who were not suffering from cancer. This trial was registered at clinicaltrials.gov as NCT02512224.

NANODELIVERY SYSTEM FOR MITOCHONDRIAL TARGETING

Mitochondria are indispensable in cellular functions such as energy production and death execution. They are emerging as intriguing therapeutic target as their dysregulation was found to be monumental in diseases such as neurodegenerative disease, obesity, and cancer etc. Despite tremendous interest being focused on therapeutically intervening mitochondrial function, few mito-active drugs were successfully developed, particularly due to challenges in delivering active compound to this organelle. In this review, effort in utilizing nanotechnology for targeted mitochondrial delivery of compound is expounded based on the nature of the nanomaterial used. The advantage and potential offered are discussed alongside the limitation. Finally the review is concluded with perspectives of the application of nanocarrier in mitochondrial medicine, given the unresolved concern on potential complications.