Advanced Phase Research Articles

Shared genetics between breast cancer and predisposing diseases identifies novel breast cancer treatment candidates.

Current effective breast cancer treatment options have severe side effects, highlighting a need for new therapies. Drug repurposing can accelerate improvements to care, as FDA-approved drugs have known safety and pharmacological profiles. Some drugs for other conditions, such as metformin, an antidiabetic, have been tested in clinical trials for repurposing for breast cancer. Here, we exploit the genetics of breast cancer and linked predisposing diseases to propose novel drug repurposing opportunities. We hypothesize that if a predisposing disease contributes to breast cancer pathology, identifying the pleiotropic genes related to the risk of cancer could prioritize drugs, among all drugs treating a predisposing disease. We aim to develop a method to not only prioritize drugs for repurposing, but also to highlight shared etiology explaining repurposing. We compile breast cancer's predisposing diseases from literature. For each predisposing disease, we use GWAS summary statistics data to identify genes in loci showing genetic correlation with breast cancer. Then, we use a network approach to link these shared genes to canonical pathways. Similarly, for all drugs treating the predisposing disease, we link their targets to pathways. In this manner, we are able to prioritize a list of drugs based on each predisposing disease, with each drug linked to a set of implicating pathways. Finally, we evaluate our recommendations against drugs currently under investigation for breast cancer. We identify 84 loci harboring mutations with positively correlated effects between breast cancer and its predisposing diseases; these contain 194 identified shared genes. Out of the 112 drugs indicated for the predisposing diseases, 74 drugs can be linked to shared genes via pathways (candidate drugs for repurposing). Fifteen out of these candidate drugs are already in advanced clinical trial phases or approved for breast cancer (OR = 9.28, p = 7.99e-03, one-sided Fisher's exact test), highlighting the ability of our approach to identify likely successful candidate drugs for repurposing. Our novel approach accelerates drug repurposing for breast cancer by leveraging shared genetics with its known predisposing diseases. The result provides 59 novel candidate drugs alongside biological insights supporting each recommendation.

Fusing global context with multiscale context for enhanced breast cancer classification

Breast cancer is the second most common type of cancer among women. Prompt detection of breast cancer can impede its advancement to more advanced phases, thereby elevating the probability of favorable treatment consequences. Histopathological images are commonly used for breast cancer classification due to their detailed cellular information. Existing diagnostic approaches rely on Convolutional Neural Networks (CNNs) which are limited to local context resulting in a lower classification accuracy. Therefore, we present a fusion model composed of a Vision Transformer (ViT) and custom Atrous Spatial Pyramid Pooling (ASPP) network with an attention mechanism for effectively classifying breast cancer from histopathological images. ViT enables the model to attain global features, while the ASPP network accommodates multiscale features. Fusing the features derived from the models resulted in a robust breast cancer classifier. With the help of five-stage image preprocessing technique, the proposed model achieved 100% accuracy in classifying breast cancer on the BreakHis dataset at 100X and 400X magnification factors. On 40X and 200X magnifications, the model achieved 99.25% and 98.26% classification accuracy respectively. With a commendable classification efficacy on histopathological images, the model can be considered a dependable option for proficient breast cancer classification.

100. Epidemiology of Mandibular Fracture Cases for Mataram University General Surgery Resident Competence in Hospital Education Center

Introduction: WHO (2024) estimates that 20–50 million individuals get non-fatal injuries and over 1.2 million people globally pass away on traffic accidents. craniomaxillofacial fracture cases can be done by multidisciplinary, depend on diagnosis and competence of surgeons. Methods: This study is quantitative descriptive study using medical record data of craniofacial trauma patients NTB Province General Hospital from January 2022 to September 2024, patients who experienced or who had been diagnosed of craniofacial trauma. Results: 388 patients were diagnosed with craniofacial trauma at NTB Province Hospital. There were had 99 lower face fractures, 120 mid face fractures, and 169 with upper face fractures. It was found male gender was more than female, age range of 21-30 years. the 99 patients with mandibular fractures, 66 simple mandibular fractures obtained that could be done by general surgery resident. In 2022-2023, Unram general surgery residents are not yet in the advanced surgical phase, cannot participate in mandibular fracture surgery. But this data can provide an overview that mandibular fracture cases are sufficient in number for they operative cases. Conclusions: This study, there are 66 cases of mandibular os fracture that can be performed operatively by unram general surgery residents according to competence of general surgeons as stated in the Decree Minister of Health. So that can help in help cranio maxilo facial cases in good interdisciplinary cooperation to get optimal results.

Research on jet ignition phases and control parameters in an active pre-chamber optical engine under ultra-lean combustion conditions

The active pre-chamber (APC) jet ignition system is one of the primary technologies for achieving ultra-lean combustion and high thermal efficiency in engines. The impact of the jet process within the engine, as well as its control parameters, on emission pollutants (particularly soot particles) remains unclear. This study focuses on examining the effects of various low-flow injection control strategies on engine combustion and emissions by using optical experiments and numerical simulations. It also explores the impact of different ignition advance angles (ignition timings) based on a short pre-chamber mixing interval to observe ignition combustion, flame propagation, and emission characteristics under ultra-lean conditions (λ = 2.0). The main conclusions are as follows. Appropriately increasing the injection mass can enhance engine load. However, further increases in injection mass significantly raise particulate emissions, resulting in an increase in particle number by up to more than 37-fold, especially for small particles in the 5–––10 nm size range. The chemical reaction between the luminous jet flame and the bright incandescent wake jet flame, as captured by high-speed photography, effectively characterizes the various stages of jet ignition. To reduce particulate matter emissions, it is crucial to avoid the foreseeable wake jet flame caused by the enrichment of the jet mixture in the pre-chamber. The low-flow injection timing should neither be too early nor close to the ignition spark timing. The early injection causes fuel to accumulate at the top of the pre-chamber, hindering the jet flame’s propagation into the main combustion chamber. Late low-flow injection leads to fuel enrichment, resulting in uneven mixing and poor atomization and diffusion due to short mixing times. Ignition after a short mixing time interval tends to increase knocking, resulting in intense combustion and an advanced phase, which slightly reduces load and combustion stability. Regarding the heat release ratio, the total heat release from the two combustion stages in the pre-chamber should ideally account for about 5–6 % of the heat release in the main chamber.

Identification of Urinary Glucose and Urinary Ketones in Pulmonary Tuberculosis Patients Receiving Anti-Tuberculosis Drug Therapy (OAT) at the Tlogosari Wetan Health Center

Tuberculosis is a contagious infection caused by Mycobacterium tuberculosis. Anti-Tuberculosis Drug Therapy (OAT) given also has side effects, one of which is hepatotoxicity. Laboratory examination of urine glucose identification can show if there is damage to the kidney glomerulus in the filtration process. OAT such as isoniazid can affect the breakdown of fat and cause increased ketone production, especially in individuals who have low carbohydrate intake so that if the excess amount will be excreted through urine (ketonuria). The purpose of this study was to identify urine glucose and urinary ketones in non-DM pulmonary TB patients with OAT treatment at the Tlogosari Wetan Health Center based on treatment phase, gender, and age. This type of research is descriptive observational with a cross sectional approach. The study sample was a urine sample from a non-DM pulmonary TB patient. The examination method used is dyeing using a reagent strip test. The results of the study from a total of 30 non-DM pulmonary TB patients with OAT therapy (100%). A total of 6 (20%) patients identified urinary glucose, with details of intensive phase treatment 2 (7%) trace urine glucose patients (±), while in advanced phase 2 (7%) patients identified trace urine glucose (±) and 2 (7%) low urine glucose patients (+1). The majority of positive urine glucose results were experienced by men with vulnerable elderly age (46-65 years) as many as 4 patients (14%). The results of urine ketone identification showed that 2 (6.6%) patients were identified with urine ketones, namely trace (±) in the intensive phase treatment, while 15 patients in the advanced phase of urine ketones were all negative.The majority of positive urinary ketone results were experienced by vulnerable men of adult age (26-45 years) as much as 2 caseins (14%). Conclusion: Of the 30 non-DM pulmonary TB patients with OAT therapy who met the inclusion criteria, there were 6 (20%) patients identified with urinary glucose and 2 (6.6%) patients identified with urinary ketones. The impact of this study is expected to encourage non-DM pulmonary TB patients to take OAT and do regular medical check-ups.

The recent progress of γδ T cells and its targeted therapies in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune condition that mostly impacts the joints. During the advanced phases of the disorder, it may be accompanied by other problems. While the precise cause of RA is uncertain, various research has been conducted to gain a better understanding of the immunological processes involved in the development of RA. T cells are acknowledged as significant contributors to the progression of RA because of their roles in cytokine secretion, antigen presentation, and facilitating B cells in the manufacture of antibodies. γδ T cells are a small subset of T cells that have significant functions in the context of infection and diseases linked with tumors. γδ T cells have been the subject of investigation in autoimmune disorders in recent years. This review focused on the involvement of γδ T lymphocytes in the development of RA. In this article, we provide an analysis of the immunological capabilities of γδ T cells, intending to comprehend their significance in RA, which could be pivotal in the creation of innovative clinical treatments.

A Rare Case of Tremor Induces by Cycloserine in Drug-Resistant Tuberculosis Patient

Background: Tuberculosis is a contagious disease that generated by Mycobacterium tuberculosis. Drug-Resistant tuberculosis (DR-TB) is inculpated the use of the second-line anti-tubercular treatment which is associated with many drug side effects or so called, Adverse Drug Reactions (ADR). Cycloserine (Cs) is an important drug against drug resistant tuberculosis (DR-TB). Cycloserine has been used in tuberculosis therapy since the late 1950s. Identical with most drug, Cycloserine can cause many Adverse Drug Reactions (ADR). Case Illustration: A 23-year-old woman diagnosed with drug-resistant tuberculosis is undergoing long-term treatment. The patient received treatment for DR-TB with the Bdq-Lfx-Cfz-Cs-E regimen. After the patient underwent the 10th month of advanced phase treatment, the patient complained of shaking in both hands (tremors). The tremor is felt to be more severe in the right hand and the patient cannot grip objects tightly. Discussion: Cycloserine (Cs) play an important role in second-line drug management of DR-TB. Cs-Induced psychosis and other neurological side-effects can be detrimental towards patients yet they are rarely reports in DR-TB cases. Cs is correlated with severe psychiatric cases and Central Nervous System related ADRs. Cs-associated ADR is most likely because of production of gamma-aminobutyric acid as a result of inhibition of glutamic decarboxylase. Study Shown that among 132 patients who reported side effects in the cycloserine group, 2 (1.4%) experienced major side effects, namely tremors. Side effects possibly or probably related to Cs appeared after a median of 71 days (range 10–331 days) of Cs treatment. Conclusion: the drug side effects such as tremors are very rare in drug-resistant tuberculosis patients. In this case, the patient's complaint of tremors could be caused by cycloserine as an anti-tuberculosis drug.

Real estate 4.0 – Experiences from the rural

This paper explores the concept of Real Estate 4.0 and how this latest phase of technological advancement is being experienced in rural areas through the medium of digital marketing. In particular, it draws upon the experiences of Estate Agents and how through adopting the latest digital marketing technologies, they can specifically target certain audiences as well as influence the perception of the rural through drawing upon popularised notions of this space, such as the rural idyll.Real Estate 4.0 builds upon the wider industrial developments occurring across the economy, known as the Fourth Industrial Revolution or Industry 4.0, and is characterised by the central role of consumer (Schmitt 2017; Morrar et al. 2017). Taken from a sample of 13 Estate Agencies, which varied in their operational structure and location, this paper examines the latest digital marketing practices being used by estate agents today in the sale of real estate, with reference to three villages in the UK, Great Missenden, Ombersley and Caldbeck. In doing so, it provides much needed research into the different digital marketing practices being used by Estate Agents and contributes towards understandings of how these technologies are being experienced in rural areas.

Health Care Language Models and Their Fine-Tuning for Information Extraction: Scoping Review.

In response to the intricate language, specialized terminology outside everyday life, and the frequent presence of abbreviations and acronyms inherent in health care text data, domain adaptation techniques have emerged as crucial to transformer-based models. This refinement in the knowledge of the language models (LMs) allows for a better understanding of the medical textual data, which results in an improvement in medical downstream tasks, such as information extraction (IE). We have identified a gap in the literature regarding health care LMs. Therefore, this study presents a scoping literature review investigating domain adaptation methods for transformers in health care, differentiating between English and non-English languages, focusing on Portuguese. Most specifically, we investigated the development of health care LMs, with the aim of comparing Portuguese with other more developed languages to guide the path of a non-English-language with fewer resources. This study aimed to research health care IE models, regardless of language, to understand the efficacy of transformers and what are the medical entities most commonly extracted. This scoping review was conducted using the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) methodology on Scopus and Web of Science Core Collection databases. Only studies that mentioned the creation of health care LMs or health care IE models were included, while large language models (LLMs) were excluded. The latest were not included since we wanted to research LMs and not LLMs, which are architecturally different and have distinct purposes. Our search query retrieved 137 studies, 60 of which met the inclusion criteria, and none of them were systematic literature reviews. English and Chinese are the languages with the most health care LMs developed. These languages already have disease-specific LMs, while others only have general-health care LMs. European Portuguese does not have any public health care LM and should take examples from other languages to develop, first, general-health care LMs and then, in an advanced phase, disease-specific LMs. Regarding IE models, transformers were the most commonly used method, and named entity recognition was the most popular topic, with only a few studies mentioning Assertion Status or addressing medical lexical problems. The most extracted entities were diagnosis, posology, and symptoms. The findings indicate that domain adaptation is beneficial, achieving better results in downstream tasks. Our analysis allowed us to understand that the use of transformers is more developed for the English and Chinese languages. European Portuguese lacks relevant studies and should draw examples from other non-English languages to develop these models and drive progress in AI. Health care professionals could benefit from highlighting medically relevant information and optimizing the reading of the textual data, or this information could be used to create patient medical timelines, allowing for profiling.

Enhancing solar flat plate collector efficiency with advanced phase change materials and expanded boron nitride

ABSTRACT Thermal energy storage, particularly through Phase Change Materials (PCMs), is gaining significant attention for its ability to enhance storage capacity and thermal conductivity. PCMs help alleviate the strain on renewable energy sources and stabilize load fluctuations. This study integrates a novel combination of LiNO3-NaSO4·10H2O-NaCl with boron nitride into Flat Plate Collectors (FPCs) to boost system performance. This Composite Phase Change Material (CPCM) increases latent heat value by up to 245.80 kJ, enhancing thermal decomposition and absorption rates while reducing heat losses. Boron nitride improves thermal conductivity by 25%, from 1.378 W/m·K to 5.543 W/m·K, increasing the CPCM's charging rate. The specific heat capacity rises from 4.2 J/g·°C to 5 J/g·°C at a maximum temperature of 90°C. As a result, the collector's efficiency improves by 15%, achieving an overall system efficiency of 88%. Water serves as the heat transfer fluid, and simulations are conducted using Python in Anaconda Jupyter Notebook.

BACE1 Inhibitors for Alzheimer's Disease: Current Challenges and Future Perspectives.

Disease-modifying therapies (DMT) for Alzheimer's disease (AD) are highly longed-for. In this quest, anti-amyloid therapies take center stage supported by genetic facts that highlight an imbalance between production and clearance of amyloid-β peptide (Aβ) in AD patients. Indeed, evidence from basic research, human genetic and biomarker studies, suggests the accumulation of Aβ as a driver of AD pathogenesis and progression. The aspartic protease β-site AβPP cleaving enzyme (BACE1) is the initiator for Aβ production. Underpinning a critical role for BACE1 in AD pathophysiology are the elevated BACE1 concentration and activity observed in the brain and body fluids of AD patients. Therefore, BACE1 is a prime drug target for reducing Aβ levels in early AD. Small-molecule BACE1 inhibitors have been extensively developed for the last 20 years. However, clinical trials with these molecules have been discontinued for futility or safety reasons. Most of the observed adverse side effects were due to other aspartic proteases cross-inhibition, including the homologue BACE2, and to mechanism-based toxicity since BACE1 has substrates with important roles for synaptic plasticity and synaptic homeostasis besides amyloid-β protein precursor (AβPP). Despite these setbacks, BACE1 persists as a well-validated therapeutic target for which a specific inhibitor with high substrate selectivity may yet to be found. In this review we provide an overview of the evolution in BACE1 inhibitors design pinpointing the molecules that reached advanced phases of clinical trials and the liabilities that precluded adequate trial effects. Finally, we ponder on the challenges that anti-amyloid therapies must overcome to achieve clinical success.

Digital transformation of the Centre for Advanced Professional Training of Kuzbass: approaches and solutions

Russian education system is currently undergoing a phase of advancement that is associated with distinctive features of post-industrial society, the main characteristic of which is informatization and digitalization of economy. The efficiency of business processes and the validity (legitimacy) of enterprises and organizations are directly correlated with their digital transformation. These global trends cannot be ignored by these educational organizations. The most untouched issue concerns the creation of digital services for facilitating interaction between educational institutions and the labor market. The purpose of research: development and implementation of the Digital Transformation Strategy of the Centre for Advanced Professional Training (CAPT) of Kuzbass. The leading methods of research include general scientific methods, methods of systematicity and analysis of scientific and methodological literature and regulatory and legal documentation, as well as empirical methods (in the collection, accumulation and recording of data), and rational method (in the interpretation of research data). The article presents the principles and mechanisms of the digital platform interaction with the external environment are described. The author examines the internal conditions for digital services transformation. The necessity of creating and utilizing a digital replica of the HR service of enterprise on the digital platform is substantiated. The presented approaches pertain to the implementation of the Strategy for the development of digital resources of the Centre for Advanced Professional Training of Kuzbass, along with the development of a digital platform with an enhanced version, which is focused on more effective interaction of labour market agents in the region, contribute to the resolution of the most pressing issues of socio-economic development of the region. These techniques can also be applied to employment assistance services and career centers of educational organizations for secondary vocational and higher education.

Identification Of Risk Factors Of Bone Metastasis Among Iraqi Breast Cancer Women

Background: The most common site of metastases in people with breast cancer is bone metastasis. Patients with advanced phases of cancer are associated with an increased prevalence of several types of metastases, one of which is bone metastasis. Object: Assessment of the risk factors for bone metastases in patients with breast cancer. Patients and Methods: This is a retrospective study of 316 patients with breast cancer who either had bone metastases at the time of diagnosis or developed it later on. The study was carried out between January 2013 and April 2018. Three hundred and sixteen patients were assigned into two groups. In the case group, 100 patients with breast cancer had been diagnosed with bone metastasis by CT, MRI, bone scan, and PET scan; in the control group, there were 216 cases in are control group with breast cancer metastasis to sites other than bone. The questionnaire was created to record all factors (with the exception of demographic information), such as age, histopathological reading for invasive lobular carcinoma, invasive ductal carcinoma, or another type of cancer, ER status, PR status, Her2neu status, lymph node status and stage, and menopausal status. Results: The majority were 45 years of age or younger, and 96.5% of them had invasive ductal carcinoma in terms of hormonal status. Positive ER and PR status is found in 67.7% and 67.1% of the cases, respectively; 40.5% of the cases had amplified Her2neu receptors, 78.5% of the cases had positive lymph nodes, and 41.9% of the cases had (N1) stage. The highest proportion of bone metastasis was associated with negative ER and PR receptors (46.2% and 49%, respectively), while no significant statistical association (P= 0.65). Conclusion: negative ER, PR status, and Her2neu receptors not amplified, lymph node involvement, age 45 and less, infiltrating lobular carcinoma (ILC) histological type, and menopausal state are significant risk factors for bone metastasis in breast cancer.

Exploring the genetic expression of Sdf1, Foxc1 and histologic changes following mandibular advancement and recovery phase in Wistar rats.

PurposeThis study evaluated the impact of mandibular advancement on Sdf1 and Foxc1 gene expression in the mandibular condylar cartilage of young Wistar rats. By examining the changes that occur during a unique one-month recovery period, it highlights the critical role of gene expression and condylar adaptation during the recovery phase. The analysis focused on whether, during the recovery period, reversal changes occur when functional appliances are removed and whether genetic expression important for condyle growth and adaptation downregulates. Material and MethodsThe study involved 30 male Wistar rats divided into 2 control groups Appliance Control and Recovery Control groups, and 2 experimental groups, the Appliance group with mandibular advancement bite-jumping appliance for 30 days, and the Recovery group with appliance for 30 days followed by a 30-day recovery. Molecular analysis of condylar cartilage using real-time RT-PCR and histological assessments was conducted. ResultsSignificant genetic expression alterations were noted in both the experimental groups for Sdf1 (p < 0.05) and Foxc1 (p < 0.05). According to histological investigations, significant alterations with an increase in the proliferative and hypertrophic layer in condylar cartilage were seen. ConclusionMandibular advancement bite-jumping appliances induce proliferative and hypertrophic layer changes in mandibular condylar cartilage, shown by elevated Foxc1 levels and decreased Sdf1 levels. Post-appliance removal, persistent gene expression reveals a true joint stimulation.

Sleep disorders in cancer patients during systemic therapy

Aim: The aim of this study was to investigate the frequency, quantity and quality of subjective sleep problems, and their correlation with accompanying factors in cancer patients undergoing systemic therapy. Materials and methods: The study included 100 patients – 50 females and 50 males – undergoing oncological treatment who filled out an anonymous questionnaire specifically designed for this research. Results: 88% of the respondents reported the duration of sleep in the range of 5 to 9 hours. 48% of the respondents declared a deterioration in the quality of sleep after the diagnosis of cancer. Following the onset of sleep problems, 66% of respondents did not pursue any treatment. Among the examined patients, symptoms of insomnia were reported by 18%, and symptoms of hypersomnia – by 6%. Mixed sleep disorders were reported by 11% of respondents. The patients undergoing surgical treatment reported a statistically significantly lower quality of sleep compared to the patients not undergoing surgery (median score in the quantitative scale 6 vs. 7 on a scale of 1–10, where 1 indicated the worst quality of sleep and 10 indicated the best quality of sleep; p = 0.04). A very small percentage of patients sought pharmacotherapy or specialist help for sleep disorders, which precludes drawing statistically significant conclusions about the impact of these interventions on sleep quality. Conclusions: Sleep problems are often reported by patients during oncological treatment (48%). The main sleep-related complaints were advanced sleep phase disorders. Due to the frequent occurrence of sleep disorders among patients, it is important to conduct a thorough medical interview to diagnose them and implement appropriate treatment.

The Relationship Between Glycemic Control And Lipid Profile In Patients With Type 2 Diabetes Mellitus In Bangli Hospital

Type 2 diabetes mellitus (DM) is prone to diabetic dyslipidemia which is one of the factors in increasing the risk of cardiovascular disease complications. The purpose of this study was to determine the relationship between glycemic control and lipid profile in patients with type 2 DM. Research with a cross-sectional study was conducted at the Internal Medicine Polyclinic of Bangli Hospital in the period January 2023-December 2023 and as many as 60 patients with type 2 DM who met the inclusion criteria. Patients were grouped into type 2 DM patients with controlled glycemic control (HbA1c &lt;7%) and uncontrolled (HbA1c ≥7%). Lower levels of total cholesterol (160,444 ± 30,608 mg/dl vs 203,476 ± 45,471 mg/dl; p = 0.001), triglycerides (125,500 ± 56,019 vs 202,047 ± 91,568; p = 0.002), low-density lipoprotein (K-LDL) (93,072 ± 28,443 vs 131,571 ± 44,590; p = 0.001) in type 2 DM patients with controlled glycemic control. High-density lipoprotein (K-HDL) levels (50,022 ± 14,050 vs 41,152 ± 12,619; p = 0.019) were higher in type 2 DM patients with controlled glycemic control. Statistical tests showed a positive correlation between total cholesterol (r = 0.277; p = 0.032), triglyceride (r = 0.386; p = 0.002) and K-LDL (r = 0.357; p = 0.005) levels with HbA1c levels. There was a negative correlation between K-HDL (r=-0.366; p=0.004) and HbA1c levels. The significant correlation between HbA1c and lipid profile shows the importance of glycemic control in type 2 DM patients. This can be explained in the pathogenesis of type 2 DM during the advanced phase. There was a positive correlation between glycemic control (HbA1c) with total cholesterol, triglycerides and K-LDL. There is a negative correlation between glycemic control (HbA1c) and K-HDL.

Efficacy of digital brief behavioural treatment for insomnia using a smartphone application in conjunction with light therapy in university students with insomnia symptoms with late chronotypes: A pilot randomized-controlled trial.

The efficacy of digital brief behavioural treatment for insomnia using a smartphone application in conjunction with light therapy was investigated in university students who had insomnia symptoms with late chronotypes. In this two-arm parallel randomized-controlled trial, participants with insomnia symptoms and late chronotypes were recruited between October and November 2023. The duration of the intervention program was 4 weeks. The smartphone application provides digital brief behavioural treatment for insomnia, including programs for advanced phases. The intervention group used blue-light-emitting diode glasses in the morning after waking up for 2-4 weeks. The primary outcome was a change in the Insomnia Severity Index during the study period. The Insomnia Severity Index was obtained weekly using a web questionnaire. Of the 28 students, 14 each were assigned to the intervention and control groups. The mean Insomnia Severity Index scores at baseline were 12.2 and 12.5; after 4 weeks, they declined to 7.2 and 10.6 in the intervention and control groups, respectively. Primary analysis using a linear mixed model showed a significant improvement in the temporal trends of the Insomnia Severity Index in the intervention group (p < 0.001). The scores on the Morningness-Eveningness Questionnaire (p = 0.008) and RU-SATED (p = 0.005) significantly improved in the intervention group relative to the control group following the intervention. This study demonstrated the effectiveness of the digital brief behavioural treatment for insomnia with light therapy in participants with both insomnia symptoms and late chronotypes.

Combined Association of Depression Interms of Gender Along with Academic Classes of Students

Every person have life experiences with variety of shifts ,turning points and stress during advancement phase of their life. College students are especially susceptible to stress since they are going through both personal and social changes. Among college students depression is becoming more and more prominent globally. The objective of this study was to show depression association interms of gender college students over the academic years (1st year and second year)students. In First year class out of 58 males (Non depression 12 and with depression 46) and out of 42 female (Non depression 22 and with depression 20) and in second year out of 42 males ( Non depression 19 and with depression 23 and out of 58 females (Non depression 41 and with depression17), Our result showed that depression is significantly associated with gender of students along their different academic classes (1st year and 2nd year ) chi square 29.72 (p&lt;0.05).

Advanced Phase Diversity Method for telescope static aberration compensation

Accurate calibration is essential for high-performance Adaptive Optics (AO) systems in astronomy. This paper presents a novel methodology for AO systems calibration that preserves the optical path integrity while achieving high-quality results. By eliminating the need for optical modifications, this approach simplifies system complexity and accounts for all static aberrations. The main novelty of this proposal is an advanced Phase Diversity (PD) method for estimating static optical aberrations. Unlike conventional PD techniques, this approach uses the AO system’s deformable mirror to introduce different diversities, eliminating the need for additional calibration hardware. Furthermore, the optimizer Adam is introduced for the first time in this field to estimate the optical aberrations. To evaluate the performance of this new methodology, a set of experiments under varying operating conditions and optimization parameters has been conducted. Results demonstrated that the presented methodology is capable of providing diffraction-limited corrected images with a Strehl Ratio (SR) exceeding 0.80 within 2 min. Furthermore, employing a Manhattan distance-based error function effectively balanced estimation speed and accuracy. The method demonstrated effectiveness across a wide range of aberration magnitudes, achieving an error of 3 nm in the best scenarios. This proposal represents an advancement in the identification and correction of static aberrations in telescope optical systems, directly improving the acquisition of high-quality references for AO sensing.

Decitabine, venetoclax, and ponatinib for advanced phase chronic myeloid leukaemia and Philadelphia chromosome-positive acute myeloid leukaemia: a single-arm, single-centre phase 2 trial

Advanced phase Philadelphia chromosome-positive myeloid disease-consisting of chronic myeloid leukaemia in the myeloid blast phase and in the accelerated phase, and Philadelphia chromosome-positive acute myeloid leukaemia-is associated with poor outcomes. Although previous studies have suggested the benefit of chemotherapy and BCR::ABL1 tyrosine kinase inhibitor combinations, the optimal regimen is uncertain and prospective studies for this rare group of diseases are scant. Preclinical and retrospective clinical data suggest possible synergy between the BCL-2 inhibitor venetoclax and BCR::ABL1 tyrosine kinase inhibitors. We therefore aimed to design a study to evaluate the safety and activity of a novel combination of decitabine, venetoclax, and the third-generation BCR::ABL1 tyrosine kinase inhibitor ponatinib in advanced phase Philadelphia chromosome-positive myeloid diseases. For this phase 2 study, patients aged 18 years or older with previously untreated or relapsed or refractory myeloid chronic myeloid leukaemia-blast phase, chronic myeloid leukaemia-accelerated phase, or advanced phase Philadelphia chromosome-positive acute myeloid leukaemia, and an Eastern Cooperative Oncology Group performance status of 0-3 were eligible. Patients were eligible regardless of the number of previous lines of therapy received or previous receipt of ponatinib. Cycle 1 (induction) consisted of a 7-day lead-in of ponatinib 45 mg orally daily (days 1-7), followed by combination therapy with decitabine 20 mg/m2 intravenously on days 8-12, venetoclax orally daily with ramp-up to a maximum dose of 400 mg on days 8-28, and ponatinib 45 mg orally daily on days 8-28. Cycles 2-24 consisted of decitabine 20 mg/m2 intravenously on days 1-5, venetoclax orally 400 mg on days 1-21, and ponatinib orally daily on days 1-28. Response-based dosing of ponatinib was implemented in consolidation cycles, with reduction to 30 mg daily in patients who reached complete remission or complete remission with an incomplete haematological recovery and a reduction to 15 mg daily in patients with undetectable BCR::ABL1 transcripts. The primary endpoint was the composite rate of complete remission or complete remission with incomplete haematological recovery in the intention-to-treat population. Safety was assessed in the intention-to-treat population. This trial was registered with ClinicalTrials.gov (NCT04188405) and is still ongoing. Between July 12, 2020, and July 8, 2023, 20 patients were treated (14 with chronic myeloid leukaemia-blast phase, four with chronic myeloid leukaemia-accelerated phase, and two with advanced phase Philadelphia chromosome-positive acute myeloid leukaemia). The median age was 43 years (IQR 32-58); 13 (65%) patients were male and seven (35%) were female; and 12 (60%) were White, three (15%) were Hispanic, four (20%) were Black, and one (5%) was Asian. 12 (60%) patients had received 2 or more previous BCR::ABL1 tyrosine kinase inhibitors, and 14 (70%) patients had at least one high-risk additional chromosomal abnormality or complex karyotype. The median duration of follow-up was 21·2 months (IQR 14·1-24·2). The complete remission or complete remission with an incomplete haematological recovery rate was 50% (10 of 20 patients); complete remission in one [5%] patient and complete remission with incomplete haematological recovery in nine [45%]). An additional six (30%) patients had a morphologic leukaemia-free state. The most common grade 3-4 non-haematological adverse events were febrile neutropenia in eight (40%) patients, infection in six (30%), and alanine or aspartate transaminase elevation in five (25%). Eight (40%) patients had at least one cardiovascular event of any grade. There were three on-study deaths, none of which was considered related to the study treatment and all from infections in the setting of refractory leukaemia. The combination of decitabine, venetoclax, and ponatinib is safe and shows promising activity in patients with advanced phase chronic myeloid leukaemia, including those with multiple previous therapies or high-risk disease features. Further studies evaluating chemotherapy and venetoclax-based combination strategies using newer-generation BCR::ABL1 tyrosine kinase inhibitors are warranted. Takeda Oncology, the National Institutes of Health, and the National Cancer Institute Cancer Center.