Miracle-dz/UniFAR-FTUs huggingface dataset:
A Real-World Evidence-Based Study of Long-Term Tyrosine Kinase Inhibitors Dose Reduction or Discontinuation in Patients with Chronic Myeloid Leukaemia

The therapeutic approach to chronic myeloid leukaemia (CML) has changed in recent years. As a result, a high percentage of current patients in the chronic phase of the disease almost have an average life expectancy. Treatment also aims to achieve a stable deep molecular response (DMR) that might allow dose reduction or even treatment discontinuation. These strategies are often used in authentic practices to reduce adverse events, yet their impact on treatment-free remission (TFR) is a controversial debate. In some studies, it has been observed that as many as half of patients can achieve TFR after the discontinuation of TKI treatment. If TFR was more widespread and globally achievable, the perspective on toxicity could be changed. We retrospectively analysed 80 CML patients treated with tyrosine kinase inhibitor (TKI) at a tertiary hospital between 2002 and 2022. From them, 71 patients were treated with low doses of TKI, and 25 were eventually discontinued, 9 of them being discontinued without a previous dose reduction. Regarding patients treated with low doses, only 11 of them had molecular recurrence (15.4%), and the average molecular recurrence free survival (MRFS) was 24.6 months. The MRFS outcome was not affected by any of the variables examined, including gender, Sokal risk scores, prior treatment with interferon or hydroxycarbamide, age at the time of CML diagnosis, the initiation of low-dose therapy and the mean duration of TKI therapy. After TKI discontinuation, all but four patients maintained MMR, with a median follow-up of 29.2 months. In our study, TFR was estimated at 38.9 months (95% CI 4.1–73.9). This study indicates that low-dose treatment and/or TKI discontinuation is a salient, safe alternative to be considered for patients who may suffer adverse events (AEs), which hinder the adherence of TKI and/or deteriorate their life quality. Together with the published literature, it shows that it appears safe to administer reduced doses to patients with CML in the chronic phase. The discontinuation of TKI therapy once a DMR has been reached is one of the goals for these patients. The patient should be assessed globally, and the most appropriate strategy for management should be considered. Future studies are needed to ensure that this approach is included in clinical practice because of the benefits for certain patients and the increased efficiency for the healthcare system.
An Adaptive TTT Handover (ATH) Mechanism for Dual Connectivity (5G mmWave—LTE Advanced) during Unpredictable Wireless Channel Behavior

Fifth Generation (5G) signals using the millimeter wave (mmWave) spectrums are highly vulnerable to blockage due to rapid variations in channel link quality. This can cause the devices or User Equipment (UE) to suffer from connection failure. In a dual connectivity (DC) network, the channel’s intermittency issues were partially solved by maintaining the UE’s connectivity to primary (LTE advanced stations) and secondary (5G mmWave stations) simultaneously. Even though the dual-connected network performs excellently in maintaining connectivity, its performance drops significantly due to the inefficient handover from one 5G mmWave station to another. The situation worsens when UE travels a long distance in a highly dense obstacle environment, which requires multiple ineffective handovers that eventually lead to performance degradation. This research aimed to propose an Adaptive TTT Handover (ATH) mechanism that deals with unpredictable 5G mmWave wireless channel behaviors that are highly intermittent. An adaptive algorithm was developed to automatically adjust the handover control parameters, such as Time-to-Trigger (TTT), based on the current state of channel condition measured by the Signal-to-Interference-Noise Ratio (SINR). The developed algorithm was tested under a 5G mmWave statistical channel model to represent a time-varying channel matrix that includes fading and the Doppler effect. The performance of the proposed handover mechanism was analyzed and evaluated in terms of handover probability, latency, and throughput by using the Network Simulator 3 tool. The comparative simulation result shows that the proposed adaptive handover mechanism performs excellently compared to conventional handovers and other enhancement techniques.
Central sensitization in osteoarthritic knee pain: A cross-sectional study

Objectives The aim of this study was to investigate central sensitization and associated factors in knee osteoarthritis (OA) patients and compare them with rheumatoid arthritis (RA) patients and healthy controls. Patients and methods This cross-sectional study was conducted with 125 participants (7 males, 118 females; mean age: 57.2±8.2 years; range, 45 to 75 years) between January 2017 and December 2018. Sixty-two patients with symptomatic knee OA, 32 RA patients with knee pain, and 31 healthy controls constituted the participants. Central sensitization was investigated with the Central Sensitization Inventory (CSI) and pressure pain threshold (PPT) measurements. Pain, functional status, and psychosocial features were assessed with self-reported questionnaires. Results The OA and RA groups had significantly lower PPT values at local, peripheral, and remote regions compared to the healthy controls. Pressure hyperalgesia was shown at the knee with a 43.5% prevalence, 27.4% at the leg, and 8.1% at the forearm of OA patients. Pressure hyperalgesia was present at the knee, leg, and forearm in 37.5%, 25%, and 9.4% of RA patients, respectively. Pressure pain threshold values, CSI scores, frequency of pressure hyperalgesia, and frequency of central sensitization according to the CSI were not statistically different between the OA and RA groups. Psychosocial features and structural damage were not correlated with PPT values in the OA group. Conclusion The severity of chronic pain and functional status may be the clinical clues to recognizing patients with central sensitization since local joint damage does not play a direct role in the etiopathogenesis of central sensitization in OA patients and severe pain persisting in the chronic process is associated with central sensitization regardless of the pathogenesis.
Rationale and design of the SenseWhy project: A passive sensing and ecological momentary assessment study on characteristics of overeating episodes

Objectives Overeating interventions and research often focus on single determinants and use subjective or nonpersonalized measures. We aim to (1) identify automatically detectable features that predict overeating and (2) build clusters of eating episodes that identify theoretically meaningful and clinically known problematic overeating behaviors (e.g., stress eating), as well as new phenotypes based on social and psychological features. Method Up to 60 adults with obesity in the Chicagoland area will be recruited for a 14-day free-living observational study. Participants will complete ecological momentary assessments and wear 3 sensors designed to capture features of overeating episodes (e.g., chews) that can be visually confirmed. Participants will also complete daily dietitian-administered 24-hour recalls of all food and beverages consumed. Analysis Overeating is defined as caloric consumption exceeding 1 standard deviation of an individual's mean consumption per eating episode. To identify features that predict overeating, we will apply 2 complementary machine learning methods: correlation-based feature selection and wrapper-based feature selection. We will then generate clusters of overeating types and assess how they align with clinically meaningful overeating phenotypes. Conclusions This study will be the first to assess characteristics of eating episodes in situ over a multiweek period with visual confirmation of eating behaviors. An additional strength of this study is the assessment of predictors of problematic eating during periods when individuals are not on a structured diet and/or engaged in a weight loss intervention. Our assessment of overeating episodes in real-world settings is likely to yield new insights regarding determinants of overeating that may translate into novel interventions.
Stem Cell Origin of Cancer: Implications of Oncogenesis Recapitulating Embryogenesis in Cancer Care

Simple Summary Often enough, revelation of an aberrant developmental process coincides with manifestation of the malignant process. This is the essence of oncology recapturing ontogeny. This is the epiphany of tumorigenesis recapitulating embryogenesis. When embryonic processes resurface and resurge in an adult person, something is amiss. It is a telltale sign and an unmistakable hallmark of cancer. In many instances, it is a clue to the malignant tumors’ stem-cell origins. When a developmental milestone is being improperly and inopportunely expressed in a fully grown individual, something is awry. This pivotal observation is fundamental to the idea that cancer is a stem-cell disease. It is key to unlocking the stem-cell and a unified theory of cancers. Abstract From this perspective, we wonder about the clinical implications of oncology recapturing ontogeny in the contexts of neoantigens, tumor biomarkers, and cancer targets. We ponder about the biological ramifications of finding remnants of mini-organs and residuals of tiny embryos in some tumors. We reminisce about classical experiments showing that the embryonic microenvironment possesses antitumorigenic properties. Ironically, a stem-ness niche—in the wrong place at the wrong time—is also an onco-niche. We marvel at the paradox of TGF-beta both as a tumor suppressor and a tumor promoter. We query about the dualism of EMT as a stem-ness trait engaged in both normal development and abnormal disease states, including various cancers. It is uncanny that during fetal development, proto-oncogenes wax, while tumor-suppressor genes wane. Similarly, during cancer development, proto-oncogenes awaken, while tumor-suppressor genes slumber. Importantly, targeting stem-like pathways has therapeutic implications because stem-ness may be the true driver, if not engine, of the malignant process. Furthermore, anti-stem-like activity elicits anti-cancer effects for a variety of cancers because stem-ness features may be a universal property of cancer. When a fetus survives and thrives despite immune surveillance and all the restraints of nature and the constraints of its niche, it is a perfect baby. Similarly, when a neoplasm survives and thrives in an otherwise healthy and immune-competent host, is it a perfect tumor? Therefore, a pertinent narrative of cancer depends on a proper perspective of cancer. If malignant cells are derived from stem cells, and both cells are intrinsically RB1 negative and TP53 null, do the absence of RB1 and loss of TP53 really matter in this whole narrative and an entirely different perspective of cancer?
Annual Prevalence of Opioid Receipt by South Carolina Medicaid-Enrolled Children and Adolescents: 2000–2020

Understanding patterns of opioid receipt by children and adolescents over time and understanding differences between age groups can help identify opportunities for future opioid stewardship. We conducted a retrospective cohort study, using South Carolina Medicaid data for children and adolescents 0–18 years old between 2000–2020, calculating the annual prevalence of opioid receipt for medical diagnoses in ambulatory settings. We examined differences in prevalence by calendar year, race/ethnicity, and by age group. The annual prevalence of opioid receipt for medical diagnoses changed significantly over the years studied, from 187.5 per 1000 in 2000 to 41.9 per 1000 in 2020 (Cochran–Armitage test for trend, p < 0.0001). In all calendar years, older ages were associated with greater prevalence of opioid receipt. Adjusted analyses (logistic regression) assessed calendar year differences in opioid receipt, controlling for age group, sex, and race/ethnicity. In the adjusted analyses, calendar year was inversely associated with opioid receipt (aOR 0.927, 95% CI 0.926–0.927). Males and older ages were more likely to receive opioids, while persons of Black race and Hispanic ethnicity had lower odds of receiving opioids. While opioid receipt declined among all age groups during 2000–2020, adolescents 12–18 had persistently higher annual prevalence of opioid receipt when compared to younger age groups.
Telmisartan Is a Promising Agent for Managing Neuropathic Pain and Delaying Opioid Analgesic Tolerance in Rats

Despite the large arsenal of analgesic medications, neuropathic pain (NP) management is not solved yet. Angiotensin II receptor type 1 (AT1) has been identified as a potential target in NP therapy. Here, we investigate the antiallodynic effect of AT1 blockers telmisartan and losartan, and particularly their combination with morphine on rat mononeuropathic pain following acute or chronic oral administration. The impact of telmisartan on morphine analgesic tolerance was also assessed using the rat tail-flick assay. Morphine potency and efficacy in spinal cord samples of treated neuropathic animals were assessed by [35S]GTPγS-binding assay. Finally, the glutamate content of the cerebrospinal fluid (CSF) was measured by capillary electrophoresis. Oral telmisartan or losartan in higher doses showed an acute antiallodynic effect. In the chronic treatment study, the combination of subanalgesic doses of telmisartan and morphine ameliorated allodynia and resulted in a leftward shift in the dose–response curve of morphine in the [35S]GTPγS binding assay and increased CSF glutamate content. Telmisartan delayed morphine analgesic-tolerance development. Our study has identified a promising combination therapy composed of telmisartan and morphine for NP and opioid tolerance. Since telmisartan is an inhibitor of AT1 and activator of PPAR-γ, future studies are needed to analyze the effect of each component.
Studying Genetic Diversity and Relationships between Mountainous Meihua Chickens Using Mitochondrial DNA Control Region

The Mountainous Meihua chicken is a unique regional germplasm resource from Tongjiang County, Bazhong City, China, but its genetic structure and evolutionary relationships with other native chicken breeds in the Sichuan region remain unclear. Here, we analyzed a total of 469 sequences, including 199 Mountainous Meihua chicken sequences generated in this study, together with 30 sequences representing 13 clades and 240 sequences from seven different Sichuan local chicken breeds downloaded from NCBI. These sequences were further used to analyze genetic diversity, patterns of population differentiation, and phylogenetic relationships between groups. We show that Mountainous Meihua chicken mtDNA sequences have high haplotypic and nucleotide diversity (0.876 and 0.012, respectively) and with a T bias that is suggestive of good breeding potential. Phylogenetic analysis showed that Mountainous Meihua chickens belong to clades A, B, E, and G and have a low affinity to other chicken breeds, with a moderate degree of differentiation. A non-significant Tajima’s D indicates that no demographic expansions occurred in the past. Finally, the four maternal lineages identified in Mountainous Meihua chicken showed unique genetic characteristics.
On the Order and Accuracy of Operator Splitting for a Fluid-Structure Interaction Problem

The purpose of the present work is to study the time splitting error for a fluid-structure interaction problem. We study the problem in a radial geometry where the model is reduced to a system of ordinary differential equations (ODEs) that can be solved to any desired accuracy. We apply Godunov and Strang splitting in time, and find the splitting error to be of order one and two respectively. Several splitting schemes of both kinds are implemented in order to study the accuracy. In conclusion, fluid-structure interaction codes could gain order of consistency at little extra computational cost by utilising Strang splitting.
Olfactory hallucinations caused by an unruptured posterior communicating artery aneurysm improved by clipping: A case report with literature review

Background: Unruptured cerebral aneurysms that lead to epilepsy are rare and olfactory hallucinations caused by such an aneurysm are extremely rare. Various treatments have been proposed, including wrapping, clipping with or without cortical resection, and coil embolization, but there is no consensus on the best approach. Case Description: We present a case of a 69-year-old female who experienced olfactory hallucinations caused by a posterior communicating artery aneurysm and was treated with clipping without cortical resection, with a positive outcome. Conclusion: According to our knowledge, there has been only one report of a posterior communicating artery aneurysm presenting with olfactory hallucinations has been reported, where clipping and cortical resection were performed. This is the first report of a posterior communicating artery aneurysm with olfactory hallucinations that was effectively treated with clipping alone. There have been a few similar reports of large middle cerebral artery aneurysms, most of which are believed to be caused by entorhinal cortex compression. Although a definitive treatment protocol for this condition remains elusive, we suggest that elimination of the pulsatile compressive stress exerted on the cerebral cortex through surgical clipping or coil embolization is crucial for achieving efficacious seizure management.
Can the Reform of Rural Collective Property Rights System Improve Agricultural Total Factor Productivity?

Based on the theory of property rights and division of labor, this paper constructs the mechanism of rural collective property rights system reform to promote agricultural total factor productivity (TFP). And using PSM-DID analysis of the impact of the reform on agricultural TFP. The results show that the reform has improved the agricultural TFP. This study is beneficial to objectively evaluate the effect of rural collective property right system reform, and is of great significance to explore the focus and key path of the new round of reform under the background of common prosperity.
Ergodic averages, correlation sequences, and sumsets

The study of multiple ergodic averages and multiple correlation sequences was initiated by Furstenberg to give an ergodic-theoretic proof of Szemerédi’s theorem on arithmetic progressions. In this dissertation we generalize some of the recent results on multiple ergodic averages and correlation sequences. We also apply some of the techniques from the study of multiple ergodic averages as a means of generalizing some of the recent results on sumsets in infinite groups.
Beta-Glucans of Cereals: Functional and Technological Properties

β-glucans are a polymeric dietary fiber characterized by β-(1,3) and β-(1,4) glycosidic bonds between glucose monomers. They are often used as thickeners, stabilizers, and fat substitutes in foods. The functional and technological quality of β-glucans is attributed to their origin/source, molecular weight, and structural properties. In particular, physical treatments such as drying, cooking, freezing, and refrigeration influence their molecular, morphological, and rheological characteristics. In addition to their useful technical qualities, β-glucans are recognized for their numerous beneficial impacts on human health. For this reason, the European Food Safety Authority (EFSA) has provided a positive opinion on health claims such as cholesterol lowering and hypoglycemic properties relating to oats and barley β-glucans. This paper provides insight into the properties of β-glucans and different treatments affecting their characteristics and then reviews the latest research on β-glucans as a functional ingredient for people with type 2 diabetes mellitus (T2DM).
Perception of Melodic and Harmonic Intonation of Two-Part Musical Fragments

Short musical fragments consisting of a melody part and a synchronous bass part were mistuned in various ways and in various degrees. Mistuning was applied to the harmonic intervals between simultaneous tones in melody and bass (harmonic mistuning), which caused at the same time a mistuning of the melodic intervals between successive tones in the melody part (melodic mistuning of melody) and/or the bass part (melodic mistuning of bass part). The fragments were presented to musically trained subjects for judgments of the perceived quality of intonation. Results showed that the melodic mistuning of the melody parts had the largest disturbing effects on the perceived quality of intonation, followed closely by the harmonic mistuning. Melodic mistuning of the bass was less influential. It could be reasoned that the deviating interval size was probably of more importance in the perception of harmonic mistuning than the presence of beats.
Ageing People Living with HIV/AIDS, PLWHA; More Dental Challenges; the Romanian Dental Professional’s Point of View

Background: In Romania, HIV (human immunodeficiency virus) and AIDS (acquired immunodeficiency syndrome) were first acknowledged in 1989. Getting older with HIV/AIDS is now possible due to antiretroviral treatment, but it can bring dental problems due to HIV itself or to the reluctance of dental professionals to treat dental problems. Our study aims to assess the attitudes, knowledge, and practices of Romanian dental professionals regarding aging PLWHA. Methods: An analytical cross-sectional observational survey based on a self-administered questionnaire was conducted for Romanian dental professionals from October 2022 to January 2023. Results: The responders’ group profile was as follows: a mean age of 39.09 ± 0.36 years (limit: 19–75), a majority of 991 (90.01%) from urban dental offices, and 364 (33.06%) with more than twenty years’ experience. A total of 517 (46.95%) responders had an unprofessional attitude and declared that, if possible, they would avoid taking part in performing dental treatments for people living with HIV/AIDS (PLWHA). There were 89 (8.08%) dental professionals that refused to work with PLWHA. Only 363 (32.97%) had worked with one previously. The dental professionals in rural areas refused PLWHA more frequently: 20% (N = 22) of rural dental professionals vs. 6.76% (N = 67) of urban dental professionals refused to work with PLWHA (OR = 0.30; 95% CI: 0.16-.56). The logistic regression applied for the 1101 responders revealed after stepwise selection that the most influential factor for their refusal to work with PLWHA in our study group was being previously exposed to HIV during dental practice (OR = 14.45; 95% CI: 8.55- 24.42; p = 0.000). Conclusions: Dental educators and health care planners should promote the knowledge of prophylaxis and positive attitudes towards the treatment of PLWHA. Successful resolution of these concerns is time consuming and expensive but necessary if dentists are to satisfy their professional obligations to HIV/AIDS patients.
Non-homogeneously paced random records and associated extremal processes

A study is made of the extremal process generated by i.i. d. random variables appearing at the events of a non-homogeneous Poisson process, 𝒫. If 𝒫 has an exponentially increasing rate function, then records eventually occur in a homogeneous Poisson process. The size of the latest record has a classical extreme value distribution.