Miracle-dz/UniFAR-FTUs huggingface dataset:
Tirzepatide for the treatment of adults with type 2 diabetes: An endocrine perspective

Tirzepatide is a novel glucose‐dependent insulinotropic polypeptide/glucagon‐like peptide 1 (GLP‐1) receptor agonist approved in the United States as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes and under investigation for use in chronic weight management, major adverse cardiovascular events and the management of other conditions, including heart failure with preserved ejection fraction and obesity and non‐cirrhotic non‐alcoholic steatohepatitis. The Phase 3 SURPASS 1‐5 clinical trial programme was designed to assess efficacy and safety of once‐weekly subcutaneously injected tirzepatide (5, 10 and 15 mg), as monotherapy or combination therapy, across a broad spectrum of people with type 2 diabetes. Use of tirzepatide in clinical studies was associated with marked reductions of glycated haemoglobin (−1.87 to −2.59%, −20 to −28 mmol/mol) and body weight (−6.2 to −12.9 kg), as well as reductions in parameters commonly associated with heightened cardiometabolic risk such as blood pressure, visceral adiposity and circulating triglycerides. In SUPRASS‐2, these reductions were greater than with the GLP‐1 receptor agonist semaglutide 1 mg. Tirzepatide was well tolerated, with a low risk of hypoglycaemia when used without insulin or insulin secretagogues and showed a generally similar safety profile to the GLP‐1 receptor agonist class. Accordingly, evidence from these clinical trials suggests that tirzepatide offers a new opportunity for the effective lowering of glycated haemoglobin and body weight in adults with type 2 diabetes.
An attention-based temporal convolutional network for rodent sleep stage classification across species, mutants and experimental environments with single-channel electroencephalogram

Objective. Sleep perturbation by environment, medical procedure and genetic background is under continuous study in biomedical research. Analyzing brain states in animal models such as rodents relies on categorizing electroencephalogram (EEG) recordings. Traditionally, sleep experts have classified these states by visual inspection of EEG signatures, which is laborious. The heterogeneity of sleep patterns complicates the development of a generalizable solution across different species, genotypes and experimental environments. Approach. To realize a generalizable solution, we proposed a cross-species rodent sleep scoring network called CSSleep, a robust deep-learning model based on single-channel EEG. CSSleep starts with a local time-invariant information learning convolutional neural network. The second module is the global transition rules learning temporal convolutional network (TRTCN), stacked with bidirectional attention-based temporal convolutional network modules. The TRTCN simultaneously captures positive and negative time direction information and highlights relevant in-sequence features. The dataset for model evaluation comprises the single-EEG signatures of four cohorts of 16 mice and 8 rats from three laboratories. Main results. In leave-one-cohort-out cross-validation, our model achieved an accuracy of 91.33%. CSSleep performed well on generalization across experimental environments, mutants and rodent species by using single-channel EEG. Significance. This study aims to promote well-standardized cross-laboratory sleep studies to improve our understanding of sleep. Our source codes and supplementary materials will be disclosed later.
On the computational complexity of inferring evolutionary trees

The process of reconstructing evolutionary trees can be viewed formally as an optimization problem. Recently, decision problems associated with the most commonly used approaches to reconstructing such trees have been shown to be NP-complete [Day87, DJS86, DS86, DS87, GF82, Kri88, KM86]. In this thesis, a framework is established that incorporates all such problems studied to date. Within this framework, the NP-completeness results for decision problems are extended by applying theorems from [CT91, Gas86, GKR02, GKR92, JVV86, KST89, Kre88, Sel91] to derive bounds on the computational complexity of several functions associated with each of these problems, namely -- • evaluation functions, which return the cost of the optimal tree(s), -- • solution functions, which return an optimal tree, -- • spanning functions, which return the number of optimal trees, -- • enumeration functions, which systematically enumerate all optimal trees, and -- • random-selection functions, which return a randomly-selected member of the set of optimal trees. -- Where applicable, bounds are also presented for the versions of these functions that are restricted to trees of a given cost or of cost less than or greater than a given limit. Based in part on these results and theorems from [BH90, GJ79, KMB81, Kre88], bounds are derived on how closely polynomial-time algorithms can approximate optimal trees. In particular, it is shown using the recent results of [ALMSS92] that no phylogenetic inference optimal-cost solution problem examined in this thesis has a polynomial-time approximation scheme unless P = NP.
Study of Serum Ferritin, Zinc, and Copper Levels in Children With Helicobacter pylori Gastritis and the Effect of the Treatment

Objectives: This study aimed to assess serum iron, zinc, and copper in symptomatic children with Helicobacter pylori infection, to correlate their serum levels with the degree of gastritis, and to evaluate the effect of H. pylori treatment on their levels. Methods: This study was carried out on 70 children with upper gastrointestinal tract symptoms. H. pylori infection was diagnosed by the H. pylori antigen test in the stool and histopathologic findings during upper gastrointestinal endoscopy. Patients were divided into 2 groups; H. pylori-positive and H. pylori-negative groups. Hemoglobin, serum ferritin, transferrin (sTfR), zinc, and copper were assessed in all included children. Results: The hemoglobin level, serum ferritin, and zinc were significantly lower in H. pylori-positive patients compared to H. pylori-negative patients. However, the serum copper level was comparable between the 2 groups. After treatment, the hemoglobin level, serum ferritin, and serum zinc significantly increased in H. pylori-positive patients, especially in those who responded to treatment compared to their levels before treatment. There was a significant negative correlation between the severity of histopathologic abnormalities and hemoglobin level, serum ferritin, and zinc levels, but a significant positive relation with sTfR concentrations in H. pylori-positive patients. Conclusions: H. pylori-infected children had low serum ferritin and zinc levels but high sTfR level with no effect on serum copper levels. After treatment, hemoglobin, serum ferritin, and zinc levels significantly improved in H. pylori-positive patients. Gastric histologic findings correlated significantly with hemoglobin, serum ferritin, zinc, and sTfR levels.
Identification of Potential ACE2-Derived Peptide Mimetics in SARS-CoV-2 Omicron Variant Therapeutics using Computational Approaches

The COVID-19 pandemic has become a global health challenge because of the emergence of distinct variants. Omicron, a new variant, is recognized as a variant of concern (VOC) by the World Health Organization (WHO) because of its higher mutations and accelerated human infection. The infection rate is strongly dependent on the binding rate of the receptor binding domain (RBD) against human angiotensin converting enzyme-2 (ACE2human) receptor. Inhibition of protein–protein (RBDs(SARS-CoV-2/omicron)-ACE2human) interaction has been already proven to inhibit viral infection. We have systematically designed ACE2human-derived peptides and peptide mimetics that have high binding affinity toward RBDomicron. Our peptide mutational analysis indicated the influence of canonical amino acids on the peptide binding process. Herein, efforts have been made to explore the atomistic details and events of RBDs(SARS-CoV-2/omicron)-ACE2human interactions by using molecular dynamics simulation. Our studies pave a path for developing therapeutic peptidomimetics against omicron.
Bedaquiline-based treatment for extensively drug-resistant tuberculosis in South Africa: A cost-effectiveness analysis

Background The treatment success rate of conventional anti-tuberculosis (TB) regimens for extensively drug-resistant TB (XDR-TB) is low, resulting in high morbidity and healthcare cost especially in the high TB burden countries. Recent clinical findings reported improved treatment outcomes of XDR-TB with the bedaquiline (BDQ)-based regimens. We aimed to evaluate the cost-effectiveness of BDQ-based treatment for XDR-TB from the perspective of the South Africa national healthcare provider. Methods A 2-year decision-analytic model was designed to evaluate the clinical and economic outcomes of a hypothetical cohort of adult XDR-TB patients with (1) BDQ-based regimen and (2) injectable-based conventional regimen. The model inputs were retrieved from literature and public data. Base-case analysis and sensitivity analysis were performed. The primary model outputs included TB-related direct medical cost and disability-adjusted life years (DALYs). Results In the base-case analysis, the BDQ group reduced 4.4152 DALYs with an incremental cost of USD1,606 when compared to the conventional group. The incremental cost per DALY averted (ICER) by the BDQ group was 364 USD/DALY averted. No influential factor was identified in the sensitivity analysis. In probabilistic sensitivity analysis, the BDQ group was accepted as cost-effective in 97.82% of the 10,000 simulations at a willingness-to-pay threshold of 5,656 USD/DALY averted (1× gross domestic product per capita in South Africa). Conclusion The BDQ-based therapy appeared to be cost-effective and showed a high probability to be accepted as the preferred cost-effective option for active XDR-TB treatment.
New Subregions of the Mouse Entopeduncular Nucleus Defined by the Complementary Immunoreactivities for Substance P and Cannabinoid Type-1 Receptor Combined with Distributions of Different Neuronal Types

Abstract The entopeduncular nucleus (EPN) and substantia nigra pars reticulata (SNr) constitute the output nuclei of the basal ganglia, but studies on the EPN are limited compared with those on the SNr. Both nuclei receive projections from the striatum with axons containing substance P (SP) and cannabinoid type-1 receptor (CB1R), and immunoreactivities for these substances show complementary patterns in the striatum and SNr. In this study, we revealed a similar complementarity in the mouse EPN, combined it with region-specific neuronal distributions, and defined subregions of the EPN. First, the EPN was divided into two areas, one showing low SP and high CB1R (lSP/hCB1R) immunoreactivities, and the other showing high SP and low CB1R (hSP/lCB1R). The former received inputs from the dorsolateral striatum that are innervated by sensorimotor cortices, whereas the latter received inputs from the medial striatum that are innervated by limbic/association cortices. Then, the lSP/hCB1R area was further divided into the dorsolateral subregion in the rostral EPN and the core subregion in the caudal EPN, the latter characterized by the concentration of parvalbumin-positive neurons targeting the ventral anterior–ventral lateral thalamic nucleus. The hSP/lCB1R area was divided into the ventromedial subregion in the rostral EPN and the shell subregion in the caudal EPN, the former characterized by the concentration of nitric oxide synthase-positive neurons targeting the lateral habenula (LHb). Somatostatin-positive neurons targeting the LHb were located diffusely in three subregions other than the core. These findings illuminate structural organization inside the basal ganglia, suggesting mechanisms for sorting diverse information through parallel loops with differing synaptic modulation by CB1R.
Effect of Titrated Exposure to Non-Traumatic Noise on Unvoiced Speech Recognition in Human Listeners with Normal Audiological Profiles

Non-traumatic noise exposure has been shown in animal models to impact the processing of envelope cues. However, evidence in human studies has been conflicting, possibly because the measures have not been specifically parameterized based on listeners’ exposure profiles. The current study examined young dental-school students, whose exposure to high-frequency non-traumatic dental-drill noise during their course of study is systematic and precisely quantifiable. Twenty-five dental students and twenty-seven non-dental participants were recruited. The listeners were asked to recognize unvoiced sentences that were processed to contain only envelope cues useful for recognition and have been filtered to frequency regions inside or outside the dental noise spectrum. The sentences were presented either in quiet or in one of the noise maskers, including a steady-state noise, a 16-Hz or 32-Hz temporally modulated noise, or a spectrally modulated noise. The dental students showed no difference from the control group in demographic information, audiological screening outcomes, extended high-frequency thresholds, or unvoiced speech in quiet, but consistently performed more poorly for unvoiced speech recognition in modulated noise. The group difference in noise depended on the filtering conditions. The dental group's degraded performances were observed in temporally modulated noise for high-pass filtered condition only and in spectrally modulated noise for low-pass filtered condition only. The current findings provide the most direct evidence to date of a link between non-traumatic noise exposure and supra-threshold envelope processing issues in human listeners despite the normal audiological profiles.
Periprosthetic Osteolysis as a Risk Factor for Revision After Total Ankle Arthroplasty: A Single-Center Experience of 250 Consecutive Cases.

BACKGROUND Periprosthetic osteolysis after total ankle arthroplasty (TAA) is a challenging problem. This study aimed to evaluate the prevalence of and predisposing factors for osteolysis and its effects on clinical outcomes. METHODS We enrolled 236 patients (250 ankles) who underwent primary TAA using a mobile-bearing HINTEGRA prosthesis, with a mean follow-up of 83.5 months (range, 36 to 182 months), and subsequently divided them into 2 groups: the osteolysis group (79 ankles) and non-osteolysis group (171 ankles). Clinical and radiographic outcomes were compared between the 2 groups, and a bivariable logistic regression analysis was performed to identify predisposing factors for the development of osteolysis. RESULTS In the osteolysis group (31.6% of the 250 ankles), the mean time of detection was 28.8 months postoperatively. Forty of these ankles were closely monitored without surgical treatment. Another 29 ankles underwent bone grafting and exchange of the polyethylene inlay, and the remaining 10 ankles underwent revision TAA or arthrodesis. All clinical outcome variables were significantly lower in patients with osteolysis, compared with those without osteolysis, at the final follow-up (p < 0.05). In the investigation of predisposing factors, only rheumatoid arthritis was identified as having a significant association with an increased prevalence of osteolysis (p = 0.030). CONCLUSIONS This study demonstrated that the prevalence of periprosthetic osteolysis after TAA was considerable and that the development of osteolysis negatively affected the clinical outcome. Therefore, the prevention and appropriate treatment of osteolysis are crucial for the satisfactory long-term survival of TAA. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
The roles of hydrogen sulfide in renal physiology and disease states

Abstract Hydrogen sulfide (H2S), an endogenous gaseous signaling transmitter, has gained recognition for its physiological effects. In this review, we aim to summarize and discuss existing studies about the roles of H2S in renal functions and renal disease as well as the underlying mechanisms. H2S is mainly produced by four pathways, and the kidneys are major H2S–producing organs. Previous studies have shown that H2S can impact multiple signaling pathways via sulfhydration. In renal physiology, H2S promotes kidney excretion, regulates renin release and increases ATP production as a sensor for oxygen. H2S is also involved in the development of kidney disease. H2S has been implicated in renal ischemia/reperfusion and cisplatin–and sepsis–induced kidney disease. In chronic kidney diseases, especially diabetic nephropathy, hypertensive nephropathy and obstructive kidney disease, H2S attenuates disease progression by regulating oxidative stress, inflammation and the renin–angiotensin–aldosterone system. Despite accumulating evidence from experimental studies suggesting the potential roles of H2S donors in the treatment of kidney disease, these results need further clinical translation. Therefore, expanding the understanding of H2S can not only promote our further understanding of renal physiology but also lay a foundation for transforming H2S into a target for specific kidney diseases.
Boredom belief moderates the mental health impact of boredom among young people: Correlational and multi‐wave longitudinal evidence gathered during the COVID‐19 pandemic

Abstract Objectives Young people's experience of boredom and its psychological health sequelae have been exacerbated by the COVID‐19 pandemic. The present study examined the moderating role of boredom beliefs—the extent to which one affectively dislikes boredom (boredom dislike) and cognitively accepts it (boredom normalcy)—on the association between boredom experience and mental well‐being. We also validated a new measure of boredom beliefs in two different samples of young people. Method We report data from a correlational study with British young people aged 12–25 (Study 1; N = 2495) and a 16‐week eight‐wave within‐subject study with Israeli adolescents aged 12–18 (Study 2; N = 314). Results Across both studies, disliking boredom was associated with higher frequency and intensity of boredom. Boredom dislike moderated the negative association between boredom and mental well‐being, such that the association was more salient among those who strongly disliked boredom. Normalizing boredom was positively associated with mental well‐being. The measure of boredom beliefs demonstrated fair validity and reliability. Conclusion Results provide novel insights into the potential buffering effect of boredom beliefs against the mental health impact of boredom, particularly at a time of reduced activity. These findings generalize across two different countries.
Functional characteristics and research trends of PDE11A in human diseases

cAMP and cGMP are important secondary messengers involved in cell regulation and metabolism driven by the G protein-coupled receptor. cAMP is converted via adenylyl cyclase (AC) and activates protein kinase A to phosphorylate intracellular proteins that mediate specific responses. cAMP signaling serves a role at multiple steps in tumorigenesis. The level of cAMP is increased in association with cancer cell formation through activation of AC-stimulatory G protein by mutation. Phosphodiesterases (PDEs) hydrolyze cAMP and cGMP to AMP and GMP. PDEs are composed of 11 families, and each can hydrolyze cAMP and cGMP or both cAMP and cGMP. PDEs perform various roles depending on their location and expression site, and are involved in several diseases, including male erectile dysfunction, pulmonary hypertension, Alzheimer's disease and schizophrenia. PDE11A is the 11th member of the PDE family and is characterized by four splice variants with varying tissue expression and N-terminal regulatory regions. Among tissues, the expression of PDE11A was highest in the prostate, and it was also expressed in hepatic skeletal muscle, pituitary, pancreas and kidney. PDE11A is the first PDE associated with an adrenocortical tumor associated genetic condition. In several studies, three PDE11A mutations have been reported in patients with Cushing syndrome with primary pigmented nodular adrenocortical disease or isolated micronodular adrenocortical disease without other genetic defects. It has been reported that an increase in PDE11A expression affects the proliferation of glioblastoma and worsens patient prognosis. The present mini-review summarizes the location of PDE11A expression, the impact of structural differences and disease relevance.
Modified photoplethysmography signal processing and analysis procedure for obtaining reliable stiffness index reflecting arteriosclerosis severity

Objective. This study aimed to describe a modified photoplethysmography (PPG) signal processing and analysis procedure to obtain a more reliable arterial stiffness index (SI). Approach. Three parameters were used to assess the PPG signal quality without prominent diastolic waves, which are similar to a sinusoidal waveform shape. The first parameter, sinusoidal ratio (S-value), was based on frequency-domain analysis: a higher S-value indicated the presence of PPG pulse wave with unapparent diastolic peak. The second parameter was the time difference between systolic peak-to-diastolic peak and the systolic peak-to-dicrotic notch. The third parameter was the percentage of sin-like waveform in the PPG signals. The applicability of these parameters was demonstrated in 40 participants, including 11 with apparent diastolic peaks in the PPG signals and 29 with unapparent diastolic peaks. Main results. An S-value of >3.5 indicated apparent diastolic peaks in the PPG signals. In addition, a systolic peak-to-diastolic peak time difference >80% and a sin-like waveform >55% may be associated with severity of vascular aging. Significance. These parameters successfully detected low-quality PPG signals with unapparent diastolic waveform before SI calculation, thereby ensuring the accuracy of subsequent evaluation of cardiovascular-related disease and clinical risk stratification.
Longitudinal Impacts of Simulated Long-Duration Spaceflight Missions on Operationally Relevant Measures of Human Performance Using a Portable Simulation Platform

Objective This project quantifies operationally relevant measures of flight performance and workload in a high-fidelity long-duration spaceflight analog, longitudinally across mission duration, using a portable simulation platform. Background Real-time performance measures allow for the objective assessment of task performance and the timely identification of performance degradations. Methods Measures of flight performance on a piloted lunar lander task were collected on 32 total crewmembers across 8 simulated space missions of 45 days each (623 total sessions). Results Mission duration demonstrated a significant effect on measures of flight performance across all campaigns. Flight measures showed a general pattern of peaking in accuracy during the middle-late quartiles of overall mission time, then degrading again towards baseline. On the workload measure, however, a general linear decrease in workload consistent with progressive task learning was observed in both campaigns. Conclusion This investigation demonstrated the disruptive effect of time in mission on some, but not all, aspects of task performance. While mission interval differentially impacted measures of flight accuracy, workload, by contrast, seemed to steadily decrease with in-mission time. Application While more work is needed, the observed discrepancy between progression of flight performance and workload assessment highlights the importance of sensitive and specific measurement tools for the tracking of distinct performance metrics.