High Mass Research Articles

The burden, trends, and projections of low back pain attributable to high body mass index globally: an analysis of the global burden of disease study from 1990 to 2021 and projections to 2050.

To systematically evaluate the global burden and trends of low back pain(LBP) associated with high Body Mass Index (BMI) and project future trends up to 2050 using Bayesian Age-Period-Cohort (BAPC) model, providing scientific evidence for prioritizing global preventive actions. Utilizing data from the Global Burden of Disease (GBD) 2021 study, this research analyzes the disease burden of low back pain linked to high BMI globally, with Disability-Adjusted Life Years (DALYs) as the primary metric. We examined trends by gender, age, and exposure rate using Estimated Annual Percentage Change (EAPC) and projected future trends with the BAPC model. In 2021, high BMI-related low back pain accounted for 8,363,759 DALYs, with an age-standardized rate of 97.66 per 100,000 population and an EAPC of 1.14. The DALYs rate varied significantly by country, with the United States, Australia, and Eastern Europe experiencing the highest rates, all exceeding 225 per 100,000 population. The burden has increased globally, with notable rises in China, Southeast Asia, South Asia, and Africa, where EAPCs surpassed 2.5. Regions with medium and high Socio-Demographic Index (SDI) showed the most substantial increases, with the DALY rate in high SDI areas rising from 118.84 to 161.80 per 100,000, and in medium SDI areas from 41.92 to 79.10 per 100,000. Throughout the period from 1990 to 2021, females consistently experienced a higher burden of high BMI-related low back pain than males, with their DALY rate increasing from 92.01 to 126.29 per 100,000. The impact of high BMI on low back pain intensified with age, peaking in the 70-74 age group at 294.13 per 100,000, and then declining to 196.43 per 100,000 in those aged 95 and above. The BAPC model projects that by 2050, the number of DALYs will reach 15,558,278, an increase of 7,806,121 from 2021. From 1990 to 2021, the global burden of low back pain attributable to high BMI has intensified, particularly affecting females, younger elderly, and developed regions. With increasing global aging and obesity rates, the burden is expected to continue rising rapidly without sustained and effective targeted interventions.

Sex differences in the prevalence of metabolic syndrome and associated factors in the general population of Mongolia: A nationwide study.

The prevalence and factors associated with metabolic syndrome (MetS) between men and women in Mongolia were compared using secondary data from the STEPwise approach to non-communicable disease risk factor surveillance conducted in 2019. In total, 5,695 participants (2,577 males and 3,118 females) aged 18-69 years old were enrolled in the study. The prevalence of MetS was 37.4% in total and the prevalence was significantly higher in women (39.2%) than men (35.2%, P = 0.002). The most prevalent MetS components were abdominal obesity in women (74.2%) and high blood glucose levels in men (58.7%). All of the 2,128 participants who were categorized into MetS met the criteria of abdominal obesity. Factors associated with MetS included being 30-69 years old compared to 18-29 years old, low and moderate physical activity levels compared to high levels, history of hypertension and diabetes mellitus, and a high body mass index (overweight and obesity) compared to a normal body mass index in both sexes. Additional factors included Buryat ethnicity compared to Khalkh ethnicity, living in Ulaanbaatar, no education compared to primary education, higher monthly income, and currently drinking in men; and smoking and sufficient fruit and vegetable intake in women. Significant differences were observed between men and women in terms of the prevalence of MetS, components of MetS, and factors associated with MetS. To reduce MetS prevalence in Mongolia, sex-specific programs should be designed to promote health behavior, such as reducing alcohol consumption in men and smoking in women.

Temporal trends in weight-based disparities in physical fitness of children: 30-years of continuous surveillance through Slovenian national system

BackgroundObesity in childhood has deleterious consequences for health while improving physical fitness can significantly reduce health risks related to high body mass index. We aimed to examine the evolution of disparities in physical fitness based on weight status among 7–15-year-olds in Slovenia between 1989 and 2019 and compare these trends across sex, age and socioeconomic status.MethodsWe used annual data collected within the SLOfit monitoring system in the period between 1989 and 2019, totalling 4,256,930 participants (about 137 000 per year). We examined cardiorespiratory fitness (600-m run test), muscular fitness (60-s sit-ups, bent arm hang, and standing broad jump test) and skill-related fitness (backwards obstacle course, 60-m dash, arm plate tapping). We grouped children according to the IOTF cut-offs for BMI to those living with normal weight or excess weight and estimated changes in physical fitness over time by fitting quantile regression models separately by sex and age group, and then using segmented regression to identify the patterns of trends over time.ResultsWeight-based disparities in physical fitness were large in 1989 and have further increased by 2019. The increase in disparities was generally around 5 percentiles larger in boys, and 10–15-year-olds compared to younger children. It was particularly pronounced for body core strength and speed in boys (up to 15 and 19 percentiles, respectively) and upper body strength and speed among girls (up to 13 percentiles). Most of the increase in disparities in health-related fitness accumulated during the 2010s, when the fitness of children generally improved, but much less so in children living with excess weight.ConclusionsDespite recent improvements in population fitness levels, children with excess weight seem to be left behind, which adds to existing health inequalities. Our results should encourage policymakers to redesign policies aimed at promoting physical activity and enhancing physical fitness to make them more equitable and ultimately lead to reducing inequalities in fitness.

The risk of chronic kidney disease or proteinuria with long or short sleep duration: a systematic review and meta-analysis of cohort studies.

Irregular sleep duration has been linked with systemic diseases as well as chronic kidney disease (CKD). However, most of the evidence is low-quality and from cross-sectional data. We hereby present a meta-analysis of cohort studies examining the longitudinal association between short and long sleep with the risk of CKD or proteinuria. Databases of Embase, PubMed, CENTRAL, Web of Science, and Scopus were searched up to 5th April 2024. The risk of CKD/proteinuria was assessed with short or long sleep duration. Nine studies were included. Both short and long sleep duration were associated with a mild increase in the risk of CKD/proteinuria. Based on different cutoffs for short sleep, we noted that sleep of ≤ 7h was not associated with a significantly increased risk of CKD/proteinuria. A mild significant risk was noted in the subgroup of ≤ 6h while a significant association was noted for sleep ≤ 5h. For longer sleep duration, individuals with ≥ 8h of sleep had an increased risk of CKD/proteinuria. However, the results were non-significant for individuals with ≥ 9h of sleep. Non-significant results were noted for separate analyses on male, female, high body mass index, and elderly (≥ 60years) individuals. Both short and long sleep durations are associated with a significant increase in the risk of CKD/proteinuria in the adult population.

Real-time four-dimensional scanning transmission electron microscopy through sparse sampling

Abstract Four-dimensional scanning transmission electron microscopy (4-D STEM) is a state-of-theart image acquisition mode used to reveal high and low mass elements at atomic resolution. The acquisition of the electron momenta at each real space probe location allows for various analyses to be performed from a single dataset, including virtual imaging, electric field analysis, as well as analytical or iterative extraction of the object induced phase shift. However, the limiting factor in 4-D STEM is the speed of acquisition which is bottlenecked by the read-out speed of the camera, which must capture a convergent beam electron diffraction (CBED) pattern at each probe position in the scan. Recent developments in sparse sampling and image inpainting (a branch of compressive sensing) for STEM have allowed for real-time recovery of sparsely acquired data from fixed monolithic detectors, Further developments in compressive sensing for 4-D STEM have also demonstrated that acquisition speeds can be increased i.e. live video rate 4D imaging is now possible. In this work, we demonstrate the first practical implementations of compressive 4-D STEM for real-time inference on two different scanning transmission electron microscopes.

On the Origin of Quenched but Gas-rich Regions at Kiloparsec Scales in Nearby Galaxies

We use resolved spectroscopy from MaNGA to investigate the significance of both local and global properties of galaxies to the cessation of star formation at kpc scales. Quenched regions are identified from a sample of isolated disk galaxies by a single-parameter criterion D n (4000) - log EW(Hα) >1.6−log2=1.3 , and are divided into gas-rich quenched regions (GRQRs) and gas-poor quenched regions according to the surface density of cold gas (Σgas). Both types of quenched regions tend to be hosted by non-AGN galaxies with relatively high mass (M * ≳ 1010 M ⊙) and red colors (NUV − r ≳ 3), as well as low star formation rate and high central density at fixed mass. They span wide ranges in other properties including structural parameters that are similar to the parent sample, indicating that the conditions responsible for quenching in gas-rich regions are largely independent of the global properties of galaxies. We train random forest classifiers and regressors for predicting quenching in our sample with 15 local/global properties. Σ* is the most important property for quenching, especially for GRQRs. These results strongly indicate the important roles of low-mass hot evolved stars, which are numerous and long-lived in quenched regions and can provide substantial radiation pressure to support the surrounding gas against gravitational collapse. The different feature importance for quenching, as found previously by A. F. L. Bluck et al., is partly due to the different definitions of quenched regions, particularly the different requirements on EW(Hα).

An upper limit on the spins of merging binary black holes formed through isolated binary evolution

As the sensitivity of ground-based gravitational wave detectors progressively increases, observations of black hole mergers will provide us with the joint distribution of their masses and spins. This will be a critical benchmark to validate different formation scenarios. Merging binary black holes formed through the evolution of isolated binary systems require both components to be stripped of their hydrogen envelopes before core-collapse. The rotation rates of such stripped stars are constrained by the critical rotation limit at their surface, including its deviation from the Keplerian value owing to the outward force provided by radiation. This sets a restriction on their angular momentum content at core-collapse. We aim to determine if this restriction plays a role in the spins of binary black hole mergers. We used detailed calculations of stripped stars with the MESA code at low metallicities ($Z=Z_ $Z_ and $Z_ to determine the dimensionless spins of black holes produced by critically rotating stellar progenitors. To study how such progenitors can arise, we considered their formation through chemically homogeneous evolution (CHE) in binary stars. We used a semi-analytical model to study the physical processes that determine the final angular momentum of CHE binaries, and compared our results against available population synthesis models that rely on detailed binary evolution calculations. We find that above black hole masses of $ 25M_ the dimensionless spin parameter of critically rotating stripped stars ($a=Jc/(GM^2)$) is below unity. This results in an exclusion region at high chirp masses and effective spins that cannot be populated by isolated binary evolution. CHE can produce binaries where both black holes hit this limit, producing a pileup at the boundary of the excluded region. High-spin black holes arise from very low-metallicity CHE systems with short delay times, which merge at higher redshifts. On the other hand, the contribution of CHE to merging binary black holes detected in the third observing run of the LVK collaboration is expected to be dominated by systems with low spins ($ eff <0.5$) that merge near redshift zero. Owing to its higher projected sensitivity and runtime, the fourth observing run of the LVK collaboration can potentially place constraints on the high-spin population and the existence of a limit set by critical rotation.

New Isocoumarins from An Endophytic Fungal Strain Diaporthe arengae M2 and Their Antibacterial Activities.

Four new isocoumarin derivatives 12-O-acetyl-isocitreoisocoumarinol (1), (+)-(10R)-O-acetyl-diaportinol (2-a), (-)-(10S)-O-acetyl-diaportinol (2-b), peyroisocoumarin E (3) and new stereoconfigurations of three isocoumarin derivatives desmethyldichlorodiaportinol A (4), threo-monochlorodiaportinol A (5-a), erytheo-monochlorodiaportinol A (5-b), together with nine known ones (6-14), were separated from the rice fermentation of endophytic fungus Diaporthe arengae M2 isolated from Camellia oleifera. The structures of new compounds were determined by extensive spectroscopic analyses including nuclear magnetic resonance (NMR) and high resolution electrospray ionization mass spectroscopy (HR-ESI-MS). Compounds 4, 7, 8, 12, 13 exhibited definite inhibition against five strains of bacteria with the MIC values range from 16 μg/mL to 64 μg/mL.

Global burden of ischemic stroke attributable to high body mass index in 204 countries and territories, 1990–2021

BackgroundA high body mass index (hBMI) is one of the major risk factors for ischemic stroke (IS), although independent estimates of the global burden and trend of IS attributable to hBMI are unclear.MethodsStudy data were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study and analysed by age, sex, year, and geographical location. The sociodemographic index (SDI) and the human development index (HDI) were used as indicators of national socioeconomic status. Geographic distributions and trends were assessed by calculating the estimated annual percentage change (EAPC). Associations between the age-standardized death rate (ASMR) or disability-adjusted life year rate (DALY) and socioeconomic status were analysed.ResultsDeaths and DALYs increased worldwide from 1990–2021, with increases of 95.74% for the former and 133.00% for the latter; the ASMR and ASDR decreased, with an ASMR and ASDR-related EAPCs of -1.10 (95% CI: -1.24–-0.96) and 0.04 (95% CI:-0.47–0.55), respectively; women had greater numbers of deaths and DALYs, and the majority of deaths and DALYs were shared by those aged ≥ 70. The highest burden rates were shared by Eastern Europe, North Africa, the Middle East, and Central Asia. The ASMR-related EAPCs were associated with the ASMR in 1990 (R = -0.35, P < 0.001) and the SDI in 2021 in different countries (R = -0.66, P < 0.001); these patterns were similar to those of the ASDR; the HDI in 2021 was associated with the ASMR-related EAPC (R = -0.71, P < 0.001) and the ASDR-related EAPC in different countries (R = -0.71, P < 0.001).ConclusionsThe number of deaths and DALYs from ischemic stroke attributable to hBMI worldwide increased substantially from 1990–2021. Successful population-wide initiatives targeting hBMI may mitigate a wide range of burdens on this disease. Taking into account variations in the SDI burden, future prevention and control strategies must be developed and implemented according to country-specific development status.

Indigestible proteins and peptide-bound AGEs in ultra-processed foods: Dulce de leche as a model of severely transformed protein food systems

Caramel milk confectioneries, such as dulce de leche, are produced by simmering whole or reconstituted milk with sugar and alkali at temperatures ranging from 115 to 130 °C for several hours. This process triggers extensive non-enzymatic browning through the Maillard reaction, leading to significant modifications in milk proteins. Our research focused on the effects of such severe processing conditions on the structural integrity and digestibility of milk proteins, using dulce de leche as a model for severely transformed food protein systems. Due to structural modifications, covalent interchain cross-links, and sugar-derived bridging moieties, milk proteins in dulce de leche form high molecular weight aggregates that are not resolvable by SDS-PAGE. Proteomic analysis revealed that all major milk proteins are involved in the formation of these covalent molecular complexes. When subjected to static gastro-duodenal digestion using both adult and infant models, these macroaggregates showed resistance to pepsin and marginal susceptibility to duodenal proteases. High pressure liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)-based peptidomic analysis of dulce de leche digests allowed identifying variously sized polypeptides bearing the hallmarks of the Maillard reaction. However, many MS signals could not be assigned due to unknown modifications. The prevalence of free and peptide-bound advanced glycated end products (AGEs) in caramel milk products and other ultra-processed foods poses significant health concerns, stressing the need for a comprehensive dedicated evaluation.

Characterization of Endophytic Streptomyces rhizosphaericola Ahn75 and Its Potential for Biocontrol against Rice Blast.

Plant endophyte Streptomyces are excellent candidates as biocontrol agents against the rice blast fungus, Magnaporthe oryzae. In this study, a novel strain Ahn75 with antifungal activity was isolated from healthy rice stem and identified as Streptomyces rhizosphaericola by phenotypic characterization and phylogenetic analysis based on 16S rRNA, multilocus and genome sequences. Inhibition test using culture filtrate showed that Ahn75 could effectively suppress M. oryzae, with mycelia growth inhibition rate of 80.88% and spore germination inhibition rate of 78.26%. Genome sequence analysis of strain Ahn75 showed 40 gene clusters of secondary metabolites and several genes related to plant growth promotion were predicted in the genome of Ahn75. Several antimicrobial compounds including valinomycin, tetrabutylammonium, and benzalkonium chloride, were also detected in the antifungal fraction from Ahn75 culture filtrate by liquid chromatography and high resolution mass spectrometry. Meanwhile, strain Ahn75 demonstrates UV tolerance under UV irradiation for 60 min, pH tolerance between pH6 and pH9, and a high halotolerance in 7% (w/v) of NaCl. Greenhouse experiments indicated that Ahn75 is able to colonize rice stems, roots, and leaves, which help rice to reduce the rice leaf blast incidence by 59.76%. All these findings suggest that strain Ahn75 could be a potential biocontrol agent for rice blast.

Analysis of Water Adsorption Capacity, Thermal Behavior, Antioxidant Activity, and Smoke Volume by Polyol Ester in Reconstituted Tobacco.

A series of ester derivatives with hydroxyl groups were created by esterification of 1,2-propanediol and glycerol with o-toluoyl chloride via the catalyst 4-dimethylaminopyridine (DMAP). All the compounds were verified using nuclear magnetic resonance (1H NMR, 13C NMR), infrared spectroscopy, and high resolution mass spectrometry. Moisture absorption and desorption experiments were carried out on the compounds' pure systems and their systems in reconstituted tobacco, while their hygroscopicity and moisturizing properties were evaluated using low-field nuclear magnetic resonance imaging. Two compounds with better absorption and moisture retention were selected: 4 (1-hydroxypropan-2-yl 2-methylbenzoate) and 6 (2,3-dihydroxypropyl 2-methylbenzoate), respectively. Moreover, the thermal stability of compounds 4 and 6 were investigated using thermogravimetric (TG) analysis. The results of TG-DTG showed that the maximum mass loss rate of compound 4 appeared at 251.67 °C, with a mass loss rate of 87.61%. At the peak temperature of 291.83 °C, 6 showed the highest decomposition rate with 49.23% mass loss rate. To explore the antioxidant properties, we constructed three different antioxidant systems. Furthermore, compound 6 showed excellent effects, with scavenging rates reaching 69.28%, 71.92%, and 75.93%, respectively. Smoke volume results indicated that the compounds optimally replaced propanediol and glycerol at a rate of 40%. The results provide a theoretical reference for the development of new moisturizing agents based on polyol esters in the tobacco industry.

Emerging pollutants: Risks in salmon fish migration. A review

The release of pollutants into the environment is a serious ecological problem due to the significant risks they pose both to ecosystems and to human health. The review considers the issues of detection and distribution of new pollutants, as well as sources of their entry into the environment and potential impact on ecosystems. The problem of wastewater pollution is especially urgent in the context of conservation of salmonid fish species. Pharmaceutical and veterinary drugs, components of personal hygiene products, microplastics, per- and polyfluorinated substances, brominated flame retardants, oil and a number of other toxicants enter freshwater bodies, which are especially important for the early stages of the salmon development and its following migration. The presence of pollutants in the aquatic environment depends on a source, their ability to bioaccumulate, as well as to degrade in the processes of biological and abiotic purification. High-resolution mass spectrometry in combination with gas or liquid chromatography can be recommended for detection of new pollutants. Due to high mass measurement accuracy and high specificity, this method is able to effectively identify pollutants even in the complex fish matrix. When conducting non-targeted and targeted screening with highly sensitive full scanning, it is advisable to use high-resolution mass analyzers (TOF, Q-TOF, Q-Orbitrap), which allow determining a number of new compounds. A promising direction in the complex assessment of the impact of pollutants on salmon fish species and the identification of indicators characterizing this impact is metabolomics. It is based on the study of low-molecular organic compounds — metabolites, both intermediate and final metabolic products in body fluids and tissues. Metabolomic profiling allows identifying important markers of the state of a water body under the influence of pollutants, which is necessary for the development of comprehensive regulations and guidelines for the effective handling of these pollutants.

An Mn-Enriched Interfacial Layer for Reversible Aqueous Mn Metal Batteries.

Aqueous manganese metal batteries have emerged as promising candidates for stationary storage due to their natural abundance, safety, and high energy density. However, the high chemical reactivity and sluggish migration kinetics of the Mn metal anode induce a severe hydrogen evolution reaction (HER) and dendrite formation, respectively. The situation deteriorates in the low-concentration electrolyte especially. Here, we propose a novel approach to construct an Mn-enriched interfacial layer (Mn@MIL) on the Mn metal anode surface to address these challenges simultaneously. The Mn@MIL acts as a physical barrier to not only suppress HER but also accelerate the Mn2+ diffusion kinetics through the Mn2+ saturated interfacial layer to inhibit dendrite growth. Therefore, in the low-concentration electrolyte (1 M MnCl2), the Mn||Mn symmetric cells and Mn||V2O5 full cells with high mass loading demonstrate promising cycling stability with minimal polarization and parasitic reactions, making them more suitable for practical applications in a smart grid.

A Proteomics Pipeline for Generating Clinical Grade Biomarker Candidates from Data-Independent Acquisition Mass Spectrometry (DIA-MS) Discovery.

Clinical biomarker development has been stymied by inaccurate protein quantification from mass spectrometry (MS) discovery data and a prolonged validation process. To mitigate these issues, we created the Targeted Extraction Assessment of Quantification (TEAQ) software package that uses data-independent acquisition analysis from a discovery cohort to select precursors, peptides, and proteins that adhere to analytical criteria required for established targeted assays. TEAQ was applied to DIA-MS data from plasma samples acquired on a new high resolution accurate mass (HRAM) mass spectrometry platform where precursors were evaluated for linearity, specificity, repeatability, reproducibility, and intra-protein correlation based on 8- or 11-point loading curves at three throughputs. This data can be used as a general resource for developing other targeted assays. TEAQ analysis of data from a case and control cohort for inflammatory bowel disease (n=492) identified 1110 signature peptides for 326 quantifiable proteins from the 1179 identified proteins. Applying TEAQ analysis to discovery data will streamline targeted assay development and the transition to validation and clinical studies.

An Alternative Polymer Material to PVDF Binder and Carbon Additive in Li-Ion Battery Positive Electrode.

Li-ion battery performance relies fundamentally on modulation at the microstructure and interface levels of the composite electrodes. Correspondingly, the binder is a crucial component for mechanical integrity of the electrode, serving to interconnect the active material and conductive additive and to firmly attach this composite to the current collector. However, the commonly used poly(vinylidenefluoride) (PVDF) binder presents several limitations, including the use of toxic solvent during processing, a low electrical conductivity which for compensation requires the addition of carbon black, and weak interactions with active materials and collectors. This study investigates Poly(3,4-ethylenedioxythiophene):poly[(4-styrenesulfonyl) (trifluoromethylsulfonyl) imide] (PEDOT:PSSTFSI) as an alternative binder and conductive additive, in replacement of both PVDF and carbon black, in Li-ion batteries with LiFe0.4Mn0.6PO4 at the positive electrode. Complex PEDOT:PSSTFSI significantly improves the electronic conductivity and lithium diffusion coefficient within the electrode, in comparison to standard PVDF binder and carbon black. This enhances significantly the electrochemical performance at high C-rates and for high active mass loading electrodes. Furthermore, an excellent long-range cyclability is achieved.

Systematisation of the causes that required revision hip replacement, methods of their solution, treatment results in Ukraine

BackgroundThe objective of this study is to organise data on complications following total hip replacement (THA) over a span of 10 years, specifically focussing on cases that necessitated revision endoprosthetic surgeries. The objective is to create a recommendation for an All-Ukrainian registry of initial and repeated hip arthroplasty (HA) and standardise the terminology used to define “revision of total hip replacement surgery”.MethodsThe retrospective analysis examined 236 instances of revision hip arthroplasty (rTHA) performed at the Institute of Traumatology and Orthopaedics Centre between January 2005 and December 2021. The primary factors for revision were identified through an analysis of the patient’s medical records, laboratory results, visual inspection, and the state of the previously implanted prosthesis. Demographic information, primary and revision HA dates, diagnoses, and causes of complications were recorded. The statistical analysis was conducted using the Statistica package (StatSoft), version 12.6 (2015), with a significance level of p < 0.05.ResultsOut of the 364 patients who were diagnosed with complications, 236 of them (55.17%) needed a procedure called 1rTHA. Among these cases, 152 (41.76%) were specifically diagnosed with aseptic component instability. Significant factors for mechanical loosening were a high body mass index (BMI ≥ 30) and older age, with respective t-values of 2.08 (p = 0.004) and 2.59 (p = 0.045). Osteoporosis significantly contributed to aseptic loosening and fractures around the implant. The occurrence of infectious complications was frequently linked to chronic infectious diseases (t = 3.37, p = 0.001). The overall percentage of need for 2rTHA was 27.22% (43 cases), with one case of infectious lesion following the revision.ConclusionsThe study emphasises the urgent requirement for standardised terminology and a comprehensive registry for hip arthroplasty procedures. Primary results indicate that cement-free fixation is more effective than cement-based fixation for revision in patients with aseptic instability and that two-stage arthroplasty is effective for treating infectious inflammation. Furthermore, the most effective treatment for femoral fractures with periprosthetic involvement was determined to be open repositioning and osteosynthesis with metal retainers. The aforementioned observations emphasise the need to create a comprehensive registry across Ukraine to support patient care, enable evidence-based practices, and enhance the overall effectiveness of hip arthroplasty operations.Clinical trial numberNot applicable.

A Proteomics Pipeline for Generating Clinical Grade Biomarker Candidates from Data‐Independent Acquisition Mass Spectrometry (DIA‐MS) Discovery

Clinical biomarker development has been stymied by inaccurate protein quantification from mass spectrometry (MS) discovery data and a prolonged validation process. To mitigate these issues, we created the Targeted Extraction Assessment of Quantification (TEAQ) software package that uses data‐independent acquisition analysis from a discovery cohort to select precursors, peptides, and proteins that adhere to analytical criteria required for established targeted assays. TEAQ was applied to DIA‐MS data from plasma samples acquired on a new high resolution accurate mass (HRAM) mass spectrometry platform where precursors were evaluated for linearity, specificity, repeatability, reproducibility, and intra‐protein correlation based on 8‐ or 11‐point loading curves at three throughputs. This data can be used as a general resource for developing other targeted assays. TEAQ analysis of data from a case and control cohort for inflammatory bowel disease (n=492) identified 1110 signature peptides for 326 quantifiable proteins from the 1179 identified proteins. Applying TEAQ analysis to discovery data will streamline targeted assay development and the transition to validation and clinical studies.

Riboflavin‐Catalyzed Photoinduced Atom Transfer Radical Polymerization

AbstractThe photoATRP of methyl acrylate (MA) is investigated using riboflavin (RF) and CuBr2/Me6TREN as a dual catalyst system under green LED irradiation (λ ≈ 525 nm). Both RF and CuBr2/Me6TREN enhanced oxygen tolerance, enabling effective ATRP in the presence of residual oxygen. High molar mass polymers (up to Mn ≈ 129 000 g·mol−1) with low dispersity (Đ ≤ 1.16) are prepared, and chain‐end fidelity is confirmed through successful chain extension. The molecular masses of the obtained polymer increased linearly with conversion and showed high initiation efficiency. Mechanistic studies by laser flash photolysis reveal that the predominant activator generation mechanism is reductive quenching of RF by Me6TREN (83%, under [CuBr2]/[Me6TREN] = 1/3 condition), supported by polymerization kinetics and thermodynamic calculations.

Coadministration of Cariprazine with a Moderate CYP3A4 Inhibitor in Patients with Schizophrenia: Implications for Dose Adjustment and Safety Monitoring.

Cariprazine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6. This study aimed to evaluate the effects of erythromycin, a moderate cytochrome P450 (CYP)3A4 inhibitor, on the pharmacokinetics of cariprazine in male patients with schizophrenia, and to assess the influence of CYP2D6 phenotypes on cariprazine metabolism. Forty-two patients received oral doses of 1.5 mg cariprazine alone for 28 days (to reach steady state), followed by a co-administration of cariprazine 1.5 mg daily with erythromycin 500 mg twice daily (BID) and Enterol 250 mg BID for 21 days, followed by a 14-day post-treatment period. Blood samples were collected at predefined time points and analysed for cariprazine, its two active metabolites: desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR), and erythromycin using validated high performance liquid chromatography-tandem mass spectrometry methods. CYP2D6 phenotypes were determined by genotyping. The pharmacokinetic parameters were calculated using non-compartmental analysis. Erythromycin increased the area under the curve (AUCτ) and peak concentration (Cmax) of Total cariprazine (cariprazine + DCAR + DDCAR) by about 40-50% but did not affect the time to peak concentration (Tmax). The CYP2D6 phenotypes had no substantial effect on the pharmacokinetics of cariprazine and its metabolites, either alone or in combination with erythromycin. Cariprazine was well tolerated and safe. The findings suggest that co-administration of cariprazine with moderate CYP3A4 inhibitors may require dose adjustment or monitoring; however, pharmacogenetic testing for CYP2D6 is not necessary for optimising cariprazine therapy. Trial registration number (EudraCT Number): 2018-003721-28. Date of registration: 21-SEP-2018.