Effective Screening Research Articles

Noninvasive multi-cancer detection using blood-based cell-free microRNAs.

Patients diagnosed with early-stage cancers have a substantially higher chance of survival than those with late-stage diseases. However, the option for early cancer screening is limited, with most cancer types lacking an effective screening tool. Here we report a miRNA-based blood test for multi-cancer early detection based on examination of serum microRNA microarray data from cancer patients and controls. First, a large multi-cancer training set that included 1,408 patients across 7 cancer types and 1,408 age- and gender-matched non-cancer controls was used to develop a 4-microRNA diagnostic model using 10-fold cross-validation. In three independent validation sets comprising a total of 4,875 cancer patients across 13 cancer types and 3,722 non-cancer participants, the 4-microRNA model achieved greater than 90% sensitivity for 9 cancer types (lung, biliary tract, bladder, colorectal, esophageal, gastric, glioma, pancreatic, and prostate cancers) and 75-84% sensitivity for 3 cancer types (sarcoma, liver, and ovarian cancer), while maintaining greater than 99% specificity. The sensitivity remained to be > 99% for patients with stage 1 lung cancer. Our study provided novel evidence to support the development of an inexpensive and accurate miRNA-based blood test for multi-cancer early detection.

Effect of interlayer stacking arrangement on the dielectric properties of hexagonal boron nitride thin films

Electrostatic properties of hexagonal boron nitride (hBN) thin films with different stacking arrangements were investigated using density functional theory combined with the effective screening medium method. Our calculations showed that the dielectric properties across layers of hBN thin films are sensitive to both the interlayer stacking arrangement and the number of layers. The polarization of bilayer hBN gradually decreases with increasing lateral displacement from AB stacking, and polarity inversion occurs for particular stacking arrangements. The polarity of bilayer hBN is sensitive to twisting displacement. The polarity monotonically increases with increasing the number of layers in hBN films with rhombohedral stacking arrangement.

Rapid, effective screening of tar seep fossils for radiocarbon and stable isotope analysis

Tar seeps trap and preserve diverse fossil assemblages that reflect unique environmental histories. While the macro preservation of the fossils is usually good, preservation of organic bone collagen is often variable. Radiocarbon dating and stable isotope analysis of tar seep taxa can reveal distinct paleoecological insights but are complicated by the contamination from tar infiltration. Additionally, the removal of tar is complex and time-consuming. Therefore identifying fossils with preserved collagen prior to further investigation minimizes unnecessary damage to fossil collections and improves success rates for analyses that require organic preservation.We used tar pit fossils where the collagen preservation state was independently known to test non-destructive (visual inspection) and minimally-destructive (infrared spectroscopy; FTIR) methods to determine the most reliable methods to identify bones with well preserved collagen. We found that while collagen is less often preserved in heavily weathered bones, visual cues alone are not a reliable indicator. Instead, the Water-Amide-on-Phosphate FTIR index is highly sensitive and specific at identifying fossils suitable for radiocarbon dating and stable isotope analysis. While our protocol and analysis code were developed using fossils from two California tar seep localities (McKittrick and Rancho La Brea), they are likely to be broadly applicable to other tar seep localities that have yielded fewer fossils, thus requiring even greater care when selecting specimens for further analysis.

Synovial fluid D-lactate- a pathogen-specific biomarker for septic arthritis: a prospective multicenter study.

The performance of synovial fluid biomarker D-lactate to diagnose septic arthritis (SA) and differentiate it from crystal-induced arthritis (CA), other non-infectious rheumatic joint diseases (RD) and osteoarthrosis (OA) was evaluated. Consecutive adult patients undergoing synovial fluid aspiration due to joint pain were prospectively included in different German and Swiss centers. Synovial fluid was collected for culture, leukocyte count and differentiation, detection of crystals, and D-lactate concentration. Youden's J statistic was used to determine optimal D-lactate cut-off value on the receiver operating characteristic (ROC) curve by maximizing sensitivity and specificity. In total 231 patients were included. Thirty-nine patients had SA and 192 aseptic arthritis (56 patients with OA, 68 with CA, and 68 with RD). The median concentration of synovial fluid D-lactate was significantly higher in patients with SA than in those with OA, CA, and RD (p<0.0001, p<0.0001 and p<0.0001, respectively). The optimal cut-off of synovial fluid D-lactate to diagnose SA was 0.033 mmol/L with a sensitivity of 92.3 % and specificity of 85.4 % independent of previous antimicrobial treatment. Sensitivity and specificity of synovial fluid leukocyte count at a cut-off of 20,000 cells/µL was 81.1 % and 80.8 %, respectively. Synovial fluid D-lactate showed a high performance for diagnosing SA which was superior to synovial fluid leukocyte count. Given its high sensitivity and specificity, it serves as both an effective screening tool for SA and a differentiator between SA and RD, especially CA.

Unveiling the effects of dissolved organic matter (DOM) extracted from coastal algae and river on the photooxidation of arsenite

The coastal environment is an important ecosystem connecting land and sea, and arsenite (As(III)) in coastal seawater can seriously affect human health through the food chain. However, the effects of dissolved organic matter (DOM) extracted from coastal algae and rivers on As(III) photooxidation remain unclear. Results show that coastal algal DOM (CA-DOM) is significantly more effective than Suwannee River natural organic matter (SRNOM) in photooxidation of As(III), with a rate 8.3 times higher after correcting for light screening effects. CA-DOM accelerates As(III) photooxidation mainly through the 3DOM⁎ pathway, contributing 78.7 % to the process, whereas 3NOM⁎ contributes only 37.2 % for SRNOM. CA-DOM consists primarily of low-excited tyrosine and tryptophan-like protein substances, whereas SRNOM consists of humic and fulvic acid-like substances. Thus, CA-DOM exhibits a higher steady-state concentration of 3DOM⁎, and the 3DOM⁎ reacts much faster with As(III) than the 3NOM⁎. The increase in CA-DOM concentration can significantly accelerate the photooxidation of As(III), whereas the effect of SRNOM concentration is negligible. Increased salinity can accelerate As(III) photooxidation for all types of DOM. Our results provide new insights into the role of DOM from different sources in the photooxidation of As(III) in the natural environment or engineering applications.

An effective screening model for subjective cognitive decline in community-dwelling older adults based on gait analysis and eye tracking.

To evaluate the effectiveness of multimodal features based on gait analysis and eye tracking for elderly people screening with subjective cognitive decline in the community. In the study, 412 cognitively normal older adults aged over 65 years were included. Among them, 230 individuals were diagnosed with non-subjective cognitive decline and 182 with subjective cognitive decline. All participants underwent assessments using three screening tools: the traditional SCD9 scale, gait analysis, and eye tracking. The gait analysis involved three tasks: the single task, the counting backwards dual task, and the naming animals dual task. Eye tracking included six paradigms: smooth pursuit, median fixation, lateral fixation, overlap saccade, gap saccade, and anti-saccade tasks. Using the XGBoost machine learning algorithm, several models were developed based on gait analysis and eye tracking to classify subjective cognitive decline. A total of 161 gait and eye-tracking features were measured. 22 parameters, including 9 gait and 13 eye-tracking features, showed significant differences between the two groups (p < 0.05). The top three eye-tracking paradigms were anti-saccade, gap saccade, and median fixation, with AUCs of 0.911, 0.904, and 0.891, respectively. The gait analysis features had an AUC of 0.862, indicating better discriminatory efficacy compared to the SCD9 scale, which had an AUC of 0.762. The model based on single and dual task gait, anti-saccade, gap saccade, and median fixation achieved the best efficacy in SCD screening (AUC = 0.969). The gait analysis, eye-tracking multimodal assessment tool is an objective and accurate screening method that showed better detection of subjective cognitive decline. This finding provides another option for early identification of subjective cognitive decline in the community.

Singlet oxygen generation by nanoassemblies containing porphyrin macrocycles: Steric and screening effects, energy transfer and competing processes

In this semi-review paper, we discuss some principal aspects that should be taken into account upon quantitative analysis of the interaction with molecular oxygen O2 and the singlet oxygen (1O2 or [Formula: see text] generation by various tetrapyrrolic photosensitizers (including monomers, chemical dimers, triads, pentads and organic-inorganic nanoassemblies). In all cases, the direct experimental measurements of 1O2 emission at [Formula: see text] = 1.27 μ need to be corrected to the solvent influence (refractive indexes, molecular polarizability) on the rate constant of the radiative transition [Formula: see text] in a 1O2 molecule. For porphyrin and chlorin chemical dimers, T1 states quenching by O2 followed by 1O2 generation depends on donor-acceptor interactions between the dimer halves, and extra-ligation effects as well as the spacer flexibility. In the case of self-assembled triads and pentads containing Zn-porphyrin dimers and pyridyl substituted porphyrin free bases (H2P) as extra-ligands, quenching rate constants of H2P T1 states by O2 are smaller compared to those found for individual monomeric H2P molecules which is explained by the spatial screening influence of a strongly quenched Zn-porphyrin dimer in multiporphyrin complexes. Finally, at 293 K for nanoassemblies of two types (semiconductor quantum dots CdSe/ZnS + coordinative linked tetra-pyridyl porphyrins, and semiconductor negatively charged quantum dots AgInS/ZnS + positively charged porphyrin molecules) it was quantitatively shown that non-radiative energy transfer FRET quantum dot [Formula: see text] porphyrin (competing with electron tunneling under conditions of quantum confinement) is only responsible for the singlet oxygen 1O2 generation by nanoassemblies.

Retinopathy of Prematurity in Eight Portuguese Neonatal Intensive Care Units: Incidence, Risk Factors, and Progression-A Prospective Multicenter Study.

Retinopathy of prematurity (ROP) is a retinal neovascular disease affecting preterm infants. Identifying risk factors for its development and progression is critical for effective screening and prevention. This study aimed to analyze the incidence of ROP and identify key risk factors for its development and progression. We conducted a prospective, observational cohort study on 455 neonates (gestational age [GA] < 32 weeks or birth weight < 1500 g) across eight Portuguese NICUs. ROP incidence was 37.8%, with 4.6% requiring treatment. Multivariate analysis identified low GA and the number of red blood cell (RBC) transfusions as significant factors for ROP development and progression. After adjusting for these variables, platelet transfusions, high maximum fraction of inspired oxygen (FiO2) in the second week, and surfactant use remained significantly associated with ROP development, while early and late sepsis, maternal chronic hypertension, and delayed enteral nutrition were associated with progression to ROP requiring treatment. These findings underscore the importance of addressing low GAs and adult RBC transfusions in ROP risk management and suggest that maximum FiO2, platelet transfusions, and sepsis also play crucial roles. Larger studies are needed to validate these results and explore preventive interventions, particularly regarding the impact of multiple adult RBC transfusions on fetal hemoglobin percentages.

Cerebrovascular pulsatility indicates preoperative subcortical cognitive impairment and an increased risk for postoperative delirium in elderly patients undergoing elective spine surgery.

Advances in spine surgery enable safe interventions in elderly patients, but perioperative neurocognitive disorders (pNCD), such as post-operative delirium (POD) and cognitive dysfunction (POCD), remain a serious concern. Pre-operative cognitive impairment is a major risk factor for pNCD. Comprehensive pre-operative cognitive assessments are not feasible in clinical practice, making effective screening methods desirable. This study investigates whether pre-operative cerebrovascular duplex sonography can assess subcortical (vascular) cognitive impairment and the risk for POD. This prospective single-center study recruited patients aged ≥60 years scheduled for elective spine surgery at a German university hospital. Patients underwent pre-operative assessments including cognitive abilities (CERAD test battery), structural MRI, and cerebrovascular duplex sonography. POD screening was conducted three times daily for at least 3 days. The primary hypothesis, that the mean pulsatility index (PI) of both internal carotid arteries (ICA) predicts POD risk, was tested using logistic regression. Secondary analyses examined the association between POD risk and ICA flow (time-averaged peak velocities, TAPV) and correlations with cognitive profiles and MRI characteristics. POD occurred in 22% of patients (n = 22/99) within three postoperative days. Patients with POD were significantly older (75.9 ± 5.4 vs. 70.0 ± 6.9 years, p < 0.01) but did not differ by gender (p = 0.51). ICA PI significantly predicted POD risk (OR = 5.46 [95%CI: 1.81-16.49], p = 0.003), which remained significant after adjustment for age and duration of surgery (ORadj = 6.38 [95% CI: 1.77-23.03], p = 0.005). TAPV did not inform the POD risk (p = 0.68). ICA PI Pre-operative cognitive scores were significantly associated with ICA PI (mean CERAD score: r = -0.32, p < 0.001). ICA PI was also significantly associated with total white matter lesion volume (τ = 0.19, p = 0.012) and periventricular white matter lesion volume (τ = 0.21, p = 0.007). This is the first study to demonstrate that cerebrovascular duplex sonography can assess the risk for POD in elderly spine surgery patients. Increased ICA PI may indicate subcortical impairment, larger white matter lesion load, and lower white matter volume, predisposing factors for POD. Pre-operative cerebrovascular duplex sonography of the ICA is widely available, easy-to-use, and efficient, offering a promising screening method for POD risk. Increased ICA PI could supplement established predictors like age to adjust surgical and peri-operative procedures to individual risk profiles.

Influence of dissolved organic matter on U(VI) removal at varying hydrogeochemical scenarios in ultrafiltration process

Uranium (U) is a chemical and radioactive groundwater contaminant that needs to be regulated in drinking water to avoid health hazards. In this study, we have investigated the mechanisms underlying ultrafiltration (UF) process, a low energy-intensive technology, for the removal of uranium from contaminated groundwater, in the presence of dissolved organic matter (i.e. Humic Acid [HA]) under environmentally-relevant conditions representative of regional scenario of Punjab, India. Stirred cell UF experiments with aqueous solutions containing uranium were performed with five different UF membranes with molecular weight cut off (MWCO) ranging from 1 kDa to 30 kDa at a pH of 8.5 that represented ambient groundwater scenario. In the absence of HA, the U(VI) removal was highest for the UF membrane with the lowest MWCO (i.e. 1 kDa) and vice-versa. Further, the effect of various solution parameters viz. pH, concentration of HA, and salinity have been studied using three different UF membranes viz. 5 kDa, 10 kDa, and 30 kDa. Uranium rejection was found to be maximum at pH 5.5 with ca. 97 %, 94 %, and 87 % rejection for 5 kDa, 10 kDa, and 30 kDa membranes, respectively. Further, U(VI) speciation results of the hydrogeochemical model corroborated that the removal of U(VI) in the presence of HA was highly dependent on feed solution pH. Moreover, U(VI) removal increased significantly with an increase in HA concentration, indicating the dominant role of U(VI)-HA complexes. Further, it was observed that increasing the salinity levels to 100 mM in the feed solution (i.e. semi-brackish water scenario) decreased U(VI) rejection primarily due to the charge screening effect. Our results show that using the UF separation process, the World Health Organization’s drinking water guideline value of 30 µg of U L−1 could be achieved in U(VI) contaminated groundwater that contains significant HA levels.

Application of machine learning algorithms in predicting carotid artery plaques using routine health assessments.

Cardiovascular diseases (CVD) constitute a grave global health challenge, engendering significant socio-economic repercussions. Carotid artery plaques (CAP) are critical determinants of CVD risk, and proactive screening can substantially mitigate the frequency of cardiovascular incidents. However, the unequal distribution of medical resources precludes many patients from accessing carotid ultrasound diagnostics. Machine learning (ML) offers an effective screening alternative, delivering accurate predictions without the need for advanced diagnostic equipment. This study aimed to construct ML models that utilize routine health assessments and blood biomarkers to forecast the onset of CAP. In this study, seven ML models, including LightGBM, LR, multi-layer perceptron (MLP), NBM, RF, SVM, and XGBoost, were used to construct the prediction model, and their performance in predicting the risk of CAP was compared. Data on health checkups and biochemical indicators were collected from 19,751 participants at the Beijing MJ Health Screening Center for model training and validation. Of these, 6,381 were diagnosed with CAP using carotid ultrasonography. In this study, 21 indicators were selected. The performance of the models was evaluated using the accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), F1 score, and area under the curve (AUC) value. Among the seven ML models, the light gradient boosting machine (LightGBM) had the highest AUC value (85.4%). Moreover, age, systolic blood pressure (SBP), gender, low-density lipoprotein cholesterol (LDL-C), and total cholesterol (CHOL) were the top five predictors of carotid plaque formation. This study demonstrated the feasibility of predicting carotid plaque risk using ML algorithms. ML offers effective tools for improving public health monitoring and risk assessment, with the potential to improve primary care and community health by identifying high-risk individuals and enabling proactive healthcare measures and resource optimization.

The sandwich feeding assay for use with first instar nymphs of the Asian citrus psyllid, Diaphorina citri confirms the high susceptibility of this life stage to bacterial pesticidal proteins

Citrus greening or huanglongbing is the most important disease of citrus and threatens citrus production worldwide. As nymphs of Diaphorina citri play a crucial role in the acquisition and transmission of the citrus greening bacterium, suppression of this life stage is particularly important. However, the lack of a tractable feeding assay for use with first instar D. citri nymphs has impeded assessment of the toxicity of bioactives. Of several bacterial pesticidal proteins (BPP) that are toxic to D. citri adults, Mpp51Aa1 and Cry1Ba1, which have LC50 values of 110 and 120 µg/mL respectively in adults, were fed to 1st instar nymphs in a newly developed assay. For this new sandwich feeding assay, parafilm layers containing feeding solution were placed on top of two 35 mm Petri dishes, with a concave surface created on each. Fifty nymphs were transferred to the membrane on one Petri dish, and the second Petri dish placed on the top to create a “sandwich” with the 1st instar nymphs in the middle. Nymphs were fed for four days and the LC50 values for Mpp51Aa1 and Cry1Ba1 were calculated at 6.7 and 41.6 µg/mL respectively. Bioassays with bioengineered plants expressing Cry1Ba1 confirmed that the majority of D. citri mortality occurs during the 1st instar nymph stage, while egg laying adults are much less susceptible. Taken together, these results confirm that 1st instar D. citri nymphs are more susceptible to BPP than adults and demonstrate the utility of the sandwich feeding assay for effective screening of BPPs prior to investment into production of transgenic plants.

Abstract A137: Enrolling a diverse sample of community health center patients for a multi-level intervention to increase colorectal cancer screening uptake and follow-up

Abstract Colorectal cancer (CRC) screening is underutilized, especially in community health centers (CHCs) that provide care to marginalized communities, including low-income, uninsured, and racial/ethnic minority populations. Stool-based tests, such as the fecal immunochemical test (FIT) and FIT-DNA, can be effective CRC screening methods if individuals with abnormal results undergo colonoscopy. The Community Collaboration to Advance Racial/Ethnic Equity in CRC Screening (CARES) study aims to enroll a diverse sample of individuals at average risk for CRC for a multi-level intervention to increase CRC screening uptake and colonoscopic follow-up after abnormal FIT or FIT-DNA results in CHCs in 3 U.S. regions. Our overall goal is to conduct a two-arm, pragmatic randomized trial that includes patients in 4 Boston and 4 Los Angeles (LA) CHCs. Two clinics in the Great Plains Tribal Leaders Health Board in South Dakota (SD) will be included in a parallel pilot study. Pre-implementation activities included qualitative interviews with providers and administrators at each CHC to understand barriers to screening and current clinic workflows, development of a central database, and tailoring intervention components for each site: study invitation letters, text message reminders, infographics, instructional videos, QR codes to informational videos, and navigation for patients with abnormal results. In the 63 semi-structured pre-implementation interviews, stakeholders reported patient barriers to screening included lack of motivation due to the absence of symptoms and difficultly understanding test instructions, while provider barriers were lack of electronic health record (EHR) past-due screening reminders, and system-level barriers included challenges referring patients for colonoscopy in outside facilities. For each clinic, we queried EHR data to identify patients ages 45-75 with a recent primary care visit and an indicated preference for English or Spanish language. In the Boston clinics, 38.3% were Non-Hispanic White, 62.1% preferred English, and 65.1% were privately insured. In LA, 91.3% were Hispanic, 86.8% preferred Spanish, and 72.4% were Medicaid insured. The mean baseline CRC screening rate was significantly higher in the Boston clinics than in the LA clinics (69.1% v. 21.2%; p&amp;lt;0.0001). Of those screened, the most common screening modality was colonoscopy in Boston (84.3%) and FIT in LA (92.2%) (p&amp;lt;0.001). Higher baseline screening and colonoscopy rates in Boston may be due to multiple factors, including differences in patient demographics, prevalence of immigrant populations, language barriers, and/or healthcare access and capacity. We randomized each CHC to either mailed FIT or FIT-DNA and enrolled 2429 patients in the FIT-arm (Boston: n=936; LA: n=1493) and 2798 patients in the FIT-DNA arm (Boston: n=1303; LA: n=1495). We intend to enroll 800 patients in a similar manner in SD. To increase CRC screening through targeted interventions among populations with limited resources, it is crucial to consider local systems, barriers and facilitators to care. Citation Format: Folasade P. May, Jessica J. Tuan, Suzanne Brodney, Sapna Syngal, Andrew T. Chan, Beth Glenn, Gina Johnson, Yuchiao Chang, David A. Drew, Beverly Moy, Nicolette J. Rodriguez, Erica T. Warner, Adjoa Anyane-Yeboa, Chinedu Ukaegbu, Anjelica Q Davis, Kimberly Schoolcraft, Samantha Kuney, Kelley Le Beaux, Catherine Jeffries, Jennifer S. Haas. Enrolling a diverse sample of community health center patients for a multi-level intervention to increase colorectal cancer screening uptake and follow-up [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A137.

Trace element abundances in mineral phases and the groundmass of ocean island basalts

Incompatible trace elements are important tracers in igneous petrogenesis for determining processes acting: (i) prior to partial melting on magma sources; (ii) during partial melting, fractional crystallization or contamination of magmas, and (iii) after emplacement of lavas or intrusive rocks close to Earth's surface. Of particular interest are the high field strength elements (HFSE: Ti, Zr, Nb, Hf, Ta) which are incompatible elements with high valence states that are also relatively immobile in aqueous fluids. Abundances of Ti, Ta, and Nb (TITAN) in ocean island basalts (OIB) have been suggested to reflect recycled oceanic crust in mantle source regions, due to retention of these elements in subducted eclogitic rutile. Some of these elements have also been used to determine ‘canonical’ trace element ratios, such as Nb/U and Ta/U, that are considered invariant during petrogenetic processes. In this contribution, we present an extensive set of in situ trace element data for olivine, clinopyroxene, oxide minerals and groundmass for a suite of well-studied ocean island basalt (OIB) lavas from the Canary Islands, Azores, Samoa, Tubuai and La Réunion. The data were obtained using laser-ablation inductively coupled plasma mass spectrometry, and we also report a new open-source reduction routine for abundance determination using this method. Mineral-groundmass partitioning behavior is determined for olivine, clinopyroxene and oxides, showing that these are consistent with published partition coefficients for clinopyroxene and olivine, but are more variable for oxide phases. This variability is due to the wide variety of oxide phases possible in OIB (e.g., Cr-spinel, ilmenite, titanomagnetite) and their formation within the crystallization sequence. The new data shows that Nb and Ta budgets are dominated by fine-grained groundmass, as are most other incompatible trace elements, while the Ti budget is divided between clinopyroxene, oxide and groundmass. Modally reconstructed TITAN anomalies closely reproduce bulk rock compositions in samples with >40 % groundmass. Olivine and clinopyroxene fractional crystallization have negligible effects on TITAN anomalies, while oxide fractionation has more marked effects, with Ti anomalies being most affected. Variability in the HFSE in OIB and their association with other elements (e.g., Nb/U and Ta/U) can reflect source characteristics, although careful screening for petrogenetic effects should be done prior to ascribing significance to TITAN anomalies or canonical trace element ratios.

Screening of psoriatic arthritis by dermatologists - a German nationwide survey.

Up to 30% of psoriasis (PsO) is clinically associated with psoriatic arthritis (PsA). A large proportion of new onset of PsA is diagnosed at a later stage, despite the necessity of early effective treatment to prevent structural damage. This study aimed to identify the routine screening practices used for PsA in patients with PsO. This non-interventional, prospective, epidemiological, cross-sectional study conducted in Germany focuses on screening activity and treatment selection of dermatological practices in suspected PsA. Descriptive statistics and patient characteristics were analyzed for different center types. One hundred ninety-five patients from 34 office-based physicians, five non-university hospitals, and nine university hospitals were included. Questionnaires or imaging techniques were not routinely used (<45%). Especially, ultrasounds (≤5%) and MRIs (<6.3%) were rarely performed. Between 30% and 75% of suspected PsA could be confirmed. Referral to rheumatologists and/or appropriate therapy initiation were the most frequent consequences. Results of this study reflect the status of PsA screening activity by dermatologists. Imaging techniques, particularly ultrasound or MRIs to detect early forms of PsA, were inadequately used, which may have contributed to continued underdiagnoses. Collaboration between dermatologists and rheumatologists should be reviewed with a view to improving effective PsA screening.

Sodium Ion-Induced Structural Transition on the Surface of a DNA-Interacting Protein.

Protein surfaces have pivotal roles in interactions between proteins and other biological molecules. However, the structural dynamics of protein surfaces have rarely been explored and are poorly understood. Here, the surface of a single-stranded DNA (ssDNA) binding protein (SSB) with four DNA binding domains that bind ssDNA in binding site sizes of 35, 56, and 65 nucleotides per tetramer is investigated. Using oligonucleotides as probes to sense the charged surface, NaCl induces a two-state structural transition on the SSB surface even at moderate concentrations. Chelation of sodium ions with charged amino acids alters the network of hydrogen bonds and/or salt bridges on the surface. Such changes are associated with changes in the electrostatic potential landscape and interaction mode. These findings advance the understanding of the molecular mechanism underlying the enigmatic salt-induced transitions between different DNA binding site sizes of SSBs. This work demonstrates that monovalent salt is a key regulator of biomolecular interactions that not only play roles in non-specific electrostatic screening effects as usually assumed but also may configure the surface of proteins to contribute to the effective regulation of biomolecular recognition and other downstream events.

Causality of multiple serum metabolites on emotional lability: A two-sample Mendelian randomization study

BackgroundEmotional lability (EL)—a transdiagnostic feature characterized by rapid emotional shifts—contributes significantly to functional impairment across psychiatric disorders, such as depression, bipolar disorder, and schizophrenia. Despite its clinical significance, its etiology remains poorly understood, hindering effective screening and interventions. Growing evidence suggests that metabolic alterations may play a crucial role in the pathophysiology of psychiatric disorders. MethodsA comprehensive Mendelian randomization (MR) design incorporated summary-level data from extensive genome-wide association studies (GWAS) on serum metabolites (8299 European participants) and EL (3268 European samples) to investigate causal associations between genetically determined metabolite levels and EL. Assumptions of instrumental variables, heterogeneity, horizontal pleiotropy, and directionality were assessed alongside sensitivity analyses. ResultsOut of 1400 metabolites and ratios analyzed, 30 metabolites demonstrated causal associations with an increased risk of EL based on the inverse-variance weighted method. Sensitivity analyses identified three potential causal metabolites: hydrocinnamate (OR: 1.277, CI: 1.071–1.522, P = 0.0063), which is associated with an increased risk, while glycolithocholate (OR: 0.779, CI: 0.667–0.911, P = 0.0017) and 3β-hydroxy-5-cholenoic acid (OR: 0.857, CI: 0.756–0.971, P = 0.015) are associated with a decreased risk. ConclusionThis MR study supports a causal link between hydrocinnamate, glycolithocholate, and 3β-hydroxy-5-cholenoic acid levels and the incidence of EL, offering potential metabolic biomarkers and therapeutic targets for EL in psychiatric disorders.

Early screening for post-stroke depression and its effect on functional outcomes, quality of life, and mortality: A meta-analysis

BACKGROUND Post-stroke depression (PSD) is a common and debilitating condition affecting stroke survivors, significantly impacting their recovery and overall quality of life. AIM To assess the effects of early PSD screening on functional outcomes, quality of life, and mortality. METHODS From an initial pool of 1065 articles, 6 studies met the inclusion criteria and were selected for analysis. Functional outcomes were measured using the functional independence measure (FIM). RESULTS The analysis revealed a significant improvement in FIM scores for a PSD screening group compared to controls [standardized mean difference (SMD) = 8.90, 95% confidence interval (CI): 4.65-13.15, P &lt; 0.01]. Quality of life was assessed using the Stroke-Specific Quality of Life Scale, with the screening group showing significantly higher scores (SMD = 20.83, 95%CI: 15.27-26.38, P &lt; 0.01). Mortality analysis indicated a reduction in five-year mortality rates for the PSD screening group. CONCLUSION Early PSD screening enhances functional recovery, improves quality of life, and reduces mortality rates in stroke survivors. Thus, integrating PSD screening into routine stroke care improves long-term outcomes for patients.

Electron transfer in the respiratory chain at low salinity

Recent studies have established that cellular electrostatic interactions are more influential than assumed previously. Here, we use cryo-EM and perform steady-state kinetic studies to investigate electrostatic interactions between cytochrome (cyt.) c and the complex (C) III2-IV supercomplex from Saccharomyces cerevisiae at low salinity. The kinetic studies show a sharp transition with a Hill coefficient ≥2, which together with the cryo-EM data at 2.4 Å resolution indicate multiple cyt. c molecules bound along the supercomplex surface. Negatively charged loops of CIII2 subunits Qcr6 and Qcr9 become structured to interact with cyt. c. In addition, the higher resolution allows us to identify water molecules in proton pathways of CIV and, to the best of our knowledge, previously unresolved cardiolipin molecules. In conclusion, the lowered electrostatic screening renders engagement of multiple cyt. c molecules that are directed by electrostatically structured CIII2 loops to conduct electron transfer between CIII2 and CIV.

Coulomb Contribution to Shockley-Read-Hall Recombination.

A nonradiative recombination channel is proposed, which does not vanish at low temperatures. Defect-mediated nonradiative recombination, known as Shockley-Read-Hall (SRH) recombination, is reformulated to accommodate Coulomb attraction between the charged deep defect and the approaching free carrier. It is demonstrated that this effect may cause a considerable increase in the carrier velocity approaching the recombination center. The effect considerably increases the carrier capture rates. It is demonstrated that, in a typical semiconductor device or semiconductor medium, the SRH recombination rate at low temperatures is much higher and cannot be neglected. This effect renders invalid the standard procedure of estimating the radiative recombination rate by measuring the light output in cryogenic temperatures, as a significant nonradiative recombination channel is still present. We also show that SRH is more effective in the case of low-doped semiconductors, as effective screening by mobile carrier density could reduce the effect.