Introduction: Hypereosinophilic syndrome (HES) is characterized by a sustained elevation in eosinophil counts in the blood and subsequent eosinophil-mediated tissue or organ damage. While the aortic valve is recognized as a pivotal determinant of central hemodynamics, aortic valve annular (AVA) involvement in a series of HES patients has not yet been investigated. Therefore, this investigation aimed to determine potential abnormalities in the AVA dimensions and dynamics in patients with HES and to assess their associations with function of the left ventricle (LV). Methods: The present retrospective study initially consisted of 17 HES patients; however, one subject was excluded because of the suboptimal image quality. The final group of HES patients comprised 16 cases (mean age: 59.7 ± 12.6 years; 11 males). A group of 21 gender- and age-matched healthy subjects served as the controls (mean age: 54.0 ± 4.9 years; 12 males). Results: Among the 16 HES patients, the end-systolic AVA area was greater than, equal to, or smaller than the end-diastolic AVA area in four (25%), three (19%) and nine (56%) cases, respectively. In the matched control group, these proportions proved to be 12 (57%), one (5%) and eight (38%), respectively. No significant differences were found in the end-systolic and end-diastolic AVA minimum and maximum perimeters, areas or diameters between the HES patients and the matched controls, suggesting that no absolute AVA dilation was observed, despite an altered end-diastolic-end-systolic AVA area distribution. The AVA plane systolic excursion (AAPSE) was significantly decreased in the HES patients (0.91 ± 0.29 cm vs. 1.12 ± 0.24 cm, p = 0.05). Among the basal LV strain parameters, only the LV longitudinal strain (LS) was significantly impaired in the HES patients (-16.63 ± 4.99% vs. -21.62 ± 4.76%, p < 0.05). Conclusions: In HES patients, the AVA is not significantly dilated. However, a greater end-diastolic AVA area is found to be more frequently present compared with age- and gender-matched healthy controls. In addition, AAPSE and basal LV-LS are significantly reduced in HES patients.
Background. Physiological remodeling resulting from chronic exercise-induced volume and pressure overload is a well-recognized characteristic of the athlete's heart. This study aimed to explore potential changes in three-dimensional speckle-tracking echocardiography-derived aortic valve annular (AVA) dimensions and dynamics in elite athletes engaged in high-dynamic sports with varying degrees of static components. Furthermore, we sought to determine whether these parameters differ depending on the magnitude of the sport's dynamic component. Methods. The athlete cohort included 56 individuals and was divided into three groups based on the static component of their sport: C. I. (high dynamic/low static) consisted of 13 elite athletes (mean age: 22.7 ± 3.8 years, 5 males), C. II. (high dynamic/moderate static) consisted of 18 elite athletes (mean age: 23.0 ± 4.6 years, 6 males) and C. III. (high dynamic/high static) consisted of 25 elite athletes (mean age: 21.7 ± 4.5 years, 9 males). Data of athletes were compared with those of 38 age- and sex-matched healthy non-athletic individuals (mean age: 23.8 ± 2.5 years, 14 males). Results. AVA dimensions did not differ significantly between athletes and controls nor among the athlete subgroups. AVA plane systolic excursion (AAPSE) was increased in all athletes compared with controls (1.31 ± 0.30 cm vs. 1.18 ± 0.36 cm, p < 0.05). All athletes showed a significantly larger proportion of individuals showing larger end-diastolic AVA than end-systolic AVA (55% vs. 24%, p < 0.05). All athletes demonstrated reduced basal LV-RS (26.5 ± 13.9% vs. 31.5 ± 13.2%, p < 0.05) and increased basal LV-LS (-21.4 ± 4.4 vs. 19.9 ± 4.2%, p < 0.05) compared with controls. This pattern of findings was consistent across all athlete subgroups. Conclusions. Although AVA is not dilated in elite athletes practicing dynamic sports, its spatial displacement, as represented by AAPSE, together with increased basal LV-LS and a higher proportion of larger end-diastolic AVA, is augmented, while basal LV-RS is reduced. These findings suggest a functional shift from radial contraction toward enhanced longitudinal dynamics. All these findings appear to be independent of the static component of dynamic sports.
Aortic valve annular (AVA) plane systolic excursion (AAPSE) is an echocardiographic measure of left ventricular (LV) function, representing the spatial AVA displacement throughout the heart cycle. This study focused on examining associations between AAPSE and LV strains, as objective features of LV contractility patterns, assessed simultaneously by three-dimensional (3D) speckle-tracking echocardiography (3DSTE) in healthy adult individuals. It was also examined what happens when these parameters are at, or smaller or larger than, their mean values. The present cohort study consisted of 111 healthy subjects (average age: 35.1±12.3 years, 70 men), In all individuals, two-dimensional Doppler echocardiography and 3DSTE have been utilized, the latter was used for simultaneous assessment of LV strains and AAPSE. Apical LV longitudinal strain proved to be increased in the presence of lower-than-average AAPSE. Midventricular, apical and global LV circumferential strain proved to be elevated in the presence of higher-than-average AAPSE. AAPSE showed no significant differences when comparing global LV strain subgroups having lower/higher than average and agerage values, but showed the lowest value for the average global LV radial, circumferential and longitudinal strains. There is a balanced sensitive relationship between AAPSE and regional LV strains as assessed during the same 3DSTE in healthy adults.
Introduction: Health problems related to cardiovascular morbidity and mortality are overrepresented in patients with schizophrenia (SCH) and their rates have not declined in parallel with those of the general population. Cardiovascular diseases in patients with SCH are less likely to be diagnosed and treated, and data regarding structural and functional cardiac abnormalities-particularly those involving the left atrium (LA)-remain limited in this population. The present study is the first to provide a detailed three-dimensional speckle-tracking echocardiography (3DSTE)-derived volumetric and functional evaluation of LA properties in patients with chronic SCH compared with age-, gender- and body mass index (BMI)-matched healthy controls (HCs). Methods: A total of 36 patients with SCH were initially enrolled, from which 19 subjects (53%) were excluded due to inferior image quality. Ultimately, 17 SCH patients (mean age: 45.2 ± 7.7 years; 9 males, 53%) were compared with 40 age- and gender-matched HCs (mean age: 42.5 ± 5.7 years; 23 males, 58%). All participants underwent comprehensive two-dimensional Doppler echocardiography and 3DSTE. Results: LA volumes respecting the cardiac cycle were lower in SCH patients compared with controls. Among LA volume-derived functional properties, total and active LA stroke volumes were reduced in patients with chronic SCH, whereas passive LA emptying fraction was increased. All global and mean segmental peak LA strain parameters tended to be increased in SCH patients, with global and mean segmental LA area strain (AS) and mean segmental LA radial strain (RS) reaching statistical significance. Regarding regional peak LA strains, basal LA circumferential strain (CS) and LA-AS, as well as superior LA longitudinal strain (LS), LA-CS, and LA-AS, differed significantly between the groups. All global and mean segmental LA strain parameters measured at atrial contraction tended to be increased in chronic SCH patients, with global and mean segmental LA-AS and mean segmental LA-RS and LA-LS reaching statistical significance. Regional LA strains during atrial contraction demonstrated increased superior LA-RS, LA-CS, LA-LS and LA-AS, along with elevated mid-atrial LA-RS, LA-AS and LA-3D strain. All these abnormalities suggest reduced LA volumes in all phases of LA function, accompanied by overcompensating functional alterations. Conclusions: Chronic schizophrenia is associated with marked volumetric and functional abnormalities of the left atrium. These findings highlight the need for comprehensive cardiac functional evaluation extending beyond left ventricular-centered analysis in patients with this severe mental illness.
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Introduction. Left ventricular (LV) function can be characterized by numerous parameters, the most well-known being the ejection fraction (EF), derived from LV end-systolic and end-diastolic volumes (ESV and EDV, respectively) throughout the cardiac cycle. M-mode echocardiography (MME-)-based determination of the longitudinal displacement of the mitral annulus (MA plane systolic excursion, MAPSE) remains a simpler and more practical parameter for assessing LV function in daily clinical routine. Although the relationships between MAPSE, LV deformation and LV rotational mechanics are well-established in healthy individuals, it remains unclear whether MAPSE also correlates with LV volumes themselves. To address this, the associations between LV-ESV and LV-EDV and MAPSE in a healthy cohort were investigated, exploring how these variables relate across average, sub-average, and above-average ranges. Methods. The present cohort study enrolled 115 healthy adult volunteers (mean age: 35.3 ± 12.1 years; 68 men). Complete two-dimensional (2D) Doppler echocardiography with MAPSE assessment and 3DSTE-derived measurement of LV volumes was performed in all cases. Results. Both end-diastolic and end-systolic LV diameters and volumes tended to be higher in individuals with lower- or higher-than-average MAPSE compared to those with average MAPSE. These differences reached statistical significance for 2D echocardiography-derived LV end-systolic diameter and volume, as well as for 3DSTE-derived LV-EDV and LV-ESV. MAPSE remained consistent regardless of the degree of LV-EDV and LV-ESV. No significant correlations were observed between MAPSE and LV-EDV or LV-ESV. Conclusions. LV longitudinal shortening, as represented by MAPSE, is not associated with 3DSTE-derived LV volumes in healthy adults. However, the observed lack of association may not necessarily reflect true physiological independence, but could instead result from limited statistical power, measurement variability, or model misspecification.
Migraine affects up to 10% of the primary school children (6-14 years old) and its diagnosis is challenging. The purpose of our study is to present the Hungarian-language validation process of the McMaster Paediatric Migraine Headache Questionnaire, which is an easy-to-use questionnaire for workers in both outpatient and inpatient care. The linguistic validation was conducted according to an international protocol: permission of the corresponding author, two independent forward translations, a synthesis of the translations, back translations and consensus team review. The comprehensibility of the resulting Hungarian version was tested during a pilot study involving 31 young children with headaches. The reliability of the questionnaire was examined by calculating the Cronbach's alpha coefficient showing the internal consistency of the items. A total of 31 people filled the questionnaire, their mean age was 12.58 ± 3.3 years (16 girls, mean age 11.56 ± 3.1 years; 15 boys, mean age 13.7 ± 3.2 years). Almost three quarters of the participants (23 people, 74.2%) reported 5 or more headache days in a month. Based on the results of the McMaster Pediatric Migraine Questionnaire, 41.9% (13 people) of the participants suffered from migraine, and 9.6% of them had migraine with aura. The respondents rated the comprehensibility of the questionnaire as 1.93 on a scale from 1 (very easy) to 10 (very hard), which indicates easy completion. The Cronbach's alpha value of the questionnaire is 0.709, which means adequate reliability, but the complex validation process requires a larger sample. The final Hungarian version of the questionnaire used is suitable for the next step of linguistic and cross-cultural adaptation, by examining a larger patient population for the screening of childhood migraines in both outpatient and inpatient care. A migrén az általános iskolás korosztály (6–14 évesek) akár 10%-át is érintheti, diagnosztizálása pedig kihívásokkal teli. Vizsgálatunk célja a McMaster Paediatric Migraine Headache Questionnaire – ami egy könnyen felhasználható kérdőív az alap- és szakellátásban dolgozók számára – magyar nyelvű validációs folyamatának bemutatása. Először az eredeti cikk levelező szerzőjének engedélyét kértük a validációs folyamatra, hozzájárulása után két szakfordító külön-külön lefordította a kérdőívet angol forrásnyelvről magyarra; egy harmadik szakfordító bevonásával elkészült a két verzió szintézise, majd azt két, angol anyanyelvű fordító visszafordította angol forrásnyelvre, amit konszenzusmegbeszélés követett. Az így kapott magyar verzió érthetőségét 31 fejfájós kisgyermek bevonásával pilótavizsgálat során teszteltük. A kérdőív megbízhatóságát a tételek belső konzisztenciáját mutató Cronbach-α együttható kiszámításával vizsgáltuk. A kérdőívet összesen 31 fő töltötte ki, átlagéletkoruk 12,58 ± 3,3 év volt (16 lány, átlagéletkor 11,56 ± 3,1 év; 15 fiú, átlagéletkor 13,7 ± 3,2 év). A résztvevők csaknem háromnegyede (23 fő, 74,2%) számolt be havi 5, vagy ennél több fejfájós napról. A McMaster Paediatric Migraine Questionnaire eredményei alapján a résztvevők 41,9%-a (13 fő) migrénben szenved, illetve 9,6%-uknál az aurás migrén diagnózisa is felmerül. A kitöltők a kérdőív érthetőségét az 1-től (nagyon könnyű) 10-ig (nagyon nehéz) terjedő skálán 1,93-ra értékelték, ami könnyű kitölthetőséget jelez. A kérdőív Cronbach-α-értéke 0,709, ami megfelelő konzisztenciát jelent, de a komplex validálási folyamathoz ennél nagyobb esetszám szükséges. A kérdőív végső magyar változata alkalmas a nyelvi és kultúrközi adaptáció következő lépésének elvégzésére, a nagyobb betegpopuláción történő vizsgálat után pedig a gyermekkori migrén szűrésére az alap- és szakellátásban.
Despite the fact that Hungarian school healthcare has a history dating back 140 years, no comprehensive study has yet been conducted to analyze the historical development and impact of system, particularly the institutionalization of the role of health visitors in educational institutions and the development of cooperation between school doctors and health visitors. 1) To explore the historical development of school health services and the takes of school doctors, 2) to analyze the involvement and role of public health visitors in school healthcare, 3) to examine the role of cooperating professionals (doctors, public health visitors, and other professionals present today), 4) to explore the challenges that determine current operations. We studied the relevant legislation, professional regulations, and literature through research, and carried out systematic and analytical work. The role of school doctors shifted from monitoring and epidemic control to preventive care and health promotion tasks. The development of school healthcare is linked to the name of József Fodor, who laid the foundations for the regular health monitoring of school-age children by introducing a public health approach. Health visitors gradually became involved in healthcare within the legal framework, and their role became increasingly important in the areas of prevention, care, and health education. Health visitors initially appeared as professionals supporting the work of doctors. Today, this cooperation extends to all areas of health visitors' professional activities and plays a fundamental role in the effective functioning of school healthcare. The cooperation between school doctors and public health visitors is one of the cornerstones of Hungarian school healthcare and plays a key role in maintaining children's health, prevention, and health promotion. Orv Hetil. 2026; 167(19): 753-764. Bevezetés: Annak ellenére, hogy a magyar iskola-egészségügyi ellátás 140 éves múltra tekint vissza, mindeddig nem készült átfogó tanulmány, amely a történeti fejlődést és annak hatását elemezve vizsgálta volna a rendszer kialakulásának folyamatát, különösen a védőnői szerep intézményesülését az oktatási intézményekben, valamint az iskolaorvos és a védőnő közötti együttműködés fejlődését. Célkitűzés: Az 1) iskola-egészségügyi szolgáltatás, az iskolaorvosok feladatainak történeti fejlődésének feltárása, 2) a védőnők iskola-egészségügyi ellátásba való bekapcsolódásának és szerepének elemzése, 3) az együttműködő szakemberek (orvos, védőnő, valamint a napjainkban jelen lévő szakemberek) szerepének vizsgálata, 4) a jelenkori működést meghatározó kihívások feltárása. Módszer: Szakirodalmi kutatómunkával tanulmányoztuk a témához kapcsolódó jogszabályokat, szakmai szabályozókat, szakirodalmi közleményeket, rendszerező, elemző munkát végeztünk. Eredmények: Az iskolaorvosok feladatköre az ellenőrző és járványügyi tevékenységektől a megelőző, gondozó és egészségfejlesztő feladatok felé mozdult. Az iskola-egészségügyi ellátás kialakulása Fodor József nevéhez fűződik, aki a közegészségügyi szemlélet meghonosításával megalapozta az iskoláskorú gyermekek rendszeres egészségügyi felügyeletét. A védőnők fokozatosan, jogszabályi keretek között kapcsolódtak be az ellátásba, és szerepük egyre hangsúlyosabbá vált a prevenció, a gondozás és az egészségnevelés területén. Megbeszélés: A védőnő kezdetben az orvos munkáját támogató szakemberként jelent meg. Napjainkban ez az együttműködés kiterjed a védőnő valamennyi szakmai tevékenységi területére, és alapvető szerepet játszik az iskola-egészségügyi ellátás hatékony működésében. Következtetés: Az iskolaorvos és a védőnő közötti együttműködés a magyar iskola-egészségügy egyik meghatározó pillére, és kulcsfontosságú a gyermekek egészségmegőrzésében, prevenciójában és egészségfejlesztésében. Orv Hetil. 2026; 167(19): 753–764.
Obesity is a major public health problem worldwide, including in Hungary, and is associated with increased cardiovascular and metabolic risk. Bariatric interventions represent effective treatment options; however, due to the invasiveness and irreversibility of surgical techniques, there is a growing demand for minimally invasive alternatives. The aim of this study was to describe the preoperative anthropometric characteristics of patients undergoing endoscopic sleeve gastroplasty (ESG) and to evaluate the short-term safety and effectiveness of the procedure. In this prospective observational study, 193 patients who underwent ESG were included. Preoperative anthropometric parameters as well as changes in body weight and body mass index (BMI) were assessed at 3, 6, 9, and 12 months after the intervention. Body fat percentage was estimated using the Deurenberg formula. The mean age of the study population was 46.1 years, with a mean BMI of 39.1 kg/m². The estimated mean body fat percentage was 47.5%. Following ESG, BMI decreased to 87.8% of the baseline value at 3 months, 83.0% at 6 months, and 81.3% at 12 months. No surgical complications were observed. Endoscopic sleeve gastroplasty is a safe, minimally invasive procedure that results in clinically relevant short-term weight loss. Orv Hetil. 2026; 167(13): 512-516. Bevezetés: Az elhízás világszerte, így Magyarországon is jelentős népegészségügyi problémát jelent, amely fokozott cardiovascularis és metabolikus kockázattal jár. A bariátriai beavatkozások hatékony kezelési lehetőséget biztosítanak, ugyanakkor a sebészi módszerek invazivitása és irreverzibilitása miatt egyre nagyobb igény mutatkozik minimálisan invazív alternatívák iránt. Célkitűzés: Vizsgálatunk célja az endoszkópos sleeve gastroplastica (ESG) műtéten átesett betegek preoperatív antropometriai jellemzőinek bemutatása, valamint a beavatkozás biztonságosságának és rövid távú hatékonyságának értékelése. Módszer: Prospektív, obszervációs vizsgálatunkba 193, ESG-beavatkozáson átesett beteget vontunk be. A preoperatív antropometriai adatokat, valamint a testsúly- és testtömegindex (BMI)-változást a beavatkozást követő 3., 6., 9. és 12. hónapban értékeltük. A testzsírszázalékot a Deurenberg-képlet alapján becsültük. Eredmények: A vizsgált populáció átlagéletkora 46,1 év volt, az átlagos BMI 39,1 kg/m². A becsült testzsírtartalom 47,5%-nak adódott. Az ESG-t követően a BMI a 3. hónapra a kiindulási érték 87,8%-ára, a 6. hónapra a 83,0%-ára, míg a 12. hónapra a 81,3%-ára csökkent. Sebészi szövődményt nem észleltünk. Következtetés: Az ESG biztonságos, minimálisan invazív eljárás, amely rövid távon klinikailag releváns testsúlycsökkentést eredményez. Orv Hetil. 2026; 167(13): 512–516.
Most everyday tasks allow for considerable freedom in task performance. Besides taking physical constraints into account, we also rely on social cues to ascertain that our performance is acceptable. The presence of an observer influences performance, and oxytocin, a neuropeptide, enhances social sensitivity. This study examined the modulatory effects of intranasal oxytocin administration and the audience effect on motor adaptation and time estimation performance in a simple timing task. 18 adult male participants performed a time-interval production task using a force-sensitive device under oxytocin versus placebo, with or without an observer. The results showed that participants produced longer time intervals when oxytocin was administered, while the presence of an observer led to a shortening of the time intervals and a decrease in applied force indicating altered motor planning. Notably, under observation, the effects of oxytocin were enhanced, manifested as a further reduction of planned force application. Motor adaptation (the reduction of applied force) was more marked with successive repetitions, and with the presence of an auditory action-effect. Anxiety levels were positively correlated with the prolongation of timing intervals and force increase, aligning with the literature on anxiety’s impact on motor performance. This shows that oxytocin and social observation independently and interactively affect time perception and motor performance, thus demonstrating oxytocin’s influence on cognitive processes beyond purely social behaviors. The present study also demonstrates how force application patterns may serve as readouts of social cue utilization behavior in simple everyday tasks. The online version contains supplementary material available at 10.1007/s00426-026-02290-w.
Openness to sugar relationships-arrangements in which companionship or sexual intimacy is exchanged for material benefits within loosely structured, mutually negotiated agreements-has garnered growing attention in psychological research. However, little is known about the underlying personality and emotion regulation patterns associated with such attitudes. In this preregistered study, we examined whether early maladaptive schemas (EMS), personality functioning (LPFS-BF 2.0), and cognitive emotion regulation strategies (CERQ) predicted openness to sugar relationships (ASR) in a large, demographically stratified sample of young Hungarian women (N = 500; ages 18-35). Participants completed validated self-report questionnaires. General linear models revealed that ASR scores were significantly predicted by impaired personality functioning and maladaptive emotion regulation strategies. Furthermore, these vulnerabilities were strongly associated with elevated EMS scores. Structural equation modeling supported a mediation model in which EMS indirectly predicted ASR via emotion regulation and personality functioning. These findings suggest that openness to sugar relationships may reflect not only strategic or permissive attitudes but also deeper vulnerabilities in self and relational functioning. By integrating dimensional models of personality pathology and emotion regulation with emerging research on transactional sexual attitudes, this study highlights the psychological underpinnings of receptivity to sugar relationships. The results underscore the need to view such relational preferences within a broader developmental and psychological framework rather than moral or economic lenses. This is the first study to establish these associations using a representative sample of young women, contributing to a more nuanced understanding of individual differences in sexual attitudes and behaviors.
The relationship between horses and humans is often described as cooperative and affective, yet empirical studies on horse-rider bond remain scarce. Previous findings on horse-human relationships yielded conflicting results on whether and how horses show bonding like behaviour toward their owners. We tested whether horses show partner-specific approach and proximity toward their primary rider compared with an unfamiliar experimenter in an adapted Strange Situation Test, and whether the rider's presence was associated with behavioural patterns indicative of safe haven and secure base effects. Thirty horse-rider pairs participated in a behavioural test conducted in an indoor riding arena, which included several episodes: recall by owner/experimenter, separation both from rider and experimenter, reunion with rider/experimenter, and exposure to a potentially frightening object in order to examine secure base effect. We compared horses' social behaviours (i.e. proximity, approach, gazing behaviour, etc.) toward their riders versus the unfamiliar experimenter, as well as their stress-related signals (i.e. manure, vocalization) across these episodes. We found that horses approached their rider significantly faster than the experimenter during recall and reunion episodes and spent significantly more time in close proximity to the rider across multiple contexts. Our findings indicate that horses' gazing behaviour is influenced more by the human's level of interactiveness than by familiarity. However, no conclusive evidence emerged for a "safe haven" effect during exposure to the frightening stimulus. Rider sex had no effect on the horses' social or stress related behaviours. These findings suggest that horses may form specific bonds with their riders, characterized by different social behaviours consistent with certain criteria of attachment theory. The study highlights the importance of incorporating socio-emotional components into analyses of human-horse relationships and underscores the relevance of comparative attachment frameworks in equine behaviour research.
Plasma cell-free DNA (cfDNA), originating from multiple organs, holds significant potential for noninvasive diagnostics and prognostics. Current cfDNA methylation assays primarily focus on single clinical indications by targeting specific genomic loci. In contrast, comprehensive profiling of cfDNA methylome can enable simultaneous detection of multiple diseases by capturing organ-specific methylation signatures, thereby offering a holistic view of health, when disease etiology is unclear or when conventional biochemical diagnostics are unavailable. However, deep sequencing required for sensitive detection of methylation abnormalities remains prohibitively expensive, limiting widespread clinical use. To overcome this barrier, we developed MethylScan, a highly cost-effective approach for cfDNA methylome sequencing. We demonstrated its broad clinical utility in a cohort of 1,061 individuals across diverse applications, including multicancer detection in general population, liver cancer surveillance in high-risk individuals, liver disease classification, identification of organ abnormalities, and race prediction from cfDNA. In multicancer detection (liver, lung, ovarian, and stomach cancers), MethylScan achieved an area under the receiver operating characteristic curve (AUROC) of 0.938 (95% CI: 0.920 to 0.954), with a sensitivity of 63.3% (95% CI: 58.9 to 67.9%) at 98.0% specificity for all cancer stages. For early-stage cancers, the AUROC was 0.916 (95% CI: 0.890 to 0.940), with 55.3% sensitivity (95% CI: 49.1 to 62.1%) at the same specificity. In liver cancer surveillance, MethylScan achieved an AUROC of 0.927 (95% CI: 0.889 to 0.959), with 79.6% sensitivity (95% CI: 70.6 to 87.8%) at 90.4% specificity. The assay also demonstrated strong performance in additional diagnostic tasks, supporting its potential as a versatile platform for comprehensive cfDNA-based health monitoring.
We developed a green and efficient method for Pd-catalyzed N-arylation of ortho-acylanilines in water using rhamnolipid-based micellar catalysis. The (cinnamylPdCl)2/tBuXPhos system enables high yields at 40°C, significantly lower than conventional methods (>100°C), with broad substrate scope. This industrially produced biodegradable surfactant system offers a sustainable alternative to organic solvents, combining enhanced reactivity with improved energy efficiency and environmental compatibility.
Pentamidine is an FDA-approved antiparasitic drug used to treat African trypanosomiasis caused by Trypanosoma brucei, as well as Pneumocystis and Leishmania infections, however, its clinical utility is limited by poor blood-brain barrier penetration and severe side effects. In human cells, pentamidine uptake is primarily mediated by the organic cation transporter OCT1 and the organic anion-transporting polypeptide OATP1A2, while efflux occurs via the multidrug transporter P-glycoprotein (ABCB1). Here, we present a comprehensive experimental and computational characterization of six pentamidine analogs and their interactions with OATP1A2, OATP2B1, and ABCB1. Fluorescence-based uptake assays revealed that all analogs potently inhibit OATP1A2, with three compounds (4 - 6) exceeding the inhibitory potency of pentamidine. In contrast, inhibition of OATP2B1 was weaker and compound-specific, demonstrating clear transporter selectivity. Cell viability assays identified all analogs as OATP1A2 substrates, whereas in accordance with the uptake assay results, viability of OATP2B1-expressing cells was not altered by any of the tested compounds. Mechanistic studies confirmed apoptosis as the primary mode of cell death. ABCB1 overexpression substantially reduced cytotoxicity, highlighting a critical interplay between uptake and efflux transporters, and also indicating that function of ABCB1 may limit bioavailability of the compounds. Molecular docking and molecular dynamics simulations revealed that steric bulk and conformational rigidity of amidino substituents - most prominently in the N,N'-cyclohexylamidino derivative - underpin high-affinity OATP1A2 binding, while all compounds were accommodated within the ABCB1 substrate-binding cavity, consistent with efflux activity. Collectively, this study identifies OATP1A2 as a key determinant of pentamidine analog uptake and highlights the importance of transporter interplay in shaping intracellular drug exposure and pharmacological response.
SMAX1-LIKE (SMXL) proteins, previously linked to strigolactone and karrikin signalling, play diverse and partially redundant roles in plant development. The divergent SMXL4 superclade-comprising SMXL3, SMXL4 and SMXL5-is not subject to strigolactone- or karrikin-dependent proteolysis. Although these proteins have been associated with phloem differentiation and primary root growth in Arabidopsis thaliana, their broader functions remain underexplored. In this present work, we used double mutants and a series of complementing lines to investigate the in vivo functions of SMXL3 and its prominent motifs. Loss of both SMXL3 and SMXL5 resulted in spontaneous adventitious root formation on the hypocotyl, a phenotype suppressed in etiolated seedlings and modulated by carotenoid-derived signals. In contrast, anchor root formation, maintenance of primary root tip dominance and vertical root growth orientation were redundantly controlled by all SMXL4 superclade members and required an intact EAR repression motif in SMXL3. Beyond the root system, SMXL3, SMXL4 and SMXL5 collectively influenced vegetative growth, while the combined activity of SMXL3 and SMXL4 limited higher-order inflorescence branching and promoted embryo development. Together, our findings reveal that SMXL4 superclade proteins act in a combinatorial manner to control developmental timing and root architecture through both EAR motif-dependent and -independent mechanisms, with root-associated phenotypes likely reflecting altered auxin redistribution or local auxin accumulation. Overall, SMXL proteins emerge as key components controlling plant development in a context-dependent manner.
We study a minimal stochastic individual-based model for a microbial population challenged by a persistent (lytic) virus epidemic. We focus on the situation in which the resident microbial host population and the virus population are in stable coexistence upon arrival of a single new "mutant" host individual. We assume that this mutant is capable of switching to a reversible state of dormancy upon contact with virions as a means of avoiding infection by the virus. At the same time, we assume that this new dormancy trait comes with a cost, namely a reduced individual reproduction rate. We prove that there is a non-trivial range of parameters where the mutants can nevertheless invade the resident population with strictly positive probability (bounded away from 0) in the large population limit. Given the reduced reproductive rate, such an invasion would be impossible in the absence of either the dormancy trait or the virus epidemic. We explicitly characterize the parameter regime where this emergence of a host dormancy trait is possible, determine the success probability of a single invader and the typical amount of time it takes the successful mutants to reach a macroscopic population size. We conclude this study by an investigation of the fate of the population after the successful emergence of a dormancy trait. Heuristic arguments and simulations suggest that after successful invasion, either both host types and the virus will reach coexistence, or the mutants will drive the resident hosts to extinction while the virus will stay in the system.
Metabolism dysregulation induces distinct thiol profiles between cancer and healthy cells, offering an attractive therapeutic target. However, systemically targeting cancer-specific thiols remains challenging due to the widespread presence of these groups in the physiological environment. Here, we design a molecular navigator (MONA) with spatiotemporally programmable thiol-reactivity to target the thiols on cancer cells upon intravenous injection. MONA operates through a bioresponsive "Hide-and-Seek" mechanism based on tunable disulfide exchange across biological compartments. In the "Hide" phase, MONA circulates stealthily through rapid conjugation with endogenous albumin via disulfide bonding. In the "Seek" phase, albumin facilitates MONA transcytosis into tumors, where elevated glutathione levels trigger disulfide exchange, releasing MONA to multivalently engage with thiols on cancer cells. When conjugated with a photosensitizer, MONA induces cancer cell membrane disruption upon light irradiation, enabling potent phototherapy. This approach leads to complete tumor regression and systemic abscopal effects in an immunosuppressive murine breast cancer model. These findings highlight MONA as a powerful strategy for precise thiol-targeted cancer therapy.
Two-layer model systems were designed by covering a 130 nm thick mesoporous silica coating (30% porosity, 1.8 nm average pore radius) with a 470 nm thick chitosan coating (degree of acetylation 18-19%) to study the accumulation and release of a cationic model molecule (rhodamine 6G dye). The coatings were impregnated in the aqueous solution of the dye (pH 6.0, 7.4 and 8.8, 12 °C, 22 °C and 32 °C) to study the effect of electrostatic interactions and morphology on the dye uptake. The accumulation of dye molecules was examined in terms of the pseudo-first-order and pseudo-second-order kinetic model, while the release (at pH 7.4, 25 °C) in terms of the Korsmeyer-Peppas and Higuchi model. The release exponents (0.43-0.71) of the Korsmeyer-Peppas model revealed the significance of an interaction of the impregnation solution with the silica pore wall during dye uptake. According to the Higuchi model, a straight line with a higher and a lower slope could be fitted to the experimental points in the first ("fast rate") and second ("slow rate") stages of the process. Interestingly, the slope values and their differences significantly depended on the conditions of dye uptake: impregnation at alkaline pH not only increased the uptake but also resulted in faster release.
All organisms have thioredoxin reductase (TR) or glutathione reductase (GR), the only enzymes that use reduced nicotinamide adenine dinucleotide phosphate to reduce cytosolic disulfides into thiols, thereby powering deoxyribonucleotide biosynthesis, elimination of oxidants, oxidative damage repair and reduction of the disulfide nutrient cystine into the thiol amino acid cysteine. Hence, TR/GR-null bacteria or yeast are inviable; yet, remarkably, mice with TR/GR-null livers thrive, in part by synthesizing life-sustaining cysteine through alternative pathways that evolved in metazoans. Although TR/GR-null livers generate some of their cysteine through the serine transsulfuration pathway, we here show that most cysteine in TR/GR-null livers comes from a pathway in which pyridoxal-phosphate-dependent cleavage of a carbon-sulfur bond in cystine generates cysteine persulfide, which decomposes nonenzymatically into cysteine. This potent yet previously unrecognized pathway is regulated by cellular levels of sulfur metabolites and represents a potent cytoprotective response that might be induced in most mammalian cells under conditions that chronically elevate cytosolic cystine levels.