Skeletal tuberculosis (TB) arthritis is an uncommon but significant cause of osteoarticular morbidity, representing less than 1% of all TB cases. Delayed diagnosis often leads to persistent joint stiffness and pain. This study aims to identify early magnetic resonance imaging (MRI) features that distinguish TB arthritis from rheumatoid arthritis (RA). The MRI scans were retrospectively analyzed from 2010 to 2017 of 21 patients diagnosed with TB arthritis and 82 patients with RA. Imaging characteristics including synovial effusion, synovial membrane thickness, abscess wall thickness, bony erosions, rice body formation, tenosynovitis, adjacent soft tissue inflammation, and joint space narrowing were compared between the 2 groups. Compared to RA, TB arthritis patients demonstrated significantly greater abscess wall thickening (P = .001) and rice body formation (P = .008), alongside less pronounced joint space narrowing. In patients presenting with chronic arthritis, the presence of thickened abscess walls, rice bodies, and relatively preserved joint space on MRI serve as early diagnostic markers favoring TB arthritis over RA. Cite this article as: Ting S, Chen J, Yu S, Hsu C, Chen Y. MRI characteristics distinguishing tuberculous arthritis from rheumatoid arthritis: A comparative study. Eur J Rheumatol. 2026, 13(2), 0058, doi: 10.5152/eurjrheum.2026.25058.
The electromechanical window (EMW), defined as the difference between mechanical and electrical systole, is an emerging marker of arrhythmic risk and ventricular dysfunction. Although cardiac resynchronization therapy (CRT) improves mechanical synchrony, the influence of different pacing strategies on EMW is not well established. This study compared the effects of conventional biventricular (BiV) pacing and left bundle branch area pacing (LBBAP) on EMW, reverse remodeling, CRT response, and arrhythmic burden. In this prospective, observational study, 80 patients with left ventricular ejection fraction (LVEF) ≤ 35% undergoing CRT received BiV pacing (n = 40) or LBBAP (n = 40). Echocardiography with simultaneous electrocardiography was performed at baseline and 6 months. The primary endpoint was change in EMW. At 6 months, LBBAP was associated with greater QRS narrowing (42 ± 15 vs. 28 ± 13 ms, p < 0.001) and EMW normalization (- 38 ± 22 to - 5 ± 18 ms vs. - 36 ± 20 to - 18 ± 19 ms; p = 0.003). Improvements in LVEF, global longitudinal strain, and left ventricular end-systolic volume were also greater with LBBAP. EMW improvement correlated with reverse remodeling and QRS narrowing. Baseline EMW predicted CRT response (AUC 0.71), while persistent EMW negativity was associated with a higher incidence of non-sustained ventricular tachycardia (45% vs. 18%, p = 0.01). LBBAP was associated with greater EMW normalization, improved reverse remodeling, and a lower arrhythmic burden than BiV pacing. EMW may represent an integrative marker of CRT response and residual arrhythmic risk. These findings are hypothesis-generating and require validation in larger multicenter randomized studies.
Acute coronary thrombosis without atherosclerosis may mimic myopericarditis, particularly in young patients. A 20-year-old woman presented with pleuritic chest pain following a viral illness. Serial electrocardiography showed dynamic ST-segment elevation in leads V3 to V6, and high-sensitivity troponin T increased from 18.6 to 1,151 ng/L. Echocardiography demonstrated regional wall motion abnormalities in the left anterior descending territory. Coronary angiography revealed a proximal left anterior descending intraluminal thrombus causing severe narrowing without underlying atherosclerosis. Conservative management with anticoagulation and dual antiplatelet therapy was initiated. Repeat angiography after 3 days showed complete thrombus resolution with no residual stenosis. Further evaluation revealed marked thrombocytosis and a JAK2 V617F mutation, confirming essential thrombocythemia. This case highlights a mechanism-based approach to myopericarditis-like presentations. JAK2-positive essential thrombocythemia represents a plausible prothrombotic contributor after the exclusion of common causes of coronary artery disease in very young patients. Dynamic regional electrocardiogram changes, rapid troponin elevation, and regional wall motion abnormalities should prompt coronary evaluation despite pleuritic symptoms.
Polyarteritis nodosa (PAN) is a rare vasculitis affecting predominately medium-sized vessels. Our evolving understanding of PAN, including the role of HBV and discovery of monogenic variants such as deficiency of adenosine deaminase 2 (DADA2), has resulted in idiopathic PAN becoming a very rare condition with an annual incidence of 0.6-19.9/million. The investigative approach is to assess organ involvement and confirm the diagnosis either by imaging or biopsy. Conventional catheter angiography is being replaced by CT or MR angiography, which provide increasingly good resolution of the typical fusiform narrowing and aneurysm. ANCA-associated vasculitis (AAV) should be excluded. DADA2 is being more frequently identified as causing a PAN-like illness, especially in children; cases presenting in adulthood are now recognised. In children and most adults, genotyping for DADA2 should be undertaken. There are no high-quality randomised controlled trials of treatment in idiopathic PAN. Current approaches have been adapted from those used to treat other types of vasculitis. The five-factor score may be used to stratify patients to identify those needing intensive therapy with glucocorticoids combined with CYC. In order to reduce the burden of glucocorticoid toxicity, the ACR has advocated the use of immunosuppressive drugs in addition to steroids in those not initially receiving CYC. Unlike AAV, there appears to be little role for rituximab in the treatment of idiopathic PAN, although it is occasionally used as salvage therapy. HBV-associated PAN is treated with immunosuppression and antiviral therapy. There is reasonably good evidence to support the use of anti-TNF to treat DADA2.
Cerebral vasospasm is a rare but devastating complication following intracranial tumor surgery, particularly in pediatric suprasellar lesions such as craniopharyngiomas. Delayed cerebral ischemia secondary to postoperative vasospasm remains insufficiently recognized and may result in fatal neurological injury. We report the case of a 5-year-old girl who underwent gross total resection of a cystic suprasellar craniopharyngioma through a subfrontal approach without intraoperative vascular injury. The immediate postoperative course was uneventful. On postoperative day 6, the patient developed sudden refractory status epilepticus associated with rapid neurological deterioration and bilateral fixed mydriasis. Brain computed tomography (CT) revealed extensive left hemispheric ischemia with severe cerebral edema. CT angiography demonstrated marked narrowing of the A1 + M1 segment of the left middle cerebral artery, consistent with malignant cerebral vasospasm. Despite intensive care management, the patient progressed to brain death and subsequently died. Delayed malignant cerebral vasospasm following pediatric craniopharyngioma resection is an unpredictable and potentially fatal complication that may occur even in the absence of intraoperative vascular injury. Prompt recognition of delayed neurological deterioration and early vascular imaging are crucial to improve diagnostic and therapeutic management.
In the injection molding industry, the shift toward small-batch production has led to a greater variety of products and smaller batch sizes, necessitating frequent mold changes and efficient quality control, which still largely relies on human operators. This study proposes a comprehensive methodology for evaluating and comparing deep learning-based automatic optical inspection (AOI) strategies to detect complex surface defects in injection-molded parts. Three inspection setups were assessed: static frontal imaging, belt conveyor inspection, and robotic-assisted inspection. The findings reveal clear differences in defect detection capabilities among the methods, with the robotic-assisted approach demonstrating superior performance, achieving higher defect detection accuracy due to its flexibility in optimizing camera angles and positions. The proposed methodology serves as a workflow to systematically evaluate and optimize inspection setups across different parameters, enabling informed decisions about AOI systems design. This research contributes to narrowing the gap between the development of advanced detection algorithms and their industrial application, offering insights into the strategic implementation of AI technologies in quality control processes and enhancing the automatic detection of challenging defects.
Despite well-established childhood immunization programs in many high-income countries, vaccination series are often delayed or not completed. Gaps in vaccination coverage are more common among children from socioeconomically disadvantaged households, among whom they are associated with higher rates of related hospitalizations. We aimed to assess the extent of these gaps in Germany, as well as the presence of socioeconomic inequality and the factors accounting for it. Using health insurance claims data from Techniker Krankenkasse for 2016-2019, we examined vaccination coverage for a comprehensive set of STIKO-recommended childhood vaccinations in six birth-year cohorts (2011-2018; approximately 430,000 children; 2.5 million recommended vaccinations). Coverage was defined as completion of the recommended series with all doses administered within the recommended age window. Socioeconomic inequality was quantified using the Erreygers-corrected concentration index and decomposed into contributions from factors such as parental education and travel time to the treating physician. Approximately 80% of vaccination series in the sample were complete and administered within the recommended age window. Vaccination coverage showed a small but statistically significant socioeconomic gradient (concentration index = 0.024, 95% confidence interval: 0.023 to 0.025) favoring children from higher socioeconomic households. In the decomposition analysis, provider type accounted for the largest share of this gradient, with lower completion rates and timeliness among children whose outpatient care was mainly delivered by general practitioners compared with pediatricians. Parental education contributed to a lesser extent, and travel time contributed little to the observed inequality. Childhood vaccination coverage in Germany remains below national targets and shows a small socioeconomic gradient. The gradient appears to be less strongly related to logistical access barriers than to differences in how vaccinations are delivered in outpatient care outside pediatric settings. These provider-type differences in vaccination delivery may therefore be more relevant for narrowing the observed gradient than further reductions in travel time.
Tetralogy of Fallot (TOF) with absent pulmonary valve (APV) spectrum is a rare congenital cardiac anomaly characterized by dysplastic or APV leaflets, leading to severe pulmonary regurgitation and aneurysmal dilatation of the pulmonary arteries. We report a 4-year-old male presenting with recurrent respiratory infections. Cardiac computed tomography (CT) revealed TOF with a subaortic ventricular septal defect, overriding aorta, right ventricular hypertrophy, and right ventricular outflow tract narrowing. The pulmonary valve was dysplastic, with marked aneurysmal dilatation of the main and branch pulmonary arteries, causing compression of the right main bronchus. This case highlights the role of cardiac CT in comprehensive anatomical assessment and its importance in preoperative planning. RésuméLa tétralogie de Fallot (TDF) avec spectre d’absence de valve pulmonaire (AVP) est une anomalie cardiaque congénitale rare caractérisée par des feuillets valvulaires pulmonaires dysplasiques ou absents, entraînant une régurgitation pulmonaire sévère et une dilatation anévrismale des artères pulmonaires. Nous rapportons le cas d’un garçon de 4 ans présentant des infections respiratoires récidivantes. La tomodensitométrie cardiaque (TDM) a révélé une TDF avec communication interventriculaire sous-aortique, aorte à cheval, hypertrophie ventriculaire droite et rétrécissement de la voie d’éjection du ventricule droit. La valve pulmonaire était dysplasique, avec une dilatation anévrismale marquée du tronc et des branches des artères pulmonaires, entraînant une compression de la bronche principale droite. Ce cas souligne le rôle de la TDM cardiaque dans l’évaluation anatomique complète et son importance dans la planification préopératoire.
Peripheral artery disease (PAD) is a prevalent and disabling vascular condition characterized by progressive atherosclerotic narrowing and stiffening of peripheral arteries. Arterial stiffness, most accurately measured by pulse wave velocity (PWV), has gained prominence as a critical biomarker in the assessment and management of PAD. Unlike traditional diagnostic tools that focus primarily on anatomical lesions, PWV offers dynamic insights into vascular function, elasticity, and systemic cardiovascular risk. Elevated PWV has been consistently associated with adverse outcomes in PAD patients, including critical limb ischemia, restenosis following angioplasty, amputation, and cardiovascular mortality. It not only reflects disease severity but also facilitates early risk stratification, informs treatment selection, and enables monitoring of therapeutic efficacy. Studies have shown that reductions in arterial stiffness following angioplasty, pharmacological therapy, or lifestyle interventions correlate with improved limb perfusion and long-term clinical outcomes. Moreover, in elderly PAD patients, arterial stiffness often coexists with frailty-another key predictor of poor prognosis. Emerging evidence suggests that both conditions may share pathophysiological pathways related to vascular aging and sarcopenia. The integration of PWV into routine PAD evaluation may thus offer a more holistic understanding of patient risk and resilience. Given its diagnostic, prognostic, and therapeutic utility, arterial stiffness-particularly as assessed by PWV-should be considered an essential parameter in PAD management. Incorporating this measurement into clinical practice holds significant potential to improve individualized care, reduce complications, and enhance overall patient outcomes.
This study investigated the haemodynamic effects by simulating simplified cerebrovascular at different stenosis levels. To improve the understanding of haemodynamic changes due to atherosclerosis, computational fluid dynamics (CFD) simulations are employed to visualise wall shear stress (WSS), pressure distribution, and flow rate within arterial models. Three different degrees of arterial atherosclerosis, specifically 25%, 50% and 75% plaque thickness have been examined. Findings show that in the severe atherosclerosis of 75%, blood flow velocity through the plaque undergoes a significant change, leading to low pressure due to extreme narrowing and resulting turbulent flow. Moreover, WSS contours reveal extensive and severe red zones when atherosclerosis reaches 75%, especially within and beyond the severely constricted region. Although the individual parameters were visualised, the velocity-pressure correlation for each atherosclerosis level showed velocity peaks around 10 m/s for 50% plaque and sharply increasing to nearly 100 m/s for 75% plaque. In mild atherosclerosis (25% plaque), both velocity and pressure profiles remain relatively stable. This study offers deeper insights and understanding on how atherosclerosis alters cerebral circulation, potentially enhancing diagnostic accuracy and treatment strategies for stroke prevention.
Metastatic involvement of the biliary tract and gastrointestinal (GI) system secondary to breast carcinoma is exceedingly rare. We hereby report a case of a 57-year-old woman with a past history of Human Epidermal Growth Factor Receptor 2-positive, estrogen and progesterone receptor-negative breast carcinoma treated 4 years earlier, who presented with jaundice, vomiting, early satiety, and significant weight loss. Biochemical evaluation revealed a cholestatic pattern of jaundice. Magnetic resonance cholangiopancreatography and contrast-enhanced computed tomography revealed intrahepatic biliary dilatation secondary to a mass at the porta hepatis compressing the distal common bile duct, along with significant narrowing of the D1-D2 segment of duodenum. Endoscopic ultrasound-guided biopsy confirmed metastatic adenocarcinoma consistent with a breast primary. Due to anatomical constraints precluding endoscopic biliary stenting, the patient underwent palliative double bypass surgery of cholecystojejunostomy and gastrojejunostomy. Postoperatively, the patient demonstrated resolution of jaundice and restoration of normal oral intake, with marked symptomatic improvement. This case highlights a rare metastatic presentation of breast carcinoma closely mimicking primary hepato-pancreato-biliary malignancies, posing a significant diagnostic challenge. A high index of suspicion is thus essential in patients with a prior history of breast cancer presenting with biliary or upper GI symptoms. In cases where endoscopic interventions are not feasible, surgical double bypass proves to be an effective palliative strategy for symptom relief. RésuméL’atteinte métastatique des voies biliaires et du tractus gastro-intestinal secondaire à un carcinome mammaire est exceptionnelle. Nous rapportons le cas d’une patiente de 57 ans, ayant des antécédents de carcinome mammaire HER2 positif, négatif pour les récepteurs hormonaux, traité quatre ans auparavant, admise pour ictère, vomissements, satiété précoce et amaigrissement. Le bilan biologique objectivait un syndrome cholestatique. La cholangiopancréatographie par résonance magnétique et la tomodensitométrie abdominale avec contraste ont révélé une dilatation des voies biliaires intra-hépatiques secondaire à une masse du hile hépatique comprimant le cholédoque distal, associée à un rétrécissement du duodénum (D1–D2). La biopsie guidée par échoendoscopie a confirmé un adénocarcinome métastatique compatible avec une origine mammaire. En raison de contraintes anatomiques rendant impossible le drainage biliaire endoscopique, une dérivation palliative par double court-circuit (cholécystojéjunostomie et gastrojéjunostomie) a été réalisée. L’évolution postopératoire a été favorable, avec régression de l’ictère et reprise de l’alimentation orale. Ce cas illustre une présentation métastatique rare mimant une néoplasie hépato-pancréato-biliaire primitive, posant un défi diagnostique. Un haut niveau de suspicion est essentiel, et en l’absence d’alternative endoscopique, le double court-circuit chirurgical constitue une option palliative efficace.
Comparative data on vessel preparation using intravascular Shockwave lithotripsy (Johnson and Johnson, New Brunswick, NJ) or the 355-nm Auryon laser (Angiodynamics, Latham, NY) in calcified femoropopliteal arterial disease is limited. This is a retrospective, single-center study evaluating the 30-day safety and effectiveness of the 355-nm laser system versus Shockwave lithotripsy in treating calcified femoropopliteal arterial disease. Angiographic images were reviewed by core laboratory. The primary endpoint of safety is freedom from major adverse limb event (MALE) at 1 month. The primary effectiveness endpoint is acute procedural success, defined as achieving less or equal 30% mean residual narrowing postfinal treatment with no bailout stenting. A total of 29 consecutive patients were included (355-nm laser 15 patients [15 vessels] and Shockwave lithoplasty 14 patients [15 vessels]). At baseline, there were no differences between the two cohorts in demographics or clinical presentation. Also, there were no difference in total occlusions (33.3 vs. 33.3%), lesion length (median: 12.0 vs. 12.1 cm), presence of moderate to severe calcium (86.7 vs. 100%). At 30-day, there were no MALEs in both groups. There were no perforations, type D dissections, or distal embolization seen in both cohorts. Bailout stent was driven by a higher residual stenosis and was 35.7 vs. 13.3% in Shockwave versus laser, respectively ( p  = 0.215). At 30-day ankle-brachial indices were similar between the two groups (median: 0.9 vs. 1.09). Both Shockwave and 355-nm laser are effective and safe in calcified femoropopliteal lesions. A numerically higher rate of bailout stenting was seen with Shockwave lithoplasty.
Accurate differentiation between periprosthetic joint infection (PJI) and aseptic osteolysis (AO) remains a major clinical challenge in revision joint arthroplasty. We examined bone biopsies for alterations in bone matrix integrity and the osteocyte lacunocanalicular network in order to differentiate between these pathologies. Bone biopsies were taken from areas of osteolysis in patients who underwent revision arthroplasty for either PJI, diagnosed according to 2018 International Consensus Meeting criteria, or AO. Controls were obtained during primary arthroplasty. Biopsies were assessed histologically by Masson's trichrome, silver and RGB trichrome staining, and for osteocyte lacunocanalicular characteristics. The diagnostic potential of histological measures was investigated using univariate area under the receiver operating characteristic curve (AUROC) analysis. RGB trichrome staining was most effective for revealing both bone matrix and lacunocanalicular features. Osteocyte lacunar area and circularity were increased in PJI relative to both AO and Control bone. PJI bone exhibited reduced canalicular density compared to AO (p < 0.001), and shorter, narrower canaliculi than AO and Controls. Predictive univariate modelling revealed that all histological parameters measured except lacunar area were potentially diagnostic for PJI. Degraded bone matrix differentially predicted PJI (AUROC = 0.875, 88% sensitivity, 80% specificity) and AO (AUROC = 0.733, 63% sensitivity, 76% specificity), as did lacunar circularity (PJI: AUROC = 0.903, 75% sensitivity, 96% specificity; AO: AUROC = 0.797, 69% sensitivity, 84% specificity). Canalicular area fraction, length, and width all predicted PJI (AUROCs = 0.915, 0.982, 0.883), with canalicular length yielding 94% sensitivity and 100% specificity. Canalicular density differentially predicted PJI (AUROC = 0.770, 69% sensitivity, 80% specificity) and AO (AUROC = 0.757, 88% sensitivity, 60% specificity). Histological assessment of bone matrix degradation and the osteocyte lacunocanalicular network reveals new potential diagnostic markers for PJI to support clinical decision-making and provides novel measures for distinguishing PJI from AO, which may be particularly useful in cases of low-grade and chronic infections. Based on these findings, larger confirmatory studies are warranted.
Klebsiella pneumoniae (KP) has emerged as a formidable nosocomial pathogen in the era of antimicrobial resistance, with mortality from pneumonia caused by carbapenem-resistant strains exceeding 50%. Phage therapy has re-emerged as a promising alternative or adjunctive strategy for managing refractory KP infections. This review consolidates the current preclinical and clinical evidence base, outlines the molecular mechanisms of phage-host interactions, and appraises evolving therapeutic approaches. Preclinical investigations in murine pneumonia models have consistently demonstrated that intranasal or nebulization phage administration markedly reduces pulmonary bacterial burden, attenuates inflammatory lung injury, and improves survival, often exhibiting synergistic effects when combined with conventional antibiotics. Clinical case reports and small compassionate-use series have further provided preliminary yet compelling evidence supporting the safety and therapeutic promise of personalized phage formulations in critically ill patients with multidrug-resistant KP pneumonia who have exhausted standard treatment options. Mechanistically, phage tropism is mediated through the specific recognition of bacterial surface receptors-principally capsular polysaccharide and, to a lesser extent, lipopolysaccharide-by phage-encoded receptor-binding proteins, culminating in bacterial lysis. In response, KP has evolved a multilayered defensive arsenal encompassing receptor modification to impede adsorption, nucleic acid interference systems (e.g., CRISPR-Cas and restriction-modification), and abortive infection mechanisms that curtail phage propagation at the population level. To surmount the inherent limitations of narrow host range and the inevitable emergence of phage-resistant mutants, a suite of optimization strategies is under active refinement, including rationally designed phage cocktails, genetically engineered phages with extended tropism, artificial intelligence-assisted host-range prediction, and innovative delivery platforms such as hydrogel encapsulation to enhance pulmonary bioavailability. Despite ongoing challenges in mechanistic complexity, manufacturing standardization, and regulatory uncertainty, current initiatives- such as the establishment of geographically diverse phage libraries, real-time surveillance of phage resistance, and the development of phage-derived enzyme products-hold promise for establishing precision phage therapy as a viable and sustainable component of the antimicrobial stewardship armamentarium. 在抗菌药物耐药时代，肺炎克雷伯菌（Klebsiella pneumoniae，KP）已成为一种棘手的院内病原体，碳青霉烯耐药菌株所致肺炎的病死率超过50%。噬菌体疗法已重新成为治疗难治性KP感染的替代或辅助策略。本综述系统梳理了当前临床前与临床证据基础，阐明了噬菌体-宿主相互作用的分子机制，并评估了不断演进的治疗策略。尽管在机制复杂性、生产标准化及监管不确定性方面仍面临持续挑战，但正在推进的各项举措——包括建立覆盖不同地域的噬菌体库、开展噬菌体耐药性的实时监测以及开发噬菌体衍生酶类产品——有望使精准噬菌体疗法成为抗菌药物管理体系中切实可行且可持续的组成部分。.
Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by thunderclap headache and reversible segmental cerebral arterial constriction. Although neurological complications are well recognized, concurrent extracerebral vasoconstriction remains under appreciated. A 53-year-old woman presented with sudden chest tightness immediately followed by a thunderclap headache. Initial brain computed tomography and magnetic resonance imaging showed no hemorrhage or infarction; however, magnetic resonance angiography demonstrated multifocal cerebral arterial narrowing, consistent with RCVS. During hospitalization, she developed recurrent nonaneurysmal subarachnoid hemorrhages (SAHs) on days 2 and 4. No bleeding source was identified on serial angiography. Recurrent episodes of chest tightness prompted coronary angiography with acetylcholine provocation, which revealed severe coronary vasospasm, establishing the diagnosis of vasospastic angina (VSA). Treatment with benidipine and nicorandil was initiated thereafter, and no recurrence of either cardiac or neurological symptoms was observed, with complete resolution of cerebral vasoconstriction on follow-up imaging. This case highlights a rare but clinically important association between RCVS, recurrent nonaneurysmal SAH, and coronary VSA confirmed by pharmacologic provocation. Although each condition is potentially reversible, their coexistence supports the concept of systemic vasoconstriction syndrome and underscores the need for vigilance regarding extracranial vascular involvement in patients with RCVS. Early recognition and targeted vasodilator therapy may be essential to prevent serious neurological and cardiovascular complications.
In this study, we report the first antibacterial evaluation of a focused library of 12 previously synthesized α-sulfamidophosphonate derivatives (4a-4l) against a panel of nine Gram-positive and Gram-negative strains, including ESBL- and carbapenemase-producing Enterobacterales. The overall hit rate was modest, as most compounds were inactive at the highest tested concentration (MIC ≥ 256 µg/mL), indicating a narrow and strain-selective profile. Nevertheless, selected derivatives showed noteworthy activity against individual isolates: 4 g inhibited Staphylococcus aureus ATCC29213 at 4 µg/mL, 4c inhibited KPC-3-producing Klebsiella pneumoniae at 2 µg/mL, and 4e and 4l inhibited VIM-producing Escherichia coli at 4 µg/mL. Density functional theory (DFT) calculations were used to examine substituent-dependent electronic features, whereas docking and 100 ns molecular dynamics (MD) simulations were employed to test whether the scaffold can adopt plausible binding modes in a dihydropteroate synthase (DHPS) model. Because no biochemical DHPS assay was performed, the computational results should be regarded as hypothesis-generating rather than mechanistic proof. In silico ADMET predictions were used as an exploratory triage step and similarly await experimental validation. Overall, the present work identifies α-sulfamidophosphonates as preliminary antibacterial hits for further optimization, while emphasizing the need for broader microbiology, cytotoxicity, bactericidal, and target-validation studies.
To investigate the transport behavior of multiple particles in microchannels under ultrasonic actuation, a strongly coupled PD-IB-CLBM framework is developed in this work. In this framework, peridynamics (PD) is employed to describe the motion and deformation of solid particles, the cascaded lattice Boltzmann method (CLBM) is used to resolve the flow field, and the immersed boundary method (IBM) is adopted to enforce fluid-solid coupling. Based on this model, the migration dynamics of single and multiple particles in single-channel, parallel multi-channel, and T-shaped microchannels are systematically studied, with emphasis on the effects of particle number, channel geometry, and ultrasonic frequency on inlet capture, stable transport, and path selection. The results show that particle transport generally undergoes a transition from an initial oscillatory stage to a stable directional transport stage. Increasing particle number intensified inlet competition and trajectory disorder, potentially hindering the smooth entry of some particles. Parallel multi-channel structures enhance the capacity for simultaneous particle transport, but also introduce more pronounced local flow disturbances. In T-shaped channels, the transport behavior is highly sensitive to ultrasonic frequency. Among the tested conditions, 2 MHz achieves the best balance among capture range, flow stability, and transport consistency, whereas excessively high frequency (5 MHz) leads to an overly narrow effective capture region and deteriorates stable multi-particle transport. These findings reveal the coupled regulatory effects of ultrasonic frequency and channel geometry on collective particle transport, and provide theoretical guidance for ultrasound-assisted microfluidic manipulation and transdermal drug delivery systems.
The accelerated pace of climate change, soil degradation, environmental pollution, and pathogen outbreaks subjects trees and crops growing in different parts of the world to multiple abiotic/biotic stress conditions, simultaneously or sequentially. Unfortunately, most studies conducted to date, including studies of two-stress combinations, do not mimic the complex multifactorial stress combination (MFSC) environment plants experience in nature. Here, we summarize evidence from recent MFSC studies of three or more stresses simultaneously impacting plants, and argue that environmental complexity, i.e., a high number of interacting stress factors, functions as a system-level variable shaping plant performance. Across different model and crop plants, the progressive increase in stress complexity results in non-additive effects that cause marked declines in growth, photosynthetic rates and yield, even when the level of each individual stress involved in such MFSC remains moderate. Multi-omics analyses reveal that MFSC does not simply induce stress-response pathways but redistributes regulatory control within hormonal networks, most prominently within abscisic acid signaling, accompanied by reduced physiological performance and repression of photosynthesis-related genes. These responses scale nonlinearly with increasing complexity and are consistent with threshold-like shifts in regulatory function, rather than simple additive effects. We further present a complexity-driven regulatory model in which rising combinatorial load progressively narrows regulatory flexibility and promotes survival-oriented strategies over plant growth. Finally, we discuss how recognizing stress complexity as an organizing variable could reshape breeding priorities and predictive crop modeling under increasingly complex environmental scenarios.
Ultra-high-resolution (UHR) examinations do not entail a dose burden in photon-counting CT (PCCT), since no post-patient filter is required to narrow the detector aperture. While this configuration is known to improve spatial sampling ("small pixel effect"), the interaction between reconstruction kernels and iterative reconstruction (IR) remains incompletely understood. This study investigated how smaller detector pixels influence signal-to-noise behavior and subjective image quality in midface PCCT. Fourteen cadaveric heads were examined using both UHR (120 × 0.2 mm) and standard collimation (144 × 0.4 mm) on twelve dose levels (0.08-10 mGy) with a first-generation cadmium-telluride PCCT scanner. UHR data were reconstructed with three dedicated head kernels with spatial frequencies of 12.8, 21.0, and 27.9 line pairs/cm at 10% of the modulation transfer function (Hr64, Hr76, and Hr84). Only Hr64 and Hr76 could also be used for standard-resolution data. Signal-to-noise ratios (SNR) were computed among all datasets. Subjective image quality was assessed by nine radiologists using a forced-choice pairwise comparison tool. Comparing reconstructions with the sharp Hr76 kernel, SNR was higher in UHR than in standard-resolution datasets on each dose level (all p<0.001). In contrast, no significant difference was established between reconstructions with the intermediate Hr64 kernel (all p≥0.300). Notably, in UHR acquisitions, increasing kernel sharpness did not lead to the expected SNR penalty: Hr76 demonstrated comparable or numerically higher SNR than Hr64 across dose levels (all p≥0.050). This counterintuitive pattern suggests a non-uniform, "bucket-like" interaction between reconstruction kernels and IR. Subjective analysis showed substantial inter-reader agreement (Fleiss κ=0.711) and consistent preference for sharper UHR reconstructions, even when acquired at lower radiation dose. In midface PCCT, smaller detector pixels enable a measurable SNR advantage when matched for reconstruction sharpness. In addition, kernel-dependent interactions with IR may lead to non-monotonic noise behavior, allowing sharper reconstructions without the expected noise penalty.
Hysteroscopes and hemorrhoid band ligators represent valuable diagnostic and therapeutic tools in medicine. These reusable devices require reprocessing, but if reprocessing failures occur, patients are at risk for exposure to pathogenic microorganisms. Experiments were conducted in a research microbiology laboratory. To test the effectiveness of a 12-minute or 4-hour immersion in ortho-phthalaldehyde (OPA) with passive filling of the hysteroscopes and hemorrhoid band ligators narrow lumens for killing the intraluminal microbes. Our results demonstrate that narrow lumens limit the full exposure of pathogenic microbes to high-level disinfectants. These experiments demonstrated that OPA disinfection of the hysteroscope would not eliminate contaminating microbes, which represents a reprocessing failure and an infection risk.