The workshop on 'Reactive and therapy induced BM changes linked to systemic infectious and non-infectious disorders including MAS/HLH' of the 22nd meeting of the European Association for Haematopathology held in Dubrovnik, 2024, included 58 cases. These encompassed a broad range of infections, autoimmune disorders, malignancies and therapy-effects, or a combination of these factors, of which 28 had an associated Hemophagocytic Lymphohistiocytosis (HLH) / Macrophage Activation Syndrome (MAS). Histoplasmosis, the infection mostly associated with HLH, showed a wide variability of BM changes, with or without focal lesions. Leishmaniasis, less often associated with HLH, induced BM changes that mimic myelodysplastic syndrome. BM changes after COVID-19 infection included myeloid and megakaryocytic hypoplasia, erythroid hyperplasia, dyserythropoiesis, hemophagocytosis, and possibly ring granulomas. Other infectious causes included viruses (HHV-8, EBV, Parvovirus B19), mycobacterial infections, and human granulocytic anaplasmosis. HLH may arise in association with the full spectrum of EBV-related disorders, including acute infection, systemic chronic active EBV disease, viral reactivation, and EBV-associated malignancies. BM changes associated with autoimmune diseases included plasmacytosis, myeloid hyperplasia and hemophagocytosis, with or without meeting the criteria of MAS/HLH, the latter often triggered by a secondary infection or exacerbation of the disease. Haematologic malignancies (EBV-positive and negative) with HLH encompassed B-cell, T-/NK-cell, and myeloid neoplasms. In addition, the workshop included therapy-induced BM changes, such as differentiation syndrome, lenalidomide-associated B-ALL, therapy-related dysplasia, gelatinous transformation, CAR-T-induced BM hypoplasia, and CAR-T-associated HLH. Finally, the workshop demonstrated the presence of T-cell expansions in a variety of conditions, which should not be misinterpreted as T-cell malignancy.
暂无摘要（点击查看详情）
Freezing of gait (FoG) is an episodic, debilitating motor phenomenon defined as paroxysmal episodes wherein there is an inability to step effectively, despite attempting to do so. Although FoG is most commonly associated with Parkinson's disease, it manifests across a spectrum of progressive neurodegenerative and potentially transient non-neurodegenerative conditions that affect overlapping locomotor circuits. The episodic nature of FoG implies transient disruptions of a distributed locomotor network rather than fixed structural lesions, rendering its neuropathological basis particularly challenging to define. This review synthesizes current knowledge of the structural, neurochemical and proteinopathic substrates that precondition and precipitate FoG. The principal disease categories implicated in FoG are reviewed, including Lewy body diseases, progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration and argyrophilic grain disease, as well as non-neurodegenerative conditions such as cerebrovascular disease and metabolic encephalopathy. Mixed and overlapping pathologies are common. Across these disorders, different disease stages and phases, and their frequent combinations, interact with selective vulnerability of distinct neuronal and glial populations, giving rise to a complex pathophysiological landscape. It is proposed that this convergence results in heightened network susceptibility, whereby cumulative damage to cortical, subcortical and brainstem locomotor nodes progressively lowers the threshold for episodic circuit failure. Understanding these multilevel neuropathological determinants is essential for developing targeted therapeutic strategies aimed at stabilizing the locomotor network and reducing FoG burden.
Traditional micro- and macrodissection techniques enable the extraction of localized regions in thin tissue sections for molecular analysis. Despite the growing use of three-dimensional (3D) microscopy, analogous methods for volumetric microdissection are lacking. Here we have developed a 3D microdissection method based on computer numerical controlled milling integrated with open-top light-sheet microscopy. We demonstrate the ability to study tumor evolution along convoluted 3D branching architectures, which is inaccessible to two-dimensional methods.
This study evaluated a combined ex vivo fundus imaging-histology protocol to improve accuracy of diagnosis in human donor eyes with limited medical history. Fifty-one formalin-fixed eyes from 32 donors underwent a standardised workflow comprising ex vivo fundus photography, selective spectral-domain optical coherence tomography (SD-OCT), and comprehensive histological examination. Medical/surgical retinal ophthalmologists independently reviewed imaging, while ophthalmic pathologists performed masked histological assessment. Diagnostic metrics were calculated using histology as the reference standard. Ex vivo imaging identified definitive pathology in 10 of 51 eyes (19.6%) and possible abnormalities in 4 eyes (7.8%). Histological analysis, however, revealed definitive pathology in 20 eyes (39.2%), detecting a broader range of diseases, including early age-related macular degeneration, hypertensive vasculopathy, and a rare choroidal tumour. Concordance was observed in 27 eyes (52.9%), mainly where no pathology was present. Significant discordance occurred in 24 eyes (47.1%), comprising 13 false negatives and 11 false positives (including misclassified pathology). Consequently, the sensitivity and specificity of ex vivo imaging for detecting pathology were 18.8% and 68.6%, respectively. While ex vivo imaging is a practical screening tool, imaging alone may miss or misclassify pathology due to postmortem artefacts and a lack of validated interpretive criteria. A combined imaging-histology approach validates the limited tissue available from eye-bank programs and maximises research value.
Atopic dermatitis (AD) is a heterogeneous disease often preceding food allergy (FA). However, it remains unclear how different developmental trajectories of AD/eczema influence the risk of FA. This study aimed to characterize longitudinal AD/eczema phenotypes from infancy to early adolescence and evaluate their specific associations with FA risk. We analyzed data from the Longitudinal Survey of Newborns in the 21st Century in Japan, including 23,767 participants followed from age 0.5 to 12 years. Distinct AD/eczema phenotypes were identified using group-based trajectory modeling derived from healthcare visit histories. Multivariable logistic regression examined the association between AD/eczema phenotypes and cumulative FA healthcare visit history, adjusting for sociodemographic factors and asthma comorbidity. Five AD/eczema phenotypes were identified: "Early-onset transient" (6.4%), "Early-onset persistent" (23.2%), "Toddler-onset persistent" (17.3%), "Late-onset" (2.1%), and "No/minimal symptoms" (51.0%). Compared with the "No/minimal symptoms" group, all AD/eczema phenotypes were associated with increased FA risk. The "Early-onset transient" (adjusted odds ratio [aOR], 2.33; 95% CI, 1.98-2.74) and "Early-onset persistent" (aOR, 2.33; 95% CI, 2.10-2.59) groups showed the strongest associations. The "Late-onset" phenotype was also associated with increased risk (aOR, 1.42; 95% CI, 1.04-1.93), with elevated risk observed in early childhood preceding the peak of overt skin symptoms. Distinct developmental trajectories of AD/eczema are differentially associated with FA risk. While early-onset phenotypes confer the highest risk, the elevated risk in "Late-onset" trajectories before peak symptoms suggests shared underlying susceptibility or subclinical pathology. Monitoring FA development is important across all clinical trajectories of AD/eczema. • Atopic dermatitis (AD) is a primary precursor for the atopic march, but how different longitudinal trajectories influence food allergy (FA) risk remains unclear. • Early-onset persistent AD is considered to pose the highest risk for FA. • Early-onset transient AD/eczema carries a high FA risk comparable to persistent cases, indicating that timing of onset is more critical than disease duration for FA development. • Late-onset AD/eczema trajectories show elevated FA risk in early childhood preceding peak skin symptoms, suggesting shared underlying susceptibility or subclinical pathology.
Accurate interpretation of pediatric elbow imaging depends on understanding the developmental relationship between the radial head and the capitellum. While the traditional sequence of pediatric elbow ossification centers provides a useful framework, it does not capture morphologic variability, asynchronous maturation, and eccentric ossification patterns that may mimic pathology. This review synthesizes current evidence on pediatric elbow ossification with particular emphasis on normal and variant radial head development. The following key questions are addressed: (1) How frequently does eccentric radial head ossification occur on MRI? (2) What is its magnitude and relationship to age and sex? (3) How should normal variants be distinguished from pathology? Recent findings reveal that the capitellum commonly ossifies eccentrically before centralizing with growth. In our cohort of 66 children, radial head ossification was eccentric in 68-71% of cases in both sagittal and coronal planes. Offsets were small (average magnitude < 3%), predominantly posterior and radial, and generally did not correlate with age except for progressive centralization in the coronal plane among males. The radiocapitellar line remained reliable on the lateral view but demonstrated expected lateral offset on AP views. Eccentric radial head ossification represents a common physiologic pattern that does not reliably centralize with age. Recognition of this variant can reduce misdiagnosis and unnecessary intervention, and has implications for fracture assessment, surgical planning, and longitudinal research. Future studies should include prospective MRI tracking across diverse populations to establish normative ranges and develop quantitative tools for clinical applications.
Friedreich ataxia (FRDA) is a progressive neuromuscular degenerative disorder caused by GAA repeat expansions in the FXN gene, leading to frataxin deficiency and multisystem pathology. Cardiomyopathy is the leading cause of mortality in individuals with FRDA. To investigate the cellular and molecular mechanisms underlying FRDA-associated cardiac dysfunction, we employed induced pluripotent stem cell (iPSC) lines derived from three individuals with FRDA, each paired with an isogenic control line generated through CRISPR/Cas9-mediated excision of the pathogenic GAA repeat expansion. Correction of the mutation restored FXN expression to levels comparable to healthy donor iPSCs, and all lines differentiated efficiently into cardiomyocytes. Functional analysis revealed significant contractile abnormalities in FRDA cardiomyocytes and multicellular cardiac microtissues, including prolonged contraction and relaxation times and faster beating rates, consistent with clinical observations of cardiac contractile dysfunction. FRDA cardiomyocytes also exhibited pathological features such as increased cell size, irregular calcium transients, elevated mitochondrial reactive oxygen species levels, increased mitochondrial fission and increased cell death. These phenotypes were exacerbated by pathological levels of iron supplementation in culture media, highlighting the heightened sensitivity of frataxin-deficient cardiomyocytes to iron-induced metabolic stress. RNA sequencing revealed a distinct transcriptional profile associated with frataxin deficiency. MEG3 and PCDHGA10 were consistently dysregulated across all three FRDA-iPSC lines and may represent early molecular markers of FRDA cardiomyopathy. Functional interrogation of these candidates demonstrated that targeted silencing of MEG3 or PCDHGA10 in FRDA cardiomyocytes significantly reduced disease‑associated cell death without affecting FXN expression. Notably, PCDHGA10 silencing also normalized elevated mitochondrial reactive oxygen species, whereas MEG3 silencing did not, highlighting gene‑specific contributions to FRDA cardiomyocyte survival. Collectively, these findings identify MEG3 and PCDHGA10 as functionally relevant regulators of FRDA cardiomyocyte pathology.
Artificial intelligence-driven image analysis has enabled significant advances in digital pathology. However, most approaches have focused on cell or organ structures. This manuscript presents a reproducible deep learning methodology for pixel-level analysis of amorphic patterns in haematoxylin and eosin-stained whole-slide histological images. This study analysed the pixel patterns in the extracellular matrix (ECM) part of connective tissue to identify differences in airway wall ECM compartments and their heterogeneity, which are microscopically similar and difficult to discern with the human eye. Through a targeted preprocessing pipeline, the deep learning model is guided to emphasise learning from pixel-level patterns in non-cellular tissue components while reducing the influence of cellular structures and artefacts. Combined with transfer learning, the model accurately distinguishes the characteristics of the airway submucosa and adventitia, achieving a test area under the curve of 0.84. Using visualisation techniques and statistical analysis, we demonstrate that random pixel imputation successfully reduces the effects of cellular structures on model learning. The framework is applied in a proof-of-principle study of lung tissue from patients with chronic obstructive pulmonary disease, illustrating how this quantitative approach can study population heterogeneity and inform novel research directions. Ultimately, this study provides an innovative and adaptable framework that unlocks the analytical potential of often-overlooked amorphic components in AI-empowered histopathology.
Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, are defined by the progressive loss of neurons through interconnected pathological mechanisms, including oxidative stress, mitochondrial dysfunction, protein aggregation, and neuroinflammation. Accumulating evidence implicates metal dyshomeostasis as a central and multifaceted contributor to these mechanisms, with roles ranging from a primary pathogenic driver in AD and PD, to a secondary amplifier of genetic pathology in HD and ALS, and as a contextual risk modifier in the presence of toxic metals. Essential trace metals such as iron, zinc, copper, manganese, selenium, iodine, and molybdenum are vital for neurotransmission, antioxidant defense, and cellular metabolism. Dysregulation of these metals disrupts redox balance, impairs proteostasis, and activates regulated cell death pathways, including ferroptosis and cuproptosis. Toxic metals, such as lead, cadmium, and mercury, exacerbate neurodegeneration by displacing essential metals, inducing oxidative injury, and promoting protein misfolding and neuroinflammation. This narrative review synthesizes mechanistic, experimental, genetic epidemiological, and clinical evidence to critically evaluate the contributions of both essential and toxic metals to neurodegeneration in AD, PD, HD, and ALS. We examine the genetic, environmental, and physiological determinants of metal homeostasis; the analytical techniques for quantifying metals in clinical samples; and clinical trial data on metal-targeted therapeutic strategies. Notably, iron chelation with deferiprone consistently reduces brain iron on neuroimaging but worsens clinical outcomes in both PD and AD, presenting a translational paradox that requires mechanistic re-evaluation. We also provide methodological recommendations for interpreting Mendelian randomization studies of metal exposures and propose translational priorities to advance metal-targeted diagnostics and therapeutics for neurodegenerative diseases.
The absence of maternal immune rejection of a haploidentical fetus remains unexplained. We hypothesize that the presence of different HLA antigens on trophoblasts and maternal cells via killer cell immunoglobulin-like receptors (KIRs) provides two-way tuning (education, licensing) of decidual natural killer cells (dNK) with the appearance of alloreactive (HvG) and autoreactive (HvH) dNK. Disturbances in dNKHvG and dNKHvH representation may lead to abnormalities in placental development and pregnancy pathology. Our data show that recurrent pregnancy loss is not associated with specific HLA and KIR genotypes in mother and fetus, although the peculiarities of tuning involving KIR3DL2 may affect pregnancy outcome. Mathematical modeling shows the dependence of dNKHvG and dNKHvH representation on the probability of random KIR gene expression. The new description of NK cell involvement in the immune response in the placenta via two-way tuning is applicable to all cases where there are target cells with normal and different "guest" HLA expression (viral infections, tumors).
Loneliness has been linked with cognitive decline and dementia. Studies show relationships between loneliness and neurodegeneration, amyloid, and tau burden. We investigated whether loneliness relates to plasma biomarkers of neurodegenerative processes among cognitively normal or mildly impaired older adults at the population level. A population-based cohort (n = 884) in southwestern Pennsylvania. Demographics; loneliness and social isolation composite scores, depression symptoms, Clinical Dementia Rating, plasma amyloid beta (Aβ) 42, Aβ40, p-tau181, p-tau217, NfL, GFAP. We examined the associations of loneliness with plasma biomarkers using regression analyses in both cross-sectional and longitudinal models. For cross-sectional analysis, we used data from 884 dementia-free participants at the closest wave to biomarker testing (within 180 days). For longitudinal analysis, we first derived loneliness trajectories from 514 participants with repeated annual loneliness measurements for up to 15 years prior to biomarker testing, then used these trajectories as predictors in regression models examining their associations with plasma biomarkers. Compared with the stable loneliness trajectory, the increasing loneliness trajectory showed nominally higher p-tau181 levels (β = 0.305 log-transformed, 95% CI: 0.022, 0.587; t_476 = 2.112; p = 0.035, uncorrected; multiple comparison-adjusted p = 0.211), adjusting for age, sex, education, social isolation, and depression symptoms. This exploratory analysis found a nominal association between increasing loneliness and p-tau181 that did not survive correction for multiple comparisons. Findings should be considered hypothesis-generating. If confirmed through replication in larger samples, associations between loneliness patterns and tau pathology could inform understanding of psychosocial contributions to neurodegeneration.
Children with severe self-injurious behaviour (SIB) are at risk of permanent injury and lack effective treatment options. Neuromodulation of the nucleus accumbens (NAc), a key node in reward and behavioural regulation circuits, may directly modulate the drivers of SIB. We report long-term outcomes from a first-in-human, single-centre trial of deep brain stimulation (DBS) targeting the NAc in children and adolescents with profound autism and treatment-refractory SIB (NCT03982888). Six participants (ages 7-14 years; mean 11.7) underwent bilateral implantation and were followed prospectively for at least 24 months (mean 32.5 months, range 25.8-56.0). One serious adverse event occurred: a device-related infection requiring hardware explantation, followed by relapse to baseline levels of self-injury. Subsequent re-implantation in this participant yielded rapid improvement in SIB, providing single-subject, causal withdrawal-rechallenge evidence of treatment-specific benefit. Across the cohort, NAc-DBS produced sustained reductions in SIB frequency and severity, repetitive and obsessive-compulsive behaviours, and clinically meaningful improvements in quality of life. The durability of these effects over multi-year follow-up suggests that circuit-targeted neuromodulation may modify the developmental course of severe behavioural pathology. These findings provide the first long-term evidence that modulation of reward circuitry can durably alter maladaptive behaviour in childhood neurodevelopmental disorders.
Intervertebral disc degeneration (IVDD) is a major contributor to chronic low back pain, yet its molecular mechanisms remain incompletely understood. Emerging evidence suggests that ferroptosis, an iron-dependent form of regulated cell death, may play a key role in the degeneration of nucleus pulposus cells (NPCs). However, its involvement in IVDD has not been systematically explored. Resveratrol (Res), a natural polyphenol with antioxidant and cytoprotective effects, shows therapeutic potential, but its regulatory role in ferroptosis during IVDD is unclear. In this study, bulk transcriptome analysis identified 22 ferroptosis-related differentially expressed genes, among which five hub genes (GPX4, FTH1, HMOX1, NCOA4, and TFRC) were strongly linked to ferroptosis and oxidative stress pathways. Single-cell transcriptome data further revealed dynamic expression of these genes in NP cells, showing decreased GPX4 and FTH1 and increased HMOX1, NCOA4, and TFRC along the differentiation trajectory. High-dimensional weighted gene co-expression network analysis (hdWGCNA) confirmed significant associations between ferroptosis-related gene modules and IVDD pathology. Validation using human clinical samples, NP cell models, and animal experiments demonstrated that Res alleviates IVDD by modulating hub gene expression and suppressing NP cell ferroptosis. Overall, this study highlights ferroptosis as a key mechanism driving IVDD and identifies resveratrol as a promising therapeutic candidate targeting NP cell ferroptosis.
Objective: To explore the independent risk factors of brain metastasis after systematic treatment in newly diagnosed non-stage Ⅳ breast cancer patients with HER-2-low expression, and to determine the recurrence risk stratification of brain metastasis, so as to guide the follow-up pattern of patients with different risk stratification. Methods: A retrospective analysis was performed on non-stage Ⅳ breast cancer patients admitted to Shandong First Medical University Affiliated Tumor Hospital from January 2012 to January 2020 with complete follow-up data. According to the immunohistochemical test results, only HER-2-low breast cancer patients confirmed by postoperative pathology were enrolled. The independent risk factors and the rate of brain metastasis were analyzed, and brain metastasis risk stratification was performed based on the number of independent risk factors. Results: 247 patients were enrolled, with a median follow-up of 51 months, 138 patients developed brain metastasis during follow-up, and the median development time was 55.5 months. Univariate analysis showed that age, menopause status, ER, tissue grade, T stage, N stage, CEA, CA125 and CA153 were associated with brain metastasis (P＜0.05). Multivariate logistic regression analysis showed that negative ER (OR=2.486, 95% CI: 1.117-5.533), tissue gradeⅡ (OR=12.175, 95% CI: 2.991-49.567), tissue grade Ⅲ (OR=14.03, 95% CI: 3.383-58.184), T2 stage (OR=2.272, 95% CI: 1.122-4.602), T3 stage (OR=9.05, 95% CI: 1.804-45.398), T4 stage (OR=6.691, 95% CI: 1.814-24.676), number of axillary lymph node metastasis≥10, N3 (OR=2.748, 95% CI: 1.041-7.260), CA125 higher than the reference value (OR=3.933, 95% CI: 1.601-9.66) and CA153 higher than the reference value (OR=2.578, 95% CI: 1.161-5.724) were independent risk factors for brain metastasis (P＜0.05). The risk of brain metastasis was assessed according to the number of independent risk factors in patients: Those with 0 risk factor were classified as low-risk group, 1-2 risk factors as medium-risk group, 3-4 risk factors as high-risk group, and 5-6 risk factors as extremely high-risk group. The incidence of brain metastases in each group were 0 (0/3), 33.33% (39/117), 74.55% (82/110) and 100.00% (17/17), respectively. Conclusion: The risk stratification of brain metastasis based on clinicopathological characteristics and levels of related tumor markers are helpful to predict the risk of brain metastasis in non-stage Ⅳ breast cancer patients with HER-2 low expression after systematic treatment, so as to accurately identify patients with high recurrence risk and formulate targeted follow-up strategies for them. 目的： 探讨初诊非Ⅳ期人表皮生长因子受体2（HER-2）低表达乳腺癌患者接受系统治疗后脑转移的独立风险因素，明确脑转移的复发风险分层，以指导不同风险分层患者的随诊。 方法： 回顾性分析2012年1月至2020年1月山东第一医科大学附属肿瘤医院收治的随访资料完整的非Ⅳ期乳腺癌患者，根据免疫组织化学检测结果，入组术后病理证实为HER-2低表达的乳腺癌患者，分析脑转移率，采用Logistic回归模型分析脑转移的独立风险因素，基于独立风险因素数目进行脑转移风险分层。 结果： 共入组247例患者，中位随访51个月，138例患者随访中出现脑转移，脑转移发生中位时间为55.5个月。单因素分析显示，脑转移与患者年龄、绝经状态、雌激素受体（ER）、组织分级、T分期、N分期、癌胚抗原、糖类抗原125（CA125）、CA153有关（P＜0.05）。多因素分析显示，ER阴性（OR=2.486，95% CI：1.117～5.533）、组织分级Ⅱ级（OR=12.175，95% CI：2.991～49.567）、组织分级Ⅲ级（OR=14.03，95% CI：3.383～58.184）、T2期（OR=2.272，95% CI：1.122～4.602）、T3期（OR=9.05，95% CI：1.804～45.398）、T4期（OR=6.691，95% CI：1.814～24.676）、腋窝淋巴结转移数目≥10枚即N3期（OR=2.748，95% CI：1.041～7.260）、CA125高于参考值（OR=3.933，95% CI：1.601～9.660）以及CA153高于参考值（OR=2.578，95% CI：1.161～5.724）是脑转移的独立风险因素（均P＜0.05）。按照患者存在独立风险因素个数进行脑转移风险评估，将具有0个风险因素者归为低危组，1～2个风险因素者归为中危组，3～4个风险因素者归为高危组，5～6个风险因素者归为极高危组，各组的脑转移发生率分别为0（0/3）、33.33%（39/117）、74.55%（82/110）和100.00%（17/17）。 结论： 根据临床病理特征及相关肿瘤标志物水平构建脑转移的风险分层，有助于预测HER-2低表达非Ⅳ期乳腺癌患者系统治疗后脑转移风险，以便准确识别高复发风险患者，对其制定有针对性的随访策略。.
Accurate survival prediction in non-small cell lung cancer (NSCLC) requires integrating clinical, radiological, and histopathological data. Multimodal deep learning (MDL) can improve precision prognosis, but small cohorts and missing modalities limit its clinical applicability, as conventional approaches enforce complete-case filtering or imputation. We present a missing-aware multimodal survival framework that combines computed tomography (CT), whole-slide histopathology images (WSI), and structured clinical variables for overall survival modeling in unresectable stage II-III NSCLC. The framework uses foundation models (FMs) for modality-specific feature extraction and a missing-aware encoding strategy that enables intermediate multimodal fusion under naturally incomplete modality profiles. By design, the architecture processes all available data without dropping patients during training or inference. Intermediate fusion outperforms unimodal baselines and both early and late fusion strategies, with the trimodal configuration reaching a C-index of 74.42. Modality-importance analyses show that the fusion model adapts its reliance on each data stream according to representation informativeness, shaped by the alignment between FM pretraining objectives and the survival task. The learned risk scores produce clinically meaningful stratification of disease progression and metastatic risk, with statistically significant log-rank tests across all modality combinations, supporting the translational relevance of the proposed framework.
Persistent pain after total hip arthroplasty (THA) is a common complication requiring extensive diagnostic effort and is often associated with potentially invasive and morbid treatment options. With THA volume expected to steadily increase there is a similarly growing need for creative and effective diagnostic and therapeutic options for these clinically challenging patients. Hip arthroscopy has emerged as a promising tool in the setting of persistent pain after THA with expanding indications and promising outcomes. The purpose of this article was to provide a review of the current state of literature regarding arthroscopic and endoscopic solutions for common causes of persistent pain after THA with a focus on patient selection, indications, surgical considerations, outcomes, and complications. The most common indication for hip arthroscopy after THA is iliopsoas tendinopathy, showing excellent outcomes with symptom resolution in greater than 90% of patients after arthroscopic iliopsoas release or lengthening. The second most common indication is diagnostic arthroscopy in the setting of otherwise negative extensive work-up, which has shown diagnostic value for occult implant loosening, capsular fibrosis, and metal hypersensitivity. Endoscopic decompression for the treatment of ischiofemoral impingement and sciatic nerve decompression has also shown consistent improvements in pain and function. In addition to these well described indications, future utilization of hip arthroscopy for loose body removal, capsular plication for instability, and management of prosthetic joint infection are potentially emerging indications. Hip arthroscopy after THA is a safe and effective tool for the management of common causes of persistent pain after THA with robust support for iliopsoas pathology and emerging evidence and outcomes for less common indications. Future research will both expand and narrow these indications as diagnostic criteria, patient selection, and surgical techniques are refined.
Between February 2024 and June 2025, surveys conducted in northwestern Morocco revealed citrus fruits (Citrus sinensis and Citrus × limon) showing atypical postharvest decay symptoms, characterized by dark, water-soaked lesions with zonation and coremia-like structures. These symptoms were detected at only two sites, with a low incidence of 1.6% in the orchard and 0.5% in market samples. Five fungal isolates were obtained from symptomatic tissues on potato dextrose agar (PDA). Morphological characterization identified all isolates as Penicillium ulaiense, based on colony and micromorphological features consistent with published descriptions. Two representative isolates (BH_B1 and BH_E2) were selected for molecular analyses. Sequencing of the ITS region and the β-tubulin (BenA) gene showed 99-100% identity with reference P. ulaiense sequences, and the concatenated alignment comprised 804 base pairs. Phylogenetic analyses placed the Moroccan isolates within a well-supported P. ulaiense clade, clearly distinct from closely related species such as P. italicum and P. expansum. Pathogenicity assays reproduced typical symptoms on C. sinensis fruits, with progressive lesion development and successful re-isolation of the pathogen, confirming its pathogenic role under experimental conditions. This study reports, for the first time, the occurrence of Penicillium ulaiense associated with postharvest whisker mold symptoms on citrus fruits in Morocco. It provides new insights into postharvest citrus pathogens in Morocco and establishes a basis for future investigations on the occurrence and epidemiology of this species.
To assess the association between parental occupational pesticide exposures at birth and adult testicular germ cell tumour (TGCT) by histological subtype and the agreement between two pesticide job-exposure matrices (JEM). TGCT cases (n=454) and matched controls (n=670) aged 18-45 years were recruited from 20 French university hospitals into the TESTIS national case-control study. Paternal and maternal jobs at birth were obtained from interviews of participants and their mothers/relatives and coded into official nomenclatures (International Standard Classification of Occupations, French nomenclature of activity-1999). Two complementary JEMs, ALOHA+ and FRIJEM, assessed occupational exposure to all pesticides, herbicides, insecticides, fungicides with ALOHA+ for each parent by linking job titles to JEM-derived probability and intensity estimates (no/low/high). Cohen's Kappa coefficient (κ) assessed their agreement. ORs and 95% CIs comparing exposure and levels of exposure with no exposure were estimated using conditional logistic regression adjusted for literature-based covariates statistically associated with TGCT and stratified by histological subtypes. Agreement between ALOHA+and FRIJEM was moderate to substantial (κ 0.52-0.80). A statistically non-significant higher TGCT risk was observed for high paternal occupational pesticide exposure with ALOHA+ (OR 1.95, CI 0.98 to 3.84) and FRIJEM (OR 1.70, CI 0.88 to 3.28). With ALOHA+, statistically significant positive associations were seen for high paternal occupational exposure to herbicides (overall: OR 4.23, CI 1.75 to 10.22; seminomas: OR 4.78, CI 1.79 to 12.77; non-seminomas: OR 3.53, CI 1.21 to 10.3) and fungicides (overall: OR 2.09, CI 1.05 to 4.18; seminomas: OR 2.31, CI 1.02 to 5.23). No statistically significant associations were observed for other levels of paternal exposure or pesticide groups nor for maternal exposure. Only high paternal occupational exposure to pesticides at birth, especially herbicides and fungicides, was positively associated with TGCT.
The human antiviral antibody reactome provides a cumulative molecular record of immune exposures. Using high-resolution VirScan profiling, we compared epitope-level antibody responses across early childhood and adulthood. Infants are born with maternal IgG antibodies, but these antibodies decay rapidly and are replaced by endogenous responses to ~22 new viral exposures within three years. Pediatric antibody reactivities remain highly dynamic until about age 7 and are broad in epitope specificity but largely short-lived. In contrast, adult reactomes are remarkably stable and individualized, enabling accurate longitudinal donor identification (Immunoprint, > 99.99% accuracy). Stability varies by viral family, with Pneumoviridae and Picornaviridae persisting more robustly than Coronaviridae or Orthomyxoviridae. Across ages, immunodominant epitopes and initial binding strength predict response persistence. Longitudinal profiling highlights biological and epidemiological drivers of reactome change. This population-level, age-stratified atlas informs our understanding of immune memory and development with applications to vaccine design, surveillance, and precision public health.