Quality Measurement of Consumer Health Questions: Content and Language Perspectives.

BACKGROUND: Health information consumers increasingly rely on question-and-answer (Q&A) communities to address their health concerns. However, the quality of questions posted significantly impacts the likelihood and relevance of received answers. OBJECTIVE: This study aims to improve our understanding of the quality of health questions within web-based Q&A communities. METHODS: We develop a novel framework for defining and measuring question quality within web-based health communities, incorporating content- and language-based variables. This framework leverages k-means clustering and establishes automated metrics to assess overall question quality. To validate our framework, we analyze questions related to kidney disease from expert-curated and community-based Q&A platforms. Expert evaluations confirm the validity of our quality construct, while regression analysis helps identify key variables. RESULTS: High-quality questions were more likely to include demographic and medical information than lower-quality questions (P<.001). In contrast, asking questions at the various stages of disease development was less likely to reflect high-quality questions (P<.001). Low-quality questions were generally shorter with lengthier sentences than high-quality questions (P<.01). CONCLUSIONS: Our findings empower consumers to formulate more effective health information questions, ultimately leading to better engagement and more valuable insights within web-based Q&A communities. Furthermore, our findings provide valuable insights for platform developers and moderators seeking to enhance the quality of user interactions and foster a more trustworthy and informative environment for health information exchange.

Cocrystal engineering for sustained release of dicamba: Mitigating secondary drift and reducing leaching.

The off-target effects of herbicides present significant challenges in agricultural practices, posing serious threats to both ecological systems and human health. Dicamba, one of the most widely used herbicides, is particularly problematic due to its high volatility and water solubility, which can lead to rapid environmental dispersal, non-target toxicity, and groundwater contamination. To mitigate these issues, we synthesized a novel cocrystal of dicamba and phenazine (DCB-PHE cocrystal) through a combination of theoretical prediction and mechanochemical screening. The DCB-PHE cocrystal was characterized using single-crystal and powder X-ray diffraction, Fourier-transform infrared spectroscopy (FT-IR), and thermal analysis. Compared to pure dicamba, the DCB-PHE cocrystal exhibited a substantial reduction in volatility by 59 % and a decrease in equilibrium solubility by up to 5.4 times across various temperatures (15 °C, 25 °C, 35 °C). Additionally, the dissolution rates were significantly lowered by over 94 %. Leaching experiments demonstrated that the DCB-PHE cocrystal reduced total leachate by 4.9 % and delayed percolation. In greenhouse trials, the DCB-PHE cocrystal caused less damage to exposed soy plants and enhanced herbicidal activity against target weeds, with fresh weight reduction of chicory and ryegrass by 32 % and 28 %, respectively, at the highest dosage. Furthermore, safety assays confirmed that the DCB-PHE cocrystal's safety profile was comparable to that of dicamba in terms of its impact on wheat, and it did not exhibit increased genotoxicity to broad beans. These findings suggest that the DCB-PHE cocrystal is a promising candidate for reducing the environmental impacts of dicamba while maintaining its herbicidal efficacy.

Inter-observer consistency on subsolid nodule follow-up recommendation based on National Comprehensive Cancer Network (NCCN) guidelines in low-dose computed tomography (LDCT) lung cancer screening.

Background: Follow-up management of pulmonary nodules is a crucial component of lung cancer screening. Consistency in follow-up recommendations is essential for effective lung cancer screening. This study aimed to assess inter-observer agreement on National Comprehensive Cancer Network (NCCN) guideline-based follow-up recommendation for subsolid nodules from low-dose computed tomography (LDCT) screening. Methods: A retrospective collection of LDCT reports from 2014 to 2017 for lung cancer screening was conducted using the Radiology Information System and keyword searches, focusing on subsolid nodules. A total of 110 LDCT cases containing subsolid nodules were identified. Two senior radiologists provided standardized follow-up recommendation. Follow-up recommendation was categorized into four groups (0-, 3-, 6-, and 12-month). To ensure overall balance and representativeness of the follow-up categories, 60 scans from 60 participants were included (distribution ratio 1:1:2:2). Cases were categorised into follow-up recommendation groups by five observers following NCCN guidelines. Fleiss' kappa statistic was used to evaluate inter-observer agreement. Results: Overall accuracy rate for follow-up recommendation among five observers was 72.3%. Chest radiologists' overall agreement was significantly higher than radiology residents (P<0.01). The overall agreement among the five observers was moderate, with a Fleiss' kappa of 0.437. For all paired readers, the mean Cohen's kappa value was 0.603, with 95% confidence interval (CI) from 0.489 to 0.716. Chest radiologists demonstrated substantial agreement, evidenced by a Cohen's kappa of 0.655 (95% CI: 0.503-0.807). In contrast, the mean Cohen's kappa among radiology residents was 0.533 (95% CI: 0.501-0.565). The majority of cases with discrepancies, accounting for 73.5%, were associated with the same risk-dominant nodules. A higher proportion of part-solid nodule was a risk factor for discrepancies. Of the 600 paired readings, major discrepancies and substantial discrepancies were observed in 27.5% and 4.8% (29/600) of the cases. Conclusions: In subsolid nodules, category evaluation of observer follow-up recommendation based on NCCN guidelines achieved moderate consistency. Disagreements were mainly caused by measurement and type disagreements of identical risk-dominant nodules. Part-solid nodule was a contributor for discrepancies in follow-up recommendation. Major and substantial management discrepancies were 27.5% and 4.8% in the paired evaluations.

Deep learning model based on primary tumor to predict lymph node status in clinical stage IA lung adenocarcinoma: a multicenter study.

Objective: To develop a deep learning model to predict lymph node (LN) status in clinical stage IA lung adenocarcinoma patients. Methods: This diagnostic study included 1,009 patients with pathologically confirmed clinical stage T1N0M0 lung adenocarcinoma from two independent datasets (699 from Cancer Hospital of Chinese Academy of Medical Sciences and 310 from PLA General Hospital) between January 2005 and December 2019. The Cancer Hospital dataset was randomly split into a training cohort (559 patients) and a validation cohort (140 patients) to train and tune a deep learning model based on a deep residual network (ResNet). The PLA Hospital dataset was used as a testing cohort to evaluate the generalization ability of the model. Thoracic radiologists manually segmented tumors and interpreted high-resolution computed tomography (HRCT) features for the model. The predictive performance was assessed by area under the curves (AUCs), accuracy, precision, recall, and F1 score. Subgroup analysis was performed to evaluate the potential bias of the study population. Results: A total of 1,009 patients were included in this study; 409 (40.5%) were male and 600 (59.5%) were female. The median age was 57.0 years (inter-quartile range, IQR: 50.0-64.0). The deep learning model achieved AUCs of 0.906 (95% CI: 0.873-0.938) and 0.893 (95% CI: 0.857-0.930) for predicting pN0 disease in the testing cohort and a non-pure ground glass nodule (non-pGGN) testing cohort, respectively. No significant difference was detected between the testing cohort and the non-pGGN testing cohort (P = 0.622). The precisions of this model for predicting pN0 disease were 0.979 (95% CI: 0.963-0.995) and 0.983 (95% CI: 0.967-0.998) in the testing cohort and the non-pGGN testing cohort, respectively. The deep learning model achieved AUCs of 0.848 (95% CI: 0.798-0.898) and 0.831 (95% CI: 0.776-0.887) for predicting pN2 disease in the testing cohort and the non-pGGN testing cohort, respectively. No significant difference was detected between the testing cohort and the non-pGGN testing cohort (P = 0.657). The recalls of this model for predicting pN2 disease were 0.903 (95% CI: 0.870-0.936) and 0.931 (95% CI: 0.901-0.961) in the testing cohort and the non-pGGN testing cohort, respectively. Conclusions: The superior performance of the deep learning model will help to target the extension of lymph node dissection and reduce the ineffective lymph node dissection in early-stage lung adenocarcinoma patients.

Real time precisely tracing the fluctuations of mitochondrial SO2 in cells during ferroptosis and tissues using a mitochondrial-immobilized ratiometric fluorescent probe.

Mitochondrial sulfur dioxide (SO2) plays important roles in physiological and pathological activities. Unfortunately, it is lack of a reliable tool to precisely visualize the mitochondrial SO2 and elaborate its complicated functions in various cytoactivities. Here we report a mitochondrial-immobilized fluorescent probe PM-Cl consisting of coumarin and benzyl chloride modified benzothiazole, which enables selective visualization of mitochondrial SO2via chemical immobilization. The spectral results demonstrated that probe PM-Cl could respond to SO2 with high selectivity and sensitivity. Co-localization and the fluorescence of cytolysis extraction verified the excellent mitochondrial targeting and anchoring abilities. Due to the chemical immobilization, probe PM-Cl could firmly retain into mitochondria after stimulation of carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and H2O2. Significantly, a series of fluorescence images are indicative of capability for detecting the fluctuations of SO2 in mitochondria during ferroptosis. Furthermore, PM-Cl also could visualize SO2 in myocardium and muscle tissues after the stimulation of CCCP. Taken together, probe PM-Cl is a very potential molecular tool for precisely detecting mitochondrial SO2 to explore its complex functions in physiological and pathological activities.

A remarkable membrane-permeable fluorescent probe for real-time imaging of mitochondrial SO2 with high fidelity during ferroptosis.

Mitochondrial sulfur dioxide (SO2) plays a double-edged role in cells, and the real-time and in situ tracing of its dynamic behaviors to elucidate its complicated functions in detail is of great significance. Here, we developed a simple mitochondria-targeted fluorescent probe ZW for tracing SO2 with good membrane permeability. In probe ZW, the 1-phenylpyrrolidine-decorated benzopyrylium unit is employed as the selective response site for SO2. Besides, it also acts as the main fluorophore for signal conversion. The spectral results displayed that ZW could emit near-infrared (NIR) fluorescence (670 nm) and has a highly sensitive and selective response to SO2 (LOD = 0.19 µM). For biological imaging, compared with the control probe ZE, concentration- and time-dependent results verified that probe ZW has remarkable cell delivery with low concentration (200 nM) and fast response time (3 min). Furthermore, the NIR emission of ZW rendered high-fidelity imaging in living cells. Owing to its positive charge, ZW showed favorable mitochondria-targeting properties by colocalization experiments. Probe ZW could detect SO2 in real-time and in situ with high photostability in cells. Significantly, it has the ability to monitor the changes of endogenous SO2 during ferroptosis.

LM11A-31, a modulator of p75 neurotrophin receptor, suppresses HIV-1 replication and inflammatory response in macrophages.

Antiretroviral drugs have made significant progress in treating HIV-1 and improving the quality of HIV-1-infected individuals. However, due to their limited permeability into the brain HIV-1 replication persists in brain reservoirs such as perivascular macrophages and microglia, which cause HIV-1-associated neurocognitive disorders. Therefore, it is highly desirable to find a novel therapy that can cross the blood-brain barrier (BBB) and target HIV-1 pathogenesis in brain reservoirs. A recently developed 2-amino-3-methylpentanoic acid [2-morpholin-4-yl-ethyl]-amide (LM11A-31), which is a p75 neutrotrophin receptor (p75NTR) modulator, can cross the BBB. In this study, we examined whether LM11A-31 treatment can suppress HIV-1 replication, oxidative stress, cytotoxicity, and inflammatory response in macrophages. Our results showed that LM11A-31 (100 nM) alone and/or in combination with positive control darunavir (5.5 µM) significantly suppresses viral replication and reduces cytotoxicity. Moreover, the HIV-1 suppression by LM11A-31 was comparable to the HIV-1 suppression by darunavir. Although p75NTR was upregulated in HIV-1-infected macrophages compared to uninfected macrophages, LM11A-31 did not significantly reduce the p75NTR expression in macrophages. Furthermore, our study illustrated that LM11A-31 alone and/or in combination with darunavir significantly suppress pro-inflammatory cytokines including IL-1ß, IL-8, IL-18, and TNF-α and chemokines MCP-1 in HIV-induced macrophages. The suppression of these cytokines and chemokines by LM11A-31 was comparable to darunavir. In contrast, LM11A-31 did not significantly alter oxidative stress, expression of antioxidant enzymes, or autophagy marker proteins in U1 macrophages. The results suggest that LM11A-31, which can cross the BBB, has therapeutic potential in suppressing HIV-1 and inflammatory response in brain reservoirs, especially in macrophages.

An efficient and successful outcome after haematopoietic stem cell transplantation in a patient with an LPS-responsive beige-like anchor gene mutation.

Lipopolysaccharide (LPS)-responsive beige ankyrin (LRBA) gene mutations were first reported as the cause of immunodeficiency syndromes and autoimmunity in 2012. The majority of LRBA patients have multiple organ system involvement and a complex clinical phenotype. Herein we present a comprehensive account on the disease progression and transplantation procedure in a patient with LRBA deficiency who exhibited progressive autoimmune disease symptoms along with recurrent pulmonary infections since the age of 6 years old. Despite receiving abatacept therapy and immunoglobulin replacement treatments to manage the symptoms, but the symptoms still progressed. Therefore, nine years after disease onset, patients were treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT). The patient experienced acute and chronic graft-versus-host disease (GVHD) and recurrent infections after transplantation. During one and a half years of follow-up, we found that allogeneic haematopoietic stem cell transplantation can relieve the symptoms of autoimmune disease in patients with LRBA deficiency, and marked clinical improvement and recovery of immune function were observed following stem cell transplantation.

A single-molecule fluorescent probe for visualizing viscosity and hypoxia in lysosomes and zebrafish embryos.

Viscosity and hypoxia, as microenvironment parameters, play important roles in maintaining normal biological processes and homeostasis. Therefore, simultaneous and sensitive detection of these elements with simple and effective methods could offer precise information in biology. Here, we report a two-site lysosome-targeting fluorescent probe, NVP, for monitoring viscosity and nitroreductase with dual emission channels (emission shift is 86 nm). The NVP probe has displayed highly sensitive and selective responses towards viscosity and nitroreductase, respectively. Significantly, the fluctuations of viscosity and NTR have been detected in vitro and in vivo. We expect that the dual-responsive fluorescent NVP probe will become a potential molecular tool for the exploration of deeper functions of viscosity and hypoxia.

Flagellin Restricts HIV-1 Infection of Macrophages through Modulation of Viral Entry Receptors and CC Chemokines.

Both bacteria product flagellin and macrophages are implicated in HIV-1 infection/disease progression. However, the impact of their interaction on HIV-1 infection and the associated mechanisms remain to be determined. We thus examined the effect of the flagellins on HIV-1 infection of primary human macrophages. We observed that the pretreatment of macrophages with the flagellins from the different bacteria significantly inhibited HIV-1 infection. The mechanistic investigation showed that the flagellin treatment of macrophages downregulated the major HIV-1 entry receptors (CD4 and CCR5) and upregulated the CC chemokines (MIP-1α, MIP-1ß and RANTES), the ligands of CCR5. These effects of the flagellin could be compromised by a toll-like receptor 5 (TLR5) antagonist. Given the important role of flagellin as a vaccine adjuvant in TLR5 activation-mediated immune regulation and in HIV-1 infection of macrophages, future investigations are necessary to determine the in vivo impact of flagellin-TLR5 interaction on macrophage-mediated innate immunity against HIV-1 infection and the effectiveness of flagellin adjuvant-based vaccines studies.

Lycium ruthenicum water extract preserves retinal ganglion cells in chronic ocular hypertension mouse models.

Lycium ruthenicum Murray (LR), known as "black goji berry" or "black wolfberry", is widely utilized in chinese herbal medicine. LR fruit showed its antioxidant and/or anti-inflammation activity in treating cardiac injury, experimental colitis, nonalcoholic fatty liver disease, fatigue, and aging. Glaucoma is the leading cause of irreversible blindness. Besides elevated intraocular pressure (IOP), oxidative stress and neuroinflammation were recognized to contribute to the pathogenesis of glaucoma. This study investigated the treatment effects of LR water extract (LRE) on retinal ganglion cells (RGCs) threatened by sustained IOP elevation in a laser-induced chronic ocular hypertension (COH) mouse model and the DBA/2J mouse strain. The antioxidation and anti-inflammation effects of LRE were further tested in the H2O2-challenged immortalized microglial (IMG) cell line in vitro. LRE oral feeding (2 g/kg) preserved the function of RGCs and promoted their survival in both models mimicking glaucoma. LRE decreased 8-hydroxyguanosine (oxidative stress marker) expression in the retina. LRE reduced the number of Iba-1+ microglia in the retina of COH mice, but not in the DBA/2J mice. At the mRNA level, LRE reversed the COH induced HO-1 and SOD-2 overexpressions in the retina of COH mice. Further in vitro study demonstrated that LRE pretreatment to IMG cells could significantly reduce H2O2 induced oxidative stress through upregulation of GPX-4, Prdx-5, HO-1, and SOD-2. Our work demonstrated that daily oral intake of LRE can be used as a preventative/treatment agent to protect RGCs under high IOP stress probably through reducing oxidative stress and inhibiting microglial activation in the retina.

The bidirectional association between the disability in activities of daily living and depression: a longitudinal study in Chinese middle-aged and older adults.

AIM: Depression and disability in activities of daily living (ADL) are common in middle-aged and older adults. This study investigated the bidirectional relationship between depression and disability in ADL in Chinese middle-aged and older adults. METHODS: Data from a baseline study of 17,596 participants from the China Health and Retirement Longitudinal Study (CHARLS) and two follow-up visits at 4 and 7 years were included. We designed Study A and Study B to explore the interaction between depression and disability in ADL in middle-aged and older people. RESULTS: Individuals with disability in ADL at baseline had adjusted odds ratios (ORs) of 1.331 (1.118, 1.584) and 1.969 (1.585, 2.448) for developing depression compared with those without disability in ADL at the 4- and 7-year follow-ups, respectively. Individuals with depression at baseline had adjusted ORs of 1.353 (1.127, 1.625) and 1.347 (1.130, 1.604), respectively, for developing disability in ADL 4 and 7 years later. CONCLUSIONS: There was a bidirectional relationship between depression and disability in ADL. Depression increased the risk of disability in ADL, but this risk did not increase with time, whereas the effect of disability in ADL on depression increased with time.

Insight into the Manipulation Mechanism of Polymorphic Transformation by Polymers: A Case of Cimetidine.

PURPOSE: Employing polymer additives is an effective strategy to realize the manipulation of polymorphic transformation. However, the manipulation mechanism is still not clear, which limit the precise selection of polymeric excipients and the development of pharmaceutical formulations. METHODS: The solubility of cimetidine (CIM) in acetonitrile/water mixtures were measured. And the polymorphic transformation from CIM form A to form B with the addition of different polymers was monitored by Raman spectroscopy. Furthermore, the manipulation effect of polymers was determined based on the results of experiments and molecular simulations. RESULTS: The solubility of form A is consistently higher than that of form B, which indicate that form B is the thermodynamically stable form within the examined temperature range. The presence of polyvinylpyrrolidone (PVP) of a shorter chain length could have a stronger inhibitory effect on the phase transformation process of metastable form, whereas polyethylene glycol (PEG) had almost no impact. The nucleation kinetics experiments and molecular dynamic simulation results showed that only PVP molecules could significantly decrease the nucleation rate of CIM, due to the ability of reducing solute molecular diffusion and solute-solute molecular interaction. A combination of crystal growth rate measurements and calculations of the interaction energies between PVP and the crystal faces of CIM indicate that smaller molecular weight PVP can suppress crystal growth more effectively. CONCLUSION: PVP K16-18 has more impact on the stabilization of CIM form A and inhibition of the phase transformation process. The manipulation mechanism of polymer additives in the polymorphic transformation of CIM was proposed.

Exposure-response modeling for nausea incidence for cotadutide using a Markov modeling approach.

Cotadutide is a dual glucagon-like peptide-1 (GLP-1)/glucagon receptor agonist. Gastrointestinal adverse effects are known to be associated with GLP-1 receptor agonism and can be mitigated through tolerance development via a gradual up-titration. This analysis aimed to characterize the relationship between exposure and nausea incidence and to optimize titration schemes. The model was developed with pooled data from cotadutide-administrated studies. Three different modeling approaches, proportional odds (PO), discrete-time Markov, and two-stage discrete-time Markov models, were employed to characterize the exposure-nausea relationship. The severity of nausea was modeled as different states (non-nausea, mild, and moderate/severe). The most appropriate model was selected to perform the covariate analysis, and the final covariate model was used to simulate the nausea event rates for various titration scenarios. The two Markov models demonstrated comparable performance and were better than the PO model. The covariate analysis was conducted with the standard Markov model for operational simplification and identified disease indications (NASH, obesity) and sex as covariates on Markov parameters. The simulations indicated that the biweekly titration with twofold dose escalation is superior to other titration schemes with a relatively low predicted nausea event rate at 600 µg (25%) and a shorter titration interval (8 weeks) to reach the therapeutic dose. The model can be utilized to optimize starting dose and titration schemes for other therapeutics in clinical trials to achieve an optimal risk-benefit balance and reach the therapeutic dose with minimal titration steps.

Assessing the efficiency of eligibility criteria for low-dose computed tomography lung screening in China according to current guidelines.

BACKGROUND: Evidence from observational studies indicates that lung cancer screening (LCS) guidelines with high rates of lung cancer (LC) underdiagnosis, and although current screening guidelines have been updated and eligibility criteria for screening have been expanded, there are no studies comparing the efficiency of LCS guidelines in Chinese population. METHODS: Between 2005 and 2022, 31,394 asymptomatic individuals were screened using low-dose computed tomography (LDCT) at our institution. Demographic data and relevant LC risk factors were collected. The efficiency of the LCS for each guideline criteria was expressed as the efficiency ratio (ER). The inclusion rates, eligibility rates, LC detection rates, and ER based on the different eligibility criteria of the four guidelines were comparatively analyzed. The four guidelines were as follows: China guideline for the screening and early detection of lung cancer (CGSL), the National Comprehensive Cancer Network (NCCN), the United States Preventive Services Task Force (USPSTF), and International Early Lung Cancer Action Program (I-ELCAP). RESULTS: Of 31,394 participants, 298 (155 women, 143 men) were diagnosed with LC. For CGSL, NCCN, USPSTF, and I-ELCAP guidelines, the eligibility rates for guidelines were 13.92%, 6.97%, 6.81%, and 53.46%; ERe for eligibility criteria were 1.46%, 1.64%, 1.51%, and 1.13%, respectively; and for the inclusion rates, they were 19.0%, 9.5%, 9.3%, and 73.0%, respectively. LCs which met the screening criteria of CGSL, NCCN, USPSTF, and I-ELCAP guidelines were 29.2%, 16.4%, 14.8%, and 86.6%, respectively. The age and smoking criteria for CGSL were stricter, hence resulting in lower rates of LC meeting the screening criteria. The CGSL, NCCN, and USPSTF guidelines showed the highest underdiagnosis in the 45-49 age group (17.4%), while the I-ELCAP guideline displayed the highest missed diagnosis rate (3.0%) in the 35-39 age group. Males and females significantly differed in eligibility based on the criteria of the four guidelines (P < 0.001). CONCLUSIONS: The I-ELCAP guideline has the highest eligibility rate for both males and females. But its actual efficiency ratio for those deemed eligible by the guideline was the lowest. Whereas the NCCN guideline has the highest ERe value for those deemed eligible by the guideline.

The Application of Surface Electromyography Technology in Evaluating Paraspinal Muscle Function.

Surface electromyography (sEMG) has emerged as a valuable tool for assessing muscle activity in various clinical and research settings. This review focuses on the application of sEMG specifically in the context of paraspinal muscles. The paraspinal muscles play a critical role in providing stability and facilitating movement of the spine. Dysfunctions or alterations in paraspinal muscle activity can lead to various musculoskeletal disorders and spinal pathologies. Therefore, understanding and quantifying paraspinal muscle activity is crucial for accurate diagnosis, treatment planning, and monitoring therapeutic interventions. This review discusses the clinical applications of sEMG in paraspinal muscles, including the assessment of low back pain, spinal disorders, and rehabilitation interventions. It explores how sEMG can aid in diagnosing the potential causes of low back pain and monitoring the effectiveness of physical therapy, spinal manipulative therapy, and exercise protocols. It also discusses emerging technologies and advancements in sEMG techniques that aim to enhance the accuracy and reliability of paraspinal muscle assessment. In summary, the application of sEMG in paraspinal muscles provides valuable insights into muscle function, dysfunction, and therapeutic interventions. By examining the literature on sEMG in paraspinal muscles, this review offers a comprehensive understanding of the current state of research, identifies knowledge gaps, and suggests future directions for optimizing the use of sEMG in assessing paraspinal muscle activity.

Successful Immune Reconstitution in a Patient with a TYK2 Deficiency after Allogeneic Stem Cell Transplantation from Unrelated Donors.

A boy with primary immunodeficiency, caused by a tyrosine kinase 2 (TYK2) mutation, presented with immune defects and a lifelong history of severe infections. Our aim was to determine whether allogeneic hematopoietic stem cell transplantation (HSCT) could restore the patient's immune defenses and reduce susceptibility to infection. In the absence of a suitable HLA-matched blood relative to act as a donor, the patient received an allogeneic HSCT from unrelated donors. The patient's clinical data were analyzed in the Children's Hospital of Chongqing Medical University (Chongqing, China) before transplantation and during the 4-year follow-up period using a combination of western blotting (e.g., TYK2 and STAT levels), qRT-PCR (e.g., T cell receptor rearrangement excision circles, kappa deletion element recombination circles, and TYK2 transcript levels), and flow cytometry (e.g., lymphocyte subpopulations and CD107α secretion). We found that HSCT significantly reduced the incidence of severe infections, restored normal TKY2 levels, and reversed defects such as impaired JAK/STAT signaling in response to interferon-α or interleukin-10 treatment. Although the patient did not develop acute graft-versus-host disease (GVHD) after transplantation, he did experience chronic GVHD symptoms in a number of organs, which were effectively managed. Our findings suggest that HSCT is a feasible strategy for reconstituting the immune system in TYK2-deficient patients; however, the factors associated with GVHD and autoimmune thyroiditis development in TYK2-deficient patients undergoing HSCT warrant further investigation.

Magnetic Resonance Elastography of Anterior Mediastinal Tumors.

BACKGROUND: Preoperative differentiation of the types of mediastinal tumors is essential. Magnetic resonance (MR) elastography potentially provides a noninvasive method to assess the classification of mediastinal tumor subtypes. PURPOSE: To evaluate the use of MR elastography in anterior mediastinal masses and to characterize the mechanical properties of tumors of different subtypes. STUDY TYPE: Prospective. SUBJECTS: 189 patients with anterior mediastinal tumors (AMTs) confirmed by histopathology (62 thymomas, 53 thymic carcinomas, 57 lymphomas, and 17 germ cell tumors). FIELD STRENGTH/SEQUENCE: A gradient echo-based 2D MR elastography sequence and a diffusion-weighted imaging (DWI) sequence at 3.0 T. ASSESSMENT: Stiffness and apparent diffusion coefficients (ADC) were measured in AMTs using MR elastography-derived elastograms and DWI-derived ADC maps, respectively. The aim of this study is to identify whether MR elastography can differentiate between the histological subtypes of ATMs. STATISTICAL TESTS: One-way analysis of variance (ANOVA), two-way ANOVA, Pearson's linear correlation coefficient (r), receiver operating characteristic (ROC) curve analysis; P < 0.05 was considered significant. RESULTS: Lymphomas had significantly lower stiffness than other AMTs (4.0 ± 0.63 kPa vs. 4.8 ± 1.39 kPa). The mean stiffness of thymic carcinomas was significantly higher than that of other AMTs (5.6 ± 1.41 kPa vs. 4.2 ± 0.94 kPa). Using a cutoff value of 5.0 kPa, ROC analysis showed that lymphomas could be differentiated from other AMTs with an accuracy of 59%, sensitivity of 97%, and specificity of 38%. Using a cutoff value of 5.1 kPa, thymic carcinomas could be differentiated from other AMTs with an accuracy of 84%, sensitivity of 67%, and specificity of 90%. However, there was an overlap in the stiffness values of individual thymomas (4.2 ± 0.71; 3.9-4.5), thymic carcinomas (5.6 ± 1.41; 5.0-6.1), lymphomas (4.0 ± 0.63; 3.8-4.2), and germ cell tumors (4.5 ± 1.79; 3.3-5.6). DATA CONCLUSION: MR elastography-derived stiffness may be used to evaluate AMTs of various histologies. TECHNICAL EFFICACY: Stage 2.

Fluoxetine Successfully Treats Intracranial Enterovirus E18 Infection in a Patient with CD79a Deficiency Arising from Segmental Uniparental Disomy of Chromosome 19.

The pre BCR complex plays a crucial role in B cell production, and its successful expression marks the B cell differentiation from the pro-B to pre-B. The CD79a and CD79b mutations, encoding Igα and Igß respectively, have been identified as the cause of autosomal recessive agammaglobulinemia (ARA). Here, we present a case of a patient with a homozygous CD79a mutation, exhibiting recurrent respiratory infections, diarrhea, growth and development delay, unique facial abnormalities and microcephaly, as well as neurological symptoms including tethered spinal cord, sacral canal cyst, and chronic enteroviral E18 meningitis. Complete blockade of the early B cell development in the bone marrow of the patient results in the absence of peripheral circulating mature B cells. Whole exome sequencing revealed a Loss of Heterozygosity (LOH) of approximately 19.20Mb containing CD79a on chromosome 19 in the patient. This is the first case of a homozygous CD79a mutation caused by segmental uniparental diploid (UPD). Another key outcome of this study is the effective management of long-term chronic enteroviral meningitis using a combination of intravenous immunoglobulin (IVIG) and fluoxetine. This approach offers compelling evidence of fluoxetine's utility in treating enteroviral meningitis, particularly in immunocompromised patients.