Femtogram-Sensitive Cantilever Platform for Dynamic Graphene Oxide Nanosheet Monitoring.

This study introduces a new approach to optimizing graphene oxide (GO) properties using liquid-phase plasma treatment in a microenvironment. Our innovation exploits atomic force microscopy (AFM) cantilever frequency tracking to monitor mass variations in GO, which are indicative of surface oxidation-reduction processes or substituent doping (boron/nitrogen). Complementary in situ Raman spectroscopy has observed D/G band shifts, and X-ray photoelectron spectroscopy (XPS) determined the C/O ratio and B/N doping levels pre- and post-treatment, confirming chemical tuning to GO. We can achieve femtogram-level precision in detecting nanomaterial mass changes by correlating elemental ratios with AFM cantilever frequency measurements. This multifaceted approach not only enhances our understanding of the chemical properties of GO but also establishes a new, versatile method for monitoring, modifying, and optimizing the properties of nanomaterials.

Highly sensitive full solar-blind ultraviolet spectrum detection and imaging based on PdSe2/Ga2O3 vdW heterojunction.

Solar-blind ultraviolet (UV) photodetectors are in great demand for both military and civilian applications. Here, we have successfully demonstrated the synthesis of the Sn-doped Ga2O3 films with controllable bandgaps to construct PdSe2/Ga2O3 van der Waals (vdW) heterojunctions achieving highly sensitive full solar-blind UV spectrum detection. The assembled device demonstrates a full solar-blind UV spectral self-powered response, with a large responsivity of 123.5 mA/W, a high specific detectivity of 1.63 × 1013 Jones, and a rapid response time of 0.15/2.3 ms. Importantly, an outstanding solar-blind UV imaging application based on an integrated PdSe2/Ga2O3 device array has been demonstrated. Our work paves a feasible path toward achieving highly sensitive solar-blind UV detecting and imaging based on wide-bandgap Ga2O3 films.

Flow cytometric immunophenotypic features of acute myeloid leukemia with mast cell differentiation.

OBJECTIVES: Acute myeloid leukemia (AML) with mast cell (MC) differentiation was recently described as an aggressive subgroup of AML cases. The objectives of this study were to assess the flow cytometric immunophenotypic features of AML-MC cases. METHODS: We characterized the immunophenotypic features of 21 AML-MC cases by flow cytometry and compared them to 20 reactive/regenerating bone marrow specimens. RESULTS: The number of MCs detected by flow cytometry in AML-MC cases ranged from 0.4% to 21.1%, with a median of 3.5%, significantly higher than that of normal/reactive bone marrow (BM) (median, 0.01%; range, 0.000%-0.396%; P < .0001). Immunophenotypically, MCs in AML-MC cases demonstrated immaturity, differing from MCs in normal/reactive BMs, including dimmer CD45 (100% vs 0%), lower side scatter (100% vs 0%), more frequent CD34 (81% vs 20%), and CD123 (100% vs 10%) positivity, and more frequent uniform/increased CD38 expression (95% vs 20%) (all P ≤ .0001). CD2 (0/5) and CD25 (2/6, 1 uniform and 1 partial) were assessed in a subset of cases. The myeloblasts in AML-MC were typically CD34+CD117+HLA-DR+ with unusually frequent expression of CD56 (57%, all partial) and CD25 (63%, mostly partial), increased CD117 (62%), and decreased CD38 (86%). The MC percentage determined by flow cytometry correlated well with MCs detected by tryptase immunohistochemistry (r = 0.76, P < .001). CONCLUSIONS: The MCs in AML-MC cases are characterized by dim CD45, low side scatter, CD34 and CD123 positivity, and uniform and increased CD38 expression. Flow cytometry is an excellent tool for identifying AML-MC cases.

From the archives of MD Anderson Cancer Center: Composite mantle cell lymphoma and lymphoplasmacytic lymphoma involving bone marrow at presentation.

Composite lymphoma, defined as two or more distinct well-defined entities involving the same anatomic site, is rare. Here we report a 79-year-old woman with composite mantle cell lymphoma (MCL) and lymphoplasmacytic lymphoma (LPL) involving bone marrow at the time of initial diagnosis. The patient presented with splenomegaly and lymphadenopathy and laboratory studies showed an elevated serum IgM level and IgM kappa paraprotein. Bone marrow evaluation showed concurrent involvement by MCL and LPL, supported by immunophenotypic studies that revealed two distinct aberrant B-cell populations. Next-generation sequencing analysis identified concurrent MYD88 and CXCR4 mutations and fluorescence in-situ hybridization showed CCND1 translocation, supporting the diagnosis of concomitant MCL and LPL. In conclusion, composite lymphoma can present in the bone marrow. The use of ancillary studies was essential in reaching the diagnosis in this case, as the results excluded the possibility of MCL lymphoma with plasmacytic differentiation, as well as other CD5- and CD10-negative small B-cell lymphomas.

Effectiveness of Exercise on Fatigue for Patients With Heart Failure: A Systematic Review and Meta-Analysis.

Exercise is the standard treatment for fatigue in heart failure (HF) patients. However, no study has investigated the effect of exercise on improving fatigue and HR-QoL in HF patients. Our study adhered to the Cochrane Handbook for Systematic Reviews of Interventions and followed the PRISMA statement. The date of the last search was October 31, 2021. We included randomized controlled trials (RCTs) using exercise to improve fatigue and HR-QoL. The combined exercise training studies showed improvement in fatigue (SMD = -.51, 95% CI = -.89 to -.12, p = .001, I2 = 48%). The IMT studies showed significantly improved fatigue (MD = -11.36, 95%CI = -15.30 to -7.41, p < .00001, I2 = 54%). However, three studies, with moderate heterogeneity (p = .10, I2 = 56%), showed non-significant changes in HR-QoL (SMD = -0.04, 95% CI = -.45 to .37, p = .83).

Clinical Outcome of an All Arthroscopic 'Whole Layer' Rotator Cuff Repair Technique with Simultaneous Biceps Tenodesis.

OBJECTIVE: To retrospectively evaluate clinical outcomes, including function and pain, of patients after our all arthroscopic "whole layer" rotator cuff repair technique with simultaneous biceps tenodesis procedure; factors influencing results were also evaluated. Given the frequent association of rotator cuff tear with long head of biceps lesion and the need for effective combined treatment strategies, this study aims to evaluate the efficacy of our technique and compare it with established methods. We hypothesized that our technique would significantly improve function and reduce pain in patients with rotator cuff tears and biceps pathology. METHODS: This is a retrospective study that included patients older than 20 years who underwent all arthroscopic "whole layer" rotator cuff repair technique with simultaneous biceps tenodesis procedures for concomitant rotator cuff tear and long head biceps pathology, from 2016 to 2020. Patients were evaluated preoperatively and at a minimum of 2 years of follow-up using the American Shoulder and Elbow Surgeons (ASES) and visual analogue scale (VAS) scores paired t-tests were used for analysis and statistical significance was set at p < 0.05(two-tailed). The satisfaction rate and complications were also evaluated. RESULTS: After an average follow-up of 2.3 years, 118 patients demonstrated significant improvement in both the ASES score (from 36.13 to 95.01, p < 0.001) and VAS score (from 6.81 to 0.89, p < 0.001). Ninety-four percent of the patients reported satisfaction with the surgical outcome. No complications related to Popeye deformity, biceps cramping pain, or ipsilateral shoulder reoperation were observed. Factors such as age, sex, body mass index (BMI), smoking status, alcohol consumption, hypertension, and diabetes did not influence the results. Patients showed significant improvement in both the ASES and VAS scores (p < 0.001). CONCLUSION: At a mean follow-up time of 2.3 years, the all arthroscopic "whole layer" rotator cuff repair technique with simultaneous biceps tenodesis is a therapeutic and efficient procedure. The procedure revealed a satisfactory functional outcome, reduced pain, and minimal complications and reoperations.

Cross-sectional Analysis of Outer Retinal Tubulation in Inherited Retinal Diseases: A Multicenter Study.

PURPOSE: This study aims to explore genetic variants that potentially lead to outer retinal tubulation (ORT), estimate the prevalence of ORT in these candidate genes, and investigate the clinical etiology of ORT in patients with inherited retinal diseases (IRDs), with respect to each gene. DESIGN: Retrospective cohort study. METHODS: A retrospective cross-sectional review was conducted on 565 patients with molecular diagnoses of IRD, confirming the presence of ORT as noted in each patient's respective spectral-domain optical coherence tomography (SD-OCT) imaging. Using SD-OCT imaging, the presence of ORT was analyzed in relation to specific genetic variants and phenotypic characteristics. Outcomes included the observed ORT frequencies across two gene-specific cohorts: non- retinal pigment epithelium (RPE)-specific genes, and RPE-specific genes; and to investigate the analogous characteristics caused by variants in these genes. RESULTS: Among the 565 patients included in this study, 104 exhibited ORT on SD-OCT. We observed ORT frequencies among the following genes from our patient cohort: 100% (23/23) forCHM, 100%(2/2) forPNPLA6, 100% (4/4) forRCBTB1, 100% formtDNA[100% (4/4) forMT-TL1and 100% (1/1) formtDNAdeletion], 100% (1/1) forOAT, 95.2% (20/21) forCYP4V2, 72.7% (8/11) forCHMfemale carriers, 66.7% (2/3) forC1QTNF5, 57.1% (8/14) forPROM1, 53.8% (7/13) forPRPH2, 42.9% (3/7) forCERKL, 28.6% (2/7) forCDHR1, 20% (1/5) forRPE65, 4% (18/445) forABCA4.In contrast, ORT was not observed in any patients with photoreceptor-specific gene variants, such asRHO(n=13),USH2A(n=118),EYS(n=70),PDE6B(n=10),PDE6A(n=4),and others. CONCLUSION: These results illustrate a compelling association between the presence of ORT and IRDs caused by variants in RPE-specific genes, as well as non-RPE-specific genes. In contrast, IRDs caused by photoreceptor-specific genes are typically not associated with ORT occurrence. Further analysis revealed that ORT tends to manifest in IRDs with milder intraretinal pigment migration (IPM), a finding that is typically associated with RPE-specific genes. These findings regarding ORT, genetic factors, atrophic patterns in the fundus, and IPM provide valuable insight into the complex etiology of IRDs. Future prospective studies are needed to further explore the association and underlying mechanisms of ORT in these contexts.

Empagliflozin Prevent High-Glucose Stimulation Inducing Apoptosis and Mitochondria Fragmentation in H9C2 Cells through the Calcium-Dependent Activation Extracellular Signal-Regulated Kinase 1/2 Pathway.

A previous study showed that high-glucose (HG) conditions induce mitochondria fragmentation through the calcium-mediated activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) in H9C2 cells. This study tested whether empagliflozin could prevent HG-induced mitochondria fragmentation through this pathway. We found that exposing H9C2 cells to an HG concentration decreased cell viability and increased cell apoptosis and caspase-3. Empagliflozin could reverse the apoptosis effect of HG stimulation on H9C2 cells. In addition, the HG condition caused mitochondria fragmentation, which was reduced by empagliflozin. The expression of mitochondria fission protein was upregulated, and fusion proteins were downregulated under HG stimulation. The expression of fission proteins was decreased under empagliflozin treatment. Increased calcium accumulation was observed under the HG condition, which was decreased by empagliflozin. The increased expression of ERK 1/2 under HG stimulation was also reversed by empagliflozin. Our study shows that empagliflozin could reverse the HG condition, causing a calcium-dependent activation of the ERK 1/2 pathway, which caused mitochondria fragmentation in H9C2 cells.

A GUCY2D variant associated cone-rod dystrophy with electronegative ERG: A case report and review.

Purpose: Cone-rod dystrophies (CORD) are inherited retinal dystrophies characterized by primary cone degeneration with secondary rod involvement. We report two patients from the same family with a dominant variant in the guanylate cyclase 2D (GUCY2D) gene with different phenotypes in the electroretinogram (ERG). Observations: A 21-year-old lady (Patient 1) was referred due to experiencing blurry vision and color vision impairment. Visual field testing revealed a central scotoma. Spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) documented macula dysfunction. Reduced amplitude was observed in the photopic responses of ERG. Her 54-year-old father (Patient 2) had similar issues with blurry vision. A dilated fundus examination displayed bilateral macular atrophy. Loss of the ellipsoid zone line and collapse of the outer nuclear segment were noted on the SD-OCT. Photopic ERG responses were extinguished, and an electronegative ERG was observed in the dark-adapted 3.0 ERG. The gene report revealed a c.2512C > T (p.Arg838Cys) variant in GUCY2D for both patients. They were respectively diagnosed as cone dystrophy (COD) and cone-rod dystrophy (CORD). Conclusions: We report two different clinical phenotypes in GUCY2D-associated COD despite sharing the same variant. A dysfunction in the synaptic junction between the photoreceptor and the secondary neuron was proposed to explain the electronegative ERG. This explanation might extend to other gene-related cases of CORD with electronegative ERG.

Impact on quality of life, health care access, and health care utilization of individuals with vitiligo: an analysis of the All of Us research program.

Vitiligo is an autoimmune skin depigmenting disorder that can negatively impact quality of life. A new FDA approved treatment for vitiligo offers considerable promise, and to maximize benefits strategies to implementation should consider disease burden, healthcare access, and healthcare utilization of individuals with vitiligo. Using the All of Us Research Program's large data set, including survey responses, we investigated these outcomes among participants with and without vitiligo. Our analysis used quality of life, delayed care due to an obstacle, and seeing a doctor in the past year as dichotomized proxies for disease burden, healthcare access, and healthcare utilization. The results show that people with vitiligo are more likely to report worse quality of life but ostensibly greater healthcare access and utilization compared to people without vitiligo. However, these relationships are not significant when adjusted for demographics, socioeconomic characteristics, and comorbidities of vitiligo. Prior research has shown non-Caucasian individuals have worse health outcomes in general, and worse quality of life within the vitiligo population. Our data demonstrated consistent findings; moreover, we found that non-Caucasian individuals with vitiligo had inferior healthcare access and lower health care utilization than Caucasian individuals. Implementation of new treatments for vitiligo should prioritize disadvantaged individuals to improve health equity.

Dynamic changes in proresolving lipid mediators and their receptors following acute vascular injury in male rats.

Acute vascular injury provokes an inflammatory response, resulting in neointimal hyperplasia (NIH) and downstream pathologies. The resolution of inflammation is an active process in which specialized proresolving lipid mediators (SPM) and their receptors play a central role. We sought to examine the acute phase response of SPM and their receptors in both circulating blood and the arterial wall in a rat angioplasty model. We found that the ratio of proresolving to pro-inflammatory lipid mediators (LM) in plasma decreased sharply 1 day after vascular injury, then increased slightly by day 7, while that in arteries remained depressed. Granulocyte expression of SPM receptors ALX/FPR2 and DRV2/GPR18, and a leukotriene B4 receptor BLT1 increased postinjury, while ERV1/ChemR23 expression was reduced early and then recovered by day 7. Importantly, we show unique arterial expression patterns of SPM receptors in the acute setting, with generally low levels through day 7 that contrasted sharply with that of the pro-inflammatory CCR2 receptor. Overall, these data document acute, time-dependent changes of LM biosynthesis and SPM receptor expression in plasma, leukocytes, and artery walls following acute vascular injury. A biochemical imbalance between inflammation and resolution LM pathways appears persistent 7 days after angioplasty in this model. These findings may help guide therapeutic approaches to accelerate vascular healing and improve the outcomes of vascular interventions for patients with advanced atherosclerosis.

Quantitative ternary network-oriented discovery of Q-markers from traditional Chinese medicine prescriptions: Bu-Zhong-Yi-Qi-Tang as a case study.

BACKGROUND: The proposal of Q-markers for traditional Chinese medicine (TCM) represents a novel avenue of research pertaining to the quality control of TCM prescriptions. However, prior exploratory studies on Q-markers with multiple properties consistently neglected the consideration of weights, hampering our ability to accurately gauge the significance of each property and potentially leading to a flawed comprehension of Q-markers. PURPOSE: In this study, a quantitative ternary network strategy was firstly proposed to visually discover the Q-markers from TCM prescriptions, and it has been successfully applied into the quality control study of Bu-Zhong-Yi-Qi-Tang (BZYQT), a classical TCM prescription. METHODS: Firstly, the contents of 34 components in BZYQT, along with the kinetic features of 17 candidate Q-markers in biosamples (plasma and small intestinal contents), were characterized by UPLC-QqQ-MS/MS, and their immunomodulatory activities in macrophages and splenic lymphocytes were also assessed. Next, the obtained data were integrated into three properties: testability, bioavailability, effectiveness, and their weights were calculated using the entropy weight method to further establish a ternary network for quantitatively screening Q-markers. Subsequently, the identified Q-markers of BZYQT were utilized for the holistic quality evaluation of 36 batches of the commercial BZYQT preparation, Bu-Zhong-Yi-Qi-Pill (BZYQP) produced by three manufacturers, through similarity evaluation of the Q-marker-based fingerprint. RESULTS: Nine compounds (hesperidin, astragaloside IV, ononin, 18ß-glycyrrhizic acid, narirutin, calycosin, cimigenoside, astragaloside II, and liquiritin) showing three core properties, including testability, bioavailability, and effectiveness, were screened out as Q-markers of BZYQT based on their rankings in terms of regression area of the ternary network. Employing Q-markers as common peaks, the similarity values of 36 batches BZYQP ranged 0.914-0.998 under HPLC-UVD mode, and 0.631-1.000 under HPLC-ELSD mode, which were less than the similarity values evaluated by the conventional common peaks (HPLC-UVD mode: 0.946-0.990; HPLC-ELSD mode: 0.957-0.997). This observation suggests that the identified Q-markers are more representative as common peaks in chromatographic fingerprints for the holistic quality evaluation of TCM-related products from different manufacturers. CONCLUSION: The quantitative discovery of Q-markers from BZYQT laid an important foundation for holistic quality assessment of its related commercially available products, and our work offering a new strategy for ensuring the consistency and efficacy of TCM prescriptions.

Unveiling the veil of RNA binding protein phase separation in cancer biology and therapy.

RNA-binding protein (RBP) phase separation in oncology reveals a complex interplay crucial for understanding tumor biology and developing novel therapeutic strategies. Aberrant phase separation of RBPs significantly influences gene regulation, signal transduction, and metabolic reprogramming, contributing to tumorigenesis and drug resistance. Our review highlights the integral roles of RBP phase separation in stress granule dynamics, mRNA stabilization, and the modulation of transcriptional and translational processes. Furthermore, interactions between RBPs and non-coding RNAs add a layer of complexity, providing new insights into their collaborative roles in cancer progression. The intricate relationship between RBPs and phase separation poses significant challenges but also opens up novel opportunities for targeted therapeutic interventions. Advancing our understanding of the molecular mechanisms and regulatory networks governing RBP phase separation could lead to breakthroughs in cancer treatment strategies.

Mitochondria in Retinal Ganglion Cells: Unraveling the Metabolic Nexus and Oxidative Stress.

This review explored the role of mitochondria in retinal ganglion cells (RGCs), which are essential for visual processing. Mitochondrial dysfunction is a key factor in the pathogenesis of various vision-related disorders, including glaucoma, hereditary optic neuropathy, and age-related macular degeneration. This review highlighted the critical role of mitochondria in RGCs, which provide metabolic support, regulate cellular health, and respond to cellular stress while also producing reactive oxygen species (ROS) that can damage cellular components. Maintaining mitochondrial function is essential for meeting RGCs' high metabolic demands and ensuring redox homeostasis, which is crucial for their proper function and visual health. Oxidative stress, exacerbated by factors like elevated intraocular pressure and environmental factors, contributes to diseases such as glaucoma and age-related vision loss by triggering cellular damage pathways. Strategies targeting mitochondrial function or bolstering antioxidant defenses include mitochondrial-based therapies, gene therapies, and mitochondrial transplantation. These advances can offer potential strategies for addressing mitochondrial dysfunction in the retina, with implications that extend beyond ocular diseases.

Expressions of sugar transporters/trehalases in relation to PTTH-stimulated ecdysteroidogenesis in the silkworm, Bombyx mori.

The prothoracic gland (PG) is the source of ecdysteoids in larval insects. Although numerous studies have been conducted on signaling networks involved in prothoracicotropic hormone (PTTH)-stimulated ecdysteroidogenesis in PGs, less is known about regulation of metabolism in PGs. In the present study, we investigated correlations between expressions of sugar transporter (St)/trehalase (Treh) genes and PTTH-stimulated ecdysteroidogenesis in Bombyx mori PGs. Our results showed that in vitro PTTH treatment stimulated expression of the St1 gene, but not other transporter genes. Expression of the Treh1 gene was also stimulated by PTTH treatment. An immunoblotting analysis showed that St1 protein levels in Bombyx PGs increased during the later stage of the last larval instar and were not affect by PTTH treatment. PTTH treatment enhanced Treh enzyme activity in a time-dependent manner. Blocking either extracellular signal-regulated kinase (ERK) signaling with U0126 or phosphatidylinositol 3-kinase (PI3K) signaling with LY294002 decreased PTTH-stimulated Treh enzyme activity, indicating a link from the ERK and PI3K signaling pathways to Treh activity. Treatment with the Treh inhibitor, validamycin A, blocked PTTH-stimulated Treh enzyme activity and partially inhibited PTTH-stimulated ecdysteroidogenesis. Treatment with either a sugar transport inhibitor (cytochalasin B) or a specific glycolysis inhibitor (2-deoxy-D-glucose, 2-DG) partially inhibited PTTH-stimulated ecdysteroidogenesis. Taken together, these results indicate that increased expressions of St1/Treh1 and Treh activity, which lie downstream of PTTH signaling, are involved in PTTH stimulation in B. mori PGs.

Improvement of early miscarriage rates in women with adenomyosis via oxytocin receptor antagonist during frozen embryo transfer-a propensity score-matched study.

BACKGROUND: Dysfunctional uterine peristalsis seems to play a pivotal role in hindering embryo implantation among women diagnosed with adenomyosis. This research aims to investigate whether administering an oxytocin receptor antagonist during a frozen embryo transfer (FET) cycle using a hormone replacement therapy (HRT) protocol can enhance in vitro fertilization (IVF) outcomes for infertile women affected by adenomyosis. METHODS: Between January 2018 and June 2022, our reproductive center conducted IVF-FET HRT cycles for infertile women diagnosed with adenomyosis. Propensity score matching was employed to select matched subjects between the two groups in a 1:1 ratio. Following this, 168 women received an oxytocin receptor antagonist during FET, constituting the study group, while the matched 168 women underwent FET without this antagonist, forming the control group. We conducted comparative analyses of baseline and cycle characteristics between the two groups, along with additional subgroup analyses. RESULTS: The study group exhibited notably lower rates of early miscarriage compared to the control group, although there were no significant differences in clinical pregnancy rates, ongoing pregnancy rates, and live birth rates between the two groups. Multivariate analysis revealed a negative correlation between the use of oxytocin receptor antagonists and early miscarriage rates in women with adenomyosis. Subgroup analyses, categorized by age, infertility types, and embryo transfer day, showed a substantial decrease in early miscarriage rates within specific subgroups: women aged ≥ 37 years, those with secondary infertility, and individuals undergoing day 3 embryo transfers in the study group compared to the control group. Furthermore, subgroup analysis based on adenomyosis types indicated significantly higher clinical pregnancy rates, ongoing pregnancy rates and live birth rates in the study group compared to the control group among women with diffuse adenomyosis. CONCLUSIONS: Administering an oxytocin receptor antagonist during FET may reduce the early miscarriage rates in women with adenomyosis.

Morphology, immunophenotype, and suggested diagnostic criteria of TCL1 family-negative T-prolymphocytic leukemia.

OBJECTIVES: We sought to investigate the morphologic and immunophenotypic characteristics of TCL1 family-negative T-cell prolymphocytic leukemia (T-PLL). METHODS: Twenty cases of TCL1 family-negative T-PLL were studied. RESULTS: The doubling time of leukemic cells ranged from less than 2 days to more than 5 years, with a median of 5.5 months. Leukemic cells were small to medium-sized, with round to irregular nuclei, variably condensed chromatin, and small amounts of agranular cytoplasm. A visible nucleolus was identified in 11 (55%) cases. Cytoplasmic blebs/protrusions were identified in all cases, but their occurrence was highly variable from case to case. Bone marrow biopsy showed an interstitial pattern in 90% of cases and a diffuse pattern in the remaining 10% of cases. Flow cytometric immunophenotypic analysis showed that the leukemic cells in all cases were CD4 positive; 3 (15%) also showed concurrent CD8 expression. All cases were positive for CD2 and CD5. Surface CD3 and CD7 were positive in 19 of 20 (95%) cases, and all CD3-positive cases expressed the T-cell receptor αß. Compared with prototypic T-PLL cases, these 2 groups shared many immunophenotypic findings, except CD8 and CD26, both of which were more commonly expressed in prototypic T-PLL cases. CONCLUSIONS: TCL1 family-negative T-PLL cases have morphologic and immunophenotypic features that are similar to prototypic T-PLL. They are characterized by neoplastic proliferation of small to medium-sized mature T cells with CD4-positive T-cell receptor αß phenotype. Tumor cells frequently maintain pan-T antigen expression. Recognizing these morphologic and immunophenotypic features will aid in accurately diagnosing this rare subset of T-PLL.

Cost-Utility Analysis of Bilateral Cochlear Implants for Children With Severe-to-Profound Sensorineural Hearing Loss in Taiwan.

OBJECTIVES: Cochlear implants are an option for children with sensorineural hearing loss who do not benefit from hearing aids. Although bilateral cochlear implantation (CI) has been shown to enhance hearing performance and quality of life, its cost-effectiveness remains unclear. This study aimed to evaluate the cost-effectiveness of bilateral CI compared with bimodal hearing for children with sensorineural hearing loss in Taiwan from both the perspectives of patients and Taiwan's National Health Insurance Administration (TNHIA). DESIGN: A four-state Markov model was utilized in the study, including "use the first internal device," "use the second internal device," "use the third internal device," and "death." Health utility values were obtained from a local survey of health professionals and then adjusted by a scale to reflect both the negative impact of aging on hearing and the time needed to develop the full benefit of treatment in the earliest years of life. The cost data were derived from a caregiver survey, hospital databases, clinical experts, and the TNHIA. The incremental cost-effectiveness ratio (ICER) was calculated over the lifetime horizon and presented as cost per quality-adjusted life year (QALY) to evaluate the cost-effectiveness of simultaneous bilateral CI, sequential bilateral CI, and bimodal hearing. In addition, one-way sensitivity analyses and probabilistic sensitivity analyses were conducted to investigate the impact of uncertainty and the robustness of the model. RESULTS: The base-case analysis showed that children with bilateral CI gained more QALYs while incurring more costs when compared with those with bimodal hearing. From the TNHIA perspective, compared with bimodal hearing, the ICER of simultaneous bilateral CI was New Taiwan Dollars 232,662 per QALY whereas from the patient perspective, the ICER was New Taiwan Dollars 1,006,965 per QALY. Moreover, simultaneous bilateral CI dominated sequential bilateral CI from both perspectives. Compared with bimodal hearing, the ICER of sequential bilateral CI did not exceed twice the gross domestic product per capita in Taiwan from either perspective. One-way sensitivity analysis demonstrated that the utility gain of bilateral CI compared with bimodal hearing was the most impactful parameter from both perspectives. Probabilistic sensitivity analysis confirmed the robustness of the base-case analysis results. CONCLUSIONS: Our findings reveal that bilateral CI was cost-effective when using the threshold of one to three times the 2022 gross domestic product per capita in Taiwan from both the TNHIA and patient perspectives. Future research incorporating cost and effectiveness data from other dimensions is needed to help decision-makers assess the cost-effectiveness of bilateral CI more comprehensively.

Clinical study of chemotherapy-related cognitive impairment in patients with non-Hodgkin lymphoma.

BACKGROUND: Chemotherapy for malignant tumors can cause brain changes and cognitive impairment, leading to chemotherapy-induced cognitive impairment (CICI). Current research on CICI has focused on breast cancer and Hodgkin's lymphoma. Whether patients with non-Hodgkin's lymphoma (NHL) undergoing chemotherapy have cognitive impairment has not been fully investigated. AIM: To investigate whether NHL patients undergoing chemotherapy had cognitive impairments. METHODS: The study included 100 NHL patients who were required to complete a comprehensive psychological scale including the Brief Psychiatric Examination Scale (MMSE) at two time points: before chemotherapy and within 2 wk of two chemotherapy courses. A language proficiency test (VFT), Symbol Number Pattern Test (SDMT), Clock Drawing Test (CDT), Abbreviated Daily Cognition Scale (ECog-12), Prospective and Retrospective Memory Questionnaire, and Karnofsky Performance Status were used to assess cognitive changes before and after chemotherapy. RESULTS: The VFT scores for before treatment (BT) and after treatment (AT) groups were 45.20 ± 15.62, and 42.30 ± 17.53, respectively (t -2.16, P < 0.05). The CDT scores were 8 (3.5-9.25) for BT and 7 (2.5-9) for AT groups (Z -2.1, P < 0.05). Retrospective memory scores were 13.5 (9-17) for BT and 15 (13-18) for AT (Z -3.7, P < 0.01). The prospective memory scores were 12.63 ± 3.61 for BT and 14.43 ± 4.32 for AT groups (t -4.97, P < 0.01). The ECog-12 scores were 1.71 (1.25-2.08) for BT and 1.79 (1.42-2.08) for AT groups (Z -2.84, P < 0.01). The SDMT and MMSE values did not show a significant difference between BT and AT groups. CONCLUSION: Compared to the AT group, the BT group showed impaired language, memory, and subjective cognition, but objective cognition and execution were not significantly affected.