Low-loss and polarization insensitive 32 × 4 optical switch for ROADM applications.

Integrated switches play a crucial role in the development of reconfigurable optical add-drop multiplexers (ROADMs) that have greater flexibility and compactness, ultimately leading to robust single-chip solutions. Despite decades of research on switches with various structures and platforms, achieving a balance between dense integration, low insertion loss (IL), and polarization-dependent loss (PDL) remains a significant challenge. In this paper, we propose and demonstrate a 32 × 4 optical switch using high-index doped silica glass (HDSG) for ROADM applications. This switch is designed to route any of the 32 inputs to the express ports or drop any channels from 32 inputs to the target 4 drop ports or add any of the 4 ports to any of the 32 express channels. The switch comprises 188 Mach-Zehnder Interferometer (MZI) type switch elements, 88 optical vias for the 44 optical bridges, and 618 waveguide-waveguide crossings with three-dimensional (3D) structures. At 1550 nm, the fiber-to-fiber loss for each express channel is below 2 dB, and across the C and L bands, below 3 dB. For each input channel to all 4 drop/add channels at 1550 nm, the loss is less than 3.5 dB and less than 5 dB across the C and L bands. The PDLs for all express and input channels to the 4 drop/add channels are below 0.3 dB over the C band, and the crosstalk is under -50 dB for both the C and L bands.

Impact of SARS-CoV-2 infection on patients with hematological malignancies: a retrospective study.

OBJECTIVES: This study aimed to evaluate the characteristics of patients with hematological malignancies (HM) and SARS-CoV-2 infection and analyze the risk factors of their severity and mortality. METHODS: A retrospective study including inpatients diagnosed HM and SARS-CoV-2 infection between December 2022 and February 2023 were conducted. Demographic information, medical history, comorbidities, diagnosis, treatment related information and outcomes were extracted from electronic medical database. The primary outcome of this study were the severity of SARS-CoV-2 infection and case-fatality rate. The clinical characteristic and outcomes of the patients were summarized and analyzed. RESULTS: A total of 74 patients with HM and SARS-CoV-2 infection were included. Out of the total cases, 85.1% (63) had a mild /moderate SARS-CoV-2 infection, and 14.9% (11) were severe/ critical infection cases. A total of 8 deaths occurred in all cases for a case-fatality rate of 10.8%. Multivariate analysis identified patients with acute myeloid leukemia (AML) (P = 0.043, OR:5.274, 95%CI:1.053-26.407), primary hematological disease in active state (P = 0.005, OR:13.905, 95%CI:2.180-88.704) were independent risk factors for the severity of SARS-CoV-2 infection and patients with AML had 11.145-fold higher risk of non-survival (P = 0.020, OR:11.145, 95%CI:1.460-85.103) in comparison to the patients with other types of HM. There were no significant differences in the severity and case-fatality rate (P > 0.05) between the patients receiving chemotherapy drugs administration waiting <14 days and ≥14 days after negative SARS-CoV-2 testing. CONCLUSION: The primary hematological disease in active state may be the main risk factor for negative outcome of the patents. Waiting 14 days for chemotherapy initiation after negative SARS-CoV-2 testing is unnecessary.

Brain amyloid-ß deposition associated functional connectivity changes of ultra-large structural scale in mild cognitive impairment.

In preclinical Alzheimer's disease, neuro-functional changes due to amyloid-ß (Aß) deposition are not synchronized in different brain lobes and subcortical nuclei. This study aimed to explore the correlation between brain Aß burden, connectivity changes in an ultra-large structural scale, and cognitive function in mild cognitive impairment. Participants with mild cognitive impairment were recruited and underwent florbetapir (F18-AV45) PET, resting-state functional MRI, and multidomain neuropsychological tests. AV-45 standardized uptake value ratio (SUVR) and functional connectivity of all participants were calculated. Of the total 144 participants, 72 were put in the low Aß burden group and 72 in the high Aß burden group. In the low Aß burden group, all connectivities between lobes and nuclei had no correlation with SUVR. In the high Aß burden group, SUVR showed negative correlations with the Subcortical-Occipital connectivity (r=-0.36, P = 0.02) and Subcortical-Parietal connectivity (r=-0.26, P = 0.026). Meanwhile, in the high Aß burden group, SUVR showed positive correlations with the Temporal-Prefrontal connectivity (r = 0.27, P = 0.023), Temporal-Occipital connectivity (r = 0.24, P = 0.038), and Temporal-Parietal connectivity (r = 0.32, P = 0.006). Subcortical to Occipital and Parietal connectivities had positive correlations with general cognition, language, memory, and executive function. Temporal to Prefrontal, Occipital, and Parietal connectivities had negative correlations with memory function, executive function, and visuospatial function, and a positive correlation with language function. In conclusion, Individuals with mild cognitive impairment with high Aß burden have Aß-related bidirectional functional connectivity changes between lobes and subcortical nuclei that are associated with cognitive decline in multiple domains. These connectivity changes reflect neurological impairment and failed compensation.

Integrated algorithm combining plasma biomarkers and cognitive assessments accurately predicts brain ß-amyloid pathology.

BACKGROUND: Accurate prediction of cerebral amyloidosis with easily available indicators is urgently needed for diagnosis and treatment of Alzheimer's disease (AD). METHODS: We examined plasma Aß42, Aß40, T-tau, P-tau181, and NfL, with APOE genotypes, cognitive test scores and key demographics in a large Chinese cohort (N = 609, aged 40 to 84 years) covering full AD spectrum. Data-driven integrated computational models were developed to predict brain ß-amyloid (Aß) pathology. RESULTS: Our computational models accurately predict brain Aß positivity (area under the ROC curves (AUC) = 0.94). The results are validated in Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Particularly, the models have the highest prediction power (AUC = 0.97) in mild cognitive impairment (MCI) participants. Three levels of models are designed with different accuracies and complexities. The model which only consists of plasma biomarkers can predict Aß positivity in amnestic MCI (aMCI) patients with AUC = 0.89. Generally the models perform better in participants without comorbidities or family histories. CONCLUSIONS: The innovative integrated models provide opportunity to assess Aß pathology in a non-invasive and cost-effective way, which might facilitate AD-drug development, early screening, clinical diagnosis and prognosis evaluation.

The numbers of people with Alzheimer's disease are increasing. People with Alzheimer's disease have changes in the brain as well as cognitive impairment, which is when a person has difficulty remembering, learning, concentrating, or making decisions. Innovative medicines and new treatments all target people with early Alzheimer's disease. However, the methods used currently to diagnose Alzheimer's disease are expensive and can be unpleasant for patients. We studied Chinese people with no cognitive impairment, some cognitive decline, mild cognitive impairment, Alzheimer's disease and non-Alzheimer's disease dementia. We established a computational model that can predict the changes seen in the brain in people with Alzheimer's disease from information including results of blood and memory tests. This non-invasive and cost-effective approach might improve early identification of those with Alzheimer's disease.

The Value of Clock Drawing Process Assessment in Screening for Mild Cognitive Impairment and Alzheimer's Dementia.

Many clock drawing test (CDT) scoring systems focus on drawing results and lack drawing process assessments. This study created a CDT scoring procedure with drawing process assessment and explored its diagnostic value in screening for mild cognitive impairment (MCI) and early Alzheimer's disease (AD) from normal control (NC). We used logistic regression and receiver operating characteristic (ROC) curves to determine a new, sensitive scoring system for AD and MCI patients in a derivation cohort. The new scoring method was then compared to two common scoring systems and externally validated in a second cohort. We developed a new scoring system named CDT5, which contained one process assessment item: remember setting time without asking. Compared with two published scoring systems, CDT5 had better discriminatory power in distinguishing AD patients from NCs in derivation (area under the ROC curve [area under the curve, AUC] = .890) and validation (AUC = .867) cohorts. Three scoring systems had poor diagnostic accuracy at discriminating MCI patients from controls, with CDT5 being the most sensitive (78.57%). Adding the drawing process in CDT helps accurately detect patients with early AD, but its role in identifying patients with MCI needs to be further explored.

Associations of plasma phosphorylated tau181 and neurofilament light chain with brain amyloid burden and cognition in objectively defined subtle cognitive decline patients.

AIMS: There is increasing evidence that plasma biomarkers are specific biomarkers for Alzheimer's disease (AD) pathology, but their potential utility in Obj-SCD (objectively defined subtle cognitive decline) remains unclear. METHODS: A total of 234 subjects, including 65 with brain amyloid beta (Aß) negative normal cognition (Aß- NC), 58 with Aß-positive NC (Aß+ NC), 63 with Aß- Obj-SCD, and 48 with Aß+ Obj-SCD were enrolled. Plasma Aß42, Aß40, Aß42/Aß40 ratio, phosphorylated tau181 (p-tau181), neurofilament light chain (NfL), and total tau (T-tau) were measured using Simoa assays. Logistic and linear regression analyses were used to examine the relationship between plasma biomarkers and brain amyloid, cognition, and imaging measures adjusting for age, sex, education, APOE ε4 status, and vascular risk scores. Receiver operating characteristics were used to evaluate the discriminative validity of biomarkers. RESULTS: After adjustment, only plasma p-tau181 and NfL were significantly elevated in Aß+ Obj-SCD participants compared to Aß- NC group. Elevated p-tau181 was associated with brain amyloid accumulation, worse cognitive performance (visual episodic memory, executive function, and visuospatial function), and hippocampal atrophy. These associations mainly occurred in Aß+ individuals. In contrast, higher NfL was correlated with brain amyloid burden and verbal memory decline. These associations predominantly occurred in Aß- individuals. The adjusted diagnostic model combining p-tau181 and NfL levels showed the best performance in identifying Aß+ Obj-SCD from Aß- NC [area under the curve (AUC) = 0.814], which did not differ from the adjusted p-tau181 model (AUC = 0.763). CONCLUSIONS: Our findings highlight that plasma p-tau181, alone or combined with NfL, contributes to identifying high-risk AD populations.

Differential associations of visual memory with hippocampal subfields in subjective cognitive decline and amnestic mild cognitive impairment.

BACKGROUND: Although previous studies have demonstrated that the hippocampus plays a role in verbal memory, the role of hippocampal subfields in visual memory is uncertain, especially in those with preclinical Alzheimer's disease (AD). This study aimed to examine relationships between hippocampal subfield volumes and visual memory in SCD (subjective cognitive decline) and aMCI (amnestic mild cognitive impairment). METHODS: The study sample included 47 SCD patients, 62 aMCI patients, and 51 normal controls (NCs) and was recruited from Shanghai Jiao Tong University Affiliated Sixth People's Hospital. Visual memory was measured by the subtests of BVMT-R (Brief Visuospatial Memory Test-Revised), PLT (Pictorial Learning Test), DMS (Delayed Matching to Sample), and PAL (Paired Associates Learning). Hippocampal subfield volumes were estimated using FreeSurfer software (version 6.0). We modeled the association between visual memory and relative hippocampal subfield volumes (dividing by estimated total intracranial volume) using Pearson's correlation and linear regression. RESULTS: Compared with the NC group, patients with SCD did not find any relative hippocampal subregion atrophy, and the aMCI group found atrophy in CA1, molecular layer, subiculum, GC-ML-DG, CA4, and CA3. After adjusting for covariates (age, sex, and APOE ε4 status) and FDR (false discovery rate) correction of p (q values) < 0.05, in NC group, DMS delay matching scores were significant and negatively associated with presubiculum (r = -0.399, FDR q = 0.024); in SCD group, DMS delay matching scores were negatively associated with CA3 (r = -0.378, FDR q = 0.048); in the aMCI group, BVMT-R immediate recall scores were positively associated with CA1, molecular layer, subiculum, and GC-ML-DG (r = 0.360-0.374, FDR q < 0.036). Stepwise linear regression analysis confirmed the association. CONCLUSIONS: Our results indicate a different and specific correction of visual memory with relative hippocampal subfield volumes between SCD and aMCI. The correlations involved different and more subfields as cognitive decline. Whether these associations predict future disease progression needs dynamic longitudinal studies.

Changes of Regional Neural Activity Homogeneity in Preclinical Alzheimer's Disease: Compensation and Dysfunction.

INTRODUCTION: Subjective cognitive decline (SCD) is the preclinical stage of Alzheimer's disease and may develop into amnestic mild cognitive impairment (aMCI). Finding suitable biomarkers is the key to accurately identifying SCD. Previous resting-state functional magnetic resonance imaging (rs-fMRI) studies on SCD patients showed functional connectivity disorders. Our goal was to explore whether local neurological homogeneity changes in SCD patients, the relationship between these changes and cognitive function, and similarities of neurological homogeneity changes between SCD and aMCI patients. MATERIALS AND METHODS: 37 cases of the healthy control (HC) group, 39 cases of the SCD group, and 28 cases of the aMCI group were included. Participants underwent rs-fMRI examination and a set of neuropsychological test batteries. Regional homogeneity (ReHo) was calculated and compared between groups. ReHo values were extracted from meaningful regions in the SCD group, and the correlation between ReHo values with the performance of neuropsychological tests was analyzed. RESULTS: Our results showed significant changes in the ReHo among groups. In the SCD group compared with the HC group, part of the parietal lobe, frontal lobe, and occipital lobe showed decreased ReHo, and the temporal lobe, part of the parietal lobe and the frontal lobe showed increased ReHo. The increased area of ReHo was negatively correlated with the decreased area, and was related to decrease on multiple neuropsychological tests performance. Simultaneously, the changed areas of ReHo in SCD patients are similar to aMCI patients, while aMCI group's neuropsychological test performance was significantly lower than that of the SCD group. CONCLUSION: There are significant changes in local neurological homogeneity in SCD patients, and related to the decline of cognitive function. The increase of neurological homogeneity in the temporal lobe and adjacent area is negatively correlated with cognitive function, reflecting compensation for local neural damage. These changes in local neurological homogeneity in SCD patients are similar to aMCI patients, suggesting similar neuropathy in these two stages. However, the aMCI group's cognitive function was significantly worse than that of the SCD group, suggesting that this compensation is limited. In summary, regional neural activity homogeneity may be a potential biomarker for identifying SCD and measuring the disease severity.

Pregnancy in neuromyelitis optica spectrum disorder: A multicenter study from South China.

OBJECTIVE: This study aimed to assess the effect of pregnancy on the course of neuromyelitis optica spectrum disorder (NMOSD), and the effect of this disease on pregnancy outcomes. METHODS: Consecutive patients with NMOSD were recruited between September 2015 and April 2016 at an outpatient clinic from four referral institutes in South China. Demographic, clinical, and pregnancy data were retrieved by questionnaires to analyze the association between NMOSD and pregnancy, as well as the potential risk factors for relapse. RESULTS: Among 249 patients with NMOSD, 55 had pregnancy-related attacks. The annual relapse rate in the first (3.20±6.82) and second (3.25±3.32) 3-month postpartum periods was marginally higher than that before pregnancy (1.44±0.92, p=0.682) and during pregnancy (1.23±1.32, p=0.758). The Kurtzke Expanded Disability Status Scale score increased from 1.55±0.38 before pregnancy to 2.88±2.14 at postpartum (p<0.001). NMOSD significantly increased the premature birth rate in patients after disease onset (8.33%) compared with before disease onset (1.95%, p=0.025). Multivariate analysis showed that negative anti-aquaporin-4 IgG, concomitance with autoimmune diseases/antibodies, and no treatment in remission were risk factors of recurrence. CONCLUSION: Our study shows a significant association between pregnancy and NMOSD in the Chinese population. Larger scale prospective studies are warranted in the future.