The phased Solanum okadae genome and Petota pangenome analysis of 23 other potato wild relatives and hybrids.

Potato is an important crop in the genus Solanum section Petota. Potatoes are susceptible to multiple abiotic and biotic stresses and have undergone constant improvement through breeding programs worldwide. Introgression of wild relatives from section Petota with potato is used as a strategy to enhance the diversity of potato germplasm. The current dataset contributes a phased genome assembly for diploid S. okadae, and short read sequences and de novo assemblies for the genomes of 16 additional wild diploid species in section Petota that were noted for stress resistance and were of interest to potato breeders. Genome sequence data for three additional genomes representing polyploid hybrids with cultivated potato, and an additional genome from non-tuberizing S. etuberosum, which is outside of section Petota, were also included. High quality short reads assemblies were achieved with genome sizes ranging from 575 to 795 Mbp and annotations were performed utilizing transcriptome sequence data. Genomes were compared for presence/absence of genes and phylogenetic analyses were carried out using plastome and nuclear sequences.

Stable, narrow-linewidth laser system with a broad frequency tunability and a fast switching time.

For a Rydberg atom-based sensor to change its sensing frequency, the wavelength of the Rydberg state excitation laser must be altered. The wavelength shifts required can be on the order of 10 nm. A fast-tunable narrow-linewidth laser with broadband tuning capability is required. Here, we present a demonstration of a laser system that can rapidly switch a coupling laser as much as 8 nm in less than 50 µs. The laser system comprises a frequency-stabilized continuous wave laser and an electro-optic frequency comb. A filter enables selection of individual comb lines. A high-speed electro-optic modulator is used to tune the selected comb line to a specific frequency, i.e., an atomic transition. Through Rydberg atom-based sensing experiments, we demonstrate frequency hopping between two Rydberg states and a fast switching time of 400 µs, which we show can be reduced to ∼50 µs with a ping-pong scheme. If updating the RF frequency is not required during frequency hopping, a 200 ns switching time can be achieved. These results showcase the potential of the laser system for advanced Rydberg atom-based radio frequency sensing applications, like communications and radar.

[Clinical and neuroelectrophysiological characteristics of primary peripheral nerve hyperexcitability syndrome].

Objective: To investigate the clinical and neuroelectrophysiological characteristics of patients with primary peripheral nerve hyperexcitability syndrome (PNHS). Methods: The clinical data of 20 patients who were diagnosed with PNHS in Beijing Tiantan Hospital from April 2016 to January 2023 were retrospectively collected. All patients underwent neuroelectrophysiological examinations. Clinical and electrophysiological characteristics were compared between the antibody positive and antibody negative groups, according to serum and cerebrospinal fluid anti-contactin-associated protein-like 2 (CASPR2) and/or anti-leucine-rich glioma-inactivated protein 1 (LGI-1) antibodies. Results: There were 12 males and 8 females, with a mean age of (44.0±17.2) years and the disease course of [M (Q1, Q3)] 2.3 (1.1, 11.5) months. Motor symptoms included fasciculations, myokymia, muscle pain, cramps, and stiffness. These symptoms were commonly seen in the lower limbs (17 patients), followed by upper limbs (11 patients), face (11 patients) and trunk (9 patients). Nineteen (19/20) patients had sensory abnormalities and/or autonomic dysfunction, 13 patients had central nervous system involvement, and 5 patients had concomitant lung cancer or thymic lesions. The characteristic spontaneous potentials on needle electromyography (EMG) were myokymia potential (19 patients), fasciculation potential (12 patients), spastic potential (3 patients), neuromyotonic potential (1 patients), etc, which were commonly seen in the lower limb muscles, especially the gastrocnemius muscle(12 patients). After-discharge potential was found in 8 patients, and 7 were in the tibial nerve. Seven patients had positive serum anti-CASPR2 antibodies, and 3 of them had concomitant anti-LGI1 antibodies. And 1 patient had positive serum anti-LGI1 antibody alone. Compared with patients in the antibody negative group (n=12), the patients who had anti-VGKC complex antibodies (n=8) had a shorter course of disease [M (Q1, Q3): 1.8 (1, 2) months vs 9.5 (3.3, 20.3) months, P=0.012], higher incidence of after-discharge potential (6/8 vs 2/12, P=0.019). The immunotherapy regimen (multi-dru, single-drug, no immunotherapy: 6, 2, 0 patients) in antibody-positive patients was different from the antibody-negative group (3, 6, 3 patients, U=21.00, P=0.023). Conclusions: The symptoms of motor nerve hyperexcitation, characteristic EMG spontaneous potentials and after-discharge potentials in PNHS patients are most commonly seen in the lower limbs. Attention should be paid to concomitant sensory and autonomic nerve hyperexcitation. PNHS patients with positive serum anti-CASPR2 antibodies may require immunotherapy with multiple drugs.

First-line treatment and overall survival in EGFR mutation-positive advanced non-small cell lung cancer: a national cohort study.

OBJECTIVE: Non-squamous non-small cell lung cancer (NSCLC) is the first leading cause of cancer-related deaths in Taiwan. This study aimed at evaluating the effectiveness of first-line targeted therapy for advanced epidermal growth factor receptor (EGFR) mutation-positive non-squamous NSCLC in Taiwan. PATIENTS AND METHODS: This was a real-world, retrospective, observational study of patients diagnosed with advanced non-squamous NSCLC (N=63,248). Between 2011 and 2019, 19,458 patients received targeted therapy and 22,994 patients received chemotherapy alone; between 2002 and 2010, 20,796 patients received chemotherapy alone. Overall survival (OS) was determined. RESULTS: The median OS for patients treated with first-line targeted therapy (22.9 months) was longer than that of patients receiving chemotherapy alone (11.7 months). HR: 0.521, log-rank test, p<0.001. CONCLUSIONS: These data represent the potential survival outcomes of Taiwanese patients with advanced EGFR mutation-positive non-squamous NSCLC in clinical practice.

Real-world results of immune checkpoint inhibitors from the Taiwan National Health Insurance Registration System.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) are a major advance in cancer treatment, but their payment benefits are unclear, resulting in financial risk. In Taiwan, the National Health Insurance Administration (NHIA) has adapted risk-sharing mechanisms to cover ICIs by collecting and assessing real-world evidence, such as case registration data, to adjust benefit packages for each medication, increase payment benefits of ICIs, and enable national health insurance sustainability. PATIENTS AND METHODS: This nationwide, multicenter, retrospective cohort study assessed the real-world use, effectiveness, and safety of ICIs reimbursed by the NHIA for treating multiple advanced cancers in Taiwan. We obtained data mainly from the NHIA Immune Checkpoint Inhibitor Registry Database. RESULTS: Between April 1, 2019, and March 31, 2020, 1644 patients received at least one dose of ICIs. The overall response rate (RR) was 29.1%. The metastatic urothelial carcinoma of patients ineligible for chemotherapy showed the highest RR. The estimated median progression-free survival (PFS) was 2.8 months (95% confidence interval [CI]=2.7-3 months), and renal cell carcinoma showed the longest PFS. The median PFS was reached in patients with most cancers except classic Hodgkin's lymphoma, which had a small sample size. The estimated survival probability was 50%. CONCLUSIONS: Under the national registration tracking system, Taiwan's high-cost drug policy has enabled access to new medicines and maximized patient benefits.

Evaluation of the performance of instruments to diagnose grief disorders: A diagnostic meta-analysis.

BACKGROUND: Prolonged or complicated grief disorder occurs in 9.8% of bereaved adults and can progress into adverse health effects if left unresolved. Evidence on the appropriate and specific diagnostic instrument for the assessment of prolonged or complicated grief disorders is lacking. OBJECTIVE: The purpose of this study was to evaluate the performance of the most widely used instruments to diagnose grief disorders, including The Inventory of Complicated Grief, The Inventory of Complicated Grief - Revised, and the Prolonged Grief Disorder-13. DESIGN: Diagnostic meta-analysis. DATA SOURCES: PubMed, EMBASE, CINAHL, Medline, Scopus, Web of Science, and Cochrane were searched up to July 1, 2020. METHODS: We included studies evaluating the sensitivity and specificity of grief disorders diagnostic tools against the comparator tests in individuals who experienced the loss of a family member. A diagnostic meta-analysis of pooled sensitivity and specificity, likelihood ratios, and area under curve were performed with a random-effect and hierarchical model. RESULTS: In the current study, 3540 participants were involved. The six studies of the Inventory of Complicated Grief had pooled sensitivity of 0.93 (95% confidence interval: 0.87 to 0.97) and specificity of 0.96 (95% confidence interval: 0.92 to 0.98). The positive likelihood ratio was 23.4 (95% confidence interval: 11.2 to 49.0) and the negative likelihood ratio was 0.07 (95% confidence interval: 0.04 to 0.14) with area under curve value at 0.96 (95% confidence interval: 0.97 to 0.99). For Prolonged Grief Disorder-13, the three included studies' pooled sensitivity was 0.51 (95% confidence interval: 0.42 to 0.60), and the pooled specificity was 0.96 (95% confidence interval: 0.93 to 0.98). The Inventory of Complicated Grief-Revised evaluation could not be performed as only two articles from the same study were identified in this meta-analysis. CONCLUSIONS: The Inventory of Complicated Grief is a highly recommend instrument to differentiate the case of grief disorders. Nurses and health care professionals can use the Inventory of Complicated Grief in the diagnosis of prolonged or complicated grief disorders due to its high sensitivity and specificity values. Further evaluations are needed for the use of Prolonged Grief Disorder-13 and Inventory of Complicated Grief-Revised. REGISTRATION: The study is registered with the Open Science Framework (https://osf.io/bs8n6/?view_only=109e76e59efb4d7699153f62564f57ed). Tweetable abstract: Inventory of Complicated Grief is a highly recommend instrument with high sensitivity and specificity for diagnosing grief disorders.

Protection procedures and preventions against the spread of coronavirus disease 2019 in healthcare settings for nursing personnel: Lessons from Taiwan.

BACKGROUND: Since coronavirus disease 2019 was first discovered, at the time of writing this article, the number of people infected globally has exceeded 1 million. Its high transmission rate has resulted in nosocomial infections in healthcare facilities all over the world. Nursing personnel account for nearly 50% of the global health workforce and are the primary provider of direct care in hospitals and long-term care facilities. Nurses stand on the front line against the spread of this pandemic, and proper protection procedures are vital. OBJECTIVES: The present study aims to share the procedures and measures used by Taiwan nursing personnel to help reduce global transmission. REVIEW METHODS: Compared with other regions, where large-scale epidemics have overwhelmed the health systems, Taiwan has maintained the number of confirmed cases within a manageable scope. A review of various national and international policies and guidelines was carried out to present proper procedures and preventions for nursing personnel in healthcare settings. RESULTS: This study shows how Taiwan's health system rapidly identified suspected cases as well as the prevention policies and strategies, key protection points for nursing personnel in implementing high-risk nursing tasks, and lessons from a nursing perspective. CONCLUSIONS: Various world media have affirmed the rapid response and effective epidemic prevention strategies of Taiwan's health system. Educating nurses on procedures for infection control, reporting cases, and implementing protective measures to prevent nosocomial infections are critical to prevent further outbreaks.

The effectiveness of eye movement desensitization and reprocessing toward anxiety disorder: A meta-analysis of randomized controlled trials.

BACKGROUND: Eye Movement Desensitization and Reprocessing (EMDR) has been well established as an effective treatment for post-traumatic stress disorder (PTSD). However, PTSD has been re-categorized as part of trauma and stressor-related disorders instead of anxiety disorders. We conducted the first meta-analysis on Randomized Controlled Trials to evaluate the effectiveness of EMDR on reducing symptoms of anxiety disorders. METHODS: A manual and systematic search using various databases and reference lists of systematic review articles published up to December 2018 was conducted. The symptoms of anxiety, phobia, panic, traumatic feelings and behaviors/somatic symptoms were examined. Hedges' g effect sizes were computed, and random effect models were used for all analyses. RESULTS: A total of 17 trials with 647 participants were included in this meta-analysis. EMDR was associated with a significant reduction of anxiety (g = -0.71; 95% CI: -0.96 to -0.47), panic (g = -0.62; 95% CI: -1.10 to -0.14), phobia (g = -0.45; 95% CI: -0.81 to -0.08), behavioural/somatic symptoms (g = -0.40; 95% CI: -0.63 to -0.12), but not traumatic feelings (g = -0.48; 95% CI: -1.14 to -0.18). Subgroup analysis revealed greater effects of EMDR if compared to passive control. However, the effects were not significantly different based on the duration, number of therapy sessions, or the number of weekly sessions. CONCLUSIONS: Our meta-analysis indicates that EMDR is efficacious for reducing symptoms of anxiety, panic, phobia, and behavioural/somatic symptoms. Further research is needed to explore EMDR's long term efficacy on anxiety disorders.

Ring-shaped replicative helicase encircles double-stranded DNA during unwinding.

Ring-shaped replicative helicases are hexameric and play a key role in cellular DNA replication. Despite their importance, our understanding of the unwinding mechanism of replicative helicases is far from perfect. Bovine papillomavirus E1 is one of the best-known model systems for replicative helicases. E1 is a multifunctional initiator that senses and melts the viral origin and unwinds DNA. Here, we study the unwinding mechanism of E1 at the single-molecule level using magnetic tweezers. The result reveals that E1 as a single hexamer is a poorly processive helicase with a low unwinding rate. Tension on the DNA strands impedes unwinding, indicating that the helicase interacts strongly with both DNA strands at the junction. While investigating the interaction at a high force (26-30 pN), we discovered that E1 encircles dsDNA. By comparing with the E1 construct without a DNA binding domain, we propose two possible encircling modes of E1 during active unwinding.

Pre-treatment quality of life as a predictor of distant metastasis-free survival and overall survival in patients with head and neck cancer who underwent free flap reconstruction.

PURPOSE: This study examined the prognostic associations of pre-treatment quality of life (QoL) with overall survival (OS) and distant metastasis-free survival (DFMS) among patients with head and neck cancer (HNC) who underwent free flap reconstruction. METHODS: A cohort of 127 HNC patients who received free flap reconstruction between November 2010 and June 2014 at a hospital were recruited. Pre-treatment QoL was measured by the University of Washington Quality of Life Questionnaire, which contains six physical domains, including speech, swallowing, appearance, saliva, taste and chewing, as well as the six social-emotional domains of pain, activity, recreation, shoulder, mood, and anxiety. Cox regression analyses were performed. RESULTS: Results showed that pre-treatment QoL was predictive of OS and DMFS. Of the domains, swallowing, chewing, speech, taste, saliva, pain and shoulder were demonstrated to be significant predictors of OS. Additionally, swallowing, chewing, speech, pain and activity were demonstrated making significant contributions to DMFS. CONCLUSION: Our data supported that physical domains of pre-treatment QoL were predictors for OS and DFMS in HNC patients with free-flap reconstruction. Longitudinal studies are warranted to clarify the prognostic abilities of social-emotional domains. Information on pre-treatment QoL should be taken into account to individualize care plan for these patients, and hence prolong their survival.

Discriminatory performance of adiponectin and leptin in the identification of impaired glucose tolerance: The Guangzhou Biobank Cohort Study - Cardiovascular Disease Subcohort.

BACKGROUND: To evaluate the additional discriminatory performance of adiponectin, leptin, and their ratio in the identification of impaired glucose tolerance (IGT) in men and women without diabetes on top of conventional risk factors. METHODS & RESULTS: A total of 698 subjects underwent an oral glucose tolerance test (oGTT) and adipocytokine measurements. A comprehensive stepwise selection procedure was performed, followed by c-statistics and integrated discrimination improvement (IDI) analysis. In males, adiponectin levels were significantly lower in the IGT group compared to the non-IGT group (Whitney U test, p < 10-4), whereas leptin levels were significantly higher (p = 0.009) in IGT group. In females, adiponectin and leptin levels were not significantly different between groups (Mann-Whitney U test, p = 0.073 and p = 0.08, respectively). Adjusting for the most informative, sex-specific, clinical and biochemical factors, adiponectin, leptin and their ratio were not found to be significant predictors of the response to the glucose load, when modelled as continuous terms or tertiles. In males, the area-under-the-curve (AUC) for adiponectin was estimated at 0.620 (95% CI: 0.558-0.682) and the addition of adiponectin into the basic model provided a ΔAUC benefit of 0.004, showing no additional discriminatory benefit on top of conventional risk factors (IDI p-value: 0.27), nor did the addition of leptin or their ratio. The results were similar in females. CONCLUSIONS: In Chinese individuals without diabetes, no significant evidence for the potential discriminatory value of adiponectin, leptin or their ratio in the identification of IGT on top of conventional risk factors was observed.

Peritumoral radiomics features predict distant metastasis in locally advanced NSCLC.

PURPOSE: Radiomics provides quantitative tissue heterogeneity profiling and is an exciting approach to developing imaging biomarkers in the context of precision medicine. Normal-appearing parenchymal tissues surrounding primary tumors can harbor microscopic disease that leads to increased risk of distant metastasis (DM). This study assesses whether computed-tomography (CT) imaging features of such peritumoral tissues can predict DM in locally advanced non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: 200 NSCLC patients of histological adenocarcinoma were included in this study. The investigated lung tissues were tumor rim, defined to be 3mm of tumor and parenchymal tissue on either side of the tumor border and the exterior region extended from 3 to 9mm outside of the tumor. Fifteen stable radiomic features were extracted and evaluated from each of these regions on pre-treatment CT images. For comparison, features from expert-delineated tumor contours were similarly prepared. The patient cohort was separated into training and validation datasets for prognostic power evaluation. Both univariable and multivariable analyses were performed for each region using concordance index (CI). RESULTS: Univariable analysis reveals that six out of fifteen tumor rim features were significantly prognostic of DM (p-value < 0.05), as were ten features from the visible tumor, and only one of the exterior features was. Multivariablely, a rim radiomic signature achieved the highest prognostic performance in the independent validation sub-cohort (CI = 0.64, p-value = 2.4×10-5) significantly over a multivariable clinical model (CI = 0.53), a visible tumor radiomics model (CI = 0.59), or an exterior tissue model (CI = 0.55). Furthermore, patient stratification by the combined rim signature and clinical predictor led to a significant improvement on the clinical predictor alone and also outperformed stratification using the combined tumor signature and clinical predictor. CONCLUSIONS: We identified peritumoral rim radiomic features significantly associated with DM. This study demonstrated that peritumoral imaging characteristics may provide additional valuable information over the visible tumor features for patient risk stratification due to cancer metastasis.

[Resting-state functional MRI studies of amyotrophic lateral sclerosis patients with various levels of cognitive impairment].

Objective: To characterize the brain functional changes of amyotrophic lateral sclerosis (ALS) patients with various levels of cognitive impairment as measured by resting-state functional MRI (RS-fMRI). Methods: From September 2013 to March 2017, a total of 55 patients diagnosed with ALS in Peking Union Medical College Hospital and 20 healthy controls (HCs) were included in this study, and all participants underwent neuropsychological assessments and diffusion tensor imaging scans. According to their cognitive performance, ALS patients were further subclassified into ALS with normal cognition (ALS-Cn, n=27), those with cognitive impairment (ALS-Ci, n=17) and ALS-FTD (n=11). Comparisons of fractional amplitude of low frequency fluctuation (fALFF) value and regional homogeneity (ReHo) value were conducted among the 4 subgroups. Results: The fALFF showed significant differences in bilateral frontal lobe, left temporal lobe and cingulate gyrus, (P<0.001, uncorrected) and the ReHo showed significant differences in left frontal lobe, right temporal lobe and left cingulate gyrus (P<0.001, FDR corrected). The differences mainly stemmed from that patients with ALS-FTD showed decreased fALFF and ReHo in these areas when compared to the other three groups, especially in relation to HCs, mainly locating in left prefrontal lobe and anterior cingulate cortex. The whole-brain comparisons of fALFF and ReHo between ALS-Ci, ALS-Cn and HCs revealed no significant difference (P<0.001, uncorrected). Conclusion: Hypoactivities are detected in extramotor areas in patients with ALS-FTD. RS-fMRI is helpful in investigating the pathophysiologic mechanism of cognitive impairment in ALS.

Comparison of lung tumor motion measured using a model-based 4DCT technique and a commercial protocol.

PURPOSE: To compare lung tumor motion measured with a model-based technique to commercial 4-dimensional computed tomography (4DCT) scans and describe a workflow for using model-based 4DCT as a clinical simulation protocol. METHODS AND MATERIALS: Twenty patients were imaged using a model-based technique and commercial 4DCT. Tumor motion was measured on each commercial 4DCT dataset and was calculated on model-based datasets for 3 breathing amplitude percentile intervals: 5th to 85th, 5th to 95th, and 0th to 100th. Internal target volumes (ITVs) were defined on the 4DCT and 5th to 85th interval datasets and compared using Dice similarity. Images were evaluated for noise and rated by 2 radiation oncologists for artifacts. RESULTS: Mean differences in tumor motion magnitude between commercial and model-based images were 0.47 ± 3.0, 1.63 ± 3.17, and 5.16 ± 4.90 mm for the 5th to 85th, 5th to 95th, and 0th to 100th amplitude intervals, respectively. Dice coefficients between ITVs defined on commercial and 5th to 85th model-based images had a mean value of 0.77 ± 0.09. Single standard deviation image noise was 11.6 ± 9.6 HU in the liver and 6.8 ± 4.7 HU in the aorta for the model-based images compared with 57.7 ± 30 and 33.7 ± 15.4 for commercial 4DCT. Mean model error within the ITV regions was 1.71 ± 0.81 mm. Model-based images exhibited reduced presence of artifacts at the tumor compared with commercial images. CONCLUSION: Tumor motion measured with the model-based technique using the 5th to 85th percentile breathing amplitude interval corresponded more closely to commercial 4DCT than the 5th to 95th or 0th to 100th intervals, which showed greater motion on average. The model-based technique tended to display increased tumor motion when breathing amplitude intervals wider than 5th to 85th were used because of the influence of unusually deep inhalations. These results suggest that care must be taken in selecting the appropriate interval during image generation when using model-based 4DCT methods.

Glycated Hemoglobin, Albuminuria and Surrogate Markers of Macrovascular Disease in Adults Without Diabetes: The Guangzhou Biobank Cohort Study, Cardiovascular Disease Subcohort.

OBJECTIVES: To explore the clinical utility of glycated hemoglobin (A1C) levels as an early marker of albuminuria, macrovascular disease and subclinical cardiovascular disease in comparison to fasting and postprandial glucose levels in a well-characterized Chinese population with no history of diabetes. METHODS: The study population consisted of 1223 individuals who were enrolled in the Guangzhou Biobank Cohort Study, Cardiovascular Disease Subcohort, and who had undergone oral glucose tolerance tests. The associations between each glycemic measure and albuminuria, carotid intima-media thickness (CIMT) and CIMT-based presence of carotid plaques and aortic arch calcification were assessed by chest radiographs. RESULTS: The overall prevalence of albuminuria, carotid plaque and any aortic arch calcification was 20.6%, 22.8% and 25.8%, respectively. All 3 glycemia indices were significantly associated with albuminuria, but only 1 (fasting glucose) was associated with carotid plaques. No significant difference was detected among them in the area under the curve for albuminuria (chi-square test; p=0.84), carotid plaques (p=0.28) or calcifications (p=0.29). In sensitivity analysis, adjusted for age and sex, the above findings remained unchanged. CONCLUSIONS: Although there was evidence suggesting differential associations, the performance of the glycemic indices was similar, and their association with macrovascular disease and albuminuria was modest.

Structural basis of the redox switches in the NAD+-reducing soluble [NiFe]-hydrogenase.

NAD+ (oxidized form of NAD:nicotinamide adenine dinucleotide)-reducing soluble [NiFe]-hydrogenase (SH) is phylogenetically related to NADH (reduced form of NAD+):quinone oxidoreductase (complex I), but the geometrical arrangements of the subunits and Fe-S clusters are unclear. Here, we describe the crystal structures of SH in the oxidized and reduced states. The cluster arrangement is similar to that of complex I, but the subunits orientation is not, which supports the hypothesis that subunits evolved as prebuilt modules. The oxidized active site includes a six-coordinate Ni, which is unprecedented for hydrogenases, whose coordination geometry would prevent O2 from approaching. In the reduced state showing the normal active site structure without a physiological electron acceptor, the flavin mononucleotide cofactor is dissociated, which may be caused by the oxidation state change of nearby Fe-S clusters and may suppress production of reactive oxygen species.