Influences of Genetic and Environmental Factors on Chronic Migraine: A Narrative Review.

PURPOSE OF REVIEW: In this narrative review, we aim to summarize recent insights into the complex interplay between environmental and genetic factors affecting the etiology, development, and progression of chronic migraine (CM). RECENT FINDINGS: Environmental factors such as stress, sleep dysfunction, fasting, hormonal changes, weather patterns, dietary compounds, and sensory stimuli are critical triggers that can contribute to the evolution of episodic migraine into CM. These triggers are particularly influential in genetically predisposed individuals. Concurrently, genome-wide association studies (GWAS) have revealed over 100 genetic loci linked to migraine, emphasizing a significant genetic basis for migraine susceptibility. In CM, environmental and genetic factors are of equal importance and contribute to the pathophysiology of the condition. Understanding the bidirectional interactions between these elements is crucial for advancing therapeutic approaches and preventive strategies. This balanced perspective encourages continued research into the complex gene-environment nexus to improve our understanding and management of CM.

Accelerating pandemic response with the emergency Omicron RT-PCR test: A comprehensive solution for COVID-19 diagnosis and tracking.

The Omicron variant of concern (VOC) has surged in many countries and replaced the previously reported VOC. To identify different Omicron strains/sublineages on a rapid, convenient, and precise platform, we report a novel multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) method in one tube based on the Omicron lineage sequence variants' information. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subvariants were used in a PCR-based assay for rapid identification of Omicron sublineage genotyping in 1000 clinical samples. Several characteristic mutations were analyzed using specific primers and probes for the spike gene, del69-70, and F486V. To distinguish Omicron sublineages (BA.2, BA.4, and BA.5), the NSP1:141-143del in the ORF1a region and D3N mutation in membrane protein occurring outside the spike protein region were analyzed. Results from the real-time PCR assay for one-tube accuracy were compared to those of whole genome sequencing. The developed PCR assay was used to analyze 400 SARS-CoV-2 positive samples. Ten samples determined as BA.4 were positive for NSP1:141-143del, del69-70, and F486V mutations; 160 BA.5 samples were positive for D3N, del69-70, and F486V mutations, and 230 BA.2 samples were without del69-70. Screening these samples allowed the identification of epidemic trends at different time intervals. Our novel one-tube multiplex PCR assay was effective in identifying Omicron sublineages.

An Innovative Customized Biomimetic Hydrogel for Drug Screening Application Potential: Biocompatibility and Cell Invasion Ability.

The ability of Pluronic F127 (PF127) conjugated with tetrapeptide Gly-Arg-Gly-Asp (GRGD) as a sequence of Arg-Gly-Asp (RGD) peptide to form the investigated potential hydrogel (hereafter referred to as 3DG bioformer (3BE)) to produce spheroid, biocompatibility, and cell invasion ability, was assessed in this study. The fibroblast cell line (NIH 3T3), osteoblast cell line (MG-63), and human breast cancer cell line (MCF-7) were cultured in the 3BE hydrogel and commercial product (Matrigel) for comparison. The morphology of spheroid formation was evaluated via optical microscopy. The cell viability was observed through cell counting Kit-8 assay, and cell invasion was investigated via Boyden chamber assay. Analytical results indicated that 3BE exhibited lower spheroid formation than Matrigel. However, the 3BE appeared biocompatible to NIH 3T3, MG-63, and MCF-7 cells. Moreover, cell invasion ability and cell survival rate after invasion through the 3BE was displayed to be comparable to Matrigel. Thus, these findings demonstrate that the 3BE hydrogel has a great potential as an alternative to a three-dimensional cell culture for drug screening applications.

Breathing-based leg exercises during hemodialysis improve quality of life: A randomized controlled trial.

OBJECTIVE: To evaluate the effect of a 12-week breathing-based leg exercises program on quality of life under stabilizing heart rate variability and reducing fatigue in regular hemodialysis patients. DESIGN: Randomized controlled trial. SETTING: A 94-bed hemodialysis department at a medical center in northern Taiwan. PARTICIPANTS: Eighty-six patients with end-stage renal disease undergoing hemodialysis were recruited and randomly assigned to the ExBr or control groups. INTERVENTIONS: The breathing-based leg exercises program comprised abdominal breathing and low-intensity leg exercise, including leg lifts, quadriceps femoris contraction and knee flexion, and lasted for 15 minutes at one time, three times a week for 12 weeks. MAIN MEASURE: Data was collected by using the World Health Organization quality of life assessment-brief, physiological signal recorder for heart rate variability and hemodialysis-related fatigue scale at baseline and on Week 4, Week 8, and Week 12. RESULTS: Average (standard deviation) age was 53.70 (10.04) years in the ExBr group and 61.19 (10.19) years in the control group. The linear mixed model with adjusted age, creatinine, heart rate variability and fatigue revealed that the ExBr group had significantly higher quality of life than did the control group (P = 0.01), especially on Week 12 (P = 0.04). Fatigue was significantly correlated with quality of life (P < 0.001). CONCLUSION: This study supported the benefits of the continued breathing-based leg exercises during hemodialysis for at least 12 weeks, which improved the quality of life of patients with end-stage renal disease and did not affect the stability of their vital signs.

Identifying genetic variants for age of migraine onset in a Han Chinese population in Taiwan.

BACKGROUND: Considering the involvement of genetics in migraine pathogenesis in diverse ethnic populations, genome-wide association studies (GWAS) are being conducted to identify migraine-susceptibility genes. However, limited surveys have focused on the onset age of migraine (AoM) in Asians. Therefore, in this study, we aimed to identify the susceptibility loci of migraine considering the AoM in an Asian population. METHODS: We conducted a GWAS in 715 patients with migraine of Han Chinese ethnicity, residing in Taiwan, to identify the susceptibility genes associated with AoM. Based on our standard demographic questionnaire, the population was grouped into different subsets. Single-nucleotide polymorphism (SNP) associations were examined using PLINK in different AoM onset groups. RESULTS: We discovered eight novel susceptibility loci correlated with AoM that reached the GWAS significance level in the Han Chinese population. First, rs146094041 in ESRRG was associated with AoM [Formula: see text] 12 years. The other SNPs including rs77630941 in CUX1, rs146778855 in CDH18, rs117608715 in NOL3, rs150592309 in PRAP1, and rs181024055 in NRAP were associated with the later AoM. CONCLUSIONS: To our knowledge, this is the first GWAS to investigate the AoM in an Asian Han Chinese population. Our newly discovered susceptibility genes may have prospective associations with migraine pathogenesis.

Use of Heart Rate Variability and Photoplethysmograph-Derived Parameters as Assessment Signals of Radiofrequency Therapy Efficacy for Chronic Pain.

BACKGROUND: Radiofrequency therapy (RFT) generates molecular motion and produces heat and electromagnetic effects on tissues, which attenuate pain sensation and thereby relieve pain. This study was to observe the altering trend of physiological parameters after RFT for chronic cervical or lumbar pain. METHODS: This study recruited 66 patients with chronic cervical or lumbar pain and recorded their physiological parameters before and after RFT using heart rate variability (HRV) and photoplethysmography (PPG) to explore the feasibility of RFT efficacy assessment. RESULTS: The patients' visual analog scale scores significantly decreased after RFT and the HRV parameters that represented parasympathetic activity significantly changed (HR decreased, and R-R interval and low- and high-frequency power increased significantly). Meanwhile, the PPG parameters that represented sympathetic activity also increased (PPG amplitude and autonomic nervous system state significantly decreased). CONCLUSIONS: This study showed significant efficacy of RFT in patients with chronic cervical or lumbar pain. The changes of HRV and PPG parameters may explain part of the mechanisms of RFT.

Sensory axonal dysfunction in cervical radiculopathy.

OBJECTIVE: The aim of this study was to evaluate changes in sensory axonal excitability in the distal nerve in patients with cervical radiculopathy. METHODS: The patients were classified by the findings of cervical MRI into two subgroups: 22 patients with C6/7 root compression and 25 patients with cervical cord and root compression above/at C6/7. Patients were investigated using conventional nerve conduction studies (NCS) and nerve excitability testing. Sensory nerve excitability testing was undertaken with stimulation at the wrist and recording from digit II (dermatome C6/7). The results were compared with healthy controls. Both preoperative and postoperative tests were performed if the patient underwent surgery. RESULTS: Sensory axonal excitability was significantly different in both cohorts compared with healthy controls, including prolonged strength-duration time constant, reduced S2 accommodation, increased threshold electrotonus hyperpolarisation (TEh (90-100 ms)), and increased superexcitability. The changes in these excitability indices are compatible with axonal membrane hyperpolarisation. In five patients who underwent surgery, the postoperative sensory excitability was tested after 1 week, and showed significant changes in TE (TEh (90-100 ms) and TEh slope, p<0.05) between presurgery and postsurgery. CONCLUSIONS: The present study demonstrated distal nerve axonal hyperpolarisation in patients with cervical radiculopathy. These findings suggest that the hyperpolarised pattern might be due to Na(+)-K(+) ATPase overactivation induced by proximal ischaemia, or could reflect the remyelinating process. Distal sensory axons were hyperpolarised even though there were no changes in NCS, suggesting that nerve excitability testing may be more sensitive to clinical symptoms than NCS in patients with cervical radiculopathy.

Tyrosine sulfation as a protein post-translational modification.

Integration of inorganic sulfate into biological molecules plays an important role in biological systems and is directly involved in the instigation of diseases. Protein tyrosine sulfation (PTS) is a common post-translational modification that was first reported in the literature fifty years ago. However, the significance of PTS under physiological conditions and its link to diseases have just begun to be appreciated in recent years. PTS is catalyzed by tyrosylprotein sulfotransferase (TPST) through transfer of an activated sulfate from 3'-phosphoadenosine-5'-phosphosulfate to tyrosine in a variety of proteins and peptides. Currently, only a small fraction of sulfated proteins is known and the understanding of the biological sulfation mechanisms is still in progress. In this review, we give an introductory and selective brief review of PTS and then summarize the basic biochemical information including the activity and the preparation of TPST, methods for the determination of PTS, and kinetics and reaction mechanism of TPST. This information is fundamental for the further exploration of the function of PTS that induces protein-protein interactions and the subsequent biochemical and physiological reactions.

Osteoporosis and the risk of symptomatic nephrolithiasis: a population-based 5-year follow-up study in Taiwan.

This study estimates the risk of symptomatic nephrolithiasis within 5 years of newly diagnosed osteoporosis in a Taiwan population. This cohort study consisted of patients with a diagnosis of osteoporosis between Jan. 2003 and Dec. 2005 (N = 1634). Four age- and gender- matched patients for every patient in the study cohort were selected using random sampling as the comparison cohort (N = 6536). All patients were tracked for 5 years from the date of cohort entry to identify whether they developed symptomatic nephrolithiasis. Cox proportional hazard regressions were performed to evaluate the 5-year nephrolithiasis-free survival rates. During the 5-year follow-up period, 60 osteoporosis patients (3.7%) and 165 non- osteoporosis patients (2.5%) developed symptomatic nephrolithiasis. The adjusted HR of symptomatic nephrolithiasis was 1.38 times greater risk for patients with osteoporosis than for the comparison cohort (95% confidence interval (CI) 1.03-1.86; P < .05). Osteoporosis is very likely to be an independent risk factor for subsequent diagnosis of symptomatic nephrolithiasis.

Osteoporosis increases subsequent risk of gallstone: a nationwide population-based cohort study in Taiwan.

BACKGROUND: Osteopontin (OPN) is a pro-inflammatory cytokine which is expressed in various tissues. It participates in the bone remodeling process and stimulates bone resorption by osteoclasts. It is also a core protein of cholesterol gallstones. We hypothesized osteoporotic patients might have higher risk in developing gallstones and conducted a population-based study to examine the risk of developing gallstone in osteoporotic patients in Taiwan. METHODS: A total of 1,638 patients diagnosed with osteoporosis between 2003 and 2005 were identified in the National Health Insurance Research Database. A comparison cohort without osteoporosis (n =6,552) was randomly matched to each osteoporosis patient at a ratio of 4: 1 based on age and sex. A Cox proportional-hazards regression analysis was performed to evaluate the 5-year gallstone-free survival rates for the 2 cohorts. RESULTS: During the 5-year follow-up period, 114 and 311 cases of gallstone occurred in the osteoporosis and comparison cohorts, respectively. After adjusting for the confounders, the Cox regression analysis of the risk of gallstone in the osteoporosis and comparison cohorts yielded a hazard ratio of 1.35 (95% confidence interval: 1.07 - 1.69; p < 0 .01). CONCLUSION: Patients with osteoporosis in Taiwan have a higher risk of developing gallstone than the general population.

Protein tyrosine phosphatase receptor type O (Ptpro) regulates cerebellar formation during zebrafish development through modulating Fgf signaling.

Protein activities controlled by receptor protein tyrosine phosphatases (RPTPs) play comparably important roles in transducing cell surface signals into the cytoplasm by protein tyrosine kinases. Previous studies showed that several RPTPs are involved in neuronal generation, migration, and axon guidance in Drosophila, and the vertebrate hippocampus, retina, and developing limbs. However, whether the protein tyrosine phosphatase type O (ptpro), one kind of RPTP, participates in regulating vertebrate brain development is largely unknown. We isolated the zebrafish ptpro gene and found that its transcripts are primarily expressed in the embryonic and adult central nervous system. Depletion of zebrafish embryonic Ptpro by antisense morpholino oligonucleotide knockdown resulted in prominent defects in the forebrain and cerebellum, and the injected larvae died on the 4th day post-fertilization (dpf). We further investigated the function of ptpro in cerebellar development and found that the expression of ephrin-A5b (efnA5b), a Fgf signaling induced cerebellum patterning factor, was decreased while the expression of dusp6, a negative-feedback gene of Fgf signaling in the midbrain-hindbrain boundary region, was notably induced in ptpro morphants. Further analyses demonstrated that cerebellar defects of ptpro morphants were partially rescued by inhibiting Fgf signaling. Moreover, Ptpro physically interacted with the Fgf receptor 1a (Fgfr1a) and dephosphorylated Fgfr1a in a dose-dependant manner. Therefore, our findings demonstrate that Ptpro activity is required for patterning the zebrafish embryonic brain. Specifically, Ptpro regulates cerebellar formation during zebrafish development through modulating Fgf signaling.

Host-Pathogen Interactions in K. pneumoniae Urinary Tract Infections: Investigating Genetic Risk Factors in the Taiwanese Population.

BACKGROUND: Klebsiella pneumoniae (K. pneumoniae) urinary tract infections pose a significant challenge in Taiwan. The significance of this issue arises because of the growing concerns about the antibiotic resistance of K. pneumoniae. Therefore, this study aimed to uncover potential genomic risk factors in Taiwanese patients with K. pneumoniae urinary tract infections through genome-wide association studies (GWAS). METHODS: Genotyping data are obtained from participants with a history of urinary tract infections enrolled at the Tri-Service General Hospital as part of the Taiwan Precision Medicine Initiative (TPMI). A case-control study employing GWAS is designed to detect potential susceptibility single-nucleotide polymorphisms (SNPs) in patients with K. pneumoniae-related urinary tract infections. The associated genes are determined using a genome browser, and their expression profiles are validated via the GTEx database. The GO, Reactome, DisGeNET, and MalaCards databases are also consulted to determine further connections between biological functions, molecular pathways, and associated diseases between these genes. RESULTS: The results identified 11 genetic variants with higher odds ratios compared to controls. These variants are implicated in processes such as adhesion, protein depolymerization, Ca2+-activated potassium channels, SUMOylation, and protein ubiquitination, which could potentially influence the host immune response. CONCLUSIONS: This study implies that certain risk variants may be linked to K. pneumoniae infections by affecting diverse molecular functions that can potentially impact host immunity. Additional research and follow-up studies are necessary to elucidate the influence of these risk variants on infectious diseases and develop targeted interventions for mitigating the spread of K. pneumoniae urinary tract infections.

Genetic Risk Loci and Familial Associations in Migraine: A Genome-Wide Association Study in the Han Chinese Population of Taiwan.

BACKGROUND AND PURPOSE: Migraine is a condition that is often observed to run in families, but its complex genetic background remains unclear. This study aimed to identify the genetic factors influencing migraines and their potential association with the family medical history. METHODS: We performed a comprehensive genome-wide association study of a cohort of 1,561 outpatients with migraine and 473 individuals without migraine in Taiwan, including Han Chinese individuals with or without a family history of migraine. By analyzing the detailed headache history of the patients and their relatives we aimed to isolate potential genetic markers associated with migraine while considering factors such as sex, episodic vs. chronic migraine, and the presence of aura. RESULTS: We revealed novel genetic risk loci, including rs2287637 in DEAD-Box helicase 1 and long intergenic non-protein coding RNA 1804 and rs12055943 in engulfment and cell motility 1, that were correlated with the family history of migraine. We also found a genetic location downstream of mesoderm posterior BHLH transcription factor 2 associated with episodic migraine, whereas loci within the ubiquitin-specific peptidase 26 exonic region, dual specificity phosphatase 9 and pregnancy-upregulated non-ubiquitous CaM kinase intergenic regions, and poly (ADP-ribose) polymerase 1 and STUM were linked to chronic migraine. We additionally identified genetic regionsassociated with the presence or absence of aura. A locus between LINC02561 and urocortin 3 was predominantly observed in female patients. Moreover, three different single-nucleotide polymorphisms were associated with the family history of migraine in the control group. CONCLUSIONS: This study has identified new genetic locations associated with migraine and its family history in a Han Chinese population, reinforcing the genetic background of migraine. The findings point to potential candidate genes that should be investigated further.

Fluorescence assay for protein post-translational tyrosine sulfation.

We developed a fluorescent assay to conveniently determine the kinetics of protein sulfation, which is essential for understanding interface between protein sulfation and protein-protein interactions. Tyrosylprotein sulfotransferase (TPST) catalyzes protein sulfation using 3'-phosphate 5'-phosphosulfate (PAPS) as sulfuryl group donor. In this report, PAPS was regenerated following sulfuryl group transfer between adenosine 3',5'-diphosphate and 4-methylumbelliferyl sulfate catalyzed by phenol sulfotransferase (PST). The TPST and PST coupled enzyme platform continuously generated fluorescent 4-methylumbelliferone (MU) that was used to real-time monitor protein sulfation. Using a recombinant N utilization substance protein A fused Drosophila melanogaster tyrosylprotein sulfotransferase, we demonstrated that the activity of TPST determined through MU fluorescence directly correlated with protein sulfation. Kinetic constants obtained with small P-selectin glycoprotein ligand-1 peptide (PSGL-1 peptide, MW 1541) or its large glutathione S-transferase fusion protein (GST-PSGL-1, MW 27833) exhibited significant variation. This assay can be further developed to a high-throughput method for the characterization of TPSTs and for the identification and screening of their protein substrates.

The application of a novel 5-in-1 multiplex reverse transcriptase-polymerase chain reaction assay for rapid detection of SARS-CoV-2 and differentiation between variants of concern.

OBJECTIVES: We have established a novel 5-in-1 VOC assay to rapidly detect SARS-CoV-2 and immediately distinguish whether positive samples represent variants of concern (VOCs). METHODS: This assay could distinguish among five VOCs: Alpha, Beta, Gamma, Delta, and Omicron, in a single reaction tube. The five variants exhibit different single nucleotide polymorphisms (SNPs) in their viral genome, which can be used to distinguish them. We selected target SNPs in the spike gene, including N501Y, P681R, K417N, and deletion H69/V70 for the assay. RESULTS: The limit of detection of each gene locus was 80 copies per polymerase chain reaction. We observed a high consistency among the results when comparing the performance of our 5-in-1 VOC assay, whole gene sequencing, and the Roche VirSNiP SARS-CoV-2 test in retrospectively analyzing 150 clinical SARS-CoV-2 variant positive samples. The 5-in-1 VOC assay offers an alternative and rapid high-throughput test for most diagnostic laboratories in a flexible sample-to-result platform. CONCLUSION: The assay can also be applied in a commercial platform with the completion of the SARS-CoV-2 confirmation test and identification of its variant within 2.5 hours.

The emergence and successful elimination of SARS-CoV-2 dominant strains with increasing epidemic potential in Taiwan's 2021 outbreak.

Taiwan's experience with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 guided its development of strategies to defend against SARS-CoV-2 in 2020, which enabled the successful control of Coronavirus disease 2019 (COVID-19) cases from 2020 through March 2021. However, in late-April 2021, the imported Alpha variant began to cause COVID-19 outbreaks at an exceptional rate in Taiwan. In this study, we aimed to determine what epidemiological conditions enabled the SARS-CoV-2 Alpha variant strains to become dominant and decline later during a surge in the outbreak. In conjunction with contact-tracing investigations, we used our bioinformatics software, CoVConvert and IniCoV, to analyze whole-genome sequences of 101 Taiwan Alpha strains. Univariate and multivariable regression analyses revealed the epidemiological factors associated with viral dominance. Univariate analysis showed the dominant Alpha strains were preferentially selected in the surge's epicenter (p = 0.0024) through intensive human-to-human contact and maintained their dominance for 1.5 months until the Zero-COVID Policy was implemented. Multivariable regression found that the epidemic periods (p = 0.007) and epicenter (p = 0.001) were two significant factors associated with the dominant virus strains spread in the community. These dominant virus strains emerged at the outbreak's epicenter with frequent human-to-human contact and low vaccination coverage. The Level 3 Restrictions and Zero-COVID policy successfully controlled the outbreak in the community without city lockdowns. Our integrated method can identify the epidemiological conditions for emerging dominant virus with increasing epidemiological potential and support decision makers in rapidly containing outbreaks using public health measures that target fast-spreading virus strains.

The Role of Folate Deficiency as a Potential Risk Factor for Nontraumatic Anterior Spinal Artery Syndrome in an Adolescent Girl.

Nontraumatic anterior spinal artery syndrome (ASAS) is an extremely rare clinical condition in pediatric populations with a mostly unknown underlying etiology. Here we discuss the case of a previously healthy 14-year-old girl presenting with sudden onset acute flaccid paralysis to the emergency department. A spinal STIR/DWI MRI revealed hyperintensities extending from cervical vertebrae C3-6, consistent with the diagnosis of ASAS. In order to determine any precipitating causes of ASAS, we also extensively investigated established potential risk factors for ASAS in our patient and noticed that she had a marked folate deficiency requiring folic acid supplementation to prevent future episodes of ASAS as well as to repair the patient's injured spinal cord. Interestingly, the patient did not display elevated levels of homocysteine nor did she possess the three pathogenic MTHFR mutations characteristic of ASAS. Although her folate deficiency did not cause responsive hyperhomocysteinemia, and she did not have pathogenic MTHFR mutations that impair the function of methylenetetrahydrofolate reductase in folate cycle, we suggest that isolated folate deficiency may play a role in adolescent cases of ASAS that, once identified, would require prompt identification and early intervention to improve the prognosis of these patients.

Can machine learning predict pharmacotherapy outcomes? An application study in osteoporosis.

BACKGROUND AND OBJECTIVE: The specific aim of this study is to develop machine learning models as a clinical approach for personalized treatment of osteoporosis. The model performance on outcome prediction was compared between four machine learning algorithms. METHODS: Retrospective, electronic clinical data for patients with suspected or confirmed osteoporosis treated at Wan Fang Hospital between 2011 to 2018 were used as inputs for building the following predictive machine learning models,i.e., artificial neural network (ANN), random forest (RF), support vector machine (SVM) and logistic regression (LR) models. The predicted outcome was defined as an increase/decrease in T-score after treatment. A genetic algorithm was employed to select relevant variables as input features for each model; the leave-one-out method was applied for model building and internal validation. The model with best performance was selected by a separate set of testing. Area under the receiver operating characteristic curve, accuracy, precision, sensitivity and F1 score were calculated to evaluate model performance. Main analysis for all the patients with subclinical or confirmed osteoporosis and subgroup analysis for the patients with confirmed osteoporosis (T score < -2.5) were carried out in this study. RESULTS: A genetic algorithm was employed to select 12 to 18 features from all 33 variables for the four models. No difference was found in accuracy (ANN, 71.7%; LR, 70.0%; RF, 75.0%; SVM, 66.7%), precision (ANN, 80.0%; LR, 59.3%; RF, 70.0%; SVM, 63.6%), and AUC (ANN, 0.709; LR, 0.731; RF, 0.719; SVM, 0.702) among the ANN, LR, RF and SVM models. Main analysis in performance revealed significant recall in the LR model, as compared to ANN and SVM model; while subgroup revealed significant recall in ANN model, compared to LR and SVM model. CONCLUSIONS: Machine learning-based models hold potential in forecasting the outcomes of treatment for osteoporosis via early initiation of first-line therapy for patients with subclinical disease; or a switch to second-line treatment for patients with a high risk of impending treatment failure. This convenient approach can assist clinicians in adjusting treatment tailored to individual patient for prevention of disease progression or ineffective therapy.

SARS-CoV-2 variants with T135I nucleocapsid mutations may affect antigen test performance.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic. Diagnostic testing for SARS-CoV-2 has continuously been challenged due to several variants with diverse spike (S) and nucleocapsid (N) protein mutations []. SARS-CoV-2 variant proliferation potentially affects N protein-targeted rapid antigen testing. In this study, rapid antigen and reverse transcription PCR (RT-PCR) tests were performed simultaneously in patients with suspected coronavirus disease 2019 (COVID-19). Direct whole genome sequencing was performed to determine the N protein variations, and the viral assemblies were uploaded to GISAID. The genomes were then compared with those of global virus strains from GISAID. These isolates belonged to the B.1.1.7 variant, exhibiting several amino acid substitutions, including D3L, R203K, G204R, and S235F N protein mutations. The T135I mutation was also identified in one variant case in which the rapid antigen test and RT-PCR test were discordantly negative and positive, respectively. These findings suggest that the variants undetected by the Panbio COVID-19 rapid antigen test may be due to the T135I mutation in the N protein, posing a potential diagnostic risk for commercially available antigen tests. Hence, we recommend concomitant paired rapid antigen tests and molecular diagnostic methods to detect SARS-CoV-2. False-negative results could be rapidly corrected using confirmatory RT-PCR results to prevent future COVID-19 outbreaks.

Identification of genetic risk loci for depression and migraine comorbidity in Han Chinese residing in Taiwan.

Introduction: The genetic association between depression and migraine has not been well investigated in Asian populations. Furthermore, the genetic basis of depression and comorbid migraine subtypes remains nebulous. Hence, in the current study we investigate the susceptibility loci associated with depression and migraine comorbidity in the Han Chinese population in Taiwan. Methods: We perform a genome-wide association study involving 966 migraine patients, with or without comorbid depression. Genotyping is performed using participant genomic DNA. Association analyses are performed for the entire migraine cohort (subgroups: episodic migraine, chronic migraine, and migraine with or without aura). Results: Results show that the single nucleotide polymorphism variants of the CDH4 intron region (rs78063755), NTRK3-AS1 downstream region (rs57729223), and between LINC01918 and GPR45 (rs2679891) are suggestively associated with depression. Twenty additional susceptibility loci occur within the subgroups. A multivariate association study demonstrated that a variant in the intron region of CDH4 rs78063755 was associated with Beck Depression Inventory and Migraine Disability Assessment scores. Discussion: The findings of this study identify several genetic loci suggestively associated with depression among migraine patients in the Han Chinese population. Moreover, a potential genetic basis has been characterized for depression and migraine comorbidity, thus providing genetic candidates for further investigation.