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Quasicrystals are a class of materials that are long-range ordered yet not periodic. These unique features make them a fascinating middle ground between order and disorder, thus providing an ideal platform for studying a wealth of physical phenomena. This thesis contains three experimental works that my colleagues and I achieved during my PhD period, in which we explored the properties of quasicrystals in many aspects. The first experiment (Chapter 5) focus on the long-range order in quasicrystals. We report on the first experimental realisation of a two-dimensional (2D) quasicrystalline optical lattice for ultracold atoms and conduct matter-wave diffraction experiment using shot, intense lattice pulses. We reveal the different diffraction dynamics between periodic and quasiperiodic lattices and demonstrate the capability to simulate quantum walks on four-dimensional tight-binding lattices using the diffraction dynamics of 2D quasicrystalline lattices on short timescales. The second (Chapter 6) and the third (Chapter 7) experiments concentrate on studying the disorder nature of quasicrystals. In particular, we investigate disorder-induced localisation transition in the ground state of non-interacting and weakly interacting Bose gases in a 2D quasicrystalline lattice. The second experiment is mainly performed in the non-interacting limit, in which we probe the localisation transition by employing triangular lattice pulses and studying the time scale required for adiabatic loading. We observe a localisation transition at around a critical lattice depth of Vloc ≈ 1.78 Erec for noninteracting systems. In addition, we demonstrate that weak repulsive interactions can shift transition to deeper lattices. In the third experiment, we further study the interplay between the interactions and disorder, and constitute the first experimental realisation of the 2D Bose glass, an insulating but compressible groundstate phase without long-range phase coherence. By probing the coherent properties of the system, we observe a Bose glass to superfluid transition and map out the phase diagram in the weakly interacting regime. Moreover, we reveal the non-ergodic nature of the Bose glass by probing the capability of restoring coherence. Our observations are in good agreement with recent quantum Monte Carlo predictions and pave the way for experimentally testing of the connection between the Bose glass and many-body localisation.

Azathioprine (AZA) is commonly used for many autoimmune disorders; however, the limitation of its clinical use is due to potential toxicities, including severe leukopenia. Recent studies have identified genetic NUDT15 variants strongly associated with AZA-induced leukopenia in Asian patients. This study aimed to investigate the strength of above genetic association and evaluate the usefulness of prospective screening of the NUDT15 variants to prevent AZA-induced leukopenia in Chinese patients. AZA-induced leukopenia in patients with autoimmune disorders were enrolled from multiple medical centers in Taiwan/China between 2012 and 2017 to determine the strength of genetic association of NUDT15 or TPMT variants by whole exome sequencing (WES). Furthermore, a prospective study was conducted between 2018 and 2021 to investigate the incidence of AZA-induced leukopenia with and without genetic screening. The WES result showed the genetic variants of NUDT15 R139C (rs116855232) (P=3.7 × 10-25 , odds ratio (OR)=21.7, 95% confidence interval (95% CI)=12.1-38.8) and NUDT15 rs746071566 (P=4.2 × 10-9 , OR=7.1, 95% CI=3.7-13.7), but not TPMT, were associated with AZA-induced leukopenia and NUDT15 R139C variant shows the highest sensitivity with 92.5%. Furthermore, the targeted screening of 1,013 participants for NUDT15 R139C enabled those identified as carriers to use alternative immunosuppressants. This strategy resulted in a significant decrease in the incidence of AZA-induced leukopenia compared with historical incidence (incidence rate=from 7.6% decreased to 0.4%; P=9.3 × 10-20 ). In conclusion, the NUDT15 R139C variant was strongly associated with AZA-induced leukopenia in Chinese patients. The genetic screening of NUDT15 R139C followed by use of alternative immunosuppressants in identified carriers effectively decreased the incidence of AZA leukopenia for patients with autoimmune disorders.

To evaluate the relationship between obstructive sleep apnea (OSA) and diabetic macular edema (DME) and the effect of OSA on refractory DME in patients with type 2 diabetes (T2DM).Retrospective clinical cohort study.A population-based study was conducted at Chang Gung Memorial Hospital from March 1, 2009, to March 1, 2020. Among 14,152 patients who had undergone polysomnography (PSG) and whose data were registered on the sleep center's PSG database, 121 patients (242 eyes) with T2DM were enrolled according to the International Classification of Diseases, Ninth Revision (ICD-9) code 3620 for diabetic retinopathy (DR). Patients with a secondary cause of macular edema and those lacking medical records were excluded. All patients with T2DM enrolled in our study received both optical coherence tomography (OCT) and PSG. The prevalence of severe (apnea-hypopnea index [AHI] ≥30) and nonsevere (AHI30) OSA was compared between patients with and without DME and refractory DME.In total, 102 eyes (54 patients) were divided into groups of 40 eyes with DME or 62 eyes without DME. Severe OSA (odds ratio, 7.36; 95% confidence interval [CI]: 1.32-40.96; P = .023) was significantly associated with DME. Refractory DME was significantly more frequent in patients with severe OSA (27%) than in those with nonsevere OSA (0%; P = .009). Cox proportional hazards regression analysis revealed that OSA (hazard ratio, 2.97; CI, 1.08-8.16; P = .034) independently increased the DME risk after adjustment for age, sex, glycohemoglobin level, hypertension, and hypercholesterolemia.Severe OSA is a risk factor for DME and is associated with having refractory DME.

The identification of key areas for conservation and protection according to science-based evidence is an important component to circumvent the negative impacts of environmental changes within geopolitical territories and across the globe. Priority areas for biodiversity played an important role to ensure the protection of many species particularly those that are unique and threatened. There are more than 200 Key Biodiversity Areas (KBAs) in the Philippines, yet many important research and biodiversity data are either unpublished or unconsolidated. Birds are commonly studied indicators for KBA identification due to their high species richness, diversity, and sensitivity to forest ecosystems. By combining data from past and present surveys, we accounted for a total of 148 bird species of 51 families, with 20 new records from recent field surveys. Our analysis showed a high level of endemism within Mt. Hilong-hilong with 36% Philippine endemic, 14% restricted to Mindanao faunal region and 11% migrant. In terms of conservation, 8% of the species were considered in threatened categories. The species richness and endemism were higher in lowland to mid-elevation areas compared to higher elevation areas of the KBA. Endemism (i.e., Mindanao endemic) and increasing body mass were important determinants of binary extinction risk for bird species in Mt. Hilong-hilong. The high biodiversity in Mt. Hilong-hilong indicates an example of the vital role of KBAs in preserving nationally and globally important bird species. Lastly, we emphasise the importance of collaboration and integrating past and present information to synthesise relevant information to complement ongoing conservation efforts in Mt. Hilong-hilong and other key habitats in the Philippines.

Background Co-trimoxazole, a sulfonamide antibiotic, is used to treat a variety of infections worldwide, and it remains a common first-line medicine for prophylaxis against Pneumocystis jiroveci pneumonia. However, it can cause severe cutaneous adverse reaction (SCAR), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. The pathomechanism of co-trimoxazole–induced SCAR remains unclear. Objective We aimed to investigate the genetic predisposition of co-trimoxazole–induced SCAR. Methods We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole–induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia. Results The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole–induced SCAR (P = 8.2 × 10−9; odds ratio [OR] = 7.7). There were weak associations of variants in co-trimoxazole–related metabolizing enzymes (CYP2D6, GSTP1, GCLC, N-acetyltransferase [NAT2], and CYP2C8). A replication study using HLA genotyping revealed that HLA-B∗13:01 was strongly associated with co-trimoxazole–induced SCAR (the combined sample comprised 91 case patients vs 2545 controls [P = 7.2 × 10−21; OR = 8.7]). A strong HLA association was also observed in the case patients from Thailand (P = 3.2 × 10−5; OR = 3.6) and Malaysia (P = .002; OR = 12.8), respectively. A meta-analysis and phenotype stratification study further indicated a strong association between HLA-B∗13:01 and co-trimoxazole–induced drug reaction with eosinophilia and systemic symptoms (P = 4.2 × 10−23; OR = 40.1). Conclusion This study identified HLA-B∗13:01 as an important genetic factor associated with co-trimoxazole–induced SCAR in Asians.

Background: Head and neck cancers (HNC) are increasingly recognized as important human papillomavirus (HPV)-related malignancies in addition to cervical cancer (CC). However, data on the socioeconomic impact of HNC and CC in Taiwan are limited. Methods: A retrospective cohort study was conducted to estimate the total direct medical cost and indirect productivity loss from CC and HNC between 2014 and 2015. Patient data from the Taiwan National Cancer Registry were analyzed, with matched non-cancer controls from the Taiwan National Healthcare Reimbursement Database. Indirect costs due to premature deaths were calculated using public data from Taiwanese government reports. Results: In the direct cost analysis, 2083 patients with newly diagnosed CC and 11,078 with newly diagnosed HNC (10,036 males) were identified between 2014 and 2015 and followed up through the end of 2016 or until death. The total direct medical costs incurred in 2014 and 2015 due to HNC were 11.54 times higher in males than in females, and 4.55 times higher than CC. Indirect cost analysis showed the total annual productivity loss was New Taiwan Dollar (NTD) $12 billion in 2019, and 79.99% was attributed to male HNC. Conclusion: In Taiwan, the socioeconomic burden associated with male HNC is high and greater than that seen with CC. While not all HNCs are attributable to HPV infection, prevention of HNC through HPV vaccination should be considered for both sexes.

Cutaneous manifestations resembling Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients with acute graft-versus-host disease (aGVHD); however, the clinicopathological characteristics of SJS/TEN-like aGVHD remain unexplored.To investigate the clinicopathology, complications, and outcomes of patients with SJS/TEN-like aGVHD.We analyzed a multicenter cohort of patients with aGVHD between 2000 and 2021.We analyzed 31 patients with aGVHD, including SJS/TEN-like (n = 15) and non-SJS/TEN-like (n = 16). Patients with SJS/TEN-like aGVHD had significantly more extensive erythema and skin detachment/mucositis. SJS/TEN-like aGVHD was significantly associated with higher aGVHD grading and systemic complications, including pancytopenia, leukopenia, anemia, severe thrombocytopenia, coagulation abnormality, hepatitis, diarrhea, renal dysfunction, and bacteremia. A significantly lower hemoglobin/red cell distribution width ratio was identified in SJS/TEN-like aGVHD. Histopathology showed significant severe dyskeratosis and interface change. Patients with SJS/TEN-like aGVHD had lower 2-month survival rates and 5.35-fold higher 5-year mortality rates than those with non-SJS/TEN-like aGVHD. Total mortality rates of patients with SJS/TEN-like aGVHD reached 80% during follow-up; sepsis predominated the causes of death.Retrospective, nonrandomized study with a small sample size.SJS/TEN-like aGVHD is associated with multiple systemic complications and high mortality. Early recognition, differential diagnosis from drug-induced-SJS/TEN, and appropriate treatment are critical.

BackgroundThe course of vitiligo is unpredictable, with periods of disease flare-ups and prolonged recovery periods. It is essential to establish a biomarker profile as a substitute marker for disease activity to predict disease activity, severity, and prognosis prediction. The use of localized skin interstitial fluid as biomarkers has recently gained interest, but extensive studies of the association between skin interstitial fluid, plasma, and the disease course is lacking. This study aims to evaluate the cytokine expression profiles in the skin and plasma and the utility of the biomarker panel in assessing disease activity, severity, and prognosis in patients with vitiligo.MethodsIn this prospective cohort study, 86 patients and 34 healthy controls were recruited from the outpatient department of a tertiary medical center from March 2019 to September 2021. All patients were of Asian ethnicity. Two independent investigators evaluated disease activity and severity with longitudinal follow-ups for treatment response for a-12 month period. Ultrasensitive multiplex cytokine panel and single-molecule counting technology immunoassays were used to study the cytokine expression in skin interstitial fluid and plasma.ResultsIFN-γ and its’ signature cytokines, including CXCL9, CXCL10, and GzmB, are most highly expressed in the vitiligo patients’ lesion skin interstitial fluid and plasma compared to healthy control. By way of comparison, no significant changes in IL-1β, IL-13, IL-15, IL-17A, IL-18 were observed. Receiver operating characteristic analysis revealed that IFN-γ is the most sensitive and specific marker in predicting disease activity, followed by CXCL10 and GzmB. CXCL-9 was sensitive and specific in diagnosing vitiligo disease severity. The decrease in IFN-γ expression level is positively correlated with the treatment response.ConclusionIFN-γ, CXCL9, CXCL10, and GzmB are highly expressed in vitiligo patients’ lesion skin and plasma and may serve as biomarkers for the clinical activity, severity, and prognosis prediction in vitiligo patients. Among all, IFN-γ exerts the highest predictive value in disease activity and treatment response, supporting the critical role of IFN-γ in the pathogenesis of vitiligo.

Acute phase response (APR), including myalgia, influenza-like symptoms, headache, arthralgia, and pyrexia, is the most common adverse reaction to initial zoledronic acid infusion. Dexamethasone plus acetaminophen is effective in significantly reducing the incidence and severity of APR. Acute phase response (APR), including myalgia, influenza-like symptoms, headache, arthralgia, and pyrexia, is due to immunomodulatory actions and is the most common adverse reaction to zoledronic acid (ZOL). The aims of our study were to compare the differences between acetaminophen and dexamethasone plus acetaminophen on the incidence and severity of APRs and to clarify the clinical factors related to APR with initial ZOL infusion. Patients with osteoporosis receiving their first ZOL infusion (N = 96) were assigned into two groups and given either acetaminophen (58 patients, control group) or acetaminophen plus dexamethasone (38 patients, study group). APRs were assessed through telephone interviews 2 weeks later post-infusion. Clinical, demographic, and serologic data were recorded. There was a significant increase in the incidence and severity of any APR in the control group than the study group (67% vs. 34%, p = 0.003; 0.69 ± 0.50 vs. 0.34 ± 0.48, p = 0.001). Among the APRs, only myalgia incidence and score were significantly higher in the control group than in the study group. Multivariate analysis demonstrated that previous use of osteoporosis medication and participation in the study group was negatively related to the occurrence of any APR or myalgia. Advanced age was shown to significantly increase myalgia. Study group participants had significantly reduced severity of myalgia. The adherence for redosing ZOL was significantly higher in the study group. Dexamethasone plus acetaminophen is effective in significantly reducing the incidence and severity of APR, especially myalgia, and increasing adherence following initial ZOL infusion.

BACKGROUND High rates of posttreatment discomfort, infection, recurrence, and increased time to return to work have been noted after nail plate avulsion resulting from epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)-induced paronychia, which may even interrupt the course of treatment for EGFR-TKI therapy. Thus, we conducted this study to determine how effectively a topical β-blocker, betaxolol, prevents EGFR-TKI-induced paronychia. METHODS This case-control cohort study included a total of 131 non-small-cell lung cancer patients. The prevention group comprised 40 patients treated with topical betaxolol 0.25% solution to prevent paronychia while they received EGFR-TKI therapy. The control group comprised 91 patients who did not preventively use topical betaxolol 0.25% solution while receiving EGFR-TKI therapy. The patients' age, gender, antineoplastic regimen, duration of antineoplastic treatment before the appearance of lesions, number of involved digits (fingernails or toenails) with lesions, grading of paronychia, and pain score were recorded. RESULTS In terms of the cumulative incidence of paronychia, significant differences (P

Vitiligo is a common, psychologically devastating pigmentary disorder. Surgical graftings are used to treat stable vitiligo when medical treatment fails. An automated epidermal micrograft harvesting (AEMH) system was first designated to treat wounds, and very few studies investigated the application of AEMH in vitiligo. In this study, we investigated the efficacy and safety of the AEMH system in patients with stable segmental and nonsegmental vitiligo. The rate of repigmentation and adverse events was recorded bimonthly for at least 12 months. We analyzed the efficacy based on patient characteristics, vitiligo subtypes, and different anatomical locations. A total of 56 depigmented lesions from 34 patients were included. 95.50% of the automated epidermal micrografts were successfully grafted at the recipient sites. There was a significant improvement in Vitiligo Area Scoring Index (VASI) and Dermatologic Life Quality Index (DLQI) in patients treated with AEMH (p < 0.001). The rate of repigmentation by VASI score improves from 96.25 ± 8.59 to 48.30 ± 28.16 after the treatment (p < 0.001). Treatment outcomes were comparable between the patients of segmental and stable nonsegmental vitiligo. The face and neck region achieved a better outcome, followed by the trunk (chest, abdomen, back, and axilla), limbs, and the worse outcome was found in the acral region (p < 0.014). Conclusively, AEMH is an effective treatment procedure with limited adverse events in patients with stable vitiligo. This harvesting method may be a feasible option for vitiligo surgical treatment.

Background: Real-life data on patients with psoriasis treated with guselkumab are few and are needed to compare with trial-based data. We investigated the effect of clinical factors on real-world effectiveness of guselkumab. Methods: This multicentre study retrospectively included 135 patients with psoriasis treated with guselkumab from June 2018 until November 2020. Effectiveness was assessed using the degree of improvement in the Psoriasis Area and Severity Index (PASI) scores at baseline and after 4, 12, 20, 28, and 36 weeks. Predictors of effectiveness were also evaluated. Results: At week 36, 67% of the patients achieved PASI 75. Multivariate logistic regression analysis revealed that heavier patients were less likely to achieve PASI 75 at week 4 than patients with lower body weights. Fewer patients exposed to only one biologic achieved PASI 75 at weeks 4, 20, 28, and 36 [odds ratio (OR) = 0.08 (95% CI, 0.01–0.48), 0.21 (95% CI, 0.05–0.74), 0.04 (95% CI, 0.00–0.35), and 0.07 (95% CI, 0.00–0.68), respectively] than biologic-naïve patients. Patients previously treated with more than one biologic were less likely to achieve PASI 75 at weeks 12, 20, 28, and 36 [OR = 0.05 (95% CI, 0.01–0.22), 0.03 (95% CI, 0.01–0.16), 0.00 (95% CI, 0.00–0.03), and 0.00 (95% CI, 0.00–0.044), respectively] than biologic-naïve patients. Patients with previous anti-interleukin (IL)-17 exposure, rather than tumour necrosis factor-α and IL-12/23 inhibitors, had lower PASI improvements to guselkumab than biologic-naïve patients at weeks 12, 20, and 28 [OR = 0.19 (95% CI, 0.03–0.90), 0.10 (95% CI, 0.02–0.55), and 0.03 (95% CI, 0.00–0.29), respectively]. Conclusions: The effectiveness of guselkumab was compromised in a real-world setting. Delayed onset of therapeutic response was noted in heavier patients. Biologic exposure, the number of previously used biologics, and previous exposure to IL-17 inhibitors were clinical predictors of a reduced response to guselkumab. Physicians may share this information with patients to make treatment decisions.