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Local dynamic range compensation for scanning electron microscope imaging system

Sim KS, Huang YH

Scanning, 2015 Nov-Dec;37(6):381-8.
PMID: 25969945 DOI: 10.1002/sca.21226

This is the extended project by introducing the modified dynamic range histogram modification (MDRHM) and is presented in this paper. This technique is used to enhance the scanning electron microscope (SEM) imaging system. By comparing with the conventional histogram modification compensators, this technique utilizes histogram profiling by extending the dynamic range of each tile of an image to the limit of 0-255 range while retains its histogram shape. The proposed technique yields better image compensation compared to conventional methods.
Rectovaginal fistula: Twenty years of rectovaginal repair

Lo TS, Huang YH, Dass AK, Karim N, Uy-Patrimonio MC

J Obstet Gynaecol Res, 2016 Oct;42(10):1361-1368.
PMID: 27354199 DOI: 10.1111/jog.13066

AIM: To identify the favorable factors in rectovaginal fistula (RVF) management.
METHODS: After Institutional Review Board approval (99-0793B), we retrospectively studied all patients diagnosed, treated and followed up with RVF at Chang Gung Memorial Hospital, Taiwan between January 1990 and December 2009. All female patients with International Classification of Diseases RVF were included. We reviewed demographic data, socioeconomic status, clinical presentation, comorbidities, method of treatment, duration of hospitalization and clinical outcome at 12 months postoperatively.
RESULTS: A total of 397 patients were included in the study. Fifty-six patients (14.1%) had conservative treatment and 341 patients (85.9%) underwent surgical intervention. A total of 125 patients underwent simple repair while 216 patients underwent reconstruction. Three hundred and forty-four patients (86.7%) had improved outcome at 12-month follow up. Age (P = 0.003), education level (P = 0.033), ability to pay insurance (P < 0.001), and choice of treatment (P < 0.0001) were identified as significant favorable factors. An etiological factor associated with favorable outcome was RVF from obstetric complication, while that resulting from malignancy had a less favorable outcome.
CONCLUSIONS: Age, education level and ability to pay insurance significantly affect 12-month outcome of RVF. Surgery is the preferred option, while medical treatment should be used only for small rectovaginal fistulas or for patients not suitable for surgery and anesthesia. More support and assistance should be offered to those patients with unfavorable factors, such as old age, low education level and inability to afford insurance. All RVF secondary to obstetrical injury had a 100% favorable outcome compared with those secondary to surgery or malignancy. Women with suspected RVF should receive prompt and extensive evaluation to ensure immediate effective management and prevention of further serious complications.
Fulltext Cerebellar α6GABAA Receptors as a Therapeutic Target for Essential Tremor: Proof-of-Concept Study with Ethanol and Pyrazoloquinolinones

Huang YH, Lee MT, Hsueh HY, Knutson DE, Cook J, Mihovilovic MD, et al.

Neurotherapeutics, 2023 Mar;20(2):399-418.
PMID: 36696034 DOI: 10.1007/s13311-023-01342-y

Ethanol has been shown to suppress essential tremor (ET) in patients at low-to-moderate doses, but its mechanism(s) of action remain unknown. One of the ET hypotheses attributes the ET tremorgenesis to the over-activated firing of inferior olivary neurons, causing synchronic rhythmic firings of cerebellar Purkinje cells. Purkinje cells, however, also receive excitatory inputs from granule cells where the α6 subunit-containing GABAA receptors (α6GABAARs) are abundantly expressed. Since ethanol is a positive allosteric modulator (PAM) of α6GABAARs, such action may mediate its anti-tremor effect. Employing the harmaline-induced ET model in male ICR mice, we evaluated the possible anti-tremor effects of ethanol and α6GABAAR-selective pyrazoloquinolinone PAMs. The burrowing activity, an indicator of well-being in rodents, was measured concurrently. Ethanol significantly and dose-dependently attenuated action tremor at non-sedative doses (0.4-2.4 g/kg, i.p.). Propranolol and α6GABAAR-selective pyrazoloquinolinones also significantly suppressed tremor activity. Neither ethanol nor propranolol, but only pyrazoloquinolinones, restored burrowing activity in harmaline-treated mice. Importantly, intra-cerebellar micro-injection of furosemide (an α6GABAAR antagonist) had a trend of blocking the effect of pyrazoloquinolinone Compound 6 or ethanol on harmaline-induced tremor. In addition, the anti-tremor effects of Compound 6 and ethanol were synergistic. These results suggest that low doses of ethanol and α6GABAAR-selective PAMs can attenuate action tremor, at least partially by modulating cerebellar α6GABAARs. Thus, α6GABAARs are potential therapeutic targets for ET, and α6GABAAR-selective PAMs may be a potential mono- or add-on therapy.
Unhealthy lifestyle habits and physical inactivity among Asian patients with non-alcoholic fatty liver disease

Zhang X, Goh GB, Chan WK, Wong GL, Fan JG, Seto WK, et al.

Liver Int, 2020 11;40(11):2719-2731.
PMID: 32799384 DOI: 10.1111/liv.14638

BACKGROUND & AIMS: Lifestyle modification is the cornerstone for the management of non-alcoholic fatty liver disease (NAFLD). We aim to understand lifestyle habits of NAFLD patients, compare across Asian regions and identify area of deficiency.
METHODS: In the multi-centre controlled attenuation parameter (CAP)-Asia study, we collected clinical data and lifestyle habit data of NAFLD patients from Singapore, mainland China, Hong Kong, Taiwan and Malaysia. Physical activity was assessed using the International Physical Activity Questionnaire.
RESULTS: A total of 555 patients were included in the final analysis (mean age 54.5 ± 11.2 years, 54.1% men and median liver stiffness 6.7 kPa). More patients from mainland China (27.4%) and Taipei (25.0%) were smokers. Modest drinking was more common in Taiwan (25.0%) and Hong Kong (18.2%); only 1.3% had binge drinking. Majority of patients drank coffee (64.0%) and tea (80.2%), with varying amounts and durations in different regions. Soft drinks consumption was most common in Singapore (62.2%) and Malaysia (57.7%). Only 29.7% of patients met the Physical Activity Guidelines Recommendations, with no major differences across regions. Patients with liver stiffness <10 kPa were more likely to report any vigorous activity, and sitting time was an independent factor associated with high CAP. Tea and coffee consumption were independently associated with high CAP and liver stiffness, respectively.
CONCLUSIONS: Despite some heterogeneity, unhealthy lifestyle and physical inactivity are common across Asian regions. Patients with liver stiffness <10 kPa were more likely to report any vigorous activity. Healthcare providers may use the comparative data to identify areas of deficiency.
Hepatic steatosis and metabolic risk factors among patients with chronic hepatitis B: The multicentre, prospective CAP-Asia study

Leow YW, Chan WK, Goh GB, Wong VW, Fan JG, Kim YS, et al.

J Viral Hepat, 2023 Apr;30(4):319-326.
PMID: 36606597 DOI: 10.1111/jvh.13796

We aimed to compare the severity of liver disease, metabolic profile and cardiovascular disease (CVD) risk of chronic hepatitis B (CHB) patients with and without hepatic steatosis and patients with non-alcoholic fatty liver disease (NAFLD). Patients with NAFLD and CHB were prospectively enrolled from 10 Asian centres. Fibroscan was performed for all patients and hepatic steatosis was defined based on controlled attenuation parameter >248 dB/m. CVD risk was assessed using the Framingham risk score. The data for 1080 patients were analysed (67% NAFLD, 33% CHB). A high proportion (59%) of CHB patients had hepatic steatosis. There was a significant stepwise increase in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, controlled attenuation parameter and liver stiffness measurement, from CHB patients without hepatic steatosis to CHB patients with hepatic steatosis to NAFLD patients (p
Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

Sun C, Goh GB, Chow WC, Chan WK, Wong GL, Seto WK, et al.

Hepatobiliary Pancreat Dis Int, 2024 Jun;23(3):241-248.
PMID: 37620227 DOI: 10.1016/j.hbpd.2023.08.004

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with impaired renal function, and both diseases often occur alongside other metabolic disorders. However, the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear. The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients.
METHODS: All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study. Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase (FAST), Agile 3+ and Agile 4 scores. Impaired renal function and chronic kidney disease (CKD) were defined by an estimated glomerular filtration rate (eGFR) with value of < 90 mL/min/1.73 m2 and < 60 mL/min/1.73 m2, respectively, as estimated by the CKD-Epidemiology Collaboration (CKD-EPI) equation.
RESULTS: Among 529 included NAFLD patients, the prevalence rates of impaired renal function and CKD were 37.4% and 4.9%, respectively. In multivariate analysis, a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+ and Agile 4 scores were independent risk factors for CKD (P< 0.05). Furthermore, increased fasting plasma glucose (FPG) and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome (P< 0.05). Compared with patients with normoglycemia, those with prediabetes [FPG ≥ 5.6 mmol/L or hemoglobin A1c (HbA1c) ≥ 5.7%] were more likely to have impaired renal function (P< 0.05).
CONCLUSIONS: Agile 3+ and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD. Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.
Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS-ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO

Chen LT, Martinelli E, Cheng AL, Pentheroudakis G, Qin S, Bhattacharyya GS, et al.

Ann Oncol, 2020 03;31(3):334-351.
PMID: 32067677 DOI: 10.1016/j.annonc.2019.12.001

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of hepatocellular carcinoma (HCC) was published in 2018, and covered the diagnosis, management, treatment and follow-up of early, intermediate and advanced disease. At the ESMO Asia Meeting in November 2018 it was decided by both the ESMO and the Taiwan Oncology Society (TOS) to convene a special guidelines meeting immediately after the Taiwan Joint Cancer Conference (TJCC) in May 2019 in Taipei. The aim was to adapt the ESMO 2018 guidelines to take into account both the ethnic and the geographic differences in practice associated with the treatment of HCC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO) Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO). The voting was based on scientific evidence, and was independent of the current treatment practices, the drug availability and reimbursement situations in the individual participating Asian countries.
Whole genome sequencing identifies genetic variants associated with co-trimoxazole hypersensitivity in Asians

Wang CW, Tassaneeyakul W, Chen CB, Chen WT, Teng YC, Huang CY, et al.

J Allergy Clin Immunol, 2021 04;147(4):1402-1412.
PMID: 32791162 DOI: 10.1016/j.jaci.2020.08.003

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.
The Medication Risk of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Asians: The Major Drug Causality and Comparison With the US FDA Label

Wang YH, Chen CB, Tassaneeyakul W, Saito Y, Aihara M, Choon SE, et al.

Clin. Pharmacol. Ther., 2019 01;105(1):112-120.
PMID: 29569740 DOI: 10.1002/cpt.1071

Specific ethnic genetic backgrounds are associated with the risk of Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) especially in Asians. However, there have been no large cohort, multiple-country epidemiological studies of medication risk related to SJS/TEN in Asian populations. Thus, we analyzed the registration databases from multiple Asian countries who were treated during 1998-2017. A total 1,028 SJS/TEN cases were identified with the algorithm of drug causality for epidermal necrolysis. Furthermore, those medications labeled by the US Food and Drug Administration (FDA) as carrying a risk of SJS/TEN were also compared with the common causes of SJS/TEN in Asian countries. Oxcarbazepine, sulfasalazine, COX-II inhibitors, and strontium ranelate were identified as new potential causes. In addition to sulfa drugs and beta-lactam antibiotics, quinolones were also a common cause. Only one acetaminophen-induced SJS was identified, while several medications (e.g., oseltamivir, terbinafine, isotretinoin, and sorafenib) labeled as carrying a risk of SJS/TEN by the FDA were not found to have caused any of the cases in the Asian countries investigated in this study.