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Fulltext Diffuse large B-cell lymphoma presenting with extensive cutaneous infiltration

Shamsudin N, Chang CC

Singapore Med J, 2012 Sep;53(9):e198-200.
PMID: 23023915

We report a case of systemic diffuse large B-cell lymphoma presenting with extensive infiltration of the skin. A 56-year-old woman presented with a two-month history of pruritic erythematous plaques and nodules over the neck, trunk and upper limbs. She also had night sweats, weight loss, lethargy and reduced effort tolerance. Systemic examination revealed a pale, ill appearance with hepatosplenomegaly and lymphadenopathy. Blood investigations showed pancytopenia (haemoglobin 6.3 g/dL, total white cell count 3.0 × 10(9)/L, platelet count 138 × 10(9)/L) with a few suspicious mononuclear cells and a mildly elevated lactate dehydrogenase level (478 U/L). Skin biopsy demonstrated diffuse sheets and nodular infiltrates of CD20 and CD79a positive neoplastic cells in the dermis and subcutis. Computed tomography revealed multiple cervical, axillary, mediastinal, para-aortic and mesenteric lymph nodes. Bone marrow aspiration and trephine biopsy confirmed marrow involvement by non-Hodgkin's lymphoma. The patient was treated with chemotherapy, which resulted in resolution of the skin lesions.
Fulltext Comorbidities associated with psoriasis - data from the malaysian psoriasis registry

Mazlin MB, Chang CC, Baba R

Med J Malaysia, 2012 Oct;67(5):518-21.
PMID: 23770870

All around the world, there is growing evidence of the association between psoriasis and comorbidities which increase the risk of cardiovascular disease. This study aims to determine the prevalence of various comorbidities among adult psoriasis patients in Malaysia. A cross-sectional study was conducted among patients in the Malaysian Psoriasis Registry from January 2007 to December 2008. A total of 2,267 adult patients with psoriasis from 13 dermatology centers were included. Prevalence of various comorbidities were: hypertension 25.9%, diabetes mellitus 17.7 %, dyslipidaemia 17.8%, overweight 33.2%, obesity 20.7%, ischaemic heart disease 5.8% and cerebrovascular disease 1.4%. These comorbidities were more prevalent in patients with psoriasis of late-onset and longer duration. Active screening of these comorbidities in all adult psoriasis patients is recommended.
Fulltext Malaysian Psoriasis Registry--preliminary report of a pilot study using a newly revised registry form

Chang CC, Gangaram HB, Hussein SH

Med J Malaysia, 2008 Sep;63 Suppl C:68-71.
PMID: 19227676

The Malaysian Psoriasis Registry, established in 1998, is the first skin disease clinical registry in Malaysia. It aims to provide useful data on various aspects of psoriasis. Following an extensive revision of the registry form in 2007, a total of 509 psoriasis patients from 10 government dermatologic centres were reviewed in a three month pilot study. The onset of psoriasis was during the second to fourth decade of life in the majority of patients. There was no sexual and ethnic predilection. A positive family history was present in 21.2%, and more common in patients with younger disease onset. The main aggravating factors of psoriasis were stress, sunlight and infection. Plaque psoriasis was the commonest clinical type (80.9%). Joint disease was present in 17.3% of patients, among which mono-/oligoarticular type being the commonest. Nail changes occurred in 68%. More psoriasis patients were overweight and obese compared to the normal population. The mean Dermatologic Life Quality Index (DLQI) score was 8.08 +/- 6.29, and changes during subsequent follow-up may reflect therapeutic effectiveness. This study enabled evaluation of the revised registry form and helped in identifying shortcomings in the implementation of the registry.
Fingerprint verification prediction model in hand dermatitis

Lee CK, Chang CC, Johor A, Othman P, Baba R

Int J Dermatol, 2015 Jul;54(7):765-70.
PMID: 25427962 DOI: 10.1111/ijd.12451

Hand dermatitis associated fingerprint changes is a significant problem and affects fingerprint verification processes. This study was done to develop a clinically useful prediction model for fingerprint verification in patients with hand dermatitis.
Fingerprint changes and verification failure among patients with hand dermatitis

Lee CK, Chang CC, Johar A, Puwira O, Roshidah B

JAMA Dermatol, 2013 Mar;149(3):295-9.
PMID: 23682364

To determine the prevalence of fingerprint verification failure and to define and quantify the fingerprint changes associated with fingerprint verification failure.
Cutaneous sporotrichosis: a six-year review of 19 cases in a tertiary referral center in Malaysia

Tang MM, Tang JJ, Gill P, Chang CC, Baba R

Int J Dermatol, 2012 Jun;51(6):702-8.
PMID: 22607289 DOI: 10.1111/j.1365-4632.2011.05229.x

Sporotrichosis is a subcutaneous fungal infection caused by a thermally dimorphic aerobic fungus, Sporothrix schenckii. It results from traumatic inoculation or contact with animals. Most cases were reported mainly in the tropics and subtropics.
Association of HLA-B*1502 allele with carbamazepine-induced toxic epidermal necrolysis and Stevens-Johnson syndrome in the multi-ethnic Malaysian population

Chang CC, Too CL, Murad S, Hussein SH

Int J Dermatol, 2011 Feb;50(2):221-4.
PMID: 21244392 DOI: 10.1111/j.1365-4632.2010.04745.x

BACKGROUND: Carbamazepine (CBZ), a frequently used anticonvulsant drug, is one of the most common causes of life-threatening cutaneous adverse drug reactions such as toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). Recent studies have revealed a strong association between HLA-B*1502 and CBZ-induced TEN/SJS in the Taiwan Han Chinese population.
OBJECTIVES: This study is aimed to investigate the association between human leucocyte antigens (HLA) and CBZ-induced TEN/SJS in the multi-ethnic Malaysian population.
METHODS: A sample of 21 unrelated patients with CBZ-induced TEN/SJS and 300 race-matched, healthy controls were genotyped for HLA-A, -B and -DR using polymerase chain reaction (PCR). Allele frequencies were compared.
RESULTS: HLA-B*1502 was present in 75.0% (12/16) of Malay patients with CBZ-induced TEN/SJS but in only 15.7% (47/300) of normal controls (odds ratio 16.15, 95% confidence interval 4.57-62.4; corrected P-value = 7.87 × 10(-6) ), which suggests a strong association between HLA and CBZ-induced TEN/SJS. Additionally, HLA-B*1502 was found in all three Chinese and two Indian patients. Existing data show that frequencies of the HLA-B*1502 allele are generally much higher in Asian populations than in White European populations, which explains the higher incidences of SJS and TEN in Asian countries.
CONCLUSIONS: HLA-B*1502 is strongly associated with CBZ-induced TEN/SJS in the Malay population in Malaysia, as has been seen in Han Chinese in Taiwan. This indicates that the genetic association apparent in the incidence of CBZ-induced TEN/SJS is linked with the presence of HLA-B*1502, irrespective of racial origin. Screening of patients for this genetic marker can help to prevent the occurrence of TEN/SJS.
Quality of life and cost of illness in patients with psoriasis in Malaysia: a multicenter study

Tang MM, Chang CC, Chan LC, Heng A

Int J Dermatol, 2013 Mar;52(3):314-22.
PMID: 23414155 DOI: 10.1111/j.1365-4632.2011.05340.x

BACKGROUND:Psoriasis is an immune-mediated, chronic, inflammatory skin disease which affects approximately 2% of the world's population. It has a major impact on the patient's quality of life (QoL), influencing career, social activities, family relationships, and all other aspects of life. Many studies have described the various ways in which psoriasis can affect a patient's life. Very little is known, however, about the impact of psoriasis on the QoL of patients treated in Malaysia and the cost of illness in this region.
OBJECTIVES: This study aims to describe the extent to which psoriasis affects the QoL of patients treated in government-run dermatology clinics in Malaysia and to estimate the cost of illness.
METHODS: A total of 250 psoriasis patients treated at eight dermatology clinics in government-run hospitals in Malaysia were studied. The severity of psoriasis was assessed by dermatologists. Quality of life was evaluated using the Dermatology Life Quality Index (DLQI) and Version 2 of the 12-Item Short-Form Health Survey (SF-12v2). Scores on the SF-12v2 of healthy subjects and of patients with other medical conditions, such as depression, diabetes mellitus, hypertension, and ischemic heart disease, were also assessed for comparison. The costs of dermatology outpatient consultant fees, medications, investigations, procedures, transportation, over-the-counter medications, and hospitalization were retrospectively estimated using questionnaires.
RESULTS: The cohort studied had a median Psoriasis Area Severity Index (PASI) score of 9.9 and a median DLQI score of 10.0. The average SF-12v2 scores were 43.68 (standard deviation [SD] 9.23) and 42.25 (SD 10.7) on the Physical Health Summary and Mental Health Summary, respectively. The impact of disease on QoL was found to be greater in those with more extensive psoriatic lesion involvement, in younger patients, and in those with psoriatic arthropathy. Psoriasis was found to affect QoL in both genders equally. Body mass index had no effect on the severity of psoriasis or QoL. Patients with psoriasis had a significantly lower SF-12v2 score than healthy subjects. Comparisons with data for patients with other chronic medical conditions demonstrated that psoriasis has a negative effect on health-related QoL similar to the impact of other chronic conditions. The estimated cost of illness for psoriasis in the current cohort was ringgit Malaysia (RM) 1307.47 per person per year excluding costs of hospitalization. Patients were noted to spend a large amount of money on over-the-counter products obtained without doctors' prescriptions.
CONCLUSIONS: The QoL of patients with psoriasis was significantly impaired compared with that of healthy subjects and was comparable with that of patients with other chronic medical illnesses. The estimated cost of illness of psoriasis in the current study was lower than in other countries, mainly because healthcare costs in public hospitals are heavily subsidized by government and because usage of newer but more expensive treatment options is low in Malaysia.
Fulltext Phosphorylation of Human Choline Kinase Beta by Protein Kinase A: Its Impact on Activity and Inhibition

Chang CC, Few LL, Konrad M, See Too WC

PLoS One, 2016;11(5):e0154702.
PMID: 27149373 DOI: 10.1371/journal.pone.0154702

Choline kinase beta (CKβ) is one of the CK isozymes involved in the biosynthesis of phosphatidylcholine. CKβ is important for normal mitochondrial function and muscle development as the lack of the ckβ gene in human and mice results in the development of muscular dystrophy. In contrast, CKα is implicated in tumorigenesis and has been extensively studied as an anticancer target. Phosphorylation of human CKα was found to regulate the enzyme's activity and its subcellular location. This study provides evidence for CKβ phosphorylation by protein kinase A (PKA). In vitro phosphorylation of CKβ by PKA was first detected by phosphoprotein staining, as well as by in-gel kinase assays. The phosphorylating kinase was identified as PKA by Western blotting. CKβ phosphorylation by MCF-7 cell lysate was inhibited by a PKA-specific inhibitor peptide, and the intracellular phosphorylation of CKβ was shown to be regulated by the level of cyclic adenosine monophosphate (cAMP), a PKA activator. Phosphorylation sites were located on CKβ residues serine-39 and serine-40 as determined by mass spectrometry and site-directed mutagenesis. Phosphorylation increased the catalytic efficiencies for the substrates choline and ATP about 2-fold, without affecting ethanolamine phosphorylation, and the S39D/S40D CKβ phosphorylation mimic behaved kinetically very similar. Remarkably, phosphorylation drastically increased the sensitivity of CKβ to hemicholinium-3 (HC-3) inhibition by about 30-fold. These findings suggest that CKβ, in concert with CKα, and depending on its phosphorylation status, might play a critical role as a druggable target in carcinogenesis.
Fulltext Predator personality and prey behavioural predictability jointly determine foraging performance

Chang CC, Teo HY, Norma-Rashid Y, Li D

Sci Rep, 2017 01 17;7:40734.
PMID: 28094288 DOI: 10.1038/srep40734

Predator-prey interactions play important roles in ecological communities. Personality, consistent inter-individual differences in behaviour, of predators, prey or both are known to influence inter-specific interactions. An individual may also behave differently under the same situation and the level of such variability may differ between individuals. Such intra-individual variability (IIV) or predictability may be a trait on which selection can also act. A few studies have revealed the joint effect of personality types of both predators and prey on predator foraging performance. However, how personality type and IIV of both predators and prey jointly influence predator foraging performance remains untested empirically. Here, we addressed this using a specialized spider-eating jumping spider, Portia labiata (Salticidae), as the predator, and a jumping spider, Cosmophasis umbratica, as the prey. We examined personality types and IIVs of both P. labiata and C. umbratica and used their inter- and intra-individual behavioural variation as predictors of foraging performance (i.e., number of attempts to capture prey). Personality type and predictability had a joint effect on predator foraging performance. Aggressive predators performed better in capturing unpredictable (high IIV) prey than predictable (low IIV) prey, while docile predators demonstrated better performance when encountering predictable prey. This study highlights the importance of the joint effect of both predator and prey personality types and IIVs on predator-prey interactions.
Fulltext Periscope: quantitative prediction of soluble protein expression in the periplasm of Escherichia coli

Chang CC, Li C, Webb GI, Tey B, Song J, Ramanan RN

Sci Rep, 2016;6:21844.
PMID: 26931649 DOI: 10.1038/srep21844

Periplasmic expression of soluble proteins in Escherichia coli not only offers a much-simplified downstream purification process, but also enhances the probability of obtaining correctly folded and biologically active proteins. Different combinations of signal peptides and target proteins lead to different soluble protein expression levels, ranging from negligible to several grams per litre. Accurate algorithms for rational selection of promising candidates can serve as a powerful tool to complement with current trial-and-error approaches. Accordingly, proteomics studies can be conducted with greater efficiency and cost-effectiveness. Here, we developed a predictor with a two-stage architecture, to predict the real-valued expression level of target protein in the periplasm. The output of the first-stage support vector machine (SVM) classifier determines which second-stage support vector regression (SVR) classifier to be used. When tested on an independent test dataset, the predictor achieved an overall prediction accuracy of 78% and a Pearson's correlation coefficient (PCC) of 0.77. We further illustrate the relative importance of various features with respect to different models. The results indicate that the occurrence of dipeptide glutamine and aspartic acid is the most important feature for the classification model. Finally, we provide access to the implemented predictor through the Periscope webserver, freely accessible at http://lightning.med.monash.edu/periscope/.
Skin eruption induced by dieting - an underdiagnosed skin disease in Malaysia

Goh SW, Adawiyah J, Md Nor N, Yap F, Ch'ng P, Chang CC

Malays Fam Physician, 2019;14(1):42-46.
PMID: 31289632

Prurigo pigmentosa is an inflammatory dermatosis characterized by a pruritic, symmetrically distributed erythematous papular or papulo-vesicular eruption on the trunk arranged in a reticulated pattern that resolves with hyperpigmentation. It is typically non-responsive to topical or systemic steroid therapy. The exact etiology is unknown, but it is more commonly described in the Far East countries. Dietary change is one of the predisposing factors. We report on nine young adult patients with prurigo pigmentosa, among whom five were on ketogenic diets prior to the onset of the eruptions. All cases resolved with oral doxycycline with no recurrence. We hope to improve the awareness of this uncommon skin condition among general practitioners and physicians so that disfiguring hyperpigmentation due to delayed diagnosis and treatment can be avoided.
Fulltext Development of the Sensing Platform for Protein Tyrosine Kinase Activity

Wei LY, Lin W, Leo BF, Kiew LV, Chang CC, Yuan CJ

Biosensors (Basel), 2021 Jul 15;11(7).
PMID: 34356711 DOI: 10.3390/bios11070240

A miniature tyrosinase-based electrochemical sensing platform for label-free detection of protein tyrosine kinase activity was developed in this study. The developed miniature sensing platform can detect the substrate peptides for tyrosine kinases, such as c-Src, Hck and Her2, in a low sample volume (1-2 μL). The developed sensing platform exhibited a high reproducibility for repetitive measurement with an RSD (relative standard deviation) of 6.6%. The developed sensing platform can detect the Hck and Her2 in a linear range of 1-200 U/mL with the detection limit of 1 U/mL. The sensing platform was also effective in assessing the specificity and efficacies of the inhibitors for protein tyrosine kinases. This is demonstrated by the detection of significant inhibition of Hck (~88.1%, but not Her2) by the Src inhibitor 1, an inhibitor for Src family kinases, as well as the significant inhibition of Her2 (~91%, but not Hck) by CP-724714 through the platform. These results suggest the potential of the developed miniature sensing platform as an effective tool for detecting different protein tyrosine kinase activity and for accessing the inhibitory effect of various inhibitors to these kinases.
Female spider aggression is associated with genetic underpinnings of the nervous system and immune response to pathogens

Chang CC, Connahs H, Tan ECY, Norma-Rashid Y, Mrinalini, Li D, et al.

Mol Ecol, 2020 07;29(14):2626-2638.
PMID: 32510793 DOI: 10.1111/mec.15502

Identifying the genetic architecture underlying phenotypic variation in natural populations and assessing the consequences of polymorphisms for individual fitness are fundamental goals in evolutionary and molecular ecology. Consistent between-individual differences in behaviour have been documented for a variety of taxa. Dissecting the genetic basis of such behavioural differences is however a challenging endeavour. The molecular underpinnings of natural variation in aggression remain elusive. Here, we used comparative gene expression (transcriptome analysis and RT-PCR), genetic association analysis and pharmacological experiments to gain insight into the genetic basis of aggression in wild-caught jumping spiders (Portia labiata). We show that spider aggression is associated with a putative viral infection response gene, BTB/POZ domain-containing protein 17 (BTBDH), in addition to a putative serotonin receptor 1A (5-HT1A) gene. Spider aggression varies with virus loads, and BTBDH is upregulated in docile spiders and exhibits a genetic variant associated with aggression. We also identify a putative serotonin receptor 5-HT1A gene upregulated in docile P. labiata. Individuals that have been treated with serotonin become less aggressive, but individuals treated with a nonselective serotonin receptor antagonist (methiothepin) also reduce aggression. Further, we identify the genetic variants in the 5-HT1A gene that are associated with individual variation in aggression. We therefore conclude that co-evolution of the immune and nervous systems may have shaped the between-individual variation in aggression in natural populations of jumping spiders.
Disposable E-Tongue for the Assessment of Water Quality in Fish Tanks

Chang CC, Saad B, Surif M, Ahmad MN, Md Shakaff AY

Sensors (Basel), 2008 Jun 01;8(6):3665-3677.
PMID: 27879900

A disposable screen-printed e-tongue based on sensor array and pattern recognition that is suitable for the assessment of water quality in fish tanks is described. The characteristics of sensors fabricated using two kinds of sensing materials, namely (i) lipids (referred to as Type 1), and (ii) alternative electroactive materials comprising liquid ion-exchangers and macrocyclic compounds (Type 2) were evaluated for their performance stability, sensitivity and reproducibility. The Type 2 e-tongue was found to have better sensing performance in terms of sensitivity and reproducibility and was thus used for application studies. By using a pattern recognition tool i.e. principal component analysis (PCA), the e-tongue was able to discriminate the changes in the water quality in tilapia and catfish tanks monitored over eight days. E-tongues coupled with partial least squares (PLS) was used for the quantitative analysis of nitrate and ammonium ions in catfish tank water and good agreement were found with the ion-chromatography method (relative error, ±1.04- 4.10 %).
Fulltext Local ablation of gastric cancer by reconstituted apolipoprotein B lipoparticles carrying epigenetic drugs

Yang CL, Chao YJ, Wang HC, Hou YC, Chen CG, Chang CC, et al.

Nanomedicine, 2021 10;37:102450.
PMID: 34332115 DOI: 10.1016/j.nano.2021.102450

Epigenetic inhibitors have shown anticancer effects. Combination chemotherapy with epigenetic inhibitors has shown high effectiveness in gastric cancer clinical trials, but severe side effect and local progression are the causes of treatment failure. Therefore, we sought to develop an acidity-sensitive drug delivery system to release drugs locally to diminish unfavorable outcome of gastric cancer. In this study, we showed that, as compared with single agents, combination treatment with the demethylating agent 5'-aza-2'-deoxycytidine and HDAC inhibitors Trichostatin A or LBH589 decreased cell survival, blocked cell cycle by reducing number of S-phase cells and expression of cyclins, increased cell apoptosis by inducing expression of Bim and cleaved Caspase 3, and reexpressed tumor suppressor genes more effectively in MGCC3I cells. As a carrier, reconstituted apolipoprotein B lipoparticles (rABLs) could release drugs in acidic environments. Orally administrated embedded drugs not only showed inhibitory effects on gastric tumor growth in a syngeneic orthotopic mouse model, but also reduced the hepatic and renal toxicity. In conclusion, we have established rABL-based nanoparticles embedded epigenetic inhibitors for local treatment of gastric cancer, which have good therapeutic effects but do not cause severe side effects.
Fulltext Klebsiella pneumoniae yggG gene product: a zinc-dependent metalloprotease

Kuan CS, Wong MT, Choi SB, Chang CC, Yee YH, Wahab HA, et al.

Int J Mol Sci, 2011;12(7):4441-55.
PMID: 21845088 DOI: 10.3390/ijms12074441

Klebsiella pneumoniae causes neonatal sepsis and nosocomial infections. One of the strains, K. pneumoniae MGH 78578, shows high level of resistance to multiple microbial agents. In this study, domain family, amino acid sequence and topology analyses were performed on one of its hypothetical protein, YggG (KPN_03358). Structural bioinformatics approaches were used to predict the structure and functionality of YggG protein. The open reading frame (ORF) of yggG, which was a putative metalloprotease gene, was also cloned, expressed and characterized. The ORF was PCR amplified from K. pneumoniae MGH 78578 genomic DNA and cloned into a pET14-b vector for heterologous expression in Escherichia coli. The purified YggG protein was subsequently assayed for casein hydrolysis under different conditions. This protein was classified as peptidase M48 family and subclan gluzincin. It was predicted to contain one transmembrane domain by TMpred. Optimal protein expression was achieved by induction with 0.6 mM isopropyl thiogalactoside (IPTG) at 25 °C for six hours. YggG was purified as soluble protein and confirmed to be proteolytically active under the presence of 1.25 mM zinc acetate and showed optimum activity at 37 °C and pH 7.4. We confirmed for the first time that the yggG gene product is a zinc-dependent metalloprotease.
Association of HLA-B*15:13 and HLA-B*15:02 with phenytoin-induced severe cutaneous adverse reactions in a Malay population

Chang CC, Ng CC, Too CL, Choon SE, Lee CK, Chung WH, et al.

Pharmacogenomics J, 2017 03;17(2):170-173.
PMID: 26927288 DOI: 10.1038/tpj.2016.10

Phenytoin (PHT) is a common cause of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Although HLA-B*15:02 is associated with PHT-induced SJS/TEN (PHT-SJS/TEN) in Han Chinese and Thais, the genetic basis for susceptibility to PHT-induced SCARs (PHT-SCAR) in other populations remains unclear. We performed a case-control association study by genotyping the human leukocyte antigen (HLA)-B alleles of 16 Malay PHT-SCAR patients (13 SJS/TEN and 3 DRESS), 32 PHT-tolerant controls and 300 healthy ethnicity-matched controls. A novel genetic biomarker, HLA-B*15:13, showed significant association with PHT-SJS/TEN (53.8%, 7/13 cases) (odds ratio (OR) 11.28, P=0.003) and PHT-DRESS (100%, 3/3 cases) (OR 59.00, P=0.003) when compared with PHT-tolerant controls (9.4%, 3/32 controls). We also confirmed HLA-B*15:02 association with PHT-SJS/TEN (61.5%, 8/13 cases vs 21.9%, 7/32 controls; OR 5.71, P=0.016) when compared with PHT-tolerant controls. These alleles may serve as markers to predict PHT-SCAR in Malays.
HLA-B*58: 01 association in allopurinol-induced severe cutaneous adverse reactions: the implication of ethnicity and clinical phenotypes in multiethnic Malaysia

Low DE, Nurul-Aain AF, Tan WC, Tang JJ, Bakhtiar MF, Murad S, et al.

Pharmacogenet Genomics, 2020 09;30(7):153-160.
PMID: 32433341 DOI: 10.1097/FPC.0000000000000408

OBJECTIVE: The association between human leukocyte antigen (HLA)-B*58:01 and risk of allopurinol-induced severe cutaneous adverse reactions (AIS) was observed across different populations. We explore the association between HLA-B*58:01 and AIS risk in multiethnic Malaysian population. The HLA-B*58:01 risk for different AIS clinical phenotypes and ethnicity was determined.
METHODS: We performed a case-control association study by genotyping the HLA-B alleles of 55 patients with AIS [11 toxic epidermal necrolysis (TEN), 21 Steven Johnson syndrome (SJS) 22 drug reaction wit eosinophilia and systemic symptoms (DRESS) and one acute generalized exanthematous pustulosis (AGEP)] and 42 allopurinol-tolerant controls (ATC).
RESULTS: HLA-B*58:01 was positive in 89.1 and 14.3% of the AIS and ATC study groups [odds ratio (OR) = 49.0, 95% confidence interval (CI) = 14.6-164.4, P < 0.0001)], respectively. Our data showed that 93.8% of the AIS-SJS/TEN patients and 86.4% of the AIS-DRESS patients were HLA-B*58:01 positive (AIS-SJS/TEN, OR = 90, 95% CI = 16.9-470.1, P < 0.0001 and AIS-DRESS OR = 38, 95% CI = 8.5-169.2, P < 0.0001). Stratification by ethnicity and clinical phenotypes revealed a significant increased risk between HLA-B*58:01 and Chinese-AIS patients (OR = 137.5, 95% CI = 11.3-1680.2, P < 0.0001), in particular Chinese patients with AIS-SJS/TEN phenotype (100% HLA-B*58:01 positive). HLA-B*58:01 was positive in 90.9% Chinese AIS-DRESS (P < 0.0001). Highly significant associations of HLA-B*58:01 were observed in Malay AIS-SJS/TEN (OR = 78, 95% CI = 9.8-619.9, P < 0.0001) and Malay AIS-DRESS (OR = 54, 95% CI = 6.6-442.9, P < 0.0001). Although the number of Indian-AIS patients was relatively small (n = 2), both were HLA-B*58:01 positive.
CONCLUSION: Our data suggest strong associations between HLA-B*58:01 and AIS in Malaysian population with Chinese and Malays ethnicity. The strong association was also observed in three different clinical phenotypes of AIS, mainly the AIS-SJS/TEN.
Phylogenomic Analysis of Ultraconserved Elements Resolves the Evolutionary and Biogeographic History of Segmented Trapdoor Spiders

Xu X, Su YC, Ho SYW, Kuntner M, Ono H, Liu F, et al.

Syst Biol, 2021 Oct 13;70(6):1110-1122.
PMID: 33367903 DOI: 10.1093/sysbio/syaa098

The segmented trapdoor spiders (Liphistiidae) are the sole surviving family of the suborder Mesothelae, which forms the sister lineage to all other living spiders. Liphistiids have retained a number of plesiomorphic traits and their present-day distribution is limited to East and Southeast Asia. Studying this group has the potential to shed light on the deep evolutionary history of spiders, but the phylogeny and divergence times of the family have not been resolved with confidence. We performed phylogenomic and molecular dating analyses of 2765 ultraconserved element loci from 185 liphistiid taxa. Our analyses show that the crown group of Liphistiidae appeared in the mid-Cretaceous at 102 Ma (95% credibility interval 92-113 Ma), but it was not until the Neogene that much of the diversification within the family occurred in mainland Southeast and East Asia. This diversification was coincident with tectonic events such as the extension of the East Asian continental margin, as well as geological upheavals in Indochina induced by the collision between India and Asia. Our study highlights the important role of major tectonic events in shaping the evolutionary history, present-day diversity, and geographical distribution of mesothele and liphistiid spiders. [biogeography; concatenation; Liphistiidae; molecular dating; summary coalescent; UCEs.].

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