Performance measurement of nonhomogeneous Hong Kong hospitals using directional distance functions.

Cook et al. (Oper Res 61(3):666-676, 2013) propose a DEA-based model for the performance evaluation of non-homogeneous decision making units (DMUs) based on constant returns to scale (CRS), extended by Li et al. (Health Care Manag Sci 22(2):215-228, 2019) to variable returns to scale (VRS). This paper locates these models into more general DDF models to deal with nonhomogeneous DMUs and applies these to Hong Kong hospitals. The production process of each hospital is divided into subunits which have the same inputs and outputs and hospital performance is measured using the subunits. The paper provides CRS and VRS versions of DDF models and compares them with Cook et al. (Oper Res 61(3):666-676, 2013) and Li et al. (Health Care Manag Sci 22(2):215-228, 2019). A kernel-based method is used to estimate the distributions as well as a DEA-based efficiency analysis adapted by Simar and Zelenyuk to test the distributions. Both DDF CRS and VRS versions produce results similar to Cook et al. (Oper Res 61(3):666-676, 2013) and Li et al. (Health Care Manag Sci 22(2):215-228, 2019) respectively. However, the statistical tests find differences for the different technologies assumed as would be expected. For hospital managers, the more generalised DDF models expand their range of options in terms of directional improvements and priorities as well as dealing with non-homogeneity.

A novel data-driven decision model based on extended belief rule base to predict China's carbon emissions.

Global warming and climate change are gaining traction in recent years. As a major cause of global warming, carbon emissions were centered to China's climate change policy initiatives. Nevertheless, the existing policy discourse has yet reached a consensus on the optimal modeling method for carbon emissions prediction that is well-informed of both policy goals and the time-series pattern of carbon emissions. This paper fills the gap by promoting a novel data-driven decision model for carbon emissions prediction that is based on the extended belief rule base (EBRB) inference model. The new decision model consists of three components: 1) an indicator integration method, which aims to generate a few group indicators from a large number of statistical indicators; 2) a new EBRB construction method, which aims to consider the management policy goals for constructing EBRB; 3) a new ER-based inference method, which aims to predict carbon emissions based on time series change of relevant factors. The effectiveness of the proposed decision model has been tested against carbon emissions management data from 30 provinces in China. Experimental results demonstrate that the model will offer powerful reference value in the policy decision-making process, which will help to meet policy requirements for carbon emissions.

A novel behavioral three-way decision model with application to the treatment of mild symptoms of COVID-19.

The Coronavirus Disease 2019 (COVID-19) has popularized since late December 2019. In present, it is still highly transmissible and has severe impact on the public health and global economy. Due to the lack of specific drug and the appearance of different variants, the selection of the antiviral therapy to treat the patients with mild symptom is of vital importance. Hence, in this paper, we propose a novel behavioral Three-Way Decision (3WD) model and apply it to the medicine selection decision. First, a new relative utility function is constructed by considering the risk-aversion behavior and regret-aversion behavior of human beings. Second, based on the relative utility function, some new rules are defined to calculate the thresholds and conditional probabilities in 3WD and some corresponding theorems are explored and proved. Next, a new information fusion mechanism in the framework of evidential reasoning algorithm is developed. Then, the decision results are obtained based on the Bayesian decision procedure and the principle of maximum utility. Finally, an example with large-scale data set and an example about medicine selection for COVID-19 are provided to show the implementation process and effectiveness of the proposed method. Comparative analysis and sensitivity analysis are also performed to illustrate the superiority and the robustness of the current proposal.

A heterogeneous multi-attribute case retrieval method based on neutrosophic sets and TODIM for emergency situations.

Heterogeneous multi-attribute case retrieval is a crucial step in generating emergency alternatives during the course of emergency decision making (EDM) by referring to historical cases. This paper develops a heterogeneous multi-attribute case retrieval method for EDM that considers five attribute formats: crisp numbers, interval numbers, intuitionistic fuzzy numbers, single-valued neutrosophic numbers (SvNNs), and interval-valued neutrosophic numbers (IvNNs). First, we propose a similarity measurement of IvNNs and calculate the attribute similarities for the five attribute formats. The attribute weights are established using an optimal model. Next, the case similarities are calculated and the set of the similar historical cases is constructed. Furthermore, the evaluated information based on heterogeneous multi-attribute from similar historical cases is provided, and the calculation method for the evaluation of utility based on TODIM (an acronym for interactive and multi-criteria decision-making in Portugese) is proposed. The most suitable historical case is determined based on the case similarity and the evaluated utility. From this, the emergency alternative is generated. Finally, we demonstrate the efficacy of the proposed method with a case study and conduct comparisons against the performance of existing methods to assess the validity and superiority of the proposed method.

Measuring work complexity for acute care services.

Case weights capture the resource cost by diagnosis-related group (DRG) but may not fully reflect the complexity of the clinical services provided. This study describes the use of a work complexity index (WCI), for assessing acute care services focusing on those provided by physicians in healthcare systems. The services are classified using relative value units (RVUs) and their point value assigned using the resource-based relative value scale. 57,559 acute inpatients from a tertiary hospital were first classified into diagnosis-related groups, which together with the relative value units assigned to services were then used to calculate a work complexity index for 38 departments. A case mix index (CMI) was also compiled as a conventional measure of complexity which had a correlation of 0.676 (p < 0.001) with the WCI. The correlation between the WCI and the RVUs representing the weighted volume of physician activities was 0.342 (p = 0.036). The WCI represents a more output or activity focused measure of complexity whereas the CMI is more patient focused and thus provides better insights into Departments' productivity. Although this paper focuses on physicians, the WCI can be easily extended to include other clinical services.

Anti-Psoriasis Effects and Mechanisms of Α-(8-Quinolinoxy) Zinc Phthalocyanine-Mediated Photodynamic Therapy.

BACKGROUND/AIMS: The aim of this study was to determine the anti-psoriasis effects of α-(8-quinolinoxy) zinc phthalocyanine (ZnPc-F7)-mediated photodynamic therapy (PDT) and to reveal its mechanisms. METHODS: HaCaT cells were used to observe the influence of ZnPc-F7-PDT on cell proliferation in vitro. The in vivo anti-psoriasis effects of ZnPc-F7-PDT were evaluated using a mouse vagina model, a propranolol-induced cavy psoriasis model and an imiquimod (IMQ)-induced nude mouse psoriasis model. Flow cytometry was carried out to determine T lymphocyte levels. Western blotting was performed to determine protein expression, and a reverse transcription-polymerase chain reaction test was performed to determine mRNA expression. RESULTS: The results showed that ZnPc-F7-PDT significantly inhibited the proliferation of HaCaT cells in vitro; when the light doses were fixed, changing the irradiation time or output power had little influence on the inhibition rate. ZnPc-F7-PDT significantly inhibited the hyperproliferation of mouse vaginal epithelium induced by diethylstilbestrol and improved propranolol- and IMQ-induced psoriasis-like symptoms. ZnPc-F7-PDT inhibited IMQ-induced splenomegaly and T lymphocyte abnormalities. ZnPc-F7-PDT did not appear to change T lymphocytes in the mouse vagina model. ZnPc-F7-PDT down-regulated the expression of proliferating cell nuclear antigen (PCNA), B-cell lymphoma-2 (Bcl-2), interleukin (IL)-17A mRNA and IL-17F mRNA, and up-regulated the expression of Bax. CONCLUSION: In conclusion, ZnPc-F7-PDT exhibited therapeutic effects in psoriasis both in vitro and in vivo and is a potential approach in the treatment of psoriasis. Potential mechanisms of these effects included the inhibition of hyperproliferation; regulation of PCNA, Bcl-2, Bax, IL-17A mRNA and IL-17F mRNA expression; and immune regulation.

Identification, synthesis and evaluation of SARS-CoV and MERS-CoV 3C-like protease inhibitors.

Severe acute respiratory syndrome (SARS) led to a life-threatening form of atypical pneumonia in late 2002. Following that, Middle East Respiratory Syndrome (MERS-CoV) has recently emerged, killing about 36% of patients infected globally, mainly in Saudi Arabia and South Korea. Based on a scaffold we reported for inhibiting neuraminidase (NA), we synthesized the analogues and identified compounds with low micromolar inhibitory activity against 3CL(pro) of SARS-CoV and MERS-CoV. Docking studies show that a carboxylate present at either R(1) or R(4) destabilizes the oxyanion hole in the 3CL(pro). Interestingly, 3f, 3g and 3m could inhibit both NA and 3CL(pro) and serve as a starting point to develop broad-spectrum antiviral agents.

Belief-Rule-Based System with Self-organizing and Multi-temporal Modeling for Sensor-based Human Activity Recognition.

Smart environment is an efficient and cost- effective way to afford intelligent supports for the elderly people. Human activity recognition (HAR) is a crucial aspect of the research field of smart environments, and it has attracted widespread attention lately. The goal of this study is to develop an effective sensor-based HAR model based on the belief-rule-based system (BRBS), which is one of representative rule-based expert systems. Specially, a new belief rule base (BRB) modeling approach is proposed by taking into account the self- organizing rule generation method and the multi-temporal rule representation scheme, in order to address the problem of combination explosion that existed in the traditional BRB modelling procedure and the time correlation found in continuous sensor data in chronological order. The new BRB modeling approach is so called self-organizing and multi-temporal BRB (SOMT-BRB) modeling procedure. A case study is further deducted to validate the effectiveness of the SOMT-BRB modeling procedure. By comparing with some conventional BRBSs and classical activity recognition models, the results show a significant improvement of the BRBS in terms of the number of belief rules, modelling efficiency, and activity recognition accuracy.

GSSCL: A framework for Graph Self-Supervised Curriculum Learning based on clustering label smoothing.

Graph self-supervised learning is an effective technique for learning common knowledge from unlabeled graph data through pretext tasks. To capture the interrelationships between nodes and their essential roles globally, existing methods use clustering labels as self-supervised signals. However, in some cases, these methods may introduce noise, leading to over-fitting of the model and a reduction in performance. To address these issues, a novel framework for Graph Self-Supervised Curriculum Learning based on clustering label smoothing called GSSCL has been proposed. GSSCL clusters knowledge in an easy-to-difficult manner, reducing the heavy dependence on the reliability of clustering and improving the generalizability of the model. Moreover, the Silhouette Coefficient is employed to evaluate the clustering confident scores for all nodes. Some nodes are selected based on high confident scores to perform self-supervised learning. To account for the possibility of complex heterophilous information in graphs (e.g., noisy links), clustering pseudo-label smoothing is performed on K-nearest neighbor graphs built upon the similarities between node features instead of the original graph structures. The obtained multi-scale knowledge is then applied to curriculum learning. Finally, comprehensive experiments conducted across diverse public graph benchmarks demonstrate the superior performance of the proposed framework. It exhibits comparable results to state-of-the-art methods across semi-supervised node classification and clustering tasks.

The Expression of LDL-R in CD8+ T Cells Serves as an Early Assessment Parameter for the Production of TCR-T Cells.

BACKGROUND/AIM: The quantity and the phenotypes of desired T cell receptor engineered T (TCR-T) cells in the final cell product determine their in vivo anti-tumor efficacy. Optimization of key steps in the TCR-T cell production process, such as T cell activation, has been shown to improve cell quality. MATERIALS AND METHODS: Using a modified TCR (mTCR) derived from mice transducing PBMCs, we assessed the proportions of low-density lipoprotein receptor (LDL-R) and mTCR expressing cells under the various activation conditions of CD3/CD28-Dynabeads or OKT3 via flow cytometry. RESULTS: We demonstrate that the proportion of T cells expressing LDL-R post activation is positively correlated with the percentage of mTCR+CD8+ T cells with their less differentiated subtypes in the final product. In addition, we show that shifting the CD3/CD28-Dynabeads activation duration from a typical 48 h to 24 h can significantly increase the production of the desired mTCR+CD8+ T cells. Importantly, the percentages of TCR-T cells with less-differentiated phenotypes, namely mTCR central memory T cells (TCM), were found to be preserved with markedly higher efficiency when T cell activation was optimized. CONCLUSION: Our findings suggest that the proportion of LDL-R+ T cells may serve as an early assessment parameter for evaluating TCR-T cell quality, possibly facilitating the functional and economical improvement of current adoptive therapy.

Sequence determination and bioinformatic comparison of ten venom serine proteases of Trimeresurus gracilis, a Taiwanese endemic pitviper with controversial taxonomy.

Trimeresurus gracilis (Tgc) is endemic to Taiwan and shown to be closely related with Ovophis okinavensis by previous phylogenetic analyses, but their taxonomic status remain controversial. Here, we cloned and sequenced ten of its venom serine-proteases (designated as Tgc-vSPs). All the Tgc-vSPs conserve the catalytic triads, six appear to be kallikrein-like (KNs) and four are plasminogen-activator homologs (PAHs and PAs). They are studied under four structural categories: (1) highly similar Tgc-KN1, Tgc-KN2 and Tgc-KN3, with four predicted N-glycosylation sites; (2) Tgc-KN4, with a single N -glycosylation site; (3) Tgc-KN5 and Tgc-KN6, with two distinct N-glycosylation sites; (4) Tgc-PAH1/PAH2, TgcPA3, and Tgc-PA4, with two conserved N-glycosylation sites. Additionally, Tgc-KN1, Tgc-KN4 and Tgc-PAH1 were purified by reversed-phase HPLC and identified by peptide-mass-fingerprinting. Results of BLAST and sequence alignments reveal that Tgc-KN1∼3 and Tgc-KN6 are most like the vSPs of rattlesnakes, while the sequences of Tgc-KN4, KN5 and Tgc-PAH1/PAH2 match closely to the partial sequences of three O. okinavensis vSPs. Thus, our results reveal non-overlapping similarities of Tgc-vSPs to the O. okinavensis vSPs and vSPs of the New World pitvipers. In addition, molecular phylogenetic analyses of the plasminogen-activator like vSPs reveal separate evolution of two clusters of the enzymes with distinct functions.

Corneal perforation associated with ocular graft-versus-host disease.

Corneal perforation is a rare and serious complication of ocular graft-versus-host disease (oGVHD) patients. This study was to retrospectively report seven corneal perforation patients after allogeneic hematopoietic stem cell transplantation (HSCT). Demographic, hematologic, and ophthalmological data of patients were clarified in detail. Nine eyes of seven corneal perforation patients were clarified (Cases 3 and 6 were bilateral and the others are unilateral). All the cases had other affected GVHD organs, especially skin involvement. The duration between HSCT and corneal perforation was usually long with 21 (17-145) months as median interval, whereas the duration between oGVHD diagnosis and corneal perforation was relatively shorter with 4 (2-81) months as median interval. Most patients presented to ophthalmology department with poor visual acuity, BUT and Schirmer's test. Eyelid marginal hyperemia and irregularity were observed in most corneal perforation eyes. Keratoplasty or conjunctival flap covering (CFC) surgeries was performed after corneal perforation. After a long-term follow-up for most patients (median 21 months, range: 2-86 months), only two eyes of two patients (22.22%) had a final BCVA of 20/100 or better. Patients involved in both cutaneous GVHD and blepharitis indicate the aggressive development of oGVHD. Early diagnosis, long-term follow-up, and effective multi-disciplinary treatments for oGVHD patients are essential. Corticosteroids and immunosuppressor remain essential, whereas the use of topical corticosteroids should be carefully considered in corneal ulceration patients. In addition, appropriate surgeries should be performed to control oGVHD development in time.

Extended SARS-CoV-2 RBD booster vaccination induces humoral and cellular immune tolerance in mice.

The repetitive applications of vaccine boosters have been brought up in face of continuous emergence of SARS-CoV-2 variants with neutralization escape mutations, but their protective efficacy and potential adverse effects remain largely unknown. Here, we compared the humoral and cellular immune responses of an extended course of recombinant receptor binding domain (RBD) vaccine boosters with those from conventional immunization strategy in a Balb/c mice model. Multiple vaccine boosters after the conventional vaccination course significantly decreased RBD-specific antibody titers and serum neutralizing efficacy against the Delta and Omicron variants, and profoundly impaired CD4+ and CD8+T cell activation and increased PD-1 and LAG-3 expressions in these T cells. Mechanistically, we confirmed that extended vaccination with RBD boosters overturned the protective immune memories by promoting adaptive immune tolerance. Our findings demonstrate potential risks with the continuous use of SARS-CoV-2 vaccine boosters, providing immediate implications for the global COVID-19 vaccination enhancement strategies.

Terminal disialylated multiantennary complex-type N-glycans carried on acutobin define the glycosylation characteristics of the Deinagkistrodon acutus venom.

Glycosylation analysis of nonmammalian sources often springs surprises and conjures up intriguing views of evolutionary adaptation. Many of the constituents of snake venoms are known to be glycosylated and yet very few were fully characterized and accorded specific functions. In the process of glycomic screening through the venoms from Asian pit vipers, a partially O-acetylated NeuAcα2-8NeuAcα2-3Galß1-4GlcNAcß1-terminal epitope was found to be the predominant glycosylation characteristic of the snake venom produced by the monotypic Deinagkistrodon acutus, with acutobin, a highly specific fibrinogenase, being identified as a primary protein carrier. Full structural definition and glycosylation site mapping were completed through advanced mass spectrometry analyses at both the glycan and glycopeptide levels in conjunction with chemical and enzymatic cleavages. Although similar occurrence of such terminal disialyl cap on the N-glycans of several mammalian glycoproteins has been implicated, most of these correspond to only minor constituents of the full glycomic heterogeneity and remain poorly characterized. In contrast, each antennae of the hybrid- and complex-type N-glycans derived from acutobin was found to be rather homogeneously disialylated. With up to eight sialic acids evenly distributed on nonextended tetraantennary core structure, these unusual N-glycans are among those of highest sialic acid density ever identified without actually carrying polysialic acid chains. It remains to be tested whether they may serve as multivalent disialyl ligands for several of the human Siglecs and thus meddle with the natural immuno-recognition systems of snakebite victims, apart from affecting the general efficacy of acutobin as anticoagulant in biomedical applications.

An extended TODIM approach for group emergency decision making based on bidirectional projection with hesitant triangular fuzzy sets.

With the recent Covid-19 outbreak, group emergency decision-making (GEDM), as a new management model to pursue both social stability and decrease the negative impact of emergencies, has become highly popular. Evaluating and choosing the best emergency response is the core of the GEDM and selecting the choices can be regarded as a multi-attribute group decision-making (MAGDM) problem. Due to the increasing complexity and fuzziness of emergency decision-making environment, decision-makers (DMs) often cannot express completely rational preference information in many real EDM situations. At the same time, the existing methods seldom consider the DM's psychological mindset at the point of decision making. In this paper, an extended TODIM (an acronym for interactive and multi-criteria decision-making in Portugese) method based on bidirectional projection is proposed to solve the GEDM problem in the context of hesitant triangular fuzzy sets (HTFSs) and the novel method is applied to a case study and compared with other existing methods. The validity and applicability of the proposed method are discussed.

Interval-valued hesitant fuzzy TODIM method for dynamic emergency responses.

Emergency responses bear the characteristics of uncertainty and possess multi-attributes in decision making. This paper applies the interval evidential reasoning approach and the interval-valued hesitant fuzzy TODIM (IVHF-TODIM) method to tackle the dynamic emergency decision-making problem. We introduce a function to obtain the gain and loss degrees through the geometric area method. The gain and loss matrices of the interval belief degrees are found probabilistically. A new approach to obtaining the dominance degree matrix is proposed. From the IVHF-TODIM method, the overall dominance degree is established to provide the ranking of the decision alternatives. A recent case of selecting an emergency decision alternative for a large bushfire is used to validate the proposed method, followed by a comparative analysis.

Research and correlation analysis on the dripper contamination of carteolol hydrochloride eye drops.

BACKGROUND: Multi-dose eye drops are easily contaminated by microorganisms, and reportedly, the highest contamination rate can reach 96.46%. The use of contaminated eye drops can cause serious eye infections. METHODS: Carteolol hydrochloride eye drops provided by glaucoma patients who visited the ophthalmic clinic of the First Affiliated Hospital of Soochow University from May 2018 to December 2019 were collected. Microbial culture was carried out on the eye drops, and the microbial species were identified by standard procedures. At the same time, the unsealing time, storage method, hand cleaning before dripping, and contact with the eyelid or the surrounding environment during infusion were recorded. Univariate and multivariate logistic regression analyses were used to analyze the risk factors associated with the contamination of carteolol hydrochloride eye drops. RESULTS: A total of 244 bottles of carteolol hydrochloride eye drops were collected, and the positive rate of flora culture was 6.6%. A total of 18 strains of bacteria were isolated. The most common bacteria were Staphylococcus epidermidis and Corynebacterium. Univariate analysis showed that the risk factors associated with contamination were the unsealing time, the frequency of daily use, contact with the eyelid or the surrounding environment during the infusion process, and the use of more than 2 kinds of eye drops at the same time. Multivariate analysis showed that the unsealing time, the frequency of daily use, and contact with the eyelid or the surrounding environment were independent risk factors associated with contamination. CONCLUSIONS: A long unsealing time, frequent use, and non-standard operation can increase the risk of eye drop contamination, which cannot be ignored.

Structural and bioinformatic analyses of Azemiops venom serine proteases reveal close phylogeographic relationships to pitvipers from eastern China and the New World.

The semi-fossil and pit-less Azemiops feae is possibly the most primitive crotalid species. Here, we have cloned and sequenced cDNAs encoding four serine proteases (vSPs) from the venom glands of Chinese A. feae. Full amino-acid sequences of the major vSP (designated as AzKNa) and three minor vSPs (designated as AzKNb, AzKNc and Az-PA) were deduced. Using Protein-BLAST search, the ten most-similar vSPs for each Azemiops vSP have been selected for multiple sequence alignment, and all the homologs are crotalid vSPs. The results suggest that the A. feae vSPs are structurally most like those of eastern-Chinese Gloydius, Viridovipera, Protobothrops and North American pitvipers, and quite different from more-specialized vSPs such as Agkistrodon venom Protein-C activators. The vSPs from Chinese A. feae and those from Vietnamese A. feae show significant sequence variations. AzKNa is acidic and contains six potential N-glycosylation sites and its surface-charge distribution differs greatly from that of AzKNb, as revealed by 3D-modeling. AzKNb and AzKNc do not contain N-glycosylation sites although most of their close homologs contain one or two. Az-PA belongs to the plasminogen-activator subtype with a conserved N20-glycosylation site. The evolution of this subtype of vSPs in Azemiops and related pitvipers has been traced by phylogenetic analysis.

Effect of Partial Fibula Osteotomy Combined with Arthroscopic Debridement Surgery in the Treatment of Medial Compartment Knee Osteoarthritis.

This study aimed to investigate the effect of partial fibula osteotomy combined with arthroscopic debridement surgery on the treatment of medial compartment knee osteoarthritis. From January 2013 to June 2016, 17 patients who suffered from medial compartment knee osteoarthritis were assigned to two groups: groups A (n = 5) and B (n = 12). Group A patients were treated with arthroscopic debridement surgery only, while group B patients received additional fibula osteotomy in addition to arthroscopic debridement operation. Visual analogue score (VAS) and hospital for special surgery (HSS) knee score were evaluated and compared between the two groups. Group B had significant reduction in the VAS after the procedure (3.1 ± 0.8) compared with that before the procedure (6.9 ± 1.0) or group A after surgery (5.4), respectively, p < 0.05. In contrast, the HSS knee score increased significantly in group B after the procedure (83.6 ± 2.5) compared with that before the procedure (63.0 ± 3.8) or group A after the surgery (68.2 ± 2.8), respectively, p < 0.05. Partial fibula osteotomy combined with arthroscopic debridement surgery is superior to arthroscopic debridement surgery only in the treatment of medial compartment knee osteoarthritis.

Venom phospholipases of Russell's vipers from Myanmar and eastern India--cloning, characterization and phylogeographic analysis.

Venoms of Russell's vipers (genus Daboia) are known for their deadly coagulopathic and other effects. We herein studied various isoforms of venom phospholipases A(2) (PLAs) from two Daboia species at their geographic boundary. From Myanmar Daboia siamensis venom (designated as DsM), four PLAs (designated DsM-aI, aI', aII' and bI') were purified, and the cDNAs encoding two acidic (DsM-aI and aII) and two basic PLAs (DsM-bI and S1) were also cloned from its venom-glands. DsM-S1 is identical to the major venom PLA of southern India Daboia russelii, but the protein is absent from the venom. Additionally, four PLAs (designated DrK-aI, aII, bI and bII) were cloned from cDNA obtained from venom glands of a Kolkata D. russelii, and the PLAs were purified from the pooled venom (designated as DrK). The acidic DrK-aI is the most neurotoxic and lethal among these PLAs; DsM-aI which differs from DrK-aI by only the Phe2 substitution shows greatly reduced enzymatic activity and lethality. Both acidic PLAs do not form dimeric complex with basic PLAs in the same venoms. DsM-bI' is neurotoxic and lethal but its orthologous DrK-bI (97% identical to DsM-bI') is a much weaker toxin. Given the fact that most of the orthologous PLAs of DrK and DsM share 97-100% sequence identity, Daboia vipers of Myanmar and Kolkata must be closely related. Molecular phylogenetic analyses on 30 venom PLAs of Eurasian vipers' revealed co-evolution of five subtypes of venom PLAs in both Daboia and Vipera genera. Our results shed light on the intra- and inter-species variations and structure-function relationships of viperid venom PLAs.