Browse publications by year: 2021

  1. Gowri Shankar P, Swamy P, Williams RC, Ganesh SR, Moss M, Höglund J, et al.
    Mol Phylogenet Evol, 2021 Dec;165:107300.
    PMID: 34474153 DOI: 10.1016/j.ympev.2021.107300
    In widespread species, the diverse ecological conditions in which the populations occur, and the presence of many potential geographical barriers through their range are expected to have created ample opportunities for the evolution of distinct, often cryptic lineages. In this work, we tested for species boundaries in one such widespread species, the king cobra, Ophiophagus hannah (Cantor, 1836), a largely tropical elapid snake distributed across the Oriental realm. Based on extensive geographical sampling across most of the range of the species, we initially tested for candidate species (CS) using Maximum-Likelihood analysis of mitochondrial genes. We then tested the resulting CS using both morphological data and sequences of three single-copy nuclear genes. We used snapclust to determine the optimal number of clusters in the nuclear dataset, and Bayesian Phylogenetics and Phylogeography (BPP) to test for likely species status. We used non-metric multidimensional scaling (nMDS) analysis for discerning morphological separation. We recovered four independently evolving, geographically separated lineages that we consider Confirmed Candidate Species: (1) Western Ghats lineage; (2) Indo-Chinese lineage (3) Indo-Malayan lineage; (4) Luzon Island lineage, in the Philippine Archipelago. We discuss patterns of lineage divergence, particularly in the context of low morphological divergence, and the conservation implications of recognizing several endemic king cobra lineages.
  2. Sun Q, Chen WJ, Pang B, Sun Z, Lam SS, Sonne C, et al.
    Bioresour Technol, 2021 Dec;341:125807.
    PMID: 34474237 DOI: 10.1016/j.biortech.2021.125807
    In recent years, visualization and characterization of lignocellulose at different scales elucidate the modifications of its ultrastructural and chemical features during hydrothermal pretreatment which include degradation and dissolving of hemicelluloses, swelling and partial hydrolysis of cellulose, melting and redepositing a part of lignin in the surface. As a result, cell walls are swollen, deformed and de-laminated from the adjacent layer, lead to a range of revealed droplets that appear on and within cell walls. Moreover, the certain extent morphological changes significantly promote the downstream processing steps, especially for enzymatic hydrolysis and anaerobic fermentation to bioethanol by increasing the contact area with enzymes. However, the formation of pseudo-lignin hinders the accessibility of cellulase to cellulose, which decreases the efficiency of enzymatic hydrolysis. This review is intended to bridge the gap between the microstructure studies and value-added applications of lignocellulose while inspiring more research prospects to enhance the hydrothermal pretreatment process.
    MeSH terms: Cellulose*; Hydrolysis; Lignin*; Biomass
  3. Jia Y, Zheng F, Zhang Q, Duan HF, Savic D, Kapelan Z
    Water Res, 2021 Oct 01;204:117594.
    PMID: 34474249 DOI: 10.1016/j.watres.2021.117594
    Hydraulic modeling of a foul sewer system (FSS) enables a better understanding of the behavior of the system and its effective management. However, there is generally a lack of sufficient field measurement data for FSS model development due to the low number of in-situ sensors for data collection. To this end, this study proposes a new method to develop FSS models based on geotagged information and water consumption data from smart water meters that are readily available. Within the proposed method, each sewer manhole is firstly associated with a particular population whose size is estimated from geotagged data. Subsequently, a two-stage optimization framework is developed to identify daily time-series inflows for each manhole based on physical connections between manholes and population as well as sewer sensor observations. Finally, a new uncertainty analysis method is developed by mapping the probability distributions of water consumption captured by smart meters to the stochastic variations of wastewater discharges. Two real-world FSSs are used to demonstrate the effectiveness of the proposed method. Results show that the proposed method can significantly outperform the traditional FSS model development approach in accurately simulating the values and uncertainty ranges of FSS hydraulic variables (manhole water depths and sewer flows). The proposed method is promising due to the easy availability of geotagged information as well as water consumption data from smart water meters in near future.
    MeSH terms: Craniofacial Dysostosis*; Humans; Probability; Sewage; Water*; Uncertainty; Waste Water
  4. Naito R, Yun Low W, Wan Yuen C
    Asia Pac J Public Health, 2021 07;33(5):530-538.
    PMID: 34137287 DOI: 10.1177/10105395211019930
    This cross-sectional study examines the prevalence of sleep deprivation and its associated factors among 1017 undergraduate students in Malaysia. Sociodemographic and lifestyle factors such as smoking, alcohol, dietary habits, Internet/smartphone use, physical activity, and sedentary behavior were assessed. Sleep deprivation was defined as sleeping less than 7 hours in a day. There were almost equal proportions of females (51.0%) and males (49.0%), and the average age was 20.71 ± 1.47 years. Prevalence of sleep deprivation was 58.1% and its associated factors were students in Year 3 and Year 4, Chinese ethnicity, Indian ethnicity, and consuming fast food more than once a week. Understanding the associated lifestyle factors with sleep deprivation among young generation will be beneficial to develop public health policies and programs to tackle the issue.
    MeSH terms: Cross-Sectional Studies; Female; Humans; Malaysia/epidemiology; Male; Risk Factors; Young Adult
  5. Guad RM, Mangantig E, Low WY, Taylor-Robinson AW, Azzani M, Sekaran SD, et al.
    BMC Infect Dis, 2021 Aug 31;21(1):893.
    PMID: 34465288 DOI: 10.1186/s12879-021-06606-6
    BACKGROUND: Several studies have reported a significant association of knowledge, attitude and preventive practice (KAP) regarding dengue infection among community's resident in endemic areas. In this study we aimed to assess and develop a reliable and valid KAP survey on the subject of dengue that is suitable for the resident population of Sabah, Malaysia.

    METHODS: A community-based cross-sectional study was conducted from October 2019 to February 2020 involving 468 respondents. Information on the socio-demographic characteristics of the participants (six items), their KAP (44, 15 and 18 items on knowledge, attitude and practice, respectively) and treatment-seeking behaviour (five items) towards dengue was collected using a structured questionnaire. Data analysis was performed using SPSS and R software in the R Studio environment. The knowledge section was analysed by two-parameter logistic item response theory (2-PL IRT) using ltm package. The construct validity and reliability of items for sections on attitude, practice and treatment-seeking behaviour were analysed using psy package.

    RESULTS: For the knowledge section, only 70.5% (31/44) of items were within or close to the parameter acceptable range of -3 to + 3 of difficulty. In terms of discrimination, 65.9% (29/44) of items were within or close to the acceptable range of 0.35 to 2.5, and 24 items (54.5%) failed to fit the 2-PL IRT model (P  0.7, while based on the communalities, 11 items in the attitude section were excluded due to very low h2, factor loading values and low correlation with the total ( 0.7. The communalities of the practice section showed that seven items had low h2 values (

    MeSH terms: Cross-Sectional Studies; Factor Analysis, Statistical; Humans; Health Knowledge, Attitudes, Practice*; Malaysia/epidemiology; Surveys and Questionnaires; Reproducibility of Results
  6. Nikbakht Nasrabadi A, Wibisono AH, Allen KA, Yaghoobzadeh A, Bit-Lian Y
    BMC Nurs, 2021 Aug 31;20(1):156.
    PMID: 34465316 DOI: 10.1186/s12912-021-00675-3
    BACKGROUND: Moral distress is a poorly defined and frequently misunderstood phenomenon, and little is known about its triggering factors during ICU end-of-life decisions for nurses in Iran. This study aimed to explore the experiences of nurses' moral distress in the long-term care of older adults via a phenomenological study.

    METHODS: A qualitative, phenomenological study was conducted with 9 participants using in-depth semi-structured interviews. The purpose was to gain insight into the lived experiences and perceptions of moral distress among ICU nurses in hospitals affiliated with Tehran University of Medical Sciences during their long-term care of older adults.

    RESULTS: Five major themes are identified from the interviews: advocating, defense mechanisms, burden of care, relationships, and organizational issues. In addition, several subthemes emerged including respectful end of life care, symptom management, coping, spirituality, futile care, emotional work, powerlessness, relationships between patients and families, relationships with healthcare teams, relationships with institutions, inadequate staffing, inadequate training, preparedness, education/mentoring, workload, and support.

    CONCLUSIONS: This qualitative study contributes to the limited knowledge and understanding of the challenges nurses face in the ICU. It also offers possible implications for implementing supportive interventions.

  7. Auliya RZ, Ooi PC, Sadri R, Talik NA, Yau ZY, Mohammad Haniff MAS, et al.
    Sci Rep, 2021 Aug 31;11(1):17432.
    PMID: 34465806 DOI: 10.1038/s41598-021-96909-0
    A new 2D titanium carbide (Ti3C2), a low dimensional material of the MXene family has attracted remarkable interest in several electronic applications, but its unique structure and novel properties are still less explored in piezoelectric energy harvesters. Herein, a systematic study has been conducted to examine the role of Ti3C2 multilayers when it is incorporated in the piezoelectric polymer host. The 0.03 g/L of Ti3C2 has been identified as the most appropriate concentration to ensure the optimum performance of the fabricated device with a generated output voltage of about 6.0 V. The probable reasons might be due to the uniformity of nanofiller distribution in the polyvinylidene difluoride (PVDF) and the incorporation of Ti3C2 in a polymer matrix is found to enhance the β-phase of PVDF and diminish the undesired α-phase configuration. Low tapping frequency and force were demonstrated to scavenge electrical energy from abundant mechanical energy resources particularly human motion and environmental stimuli. The fabricated device attained a power density of 14 µW.cm-2 at 10.8 MΩ of load resistor which is considerably high among 2D material-based piezoelectric nanogenerators. The device has also shown stable electrical performance for up to 4 weeks and is practically able to store energy in a capacitor and light up a LED. Hence, the Ti3C2-based piezoelectric nanogenerator suggests the potential to realize the energy harvesting application for low-power electronic devices.
  8. Wu X, Li C, Zhou Z, Nie X, Chen Y, Zhang Y, et al.
    Int J Adv Manuf Technol, 2021;117(9-10):2565-2600.
    PMID: 34465936 DOI: 10.1007/s00170-021-07854-1
    Cutting fluid has cooling and lubricating properties and is an important part of the field of metal machining. Owing to harmful additives, base oils with poor biodegradability, defects in processing methods, and unreasonable emissions of waste cutting fluids, cutting fluids have serious pollution problems, which pose challenges to global carbon emissions laws and regulations. However, the current research on cutting fluid and its circulating purification technique lacks systematic review papers to provide scientific technical guidance for actual production. In this study, the key scientific issues in the research achievements of eco-friendly cutting fluid and waste fluid treatment are clarified. First, the preparation and mechanism of organic additives are summarized, and the influence of the physical and chemical properties of vegetable base oils on lubricating properties is analyzed. Then, the process characteristics of cutting fluid reduction supply methods are systematically evaluated. Second, the treatment of oil mist and miscellaneous oil, the removal mechanism and approach of microorganisms, and the design principles of integrated recycling equipment are outlined. The conclusion is concluded that the synergistic effect of organic additives, biodegradable vegetable base oils and recycling purification effectively reduces the environmental pollution of cutting fluids. Finally, in view of the limitations of the cutting fluid and its circulating purification technique, the prospects of amino acid additive development, self-adapting jet parameter supply system, matching mechanism between processing conditions and cutting fluid are put forward, which provides the basis and support for the engineering application and development of cutting fluid and its circulating purification.
  9. Rauf U, Ali M, Dehele I, Paudyal V, Elnaem MH, Cheema E
    J Pain Res, 2021;14:2601-2614.
    PMID: 34466028 DOI: 10.2147/JPR.S312227
    Objective: Mortalities due to fentanyl derivatives are on the rise with novel fentanyl analogues and still emerging on the global illicit drug market. They are highly potent and very fatal in low doses, yet there has been a lack of systematic research surrounding this subject. This review aims to assess the causes, nature, and toxicology of fatalities associated with fentanyl analogues.

    Methods: Five databases: Scopus, Embase, Medline, PubMed and Google Scholar were searched from inception to October 2020 to identify case studies and case series reporting fentanyl analogue-related fatalities. Two independent reviewers screened and selected the articles followed by the data extraction from each article, which included demography, route of administration, causes and nature of death, and the fentanyl analogue implicated. All articles were then subject to quality assessment tools developed by the Joanna Briggs Institute (JBI). A narrative synthesis was undertaken.

    Results: The initial data search yielded 834 articles, only 14 of which met the inclusion criteria - this included nine case reports and five case series. Of the 1079 fentanyl-analogue related deaths reported, the majority of them occurred in the US (n=1044, 96.8%). The majority of fatalities were male (n=766, 71%), white (n=884, 87%) and in the age ranges 25-34 and 35-44 years (30.5% and 29.6%, respectively). The most common route of administration was intravenous (n=319, 66%) and the manner of death was almost exclusively accidental (99.7%). The predominant cause of death was fentanyl-analogue toxicity (n=292, 85.4%) and involved mixed drug toxicity (n=47, 13.7%). The mean post-mortem fentanyl analogue concentration was 31.6 ng/mL.

    Conclusion: Most fatalities were reported in the US involving young white males. Overdose through intravenous administration and by mixed drug toxicities with other opioids were the major causes of death. Deaths reported in peer-reviewed literature were relatively less than those reported by real-world data.

  10. Asif Rasheed M, Awais M, Aldhahrani A, Althobaiti F, Alhazmi A, Sattar S, et al.
    Saudi J Biol Sci, 2021 Sep;28(9):4859-4866.
    PMID: 34466059 DOI: 10.1016/j.sjbs.2021.06.082
    Objective: Serious non-gastrointestinal-tract infections and food poisoning are caused by Bacillus cereus. Vaccination against B. cereus is very important. The aim of this study was to identify and analyze B and T cell epitopes for chromate transporter protein of the bacteria.

    Methods: Multiple sequence alignment with the Clustal Omega method was used to identify conserved regions and Geneious Prime was used to produce a consensus sequence. T and B cell epitopes were predicted by various computational tools from the NetCTL and Immune Epitope Database (IEDB), respectively.

    Results: Altogether, 6 HTL cells and 11 CTL epitopes were predicted. This vaccine's molecular docking is done with Patch Dock and LigPlot to verify interactions. The immune server (C-IMMSIM) was used to develop In silico immune response in order to assess the multi-epitope vaccine's immunogenic profile.

    Conclusion: We designed universal vaccine against B. cereus responsible for food poisoning. The disease may be avoided with the aid of the proposed epitope-based vaccine.

  11. Chaudhary A, Hussain Z, Aihetasham A, El-Sharnouby M, Abdul Rehman R, Azmat Ullah Khan M, et al.
    Saudi J Biol Sci, 2021 Sep;28(9):4867-4875.
    PMID: 34466060 DOI: 10.1016/j.sjbs.2021.06.081
    Unwanted agricultural waste is largely comprised of lignocellulosic substrate which could be transformed into sugars. The production of bioethanol from garbage manifested an agreeable proposal towards waste management as well as energy causation. The goal of this work is to optimize parameters for generation of bioethanol through fermentation by different yeast strains while Saccharomyces cerevisiae used as standard strain. The low cost fermentable sugars from pomegranate peels waste (PPW) were obtained by hydrolysis with HNO3 (1 to 5%). The optimum levels of hydrolysis time and temperature were elucidated via RSM (CCD) ranging from 30 to 60 min and 50 to 100 °C respectively. The result shows that optimum values (g/L) for reducing sugars was 61.45 ± 0.01 while for total carbohydrates was 236 ± 0.01. These values were found when PPW was hydrolyzed with 3% HNO3, at 75 °C for one hour. The hydrolyzates obtained from the dilute HNO3 pretreated PPW yielded a maximum of 0.43 ± 0.04, 0.41 ± 0.03 g ethanol per g of reducing sugars by both Metchnikowia sp. Y31 and M. cibodasensis Y34 at day 7 of ethanologenic experiment. The current study exhibited that by fermentation of dilute HNO3 hydrolyzates of PPW could develop copious amount of ethanol by optimized conditions.
  12. Najwa-Sawawi S, Azman NM, Rusli MU, Ahmad A, Fahmi-Ahmad M, Fadzly N
    Saudi J Biol Sci, 2021 Sep;28(9):5053-5060.
    PMID: 34466082 DOI: 10.1016/j.sjbs.2021.05.021
    Sea turtle eggs incubation involves natural and artificial incubation of eggs, and indeed the depth will be varied and presumably affect the development of hatchlings. For nest relocation, the researcher needs to decide on the depth to incubate the eggs. Sea turtle eggs clutches may vary between 40 and 120 eggs for the green turtle, thus using a single value as the standard procedure might affect the quality of hatchlings. Here we quantify the dimension of the natural (in-situ) nest constructed by the nester and the artificial (ex-situ) built by our ranger during nest relocation. We suggest a linear regression calculation of Y = 0.2366X + 59.3267, better predict a more accurate nest depth based on the number of eggs to imitate the natural nest.
  13. Thanigaivel S, Vickram AS, Anbarasu K, Gulothungan G, Nanmaran R, Vignesh D, et al.
    Saudi J Biol Sci, 2021 Sep;28(9):5168-5174.
    PMID: 34466094 DOI: 10.1016/j.sjbs.2021.05.048
    Our review focused on nanomaterials-based toxicity evaluation and its exposure to the human and aquatic animals when it was leached and contaminated in the environment. Ecotoxicological assessment and its mechanism mainly affect the skin covering layers and its preventive barriers that protect the foreign particles' skin. Nanoscale materials are essential in the medical field, especially in biomedical and commercial applications such as nanomedicine and drug delivery, mainly in therapeutic treatments. However, various commercial formulations of pharmaceutical drugs are manufactured through a series of clinical trials. The role of such drugs and their metabolites has not met the requirement of an individual's need at the early stage of the treatments except few drugs and medicines with minimal or no side effects. Therefore, biology and medicines are taken up the advantages of nano scaled drugs and formulations for the treatment of various diseases. The present study identifies and analyses the different nanoparticles and their chemical components on the skin and their effects due to penetration. There are advantageous factors available to facilitate positive and negative contact between dermal layers. It creates a new agenda for an established application that is mainly based on skin diseases.
  14. Shujaa Edin HY, Al-Haj NA, Rasedee A, Banu Alitheen N, Abdul Kadir A, Wun How C, et al.
    Saudi J Biol Sci, 2021 Sep;28(9):5214-5220.
    PMID: 34466099 DOI: 10.1016/j.sjbs.2021.05.043
    Erythropoietin (EPO) is widely used to treat anemia in patients undergoing chemotherapy for cancers. The main objective of this study was to investigate the effect of rHuEPO on the response of spheroid breast cancer, MCF-7, cells to tamoxifen treatment. The MCF-7 spheroids were treated with 10 mg/mL tamoxifen in combination with either 0, 10, 100 or 200 IU/mL rHuEPO for 24, 48 or 72 h. The viability of the MCF-7 cells was determined using the annexin-V, cell cycle, caspases activation and acridine orange/propidium iodide staining. rHuEPO-tamoxifen combination significantly (p greater than 0.05) increased the number of spheroid MCF-7 cells entering early apoptotic phase after 12 h and late apoptotic phase after 24 h of treatment; primarily the result of the antiproliferative effect tamoxifen. Tamoxifen alone significantly (p 
  15. Amran MS, Zain SM, Jamaludin KA, Surat S
    Front Psychol, 2021;12:727116.
    PMID: 34466138 DOI: 10.3389/fpsyg.2021.727116
    Studies on metacognitive skills have started in the past 30 years and cover various fields, including education. In general, metacognitive skills refer to awareness and monitoring cognitive processes and their ability to sharpen the mind enhancement process. However, much attention has been given to metacognition alone and less focusing on its manifestation in behaviors. Thus, this study aims to conceptualize how metacognitive concepts can be adapted in the context of behaviors. In achieving this, an in-depth analysis of relevant behavioral theories and metacognitive models was conducted. The proposed conceptual framework, named the meta-behavior framework, underscores the importance of the thinking process before an individual engages in action. Undoubtfully, this skill is vital in influencing an individual to plan, monitor and evaluate his/her actions in daily life. In short, the proposed framework is essential in expanding the current knowledge terrain on psychology, which specifically provides a new perspective in understanding how the thinking process determines behavior.
  16. Md Noh MSF
    Clin Case Rep, 2021 Aug;9(8).
    PMID: 34466227 DOI: 10.1002/ccr3.3319
    The middle cerebral artery (MCA) dot sign is an important radiological sign in patients presenting with acute ischemic stroke (AIS). If identified and intervened early, a good clinical outcome may be achieved.
  17. Madrim MF, Ja'afar MH, Hod R
    PeerJ, 2021;9:e12014.
    PMID: 34466292 DOI: 10.7717/peerj.12014
    Background: The prevalence of chronic kidney disease is increasing globally, ranking 27th as the cause of death in the 1990s, rising to 18th in 2010 and 10th in 2019. Non-communicable diseases such as diabetes and hypertension have been identified as the common contributing factors, while there is also evidence linking environmental pollutants, especially cadmium, to kidney disease. This study aimed at investigating the level of urinary cadmium and its relationship to albuminuria as an early indicator of kidney problems in the Kepong community.

    Methods: Respondents were surveyed as part of several health-related programs organized by the Kepong District Health Office involving local communities in and around the district from April 2019 to December 2019. Urinalysis of two urine samples was carried out using a Mission reagent strip and an Inductively Coupled Plasma Mass Spectrometry (ICP-MS) test to detect the presence and level of urinary cadmium.

    Results: A total of 240 respondents were enrolled from April 2019 to December 2019. Urinalysis of two urine samples was carried out using a Mission reagent strip and an Inductively Coupled Plasma Mass Spectrometry (ICP-MS) test to detect the level of urinary cadmium. The respondents' average age was 41-year-old (±13.23). Among them, 49.6% were male, 85.0% Malay, 5.8% Chinese and 8.3% Indian. 55.0% had background of tertiary, 39.6% secondary and 5.4% primary level of education. 52.1% were categorized in B40, 34.6% in M40 and 13.3% in T20 based on monthly household income category. 26.7% were hypertensive, 6.7% diabetic, 4.2% had dyslipidemia, 51.7% had urinary cadmium above the alert level, and 27.1% had albuminuria.

    Discussion: Risk factors for albuminuria that have been identified are age with adjusted odds ratio (AOR) 3.53 (1.41-8.83; p 

  18. Cheah WL, Law LS, Teh KH, Kam SL, Voon GEH, Lim HY, et al.
    Health Sci Rep, 2021 Sep;4(3):e362.
    PMID: 34466663 DOI: 10.1002/hsr2.362
    Background and Aims: This study aimed to examine the quality of life (QoL) and health satisfaction of undergraduate university students in Sarawak during MCO and its association with socio-demographic profiles.

    Methods: In this cross-sectional study, QoL and satisfaction of health of 503 undergraduate university students (63.4% females) from a public university was assessed online using the World Health Organization QoL (WHOQOL)-BREF instrument.

    Results: The overall QoL and satisfaction with health were 3.7 ± 0.87 and 3.9 ± 0.82, respectively. Male students showed significantly lower mean scores for the environmental domains than female students (63.37 ± 16.21 vs 68.10 ± 14.00, P 

  19. Munawar K, Choudhry FR, Lee SH, Siau CS, Kadri NBM, Binti Sulong RM
    Heliyon, 2021 Aug;7(8):e07842.
    PMID: 34466706 DOI: 10.1016/j.heliyon.2021.e07842
    OBJECTIVES: Acceptance and commitment therapy (ACT) has accumulated increasing evidence-base for a broad range of mental health issues. Considering that ACT encourages broad and flexible patterns of behaviour and neutralizes the pervasive psychological processes proposed to be caused by most individuals' distress, such a modality may be effective for ADHD. This review aimed to give a synthesis of the studies, so far, focusing on the usefulness of ACT approaches among individuals having ADHD.

    DESIGN/METHODS: This scoping review searched studies exploring the effectiveness of ACT approaches for individuals with ADHD across eight electronic databases (Medline, Embase, PsycInfo, ScienceDirect, PubMed, Emcare, Scopus, and Google Scholar). This review was based on a total of two quasi-experimental and four experimental studies.

    RESULTS: A thematic analysis was suggested based on the PRISMA guidelines. Overall, the review presented preliminary evidence demonstrating the use of ACT among individuals with ADHD. It was found that the ACT was used to treat a variety of behavioural and psychosocial outcomes, which included reducing ADHD symptoms (e.g., impulsivity, inattention, inflexibility, etc.) and other sequelae related to the ADHD diagnosis such as poor quality of life, academic procrastination, depression and anxiety symptoms, and psychological maladjustment.

    CONCLUSIONS: This review revealed that ACT was a flexible approach that could be adapted to deliver both targeted treatment of ADHD symptomatology and more general psychosocial issues. It could also be delivered in group or individual formats. Nevertheless, although the findings of the present scoping review indicate promising results, more research is needed.

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