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Anxiety disorders are one of the most common mental disorders, yet only less than 20% of people with anxiety disorders receive adequate treatment. Digital interventions for anxiety disorders can potentially increase access to evidence-based treatment. However, there is no comprehensive meta-analysis study that covers all modalities of digital interventions and all anxiety disorders.
Objectives
A preliminary meta-analysis was conducted to examine the treatment efficacy of digital interventions [e.g., virtual reality (VR)-, mobile application-, internet-based interventions] for anxiety disorders and to identify potential moderators that may lead to better treatment outcomes.
Methods
We searched Embase, PubMed, PsycINFO, Web of Science, and the Cochrane Library for randomized controlled trials examining the therapeutic efficacy of digital interventions for individuals with anxiety disorders from database inception to April 18, 2023. Search keywords were developed by combining the PICOS framework and MeSH terms. Data screening and extraction adhered to PRISMA guidelines. We used a random-effects model with effect sizes expressed as Hedge’s g. The quality of the studies was assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The study protocol was registered in PROSPERO on April 22, 2023 (CRD42023412139).
Results
A systematic literature search identified 19 studies with randomized controlled trials (21 comparisons; 1936 participants) with high overall heterogeneity (Q = 104.49; P < .001; I2 = 80.9%). Digital interventions reduced anxiety symptoms with medium to large effect sizes (g = 0.78; 95% CI: 0.55-1.02; P < .001), with interventions for specific phobia showing the largest effect size (n = 6; g = 1.22; 95% CI: 0.51-1.93; P < .001). VR-based interventions had a larger effect size (n = 6; g = 0.98; 95% CI: 0.39-1.57; P < .001) than mobile- or internet-based interventions, which had medium effect sizes. Meta-regression results exhibited that effect sizes of digital interventions were associated with the mean age of participants (β = 0.04; 95% CI: 0.02-0.06; P < .001).
Conclusions
The results of this study provide evidence for the efficacy of digital interventions for anxiety disorders. However, this also suggests that the degrees of effectiveness in reducing anxiety symptoms can be moderated by the specific diagnosis, the modalities of digital technologies, and mean age, implying that the application of digital interventions for anxiety disorders should be accompanied by personalized guidance.
Plant growth requires the integration of internal and external cues, perceived and transduced into a developmental programme of cell division, elongation and wall thickening. Mechanical forces contribute to this regulation, and thigmomorphogenesis typically includes reducing stem height, increasing stem diameter, and a canonical transcriptomic response. We present data on a bZIP transcription factor involved in this process in grasses. Brachypodium distachyon SECONDARY WALL INTERACTING bZIP (SWIZ) protein translocated into the nucleus following mechanostimulation. Classical touch-responsive genes were upregulated in B. distachyon roots following touch, including significant induction of the glycoside hydrolase 17 family, which may be unique to grass thigmomorphogenesis. SWIZ protein binding to an E-box variant in exons and introns was associated with immediate activation followed by repression of gene expression. SWIZ overexpression resulted in plants with reduced stem and root elongation. These data further define plant touch-responsive transcriptomics and physiology, offering insights into grass mechanotranduction dynamics.
Meat quality is not only influenced by breed but also rearing environment. The aim of this study was to evaluate the influence of different housing environments on growth performance, carcase traits, meat quality, physiological response pre-slaughter and fatty acid composition in two pig breeds. A total of 120 growing pigs at 60-70 days of age were arranged in a 2 × 2 factorial design with the breeds (Duroc × Landrace × Large White [D × L × LW] and Duroc × Landrace × Min pig [D × L × M]) and environmental enrichment (barren concrete floor or enriched with straw bedding) as factors. Each treatment was performed in triplicate with ten pigs per replicate. The pigs housed in the enriched environment exhibited a higher average daily gain, average daily feed intake, saturated fatty acid percentage and backfat depth than the pigs reared in the barren environment. Plasma cortisol levels were lower and growth hormone higher in enriched compared to barren pens. The D × L × M pigs showed lower cooking loss compared with the D × L × LW pigs. Moreover, the D × L × M pigs exhibited poor growth performance but had a better water-holding capacity. Only carcase traits and meat quality interaction effects were observed. We concluded that an enriched environment can reduce preslaughter stress and improve the growth performance of pigs and modulate the fatty acid composition of pork products.
We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.
To examine associations between serum micronutrients and neurobehavioural function and the mediating role of sleep quality in early adolescents.
Design:
In this cross-sectional study, peripheral blood samples were analysed for Fe and Zn levels. The Pittsburgh Sleep Quality Index and Penn Computerized Neurocognitive Battery were used to assess sleep quality and neurobehavioural function, respectively. The logistic/linear regressions and generalised structural equation modelling were performed to estimate the associations.
Setting:
Jintan, China
Participants:
In total, 226 adolescents (106 females) from the Jintan Child Cohort study.
Results:
Adolescents with low Fe (<75 μg/dl) (OR = 1·29, P = 0·04) and low Zn (<70 μg/dl) (OR = 1·58, P < 0·001) were associated with increased odds for poor sleep quality. Adolescents with low Fe and Zn were associated with fast (Fe: β = –1353·71, P = 0·002, Zn: β = –2262·01, P = 0·02) but less-accurate (Fe: β = –0·97, P = 0·04; Zn: β = –1·76, P = 0·04) performance on non-verbal reasoning task and poor sleep quality partially mediated the associations between low Fe/Zn and non-verbal reasoning (P < 0·05). Additionally, low Fe was associated with a slower reaction on spatial processing task (β = 276·94, P = 0·04), and low Zn was associated with fast (β = –1781·83, P = 0·03), but error-prone performance (β = –1·79, P = 0·04) on spatial processing ability and slower reaction speed (β = 12·82, P = 0·03) on the attention task. We observed similar trends using a cut-off point of 75 μg/dl for low serum Zn, except for the association with attention task speed (P > 0·05).
Conclusion:
Fe and Zn deficiencies may possibly be associated with poor sleep and neurobehavioural function among early adolescents. Poor sleep may partially mediate the relationship between micronutrients and neurobehavioural function.
The onset of magnetic reconnection in space, astrophysical and laboratory plasmas is reviewed discussing results from theory, numerical simulations and observations. After a brief introduction on magnetic reconnection and approach to the question of onset, we first discuss recent theoretical models and numerical simulations, followed by observations of reconnection and its effects in space and astrophysical plasmas from satellites and ground-based detectors, as well as measurements of reconnection in laboratory plasma experiments. Mechanisms allowing reconnection spanning from collisional resistivity to kinetic effects as well as partial ionization are described, providing a description valid over a wide range of plasma parameters, and therefore applicable in principle to many different astrophysical and laboratory environments. Finally, we summarize the implications of reconnection onset physics for plasma dynamics throughout the Universe and illustrate how capturing the dynamics correctly is important to understanding particle acceleration. The goal of this review is to give a view on the present status of this topic and future interesting investigations, offering a unified approach.
The aim of this study was to clarify effects of Clozapine and its metabolites on insulin resection and expression of glucose transporter 2 (GLUT2) located in cell membrane of isolated rat's islets.
Methods
The cells of isolated rat's islets were prepared by a modified collagenase digestion methods. At 5.5 mmol/L glucose, the cells of islets was treated with 1mmol/L clozapine, desmethyl-clozapine(DCLO), clozapine N-oxide(CNO), respectively, blank control group was also set.
1. After incubation 48h, the insulin in supernatant was assayed by radioimmunoassay.
2. The cells of isolated rat's islets in each group were detected GLUT2 mRNA level with RT-PCR and its protein expression with Western-blot.
Results
1. Compared to control group, clozapine significantly inhibited insulin secretion (P=0.007< 0.01); DCLO has a tendency to inhibit insulin secretion after 48h of incubation, but no significant difference was found (P=0.154>0.05). There was no difference of insulin secretion between CNO group and the control group after 48h of incubation (P>0.05).
2. The mRNA and protein expression of GLUT2 located in cell membrane of slets: clozapine group was significantly lower than control group (P=0.017< 0.05, P=0.035< 0.05), DCLO group was also lower than control group, but no significant difference was found (P>0.05), and no significant difference between CNO group and control group (P>0.05).
Conclusion
Clozapine can inhibit GLUT2 expression of cells of islets, and then hamper glucose transport through cell membrane, which was one of mechanisms to explain the effect of clozapine on insulin secretion.
The aim of this study was to compare the clinical efficacy and the safety of venlafaxine and fluoxetine in the treatment of obsessive-compulsive disorder (OCD).
Methods
One hundred and Eight inpatients who met the Diagnostic and Statistical Manual of Mental Disorders, the Forth Edition(DSM-IV) for OCD were involved in this study. The subjects were randomly divided into venlafaxine group or fluoxetine group. Efficacy of venlafaxine and fluoxetine in treatment of OCD were assessed with Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Clinical Global Impression-Severity(CGI-S), the side effects were evaluated with Treatment Emergent Symptom Scale (TESS).
Results
The therapeutic efficacy in venlafaxine group was similar to that in fluoxetine (70.36%vs68.29%, P>0.05) after eight weeks’ therapy. The improve-rates of Y-BOCS after 2 weeks’ therapy of venlafaxine were significant higher than those of baseline, while the improve-rates of Y-BOCS after 4 weeks’ therapy of fluoxetine were significant higher than those of baseline(P< 0.05). The side effects of venlafaxine group were similar to fluoxetine group (P>0.05).
Conclusion
The results indicate that both venlafaxine and fluoxetine is effective in the treatment of OCD, but venlafaxine work faster than fluoxutine.
Tuberculosis (TB) is the leading cause of death among infectious diseases. China has a high burden of TB and accounted for almost 13% of the world's cases of multi-drug resistant (MDR) TB. Spinal TB is one reason for the resurgence of TB in China. Few large case studies of MDR spinal TB in China have been conducted. The aim of this research was to observe the epidemiological characteristics of inpatients with MDR spinal TB in six provinces and cities of China from 1999–2015. This is a multicentre retrospective observational study. Patients' information was collected from the control disease centre and infectious disease database of hospitals in six provinces and cities in China. A total of 3137 patients with spinal TB and 272 patients with MDR spinal TB were analysed. The result showed that MDR spinal TB remains a public health concern and commonly affects patients 15–30 years of age (34.19%). The most common lesions involved the thoracolumbar spine (35.66%). Local pain was the most common symptom (98.53%). Logistic analysis showed that for spinal TB patients, reside in rural district (OR 1.79), advanced in years (OR 1.92) and high education degree (OR 2.22) were independent risk factors for the development of MDR spinal TB. Women were associated with a lower risk of MDR spinal TB (OR 0.48). The most common first-line and second-line resistant drug was isoniazid (68.75%) and levofloxacin (29.04%), respectively. The use of molecular diagnosis resulted in noteworthy clinical advances, including earlier initiation of MDR spinal TB treatment, improved infection control and better clinical outcome. Chemotherapy and surgery can yield satisfactory outcomes with timely diagnosis and long-term treatment. These results enable a better understanding of the MDR spinal TB in China among the general public.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Co-receptor tropism has been identified to correlate with HIV-1 transmission and the disease progression in patients. A molecular epidemiology investigation of co-receptor tropism is important for clinical practice and effective control of HIV-1. In this study, we investigated the co-receptor tropism on HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%. Our data showed that a majority of the subjects harboured the CCR5-tropic virus (81.2%, 69/85). No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes were observed between subjects infected with CXCR4-tropic or CCR5-tropic virus. The co-receptor tropism appeared to be associated with the virus genotype; a significantly more CXCR4-use was predicted in CRF01_AE infections whereas all CRF07_BC and CRF08_BC were predicted to use CCR5 co-receptor. Sequences analysis of V3 revealed a higher median net charge in the CXCR4 viruses over CCR5 viruses (4.0 vs. 3.0, P < 0.05). The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region was conserved in CCR5 viruses, but not in CXCR4 viruses. Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B. These findings may offer important implications for clinical practice and enhance our understanding of HIV-1 biology.
Clay mineralogy and its palaeoclimatic interpretation of the early-Eocene (∼53.3–49.70 Ma) sediments at Lulehe, Qaidam basin, northwest China, were investigated using optical microscopy, scanning electron microscopy (SEM), and X-ray diffraction (XRD). The interval of ∼53.3–49.70 Ma, including the early-Eocene climate optimum (EECO) with isotopic events, was the transition period of “greenhouse” to “icehouse”. Climate changes during the episode were documented in the sediments and were expressed by the proportion of clay species and clay indices, as well as by the proportion of non-clay minerals, gypsum, halite and calcite. Our results suggest that a warm and humid climate prevailed over the period ∼53.3–52.90 Ma, followed by a warm and seasonally dry and humid climate in the period ∼52.90–51.0 Ma and a subsequently warm and humid climate in the period ∼51.0–49.70 Ma. Three warmer and more humid intervals were observed at 52.7, 51.0 and 50.5 Ma based on clay indices. The climate evolution in the Qaidam Basin during the period derived from the clay mineralogical study is in good agreement with the early Eocene global climate change, and the warm and seasonally dry and humid episode in the early Eocene in Qaidam basin is a regional response to the global early-Eocene climate optimum.
Phenoloxidase (PO) plays a key role in melanin biosynthesis during insect development. Here, we isolated the 2310-bp full-length cDNA of PPO1 from Zeugodacus tau, a destructive horticultural pest. qRT-polymerase chain reaction showed that the ZtPPO1 transcripts were highly expressed during larval–prepupal transition and in the haemolymph. When the larvae were fed a 1.66% kojic acid (KA)-containing diet, the levels of the ZtPPO1 transcripts significantly increased by 2.79- and 3.39-fold in the whole larvae and cuticles, respectively, while the corresponding PO activity was significantly reduced; in addition, the larval and pupal durations were significantly prolonged; pupal weights were lowered; and abnormal phenotypes were observed. An in vitro inhibition experiment indicated that KA was an effective competitive inhibitor of PO in Z. tau. Additionally, the functional analysis showed that 20E could significantly up-regulate the expression of ZtPPO1, induce lower pupal weight, and advance pupation. Knockdown of the ZtPPO1 gene by RNAi significantly decreased mRNA levels after 24 h and led to low pupation rates and incomplete pupae with abnormal phenotypes during the larval-pupal interim period. These results proved that PO is important for the normal growth of Z. tau and that KA can disrupt the development of this pest insect.
Plant height and lodging resistance can affect rice yield significantly, but these traits have always conflicted in crop cultivation and breeding. The current study aimed to establish a rapid and accurate plant type evaluation mechanism to provide a basis for breeding tall but lodging-resistant super rice varieties. A comprehensive approach integrating plant anatomy and histochemistry was used to investigate variations in flexural strength (a material property, defined as the stress in a material just before it yields in a flexure test) of the rice stem and the lodging index of 15 rice accessions at different growth stages to understand trends in these parameters and the potential factors influencing them. Rice stem anatomical structure was observed and the lignin content the cell wall was determined at different developmental stages. Three rice lodging evaluation models were established using correlation analysis, multivariate regression and artificial radial basis function (RBF) neural network analysis, and the results were compared to identify the most suitable model for predicting optimal rice plant types. Among the three evaluation methods, the mean residual and relative prediction errors were lowest using the RBF network, indicating that it was highly accurate and robust and could be used to establish a mathematical model of the morphological characteristics and lodging resistance of rice to identify optimal varieties.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
The Universe is permeated by hot, turbulent, magnetized plasmas. Turbulent plasma is a major constituent of active galactic nuclei, supernova remnants, the intergalactic and interstellar medium, the solar corona, the solar wind and the Earth’s magnetosphere, just to mention a few examples. Energy dissipation of turbulent fluctuations plays a key role in plasma heating and energization, yet we still do not understand the underlying physical mechanisms involved. THOR is a mission designed to answer the questions of how turbulent plasma is heated and particles accelerated, how the dissipated energy is partitioned and how dissipation operates in different regimes of turbulence. THOR is a single-spacecraft mission with an orbit tuned to maximize data return from regions in near-Earth space – magnetosheath, shock, foreshock and pristine solar wind – featuring different kinds of turbulence. Here we summarize the THOR proposal submitted on 15 January 2015 to the ‘Call for a Medium-size mission opportunity in ESAs Science Programme for a launch in 2025 (M4)’. THOR has been selected by European Space Agency (ESA) for the study phase.
A scheme for the improvement of proton beam quality by the optimized dragging field from the interaction of ultraintense laser pulse with a complex double-layer target is proposed and demonstrated by one-dimensional particle-in-cell (Opic1D) simulations. The complex double-layer target consists of an overdense proton thin foil followed by a mixed hydrocarbon (CH) underdense plasma. Because of the existence of carbon ions, the dragging field in the mixed CH underdense plasma becomes stronger and flatter in the location of the proton beam than that in a pure hydrogen (H) underdense plasma. The optimized dragging field can keep trapping and accelerating protons in the mixed CH underdense target to high quality. Consequently, the energy spread of the proton beam in the mixed CH underdense plasma can be greatly reduced down to 2.6% and average energy of protons can reach to 9 GeV with circularly polarized lasers at intensities 2.74 × 1022 W/cm2.
Salience network (SN) dysconnectivity has been hypothesized to contribute to schizophrenia. Nevertheless, little is known about the functional and structural dysconnectivity of SN in subjects at risk for psychosis. We hypothesized that SN functional and structural connectivity would be disrupted in subjects with At-Risk Mental State (ARMS) and would be associated with symptom severity and disease progression.
Method
We examined 87 ARMS and 37 healthy participants using both resting-state functional magnetic resonance imaging and diffusion tensor imaging. Group differences in SN functional and structural connectivity were examined using a seed-based approach and tract-based spatial statistics. Subject-level functional connectivity measures and diffusion indices of disrupted regions were correlated with CAARMS scores and compared between ARMS with and without transition to psychosis.
Results
ARMS subjects exhibited reduced functional connectivity between the left ventral anterior insula and other SN regions. Reduced fractional anisotropy (FA) and axial diffusivity were also found along white-matter tracts in close proximity to regions of disrupted functional connectivity, including frontal-striatal-thalamic circuits and the cingulum. FA measures extracted from these disrupted white-matter regions correlated with individual symptom severity in the ARMS group. Furthermore, functional connectivity between the bilateral insula and FA at the forceps minor were further reduced in subjects who transitioned to psychosis after 2 years.
Conclusions
Our findings support the insular dysconnectivity of the proximal SN hypothesis in the early stages of psychosis. Further developed, the combined structural and functional SN assays may inform the prognosis of persons at-risk for psychosis.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
Enterotoxigenic Escherichia coli (ETEC) is a type of pathogenic bacteria that cause diarrhea in piglets through colonizing pig small intestine epithelial cells by their surface fimbriae. Different fimbriae type of ETEC including F4, F18, K99 and F41 have been isolated from diarrheal pigs. In this study, we performed a genome-wide association study to map the loci associated with the susceptibility of pigs to ETEC F41 using 39454 single nucleotide polymorphisms (SNPs) in 667 F2 pigs from a White Duroc×Erhualian F2 cross. The most significant SNP (ALGA0022658, P=5.59×10−13) located at 6.95 Mb on chromosome 4. ALGA0022658 was in high linkage disequilibrium (r2>0.5) with surrounding SNPs that span a 1.21 Mb interval. Within this 1.21 Mb region, we investigated ZFAT as a positional candidate gene. We re-sequenced cDNA of ZFAT in four pigs with different susceptibility phenotypes, and identified seven coding variants. We genotyped these seven variants in 287 unrelated pigs from 15 diverse breeds that were measured with ETEC F41 susceptibility phenotype. Five variants showed nominal significant association (P<0.05) with ETEC F41 susceptibility phenotype in International commercial pigs. This study provided refined region associated with susceptibility of pigs to ETEC F41 than that reported previously. Further works are needed to uncover the underlying causal mutation(s).