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Mahvash disease, a rare autosomal recessive metabolic disorder characterized by biallelic loss-of-function mutations in the glucagon receptor gene (GCGR), induces significant pancreatic hyperglucagonemia, resulting in α-cell hyperplasia and occasional hypoglycemia. Utilizing CRISPR-Cas9 technology, we engineered a mouse model, designated as GcgrV369M/V369M, harboring a homozygous V369M substitution in the glucagon receptor (GCGR). Although wild-type (WT) and GcgrV369M/V369M mice exhibited no discernible difference in appearance or weight, adult GcgrV369M/V369M mice, approximately 12 months of age, displayed a notable decrease in fasting blood glucose levels and elevated the levels of cholesterol and low-density lipoprotein-cholesterol. Moreover, plasma amino acid levels such as alanine (Ala), proline (Pro) and arginine (Arg) were elevated in GcgrV369M/V369M mice contributing to α-cell proliferation and hyperglucagonemia. Despite sustained α-cell hyperplasia and increased circulating glucagon levels in GcgrV369M/V369M mice, metabolic disparities between the two groups gradually waned with age accompanied by a reduction in α-cell hyperplasia. Throughout the lifespan of the mice (up to approximately 30 months), pancreatic neuroendocrine tumors (PNETs) did not manifest. This prolonged observation of metabolic alterations in GcgrV369M/V369M mice furnishes valuable insights for a deeper comprehension of mild Mahvash disease in humans.

IntroductionAging is a complex, time-dependent biological process that involves a decline of overall function. Over the past decade, the field of intestinal microbiota associated with aging has received considerable attention. However, there is limited information surrounding microbiota-gut-brain axis (MGBA) to further reveal the mechanism of aging.MethodsIn this study, locomotory function and sensory function were evaluated through a series of behavioral tests.Metabolic profiling were determined by using indirect calorimetry.16s rRNA sequence and targeted metabolomics analyses were performed to investigate alterations in the gut microbiota and fecal short-chain fatty acids (SCFAs). The serum cytokines were detected by a multiplex cytokine assay.The expression of proinflammatory factors were detected by western blotting.ResultsDecreased locomotor activity, decreased pain sensitivity, and reduced respiratory metabolic profiling were observed in aged mice. High-throughput sequencing revealed that the levels of genus Lactobacillus and Dubosiella were reduced, and the levels of genus Alistipes and Bacteroides were increased in aged mice. Certain bacterial genus were directly associated with the decline of physiological behaviors in aged mice. Furthermore, the amount of fecal SCFAs in aged mice was decreased, accompanied by an upregulation in the circulating pro-inflammatory cytokines and increased expression of inflammatory factors in the brain.DiscussionAging-induced microbial dysbiosis was closely related with the overall decline in behavior, which may attribute to the changes in metabolic products, e.g., SCFAs, caused by an alteration in the gut microbiota, leading to inflammaging and contributing to neurological deficits. Investigating the MGBA might provide a novel viewpoint to exploring the pathogenesis of aging and expanding appropriate therapeutic targets.

Despite the fact that physical and chemical processes have been widely proposed to explicate the stabilization mechanisms of soil organic carbon (SOC), thebioavailability of SOC linked to soil physical structure, microbial community structure, and functional genes remains poorly understood. This study aims to investigate the SOC division based on bioavailability differences formed by physical isolation, and to clarify the relationships of SOC bioavailability with soil elements, pore characteristics, and microbial activity. Results revealed that soil element abundances such as SOC, TN, and DOC ranked in the same order as the soil porosity as clay > silt ≥ coarse sand > fine sand in both top and sub soil. In contrast to silt and clay, which had reduced SOC bioavailability, fine sand and coarse sand had dramatically enhanced SOC bioavailability compared to the bulk soil. The bacterial and fungal community structure was significantly influenced by particle size, porosity, and soil elements. Copiotrophic bacteria and functional genes were more prevalent in fine sand than clay, which also contained more oligotrophic bacteria. The SOC bioavailability was positively correlated with abundances of functional genes, C degradation genes, and copiotrophic bacteria, but negatively correlated with abundances of soil elements, porosity, oligotrophic bacteria, and microbial biomass (p

Abstract Spinal cord injury (SCI) can reshape gut microbial composition, significantly affecting clinical outcomes in SCI patients. However, mechanisms regarding gut–brain interactions and their clinical implications have not been elucidated. We hypothesized that short-chain fatty acids (SCFAs), intestinal microbial bioactive metabolites, may significantly affect the gut–brain axis and enhance functional recovery in a mouse model of SCI. We enrolled 59 SCI patients and 27 healthy control subjects and collected samples. Thereafter, gut microbiota and SCFAs were analyzed using 16 S rDNA sequencing and gas chromatography–mass spectrometry, respectively. We observed an increase in Actinobacteriota abundance and a decrease in Firmicutes abundance. Particularly, the SCFA-producing genera, such as Faecalibacterium, Megamonas, and Agathobacter were significantly downregulated among SCI patients compared to healthy controls. Moreover, SCI induced downregulation of acetic acid (AA), propionic acid (PA), and butyric acid (BA) in the SCI group. Fecal SCFA contents were altered in SCI patients with different injury course and injury segments. Main SCFAs (AA, BA, and PA) were administered in combination to treat SCI mice. SCFA supplementation significantly improved locomotor recovery in SCI mice, enhanced neuronal survival, promoted axonal formation, reduced astrogliosis, and suppressed microglial activation. Furthermore, SCFA supplementation downregulated NF-κB signaling while upregulating neurotrophin-3 expression following SCI. Microbial sequencing and metabolomics analysis showed that SCI patients exhibited a lower level of certain SCFAs and related bacterial strains than healthy controls. SCFA supplementation can reduce inflammation and enhance nourishing elements, facilitating the restoration of neurological tissues and the improvement of functional recuperation. Trial registration: This study was registered in the China Clinical Trial Registry ( www.chictr.org.cn ) on February 13, 2017 (ChiCTR-RPC-17010621).

In recent years, short-term composting techniques have been widely applied in oyster mushroom cultivation, but there is still a lack of systematic research on their impact on the nutritional and functional properties of fruiting bodies. In this study, the microbial inoculant Streptomyces thermoviolaceus BUA-FM01 (ST) was applied in the short-term composting process for oyster mushroom cultivation. The agronomic traits, nutritional composition, flavor compounds, and antioxidant activity of fruiting bodies from the first three flushes were evaluated. The results show that microbial inoculation significantly (p < 0.05) reduced the total carbon content and C/N ratio of the composted substrates and, furthermore, increased the total yield of the fruiting bodies. Moreover, microbial inoculation significantly (p < 0.05) increased the crude protein, crude polysaccharide, total amino acid, and essential amino acid contents of the fruiting bodies. The fruiting bodies of the first flush of ST treatment possessed the highest umami amino acid content and equivalent umami concentration value. Furthermore, microbial inoculation significantly (p < 0.05) enhanced the scavenging ability of crude polysaccharides toward free radicals. The results indicate that microbial inoculation has many benefits for the composting cultivating process of oyster mushrooms and good application prospects.

BackgroundEndometrioid adenocarcinoma is usually diagnosed by endometrial curettage with a positive rate of 94%, while a hysteroscopic examination can increase the positive rate. Differently, endometrioid adenocarcinoma arising from adenomyosis (EAAFA) is always misdiagnosed, even after endometrial curettage or hysteroscopy. EAAFA is rarely reported.Case descriptionWe reported two cases of EAAFA with long-term follow-ups of 9–10 years. The two cases were misdiagnosed even if endometrial curettage or hysteroscopy was performed. One case complained of postmenopausal vaginal bleeding with elevated CA199, and she was diagnosed by fast-frozen pathology during hysterectomy, followed by bilateral salpingo-oophorectomy and pelvic lymphadenectomy. In another case, a premenopausal woman with acquired progressive dysmenorrhea was diagnosed as EAAFA by the histopathological result after a transvaginal hysterectomy and had to undergo reoperation. The FIGO stage was IB in both cases. Chemotherapy or radiotherapy was performed after the operation. Patients were followed up for 9–10 years, with no metastasis or recurrence being observed.ConclusionThe diagnosis of EAAFA is always delayed because of tumor-free eutopic endometrium and negative results of the endometrial curettage or hysteroscopy examination. Fast-frozen pathology of the whole uterus helps diagnose EAAFA precisely and avoids reoperation. Adenocarcinoma foci of EAAFA usually involve the myometrium deeply. A better prognosis of EAAFA should be expected due to good differentiation and negative lymphovascular space invasion.

ABSTRACT The primary traumatic event that causes spinal cord injury (SCI) is followed by a progressive secondary injury featured by vascular disruption and ischemia, inflammatory responses and the release of cytotoxic debris, which collectively add to the hostile microenvironment of the lesioned cord and inhibit tissue regeneration and functional recovery. In a previous study, we reported that fecal microbiota transplantation (FMT) promotes functional recovery in a contusion SCI mouse model; yet whether and how FMT treatment may impact the microenvironment at the injury site are not well known. In the current study, we examined individual niche components and investigated the effects of FMT on microcirculation, inflammation and trophic factor secretion in the spinal cord of SCI mice. FMT treatment significantly improved spinal cord tissue sparing, vascular perfusion and pericyte coverage and blood-spinal cord-barrier (BSCB) integrity, suppressed the activation of microglia and astrocytes, and enhanced the secretion of neurotrophic factors. Suppression of inflammation and upregulation of trophic factors, jointly, may rebalance the niche homeostasis at the injury site and render it favorable for reparative and regenerative processes, eventually leading to functional recovery. Furthermore, microbiota metabolic profiling revealed that amino acids including β-alanine constituted a major part of the differentially detected metabolites between the groups. Supplementation of β-alanine in SCI mice reduced BSCB permeability and increased the number of surviving neurons, suggesting that β-alanine may be one of the mediators of FMT that participates in the modulation and rebalancing of the microenvironment at the injured spinal cord. IMPORTANCE FMT treatment shows a profound impact on the microenvironment that involves microcirculation, blood-spinal cord-barrier, activation of immune cells, and secretion of neurotrophic factors. Analysis of metabolic profiles reveals around 22 differentially detected metabolites between the groups, and β-alanine was further chosen for functional validation experiments. Supplementation of SCI mice with β-alanine significantly improves neuronal survival, and the integrity of blood-spinal cord-barrier at the lesion site, suggesting that β-alanine might be one of the mediators following FMT that has contributed to the recovery.

This study was to investigate the association between food insecurity (FI) and sleep disturbance among adolescents. Based on the cross-sectional data of the Global School-based Student Health Survey, this study analyzed self-reported data from adolescents in 68 countries. Multivariate logistic regression and meta-analysis were used to evaluate the association between FI and sleep disturbance. The final sample included 223,561 adolescents. The prevalence of severe FI and sleep disturbance was 6.4% and 8.0%, respectively. Severe FI was significantly associated with a higher risk of sleep disturbance in 48 of the 68 countries after adjusting for covariates, with a pooled OR (95% CI) of 1.94 (1.79–2.09). Overall, the association between FI and sleep disturbance was similar across countries and gender, though a large level of heterogeneity existed across upper- and middle-income countries. Identifying adolescents suffering from FI and remedying the FI severity may be important to improve sleep quality in global adolescents.

Metformin (MET), the most common medicine for type 2 diabetes (T2DM), improves insulin sensitivity by targeting the liver, intestine and other organs. Its impact on expression of the solute carrier (Slc) transporter genes have not been reported in the mechanism of insulin sensitization. In this study, we examined Slc gene expression in the liver and colon of diet-induced obese (DIO) mice treated with MET by transcriptomic analysis. There were 939 differentially expressed genes (DEGs) in the liver of DIO mice vs lean mice, which included 34 Slc genes. MET altered 489 DEGs in the liver of DIO mice, in which 23 were Slc genes. Expression of 20 MET-responsive Slc DEGs was confirmed by qRT-PCR, in which 15 Slc genes were altered in DIO mice and their expressions were restored by MET, including Slc2a10, Slc2a13, Slc5a9, Slc6a14, Slc7a9, Slc9a2, Slc9a3, Slc13a2, Slc15a2, Slc26a3, Slc34a2, Slc37a1, Slc44a4, Slc51b and Slc52a3. While, there were only 97 DEGs in the colon of DIO mice with 5 Slc genes, whose expression was not restored by MET. The data suggest that more genes were altered in the liver over the colon by the high fat diet (HFD). There were 20 Slc genes with alteration confirmed in the liver of DIO mice and 15 of them were restored by MET, which was associated with improvement of insulin sensitivity and obesity. The restoration may improve the uptake of glucose, amino acids, mannose, fructose, 1,5-anhydro-D-glucitol and bumetanide in hepatocytes of the liver of DIO mice. The study provides new insight into the mechanism of metformin action in insulin sensitization and obesity.

The integrated INS/magnetometer measurement is widely used in low-cost navigation systems. The integration has proven more effective in suppressing the divergence of heading than relying solely on a magnetometer because this is susceptible to local magnetic field interference, reducing heading accuracy. Magnetometers sense the local magnetic field that may be interfered by the nearby ferromagnetic material or strong electric currents. Hence, the magnetometer must be calibrated in the vehicle before use. When a magnetometer is installed near power components (engines, etc.), soft iron interference can be ignored. In the vehicle’s external environment, the time-varying hard iron interference can reach 100 times the strength of the geomagnetic field, meaning that a magnetometer cannot function efficiently because its accuracy is so reduced. Hence, the constant hard magnetic interference inside the vehicle is mainly concerned in this paper. An INS/Magnetometer heading estimation algorithm based on a two-stage Kalman filter is proposed to solve the problem by combining inertial sensor and magnetometer with attitude information. In the first stage filter, the constant hard iron interference is estimated by setting upward standing the three IMU axes. In the second stage filter, the INS/Magnetometer heading estimation is implemented. Finally, the results show that the algorithm improves the accuracy of vehicle heading calculations.

Research has consistently found that poor family functioning is a risk factor for adolescents' internalizing problems. However, studies of the mediating and moderating mechanisms underlying this relation are insufficient. In this study, we explore the association between family functioning and adolescents' internalizing problems by testing the mediating roles of positive youth development (PYD) attributes and the moderating role of migrant status. A large cross-sectional sample of 11,865 Chinese adolescents (mean age = 14.45 years, standard deviation = 1.55 years) were used to measure internalizing problems, family functioning, PYD, migrant status, and other demographic information. After controlling for covariates (age, gender, grade, and socioeconomic status), the results revealed that PYD mediated the relation between family functioning and internalizing problems. Moreover, migrant status moderated the relationship between family functioning and internalizing problems. Specifically, the effects of family functioning on internalizing problems were stronger among local-born adolescents than among migrant adolescents. The findings indicate that improving family functioning and PYD attributes may be promising approaches to prevent/reduce adolescent internalizing problems.

Abstract Metabonomics/metabolomics is a rapid technology for comprehensive profiling of small molecule metabolites in cells, tissues, or whole organisms, the application of which has led to understanding pathophysiologic mechanisms of cardiometabolic diseases, defining predictive biomarkers for those diseases, and also assessing the efficacious effects of incident drugs. In this study, proton nuclear magnetic resonance (NMR)-based metabonomics was employed to identify the metabolic changes in rat plasma caused by myocardial ischemia-reperfusion injury (MIRI), and to compare the metabolic regulatory differences between traditional Chinese medicine Wenxin Keli (WXKL) and Western medicine verapamil. The results revealed that energy-substrate metabolism were significantly disturbed by ischemia-reperfusion (I/R) in myocardium and bulk of the key metabolites could be further modulated by verapamil and/or WXKL. Lipid metabolism and amino acid transamination occurred mainly following the treatment of verapamil, whereas glucose oxidation and BCAA degradation were prominently ameliorated by WXKL to content the energy demands of heart. Moreover, both WXKL and verapamil improved the secretions of taurine and ketone bodies to overcome the oxidative stress and the shortage of energy sources induced by ischemia-reperfusion.

In this study, we analyzed microbial community composition and the functional capacities of degraded sites and restored/natural sites in two typical wetlands of Northeast China—the Phragmites marsh and the Carex marsh, respectively. The degradation of these wetlands, caused by grazing or land drainage for irrigation, alters microbial community components and functional structures, in addition to changing the aboveground vegetation and soil geochemical properties. Bacterial and fungal diversity at the degraded sites were significantly lower than those at restored/natural sites, indicating that soil microbial groups were sensitive to disturbances in wetland ecosystems. Further, a combined analysis using high-throughput sequencing and GeoChip arrays showed that the abundance of carbon fixation and degradation, and ~95% genes involved in nitrogen cycling were increased in abundance at grazed Phragmites sites, likely due to the stimulating impact of urine and dung deposition. In contrast, the abundance of genes involved in methane cycling was significantly increased in restored wetlands. Particularly, we found that microbial composition and activity gradually shifts according to the hierarchical marsh sites. Altogether, this study demonstrated that microbial communities as a whole could respond to wetland changes and revealed the functional potential of microbes in regulating biogeochemical cycles.

In this paper, an improved inertial frame alignment algorithm for a marine SINS under mooring conditions is proposed, which significantly improves accuracy. Since the horizontal alignment is easy to complete, and a characteristic of gravity is that its component in the horizontal plane is zero, we use a clever method to improve the conventional inertial alignment algorithm. Firstly, a large misalignment angle model and a dimensionality reduction Gauss-Hermite filter are employed to establish the fine horizontal reference frame. Based on this, the projection of the gravity in the body inertial coordinate frame can be calculated easily. Then, the initial alignment algorithm is accomplished through an inertial frame alignment algorithm. The simulation and experiment results show that the improved initial alignment algorithm performs better than the conventional inertial alignment algorithm, and meets the accuracy requirements of a medium-accuracy marine SINS.

Two different coarse alignment algorithms for Fiber Optic Gyro (FOG) Inertial Navigation System (INS) based on inertial reference frame are discussed in this paper. Both of them are based on gravity vector integration, therefore, the performance of these algorithms is determined by integration time. In previous works, integration time is selected by experience. In order to give a criterion for the selection process, and make the selection of the integration time more accurate, optimal parameter design of these algorithms for FOG INS is performed in this paper. The design process is accomplished based on the analysis of the error characteristics of these two coarse alignment algorithms. Moreover, this analysis and optimal parameter design allow us to make an adequate selection of the most accurate algorithm for FOG INS according to the actual operational conditions. The analysis and simulation results show that the parameter provided by this work is the optimal value, and indicate that in different operational conditions, the coarse alignment algorithms adopted for FOG INS are different in order to achieve better performance. Lastly, the experiment results validate the effectiveness of the proposed algorithm.

Foot-mounted Inertial Pedestrian-Positioning Systems (FIPPSs) based on Micro Inertial Measurement Units (MIMUs), have recently attracted widespread attention with the rapid development of MIMUs. The can be used in challenging environments such as firefighting and the military, even without augmenting with Global Navigation Satellite System (GNSS). Zero Velocity Update (ZUPT) provides a solution for the accumulated positioning errors produced by the low precision and high noise of the MIMU, however, there are some problems using ZUPT for FIPPS, include fast-initial alignment and unobserved heading misalignment angle, which are addressed in this paper. Our first contribution is proposing a fast-initial alignment algorithm for foot-mounted inertial/magnetometer pedestrian positioning based on the Adaptive Gradient Descent Algorithm (AGDA). Considering the characteristics of gravity and Earth’s magnetic field, measured by accelerometers and magnetometers, respectively, when the pedestrian is standing at one place, the AGDA is introduced as the fast-initial alignment. The AGDA is able to estimate the initial attitude and enhance the ability of magnetic disturbance suppression. Our second contribution in this paper is proposing an inertial/magnetometer positioning algorithm based on an adaptive Kalman filter to solve the problem of the unobserved heading misalignment angle. The algorithm utilizes heading misalignment angle as an observation for the Kalman filter and can improve the accuracy of pedestrian position by compensating for magnetic disturbances. In addition, introducing an adaptive parameter in the Kalman filter is able to compensate the varying magnetic disturbance for each ZUPT instant during the walking phase of the pedestrian. The performance of the proposed method is examined by conducting pedestrian test trajectory using MTi-G710 manufacture by XSENS. The experimental results verify the effectiveness and applicability of the proposed method.

In the current study, we employed high-resolution proton and carbon nuclear magnetic resonance spectroscopy (1H and 13C NMR) for quantitative analysis of glycerol in drug injections without any complex pre-treatment or derivatization on samples. The established methods were validated with good specificity, linearity, accuracy, precision, stability, and repeatability. Our results revealed that the contents of glycerol were convenient to calculate directly via the integration ratios of peak areas with an internal standard in 1H NMR spectra, while the integration of peak heights were proper for 13C NMR in combination with an external calibration of glycerol. The developed methods were both successfully applied in drug injections. Quantitative NMR methods showed an extensive prospect for glycerol determination in various liquid samples.

Pedestrian-positioning technology based on the foot-mounted micro inertial measurement unit (MIMU) plays an important role in the field of indoor navigation and has received extensive attention in recent years. However, the positioning accuracy of the inertial-based pedestrian-positioning method is rapidly reduced because of the relatively low measurement accuracy of the measurement sensor. The zero-velocity update (ZUPT) is an error correction method which was proposed to solve the cumulative error because, on a regular basis, the foot is stationary during the ordinary gait; this is intended to reduce the position error growth of the system. However, the traditional ZUPT has poor performance because the time of foot touchdown is short when the pedestrians move faster, which decreases the positioning accuracy. Considering these problems, a forward and reverse calculation method based on the adaptive zero-velocity interval adjustment for the foot-mounted MIMU location method is proposed in this paper. To solve the inaccuracy of the zero-velocity interval detector during fast pedestrian movement where the contact time of the foot on the ground is short, an adaptive zero-velocity interval detection algorithm based on fuzzy logic reasoning is presented in this paper. In addition, to improve the effectiveness of the ZUPT algorithm, forward and reverse multiple solutions are presented. Finally, with the basic principles and derivation process of this method, the MTi-G710 produced by the XSENS company is used to complete the test. The experimental results verify the correctness and applicability of the proposed method.

The primary metabolites in aqueous extract of mulberry (Morus alba L.) leaves were characterized by using proton nuclear magnetic resonance (1H-NMR) spectroscopy. With the convenience of resonance assignment, GABA together with the other 10 primary metabolites was simultaneously identified and quantified in one 1H-NMR spectrum. In this study, external calibration curves for metabolites were employed to calculate the concentrations of interests. The proposed quantitative approach was demonstrated with good linearity (r2 ranged in the interval of 0.9965–0.9999), precision, repeatability, stability (RSD values in the ranges of 0.35–4.89%, 0.77–7.13% and 0.28–2.33%, respectively) and accuracy (recovery rates from 89.2% to 118.5%). The established 1H-NMR method was then successfully applied to quantify 11 primary metabolites in mulberry leaves from different geographical regions within a rapid analysis time and a simple sample preparation procedure.

To improve the ability of autonomous navigation for Unmanned Surface Vehicles (USVs), multi-sensor integrated navigation based on Inertial Navigation System (INS), Celestial Navigation System (CNS) and Doppler Velocity Log (DVL) is proposed. The CNS position and the DVL velocity are introduced as the reference information to correct the INS divergence error. The autonomy of the integrated system based on INS/CNS/DVL is much better compared with the integration based on INS/GNSS alone. However, the accuracy of DVL velocity and CNS position are decreased by the measurement noise of DVL and bad weather, respectively. Hence, the INS divergence error cannot be estimated and corrected by the reference information. To resolve the problem, the Adaptive Information Sharing Factor Federated Filter (AISFF) is introduced to fuse data. The information sharing factor of the Federated Filter is adaptively adjusted to maintaining multiple component solutions usable as back-ups, which can improve the reliability of overall system. The effectiveness of this approach is demonstrated by simulation and experiment, the results show that for the INS/CNS/DVL integrated system, when the DVL velocity accuracy is decreased and the CNS cannot work under bad weather conditions, the INS/CNS/DVL integrated system can operate stably based on the AISFF method.

Adsorption behavior of 17α-ethinylestradiol (EE2) in northern Taihu Lake sediment was analyzed by using batch equilibrium experiment. Freundlich isotherm could describe the adsorption thermodynamic behavior of EE2 in sediment. Sediment organic matter (SOM) contents had important impacts on the adsorption capacity for EE2. The pH values also influenced the adsorption capacity for EE2. Increase of pH value could decrease the EE2 adsorption, which might be due to the electrostatic repulsion between the anionic form of EE2 and sediments with negative charge under high pH values. Competitive effects of bisphenol A (BPA) on EE2 adsorption were further analyzed. The results showed that low concentration BPA did not have significant influences on EE2 adsorption. However, high concentration BPA could reduce EE2 adsorption, which might be due to the similar molecular diameter of BPA with adsorption sites and one more benzene ring with a hydroxyl group in BPA. These results provide primary information of EE2 adsorption in sediment-water system in Taihu Lake, which is useful for the environmental risk assessment and management of EE2 in studied area.

This special issue expands our understanding of literacy and language development of individuals who are d/Deaf and hard of hearing (d/DHH), with a focus on those with a Southeast Asian background. These studies highlight the different research methodologies that can be utilized when researching a low-incidence population in a particular region (e.g., single case design, case study). With six manuscripts, this special issue provided a glimpse into research being conducted with learners who are d/DHH and multilingual in Southeast Asia and in the immigrant population within the United States and Canada.