Search Results (75,868)

We report on a sporadic patient suffering Leigh syndrome characterized by bilateral lesions in the lenticular nuclei and spastic dystonia, intellectual disability, sensorineural deafness, hypertrophic cardiomyopathy, exercise intolerance, and retinitis pigmentosa. Complete sequencing of mitochondrial DNA revealed the heteroplasmic nucleotide change m.15635T>C affecting a highly conserved amino acid position (p.Ser297Pro) in the cytochrome b (MT-CYB) gene on a haplogroup K1c1a background, which includes a set of four non-synonymous polymorphisms also present in the same gene. Biochemical studies documented respiratory chain impairment due to complex III defect. This variant fulfils the criteria for being pathogenic and was previously reported in a sporadic case of fatal neonatal polyvisceral failure. Full article

Background: As individuals age, there is a gradual loss of muscle mass and strength, which not only impairs physical functionality but also heightens the risk of falls and diminishes independence among older adults. Probiotics have emerged as a focus of recent research due to their potential role in enhancing muscle health via the gut–muscle axis. This study evaluates the effects of live and heat-treated Lacticaseibacillus paracasei PS23 (PS23) supplementation on muscle strength and mass in the elderly. Methods: This study recruited 119 participants, aged 65–85 years, and randomly assigned them to receive a placebo (0 × 10¹⁰ CFU/day), L-PS23 (live PS23, 2 × 10¹⁰ CFU/day), or HT-PS23 (heat-treated PS23, 2 × 10¹⁰ cells/day) for a duration of 12 weeks. Assessments of blood pressure, body composition, muscle strength, functional physical fitness, and biochemical parameters were conducted at baseline, 6 weeks, and 12 weeks. Results: Among the 100 subjects who completed the trial, supplementation with both L-PS23 and HT-PS23 significantly enhanced lower limb muscle strength and endurance compared to the placebo (p < 0.05), although no significant differences were observed in muscle mass or upper limb muscle strength across the groups. Additionally, while most muscle anabolism-related markers showed no significant changes, both supplements effectively decreased inflammatory markers related to aging—C-reactive protein (CRP: L-PS23, p = 0.016; HT-PS23, p = 0.013) and interleukin-6 (IL-6: L-PS23, p = 0.003; HT-PS23, p < 0.001)—and increased interleukin-10 levels (L-PS23, p = 0.014; HT-PS23, p = 0.005). Notably, only the HT-PS23 group demonstrated a significant increase in testosterone levels (p = 0.029). Conclusions: 12 weeks of supplementation with L-PS23 and HT-PS23 improved lower limb muscle strength and endurance but did not significantly enhance muscle mass in older adults. Both supplements also proved effective in reducing inflammatory markers and elevating testosterone levels. HT-PS23, administered as a heat-treated probiotic, provided more pronounced benefits to the elderly compared with its probiotic counterpart, L-PS23. Full article

Objectives: The primary aim of this phase 1 trial is to establish the recommended phase 2 dose (RP2D) of tazemetostat given with a fixed dose of pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinomas (RM-HNSCCs). Methods: A 3 + 3 dose-escalation phase 1 design was used to assess three dose-levels of tazemetostat (400, 600, and 800 mg orally, twice daily) with pembrolizumab (200 mg intravenously). Cycle 1 was 35 days (tazemetostat days 1–35; pembrolizumab day 15). Subsequent cycles were 21 days (tazemetostat days 1–21; pembrolizumab day 1). Dose-limiting toxicity (DLT), assessed during cycle 1, was defined as study-drug-related grade 4 neutropenia or thrombocytopenia, grade 3 febrile neutropenia, or grade 3–4 non-hematologic adverse events (AEs). Patients had to have completed cycle 1 to be evaluable for the DLT assessment; otherwise, an equal number of additional patients were enrolled. The RP2D was defined as the highest dose level in which zero of three or less than or equal to one of six patients experienced a DLT. Results: Twelve patients were enrolled: three on 400 mg, three on 600 mg, and six on the 800 mg dose level of tazemetostat. Three patients on the 800 mg dose level did not complete cycle 1 and were not evaluable for DLT. In the other nine patients, DLTs did not occur during cycle 1. In all 12 patients, the most common AEs included anemia (10 patients), fatigue (eight), and hyponatremia (seven). Conclusions: Among the patients with RM-HNSCCs, the RP2D of tazemetostat was 800 mg and administered twice daily when given with pembrolizumab. Full article

A limp is an abnormal, uneven or laboured gait typically resulting from pain, weakness, or structural deformity involving the hip, lower limb, spine or abdominopelvic abnormalities. Limps in children are common and have diverse causes that can be benign to life-threatening including trauma, congenital malformations, and neoplastic diseases. Diagnosis involves identifying gait abnormality thoroughly examining history and physical exam, assessing tenderness and range of motion, and completing targeted lab and radiographic studies. We present an imaging review of various usual and unusual causes of limp in different age groups such as in toddlers (1–3 years), children (4–10 years), and adolescents (11–16 years) with a comprehensive literature review. Full article

Salt stress significantly reduces rice yield and deteriorates rice quality. The present study was conducted to explore the regulatory effects of sole and combined application of S-abscisic acid (S-ABA) and soil conditioner on rice under high salt stress. The experimental treatments comprised 0.1% S-ABA alone (T1), the application of soil conditioner (T2), the combined application of both S-ABA and halotolerant microorganism soil conditioner (T3), and a control without any regulatory substance (CK). The treatments were arranged in a randomized complete block design in triplicate. To simulate high salinity stress, a 0.6% saltwater solution (by mixing natural seawater with freshwater) was used for irrigation. The results showed that T3 alleviated the phytotoxic effects of high salt stress and substantially improved rice yield. Furthermore, the numbers of effective panicles, grains per panicle, and 1000-grain weight under T3 treatment were 13.3–14.5%, 8.9–14.1%, and 4.9–5.5% higher than CK owing to improvement in dry matter accumulation, SPAD values, leaf area index, antioxidant enzyme activity, and reduced malondialdehyde and sodium ion content in rice. Moreover, the T3 treatment increased the output, output rate, and conversion rate of stem sheath matter after the heading stage; improved the milling yield, starch paste viscosity, starch stickiness, and gelatinization enthalpy; and reduced rice chalkiness. In addition, the T3 treatment also increased the amylose contents and decreased the total protein contents, thereby improving the taste of the rice. Overall, the results indicated that the application of exogenous S-ABA and soil conditioner is an effective strategy to alleviate the severity of salt stress in rice. Full article

Dentine hypersensitivity (DH) causes pain from exposed dentine, triggered by external stimuli. Limited evidence exists on its impact on quality of life (QoL), the effectiveness of hypersensitivity toothpaste (HT) and the dental behaviors of DH sufferers. This study therefore aimed to generate evidence to address these evidence gaps and validate the existing science behind the effectiveness of HT. An observational retrospective cross-sectional survey was conducted in Indonesia, which included the Dentine Hypersensitivity Experience Questionnaire-15 (DHEQ-15), items related to the perceived effectiveness of HT and self-reported dental health behaviors. A total of 511 respondents completed the survey. The mean (standard deviation) DHEQ score of participants was 82.44 (14.41), showing the substantial impact of DH on QoL. Nearly all HT users (97.7%) reported relief from DH, with additional benefits like long-lasting fresh breath (96.4%) and cleaner teeth (97.1%), with regular HT users experiencing greater benefits such as improvements in DH (R-HT users [4.65 (0.55)] vs. E-HT users [4.46 (0.65)], p < 0.01). Compared to HT users, mainstream toothpaste (MT) users were significantly less likely to brush their teeth at least three times a day (HT users [41.9%], MT users [18.7%], p < 0.05) and to have had a dental check-up within the past year (HT users [82.5%], MT users [47.3%], p < 0.05). This study found that DH significantly impacts QoL, and that HT effectively relieves DH symptoms, particularly for regular users, who also show better dental health behaviors than users of mainstream toothpaste. The preliminary results indicate that educating users about dental products, like hypersensitivity toothpaste, can improve oral health behaviors and outcomes. Full article

Lake ice has a major impact on the functioning of lake ecosystems, the thermal and gas regimes of lakes, habitat conditions, socio-economic aspects of human life, local climate, etc. The multifaceted influence of lake ice makes it important to study its changes associated with global warming, including lake ice phenology, ice thickness, and the snow–ice fraction. This article presents a study of lake ice changes in different regions of Eurasia: the Arctic (Lake Imandra in the Murmansk region and Lake Kilpisjärvi in Finland), the temperate zone (six small and medium lakes in Karelia, Mozhaysk Reservoir in the Moscow region, and Lake Pääjärvi in Finland), the arid zone (Lake Ulansuhai in China), and the highlands (lakes Arpi and Sevan in Armenia). In the study regions, a statistically significant increase in winter air temperature has been recorded over the past few decades. The number of days with thaw (air temperature above 0 °C) has increased, while the number of days with severe frost (air temperature below −10 °C and −20 °C) has decreased. The share of liquid or mixed precipitation in winter increases most rapidly in the temperate zone. For two Finnish lakes, lakes Vendyurskoe and Vedlozero in Karelia, and Mozhaysk Reservoir, a decrease in the duration of the ice period was revealed, with later ice-on and earlier ice-off. The most dramatic change occurred in the large high-mountain Lake Sevan, where the water area has no longer been completely covered with ice every winter. In contrast, the small high-mountain Lake Arpi showed no significant changes in ice phenology over a 50-year period. Changes in the ice composition with an increase in the proportion of white ice and a decrease in the proportion of black ice have occurred in some lakes. In the temperate lakes Pääjärvi and Vendyurskoe, inverse dependences of the thickness of black ice on the number of days with thaw and frost in December–March for the first lake and on the amount of precipitation in the first month of ice for the second were observed. In the arid study region of China, due to the very little winter precipitation (usually less than 10 mm) only black ice occurs, and significant interannual variability in its thickness has been identified. Full article

China’s carrot planting area and total output rank first in the world, but China’s mechanized carrot harvesting level is relatively backward. There are many problems in the existing machine operation process, among which the problems of a high leakage rate and high damage rate are the main difficulties faced. In order to study this problem, a test platform composed of clamping and pulling devices and conveying devices is designed, and it can complete the experiments of clamping, pulling and conveying carrot plants and collecting carrot stalks at one time. During the test, the clamping speed was divided into four test levels: 0.40 m/s (T1), 0.85 m/s (T2), 1.30 m/s (T3), and control test (CK), and each test level was carried out three times at different forward speeds. Finally, the leakage rate and damage rate were statistically analyzed. The results show that the average damage rate of Xiahong2 is 6.13%, 3.53%, and 9.36% and that of Sanhong is 6.22%, 3.76%, and 9.88% under the clamping and conveying speeds of T1, T2, and T3 in two years. The average carrot missed-pulling rate of two consecutive years corresponding to two carrot varieties, Xiaohong2 and Sanhong, was 3.68% and 4.14%, respectively. The carrot missed-pulling rate of CK in the control group of two carrot varieties, Xiaohong2 and Sanhong, was high and stable at 96.2% to 97.5%. At the same time, T1, T2, and T3 had similar overall trends of high carrot leakage rates for two carrot varieties at different clamping and conveying speeds. This control experiment also proves that the experimental arrangement is scientific and accurate. The average carrot leakage rate of T1, T2, and T3 for Xiahong2 is 3.91%, 3.42%, and 6.22%, and that of T1, T2, and T3 for Sanhong is 4.06%. The research results can provide a theoretical basis and reference for the optimization and improvement of carrot clamping and conveying devices, and this research can provide a reference for how to reduce the harvest loss of carrot combine harvesters in China. Full article

Plant growth-promoting rhizobacteria (PGPR) are beneficial bacteria residing in the rhizosphere and are capable of enhancing plant growth through various mechanisms. Streptomyces sp. GD-4 is a plant growth-promoting bacterium isolated from the rhizosphere soil of Leymus secalinus. To further elucidate the molecular mechanisms underlying the beneficial effects of the strain on plant growth, we evaluated the growth-promoting effects of Streptomyces sp. GD-4 on forage grasses and conducted comprehensive genome mining and comparative genomic analysis of the strain. Strain GD-4 effectively colonized the rhizosphere of three forages and significantly promoted the growth of both plant roots and leaves. Genome sequence functional annotation of GD-4 revealed lots of genes associated with nitrogen, phosphorus, and sulfur metabolism. Additionally, genes potentially involved in plant growth promotion such as indole-3-acetic acid (IAA) biosynthesis, trehalose production, siderophore production, and phosphate solubilization were annotated. Whole-genome analysis revealed that GD-4 may possess molecular mechanisms involved in soil nutrient cycling in rhizosphere soil and plant growth promotion. The bacteria also possess genes associated with adaptability to abiotic stress conditions, further supporting the ability of Streptomyces sp. GD-4 to colonize nutrient-poor soils. These findings provide a foundation for further research into soil remediation technologies in plateau regions. Full article

Globally, there are two major poxvirus outbreaks: mpox, caused by the monkeypox virus, and lumpy skin disease, caused by the lumpy skin disease virus. While vaccines for both diseases exist, there is a need for improved vaccines. The original vaccines used to eradicate smallpox, which also protect from the disease now known as mpox, are no longer acceptable. This is mainly due to the risk of serious adverse events, particularly in HIV-positive people. The next-generation vaccine for mpox prevention is modified vaccinia Ankara, which does not complete the viral replication cycle in humans and, therefore, has a better safety profile. However, two modified vaccinia Ankara immunizations are needed to give good but often incomplete protection, and there are indications that the immune response will wane over time. A better vaccine that induces a long-lived response with only one immunization is desirable. Another recently available smallpox vaccine is LC16m8. While LC16m8 contains replicating vaccinia virus, it is a more attenuated vaccine than the original vaccines and has limited side effects. The commonly used lumpy skin disease vaccines are based on attenuated lumpy skin disease virus. However, an inactivated or non-infectious vaccine is desirable as the disease spreads into new territories. This article reviews novel vaccine approaches, including mRNA and subunit vaccines, to protect from poxvirus infection. Full article

Frequent agricultural irrigation events continuously raise the groundwater table on loess platforms, triggering numerous loess landslides and significantly contributing to soil erosion in the Chinese Loess Plateau. The movement of irrigation water within the surficial loess layer is crucial for comprehending the mechanisms of moisture penetration into thick layers. To investigate the infiltration and evaporation processes of irrigation water, a large undisturbed soil column with a 60 cm inner diameter and 100 cm height was extracted from the surficial loess layer. An irrigation simulation event was executed on the undisturbed soil column and the ponding infiltration and subsequent evaporation processes were systematically monitored. A ruler placed above the soil column recorded the ponding height during irrigation. Moisture probes and tensiometers were installed at five depths to monitor the temporal variations in volumetric water content (VWC) and matric suction. Additionally, an evaporation gauge and an automatic weighing balance measured the potential and actual evaporation. The results revealed that the initially high infiltration rate rapidly decreased to a stable value slightly below the saturated hydraulic conductivity (K_s). A fitted Mezencev model successfully replicated the ponding infiltration process with a high correlation coefficient of 0.995. The monitored VWC of the surficial 15 cm-thick loess approached a saturated state upon the advancing of the wetting front, while the matric suction sharply decreased from an initial high value of 65 kPa to nearly 0 kPa. The monitored evaporation process of the soil column was divided into an initial constant rate stage and a subsequent decreasing rate stage. During the constant rate stage, the actual evaporation closely matched or slightly exceeded the potential evaporation rate. In the decreasing rate stage, the actual evaporation rate fell below the potential evaporation rate. The critical VWC ranged from 26% to 28%, with the corresponding matric suction recovering to approximately 25 kPa as the evaporation process transitioned between stages. The complete evaporation process was effectively modeled using a fitted Rose model with a high correlation coefficient (R² = 0.971). These findings provide valuable insights into predicting water infiltration and evaporation capacities in loess layers, thereby enhancing the understanding of water movement within thick loess deposits and the processes driving soil erosion. Full article

This study investigates the viability of incorporating bicycles into the Dhaka Metro system, a groundbreaking urban transit project for Bangladesh. As Dhaka’s inaugural metro rail network, the system signifies a substantial advancement in addressing urban congestion and enhancing transportation alternatives in one of the world’s most densely populated cities. The current design of the metro fails to accommodate bicycles, hindering efficient first- and last-mile connectivity. The investigation utilized data from 382 fully completed questionnaires, obtained through purposive sampling, about metro–cycle integration in Dhaka. The research employed RIDIT and TOPSIS analyses to rank the characteristics deemed most essential for bicycle–metro integration according to user opinions. Research indicates that secure bicycle parking, multi-modal ticketing, route comfort, and safety measures are the foremost objectives for commuters. The high emphasis on secure parking indicates the need for safe and accessible storage options that would make cycling a viable mode for reaching metro stations. A multi-modal ticketing system further enhances convenience, providing seamless transitions between transit modes. Journey comfort and the need to mitigate risks posed by motorized vehicles underscore the importance of safe and user-friendly commuting environments. While features like road and station design were ranked lower in priority, the study emphasizes that a well-integrated bicycle infrastructure is essential to ensure the metro system’s success. With these improvements, Dhaka’s metro system can meet the growing demands for sustainable and inclusive urban mobility, setting a precedent for future infrastructure projects in Bangladesh. Full article

Background/Objectives: Randomized controlled trials (RCTs) are needed to evaluate the impact of food is medicine (FIM) programs, such as medically tailored groceries (MTGs) to treat hypertension among diverse populations. Partnerships between academic centers’ student-run organizations (SROs) and community-based organizations (CBOs) offer critical safety nets for historically underserved groups, positioning these organizations to effectively undertake FIM programs among populations disproportionately affected by hypertension. We conducted an unblinded pilot RCT whose objectives were to assess the feasibility and acceptability of an SRO-coordinated, CBO-partnered MTGs intervention targeting blood pressure (BP) and food insecurity (FI) in underserved groups. Methods: Adult Black/African American and Hispanic/Latinx patients in Durham, North Carolina, where essential hypertension and FI were randomized (parallel arm, computerized 1:1 ratio) to 12 weeks of home-delivered, hypertension-focused MTGs plus in-person nutrition education sessions with compensation (intervention) versus data collection sessions with compensation (control). We offered transportation, childcare, and home visits to facilitate session attendance. The primary outcomes were the eligibility, enrollment, and retention rates (feasibility), and the survey feedback from the participants and CBO partners (acceptability). The secondary outcomes included the changes in the mean BP and median FI score with associated 95% confidence intervals. Results: Medical record screening identified 1577 eligible participants. Of the 94 reached to confirm eligibility, 77 met the enrollment criteria, and 50 were randomized (82% post-screen eligibility, 65% enrollment). A conventional content analysis of 15 participant surveys and CBO partner feedback affirmed the acceptability, noting intervention components that enhanced the retention (e.g., home delivery, transportation support, home visits). Pre–post analyses of secondary outcomes for 13/25 intervention and 15/25 control participants completing ≥2 sessions ≥2 months apart were performed. The intervention was associated with an average change in systolic BP of −14.2 mmHg (−27.5, −4.5) versus −3.5 mmHg (−11.7, 5.9) in the control group. The FI scores improved by −2 (−2.2, −0.5) in the intervention group and −1 (−1.3, −0.2) in the control group. No adverse events were reported. Conclusions: SRO-CBO partnerships could be feasible and acceptable avenues for conducting FIM trials among underserved populations. This multi-component FIM approach enhanced the study equity by addressing the participants’ disease-related social needs and warrants expansion into a powered RCT. Full article

Background/Objectives: Depressive disorders are diagnosed using categorical definitions provided by DSM-5 and ICD-11. However, categorization for diagnostic purposes fails to account for the inherently dimensional nature of depression. Artificial categorization may impede research and obstruct the achievement of optimal treatment outcomes. Methods: The current study utilized a Canadian historical dataset called the National Population Health Survey (NPHS) to explore a simple alternative approach that does not depend on categorization. The NPHS collected complete data from 5029 participants through biannual interviews conducted in 1994–2010. Data collection included the K6 Distress Scale as well as the Composite International Diagnostic Interview Short Form for Major Depression. Data from the National Population Health Survey (NPHS) were used to quantify vulnerability to depressive symptoms through longitudinal K6 Distress Scale assessments. Variability of symptoms across this dimension of apparent vulnerability was quantified using ordinal regression, adjusting for age and sex. Results: Predicted probabilities from these models were used in simulations to produce a visualization of the epidemiology and to explore clinical implications. Conclusions: Consideration of these two dimensional factors (estimated overall level of vulnerability to depression and variability over time) is already a component of clinical assessment and is also accessible to repeated measurement in settings adopting measurement-based care. More formal consideration of these elements may provide a complementary approach to categorical diagnostic assessment and an opportunity for greater personalization of care and improved clinical outcomes. Future studies should validate these findings in diverse clinical settings to ensure their applicability in real-world contexts. Full article

Estimating the sparse covariance matrix can effectively identify important features and patterns, and traditional estimation methods require complete data vectors on all subjects. When data are left-censored due to detection limits, common strategies such as excluding censored individuals or replacing censored values with suitable constants may result in large biases. In this paper, we propose two penalized log-likelihood estimators, incorporating the $L_1$ penalty and SCAD penalty, for estimating the sparse covariance matrix of a multivariate normal distribution in the presence of left-censored data. However, the fitting of these penalized estimators poses challenges due to the observed log-likelihood involving high-dimensional integration over the censored variables. To address this issue, we treat censored data as a special case of incomplete data and employ the Expectation Maximization algorithm combined with the coordinate descent algorithm to efficiently fit the two penalized estimators. Through simulation studies, we demonstrate that both penalized estimators achieve greater estimation accuracy compared to methods that replace censored values with constants. Moreover, the SCAD penalized estimator generally outperforms the $L_1$ penalized estimator. Our method is used to analyze the proteomic datasets. Full article