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Yoga MAT: A factorial randomized study using the Multiphase Optimization Strategy to develop a multicomponent yoga intervention for people with chronic pain taking medications for opioid use disorder.

BACKGROUND: People taking medications for opioid use disorder (MOUD) commonly experience chronic pain. Yoga interventions show promise for decreasing pain-related disability in other populations. More time spent in yoga practice may improve pain-related outcomes. METHODS: The Multiphase Optimization Strategy (MOST) provided the framework for developing an optimized yoga intervention package. In a 2x2x2x2 factorial experiment, we evaluated four candidate intervention components which, when added to a weekly yoga class, might increase yoga engagement. The primary outcome was minutes per week of yoga practice (classes and other yoga practice) over the 12-week intervention period. We sought to determine which combination of intervention components was associated with the most yoga practice for people with chronic pain taking buprenorphine or methadone as MOUD. RESULTS: We enrolled 192 adults. There was a significant main effect for Component "B" (having two private sessions with a yoga teachers; IRR = 1.10, 90%CI 1.02; 1.18), and a synergistic interaction between Components "B" and "D" (D was financial incentives for attending class; IRR = 1.11, 90%CI 1.02; 1.19). This combination of these two components (without other potential components) was associated with the second highest model-predicted mean minutes of yoga per week (157.1min; 90% CI = 120.1-194.0) which was only 4min less than the combination including all four components. CONCLUSIONS: We identified a combination of intervention components as the optimized intervention. A next step will be to test the effect of this optimized intervention on pain and substance use outcomes in a randomized controlled clinical trial.

Humans

Diversification of yeast proteins as an approach for the development of sustainable food systems.

Despite growing trend in sustainable protein sources, yeast proteins have mainly been explored as a source of bioactive peptides using a monospecies and general protein approach. The contribution of highly abundant protein fractions in the yeast proteome to peptide formation remains insufficiently investigated, limiting a comprehensive understanding of yeast proteins as optimized peptide sources. The current review presents a systematic analysis of yeast proteins as emerging protein sources and evaluates the suitability of high-abundance proteins as bioactive peptide precursors by in silico techniques. Moreover, brewery by-product and single-cell yeast protein approaches are compared in terms of composition and techno-functionality whereas peptide formation mechanisms (in situ and ex situ) and regulatory aspects for food applications are also addressed. Cytoplasmic metabolic proteins, particularly glycolytic enzymes (GAPDH), are identified as highly abundant fractions of the yeast proteome. Proteins associated with cell and organelle membranes also contribute substantially based on cellular localization. These findings imply that such proteins may act as key precursors of yeast-derived bioactive peptides. In silico hydrolysis with Alcalase suggests a tendency toward the generation of short-chain peptides (3-11/14 aa), which may support biological activity. Moreover, peptide profiles appear to vary across yeast species, highlighting the role of species diversity in peptide generation. While single-cell yeast protein allows more controlled production than brewery by-products, nucleic acid content in both may limit applications. Overall, yeast proteins appear to be metabolically adaptable and species-diverse sources for various biological peptides.

Saccharomyces cerevisiae

Microbial allies in a cotton pest: A descriptive account of associated microbiota dynamics in Dysdercus cingulatus across development.

BACKGROUND: Hemipteran insects harbour several symbiotic partners, mainly bacteria, which play pivotal roles for hosts like dietary provision, support overall physiology, xenobiotic degradation and manipulate/regulate behaviour. Most of these symbionts usually reside and operate from the digestive tracts of the animals. Cotton is one of the major cash crops in India and Dysdercus cingulatus (D. cingulatus) though a secondary pest, is causing significant destruction of cotton bolls, poor lint quality and reduce oil content of seeds. Premature opening of cotton bolls often leads to bacterial and fungal infections, thus resulting in extensive economic loss worldwide. D. cingulatus is a hemimetabolous insect that comprises of developmental stages like egg, nymph (5 instar stages), and adult. The present work explored the ontogeny specific diversity in the associated microbiota and predicted their probable functional inputs in D. cingulatus. RESULTS: The data obtained using 16S rRNA gene sequencing (NovaSeq 6000) revealed presence of members of Proteobacteria (65.83%), Firmicutes (24%), Actinobacteria (10%) phyla throughout the ontogeny of D. cingulatus. Highest alpha diversity of these symbiotic bacteria was recorded in the third instar nymphs in contrast to rest of the developmental stages. Among all the observed genera, Stenotrophomonas, Hungatella and Glutamicibacter were predominant from egg to adult stages. MicFunPred, a tool used for predicting the probable functional inputs of these symbionts, hinted at their probable stage specific contribution in crucial biochemical pathways such as polyketide biosynthesis, ascorbate/aldarate metabolism, pentose phosphate and glyoxylate cycles, steroid hormone and peptidoglycan biosynthesis, and glycolysis/pyruvate metabolism. CONCLUSIONS: The primary investigations on the ontogenetic composition and diversity of associated microbiota, suggest dynamic shifts in D. cingulatus, concurrent with their probable functions/roles in the host development and metabolism. To the best of our knowledge, this is the first report on symbiotic microbiota variation across the developmental stages of D. cingulatus that provides preliminary descriptive observations that may guide future functional and experimental investigations into microbiota-based pest management.

Animals

The musculoskeletal pain literacy questionnaire (MSK-PLq) - Part 1: Development of a preliminary version through a systematic review and Delphi consensus.

OBJECTIVE: Chronic musculoskeletal (MSK) pain is a leading cause of disability worldwide, and self-management is a first-line approach recommended by international clinical guidelines. Access to evidence-based information that enhances health literacy may support patients' engagement in their self-management and treatment decision-making, potentially reducing disease burden and pain. However, no tool currently exists to assess health literacy specifically in MSK pain. This study aimed to develop and describe the preliminary version of a knowledge-based questionnaire to evaluate MSK pain literacy, the Musculoskeletal Pain-Literacy questionnaire (MSK-PLq). METHODS: A systematic literature review identified existing health literacy instruments and generated a preliminary list of domains. A two-round Delphi study with 22 panellists (19 experts and three people living with chronic MSK pain), followed by consensus meetings, was used to refine domains and items (≥70% agreement). Readability was assessed using the Flesch Reading Ease (FRE) score and three stakeholders were consulted to review the questionnaire for comprehensibility, clarity, and face validity. RESULTS: Six domains were retained (Understand, Access, Appraise, Apply, Digital, Beliefs), comprising 20 items in the preliminary version of MSK-PLq. Readability was acceptable (mean FRE 74, indicating fairly easy reading), and subject feedback supported the questionnaire's clarity and face validity. CONCLUSIONS: The preliminary version of the MSK-PLq is proposed as the first knowledge-based tool to assess functional, interactive, and critical aspects of MSK pain literacy. It may have applications in clinical practice, research, education, and digital health, by informing tailored patient education and supporting self-management strategies, although further psychometric validation is required.

Humans

Pregnancy diet based on ancestral patterns increases growth in subcortical fetal brain regions.

Evidence on the biological basis for maternal nutrition effects on fetal and newborn neurodevelopment remains limited. This randomized controlled trial in Ecuador tested a maternal dietary pattern-derived from empirical studies of nutrition in human evolution and adapted locally-on offspring growth and brain development. Pregnant women (n = 215) in their first trimester were randomized to: 1) control (n = 104); or 2) Mikhuna ("nourish" in Kichwa) intervention (n = 111). The intervention, from 12 wk gestation to birth, consisted of a weekly food delivery (8 eggs, 500 g fish, and a variety of sustainably sourced fruits and vegetables) and a behavior change communication strategy encouraging diet diversity and limiting highly processed foods. Longitudinal data collection occurred at 12 wk, 21 wk, 35 wk gestation, and 2 wk postpartum, and included ultrasound imaging of fetal bone and brain parameters, maternal dietary intakes, anthropometry, socioeconomic and demographic variables, and other biomarkers. At close of intervention, a significantly higher percentage of women met the minimum dietary diversity threshold in Mikhuna (74.5%) vs. control groups (55.8%) (P = 0.004). Generalized linear regression models showed significant differences in Mikhuna compared to control for: corpus callosum length 0.19 cm (95% CI [0.02, 0.35]), gangliothalamic ovoid height 0.15 cm (95% CI [0.03 to 0.26]), and femur length -0.10 cm (95% CI [-0.19, -0.02]) from 21 wk to 35 wk; and corpus callosum Z 0.56 (95% CI [0.03, 1.09]) and femur length Z -0.21 (95% CI [-0.42, 0.00]) at 35 wk. The Mikhuna intervention increased the growth of subcortical fetal brain structures, which have established roles in motor control, cognition, and signal transmission.

Female

The HOXA gene cluster: a critical regulator in bone-related disorders.

BACKGROUND: Skeletal homeostasis relies on the dynamic balance between bone formation and bone resorption. The disruption of this balance acts as the central pathological mechanism of multiple metabolic bone diseases including osteoporosis, and is closely correlated with the progression of various other bone-related disorders. As pivotal transcription factors regulating embryonic development and cell fate, the homeobox A (HOXA) gene family plays an essential role in skeletal physiological and pathological processes. METHODS: This review systematically summarizes recent research advances of the HOXA gene family in bone-related diseases, concludes the evolutionarily conserved regulatory patterns of HOXA members, and clarifies the molecular mechanisms by which HOXA genes mediate bone metabolic disorders and the occurrence as well as development of bone diseases. RESULTS: Accumulating evidence demonstrates that HOXA family members present complex functions and strong heterogeneity in bone-related diseases. They participate in the pathogenesis of bone diseases via three evolutionarily conserved regulatory manners: determining regional patterning, modulating signaling pathways, and integrating epigenetic and non-coding RNA (ncRNA) regulatory networks. CONCLUSION: Further exploring the underlying mechanisms of the HOXA family in bone-related diseases provides novel insights into the pathogenesis of bone disorders. Meanwhile, it also supplies solid theoretical basis and potential therapeutic targets for the development of novel HOXA-targeted therapeutic strategies against bone diseases.

Humans

Design, rationale, and baseline patient characteristics for the Sickle Cell Disease and CardiovAscular Risk-Red cell Exchange (SCD-CARRE) trial.

BACKGROUND: Despite wide utilization of automated red blood cell exchange (RBCX) transfusion in adult patients with sickle cell disease (SCD), no consensus or quality efficacy data exist on its use. The Sickle Cell Disease and CardiovAscular Risk- Red cell Exchange (SCD-CARRE) trial tests the hypothesis that an automated chronic RBCX transfusion strategy reduces acute health care encounters and death while improving quality of life and end-organ function (cardiac, pulmonary and renal) in participants with SCD that are at high risk of death. METHODS: Adult patients with SCD with elevated tricuspid regurgitant jet velocity (TRV) and/or chronic kidney disease were considered to be at high risk of death and were randomly assigned to RBCX plus standard of care vs standard of care alone. Participants assigned to RBCX received 12 months of exchange transfusions to maintain target pretransfusion hemoglobin S% < 30%, post-transfusion hemoglobin S% < 20%, and post-transfusion hemoglobin concentration &#x2265;10 g/dL. All study participants were managed according to NHLBI/ASH/ATS Expert Panel guidelines. The primary endpoint was the number of SCD acute health care encounters or death over 13 months. Secondary endpoints included measures of cardiovascular and renal function, exercise capacity, patient reported outcomes (all collected at baseline, and months 4, 8, and 12), and transfusion-related adverse events (collected monthly). RESULTS: Between 2020 and 2025, the SCD-CARRE trial randomized 173 participants at 23 sites across 3 countries. Enrolled participants had mean (SD) age of 45.8 (11.8) years and 54% were female. At baseline, participants had average TRV of 2.8 (0.5) m/s such that 45.9% had a TRV between 2.5 to 2.9 m/sec and 28.1% had a TRV &#x2265; 3.0 m/sec. The median (Q1, Q3) eGFR in this cohort was 60 (36, 110) mL/min/1.73 m2. The median (Q1, Q3) 6-minute walk test distance was 375 meters (309, 439), the median daily steps were 3,728 (2,187, 5,821), and participants experienced a median (Q1, Q3) of 2 (1, 5) pain episodes in the year prior to randomization. The trial results are pending. CONCLUSIONS: The SCD-CARRE trial successfully enrolled a cohort of n = 173 adults with SCD. This study highlights a rationale to evaluate the effect of automated chronic RBCX transfusion strategy plus standard of care as compared to standard of care alone in SCD patients at high risk of death with a focus on patient centered outcomes, preservation of cardiovascular function, end-organ complications and death. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT04084080, https://clinicaltrials.gov/study/NCT04084080.

Adult

The Impact of PCSK9 Inhibitors on Development of Retinal Vascular Occlusions.

PURPOSE: PCSK9 inhibitors (PCSK9i) are a newer class of lipid-lowering drug that may be effective at lowering risk for retinal artery occlusion (RAO) and retinal vein occlusion (RVO). This study aims to investigate the relationship between PCSK9i use and retinal vascular occlusion among patients with hyperlipidemia. DESIGN: Retrospective, comparative clinical cohort study SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Patients with hyperlipidemia, defined as serum low-density lipoprotein level of &#x2265;130 mg/dL and total cholesterol level of &#x2265;220 mg/dL, prescribed a lipid-lowering medication were identified. Patients prescribed a PCSK9i were included in the study group and compared with control patients prescribed any other type of lipid-lowering drug. METHODS: This study was conducted using electronic health record data from health organizations in the United States through the TrinetX platform. Propensity score matching was completed based on relevant patient demographics, comorbidities, and laboratory values. Comparison of main outcomes between the PCSK9i and non-PCSK9i groups was performed using measures of association analysis to determine risk ratio (RR) with 95% CI. MAIN OUTCOME MEASURES: The outcomes measured consisted of occurrence of retinal vascular occlusion, RAO, RVO, central RAO, and central RVO at 3-year, 5-year, and 7-year time points. RESULTS: After propensity score matching, a total of 12,960 patients were included in each cohort. The analysis revealed that the PCSK9i cohort had a significantly lower risk for development of retinal vascular occlusions at multiple points, including 3-year (RR = 0.56, CI = 0.39-0.79), 5-year (RR = 0.50, CI = 0.37-0.67), and 7-year (RR = 0.46, CI 0.35-0.61) time points. This lower risk was also found in the PCSK9i group for an outcome of RVO at 5 years (RR = 0.50, CI = 0.34-0.73) and 7 years (RR = 0.47, CI = 0.33-0.67). For occurrence of RAOs (RR = 0.47, CI = 0.30-0.76) and central RVO (RR = 0.46, CI = 0.29-0.74) separately, the PCSK9i cohort had a lower risk at 7 years. CONCLUSION: These findings suggest that PCSK9i may reduce the risk of retinal vascular occlusion compared with other classes of lipid-lowering medications.

Humans

Phosphorus modulates starch granule development and metabolic partitioning in wheat grain: Insights from SGAP proteomics and nutrition and processing quality.

This study investigates how phosphorus (P) levels are associated with carbon-nitrogen metabolism in wheat grains. Optimal P application (105&#x202f;kg&#x202f;P&#x2082;O&#x2085; ha&#x207b;&#xb9;) was associated with enhanced pericarp-endosperm coordination, increased carbon allocation to the endosperm, and early B&#x2011;type starch granule formation. Starch granule&#x2011;associated protein (SGAP) proteomics showed that optimal P upregulated cytoskeletal and starch&#x2011;synthesis proteins bound to starch granules in the endosperm, while reducing storage protein degradation&#x2011;related SGAPs in the pericarp. These metabolic adjustments were correlated with increased grain&#x2011;filling intensity and duration, and were associated with the highest theoretical grain weight (50.70&#x202f;mg). Furthermore, optimal P was associated with enrichment of amino acid biosynthesis pathways and with higher levels of essential amino acids (e.g., lysine and threonine by 17.0--26.8%) and an improved essential amino acid profile without altering total protein content. In contrast, excessive P (210&#x202f;kg&#x202f;P&#x2082;O&#x2085; ha&#x207b;&#xb9;) was associated with disrupted inter&#x2011;tissue coordination but did not simply impair grain filling; instead, HP corresponded to a unique developmental program: it was linked to an early burst of C&#x2011;type starch granules (0&#x223c;5&#x202f;&#xb5;m) at 7 DPA, yet by maturity achieved the highest proportion of large A&#x2011;type granules (56.8%) and the highest total starch content (63.5%), together with elevated endosperm phosphorus at 14 DPA and enrichment of spliceosome&#x2011;related pathways. HP also showed higher levels of several functional amino acids (glutamate, cysteine, histidine, proline) compared to P0. However, HP was associated with a higher gliadin/globulin ratio and did not improve grain yield. These findings suggest that phosphorus supply is associated with grain quality through tissue&#x2011;specific metabolic reprogramming, and that precision management-rather than maximized application-warrants consideration for optimizing both yield and processing quality.

Triticum

Development and validation of a comprehensive prognostic model for 28-day ICU mortality in non-traumatic subarachnoid hemorrhage: an analysis based on the MIMIC-IV database.

BACKGROUND: Due to the complex pathophysiology of non-traumatic subarachnoid hemorrhage (SAH), accurate risk prediction remains a challenge. Our aim is to develop and validate a comprehensive prognostic model that integrates demographic characteristics, vital signs, laboratory parameters, and more, to provide clinical decision-making support in real-world practice. METHODS: We conducted a retrospective cohort study of 785 Non-traumatic subarachnoid hemorrhage patients. The cohort was randomly divided into a training set (n&#xa0;=&#xa0;549) and a validation set (n&#xa0;=&#xa0;236). Feature selection was performed using LASSO regression, followed by backward stepwise Cox regression for optimization. A nomogram was constructed based on independent predictive factors, and model performance was assessed using discrimination, calibration, and decision curve analysis. To prevent immortal-time bias, all predictors were anchored to a fixed early (first-24-hour) measurement window, treatment variables were modelled as binary indicators rather than cumulative exposures, and a five-model sensitivity analysis with baseline-severity adjustment was performed. RESULTS: The development of our model followed a systematic approach: first, 15 potential predictive factors were selected via LASSO regression, which were then refined to 12 independent predictors using backward stepwise Cox regression. The final predictive factors included: Ventilation, AHT, Nimodipine 60&#xa0;mg, Age, SAPS.II, Input amount, Calcium total, Platelet count, White blood cells, Anion gap, pH, and Chloride. The integrated model demonstrated excellent predictive ability for 7-day, 14-day, and 21-day mortality in both the training set (AUC: 0.972, 0.934, 0.898) and the validation set (AUC: 0.968, 0.948, 0.911). Calibration curves and decision curve analysis confirmed the model's reliability and clinical utility across different time points. We constructed a nomogram for individualized risk prediction. Univariate Kaplan-Meier survival analysis demonstrated significant stratification of survival outcomes by each predictor, while restricted cubic spline analysis revealed non-linear relationships between continuous variables and mortality risk. Random survival forest analysis identified the top three predictive factors (Nimodipine 60&#xa0;mg, Ventilation, AHT) and compared them with our full 12-variable model, confirming superior performance of the integrated model at all time points. At the 28-day primary endpoint, the model achieved a time-dependent AUC of 0.898 (training) and 0.904 (validation); after restricting predictors to the early baseline window, the leakage-controlled model retained good discrimination (validation C-index 0.803). CONCLUSIONS: Our ICU 28-day mortality prognosis model demonstrated robust performance in predicting ICU 28-day mortality in non-traumatic subarachnoid hemorrhage. The model, through the nomogram, provides individualized risk assessment, aiding clinical decision-making and patient stratification.

Humans

Origins and timing of somatic variants in the brain.

Somatic variants accumulate in human brain cells throughout the lifespan. Variant allele fraction has traditionally been used as a proxy for both the developmental timing of somatic variants and their functional effect, based on the assumption that earlier mutations are shared by larger cell populations and therefore have greater potential for severe phenotypes. However, recent discoveries challenge this simplified model. Variables such as developmental bottlenecks, lineage restriction, and cellular and molecular context play critical roles in shaping the distribution and functional impact of somatic variants in the brain. These insights support a shift toward a context-dependent framework for interpreting somatic mosaicism.

Humans

Developing low-carbon metered-dose inhalers: effects of propellant HFA-152a on mucociliary clearance and bronchoconstriction in two Phase 1 randomised trials.

BACKGROUND: To reduce the impact of respiratory care on climate change, metered-dose inhalers (MDIs) are being reformulated with low-global warming potential (GWP) propellants. Next-generation propellant hydrofluoroalkane (HFA)-152a has >90% lower GWP than HFA-134a. As part of the safety evaluation for HFA-152a, mucociliary clearance (MCC), bronchoconstriction and safety were compared with HFA-134a. METHODS: Two Phase 1, randomised, two-way crossover studies (NCT06506266/NCT06702462) were conducted. MCC study: healthy participants inhaled HFA-152a and HFA-134a in two 7-day sequences. MCC was quantified as area under radiolabelled particle retention time curve over 4&#x202f;h (AUC0-4h) after nebulised 99mTc sulphur colloid, following each propellant. Bronchoconstriction study: patients with mild asthma inhaled single doses of HFA-152a and HFA-134a. Non-inferiority of HFA-152a versus HFA-134a was defined as percent change in FEV1 (litres), 15&#x202f;min post dose (95% confidence intervals [CI]: lower limit >-10%, upper limit >0%). Both studies assessed safety. RESULTS: In 22 healthy participants, the impact on MCC did not differ between HFA-134a and HFA-152a (AUC0-4h geometric mean ratio [90% CI]: 1.00 [0.99,&#xa0;1.01]). In 19 patients with mild asthma, neither HFA-152a nor HFA-134a induced bronchoconstriction (percent change in FEV1 at 15&#x202f;min: -0.37% [HFA-152a] vs -0.60% [HFA-134a]); HFA-152a was non-inferior to HFA-134a (mean difference [95% CI]: 0.23% [-3.61,&#xa0;4.07]). Adverse event (AE) rates were low and similar for both propellants in both studies; all AEs were mild, with no serious AEs or deaths. CONCLUSION: HFA-152a and HFA-134a had almost identical effects on MCC, neither induced bronchoconstriction, supporting MDI reformulation with the low-GWP propellant HFA-152a.

Humans

Long-term motor outcomes after parent-administered early physiotherapy in children born very preterm.

OBJECTIVE: This observational follow-up study investigated whether early parent-administered physiotherapy during the neonatal period was associated with motor outcomes in childhood, and compared these outcomes between two preterm groups and a term-born control group. STUDY DESIGN: This is a follow-up of a pragmatic randomised controlled trial that initially included 153 infants born very preterm (&#x2264;32&#xa0;weeks' gestation), randomised to either early parent-administered physiotherapy or standard care, between 34 and 37&#xa0;weeks' gestation. At 7-10&#xa0;years, motor outcomes were assessed in 92 children (intervention, n&#xa0;=&#xa0;43; standard care, n&#xa0;=&#xa0;49) and in 83 term-born controls. The primary outcome was the Movement Assessment Battery for Children-Second Edition (MABC-2). Group differences were analysed using linear mixed models adjusted for age, sex, and parental education. Odds ratios (ORs) were calculated for scores &#x2264;5th and&#xa0;&#x2264;&#xa0;15th percentiles to estimate the likelihood of having or being at risk for movement difficulties. RESULTS: Mean MABC-2 total score was 9.0 (SD3.0) in the intervention group, 9.6 (SD3.0) in the standard care group, and 10.8 (SD2.9) in the control group. Adjusted mean difference between the intervention and the standard care groups did not differ but both the intervention and standard care groups had lower scores than the control group (-1.2; 95% CI: -2.3 to -0.2 and -0.6; 95% CI: -1.6 to 0.3, respectively). Adjusted ORs for scoring &#x2264;5th or &#x2264;15th percentile did not differ in either preterm group compared with the control group. CONCLUSION: At 7-10&#xa0;years, motor outcomes did not differ between children born very preterm who received three-week parent-administered physiotherapy and those who received standard care during the neonatal period. However, both preterm groups had lower motor scores than term-born peers.

Humans

Ossicle occurrence characteristics and related molecular mechanisms in the sea cucumber Apostichopus japonicus.

To investigate the morphogenetic pattern and molecular mechanism of ossicle formation in the sea cucumber Apostichopus japonicus, this study systematically examined the morphological development and temporal sequence of spicules using the NaClO maceration method, in-situ squash preparation and microscopic observation. Comparative transcriptome sequencing was performed between doliolaria and pentactula larvae to screen differentially expressed genes (DEGs) related to ossicles formation, followed by pathway enrichment analysis. The function of the candidate key gene papilin-like was verified using siRNA-mediated gene silencing. The results were as follows: 1) Ossicles of A. japonicus first appeared at the late auricularia stage, initiating as X-shaped ossicles at the base of the oral tentacles. The number of X-shaped ossicles increased dramatically during the doliolaria stage. X-shaped ossicles were gradually replaced by table-shaped and rosette-shaped ossicles at the pentactula stage, suggesting that X-shaped ossicles may differentiate into these two ossicle types. The morphology of table-shaped ossicles showed a "simple-complex-simple" pattern with development. 2) Key genes related to ossicles formation, including CA1, COL1A2, and papilin-like, were identified by transcriptome analysis. After papilin-like knockdown, abnormal morphologies were observed in table-shaped ossicles of 1-year-old A. japonicus, such as spine-like protrusions on the outer margin of the disc and loss of table legs, confirming its crucial roles in maintaining ossicle morphology. This study clarified the morphological development pattern of ossicles in A. japonicus and identified a key regulatory gene (papilin-like) involved in ossicle morphogenesis, providing preliminary insights into the underlying molecular regulatory mechanism. These findings enrich our understanding on ossicles formation in echinoderms, and provide important morphological and molecular biological information for further studies on the developmental mechanism of ossicles in A. japonicus.

Animals

PGPR inoculation and growth enhancement of crops cultivated in hydroponic systems.

Plant growth-promoting rhizobacteria (PGPR) are ubiquitous rhizosphere microorganisms that promote plant health through various mechanisms. Although the study of PGPR inoculants in soil has been done for ages, their application in hydroponic systems has received relatively limited attention. This review identifies PGPR inoculants that are commonly used in hydroponics, methods of application, and their effects on plant growth and nutrient use efficiency. Literature shows that PGPR inoculants improve plant performance in controlled hydroponic systems through the production of growth-stimulating substances, nitrogen fixation, and improved nutrient acquisition. However, the plant growth responses are highly variable depending on the composition of nutrient solutions, environmental factors, crop and microbe species, and the type of hydroponic system. The review identifies various challenges of PGPR inoculation in hydroponic systems and future research directions to address the current gaps. Generally, the productivity of hydroponic systems can be enhanced through advanced inoculation strategies and the development of suitable carrier materials to improve inoculant survival, viability, and functions. Emphasis should also be placed on designing system-specific microbial consortia and Synthetic communities that are tailored to the unique ecological conditions of hydroponic systems.

Hydroponics

Ketoacidosis with SGLT2 inhibitors in routine clinical practice of type 2 diabetes: Scandinavian cohort and nested case-control study.

BACKGROUND: SGLT2 inhibitors increase the risk of ketoacidosis, but data from routine clinical practice are scarce. We used nationwide registers with the aim of assessing the incidence, risk factors, and prognosis of ketoacidosis during SGLT2 inhibitor treatment in patients with type 2 diabetes. METHODS: In this cohort and nested case-control study we used data from three Scandinavian countries. In a cohort of SGLT2 inhibitor-treatment episodes among patients with type 2 diabetes aged at least 18 years in Sweden, Denmark, and Norway, we estimated ketoacidosis incidence. Using a nested case-control design (matched on age, sex, region of birth, calendar time, and time since treatment initiation), we assessed risk factors and precipitating or co-occurring events. Changes in diabetes medications were evaluated. FINDINGS: The study period was Jan 1, 2013, to Dec 31, 2021, in Denmark and Sweden, and Jan 1, 2013, to Dec 31, 2022, in Norway. We included 322&#x2008;597 treatment episodes among 282&#x2008;282 patients with type 2 diabetes (mean age 63 years, 116&#x2008;521 [36&#xb7;1%] of 322&#x2008;597 women). During a median (IQR) follow-up of 1&#xb7;3 (0&#xb7;7-2&#xb7;8) years, 1452 ketoacidosis events occurred (incidence 2&#xb7;43 per 1000 person-years). Although highest shortly after initiation, risk persisted throughout follow-up. Strong risk factors included high HbA1c (&#x2265;83 vs &#x2264;52 mmol/mol: odds ratio [OR] 15&#xb7;37 [95% CI 11&#xb7;50-20&#xb7;53]), malnutrition (OR 10&#xb7;54 [7&#xb7;32-15&#xb7;18]), previous ketoacidosis (OR 10&#xb7;40 [7&#xb7;09-15&#xb7;24]), low BMI (<20 kg/m2vs 20 to <25 kg/m2: OR 9&#xb7;98 [5&#xb7;68-17&#xb7;53]), and recent hypoglycaemia (OR 5&#xb7;22 [2&#xb7;60-10&#xb7;49]). Infection was the most common precipitating or co-occurring event (454 [31&#xb7;8%] of 1428 vs 862 [6&#xb7;1%] of 14&#x2008;233 for ketoacidosis cases vs controls; OR 7&#xb7;60 [6&#xb7;62-8&#xb7;71]). The strongest associations were observed for alcohol intoxication, acute renal events, acute abdomen, stroke, and major surgery, although associations for some transient exposures, particularly milder conditions, might have been overestimated because of under-registration among controls. Exploratory analyses suggested that the observed associations were largely general to patients with type 2 diabetes rather than specific to SGLT2 inhibitor use. At 1 year after ketoacidosis, 211 (25&#xb7;1%) of 842 remained on SGLT2 inhibitors and insulin use increased from 269 (31&#xb7;9%) of 842 to 615 (73&#xb7;0%) of 842. INTERPRETATION: Ketoacidosis risk with SGLT2 inhibitors varies greatly by patient characteristics and is not confined to early in treatment. Risk should be assessed throughout treatment, and patients should be instructed to pause treatment during acute illness and stress. FUNDING: Region Stockholm, Swedish Society of Medicine, Karolinska Institutet.

Journal Article

Novel Proactive Speech-Language Intervention Is More Effective Than Usual Care: Randomized Controlled Trial of Babble Boot Camp for Infants With Classic Galactosemia.

PURPOSE: Speech and language disorders cannot be diagnosed and treated until children are approximately 2-4 years old. To investigate whether these disorders can be prevented, we developed and trialed Babble Boot Camp (BBC), the first proactive sustained intervention starting with precursor skills including cooing and babbling. METHOD: Participants were two randomly assigned groups of 22 infants with classic galactosemia, a metabolic disease with known risks for severe speech and language disorders. One group started BBC at under 6 months of age, and the other started at 15 months of age, both completing BBC at 24 months of age. Coached by a speech-language pathologist in weekly telehealth sessions, caregivers implemented BBC activities and routines daily at home. A typical control group and a group of children with classic galactosemia who received usual care participated as well. All children completed standardized assessments of speech and language at postintervention. RESULTS: Assessment scores showed that BBC was more effective than usual care for both intervention groups. Greatest benefits were seen in the group that started at or before 6 months of age, with a proportion of clinically concerning scores equal to that in the typically developing peers. No effects of sex, genotype, or milk consumption were evident in the outcomes. CONCLUSIONS: Findings motivate a paradigm shift from deficit-based to proactive approaches for infants with classic galactosemia. BBC is extensible to many other disorders, with trials currently underway for infants with Down syndrome and infants born preterm.

Humans

Epithelial regeneration in the gastrointestinal tract.

The gastrointestinal tract possesses a remarkable regenerative capacity to maintain tissue homeostasis against various injuries. However, the intestine and stomach exhibit distinct regenerative strategies. In the intestine, damage to Lgr5-positive (Lgr5+) stem cells induces cellular plasticity and the emergence of transient Revival stem cells (RevSCs), a process critically dependent on YAP/TAZ signaling. Conversely, the stomach utilizes paligenosis, where quiescent p57-positive (p57+) mature chief cells act as reserve stem cells, dedifferentiating to restore damaged tissue. Although the cellular origins differ, both organs appear to share some common regenerative features, including transient activation of pro-proliferative programs such as YAP/TAZ signaling. In contrast, whether Retinoic Acid (RA) signaling also serves as a conserved mechanism for regenerative resolution in the stomach remains to be determined. In this review, we discuss the cellular and molecular mechanisms governing regeneration in these two organs. This comparative analysis provides a framework for future research.

Regeneration