Experimental Treatments Research Articles

Source-dependent effects of early-life zinc supplementation in milk on growth performance and starter intake of pre-weaned dairy calves

This study aimed to evaluate the effects of milk supplementation with different zinc (Zn) sources on growth rate, starter intake, diarrhea incidence, and nutrient digestibility in dairy calves during the pre-weaning period. Forty newborn Holstein heifer calves were assigned to four treatments: control (no Zn supplementation; CON) or supplementation with 80 mg/day Zn from zinc sulfate (Zn-Sul), chelated zinc (Zn-Bon), or zinc methionine (Zn-Met). The Zn supplements were provided via milk from days 3 to 14 of age. Body weight (BW) and starter intake (SI) were monitored until weaning on day 70. Serum metabolite concentrations were determined in blood samples collected on days 15 and 70. Fecal consistency index (FCI) and frequency of medical treatments were measured during the first 21 days of life. Apparent total tract digestibility (ATTD) was determined in the 10th week of life. Although the effects of Zn supplementation on BW gain or body measurements were non-significant, a tendency for treatment × time interaction on BW was observed, with variations among the experimental groups becoming more pronounced on days 56 and 70, showing higher values in Zn-supplemented calves compared to CON. SI was improved by Zn supplementation, with the greatest response in the Zn-Bon group. Compared to control, ATTD of organic matter, neutral detergent fiber, and starch tended to increase with Zn supplementation. Blood metabolites and FCI did not differ among the experimental treatments. Although no significant difference was detected between Zn-Met and CON, the frequency of medical treatment was significantly lower in Zn-Bon and Zn-Sul compared to CON calves. In conclusion, zinc supplementation in milk, particularly with the organic chelated zinc source (Zn-Bon), showed promising effects on increasing starter intake and reducing medical treatments, along with trends toward enhanced growth and nutrient digestibility in pre-weaned calves.

Dynamics of Gut Microbiota after Fecal Microbiota Transplantation in Ulcerative Colitis: Success Linked to Control of Prevotellaceae.

Fecal microbiota transplantation (FMT) is an experimental treatment for ulcerative colitis (UC). We aimed to study microbial families associated with FMT treatment success. We analyzed stools from 24 UC patients treated with four FMTs weekly after randomization for pretreatment during three weeks with budesonide (n = 12) or placebo (n = 12). Stool samples were collected nine times pre-, during, and post FMT. Clinical and endoscopic response was assessed 14 weeks after initiation of the study using the full Mayo score. Early withdrawal due to worsening of UC symptoms was classified as non-response. Nine patients (38%) reached remission at week 14, and 15 patients had a partial response or non-response at or before week 14. With a Dirichlet Multinomial Mixture model we identified five distinct clusters based on the microbiota composition of 180 longitudinally collected patient samples and 27 donor samples. A Prevotellaceae-dominant cluster was associated with poor response to FMT treatment. Conversely, the families Ruminococcaceae and Lachnospiraceae were associated with a successful clinical response. These associations were already visible at the start of the treatment for a subgroup of patients and were retained in repeated measures analyses of family-specific abundance over time. Responders were also characterized by a significantly lower Simpson dominance compared to non-responders. The success of FMT treatment of UC patients appears to be associated with specific gut microbiota families, such as control of Prevotellaceae. Monitoring the dynamics of these microbial families could potentially be used to inform treatment success early during FMT.

Effect of D-mannitol and Gibberellic Acid on Physiological Parameters, Early Seedling Growth Characteristics, and Some of the Most Important Chemical Components of Barberry (Berberis vulgaris L.)

Background: One of the important medicinal plants and agricultural products in Asia, particularly in Iran, is barberry, and both salinity and drought can cause osmotic or ionic imbalance in plant cells. In order to study the impacts of D-Mannitol and gibberellic acid on seed germination, physiological parameters, early seedling growth characteristics, and some of the most important chemical ingredients of barberry, one experiment is designed. Methods: The experimental design was Completely Randomized Design (CRD) with three replicates, and drought stress was done by D-mannitol at various stress levels, namely, 0 MPa, 40 MPa, and 80 MPa, and the reaction of studied cultivar was assessed on the basis of experimental characteristics associated to germination and seedling growth, and Gibberellic acid treatments were 0 mgL-1, 300 mgL-1, 600 mgL-1, and 900 mgL-1. Results: The effects of D-mannitol were significant in germination percentage, germination rate, seedling vigor index, chlorophyll a, total chlorophyll, leaf dry weight and total sugar. Experimental treatments such as germination percentage, germination rate, and total chlorophyll were also influenced by the application of gibberellic acid. The interaction between D-mannitol and gibberellic acid had significant effect on peroxidase activity. The highest germination percentage, germination rate, seedling vigor index, catalase activity, peroxide activity, and Chlorophyll a were obtained for 0 MPa application of D-Mannitol, followed by usage of 40 MPa, and 80 Mpa, respectively. The maximum total chlorophyll, relative water content, and leaf dry weight were also related to control treatment (0 MPa D-Mannitol), while the higher values of proline content, carotenoids and total sugar were obtained for 80 MPa application of D-Mannitol. The maximum values of germination rate, germination percentage, seedling vigor index, peroxidase activity, and chlorophyll a were related to control treatment (0 mgL-1 gibberellic acid), and the highest CAT activity was related to the application of 300 mgL-1 gibberellic acid. The highest total chlorophyll content and relative water content were related to 0 mgL-1 gibberellic acid, while the maximum praline content and leaf dry weight were obtained for the application of 600 mgL-1 and 0 mgL-1 gibberellic acid. There was not any significant difference in carotenoids between gibberellic acid treatments, while the application of 900 mgL-1 gibberellic acid obtained the highest value of total sugar of barberry. Conclusion: Conclusively, on the basis of the results, the application of 80 MPa D-Mannitol and 600 mgL-1 could be recommended as they can increase the absorption of nutrients and water.

Case report: Carnivore–ketogenic diet for the treatment of inflammatory bowel disease: a case series of 10 patients

BackgroundVery-low-carbohydrate diets, including ketogenic and carnivore diets, are gaining popularity for the experimental treatment of a wide range of disorders, including inflammatory bowel disease (IBD).MethodsParticipants were recruited through a social media survey. Final inclusion required a histologically confirmed diagnosis of ulcerative colitis (UC) or Crohn’s disease that was responsive to treatment with a ketogenic or carnivore diet without medication or with successful medication cessation on the diet. Clinical improvement was measured with the Inflammatory Bowel Disease Questionnaire (IBDQ).ResultsWe report on 10 cases of IBD responsive to ketogenic, mostly carnivore, diets. Clinical presentations were diverse, including six cases of UC and four of Crohn’s disease. Clinical improvements were universal, with clinical improvement scores ranging between 72 and 165 points on the IBDQ. Patients’ diets comprised mostly meat, eggs, and animal fats. Patients report their diets are pleasurable, sustainable, and unequivocally enhance their quality of life.ConclusionKetogenic and carnivore diets hold promise for the treatment of IBD, including UC and Crohn’s disease. These cases are consistent with clinical literature that shows an inverse association between intestinal ketone levels and IBD activity, as well as the therapeutic effects of low residue elimination diets on colonic microbiota metabolism.

Construction of ZnAl LDH-Derived Sulfides with Etching Modification to Trigger Photocatalytic H2 Production and Degradation Oxidation.

Constructing novel functional photocatalysts represents a promising approach to optimize the energy band structure and facilitate the separation of photogenerated carriers. Layered double hydroxides (LDHs) exhibit notable advantages in photocatalysis due to the exceptional photoelectrochemical properties and elevated number of active surface atoms. However, an unsuitable band gap and limited carrier migration have inhibited their development in photocatalysis. Herein, we propose a novel in situ topological vulcanization strategy for optimizing the photocatalytic activity of ZnAl LDH-derived sulfides (ZnAlSx). The subsequent etching process via a 1 M NaOH solution was introduced to construct the ZnSx photocatalysts. Then, the crystallinity of the crystals was enhanced by etching to further improve the catalytic activity and stability of ZnSx. The as-synthesized ZnSx shows an excellent photocatalytic hydrogen production rate (11.89 mmol/g/h) and tetracycline degradation efficiency (91.94%) under light illumination, and its hydrogen evolution efficiency is approximately 176 and 2 times greater than that of ZnAl LDH and ZnAlSx, respectively. The characterization and density functional theory (DFT) analysis confirmed that the surface electronic properties and energy band structure of ZnAl LDH were significantly optimized after experimental treatment, resulting in enhanced carrier separation and photooxidative reduction capacity. Combining in situ topological vulcanization and etching to realize the functional conversion of ZnAl LDH provides promising insights into the construction of high-performance, low-cost photocatalysts.

Successive Years of Rice Straw Return Increased the Rice Yield and Soil Nutrients While Decreasing the Greenhouse Gas Intensity

Straw return has important impacts on black soil protection, food security, and environmental protection. One year of straw return (S1) reduces rice yield and increases greenhouse gas (GHG) emissions. However, the effects of successive years of straw return on rice yield, soil nutrients, and GHG emissions in the northeast rice region are still unclear. Therefore, we conducted four successive years of straw return (S4) in a positional experiment to investigate the effects of different years of straw return on rice yield, soil nutrients, and GHG emissions in the northeast rice region. The experimental treatments included the following: no straw return (S0), a year of straw return (S1), two successive years of straw return (S2), three successive years of straw return (S3), and four successive years of straw return (S4). Compared with S1, the rice yields of S2, S3, and S4 increased by 10.89%, 15.46%, and 16.98%, respectively. But only S4 increased by 4.64% compared to S0, while other treatments were lower than S0. S4 increased panicles per m2 and spikelets per panicle by 9.34% and 8.93%, respectively, compared to S1. Panicles per m2 decreased by 8.06% at S4 compared to S0, while spikelets per panicle increased by 13.23%. Compared with S0, the soil organic carbon, total nitrogen, NH4+-N, NO3−-N, available phosphorus, and available potassium of S4 increased by 11.68%, 10.15%, 24.62%, 21.38%, 12.33%, and 13.35%, respectively. Successive years of rice straw return decreased GHG intensity (GHGI). Compared with S1, the GHGI of S4, S3, and S2 decreased by 16.2%, 11.84%, and 9.36%, respectively. Thus, S4 increased rice yield and soil nutrients, reducing GHGI.

Compost incorporation and wildflowers introduction for stormwater infiltration and erosion-control vegetation cover establishment in post-construction landscapes

Urban and suburban development frequently disturbs and compacts soils, reducing infiltration rates and fertility, posing challenges for post-development vegetation establishment, and contributing to soil erosion. This study investigated the effectiveness of compost incorporation in enhancing stormwater infiltration and vegetation establishment in urban landscapes. Experimental treatments comprised a split-split plot design of vegetation mix (grass, wildflowers, and grass-wildflowers) as main plot, ground cover (hydro-mulch and excelsior) as subplot, and compost (30% Compost and No-Compost) as sub-subplot factors. Wildflower inclusion was motivated by their recognized ecological benefits, including aesthetics, pollinator habitat, and deep root systems. Vegetation cover was assessed using RGB (Red-Green-Blue) imagery and ArcGIS-based supervised image classification. Over a 24-month period, bulk density, infiltration rate, soil penetration resistance, vegetation cover, and root mass density were assessed. Results highlighted that Compost treatments consistently reduced bulk density by 19–24%, lowered soil penetration resistance to under 2 MPa at both field-capacity and water-stressed conditions, and increased infiltration rate by 2–3 times compared to No-Compost treatments. Vegetation cover assessment revealed rapid establishment with 30% compost and 60:40 grass-wildflower mix, persisting for an initial 12 months. Subsequently, all treatments exhibited similar vegetation coverage from 13 to 24 months, reaching 95–100% cover. Compost treatments had significantly higher root mass density within the top 15 cm than No-Compost, but compost addition did not alter the root profile beyond the 15 cm depth incorporation depth. The findings suggest that incorporating 30% compost and including a wildflower or grass-wildflower mix appears to be effective in enhancing stormwater infiltration and provides rapid erosion control vegetation cover establishment in post-construction landscapes.

Antifungal Mechanisms and Characteristics of Pseudomonas fluorescens: Promoting Peanut Growth and Combating Fusarium oxysporum-Induced Root Rot

Continuous cropping of peanuts presents significant challenges to sustainable production due to soil-borne diseases like root rot caused by Fusarium species. In this study, field inoculation experiments treatments and in vitro agar plate confrontation tests were conducted, including non-inoculated controls (CK), inoculation with Pseudomonas fluorescens (PF), Fusarium oxysporum (FO), and co-inoculation with both (PF+FO). The aim was to explore the antifungal mechanisms of Pseudomonas fluorescens in mitigating root rot and enhancing peanut yield. The results indicated that PF and PF+FO significantly enhanced peanut root activity, as well as superoxide dismutase, catalase, and glutathione S-transferase activities, while simultaneously decreasing the accumulation of reactive oxygen species and malondialdehyde contents, compared to FO treatment. Additionally, PF treatment notably increased lignin content through enhanced phenylalanine ammonia lyase, cinnamate 3-hydroxylase, and peroxidase activity compared to CK and FO treatment. Moreover, PF treatment resulted in longer roots and a higher average diameter and surface area, potentially due to increased endogenous levels of auxin and zeatin riboside, coupled with decreased abscisic acid content. PF treatment significantly elevated chlorophyll content and the maximum photochemical efficiency of PSII in the light-adapted state, the actual photochemical efficiency and the proportion of PSII reaction centers open, leading to improved photosynthetic performance. Confrontation culture assays revealed PF's notable inhibitory effects on Fusarium oxysporum growth, subsequently reducing rot disease incidence in the field. Ultimately, PF treatment led to increased peanut yield by enhancing plant numbers and pod weight compared to FO treatment, indicating its potential in mitigating Fusarium oxysporum-induced root rot disease under continuous cropping systems.

Combined Application of Biochar and Silicon Fertilizer for Improved Soil Properties and Maize Growth

Biochar can be a good soil amendment to reduce the soil pH, increase crop growth rate, and improve the efficient use of fertilizer. Other than that, silicon fertilizer also would promote photosynthetic ability on plant development that would help to produce high yield. In this work, a series of experiments was conducted to observe the effect of rice husk biochar and silicon fertilizer on the maize growth rate and soil pH. A 45-day pot experiment in the greenhouse with three replicates of 9 experimental treatment combinations of RHB at two rates (5 and 2.5 t.ha-1) with silicon fertilizer at three rates (125%, 100%, 75%), sole biochar (10 t.ha-1), sole silicon fertilizer (100%) and control (NPK) to observe the best rate and combination to improve growth rate and change in soil chemical in acid soil. The result showed that the co-application of sole biochar and biochar with Silicon significantly improved growth development, increased photosynthesis rate, altered soil pH, and reduced Fe concentration compared to control. The plant height increased 88.35% from T4 (5 t.ha-1 RHB + 100% Si) compared to the control and the conductance was higher in T4 (0.53) followed by T8 (0.438) while T1 (0.071) recorded the lowest conductance. The shoot fresh weight was higher in T4 (127.83 g) followed by T8 (57.14 g). However, the weight increased by 343.7% at T4 followed by T8 (2.5 t.ha-1 RHB + 75% Si) at 98.33%. The highest pH increment of 1.24 units (T1 = 5.53, T4 = 6.77) of soil pH was noted from T4 (5 t.ha-1 RHB + 100% Si) compared to control (NPK), and the highest total Fe in soil was observed from T1 (442.30 mg.kg-1). The current study results showed that T4 (50% RHB + 100% Silicon) was the best treatment over the other rates of RHB and silicon increased plant height, photosynthetic rate, and biomass.

Microbial biofertilizers and algae-based biostimulant affect fruit yield characteristics of organic processing tomato.

Microbial biofertilizers and algae-based biostimulants have been recognized for supporting sustainable agriculture. Field experiments were conducted in 2022 and 2023 growing seasons in an organic farm located in Ferrara (Italy) with the aim of evaluating plant growth-promoting microorganisms (PGPMs) and algae-based biostimulants (Biost) in tomato (Solanum lycopersicum L.). The experimental treatments were: (i) two microbial biofertilizers (PGPM_1, PGPM_2) and no inoculated plants (No_PGPM); and (ii) two algae-based biostimulant rates (0.5% (Biost_0.5%), 1.0% (Biost_1.0%)) and no application (No_Biost). PGPMs were applied at transplanting, while biostimulants at 15 and 30 days after transplanting. Treatments were replicated three times according to a split-plot experimental design. Plant characteristics were evaluated at 30 days after transplanting in No_Biost treatments. During tomato cultivation, soil plant analysis development (SPAD), nitrogen difference vegetation index (NDVI), leaf area index (LAI) and photosynthetic photon flux density (PPFD) were monitored. Tomato yield was determined. PGPM_2 showed the highest shoot biomass (132.9 g plant-1), plant height (44.7 cm), leaf number (34.0 plant-1) and root biomass (9.22 g plant-1). Intermediate values were observed in PGPM_1, while all parameters were lower in No_PGPM. Both PGPMs achieved higher values of SPAD, NDVI, PPFD and LAI than No_PGPM. Biost_1.0% increased all measured growth parameters followed by Biost_0.5% and No_Biost, respectively. Tomato yield was the highest for PGPM_2-Biost_1.0% (67.2 t ha-1). PGPMs affected fruit size and sugar content, while biostimulants were associated with color and lycopene. The application of microbial biofertilizers and algae-based biostimulants could be part of environment-friendly practice in organic farming. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Weed smothering efficiency of mulching types on groundnut (Arachis hypogea L.) productivity in the dry savanna region of Nigeria

In order to increase groundnut productivity, a field experiment was carried out in the dry season of 2020 to assess the effectiveness of various mulching materials at suppressing weeds. The experimental treatments comprised of five mulching types; Control (no mulch), transparent polythene mulch, black polythene mulch, rice straw mulch and saw dust mulch) and three groundnut varieties (SAMNUT 23, SAMNUT 24 and SAMNUT 26). These were factorially combined and laid out in a Randomized complete block design with three replications. Findings revealed that mulching had a significant (p < 0.05) impact on crop qualities including canopy cover, chlorophyll content, pod yield, 100 kernel weight, and groundnut kernel yield as well as weed attributes like weed cover scores, weed density, weed dry weight, and weed control efficiency in both BUK and Wasai, respectively. The weed compositions were further grouped into various families comprising Poaceae (11), Euphorbiaceae (3), Amaranthaceae (4), Asteraceae (3), Cyperaceae (2), Cucurbitaceae, and Aizoaceae, each having one species with a different level of occurrence across the two locations. On the other hand, SAMNUT 26 significantly produced higher pod (2798 & 2119) and kernel yields (1198 & 1191), although SAMNUT 23 produced a heavier 100 kernel weight (55.51 & 54.52) at BUK and Wasai, respectively. In comparison to the other mulching types, applying black polythene mulch or transparent mulch lowered weed density and dry weight by limiting the amount of sunlight that the weeds got, preventing them from growing. Therefore, for dry season production of groundnut in the Sudan savannah ecology of Nigeria, mulching with black or transparent polythene film using the SAMNUT 26 variety was found to be effective in conserving soil moisture for optimum crop growth and development, while on the other hand, weed populations were suppressed.

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for Gastric Cancer Peritoneal Metastases: Results from the Lithuanian PIPAC Program

Background: Peritoneal metastases (PM) of gastric cancer (GC) are considered a terminal condition, with reported median survival ranging from 2 to 9 months. Standard treatment typically involves systemic chemotherapy alone or combined with targeted therapy or immunotherapy, though efficacy is limited. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a novel technique for treating GC PM, although it remains an experimental treatment under investigation. This study aimed to summarize the outcomes of GC PM treatment with PIPAC from the Lithuanian PIPAC program. Methods: All patients who underwent PIPAC for GC PM at Vilnius University Hospital Santaros Klinikos between 2015 and 2022 were included in this retrospective study. The safety of PIPAC was assessed by postoperative complications according to the Clavien–Dindo classification. Efficacy was evaluated based on the peritoneal carcinomatosis index (PCI), ascites dynamics throughout the treatment, and long-term outcomes. Results: In total, 32 patients underwent 71 PIPAC procedures. Intraoperative and postoperative morbidity related to PIPAC occurred after three (4.2%) procedures. Following PIPAC, there was a tendency towards a decrease in median PCI from 10 (Q1 3; Q3 13) to 7 (Q1 2; Q3 12), p = 0.75, and a decrease in median ascites volume from 1300 mL (Q1 500; Q3 3600) at the first PIPAC to 700 mL (Q1 250; Q3 4750) at the last PIPAC, p = 0.56; however, these differences were not statistically significant. The median overall survival after PM diagnosis was 12.5 months (95% CI 10–17), and the median survival after the first PIPAC procedure was 5 months (95% CI 4–10). Conclusions: PIPAC is a safe and feasible treatment option for GC PM; however, well-designed prospective studies are needed to fully assess its efficacy.

Estimands in clinical trials of complex disease processes.

Clinical trials with random assignment of treatment provide evidence about causal effects of an experimental treatment compared to standard care. However, when disease processes involve multiple types of possibly semi-competing events, specification of target estimands and causal inferences can be challenging. Intercurrent events such as study withdrawal, the introduction of rescue medication, and death further complicate matters. There has been much discussion about these issues in recent years, but guidance remains ambiguous. Some recommended approaches are formulated in terms of hypothetical settings that have little bearing in the real world. We discuss issues in formulating estimands, beginning with intercurrent events in the context of a linear model and then move on to more complex disease history processes amenable to multistate modeling. We elucidate the meaning of estimands implicit in some recommended approaches for dealing with intercurrent events and highlight the disconnect between estimands formulated in terms of potential outcomes and the real world.

Correlation between compulsive behaviors and plastic changes in the dendritic spines of the prefrontal cortex and dorsolateral striatum of male rats

Obsessive-compulsive disorder (OCD) is a mental affliction characterized by compulsive behaviors often manifested in intrusive thoughts and repetitive actions. The quinpirole model has been used with rats to replicate compulsive behaviors and study the neurophysiological processes associated with this pathology. Several changes in the dendritic spines of the medial prefrontal cortex (mPFC) and dorsolateral striatum (DLS) have been related to the occurrence of compulsive behaviors. Dendritic spines regulate excitatory synaptic contacts, and their morphology is associated with various brain pathologies. The present study was designed to correlate the occurrence of compulsive behaviors (generated by administering the drug quinpirole) with the morphology of the different types of dendritic spines in the mPFC and DLS. A total of 18 male rats were used. Half were assigned to the experimental group, the other half to the control group. The former received injections of quinpirole, while the latter rats were injected with physiological saline solution, for 10 days in both cases. After the experimental treatment, the quinpirole rats exhibited all the parameters indicative of compulsive behavior and a significant correlation with the density of stubby and wide neckless spines in both the mPFC and DLS. Dendritic spines from both mPFC and DLS neurons showed plastic chnges correlatively with the expression of compulsive behavior induced by quinpirole. Further studies are suggested to evaluate the involvement of glutamatergic neurotransmission in the neurobiology of OCD.

Halotolerant Microorganism-Based Soil Conditioner Application Improved the Soil Properties, Yield, Quality and Starch Characteristics of Hybrid Rice under Higher Saline Conditions.

Soil salinity represents a significant factor affecting agricultural productivity and crop quality. The present study was conducted to investigate the effects of soil conditioner (SC) comprising halotolerant microorganisms on the soil fertility, yield, rice quality, and the physicochemical and structural properties of starch in hybrid rice under saline conditions. The experimental treatments were composed of two high-quality hybrid rice varieties, i.e., 'Y Liangyou 957' (YLY957) and Jing Liangyou 534 (JLY534), and two soil amendment treatments, i.e., the application of SC at control levels and 2250 kg hm-2, or 'CK and SC', respectively. The crop was subjected to a mixture of fresh and sea water (EC 11 dS/m). The results demonstrated that the application of SC significantly enhanced the rice yield under salt stress conditions owing to an increase in the number of grains per panicle. Furthermore, SC was found to be effective in improving the organic matter and soil nutrient content. Furthermore, the application of SC resulted in an improvement in antioxidant defense, higher leaf SPAD values, and greater crop biomass, as well as the translocation of photo-assimilates at the heading stage. The application of SC not only improved the milling and appearance quality but also enhanced the taste value of rice by increasing the amylose and reducing the protein content. Furthermore, the application of SC also decreased the indentations on the surfaces of starch granules and cracks on the edges of the granules. The rice varieties subjected to SC exhibited excellent pasting properties, characterized by reduced proportions of amylopectin short chains and a lower gelatinization temperature and enthalpy of gelatinization. Overall, these findings serve to reinforce the efficacy of soil conditioner as a valuable tool to improve rice productivity and sustainability with improved rice grain quality under saline conditions.

Combining Recurrent and Terminal Events Into a Composite Endpoint May Be Problematic

In clinical trials for chronic heart failure (CHF), time to a composite of first hospitalization for worsening heart failure or death is a widely accepted primary efficacy measure. Motivated by lower event rates in recent CHF trials, there are proposals to use endpoints accounting for recurrent heart failure hospitalization (HFH) events (e.g. recurrent HFH events plus death as an additional event) as the primary endpoint to better quantify disease burden and to improve trial efficiency. However, analysis and interpretation of recurrent event endpoints may be complicated by the terminal event death. In a previous simulation study it was shown that the type I error rate was well-controlled for the analysis of the composite recurrent event endpoint using the negative binomial (NB) model and the Lin-Wei-Yang-Ying (LWYY) model. As these results were based on limited scenarios, we extended the previous simulation study and identified situations where the type I error rate is no longer controlled for the analysis of the composite recurrent event endpoint using the LWYY model, despite a neutral effect on HFH and a detrimental effect on death of the experimental treatment. Therefore, depending on clinical settings, the LWYY model should be applied and interpreted with more caution.

Exogenous Increases in Basic Income Provisions Increase Preventive Health-Seeking Behavior: A Quasi-Experimental Study

IntroductionUniversal Basic Income (UBI) policies have the potential to promote a wide range of public health objectives by providing those who qualify with direct cash payments. One overlooked mechanism of particular importance to health researchers is the possibility that guaranteed income might increase consultation of primary and preventive care (e.g., annual doctors’ visits; regular vaccination against infectious disease) by providing people with both the time and monetary resources to do so, thereby improving general health. MethodsThis study assesses the effects of an exogenous shock to Alaska's UBI payments to all state residents: a 2022 decision to reclassify dividend “energy relief” provisions as non-taxable (thereby increasing payments by approximately $2,000 inflation-adjusted dollars). It estimates quasi- experimental treatment effects (in 2022 vs. 2021) via mixed linear probability models that compare pre/post policy change in primary care seeking behavior in Alaska vs. the US adult population; controlling for respondent-level fixed effects and state-level random effects. Data were collected in 2021-2022, and analyzed in 2024. ResultsThe likelihood that Alaskans sought primary care post-reform (relative to beforehand) increased by 6pp, which was significantly greater than the same difference (2pp) observed across all other (non- UBI) US States (∆ = 4pp, p < 0.01). The study provides suggestive evidence that comparatively fewer Alaskans had difficulty affording primary care during this period, with less-consistent evidence of increased flu vaccine uptake. ConclusionsEnhanced UBI payments ought to be thought about as a form of health policy, as they have the potential to advance a wide range of health objectives related to preventive care.

Evaluation of the effects of black pepper extract on the growth performance of grower pigs

This study aimed to evaluate the effects of black pepper (BP) extract on growth performance, nutrient digestibility, serum total protein, blood urea nitrogen (BUN), creatinine, counts of Lactobacillus and Escherichia coli (E. Coli), back fat thickness, lean meat percentage (LMP), and fecal gas emission in grower pigs. A total of 160 crossbred grower pigs [(Landrace × Yorkshire) × Duroc] with an average initial body weight (BW) of 25.31 ± 1.29 kg were used in a 42-day feeding trial. Pigs were randomly assigned to four experimental treatments. The basal diet was composed of soybeans and corn to meet or exceed the NRC (2012) recommendations. The dietary treatments included: basic diet, basic diet + 0.025 %, 0.05 %, and 0.1 % BP extract. There were eight replicates per treatment, each comprising five pigs (three gilts and two barrows). All data were subjected to statistical analysis using general linear model procedures (SAS 2001, SAS Institute Inc., Cary, NC, USA), with the pen serving as the experimental unit. The results indicated a linear improvement in BW and average daily gain of pigs during days 1–28, 28–42, and the overall period with increasing levels of BP extract in the diet. The apparent total tract digestibility (ATTD) of crude protein (CP) and lean meat percentage (LMP) increased linearly with BP treatment at the end of the experiment (p < 0.05). In addition, total protein, BUN, and creatinine levels were not affected by the BP extract (p > 0.05). Some fecal microbes, such as Lactobacillus and E. coli, did not change considerably when pigs were fed BP extract (p > 0.05). No apparent response to faecal gas emission of NH3, total mercaptans, or H2S was observed in relation to the BP extract in the pig diet (p < 0.05). Dietary supplementation with 0.1 % BP extract improved growth performance by increasing the ATTD of CP and improving LMP without adverse effects in grower pigs.

Exact test and exact confidence interval for the Cox model.

The Cox proportional hazards model is commonly used to analyze time-to-event data in clinical trials. Standard inference procedures for the Cox model are based on asymptotic approximations and may perform poorly when there are few events in one or both treatment groups, as may be the case when the event of interest is rare or when the experimental treatment is highly efficacious. In this article, we propose an exact test of equivalence and efficacy under a proportional hazard model with treatment effect as the only fixed effect, together with an exact confidence interval that is obtained by inverting the exact test. The proposed test is based on a conditional error method originally proposed for sample size reestimation problems. In the present context, the conditional error method is used to combine information from a sequence of hypergeometric distributions, one at each observed event time. The proposed procedures are evaluated in simulation studies and illustrated using real data from an HIV prevention trial. A companion R package "ExactCox" is available for download on CRAN.

Enzyme-Dynamic Extracellular Vesicles for Metalloimmunotherapy of Malignant Pleural Effusions.

Malignant pleural effusions (MPEs) are hard to treat, and their onset usually signals terminal cancer. Immunotherapies hold promise but must overcome the immunosuppressive MPE microenvironment. Herein, we treat MPEs via synergistically combining two emerging cancer therapy modalities: enzyme-dynamic therapy (EDT) and metalloimmunotherapy. To do so, a nanoplatform termed "A-R-SOME" was developed which comprises MPE-targeted M1 type extracellular vesicles (EVs) loaded with (1) a manganese-based superoxide dismutase (SOD) enzyme, (2) stimulator of interferon genes (STING) agonist diABZI-2, and (3) signal transducer and an activator of transcription 3 (STAT3) small interfering RNA. Endogenous reactive oxygen species within tumors induced immunogenic cell death by EDT, along with STING activation by both Mn and diABZI-2, and suppression of the STAT3 pathway. Systemically administered A-R-SOME alleviated the MPE immunosuppressive microenvironment, triggered antitumor systemic immunity, and long-term immune memory, leading to the complete eradication of MPE and pleural tumors with 100% survival rate in an aggressive murine model. A-R-SOME-induced immune effects were also observed in human patient-derived MPE, pointing toward the translation potential of A-R-SOME as an experimental malignancy treatment.