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Downstream process (DSP) intensification technologies have the potential to provide faster, more sustainable, and more profitable processes. Nevertheless, the calculation of the possible benefits obtained from the implementation of these technologies is not always evident and usually depends on a particular production scenario. In the present work, we developed a framework for techno-economic feasibility analysis to assess the impact of changes in protein A capture, polishing, and viral filtration on process performance. The simulation used in this analysis is based on fundamental knowledge of the process and incorporates previously developed tools for calculating multi-column chromatography (MCC) and ultrafiltration-diafiltration variables. This framework was used to simulate production scenarios featuring intensified production schedules, increases in feed titers, MCC, integrated batch polishing, and high throughput viral filtration. These process alternatives were compared through key performance indicators that were selected to address specific questions on the suitability of these process intensification strategies in a particular context. Results were presented graphically for decision-makers to easily identify the best process alternatives for a given production scenario. For the conditions proposed in this work, we find that the scheduling practices, and not the unit operation processing times, have the greatest impact on process productivity. For instance, doubling the harvesting frequency resulted in a productivity increase of up to 61 %. Meanwhile, technological intensification strategies like MCC cause the greatest impact on operating costs, reducing cost of goods of the DSP by up to 27 %. Overall, intensification of individual unit operations can yield benefits from a sustainability and cost perspective, but to achieve higher throughputs, it is necessary to have fully intensified DSP and scheduling practices., Competing Interests: Declaration of competing interest Scott Husson has an ongoing financial interest in Purilogics and provides consulting services to the Company. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. The remaining authors declare no known competing interests that could affect the work reported in this article., (Copyright © 2024. Published by Elsevier B.V.)

Background: Infection prevention and control (IPC) programs are essential to prevent and control the spread of multidrug-resistant organisms in healthcare facilities (HCFs). The current implementation of these programs in Latin America remains largely unknown., Methods: We conducted a mixed-methods evaluation of IPC program implementation in HCFs from Guatemala, Panama, Ecuador, and Argentina, March-July 2022. We used the World Health Organization (WHO) IPC Assessment Framework (IPCAF) survey, a previously validated structured questionnaire with an associated scoring system that evaluates the eight core components of IPC (IPC program; IPC guidelines; IPC education and training; healthcare-associated infection [HAI] surveillance; multimodal strategies; monitoring and audit of IPC practices and feedback; workload, staffing, and bed occupancy; and the built environment and materials and equipment for IPC). Each section generates a score 0-100. According to the final score, the HCF IPC program implementation is categorized into four levels: inadequate (0-200), basic (201-400), intermediate (401-600), or advanced (601-800). Additionally, we conducted semi-structured interviews among IPC personnel and microbiologists using the Systems Engineering Initiative for Patient Safety model to evaluate barriers and facilitators for IPC program implementation. We performed directed content analysis of interview transcripts to identify themes that focused on barriers and facilitators of IPC program implementation which are summarized descriptively., Results: Thirty-seven HCFs (15 for-profit and 22 non-profit) completed the IPCAF survey. The overall median score was 614 (IQR 569, 693) which corresponded to an "advanced" level of IPC implementation (32% [7/22] non-profit vs. 93% [14/15] for-profit HCFs in this category). The lowest scores were in workload, staffing and bed occupancy followed by IPC training and multimodal strategies. Forty individuals from 16 HCFs were interviewed. They perceived inadequate staffing and technical resources, limited leadership support, and cultural determinants as major barriers to effective IPC guideline implementation, while external accreditation and technical support from public health authorities were perceived as facilitators., Conclusions: Efforts to strengthen IPC activities in Latin American HCFs should focus on improving support from hospital leadership and public health authorities to ensure better resource allocation, promoting safety culture, and improving training in quality improvement., (© 2024. The Author(s).)

Background: The objective of this study was to identify antibiotic stewardship (AS) opportunities in Latin American medical-surgical intensive care units (MS-ICUs) and general wards (Gral-wards)., Methods: We conducted serial cross-sectional point prevalence surveys in MS-ICUs and Gral-wards in 41 Latin American hospitals between March 2022 and February 2023. Patients >18 years of age in the units of interest were evaluated for antimicrobial use (AU) monthly (MS-ICUs) or quarterly (Gral-wards). Antimicrobial data were collected using a standardized form by the local AS teams and submitted to the coordinating team for analysis., Results: We evaluated AU in 5780 MS-ICU and 7726 Gral-ward patients. The hospitals' median bed size (interquartile range) was 179 (125-330), and 52% were nonprofit. The aggregate AU prevalence was 53.5% in MS-ICUs and 25.5% in Gral-wards. Most (88%) antimicrobials were prescribed to treat infections, 7% for surgical prophylaxis and 5% for medical prophylaxis. Health care-associated infections led to 63% of MS-ICU and 38% of Gral-ward AU. Carbapenems, piperacillin-tazobactam, intravenous (IV) vancomycin, and ampicillin-sulbactam represented 50% of all AU to treat infections. A minority of IV vancomycin targeted therapy was associated with documented methicillin-resistant Staphylococcus aureus infection or therapeutic drug monitoring. In both units, 17% of antibiotics prescribed as targeted therapy represented de-escalation, while 24% and 15% in MS-ICUs and Gral-wards, respectively, represented an escalation of therapy. In Gral-wards, 32% of antibiotics were used without a microbiologic culture ordered. Half of surgical prophylaxis antibiotics were prescribed after the first 24 hours., Conclusions: Based on this cohort, areas to improve AU in Latin American hospitals include antibiotic selection, de-escalation, duration of therapy, and dosing strategies., Competing Interests: Potential conflicts of interest. The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Limited information exists regarding health care workers' (HCWs) perceptions about infection prevention and control (IPC) in Latin America., Methods: We conducted an electronic voluntary anonymous survey to assess HCWs' perceptions toward IPC in 30 hospitals in Latin America during August to September 2022. Nurses, physicians, and environmental cleaning (EVC) staff were prioritized for recruitment., Results: Overall, 1,340 HCWs completed the survey. Of these, 28% were physicians, 49% nurses, 8% EVC staff, and 15% had "other" roles. Self-compliance with hand hygiene and prevention bundles was perceived to be high by 95% and 89% of respondents, respectively; however, ratings were lower when asked about compliance by their peers (reported as high by 81% and 75%, respectively). Regular training on IPC and access to health care-associated infections (HAI) rates were more limited among physicians than other HCWs (eg, 87% of EVC staff and 45% of physicians reported training upon hiring and thereafter, 60% of nurses and 51% of physicians reported regular access to HAI rate reports)., Conclusions: We identified several opportunities to strengthen IPC practices in Latin American hospitals, including improving HCW education and training on IPC and their awareness of HAI rates and compliance with prevention measures., (Copyright © 2024. Published by Elsevier Inc.)

Lignin represents one of the most abundant plant-derived polymers. It is mostly present in the cell wall, and its primary role is to provide mechanical support to the plant. Chemical processes during wood-pulping yield diverse technical lignins with distinct characteristics. Due to their complex and variable nature, technical lignins are often undervalued and are mainly used as burning fuel in mills. However, various technical lignins have been shown to possess antimicrobial properties. Consequently, there is an increasing interest in understanding the properties and conditions that underlie their antimicrobial characteristics and how we can utilize them for practical applications. This review, for the first time, comprehensively summarized the antimicrobial activities of technical lignins and their potential antimicrobial applications.

Background: The burden of antimicrobial resistance (AMR) in Latin America is high. Little is known about healthcare workers' (HCWs) knowledge, attitudes, and perceptions of antimicrobial stewardship (AS), AMR, and antibiotic use (AU) in the region., Methods: HCWs from 42 hospitals from 5 Latin American countries were invited to take an electronic, voluntary, anonymous survey regarding knowledge, attitudes, and perceptions of AS, AMR, and AU between March-April 2023., Findings: Overall, 996 HCWs completed the survey (52% physicians, 32% nurses, 11% pharmacists, 3% microbiologists, and 2% "other"). More than 90% of respondents indicated optimizing AU was a priority at their healthcare facility (HCF), 69% stated the importance of AS was communicated at their HCF, and 23% were unfamiliar with the term "antibiotic stewardship". Most (> 95%) respondents acknowledged that appropriate AU can reduce AMR; however, few thought AU (< 30%) or AMR (< 50%) were a problem in their HCF. Lack of access to antibiogram and to locally endorsed guidelines was reported by 51% and 34% of HCWs, respectively. Among prescribers, 53% did not consider non-physicians' opinions to make antibiotic-related decisions, 22% reported not receiving education on how to select antibiotics based on culture results and 60% stated patients and families influence their antibiotic decisions., Conclusions: Although HCWs perceived improving AU as a priority, they did not perceive AU or AMR as a problem in their HCF. AS opportunities include improved access to guidelines, access to AMR/AU data, teamwork, and education on AS for HCWs and patients and families., (© 2024. The Author(s).)

Ballon d'Or is the most important individual award in football, and is a significant measure of excellence. From our knowledge, this is the first study that explored the relative age effect (RAE) throughout the history of the Ballon d'Or. A total of 1899 football players nominated for the award from the first edition in 1956 to the most recent edition (2023) were analyzed. To assess the RAE, the birthdate distributions were categorized into four trimesters. The comparison involved correcting for the uniform distribution using chi-square analysis, with Cramer's V serving as a measure of effect size. Standardized residuals were computed to identify quarters that exhibited significant deviation from the expected values. Odds Ratio and 95% confidence intervals were used to identify discrepancies between trimesters. The results indicated a pronounced presence of an RAE at the global level. However, the longitudinal analysis revealed variations in the behavior of the RAE over time. In the initial decades, there is an overrepresentation of players born in the last months of the year. Subsequently, there is no discernible RAE. In the most recent decades, there has been a clear resurgence of RAE, with an overrepresentation of players born in the first quarters of the year.

We evaluate depletion forces in molecular dynamics simulation of a binary mixture of spheres (depleted particles) and rods (depletant particles) for a wide range of densities for both species. This evaluation was carried out using a recently proposed least squares fitting algorithm. We found that the restriction of the rods' rotational degrees of freedom, when the distance between two spheres is less than the rods length, creates a shallow, and apparently linear, attractive force ramp. For intersphere distances smaller than the rods' diameter, a much stronger attractive force is found, and a large repulsive barrier appears between these aforementioned regimes, roughly at the distance of the rods' thickness. The evaluated forces are validated via a comparison of the pairwise correlation functions obtained from molecular dynamics simulation of a mono-disperse sphere fluid, using the evaluated effective forces, against the original (full system) pairwise correlation functions. Agreement is excellent. We also record the angular pairwise correlation function, using the P2(x) Legendre polynomial, and find that for high densities of both species, a local nematic ordering starts to appear. This nematic order may be a factor in the small differences found between original and effective pairwise correlation functions at high densities of rods., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Purpose: A variable number of tandem repeats (VNTR) in the insulin gene (INS) control region may be involved in type 2 diabetes (T2D). The TH01 microsatellite is near INS and may regulate it. We investigated whether the TH01 microsatellite and INS VNTR, assessed via the surrogate marker single nucleotide polymorphism rs689, are associated with T2D and serum insulin levels in a Mexican population., Methods: We analyzed a main case-control study (n = 1986) that used univariate and multivariate logistic regression models to calculate the risk conferred by TH01 and rs689 loci for T2D development; rs689 results were replicated in other case-control (n = 1188) and cross-sectional (n = 1914) studies., Results: TH01 alleles 6, 8, 9, and 9.3 and allele A of rs689 were independently associated with T2D, with differences between sex and age at diagnosis. TH01 alleles with ≥ 8 repeats conferred an increased risk for T2D in males compared with ≤ 7 repeats (odds ratio, ≥ 1.46; 95% confidence interval, 1.1-1.95). In females, larger alleles conferred a 1.5-fold higher risk for T2D when diagnosed ≥ 46 years but conferred protection when diagnosed ≤ 45 years. Similarly, rs689 allele A was associated with T2D in these groups. In males, larger TH01 alleles and the rs689 A allele were associated with a significant decrease in median fasting plasma insulin concentration with age in T2D cases; the reverse occurred in controls., Conclusion: Larger TH01 alleles and rs689 A allele may potentiate insulin synthesis in males without T2D, a process disabled in those with T2D., (© 2023. The Author(s).)

Background: Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM); its diagnosis and treatment are based on symptomatic improvement. However, as pharmacological therapy causes multiple adverse effects, the implementation of acupunctural techniques, such as electroacupuncture (EA) has been suggested as an alternative treatment. Nonetheless, there is a lack of scientific evidence, and its mechanisms are still unclear. We present the design and methodology of a new clinical randomized trial, that investigates the effectiveness of EA for the treatment of DPN., Methods: This study is a four-armed, randomized, controlled, multicenter clinical trial (20-week intervention period, plus 12 weeks of follow-up after concluding intervention). A total of 48 T2DM patients with clinical signs and symptoms of DPN; and electrophysiological signs in the Nerve Conduction Study (NCS); will be treated by acupuncture specialists in outpatient units in Mexico City. Patients will be randomized in a 1:1 ratio to one of the following four groups: (a) short fibre DPN with EA, (b) short fibre DPN with sham EA, (c) axonal DPN with EA and (d) axonal DPN with sham EA treatment. The intervention will consist of 32 sessions, 20 min each, per patient over two cycles of intervention of 8 weeks each and a mid-term rest period of 4 weeks. The primary outcome will be NCS parameters, and secondary outcomes will include DPN-related symptoms and pain by Michigan Neuropathy Screening Instrument (MNSI), Michigan Diabetic Neuropathy Score (MDNS), Dolour Neuropatique Score (DN-4), Semmes-Westein monofilament, Numerical Rating Scale (NRS) for pain assessment, and the 36-item Short Form Health Survey (SF-36). To measure quality of life and improve oxidative stress, the inflammatory response; and genetic expression; will be analysed at the beginning and at the end of treatment., Discussion: This study will be conducted to compare the efficacy of EA versus sham EA combined with conventional diabetic and neuropathic treatments if needed. EA may improve NCS, neuropathic pain and symptoms, oxidative stress, inflammatory response, and genetic expression, and it could be considered a potential coadjutant treatment for the management of DPN with a possible remyelinating effect., Trial Registration: ClinicalTrials.gov. NCT05521737 Registered on 30 August 2022. International Clinical Trials Registry Platform (ICTRP) ISRCTN97391213 Registered on 26 September 2022 [2b]., (© 2024. The Author(s).)

In this work, we discuss the use of surrogate functions and a new optimization framework to create an efficient and robust computational framework for process design. Our model process is the capture chromatography unit operation for monoclonal antibody purification, an important step in biopharmaceutical manufacturing. Simulating this unit operation involves solving a system of non-linear partial differential equations, which can have high computational cost. We implemented surrogate functions to reduce the computational time and make the framework more attractive for industrial applications. This strategy yielded accurate results with a 93% decrease in processing time. Additionally, we developed a new optimization framework to reduce the number of simulations needed to generate a solution to the optimization problem. We demonstrate the performance of our new framework, which uses MATLAB built-in tools, by comparing its performance against individual optimization algorithms for problems with integer, continuous, and mixed-integer variables., Competing Interests: Scott M Husson reports a relationship with Purilogics that includes: equity or stocks.

Hibiscus sabdariffa possess great versatility to be used as an ingredient for a whole range of products with natural-based ingredients, which are growing in popularity due to the health benefits of bioactive compounds (BC). Therefore, the objective of this study was to characterize the BC content in Hibiscus beverages and to evaluate their in vitro bioaccessibility. Results showed significant differences ( p < 0.05) in the total contents of BC prior to the in vitro intestinal digestion. Hibiscus acid was the most abundant compound identified. Thirty-five compounds were identified in the Hibiscus beverage at the initial stage, while a maximum of 15 compounds were quantified in the different fractions of gastrointestinal digestion. After digestion, significant differences were found compared with the initial content of BC. That phenolic acids were the less bioaccessible group, while flavonoids were the most diverse. Principal components analysis showed different clusters and changes in the profiles of BC present at the initial stage and those bioaccessible, showing that intestinal digestion significantly affects the BC profile of the beverage.

We developed a computational framework that integrates commercial software components to perform customizable technoeconomic feasibility analyses. The use of multiple software packages overcomes the shortcomings of each to provide a detailed simulation that can be used for sensitivity analyses and optimizations. In this paper, the framework was used to evaluate the performance of monoclonal antibody capture processes. To this end, the simulation framework incorporated dynamic models for the affinity chromatography step that were validated with experimental breakthrough curves. The results were integrated with an Intelligen SuperPro Designer process simulation for the evaluation of key performance indicators of the operations. As proof of concept, the framework was used to perform a sensitivity analysis and optimization for a case study in which we sought to compare membrane and resin chromatography for disposable and reusable batch capture platforms. Two membranes and one resin were selected for the capture media, which yielded six process alternatives to compare. The objective functions were set to be cost of goods, process time, and buffer utilization. The results of the optimization of these process alternatives were a set of operating conditions that display tradeoffs between competing objectives. From this application exercise, we conclude that the framework can handle multiple variables and objectives, and it is adaptable to platforms with different chromatography media and operating modes. Additionally, the framework is capable of providing ad hoc analyses for decision making in a specific production context., Competing Interests: Declaration of Competing Interest Scott Husson has an ongoing financial interest in Purilogics and provides consulting services to the Company., (Copyright © 2022. Published by Elsevier B.V.)

The identification and selection of genetically superior animals for residual feed intake (RFI) could enhance productivity and minimize environmental impacts. The aim of this study was to use RNA-seq data to identify the differentially expressed genes (DEGs), known non-coding RNAs (ncRNAs), specific biomarkers and enriched biological processes associated with RFI of the liver in Nellore cattle in two genetic groups. In genetic group 1 (G1), 24 extreme RFI animals (12 low RFI (LRFI) versus 12 high RFI (HRFI)) were selected from a population of 60 Nellore bulls. The RNA-seq of the samples from their liver tissues was performed using an Illumina HiSeq 2000. In genetic group 2 (G2), 20 samples of liver tissue of Nellore bulls divergent for RFI (LRFI, n = 10 versus HRFI, n = 10) were selected from 83 animals. The raw data of the G2 were chosen from the ENA repository. A total of 1811 DEGs were found for the G1 and 2054 for the G2 ( p -value ≤ 0.05). We detected 88 common genes in both genetic groups, of which 33 were involved in the immune response and in blocking oxidative stress. In addition, seven ( B2M , ADSS , SNX2 , TUBA4A , ARHGAP18 , MECR , and ABCF3 ) possible gene biomarkers were identified through a receiver operating characteristic analysis (ROC) considering an AUC > 0.70. The B2M gene was overexpressed in the LRFI group. This gene regulates the lipid metabolism protein turnover and inhibits cell death. We also found non-coding RNAs in both groups. MIR25 was up-regulated and SNORD16 was down-regulated in the LRFI for G1. For G2, up-regulated RNase&#95;MRP and SCARNA10 were found. We highlight MIR25 as being able to act by blocking cytotoxicity and oxidative stress and RMRP as a blocker of mitochondrial damage. The biological pathways associated with RFI of the liver in Nellore cattle in the two genetic groups were for energy metabolism, protein turnover, redox homeostasis and the immune response. The common transcripts, biomarkers and metabolic pathways found in the two genetic groups make this unprecedented work even more relevant, since the results are valid for different herds raised in different ways. The results reinforce the biological importance of these known processes but also reveal new insights into the complexity of the liver tissue transcriptome of Nellore cattle.

Cryptographic algorithms (RSA, DSA, and ECC) use modular exponentiation as part of the principal operation. However, Non-profiled Side Channel Attacks such as Simple Power Analysis and Differential Power Analysis compromise cryptographic algorithms that use such operation. In this work, we present a modification of a modular exponentiation algorithm implemented in programmable devices, such as the Field Programmable Gate Array, for which we use Virtex-6 and Artix-7 evaluation boards. It is shown that this proposal is not vulnerable to the attacks mentioned previously. Further, a comparison was made with other related works, which use the same family of FPGAs. These comparisons show that this proposal not only defeats physical attack but also reduces the number of resources. For instance, the present work reduces the Look-Up Tables by 3550 and the number of Flip-Flops was decreased by 62,583 compared with other works. Besides, the number of memory blocks used is zero in the present work, in contrast with others that use a large number of blocks. Finally, the clock cycles (latency) are compared in different programmable devices to perform operations.

Our objectives were to compare the antifungal activity of 5 lignosulfonates, and 2 chitosans against fungi isolated from spoiled hay, and assess the effects of an optimized lignosulfonate, chitosan, and propionic acid (PRP) on high-moisture alfalfa hay. In experiment 1, we determined the minimum inhibitory concentration and minimum fungicidal concentration of 4 sodium lignosulfonates, 1 magnesium lignosulfonate, 2 chitosans, and PRP (positive control) against Aspergillus amoenus, Mucor circinelloides, Penicillium solitum, and Debaromyces hansenii at pH 4 and 6. Among sodium lignosulfonates, the one from Sappi Ltd. (NaSP) was the most antifungal at pH 4. However, chitosans had the strongest fungicidal activity with the exception of M. circinelloides at both pH 4 and 6. PRP had more antifungal effects than NaSP and was only better than chitosans for M. circinelloides. In experiment 2, we evaluated the effects of 3 additives (ADV): optimized NaSP (NaSP-O, UMaine), naïve chitosan (ChNv, Sigma-Aldrich), and PRP on high-moisture alfalfa hay. The experimental design was a randomized complete block design replicated 5 times. Treatment design was the factorial combination of 3 ADV× 5 doses (0, 0.25, 0.5, 1, and 2% w/w fresh basis). Additives were added to 35 g of sterile alfalfa hay (71.5 ± 0.23% DM), inoculated with a mixture of previously isolated spoilage fungi (5.8 log cfu/fresh g), and aerobically incubated in vitro for 23 d (25°C). After incubation, DM losses were reduced by doses as low as 0.25% for both NaSP-O and PRP (x¯=1.61) vs. untreated hay (24.0%), partially due to the decrease of mold and yeast counts as their doses increased. Also, hay NH3-N was lower in NaSP-O and PRP, with doses as low as 0.25%, relative to untreated hay (x¯=1.13 vs. 7.80% of N, respectively). Both NaSP-O and PRP increased digestible DM recovery (x¯=69.7) and total volatile fatty acids (x¯=94.3), with doses as low as 0.25%, compared with untreated hay (52.7% and 83.8 mM, respectively). However, ChNv did not decrease mold nor yeast counts (x¯=6.59 and x¯=6.16 log cfu/fresh g, respectively) and did not prevent DM losses relative to untreated hay. Overall, when using an alfalfa hay substrate in vitro, NaSP-O was able to prevent fungal spoilage to a similar extent to PRP. Thus, further studies are warranted to develop NaSP-O as a hay preservative under field conditions., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Nowadays, the nitrates have been established as carcinogenic components due to the endogenous formation of N -nitroso compounds, however, the consumption of water contaminated with nitrates has only been strongly related to the presence of methemoglobinemia in infants, as an acute effect, leaving out other side effects that demand attention. The thyroid gland takes relevance because it can be altered by many pollutants known as endocrine disruptors, which are agents capable of interfering with the synthesis of hormones, thus far, it is known that nitrates may disrupt the amount of iodine uptake causing most of the time hypothyroidism and affecting the metabolic functions of the organism in all development stages, resulting in an important health burden for the exposed population. Here, this review and update highlighted the impact of consumption of water contaminated with nitrates and effects on the thyroid gland in humans, concluding that nitrates could act as true endocrine disruptor.

This study evaluated the effects of chemical and biological preservatives and ensiling stage on spoilage, ruminal in vitro fermentation, and methane production of wet brewer's grain (WBG) silage. Treatments (TRT) were sodium lignosulfonate at 10 g/kg fresh WBG (NaL1) and 20 g/kg (NaL2), propionic acid at 5 g/kg fresh WBG (PRP, 99%), a combination inoculant (INO; Lactococcus lactis and Lactobacillus buchneri each at 4.9 log cfu per fresh WBG g), and untreated WBG (CON). Fresh WBG was treated and then ensiled for 60 d, after which mini silos were opened and aerobically exposed (AES) for 10 d. Data were analyzed as an RCBD (five blocks) with a 5 TRT × 3 stages (STG; fresh, ensiled, and AES) factorial arrangement. Results showed that ensiled PRP-treated WBG markedly preserved more water-soluble carbohydrates and starch than all other ensiled TRT (P < 0.001). Dry matter losses of ensiled PRP-treated WBG were 48% lower than all other ensiled TRT (P = 0.009) but were not different than CON in AES (P = 0.350). Due to its greater concentration of digestible nutrients, PRP-treated AES was less aerobically stable than CON (P = 0.03). Preservation was not improved by INO, NaL1, or NaL2 but the latter prevented the increase of neutral detergent fiber across STG (P = 0.392). Apparent in vitro DM digestibility (IVDMD) decreased only in ensiled CON, INO, and NaL1 relative to fresh WBG and AES NaL2 had greater IVDMD than all other AES TRT (P ≤ 0.032). In vitro ruminal fermentation of fresh WBG resulted in a greater methane concentration and yield than the other STG (P < 0.033). In conclusion, PRP was the most effective at preserving WBG during ensiling but failed to improve aerobic stability under the conditions tested., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A meta-analysis was performed to evaluate the effects of chemical (50 articles) and microbial (21 articles) additives on hay preservation during storage. Multilevel linear mixed-effects models were fit with response variables calculated as predicted differences (Δ) between treated and untreated samples. Chemical preservatives were classified into five groups such as propionic acid (PropA), buffered organic acids (BOA), other organic acids (OOA), urea, and anhydrous ammonia (AA). Moderators of the models included preservative class (PC), forage type (FT; grass, legumes, and mixed hay), moisture concentration (MC), and application rate (AR). Dry matter (DM) loss during storage was affected by PC × FT (P = 0.045), PC × AR (P < 0.001), and PC × MC (P = 0.009), relative to the overall effect of preservatives (-0.37%). DM loss in PropA-treated hay was numerically reduced to a greater extent in grasses (-16.2), followed by mixed hay (-1.76), but it increased (+2.2%) in legume hay. Increasing AR of PropA resulted in decrease in DM loss (slope = -1.34). Application of BOA, OOA, PropA, and AA decreased visual relative moldiness by -22.1, -29.4, -45.5, and -12.2 percentage points, respectively (PC; P < 0.001). Sugars were higher in treated grass hay (+1.9) and lower in treated legume hay (-0.8% of DM) relative to their untreated counterparts (P < 0.001). The application of all preservatives resulted in higher crude protein (CP) than untreated hay, particularly urea (+7.92) and AA (+5.66% of DM), but PropA, OOA, and BOA also increased CP by 2.37, 2.04, and 0.73 percentage points, respectively. Additionally, preservative application overall resulted in higher in vitro DM digestibility (+1.9% of DM) relative to the untreated hay (x¯=58.3%), which increased with higher AR (slope = 1.64) and decreased with higher MC (slope = -0.27). Microbial inoculants had small effects on hay spoilage because the overall DM loss effect size was -0.21%. Relative to untreated (x¯=4.63% DM), grass hay preserved more sugars (+1.47) than legumes (+0.33) when an inoculant was applied. In conclusion, organic acid-based preservatives prevent spoilage of hay during storage, but their effectiveness is affected by FT, MC, and AR. Microbial inoculants had minor effects on preservation that were impaired by increased MC. Moreover, legume hay was less responsive to the effects of preservatives than grass hay., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The cytoskeleton is a key component of the system responsible for transmitting mechanical cues from the cellular environment to the nucleus, where they trigger downstream responses. This communication is particularly relevant in embryonic stem (ES) cells since forces can regulate cell fate and guide developmental processes. However, little is known regarding cytoskeleton organization in ES cells, and thus, relevant aspects of nuclear-cytoskeletal interactions remain elusive., Results: We explored the three-dimensional distribution of the cytoskeleton in live ES cells and show that these filaments affect the shape of the nucleus. Next, we evaluated if cytoskeletal components indirectly modulate the binding of the pluripotency transcription factor OCT4 to chromatin targets. We show that actin depolymerization triggers OCT4 binding to chromatin sites whereas vimentin disruption produces the opposite effect. In contrast to actin, vimentin contributes to the preservation of OCT4-chromatin interactions and, consequently, may have a pro-stemness role., Conclusions: Our results suggest roles of components of the cytoskeleton in shaping the nucleus of ES cells, influencing the interactions of the transcription factor OCT4 with the chromatin and potentially affecting pluripotency and cell fate., (© 2021. The Author(s).)