Indirect Evidence Research Articles

Neuroimaging meta-analyses reveal convergence of interoception, emotion, and social cognition across neurodegenerative diseases.

Simultaneous interoceptive, emotional, and social cognition deficits are observed across neurodegenerative diseases. Indirect evidence suggests shared neurobiological bases underlying these impairments, termed the allostatic-interoceptive network (AIN). However, no study has yet explored the convergence of these deficits in neurodegenerative diseases or examined how structural and functional changes contribute to cross-domain impairments. A PRISMA Activated Likelihood Estimate (ALE) metanalyses encompassed studies meeting inclusion criteria: interoception, emotion, or social cognition tasks; neurodegenerative diseases (behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasias (PPAs) Alzheimer's disease (AD), Parkinson's Disease (PD), multiple sclerosis (MS)); and neuroimaging (structural: MRI voxel-based morphometry; functional: fMRI and FDG-PET). From 20,593 studies, 170 met inclusion criteria (58 interoception, 65 emotion, and 47 social cognition) involving 7032 participants (4963 patients and 2069 healthy controls). In all participants combined, conjunction analyses revealed AIN involvement of the insula, amygdala, orbitofrontal cortex, anterior cingulate, striatum, thalamus, and hippocampus across domains. In bvFTD this conjunction was replicated across domains, with further involvement of the temporal pole, temporal fusiform cortex, and angular gyrus. A convergence of interoception and emotion in the striatum, thalamus, and hippocampus in PD and the posterior insula in PPAs was also observed. In AD and MS, disruptions in the AIN were observed during interoception, but no convergence with emotion was identified. Neurodegeneration induces dysfunctional AIN across atrophy, connectivity, and metabolism, more accentuated in bvFTD. Findings bolster the predictive coding theories of large-scale AIN, calling for more synergistic approaches to understanding interoception, emotion, and social cognition impairments in neurodegeneration.

The Generation of Seismogenic Anomalous Electric Fields in the Lower Atmosphere, and Its Application to Very-High-Frequency and Very-Low-Frequency/Low-Frequency Emissions: A Review

The purpose of this paper is, first of all, to review the previous works on the seismic (or earthquake (EQ)-related) direct current (DC) (or quasi-stationary) electric fields in the lower atmosphere, which is likely to be generated by the conductivity current flowing in the closed atmosphere–ionosphere electric circuit during the preparation phase of an EQ. The current source is electromotive force (EMF) caused by upward convective transport and the gravitational sedimentation of radon and charged aerosols injected into the atmosphere by soil gasses during the course of the intensification of seismic processes. The theoretical calculations predict that pre-EQ DC electric field enhancement in the atmosphere can reach the breakdown value at the altitudes 2–6 km, suggesting the generation of a peculiar seismic-related thundercloud. Then, we propose to apply this theoretical inference to the observational results of seismogenic VHF (very high frequency) and VLF/LF (very low frequency/low frequency) natural radio emissions. The formation of such a peculiar layer initiates numerous chaotic electrical discharges within this region, leading to the generation of VHF electromagnetic radiation. Earlier works on VHF seismogenic radiation performed in Greece have been compared with the theoretical estimates, and showed a good agreement in the frequency range and intensity. The same idea can also be applied, for the first time, to seismogenic VLF/LF lightning discharges, which is completely the same mechanism with conventional cloud-to-ground lightning discharges. In fact, such seismogenic VLF/LF lightning discharges have been observed to appear before an EQ. So, we conclude in this review that both seismogenic VHF radiation and VLF/LF lightning discharges are regarded as indirect evidence of the generation of anomalous electric fields in the lowest atmosphere due to the emanation of radioactive radon and charged aerosols during the preparation phase of EQs. Finally, we have addressed the most fundamental issue of whether VHF and VLF/LF radiation reported in earlier works is either of atmospheric origin (as proposed in this paper) or of lithospheric origin as the result of microfracturing in the EQ fault region, which has long been hypothesized. This paper will raise a question regarding this hypothesis of lithospheric origin by proposing an alternative atmospheric origin outlined in this review. Also, the data on seismogenic electromagnetic radiation and its inference on perturbations in the lower atmosphere will be suggested to be extensively integrated in future lithosphere–atmosphere–ionosphere coupling (LAIC) studies.

Опыт изучения трансформации подзолистых почв в условиях городской среды Севера

The results of soil studies of one of the medium-sized cities of the Russian European Northeast – Syktyvkar (Russia, Komi Republic, middle taiga subzone) are presented in the article. The series from a podzolic soil with a microprofile of podzol (Albic Retisol (Loamic, Protospodic)) typical for the region to various variants of its human transformation in urban conditions – cultivated agrodernovo-podzolic soil (Eutric Albic Retisol (Loamic, Aric, Humic)), represented on the site of the Botanical Garden, to urbodernovo-podzolic soil (Eutric Albic Retisol (Loamic, Humic, Transporti-Novic, Thaptoaric)) and urbostratozem (Urbic Technosol (Loamic, Eutric, Humic Transport)) described in the central part of the city, included in the urban development in the first half of the XX century is considered. In urbo-soil and urbanostratozem the thickness of urbogenic horizons is approximately 40 and 70 cm. It is shown the first stages of the development of the territory of Syktyvkar city are associated with the agricultural impact. Subsequently, the arable horizons overlap with the horizons of the urban cultural layer. In the considered series of soils, weak alkalinization, an increase in the absorbed bases and the total mineralization of the soil solution were found. A noticeable increase in the concentration of organic carbon in modern arable and urban horizons, as well as the thickness of horizons with the organic carbon content of more than 0.6% was revealed. An indirect evidences of changes in the composition of iron and manganese minerals (due to an increase in the pH) with partial preservation of zonal soil formation trends has been found. The revealed direction of soil evolution is consistent with the one previously described in the cities of the European part of Russia.

Are Mondays different? Evidence from initial public offerings

This paper investigates how and why initial public offerings (IPOs) issued on Mondays differ from those on other days. We provide evidence that Monday IPOs make a significantly larger number of filing price amendments during the road show and set offer prices that exceed the filing price range, resulting in higher positive offer price revisions. We also find that Monday IPOs receive less analyst coverage than other-day IPOs, despite their underwriting fees being the same and their total underwriter compensation being higher. Therefore, Monday IPOs are more likely to change lead underwriters in subsequent equity offerings and have a higher risk of delisting as aftermarket support and maintaining good relations with investment banks are critical for their long run survival. We also investigate why underwriters issue IPOs on Mondays. We suggest four possible explanations for Monday IPOs and find indirect evidence that supports the deliberate road show extension explanation.

Seasonal and genetic effects on lipid profiles of juvenile Atlantic salmon

Seasonality can influence many physiological traits requiring optimal energetic capacity for life-history stage transitions. In Atlantic salmon, high-energy status is essential for the initiation of maturation. Earlier studies have linked a genomic region encoding vgll3 to maturation age, potentially mediated via body condition. Vgll3 has also been shown to act as an inhibitor of adipogenesis in mice. Here we investigate the influence of season and vgll3 genotypes associating with early (EE) and late (LL) maturation on lipid profiles in the muscle and liver of juvenile Atlantic salmon. We reared Atlantic salmon for two years from fertilization and sampled muscle and liver during the spring and autumn of the second year (at which time some males were sexually mature). We found no seasonal or genotype effect in the muscle lipid profiles of immature males or females. However, in the liver we detected a triacylglycerol enrichment and a genotype specific direction of change in membrane lipids, phosphatidylcholine and phosphatidylethanolamine, from spring to autumn. Specifically, from spring to autumn membrane lipid concentrations increased in vgll3*EE individuals but decreased in vgll3*LL individuals. This could be explained by 1) a seasonally more stable capacity of endoplasmic reticulum (ER) functions in vgll3*EE individuals compared to vgll3*LL individuals or 2) vgll3*LL individuals storing larger lipid droplets from spring to autumn in the liver compared to vgll3*EE individuals at the expense of ER capacity. This genotype specific seasonal direction of change in membrane lipid concentrations provides more indirect evidence of a potential mechanism linking vgll3 with lipid metabolism and storage.

Network meta-analysis: a powerful tool for clinicians, decision-makers, and methodologists

Network Meta-analysis (NMA) is an advanced statistical method that combines direct evidence (ie, from head-to-head comparisons) and indirect evidence (ie, estimated from the direct available evidence) to obtain network estimates. NMAs are helpful to determine the comparative effectiveness of interventions that have not been directly compared and may provide more precise estimates for those comparisons that have been directly compared. NMA provides hierarchies which can be helpful for decision-making, much more in scenarios when multiple interventions exist for the same indication. In this article we provide a summary of the key concepts that users, namely, clinicians and methodologists need to consider when using an NMA to inform decision making.

Vibration of effects resulting from treatment selection in mixed-treatment comparisons: a multiverse analysis on network meta-analyses of antidepressants in major depressive disorder

ObjectiveIt is frequent to find overlapping network meta-analyses (NMAs) on the same topic with differences in terms of both treatments included and effect estimates. We aimed to evaluate the impact...

Understanding Network Meta‐Analysis: A Practical Introduction for Nurses

ABSTRACTAimsThis paper examines network meta‐analysis (NMA) as a methodological advancement in nursing research and discusses considerations for interpreting and applying NMA results in clinical practice.Design and MethodsMethodological discussion.ResultsThe NMA method simultaneously evaluates multiple interventions by combining direct and indirect evidence. The publication of NMA articles in nursing journals has been increasing. However, interpreting NMA results can be complex and challenging. In this paper, we outline the prerequisites and assumptions of NMA, provide a graphical representation, discuss effect estimation and quality of evidence and give an overview of applying NMA results in clinical practice.ConclusionNMA is a valuable analytical approach in nursing research that can provide high‐level evidence to guide clinical decision‐making. Accurate interpretation of NMA findings is necessary to inform clinical practice. This paper serves as an introduction to NMA for nurses unfamiliar with the approach.Implications for the ProfessionNMA is a powerful statistical technique for assessing the relative effectiveness of different nursing interventions and informing evidence‐based nursing guidelines. When interpreting the results, nurses should consider the certainty of evidence and the practical value of the results and be cautious of misleading conclusions.ImpactNMA is a recent analytical method in nursing research. This practical introduction seeks to enhance comprehension of NMA and the interpretation and application of NMA findings in clinical practice. NMA is a robust statistical technique to assess the relative effectiveness of various nursing interventions.Reporting MethodIn the methodological discussion guide, no new data was generated. A hypothetical dataset was used.Patient or Public ContributionThis methodological paper contributes to understanding NMA and interpreting its results, integrating it into clinical practice, and improving patient outcomes.

Novel evidence that elk were historically native to the Sierra Nevada, and recent range expansions into the region.

Elk (Cervus canadensis) have been considered non-native to the Sierra Nevada mountain range of California and Nevada. However, elk have steadily increased their range southward from the Cascade Range into the northern Sierra Nevada over the last century. Recent reports also reveal Rocky Mountain elk moving northwards into the southern Sierra Nevada. Dispersals of lone bull elk from 2019-2022 have occurred to the central Sierra Nevada south of Lake Tahoe. These recent range expansions of elk herds and long-distance dispersals of individual elk raised questions about the possible historical presence of elk throughout this mountain range. Herein we conducted a broad investigation into historical newspaper accounts and other early explorer and naturalist observer records, museum specimens, Late Holocene zooarchaeological records, and indirect evidence including toponomastic references and Native American ethnographic and ethnolinguistic information. Taken in total, a variety of data sources suggest elk inhabited portions of the Sierra Nevada and the adjacent northwest Great Basin from the Late Holocene through historical times. Positive records were not numerous, suggesting that historically elk were not abundant, and nearly extirpated during the California Fur Rush of the early nineteenth century.

The imprint of the first stars on the faint end of the white dwarf luminosity function

ABSTRACT Population III stars are characterized by extremely low metallicities as they are thought to be formed from a pristine gas in the early Universe. Although the existence of Population III stars is widely accepted, the lack of direct observational evidence hampers the study of the nature of the putative stars. In this article, we explore the possibilities of constraining the nature of the oldest stars by using the luminosity function of their remnants – white dwarfs. We study the formation and evolution of white dwarf populations by following star formation in a Milky Way-like galaxy using the semi-analytic model a-sloth. We derive the white dwarf luminosity function by applying a linear initial-final mass relation and Mestel’s cooling model. The obtained luminosity function is generally in agreement with available observations and theoretical predictions – with an exponential increase to a maximum of $M_{\mathrm{abs}} = 16$ and a sudden drop for $M_{\mathrm{abs}} \gt 16$. We explore the uncertainties of our model and compare them to the observational estimates. We adopt two different models of the initial mass function of Population III stars to show that the faint end of the luminosity function imprints the signature of Population III remnants. If the feature is detected in future observations, it would provide a clue to Population III stars and would also be an indirect evidence of low- to intermediate-mass Population III stars. We discuss the challenges and prospects for detecting the signatures.

The effect of hemicelluloses on biosynthesis, structure and mechanical performance of bacterial cellulose-hemicellulose hydrogels

The primary plant cell wall (PCW) is a specialized structure composed predominantly of cellulose, hemicelluloses and pectin. While the role of cellulose and hemicelluloses in the formation of the PCW scaffold is undeniable, the mechanisms of how hemicelluloses determine the mechanical properties of PCW remain debatable. Thus, we produced bacterial cellulose–hemicellulose hydrogels as PCW analogues, incorporated with hemicelluloses. Next, we treated samples with hemicellulose degrading enzymes, and explored its structural and mechanical properties. As suggested, difference of hemicelluloses in structure and chemical composition resulted in a variety of the properties studied. By analyzing all the direct and indirect evidences we have found that glucomannan, xyloglucan and arabinoxylan increased the width of cellulose fibers both by hemicellulose surface deposition and fiber entrapment. Arabinoxylan increased stresses and moduli of the hydrogel by its reinforcing effect, while for xylan, increase in mechanical properties was determined by establishment of stiff cellulose–cellulose junctions. In contrast, increasing content of xyloglucan decreased stresses and moduli of hydrogel by its weak interactions with cellulose, while glucomannan altered cellulose network formation via surface deposition, decreasing its strength. The current results provide evidence for structure–dependent mechanisms of cellulose–hemicellulose interactions, suggesting the specific structural role of the latter.

‘I think you’d strike’: Interpreting Preston in The Strike

The literary aftermath of the Preston lock-out has been dominated by Charles Dickens’s Hard Times (1854) and Elizabeth Gaskell’s North and South (1854–1855). Far less well known is The Strike , an anonymous tale published in 1855 by the Oxford publishing firm John Henry Parker. This article explores the relationships between The Strike and the ‘industrial novel’ (particularly Hard Times and North and South ) as well as comparing their respective handling of the historical reality of the Preston lock-out. It analyses the similarities and differences in the literary handling of the lock-out across all three texts and argues that, in terms of historical verisimilitude, The Strike generally demonstrates a greater degree of historical accuracy than either of its better-known counterparts. Additionally, it argues that the tale’s interest in co-operation suggests an author with Christian Socialist affiliations and, in its closing paragraphs, offers circumstantial evidence pointing to the Rev. Charles Marriott as a potential author of The Strike .

Nutraceutical interventions for erectile dysfunction: a systematic review and network meta-analysis.

Although nutraceutical-based treatments are often offered for erectile dysfunction (ED), their efficacy remains doubtful, and the choice of one substance over the other is challenged by the dearth of head-to-head comparative studies. We aimed to compare the efficacy of available nutraceutical interventions, alone or in combination with phosphodiesterase type 5 inhibitors (PDE5i), in improving erectile function in men with ED through a network meta-analysis (NMA), which incorporates direct and indirect evidence into one model thus generating a hierarchy of effectiveness. PubMed, Scopus, Web of Sciences, and Cochrane Library databases were searched for randomized placebo-controlled trials (RCTs) assessing the effect of any nutraceutical regimen in improving erectile function when compared to each other, placebo, and/or PDE5i in men with ED. Data were included in a random-effects NMA, where efficacy of treatments was ranked by surface under the cumulative ranking curve (SUCRA). Two NMAs were also conducted separately for organic and non-organic ED. Reciprocal comparisons between all treatments were analyzed by league tables. The main outcome was the standardized mean difference in the score of the International Index of Erectile Function (IIEF)-5 or IIEF-6. Fifteen RCTs provided information on 1000 men with ED. In the overall NMA, compared to placebo, the combination propionyl L-carnitine (PLC) + acetyl L-carnitine (ALC) + Sildenafil was associated with the highest SUCRA (97%) in improving erectile function score, followed by L-Arginine + Tadalafil (84%), Sildenafil (79%), Tadalafil (72%), and L-Arginine (52%). No other treatment regimen showed efficacy with statistical significance. In patients with organic ED, the efficacy of Sildenafil and Tadalafil was significantly improved by PLC + ALC and L-Arginine, respectively. On the contrary, in non-organic ED, nutraceuticals did not improve the therapeutic performance of daily Tadalafil. This NMA contributes valuable insights into the potential of nutraceutical interventions for ED. We employed strict inclusion criteria related to study design and diagnostic tool, ensuring the assumption of transitivity and the consistency of the analysis. Against a background of general ineffectiveness of most nutraceutical interventions, L-Arginine and the mix PLC + ALC appeared to be of some usefulness in improving erectile function, especially in combination with PDE5i in organic ED.

Indirect Evidence of the Effect of Informal Economy in the Behavior of the Foreign Currency’s Prices: A Case Study

The effect of informal economy on the behavior of exchange rate is complex and difficult to evaluate in common economic conditions. But if informal sector is sizeable and a certain foreign currency is used for transactions therein without being converted, the supply and the demand for this currency, the velocity of the money circulation, and several other variables would be impacted, implicating a measurable response in the corresponding FX rates’ behavior, while the other currencies’ prices will be less affected. Consequently, distinguishable dissimilarities regarding dynamics and statistical features are expected for the exchange rates of the currencies traded in the country. By evidencing and analyzing them, we can proceed with a backward analysis to identify the hidden relationships between informal economy and exchange rates. As a case study we analyzed the FX rates of main currencies traded in Albania, considering that specifically the Euro is used at a non-neglected volume as national currency substitute in the informal sector. Recognizing the complexity of the relationship under investigation, we have employed an interdisciplinary approach by incorporating econometrics and econophysics approaches. After examining the multifractal features of each FX series, the non-stationarity measure for distributions of the corresponding rate of returns, and the significance of self-organizing regimes on FX time series, we noticed that the price of the EU currency behaves distinguishably different. We described the specific features observed for the Euro-ALL exchange rates as an indication of their response to the informal economy and partial usage of the Euro in the role of national currency in this sector. Those findings are used also for opinionizing regarding formalization issues and scenarios of replacement of national currency by the Euro. Acknowledging that informality is undoubtedly harmful for the economy, this work is limited to providing an alternative explanation of specific FX rates comportment observed in the country, and to offer a descriptive analysis for similar systems.

Show me the evidence to guide nutrition practice: Scoping review of macronutrient dietary treatments after metabolic and bariatric surgery.

Clinical practice recommendations for macronutrient intake in Metabolic and Bariatric Surgery (MBS) are insufficiently grounded in the research, possibly due to a paucity of research in key areas necessary to support macronutrient recommendations. An initial scoping review, prior to any systematic review, was determined to be vital. To identify topical areas in macronutrients and MBS with a sufficient evidence base to guide nutrition recommendations. PubMed, Cochrane, Ovid Medline, and Embase were initially searched in January 2019 (updated November 1, 2023) with terms encompassing current bariatric surgeries and macronutrients. Out of 757 records identified, 98 were included. A template was created. Five types of outcomes were identified for extraction: dietary intake, anthropometrics, adverse symptoms, health, and metabolic outcomes. All stages of screening and extraction were conducted independently by at least two authors and disagreements were resolved via team discussion. Macronutrient-related dietary treatments were classified as either innovative or standard of care. Descriptions of dietary arms were extracted in detail for a qualitatively generated typology of dietary or nutritional treatments. Heatmaps (treatments by outcomes) were produced to identify promising topics for further systematic analyses. We identified protein supplementation and "food-focused" (e.g., portion-controlled meals, particular foods in the diet, etc.) topical areas in MBS nutrition care with potentially sufficient evidence to create specific MBS Macronutrients guidelines and identified topical areas with little research. Clinical practice regarding macronutrient intake remains guided by consensus and indirect evidence. We detail ways that leadership at the profession level may remedy this.

Unravelling the enigma: Autopsy challenges in alleged snakebite deaths

Snakebites account for a substantial public health burden in India, contributing to 80 % of global snakebite fatalities. This case series explores the intricacies of two alleged neurotoxic snakebite deaths, delving into the complexities of diagnosing neurotoxic snakebite deaths in India through meticulous medico-legal autopsies. Despite initial suspicions and circumstantial evidence suggesting snakebite involvement, the autopsies revealed surprising causes of death. The article discusses challenges in accurately attributing deaths to snakebites, and the potential for false claims, and underscores the crucial role of Forensic pathologists in dispelling enigmas. Forensic pathologists are urged to maintain an unbiased approach, allowing postmortem findings to guide conclusions amidst deliberate attempts to mislead. The cases described highlight that ruling out snake bites in cases with positive history is as challenging as opining a case of neurotoxic snake bite as they are mainly the diagnosis of exclusion in autopsy.

Comparison of weight loss effects among overweight/obese adults: A network meta-analysis of mediterranean, low carbohydrate, and low-fat diets

Eating patterns significantly impact the weight loss process. This study aimed to investigate the influence of primary eating patterns on weight loss measures in overweight and obese adults using network meta-analysis. We systematically searched PubMed, Scopus, Web of Science (WOS), and Google Scholar until May 2, 2023. Our network meta-analysis followed the PRISMA extension guidelines for Comparing Mediterranean, low carbohydrate and low fat diet effects on weight loss among overweight/obese adults. We conducted a Frequentist random-effects network meta-analysis. Summary effects were presented as mean differences (MD) along with corresponding standard deviations (SD). P-scores were used for treatment ranking within the network. Initial literature searches yielded 1574 citations. Ultimately, 1004 participants from 7 RCTs (or 9 trials) met inclusion criteria. All diets resulted in weight loss. Comparatively, the low-carbohydrate diet exhibited a significant decrease in weight loss compared to the Mediterranean diet (MD=-2.70kg, 95% CI:-4.65,-0.75). Indirect evidence revealed that both the low-carbohydrate diet (MD=-6.31kg, 95% CI:-11.23,-1.39) and the low-fat diet (MD=-5.61kg, 95% CI:-10.61,-0.61) significantly reduced weight among overweight/obese adults compared to the standard hypolipemic diet. Rankings indicated the low-carbohydrate diet as the most effective dietary intervention for enhancing weight loss (P-score=0.8994) and reducing body fat (P-score=0.7060). Overall, a low-carb diet appears to be among the most effective approaches for weight loss and body fat reduction. However, it's essential to consider that its efficacy may vary based on factors such as age, gender, genetics, and lifestyle habits.

The Legal Status of Circumstantial Evidence in the Context of Criminal Cases in Indonesia

In practice, there are several instances of criminal decisions that are not in accordance with the law. In such instances, the judge interprets the law or legal findings based on circumstantial evidence. As a result, the action taken does not achieve the highest degree of justice and legal certainty in a decision. This is because the decision is not based on the minimum requirements of two pieces of evidence that must be met in terms of evidence to impose a sentence. The objective of this research was to analyze the legal status of circumstantial evidence in the context of criminal cases. Our research findings indicate that the philosophy of circumstantial evidence, as it pertains to criminal procedural law, represents a form of evidence that can be considered by judges in relation to the absence of facts that are not directly visible by eyewitnesses. This evidence is intended to provide a comprehensive depiction of the truth of an event, thereby facilitating the acceptance of a reasonable account of events. Establishing circumstantial evidence is distinct from providing instructions, however. To do so, one must obtain clues from facts presented at trial in the form of witness statements, letters and statements of the accused. The ius constituendum application of circumstantial evidence in the process of proving a criminal case is to provide the judge with the authority to utilise circumstantial evidence in the process of proving a crime as an additional legal means of evidence in sentencing. The role of indirect evidence in the imposition of criminal penalties is a doctrine that is confined to be the domain of legal experts.

Interorgan, intraorgan and interplant communication mediated by nitric oxide and related species.

Plant survival to a potential plethora of diverse environmental insults is underpinned by coordinated communication amongst organs to help shape effective responses to these environmental challenges at the whole plant level. This interorgan communication is supported by a complex signal network that regulates growth, development and environmental responses. Nitric oxide (NO) has emerged as a key signalling molecule in plants. However, its potential role in interorgan communication has only recently started to come into view. Direct and indirect evidence has emerged supporting that NO and related species (S-nitrosoglutathione, nitro-linolenic acid) are mobile interorgan signals transmitting responses to stresses such as hypoxia and heat. Beyond their role as mobile signals, NO and related species are involved in mediating xylem development, thus contributing to efficient root-shoot communication. Moreover, NO and related species are regulators in intraorgan systemic defence responses aiming an effective, coordinated defence against pathogens. Beyond its in planta signalling role, NO and related species may act as ex planta signals coordinating external leaf-to-leaf, root-to-leaf but also plant-to-plant communication. Here, we discuss these exciting developments and emphasise how their manipulation may provide novel strategies for crop improvement.

Efficacy and Safety of Bone Marrow Derived Stem Cell Therapy for Ischemic Stroke: Evidence from Network Meta-analysis.

Several types of stem cells are available for the treatment of stroke patients. However, the optimal type of stem cell remains unclear. To analyze the effects of bone marrow-derived stem cell therapy in patients with ischemic stroke by integrating all available direct and indirect evidence in network meta-analyses. We searched several databases to identify randomized clinical trials comparing clinical outcomes of bone marrow-derived stem cell therapy vs. conventional treatment in stroke patients. Pooled relative risks (RRs) and mean differences (MDs) were reported. The surface under the cumulative ranking (SUCRA) was used to rank the probabilities of each agent regarding different outcomes. Overall, 11 trials with 576 patients were eligible for analysis. Three different therapies, including mesenchymal stem cells (MSCs), mononuclear stem cells (MNCs), and multipotent adult progenitor cells (MAPCs), were assessed. The direct analysis demonstrated that stem cell therapy was associated with significantly reduced all-cause mortality rates (RR 0.55, 95% CI 0.33 to 0.93; I2=0%). Network analysis demonstrated MSCs ranked first in reducing mortality (RR 0.42, 95% CrI 0.15 to 0.86) and improving modified Rankin Scale score (MD -0.59 95% CI -1.09 to -0.09), with SUCRA values 80%, and 98%, respectively. Subgroup analysis showed intravenous transplantation was superior to conventional therapy in reducing all-cause mortality (RR 0.53, 95% CrI 0.29 to 0.88). Using stem cell transplantation was associated with reduced risk of death and improved functional outcomes in patients with ischemic stroke. Additional large trials are warranted to provide more conclusive evidence.