Substantial Heterogeneity Research Articles

Induced Pluripotent Stem Cell-Derived Cardiomyocytes Therapy for Ischemic Heart Disease in Animal Model: A Meta-Analysis.

Ischemic heart disease (IHD) poses a significant challenge in cardiovascular health, with current treatments showing limited success. Induced pluripotent derived-cardiomyocyte (iPSC-CM) therapy within regenerative medicine offers potential for IHD patients, although its clinical impacts remain uncertain. This study utilizes meta-analysis to assess iPSC-CM outcomes in terms of efficacy and safety in IHD animal model studies. A meta-analysis encompassing PUBMED, ScienceDirect, Web of Science, and the Cochrane Library databases, from inception until October 2023, investigated iPSC therapy effects on cardiac function and safety outcomes. Among 51 eligible studies involving 1012 animals, despite substantial heterogeneity, the iPSC-CM transplantation improved left ventricular ejection fraction (LVEF) by 8.23% (95% CI, 7.15 to 9.32%; p < 0.001) compared to control groups. Additionally, cell-based treatment reduced the left ventricle fibrosis area and showed a tendency to reduce left ventricular end-systolic volume (LVESV) and end-diastolic volume (LVEDV). No significant differences emerged in mortality and arrhythmia risk between iPSC-CM treatment and control groups. In conclusion, this meta-analysis indicates iPSC-CM therapy's promise as a safe and beneficial intervention for enhancing heart function in IHD. However, due to observed heterogeneity, the efficacy of this treatment must be further explored through large randomized controlled trials based on rigorous research design.

Combined anesthesia of acupuncture-pharmacotherapy in pulmonary resection surgery: systematic review and Meta-analysis.

To evaluate the clinical value and safety of combined anesthesia of acupuncture-pharmacotherapy in pulmonary resection surgery. The randomized controlled trials (RCTs) related to combined anesthesia of acupuncture-pharmacotherapy in pulmonary resection surgery were searched in PubMed, EMbase, Cochrane Library, Web of Science, SinoMed, CNKI, VIP database, Wanfang database, ClinicalTrials.gov, and the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) from the inception of each database up to July 12, 2022. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool, and Meta-analysis was conducted using RevMan5.4. A total of 33 RCTs were included, involving 2 526 participants. The Meta-analysis results showed that compared to conventional anesthesia, the patients receiving combined anesthesia of acupuncture-pharmacotherapy had more stable vital signs during surgery, reduced intraoperative fentanyl usage [SMD=-3.73, 95%CI(-5.28, -2.18), Z=4.72, P<0.000 01], decreased postoperative sufentanil consumption [MD=-20.85, 95%CI(-24.84, -16.86), Z=10.24, P<0.000 01], reduced total/effective presses of the postoperative patient-controlled analgesia pump [MD=-5.70, 95% CI(-9.04, -2.36), Z=3.35, P=0.000 8], lowered postoperative pain visual analogue scale (VAS) [MD=-1.63, 95%CI(-2.02, -1.23), Z=7.97, P<0.000 01], shorter length of postoperative hospital stay [MD=-1.14, 95%CI(-1.85, -0.43), Z=3.15, P=0.002], and higher levels of CD 4+ T lymphocytes, CD 8+ T lymphocytes, natural killer (NK) cell activity, and superoxide dismutase (SOD). Additionally, tumor necrosis factor-alpha (TNF-α), adrenaline and cortisol levels were decreased (P<0.05). No adverse events related to acupuncture or electrical stimulation were reported, and the incidence of postoperative complications was lower than that of conventional anesthesia [RR=0.47, 95%CI(0.36, 0.62), Z=5.36, P<0.000 01]. The combined anesthesia of acupuncture-pharmacotherapy in pulmonary resection surgery could improve anesthesia and analgesia effectiveness, reduce anesthesia drug usage, regulate immune responses, suppress stress reactions, and the safety is satisfactory. However, there is substantial heterogeneity among the included studies, and outcome measures vary widely. Further large-sample, high-quality, internationally standardized clinical trials are needed to clarify its clinical value and safety, providing reliable evidence for clinical practice.

Prevalence of epileptiform electroencephalographic abnormalities in people without a history of seizures: A systematic review and meta-analysis.

Abnormal patterns identified on electroencephalogram (EEG) are one of the primary diagnostic tests for epilepsy. However, epidemiological studies have established that both benign and epileptiform abnormalities (EAs) occur on the EEG of nonepileptic, seizure-free people as well. The reported rates of EAs in nonepileptic, seizure-free populations vary, and the true prevalence is unknown. The primary objective of this systematic review and meta-analysis was to estimate the overall prevalence of EAs in the EEG of people without a history of seizures. Secondary aims were to characterize (1) the cortical localization of focal abnormalities, (2) the proportion of findings that occurred during standard EEG stimulation protocols, and (3) the persistence and implications of abnormalities at follow-up. A comprehensive electronic search of six bibliographic databases was completed: Embase, MEDLINE, PsycInfo, Cumulative Index of Nursing and Allied Health Literature, Cochrane Central Register for Controlled Trials, and Web of Science. No search date restrictions were applied. Overall effect size was calculated using a generalized linear mixed-effects model. Fifty-three studies, totaling 73 990 individuals, met our inclusion criteria. The overall point prevalence of EAs was 1.74% (95% confidence interval [CI] = 1.13-2.67). Due to the risk of bias in the literature, especially from participant selection, we believe this to be an overestimate of the true prevalence. Prevalence of EAs was greater in children (2.45%, 95% CI = 1.41-4.21) and the elderly (5.96%, 95% CI = 1.39-22.13) compared with adults (.93%, 95% CI = .48-1.80). Reports of developing epilepsy after an EA-positive EEG were rare. The likelihood of subsequent positive findings on follow-up EEG may be as high as 50%. Our study has limitations in that males were overrepresented in the study samples, there is substantial heterogeneity among studies, and many studies provided insufficient detail about their exclusion criteria. Nonetheless, our estimates provide benchmark data for future studies examining EAs in clinical populations, particularly behavioral and psychiatric populations.

A Non‐parametric Estimation of Productivity with Idiosyncratic and Aggregate Shocks: The Role of Research and Development (R&amp;D) and Corporate Tax

We develop a non‐parametric technique framework for estimating firm‐level Total Factor Productivity (TFP). Our paper has two major novelties: first, we propose a modelling of productivity with both firm‐idiosyncratic factors and aggregate shocks. Second, we apply the Bayesian Markov Chain Monte Carlo (MCMC) technique that offers a numerical integration of productivity outside the posterior overcoming the restrictive assumptions about the relationship between productivity and variable production inputs. We implement our methodology in a group of 4,286 manufacturing firms from France, Germany, Italy, and the UK (2001–14). The results show that: (i) aggregate shocks matter for firm TFP evolution. The global financial crisis of 2008 caused severe, albeit short, adverse effects on TFP; (ii) there is substantial heterogeneity across countries in the way firms react to changes in R&amp;D and taxation. German and UK firms are more sensitive to fiscal changes than R&amp;D, while the opposite is true for Italian firms. R&amp;D and taxation effects are symmetrical for French firms; (iii) the UK productivity handicap continues for years after the financial crisis; and (iv) there are substantial knowledge spillovers among German and Italian firms.

Statistically downscaled CMIP6 ocean variables for European waters

Climate change impact studies need climate projections for different scenarios and at scales relevant to planning and management, preferably for a variety of models and realizations to capture the uncertainty in these models. To address current gaps, we statistically downscaled (SD) 3–7 CMIP6 models for five key indicators of marine habitat conditions: temperature, salinity, pH, oxygen, and chlorophyll across European waters for three climate scenarios SSP1-2.6, SSP2-4.5, and SSP5-8.5. Results provide ensemble averages and uncertainty estimates that can serve as input data for projecting the potential success of a range of Nature-based Solutions, including the restoration of habitat-forming species such as seagrass in the Mediterranean and kelp in coastal areas of Portugal and Norway. Evaluation of the ensemble with observations from four European regions (North Sea, Baltic Sea, Bay of Biscay, and Mediterranean Sea) indicates that the SD projections realistically capture the climatological conditions of the historical period 1993–2020. Model skill (Liu-mean efficiency, Pearson correlation) clearly improves for both surface temperature and oxygen across all regions with respect to the original ESMs demonstrating a higher skill for temperature compared to oxygen. Warming is evident across all areas and large differences among scenarios fully emerge from the background uncertainties related to internal variability and model differences in the second half of the century. Scenario-specific differences in acidification significantly emerge from model uncertainty and internal variability leading to distinct trajectories in surface pH starting before mid-century (in some cases starting from present day). Deoxygenation is also present across all domains, but the climate signal was significantly weaker compared to the other two indicators when compared to model uncertainty and internal variability, and the impact of different greenhouse gas trajectories is less distinct. The substantial regional and local heterogeneity in these three abiotic indicators underscores the need for highly spatially resolved physical and biogeochemical projections to understand how climate change may impact marine ecosystems.

Reliability of Municipal Solid Waste Landfills within the Eurocode Framework

Municipal solid waste (MSW) landfill slope failures can have significant consequences for the economy, environment, and human health. One potential cause of slope failure is insufficient reliability, resulting from inadequate design. The usual practice in the design of MSW landfills involves utilizing established geotechnical codes, such as Eurocode 7 (EC7), to perform slope stability assessments. Considering the substantial heterogeneity of MSW relative to soil, questions arise regarding the justification of such an approach in the design of MSW landfills. This study examines the suitability of applying EC7 in MSW landfill design, analyzing the stability and reliability of landfill slopes across various heights, front slope angles, design approaches, and consequence classes. This study finds that, in most cases considered, EC7 does not ensure an adequate level of reliability for MSW landfill slopes. Therefore, it is suggested that EC7 should be complemented with specific guidelines for incorporating MSW in geotechnical analyses to achieve the desired structural reliability. Adopting this strategy will not only enhance the reliability of landfill design but also promote the development of solutions that are economically and environmentally sustainable.

Does brain entrainment using binaural auditory beats affect pain perception in acute and chronic pain?: a systematic review

BackgroundPain is a major clinical problem across all ages with serious social and economic consequences and a great negative impact on quality of life. Brain entrainment using binaural beats is a non-pharmaceutical intervention that is claimed to have analgesic effects in acute and chronic pain. We aimed to systematically review the available randomized clinical trials on the efficacy of binaural auditory beats in reducing adults’ pain perception in acute and chronic pain. A systematic search in electronic databases including Medline (via PubMed), Web of Science, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase was performed. The search was completed through Google Scholar and a manual search of the reference lists of all included studies. Randomized clinical trials with full text available in English that investigated the effect of binaural auditory beats on pain perception in acute and chronic pain in adults were included. The risk of bias was assessed by the revised Cochrane risk-of-bias (RoB 2) tool. Furthermore, The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to assess the quality of the evidence. Sixteen studies (three on chronic pain and thirteen on acute pain perception) fulfilled the eligibility criteria. Because of substantial heterogeneity of the studies, a meta-analysis was inappropriate and this review focused on the narrative interpretation of the results. The risk of bias in most studies was high and the quality of evidence was low to very low. Although the effects of binaural beats on pain perception seem to be influenced by the etiology of pain or medical procedures, our review identifies alpha or a combination of tones in the range of delta to alpha as a potential non-pharmacological intervention in reducing acute pain. However, drawing a conclusion regarding the efficacy of binaural beats for chronic pain requires more high-quality studies.RegistrationThe protocol of this review was registered in PROSPERO (No. CRD42023425091).

Evaluation of lablab bean [Lablab purpureus (L.) sweet] genotypes: unveiling superior pod yield, nutritional quality, and collar rot resistance.

Malnutrition continues to be a significant concern at unacceptably high levels globally. There is significant potential for addressing malnutrition of human population through the biofortification of climate-resilient vegetables using strategic breeding strategies. Lablab bean [Lablab purpureus (L.) Sweet], a underutilized nutrient-dense crop holds great potential in this aspect. Despite its advantageous nutritional profile, the production, research, and consumption of lablab bean are currently limited. Addressing these limitations and unlock the nutritional benefits of lablab beans needs to prioritized for fighting malnutrition in local inhabitants on a global scale. Twenty five genotypes of lablab bean collected through exploration survey in Eastern India and were evaluated in 2020-2021. Among them, the nine highly diverse well adapted genotypes were again evaluated at the experimental farm of ICAR-Research Complex for Eastern Region, Patna, Bihar, India in 2021-2022. Horticultural important traits of lablab bean were recorded by using the minimum descriptors developed by ICAR-NBPGR in New Delhi and biochemical analysis was done by using standard protocols. Genotypic and phenotypic correlation and path coefficient analysis was done used understand relationships, interdependencies, and causal pathways between different traits. The outcome was revalidated by using principal component analysis (PCA). Descriptive statistics revealed substantial heterogeneity across the traits of lablab bean evaluated. Vitamin A content showed nearly a five-fold variation, Fe ranged from 5.97 to 10.5 mg/100 g, and Vitamin C varied from 4.61 to 9.45 mg/100 g. Earliness and dwarf growth was observed in RCPD-1 (60 cm) and early flowering (41 days). RCPD-3 and RCPD-12 had high pod yield due to their high number of pods and pod weight. Pod yield was significantly correlated with number of pod per plant (NPP) (rg = 0.995) and with average pod weight (APW) (rg = 0.882). A significant positive correlation was also found between protein and Zn content (rg = 0.769). Path coefficient analysis revealed that average pod weight had the most direct positive effect on pod yield, followed by NPP and protein content. The reaction of lablab bean genotypes to collar rot disease was also evaluated and significant differences in disease intensity were observed among the genotypes, with the resistant check RCPD-15 exhibiting the lowest disease intensity. The study highlights the substantial heterogeneity in lablab bean traits, particularly in nutritional components such as vitamin A, iron, and vitamin C concentrations. Early flowering and dwarf growth habit are desirable qualities for lablab bean, and certain genotypes were found to exhibit these traits. Positive correlations, both phenotypic and genotypic, existed among different traits, suggesting the potential for simultaneous improvement. Path coefficient and PCA revealed genotypes with high yield and nutritional traits. Finally, resistant and moderately resistant lablab bean genotypes to collar rot disease were identified. These findings contribute to the selection and breeding strategies for improving lablab bean production and nutritional value.

The flexural strength of 3D-printed provisional restorations fabricated with different resins: a systematic review and meta-analysis

BackgroundThree-dimensional (3D) printing technology has revolutionized dentistry, particularly in fabricating provisional restorations. This systematic review and meta-analysis aimed to thoroughly evaluate the flexural strength of provisional restorations produced using 3D printing while considering the impact of different resin materials.MethodsA systematic search was conducted across major databases (ScienceDirect, PubMed, Web of Sciences, Google Scholar, and Scopus) to identify relevant studies published to date. The inclusion criteria included studies evaluating the flexural strength of 3D-printed provisional restorations using different resins. Data extraction and quality assessment were performed using the CONSORT scale, and a meta-analysis was conducted using RevMan 5.4 to pool results.ResultsOf the 1914 initially identified research articles, only 13, published between January 2016 and November 2023, were included after screening. Notably, Digital Light Processing (DLP) has emerged as the predominant 3D printing technique, while stereolithography (SLA), Fused Deposition Modeling (FDM), and mono-liquid crystal displays (LCD) have also been recognized. Various printed resins have been utilized in different techniques, including acrylic, composite resins, and methacrylate oligomer-based materials. Regarding flexural strength, polymerization played a pivotal role for resins used in 3D or conventional/milled resins, revealing significant variations in the study. For instance, SLA-3D and DLP Acrylate photopolymers displayed distinct strengths, along with DLP bisacrylic, milled PMMA, and conventional PMMA. The subsequent meta-analysis indicated a significant difference in flexure strength, with a pooled Mean Difference (MD) of − 1.25 (95% CI − 16.98 - 14.47; P < 0.00001) and a high I2 value of 99%, highlighting substantial heterogeneity among the studies.ConclusionsThis study provides a comprehensive overview of the flexural strength of 3D-printed provisional restorations fabricated using different resins. However, further research is recommended to explore additional factors influencing flexural strength and refine the recommendations for enhancing the performance of 3D-printed provisional restorations in clinical applications.

Artificial intelligence-based analysis of the spatial distribution of abnormal computed tomography patterns in SARS-CoV-2 pneumonia: association with disease severity

BackgroundThe substantial heterogeneity of clinical presentations in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia still requires robust chest computed tomography analysis to identify high-risk patients. While extension of ground-glass opacity and consolidation from peripheral to central lung fields on chest computed tomography (CT) might be associated with severely ill conditions, quantification of the central-peripheral distribution of ground glass opacity and consolidation in assessments of SARS-CoV-2 pneumonia remains unestablished. This study aimed to examine whether the central-peripheral distributions of ground glass opacity and consolidation were associated with severe outcomes in patients with SARS-CoV-2 pneumonia independent of the whole-lung extents of these abnormal shadows.MethodsThis multicenter retrospective cohort included hospitalized patients with SARS-CoV-2 pneumonia between January 2020 and August 2021. An artificial intelligence-based image analysis technology was used to segment abnormal shadows, including ground glass opacity and consolidation. The area ratio of ground glass opacity and consolidation to the whole lung (GGO%, CON%) and the ratio of ground glass opacity and consolidation areas in the central lungs to those in the peripheral lungs (GGO(C/P)) and (CON(C/P)) were automatically calculated. Severe outcome was defined as in-hospital death or requirement for endotracheal intubation.ResultsOf 512 enrolled patients, the severe outcome was observed in 77 patients. GGO% and CON% were higher in patients with severe outcomes than in those without. Multivariable logistic models showed that GGO(C/P), but not CON(C/P), was associated with the severe outcome independent of age, sex, comorbidities, GGO%, and CON%.ConclusionIn addition to GGO% and CON% in the whole lung, the higher the ratio of ground glass opacity in the central regions to that in the peripheral regions was, the more severe the outcomes in patients with SARS-CoV-2 pneumonia were. The proposed method might be useful to reproducibly quantify the extension of ground glass opacity from peripheral to central lungs and to estimate prognosis.

Novel subgroups of obesity and their association with outcomes: a data-driven cluster analysis

BackgroundObesity is associated with various complications and decreased life expectancy, and substantial heterogeneity in complications and outcomes has been observed. However, the subgroups of obesity have not yet been clearly defined. This study aimed to identify the subgroups of obesity especially those for target of interventions by cluster analysis.MethodsIn this study, an unsupervised, data-driven cluster analysis of 9,494 individuals with obesity (body mass index ≥ 35 kg/m2) was performed using the data of ICD-10, drug, and medical procedure from the healthcare claims database. The prevalence and clinical characteristics of the complications such as diabetes in each cluster were evaluated using the prescription records. Additionally, renal and life prognoses were compared among the clusters.ResultsWe identified seven clusters characterised by different combinations of complications and several complications were observed exclusively in each cluster. Notably, the poorest prognosis was observed in individuals who rarely visited a hospital after being diagnosed with obesity, followed by those with cardiovascular complications and diabetes.ConclusionsIn this study, we identified seven subgroups of individuals with obesity using population-based data-driven cluster analysis. We clearly demonstrated important target subgroups for intervention as well as a metabolically healthy obesity group.

Inside the Black Box: Uncovering Dynamics and Characteristics of the Chilean Central Government Bureaucracy with a Novel Dataset

ABSTRACTThis article examines bureaucracies using a novel dataset of Chilean central government employees from 2006 to 2020. Unlike perception-based sources, this dataset provides objective, disaggregated, and longitudinal insights into bureaucrats’ characteristics and careers. The authors validate it against official employment statistics and conduct an exploratory and descriptive analysis, presenting six descriptive findings about the Chilean bureaucracy that cannot be discovered using available aggregate data. The analysis reveals significant degrees of personnel stability and professionalization in the civil service, but with considerable rigidity in careers and substantial interagency heterogeneity in turnover, wages, and exposure to political cycles. These findings suggest that the Chilean national bureaucracy is mostly well developed along Weberian lines, though not uniformly so. These measurements also serve as a benchmark for comparing other Latin American bureaucracies in the future.

Deprivation-Induced Plasticity in the Early Central Circuits of the Rodent Visual, Auditory, and Olfactory Systems.

Activity-dependent neuronal plasticity is crucial for animals to adapt to dynamic sensory environments. Traditionally, it has been investigated using deprivation approaches in animal models primarily in sensory cortices. Nevertheless, emerging evidence emphasizes its significance in sensory organs and in subcortical regions where cranial nerves relay information to the brain. Additionally, critical questions started to arise. Do different sensory modalities share common cellular mechanisms for deprivation-induced plasticity at these central entry points? Does the deprivation duration correlate with specific plasticity mechanisms? This study systematically reviews and meta-analyzes research papers that investigated visual, auditory, or olfactory deprivation in rodents of both sexes. It examines the consequences of sensory deprivation in homologous regions at the first central synapse following cranial nerve transmission (vision - lateral geniculate nucleus and superior colliculus; audition - ventral and dorsal cochlear nucleus; olfaction - olfactory bulb). The systematic search yielded 91 papers (39 vision, 22 audition, 30 olfaction), revealing substantial heterogeneity in publication trends, experimental methods, measures of plasticity, and reporting across the sensory modalities. Despite these differences, commonalities emerged when correlating plasticity mechanisms with the duration of sensory deprivation. Short-term deprivation (up to 1 d) reduced activity and increased disinhibition, medium-term deprivation (1 d to a week) involved glial changes and synaptic remodeling, and long-term deprivation (over a week) primarily led to structural alterations. These findings underscore the importance of standardizing methodologies and reporting practices. Additionally, they highlight the value of cross-modal synthesis for understanding how the nervous system, including peripheral, precortical, and cortical areas, respond to and compensate for sensory inputs loss.

Vitamin B12 supplementation during pregnancy for maternal and child health outcomes.

Vitamin B12 deficiency is a major public health problem worldwide, with the highest burden in elderly people, pregnant women, and young children. Due to its role in DNA synthesis and methylation, folate metabolism, and erythropoiesis, vitamin B12 supplementation during pregnancy may confer longer-term benefits to maternal and child health outcomes. To evaluate the benefits and harms of oral vitamin B12 supplementation during pregnancy on maternal and child health outcomes. We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) on 2 June 2023, and reference lists of retrieved studies. Randomised controlled trials (RCTs), quasi-RCTs, or cluster-RCTs evaluating the effects of oral vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation during pregnancy. We used standard Cochrane methods. Four review authors independently assessed trial eligibility. Two review authors independently extracted data from included studies and conducted checks for accuracy. Three review authors independently assessed the risk of bias of the included studies using the Cochrane RoB 1 tool. We used GRADE to evaluate the certainty of evidence for primary outcomes. The review included five trials with 984 pregnant women. All trials were conducted in low- and middle-income countries, including India, Bangladesh, South Africa, and Croatia. At enrolment, 26% to 51% of pregnant women had vitamin B12 deficiency (less than 150 pmol/L), and the prevalence of anaemia (haemoglobin less than 11.0 g/dL) ranged from 30% to 46%. The dosage of vitamin B12 supplementation varied from 5 μg/day to 250 μg/day, with administration beginning at 8 to 28 weeks' gestation through to delivery or three months' postpartum, and the duration of supplementation ranged from 8 to 16 weeks to 32 to 38 weeks. Three trials, involving 609 pregnant women, contributed data for meta-analyses of the effects of vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation. Maternal anaemia: there may be little to no difference for maternal anaemia by intervention group, but the evidence is very uncertain (70.9% versus 65.0%; risk ratio (RR) 1.08, 95% confidence interval (CI) 0.93 to 1.26; 2 trials, 284 women; very low-certainty evidence). Maternal vitamin B12 status: vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain (25.9% versus 67.9%; RR 0.38, 95% CI 0.28 to 0.51; 2 trials, 272 women; very low-certainty evidence). Women who received vitamin B12 supplements during pregnancy may have higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (mean difference (MD) 60.89 pmol/L, 95% CI 40.86 to 80.92; 3 trials, 412 women). However, there was substantial heterogeneity (I2 = 85%). Adverse pregnancy outcomes: the evidence is uncertain about the effect on adverse pregnancy outcomes, including preterm birth (RR 0.97, 95% CI 0.55 to 1.74; 2 trials, 340 women; low-certainty evidence), and low birthweight (RR 1.50, 95% CI 0.93 to 2.43; 2 trials, 344 women; low-certainty evidence). Two trials reported data on spontaneous abortion (or miscarriage); however, the trials did not report quantitative data for meta-analysis and there was no clear definition of spontaneous abortion in the study reports. No trials evaluated the effects of vitamin B12 supplementation during pregnancy on neural tube defects. Infant vitamin B12 status: children born to women who received vitamin B12 supplementation had higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (MD 71.89 pmol/L, 95% CI 20.23 to 123.54; 2 trials, 144 children). Child cognitive outcomes: three ancillary analyses of one trial reported child cognitive outcomes; however, data were not reported in a format that could be included in quantitative meta-analyses. In one study, maternal vitamin B12 supplementation did not improve neurodevelopment status (e.g. cognitive, language (receptive and expressive), motor (fine and gross), social-emotional, or adaptive (conceptual, social, practical) domains) in children compared to placebo (9 months, Bayley Scales of Infant and Toddler Development Third Edition (BSID-III); 1 trial; low-certainty evidence) or neurophysiological outcomes (72 months, event-related potential measures; 1 trial; low-certainty evidence), though children born to women who received vitamin B12 supplementation had improved expressive language domain compared to placebo (30 months, BSID-III; 1 trial; low-certainty evidence). Oral vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency and may improve maternal vitamin B12 concentrations during pregnancy or postpartum compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain. The effects of vitamin B12 supplementation on other primary outcomes assessed in this review were not reported, or were not reported in a format for inclusion in quantitative analyses. Vitamin B12 supplementation during pregnancy may improve maternal and infant vitamin B12 status, but the potential impact on longer-term clinical and functional maternal and child health outcomes has not yet been established.

Profiling DNA Cargos in Single Extracellular Vesicles via Hydrogel-Based Droplet Digital Multiple Displacement Amplification.

Due to the substantial heterogeneity among extracellular vesicle (EV) subpopulations, single-EV analysis has the potential to elucidate the mechanisms behind EV biogenesis and shed light on the myriad functions, leading to the development of novel diagnostics and therapeutics. While many studies have been devoted to reveal between-EV variations in surface proteins and RNAs, DNA cargos (EV-DNA) have received little attention. Here, we report a hydrogel-based droplet digital multiple displacement amplification approach for the comprehensive analysis of EV-DNA at the single-EV level. Single EVs are dispersed in thousands of hydrogel droplets and lysed for DNA amplification and identification. The droplet microfluidics strategy empowers the assay with single-molecule sensitivity and capability for absolute quantification of DNA-containing EVs. In particular, our findings indicate that 5-40% EVs are associated with DNA, depending on the cell of origin. Large EVs exhibit a higher proportion of DNA-containing EVs and a more substantial presence of intraluminal DNA, compared to small EVs. These DNA-containing EVs carry multiple DNA fragments on average. Furthermore, both double-stranded DNA and single-stranded DNA were able to be detected at the single-EV level. Utilizing this method, the abundance, distribution, and biophysical properties of EV-DNA in various EV populations are evaluated. The DNA level within EVs provides insight into the status of the originating cells and offers valuable information on the outcomes of anticancer treatments. The utilization of single-EV analysis for EV-DNA holds significant promise for early cancer detection and treatment response monitoring.

Household willingness to pay for various attributes of residential solar panels: Evidence from a discrete choice experiment

The predominant approach in the US environmental policy so far has been to offer financial incentives for renewable energy as a more politically palatable alternative to market based policies. The policies around residential rooftop solar have generally aligned with this approach. However, recent years have witnessed a reversal in the once favorable financial terms for residential solar energy in many states largely due to concerns regarding unfair cost shifting and efficiency. Consequently, solar vendors appear to increasingly hinge their marketing strategies on the narrative of “self-reliance”. A pertinent question is whether there is enough willingness to pay for such non-market, private benefits to sustain the growth of residential solar. To address this, we designed and implemented a discrete choice experiment within a stated preference framework. Respondents were asked to make a choice among different home energy options offering varying financial terms and other attributes such as self-reliance and home battery. Notably, a random subset of the respondents was presented with the net present value (NPV) of the dollar cost of each alternative, while this information was withheld from the rest of the sample. We estimated the utility coefficients through hierarchical Bayes (HB) mixed logit and subsequently derived the marginal willingness to pay (mWTP) for each attribute, along with their individual-level confidence intervals. Our findings indicate substantial heterogeneity in preferences among decision-makers. On average, the willingness to pay for self-reliance falls short of supporting residential solar growth without financial incentives. Furthermore, respondents exposed to NPV information exhibited significantly lower mWTP values, underscoring the potential efficacy of NPV information in improving willingness to pay estimates within investment-oriented settings.

Efficacy and Safety of Propolis for Treating Recurrent Aphthous Stomatitis (RAS): A Systematic Review and Meta-Analysis.

The systematic review assessed the efficacy and safety of propolis for treating recurrent aphthous stomatitis (RAS). The review adopted the PICO framework to examine the effects of topical and systemic propolis on RAS while also comparing it to established treatments, placebos, or no treatment. The main focus was on the healing time, pain levels, adverse effects, the likelihood of ulcer recurrence, and accompanying symptoms such as redness. The team included randomised controlled trials (RCTs) and quasi-randomised trials, excluding case reports and studies on oral ulcers other than RAS. In May 2022, the review team comprehensively searched nine databases and trial registries following the PRISMA guidelines. The protocol was registered in the PROSPERO database under the registration number CRD42022327123. Two review authors conducted a comprehensive and autonomous search for pertinent papers and extracted essential data. Where data permitted, the team utilised Review Manager 5 to conduct a random-effects meta-analysis, assessing the risk of bias and heterogeneity of the included studies. Where possible, the GRADE Pro programme was used to assess the certainty of the evidence for all the outcomes. This review included 10 RCTs, comprising 825 participants aged between 18 and 69 years. Seven studies evaluated the efficacy and safety of propolis when applied topically, all of which used different formulations, concentrations, and carriers. The remaining three studies assessed systemic administration in tablet form. The duration of investigations ranged from 5 days to 3 years. The review team classified two studies as having an overall 'high risk' of bias, while the remaining studies were categorised as having an overall 'uncertain risk'. The overall certainty of the evidence was 'very low'. The results indicate that topical and systemic propolis may decrease the duration of healing, alleviate pain, and reduce redness in patients with RAS compared to a placebo. However, the certainty of the evidence is very low. These may be due to the high risk of bias, substantial heterogeneity, and limited sample sizes in the included studies. For these reasons, the results of this review should be interpreted with caution. Nevertheless, the limited number of adverse effects observed suggests that propolis may have a favourable safety profile when used for a short period in treating RAS.

Systematic review of the significance of neutrophil to lymphocyte ratio in anastomotic leak after gastrointestinal surgeries

IntroductionThe inflammatory response is thought to be a critical initiator of epigenetic alterations. The neutrophil to lymphocyte ratio (NLR), a biomarker of inflammation, is computed by dividing the number of neutrophils by the number of lymphocytes. The primary goal of this systematic review and meta-analysis was to evaluate the pre-operative NLR of gastrointestinal surgery patients who had an anastomotic leak (AL) in comparison to those who did not AL.MethodsWe performed a comprehensive search for relevant papers published before May 4, 2022, using PubMed, Scopus, and Web of Science. Standardized mean difference (SMD) with a 95% confidence interval (CI) was pooled in meta-analysis to yield a summary estimate. We utilized the random-effects model to create pooled effects since we discovered a substantial heterogeneity level. For evaluating quality, the Newcastle-Ottawa scale (NOS) was implemented.ResultsThe research comprised 12 studies with a total of 2940 individuals who had GI operations, 353 of whom went on to develop AL. We discovered that patients who had GI surgeries and acquired AL had significantly higher NLR levels than those who did not (random-effects model: SMD = 0.75, 95% CI = 0.11–1.38, p = 0.02). Patients with AL showed significantly higher NLR levels than control group in retrospective studies (SMD = 0.93, 95% CI = 0.20–1.66, p=0.01) but not in prospective studies (SMD = − 0.11, 95% CI = − 0.65–0.43, p = 0.69), according to the subgroup analysis based on research design. Subgroup analysis based on ethnicity yielded that white patients with AL exhibited significantly higher NLR values than the control group (SMD = 1.35, 95% CI = 0.01–2.68, p = 0.04) but this result was not applied to East Asian patients (SMD = 0.14, 95% CI = -0.13–0.41, p = 0.29).ConclusionOur research suggests a potential association between preoperative NLR and postoperative AL. However, it is essential to acknowledge the variability in the findings, with significantly higher NLR levels observed in retrospective studies and among white patients, but not consistently replicated in prospective studies and among East Asian patients. Further investigations with larger and more diverse cohorts are warranted to validate these findings and explore potential factors contributing to the observed discrepancies.

Minimally invasive periodontal regeneration with the buccal approach: a systematic review and meta-analysis of clinical studies.

The aim of this study was to investigate clinical periodontal parameters after treatment using the Minimally Invasive Surgical Technique (MIST), Modified Minimally Invasive Surgical Technique (M-MIST), and/or any technique for papilla preservation, such as Entire Papilla Preservation (EPP), modified-papilla preservation technique (M-PPT), or simplified-papilla preservation technique (SPPT). The focus question was "For patients with periodontal intrabony defects (P), what is the best minimally invasive regenerative approach (I), comparing MIST, M-MIST, and papilla preservation techniques' outcomes (C) to improve PD, CAL, GR, and periodontal stability(O)?" An online search was conducted on PubMed, Cochrane Library, and Embase. Only randomized clinical trials and case series with a minimum of 10 enrolled patients were included. The risk of bias was evaluated using the Critical Appraisal tools in JBI Systematic Reviews. The meta-analysis compared the data obtained for the periodontal parameters analyzed, and the heterogeneity was verified. After the screening, nine articles were included. Seven studies applied MIST and its modifications; two used M-PPT, one SPPT, and one approached EPP. A general statistically significant PD reduction and CAL gain were noted between the groups, comparing baseline and follow-up for all articles, independently of the technique or materials used. Also, all studies showed a non-significant increase in the gingival recession. Four studies had a low risk of bias, four had a moderate risk, and only 1 had a high risk. Moderate heterogeneity was found in one analysis for CAL (65.73%); moderate and substantial heterogeneity was found in the PD results (71.91% and 89.19%); and no heterogeneity was found within all analyses for gingival recession (0%). MIST, M-MIST, and papilla preservation techniques demonstrated their potential and efficacy to improve periodontal conditions of sites with intrabony defects with minimal morbidity.

Do responses to news matter? Evidence from interventional cardiology

We examine physician responses to a global information shock and how these impact their patients. We exploit international news over the safety of an innovation in healthcare, the drug-eluting stent. We use data on interventional cardiologists’ use of stents to define and measure cardiologists’ responsiveness to the initial positive news and link this to their patients’ outcomes. We find substantial heterogeneity in responsiveness to news. Patients treated by cardiologists who respond slowly to the initial positive news have fewer adverse outcomes. This is not due to patient–physician sorting. Instead, our results suggest that the differences are partially driven by slow responders being better at deciding when (not) to use the new technology, which in turn affects their patient outcomes.