High Level Of Heterogeneity Research Articles

The tumor microenvironment in hepatocarcinoma: dissecting the functions of cancer-associated fibroblasts

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, deriving from the neoplastic transformation of hepatocytes, most often forced to long-lasting regeneration by the cirrhotic background. HCC is an extremely aggressive tumor with still limited effective treatments, and is characterized by the presence of a very complex and multifaceted tumor microenvironment (TME). Among the variety of cell types populating the TME of HCC, cancer-associated fibroblasts (CAFs) are the most prevalent. CAFs are a specific population of fibroblasts in a persistent state of activation, with a high level of heterogeneity, partly dependent on a wide range of cell origin, which are endowed with a repertoire of functions, profoundly modulating the biology of the tumor. Given the close relationship of HCC with cirrhosis, CAFs are paradigmatic of the role played by activated fibroblasts in promoting the evolution of a chronic, non-resolving, fibro-inflammatory condition towards a neoplastic disease and its aggressive phenotype. In this review, we will discuss the most recent findings regarding the interplay of CAFs with the tumoral epithelial compartment, with the multiple cell elements of the TME (macrophages, neutrophils, myeloid-derived suppressor cells, vascular cells), and with the extracellular matrix. Finally, we will address the translational value of CAF manipulation in HCC to unveil possible ameliorations for the treatment of a still worrisome disease.

Efficacy and safety of SBRT for spine metastases: A systematic review and meta-analysis for preparation of an ESTRO practice guideline

Background and purposeAdvances in characterizing cancer biology and the growing availability of novel targeted agents and immune therapeutics have significantly changed the prognosis of many patients with metastatic disease. Palliative radiotherapy needs to adapt to these developments. In this study, we summarize the available evidence for stereotactic body radiotherapy (SBRT) in the treatment of spinal metastases. Materials and methodsA systematic review and meta-analysis was performed using PRISMA methodology, including publications from January 2005 to September 2021, with the exception of the randomized phase III trial RTOG-0631 which was added in April 2023. Re-irradiation was excluded. For meta-analysis, a random-effects model was used to pool the data. Heterogeneity was assessed with the I2-test, assuming substantial and considerable as I2 > 50 % and I2 > 75 %, respectively. A p-value < 0.05 was considered statistically significant. ResultsA total of 69 studies assessing the outcomes of 7236 metastases in 5736 patients were analyzed. SBRT for spine metastases showed high efficacy, with a pooled overall pain response rate of 83 % (95 % confidence interval [CI] 68 %-94 %), pooled complete pain response of 36 % (95 % CI: 20 %-53 %), and 1-year local control rate of 94 % (95 % CI: 86 %-99 %), although with high levels of heterogeneity among studies (I2 = 93 %, I2 = 86 %, and 86 %, respectively). Furthermore, SBRT was safe, with a pooled vertebral fracture rate of 9 % (95 % CI: 4 %-16 %), pooled radiation induced myelopathy rate of 0 % (95 % CI 0–2 %), and pooled pain flare rate of 6 % (95 % CI: 3 %-17 %), although with mixed levels of heterogeneity among the studies (I2 = 92 %, I2 = 0 %, and 95 %, respectively). Only 1.7 % of vertebral fractures required surgical stabilization. ConclusionSpine SBRT is characterized by a favorable efficacy and safety profile, providing durable results for pain control and disease control, which is particularly relevant for oligometastatic patients.

What is in common between preeclampsia, HPS70 and medieval headwear? Part I. Serum HPS70 in preeclampsia: systematic review and meta-analysis

The objective: to investigate the relationship between HSP70 concentrations in maternal serum and preeclampsia and assess the prospects of using HSP70 as a preeclampsia predictor.Materials and methods. The original publications, which study HSP70 in maternal serum of preeclamptic women, were searched and analyzed. Papers were identified with Scopus, PubMed Central, Virtual Health Library databases, published before January 2023, the keywords were «HSP70», «preeclampsia», «heat shock protein 70», «pregnant». Statistical analysis was performed via software EZR 1.55.Results. 16 case-control studies were included, making a total of 751 pregnant women with preeclampsia and 719 healthy pregnant women. The analysis found the statistically significant difference between HSP70 concentrations in maternal serum of preeclamptic and healthy pregnant patients. Cochrane Q-test showed high heterogeneity among studies (p&lt;0.01), the value of the І2 statistic was 97%. Dividing the studies into groups made it possible to reduce or remove heterogeneity completely. This high level of heterogeneity for publications together, but low within most groups, suggests that there are certain factors that significantly influence some studies.Conclusions. The conducted systematic review and meta-analysis confidently indicate an increased average serum concentration of HSP70 in pregnant women with preeclampsia compared to healthy pregnant women at the corresponding gestational age.No statistically significant relationship was found between increased HSP70 concentration in preeclampsia and pregnant women’s age, gestational age, systolic and diastolic blood pressure. Quantitative assessment of HSP70 levels is complicated by the lack of a single standard for laboratory diagnostics. The case-control design of the presented studies limits their significance.The use of HSP70 as a predictor of preeclampsia is promising, but requires further study and prospective cohort studies.

A scoping review of psychological interventions and outcomes for avoidant and restrictive food intake disorder (ARFID).

This scoping review identifies and describes psychological interventions for avoidant restrictive food intake disorder (ARFID) and summarizes how outcomes are measured across such interventions. Five databases (Cochrane, Embase, Medline, PsycInfo, Web of Science) were searched up to December 22, 2022. Studies were included if they reported on psychological interventions for ARFID. Studies were excluded if participants did not have an ARFID diagnosis and if psychological interventions were not delivered or detailed. Fifty studies met inclusion criteria; almost half were single-case study designs (23 studies) and most studies reported on psychological interventions for children and adolescents with ARFID (42 studies). Behavioral interventions (16 studies), cognitive-behavioral therapy (10 studies), and family therapy (5 studies), or combinations of these therapeutic approaches (19 studies) were delivered to support patients with ARFID. Many studies lacked validated measures, with outcomes most commonly assessed via physical health metrics such as weight. This review provides a comprehensive summary of psychological interventions for ARFID since its introduction to the DSM-5. Across a range of psychological interventions and modalities for ARFID, there were common treatment components such as food exposure, psychoeducation, anxiety management, and family involvement. Currently, studies reporting on psychological interventions for ARFID are characterized by small samples and high levels of heterogeneity, including in how outcomes are measured. Based on reviewed studies, we outline suggestions for clinical practice and future research. Avoidant restrictive food intake disorder (ARFID) is an eating disorder characterized by avoidance or restriction of food due to fear, sensory sensitivities, and/or a lack of interest in food. We reviewed the literature on psychological interventions for ARFID and the outcomes used to measure change. Several psychological interventions have been developed and applied to patients with ARFID. Outcome measurement varies widely and requires further development and greater consensus.

Improving the governance of a regional research network: from needs’ assessment to policy making

Abstract Clinical research is a pivotal element for the Emilia-Romagna (Italy) healthcare system. Since 2009, several regional legislative acts established that clinical research was one of healthcare workers’ institutional activity as well as healthcare assistance and recommended each public Hospitals and Local Health Trusts (LHTs) to set up a research infrastructure (RI) to support clinical researchers. The goal of this intervention was both to assess the regional RI organization and to design a policy fostering the development of a RIs’ regional network. Our work, that took place in one year, consists of three-steps conducting: (I) a survey on all 15 RIs to assess their organizational model; (II) an interview to the key informants of each RIs to assess their strengths and weaknesses; (III) a three-round Delphi survey to evaluate the stratification of the activities in terms of complexity. The survey showed a high level of heterogeneity among RIs in terms of organizational structure, activities, human and instrumental resources and strengths and weaknesses. For example technological, economic, and human resources were considered opportunities, although difficulty at hiring data managers emerged as a potential threat. The Delphi panel assigned 3 levels of complexity (low, medium, high) to each activity carried out by RIs: 14 (47%) were considered low (mandatory for all RIs); 11 (37%) were considered medium (needed in RIs with medium volume/complexity of research activities) and, lastly, only 1 (3%) was considered high (needed in RIs with high complexity of research activities); for 4 (13%) activities no consensus was reached. The survey showed high level of heterogeneity and fragmentation among regional RIs in terms of organization, activities, resources and support offered to researchers. It also identified which level of complexity each RI should have and proposed possible solutions fostering a regional network of RIs to improve research activities in our Region. Key messages • Research is a key element of any innovative healthcare system. Public research needs a strong coordination. • This work enabled policymakers to draft a policy based on evidence coming from stakeholders.

Effects of vitamin D supplementation on cardiometabolic parameters among patients with metabolic syndrome: A systematic review and GRADE evidence synthesis of randomized controlled trials

Various pathophysiologic mechanisms were proposed to underlie the effect of vitamin D on MetS components. In this systematic review, we reviewed randomized control clinical trials to verify whether vitamin D supplementation (VDS) at different doses is effective concomitantly in controlling high-density lipoprotein cholesterol (HDL-c), triglycerides (TG), fasting glucose level, blood pressure, and central obesity in adults diagnosed with MetS. The following scientific databases were searched from 1998 until April 2023: EMBASE, MEDLINE (PubMed), Web of Science, Latin American and Caribbean Health Sciences Literature (Lilacs), the Cochrane Central Register of Controlled Trials, clinicaltrial.gov, and Google Scholar. No language restrictions were applied. Seven studies were included, and they showed a high level of heterogeneity. All studies reported a significant increase in serum 25(OH)D levels in the intervention groups. Of these, only two noted a significant decrease in triglyceride (TG) level and waist circumference. However, the certainty levels of the evidence rating were very low and low for triglyceride (TG) level and waist circumference, respectively, and moderate for fasting glucose level, blood pressure, and HDL-c. In conclusion, despite these benefits, considering the low certainty, the evidence does not support that VDS decreases triglyceride (TG) level and waist circumference in adults with MetS.

Mobile audiometry for hearing threshold assessment: A systematic review and meta-analysis.

Technological advancements in mobile audiometry (MA) have enabled hearing assessment using tablets and smartphones. This systematic review (PROSPERO ID: CRD42021274761) aimed to identify MA options available to health providers, assess their accuracy in measuring hearing thresholds, and explore factors that might influence their accuracy. A systematic search of online databases including PubMed, Embase, Cochrane, Evidence Search and Dynamed was conducted on 13th December 2021, and repeated on 30th October 2022, using appropriate Medical Subject Headings (MeSH) terms. Eligible studies reported the use of MA to determine hearing thresholds and compared results to conventional pure-tone audiometry (CA). Studies investigating MA for hearing screening (i.e. reporting just pass/fail) were ineligible for inclusion. Two authors independently reviewed studies, extracted data, and assessed methodological quality and risk of bias using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Adults and children, with and without diagnosis of hearing impairment. A meta-analysis was performed to obtain the mean difference between thresholds measured using MA and CA in dB HL. Searches returned 858 articles. After systematic review, 17 articles including 1032 participants were analysed. The most used software application was ShoeboxTM (6/17) followed by Hearing TestTM (3/17), then HearTestTM (2/17). Tablet computers were used in ten studies, smartphones in six, and a computer in one. The mean difference between MA and CA thresholds was 1.36 dB (95% CI, 0.07-2.66, p = 0.04). Significant differences between mobile audiometry (MA) and conventional audiometry (CA) thresholds were observed in thresholds measured at 500Hz, in children, when MA was conducted in a sound booth, and when MA was self-administered. However, these differences did not exceed the clinically significant threshold of 10 decibels (dB). Included studies exhibited high levels of heterogeneity, high risk of bias and low concerns about applicability. MA compares favourably to CA in measuring hearing thresholds and has role in providing access to hearing assessment in situations where CA is not available or feasible. Future studies should prioritize the integration of pure-tone threshold assessment with additional tests, such as Speech Recognition and Digits-in-Noise, for a more rounded evaluation of hearing ability, assesses acceptability and feasibility, and the cost-effectiveness of MA in non-specialist settings.

THU394 Disease Burden Of X-Linked Hypophosphatemia Focused On The United States And Canada: A Targeted Literature Review

Abstract Disclosure: Z. Li: Employee; Self; Employee of Kyowa Kirin, Inc., Princeton, NJ, USA. O. Zaidi: Other; Self; Employee of OPEN Health and received funding to complete this research. C. Chukwu: Other; Self; Employee of OPEN Health and received funding to complete this research. H. Heerssen: Other; Self; Employee of Kyowa Kirin, Inc., Princeton, NJ, USA. Y. Zhao: Other; Self; Employee of Kyowa Kirin, Inc., Princeton, NJ, USA. A. Dale: Other; Self; Employee of Kyowa Kirin, Inc., Princeton, NJ, USA. M. Bernauer: Other; Self; Employee of OPEN Health and received funding to complete this research. Introduction: X-linked hypophosphatemia (XLH) is a rare genetic musculoskeletal disease and the most common form of heritable hypophosphatemic rickets. The objective of this review was to summarize the disease burden and treatment patterns of XLH in the United States (US) and Canada. Methods: Publications from January 1, 2015, to June 3, 2022, were searched using the Medline, Embase, and EconLit databases. Observational studies reporting epidemiology, humanistic burden, economic burden, and treatment patterns in the US and Canada were included. Evidence on epidemiology, humanistic burden, and treatment patterns was expanded to other countries as limited US and Canada studies were identified. Results: A total of 1,218 publications were screened; 42 publications were included (6 from US or Canada; 36 did not report location or were from other countries). Epidemiology data (i.e., incidence, prevalence, mortality) were limited for patients with XLH in the US and Canada. The estimated number of people in the US with XLH was &amp;lt;50,000 in 2021. Globally, the incidence of XLH was estimated at 3.9 per 100,000 live births, and the prevalence ranged from 1.4 per 100,000 to 4.8 per 100,000. One United Kingdom-based study estimated an XLH mortality rate of 12.1 per 1,000 person-years. Sixteen publications reported clinical manifestations of XLH, which showed a high level of heterogeneity. Among children with XLH, frequent clinical manifestations (&amp;gt;80% in 1 or more publications) included active rickets, diminished height, gait disturbance, bone or joint pain, and leg bowing. Among adults with XLH, frequent clinical manifestations (&amp;gt;80% in 1 or more publications) included short stature, leg deformity, musculoskeletal pain, fatigue, osteoarthritis, enthesophytes, gait disturbance, dental abscesses, and joint stiffness or restricted range of motion. Humanistic burden data from the US was limited to 2 non-trial publications, which used, respectively, the 36-Item Short Form Survey (SF-36) and the Knee Injury and Osteoarthritis Outcome Score-Physical Function Shortform (KOOS-PS) instruments. These 2 publications reported lower health-related quality of life for patients with XLH compared with the general population. No publication was identified on economic burden, treatment patterns, or XLH guidelines in the US or Canada. A consensus statement from a US panel of experts recommends individualization of monitoring and disease management due to clinical heterogeneity. Conclusions: There are limited published data on disease burden or treatment patterns for XLH in the US or Canada. Further research should consider the epidemiological, humanistic, and economic burden of XLH among pediatric and adult populations in these countries. Presentation: Thursday, June 15, 2023

Relationship between severe mental illness and physical multimorbidity: a meta-analysis and call for action

BackgroundPeople with severe mental illness (SMI) have a higher prevalence of several chronic physical health conditions, and the prevalence of physical multimorbidity is expected to rise. The aim of this...

Efficacy of Prophylactic Anti-VEGF in Preventing Radiation Retinopathy: A Systematic Review and Meta-Analysis.

In patients predisposed to radiation retinopathy (RR), administration of therapy after apparent clinical signs and symptoms are considered too late, resulting in substantial vision loss and blindness. Early initiation of anti-vascular endothelial growth factor (anti-VEGF) might serve as a strategy to slow disease progression and prolong good eyesight. To evaluate the efficacy of prophylactic anti-VEGF in preventing RR and preserving vision in patients at high risk of radiation-induced vision loss. A systematic literature search was performed from inception to 4 June 2023 using Cochrane Library, EMBASE, PubMed (MEDLINE), and Scopus. Eligible studies were clinical trials and observational studies investigating the incidence of radiation maculopathy (RM), radiation optic neuropathy (RON), moderate vision loss (loss of more than or equal to 3 lines of baseline visual acuity [VA]) and final VA, whether good (20/40 or better) or poor (20/200 or worse), following prophylactic anti-VEGF. Three reviewers independently conducted article screening, data extraction and risk of bias assessment. Random effects models were used to determine the cumulative effects of each outcome. Four studies (one clinical trial and three observational studies), involving 2109 patients, were included in our analysis. Across all studies, there were significant reductions in the events of RM (pooled odds ratio [OR] 0.50; 95% CI, 0.34-0.74; p = 0.001), RON (pooled OR 0.62; 95% CI, 0.42-0.90; p = 0.012) and poor final VA (pooled OR 0.50; 95% CI, 0.37-0.68; p = 0.003). The association of moderate vision loss and good final VA with the use of prophylactic anti-VEGF between the groups was unclear owing to the high level of heterogeneity. Prophylactic anti-VEGF therapy might delay RM and RON, preventing high-risk patients from developing poor VA by approximately 50%. However, this evidence should be interpreted with caution because of its low level of certainty. Future robust studies are warranted to confirm this finding.

An Updated Meta-Analysis of Clinical Trials and Observational Studies of Intravascular Ultrasound- versus Angiography-guided Left Main Stenting

Objectives: This updated meta-analysis aimed to consolidate clinical evidence comparing the clinical outcomes of intravascular ultrasound (IVUS)-guided LMCA stenting versus conventional angiography-guided LMCA stenting. Methodology: We included “randomized controlled trials” and “observational studies” published in peer-reviewed English language journals that compared the clinical outcomes of LMCA revascularization using “drug-eluting stents (DES)” via “IVUS-guided” versus “angiography-guided” stenting. The primary outcome of interest was “major adverse cardiovascular events (MACE)”, while secondary outcome variables included “all-cause mortality”, “myocardial infarction (MI)”, “target vessel/lesion revascularization (TVR/TLR)”, and “stent thrombosis (ST)”. Risk ratios (RRs) for each outcome variable were calculated using the “Mantel-Haenszel method”. Results: The analysis included nine studies involving a total of 5,344 patients, with 2,282 undergoing “IVUS-guided” LMCA stenting and 3,062 undergoing “angiography-guided” LMCA stenting. “IVUS-guided” LMCA stenting showed a significant reduction in the risk of MACE compared to “angiography-guided” LMCA stenting, with a RR of 0.46 [95% CI: 0.27 - 0.79]. However, a high level of heterogeneity (I2=94%; p&lt;0.01) was observed among the included studies. Additionally, “IVUS-guided” LMCA stenting was associated with significant reductions in all-cause mortality, MI, and ST, with RRs of 0.38 [0.21 - 0.66], 0.45 [0.26 - 0.77], and 0.24 [0.10 - 0.57], respectively. There was no statistically significant difference in TVR/TLR between “IVUS-guided” and “angiography-guided” LMCA stenting, with an RR of 0.64 [0.27 - 1.51]. Conclusion: “IVUS-guided” LMCA revascularization using DES was associated with a lower risk of MACE, death, MI, and ST compared to conventional “angiography-guided” LMCA stenting.

Radiomics diagnostic performance in predicting lymph node metastasis of papillary thyroid carcinoma: A systematic review and meta-analysis

PurposeTo evaluate the diagnostic performance of radiomics in lymph node metastasis (LNM) prediction in patients with papillary thyroid carcinoma (PTC) through a systematic review and meta-analysis. MethodA literature search of PubMed, EMBASE, and Web of Science was conducted to find relevant studies published until February 18th, 2023. Studies that reported the accuracy of radiomics in different imaging modalities for LNM prediction in PTC patients were selected. The methodological quality of included studies was evaluated by radiomics quality score (RQS) and quality assessment of diagnostic accuracy studies (QUADAS-2) tools. General characteristics and radiomics accuracy were extracted. Overall sensitivity, specificity, and area under the curve (AUC) were calculated for diagnostic accuracy evaluation. Spearman correlation coefficient and subgroup analysis were performed for heterogeneity exploration. ResultsIn total, 25 studies were included, of which 22 studies provided adequate data for meta-analysis. We conducted two types of meta-analysis: one focused solely on radiomics features models and the other combined radiomics and non-radiomics features models in the analysis. The pooled sensitivity, specificity, and AUC of radiomics and combined models were 0.75 [0.68, 0.80] vs. 0.77 [0.74, 0.80], 0.77 [0.74, 0.81] vs. 0.83 [0.78, 0.87] and 0.80 [0.73, 0.85] vs 0.82 [0.75, 0.88], respectively. The analysis showed a high heterogeneity level among the included studies. There was no threshold effect. The subgroup analysis demonstrated that utilizing ultrasonography, 2D segmentation, central and lateral LNM detection, automatic segmentation, and PyRadiomics software could slightly improve diagnostic accuracy. ConclusionsOur meta-analysis shows that the radiomics has the potential for pre-operative LNM prediction in PTC patients. Although methodological quality is sufficient but we still need more prospective studies with larger sample sizes from different centers.

Оцінка генетичної мінливості племінних стад амурського сазана (Cyprinus rubrofuscus Lacépède, 1803)

Purpose. To study the genetic peculiarities of pedigree tocksof Amur carp and evaluate its genetic variability by analyzing distribution of alleles and genotypes by the specific protein systems and cytogenetic parameters. Methodology. Analysis of polymorphism of protein systems was performed using electrophoresis in polyacrylamide gel. As protein markers to evaluate the genetic structure of Amur carp stocks, the separation of allelic and genotypic frequencies by loci, which encode a number of fish blood proteins, were used: transferrin (TF), albumin (ALB) and esterase (EST, 3.1.1.1). Cytogenetic analysis was performed using the micronucleus test and analysis of apoptosisfrequencies. Collection and processing of biological material of fish as well as statistical processing of the obtained data was performed using generally accepted methods. Findings. A comprehensive analysis of the genetic structure of Amur carp from three farms in Ukraine was carried out by protein systems and cytogenetic markers. The results of the study showed that all pedigree groups of Amur carp were characterized by a deviation towards the predominance of heterozygotes (Fis = from –0.084 to –0.344). A minimal imbalance was observed in the group of carp from the farm “Karpatskyi Vodogray” LLC (Fis = –0.084). The maximum violation of the genetic balance was found in carp from the farm of JSC “Sumyrybhosp” (Fis = –0.308) and in the group from the experimental farm “Veliky Lyubin” (Fis = –0.344). In general, the analysis of the protein systems of fish blood showed a high level of heterogeneity of pedigree stocks of Amur carp from different farms in Ukraine. The analysis of frequencies of cytogenetic parameters of Amur carp from three fish farms showed that fish from fish farms of JSC “Sumyrybhosp” and PFE “Dzherelo” were characterized by a lower frequency of erythrocytes with micronuclei (EMN) (3.3±0.3 ‰), (3.2±0.3 ‰), lymphocytes with micronuclei (LMN) (2.1±0, 2 ‰), (1.9±0.2 ‰), and apoptosis (4.2±0.3‰), (4,3±0,3‰) compared to the group from fish farm “Karpatskyi Vodogray” LLC, where these values were as follows: EMN (4.7±0.3 ‰), LMN (2.4±0.2‰), apoptosis (5.6±0.4‰). These results indicates a lower level of destabilization of chromosomal apparatus of Amur carp from the fish farm JSC “Sumyrybhosp” at the time of the study. Originality. A comprehensive evaluation of the level of variability of the genetic structure of pedigree stocks of Amur carp from different regions of Ukraine was performed for the first time. Practical Value. Pedigree socksof Amur carp have important practical value in selective breeding work with carps, including works for obtaining hybrid lines to increase the resistance of breeding material. Keywords: Amur carp, genetic structure, locus, alleles, genotype, heterozygosity, micronucleus test, cytogenetic analysis.

Efficacy, Safety, and Evaluation Criteria of mHealth Interventions for Depression: Systematic Review.

Depression is a significant public health issue that can lead to considerable disability and reduced quality of life. With the rise of technology, mobile health (mHealth) interventions, particularly smartphone apps, are emerging as a promising approach for addressing depression. However, the lack of standardized evaluation tools and evidence-based principles for these interventions remains a concern. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of mHealth interventions for depression and identify the criteria and evaluation tools used for their assessment. A systematic review and meta-analysis of the literature was carried out following the recommendations of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Studies that recruited adult patients exhibiting elevated depressive symptoms or those diagnosed with depressive disorders and aimed to assess the effectiveness or safety of mHealth interventions were eligible for consideration. The primary outcome of interest was the reduction of depressive symptoms, and only randomized controlled trials (RCTs) were included in the analysis. The risk of bias in the original RCTs was assessed using version 2 of the Cochrane risk-of-bias tool for randomized trials. A total of 29 RCTs were included in the analysis after a comprehensive search of electronic databases and manual searches. The efficacy of mHealth interventions in reducing depressive symptoms was assessed using a random effects meta-analysis. In total, 20 RCTs had an unclear risk of bias and 9 were assessed as having a high risk of bias. The most common element in mHealth interventions was psychoeducation, followed by goal setting and gamification strategies. The meta-analysis revealed a significant effect for mHealth interventions in reducing depressive symptoms compared with nonactive control (Hedges g=-0.62, 95% CI -0.87 to -0.37, I2=87%). Hybrid interventions that combined mHealth with face-to-face sessions were found to be the most effective. Three studies compared mHealth interventions with active controls and reported overall positive results. Safety analyses showed that most studies did not report any study-related adverse events. This review suggests that mHealth interventions can be effective in reducing depressive symptoms, with hybrid interventions achieving the best results. However, the high level of heterogeneity in the characteristics and components of mHealth interventions indicates the need for personalized approaches that consider individual differences, preferences, and needs. It is also important to prioritize evidence-based principles and standardized evaluation tools for mHealth interventions to ensure their efficacy and safety in the treatment of depression. Overall, the findings of this study support the use of mHealth interventions as a viable method for delivering mental health care. PROSPERO CRD42022304684; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=304684.

Glucometabolic outcomes of GLP-1 receptor agonist-based therapies in patients with type 2 diabetes: a systematic review and network meta-analysis

Innovative GLP-1 receptor agonist (GLP-1RA)-based treatment strategies-such as tirzepatide, GLP-1RA plus basal insulin fixed-ratio combinations [FRC], GLP-1RA plus sodium glucose cotransporter-2 inhibitors [SGLT-2i] combinations, and high-dose GLP-1RA-have been listed among the most efficacious options for type 2 diabetes management. However, differences in their glucometabolic effects have not been assessed in dedicated head-to-head trials. In the absence of such trials, we aimed to provide a useful comparison among these treatment strategies to guide clinical practice. In this network meta-analysis, we searched PubMed, MEDLINE, and Web of Science (from database inception to June 24, 2023) for randomised controlled studies, published in English, that enrolled individuals with type 2 diabetes treated with tirzepatide, iGlarLixi, iDegLira, GLP-1RA plus SGLT-2i combination, or high-dose GLP-1RA (dulaglutide 3mg and 4.5mg, semaglutide 2mg) compared with placebo or active comparators. Eligible studies reported change from baseline in HbA1c as an outcome, which was the primary outcome of this analysis. Secondary outcomes were changes in fasting and post-prandial glucose, bodyweight, LDL-cholesterol, blood pressure and risk of hypoglycaemia. We assessed risk of bias through the Cochrane Collaboration's tool (RoB2 tool), publication bias through visual inspection of funnel plots and Egger's test, and heterogeneity by comparing the magnitude of the common between-study variance (τ2) for each outcome with empirical distributions of heterogeneity variances. This network meta-analysis was registered in PROSPERO (CRD42022329878). 40 trials were included. Tirzepatide 15 mg ranked first in terms of HbA1c reduction compared to other GLP-1RA-based strategies, even those including insulin (vs. iDegLira MD -0.40%, 95% CI [-0.66; -0.14], low certainty; vs. iGlarLixi MD -0.48%, 95% CI [-0.75; -0.21], low certainty), without increasing the risk of hypoglycaemia (vs. iDegLira OR 0.35, 95% CI [0.16; 0.79], high certainty; vs. iGlarLixi OR 0.31, 95% CI [0.20; 0.48], high certainty). Tirzepatide 15 mg was also the most efficacious on weight lowering, even compared to high-dose GLP-1RA (eg, semaglutide 2 mg MD -6.56 kg, 95% CI [-7.38; -5.73], low certainty) and GLP-1RA plus SGLT-2i combination (MD -4.61 kg, 95% CI [-5.29; -3.93], low certainty). Risk of bias and publication bias were generally low throughout studies, while high levels of heterogeneity were detected for most outcomes. Aiming to support clinicians in tailoring treatment to patients' needs, we suggest that a hierarchy among treatment strategies be devised considering the best options for type 2 diabetes. Tirzepatide, followed by GLP-1RA plus basal insulin FRC and GLP-1RA plus SGLT-2i combination, was associated with greater benefit on HbA1c than high-dose GLP-1RA. Fondazione per la Ricerca Biomedica "Saverio e Isabella Cianciola" and Next Generation EU, in the context of the National Recovery and Resilience Plan, Investment PE8-Project Age-It: Ageing Well in an Ageing Society.

A Bayesian method for capacity degradation prediction of lithium-ion battery considering both within and cross group heterogeneity

Accurate assessment and prediction of lithium-ion batteries’ (LIBs’) state-of-health (SOH) are crucial for the safety and timely maintenance of LIB-powered systems. During the aging process, due to the variation of initial health status and working conditions, the degradation paths of different LIBs usually manifest a high level of heterogeneity, including within and cross group heterogeneity. However, existing methods usually neglect the heterogeneity among different groups and put LIBs together for model development, leading to inferior prediction performance. To address this gap, a Bayesian estimation method is proposed to model both within and cross group heterogeneity. Specifically, the Gaussian mixture model (GMM) is employed to automatically separate LIBs into different groups, and, within each group, the linear mixed effects (LME) model is further applied to model the degradation path of each LIB. This leads to an LME model with mixture prior (LME-MP), which can effectively capture both within and cross group heterogeneity to provide accurate degradation prediction for the target battery. The accuracy and superiority of the proposed method are validated through the comparison with different benchmark methods using LIBs from the NASA data repository under randomized cycling conditions.

Microfluidic single-cell measurements of oxidative stress as a function of cell cycle position.

Single-cell measurements routinely demonstrate high levels of variation between cells, but fewer studies provide insight into the analytical and biological sources of this variation. This is particularly true of chemical cytometry, in which individual cells are lysed and their contents separated, compared to more established single-cell measurements of the genome and transcriptome. To characterize population-level variation and its sources, we analyzed oxidative stress levels in 1278 individual Dictyostelium discoideum cells as a function of exogenous stress level and cell cycle position. Cells were exposed to varying levels of oxidative stress via singlet oxygen generation using the photosensitizer Rose Bengal. Single-cell data reproduced the dose-response observed in ensemble measurements by CE-LIF, superimposed with high levels of heterogeneity. Through experiments and data analysis, we explored possible biological sources of this heterogeneity. No trend was observed between population variation and oxidative stress level, but cell cycle position was a major contributor to heterogeneity in oxidative stress. Cells synchronized to the same stage of cell division were less heterogeneous than unsynchronized cells (RSD of 37-51% vs 93%), and mitotic cells had higher levels of reactive oxygen species than interphase cells. While past research has proposed changes in cell size during the cell cycle as a source of biological noise, the measurements presented here use an internal standard to normalize for effects of cell volume, suggesting a more complex contribution of cell cycle to heterogeneity of oxidative stress.

How do different types and characteristics of green space impact mental health? A scoping review

Abstract Green space matters for mental health but is under constant pressure in an increasingly urbanising world. Often there is little space available in cities for green areas, so it is vital to optimise the design and usage of these available green spaces. To achieve this, experts in planning, design and nature conservation need to know which types and characteristics of green spaces are most beneficial for residents' mental health. A scoping review of studies that compare different green space types and characteristics on mental health was conducted. A total of 215 (experimental, observational and qualitative) papers were included in the scoping review. This review highlights a high level of heterogeneity in study design, geographical locations, mental health outcomes and green space measures. Few of the included studies were specifically designed to enable direct comparisons between green space types and characteristics (e.g. between parks and forests). The included studies have predominantly experimental research designs looking at the effects of short‐term exposure to green space on short‐term mental health outcomes (e.g. affect and physiological stress). More studies enabled only indirect comparisons, either within the same study or between different studies. Analysis of the direction of the mental health outcomes (positive, neutral, negative) from exposure to various types and characteristics of green space found positive (i.e. beneficial) effects across all green space types. However, green space characteristics did appear to render more diverse effects on mental health, which is especially the case for vegetation characteristics (e.g. higher vegetation density can be negative for mental health). The scoping review reveals gaps in the present evidence base, with a specific need for more studies directly comparing green space types and characteristics within the same study. Proposed future research directions include the use of longitudinal research designs focusing on green space characteristics, considering actual exposure and systematically addressing heterogeneity in factors influencing the relation between green spaces and mental health (e.g. type of interaction, user experience). Read the free Plain Language Summary for this article on the Journal blog.

Phenotypic and genotypic antimicrobial resistance correlation and plasmid characterization in Salmonella spp. isolates from Italy reveal high heterogeneity among serovars.

The spread of antimicrobial resistance among zoonotic pathogens such as Salmonella is a serious health threat, and mobile genetic elements (MGEs) carrying antimicrobial resistance genes favor this phenomenon. In this work, phenotypic antimicrobial resistance to commonly used antimicrobials was studied, and the antimicrobial resistance genes (ARGs) and plasmid replicons associated with the resistances were determined. Eighty-eight Italian Salmonella enterica strains (n = 88), from human, animal and food sources, isolated between 2009 and 2019, were selected to represent serovars with different frequency of isolation in human cases of salmonellosis. The presence of plasmid replicons was also investigated. Resistances to sulphonamides (23.9%), ciprofloxacin (27.3%), ampicillin (29.5%), and tetracycline (32.9%) were the most found phenotypes. ARGs identified in the genomes correlated with the phenotypical results, with blaTEM-1B, sul1, sul2, tetA and tetB genes being frequently identified. Point mutations in gyrA and parC genes were also detected, in addition to many different aminoglycoside-modifying genes, which, however, did not cause phenotypic resistance to aminoglycosides. Many genomes presented plasmid replicons, however, only a limited number of ARGs were predicted to be located on the contigs carrying these replicons. As an expectation of this, multiple ARGs were identified on contigs with IncQ1 plasmid replicon in strains belonging to the monophasic variant of Salmonella Typhimurium. In general, high variability in ARGs and plasmid replicons content was observed among isolates, highlighting a high level of heterogeneity in Salmonella enterica. Irrespective of the serovar., many of the ARGs, especially those associated with critically and highly important antimicrobials for human medicine were located together with plasmid replicons, thus favoring their successful dissemination.

Unique miRNome and transcriptome profiles underlie microvascular heterogeneity in mouse kidney.

Endothelial cells in blood vessels in the kidney exert different functions depending on the (micro)vascular bed they are located in. The present study aimed to investigate microRNA and mRNA transcription patterns that underlie these differences. We zoomed in on microvascular compartments in the mouse renal cortex by laser microdissecting the microvessels prior to small RNA- and RNA-sequencing analyses. By these means, we characterized microRNA and mRNA transcription profiles of arterioles, glomeruli, peritubular capillaries, and postcapillary venules. Quantitative RT-PCR, in situ hybridization, and immunohistochemistry were used to validate sequencing results. Unique microRNA and mRNA transcription profiles were found in all microvascular compartments, with dedicated marker microRNAs and mRNAs showing enriched transcription in a single microvascular compartment. In situ hybridization validated the localization of microRNAs mmu-miR-140-3p in arterioles, mmu-miR-322-3p in glomeruli, and mmu-miR-451a in postcapillary venules. Immunohistochemical staining showed that von Willebrand factor protein was mainly expressed in arterioles and postcapillary venules, whereas GABRB1 expression was enriched in glomeruli, and IGF1 was enriched in postcapillary venules. More than 550 compartment-specific microRNA-mRNA interaction pairs were identified that carry functional implications for microvascular behavior. In conclusion, our study identified unique microRNA and mRNA transcription patterns in microvascular compartments of the mouse kidney cortex that underlie microvascular heterogeneity. These patterns provide important molecular information for future studies into differential microvascular engagement in health and disease.NEW & NOTEWORTHY Renal endothelial cells display a high level of heterogeneity depending on the (micro)vascular bed they reside in. The molecular basis contributing to these differences is poorly understood yet of high importance to increase understanding of microvascular engagement in the kidney in health and disease. This report describes m(icro)RNA expression profiles of microvascular beds in the mouse renal cortex and uncovers microvascular compartment-specific m(icro)RNAs and miRNA-mRNA pairs, thereby revealing important molecular mechanisms underlying renal microvascular heterogeneity.