Do serum biomarkers really measure breast cancer?

Background Because screening mammography for breast cancer is less effective for premenopausal women, we investigated the feasibility of a diagnostic blood test using serum proteins. Methods This study used a set of 98 serum proteins and chose diagnostically relevant subsets via various feature-selection techniques. Because of significant noise in the data set, we applied iterated Bayesian model averaging to account for model selection uncertainty and to improve generalization performance. We assessed generalization performance using leave-one-out cross-validation (LOOCV) and receiver operating characteristic (ROC) curve analysis. Results The classifiers were able to distinguish normal tissue from breast cancer with a classification performance of AUC = 0.82 ± 0.04 with the proteins MIF, MMP-9, and MPO. The classifiers distinguished normal tissue from benign lesions similarly at AUC = 0.80 ± 0.05. However, the serum proteins of benign and malignant lesions were indistinguishable (AUC = 0.55 ± 0.06). The classification tasks of normal vs. cancer and normal vs. benign selected the same top feature: MIF, which suggests that the biomarkers indicated inflammatory response rather than cancer. Conclusion Overall, the selected serum proteins showed moderate ability for detecting lesions. However, they are probably more indicative of secondary effects such as inflammation rather than specific for malignancy.United States. Dept. of Defense. Breast Cancer Research Program (Grant No. W81XWH-05-1-0292)National Institutes of Health (U.S.) (R01 CA-112437-01)National Institutes of Health (U.S.) (NIH CA 84955

Evapotranspiration Dynamics and Partitioning in a Grassed Vineyard: Ecophysiological and Computational Modeling Approaches

Plenty of information on evapotranspiration (ET) dynamics and partitioning into nonbiological (evaporation, E) and biological (transpiration, T) components is available in literature. However, in agro-ecosystems where more than one vegetation group is found, like intercropping or grassed orchards and vineyards, it is of great use to understand the contribution to T due to the single plant type or group of plants. We deployed empirical and modeling methods to study the ecosystem evapotranspiration (ETEC) components in a grassed vineyard in Caldaro (Italy) aiming to assess (a) which process, E or T, had greater influence on ETEC dynamics; (b) which component among grapevines and understorey portion dominated the ETEC; and (c) how rainfall influences ETEC components. A top-down approach combined the eddy covariance method to estimate ETEC, and the Transpiration Estimation Algorithm method to partition it. A bottom-up approach integrated the understorey evapotranspiration (ETu) with modeled vines transpiration (Tv((mod))). Measured and modeled fluxes showed high daily variability, consistently with meteorological conditions (vapor pressure deficit, Rn and Tair). The mean daily ETEC integrals were 3.45 and 3.40 mm d(-1) (2021 and 2022), being T-EC (estimated transpiration fraction of ETEC) the higher contributor (T-EC/ETEC of 0.77 and 0.79, same years). From the bottom-up approach, ETu assessed during ground flux chamber campaigns (0.74-1.65 mm d(-1)) was lower than Tv((mod)). A high agreement (R-2 = 0.85) was found between the eddy covariance ET hourly values and ET by summing Tv((mod)) and ETu. We concluded that the T process represented major fluxes in the agroecosystem during the warm season. Furthermore, the bottom-up approach indicated the vines as primary contributors to ecosystem T, particularly noticeable after rainfall, as the understorey T fraction (Tu) increased when the system became drier. This study helps disentangling grapevine contribution to evapotranspiration from adjacent herbaceous vegetation in a vineyard, and emphasizes the dominance of biologically mediated transpiration influenced by meteorological conditions. This novel combination of approaches not only enhances understanding of Mediterranean viticulture but also illuminates broader applications in sparsely vegetated environments, such as agroforestry systems and orchards, advancing ecological management practices

Major threats caused by climate change to grapevine

The main worrying feature of climate change is its rapid evolution, in extent and variation, becoming less and less predictable. In this paper, we have reviewed the available literature and elaborated original data to outline how climate change will affect the grapevine cultivation and wine quality. We start by discussing which features of climate change will impact grapevine production most. The effects of heatwaves, air and soil temperature, extreme rainfall events, atmospheric evaporative demand, wildfires, and smoke are addressed. An increased frequency and intensity of heat waves since 2010 is shown in four grapevine production areas of Northern Italy. The focus then shifts to the impacts of the predicted increase in temperature and drought on frost risks, grapevine phenology, yield, berry quality and water needs as well as vine and vineyard carbon budgets. Climate change will challenge the achievement of current yields and wine quality as well as the ability of vineyards to sequester atmospheric carbon, but such effects will likely depend on the characteristics of the growing environments and on the varieties present. Climate change-related threats to grapevine call for a rapid implementation of adaptation strategies

Psychotherapies for borderline personality disorder:A focused systematic review and meta-Analysis

Background A recently updated Cochrane review supports the efficacy of psychotherapy for borderline personality disorder (BPD). Aims To evaluate the effects of standalone and add-on psychotherapeutic treatments more concisely. Method We applied the same methods as the 2020 Cochrane review, but focused on adult samples and comparisons of active treatments and unspecific control conditions. Standalone treatments (i.e. necessarily including individual psychotherapy as either the sole or one of several treatment components) and add-on interventions (i.e. complementing any ongoing individual BPD treatment) were analysed separately. Primary outcomes were BPD severity, self-harm, suicide-related outcomes and psychosocial functioning. Secondary outcomes were remaining BPD diagnostic criteria, depression and attrition. Results Thirty-one randomised controlled trials totalling 1870 participants were identified. Among standalone treatments, statistically significant effects of low overall certainty were observed for dialectical behaviour therapy (self-harm: standardised mean difference (SMD)-0.54, P = 0.006; psychosocial functioning: SMD-0.51, P = 0.01) and mentalisation-based treatment (self-harm: risk ratio 0.51, P &lt; 0.0007; suicide-related outcomes: risk ratio 0.10, P &lt; 0.0001). For adjunctive interventions, moderate-quality evidence of beneficial effects was observed for DBT skills training (BPD severity: SMD-0.66, P = 0.002; psychosocial functioning: SMD-0.45, P = 0.002), and statistically significant low-certainty evidence was observed for the emotion regulation group (BPD severity: mean difference-8.49, P &lt; 0.00001), manual-Assisted cognitive therapy (self-harm: mean difference-3.03, P = 0.03; suicide-related outcomes: SMD-0.96, P = 0.005) and the systems training for emotional predictability and problem-solving (BPD severity: SMD-0.48, P = 0.002). Conclusions There is reasonable evidence to conclude that psychotherapeutic interventions are helpful for individuals with BPD. Replication studies are needed to enhance the certainty of findings. </p

Pharmacological interventions for co-occurring psychopathology in people with borderline personality disorder:Secondary analysis of the Cochrane systematic review with meta-analyses

Background: Medications are commonly used to treat co-occurring psychopathology in persons with borderline personality disorder (BPD).Aims: To systematically review and integrate the evidence of medications for treatment of co-occurring psychopathology in people with BPD, and explore the role of comorbidities.Method: Building on the current Cochrane review of medications in BPD, an update literature search was done in March 2024. We followed the methods of this Cochrane review, but scrutinised all identified placebo-controlled trials post hoc for reporting of non BPD-specific ('co-occurring') psychopathology, and explored treatment effects in subgroups of samples with and without defined co-occurring disorders. GRADE ratings were done to assess the evidence certainty.Results: Twenty-two trials were available for quantitative analyses. For antipsychotics, we found very-low-certainty evidence (VLCE) of an effect on depressive symptoms (standardised mean difference (SMD) -0.22, P = 0.04), and low-certainty evidence (LCE) of an effect on psychotic-dissociative symptoms (SMD -0.28, P = 0.007). There was evidence of effects of anticonvulsants on depressive (SMD -0.44, P = 0.02; LCE) and anxious symptoms (SMD -1.11, P &lt; 0.00001; VLCE). For antidepressants, no significant findings were observed (VLCE). Exploratory subgroup analyses indicated a greater effect of antipsychotics in samples including participants with co-occurring substance use disorders on psychotic-dissociative symptoms (P = 0.001).Conclusions: Our findings, based on VLCE and LCE only, do not support the use of pharmacological interventions in people with BPD to target co-occurring psychopathology. Overall, the current evidence does not support differential treatment effects in persons with versus without defined comorbidities. Medications should be used cautiously to target co-occurring psychopathology.<p/

Psychotherapies for borderline personality disorder : a focused systematic review and meta-analysis

Background: A recently updated Cochrane review supports the efficacy of psychotherapy for borderline personality disorder (BPD). Aims: To evaluate the effects of standalone and add-on psychotherapeutic treatments more concisely. Method: We applied the same methods as the 2020 Cochrane review, but focused on adult samples and comparisons of active treatments and unspecific control conditions. Standalone treatments (i.e. necessarily including individual psychotherapy as either the sole or one of several treatment components) and add-on interventions (i.e. complementing any ongoing individual BPD treatment) were analysed separately. Primary outcomes were BPD severity, self-harm, suicide-related outcomes and psychosocial functioning. Secondary outcomes were remaining BPD diagnostic criteria, depression and attrition. Results: Thirty-one randomised controlled trials totalling 1870 participants were identified. Among standalone treatments, statistically significant effects of low overall certainty were observed for dialectical behaviour therapy (self-harm: standardised mean difference (SMD) −0.54, P = 0.006; psychosocial functioning: SMD −0.51, P = 0.01) and mentalisation-based treatment (self-harm: risk ratio 0.51, P < 0.0007; suicide-related outcomes: risk ratio 0.10, P < 0.0001). For adjunctive interventions, moderate-quality evidence of beneficial effects was observed for DBT skills training (BPD severity: SMD −0.66, P = 0.002; psychosocial functioning: SMD −0.45, P = 0.002), and statistically significant low-certainty evidence was observed for the emotion regulation group (BPD severity: mean difference −8.49, P < 0.00001), manual-assisted cognitive therapy (self-harm: mean difference −3.03, P = 0.03; suicide-related outcomes: SMD −0.96, P = 0.005) and the systems training for emotional predictability and problem-solving (BPD severity: SMD −0.48, P = 0.002). Conclusions: There is reasonable evidence to conclude that psychotherapeutic interventions are helpful for individuals with BPD. Replication studies are needed to enhance the certainty of findings

Pharmacological interventions for people with borderline personality disorder

Background: Among people with a diagnosis of borderline personality disorder (BPD) who are engaged in clinical care, prescription rates of psychotropic medications are high, despite the fact that medication use is off-label as a treatment for BPD. Nevertheless, people with BPD often receive several psychotropic drugs at a time for sustained periods. Objectives: To assess the effects of pharmacological treatment for people with BPD. Search methods: For this update, we searched CENTRAL, MEDLINE, Embase, 14 other databases and four trials registers up to February 2022. We contacted researchers working in the field to ask for additional data from published and unpublished trials, and handsearched relevant journals. We did not restrict the search by year of publication, language or type of publication. Selection criteria: Randomised controlled trials comparing pharmacological treatment to placebo, other pharmacologic treatments or a combination of pharmacologic treatments in people of all ages with a formal diagnosis of BPD. The primary outcomes were BPD symptom severity, self-harm, suicide-related outcomes, and psychosocial functioning. Secondary outcomes were individual BPD symptoms, depression, attrition and adverse events. Data collection and analysis: At least two review authors independently selected trials, extracted data, assessed risk of bias using Cochrane's risk of bias tool and assessed the certainty of the evidence using the GRADE approach. We performed data analysis using Review Manager 5 and quantified the statistical reliability of the data using Trial Sequential Analysis. Main results: We included 46 randomised controlled trials (2769 participants) in this review, 45 of which were eligible for quantitative analysis and comprised 2752 participants with BPD in total. This is 18 more trials than the 2010 review on this topic. Participants were predominantly female except for one trial that included men only. The mean age ranged from 16.2 to 39.7 years across the included trials. Twenty-nine different types of medications compared to placebo or other medications were included in the analyses. Seventeen trials were funded or partially funded by the pharmaceutical industry, 10 were funded by universities or research foundations, eight received no funding, and 11 had unclear funding. For all reported effect sizes, negative effect estimates indicate beneficial effects by active medication. Compared with placebo, no difference in effects were observed on any of the primary outcomes at the end of treatment for any medication. Compared with placebo, medication may have little to no effect on BPD symptom severity, although the evidence is of very low certainty (antipsychotics: SMD -0.18, 95% confidence interval (CI) -0.45 to 0.08; 8 trials, 951 participants; antidepressants: SMD −0.27, 95% CI −0.65 to 1.18; 2 trials, 87 participants; mood stabilisers: SMD −0.07, 95% CI −0.43 to 0.57; 4 trials, 265 participants). The evidence is very uncertain about the effect of medication compared with placebo on self-harm, indicating little to no effect (antipsychotics: RR 0.66, 95% CI 0.15 to 2.84; 2 trials, 76 participants; antidepressants: MD 0.45 points on the Overt Aggression Scale-Modified-Self-Injury item (0-5 points), 95% CI −10.55 to 11.45; 1 trial, 20 participants; mood stabilisers: RR 1.08, 95% CI 0.79 to 1.48; 1 trial, 276 participants). The evidence is also very uncertain about the effect of medication compared with placebo on suicide-related outcomes, with little to no effect (antipsychotics: SMD 0.05, 95 % CI −0.18 to 0.29; 7 trials, 854 participants; antidepressants: SMD −0.26, 95% CI −1.62 to 1.09; 2 trials, 45 participants; mood stabilisers: SMD −0.36, 95% CI −1.96 to 1.25; 2 trials, 44 participants). Very low-certainty evidence shows little to no difference between medication and placebo on psychosocial functioning (antipsychotics: SMD −0.16, 95% CI −0.33 to 0.00; 7 trials, 904 participants; antidepressants: SMD −0.25, 95% CI -0.57 to 0.06; 4 trials, 161 participants; mood stabilisers: SMD −0.01, 95% CI -0.28 to 0.26; 2 trials, 214 participants). Low-certainty evidence suggests that antipsychotics may slightly reduce interpersonal problems (SMD −0.21, 95% CI −0.34 to -0.08; 8 trials, 907 participants), and that mood stabilisers may result in a reduction in this outcome (SMD −0.58, 95% CI -1.14 to -0.02; 4 trials, 300 participants). Antidepressants may have little to no effect on interpersonal problems, but the corresponding evidence is very uncertain (SMD −0.07, 95% CI -0.69 to 0.55; 2 trials, 119 participants). The evidence is very uncertain about dropout rates compared with placebo by antipsychotics (RR 1.11, 95% CI 0.89 to 1.38; 13 trials, 1216 participants). Low-certainty evidence suggests there may be no difference in dropout rates between antidepressants (RR 1.07, 95% CI 0.65 to 1.76; 6 trials, 289 participants) and mood stabilisers (RR 0.89, 95% CI 0.69 to 1.15; 9 trials, 530 participants), compared to placebo. Reporting on adverse events was poor and mostly non-standardised. The available evidence on non-serious adverse events was of very low certainty for antipsychotics (RR 1.07, 95% CI 0.90 to 1.29; 5 trials, 814 participants) and mood stabilisers (RR 0.84, 95% CI 0.70 to 1.01; 1 trial, 276 participants). For antidepressants, no data on adverse events were identified. Authors' conclusions: This review included 18 more trials than the 2010 version, so larger meta-analyses with more statistical power were feasible. We found mostly very low-certainty evidence that medication may result in no difference in any primary outcome. The rest of the secondary outcomes were inconclusive. Very limited data were available for serious adverse events. The review supports the continued understanding that no pharmacological therapy seems effective in specifically treating BPD pathology. More research is needed to understand the underlying pathophysiologic mechanisms of BPD better. Also, more trials including comorbidities such as trauma-related disorders, major depression, substance use disorders, or eating disorders are needed. Additionally, more focus should be put on male and adolescent samples.</p

Genome-wide association study reveals a locus in ADARB2 for complete freedom from headache in Danish Blood Donors

Headache disorders are the most common disorders of the nervous system. The lifetime prevalence of headache disorders show that some individuals never experience headache. The etiology of complete freedom from headache is not known. To assess genetic variants associated with complete freedom from headache, we performed a genome-wide association study of individuals who have never experienced a headache. We included 63,992 individuals (2,998 individuals with complete freedom from headache and 60,994 controls) from the Danish Blood Donor Study Genomic Cohort. Participants were included in two rounds, from 2015 to 2018 and in 2020. We discovered a genome-wide significant association, with the lead variant rs7904615[G] in ADARB2 (EAF = 27%, OR = 1.20 [1.13–1.27], p = 3.92 × 10−9). The genomic locus was replicated in a non-overlapping cohort of 13,032 individuals (539 individuals with complete freedom from headache and 12,493 controls) from the Danish Blood Donor Study Genomic Cohort (p < 0.05, two-sided). Participants for the replication were included from 2015 to 2020. In conclusion, we show that complete freedom from headache has a genetic component, and we suggest that ADARB2 is involved in complete freedom from headache. The genomic locus was specific for complete freedom from headache and was not associated with any primary headache disorders.publishedVersio