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Abstract Background This article applies a variant of the Markov chain that explicitly incorporates spatial effects. It is an extension of the Markov class allowing a more complete analysis of the spatial dimensions of transition dynamics. The aim is to provide a methodology for applying the explicit model to spatial dependency analysis. Methods Here, the question is to study and quantify whether neighborhood context affects transitional dynamics. Rather than estimating a homogeneous law, the model requires the estimation of k transition laws each dependent on spatial neighbor state. This article used published data on confirmed cases of Covid’19 in the 22 regions of Madagascar. These data were discretized to obtain a discrete state of propagation intensity. Results The analysis gave us the transition probabilities between Covid’19 intensity states knowing the context of neighboring regions, and the propagation time laws knowing the spatial contexts. The results showed that neighboring regions had an effect on the propagation of Covid’19 in Madagascar. Conclusion After analysis, we can say that there is spatial dependency according to these spatial transition matrices.

Background This study aims to examine whether the Edinburgh Postnatal Depression Scale (EPDS), excluding the self-harm item (EPDS-9), performs as effectively as the full EPDS in identifying depression among perinatal women.Methods A total of 3571 pregnant women and 3850 postpartum women participated in this observational study. Participants who scored ≥ 9 on the EPDS underwent further diagnostic evaluations by a clinical psychologist and/or psychiatrist.Results The EPDS-9 and full EPDS demonstrated a near-perfect correlation in both the antepartum (r = 0.996) and postpartum (r = 0.998) cohorts. EPDS-9 showed exceptional precision in identifying depression as screened by the full EPDS at cutoff points ranging 9–14, with areas under the curve ≥0.998. The sensitivity of EPDS-9 and full EPDS to detect depression that requires psychotropic medications was poor. The highest accuracy for both versions was at a cutoff score of 9: sensitivity of 0.579 for the full EPDS and 0.526 for the EPDS-9. At the cutoff point of 9, EPDS-9 performed adequately in predicting the response of the participants to the self-harm item.Conclusion The EPDS-9 represents a solid and effective replacement for the full EPDS in clinical settings. If the presence of suicidal thoughts needs to be assessed, specialized scales should be used.

ABSTRACTAntibodies are one of the most important reagents used in biomedical and fundamental research, used to identify, and quantify proteins, contribute to knowledge of disease mechanisms, and validate drug targets. Yet many antibodies used in research do not recognize their intended target, or recognize additional molecules, compromising the integrity of research findings and leading to waste of resources, lack of reproducibility, failure of research projects, and delays in drug development. Researchers frequently use antibodies without confirming that they perform as intended in their application of interest. Here we argue that the determinants of end-user antibody choice and use are critical, and under-addressed, behavioral drivers of this problem. This interacts with the batch-to-batch variability of these biological reagents, and the paucity of available characterization data for most antibodies, making it more difficult for researchers to choose high quality reagents and perform necessary validation experiments. The open-science company YCharOS works with major antibody manufacturers and knockout cell line producers to characterize antibodies, identifying high-performing renewable antibodies for many targets in neuroscience. This shows the progress that can be made by stakeholders working together. However, their work so far applies to only a tiny fraction of available antibodies. Where characterization data exists, end-users need help to find and use it appropriately. While progress has been made in the context of technical solutions and antibody characterization, we argue that initiatives to make best practice behaviors by researchers more feasible, easy, and rewarding are needed. Global cooperation and coordination between multiple partners and stakeholders will be crucial to address the technical, policy, behavioral, and open data sharing challenges. We offer potential solutions by describing our Only Good Antibodies initiative, a community of researchers and partner organizations working toward the necessary change. We conclude with an open invitation for stakeholders, including researchers, to join our cause.

BackgroundRoutine process and outcome monitoring interventions added to psychotherapy are known to improve treatment outcomes, although they vary in format and effectiveness. ObjectiveThis study aimed to evaluate whether a therapist-independent, internet-based routine process monitoring and feedback system could significantly reduce psychological distress and enhance the quality of the therapeutic relationship compared with a treatment-as-usual control group among individuals already engaged in individual psychotherapy. MethodsWe randomized 475 participants into either the intervention group, which received access to an internet-based routine process monitoring and feedback system in addition to psychotherapy, or the control group, which received only psychotherapy. The trial lasted for 10 weeks. Follow-up assessments at 5 weeks and 10 weeks used the Clinical Outcomes in Routine Evaluation-Outcome Measure as the primary outcome, with the Working Alliance Inventory-Short Revised and the Real Relationship Inventory-Client form as secondary outcomes. ResultsPer-protocol analyses (n=166) showed that psychological distress decreased in both groups, but there was no significant advantage for the intervention group. The intervention group experienced a decline in the genuineness dimension score of the real relationship, with an effect size of d=–0.27, compared with d=0.01 in the control group. In the intervention group (but not in the control group), dropouts showed significantly lower real relationship levels (P=.002), working alliance quality (P=.051), and emotional disclosure (P=.01) compared with those who completed the study. Additionally, logistic regression revealed distinct predictors of dropout within the control group and intervention group. ConclusionsThe findings do not provide conclusive evidence for the efficacy of the new internet-based intervention in enhancing self-monitoring and prompting reflection on patients’ emotional responses to their therapists. However, the intervention appears to influence patients’ perceptions of the genuineness dimension in the therapeutic relationship, warranting further investigation. We hypothesize that this alteration in the genuineness dimension could be attributed to the intervention facilitating a more realistic and accurate perception of the therapeutic relationship among participants. Trial RegistrationClinicalTrials.gov NCT06038747; https://clinicaltrials.gov/study/NCT06038747 International Registered Report Identifier (IRRID)RR2-10.2196/55369

Abstract Radiation delivery at ultrahigh dose rates (UHDRs) has potential for use as a new anticancer therapeutic strategy. The FLASH effect induced by UHDR irradiation has been shown to maintain antitumour efficacy with a reduction in normal tissue toxicity; however, the FLASH effect has been difficult to demonstrate in vitro. The objective to demonstrate the FLASH effect in vitro is challenging, aiming to reveal a differential response between cancer and normal cells to further identify cell molecular mechanisms. New high-intensity petawatt laser-driven accelerators can deliver very high-energy electrons (VHEEs) at dose rates as high as 1013 Gy/s in very short pulses (10–13 s). Here, we present the first in vitro experiments carried out on cancer cells and normal non-transformed cells concurrently exposed to laser-plasma accelerated (LPA) electrons. Specifically, melanoma cancer cells and normal melanocyte co-cultures grown on chamber slides were simultaneously irradiated with LPA electrons. A non-uniform dose distribution on the cell cultures was revealed by Gafchromic films placed behind the chamber slide supporting the cells. In parallel experiments, cell co-cultures were exposed to pulsed X-ray irradiation, which served as positive controls for radiation-induced nuclear DNA double-strand breaks. By measuring the impact on discrete areas of the cell monolayers, the greatest proportion of the damaged DNA-containing nuclei was attained by the LPA electrons at a cumulative dose one order of magnitude lower than the dose obtained by pulsed X-ray irradiation. Interestingly, in certain discrete areas, we observed that LPA electron exposure had a different effect on the DNA damage in healthy normal human epidermal melanocyte (NHEM) cells than in A375 melanoma cells; here, the normal cells were less affected by the LPA exposure than cancer cells. This result is the first in vitro demonstration of a differential response of tumour and normal cells exposed to FLASH irradiation and may contribute to the development of new cell culture strategies to explore fundamental understanding of FLASH-induced cell effect.

Background: Abdominoperineal resection (APR)—the standard surgical procedure for low-lying rectal cancer (LRC)—leads to significant perineal defects, posing considerable reconstruction challenges that, in selected cases, necessitate the use of plastic surgery techniques (flaps). Purpose: To develop valuable decision algorithms for choosing the appropriate surgical plan for the reconstruction of perineal defects. Methods: Our study included 245 LRC cases treated using APR. Guided by the few available publications in the field, we have designed several personalized decisional algorithms for managing perineal defects considering the following factors: preoperative radiotherapy, intraoperative position, surgical technique, perineal defect volume, and quality of tissues and perforators. The algorithms have been improved continuously during the entire period of our study based on the immediate and remote outcomes. Results: In 239 patients following APR, the direct closing procedure was performed versus 6 cases in which we used various types of flaps for perineal reconstruction. Perineal incisional hernia occurred in 12 patients (5.02%) with direct perineal wound closure versus in none of those reconstructed using flaps. Conclusion: The reduced rate of postoperative complications suggests the efficiency of the proposed decisional algorithms; however, more extended studies are required to categorize them as evidence-based management guide tools.

Abstract In this study we carried out a behavioral experiment comparing action language comprehension in L1 (Italian) and L2 (English). Participants were Italian native speakers who had acquired the second language late (after the age of 10). They performed semantic judgments on L1 and L2 literal, idiomatic and metaphorical action sentences after viewing a video of a hand performing an action that was related or unrelated to the verb used in the sentence. Results showed that responses to literal and metaphorical L1 sentences were faster when the action depicted was related to the verb used rather than when the action depicted was unrelated to the verb used. No differences were found for the idiomatic condition. In L2 we found that all responses to the three conditions were facilitated when the action depicted was related to the verb used. Moreover, we found that the difference between the unrelated and the related modalities was greater in L2 than in L1 for the literal and the idiomatic condition but not for the metaphorical condition. These findings are consistent with the embodied cognition hypothesis of language comprehension.

Since the emergence and spread of carbapenemase-producing Enterobacterales, particularly those carrying metallo-β-lactamases with 16S rRNA methyltransferases for which newly introduced antibiotics are inactive, colistin is a last resort therapy for life-threatening extensively drug-resistant infections. This requires that laboratories use an accurate and reliable method for routine colistin susceptibility testing. The aim of this study was to evaluate the performance and applicability of a colistin screening medium for detection of colistin-resistant isolates simultaneously with routine susceptibility testing. It was evaluated with fifty colistin-resistant and the same number of colistin-susceptible comparator isolates. Our results showed that all colistin-resistant isolates grew on DiaPlate™ EMB Agar + Colistin medium within the standard antibiogram period. In contrast, no growth was observed among the colistin susceptible comparators. DiaPlate™ EMB Agar + Colistin is a screening medium that can detect colistin- resistant Enterobacterales isolates when pure bacterial cultures are tested. As this method for detecting colistin-resistant isolates uses the same inoculum as the Kirby-Bauer method, the screening test for colistin resistance can be conveniently performed on clinical isolates along with routine antimicrobial susceptibility testing.

Objective To highlight progress in facilitating and supporting pan-Canadian data analysis research that is supported by a central coordinating center. This process will be illustrated with the use of a recently completed project that has been supported using data from Alberta, British Columbia, and Ontario. Approach The project represents a significant endeavor within the central coordinating center, as it necessitates coordination for data access, data importation and analytical support across three provinces. The focus will be on the administrative processes refined to support collaborative research endeavors. While specific project details will remain undisclosed, procedural enhancements within the central coordinating center framework will be highlighted. Key discussion points include standardized protocols for data access, collaborative efforts to streamline data importation, and facilitation of analytical support across jurisdictions. The type of cross-jurisdictional analytic support will as well be highlighted; data variables harmonization and sharing of data algorithms cohorts across the participating provincial data centers in support of the meta-analysis. Results The successful completion of the final data analysis underscores the effectiveness of a unified data access coordination center for researchers seeking multi-regional health data in Canada. By highlighting advancements enabled by the central coordinating center and provincial data centers, this submission aims to inform researchers about the current landscape of pan-Canadian research and foster opportunities for future collaboration. Implications Sharing insights and lessons from this project emphasizes the advancements facilitated by the central coordinating center and provincial data centers, informing researchers about the potential of pan-Canadian research, and encouraging future collaborative endeavors.

Objective To highlight the partnership between the Canadian Partnership for Tomorrow’s Health (CanPath) and Health Data Research Network (HDRN Canada), which enables researchers to link CanPath’s health and lifestyle survey data to health records and related data across multiple regions. Background CanPath is a population health study of over 350,000 Canadians from seven regional cohorts across all ten provinces, making it one of the world's largest population cohorts. HDRN Canada is a network of member organizations, including provincial, territorial, and pan-Canadian data centres. Approach This partnership leveraged collective expertise and resources to facilitate the linkage of CanPath’s harmonized data to multi-regional health and health-related administrative data held at HDRN Canada’ s data centres. Researchers can access these data for multi-regional projects through HDRN Canada’s Data Access Support Hub, which provides a single access portal. Results Researchers were able to successfully link CanPath’s survey data to provincial administrative health data. The collaboration’s streamlined process for data access enhances efficiency and facilitates pan-Canadian population health research. Conclusion This collaboration demonstrates the feasibility and value of linking population health datasets while demonstrating the challenges and opportunities associated with accessing national administrative health data within a federated health data system. Implications The partnership between CanPath and HDRN Canada has significant implications for advancing population health research in Canada. By providing researchers with access to linked data from diverse sources, the partnership enables comprehensive investigations into health determinants, disease patterns, and clinical outcomes. This enhances the scope and depth of population health research in Canada, thereby leading to a better understanding of the most pressing health challenges.

In this study, we examined how four components of the therapeutic relationship—working alliance, real relationship, and positive and negative affective reactions of the patient toward their therapist—relate to each other and to the psychotherapy session outcome, from the patient’s point of view. Our simple comprised 700 adult patients in individual psychotherapy who were recruited and participated online. They underwent a baseline evaluation of their most recent therapy session, which encompassed a series of validated self-report measures focused on specific elements of the therapeutic relationship. The results revealed that, from the patient’s perspective, working alliance, real relationship, and positive affective reactions toward the therapist were positively correlated with session outcome, while negative affective reactions were negatively correlated. All components predicted session outcome when simultaneously included in a regression model. Collectively, these four components accounted for 30% of the variance in session outcome. Factor analysis revealed four distinct factors, underlying perceptions of the therapeutic relationship. Notably, the bond dimension of the alliance was sufficiently different from the task and goal dimensions, warranting consideration as a distinct construct. These findings, although cross-sectional, lay the groundwork for a more nuanced investigation of multiple dimensions of the therapeutic relationship.

Oligoarginine cell-penetrating peptides (CPPs) are short peptides that can enhance drug delivery into cells and are of particular interest in ocular topical formulations for age-related macular degeneration (AMD) treatments. The length and structural characteristics of these peptides are considered crucial for drug delivery. This study investigates how oligoarginine length (Rn) affects their penetration mechanism, drug delivery capabilities, and antimicrobial properties, providing insights into their potential roles in AMD treatment delivery. In this study, oligoarginine peptides showed limited pore-forming abilities in a carboxyfluorescein-containing liposomal model, with R9 being the only oligoarginine length recording a significant pore-formation level. Their antibacterial efficacy depended on both the CPP length and bacterial class, with longer peptides exhibiting stronger antibacterial effects. Importantly, oligoarginine was found nontoxic to relevant mammalian cells for ocular delivery. The membrane translocation abilities of oligoarginine were consistent regardless of cargo presence. Additionally, cargo delivery by oligoarginine across in vitro cellular models for ocular delivery was dependent on peptide length and cell type, with longer chains being more effective at cargo uptake in a corneal epithelium cell line, and with shorter chains proving more effective for cargo delivery in a retinal epithelium cell line. This proposes that the chain length of oligoarginine could be used as a strategic tool in the formulation process to selectively target distinct regions of the eye. Overall, this study expands our understanding of how oligoarginine CPPs can be applied as penetration enhancers to improve the delivery of therapeutics in an ocular topical formulation within the clinical context of AMD.