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Abstract Proteins interact with each other in complex ways to perform significant biological functions. These interactions, known as protein–protein interactions (PPIs), can be depicted as a graph where proteins are nodes and their interactions are edges. The development of high-throughput experimental technologies allows for the generation of numerous data which permits increasing the sophistication of PPI models. However, despite significant progress, current PPI networks remain incomplete. Discovering missing interactions through experimental techniques can be costly, time-consuming, and challenging. Therefore, computational approaches have emerged as valuable tools for predicting missing interactions. In PPI networks, a graph is usually used to model the interactions between proteins. An edge between two proteins indicates a known interaction, while the absence of an edge means the interaction is not known or missed. However, this binary representation overlooks the reliability of known interactions when predicting new ones. To address this challenge, we propose a novel approach for link prediction in weighted protein–protein networks, where interaction weights denote confidence scores. By leveraging data from the yeast Saccharomyces cerevisiae obtained from the STRING database, we introduce a new model that combines similarity-based algorithms and aggregated confidence score weights for accurate link prediction purposes. Our model significantly improves prediction accuracy, surpassing traditional approaches in terms of Mean Absolute Error, Mean Relative Absolute Error, and Root Mean Square Error. Our proposed approach holds the potential for improved accuracy in predicting PPIs, which is crucial for better understanding the underlying biological processes.

Introduction Persistent throat symptoms (PTS) are indicators for over 60 000 new patient referrals to NHS secondary care annually. PTS have been attributed to manifestation of gastro-oesophageal reflux disease (GORD) with the hypothesis that gastric refluxate damages and irritates the mucosa of the upper aerodigestive tract. Symptoms of PTS and GORD are commonly treated with proton pump inhibitors (PPIs) or alginates are often, incorrectly, advocated. The Trial of PPIs in Throat Symptoms trial definitively demonstrated that lansoprazole is no more effective than placebo in treating symptoms of PTS, indicating that empirical PPI treatment for PTS should be discouraged. The impact of this is an anticipated increase in prescriptions of alginates for PTS, however, there is a lack of evidence of the efficacy of alginates in treating this condition. Trial of alginates in throat symptoms aims to compare symptomatic response of the symptoms of PTS in liquid alginate (Gaviscon Advance) in comparison to a near matched placebo over an 8-week period to provide definitive evidence of the use of alginates in treating PTS.Methods and analysis This is a multicentre, pragmatic, double blind, parallel, randomised controlled trial. 250 adults with PTS will be recruited from NHS secondary care sites and randomised to either liquid alginate (Gaviscon Advance) or near matched placebo in a 1:1 ratio. The primary objective is to compare the symptomatic response in patients with PTS to liquid alginate (Gaviscon Advance) compared with placebo using the outcome measure of total Reflux Symptom Index questionnaire score at 8 weeks.Ethics and dissemination Favourable ethical opinion was received from the East Midlands—Leicester South Research Ethics Committee (reference: 22/EM/0205). All participants will provide informed consent prior to any trial specific activity taking place. Results will be disseminated in peer reviewed publications, at national and international conferences, in peer reviewed journals and to participants and the public (using lay language).Trial registration number ISRCTN13949559

Summary: Background: The metabolic environment plays a crucial role in the development of heart failure (HF). Our prior research demonstrated that myo-inositol, a metabolite transported by the sodium-myo-inositol co-transporter 1 (SMIT-1), can induce oxidative stress and may be detrimental to heart function. However, plasmatic myo-inositol concentration has not been comprehensively assessed in large cohorts of patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Methods: Plasmatic myo-inositol levels were measured using mass spectrometry and correlated with clinical characteristics in no HF subjects and patients with HFrEF and HFpEF from Belgian (male, no HF, 53%; HFrEF, 84% and HFpEF, 40%) and Canadian cohorts (male, no HF, 51%; HFrEF, 92% and HFpEF, 62%). Findings: Myo-inositol levels were significantly elevated in patients with HF, with a more pronounced increase observed in the HFpEF population of both cohorts. After adjusting for age, sex, body mass index, hypertension, diabetes, and atrial fibrillation, we observed that both HFpEF status and impaired kidney function were associated with elevated plasma myo-inositol. Unlike HFrEF, abnormally high myo-inositol (≥69.8 μM) was linked to unfavourable clinical outcomes (hazard ratio, 1.62; 95% confidence interval, [1.05–2.5]) in patients with HFpEF. These elevated levels were correlated with NTproBNP, troponin, and cardiac fibrosis in this subset of patients. Interpretation: Myo-inositol is a metabolite elevated in patients with HF and strongly correlated to kidney failure. In patients with HFpEF, high myo-inositol levels predict poor clinical outcomes and are linked to markers of cardiac adverse remodelling. This suggests that myo-inositol and its transporter SMIT1 may have a role in the pathophysiology of HFpEF. Funding: BECAME-HF was supported by Collaborative Bilateral Research Program Québec – Wallonie-Brussels Federation.

Prompted by William Newell's 2013 call for the Association of Interdisciplinary Studies (AIS) to consider whether to rethink its mission in light of other organizations' interests, this article begins by reflecting on similarities and differences among five of the founding organizations of a recently formed Global Alliance for Inter- and Transdisciplinarity. In chronological order of their own founding dates they are AIS, the Network of Transdisciplinary Research, the Integration and Implementation Sciences network, the International Network for the Science of Team Science, and the Center for Interdisciplinarity at Michigan State University. Descriptions of the five in Part I account for their emergence, communication venues, keywords of representation, website features, and prominent outputs. Given the centrality of integration in both inter- and trans-disciplinarity, it also describes their stances on this prominent topic. Part II reflects on implications of the current heterogeneity of the core concepts, focusing initially on generalizations including distinctions between Zurich and Nicolescuian approaches to transdisciplinarity followed by the premise of distinct Franco and U.S. traditions of the field of nanomedicine. It then draws further insights from case studies of institutionalizing interdisciplinarity across Europe, Russia and the South Caucuses, Africa, Latin and North America, Australia, and Asia. After commenting on signs of change in AIS, discussion turns to historical precedents for prioritizing problem solving, followed by future horizons for both inter- and trans-disciplinarity with emphasis on implications of their heterogeneity and overlaps with other prominent concepts such as Convergence and Mode 2 Knowledge Production. The closing section presents final reflections for answering Newell's challenge for AIS members to consider expanding its definition of interdisciplinary studies and conception of integrative process in light of other organizations' interests.

Abstract Chagas disease is a leading cause of non-ischemic cardiomyopathy in endemic regions of Central and South America. In Belize, Triatoma dimidiata sensu lato has been identified as the predominate taxon but vectorial transmission of Chagas disease is considered to be rare in the country. We recently identified an acute case of vector-borne Chagas disease in the northern region of Belize. Here we present a subsequent investigation of triatomines collected around the case-patient’s home. We identified yet undescribed species, closely related to Triatoma huehuetenanguensis vector by molecular systematics methods occurring in the peridomestic environment. The identification of a T. cruzi-positive, novel species of Triatoma in Belize indicates an increased risk of transmission to humans in the region and warrants expanded surveillance and further investigation.

Abstract Aim Phenobarbital, a long‐acting barbiturate, presents an alternative to conventional benzodiazepine treatment for alcohol withdrawal syndrome (AWS). Currently, existing research offers only modest guidance on the safety and effectiveness of phenobarbital in managing AWS in hospital settings. The study objective was to assess if a phenobarbital protocol for the treatment of AWS reduces respiratory complications when compared to a more traditionally used benzodiazepine protocol. Methods A retrospective cohort study analyzing adults who received either phenobarbital or benzodiazepine‐based treatment for AWS over a 4‐year period, 2015–2019, in a community teaching hospital in a large academic medical system. Results A total of 147 patient encounters were included (76 phenobarbital and 71 benzodiazepine). Phenobarbital was associated with a significantly decreased risk of respiratory complications, defined by the occurrence of intubation (15/76 phenobarbital [20%] vs. 36/71 benzodiazepine [51%]) and decreased incidence of the requirement of six or greater liters of oxygen when compared with benzodiazepines (10/76 [13%] vs. 28/71 [39%]). There was a significantly higher incidence of pneumonia in benzodiazepine patients (15/76 [20%] vs. 33/71 [47%]). Mode Richmond Agitation Sedation Scale (RASS) scores were more frequently at goal (0 to −1) between 9 and 48 h after the loading dose of study medication for phenobarbital patients. Median hospital and ICU length of stay were significantly shorter for phenobarbital patients when compared with benzodiazepine patients (5 vs. 10 days and 2 vs. 4 days, respectively). Conclusion Parenteral phenobarbital loading doses with an oral phenobarbital tapered protocol for AWS resulted in decreased risk of respiratory complications when compared to standard treatment with benzodiazepines.

Despite independence as a country, Canada belongs to the Commonwealth and has deep colonial roots and the British educational system was key in creating Canadian curricula. Given the centrality of Shakespeare’s work in the British literary canon, it follows that it would also figure heavily in the academic requirements for Canadian students. At the dawn of the Confederation (1867), the high school curriculum used Shakespeare to emphasize a “humanist” approach to English literature using the traditional teaching methods of reading, rhetoric, and recitation. Presently, Shakespeare continues to be the only author in the high school curriculum to whom an independent area of study is dedicated. The origin of Shakespeare in Canada through curriculum and instruction is, thus, a result from the canonic tradition imported from Britain. This traditional model no longer fits the imperative of multiculturalism, as reflected in the Canadian Constitution Act (1982). Yet, with the appropriate methodology Shakespeare’s texts can be a vehicle for multiculturalism, social justice, and inclusivity. In light of recent disillusionments concerning the relevance of Shakespearean texts in high school curricula, this paper proposes an alternative pedagogical approach that envisages changing this paradigm and fostering a re-origin of Shakespeare studies in Canada through an intentional pedagogical process grounded in individual experience. Scholarship has highlighted the importance of autobiographies in the learning process and curriculum theorists William Pinar and Madeleine Grumet designed a framework that prioritizes individual experience. Our approach to teaching Shakespeare’s works aligns with the four steps of their currere method, presented as: (1) contemplative, (2) translational, (3) experiential, and (4) reconceptual, fostering an opportunity for self-transformation through trans-historical social themes present in the text. The central argument is that Shakespeare’s text can undergo a re-origin when lived, given its initial conception as embodied, enacted narrative in the early modern period. In this method, students immerse themselves in Shakespeare’s text through films and stage productions and then manifest their interpretations by embodying the literature based on their autobiographical narratives. To undergo a re-origin in the Canadian secondary curriculum, current pedagogical approaches to teaching Shakespeare require a paradigm shift.

Leigh syndrome French Canadian type (LSFC) is a recessive neurodegenerative disease characterized by tissue-specific deficiency in cytochrome c oxidase (COX), the fourth complex in the oxidative phosphorylation system. LSFC is caused by mutations in the leucine rich pentatricopeptide repeat containing gene (LRPPRC). Most LSFC patients in Quebec are homozygous for an A354V substitution that causes a decrease in the expression of the LRPPRC protein. While LRPPRC is ubiquitously expressed and is involved in multiple cellular functions, tissue-specific expression of LRPPRC and COX activity is correlated with clinical features. In this proof-of-principle study, we developed human induced pluripotent stem cell (hiPSC)-based models from fibroblasts taken from a patient with LSFC, homozygous for the LRPPRC*354V allele, and from a control, homozygous for the LRPPRC*A354 allele. Specifically, for both of these fibroblast lines we generated hiPSC, hiPSC-derived cardiomyocytes (hiPSC-CMs) and hepatocyte-like cell (hiPSC-HLCs) lines, as well as the three germ layers. We observed that LRPPRC protein expression is reduced in all cell lines/layers derived from LSFC patient compared to control cells, with a reduction ranging from ∼70% in hiPSC-CMs to undetectable levels in hiPSC-HLC, reflecting tissue heterogeneity observed in patient tissues. We next performed exploratory analyses of these cell lines and observed that COX protein expression was reduced in all cell lines derived from LSFC patient compared to control cells. We also observed that mutant LRPPRC was associated with altered expression of key markers of endoplasmic reticulum stress response in hiPSC-HLCs but not in other cell types that were tested. While this demonstrates feasibility of the approach to experimentally study genotype-based differences that have tissue-specific impacts, this study will need to be extended to a larger number of patients and controls to not only validate the current observations but also to delve more deeply in the pathogenic mechanisms of LSFC.

Objective To develop evidence-based guidance for topical steroid use in paediatric eosinophilic oesophagitis (pEoE) in the UK for both induction and maintenance treatment.Methods A systematic literature review using Cochrane guidance was carried out by the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) Eosinophilic Oesophagitis (EoE) Working Group (WG) and research leads to determine the evidence base for preparation, dosing and duration of use of swallowed topical steroid (STS) formulations in EoE. Seven themes relating to pEoE were reviewed by the WG, alongside the Cochrane review this formed the evidence base for consensus recommendations for pEoE in the UK. We provide an overview of practical considerations including treatment regimen and dosing. Oral viscous budesonide (OVB) and, if agreed by local regulatory committees, orodispersible budesonide (budesonide 1 mg tablets) were selected for ease of use and with most improvement in histology. A practical ‘how to prepare and use’ OVB appendix is included. Side effects identified included candidiasis and adrenal gland suppression. The use of oral systemic steroids in strictures is discussed briefly.Results 2638 citations were identified and 18 randomised controlled trials were included. Evidence exists for the use of STS for induction and maintenance therapy in EoE, especially regarding histological improvement. Using the Appraisal of Guidelines, Research and Evaluation criteria, dosing of steroids by age (0.5 mg two times per day

This article places William Newell's work on interdisciplinary studies (IDS) within the larger landscape of definitions, theories, and practices of interdisciplinarity. It begins by benchmarking three of his major contributions to the field of interdisciplinary studies read in the context of expanding literature on related topics: specifically his efforts to make integration the foundation of process-based best practices, to establish a theoretical framework grounded in complexity, and to professionalize the field of IDS. It then examines two challenges to AIS today that Newell alerted members to in a 2013 reflection on the state of the field -- transdisciplinarity and team science -- followed by added insights from two areas -- policy sciences and interprofessionalism. The article closes by reflecting on current conflicting priorities, renewed debate on the relationship of disciplinarity and interdisciplinarity, and efforts to explore intersections of multiple organizations vested in inter- and transdisciplinarity today.

OBJECTIVE Increasing workforce capacity to provide knowledgeable, skilled, and affirming care for transgender and gender diverse people is critical to reduce health inequities; however, few clinicians receive sufficient training on this topic. This article describes Advancing Excellence in Transgender Health (AETH), an annual international conference that offers continuing professional development on evidence-based medical and behavioral healthcare for transgender and gender diverse people across the lifespan . METHODS Registration data and post-conference evaluation data were descriptively analyzed to assess conference reach, participant satisfaction, and participant intentions to change practice. RESULTS Between 2015 and 2022, AETH trained 2677 participants from all US states and 24 countries. Based on post-conference evaluations, 2017-2022, participant satisfaction was high (mean ≥4.4 on a 5-point scale) on all measures, including meeting learning objectives, quality of presentations, and relevance to practice. Participants reported intentions to: implement new information or skills (86.7%); create or revise protocols, policies, and/or procedures (63.2%); and seek additional information (64.2%). To increase equity, the conference waives fees for transgender and gender diverse participants and offers free online sessions. The conference also holds sessions specifically for transgender and gender diverse participants to promote opportunities for community-building, self-care, and professional networking. CONCLUSION The broad reach of AETH demonstrates a large demand for more continuing professional development on transgender and gender diverse healthcare. This conference has expanded the availability of training designed to increase and enhance clinical workforce capacity to meet the health needs of transgender and gender diverse communities in the US and across the world.

Abstract Integration is often considered the core challenge and the defining characteristic of inter- and trans-disciplinary (ITD) research. Given its importance, it is surprising that the current system of higher education does not provide permanent positions for integration experts; i.e., experts who lead, administer, manage, monitor, assess, accompany, and/or advise others on integration within ITD projects or programs. Based on empirical results of an ITD 2019 Conference Workshop entitled “Is there a new profession of integration experts on the rise?” held in Gothenburg, Sweden, and our own experience in leading and studying ITD integration, the present article sheds light on the overarching question, “What are integration experts?”, thus contributing to the emerging literature on integration and integration expertise. We use direct quotes from participants to substantiate workshop results and triangulate them with recent literature on ITD research as well as Science of Team Science (SciTS) and Science and Technology Studies (STS). We conclude our article by discussing possible unintended consequences of establishing academic careers for integration experts, and suggest four complementary ways to support them, while mitigating potentially negative consequences: (a) establishing an international Community of Practice (CoP) to foster peer-to-peer exchange among integration experts, create greater visibility, and develop ideas for transforming academic structures; (b) studying academic careers of integration experts to provide empirical evidence of “successful” examples and disclose different ways of establishing related academic positions; (c) funding respective positions and aligning metrics for ITD research to foster integration within ITD projects or programs; and (d) engaging in collaborative dialog with academic institutions and funding agencies to present empirical results and lessons learnt from (a) and (b) to support them in establishing and legitimating careers for integration experts. If academia is to be serious about addressing the most pressing environmental and societal problems of our time, it needs to integrate its integrators.

Iron overload cardiomyopathy has been described in patients who develop acute heart failure after liver transplantation but few reports of this are available. We present a case of a patient with end-stage liver disease who underwent a deceased donor liver transplantation and developed acute onset systolic heart failure with reduced left ventricular ejection fraction. A cardiac magnetic resonance image demonstrated late gadolinium enhancement with diffuse enhancement globally and T1 mapping with severely decreased pre-contrast T1 values suggesting iron overload cardiomyopathy. The patient was treated with iron chelating therapy as well as heart failure guideline-directed medical therapy with subsequent improvement in cardiac function on follow-up magnetic resonance images. Despite our patient’s diagnosis of iron overload cardiomyopathy, her iron studies showed normal serum iron and ferritin levels and no evidence of hepatic iron deposition in the transplanted liver.

Objective: The objective of this quality improvement project was to evaluate the effectiveness of a succinct health literacy training for providers at a demanding federally qualified health center. Methods: One group, pretest-posttest design was used to measure for a change in knowledge regarding the effects of limited health literacy, a change in self-reported measure of routine screening for limited health literacy and a change in self-reported utilization of patient-centered communication techniques. Results: The average percentage of correct responses on the Health Literacy Knowledge Check showed significant improvement from 23.6% (SD = 18.1%) to 63.9% (SD = 25.3%), p < .001. There were no significant changes in median responses at pre- and post-intervention for self-reported use of screening and communication techniques (all p > .05). Conclusion: This brief training was effective at improving participants' knowledge of health literacy but did not improve use of recommended communication techniques or screening for health literacy. The results suggest that emphasizing a universal precautions approach to health literacy may be more effective with participants who work in high-volume clinics. Practice implications: For high-volume clinics, a brief training may improve participants' knowledge but does not increase use of actual communication techniques based on self-report.

In 2013 and 2014, several methods of managing dense skunk cabbage (Symplocarpus foetidus) using aquatic glyphosate were tested in a wetland in Carroll County, Maryland, as part of an adaptive management plan for enhancing bog turtle (Glyptemys muhlenbergii) habitat. Using a backpack sprayer with a 3–5% aquatic glyphosate solution and surfactant in late May to mid-June was found to be effective in reducing skunk cabbage coverage without reducing the vegetation species richness in the treated areas. [ABSTRACT FROM AUTHOR]

Abstract Background To assess the efficacy and viability of implementing Helping Babies Breathe, a neonatal resuscitation program for resource-limited environments on a small budget in two of the largest delivery centers in Zanzibar, Tanzania. The quality improvement initiative concentrated on training midwives, who directly care for neonates at birth on Helping Babies Breathe to address high rates of neonatal mortality secondary to birth asphyxia. Methods The convenience sample was 59 midwives working in the two delivery centers of interest in Zanzibar, Tanzania. The train-the-trainer implementation strategy with repeated measures design was used to assess knowledge and skills at three time points. Observations were completed through supportive supervision of deliveries in both facilities. A budget was kept throughout the implementation. Results Knowledge scores and resuscitation skills significantly improved and were sustained over a 6-month period of time, Ps

The health issue addressed is the unmet need to universally screen and treat depression, which is one of the most common mental health disorders among adults in the United States. The US Preventive Services Task Force recommends screening adults for depression in primary care and using evidence-based protocols. This quality improvement project implemented VitalSign6, a measurement-based care program, to improve depression screening and treatment of adults in primary care at an academic medical center. A pre-post design was used to determine effectiveness of changes in screening, outcomes, and satisfaction. Of 1200 unique adult patients, 95.4% received initial screening. Providers diagnosed and administered measurement-based care to 236 patients. After 14 weeks, 27.5% returned for at least 1 follow-up. Results showed a statistically significant decrease in self-reported depression scores from baseline to follow-up. VitalSign6 was effective in improving identification and management of depression in primary care.