bluuebunny/crossref_metadata_2025 huggingface dataset:
The perceptions of study abroad coordinators about digitalisation and Erasmus + virtual mobility
Authors: Konaklı Tuğba , Alkanat Akman Tuba , Mert Mahmut , Yuksel Dogan
Published: November 2024

Most study abroad research focused on the experiences of students, perceptions of study abroad coordinators received little attention in research. Addressing this gap, this study examines how changes after 2020 (i.e. digitalisation of the Erasmus + processes and virtual mobility) impacted the perceptions of study abroad coordinators ( N = 23) in a large public university in Turkiye. An open-ended online questionnaire was prepared and shared with the participants who were active in the last 4 years and who experienced both traditional and virtual mobility processes and analysed via the content analysis method. Our results revealed that our participants mostly welcomed changes in digitalisation and virtual mobility in terms of their impact on their duties and responsibilities. However, they thought that the impact of virtual mobility was limited on their students’ academic, communicative and cultural development. Our study also includes a discussion of these findings and implications for mobility staff and/or administrators.
Physical collisions during elite rugby league match play and training: A stakeholder's perspective
Authors: Dixon Andrew J , Littlewood Martin A , Cronin Colum J , Twist Craig , Close Graeme L
Published: November 2024

The purpose of this study was to explore rugby league stakeholders’ perspectives of the tackle event, utilising qualitative approaches to gain further insight into this phenomenon. Nineteen stakeholders, comprising tactical coaches (n = 5), physiotherapists (n = 5), doctors (n = 5) and strength and conditioning coaches (n = 4) from every European 2023 Super League team (ESL), were recruited to participate in an online semi-structured interview, via the Microsoft Teams platform, facilitated by a moderator. Braun and Clarke's (2019) reflexive thematic analysis was performed to code and analyse the transcribed data; this established pattern-based interpretation and reporting from the dataset. The research findings can be divided into five crucial segments that illuminate our understanding of collision in rugby league: 1) simultaneous contact and the three-person tackle, 2) tackle height – calibration is critical, 3) the fundamental factors influencing tackle-related risks. 4) the graded exposure and philosophical approaches to contact training and games, 5) replacing toughness with resilience - the impact of game identity. The themes generated here provide comprehensive insights into stakeholders’ perceptions of the optimal ways to perform collisions. This has implications for the identity of the game, and the subsequent law changes/ behavioural change models that aim to make the game safer, specific to rugby league. In line with previous research, the conclusions underline high-risk events in match play (blind-sided collisions and fatigue), providing a focus for areas of future research. Lastly, psychology in the tackle event is explored, highlighting the need for graded contact exposure from a physical and psychological perspective during tackle technique training.
Real-time intervention to increase daily chlorhexidine bathing and reduce central line–associated bloodstream infections
Authors: Krier Brad A , Bhandari Pawan , Brooks Ashley M , Schultz Kristin J , Zarbano Jonna J , Anil Gokhan
Published: November 2024

Background

After an increase of central line–associated bloodstream infections (CLABSIs) at our community hospital in 2021, a case-control study suggested that patients with CLABSIs were 3.0 times more likely to have missed daily chlorhexidine gluconate (CHG) bathing than patients without CLABSIs.

Objective

To increase the rate of daily CHG bathing in hospitalized patients with central lines and subsequently reduce the number of CLABSIs.

Methods

Our pre-post intervention was launched on September 2022 and consisted of enhancements to the electronic health record (EHR) to simplify the identification of overdue CHG bathing instances to increase compliance, and therefore decrease the CLABSI rate at our hospital. A workflow was implemented Monday–Friday utilizing these EHR enhancements for active surveillance to engage frontline nursing staff and address gaps in care in real time.

Results

After the initiative was implemented, adherence to daily CHG bathing increased from 94.9% to 95.3%, with a considerable disparity between weekdays (97.6%) and weekends (89.3%). After weekend data were excluded, the post-intervention increase in the adherence rate was statistically significant ( p = .003).

Discussion

This initiative underscored the importance of involving health care informatics partners and showed how technology can bridge gaps in health care quality. Outreach and reminders effectively improved CHG bathing adherence by emphasizing the importance of consistent communication and follow-up.
SUNLAND: a randomized, double-blinded phase II GERCOR trial of sunitinib versus placebo and lanreotide in patients with advanced progressive midgut neuroendocrine tumors
Authors: Hammel Pascal , Smith Denis , Afchain Pauline , Dominguez-Tinajero Sophie , Seitz Jean-François , Lievre Astrid , Van Cutsem Eric , Assenat Eric , Di Fiore Frédéric , Peeters Marc , Sobhani Iradj , Raymond Eric , Charton Emilie , Vernerey Dewi , De Mestier Louis , Lombard-Bohas Catherine
Published: November 2024

Background:

Sunitinib, a multitarget tyrosine kinase inhibitor, showed encouraging antitumor activity and manageable toxicity in patients with advanced midgut neuroendocrine tumors (NETs) in earlier results from phase I and II trials.

Patients and methods:

In this phase II trial, patients with a nonresectable grade 1 or 2 midgut progressive NET and Eastern Cooperative Oncology Group performance status 0–1 were randomly assigned 1:1 to receive 37.5 mg sunitinib or a placebo, combined with 120 mg lanreotide autogel every 28 days. The planned sample size was 104 patients. The primary outcome was investigator-assessed progression-free survival (PFS).

Results:

The study was stopped early because of insufficient patient recruitment. Between January 2013 and December 2016, 44 patients were enrolled and received sunitinib ( n = 22) or placebo ( n = 22). The median age was 63.7 years ( Q1– Q3 range, 56.6–68.1) and 26 patients (59.1%) were male. The main localization was ileum ( N = 37, 84.1%) and the majority were grade 2 ( n = 25, 56.8%). The median follow-up was 36.7 months (95% confidence interval (CI) 34.6–48.2). The median PFS was 9.84 months (95% CI 6.8–23.3) with sunitinib and 11.47 months (95% CI 5.4–15.3) with placebo (hazard ratio (HR) = 0.80, 95% CI 0.41–1.56, p = 0.51). There was no difference in overall survival between treatment arms (HR = 0.81, (95% CI 0.32–2.01), p = 0.64). The objective response rate was 9.1% with sunitinib and 0.0% with placebo, and 19 patients (86.4%) had stable disease. Thirty-nine patients (88.6%) completed the baseline QLQ-C30 questionnaire. Baseline health-related quality of life level was similar between treatment arms, except for physical and emotional functioning which were higher ( p = 0.089) and lower ( p = 0.023) in the sunitinib arm, respectively. Trends toward longer time until a definitive deterioration in favor of the sunitinib arm were observed for 10 out of 15 dimensions (HRs < 1), with a significant result for financial difficulties (HR = 0.31, (90% CI 0.10–0.94)). Twenty-seven patients (61.4%) had at least one adverse event grade ⩾3 (sunitinib: 72.7%, placebo: 50.0%), with only one patient grade 4 for hypertension and vomiting. Eleven deaths non-related to treatment occurred (sunitinib arm: n = 5, placebo arm: n = 6).

Conclusion:

Our study does not provide enough evidence to conclude the role of sunitinib in advanced midgut NETs, primarily due to a lower-than-expected number of enrolled patients. While we cannot entirely rule out the efficacy of sunitinib, lanreotide alone may play a significant role.

Trial registration:

EudraCT: 2012-001098-94.
Addressing Inequity in Continuous Glucose Monitoring Access: Leveraging the Hospital in the Continuum of Care
Authors: Rickards Gabriella M. , Harrod Julia C. , Del Valle Kayla , Caballero A. Enrique , Palermo Nadine E. , McDonnell Marie E.
Published: November 2024

Background:

While continuous glucose monitoring (CGM) has transformed the care of people with diabetes (PWD) in the ambulatory setting, there continue to be significant barriers to access. With CGM on the horizon in the acute care setting, it is important to consider the potential for this shift to improve ambulatory CGM access to those at the highest risk of morbidity and mortality.

Methods:

In this commentary, we review the existing literature on the specific barriers to CGM access for individuals with diabetes in the United States including racial disparities, provider bias, cost and shortage of specialty diabetes care. Key areas explored include the importance of CGM in diabetes management, the consequences of disparities in access to CGM, and leveraging the inpatient setting to promote equitable care and better outcomes for PWD.

Results:

We present a vision for a new care model, which leverages the transition of care from the hospital to successfully incorporate CGM into the discharge plan.

Conclusions:

Given that CGM utilization is associated with improved outcomes and reduced rates of hospitalization and emergency department visits, a care model that facilitates CGM access upon transition from inpatient to ambulatory care can enhance health equity and quality of life for people with diabetes.
Providing personalised care for people with tuberculosis: an evaluation of enhanced case management in a UK TB Network 2013 to 2021
Authors: Crocker-Buque Tim , Hayden Harry , White Jacqui , Dekoningh Jennifer , Belton Moerida , Boparai Narinder , Brown James , Brown Mike , Hawley Danielle , Lozewicz Stefan , Miller Rob , Moores Rachel , Moshal Karyn , Potter Jessica , Lipman Marc ,   on behalf of the North Central London Tuberculosis Service
Published: November 2024

Objectives

Evaluating the outcomes of enhanced case management (ECM) for patients with tuberculosis (TB) in the North Central London TB Service (NCLTBS).

Design

Retrospective cohort study.

Setting

The NCLTBS provides care for persons diagnosed with TB across north and central London. Management involves both medical and psychosocial support, leading to the implementation ECM to provide additional non-clinical assistance to patients at risk of treatment non-completion. However, there has been limited evaluation of its outcomes.

Participants

All adults with TB notified to NCLTBS between January 2013 and June 2021.

Main outcome measures

Descriptive socio-economic and clinical characteristics grouped by binary ECM status (yes/no) and level (0–3). Clinical outcomes at 12 months (completed treatment, death, lost-to-follow-up, continuing on treatment) were compared using multivariable logistic regression.

Results

Totally, 2437 patients were included (57.2% male, 79.1% born outside the UK). Overall, 82.3% completed treatment and 4.1% died. Factors associated with mortality included older age (over 70 years odds ratio (OR) 3.3), inpatient diagnosis (OR 4.4), and mental health issues (OR 2.2). 52.8% received ECM, with the proportion increasing over time, and 76% of this group successfully competed treatment.

Conclusions

This comprehensive evaluation of ECM in a diverse London population indicates high treatment completion rates even among those with multiple social risk factors. However, ECM needs of patients has increased over time, with a particular rise in patients requiring the highest support level. Given the small difference between standard care and ECM categories 1 and 2, there may be scope to simplify the system.
Reconfiguring life after a prison sentence. The lived experience of persons on parole in Switzerland
Authors: Emprechtinger Julia , Richter Marina , Franz Lucile , Lambelet Daniel
Published: November 2024

Time on parole is not only marked by the supervision and support of probation officers but constitutes a particular time in the concerned people’s lives. The experience of this transition period has constituted a topic of research, but most studies have neglected a thorough conceptualisation of the notion of experience and relied empirically on oral data such as interviews. We propose a conceptualisation of experience as lived and embodied, reflected and communicated, and, finally, sedimented. To capture these various dimensions, we developed a multisensorial methodology that explores emotions and places as well as narratives on the experience of the time on parole. Our results concentrate on a group of formerly incarcerated people who are rarely discussed in research: people who were well integrated into society before and who manage to organise their lives afterwards fairly well. They experience distinct challenges and encounter obstacles produced by the criminal justice system itself.
Management of Tricuspid Atresia With Normally Related Great Arteries and Left-Sided Obstruction
Authors: Palacio Andres M. , Williams William G. , Barron David J. , Argo Madison B. , Jegatheeswaran Anusha , Jacobs Marshall L. , Bondarenko Igor , Welke Karl F. , Kirklin James K. , Karamlou Tara , Alsoufi Bahaaldin , McCrindle Brian W. ,   for the Congenital Heart Surgeons Society
Published: November 2024

Background

Tricuspid atresia (TA) is the second most common form of functionally univentricular heart. For patients with TA and normally related great arteries (Type I), left ventricular outflow tract obstruction (LVOTO) is rare.

Methods

From the Congenital Heart Surgeons’ Society multi-institutional cohort of 445 patients with Type I TA enrolled from 1999 to 2024 from 42 sites, 14 infants (3%) had interventions for associated LVOTO, either at presentation or after their first TA-related intervention.

Results

Of seven infants initially undergoing Norwood/Damus-Kaye-Stansel (DKS), six survived to Stage II, of whom five survived with one developing pulmonary hypertension and four achieving Fontan. An additional seven infants who were first managed with pulmonary artery band placement subsequently had bidirectional superior cavopulmonary anastomosis (BCPA) and a DKS procedure; there were six survivors, all achieving Fontan. All ten survivors who underwent the Fontan procedure had normal left ventricular and mitral valve function at the latest follow-up. The overall Kaplan-Meier survival estimate at 20 years for these 14 patients was 79% (70% CI, 66%-88%), and the median follow-up was 8.3 years (0.24-21.5).

Conclusions

While infants with TA and transposition of the great arteries are more likely to have LVOTO, this can also occur in the setting of normally related great arteries. Infants with Type I TA and LVOTO can be managed in the neonatal period with the Norwood procedure ensuring complete arch relief with acceptable outcomes. If LVOTO becomes evident after initial pulmonary artery band placement, a subsequent DKS procedure facilitates satisfactory success to Fontan.
Reading Anxiety in Arabic University Students
Authors: Tibi Sana , Edwards Ashley A. , Kirby John R. , Salha Soheil H.
Published: November 2024

Reading anxiety measures are newly available in English, but none is available in Arabic. The goals of the present study were to adapt the English Reading Anxiety in College Students (RACS) scale to Arabic-speaking college students (RACS-Arabic), evaluate its reliability and other psychometric properties in comparison to the English US sample, and assess its relation to self-assessments of reading ability and measured reading ability. A sample of 226 undergraduate university Arabic-speaking students completed measures of reading anxiety, general and social anxiety, reading self-concept, perception of reading ability, and reading skills. Results showed the brief 10-item RACS-Arabic demonstrated high reliability. Factor loadings were compared to the original RACS English US sample, suggesting reading anxiety in Arabic to be more about reading out loud in front of people and less about not understanding what is read. Results also indicated that reading anxiety was a significant predictor of reading self-concept and self-perception of reading ability after controlling for general and social anxiety, demonstrating the reading-specific nature of reading anxiety. Unlike the English US sample, which demonstrated small but significant associations between reading anxiety and reading fluency, no significant correlation was observed in this sample between RACS-Arabic and oral vowelized word reading efficiency. Future research is needed to explore the relationship between reading anxiety and different measures of Arabic reading ability.
Reading Cards: Chinese Students’ Rationales for Their Language-related Epistemic Beliefs
Authors: Wang Yanyan , Nikitina Larisa
Published: November 2024

Studies on epistemic beliefs in L2 research are in a nascent stage. Acknowledging deeply rooted and complex intersections between prevalent cultural norms within a society, individually held beliefs, and mutually shared opinions among members of a social group, this Q methodological study explored Chinese university students’ rationales for holding particular language-related epistemic beliefs. Twenty students learning English as a foreign language participated in post Q-sorting interviews, where they explained the rationales for holding certain sets of beliefs about knowing and learning the English language. We analyzed the data using Card Content Analysis (CCA), a particularly suitable approach for the Q methodology. The findings revealed that the students held fairly sophisticated epistemic beliefs, and these beliefs were culturally rooted. The students placed a high premium on making a conscientious effort to learn English; they prioritized commitment and perseverance over having a special talent for learning languages. The respondents also believed that English, as any language, is evolving over time. Notably, while respecting their language instructors, the students realized that teachers, or even people for whom English is the mother tongue, might occasionally make linguistic errors. Several students stated that there are many sources from which one can learn English, and they also asserted the importance of being able to gage the veracity of the linguistic information one receives. The article concludes by drawing some pedagogical implications.
Enhancing Speaker Credibility: Looking to Critical Literacy’s “Power” Through Strategic Presentation Skills
Authors: Tan Daisy
Published: November 2024

The concept of speaker credibility is proposed as mitigation to address two issues of confidence and anxiety, and gender differences, gathered from anecdotal feedback of business communication students. This article reviews the definition of speaker credibility and draws on two components—presentation skills and power—from Kenton’s source credibility model. It then discusses the two issues of confidence and anxiety, and gender differences. A speaker credibility framework is outlined from reviewing research on three specific presentation skills and proposing power from Janks’s critical literacy. Limitations and future research include testing the framework’s validity discussed at the end.
Microbiological Spectrum of Osteoarticular Infections and Their Management in Mongolian Children
Authors: Ulziibat Munkhtulga , Buettcher Michael , Altankhuyag Uuganbayar , Chuluunbaatar Battulga , Mikhlay Zorigtbaatar , Sharav Chimgee , Bira Sarantsetseg , Essig Stefan , Ritz Nicole , Munkhuu Bayalag
Published: November 2024

Introduction. Osteoarticular infections (OI) in children cause considerable morbidity with associated long-lasting sequelae. Comprehensive clinical and microbiological data in Mongolian children are missing. Objectives. To generate epidemiological, clinical and microbiological data on osteoarticular infections (OI) in Mongolian children after the introduction of a standardized management protocol. Methods. A prospective study was done between 2019 and 2022 at the only tertiary pediatric hospital in Mongolia. Results. Forty-two children presented with septic arthritis (SA), 6 with osteomyelitis (OM) and 23 with combined SA and OM. Newborns and young infants (≤3 months) comprised 38.%. A causative organism was identified in 38 children: Staphylococcus aureus (n = 31), Klebsiella spp (n = 3), Enterobacter spp (n = 2), Enterobacter spp + Klebsiella spp (n = 1) and Candida albicans (n = 1). Five children (7%) had sequelae. Mongolian children with OI were younger compared to other cohorts. Conclusion. A standardized protocol for the management of OI in children was taken up well by the patients and treating staff leading to improved pathogen detection, facilitating antimicrobial stewardship in the future.
Bivalent CD47 immunotoxin for targeted therapy of T-cell acute lymphoblastic leukemia
Authors: Ma Jihong , Wang Zhaohui , Mintzlaff Danielle , Zhang Huiping , Ramakrishna Rashmi , Davila Eduardo , Witkowski Matthew T. , Lucia M. Scott , Schwartz Marc S. , Pomfret Elizabeth A. , Mathes David W. , Wang Zhirui
Published: November 2024

CD47 is overexpressed on the surface of many types of cancer cells, including T-cell acute lymphoblastic leukemia (T-ALL) cells. In this study, we have developed a diphtheria toxin (DT)–based bivalent anti-human CD47 immunotoxin (bi-CD47-IT) for the targeted therapy of CD47+ cancers using a unique DT-resistant yeast Pichia pastoris expression system. Bi-CD47-IT demonstrated compelling in vivo efficacy in multiple T-ALL cell line–derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. Bi-CD47-IT significantly prolonged the median survival of the tumor-bearing mice and highly effectively depleted the T-ALL blast cells in the peripheral blood, spleen, liver, bone marrow, brain, and spinal cord in the T-ALL CDX and PDX mouse models. Bi-CD47-IT cured 60% of tumor-bearing mice in a T-ALL Molt-4 CDX mouse model. Because CD47 is also expressed on normal tissues, including red blood cells and lymphocytes, specificity is a concern. We thus analyzed the in vitro binding avidity and hemagglutination of bi-CD47-IT in human red blood cells, finding no binding or hemagglutination. We further performed a toxicity study of bi-CD47-IT in humanized mice, which showed that bi-CD47-IT transiently depleted the human lymphocytes for ∼4 weeks after the 10-day treatment. No clinical adverse events were observed. As a result, bi-CD47-IT appears to possess the “optimal” binding avidity, with effective binding to human CD47+ T-ALL tumor cells, no binding to human red blood cells, and weak binding to human lymphocytes. We believe that bi-CD47-IT is a promising and safe therapeutic drug candidate for the targeted therapy of CD47+ cancers.
Preclinical efficacy of CDK7 inhibitor–based combinations against myeloproliferative neoplasms transformed to AML
Authors: Fiskus Warren , Mill Christopher P. , Bose Prithviraj , Masarova Lucia , Pemmaraju Naveen , Dunbar Andrew , Birdwell Christine E. , Davis John A. , Das Kaberi , Hou Hanxi , Manshouri Taghi , Jain Antrix , Malovannaya Anna , Philip Kevin , Alhamadani Noor , Matthews Alicia , Lin Katie , Flores Lauren B. , Loghavi Sanam , DiNardo Courtney , Su Xiaoping , Rampal Raajit K. , Bhalla Kapil N.
Published: November 2024

Rising blast percentage or secondary acute myeloid leukemia (sAML) transformation in myeloproliferative neoplasms (MPNs) leads to JAK1/2 inhibitor (JAKi) therapy resistance and poor survival. Here, we demonstrate that treatment with the CDK7 inhibitor (CDK7i) SY-5609 depletes phenotypically characterized post-MPN sAML stem/progenitor cells. In cultured post-MPN sAML SET2, HEL and patient-derived (PD) post-MPN sAML cells, SY-5609 treatment inhibited growth and induced lethality while sparing normal cells. RNA-sequencing analysis after SY-5609 treatment reduced mRNA expression of MYC, MYB, CDK4/6, PIM1, and CCND1 but increased expression of CDKN1A and BCL2L1. Mass spectrometry of SY-5609–treated MPN-sAML cells also reduced c-Myc, c-Myb, PIM1, and CDK4/6 but increased p21, caspase-9, and BAD protein levels. CRISPR-mediated CDK7 depletion also reduced cell viability of HEL cells. Cytometry by time of flight (CyTOF) analysis of SY-5609–treated PD post-MPN sAML stem/progenitor cells showed reduced c-Myc, CDK6, and PU.1 but increased protein levels of CD11b, p21, and cleaved caspase-3. Cotreatment with SY-5609 and ruxolitinib was synergistically lethal in HEL, SET2, and PD post-MPN sAML cells. A CRISPR screen in sAML cells revealed BRD4, CBP, and p300 as codependencies with CDK7i. Accordingly, cotreatment with SY-5609 and the bromodomain and extra-terminal protein inhibitor (BETi) OTX015 or pelabresib or the CBP/p300 inhibitor GNE-049 was synergistically lethal in MPN-sAML cells (including those exhibiting TP53 loss). Finally, in the HEL-Luc/GFP xenograft model, compared with each agent alone, cotreatment with SY-5609 and OTX015 reduced sAML burden and improved survival without host toxicity. These findings demonstrate promising preclinical activity of CDK7i-based combinations with BETi or CBP/p300 inhibitor against advanced MPNs, including post-MPN sAML.
Formoterol dynamically alters endocannabinoid tone in the periaqueductal gray inducing headache
Authors: Peterson Ingrid L. , Liktor-Busa Erika , Karlage Kelly L. , Young Sally J. , Scholpa Natalie E. , Schnellmann Rick G. , Largent-Milnes Tally M.
Published: November 2024

Background

Headache is a pain disorder present in populations world-wide with a higher incidence in females. Specifically, the incidences of medication overuse headache (MOH) have increased worldwide. Comorbidities of MOH include photosensitivity, anxiety, “brain fog”, and decreased physical activity. The FDA-approved long-lasting selective β2-adrenergic receptor agonist, formoterol, is currently approved for use in severe asthma and chronic obstructive pulmonary disease. Recently, interest in repurposing formoterol for use in other disorders including Alzheimer’s disease, and neuropathic pain after spinal cord injury and traumatic brain injury has gained traction. Thus, revisiting known side-effects of formoterol, like headache and anxiety, could inform treatment paradigms. The endocannabinoid (eCB) system is implicated in the etiology of preclinical headache, with observed decreases in the circulating levels of endogenous cannabinoids, referred to as Clinical Endocannabinoid Deficiency. As cross-talk between the eCB system and adrenergic receptors has been reported, this study investigated the role of the eCB system and ability of formoterol to induce headache-like periorbital allodynic behavior.

Methods

Female 8-week-old C57Bl/6J mice were treated daily with formoterol (0.3 mg/kg, i.p.) for up to 42-days, during which they were assessed for periorbital allodynia, open field/novel object recognition, and photosensitivity. At the end of the study, the periaqueductal grey (PAG), a brain region known to contribute to both headache induction and maintenance, was collected and subjected to LC-MS to quantify endocannabinoid levels.

Results

Mice exhibited periorbital allodynia at nearly all time points tested and photosensitivity from 28-days onward. Levels of endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), along with cannabinoid receptor 1 (CB1R) expression were altered by both age and upon treatment with formoterol. Administration of FAAH/MAGL inhibitors, to target the eCB system, and a non-selective cannabinoid receptor agonist, WIN 55,212 reversed the formoterol-induced periorbital allodynia.

Conclusions

These results suggest that formoterol is dysregulates eCB tone to drive headache-like periorbital allodynic behaviors. These results could help inform preventative treatment options for individuals receiving formoterol, as well as provide information on the interaction between the eCB and adrenergic system.

Graphical Abstract
Development of a core outcome set for psychological therapy trials on acute psychiatric inpatient wards
Authors: Jacobsen Pamela , Berry Katherine , Clarkson Lucy , Hiscocks Rebecca , Hopkins India , Morgan Ceri , Tandon Dhaarna , Teale Ashley-Louise , Tyler Natasha , Wood Lisa
Published: November 2024

Background

Consensus on what outcomes should be included in trials of psychological therapies on acute psychiatric inpatient wards is currently lacking. Inclusion of different viewpoints, including service user perspectives, is crucial in ensuring that future trials measure outcomes which are meaningful and important. Development of a Core Outcome Set (COS), a minimum standardised set of outcomes to be measured and reported, would help improve synthesis and interpretation of clinical trial data in this area.

Methods

Stage 1 of the COS development involved compiling a comprehensive long-list of outcomes from key sources including i) a systematic review of outcomes from published trials, ii) online survey of key stakeholders (service users, carers, healthcare professionals, researchers, and end users of research), iii) qualitative interviews with service users and carers. Stage 2 involved stakeholder groups short-listing the outcomes using consensus methods (e-Delphi survey). The final outcome set was derived from the short-list at a consensus meeting of stakeholders, facilitated by an Independent Chair.

Results

A long-list of 68 outcomes was compiled from the systematic review (n = 30 trials), online stakeholder survey (n = 100 participants) and qualitative interviews (n = 15 participants). Fifty stakeholders took part in the e-Delphi study, where the long-list was cut down to a short-list of 12 outcomes over 2 rounds. Nine stakeholders took part in the final consensus meeting, and after some outcomes were removed and/or amalgamated, a final set of 6 outcomes was recommended for inclusion in the COS. These were Ability to Cope, Hopefulness, Quality of Life, Psychosis Symptoms, Mood, and Self-Harm Behaviours.

Conclusions

Widespread future adoption of the COS will reduce research waste by ensuring that outcomes are more easily comparable across trials, and that the full range of stakeholder priorities are represented in trial outcomes. This makes it more likely that effective therapies will be identified in a timely fashion and successfully implemented in routine clinical practice. The final 6-outcome COS should be feasible to implement given the need keep participant burden to a minimum in inpatient trials. Further work is needed to make recommendations for the best outcome measurement instruments to use, including the use of patient-reported outcomes alongside clinician-rated measures.

Trial registration

Not applicable.
Lipoxin A4 improves cardiac remodeling and function in diabetes-associated cardiac dysfunction
Authors: Fu Ting , Mohan Muthukumar , Bose Madhura , Brennan Eoin P. , Kiriazis Helen , Deo Minh , Nowell Cameron J. , Godson Catherine , Cooper Mark E. , Zhao Peishen , Kemp-Harper Barbara K. , Woodman Owen L. , Ritchie Rebecca H. , Kantharidis Phillip , Qin Cheng Xue
Published: November 2024

Background

Diabetic heart disease may eventually lead to heart failure, a leading cause of mortality in diabetic individuals. The lack of effective treatments for diabetes-induced heart failure may result from a failure to address the underlying pathological processes, including chronic, low-grade inflammation. Previous studies have reported that lipoxin A4 (LXA4), known to promote resolution of inflammation, attenuates diabetes-induced atherosclerosis, but its impact on diabetic hearts has not been sought. Thus, we aimed to determine whether LXA4 therapeutic treatment attenuates diabetes-induced cardiac pathology.

Methods

Six-week-old male apolipoprotein E-deficient (ApoE−/−) mice were followed for 16 weeks after injection of streptozotocin (STZ, 55 mg/kg/day, i.p. for 5 days) to induce type-1 diabetes (T1DM). Treatment with LXA4 (5 μg/kg, i.p.) or vehicle (0.02% ethanol, i.p.) was administered twice weekly for the final 6 weeks. One week before endpoint, echocardiography was performed within a subset of mice from each group. At the end of the study, mice were euthanized with sodium pentobarbital (100 mg/kg i.p.) and hearts were collected for ex vivo analysis, including histological assessment, gene expression profiling by real-time PCR and protein level measurement by western blot.

Results

As expected diabetic mice showed a significant elevation in plasma glycated hemoglobin (HbA1c) and glucose levels, along with reduced body weight. Vehicle-treated diabetic mice exhibited increased cardiac inflammation, macrophage content, and an elevated ratio of M1-like to M2-like macrophage markers. In addition, myocardial fibrosis, cardiomyocytes apoptosis and hypertrophy (at the genetic level) were evident, with echocardiography revealing early signs of left ventricular (LV) diastolic dysfunction. Treatment with LXA4 ameliorated diabetes-induced cardiac inflammation, pro-inflammatory macrophage polarization and cardiac remodeling (especially myocardial fibrosis and cardiomyocytes apoptosis), with ultimate improvement in cardiac function. Of note, this improvement was independent of glucose control.

Conclusions

These findings demonstrated that LXA4 treatment attenuated the extent of cardiac inflammation in diabetic hearts, resulting in limited cardiac remodeling and improved LV diastolic function. This supports further exploration of LXA4-based therapy for the management of diabetic heart disease. The recent development of stable LXA4 mimetics holds potential as a novel strategy to treat cardiac dysfunction in diabetes, paving the way for innovative and more effective therapeutic strategies.

Graphical Abstract
Co-expression gene module analysis in response to attenuated cercaria vaccine reveals a critical role for NK cells in protection against Schistosoma mansoni
Authors: Neto Almiro Pires da Silva , Vitoriano-Souza Juliana , Khouri Mariana Ivo , Favaro Regiane Degan , Wilson Robert Alan , Leite Luciana Cezar de Cerqueira , Ramos Pablo Ivan Pereira , Farias Leonardo Paiva
Published: November 2024

Background

Despite decades of research, an effective schistosomiasis vaccine remains elusive. The radiation-attenuated (RA) cercarial vaccine remains the best model for eliciting high levels of protection. We have recently explored this model in mice to identify potentially protective pathways by examining gene expression patterns in peripheral blood mononuclear cells (PBMC).

Methods

Herein, we reanalyzed the transcriptomic data from PBMC obtained from vaccinated and infected C57BL/6 mice in three timepoints (Days 7 and 17 after infection or vaccination and Day 7 post-challenge). In addition, we generated new data on PBMC collected 35 days after infection. Deconvolution analysis was performed to estimate immune cell composition by CIBERSORTx. Gene co-expression networks and over-representation analysis (ORA) were performed using the CEMiTool package. Protein-protein interaction networks were constructed using STRING, and the hub proteins for each module were identified using Cytoscape.

Results

Co-expression network analysis identified a module (M2) associated with the infection process, grouping genes related to a Th2 immune response, and a second module (M6) associated with the vaccination process, displaying pathways related to a Th1 response, CD8 + T cells and NK cells. Within each module, five hub proteins were identified based on protein-protein interaction networks. The M2 infection module revealed Chil3, Il4, Cx3cr1, Emr1 and Ccl2 as hubs, while module M6, associated with vaccination, disclosed Prf1, Klrc1, IFN-γ, Ncr1 and Tbx21 as hub proteins.

Conclusions

Our data point to the potentiald role of NK cells that may contribute to the RA vaccine response through the production of IFN-γ orchestrated by the T-bet transcription factor (Tbx21).

Graphical Abstract
Efficacy of probiotics as adjuvant therapy in bronchial asthma: a systematic review and meta-analysis
Authors: Balan Divya , Baral Tejaswini , Manu Mohan K. , Mohapatra Aswini Kumar , Miraj Sonal Sekhar
Published: November 2024

Background

Asthma is a chronic, heterogeneous disease characterized by airway inflammation. Asthma exacerbations significantly increase the disease burden, necessitating new therapeutic approaches. Emerging evidence suggests probiotics, through the gut-lung axis, may benefit asthma management by modulating immune responses and reducing inflammation.

Methods

This systematic review and meta-analysis adhered to PRISMA guidelines and was registered with PROSPERO (CRD42023480098). A comprehensive search of PubMed, Scopus, Web of Science, and Embase was conducted up to March 2024. Inclusion criteria encompassed randomized controlled trials (RCTs) evaluating probiotic interventions in asthma patients. Statistical analysis was done using RevMan 5.3, with odds ratios (OR) and 95% confidence intervals (CI) calculated, and heterogeneity assessed using I2 statistics.

Results

Twelve RCTs, comprising 1401 participants, met the inclusion criteria. The probiotic strains investigated included various Lactobacillus and Bifidobacterium species. Meta-analysis revealed significant improvements in asthma control test scores (OR 1.18, 95% CI: 1.18–3.64, p = 0.0001) following probiotic supplementation. Probiotics also improved fractional exhaled nitric oxide (FeNO) in one study, but pooled FeNO and eosinophil data were not statistically significant (p = 0.46 and p = 0.29, respectively). One study observed fewer asthma exacerbations in the probiotic group (24/212) compared to placebo (67/210), with no difference in exacerbation duration.

Conclusion

Probiotic supplementation may be beneficial in improving asthma symptom control with no significant impact on lung function indices or eosinophil levels. Probiotics can be a potential adjunctive therapy in asthma management, particularly for asthma symptom control.
First-in-human study of 99mTc-labeled fucoidan, a SPECT tracer targeting P-selectin
Authors: Oostveen Reindert F. , Zheng Kang H. , Kaiser Yannick , Nurmohamed Nick S. , Kroon Jeffrey , de Wit Tim C. , Poel Edwin , Aerts Joel , Rouzet Francois , Stroes Erik S. G. , Letourneur Didier , Verberne Hein J. , Chauvierre Cédric , Ståhle Mia R.
Published: November 2024

Background

Activation of endothelial cells and platelets in atherothrombosis is characterized by upregulation of P-selectin. As a consequence, P-selectin represents a potential target for molecular imaging to identify thrombosis at an early stage. Fucoidan is a polysaccharide ligand extracted from brown algae with nanomolar affinity for P-selectin. This first-in-human study evaluated in healthy volunteers the safety, whole-body biodistribution, and dosimetry of 99mTc-fucoidan (Good Manufacturing Practices grade). We also investigated whether we could observe binding of 99mTc-fucoidan to human thrombi ex vivo and in vivo. In ten healthy volunteers, conjugate whole-body scans were performed up to 24 h following intravenous injection of 99mTc-fucoidan (370 MBq). Moreover, 99mTc-fucoidan uptake in ex vivo human thrombi (n = 11) was measured by gamma counting. Additionally, three patients with a newly diagnosed deep vein thrombosis (DVT) were subjected to 99mTc-fucoidan SPECT/CT imaging.

Results

99mTc-fucoidan was well tolerated in all participants without any drug-related adverse events. The total-body absorbed dose in males was comparable to females (0.012 ± 0.004 vs. 0.011 ± 0.005 mSv/MBq; p = 0.97). Gamma counting experiments demonstrated binding of tracer to ex vivo human thrombi that was 16% lower after blocking with a natural P-selectin ligand, Sialyl Lewis X. 99mTc-fucoidan demonstrated specific uptake at the thrombus site in one out of three scanned patients with DVT.

Conclusions

99mTc-Fucoidan has a favorable biodistribution and safety profile. 99mTc-fucoidan exhibited specific binding to human thrombi in both in vivo and ex vivo settings. Nonetheless, the in vivo results do not support further clinical investigation of 99mTc-fucoidan as an imaging modality for DVT. Other clinical implementations of a technetium− 99m-labeled P-selectin tracer should be considered.

Trial registration: Clinicaltrials,NCT03422055.Registered 01/15/2018. URL: https://clinicaltrials.gov/study/NCT03422055Landelijk Trial Register, NL7739. Registered 4/2/2019 . https://onderzoekmetmensen.nl/en/trial/26785
Estimation of shallow structure along the hinagu fault by applying seismic interferometry to DAS observations conducted along national route 3 in Kumamoto prefecture, Japan
Authors: Hamanaka Satoru , Emoto Kentaro
Published: November 2024

Distributed acoustic sensing (DAS) is a newly developed geophysical observation method and has attracted wide attention in seismology for realizing ultra-high-density observations. DAS uses fiber-optic cables and measures the strain at every point along the cable. This advantage renders DAS an effective tool for investigating near-surface geotechnical properties. Near fault zones, it is important to obtain detailed geotechnical information in advance because of the potential for significant damage in an earthquake. In this study, we recorded continuous ground motion for approximately 1 month using a 40 km-long fiber-optic communication cable running under National Route 3 in Kumamoto Prefecture, Japan. The cross-correlation function (CCF) was calculated using ambient noise, and three-station interferometry was applied to improve the signal-to-noise ratio of the CCF. Using the reconstructed CCF between channels, we calculated the dispersion curves by conducting multichannel surface wave analysis and estimated the one-dimensional velocity structure of each section from the fundamental modes of the dispersion curves. We obtained the detailed shallow S-wave velocity structure to a depth of 180 m along the Hinagu Fault for approximately 2.5 km. The obtained velocity structure showed that the low-velocity region increased abruptly with depth from the center to the latter half of the analyzed section. This velocity change occurs when the national highway running parallel to the fault gradually leaves the fault, suggesting a structural change from solid volcanic layers to thick shallow sedimentary layers derived from the Yatsushiro Plain.

Graphical abstract
Effects of the intrayear fluctuation in serum albumin levels on the prognosis of patients on hemodialysis: a six-center, 3-year observational study in Japan
Authors: Kida Nanami , Ohta Yuto , Kato Satoki , Kamoto Akihito , Mizuguchi Sachiyo , Hikita Hidetsugu , Yoshida Kiyoshi , Tsubakihara Yoshiharu
Published: November 2024

Background

Malnutrition and hypoalbuminemia are prognostic factors for mortality in patients undergoing hemodialysis (HD). We hypothesized that the monthly variability in albumin levels was a stronger prognostic factor than its baseline level. Therefore, in this study, we aimed to investigate the association between the 3-year prognosis and 1-year fluctuations in serum albumin levels of patients on HD.

Methods

In this retrospective follow-up study, we enrolled patients on HD from six centers between January 2014 and December 2014. Serum albumin levels were obtained every month during this period. We calculated the fluctuation rate of serum albumin levels using the following equation: (highest value – lowest value of the year)/average value of albumin during the year. We divided the patients into two groups on the basis of the median fluctuation rate. All patients were followed up from January 2015 to January 2017. The primary outcome of this study was all-cause mortality, and the secondary outcome was the combined endpoint of mortality and major cardio-cerebrovascular adverse events (MACCEs).

Results

Overall, 621 patients on HD were included in this study. The median rate of fluctuation in albumin levels in all patients was 14.5%. Compared with patients in the low fluctuation (LF) group (< 14.5%) (n = 308), those in the high fluctuation (HF) group (≥ 14.5%) (n = 313) were significantly older (67 versus 65 years; p = 0.009). During a mean follow-up period of 31.0 ± 10.1 months, there were 121 (19.5%) and 191 (30.5%) cases of all-cause death and combined endpoint, respectively. Kaplan–Meier analysis results showed that the HF group had a significantly worse prognosis in terms of all-cause mortality (log-rank test, p = 0.005) and combined endpoints (log-rank test, p = 0.001) than the LF group. Among patients with low albumin levels (< 3.7 g/dL), multivariate analysis results demonstrated that HF was independently associated with an increased risk of all-cause mortality and composite endpoint (hazard ratio [HR]: 1.02, 95% confidence interval [CI] 1.00–1.04, p = 0.011; HR: 1.02, 95% CI 1.00–1.03, p = 0.002).

Conclusion

In patients on HD, high fluctuations in serum albumin levels were significantly associated with increased all-cause mortality risk. Thus, attention should be paid not only to the monthly albumin level but also to its fluctuations.
Zdania – Piosenki – Literatura. Język Polski dla obcokrajowców. Poziom B1.2
Authors: Obremski Krzysztof , Wróblewski Maciej
Published: November 2024

Note about the book The intention of the authors of this book is for it to be helpful in learning Polish as a foreign language. Therefore, it cannot and should not replace systematic learning of the Polish language and the literature created in it. Moreover, it is impossible to predict from what different parts of the world its Readers may come. Therefore, difficult problems related to intercultural dialogue will remain challenges which in this book are taken up only to a limited extent.
Ksiądz Zbigniew Jan Marek SJ (1947–2024) – pedagog religii
Authors: Szulakiewicz Władysława
Published: November 2024

W lutym 2024 roku zmarł ks. prof. Zbigniew Marek, teolog, katechetyk i pedagog. Był długoletnim pracownikiem Uniwersytetu Ignatianum w Krakowie. Celem artykułu jest przedstawienie jego sylwetki jako pedagoga religii. W rozważaniach skrótowo ukazano drogę edukacji tego duchownego, uzyskiwanie przez niego stopni i tytułów naukowych, w tym stopnia doktora habilitowanego w dyscyplinie pedagogika. Ponadto zarysowano istotę badań naukowych ks. Marka, zwłaszcza w zakresie jego twórczości pedagogicznej, oraz wymieniono czasopisma, w których badania te popularyzował. W refleksji odniesiono się także do jego dokonań organizacyjnych i dydaktycznych oraz osiągnięć w zakresie kształcenia kadry naukowej. Tekst powstał na podstawie analizy publikacji duchownego oraz źródeł archiwalnych i drukowanych, dokumentujących jego działalność dydaktyczną i organizacyjną.
Code and Data Repository for A New Multicommodity Network Flow Model and Branch and Cut for Optimal Quantum Boolean Circuit Synthesis
Authors: Jung Jihye , Choi In-Chan
Published: November 2024

This directory contains the entire set of result files that are reported in our paper.
Snowballing sustainability
Authors: Jones Simon
Published: November 2024

Simon Jones talks to Eastman Chemical's Rachel Oakley about the company's efforts to make the eyewear industry more sustainable
Surfing the latest in optometry
Authors: Harvey Bill
Published: November 2024

In the first of two features, Bill Harvey reports on some of the highlights from the scientific programme at the recent American Academy of Optometry annual conference
Taking festive fun too far
Authors: Morris Rowberry
Published: November 2024

An explanation of the legal ramifications of allowing the festive fun to get out of hand from the employment team at Rowberry Morris Solicitors
Thought for the day
Authors: Harvey Bill
Published: November 2024

Bill Harvey considers the growing influence of artificial intelligence in eye care and recommends two newly published books on the subject; one for clinicians and one for patients
CPD: Age-related macular degeneration 2
Authors: Narayan Rohit , Harvey Bill
Published: November 2024

In the second in a four-part series looking at age-related macular degeneration, Dr Rohit Narayan and Bill Harvey discuss the clinical assessment and diagnosis of age-related macular degeneration (C104534, suitable for logging as one provider-led distance learning CPD point for optometrists and dispensing opticians)
Diary of a Spectacle Designer
Authors: Davies Tom
Published: November 2024

It might be the last time Tom Davies makes a Covid prediction