bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular procedures in ambulatory cardiac procedures: really?
Authors: Davila Victor R. , Saklayen Samiya , Tang Jonathan
Published: October 2024

Purpose of review

To evaluate the current trends, safety, and feasibility of same-day discharge (SDD) in ambulatory cardiac procedures, with a focus on percutaneous coronary interventions (PCI). This review also discusses the impact of technological advancements and explores future directions for expanding the scope of SDD in more complex cardiac procedures.

Recent findings

Recent studies have demonstrated that SDD after PCI is both well tolerated and effective for appropriately selected patients, with outcomes comparable with those of patients who remain hospitalized overnight. Advancements in PCI technology, including improved stent designs, smaller sheath sizes, and the adoption of the transradial approach, have significantly enhanced the feasibility of SDD. Enhanced recovery after surgery (ERAS) pathways, adapted for ambulatory settings, further improve patient safety, particularly as more complex procedures are attempted. However, challenges remain in determining SDD eligibility, particularly in settings with limited emergency care capabilities.

SDD is a viable and cost-effective option for low-risk patients undergoing PCI and other ambulatory cardiac procedures. The successful implementation of SDD requires careful patient selection, adherence to standardized protocols, and vigilant postprocedural monitoring. Future research should focus on refining patient selection tools, expanding the scope of SDD to include more complex procedures, and enhancing postdischarge monitoring through advanced technologies. Multidisciplinary collaboration and ongoing education are essential to support the well tolerated and effective adoption of SDD in ambulatory cardiac care.
Evaluation of Vancomycin Dose Needed to Achieve 24-Hour Area Under the Concentration-Time Curve to Minimum Inhibitory Concentration Ratio Greater Than or Equal to 400 Using Pharmacometric Approaches in Pediatric Intensive Care Patients
Authors: Jung Dawoon , Kishk Omayma A. , Bhutta Adnan T. , Cummings Ginny E. , El Sahly Hana M. , Virk Manpreet K. , Moffett Brady S. , Morris Daniel Jennifer L. , Watanabe Amy , Fishbane Nicholas , Kotloff Karen L. , Gu Kenan , Ghazaryan Varduhi , Gobburu Jogarao V. S. , Akcan-Arikan Ayse , Campbell James D.
Published: October 2024

OBJECTIVES:

To investigate which independent factor(s) have an impact on the pharmacokinetics of vancomycin in critically ill children, develop an equation to predict the 24-hour area under the concentration-time curve from a trough concentration, and evaluate dosing regimens likely to achieve a 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC24/MIC) greater than or equal to 400.

DESIGN:

Prospective population pharmacokinetic study of vancomycin.

SETTING:

Critically ill patients in quaternary care PICUs.

PATIENTS:

Children 90 days old or older to younger than 18 years who received IV vancomycin treatment, irrespective of the indication for use, in the ICUs at the University of Maryland Children’s Hospital and Texas Children’s Hospital were enrolled.

INTERVENTIONS:

Vancomycin was prescribed at doses and intervals chosen by the treating clinicians.

MEASUREMENTS AND MAIN RESULTS:

A median of four serum levels of vancomycin per patient were collected along with other variables for up to 7 days following the first administration. These data were used to characterize vancomycin pharmacokinetics and evaluate the factors affecting the variability in achieving AUC24/MIC ratio greater than or equal to 400 in PICU patients who are not on extracorporeal therapy. A total of 302 children with a median age of 6.0 years were enrolled. A two-compartment model described the pharmacokinetics of vancomycin with the clearance of 2.76 L/hr for a typical patient weighing 20 kg. The glomerular filtration rate estimated using either the bedside Schwartz equation or the chronic kidney disease in children equation was the only statistically significant predictor of clearance among the variables evaluated, exhibiting equal predictive performance. The trough levels achieving AUC24/MIC = 400 were 5.6–10.0 μg/mL when MIC = 1 μg/mL. The target of AUC24/MIC greater than or equal to 400 was achieved in 60.4% and 36.5% with the typical dosing regimens of 15 mg/kg every 6 and 8 hours (q6h and q8h), respectively.

CONCLUSIONS:

The pharmacokinetics of vancomycin in critically ill children were dependent on the estimated glomerular filtration rate only. Trough concentrations accurately predict AUC24. Typical pediatric vancomycin dosing regimens of 15 mg/kg q6h and q8h will often lead to AUC24/MIC under 400.
Causes, Diagnostic Testing, and Treatments Related to Clinical Deterioration Events Among High-Risk Ward Patients
Authors: Churpek Matthew M. , Ingebritsen Ryan , Carey Kyle A. , Rao Saieesh A. , Murnin Emily , Qyli Tonela , Oguss Madeline K. , Picart Jamila , Penumalee Leena , Follman Benjamin D. , Nezirova Lily K. , Tully Sean T. , Benjamin Charis , Nye Christopher , Gilbert Emily R. , Shah Nirav S. , Winslow Christopher J. , Afshar Majid , Edelson Dana P.
Published: October 2024

IMPORTANCE:

Timely intervention for clinically deteriorating ward patients requires that care teams accurately diagnose and treat their underlying medical conditions. However, the most common diagnoses leading to deterioration and the relevant therapies provided are poorly characterized.

OBJECTIVES:

We aimed to determine the diagnoses responsible for clinical deterioration, the relevant diagnostic tests ordered, and the treatments administered among high-risk ward patients using manual chart review.

DESIGN, SETTING, AND PARTICIPANTS:

This was a multicenter retrospective observational study in inpatient medical-surgical wards at four health systems from 2006 to 2020. Randomly selected patients (1000 from each health system) with clinical deterioration, defined by reaching the 95th percentile of a validated early warning score, electronic Cardiac Arrest Risk Triage, were included.

MAIN OUTCOMES AND MEASURES:

Clinical deterioration was confirmed by a trained reviewer or marked as a false alarm if no deterioration occurred for each patient. For true deterioration events, the condition causing deterioration, relevant diagnostic tests ordered, and treatments provided were collected.

RESULTS:

Of the 4000 included patients, 2484 (62%) had clinical deterioration confirmed by chart review. Sepsis was the most common cause of deterioration (41%; n = 1021), followed by arrhythmia (19%; n = 473), while liver failure had the highest in-hospital mortality (41%). The most common diagnostic tests ordered were complete blood counts (47% of events), followed by chest radiographs (42%) and cultures (40%), while the most common medication orders were antimicrobials (46%), followed by fluid boluses (34%) and antiarrhythmics (19%).

CONCLUSIONS AND RELEVANCE:

We found that sepsis was the most common cause of deterioration, while liver failure had the highest mortality. Complete blood counts and chest radiographs were the most common diagnostic tests ordered, and antimicrobials and fluid boluses were the most common medication interventions. These results provide important insights for clinical decision-making at the bedside, training of rapid response teams, and the development of institutional treatment pathways for clinical deterioration.
Perioperative immunotherapy for nonsmall cell lung cancer
Authors: Huang Jingya , Li Wenyuan , Guo Hui
Published: October 2024

Purpose of review

Recent years have witnessed significant advancements in the treatment of lung cancer with immunotherapy, primarily centered on immune checkpoint inhibitors (ICIs). Numerous clinical studies have evaluated or are currently evaluating the clinical benefits of neoadjuvant, adjuvant, and perioperative use of ICIs. These findings have notably reshaped the landscape of perioperative treatment for nonsmall cell lung carcinoma (NSCLC).

Recent findings

Comparing different treatment modes, adding ICIs in the adjuvant phase to neoadjuvant treatment with ICIs and chemotherapy may not improve survival outcomes for patients with resectable NSCLC and may be associated with increased adverse events. For prognostic factors, ctDNA minimal residual disease (MRD) status might serve as an early predictor of achieving pathological remission. For study endpoints, a positive result with PFS as the primary endpoint may not necessarily translate into overall survival benefits.

For perioperative immunotherapy, challenges persist, including the current lack of sensitive and reliable biomarkers, the effect of neoadjuvant therapy on surgical risk as well as the selection of the appropriate study endpoint. In this review, we discuss recent and ongoing trials investigating strategies of neoadjuvant, adjuvant and perioperative immunotherapy in NSCLC, while also proposing considerations for future directions in this continuously evolving field.
Thymic malignancies: role of immunotherapy and novel approaches
Authors: Kiesewetter Barbara , Melhorn Philipp , Fuereder Thorsten
Published: October 2024

Purpose of review

Thymic epithelial tumors (TETs) are a diverse group of malignancies that include thymomas (T), thymic carcinomas (TC), and thymic neuroendocrine tumors. Given the rarity of this disease, evidence defining the optimal treatment approach in the advanced/metastatic setting is limited. This article reviews the latest advances in systemic therapy for TETs, with a special focus on immunotherapy and targeted therapy strategies.

Recent findings

Multiple recent efforts have been made to integrate novel immunotherapies and targeted therapy approaches into the current treatment algorithm for T and TC. In addition to trials of checkpoint inhibitor monotherapy, combinatorial approaches with novel immunotherapies or targeted therapies are being explored. Molecular profiling may help identify druggable targets, further optimizing outcomes in this population.

Immune checkpoint inhibitor therapy has shown promising activity in TETs patients. However, toxicity in an unselected cohort, particularly in T patients, can be substantial, and therefore it is not recommended outside of clinical trials. Until additional research validates biomarkers to safely select patients for immunotherapy, targeted therapies remain a reasonable second-line option. Contemporary next-generation sequencing panels may be applied to identify druggable targets in the absence of standard treatment.
Risk Perceptions of Health Care Workers and Occupational Health Experts on Psychological Distress
Authors: Emal Lima M. , Tamminga Sietske J. , Beumer Annechien , Kezic Sanja , Timmermans Danielle R. , Schaafsma Frederieke G. , van der Molen Henk F.
Published: October 2024

Background

The objectives of this study are to explore healthcare workers’ (HCWs’) mental models regarding psychological distress and to compare these with that of experts.

Methods

Semistructured interviews were conducted (n = 28 HCWs, n = 13 experts). The topic list encompassed risk perception, early stress symptoms, causes, consequences, and preventive measures of psychological distress. Interviews were transcribed verbatim and thematically analyzed using MAXQDA (VERBI Software, Berlin).

Results

Similarities were found in risk perception, symptoms, causes, and consequences. Differences arose in HCWs’ reliance on personal experiences and values versus experts’ scientific perspective. Preventive measures also showed discrepancies. Variation within HCWs was found on all aspects of their mental model.

Conclusion

For effective preventive interventions regarding psychological distress, experts should consider HCWs’ personal values and experiences, acknowledging the variation in their mental models. This approach may enhance HCWs’ engagement in preventive behaviors.
In-depth cerebrovascular lipidomics profiling for discovering novel biomarkers and mechanisms in moyamoya and intracranial atherosclerotic disease
Authors: He Kangmin , Wang Xinmei , Gu Yu , Tong Xiao , Qin Xuanfeng , Liao Yujun , Huang Li-Hao , Wang Jiaxi , Xu Bin
Published: October 2024

Background:

Despite considerable research efforts, the precise etiology and underlying pathways contributing to moyamoya disease (MMD) remain poorly understood. Moreover, the overlapping vascular pathologies shared between MMD and intracranial atherosclerotic disease (ICAD) pose challenges in clinical differentiation, even with gold-standard cerebral angiography. An in-depth exploration of lipidomic alterations in cerebral intracranial MMD vessels could offer valuable insights into the pathogenesis of MMD-related mechanisms, encompassing MMD and ICAD, and unveil novel biomarkers and potential therapeutic targets. However, to date, comprehensive lipidomic profiling has been lacking.

Materials and methods:

To discover novel biomarkers and unravel the pathophysiological mechanisms underlying MMD, we conducted a lipidomics analysis to characterize various lipid species in matched human extracranial and intracranial artery tissues from patients diagnosed with MMD (n=99) and ICAD (n=12).

Results:

Our analysis identified 569 lipid species and delineated a robust panel of lipidomic biomarkers capable of effectively distinguishing MMD from ICAD (area under curve=0.98), as determined by receiver operating characteristic curve analysis. Notably, we observed a significantly more pronounced positive correlation of diacylglycerols and a negative association of triglycerides in intracranial artery tissues of MMD patients compared to those with ICAD, suggesting a potential role of dysregulated diacylglycerol-induced signaling in MMD pathogenesis. Furthermore, our investigation into the correlations of critical differential intracranial artery vessel lipid species between MMD and ICAD and clinical parameters revealed negative associations with plasma iron levels, implying a potential link between plasma iron metabolism and artery lipid homeostasis during MMD pathogenesis.

Conclusion:

These findings offer promising prospects for advancing clinical diagnosis for enhanced differentiation between the two disease conditions. Additionally, they shed light on the fundamental mechanisms implicated in MMD pathogenesis and suggest potential therapeutic avenues through targeting artery vessel lipids or plasma iron levels.
RRFERV stabilizes TEAD1 expression to mediate nasopharyngeal cancer radiation resistance rendering tumor cells vulnerable to ferroptosis
Authors: Xu Qingqing , Wen Xin , Huang Chenglong , Lin Zaishan , Xu Zhen , Sun Ciming , Li Li , Zhang Suixian , Song Shuanghong , Lou Jiahao , Hou Zan , Chen Yuanyuan , Li Xuan , Chen Lei
Published: October 2024

Background:

Long noncoding RNAs (lncRNAs) regulate various essential biological processes, including cell proliferation, differentiation, apoptosis, migration, and invasion. However, in nasopharyngeal carcinoma (NPC), the clinical significance and mechanisms of lncRNAs in malignant progression are unknown.

Methods:

RNA sequencing and bioinformatic analysis were used to determine the potential function of RRFERV (radiation-resistant but ferroptosis-vulnerable), and its biological effects were investigated using in vitro and in vivo experiments. Western blotting, quantitative real-time reverse transcription PCR, RNA immunoprecipitation (RIP) assays, and flow cytometry detected RRFERV expression. Ferroptosis and lipid peroxidation were added to evaluate the relationship between it and radiotherapy resistance.

Results:

LncRNA–RRFERV was both highly expressed in NPC tissues and radiation-resistant cells. RRFERV is associated with poor clinical outcomes of NPC patients and stabilizes TEAD1 by competitive binding with microRNA-615-5p and microRNA-1293. RRFERV–TEAD1 signaling axis leads to malignant progression and radiotherapy resistance of NPC. Furthermore, we observed that NPC radiotherapy-resistance cells exist in a fragile oxidative stress equilibrium, which makes them more sensitive to ferroptosis inducers. Surprisingly, we found that RRFERV–TEAD1 signaling axis also plays a key role in mediating the lipid peroxidation levels of NPC radiotherapy-resistance cells through transcriptional activation of ACSL4/TFRC.

Conclusions:

RRFERV serves as an independent prognostic factor in NPC. During the malignant progression of NPC caused by high expression of RRFERV, ferroptosis can be induced to effectively kill cancer cells and reverse the radiotherapy resistance of NPC cells, suggesting a potential treatment approach for recurrent and refractory NPC.
Analysis of Burnout and Self-Efficacy of Teachers of Physical Education During Online Learning
Authors: Ran Xu
Published: October 2024

The research is based on interpretive phenomenological analysis and the interview method. The sample involved 100 secondary school students from five to nine grades and eight physical education teachers. All participants studied the proposed physical education program in-person for one academic semester, as well as studied the program online for one academic semester. It was found that online learning was viewed unfavorably by 87% of teachers. However, 65% of participants admitted that learning opportunities were limited, and they experienced difficulties with appropriate lesson content, equipment, and space to foster a positive learning environment and a productive working context. In addition, marginalization occurred as parents and students paid more attention to other subject areas except for physical education. The research suggested that the majority of teachers (89%) were looking forward to full-time and face-to-face physical education training because they lacked personal relationships and interaction with their students.
Nurse-led self-management support to improve symptom management and self-reported outcomes in people with irritable bowel syndrome
Authors: Barandouzi Zahra A. , Chen Jie , Henderson Wendy A. , Starkweather Angela R. , Cong Xiaomei S.
Published: October 2024

Objectives:

Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction with an unknown precise etiology. Intricate mechanisms underlying the disruption of bidirectional communication between the brain and the gut may influence the severity of symptoms as well as the response to self-management interventions. Management of IBS can be particularly challenging due to recurrent and resistant symptoms to therapeutic approaches. The present study aimed to evaluate the role of nurse-led self-management support on symptom management and self-reported outcomes in people with IBS.

Methods:

In the current study, which was part of a parent randomized controlled trial, participants with IBS received one-on-one self-management intervention either by phone or in-person by Registered Nurses (RNs) in 3 sessions over 12 weeks. Each intervention was between 15 and 30 minutes. During the first intervention, the RN asked open-ended questions on symptom episodes, stress, physical activity, Quality of Life (QOL), and diet to provide recommendations for improved self-management. At the second and the third nurse-led self-management sessions, the RN helped in problem-identification and solving throughout the intervention. Quantitative content analysis was performed using the coding system developed by 2 authors for analyzing the participants’ responses.

Results:

In total, 24 participants with IBS completed the 3 nurse-led self-management sessions. Participants’ mean age was 21.37 (±2.55) years old, and 83.33% were female. At the first nurse-led self-management session, 79% of participants reported pain, 62.5% reported bloating, 50% reported diarrhea, 37.5% reported constipation, 100% reported stress, and 95.6% had physical activity as part of their routines, while only 33.3% of the participants reported having a “high” QOL. After 3 nurse-led self-management sessions, participants reported improved IBS symptoms in pain 73%, bloating 73.7%, diarrhea 76.8%, constipation 50%, stress 42.1%, and physical activity 45%, as well as 66.7% of the participants experienced a “high” QOL. Dairy, fast/processed foods, and high-fat foods were the most frequent triggers of the symptoms, with a frequency of 40%, 24.5%, and 12%, respectively. After receiving nurse-led support, 69.20% of the participants reported improved dietary habits.

Conclusions:

Nurse-led self-management can support participants to manage various IBS symptoms and improve their QOL. The unique strength of this study was evaluating participant needs and offering individualized solutions. A further study utilizing novel nurse-led self-management approaches may provide a valuable platform for empowering IBS patients’ self-management.
Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus
Authors: Kristó Ildikó , Kovács Zoltán , Szabó Anikó , Borkúti Péter , Gráf Alexandra , Sánta Ádám Tamás , Pettkó-Szandtner Aladár , Ábrahám Edit , Honti Viktor , Lipinszki Zoltán , Vilmos Péter
Published: October 2024

The members of the evolutionary conserved actin-binding Ezrin, Radixin and Moesin (ERM) protein family are involved in numerous key cellular processes in the cytoplasm. In the last decades, ERM proteins, like actin and other cytoskeletal components, have also been shown to be functional components of the nucleus; however, the molecular mechanism behind their nuclear activities remained unclear. Therefore, our primary aim was to identify the nuclear protein interactome of the single
Drosophila
ERM protein, Moesin. We demonstrate that Moesin directly interacts with the Mediator complex through direct binding to its Med15 subunit, and the presence of Moesin at the regulatory regions of the
Hsp70Ab
heat shock gene was found to be Med15-dependent. Both Moesin and Med15 bind to heat shock factor (Hsf), and they are required for proper
Hsp
gene expression under physiological conditions. Moreover, we confirmed that Moesin, Med15 and Hsf are able to bind the monomeric form of actin and together they form a complex in the nucleus. These results elucidate a mechanism by which ERMs function within the nucleus. Finally, we present the direct interaction of the human orthologues of
Drosophila
Moesin and Med15, which highlights the evolutionary significance of our finding.
Replication marketplaces would help science to become more self-correcting
Authors: Hüffmeier Joachim , Kühner Clara
Published: October 2024

Independent replications are very rare in the behavioural and social sciences. This is problematic because they can help to detect ‘false positives’ in published research and, in turn, contribute to scientific self-correction. The lack of replication studies is, among other factors, due to a rather passive editorial approach concerning replications by many journals, which does not encourage and may sometimes even actively discourage submission of replications. In this Perspective article, we advocate for a more proactive editorial approach concerning replications and suggest introducing journal-based
replication marketplaces
as a new publication track. We argue that such replication marketplaces could solve the long-standing problem of lacking independent replications. To establish these marketplaces, a designated part of a journal’s editorial board identifies the most relevant new findings reported within the journal’s pages and publicly offers them for replication. This public offering could be combined with small grants for authors to support these replications. Authors then compete for the first accepted registered report to conduct the related replications and can thus be sure that their replication will be published independent of the later findings. Replication marketplaces would not only increase the prevalence of independent replications but also help science to become more self-correcting.
Trade-off between photosymbiosis and innate immunity influences cnidarian’s response to pathogenic bacteria
Authors: Emery Madison A. , Beavers Kelsey M. , Van Buren Emily W. , Batiste Renee , Dimos Bradford , Pellegrino Mark W. , Mydlarz Laura D.
Published: October 2024

Mutualistic relationships with photosynthetic organisms are common in cnidarians, which form an intracellular symbiosis with dinoflagellates in the family Symbiodiniaceae. The establishment and maintenance of these symbionts are associated with the suppression of key host immune factors. Because of this, there are potential trade-offs between the nutrition that cnidarian hosts gain from their symbionts and their ability to successfully defend themselves from pathogens. To investigate these potential trade-offs, we utilized the facultatively symbiotic polyps of the upside-down jellyfish
Cassiopea xamachana
and exposed aposymbiotic and symbiotic polyps to the pathogen
Serratia marcescens
. Symbiotic polyps had a lower probability of survival following
S. marcescens
exposure. Gene expression analyses 24 hours following pathogen exposure indicate that symbiotic animals mounted a more damaging immune response, with higher levels of inflammation and oxidative stress likely resulting in more severe disruptions to cellular homeostasis. Underlying this more damaging immune response may be differences in constitutive and pathogen-induced expression of immune transcription factors between aposymbiotic and symbiotic polyps rather than broadscale immune suppression during symbiosis. Our findings indicate that in facultatively symbiotic polyps, hosting symbionts limits
C. xamachana’
s ability to survive pathogen exposure, indicating a trade-off between symbiosis and immunity that has potential implications for coral disease research.
Tolerant mothers: aggression does not explain solitary living in the bush Karoo rat
Authors: Makuya Lindelani , Pillay Neville , Sangweni Siyabonga Patrick , Schradin Carsten
Published: October 2024

Many mammal species are thought to adopt solitary living owing to mothers becoming intolerant of adult offspring and the occurrence of social intolerance between adults. However, field studies on how solitary mammals interact are rare. Here we show that solitary living can occur without social intolerance. Over 3 years, we recorded interactions between free-living bush Karoo rats (
Otomys unisulcatus
) and conducted dyadic encounter experiments between kin and non-kin female neighbours, both in a neutral test arena and in field intruder experiments. Social interactions were rare (230/2062 observations), and they were aggressive in only 34% of cases. In dyadic encounters, mothers interacted amicably with young offspring. Aggression between mothers and offspring was almost absent. This mother–offspring relationship remained amicable even after adult offspring had dispersed. Aggression between neighbouring adult females was low in neutral arena tests, independent of kinship and season. However, in the field, females reacted more aggressively towards non-kin than kin intruders, especially during the breeding season. Tolerance between mothers and adult offspring indicates that aggression is not the mechanism leading to dispersal and solitary living. We found a solitary social system characterized by social tolerance, suggesting that dispersal and lack of social attraction rather than aggression can lead to solitary living.
Oropouche Virus: An Emerging Orthobunyavirus
Authors: Tilston-Lunel Natasha L.
Published: October 2024

On 2 February 2024, the Pan American Health Organization/World Health Organization issued an epidemiological alert on rising Oropouche virus (OROV) infections in South America. By 3 August 2024, this alert level had escalated from medium to high. OROV has been a public health concern in Central and South America since its emergence in Brazil in the 1960s. However, the 2024 outbreak marks a turning point, with the sustained transmission in non-endemic regions of Brazil, local transmission in Cuba, two fatalities and several cases of vertical transmission. As of the end of August 2024, 9852 OROV cases have been confirmed. The 2024 OROV outbreak underscores critical gaps in our understanding of OROV pathogenesis and highlights the urgent need for antivirals and vaccines. This review aims to provide a concise overview of OROV, a neglected orthobunyavirus.
Self-management of multimorbidity in sub-Saharan Africa: a systematic review and meta-synthesis with focus on diabetes, hypertension, chronic kidney disease and HIV infection
Authors: Salimu Sangwani Nkhana , Taylor Melissa , Spencer Stephen A , Nyirenda Deborah , Desmond Nicola , Morton Ben
Published: October 2024

Background

The increasing prevalence of multimorbidity in sub-Saharan Africa (SSA) is an urgent concern for health systems delivery. It is uncertain how best to promote self-management approaches or the actions that patients and carers take to maintain physical and mental health, in this context. This review aims to identify, critically appraise, and synthesize qualitative evidence that describes self-management of multimorbidity among patients and their carers in SSA.

Methods

We systematically searched PubMed, MEDLINE, CINAHL Global Health, Google Scholar and grey literature for studies on self-management of multimorbidity or common individual chronic diseases (HIV, diabetes, hypertension or chronic kidney disease) in SSA published between 1 January 2000 and 28 to 15thSeptember 2024. Using qualitative meta-synthesis techniques to formulate the questions and synthesize findings. We used a 10-point Critical Appraisal Skills Program (CASP)-Qualitative-Checklist to assess the quality of the studies and NVivo 12 software to facilitate a thematic analysis approach.

Results

We screened 2010 articles for inclusion and 20 studies met inclusion criteria. We identified themes related to medical, diet, emotional and physical self-management activities. Patients negotiate self-management based on immediacy of needs and available family support. Patients are motivated to apply biomedical management but are limited by factors such as drug stock-outs and out-of-pocket expenditure. Limited knowledge and low self-efficacy toward self-management of multimorbidity impact decision making and problem solving. We found that diabetes mellitus presents the biggest stressor in terms of burden of treatment; temporal discontinuation of medications is more prevalent amongst patients with hypertension; and patients with multimorbidity are frequently hypervigilant about their health, more likely to suffer from stress and to seek healthcare.

Conclusions

We found that there is relative lack of data on self-management of multimorbidity among patients and their carers in SSA. Where data exists, we observed significant health literacy gaps, low health literacy support and limited self-efficacy as barriers to implementation of self-management. Context sensitive programmes are required to improve health literacy to increase patient autonomy and their toolkit of options to manage chronic disease.
Inversed association of locus coeruleus MRI integrity with structural volume and its impact on individual’s inattentiveness
Authors: Neal Joshua , Kim Sun Hyung , Katz Benjamin , Kim Il Hwan , Lee Tae-Ho
Published: October 2024

The locus coeruleus (LC) is a nucleus within the brainstem associated with physiological arousal and altered structure and function in the context of neurodegenerative disorders. Pathologies related to difficulties with attention have previously been associated with abnormalities in neurotransmitter production and sensitivity, suggesting the possibility of abnormality in neurotransmitter producing neural regions. One such region is the LC, associated with norepinephrine production. To examine the possibility that LC alteration is associated with inattentive symptom reporting, a set of analyses have been performed with 141 individuals age-ranged from 8 to 54. We found that the structural integrity value of the LC, especially on the right hemisphere, showed a significant negative association with the level of individual’s inattentiveness score. Furthermore, LC volume size was significantly positively associated with inattention, and this finding was also lateralized to the right LC. Interestingly, an inverse association was found between structural integrity and volume size. These findings support the relationship between LC and attention-related behavior through both neuromelanin-sensitive and structural imaging, with important implications for the association between regional structure and function.
CAYSS: package for automatic Cytometry Analysis of Yeast Spore Segregation
Authors: Raffoux Xavier , Falque Matthieu
Published: October 2024

Meiotic recombination is a powerful source of haplotypic diversity, and thus plays an important role in the dynamics of short-term adaptation. However, high-throughput quantitative measurement of recombination parameters is challenging because of the large size of offspring to be genotyped. One of the most efficient approaches for large-scale recombination measurement is to study the segregation of fluorescent markers in gametes. Applying this to yeast spores by flow cytometry has already been proved to be highly efficient, but manual analyses of density distributions of signal intensities is time-consuming and produces non-perfectly reproducible results. Such analyses are required to identify events corresponding to spores and to assign each of them to a genotypic class depending on their fluorescence intensity. The CAYSS package automatically reproduces the manual process that we’ve been developing to analyze yeast recombination for years, including Maximum-Likelihood estimation of fluorescence extinction (Raffoux et al. 2018a). When comparing the results of manualvsCAYSS automatic analyses of the same cytometry data, recombination rates and interference were on average very similar, with less than 3% differences on average and strong correlations (R2>0.9). In conclusion, as compared to manual analysis, CAYSS allows to save a lot of human time and produces totally reproducible results.

The CAYSS software is freely available under GPL license fromhttps://forgemia.inra.fr/gqe-base/cayss/-/releases. The package is also provided as Supplementary Material 1 and a tutorial may be found as Supplementary Material 2.

TAKE AWAY

The CAYSS R package measures recombination rate and crossover interference from flow cytometry data of isolated yeast spores segregating for fluorescent markers. The analysis is fully automatic and reproducible. It includes spore identification from FSC and SSC data, genotype determination from fluorescence intensities, and Maximum Likelihood estimation of recombination parameters.
Chromosome-level genome assembly of a doubled haploid brook trout (Salvelinus fontinalis)
Authors: Lecomte Laurie , Ferchaud Anne-Laure , Normandeau Eric , Mérot Claire , Langlois-Parisé Isabelle , Therrien Jean-Christophe , Bérubé Pierre , Djambazian Haig , Nawarathna Pubudu Manoj , Fraser Dylan , Ragoussis Jiannis , Bernatchez Louis
Published: October 2024

Brook trout (Salvelinus fontinalis) is a socioeconomically important fish species for fisheries, aquaculture and aquatic conservation. We produced a 2.5 Gb reference assembly by combining Hi-C chromosome conformation capture with high-coverage short- and long-read sequencing of a fully homozygous mitotic gynogenic doubled haploid fish, which facilitates assembly of highly complex salmonid genomes. The assembly has a N50 of 50.98 Mb and 88.9% of the total assembled sequence length is anchored into 42 main chromosomes, of which 63.44% represents repeated contents, including 1,461,010 DNA transposons. 56,058 genes were found with the NCBI annotation pipeline, with 99% of the 3,640 expected conserved orthologs BUSCO genes (actinopterygii_odb10 lineage database). Additionally, we found significant homology within the 42 chromosomes, as expected for this pseudo-tetraploid species, as well as with the sister species lake trout (Salvelinus namaycush) and Atlantic salmon (Salmo salar). This assembly will serve as a reliable genomic resource for brook trout, thus enabling a wider range of reference-based applications to support ongoing research and management decision-making for the species.
Mapping the Microstructure of Human Cerebral Cortex In Vivo with Diffusion MRI
Authors: Sadikov Amir , Choi Hannah , Xiao Jaclyn , Cai Lanya T. , Mukherjee Pratik
Published: October 2024

Despite advances in diffusion MRI, which have led to remarkable progress in mapping white matter of the living human brain, the understanding of cerebral cortical microstructure in vivo and its relationship to macrostructure, myeloarchitecture, cytoarchitecture, chemoarchitecture, metabolism, and function lag far behind. We present neuromaps of 21 microstructural metrics derived from diffusion tensor, diffusion kurtosis, mean apparent propagator, and neurite orientation dispersion and density imaging of the young adult cerebral cortex. These 21 metrics are explained by four composite factors that correspond to diffusion kurtosis (intracellular volume fraction/neurite density), isotropic diffusion (free water fraction), heterogenous diffusion (extracellular volume fraction) and diffusion anisotropy (neurite orientation dispersion), respectively. We demonstrate how cortical microstructure follows cytoarchitectural and laminar differentiation, aligns with the macroscale sensory-fugal and sensorimotor-association axes, and contributes to functional brain networks, neural oscillatory dynamics, neurotransmitter receptor/transporter distributions, and cognition and behavior. We show that cortical dMRI metrics are heritable and can better predict participant age and cognition than can cortical thickness or myelination. We find cortical microstructural covariation across individuals to encode functional and structural connectivity as well as gene expression and neurotransmitter similarity. Finally, our exploratory analysis suggests cortical microstructure from diffusion MRI could prove useful in investigating a broad array of neuropsychiatric disorders.
Quantifying Cancer Drug Targetability across Biochemical Pathways
Authors: Hagler Stuart
Published: October 2024

The evaluation of cancer drug treatments within the complex context of biological networks and pathways is challenging. Drugs can be "promiscuous," targeting multiple genes or pathways, not just the ones of interest. This complexity makes it difficult to assess the full impact of a drug solely based on individual knowledgebases. We make the impact more comprehensible through the characterization of drug targetability in terms of a combination of biochemical pathway data from the Reactome Knowledgebase and drug-target interaction data from the Cancer Targetome. This leads to a graphical representation of drug targetability. We further improve comprehensibility by developing metrics to quantify the graph structures in order to evaluate drug target specificity and navigate the hierarchical nature of biological networks and identify candidate treatment options to increase specificity and minimize off-target effects. We have developed software that calculates these metrics for drugs in the Cancer Targetome. The software is available for research purposes only at https://github.com/sehagler/drug_targetability.
Optimization of methods for rapid and robust generation of cardiomyocyte-specificcrispantsin zebrafish using thecardiodeletersystem
Authors: Keeley Sean , Fernández-Lajarín Miriam , Bergemann David , John Nicolette , Parrott Lily , Andrea Brittany E. , González-Rosa Juan Manuel
Published: October 2024

CRISPR/Cas9 has massively accelerated the generation of gene loss-of-function models in zebrafish. However, establishing tissue-specific mutant lines remains a laborious and time-consuming process. Although a few dozen tissue-specific Cas9 zebrafish lines have been developed, the lack of standardization of some key methods, including gRNA delivery, has limited the implementation of these approaches in the zebrafish community. To tackle these limitations, we have established a cardiomyocyte-specific Cas9 line, thecardiodeleter, which efficiently generates biallelic mutations in combination with gene-specific gRNAs. We have also optimized the development of transposon-basedguide shuttlesthat carry gRNAs targeting a gene of interest and permanently label the cells susceptible to becoming mutant. We validated this modular approach by deleting five genes (ect2,tnnt2a,cmlc2,amhc, anderbb2), all resulting in the loss of the corresponding protein or phenocopying established mutants. Additionally, we provide detailed protocols describing how to generateguide shuttles, which will facilitate the dissemination of these techniques in the zebrafish community. Our approach enables the rapid generation of tissue-specificcrispantsand analysis of mosaic phenotypes, bypassing limitations such as embryonic lethality, making it a valuable tool for cell-autonomous studies and genetic screenings.
Capsanthin/Capsorubin Synthase Expression in Tomato Alters Carotenoid Pools, Enhancing Provitamin A and Flavor Volatiles
Authors: Fu Jingwei , Tieman Denise , Rathinasabapathi Bala
Published: October 2024

We conceptualized a tomato biofortification strategy via engineering simultaneous accumulation ofβ-carotene, a provitamin A and pepper-specialized ketocarotenoids, capsanthin, and capsorubin. Capsanthin/capsorubin synthase (CCS) in pepper, an enzyme phylogenetically related to lycopene β-cyclases (LCYB) known forβ-carotene synthesis, was investigated for itsin vivorole in ripening fruit. In pepper, silencing ofCCSvia virus-induced gene silencing reduced the flux from lycopene toβ-carotene (theβ-branch) with significant changes in carotenoid compositions. In a carotenogenic bacterial expression system, pepper CCS was more effective than tomato LCYB1 or LCYB2 in lycopene cyclization toβ-carotene and CCS synthesized capsanthin, but the LCYBs did not. Therefore, we overexpressed pepperCCSin different tomato varieties, including ‘Micro-Tom’ WT, ‘Micro-Tom’ mutant,pyp1-1(H7L)(defective in xanthophyll esterification), and five inbreds and characterized their carotenoid profiles. InCCS-transformed tomato fruit (WT and selected varieties), besides the biosynthesis of capsanthin and capsorubin, total carotenoids,β-carotene, and xanthophyll esters remarkably increased compared to the controls, while such increments were weaker in thepyp1-1(H7L). CCS expression had a positive influence on the flux toward theβ-branch and the storage pool of xanthophyll esters consistent with its dual functions in lycopene cyclization and ketocarotenoid biosynthesis. The data further supported that xanthophyll esters facilitated carotenoid accumulation. While CCS-expression had no significant impact on growth or yield, fruit ofCCS-transformed tomato had greater levels ofβ-carotene-derived flavor volatiles than the controls. Consumption of 37–131-gram ofCCS-derived hybrid fruit meets the provitamin A recommended dietary allowance, indicating greatly improved nutritional value.
The topography of gene tree topology space in a plant genus with a legacy of recent polyploidy and introgression
Authors: Landis Jacob B. , Farmer Andrew D. , Garcia Lucio , McNair Racella , Ruiz Mariana Franco , Liu Qingli , Doyle Jeff J.
Published: October 2024

The eukaryotic genome has been described as a collection of different histories; for any set of taxa one of these histories is the record of cladogenic events that together comprise the species tree. Among the other histories expected to occur are those attributable to deep coalescence/lineage sorting; to biological causes such as introgression and horizontal transfer; or to pseudo-orthology, long branch attraction, and other technical issues. Gene tree topology space is the portion of tree space occupied by the gene trees reconstructed for a particular dataset of sampled genetic loci. Because coalescent theory predicts that the species tree topology will generally be the most frequent among gene trees, a reasonable expectation is that there will be a peak in gene tree topology space at the species tree topology, with secondary peaks present due to trees tracking other histories. Gene tree topology space in the small (∼30 species, including the cultivated soybean) legume genus,Glycineshould not only have signals from the species tree and from lineage sorting, but also from a likely introgression event that created incongruence between the plastid and nuclear genomes. Additionally,Glycineis the product of a relatively recent (<13 million years) whole genome duplication, raising the possibility of pseudo-orthology. We explored this space using a set of 2389 nuclear genes and representative accessions from a 570-taxon concatenation tree, reconstructing gene trees for all nuclear loci and from complete plastid genomes and partial mitochondrial genomes. Species trees (ASTRAL) and maximum likelihood (ML) concatenation trees were congruent for a 61-taxon dataset but were incongruent with organellar genome trees. Gene tree topology space was flat: No topology was represented by more than one gene tree. This was also true for a reduced dataset of 27 taxa; only when the dataset was reduced to six ingroup taxa were multiple gene trees having the species tree topology observed, along with a topology congruent with the chloroplast genome topology, presumably representing nuclear loci introgressed along with the plastome. Clustering failed to identify any regional differentiation of gene tree topology space populated by loci with similar topologies. Pseudo-orthology did not contribute meaningfully to incongruence, in agreement with recent modeling work that minimizes concerns about this phenomenon. Clearly, different genes have different historical signals, but these signals are complex and exist at the level of clades within trees rather than as entire gene trees.