bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling mucus clearance in sinuses: thin-film flow inside a fluid-producing cavity lined with an active surface
Authors: Desai Nikhil , Lauga Eric
Published: September 2024

The paranasal sinuses are a group of hollow spaces within the human skull, surrounding the nose. They are lined with an epithelium that contains mucusproducing cells and tiny hairlike active appendages called cilia. The cilia beat constantly to sweep mucus out of the sinus into the nasal cavity, thus maintaining a clean mucus layer within the sinuses. This process, called mucociliary clearance, is essential for a healthy nasal environment and disruption in mucus clearance leads to diseases such as chronic rhinosinusitis, specifically in the maxillary sinuses, which are the largest of the paranasal sinuses. We present here a continuum mathematical model of mucociliary clearance inside the human maxillary sinus. Using a combination of analysis and computations, we study the flow of a thin fluid film inside a fluid-producing cavity lined with an active surface: fluid is continuously produced by a wall-normal flux in the cavity and then is swept out, against gravity, due to an effective tangential flow induced by the cilia. We show that a steady layer of mucus develops over the cavity surface only when the rate of ciliary clearance exceeds a threshold, which itself depends on the rate of mucus production. We then use a scaling analysis, which highlights the competition between gravitational retention and cilia-driven drainage of mucus, to rationalise our computational results. We discuss the biological relevance of our findings, noting that measurements of mucus production and clearance rates in healthy sinuses fall within our predicted regime of steady-state mucus layer development.
Mis-regulation of GSK-3β causes axonal microtubule curling through Shot and Tau
Authors: Voelzmann Andre , Nuhu-Soso Lubna , Roof Alex , Patel Sanjai , Bennett Hayley , Adamson Antony , Bentley Marvin , Evans Gareth J. O. , Hahn Ines
Published: September 2024

Glycogen Synthase Kinase 3β (GSK-3β) is a key coordinator of neuronal development and maintenance; overactive GSK-3β is linked to neurodevelopmental and -degenerative diseases making it a highly promising therapeutic target. One of GSK-3β’s key roles in neurons is to coordinate the cytoskeleton by directly phosphorylating microtubule binding proteins. However, how GSK-3β orchestrates the activities of a range of microtubule regulators, to jointly maintain microtubule bundles is not well understood. We study the function of GSK-3β using fly primary neurons, a uniquely tractable system which has allowed us to unravel the function of >50 cytoskeletal regulators in the past. Here we report a novel function of GSK-3β. We find that kinase activity needs to be tightly regulated to maintain parallel microtubule bundles in axons. Functional up-as well as down-regulation of GSK-3β leads to axons forming pathological swellings where microtubule bundles disintegrate into criss-crossed curling microtubules. Mechanistically, we have identified Shot and Tau as key GSK-3β targets, providing a means to change microtubule behaviours in a time and location-specific manner. By modifying the ability of Shot and Tau to attach to microtubules and Eb1, both hyperactivity as well as inhibition of GSK-3β leads to the loss of Eb1-Shot-mediated guidance of polymerising microtubules into parallel bundles, thus causing disorganisation. Our findings provide new explanations how overactivity of GSK-3β could lead to neurodegeneration in neurodegenerative diseases and why global inhibition of GSK-3β has not been successful in clinical trials for those disorders.
Topology-Driven Discovery of Transmembrane ProteinS-Palmitoylation
Authors: Forrester Michael T. , Egol Jacob R. , Ozbay Sinan , Singh Rohit , Tata Purushothama Rao
Published: September 2024

ProteinS-palmitoylation is a reversible lipophilic posttranslational modification regulating a diverse number of signaling pathways. Within transmembrane proteins (TMPs),S-palmitoylation is implicated in conditions from inflammatory disorders to respiratory viral infections. Many small-scale experiments have observedS-palmitoylation at juxtamembrane Cys residues. However, most large-scaleS-palmitoyl discovery efforts rely on trypsin-based proteomics within which hydrophobic juxtamembrane regions are likely underrepresented. Machine learning– by virtue of its freedom from experimental constraints – is particularly well suited to address this discovery gap surrounding TMPS-palmitoylation. Utilizing a UniProt-derived feature set, a gradient boosted machine learning tool (TopoPalmTree) was constructed and applied to a holdout dataset of viralS-palmitoylated proteins. Upon application to the mouse TMP proteome, 1591 putativeS-palmitoyl sites (i.e. not listed in SwissPalm or UniProt) were identified. Two lung-expressedS-palmitoyl candidates (synaptobrevin Vamp5 and water channel Aquaporin-5) were experimentally assessed. Finally, TopoPalmTree was used for rational design of anS-palmitoyl site on KDEL-Receptor 2. This readily interpretable model aligns the innumerable small-scale experiments observing juxtamembraneS-palmitoylation into a proteomic tool for TMPS-palmitoyl discovery and design, thus facilitating future investigations of this important modification.
Feather keratin inPavo cristatus: A tentative structure
Authors: Russ Peter , Kirchner Helmut O. K. , Peterlik Herwig , Weiss Ingrid M.
Published: September 2024

The filament of the F-keratin polymer is an alternating arrangement of two tetrameric sequence segments, the “N-block” made of four strands AA 1–52, a twisted parallelepiped and the “C-block”, a sandwich of four strands AA 81–100. The N-blocks have 89°internal rotation within eight levels ofβ-sandwiches strengthened by three disulfide bonds per monomer. The C-blocks contain 5 aromatic residues, they provide resilience, like vertebral discs in a spinal column. The pitch of an N+C-block octamer is 10 nm. Solidification of F-keratin may involve the “C-blocks” to temporarily mold into “C-wedges” of 18° tilt, which align the polymer filaments into laterally amorphous fiber-reinforced composites of 9.5 nm axial periodicity. This distance corresponds to the length of the fully stretched AA 53–80 matrix segment. The “spinal column” is deformed like in scoliosis and unwinds under compression when F-keratin filaments perfectly align horizontally and form stacked sheets in the solid state.
Relationship between nonexercise activity and mood in patients with eating disorders
Authors: Olfermann Robin , Schlegel Sabine , Vogelsang Anna , Ebner‐Priemer Ulrich , Zeeck Almut , Reichert Markus
Published: September 2024

Introduction

Many patients with eating disorders (EDs) engage in excessive and compulsive physical activity (pathological exercise, PE) to regulate negative mood or to “burn calories.” PE can lead to negative health consequences. Non‐exercise activity (NEA) bears the potential to serve as intervention target to counteract PE and problematic eating behaviors since it has been associated with positive mood effects. However, to date, there is no investigation on whether the positive link between NEA and mood seen in the healthy translates to patients with ED.

Material and Methods

To study potential associations of NEA and mood in ED, we subjected 29 ED‐patients and 35 healthy controls (HCs) to an ambulatory assessment study across 7 days. We measured NEA via accelerometers and repeatedly assessed mood on electronic smartphone diaries via a mixed sampling strategy based on events, activity and time. Within‐ and between‐subject effects of NEA on mood, PE as moderator, and the temporal course of effects were analyzed via multilevel modeling.

Results

NEA increased valence (β = 2.12, p < 0.001) and energetic arousal (β = 4.02, p < 0.001) but showed no significant effect on calmness. The effects of NEA on energetic arousal where significantly stronger for HCs (β
HC = 6.26, p < 0.001) than for EDs (β
ED = 4.02, p < 0.001; β
interaction = 2.24, p = 0.0135). Effects of NEA were robust across most timeframes of NEA and significantly moderated by PE, that is, Lower PE levels exhibited stronger NEA effects on energetic arousal.

Conclusion

Patients with ED and HC show an affective benefit from NEA, partly depending on the level of PE. If replicated in experimental daily life studies, this evidence may pave the way towards expedient NEA interventions to cope with negative mood. Interventions could be especially promising if delivered as Just‐in‐time adaptive interventions (JITAIs) and should be tailored according to the PE level.
How did the elephant cross the fence? Electric fence crossing by elephants in Udawalawe, Sri Lanka
Authors: Ranjeewa A. D. G. , Thomas R. J. , Weerakoon D. K. , Sandanayake G. H. N. A. , Fernando P.
Published: September 2024

Electric fences are widely used in human–elephant conflict mitigation. However, elephants constantly challenge and overcome fences, which is a growing concern. We studied how elephants crossed the perimeter electric fence around the Udawalawe National Park (UWNP), Sri Lanka. Using camera traps, we monitored 18 fence posts and an open gate in the fence over 605 days from 2016 to 2019. Photographs of 3097 fence crossings were analysed to obtain demographic data for fence crossing elephants, crossing methods, and the daily and seasonal timing of fence crossing. We identified 77 adult males and 12 adult females that crossed the fence, which represent about 17% of the adult elephants in UWNP. Most of the crossings were through the open gate at night. Elephants used a variety of crossing methods, comprised of crossing at the open gate, at previously toppled posts, by crashing through wires and stepping over wires, as well as by using the trunk or forefeet to topple posts. Fence voltage was not a determinant of fence crossing. The frequency and timing of fence crossings varied between locations with later exits and less time spent outside, at crossing points bordering human dominated areas. Our results emphasis on the importance of taking into account the problem solving abilities of elephants in fence design and location, such as energising fence posts and constructing exclosure fences at the boundaries of crop fields and settlements, in employing electric fences to mitigate human‐elephant conflict.
The clinical utility of autologous tumor lysate‐loaded dendritic cell vaccination for patients with glioma: A systematic review and meta‐analysis
Authors: Habibi Mohammad Amin , Mirjani Mohammad Sina , Ahmadvand Muhammad Hussain , Delbari Pouria , Arab Shayan , Minaee Poriya , Eazi SeyedMohammad , Ahmadpour Sajjad
Published: September 2024

Background

Dendritic cell (DC) vaccines show promise for glioma treatment, but optimal use remains uncertain. This meta‐analysis examined DC vaccine efficacy and safety for gliomas.

Methods

This systematic review and meta‐analysis study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses. From the date of inception to October 23, 2023, electronic databases PubMed, Embase, Web of Science, and Scopus have been thoroughly evaluated.

Results

A total of 12 studies with 998 patients and a mean age ranging from 40.2 to 56 years were included. Across 12 articles, DC vaccine 6‐month overall survival (OS) was 100% [95% confidence interval {95%CI}: 100%–100%]. Respectively, 12‐month OS reported 75% [95%CI: 65%–85%] but declined to 32% [95%CI: 20%–43%] for 24‐month OS. 6‐ and 12‐month progression‐free survival reached 49% [95%CI: 21%–77%] and 19% [95%CI:8%–30%]. Studying radiological outcomes shows that complete response and partial response rates were 13% [95%CI: 17%–42%], and 26% [95%CI: 10%–42%], though stable disease reached 33% [95%CI: 15%–51%], suggesting predominant antineoplastic effects. The progressive disease rate also was 24% [95%CI: 9%–57%].

Conclusions

In gliomas, DC vaccinations show a temporary efficacy; stability is more prevalent than regression. Impacts favor decreased resistance to early disease. Enhancing efficacy remains critical. Early therapy can be enhanced by appropriate supplementary therapy integration.
Predicting alcohol consumption: Application of an integrated social cognition model of intentions, habits, and cue consistency
Authors: Simpson‐Rojas Danielle , Phipps Daniel J. , Jenkins Kailas , Fleig Lena , Hagger Martin S. , Hamilton Kyra
Published: September 2024

Drinking alcohol in excess is associated with deleterious health outcomes, highlighting the need for research to identify potentially modifiable correlates of excessive alcohol consumption to target in behavioral interventions. The present two‐wave prospective correlational study applied an integrated theoretical model that included theory of planned behavior constructs alongside habit, cue consistency, affective attitudes, and past behavior as predictors of two alcohol‐related behaviors, drinking within safe limits and regular alcohol drinking, in separate samples of Australian undergraduate students (total N = 474). Structural equation models identified direct effects of habit, affective attitude, and subjective norms on intention for both behaviors. Habit at follow‐up, cue consistency, and past behavior directly predicted behavior in both samples, whereas intention predicted behavior only for drinking within safe limits, and affective attitude only predicted behavior for regular drinking. Cue consistency moderated the effects of habit on behavior for both behaviors and moderated the effect of past behavior on regular drinking. Results corroborate past behavior and habit as key correlates of behavior and provide preliminary evidence of the importance of integrating cue consistency, a defining characteristic of habit, as a moderator of habit and past behavior effects an integrated theory test.
Age‐stage, two‐sex life table and transcriptome analysis reveal the adaptation of Liriomyza trifolii to different host plants
Authors: Yan Yu‐Qing , Chang Ya‐Wen , Gong Wei‐Rong , Hu Jie , Du Yu‐Zhou
Published: September 2024

Liriomyza trifolii (Burgess) (Diptera: Agromyzidae) is a polyphagous insect that is widely known for its invasiveness. Understanding the adaptation of L. trifolii to different host plants is critical in formulating effective approaches for integrated pest management (IPM). In this study, the effects of various host plants on L. trifolii were investigated by age‐stage, two‐sex life tables and transcriptome analysis. Our results show that the growth rate of immature L. trifolii on sponge gourd increased significantly relative to bean, but mortality was high. Mature L. trifolii adapted to sponge gourd had significantly increased longevity as compared to flies adapted to bean but exhibited reduced fecundity. The net reproductive rate, the intrinsic rate of increase, and the finite rate of increase of L. trifolii adapted to sponge gourd were significantly lower than those of flies adapted to bean. Transcriptome analysis showed the presence of 150 up‐ and 617 downregulated differentially expressed genes in L. trifolii adapted to sponge gourd as compared to flies adapted to bean. Genes encoding glutathione‐S‐transferase, cytochrome P450, and trypsin were significantly downregulated in L. trifolii adapted to sponge gourd as compared to bean. This study provides valuable insight into host plant effects on L. trifolii and provides a basis for the subsequent development of IPM measures such as push and pull, crop rotation, and biopesticide development.
Characterisation of chicken breast and soy proteins glycated with konjac glucomannan hydrolysate
Authors: Pomsang Pachara , Phumsombat Putthapong , Borompichaichartkul Chaleeda
Published: September 2024

This study investigated the enhancement of food proteins through glycation with bioactive saccharides derived from Konjac glucomannan hydrolysate (KGMH) via the Maillard reaction. The focus was on how the degree of polymerisation (DP) of KGMH influences the glycation process and the properties of conjugates with chicken breast and soy proteins. KGMH samples with low, medium, and high DPs (4.20, 5.21, and 6.11, respectively) were glycated under wet‐heating conditions with varying pH levels (8, 9, and 10) at 70 °C for 15 min to 6 h. Results demonstrated that higher pH and longer reaction times significantly enhanced (P < 0.05) glycation and browning, particularly with lower DP saccharides. The optimal conjugates markedly improved protein solubility (1.3 to 1.9 times), heat stability (1.1 to 2.4 times), and emulsification properties (1.2 to 1.5 times), with the highest DP showing the strongest correlation. Additionally, these conjugates exhibited significantly enhanced in vitro bioaccessibility (58.69% to 66.65%) and antioxidant activity (P < 0.05). This study highlights the novel potential of KGMH‐protein conjugation through the Maillard reaction for developing functional food ingredients with superior quality.
The effect of debittering by sonication in brine, NaOH and water on bioactive compounds, antioxidant activity of caper (Capparis ovata Desf.) young shoot and buds
Authors: Qasem Akram A. , Mohamed Ahmed Isam A. , Mohammed Belal M. , Brennan Charles S. , Özcan Mehmet Musa , Uslu Nurhan
Published: September 2024

The total carotenoid amounts of the caper young shoot and buds debittered by sonication in brine, NaOH and tap water were reported to be between 19.99 (control) and 37.23 μg g−1 (water) to 4.36 (control) and 20.38 μg g−1 (NaOH), respectively. Total phenolic contents of sonicated caper young shoot and buds in brine, NaOH and tap water were specified to be between 34.96 (NaOH) and 299.84 mg gallic acid equivalent (GAE)/100 g (control) to 45.04 (NaOH) and 373.12 mg GAE/100 g (control), respectively. Radical scavenging activity values of sonicated young shoots were measured between 1.26 (NaOH) and 7.58 mmol trolox equivalent (TE) kg−1 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) (control). In addition to DPPH, antioxidant activity values of sonicated caper young shoot and buds were measured to be between 2.06 (NaOH) and 17.72 Ferric reducing antioxidant power (FRAP), mg g−1 (control) to 1.70 (NaOH) and 13.44 FRAP mg g−1 (control), respectively. Kaempferol quantities of sonicated caper young shoot were identified between 40.08 (control) and 53.83 mg/100 g (Brine). In general, the most reduction in phenolic components was observed in caper young shoot and buds sonicated in NaOH solution. The phenolic components of the caper young shoot and buds sonicated in different solutions showed changes on the solution type when compared to the control.
Improved antioxidant properties and sustainability of whole‐fruit yellow tomato puree
Authors: Pizzolongo Fabiana , Sorrentino Giovanni , Graci Salvatore , Barone Amalia , Romano Raffaele
Published: September 2024

In this study, a new process was proposed to make the yellow tomato puree more sustainable, avoiding any waste during production and including peels and seeds in it. In addition, as raw material tomatoes grown without irrigation and fertilisation procedures were used to increase the sustainability. With respect to a traditional puree, the whole‐fruit yellow tomato puree contained more β‐carotene and polyphenols, exhibiting greater antioxidant capacity, and showed greater consistency due to the high content of pectin in peels. Moreover, a higher content of glutamic acid, responsible for the umami taste, was detected particularly in products from GiaGiù ecotype. Sensory analysis assessed that whole‐fruit yellow tomato puree has good acceptability and consumers preferred it for the texture. In conclusion, the whole‐fruit yellow tomato puree is not only a sustainable product but can be also used as an excellent ingredient in food formulation with antioxidant properties.
Improving physicochemical and biological properties of gelatin‐xylooligosaccharide conjugates by Maillard reaction
Authors: Li Huiyu , Xiong Tao , Du Tonghao , Huang Siyun , Peng Fei
Published: September 2024

Maillard reaction can enhance the functional characteristics of the protein. Herein, we investigated changes in the physicochemical and biological properties of gelatin (GA)‐xylooligosaccharide (XOS) conjugates following Maillard reaction. The results showed that the browning intensity of the conjugates increased with the prolongation of heating time. Additionally, sodium dodecyl sulphate‐polyacrylamide gel electrophoresis revealed some macromolecule polymer formed, and the grafting degree of GA was augmented to 40.05% with prolongation of heating time. GA glycation with XOS decreased α‐Helix content and increased level of β‐Turn level, and exerted a slight impact on contact angle. Moreover, the results of in vitro simulated gastrointestinal digestion analysis showed that the GA‐XOS mixture enhanced resistance to digestion after Maillard reaction for 60 min, affording hydrolysis ratios ranging from 17.86–27.79% and 25.03–35.47% in simulated gastric fluid and intestinal fluid, respectively. The antioxidant ability and heat stability of the conjugates was visibly enhanced following heating treatment. Additionally, increasing the mass of XOS accelerated the antioxidant capacities of GA‐XOS conjugates. The finding will assist the fabrication of GA‐XOS conjugates with highly functional properties by Maillard reaction.
Comparisons of healthcare personnel relating to awareness, concern, motivation, and behaviours of climate and health: A cross‐sectional study
Authors: Rangel Teresa , Johnson Sarah E. , Joubert Patricia , Timmerman Rosemary , Smith Stephan , Springer Gale , Schenk Elizabeth
Published: September 2024

Aim(s)

To describe a sample of healthcare professionals' responses to the valid and reliable Climate and Health Tool and compare participant characteristics relating to Climate and Health Tool subscales.

Design

Observational, cross‐sectional, multi‐site study.

Methods

An electronic survey containing the Climate and Health Tool was administered to healthcare professionals across a large, multi‐state health system in the Western United States with a committed effort to reducing carbon emissions.

Results

One thousand three hundred and sixty‐three participants reported moderately elevated levels of awareness and concern around climate impacts on health and motivation to participate in climate protective actions. Respondents reported moderate levels of climate‐protecting behaviours at home and low levels at work. Females were more concerned and motivated. Medical staff and respondents reporting familiarity with system environmental initiatives reported more awareness and behaviours at home to preserve climate health.

Conclusion

Healthcare professionals are concerned and motivated to decrease climate impacts on health yet take little action at work to preserve the climate. Because of the intersection of climate change, health, and healthcare, healthcare organizations should prioritize and support meaningful action for healthcare professionals to meet community climate health needs.

Implications for the Profession and/or Patient Care

Healthcare organizations committed to contributing to climate solutions can use this research to increase healthcare professionals' education, engagement, and impact to preserve the climate and health of communities.

Impact

Healthcare is a major contributor to carbon emissions, yet healthcare professionals' awareness, motivation, concern, and behaviours related to climate change and health were not clear.

Our research showed healthcare professionals are aware and concerned about climate impacts on health but reported low levels of workplace behaviours to protect the climate.

The findings of our research will impact healthcare professionals and healthcare organizations to focus efforts on climate‐preserving behaviours.

Reporting Method

This manuscript followed the STROBE guidelines.

Patient or Public Contribution

None.
Quantifying the Capacity for Assisted Migration to Achieve Conservation and Forestry Goals Under Climate Change
Authors: Zou Yibiao , Backus Gregory A. , Safford Hugh D. , Sawyer Sarah , Baskett Marissa L.
Published: September 2024

Aim

Many tree species may be threatened with declines in range and biomass, or even extinction, if they cannot disperse or adapt quickly enough to keep pace with climate change. One potential, and potentially risky, strategy to mitigate this threat is assisted migration (AM), the intentional movement of species to facilitate population range shifts to more climatically suitable locations under climate change. The ability for AM to minimise risk and maximise conservation and forestry outcomes depends on a multi‐faceted decision process for determining, what, where and how much to move. We provide an assessment on how the benefits and risks of AM could affect the decision‐making process.

Location

Mountainous coastal western United States.

Taxon

Trees.

Methods

We used a dynamic vegetation model parameterised with 23 tree species.

Results

We found that most of the modelled species are likely to experience a substantial decline in biomass, with many potentially facing regional extinction by 2100 under the high‐emission SSP5‐85 climate‐change scenario. Though simulations show AM had little effect on the forestry goal of total biomass across all species, its effects on the conservation goal of promoting individual species' persistence were far more substantial. Among eight AM strategies (differing in the life cycle stage of movement and target destination selection criteria), the approach that conserved the highest biomass for individual species involved relocating target seedlings to areas that recently experienced fire. Although this strategy significantly reduced extinction risk for six at‐risk species compared with no action, it also slightly reduced biomass of four species, due to increasing competition. Species with relatively weak tolerance to drought, fire or high temperature were the most likely candidate groups for AM.

Main Conclusions

Our simulations indicate that AM can aid conservation by reducing extinction risks for species vulnerable to climate change, but it has limited impact on forestry‐specific goals, affecting overall biomass minimally. This model framework could be applied to other forest ecosystems to evaluate the efficacy of AM globally.
Synthesis of 6‐bromo‐7‐arylaminoisoquinoline‐5,8‐quinones and its effects on Piscirickettsia salmonis infection in vitro
Authors: Ibacache Juana A. , Espinoza Mario , Basualto‐Díaz Paz , Pinto Victoria , Modak Brenda , Zapata Paula , Valenzuela Beatriz
Published: September 2024

Among the most important aquaculture resources for our country, salmon and trout stand out. Their production has increased significantly in recent decades, making them two of the most valuable resources in economic terms. However, high aquaculture production has allowed many pathogens to proliferate, causing infectious diseases and significant production losses. Piscirickettsia salmonis is a gram‐negative, facultative intracellular bacterium that is responsible for causing severe disease in a variety of salmonid fish species. Despite the significant impact of P. salmonis on aquaculture, effective treatments for this disease remain limited. Current prevention and control strategies often include antibiotics and vaccines. However, these treatments have shown varying degrees of efficacy. A promising approach involves synthesizing bioactive analog compounds with antibacterial properties. Quinones, secondary metabolites that are abundant in nature, have become a focal point of interest due to their diverse physiological activities, including antibiotic, insecticidal, antifungal, and anticancer properties. In this study, it is shown the synthesis of series 6‐bromo‐7‐arylaminoisoquinoline‐5,8‐quinones, the characterization of these compounds using classical spectroscopic methods such as one‐dimensional nuclear magnetic resonance (NMR), FT‐IR (infrared), mass spectrometry, and the biological activity against Piscirickettsia salmonis. The brominated derivative compounds showed no cytotoxicity at any concentration evaluated. Furthermore, the infectivity of P. salmonis after treatment with the analog compounds indicated that derivatives methyl 6‐bromo‐7‐((4‐methoxyphenyl)amino)‐1,3‐dimethy‐5,8‐dioxo‐5,8‐dihydroisoquinoline‐4‐carboxylate (4b) and methyl 7‐((4′‐amino‐[1,1′‐biphenyl]‐4‐yl)amino)‐6‐bromo‐1,3‐dimethy‐5,8‐dioxo‐5,8‐dihydroisoquinoline‐4‐carboxylate (4g) reduced the bacterial load at 25 μg/mL concentration.
PRRT in high‐grade digestive neuroendocrine neoplasms (NET G3 and NEC)
Authors: Sorbye Halfdan , Kong Grace , Grozinsky‐Glasberg Simona , Strosberg Jonathan
Published: September 2024

Peptide receptor radionuclide therapy (PRRT) has been primarily studied in low and intermediate‐grade digestive neuroendocrine tumors (NET G1‐G2). The documentation of a similar benefit for high‐grade digestive neuroendocrine neoplasms (NEN) has been limited. This review evaluates the use of PRRT for high‐grade digestive NEN (well‐differentiated NET G3 and poorly differentiated neuroendocrine carcinomas [NEC]). We identified one phase III trial and seven retrospective studies reporting specifically on PRRT outcome of >10 digestive high‐grade NEN patients. The retrospective single‐arm studies indicate a benefit for PRRT in NET G3. The randomized phase III NETTER‐2 trial demonstrates major PFS superiority of PRRT versus somatostatin analog therapy as the first‐line treatment for the NET G3 subgroup. PRRT can now be considered a potential first‐line treatment for somatostatin receptor‐positive NET G3 patients, but whether it should be the first‐line standard of care for all NET G3 patients is still not clarified. For NEC, scarce data are available, and pathologic distinction between NEC and NET G3 can be difficult when Ki‐67 is below 55%. PRRT could be considered as a treatment for refractory NEC in very selected cases when there is a high uptake on somatostatin receptor imaging, Ki‐67 is below 55%, and there is no rapid tumor progression.
Help‐Seeking Needs Related to Suicide Prevention for Individuals in Contact With Mental Health Services: A Rapid Scoping Review
Authors: Shin Hwayeon Danielle , Kemp Jessica , Groves Samantha , Bennett‐Poynter Laura , Pape Charlotte , Lascelles Karen , Strudwick Gillian
Published: September 2024

Introduction

Prior mental healthcare utilisation presents an important window of opportunity for providing suicide prevention interventions. To date, no reviews have consolidated the help‐seeking needs of individuals in contact with mental health services. This warrants further attention given this group may have different needs for interventions compared with the general population who have not sought help previously.

Aim

The purpose of this rapid scoping review was to summarise the available literature on help‐seeking needs related to suicide prevention among individuals in contact with mental health services from healthcare settings.

Method

Cochrane rapid review and Joanna Briggs Institute scoping review methodologies were adapted, and databases, including MEDLINE, Scopus, CINAHL, PsycInfo and EMBASE, were searched.

Results

A total of 42 primary studies were included in analysis. Reported barriers and facilitators to help‐seeking behaviours identified within studies were mapped onto the socio‐ecological model. Barriers and facilitators identified included knowledge and attitudes towards healthcare utilisation, family and peer support, interactions with healthcare professionals, provision of holistic care, and the creation of a supportive atmosphere and safe space to promote open discussions of suicide‐related concerns.

Discussion

The findings of this review offer valuable insights into areas for improvement in addressing help‐seeking needs for individuals who are in contact with health services related to suicide prevention.

Implication for Research

The findings serve as a foundation for shaping mental health initiatives informing approaches and care delivery tailored towards individuals who are in contact with health services. The reported barriers and facilitators offer insights to inform the development of mental health support tools to enhance care and considerations for evaluations.
O le Fau Gagana: A Samoan Mental Health Nurse in Aotearoa‐New Zealand
Authors: Mulipola Taavale Ioana
Published: September 2024

Introduction

This article explores my journey as a Samoan woman who migrated as a young mother to Aotearoa‐New Zealand, completed nursing qualifications, later specialising in mental health nursing, and eventually completed doctoral studies. Since July 2023 I have been a Lecturer in the Department of Nursing, Faculty of Health and Environmental Studies, Auckland University of Technology.

Methods

This article uses autoethnographic and narrative methods to collect data from my own life, to explore the experiences of Samoan people in the mental health system of Aotearoa‐New Zealand. Criteria for reporting qualitative research was used to prepare the paper.

Findings

My story showcases the benefits of having both clinical and cultural understandings in the context of mental health care in Aotearoa‐New Zealand. The gap between the rhetoric and the reality of the ‘New Zealand dream’ for Samoan people mirrors the gap between policy and practice in relation to Pacific strategy plans for mental health care.

Conclusions

By writing about my experiences, I aim to support better understanding of core concerns for Samoan people when they are engaging with mental healthcare services.
Transcriptomic and functional analyses on a Botrytis cinerea multidrug‐resistant (MDR) strain provides new insights into the potential molecular mechanisms of MDR and fitness
Authors: Sofianos Georgios , Piombo Edoardo , Dubey Mukesh , Karlsson Magnus , Karaoglanidis George , Tzelepis Georgios
Published: September 2024

Botrytis cinerea is a notorious pathogen causing pre‐ and post‐harvest spoilage in many economically important crops. Excessive application of site‐specific fungicides to control the pathogen has led to the selection of strains possessing target site alterations associated with resistance to these fungicides and/or strains overexpressing efflux transporters associated with multidrug resistance (MDR). MDR in B. cinerea has been correlated with the overexpression of atrB and mfsM2, encoding an ATP‐binding cassette (ABC) and a major facilitator superfamily (MFS) transporter, respectively. However, it remains unknown whether other transporters may also contribute to the MDR phenotype. In the current study, the transcriptome of a B. cinerea multidrug‐resistant (MDR) field strain was analysed upon exposure to the fungicide fludioxonil, and compared to the B05.10 reference strain. The transcriptome of this field strain displayed significant differences as compared to B05.10, including genes involved in sugar membrane transport, toxin production and virulence. Among the induced genes in the field strain, even before exposure to fludioxonil, were several putatively encoding ABC and MFS transmembrane transporters. Overexpression of a highly induced MFS transporter gene in the B05.10 strain led to an increased tolerance to the fungicides fluopyram and boscalid, indicating an involvement in efflux transport of these compounds. Overall, the data from this study give insights towards better understanding the molecular mechanisms involved in MDR and fitness cost, contributing to the development of more efficient control strategies against this pathogen.
Impact of single centre kidney‐exchange transplantation to increase living donor pool in India: A cohort study involving non‐anonymous allocation
Authors: Kute Vivek B. , Patel Himanshu V. , Banerjee Subho , Engineer Divyesh P. , Dave Ruchir B. , Shah Nauka , Chauhan Sanshriti , Meshram Harishankar , Tambi Priyash , Shah Akash , Saxena Khushboo , Balwani Manish , Parmar Vishal , Shah Shivam , Prakash Ved , Patel Sudeep , Patel Dev , Desai Sudeep , Rizvi Jamal , Patel Harsh , Parikh Beena , Kanodia Kamal , Gandhi Shruti , Rees Michael A. , Roth Alvin E. , Modi Pranjal
Published: September 2024

Aim

In India, 85% of organ donations are from living donors and 15% are from deceased donors. One‐third of living donors were rejected because of ABO or HLA incompatibility. Kidney exchange transplantation (KET) is a cost‐effective and legal strategy to increase living donor kidney transplantation (LDKT) by 25%–35%.

Methods

We report our experience with 539 KET cases and the evolution of a single‐centre program to increase the use of LDKT.

Results

Between January 2000 and 13 March, 2024, 1382 deceased donor kidney transplantations and 5346 LDKT were performed at our centre, including 10% (n = 539) from KET. Of the 539 KET, 80.9% (n = 436) were ABO incompatible pairs, 11.1% (n = 60) were compatible pairs, and 8% (n = 43) were sensitized pairs. There were 75% 2‐way (n = 2 × 202 = 404), 16.2% 3‐way (n = 3 × 29 = 87), 3% 4‐way (n = 4 × 4 = 16), 1.8% 5‐way (n = 5 × 2 = 10), 2.2% 6‐way (n = 6 × 2 = 12), and 1.8% 10‐way KET (n = 10 × 1 = 10). Of the recipients 81.2% (n = 438) were male and 18.8% (n = 101) were female, while of the donors, 78.5% (n = 423) were female and 21.5% (n = 116) were male. All donors were near relatives; wives (54%, n = 291) and mothers (20%, n = 108) were the most common donors. At a median follow‐up of 8.2 years, patient survival, death censored graft survival, acute rejection, and median serum creatinine levels of functioning grafts were 81.63% (n = 440), 91% (n = 494), 9.8% (n = 53) and 1.3 mg/dL respectively. We credited the success to maintaining a registry of incompatible pairs, high‐volume LDKT programs, non‐anonymous allocation and teamwork.

Conclusion

This is the largest single‐centre KET program in Asia. We report the challenges and solutions to replicate our success in other KET programs.

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Impact of maxillary expansion on the sagittal skeletal and dental parameters of growing Class II patients: A systematic review with meta‐analysis
Authors: Cannatà Davide , Galdi Marzio , Scelza Carmine , Simeon Vittorio , Giordano Francesco , Martina Stefano
Published: September 2024

A “spontaneous” correction of the Class II malocclusion has been described after maxillary expansion (ME) treatment. The aim of the present review was to systematically summarize changes in the sagittal dentoskeletal parameters of growing Class II patients after ME. The study protocol was developed according to the PRISMA statement and registered in PROSPERO before literature search, data extraction and analysis. The PICO model was followed in the definition of the research question, search strategies and study selection criteria. Randomized and non‐randomized studies on the sagittal effects of ME published in English language without date restrictions were electronically searched across the Cochrane Library, Scopus and MEDLINE/PubMed databases. Changes in sagittal dentoskeletal cephalometric parameters were analysed. The risk of bias in randomized and nonrandomized studies was assessed using the Rob2 and ROBINS‐I tools, respectively. A narrative synthesis was performed, focusing on the investigated population, intervention, comparison, and main outcomes. Pairwise meta‐analyses were used to compare the outcomes assessed in subjects who underwent ME versus untreated subjects. Ten studies met the inclusion criteria, four were included in the pairwise meta‐analyses due to the presence of a control group. Slight but significant improvements in OVJ (MD: −0.36; 95%; CI [−0.69 to −0.01]; p = .04) and 6/6 molar relation (MD: 1.5; 95%; CI [0.69 to 1.61]; p < .0001) were found in patients who underwent ME compared with untreated subjects, whereas no improvement in skeletal parameters was observed. However, the limitations of a small body of moderate‐quality evidence and possible confounding factors should be considered. Evidence on the sagittal skeletal and dental effects of ME in Class II patients is still ambiguous, suggesting the need for more clinical trials, including appropriate control subjects, randomization and blinding during outcome assessment.
Accuracy of measurements on CBCT‐generated digital models using different exposure parameters (in vitro study)
Authors: Ibrahim Noura , Abouelkheir Hassan Mohamed , Elkersh Noha Mohamed
Published: September 2024

Introduction

Dental imaging comprises a wide range of techniques and modalities, each with different diagnostic features influenced by numerous parameters, all of which contribute to the precision and effectiveness of dental evaluations and treatments. This study examined the dimensional reproducibility of arch measurements from CBCT scans with different voxel sizes and exposure parameters compared to a reference model from Extra‐oral scanners (EOS) and how these parameters affected digital matching and diagnostic image quality.

Methods

A diagnostic observational study of arch dimensions, including inter‐canine, inter‐premolar, intermolar, arch width and arch length, was conducted on digital models (DMs) created from 65 CBCT scans of a full dentate epoxy maxillary model. The measurements obtained from EOS scans served as the control for the study. Normality was tested with the Shapiro–Wilk test, comparisons used the Kruskal–Wallis test with Bonferroni‐adjusted pairwise comparisons for significant results, and data were analysed using IBM SPSS (Version 26.0), with significance set at p < .05.

Results

Significant deviations were revealed among study groups, with group I (smallest voxel size) consistently displaying the lowest values, mean (SD) deviation was reported as 0.01 (0.006) and group IV (lowest kV value) exhibiting the highest deviations, mean (SD) deviation of 0.16 (0.17).

Conclusion

Combining a small voxel size (0.12 mm) with high milliampere (8 mA) and kilovoltage (90 kV) settings in CBCT ensured detailed anatomical visualization and accurate linear measurements, crucial for precise dental assessments, and emphasizing the necessity for strict control over CBCT parameters in dental applications.
Vaccines and allergy: Back to the right places
Authors: Moschese Viviana , Montin Davide , Ottaviano Giorgio , Sgrulletti Mayla , Beni Alessandra , Costagliola Giorgio , Sangerardi Maria , Santilli Veronica , Miraglia Del Giudice Michele , Rizzo Caterina , Martire Baldassarre ,   within the Italian Society of Pediatric Allergology and Immunology (SIAIP) Vaccine Committee
Published: September 2024

Hypersensitivity reactions represent one of the most common causes of hesitancy for adherence to national vaccination programs. The majority of hypersensitivity reactions after vaccination are mild, and anaphylaxis is reported to be rare, although it remains challenging to estimate the frequency attributed to each single vaccine, either because of the lower number of administered doses of less common vaccines, or the administration of simultaneous vaccine in most of the vaccination programs. Although literature remains scattered, international consensus guides clinicians in identifying patients who might need the administration of vaccines in protected environments due to demonstrated hypersensitivity to vaccine components or adjuvants. Here we provide the current guidance on hypersensitivity reactions to vaccines and on vaccination of children with allergy disorders.
A review of the perioperative management of direct oral anticoagulants for pediatric anesthesiologists
Authors: Furman Kara , Giustini Andrew , Branstetter Joshua , Woods Gary , Downey Laura A.
Published: September 2024

Background

Although direct oral anticoagulants (DOACs) have been used in the adult population for over a decade, DOACs use has begun to rise in pediatric populations since FDA approval of rivaroxaban and dabigatran, DOACs offer several advantages for pediatric patients, to other anticoagulants, including a similar safety profile, minimal lab monitoring, and ease of administration. The rise in DOAC use has led to an increasing number of pediatric patients managed on DOACs presenting for elective and urgent procedures. Perioperative management of anticoagulation is often challenging for providers due to the lack of expert consensus guidelines and the difficulty in balancing a patient's thrombotic risk with bleeding risk for a given procedure.

Aims

Using the most up to date literature, we provide a focused review on the perioperative management of DOACs in pediatric patients.

Conclusions

This work presents a focused review for pediatric anesthesiologists on clinically available DOACs, perioperative monitoring and management of DOACs, as well as options and indications for reversal. While consensus expert practice guidelines are still needed, we hope this work will familiarize perioperative physicians with these agents, recommended uses, and potential perioperative management.
Perioperative anesthetic management of patients with hypoplastic left heart syndrome undergoing the comprehensive stage II surgery—A review of 148 cases
Authors: Müller Matthias , Lurz Florian , Zajonz Thomas , Edinger Fabian , Yörüker Uygar , Thul Josef , Schranz Dietmar , Akintürk Hakan
Published: September 2024

Background

Patients with hypoplastic left heart syndrome undergo the comprehensive stage 2 procedure as the second stage in the hybrid approach toward Fontan circulation. The complexity of comprehensive stage 2 procedure is considered a potential limitation, and limited information is available on its anesthetic management. This study aims to address this gap.

Methods

A single‐center retrospective cohort study analyzed 148 HLHS patients who underwent comprehensive stage 2 procedure, divided into Group A (stable condition, n = 116) and Group B (requiring preoperative intravenous inotropic therapy, n = 32). Demographic data, intraoperative hemodynamics, anesthetic management, and postoperative outcomes were collected.

Results

Etomidate (40%) was the most common induction agent, followed by esketamine (24%), midazolam (16%), and propofol (13%). Inhaled induction was rarely necessary (2%), occurring only in Group A patients. No statistical differences were found between groups for induction drug choice. Post‐cardiopulmonary bypass management included moderate hypoventilation, inhaled nitric oxide (100%), and hemodynamic support with milrinone (97%) and norepinephrine (77%). Group B patients more frequently required additional levosimendan (20%) and epinephrine (18%). Extracorporeal membrane oxygenation was necessary in 8 patients (5%) with no between‐group differences. Switching from fentanyl to remifentanil reduced postoperative ventilation time overall. However, Group B experienced significantly longer ventilation (6.3 vs. 3.5 h) and ICU stay (22 vs. 14 days). In‐hospital mortality was 5% overall (Group A: 4%, Group B: 9%). Long‐term survival analysis revealed a significant advantage for Group A.

Conclusion

The use of short‐acting opioids and adjusted ventilation modes enables optimal pulmonary blood flow and rapid transition to spontaneous breathing. Differentiated hemodynamic support with milrinone, norepinephrine, supplemented by levosimendan and epinephrine in high‐risk patients, can mitigate the effects on the preoperatively volume‐loaded right ventricle. However, differences in long‐term survival probability were observed between groups.

Trial Registration

Local ethics committee, Medical Faculty, Justus‐Liebig‐University‐Giessen (Trial Code Number: 216/14).