bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing a head‐mounted virtual reality perimeter and the Humphrey Field Analyzer for visual field testing in healthy and glaucoma patients
Authors: Phu Jack , Wang Henrietta , Kalloniatis Michael
Published: October 2023

Purpose

To compare clinical visual field outputs in glaucoma and healthy patients returned by the Humphrey Field Analyzer (HFA) and virtual reality (Virtual Field, VF) perimetry.

Methods

One eye of 54 glaucoma patients and 41 healthy subjects was prospectively tested (three times each in random order) using the HFA and VF perimeters (24‐2 test grids). We extracted and compared global indices (mean deviation [MD] and pattern standard deviation [PSD]), pointwise sensitivity (and calculated ‘equivalent’ sensitivity after accounting for differences in background luminance) and pointwise defects. Bland–Altman (mean difference [Mdiff] and 95% limits of agreement [LoA]) and intraclass correlation analyses were performed.

Results

The VF test was shorter (by 76 s) and had lower fixation losses (by 0.08) and false‐positive rate (by 0.01) compared to the HFA (all p < 0.0001). Intraclass correlations were 0.86, 0.82 and 0.47 for MD, PSD and pointwise sensitivity between devices, respectively. Test–retest variability was higher for VF (Mdiff 0.3 dB, LoA −7.6 to 8.2 dB) compared to the HFA (Mdiff −0.3 dB, LoA −6.4 to 5.9 dB), indicating greater test–retest variability. When using each device's underlying normative database, the HFA detected, on average, 7 more defects (at the p < 0.05 level) out of the 52 test locations compared to this iteration of VF in the glaucoma cohort.

Conclusions

Virtual Field returns global results that are correlated with the HFA, but pointwise sensitivities were more variable. Differences in test–retest variability and defect detection by its current normative database raise questions about the widespread adoption of VF in lieu of the HFA.
The presentation of anxiety and depression among children and youth diagnosed with hidradenitis suppurativa: A review
Authors: Shojaei Delaram , Liu Chaocheng , Lam Joseph
Published: October 2023

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition with painful lesions in friction‐prone areas, impacting patients' physical and mental well‐being. Adults with HS experience higher rates of depression, anxiety, and reduced quality of life. Children with HS may also face these challenges, but a comprehensive review of their mental health implications is lacking. A narrative review was conducted using PubMed and Ovid Medline databases to investigate the association between HS and anxiety or depression in pediatric populations. A total of 4498 pediatric patients from six studies were included in this study: six examined depression alone, and three also studied anxiety. Two studies found a significant correlation between HS and depression in pediatric patients (p < .001), while two reported statistical significance for anxiety (p < .001). Two studies comparing pediatric and adult populations also reported a higher prevalence and incidence of depression among pediatric populations (p < .05). Another study found no incidences of depression or anxiety in HS or control patients. Despite heterogeneity in control groups, methodologies, and health system databases, the included studies suggest that pediatric patients with HS have a higher likelihood of developing depression compared to healthy pediatric patients and exhibit higher depression rates and lower anxiety rates compared to adults. These findings and the limited availability of data regarding this topic underscore the imperative for increased screening, evaluation, and reporting of psychiatric disorders among pediatric populations. This can help understand the connection between HS and depression or anxiety and ultimately enhance the mental well‐being and quality of life for affected children.
Incidence and clinical risk factors of Bednar's aphthae in Japanese newborns
Authors: Narukama Risako , Takahashi Keigo , Arimitsu Takeshi , Hara‐Isono Kaori , Shimizu Hajime , Ikeda Kazushige
Published: October 2023

Background

The etiology of Bednar's aphthae remains unclear. Our aim was to investigate the incidence of, and factors associated with, Bednar's aphthae in a Japanese newborn cohort.

Methods

A retrospective cross‐sectional study was conducted on neonates discharged from the well‐baby nursery at Saitama City Hospital, Japan. The principal investigator carefully examined each neonate's oral cavity, up to and including the pharynx, with a light‐emitting diode (LED) headlight to determine the presence of Bednar's aphthae. Maternal and neonatal clinical characteristics were first compared between neonates with and those without Bednar's aphthae by univariate analysis. Variables with significant inter‐group differences upon univariate analysis were entered into a multivariable logistic‐regression model.

Results

This study enrolled 1996 infants. We observed Bednar's aphthae in 9.3% of the Japanese newborn infants who were included. When restricted to infants who were born via vaginal delivery, 13.2% of them had aphthae. Multivariable logistic regression analysis identified vaginal delivery (odds ratio = 6.19, p < 0.0001) in Model 1, and vaginal delivery (odds ratio = 6.73, p < 0.0001) and birth weight (odds ratio = 0.9995, p = 0.034) in Model 2 as independent risk factors for the disease.

Conclusion

This is the first report of the prevalence of Bednar's aphthae among Japanese neonates. Vaginal delivery was identified as the strongest risk factor. Although confounding between mode of delivery and mechanical stimuli associated with sucking was not found in this study, the findings pave the way for a better understanding of the etiology of Bednar's aphthae.
A 2‐week intensive gastrointestinal endoscopy training program for pediatricians
Authors: Nishimoto Satomi , Kudo Takahiro , Horiuchi Akira , Horiuchi Ichitaro , Yabe Kiyoaki
Published: October 2023

Background

In Japan there are limited opportunities for pediatricians to learn gastrointestinal (GI) endoscopy. This study investigated whether a short‐term intensive training for 2 weeks in an adult GI setting enabled pediatricians to acquire basic technical competence for pediatric GI endoscopic procedures.

Methods

This was a retrospective case series of pediatricians who underwent 2 weeks of intensive endoscopy training at an adult endoscopy unit in a community hospital. The numbers of esophagogastroduodenoscopy (EGD) and ileocolonoscopy procedures each pediatrician performed were evaluated. All enrolled pediatricians were asked to answer questionnaires regarding the 2 week intensive GI endoscopy training program.

Results

There were 17 enrolled pediatricians, of whom 13 were men; average age 32 years (range 27–54). The median (range) numbers of EGDs and ileocolonoscopies performed by each pediatrician during the 2‐week training period were 102 (66–144) and 14 (1–48), respectively. Fifteen out of 17 pediatricians experienced more than 100 GI endoscopies during the 2 weeks. All pediatricians performed biopsies as part of some EGD procedures. All 17 pediatricians found this program satisfactory. All pediatricians became cable of performing pediatric EGD (i.e., for children ≤15 years) after this training program. Sixteen pediatricians have continued to perform pediatric GI endoscopy since this training program.

Conclusions

A short‐term intensive training program for 2 weeks in an adult GI setting enabled pediatricians to acquire basic technical competence for pediatric endoscopic procedures.
Challenging the status quo in a non‐challenging way: A dominance complementarity view of voice inquiry
Authors: Lam Chak Fu , Romney Alexander C. , Newton Daniel W. , Wu Wen
Published: October 2023

Speaking up directly promotes voice endorsement because it enhances communication clarity. Yet, voicers may hesitate to engage in direct voice because it is a dominant communication tactic that may upset, impose on, embarrass, or undermine their leader, potentially resulting in a backlash, greater workload, or a tainted image. These concerns present a puzzle regarding whether alternative communication tactics exist whereby voicers can secure endorsement for improvement‐oriented initiatives without directly challenging their leader. To address this puzzle, we introduce voice inquiry—expressing improvement‐oriented suggestions or concerns in the form of a question—as a submissive communication tactic to secure endorsement. Drawing upon dominance complementarity theory, we argue that voice inquiry prompts endorsement because it enhances leader's sense of power. Given the complementary effect of submissiveness and dominance, we further predict that this effect will be stronger when leader dominance is high. We conducted three Pilot Studies to unpack the content, motivation, prevalence, and submissive nature of voice inquiry. Building on this foundation, we conducted a multi‐wave field study with 373 employees and 178 leaders in a transportation company (Study 1) and a vignette experiment with 243 full‐time workers (Study 2). Across studies, our research demonstrates voice inquiry as a theoretically driven communication tactic that increases endorsement by activating leader sense of power, particularly among dominant leaders.
Draft genome sequence of Colletotrichum fructicola causing leaf spot on tea plants (Camellia sinensis)
Authors: Lv Wuyun , Jiang Hong , Li Xiaolong , Lu Qinhua , Wang Xinchao , Wang Yuchun
Published: October 2023

Colletotrichum fructicola, one of the dominant pathogens isolated from the main tea region in China, causes leaf spot in mature leaves of tea plants, affecting their growth and yield. Here, we present the draft whole‐genome sequence of the C. fructicola strain SX‐6 previously used for morphological and transcriptomic analyses. The assembly consists of 510 contigs with an estimated genome size of 56.8 Mb. A total of 15,243 predicted protein‐coding genes in the SX‐6 genome were annotated using NR, Swiss‐Prot, KEGG, KOG, TCDB, GO, PHI, DFVF, P450, SignalP and CAZy databases. We identified 833 carbohydrate‐active enzymes, 1803 secreted proteins, 79 secondary metabolite gene clusters and 576 fungal virulence factors that may be involved in the pathogenicity of this fungus. Comparative genome analyses with 25 Colletotrichum species revealed their evolutionary relationships via a constructed phylogenetic tree and identified four gene families whose genes were significantly more abundant in strain SX‐6. The resulting assembly will provide a valuable resource for further research on the gene functions of C. fructicola.
Relationship between eating problems and the risk of dementia: A retrospective study
Authors: Sun Weiyi , Matsuoka Teruyuki , Imai Ayu , Narumoto Jin
Published: October 2023

Background

Older adults and individuals with decreased cognition often experience appetite changes and weight loss. As weight loss can result in cognitive decline, change in appetite may be an important contributor to the onset of dementia. However, there is a lack of relevant studies on this topic. This study aimed to determine the relationship between appetite changes, weight loss, and dementia onset.

Methods

A total of 135 patients with normal cognitive function, subjective cognitive impairment, and mild cognitive impairment who were assessed using the Neuropsychiatric Inventory 12 item version (NPI‐12) and followed up for at least 1 month were enrolled in the study. All patients underwent a Mini‐Mental State Examination (MMSE). Eating problems were assessed using the NPI Eating Problems Score. Appetite and weight loss were assessed at the first visit by caregivers. Kaplan–Meier survival analyses with a log‐rank test were used to compare the time to the onset of dementia between the presence or absence of the NPI eating problems, appetite loss, weight loss, or NPI depression scores. Cox proportional hazards regression models using the forced entry method were employed to estimate the hazard ratio (HR) for dementia.

Results

Weight loss was significantly related to dementia onset (P = 0.027) in the Kaplan–Meier survival analyses, while eating problems, appetite loss, and depression showed no significant association (P = 0.519, P = 0.326, and P = 0.317, respectively). In the Cox proportional hazards regression models, the MMSE score was found to be a significant factor (P = 0.021, HR = 0.871); moreover, weight loss tended to increase the risk of dementia onset (P = 0.057, HR = 1.694).

Conclusions

Weight loss experienced by older adults could contribute to an increased risk of developing dementia.
Asymmetric nexus between pandemic uncertainty and public health spendings: Evidence from quantile estimation
Authors: Teng Chenmei , Zhu Xiaoya , Nazar Raima , Kanwal Tahira
Published: October 2023

The COVID‐19 pandemic has brought significant challenges to healthcare systems worldwide, prompting governments to allocate substantial resources toward public health spendings (PHS). However, the uncertainties surrounding the pandemic have raised questions about the effectiveness and sustainability of such expenditures. This research analyzes the nonlinear link between pandemic uncertainty (PNU) and PHS in countries with highest PNU (USA, India, France, Germany, UK, Saudi Arabia, South Korea, Indonesia, Japan, and China). Previous studies have employed panel data methodologies to establish consistent findings regarding the relationship between pandemics and health spendings, regardless of the fact that several countries have not autonomously recognized this connection. In contrast, this current research adopts a distinctive tool called “quantile‐on‐quantile,” which enables the examination of time series dependency within each economy, providing both international and country‐specific perspectives on the relationship between the variables. The estimations indicate that PNU leads to an increase in PHS in the vast majority of economies chosen by us, focusing on definite segments of the data distribution. Moreover, the data demonstrates that there are differences in the asymmetry between the variables across various nations. This underscores the need for policymakers to take careful deliberation when formulating policies related to health spendings and addressing the challenges posed by pandemic uncertainty.
Interleukin‐1β triggers muscle‐derived extracellular superoxide dismutase expression and protects muscles from doxorubicin‐induced atrophy
Authors: Yamada Mami , Okutsu Mitsuharu
Published: October 2023

Doxorubicin, a conventional chemotherapeutic agent prescribed for cancer, causes skeletal muscle atrophy and adversely affects mobility and strength. Given that doxorubicin‐induced muscle atrophy is attributable primarily to oxidative stress, its effects could be mitigated by antioxidant‐focused therapies; however, these protective therapeutic targets remain ambiguous. The aim of this study was to demonstrate that doxorubicin triggers severe muscle atrophy via upregulation of oxidative stress (4‐hydroxynonenal and malondialdehyde) and atrogenes (atrogin‐1/MAFbx and muscle RING finger‐1) in association with decreased expression of the antioxidant enzyme extracellular superoxide dismutase (EcSOD), in cultured C2C12 myotubes and mouse skeletal muscle. Supplementation with EcSOD recombinant protein elevated EcSOD levels on the cellular membrane of cultured myotubes, consequently inhibiting doxorubicin‐induced oxidative stress and myotube atrophy. Furthermore, doxorubicin treatment reduced interleukin‐1β (IL‐1β) mRNA expression in cultured myotubes and skeletal muscle, whereas transient IL‐1β treatment increased EcSOD protein expression on the myotube membrane. Notably, transient IL‐1β treatment of cultured myotubes and local administration in mouse skeletal muscle attenuated doxorubicin‐induced muscle atrophy, which was associated with increased EcSOD expression. Collectively, these findings reveal that the regulation of skeletal muscle EcSOD via maintenance of IL‐1β signalling is a potential therapeutic approach to counteract the muscle atrophy mediated by doxorubicin and oxidative stress.

image

Key points

Doxorubicin, a commonly prescribed chemotherapeutic agent for patients with cancer, induces severe muscle atrophy owing to increased expression of oxidative stress; however, protective therapeutic targets are poorly understood.

Doxorubicin induced muscle atrophy owing to increased expression of oxidative stress and atrogenes in association with decreased protein expression of extracellular superoxide dismutase (EcSOD) in cultured C2C12 myotubes and mouse skeletal muscle.

Supplementation with EcSOD recombinant protein increased EcSOD levels on the cellular membrane of cultured myotubes, resulting in inhibition of doxorubicin‐induced oxidative stress and myotube atrophy.

Doxorubicin treatment decreased interleukin‐1β (IL‐1β) expression in cultured myotubes and skeletal muscle, whereas transient IL‐1β treatment in vivo and in vitro increased EcSOD protein expression and attenuated doxorubicin‐induced muscle atrophy.

These findings reveal that regulation of skeletal muscle EcSOD via maintenance of IL‐1β signalling is a possible therapeutic approach for muscle atrophy mediated by doxorubicin and oxidative stress.
Effect of Fuel Reactivity and Operating Conditions on Flame Anchoring in the Premixing Zone of a Swirl Stabilized Gas Turbine Combustor
Authors: Tartsch Simon , Flebbe Saskia , Marques de Sousa Ponte Germano J. , Sattelmayer Thomas
Published: October 2023

Flashback with subsequent flame anchoring (FA) is an inherent risk of lean premixed gas turbine combustors operated with highly reactive fuel. The present study has been performed to characterize flame stabilization in the premixing zone of a lean premixed swirl stabilized burner and to identify critical combustion characteristics. An optically accessible burner was used for experimental investigations under atmospheric pressure and elevated preheat temperatures. The air mass flowrate, global equivalence ratio and preheat temperature were systematically varied to identify critical operating parameters. Hydrogen-natural gas mixtures with hydrogen mass fractions from 15 to 100% were studied to evaluate the impact of fuel reactivity. The air-fuel mixture was ignited with a focused single laser pulse to trigger FA in the premixing zone during steady operation. High speed imaging with OH*-chemiluminescence were applied to observe flame characteristics and evaluate flame anchoring propensity. Flame anchoring limits (FAL) are reported in terms of the minimum global equivalence ratio at which the flame was blown out of the premixing zone within a critical time period. A comparison of characteristic time scales at FAL shows that the main impact during flame anchoring is given by the fuel reactivity and to some ex tent by preheat temperature. A Damköhler criterion is derived from the FAL that allows prediction of FA propensity based on operating conditions and 1-D reacting simulations.
Validation of Rotating Detonation Combustor Computational Fluid Dynamics Simulations for Predicting Unsteady Supersonic–Subsonic Flow Field at the Exit
Authors: Raj Piyush , Talukdar Shaon , Langer Dalton , Gupta Apurav , Meadows Joseph , Agrawal Ajay
Published: October 2023

Rotating detonation combustors (RDCs) have gained increased interest for integration with power-generating gas turbines due to the potential to increase thermal efficiency. The unsteady flow field exiting the RDC is fundamentally different compared to traditional swirl-stabilized combustors. Successful integration of RDC with gas turbines will depend on the ability to properly condition the unsteady flow to achieve performance levels comparable to swirl-stabilized combustors. RDC simulations require significant computational resources due to the small spatial and temporal time scales required to resolve the detonation phenomenon. Furthermore, traditional steady-state computational fluid dynamics (CFD) analyses are not possible for RDC simulations. The present study develops and validates a computationally efficient approach for predicting unsteady flow fields exiting the combustor using 2D, transient reacting CFD with periodic boundary conditions in the combustor and a downstream plenum. Validation is performed by comparing the CFD results to various experimental measurements: (i) wave speed obtained from high-speed ion probe and dynamic pressure data, (ii) average wall static pressure measurements, and (iii) time-resolved particle image velocimetry (PIV) at 100 kHz at the RDC exit. Results indicate good agreement between CFD and experiments with respect to velocity field exiting the RDC, detonation wave speed, and static pressure distribution.
Experimental and Numerical Investigations of Steam Expansion Rate in Low Pressure Steam Turbine
Authors: Tabata Soichiro , Segawa Kiyoshi , Takahashi Tadashi , Aoyagi Jin
Published: October 2023

This study focused on the expansion rate of steam; the effect on efficiency was investigated experimentally and numerically by varying the expansion rate of steam in the stage, where condensation occurs by varying the flowrate and inlet temperature using a five-stage model steam turbine. The steam expansion rate of the stator blades in each stage was evaluated from the measured wall pressure and total pressure. In addition, the turbine efficiency was evaluated from the measured torque and mass flowrate, and the effect of flowrate and condensing stage can be taken into account for losses caused by condensation. In addition, numerical calculations to account for the effects of nonequilibrium condensation were performed using ANSYS CFX. The numerical calculations were able to show the details of the nucleation situation and the resulting changes in flow patterns. Numerical evaluation of the subcooling loss showed that there was no difference in subcooling loss between different mass flow rates. The steam expansion rate was evaluated from the measurement results, and it was found that there was no difference in the steam expansion rate due to differences in mass flowrate. This corresponds to the numerical result that the subcooling loss does not vary with flowrate.
Characterization of Tool Surface Properties Generated by Directed Energy Deposition and Subsequent Ball Burnishing
Authors: Komodromos Anna , Grodotzki Joshua , Kolpak Felix , Tekkaya A. Erman
Published: October 2023

By directed energy deposition (DED), a flexible design of cooling channels in forming tools, e.g., hot stamping, with a variety of sizes and a high positioning flexibility compared to machining processes is possible. The subsequent ball burnishing of the tool surfaces, in combination with a variation of the DED process parameters, enables control of the tool surface properties and friction behavior. Parameters such as the ball-burnishing pressure or the path overlapping in the DED process are investigated to quantify their effects on roughness, hardness, friction, residual stresses, and heat transfer coefficient of generic tool surfaces. The friction coefficient at elevated temperatures depends strongly on the surface roughness of the tool steel surfaces generated by DED and ball burnishing. The latter process improves the surface integrity: the roughness peaks are leveled by up to 75%, and the hardness and the residual stresses are enhanced by up to 20% and 70%, respectively. However, the roughness of the tool surfaces is determined mainly by the path overlapping of the welded beads in the DED process. Despite the higher surface roughness, the heat transfer coefficient is in the range of conventionally manufactured tool surfaces of up to 2700 W/m2K for contact pressures up to 40 MPa. First hot stamping experiments demonstrate that the tools manufactured by the novel process combination are able to manufacture 22MnB5 hat profiles with an increased and more homogeneous hardness, as well as more homogeneous thickness distribution, compared to conventionally manufactured tools.
Design and Analysis of Bionic Continuum Robot With Helical Winding Grasping Function
Authors: Jiang Xiong , Li Shouzhong , Ma Chong , Kuang Xinyu , Zhang Wenlong , Zhao Hongzhe
Published: October 2023

In the field of grasping application, continuum robots are characterized by flexible grasping and high adaptability. Based on research on the physiological structure and winding method of seahorses, a continuum robot with a helical winding grasping function is presented in this paper. The continuum robot is driven by cables and uses a new flexural pivot with large deformation as a rotation joint. Firstly, based on the Serret–Frenet frame of the spatial cylindrical helix, the helical winding continuum robot is modeled and solved. The change rules of parameters such as the rotation angle of the joint and the helix parameters under the helical winding method are derived. Then, the compliance matrix of the joint is solved using the structural matrix method, and a stiffness model is established to analyze the relationship between the load and deformation of the continuum robot. The kinematics model of the continuum robot is established by using the modified Denavit–Hartenberg parameter method. The static model of the continuum robot is solved by vector analysis under the condition of considering gravity, and the relationship between the length change of cables and joint curvature is obtained. Finally, the stiffness model and static model of the continuum robot are verified by simulations and experiments. The test results show that within a certain radial range, the continuum robot has the function of helical winding and grasping for objects. Compared to the previous imitation seahorse tail robot, the helical winding structure not only provides a larger grasping area compared to in-plane form but also achieves a better bionic effect.
The mRNA enthusiast’s memoirs
Breaking Through: My Life in Science
Katalin Karikó
Crown, 2023. 336 pp.
Authors: Venkatraman Vijaysree
Published: October 2023

A molecular biologist documents how her passion for the messenger molecule paid off
Seneca Valley virus 3C
pro
antagonizes type I interferon response by targeting STAT1-STAT2-IRF9 and KPNA1 signals
Authors: Song Jiangwei , Guo Yitong , Wang Dan , Quan Rong , Wang Jing , Liu Jue
Published: October 2023

The Seneca Valley virus (SVV) is an emerging pathogen that causes vesicular disease in pigs, posing a threat to the pork industry. The type I interferon (IFN) signaling pathway is the major defense mechanism of host innate immune responses, and SVV has developed numerous strategies to antagonize the IFN signaling and promote viral replication. However, the molecular mechanisms by which SVV affects IFN signaling components have not been fully elucidated. Here, we revealed that SVV proteinase (3C
pro
) inhibited IFN-α signaling by degrading signal transducer and activator of transcription (STAT) 1, STAT2, and interferon regulatory factor 9 (IRF9) through its protease activity, which is dependent on the caspase pathway. 3C
pro
was further found to cleave STAT2 at glutamine 758 (Q758) within the transactivation domain, and the cleaved STAT2 products attenuated its ability to activate IFN-stimulated responsive element activity and induce the production of IFN-stimulated genes. Additionally, 3C
pro
impaired the nuclear import and formation of the IFN-stimulated gene factor 3 complex. 3C
pro
also induced karyopherin 1 degradation to block STAT1/STAT2 nuclear localization. Collectively, SVV 3C
pro
is capable of subverting the type I IFN response by targeting STAT1-STAT2-IRF9 and karyopherin α1 signals, which uncovers a novel mechanism exploited by SVV to evade host type I IFN response for efficient replication.

IMPORTANCE

Type I interferon (IFN) signaling plays a principal role in host innate immune responses against invading viruses. Viruses have evolved diverse mechanisms that target the Janus kinase-signal transducer and activator of transcription (STAT) signaling pathway to modulate IFN response negatively. Seneca Valley virus (SVV), an emerging porcine picornavirus, has received great interest recently because it poses a great threat to the global pork industry. However, the molecular mechanism by which SVV evades host innate immunity remains incompletely clear. Our results revealed that SVV proteinase (3C
pro
) antagonizes IFN signaling by degrading STAT1, STAT2, and IRF9, and cleaving STAT2 to escape host immunity. SVV 3C
pro
also degrades karyopherin 1 to block IFN-stimulated gene factor 3 nuclear translocation. Our results reveal a novel molecular mechanism by which SVV 3C
pro
antagonizes the type I IFN response pathway by targeting STAT1-STAT2-IRF9 and karyopherin α1 signals, which has important implications for our understanding of SVV-evaded host innate immune responses.
Stability of magistral phage preparations before therapeutic application in patients with chronic rhinosinusitis, sepsis, pulmonary, and musculoskeletal infections
Authors: Uyttebroek Saartje , Bessems Laura , Metsemakers Willem-Jan , Debaveye Yves , Van Gerven Laura , Dupont Lieven , Depypere Melissa , Wagemans Jeroen , Lavigne Rob , Merabishvili Maya , Pirnay Jean-Paul , Devolder David , Spriet Isabel , Onsea Jolien
Published: October 2023

Bacteriophages have (re)gained popularity as an adjunct antibacterial therapy. On top of the self-amplifying character of phages, their titer can be influenced by several factors which could lead to reduced titers after preparation and storage. The stability of phage preparations, used for the treatment of chronic rhinosinusitis (CRS), sepsis, pulmonary, and musculoskeletal infections, was investigated.
Staphylococcus aureus
phage ISP and
Pseudomonas aeruginosa
phages PNM, 14-1 and PT07 were evaluated. These phages were magistrally prepared by diluting active pharmaceutical products and storing them in different polypropylene/polycarbonate syringes at 4°C. Titers were monitored for 7–21 days using the double-agar overlay method. For 7 days, titers remained stable. Afterwards, the phage titer reduced for all phages with an average reduction of 0.78 log (
P
< 0.0001) plaque-forming units (PFUs)/mL after 14 days and 1 log PFU/mL after 21 days (
P
< 0.0001). PT07 titers dropped below the predefined threshold after 2 days in polycarbonate syringes. In addition, the stability after irrigation using a nasal douche (CRS) and infusion through a catheter (sepsis) was assessed. No changes were observed after using these devices with a mean change in titer of −0.07 log PFU/mL (
P
= 0.9062) and −0.03 log PFU/mL (
P
= 0.7350), respectively. In conclusion, a decreased titer after storage of a phage solution can lead to administration of subtherapeutic concentrations. In our experiments, we demonstrated that liquid phage solutions can be stored in syringes at 4°C for 5–7 days. PT07 appeared to be less stable, especially in polycarbonate syringes. Irrigation using a nasal douche or infusion through a catheter does not impact phage titer.

IMPORTANCE

As antimicrobial resistance becomes more prevalent, the application of (bacterio)phage therapy as an alternative treatment for difficult-to-treat infections is (re)gaining popularity. Over the past decade, numerous promising case reports and series have been published demonstrating the therapeutic potential of phage therapy. However, important questions remain regarding the optimal treatment protocol and, unlike for medicinal products, there are currently no predefined quality standards for the stability of phage preparations. Phage titers can be influenced by several factors which could lead to reduced titers after preparation and storage and, ultimately, subtherapeutic applications. Determining the stability of different phages in different recipients according to the route of administration is therefore one of the first important steps in establishing a standardized protocol for phage therapy.
Proteomic analysis of anti-MRSA activity of caerin 1.1/1.9 in a murine skin infection model and their
in vitro
anti-biofilm effects against
Acinetobacter baumannii
Authors: Zhang Pingping , Tang Shuxian , Fu Quanlan , Luo Yuandong , Li Junjie , Chen Zhu , Li Hejie , Ni Guoying , Wang Tianfang , Chen Guoqiang , Liu Xiaosong
Published: October 2023

Caerin 1 is a family of host defense peptides with antimicrobial properties originally isolated from the Australian tree frog. Both caerin 1.1 and caerin 1.9 have been demonstrated to inhibit infections caused by multiple antibiotic-resistant bacteria, both
in vitro
and
in vivo
. In this current study, we conducted a comparison of the minimum inhibitory concentrations of caerin 1.1 and caerin 1.9 (referred to as caerin 1.1/1.9) with commonly used antibiotics against various bacteria, including
Staphylococcus aureus
, Copper-Green
Pseudomonas aeruginosa
,
Acinetobacter baumannii
, and
Streptococcus haemolyticus
. Our findings reveal that caerin 1.1/1.9 not only prevent the formation of biofilms by
A. baumannii
but also exhibit a therapeutic effect on established biofilms. Furthermore, our study demonstrates that caerin 1.1/1.9 significantly inhibit the growth of methicillin-resistant
Staphylococcus aureus
(MRSA) strains in a murine skin infection model. A quantitative proteomic analysis conducted as part of our study indicates that caerin 1.1/1.9 primarily activate oxidative phosphorylation pathways, along with several pathways associated with tissue repair and growth. These findings were observed in comparison to untreated tissues that were infected with MRSA in mice. In summary, our research outcomes suggest that caerin 1.1/1.9 exhibit the potential to serve as promising drug candidates for treating complicated antibiotic-resistant bacterial infections in humans.

IMPORTANCE

Caerin 1.1 and caerin 1.9, natural antimicrobial peptides derived from tree frogs, have demonstrated the ability to inhibit the growth of antibiotic-resistant bacteria, comparable to certain widely used antibiotics. Additionally, these peptides exhibit the capacity to prevent or treat biofilms formed by bacteria in conjunction with bodily components. The mechanisms underlying their antibacterial effects were investigated through a mouse model of bacterial skin infection, utilizing proteomic analysis as a technological approach.
Association between self-reported alcohol consumption and diastolic dysfunction: a cross-sectional study
Authors: Daka Bledar , Bennet Louise , Råstam Lennart , Hellgren Margareta I , Li Ying , Magnusson Martin , Lindblad Ulf
Published: October 2023

Background and objectives

While alcohol consumption is associated with common risk factors for diastolic dysfunction the independent impact of low levels of alcohol consumption on this condition in a community setting is still unclear.

Thus, the aim of this study was to explore this association in a representative population sample employing optimal echocardiographic techniques.

Design

Cross-sectional observational study in community-based population.

Settings, participants and methods

Participants between 30 and 75 years of age were consecutively invited to a physical examination, interview, conventional echocardiography, including Tissue Velocity Imaging. Diastolic dysfunction was defined according to the European Society of Cardiology criteria, excluding subjects with ejection fraction <45%, self-reported history of heart failure or atrial fibrillation on ECG. Self-reported alcohol intake using a validated questionnaire was categorised asno intake, low and medium-highintake.

Results

In total, 500 men and 538 women (mean age 55.4±13) were successfully examined. Diastolic dysfunction was identified in 16% (79/500) of the men and 13% (58/538) of the women. The multivariable adjusted model revealed a strong and independent association between alcohol intake and diastolic dysfunction. In fact, using no alcohol intake as reference, diastolic dysfunction was independently associated with alcohol consumption in a dose-dependent fashion;low consumption,OR 2.3 (95% CI 1.3 to 4.0) andmedium-high consumptionOR 3.1 (95% CI 1.6 to 6.2), respectively.

Conclusion

There was a significant association between alcohol consumption and diastolic dysfunction starting already at low levels that was supported by a dose-dependent pattern. These results need confirmatory studies and are important in public health policies.
Effects of COVID-19 on malaria elimination initiatives in sub-Saharan Africa: a scoping review protocol
Authors: Nunu Wilfred Njabulo , Ndirangu James , Tsoka-Gwegweni Joyce
Published: October 2023

Introduction

The occurrence of the COVID-19 pandemic significantly impacted health systems, resulting in varied outcomes of different variables in terms of health. Due to the nature of the causative organism that is spread mainly in the air, the disease rapidly spread to numerous countries, leading to a series of mitigation measures being proposed and implemented, including but not limited to travel restrictions, decongesting and in some instances closure of workplaces and schools and banning of social gatherings. This could have negatively impacted implementing strategies meant to ensure the effective management of malaria, hoping to eliminate it in different countries in sub-Saharan Africa (SSA). This review seeks to explore the effect of the COVID-19 pandemic on malaria elimination initiatives in SSA.

Methods and analysis

An exploratory scoping review will be conducted on literature (searched using keywords and a search strategy) sources published in English on Web of Science, Cochrane Library, PUBMED, Dimensions, ProQuest, Scopus and African Journals Online. These would then be imported to Rayyan Software for screening for possible inclusion. The JBI Guidelines on Reviews, Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist would guide the data collection, extraction and analysis from the accessed literature. Furthermore, charting, trends and developing themes would ensure the findings are presented comprehensively and yet understandable. The data collection and analysis process leading to the final submission of a review paper to a journal will be conducted from September 2023 to February 2024.

Ethics and dissemination

An application for ethical approval was lodged with the Health Sciences Research Ethics Committee at the University of the Free State in Bloemfontein, South Africa. This ethics committee granted ethics clearance (ethics number: UFS-HSD2022/1754). Results will be communicated through peer-reviewed publications, presentations, conferences, workshops and other means and forums to reach the critical stakeholders.
Chronic abdominal pain in inflammatory bowel disease: a practical guide
Authors: Baillie Samantha , Norton Christine , Saxena Sonia , Pollok Richard
Published: October 2023

Pain is common in inflammatory bowel disease (IBD), yet many patients feel their pain is not addressed by healthcare professionals. Listening to a patient’s concerns about pain, assessing symptoms and acknowledging the impact these have on daily life remain crucial steps in addressing pain in IBD. While acute pain may be effectively controlled by pain medication, chronic pain is more complex and often pharmacological therapies, particularly opioids, are ineffective. Low-dose tricyclic antidepressants and psychological approaches, including cognitive–behavioural therapy, have shown some promise in offering effective pain management while lifestyle changes such as a trial of low-fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet in those with overlapping irritable bowel syndrome may also reduce pain. Patients benefit from a long-term, trusting relationship with their healthcare professional to allow a holistic approach combining pharmacological, psychological, lifestyle and dietary approaches to chronic pain. We present a practical review to facilitate management of chronic abdominal pain in IBD.
Bayesian inference of transition matrices from incomplete graph data with a topological prior
Authors: Perri Vincenzo , Petrović Luka V. , Scholtes Ingo
Published: October 2023

Many network analysis and graph learning techniques are based on discrete- or continuous-time models of random walks. To apply these methods, it is necessary to infer transition matrices that formalize the underlying stochastic process in an observed graph. For weighted graphs, where weighted edges capture observations of repeated interactions between nodes, it is common to estimate the entries of such transition matrices based on the (relative) weights of edges. However in real-world settings we are often confronted with incomplete data, which turns the construction of the transition matrix based on a weighted graph into an inference problem. Moreover, we often have access to additional information, which capture topological constraints of the system, i.e. which edges in a weighted graph are (theoretically) possible and which are not. Examples include transportation networks, where we may have access to a small sample of passenger trajectories as well as the physical topology of connections, or a limited set of observed social interactions with additional information on the underlying social structure. Combining these two different sources of information to reliably infer transition matrices from incomplete data on repeated interactions is an important open challenge, with severe implications for the reliability of downstream network analysis tasks.

Addressing this issue, we show that including knowledge on such topological constraints can considerably improve the inference of transition matrices, especially in situations where we only have a small number of observed interactions. To this end, we derive an analytically tractable Bayesian method that uses repeated interactions and a topological prior to perform data-efficient inference of transition matrices. We compare our approach against commonly used frequentist and Bayesian approaches both in synthetic data and in five real-world datasets, and we find that our method recovers the transition probabilities with higher accuracy. Furthermore, we demonstrate that the method is robust even in cases when the knowledge of the topological constraint is partial. Lastly, we show that this higher accuracy improves the results for downstream network analysis tasks like cluster detection and node ranking, which highlights the practical relevance of our method for interdisciplinary data-driven analyses of networked systems.
Effective elastic properties of one-dimensional hexagonal quasicrystal composites with spring-type imperfect interfaces
Authors: Li Lu , Li Xinpei , Li Lianhe
Published: October 2023

Considering the spring-type imperfect interfaces, the effective elastic properties of one-dimensional (1D) hexagonal quasicrystal (QC) are investigated systematically. The spring-type imperfect interface between QC matrix and inclusion is an ultra-thin, soft and weakly conductive interface. The Mori–Tanaka method is presented to determine the effective elastic constants of phonon, phason and phonon–phason coupling field. The numerical results are provided to show that the existence of imperfect interfaces reduces the effective elastic constants to some extent. It indicates that the interface plays an important role in the elastic properties of QC composites. Besides, the effective elastic constants are also subject to the aspect ratio and the volume fraction of inclusions.
BIFURCATION ANALYSIS OF AN SIR MODEL WITH SATURATED INCIDENCE RATE AND STRONG ALLEE EFFECT
Authors: ZHANG JIAJIA , QIAO YUANHUA
Published: October 2023

In this paper, rich dynamics and complex bifurcations of an SIR epidemic model with saturated incidence rate and strong Allee effect are investigated. First, the existence of disease-free and endemic equilibria is explored, and we prove that the system has at most three positive equilibria, which exhibit different types such as hyperbolic saddle and node, degenerate unstable saddle (node) of codimension 2, degenerate saddle-node of codimension 3 at disease-free equilibria, and cusp, focus, and elliptic types Bogdanov–Takens singularities of codimension 3 at endemic equilibria. Second, bifurcation analysis at these equilibria are investigated, and it is found that the system undergoes a series of bifurcations, including transcritical, saddle node, Hopf, degenerate Hopf, homoclinic, cusp type Bogdanov–Takens of codimensional 2, and focus and elliptic type Bogdanov–Takens bifurcation of codimension 3 which are composed of some bifurcations with lower codimension. The system shows very rich dynamics such as the coexistence of multiple periodic orbits and homoclinic loops. Finally, numerical simulations are conducted on the theoretical results.
Two topologies on the set of minimal prime elements of a continuous frame
Authors: Lu Chongxia , Li Qingguo
Published: October 2023

In this paper, we discuss the properties of the hull-kernel topology and the inverse topology on the set [Formula: see text] of minimal prime elements of a continuous frame [Formula: see text]. We prove that the set [Formula: see text] endowed with the hull-kernel topology and the inverse topology, respectively, is a [Formula: see text]-space. Moreover, we obtain that there is a bijective correspondence between the set [Formula: see text] of all maximal Scott open filters of [Formula: see text] and the set [Formula: see text] when [Formula: see text] is a stably continuous frame. By considering the bijective correspondence between the sets [Formula: see text] and [Formula: see text], we propose some sufficient conditions for the topological spaces [Formula: see text] endowed with the hull-kernel topology and the inverse topology, respectively, to be sober, Hausdorff, compact, extremely disconnected and zero-dimensional spaces, respectively, when [Formula: see text] is a stably continuous frame.
A Deep Reinforcement Learning Approach for UAV Path Planning Incorporating Vehicle Dynamics with Acceleration Control
Authors: Sabzekar Sina , Samadzad Mahdi , Mehditabrizi Asal , Tak Ala Nekouvaght
Published: October 2023

Unmanned aerial vehicles (UAVs) are experiencing a rapid expansion in their applications across various domains, including goods delivery, video capturing, and traffic control. The crucial aspect for UAVs to execute successful target tracking and obstacle avoidance maneuvers lies in the accuracy of their path planning operations. This research paper aims to contribute to the existing body of knowledge by presenting a novel model that incorporates acceleration control, accounting for changing variables such as UAV velocity and altitude, while also incorporating vehicle dynamics. To enhance the realism of the model, we include drag force as a factor. In this study, we focus on exploring the potential of deep reinforcement learning (DRL), specifically the deep deterministic policy gradient (DDPG) algorithm, for modeling a 3D continuous environment with a continuous set of actions. In order to improve the UAV’s performance in executing target tracking and obstacle avoidance maneuvers, we propose an innovative reward function based on the inner product. The training results show that the UAV successfully learns to perform the aforementioned tasks. Also, simulation results demonstrate the superior performance of the proposed UAV modeling and reward function compared to existing works.