bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with bleeding complications in patients with coronavirus disease 2019 admitted to intensive care units: A multicenter retrospective cohort study
Authors: Imai Dan , Ushigome Emi , Hamaguchi Masahide , Hashimoto Satoru , Fukui Michiaki
Published: August 2023

Aims/Introduction

Diabetes is a major risk factor for coronavirus disease 2019 (COVID‐19) severity. We aimed to retrospectively investigate the rates of patients with no diabetes, untreated diabetes, treated diabetes, COVID‐19‐related diabetes and the factors associated with bleeding complications in a cohort of patients with severe COVID‐19.

Materials and Methods

This was a multicenter, retrospective, observational study. Participants were COVID‐19 patients enrolled in the Cross‐sectional ICU Information Search System (CRISIS) from February 2020 to March 2022. Patients were classified into four groups according to diabetes status and treatment status. Hemorrhagic complications were defined as bleeding requiring transfusion of four or more red blood cell units, a drop of hemoglobin of ≥2 g in 24 h and retroperitoneal, airway or intracranial bleeding. Logistic regression analysis was carried out to examine factors associated with bleeding complications.

Results

A total of 1,076 patients were included in the analysis. The rates of patients in the no diabetes, untreated diabetes, treated diabetes and COVID‐19‐related diabetes groups were 17.4, 23.0, 23.9 and 35.7%, respectively. Bleeding complications were observed in 7.5% of all patients. Glycated hemoglobin level and renal failure were significantly correlated with bleeding complications (odds ratio 1.16, 95% confidence interval 1.02–1.33 and 2.77, 95% confidence interval 1.16–6.63, respectively). Patients with diabetes, including those with COVID‐19‐related diabetes, accounted for approximately 83% of all cases.

Conclusions

In patients with severe COVID‐19 with high glycated hemoglobin and renal failure, we recommend additional attention to the course of COVID‐19, given the risk of bleeding complications.
Fasting increases circulating angiotensin levels and brain Agtr1a expression in male rats
Authors: Paes‐Leme Bruno , Monteiro Lívia da Rocha Natalino , Gholami Khadijeh , Hoe See Ziau , Ferguson Alastair Victor , Murphy David , Antunes‐Rodrigues José , Rorato Rodrigo , Reis Luis Carlos , Mecawi André Souza
Published: August 2023

In addition to being recognised for involvement in cardiovascular control and hydromineral balance, the renin‐angiotensin system (RAS) has also been associated with the neuroendocrine control of energy balance. One of the main brain sites for angiotensin II (ANG II)/type 1 receptor (AT1R) signalling is the subfornical organ (SFO), a circumventricular organ related to the control of autonomic functions, motivated behaviours and energy metabolism. Thus, we hypothesised that circulating ANG II may act on the SFO AT1R receptors to integrate metabolic and hydromineral balance. We evaluated whether food deprivation can modulate systemic RAS activity and Agrt1a brain expression, and if ANG II/AT1R signalling influences the hypothalamic expression of mRNAs encoding neuropeptides and food and water ingestion in fed and fasted Wistar rats. We found a significant increase in both ANG I and ANG II plasma levels after 24 and 48 h of fasting. Expression of Agrt1a mRNA in the SFO and paraventricular nucleus (PVN) also increased after food deprivation for 48 h. Treatment of fasted rats with low doses of losartan in drinking water attenuated the decrease in glycemia and meal‐associated water intake without changing the expression in PVN or arcuate nucleus of mRNAs encoding selected neuropeptides related to energy homeostasis control. These findings point to a possible role of peripheral ANG II/SFO‐AT1R signalling in the control of refeeding‐induced thirst. On the other hand, intracerebroventricular losartan treatment decreased food and water intake over dark time in fed but not in fasted rats.
Should credit card rewards be taxed?
Authors: Shy Oz
Published: August 2023

Rewards that consumers receive on credit card payments influence their payment choice. They are not taxed but merchants deduct card fees from their taxes. This article analyzes the tax effects in a model where card companies set interchange fees, merchants decide whether to accept card payments, and consumers choose their preferred payment method. I find that card companies raise interchange fees when merchants are allowed to deduct these fees from their taxes. Taxing consumers' card rewards reduces interchange fees. The optimal distribution of cash and card payments cannot be supported without a policy combination of taxes and regulated interchange fees.
Neuromodulators and neuroepigenetics of social behavior in ants
Authors: Sorek Matan , Berger Shelley L.
Published: August 2023

Eusocial insects exemplify a remarkable system of division of labor within the same colony. This behavioral range, which is sometimes accompanied by morphological or physiological differences, provides an opportunity to study the relationship between complex behaviors and their underlying molecular mechanisms. This is especially true in ants because certain genera have an elaborate caste system and can dramatically change their stereotypical behavior over their lifetime. Recent studies experimentally alter ant behavior over short times, thus opening the study of underlying plasticity pathways. The molecular underpinnings of these behaviors are neuromodulators as well as the regulation of chromatin. Here, we concisely review the current understanding of the relationship between neuromodulators, epigenetics, and social behavior in ants. We discuss future directions in light of experimental limitations of the ant system.
The effect of a nurse‐led home visit program on the care burden of caregivers of adults with asthma: A randomized controlled trial
Authors: Şanlıtürk Döndü , Ayaz‐Alkaya Sultan
Published: August 2023

Objective

This study aimed to determine the effect of a home visit program on the perceived care burden of family caregivers of adults with asthma.

Design

A single‐blind randomized controlled trial.

Sample

The study was conducted with 30 participants in both the intervention and control groups.

Measurements

Care burden was measured via the Zarit Caregiver Burden Scale during the first interview at the pulmonology outpatient clinic and after the last home visit.

Intervention

A nurse‐led home visit program with five visits over three months included education and health counseling with the intervention group. Control group received standard education given in the outpatient clinic.

Results

The mean Zarit Caregiver Burden Scale scores of the intervention group in the post‐test were significantly lower than the control group.

Conclusions

The current study revealed that the nurse‐led home visit program, including education and health counseling, was effective in reducing the care burden for family caregivers of adults with asthma. Nurses can play an active role in preventing the negative effects of caregivers’ burden of care, protecting their sense of control, and improving their health. Home visits integrated into the health care system could be effective in reducing the care burden of family members.
Effect of Upstream Leakage Flow on Film Cooling Characteristic of a Turbine Convex Endwall
Authors: Zhang Jie , Liu Cunliang , Niu Xiying , Xu Weijiang , Zhang Li , Liu Xuyang
Published: August 2023

This paper investigates the effect of upstream leakage coolant flow on the film cooling performance of the convex endwall. The experiment is conducted in an annular passage with four vanes, and the endwall film cooling effectiveness distribution is measured by the pressure-sensitive paint technique. The near-wall flow field distribution predicted by computational fluid dynamics is employed to gain a deeper understanding of the influence of the passage secondary flow on the film cooling characteristic of the endwall. Furthermore, the effect of mass flow ratios (MFR = 0.75%, 1.0%, 1.25%, and 1.5%), leakage slot inclination angles (α = 30 deg, 45 deg, and 60 deg), density ratios (DR = 1.0, 1.5, and 2.0), as well as Reynolds number (Re = 2.0 × 105, 3.0 × 105, and 4.0 × 105) on the endwall film cooling is also investigated. Results indicate that the mass flow ratio has a great influence on the endwall film cooling effectiveness distribution, and a larger uncooled region can be observed when MFR is less than 1.25% due to the cooling air more easily being entrained by the secondary flow near the endwall. Reducing the inclination angle of the leakage slot enhances the axial velocity component of the coolant flow, thereby weakening the secondary flow near the endwall and improving the film cooling effectiveness distribution of the endwall. As the density ratio increases, the jet momentum of the leakage flow is reduced, particularly for higher MFR cases, which results in a significant reduction in the film cooling performance of the endwall. Besides, thinning the incoming boundary layer of the passage reduces the strength and size of the secondary flow in the passage and improves the endwall adiabatic effectiveness distribution when the Reynolds number is increased.
Structural Stress Intensity Analysis of Hybrid Heat Exchangers Based on Thermal Hydraulic Performance in S-CO2 Power Cycle
Authors: Wang Jiawei , Sun Yuwei , Lu Mingjian , Yan Xinping
Published: August 2023

Hybrid heat exchangers (H2Xs) can be used for heat exchange equipment between high-temperature exhaust gas from ships and high-pressure supercritical carbon dioxide (S-CO2) from the S-CO2 power cycle. We investigate structural stress intensity characteristics of the H2Xs based on thermal-hydraulic performance. Air and S-CO2 are employed as the working fluids and the Stainless Steel 316 (SS316) as the solid substrate. The thermal-hydraulic performance and structural stress intensity characteristics of the H2Xs are conducted by Ansys Fluent and Mechanical, respectively. The results show the mechanical stress induced by pressure loading and the thermal stress induced by temperature gradient are found to be equally important sources of stress intensity. At the inlet and outlet of the H2Xs, the total stress intensity along all paths is not smooth and continuous, and there will be a significant change due to the change in the temperature gradient. The mechanical stress caused by the fluid pressure loss is almost negligible. The change in inlet mass flowrate and temperature mainly affects the stress intensity distribution of the left and right walls on the fin channel. The pressure variation of the diesel engine has little effect on the total stress intensity. Importantly, the total stress intensity of the H2X is mainly affected by the change in S-CO2 fluid pressure.
Time reversal imaging of complex sources in a three-dimensional environment using a spatial inverse filter
Authors: Kingsley Adam D. , Basham Andrew , Anderson Brian E.
Published: August 2023

Time reversal focusing above an array of resonators creates subwavelength–sized features when compared to wavelengths in free space. Previous work has shown the ability to focus acoustic waves near the resonators with and without time reversal with an array placed coplanar with acoustic sources, principally using direct sound emissions. In this work, a two-dimensional array of resonators is studied with a full three-dimensional aperture of waves in a reverberation chamber and including significant reverberation within the time reversed emissions. The full impulse response is recorded, and the spatial inverse filter is used to produce a focus among the resonators. Additionally, images of complex sources are produced by extending the spatial inverse filter to create focal images, such as dipoles and quadrupoles. Although waves at oblique angles would be expected to degrade the focal quality, it is shown that complex focal images can still be achieved with super resolution fidelity when compared to free space wavelengths.
Daytime boat sound does not affect the behavior of wild thorny oysters (Spondylus americanus): A field-based study
Authors: Jézéquel Youenn , Aoki Nadège , Cones Seth F. , Mooney T. Aran
Published: August 2023

There is increasing awareness of boat sound effects on coral reef assemblages. While behavioral disturbances have been found in fishes, the effects on marine invertebrates remain largely unknown. Here, the behavioral effects of recreational boat sound on thorny oysters at two coral reef habitats within the U.S. Virgin Island National Park were assessed. The “treatment” site was characterized by frequent boat traffic, which increased daytime mean particle acceleration levels (PALrms) by more than 6 dB, while mean PALrms at the “control” site were not contaminated by boat sound. Despite these contrasting soundscapes, all oysters showed the same diurnal cycle, with their valves open at night and partially closed during the day. There was no statistical evidence of behavioral responses in oysters exposed to daytime boat sound. This can be explained by low auditory sensitivity, habituation to a noisy environment due to the pervasiveness of boat sound pollution, or that boat sound may not represent an immediate concern for this species. These findings contrast with laboratory studies that have shown behavioral responses in bivalves exposed to boat sound, highlighting the need for more realistic field-based studies when evaluating potential effects of anthropogenic sounds on this group.
Open Foot Stance Reduces Lead Knee Joint Loading During Golf Swing
Authors: Stokes Hannah , Escamilla Rafael , Bellapianta Joseph , Wang Hongsheng , Beach Tyson , Frost Dave , Zheng Naiquan
Published: August 2023

Foot stance and club type’s relationship with lead knee joint biomechanics and possible involvement with injury incidences in amateur golfers have not been evaluated. This study included 16 male right-handed amateur golfers who performed golf swings with 2 different foot stances (straight and open) using 4 different club types (driver, 3 iron, 6 iron, and 9 iron) while standing on 2 force plates in a motion capture laboratory. A custom program calculated the kinematics and kinetics of the lead knee. Overall, the open stance reduced most translations, rotations, forces, and torques of the lead knee in all 4 club types when compared with the straight stance. The open stance reduced the rotation motion (−28%), compressive force (−5%), and rotation torque (−9%) when compared with the straight stance, which are the highest contributors to grinding of cartilage. The driver club had significantly larger values in most translations, rotations, forces, and torques when compared among the 4 club types. The open stance reduced the rotation motion, compressive force, and rotation torque in the lead knee joint compared with the straight stance. Lead knee joint biomechanics should be monitored to reduce injury in amateur golfers.
Relationships Between Throwing Yips in Baseball, Experiential Avoidance, Cognitive Fusion, Values, and Social Factors
Authors: Inoue Kazuya , Yamada Tatsuto , Ohtsuki Tomu
Published: August 2023

Despite the high prevalence of yips, a psychoneuromuscular impairment affecting fine motor skills in sports performance, the specific aspects of its causality and treatment have not been identified or verified. This cross-sectional study examined psychosocial factors relating to throwing yips in baseball. Amateur baseball players (N = 292) living in Japan completed a self-report questionnaire on their anxiety/fear about throwing the ball, the Acceptance and Action Questionnaire-II, the Cognitive Fusion Questionnaire, the Short Fear of Negative Evaluation Scale, and self-reports evaluating values and social factors relevant to baseball. A hierarchical multiple regression analysis indicated that a low values-based throwing score, a high Cognitive Fusion Questionnaire score, and overreprimanding others’ mistakes were positively associated with baseball players’ yips symptoms. These results suggest that changing the context of playing baseball, reducing cognitive fusion, and improving coaching methods could reduce the risk of baseball players’ throwing yips.
Greek Cross-Cultural Adaptation, Reliability, and Validity of the Quick Foot and Ankle Ability Measure Questionnaire
Authors: Koumantakis George A. , Galazoulas Anastasios , Stefanakis Marios , Paraskevopoulos Eleftherios , Gioftsos George , Papandreou Maria
Published: August 2023

Context: An easy-to-administer, function-based questionnaire to assess patients with various foot problems was required for a Greek-speaking population. This study aimed to translate and cross-culturally adapt the Quick Foot and Ankle Ability Measure (Quick-FAAM) into Greek and evaluate its reliability and validity. Design: Cross-sectional study. Methods: Established international guidelines for the cross-cultural adaptation of questionnaires were followed. The face and content validity of the Greek version of the Quick-FAAM (Quick-FAAM-GR), as well as the internal consistency and test–retest reliability upon repeated administration after 5 days, were examined. In addition, the construct validity of the scale was examined via exploratory factor analysis as well as by testing for associations with the Manchester Foot Pain and Disability Index, the 12-item Short-Form Survey (version 2), and a functional balance assessment test—the Y-Balance Test. Results: Sixty participants (18 women) with self-reported chronic ankle instability symptoms, with a median (interquartile range) age of 27 (7.7) years, participated in the study. Half of the participants were included in the test–retest reliability study. The Quick-FAAM-GR demonstrated face and content validity. Excellent internal consistency (Cronbach α = .961) and intrarater test–retest reliability (intraclass correlation coefficient ICC[2,1] = .93) were demonstrated, with a comparable error margin to the original version (standard error of the measurement = 2.1, 95% minimum detectable change = 5.9). Associations of the Quick-FAAM-GR scores to other questionnaires ranged from weak to strong (Spearman rho), all being statistically significant (Manchester Foot Pain and Disability Index from −.26, P = .04, to −.67, P < .001, and 12-item Short-Form Survey, version 2, between .41 and .72, P < .001), and to the Y-Balance Test between lower-limb differences (−.35 to −.58, P < .001). The exploratory factor analysis confirmed the single-factor structure of this scale. No floor/ceiling effects were observed. Conclusions: The Greek Quick-FAAM has proven to be a valid and reliable tool for evaluating chronic ankle instability and can be used for clinical and research purposes in Greek-speaking individuals.
α-Synuclein liquid condensates fuel fibrillar α-synuclein growth
Authors: Piroska Leonard , Fenyi Alexis , Thomas Scott , Plamont Marie-Aude , Redeker Virginie , Melki Ronald , Gueroui Zoher
Published: August 2023

α-Synuclein (α-Syn) aggregation into fibrils with prion-like features is intimately associated with Lewy pathology and various synucleinopathies. Emerging studies suggest that α-Syn could form liquid condensates through phase separation. The role of these condensates in aggregation and disease remains elusive and the interplay between α-Syn fibrils and α-Syn condensates remains unexplored, possibly due to difficulties in triggering the formation of α-Syn condensates in cells. To address this gap, we developed an assay allowing the controlled assembly/disassembly of α-Syn condensates in cells and studied them upon exposure to preformed α-Syn fibrillar polymorphs. Fibrils triggered the evolution of liquid α-Syn condensates into solid-like structures displaying growing needle-like extensions and exhibiting pathological amyloid hallmarks. No such changes were elicited on α-Syn that did not undergo phase separation. We, therefore, propose a model where α-Syn within condensates fuels exogenous fibrillar seeds growth, thus speeding up the prion-like propagation of pathogenic aggregates.
Profiling single cancer cell metabolism via high-content SRS imaging with chemical sparsity
Authors: Tan Yuying , Lin Haonan , Cheng Ji-Xin
Published: August 2023

Metabolic reprogramming in a subpopulation of cancer cells is a hallmark of tumor chemoresistance. However, single-cell metabolic profiling is difficult because of the lack of a method that can simultaneously detect multiple metabolites at the single-cell level. In this study, through hyperspectral stimulated Raman scattering (hSRS) imaging in the carbon-hydrogen (C–H) window and sparsity-driven hyperspectral image decomposition, we demonstrate a high-content hSRS (h2SRS) imaging approach that enables the simultaneous mapping of five major biomolecules, including proteins, carbohydrates, fatty acids, cholesterol, and nucleic acids at the single-cell level. h2SRS imaging of brain and pancreatic cancer cells under chemotherapy revealed acute and adapted chemotherapy-induced metabolic reprogramming and the unique metabolic features of chemoresistance. Our approach is expected to facilitate the discovery of therapeutic targets to combat chemoresistance. This study illustrates a high-content, label-free chemical imaging approach that measures metabolic profiles at the single-cell level and warrants further research on cellular metabolism.
Electrically and all-optically switchable nonlocal nonlinear metasurfaces
Authors: Sharma Mukesh , Tal Mai , McDonnell Cormac , Ellenbogen Tal
Published: August 2023

Nonlocal effects on metasurfaces play an important role to achieve high-
Q
spectral selectivity, beneficial for development of multifunctional, multispectral integrated optics. In addition, they enhance the optical interaction and promote a variety of nonlinear effects, including frequency conversion and stimulated scattering. Active tuning of nonlocal nonlinearity is highly desirable for sensing and signal processing but was hardly explored until now. Here, we show drastic electric and all-optical tunability of nonlocal second-harmonic generation (SHG) from nonlinear metasurface, functionalized with a twisted nematic liquid-crystal (LC) layer. The addition of LC results in the emergence of strong nonlocal SHG, due to a surface lattice resonance of the system. We demonstrate a notable enhancement of SHG on resonance, more than 25 dB electrical switching amplitude, and all-optically induced phase transition imprinted on SHG. Our results on dynamic nonlocal effects introduce a very promising route for active nonlinear optical metadevices at the nanoscale.
Fundamental mechanistic insights into the catalytic reactions of Li─S redox by Co single-atom electrocatalysts via operando methods
Authors: Xu Weixuan , Lang Shuangyan , Wang Kaiyang , Zeng Rui , Li Huiqi , Feng Xinran , Krumov Mihail R. , Bak Seong-Min , Pollock Christopher J. , Yeo Jingjie , Du Yonghua , Abruña Héctor D.
Published: August 2023

Lithium-sulfur batteries represent an attractive option for energy storage applications. A deeper understanding of the multistep lithium-sulfur reactions and the electrocatalytic mechanisms are required to develop advanced, high-performance batteries. We have systematically investigated the lithium-sulfur redox processes catalyzed by a cobalt single-atom electrocatalyst (Co-SAs/NC) via operando confocal Raman microscopy and x-ray absorption spectroscopy (XAS). The real-time observations, based on potentiostatic measurements, indicate that Co-SAs/NC efficiently accelerates the lithium-sulfur reduction/oxidation reactions, which display zero-order kinetics. Under galvanostatic discharge conditions, the typical stepwise mechanism of long-chain and intermediate-chain polysulfides is transformed to a concurrent pathway under electrocatalysis. In addition, operando cobalt K-edge XAS studies elucidate the potential-dependent evolution of cobalt’s oxidation state and the formation of cobalt-sulfur bonds. Our work provides fundamental insights into the mechanisms of catalyzed lithium-sulfur reactions via operando methods, enabling a deeper understanding of electrocatalysis and interfacial dynamics in electrical energy storage systems.
Unique features of
Entamoeba histolytica
glycerophospholipid metabolism; has the
E
.
histolytica
lipid metabolism network evolved through gene loss and gain to enable parasitic life cycle adaptation?
Authors: Mi-ichi Fumika , Tsugawa Hiroshi , Yoshida Hiroki , Arita Makoto
Published: August 2023

Entamoeba histolytica
, a protozoan parasite, causes amoebiasis, which is a global public health problem. During the life cycle of this parasite, the properties of the cell membrane are changed markedly. To clarify the mechanism of membrane lipid changes, we exploited state-of-the-art untargeted lipidomic analysis, and atypical features of glycerophospholipids, lysoglycerophospholipids, and sphingolipids were observed compared with human equivalents. Here, we overview an entire
E. histolytica
glycerophospholipid metabolic pathway based on re-evaluated whole lipidome and genome along with the results of metabolic labeling experiments. We also discuss whether the
E. histolytica
lipid metabolism network, including the glycerophospholipid metabolic pathway, has unique features necessary for parasitic life cycle adaptation through gene loss and/or gain, and raise important questions involving biochemistry, molecular cell biology, and physiology underlying this network. Answering these questions will advance the understanding of
Entamoeba
physiology and will provide potential targets to develop new anti-amoebiasis drugs.
Investigating
in vivo Mycobacterium avium
subsp.
paratuberculosis
microevolution and mixed strain infections
Authors: Byrne Alexander , Bissonnette Nathalie , Ollier Séverine , Tahlan Kapil
Published: August 2023

Mycobacterium avium
subsp.
paratuberculosis
(MAP) causes Johne’s Disease (JD) in ruminants, which is responsible for significant economic loss to the global dairy industry. Mixed strain infection (MSI) refers to the concurrent infection of a susceptible host with genetically distinct strains of a pathogen, whereas within-host changes in an infecting strain leading to genetically distinguishable progeny is called microevolution. The two processes can influence host-pathogen dynamics, disease progression and outcomes, but not much is known about their prevalence and impact on JD. Therefore, we obtained up to 10 MAP isolates each from 14 high-shedding animals and subjected them to whole-genome sequencing. Twelve of the 14 animals examined showed evidence for the presence of MSIs and microevolution, while the genotypes of MAP isolates from the remaining two animals could be attributed solely to microevolution. All MAP isolates that were otherwise isogenic had differences in short sequence repeats (SSRs), of which SSR1 and SSR2 were the most diverse and homoplastic. Variations in SSR1 and SSR2, which are located in
ORF1
and
ORF2
, respectively, affect the genetic reading frame, leading to protein products with altered sequences and computed structures. The ORF1 gene product is predicted to be a MAP surface protein with possible roles in host immune modulation, but nothing could be inferred regarding the function of ORF2. Both genes are conserved in
Mycobacterium avium
complex members, but SSR1-based modulation of
ORF1
reading frames seems to only occur in MAP, which could have potential implications on the infectivity of this pathogen.

IMPORTANCE

Johne’s disease (JD) is a major problem in dairy animals, and concerns have been raised regarding the association of
Mycobacterium avium
subsp.
paratuberculosis
(MAP) with Crohn’s disease in humans. MAP is an extremely slow-growing bacterium with low genome evolutionary rates. Certain short sequence repeats (SSR1 and SSR2) in the MAP chromosome are highly variable and evolve at a faster rate than the rest of the chromosome. In the current study, multiple MAP isolates with genetic variations such as single-nucleotide polymorphisms, and more noticeably, diverse SSRs, could simultaneously infect animals. Variations in SSR1 and SSR2 affect the products of the respective genes containing them. Since multiple MAP isolates can infect the same animal and the possibility that the pathogen undergoes further changes within the host due to unstable SSRs, this could provide a compensative mechanism for an otherwise slow-evolving pathogen to increase phenotypic diversity for overcoming host responses.
‘Retrograde’ balloon-assisted tracking to rescue a kinked guide catheter in the radial artery
Authors: Enany Basem Elsaid Mohamed
Published: August 2023

After a successful percutaneous coronary intervention to the left anterior descending artery, the guide catheter was pulled without a wire inside and so was kinked in the radial artery. It was not possible to pull or push the kinked catheter due to severe pain and fear of radial artery injury/perforation due to ‘razor effect’ of the two sharp edges of the kinked segment. Retrograde balloon-assisted tracking technique was used through femoral access, 7 F guide catheter, percutaneous transluminal coronary angioplasty wire and inflated 2.5×15 mm balloon partially outside the catheter tip to facilitate moving the kinked catheter to the aorta where unravelling was possible using a snare and a 0.035’ wire. This technique helped to keep control of both catheters, and avoid the ‘razor effect’ and radial artery injury. It could be suggested as the initial solution to sort similar problems due to its safety and efficacy.
Surviving cardiac arrest from severe metformin-associated lactic acidosis using extracorporeal membrane oxygenation and double continuous venovenous haemodialysis
Authors: Akkaoui Kirstine Krushave , Andersen Ljubica Vukelic , Nørgaard Martin Agge , Andreasen Jo Bønding
Published: August 2023

Metformin-associated lactic acidosis (MALA) is a serious condition with high mortality. This case describes a man in the mid-60s with diabetes mellitus type 2 treated with metformin developing MALA 4 days after coronary stenting for non-ST-elevation myocardial infarction. He presented acutely with severe abdominal pain, a lactate of 19 mmol/L and pH 6.74. Despite treatment for MALA, he went into refractory cardiac arrest and was connected to venoarterial extracorporeal membrane oxygenation (VA-ECMO). He suffered a massive haemothorax due to perforation of the right atrial appendage. It was repaired through a sternotomy while being given massive blood transfusions. The following days, he was on VA-ECMO and double continuous venovenous haemodialysis (CVVHD). He survived with only mild paresis of the left hand. VA-ECMO should be considered a rescue therapy alongside treatment with CVVHD in case of cardiac arrest due to severe MALA.
Immune checkpoint inhibitor-associated myocarditis and fulminant type I diabetes in a patient with metastatic non-small cell lung cancer
Authors: Davis Brandon Matthew , Fordjour Isaac , Chahin Michael , Guha Avirup
Published: August 2023

A woman in her mid-60s presented to the hospital due to a history of nausea, vomiting, shortness of breath, dyspnoea on exertion and polyuria. She was receiving medical therapy for advanced non-small cell lung cancer and recently initiated immune checkpoint inhibitor (ICI) immunotherapy. Investigations revealed lab results consistent with diabetic ketoacidosis (DKA), elevated cardiac biomarkers, multiple cardiac arrhythmias and reduced ejection fraction on transthoracic echocardiogram. Cardiac catheterisation showed non-obstructive coronary arteries.

The patient was diagnosed with an ICI-associated myocarditis and type I diabetes due to recent initiation of the ICI durvalumab. She was treated with the institutional DKA protocol and received corticosteroid therapy for drug toxicity according to guidelines. She was discharged with marked improvement in symptoms. The patient had good recovery after discharge with further investigations showing improvement in her cardiac ejection fraction on cardiac MRI. She remains on medical therapy with an insulin regimen for diabetes management.
Unravelling the determinants of medical practice variation in referrals among primary care physicians: insights from a retrospective cohort study in Southern Israel
Authors: Shashar Sagi , Ellen Moriah , Codish Shlomi , Davidson Ehud , Novack Victor
Published: August 2023

Objectives

Reducing medical practice variation (MPV) is a central theme of system improvement because it is associated with poor health outcomes, increased costs and disparities in care. This study aimed to estimate the extent to which each determinant (patient, physician, clinic) explains MPV among primary care physicians and to identify the characteristics of health services with a greater explained variance.

Methods

A retrospective cohort study of primary care physicians practising in non-private clinics of Clalit Health Services in Southern Israel, for longer than a year between 2011 and 2017 and with more than 100 adult patients per practice. We assessed the variation in referral rates among 17 health services and the proportion explained by each domain (patient, physician and clinic). We used generalised linear negative binomial mixed models and the Nakagawa’s R2, computing the marginal r2.

Results

The study included 243 physicians working in 295 practices and 139 clinics. The mean-explained variance was 28.5%±10.0%, where physician characteristics explained 4.5% of the variation. The intrapractice variation (within a single physician between the years) was explained better than the interphysician (between physicians). Health services with high explained variation were blood tests characterised by both low intrapractice variation (Rs=−0.65, p value=0.005) and high referral rates (Rs=0.46, p value=0.06).

Conclusion

Over 70% of MPV is not explained by the patient, clinic and physician demographic and professional characteristics. Future research should focus on the fraction of MPV that is explained by the physicians’ psychological characteristics, and thus potentially identify psychological targets for behavioural modifications aimed at reducing MPV.
Cepharanthine and Oral Lichen Planus Efficacy (COLE) study: protocol for a multicentre randomised controlled study assessing the efficacy and safety of cepharanthine with topical corticosteroids in oral lichen planus
Authors: Yagyuu Takahiro , Isogawa Masahiro , Yamamoto Kazuhiko , Sugiura Tsutomu , Matsusue Yumiko , Kasahara Masato , Kirita Tadaaki
Published: August 2023

Introduction

Oral lichen planus (OLP) is a chronic, inflammatory oral condition leading to a range of symptoms from mild discomfort to severe pain, affecting patients’ quality of life. Standard therapy involves the use of topical corticosteroids, although some patients respond insufficiently or develop resistance to therapy. We aim to explore if adding cepharanthine, an herbal extract fromStephania cepharanthaHayata, can enhance the efficacy of corticosteroid therapy in symptomatic OLP.

Methods and analysis

This open-label, parallel-group, multi-centre, randomised controlled study will be conducted at three Japanese hospitals. It will compare safety and efficacy of integrated oral cepharanthine and corticosteroid therapy versus standard corticosteroid therapy. 50 symptomatic OLP patients will be randomised 1:1 to receive cepharanthine (30 mg/day) plus topical dexamethasone, or topical dexamethasone alone for 8 weeks. The primary outcome will be changed in pain intensity while drinking room-temperature water, measured on a visual analogue scale. The primary outcome is the change in pain intensity from baseline when drinking room-temperature water, evaluated using a visual analogue scale. Secondary outcomes are changes in the longest diameter of the target lesion from baseline to weeks 4 and 8, improvement and deterioration rates according to appearance and severity criteria at weeks 4 and 8, change in pain intensity when drinking room-temperature water from baseline to week 4, changes in pain intensity at rest from baseline to weeks 4 and 8, and the rates of adverse events.

Ethics and dissemination

This protocol was approved by the Certified Review Board of Nara Medical University (CRB5200002). Participants will provide informed consent. Results will be disseminated in peer-reviewed journals and conferences.

Trial registration number

Japan Registry of Clinical Trials (jRCTs051220130).
Randomised controlled trial of perinatal vitamin D supplementation to prevent early-onset acute respiratory infections among Australian First Nations children: the ‘D-Kids’ study protocol
Authors: Binks Michael J , Bleakley Amy S , Pizzutto Susan J , Lamberth Michelle , Powell Verity , Nelson Jane , Kirby Adrienne , Morris Peter S , Simon David , Mulholland E Kim , Rathnayake Geetha , Leach Amanda J , D'Antoine Heather , Licciardi Paul V , Snelling Tom , Chang Anne B
Published: August 2023

Introduction

Globally, acute respiratory infections (ARIs) are a leading cause of childhood morbidity and mortality. While ARI-related mortality is low in Australia, First Nations infants are hospitalised with ARIs up to nine times more often than their non-First Nations counterparts. The gap is widest in the Northern Territory (NT) where rates of both acute and chronic respiratory infection are among the highest reported in the world. Vitamin D deficiency is common among NT First Nations neonates and associated with an increased risk of ARI hospitalisation. We hypothesise that perinatal vitamin D supplementation will reduce the risk of ARI in the first year of life.

Methods and analysis

‘D-Kids’ is a parallel (1:1), double-blind (allocation concealed), randomised placebo-controlled trial conducted among NT First Nations mother–infant pairs. Pregnant women and their babies (n=314) receive either vitamin D or placebo. Women receive 14 000 IU/week or placebo from 28 to 34 weeks gestation until birth and babies receive 4200 IU/week or placebo from birth until age 4 months. The primary outcome is the incidence of ARI episodes receiving medical attention in the first year of life. Secondary outcomes include circulating vitamin D level and nasal pathogen prevalence. Tertiary outcomes include infant immune cell phenotypes and challenge responses. Blood, nasal swabs, breast milk and saliva are collected longitudinally across four study visits: enrolment, birth, infant age 4 and 12 months. The sample size provides 90% power to detect a 27.5% relative reduction in new ARI episodes between groups.

Ethics and dissemination

This trial is approved by the NT Human Research Ethics Committee (2018-3160). Study outcomes will be disseminated to participant families, communities, local policy-makers, the broader research and clinical community via written and oral reports, education workshops, peer-reviewed journals, national and international conferences.

Trial registration number

ACTRN12618001174279.
Finding Voices: a survey of young people’s experiences of the ED
Authors: Keating Liza , Wilson Sarah , Dainty Jack , Jones Dominic , Hill Jonathan
Published: August 2023

Background

Mental health presentations in young people are increasing. Recurrence of self-harm (SH) presentations is common and of great concern since self-harm is known to be a risk factor for suicide. Previous reports suggest that the ED experience for this group is poor. A study was carried out at the Royal Berkshire NHS Foundation Trust. The objective was to pilot new and existing measures to capture the perceived needs and expectations of young people attending ED following SH compared with those attending with suspected fractures (SFs).

Methods

Young people were approached to complete a questionnaire as they arrived in ED and again before they left. Questionnaires were a combination of pre-existing tools as well as piloting novel questions specific to the ED where no suitable tool previously existed. Satisfaction with the ED treatment was measured along with reattendance up to one year later.

Results

The survey was started in 2019 and suspended in March 2020 at the outset of the COVID-19 pandemic and subsequently closed, having screened 917 and recruited 104 adolescents. All the measures showed satisfactory psychometric properties with internal consistencies (alpha) of over 0.75. The two patient groups differed at baseline: it was found that the SH group had lower mood on the Short Mood and Feelings Questionnaire (p<0.001) and scored more highly on the Borderline Personality Features Scale for Children than the SF group (p<0.001) but the expectations of care across both groups was similar. Using the experience measures, the SH group was less satisfied with treatment than the SF group (p=0.0263).

Conclusion

Our findings underline the similarities between the two groups in terms of their expectations of care. Terminating the study early at the outset of the COVID-19 pandemic has precluded any further firm conclusions to be drawn. Further research is needed.
Impact of leaflet thrombosis on valve haemodynamic status after transcatheter aortic valve replacement
Authors: Jang Mi Hee , Ahn Jung-Min , Kang Do-Yoon , Kim Kyung Won , Koo Hyun Jung , Yang Dong Hyun , Jung Seung Chai , Kim Byungjun , Wong Yiu Tung Anthony , Lam Cheung Chi Simon , Yin Wei-Hsian , Wei Jeng , Lee Yung-Tsai , Kao Hsien-Li , Lin Mao-Shin , Ko Tsung-Yu , Kim Won-Jang , Kang Se Hun , Ko Euihong , Lee Seung-Ah , Kim Dae-Hee , Kim Hoyun , Choi Yeonwoo , Lee Jinho , Park Seung-Jung , Park Duk-Woo
Published: August 2023

Objectives

The effect of subclinical leaflet thrombosis, characterised by hypoattenuated leaflet thickening (HALT), on the valve haemodynamic function and durability of the bioprosthetic valve, is not yet determined. We determined the impact of HALT on valve haemodynamics after transcatheter aortic valve replacement (TAVR) and the predictors of haemodynamic structural valve deterioration (SVD).

Methods

The Anticoagulation vs Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization after Transcatheter Aortic Valve Replacement(ADAPT-TAVR) trial is a multicenter, randomised trial that compared edoxaban and dual antiplatelet therapy in patients who had undergone successful TAVR. The presence of HALT was evaluated by four-dimensional CT at 6 months and serial echocardiography performed at baseline, immediately post-TAVR and after 6 months. SVD was defined as at least one of the following: (1) mean transprosthetic gradient ≥20 mm Hg, (2) change in the mean gradient ≥10 mm Hg from baseline, or (3) new or increase in intraprosthetic aortic regurgitation of at least ≥1 grade, resulting in moderate or greater regurgitation.

Results

At 6 months, HALT was found in 30 of 211 (14.2%) patients. The presence of HALT did not significantly affect aortic valve mean gradients (with vs without HALT; 14.0±4.8 mm Hg vs 13.7±5.5 mm Hg; p=0.74) at 6 months. SVD was reported in 30 of 206 patients (14.6%) at 6-month follow-up echocardiography. Older age (OR: 1.138; 95% CI: 1.019 to 1.293; p=0.033), use of aortic valve size ≤23 mm (OR: 6.254; 95% CI: 2.230 to 20.569; p=0.001) and mean post-TAVR pressure gradient (OR: 1.233; 95% CI: 1.123 to 1.371; p<0.001) were independent predictors of haemodynamic SVD; however, the presence of HALT was not identified as a predictor of SVD.

Conclusions

In patients who had undergone successful TAVR, aortic valve haemodynamic status was not influenced by the presence of HALT. Although HALT was not a predictor of haemodynamic SVD at 6 months, it warrants further longer-term follow-up to evaluate the effect on long-term valve durability.

Trial registration number

NCT03284827(https://www.clinicaltrials.gov).
Nuclear staining for pan-Trk by immunohistochemistry is highly specific for secretory carcinoma of breast: pan-Trk in various subtypes of breast carcinoma
Authors: Ye Qiqi , Chen Hui , Han Cody , Peng Yan , Huang Xiao , Sun Hongxia , Wu Yun , Albarracin Constance T , Middleton Lavinia P , Sahin Aysegul A , Huo Lei , Ding Qingqing
Published: August 2023

Aims

Secretory carcinoma of breast (SCB) typically harboursETV6-NTRK3gene fusion. Pan-Trk immunohistochemistry analysis (IHC) has been shown to be sensitive for SCB diagnosis. However, weak focal pan-Trk nuclear staining was previously found in 10% of non-secretory breast carcinomas. To further examine pan-Trk IHC specificity, we evaluated pan-Trk staining in various breast carcinoma subtypes.

Methods

The study cohort consisted of 346 invasive breast carcinomas (IBCs), including 8 SCBs and 48 triple-negative histological mimickers (36 metaplastic carcinomas, including 12 matrix-producing carcinomas; 5 adenoid cystic carcinomas; 5 apocrine carcinomas; 2 acinic cell carcinomas), 101 triple-negative IBCs of no special type, 101 estrogen receptor (ER)-positive/HER2-negative IBCs and 88 HER2-positive IBCs. Six salivary gland secretory carcinomas were also included. Pan-Trk IHC was performed on tumours using a rabbit monoclonal pan-Trk antibody. Any nuclear staining in the invasive carcinoma cells was considered positive.

Results

All 14 secretory carcinomas from breast and salivary gland exhibited moderate to strong pan-Trk nuclear staining. In contrast, no pan-Trk nuclear staining was identified in any of the 338 non-secretory IBCs. Focal cytoplasmic pan-Trk staining was observed in nine non-secretory IBCs (2.7%), and was considered nonspecific and negative.

Conclusions

Our results indicate that pan-Trk nuclear staining is highly specific for SCB. In low-grade to intermediate-grade IBCs that share histological features with SCB, adding pan-Trk to a routing panel of estrogen receptor/progesterone receptor/HER2 is highly diagnostic. Our results also support using pan-Trk IHC to differentiate SCB from its triple-negative histological mimickers, such as adenoid cystic carcinoma, matrix-producing carcinoma, apocrine carcinoma and acinic cell carcinoma.
Treating solid tumors with TCR-based chimeric antigen receptor targeting extra domain B-containing fibronectin
Authors: Zhang Zhijie , Liu Chang , Wang Muhan , Sun Rongcheng , Yang Zhe , Hua Zhen , Wu Yushuang , Wu Mengting , Wang Hang , Qiu Wen , Yin Hongping , Yang Meijia
Published: August 2023

Background

The suppression of chimeric antigen receptor (CAR) T cells by the tumor microenvironment (TME) is a crucial obstacle in the T-cell-based treatment of solid tumors. Extra domain B (EDB)-fibronectin is an oncofetal antigen expressed on the endothelium layer of the neovasculature and cancer cells. Though recognized as a T cell therapy target, engineered CAR T cells thus far have failed to demonstrate satisfactory in vivo efficacy. In this study, we report that targeting EDB-fibronectin by redirected TCR-CAR T cells (rTCR-CAR) bypasses the suppressive TME for solid tumor treatment and sufficiently suppressed tumor growth.

We generated EDB-targeting CAR by fusing single-chain variable fragment to CD3ε, resulting in rTCR-CAR. Human primary T cells and Jurkat cells were used to study the EDB-targeting T cells. Differences to the traditional second-generation CAR T cell in signaling, immune synapse formation, and T cell exhaustion were characterized. Cytotoxicity of the rTCR-CAR T cells was tested in vitro, and therapeutic efficacies were demonstrated using xenograft models.

Methods

Results

In the xenograft models, the rTCR-CAR T cells demonstrated in vivo efficacies superior to that based on traditional CAR design. A significant reduction in tumor vessel density was observed alongside tumor growth inhibition, extending even to tumor models established with EDB-negative cancer cells. The rTCR-CAR bound to immobilized EDB, and the binding led to immune synapse structures superior to that formed by second-generation CARs. By a mechanism similar to that for the conventional TCR complex, EDB-fibronectin activated the rTCR-CAR, resulting in rTCR-CAR T cells with low basal activation levels and increased in vivo expansion.

Conclusion

Our study has demonstrated the potential of rTCR-CAR T cells targeting the EDB-fibronectin as an anticancer therapeutic. Engineered to possess antiangiogenic and cytotoxic activities, the rTCR-CAR T cells showed therapeutic efficacies not impacted by the suppressive TMEs. These combined characteristics of a single therapeutic agent point to its potential to achieve sustained control of solid tumors.