bluuebunny/crossref_metadata_2025 huggingface dataset:
Boundary integral simulations of boundary layers in linear viscoelastic flow
Authors: Feng Hualong , Barua Amlan , Li Shuwang , Li Xiaofan
Published: February 2023

We investigate the disturbance flow generated by the oscillatory motion of a solid particle in linear viscoelastic (LVE) fluids. We begin with one-mode Maxwell fluids and then add Newtonian components so we can examine a spectrum of Weissenberg numbers and frequency parameters. We compute the fluid dynamics using an accurate boundary integral method with third-order accuracy in space. A unique feature of our method is that we can calculate the stress on the particle surface for a prescribed particle velocity profile. It is well known that a boundary layer develops along an infinite plate under oscillatory motion in a Newtonian fluid. However, when the flow becomes viscoelastic, the boundary layers are fundamentally different from those observed in Newtonian fluids. We perform a series of numerical simulations for the geometry of spheroids, dumbbells, and biconcave disks, and characterize streamlines around these particles and shear stress distributions on the surface of the particles. Specifically, two main results emerge from our investigations: (i) there is a sequence of eddies produced in LVE rather than a single one as in the Newtonian fluid case; and (ii) the eddies develop in the interior of the LVE and barely travel, while in the Newtonian fluid, the eddy is generated on the particle surface and propagates into the fluid. Our numerical findings go beyond the well-known dynamical regimes for Newtonian fluids and highlight the level of complexity of particle dynamics in viscoelastic fluids.
Heat transfer modulation in Rayleigh–Bénard convection by an oscillatory bottom plate
Authors: Liu Zheheng , Jia Pan , Li Min , Zhong Zheng
Published: February 2023

In this paper, we consider a heat transfer modulation in Rayleigh–Bénard convection by imposing a periodic sinusoidal oscillation to the bottom hot plate parallel to itself. Two-dimensional numerical simulations are carried out under lateral periodic conditions, over a Rayleigh number range of 106≤Ra≤109 and for a fixed Prandtl number of Pr = 7.1. For a given Rayleigh number, it is found that the Nusselt number, characterizing the global heat transfer efficiency of the system, shows a counter-intuitive initial drop and subsequent rise behavior, as the characteristic oscillatory velocity Vosc increases. Accordingly, taking the classical Rayleigh–Bénard convection as a reference, a heat transfer reduction regime for low Vosc and a heat transfer enhancement regime for high Vosc are recognized. The reduction regime is resulted from the thickening of the thermal boundary layer due to the amplified viscous effect by the oscillation, which increases the thermal resistance of the system. In addition to thickening the thermal boundary layer, a stronger oscillation could also trigger a thermal boundary layer instability, inducing massive emission of the thermal plumes and eventually giving rise to a significant global heat transfer enhancement. Moreover, the combined effect of thickening and destabilizing of the thermal boundary layer leads to a temporal periodic evolution of the Nusselt number at the bottom plate in the enhancement regime. A critical oscillatory velocity Vc is selected at the crossover between two regimes, and it is found decreasing with an increasing Ra as Vc∼Ra−0.2. Through dimensional analysis, we provide a physical explanation for this dependence.
Coronavirus peplomer charge heterogeneity
Authors: Chaurasia V. , Kanso M. A. , Fried E. , Giacomin A. J.
Published: February 2023

Recent advancements in viral hydrodynamics afford the calculation of the transport properties of particle suspensions from first principles, namely, from the detailed particle shapes. For coronavirus suspensions, for example, the shape can be approximated by beading (i) the spherical capsid and (ii) the radially protruding peplomers. The general rigid bead-rod theory allows us to assign Stokesian hydrodynamics to each bead. Thus, viral hydrodynamics yields the suspension rotational diffusivity, but not without first arriving at a configuration for the cationic peplomers. Prior work considered identical peplomers charged identically. However, a recent pioneering experiment uncovers remarkable peplomer size and charge heterogeneities. In this work, we use energy minimization to arrange the spikes, charged heterogeneously to obtain the coronavirus spike configuration required for its viral hydrodynamics. For this, we use the measured charge heterogeneity. We consider 20 000 randomly generated possibilities for cationic peplomers with formal charges ranging from 30 to 55. We find the configurations from energy minimization of all of these possibilities to be nearly spherically symmetric, all slightly oblate, and we report the corresponding breadth of the dimensionless rotational diffusivity, the transport property around which coronavirus cell attachment revolves.
Wronskian solutions and Pfaffianization for a (3 + 1)-dimensional generalized variable-coefficient Kadomtsev-Petviashvili equation in a fluid or plasma
Authors: Cheng Chong-Dong , Tian Bo , Zhou Tian-Yu , Shen Yuan
Published: February 2023

In this paper, we investigate a (3 + 1)-dimensional generalized variable-coefficient Kadomtsev-Petviashvili (GVCKP) equation in a fluid or plasma. The Nth-order Wronskian solutions for that equation are derived and proved under certain variable-coefficient constraints, where N is a positive integer. One-, two-, and three-soliton solutions in the Wronskian for that equation are given. By means of the Pfaffianization procedure, a coupled (3 + 1)-dimensional GVCKP system is constructed from that equation. Bilinear form for that coupled system is exported. Under certain variable-coefficient constraints, those Wronski-type and Gramm-type Pfaffian solutions for that coupled system are obtained and proved with the help of the Pfaffian identities.
Locomotion through soft materials of paired solid spheres as a miniature robot
Authors: Volchonok David , Tur John , Friedman G.
Published: February 2023

Locomotion of a small device through soft media such as living tissue remotely actuated by magnetic field is analyzed. The device consists of two differently sized magnetized or magnetizable spheres of millimeter or sub-millimeter diameter interacting with each other magnetically, but otherwise disconnected from each other. The magnetic field transfers energy to the pair by changing direction and magnitude, while the pair executes a reversible motion gait by increasing and decreasing the distance between the sphere centers. The locomotion model is based on previously developed model of solid sphere motion through soft medium.
A small-molecule drug inhibits autophagy gene expression through the central regulator TFEB
Authors: Lin Yuqi , Shi Qiqi , Yang Guang , Shi Fuchun , Zhou Yang , Wang Tongtong , Xu Peng , Li Peifeng , Liu Zaizhou , Sun Hanyin , Zhao Zhixin , Ding Ke , Wang Zhen , Feng Haizhong , Yu Biao , Fang Pengfei , Wang Jing
Published: February 2023

Autophagy supports the fast growth of established tumors and promotes tumor resistance to multiple treatments. Inhibition of autophagy is a promising strategy for tumor therapy. However, effective autophagy inhibitors suitable for clinical use are currently lacking. There is a high demand for identifying novel autophagy drug targets and potent inhibitors with drug-like properties. The transcription factor EB (TFEB) is the central transcriptional regulator of autophagy, which promotes lysosomal biogenesis and functions and systematically up-regulates autophagy. Despite extensive evidence that TFEB is a promising target for autophagy inhibition, no small molecular TFEB inhibitors were reported. Here, we show that an United States Food and Drug Administration (FDA)-approved drug Eltrombopag (EO) binds to the basic helix-loop-helix-leucine zipper domain of TFEB, specifically the bottom surface of helix-loop-helix to clash with DNA recognition, and disrupts TFEB-DNA interaction in vitro and in cellular context. EO selectively inhibits TFEB’s transcriptional activity at the genomic scale according to RNA sequencing analyses, blocks autophagy in a dose-dependent manner, and increases the sensitivity of glioblastoma to temozolomide in vivo. Together, this work reveals that TFEB is targetable and presents the first direct TFEB inhibitor EO, a drug compound with great potential to benefit a wide range of cancer therapies by inhibiting autophagy.
Behavioral encoding across timescales by region-specific dopamine dynamics
Authors: Jørgensen Søren H. , Ejdrup Aske L. , Lycas Matthew D. , Posselt Leonie P. , Madsen Kenneth L. , Tian Lin , Dreyer Jakob K. , Herborg Freja , Sørensen Andreas T. , Gether Ulrik
Published: February 2023

The dorsal (DS) and ventral striatum (VS) receive dopaminergic projections that control motor functions and reward-related behavior. It remains poorly understood how dopamine release dynamics across different temporal scales in these regions are coupled to behavioral outcomes. Here, we employ the dopamine sensor dLight1.3b together with multiregion fiber photometry and machine learning-based analysis to decode dopamine dynamics across the striatum during self-paced exploratory behavior in mice. Our data show a striking coordination of rapidly fluctuating signal in the DS, carrying information across dopamine levels, with a slower signal in the VS, consisting mainly of slow-paced transients. Importantly, these release dynamics correlated with discrete behavioral motifs, such as turns, running, and grooming on a subsecond-to-minute time scale. Disruption of dopamine dynamics with cocaine caused randomization of action selection sequencing and disturbance of DS–VS coordination. The data suggest that distinct dopamine dynamics of DS and VS jointly encode behavioral sequences during unconstrained activity with DS modulating the stringing together of actions and VS the signal to initiate and sustain the selected action.
Estimating perceptions of the relative COVID risk of different social-distancing behaviors from respondents’ pairwise assessments
Authors: Heffetz Ori , Rabin Matthew
Published: February 2023

How do people compare the effectiveness of different social-distancing behaviors in avoiding the spread of viral infection? During the COVID pandemic, we showed 676 online respondents in the United States, United Kingdom, and Israel 30 pairs of brief videos of acquaintances meeting. We asked respondents to indicate which video from each pair depicted greater risk of COVID infection. Their choices imply that on average, respondents considered talking 14 min longer to be as risky as standing 1 foot closer, being indoors as standing 3 feet closer, being exposed to coughs or sneezes as 3 to 4 ft closer, greeting with a hug as 7 ft closer, and with a handshake as 5 ft closer. Respondents considered properly masking as protecting the wearer and interlocutor equally, removing the mask entirely or only when talking as standing 4 to 5 ft closer but wearing it under the nose as only 1 to 2 ft closer. We provide weaker evidence on beliefs about the interaction effects of different behaviors. In a more limited, ex post analysis, we find little evidence of differences in beliefs across subpopulations.
Multidimensional visualization of the dynamic evolution of Li metal via in situ/operando methods
Authors: Lang Shuangyan , Colletta Michael , Krumov Mihail R. , Seok Jeesoo , Kourkoutis Lena F. , Wen Rui , Abruña Héctor D.
Published: February 2023

The growing demands for high-energy density electrical energy storage devices stimulate the coupling of conversion-type cathodes and lithium (Li) metal anodes. While promising, the use of these “Li-free” cathodes brings new challenges to the Li anode interface, as Li needs to be dissolved first during cell operation. In this study, we have achieved a direct visualization and comprehensive analysis of the dynamic evolution of the Li interface. The critical metrics of the interfacial resistance, Li growth, and solid electrolyte interface (SEI) distribution during the initial dissolution/deposition processes were systematically investigated by employing multidimensional analysis methods. They include three-electrode impedance tests, in situ atomic force microscopy, scanning electrochemical microscopy, and cryogenic scanning transmission electron microscopy. The high-resolution imaging and real-time observations show that a loose, diffuse, and unevenly distributed SEI is formed during the initial dissolution process. This leads to the dramatically fast growth of Li during the subsequent deposition, deviating from Fick’s law, which exacerbates the interfacial impedance. The compactness of the interfacial structure and enrichment of electrolyte species at the surface during the initial deposition play critical roles in the long-term stability of Li anodes, as revealed by operando confocal Raman spectroscopic mapping. Our observations relate to ion transfer, morphological and structural evolution, and Li (de)solvation at Li interfaces, revealing the underlying pathways influenced by the initial dissolution process, which promotes a reconsideration of anode investigations and effective protection strategies.
Early Vedic compounds
Authors: Biagetti Erica
Published: February 2023

Despite a longstanding tradition of studies in Sanskrit compounds, a description that enables comparisons in
cross-linguistic perspective has not yet been worked out. The present article follows classificatory criteria introduced by
Bisetto & Scalise (2005, 2009) and
sketches a typology of compounds in the most archaic variety of Sanskrit, Early Vedic, as transmitted by the
RigVeda. Analyzing compounds on the basis of the grammatical relations holding between their constituents
provides a classification into coordinate, subordinate, and attributive compounds, with the endocentric/exocentric divide cutting
across all classes. In order to identify the position of Early Vedic compounds on the syntax-morphology continuum,
the article investigates the degree of cohesiveness at the level of morphology, prosody, syntax, and semantics. With this respect,
the RigVeda offers a varied picture where relics of archaic, less cohesive forms occur side-to-side with more
productive and word-like ones.
Asymmetric supercapacitors based on SnNiCoS ternary metal sulfide electrodes
Authors: Dai Tingting , Cai Bin , Yang Xijia , Jiang Yi , Wang Liying , Wang Jiusheng , Li Xuesong , Lü Wei
Published: February 2023

While metal sulfides have extensively investigated as electrode materials for supercapacitors, the further optimization of their material system is still necessary to achieve satisfied performance. In this work, we reported the synthesis of ternary metal sulfide SnNiCoS and its application as electrode material of asymmetric supercapacitors, in which active carbon is used as the other electrode. For control experiments, asymmetric supercapacitors based on single metal sulfide CoS and binary metal sulfide NiCoS are also fabricated and investigated. The results show that the nanospherical SnNiCoS achieves the best performance. Ternary sulphide materials offer more redox than corresponding single-metal sulphides due to the synergy among various transition metal elements. The specific capacitance is 18.6 F cm−2 at current density of 5 mA·cm−2. An energy density of 937.2 μWh cm−2 is achieved at a power density of 4000 μW·cm−2. After 8000 cycles, the capacity retention rate is 82.9%. Present work indicates that SnNiCoS ternary metal sulfide could be a promising composite for high performance supercapacitors.
Chaotic image encryption based on spiral traversal and finite field bidirectional diffusion
Authors: Huang Lilian , Chai Bin , Xiang Jianhong , Zhang Zefeng , Liu Jin
Published: February 2023

In this paper, a new sinusoidal cascade chaotic map model is proposed, which constructs chaotic system by sinusoidal cascade of two identical 1D chaotic maps. This model can generate 1D chaotic system with wider parameter range and wider chaotic region. To verify its application in image encryption, a chaotic image encryption algorithm based on spiral traversal and finite field bidirectional diffusion is proposed. The pseudo-random sequences generated by three kinds of 1D chaotic maps improved by the sinusoidal cascade chaotic map model are used as the ciphers of the cryptosystem. Among them, SHA-256, SHA-512 and plain image are combined to generate the initial value of the system. The experimental results and security analysis show that the encryption algorithm designed in this paper can effectively resist exhaustive attack, differential attack, noise attack and so on, and the proposed model has superior performance in encryption speed and security.
The COLUTA ADC ASIC and the ATLAS HL-LHC Liquid Argon Front-End Readout
Authors: Matos G.
Published: February 2023

The upgraded High-Luminosity Large Hadron Collider (HL-LHC) requires a new radiation tolerant ATLAS Liquid Argon (LAr) Calorimeter readout operating at 40 MHz with 16-bit dynamic range. The Front-End Board 2 (FEB2) will provide the front-end readout for the calorimeter, and will interface a series of custom ASICs due to radiation tolerance requirements of the HL-LHC. The COLUTA is a 65 nm CMOS custom 8-channel 15-bit 40 MSPS ADC ASIC developed for this application. This contribution will present performance results of the final prototype of the COLUTA, surpassing specifications at >11.5 ENOB for relevant frequencies, as well as non-linearity and radiation requirements. Preliminary integration results of the front-end readout components will also be described by means of the FEB2 Pre-Prototype, the “Slice Testboard”.
Increased floodplain inundation in the Amazon since 1980
Authors: Fleischmann Ayan S , Papa Fabrice , Hamilton Stephen K , Fassoni-Andrade Alice , Wongchuig Sly , Espinoza Jhan-Carlo , Paiva Rodrigo C D , Melack John M , Fluet-Chouinard Etienne , Castello Leandro , Almeida Rafael M , Bonnet Marie-Paule , Alves Luna G , Moreira Daniel , Yamazaki Dai , Revel Menaka , Collischonn Walter
Published: February 2023

Extensive floodplains throughout the Amazon basin support important ecosystem services and influence global water and carbon cycles. A recent change in the hydroclimatic regime of the region, with increased rainfall in the northern portions of the basin, has produced record-breaking high water levels on the Amazon River mainstem. Yet, the implications for the magnitude and duration of floodplain inundation across the basin remain unknown. Here we leverage state-of-the-art hydrological models, supported by in-situ and remote sensing observations, to show that the maximum annual inundation extent along the central Amazon increased by 26% since 1980. We further reveal increased flood duration and greater connectivity among open water areas in multiple Amazon floodplain regions. These changes in the hydrological regime of the world’s largest river system have major implications for ecology and biogeochemistry, and require rapid adaptation by vulnerable populations living along Amazonian rivers.
A greener Loess Plateau in the future: moderate warming will expand the potential distribution areas of woody species
Authors: Guo Yanlong , Zhao Zefang , Yuan Shiwei , Li Xin
Published: February 2023

Understanding the effect of future global warming on the distribution and diversity of woody species in the Loess Plateau is critical to the vegetation restoration and rebuilding of this area and yet is highly challenging. In the absence of enough experimental data, projection based on species distribution models is the best option for assessing the future shift in species distribution areas. Here, via a comprehensive habitat suitability model, we present an assessment of potential distribution area change for two plant life forms with a total of 42 key woody species, including 21 tree species and 21 shrub species, on the Loess Plateau under multiple scenarios, and based on this information, we explore the responses of regional potential woody species diversity to future global warming. The results showed that moderate warming will promote the expansion of potential distribution areas for most woody species and generally increase regional species diversity, which will result in a greener Loess Plateau. Our results also show that shrub species are more drought-tolerant and less adversely affected by climate change and thus should be considered a priority in vegetation restoration, especially in the arid area of the northern Loess Plateau. These results are helpful for identifying priority restoration areas, selecting appropriate species for artificial planting, and providing useful information for vegetation restoration and management in the future.
Evaluating the performance of static mixers using the

M

-number: the case of the Koflo® mixer
Authors: Medina Hector , Anthony Joby M , Eldredge Thomas
Published: February 2023

Static mixers (SMs) are widely used in applications that involve chemical reactions, heat transfer, blending of fluids, or some combination of these. Accurately evaluating the performance of SMs is critical for the appropriate selection of these devices. Traditional approaches involve parameters that separately evaluate the mixing level and the energy spent in mixing (i.e., pressure drop) but do not account for both simultaneously. The

M

-number has been recently proposed as a means to simultaneously evaluate the quality of mixing as well as the pressure drop across the static mixer (SM). This work demonstrates an implementation of the

M

-number by evaluating the performance of a KOFLO® static mixer (KSM) for mixing water vapor and air via Computational Fluid Dynamics (CFD), for Schmidt number of approximately unity. Pipe and mixer sizes as well as inlet profile distribution were varied. A single-element KSM was used based on the impetus of our study: Selective Catalytic Reactor (SCR) applications, which requires minimization of the pressure drop. The results are shown to be reasonably comparable with respect to previous works containing experimental data.
The Impact of the Pathologist in Multidisciplinary Cancer Conferences on Patient Care : Evidence From the Literature
Authors: Plotkin Anna , Olkhov-Mitsel Ekaterina , Gagliardi Anna R
Published: February 2023

Objectives

Multidisciplinary cancer conferences (MCCs) are important tools in the treatment of patients with complex health issues, helping clinicians achieve optimal outcomes in oncological practice. To explore the role of pathologists at MCCs, we conducted a review of prior research on this topic.

Methods

We conducted a scoping review by searching MEDLINE, EMBASE, and the Cochrane Library for English-language qualitative, quantitative, or multiple/mixed methods studies on the role and impact of pathologists on MCCs. We used Microsoft Excel to extract data.

Results

Of 76 research results, we included only 3 studies that involved review of cancer cases by pathologists for MCCs. All 3 studies showed that expert pathology review improved the accuracy of diagnosis and refined disease staging, leading to changes in the management of melanoma, breast cancer, and gynecologic cancer. No studies explored the barriers to pathologists participating in MCCs or the strategies or interventions employed to promote or support pathologist involvement.

Conclusions

We identified a paucity of studies on the role of pathologists in MCCs. Given the positive impact of MCCs involving pathologists on the accuracy of diagnosis and optimization of treatment, future research is warranted to further establish the role and impact of pathologists in MCCs and how to promote or support pathologists’ involvement.
Can an inexpensive light-emitting diode loupe magnification device be as good as an expensive dermatoscope?
Authors: Lun Andie I , Soriano Livia , Parmar Sanjay , Sahota Anshoo
Published: February 2023

Background

Dermoscopy is an invaluable technique used in both primary and secondary care to provide clinical information for diagnosis of skin disorders. Access to dermatoscopes is limited because of their high cost that limits clinicians at early levels of training, as well as those in low-resource settings, from developing the essential skills of dermoscopy. Previous solutions that have been proposed to address this issue have failed to demonstrate sufficient evidence for their use as an alternative compared with the gold standard of a dermatoscope, making it difficult to justify adoption of such solutions.

Aim

To assess the noninferiority of an inexpensive light-emitting diode (LED) loupe magnification device compared with a nonpolarized dermatoscope.

Method

This study looked at 100 paired photographs of lesions taken with both devices and asked 26 clinicians to categorize the lesions.

Results

Considering the consistency of the responses, this study confirmed noninferiority of the inexpensive LED loupe magnification device. Our results showed that the LED loupe magnification device is noninferior within a 25% margin and performs 82% as well as a nonpolarized dermatoscope.

Conclusion

Our findings encourage the implementation of use of the cheaper LED loupe magnification device both in the early stages of medical training and in settings where expensive dermatoscopes are not available.
Athena: Specialty Certificate Examination case for paediatrics and genetics
Authors: Olsen Eric , Farahbakhsh Navid , Lavery Michael Joseph , Saikaly Sami Kameel
Published: February 2023

This Athena case describes a young girl with a history of a mildly tender flesh-coloured papule on her parietal scalp with surrounding poliosis.
Inactivated whole-virion SARS-CoV-2 vaccines and long-term clinical outcomes in patients with coronary atherosclerosis disease in China: a prospective cohort study
Authors: Xu Huajie , Zheng Jiaojiao , Zhao Xin , Zhou Qi , Fan Bing , Wu Hongyi , Zhang Si , Ge Junbo
Published: February 2023

Aims

Publicized adverse events after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raised concern among patients with coronary atherosclerosis disease (CAD). We sought to study the association between SARS-CoV-2 vaccines and long-term clinical outcomes including ischaemic and bleeding events among patients with CAD.

Methods and results

Inpatients diagnosed with CAD by coronary angiography, without a history of SARS-CoV-2 infection and vaccination, were included between 1 January and 30 April 2021, and underwent follow-up until 31 January 2022. Two doses of inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac, BBIBPCorV, or WIBP-CorV) were available after discharge, and the group was stratified by vaccination. The primary composite outcomes were cardiovascular death, non-fatal myocardial infarction, stent thrombosis, unplanned revascularization, ischaemic stroke, venous thrombo-embolism, or peripheral arterial thrombosis. The bleeding outcomes were Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. Cox regression models with vaccination status as a time-dependent covariate were used to calculate the hazard ratio (HR) for the outcomes. A propensity score matching method was used to reduce confounding biases. This prospective cohort study included 2078 individuals with CAD, 1021 (49.1%) were vaccinated. During a median follow-up of 9.1 months, 45 (4.3%) primary composite outcomes occurred in the unvaccinated group, and 33 (3.2%) in the vaccinated group. In Cox regression, the adjusted HR was 1.13 [95% confidence interval (CI) 0.65–1.93]. The adjusted HR for the bleeding outcomes associated with vaccination was 0.81 [95% CI 0.35–1.19]. After matching, the adjusted HR for the primary composite outcomes associated with vaccination was 1.06 [95% CI 0.57–1.99] and for the bleeding outcomes was 0.91 [95% CI 0.35–2.38]. Similar results were found in the seven prespecified subgroups. No grade 3 adverse reactions after vaccination were recorded.

Conclusion

Our results indicated no evidence of an increased ischaemic or bleeding risk after vaccination with inactivated SARS-CoV-2 vaccine among Chinese patients with CAD, with limited statistical power.
Isolated left ventricular apical hypoplasia: case report
Authors: Román Ricardo , Anchante Henry , Menacho Katia , Medina Félix
Published: February 2023

Background

Isolated left ventricular apical hypoplasia (ILVAH) is a rare, probably congenital, cardiac condition recently reported in the last two decades. Although most cases are asymptomatic or mildly symptomatic, some severe and fatal cases have been reported, leading to more efforts for appropriate diagnosis and treatment. We describe the first, and severe, case of this pathology in Peru and Latin America.

Case summary

A 24-year-old male with a history of long-standing alcohol and illicit drug use presented with symptoms of heart failure (HF) and atrial fibrillation (AF). Transthoracic echocardiography showed biventricular dysfunction along with spherical left ventricle, abnormal papillary muscles’ origin from the left ventricular apex, and an elongated right ventricle wrapping around the deficient left ventricular apex. Cardiac magnetic resonance confirmed these findings and revealed subepicardial fatty replacement at the left ventricular apex. The diagnosis of ILVAH was made. He was discharged from hospital with carvedilol, enalapril, digoxin, and warfarin. Eighteen months later he remains mildly symptomatic at New York Heart Association functional class II without worsening HF nor thrombo-embolism.

Discussion

This case highlights the usefulness of multimodality non-invasive cardiovascular imaging for accurate diagnosis of ILVAH as well as the importance of close follow-up and treatment of established complications (HF and AF).
Cardiac sarcoidosis in a carrier of transthyretin gene mutation: a case report
Authors: Menale Silvia , Scheggi Valentina , Vanni Francesco , Di Mario Carlo
Published: February 2023

Background

Sarcoidosis is a rare multiorgan inflammatory disorder of unknown aetiology, characterized by the formation of non-caseating granulomas in the affected organs. Cardiac involvement is underrecognized and observed in up to 25% of cases in autopsy studies, and is associated with a high mortality rate, especially due to sudden cardiac death due to ventricular arrhythmias.

Case summary

A 41-year-old man well known to our hospital because of his father’s diagnosis of cardiac amyloidosis, and carrier of transthyretin (TTR) gene mutation, was hospitalized following a resuscitated cardiac arrest. The patient was hospitalized a month before for a syncopal episode with demonstration of preserved left ventricular ejection fraction (LVEF) with akinetic basal septum at heart ultrasound and normal coronary. Chest computed tomography, performed in the emergency department, was significant for hilar lymphadenopathies and pulmonary nodules highly suggestive of sarcoidosis. A subsequent 18-fluorodeoxyglucose-positron emission tomography (FDG-PET) showed multiorgan phlogistic involvement, including the myocardium. After the diagnosis of cardiac sarcoidosis, the patient was started on steroids therapy and underwent ICD implantation. A follow-up 18-FDG-PET showed a reduction of organs glucose uptake and a follow-up echo an improvement in LVEF. Despite that, he occurs occasional recording of repetitive ventricular arrhythmias and one appropriate ICD shock during the next 12 months.

Discussion

Cardiac sarcoidosis is an insidious disease. Its diagnosis can be challenging, with no specific finding in echocardiography. The best strategy would be multi-modality imaging involving both magnetic resonance imaging with late gadolinium enhancement and 18-FDG-PET, followed by biopsy to confirm the diagnosis. Multi-modality imaging should be further used to evaluate the response to treatment and assess prognosis. Since the patient was a known carrier of the TTR gene mutation, many efforts were made in order to come up with the correct diagnosis considering that both cardiac amyloidosis and cardiac sarcoidosis are non-ischaemic cardiomyopathy with systemic involvement.
The association of electronic health literacy with behavioural and psychological coronary artery disease risk factors in patients after percutaneous coronary intervention: a 12-month follow-up study
Authors: Brørs Gunhild , Dalen Håvard , Allore Heather , Deaton Christi , Fridlund Bengt , Norman Cameron D , Palm Pernille , Wentzel-Larsen Tore , Norekvål Tone M
Published: February 2023

Aims

Fundamental roadblocks, such as non-use and low electronic health (eHealth) literacy, prevent the implementation of eHealth resources. The aims were to study internet usage for health information and eHealth literacy in patients after percutaneous coronary intervention (PCI). Further, we aimed to evaluate temporal changes and determine whether the use of the internet to find health information and eHealth literacy were associated with coronary artery disease (CAD) risk factors at the index admission and 12-month follow-up of the same population.

Methods and results

This prospective longitudinal study recruited 2924 adult patients with internet access treated by PCI in two Nordic countries. Assessments were made at baseline and 12-month follow-up, including a de novo question Have you used the internet to find information about health?, the eHealth literacy scale, and assessment of clinical, behavioural, and psychological CAD risk factors. Regression analyses were used. Patients’ use of the internet for health information and their eHealth literacy were moderate at baseline but significantly lower at 12-month follow-up. Non-users of the internet for health information were more often smokers and had a lower burden of anxiety symptoms. Lower eHealth literacy was associated with a higher burden of depression symptoms at baseline and lower physical activity and being a smoker at baseline and at 12-month follow-up.

Conclusion

Non-use of the internet and lower eHealth literacy need to be considered when implementing eHealth resources, as they are associated with behavioural and psychological CAD risk factors. eHealth should therefore be designed and implemented with high-risk CAD patients in mind.

Clinical trial registration

ClinicalTrials.gov NCT03810612 https://clinicaltrials.gov/ct2/show/NCT03810612
Real world evidence: Perspectives from a European Society of Cardiology Cardiovascular Round Table with contribution from the European Medicines Agency
Authors: Szymański Piotr , Weidinger Franz , Lordereau-Richard Isabelle , Himmelmann Anders , Arca Marcello , Chaves Jose , Lee Charles , Jonker Carla , Kotecha Dipak , O'Kelly James , Plueschke Kelly , Ryś Andrzej , Segec Andrej , Wallentin Lars , Veltrop Rogier , James Stefan
Published: February 2023

Real world data (RWD) refers to healthcare information that is routinely collected in electronic healthcare records (EHR), hospital and pharmacy records, patient and disease registries, and health insurance databases. The collection and analysis of this vast amount of data is an important complement to that obtained from conventional randomised controlled trials (RCT). Real world data has been used for healthcare quality improvements, to conduct clinical trials, to support drug and device development, and to inform medical guidelines. The utility of RWD may be facilitated by common data models, which standardise format and content, and allow data from different health systems to be analysed together.

The European Society of Cardiology (ESC) supports the use of RWD in collaboration with national cardiac societies, regulatory authorities, and industry to encourage continuous quality of care improvements at the hospital and country level, to conduct registry-based randomised clinical trials (R-RCT) and to facilitate safety surveillance of novel drugs and devices.

The European Medicines Agency (EMA) is developing systems and processes to enable the use of RWD that can help in trial planning, defining clinical contexts, and enhancing outcome assessments. RWD can also contribute to the measurement of the impact of regulatory actions, such as contraindications or restriction of indications by looking at medicines use patterns over time across European Member States. A number of other initiatives from the European Commission and the EMA are underway to strengthen the EU's health security framework, and foster the collection and utilisation of RWD.
French national addictovigilance follow-up of zolpidem between 2014 and 2020: evolution of drug abuse, misuse and dependence before and after the regulatory change
Authors: Aquizerate Aurélie , Laforgue Edouard-Jules , Istvan Marion , Rousselet Morgane , Gerardin Marie , Jouanjus Emilie , Libert Frédéric ,   French Addictovigilance Network, Caous Anne-Sylvie , Chaouachi Leila , Chevallier Cécile , Daveluy Amélie , Eiden Céline , Fauconneau Bernard , Fournier-Choma Christine , Gibaja Valérie , Lacroix Clémence , Lapeyre-Mestre Maryse , Le Boisselier Reynald , Revol Bruno , Guerlais Marylène , Victorri-Vigneau Caroline
Published: February 2023

Background

Since the appearance of zolpidem on the market, the occurrence of serious cases of abuse, misuse and dependence have come to the attention of authorities. In view of the increase in the number and severity of cases among zolpidem users and the predominant presence of zolpidem in falsified prescriptions, the French Health Authorities implemented part of the narcotics regulation for zolpidem in April 2017. The objective of this article was to describe the evolution of the abuse, dependence and misuse of zolpidem.

Methods

We used three data sources: (i) zolpidem is a reimbursable and strictly prescription drug in France. Medic’AM is a public database that indicates the number of tablets reimbursed each month in France for each reimbursable drug. This database has been analyzed as a proxy of the exposure of the French population to zolpidem; (ii) all French cases of drug dependence or abuse reported by health professionals (regulatory obligation) and (iii) an epidemiological tool based on the surveillance of falsified prescriptions over two periods: the 3-year period before the regulatory measure (2014–16) and the 3-year period after the regulatory measure (2018–20).

Results

This regulatory change had two immediate consequences: a sharp decline in falsified prescriptions and a decrease of ∼57% between the two study periods in the zolpidem reimbursement data. Markers of problematic consumption remained after the regulatory change with worsening cases, particularly for people who were genuinely dependent and/or had comorbidities or misusers for whom zolpidem was the substance of interest, whose proportion increased significantly in the addictovigilance notification system, from 43.6% (N = 107) to 59.3% (N = 127) (P < 0.01).

Conclusions

Further monitoring is needed in light of these persistent markers of problematic consumption.
Effect-directed analysis and beyond: how to find causal environmental toxicants
Authors: Tian Zhenyu , McMinn Madison H , Fang Mingliang
Published: February 2023

Humans and wildlife are exposed to complex environmental mixtures. Identifying causal toxic pollutants in environmental samples remains challenging because of the high complexity of sample mixtures and the unknown nature of the potential toxicants. In the field of environmental chemistry and toxicology, this pursuit of causal toxicants leads us to the method of effect-directed analysis (EDA), an integrated method comprised of three iterative modules: (1) bioassays to guide component prioritization; (2) fractionation to reduce the mixture complexity; and (3) chemical analysis to identify the toxicants. In this commentary review, we try to provide a concise guideline for EDA beginners by summarizing good practices from successful EDA studies, categorized by sample-toxicity pair selection, efficient separation, and chemical analysis. We also discussed the practical challenges faced with current EDA practices. Based on these above, we try to provide suggestions and perspectives for future EDA studies. Specifically, we discussed the potential of applying EDA on human biological examples to identify the environmental causes of human diseases. We proposed future collaboration between environmental chemists and toxicologists, environmental health scientists, epidemiologists, physicians, and social scientists.
Experimental considerations for study of C. elegans lysosomal proteins
Authors: Clancy John C , Vo An A , Myles Krista M , Levenson Max T , Ragle James Matthew , Ward Jordan D
Published: February 2023

Lysosomes are an important organelle required for the degradation of a range of cellular components. Lysosome function is critical for development and homeostasis as dysfunction can lead to inherited genetic disorders, cancer, and neurodegenerative and metabolic diseases. The acidic and protease-rich environment of lysosomes poses experimental challenges. Many fluorescent proteins are quenched or degraded, while specific red fluorescent proteins can be cleaved from translational fusion partners and accumulate. While studying MLT-11, a Caenorhabditis elegans molting factor that localizes to lysosomes and the cuticle, we sought to optimize several experimental parameters. We found that, in contrast to mNeonGreen fusions, mScarlet fusions to MLT-11 missed cuticular and rectal epithelial localization. Rapid sample lysis and denaturation were critical for preventing MLT-11 fragmentation while preparing lysates for western blots. Using a model lysosomal substrate (NUC-1), we found that rigid polyproline linkers and truncated mCherry constructs do not prevent cleavage of mCherry from NUC-1. We provide evidence that extended localization in lysosomal environments prevents the detection of FLAG epitopes in western blots. Finally, we optimize an acid-tolerant green fluorescent protein (Gamillus) for use in C. elegans. These experiments provide important experimental considerations and new reagents for the study of C. elegans lysosomal proteins.
Hepcidin and Iron Status in Patients With Inflammatory Bowel Disease Undergoing Induction Therapy With Vedolizumab or Infliximab
Authors: Loveikyte Roberta , Bourgonje Arno R , van der Reijden Johannes J , Bulthuis Marian L C , Hawinkels Lukas J A C , Visschedijk Marijn C , Festen Eleonora A M , van Dullemen Hendrik M , Weersma Rinse K , van Goor Harry , van der Meulen-de Jong Andrea E , Dijkstra Gerard
Published: February 2023

Background

Hepcidin, the systemic iron regulator, could be critical in differentiating iron deficiency (ID) from functional iron restriction in inflammatory bowel disease (IBD). We assessed hepcidin as a diagnostic ID marker and explored the relationship between hepcidin and its regulators in patients with IBD undergoing induction therapy with infliximab (IFX) or vedolizumab (VEDO).

Methods

Patients with active IBD receiving induction therapy with IFX or VEDO were included. Serum samples at baseline and after 6 weeks of induction therapy were analyzed for hepcidin, inflammation- and hypoxia-associated cytokines, and oxidative stress. Data were analyzed by stratifying based on the response at week 14. Results were compared with samples from age- and sex-matched healthy control subjects.

Results

Patients receiving induction therapy with IFX (n = 71) or VEDO (n = 51) and healthy control subjects (n = 50) were included. At baseline, hepcidin correlated positively with ferritin and negatively with soluble transferrin receptor/log ferritin index (P < .001). ID was prevalent in 96.7% of patients who had hepcidin levels below the median. Hepcidin accurately identified ID: the area under the curve (hepcidin) was 0.89 (95% confidence interval, 0.82-0.95; P < .001). In total, 75.4% of patients responded to induction therapy; inflammation, hepcidin, and ferritin decreased significantly, while transferrin increased during induction therapy. These changes were observed only in patients who responded to the therapy.

Conclusions

Hepcidin levels in IBD are primarily determined by ID, even in an inflammatory state. In addition, induction therapy can decrease hepcidin levels, which might lead to better bioavailability of iron supplements. Therefore, hepcidin is a potential diagnostic ID biomarker that could assist therapeutic decision making.
Community pharmacists’ knowledge of substandard and falsified medicines in clinical practice: a cross-sectional survey in Saudi Arabia
Authors: Bashayr Ali Alsaeed , Barrett Ravina
Published: February 2023

Aim

The main objective of this study was to explore community pharmacists’ knowledge of substandard and falsified medicines (SFs).

Method

A descriptive cross-sectional study was conducted with community pharmacists in the Kingdom of Saudi Arabia using a pre-validated electronic survey.

Key findings

Ninety-two community pharmacists participated in this study. Many of the respondents (68.5%) had no experience with identifying SFs. We identified a concerning trend of under-reporting SFs (P < 0.003). Respondents reported that SFs constitutes 1–5% of medicines, with weight loss medicines being the most targeted for falsification. Most of the respondents had a low level of awareness about the newly implemented anti-counterfeit system in Saudi Arabia called the ‘Drug Track and Trace System’ (28.3% not really, 23.1% not at all). Respondents showed low levels of knowledge about technologies available to detect SFs (P < 0.01).

Conclusions

Community pharmacists’ self-reported awareness and knowledge of SFs in Saudi Arabia was inadequate; this deficiency may affect their ability to protect their patients from potential harm by combating SFs. As a regulatory body responsible for issues related to SFs, the Saudi Food and Drug Authority should develop an action plan to equip community pharmacists with training in SFs to enhance their ability to respond to SFs.
Nichols Algebras and Quantum Principal Bundles
Authors: Krutov Andrey O , Ó Buachalla Réamonn , Strung Karen R
Published: February 2023

We introduce a general framework for associating to a homogeneous quantum principal bundle a Yetter–Drinfeld module structure on the cotangent space of the base calculus. The holomorphic and anti-holomorphic Heckenberger–Kolb calculi of the quantum Grassmannians are then presented in this framework. This allows us to express the calculi in terms of the corresponding Nichols algebras. The extension of this result to all irreducible quantum flag manifolds is then conjectured.
Clinical information system (CIS) implementation in developing countries: requirements, success factors, and recommendations
Authors: Tun Soe Ye Yint , Madanian Samaneh
Published: February 2023

Objective

Clinical Information System (CIS) usage can reduce healthcare costs over time, improve the quality of medical care and safety, and enhance clinical efficiency. However, CIS implementation in developing countries poses additional, different challenges from the developed countries. Therefore, this research aimed to systematically review the literature, gathering and integrating research findings on Success Factors (SFs) in CIS implementation for developing countries. This helps to integrate past knowledge and develop a set of recommendations, presented as a framework, for implementing CIS in developing countries.

Materials and Methods

A systematic literature review was conducted, followed by qualitative data analysis on the published articles related to requirements and SF for CIS implementation. Eighty-three articles met the inclusion criteria and were included in the data analysis. Thematic analysis and cross-case analysis were applied to identify and categorize the requirements and SF for CIS implementation in developing countries.

Results

Six major requirement categories were identified including project management, financial resources, government involvement and support, human resources, organizational, and technical requirements. Subcategories related to SF are classified under each major requirement. A set of recommendations is provided, presented in a framework, based on the project management lifecycle approach.

Conclusion

The proposed framework could support CIS implementations in developing countries while enhancing their rate of success. Future studies should focus on identifying barriers to CIS implementation in developing countries. The country-specific empirical studies should also be conducted based on this research’s findings to match the local context.