bluuebunny/crossref_metadata_2025 huggingface dataset:
Review of SIRIO interferometer experimental results
Authors: Mazzotta C.
Published: August 2023

The SIRIO (Scanning InfraRed Interferometer) interferometer [1], recently disassembled together with the FTU (Frascati Tokamak Upgrade) experiment [2], worked continuously from 2004 to 2019.

An extremely important contribution was made in all the experiments conducted on this tokamak. By virtue of its characteristics, in terms of spatial (1 cm) and temporal resolution (density profiles every 62 μs), combined with its capability to scan the entire plasma column. This interferometer produced all the density feedbacks for operations. Above all, it collected accurate density measurements in plasma physics, among the best data of all tokamak interferometers.

In this review, it is reported the highly valuable experimental work of this powerful diagnostics. Indeed, high density observations were analyzed, as well as fast variations were measured; some examples: the detection of plasma instabilities (MARFE), the trace and the speed of the pellets, the measurement of the particle transport efficiencies in important transients etc.

In order to improve the knowledge for future interferometry in plasma density measurements projects, some topics related to data analysis are also exposed, as well as local density reconstruction methods.
Active wing-pitching mechanism in hummingbird escape maneuvers
Authors: Nasirul Haque Mohammad , Cheng Bo , Tobalske Bret W , Luo Haoxiang
Published: August 2023

Previous studies suggested that wing pitching, i.e. the wing rotation around its long axis, of insects and hummingbirds is primarily driven by an inertial effect associated with stroke deceleration and acceleration of the wings and is thus passive. Here we considered the rapid escape maneuver of hummingbirds who were initially hovering but then startled by the frontal approach of a looming object. During the maneuver, the hummingbirds substantially changed their wingbeat frequency, wing trajectory, and other kinematic parameters. Using wing kinematics reconstructed from high-speed videos and computational fluid dynamics modeling, we found that although the same inertial effect drove the wing flipping at stroke reversal as in hovering, significant power input was required to pitch up the wings during downstroke to enhance aerodynamic force production; furthermore, the net power input could be positive for wing pitching in a complete wingbeat cycle. Therefore, our study suggests that an active mechanism was present during the maneuver to drive wing pitching. In addition to the powered pitching, wing deviation during upstroke required twice as much power as hovering to move the wings caudally when the birds redirected the aerodynamic force vector for escaping. These findings were consistent with our hypothesis that enhanced muscle recruitment is essential for hummingbirds’ escape maneuvers.
Efferocytosis-inspired nanodrug treats sepsis by alleviating inflammation and secondary immunosuppression
Authors: Guo Xiaoyu , Shen Peiming , Shao Rongjiao , Hong Ting , Liu Weizhuo , Shen Yi , Su Fan , Wang Qinlan , He Bin
Published: August 2023

Uncontrolled inflammation storm induced by sepsis may lead to severe organ dysfunction and secondary immunosuppression, which is one of the main reasons for high mortality and prolonged hospitalization of septic patients. However, there is a lack of effective treatments for it at present. Here, we report an efferocytosis-inspired nanodrug (BCN@M) to treat sepsis and secondary immunosuppression via regulating the macrophage function. Bioactive molecular curcumin was loaded with bovine serum albumin and then coated with the damaged erythrocyte membrane derived from septic mice. It was found that the septic erythrocytes promoted the efferocytosis signal and BCN@M uptake efficiency by macrophages. The well-constructed BCN@M nanodrug reduced the hyperinflammation in sepsis and restored the bacterial clearance ability of macrophage in the secondary immunosuppression state. This study highlights BCN@M as an efferocytosis-inspired nanodrug to alleviate hyperinflammation and secondary immunosuppression of sepsis.
Wildfire smoke exposure has significant economic impacts on California’s licensed cannabis industry
Authors: Dillis Christopher , Butsic Van , Martin Jeffrey Vance , Reiman Amanda , Starrs Genoa , Grantham Theodore E
Published: August 2023

California (USA) supports the largest legal cannabis market in the world, yet faces increasing risk from wildfire. While anecdotal evidence of impacts to cannabis crops has been documented during recent extreme fire seasons, the economic losses resulting from smoke exposure and other indirect effects (e.g., ash fall, mandatory evacuations, power outages) are not well understood. We conducted an online survey of licensed cannabis farms across the state, reporting wildfire impacts on cannabis crops from 2018 through 2021. We summarized regional variation in reported cannabis crop losses, fit a hierarchical multinomial model to assess the effects of proximity to fire and smoke exposure on crops, and trained a random forest model to make impact predictions for all state-licensed outdoor cannabis farms. We found that cannabis farms experienced wildfire-related crop losses across all cannabis growing regions in 2020, but that northern regions experienced particularly high crop loss across all four study years. We also found that exposure to wildfire smoke was a stronger predictor of reported impacts than proximity to wildfire. The output of our random forest model suggested substantial impacts for the cannabis industry in 2020, with predicted crop losses between 4.54% and 21.61% statewide, and between 9.09% and 42.83% in the northernmost counties. Estimated potential economic losses in 2020 and 2021 were as high as $1.44 billion and $970.04 million, respectively—losses which themselves exceed annual values of many of California’s other agricultural commodities. Together our results indicate substantial impacts of wildfire for the California cannabis industry as a whole. We suggest that more attention be given to strategies for mitigating cannabis crop losses from wildfires, especially in light of increasing fire occurrence and severity under climate change.
A clustering-based multi-model ensemble projection of near-term precipitation changes over East China and its uncertainty
Authors: Zhao Zihui , Guo Yan , Dong Buwen , Zhu Jiangshan , Luo Neng , Gao Zhibo
Published: August 2023

An ensemble of 28 models from the 6th Coupled Model Intercomparison Project was used to project future changes in annual mean precipitation over East China during 2046–2065 relative to 1995–2014 under the SSP2-4.5 scenario. A precipitation increase of 0.16 mm d−1 is projected over North China by the multi-model ensemble (MME) mean. However, large model uncertainty exists over South China (SC), reducing the fidelity of the MME mean projection. Thus, a clustering-based MME probabilistic projection is presented that projects four possible SC precipitation changes in the future. Precipitation increases are projected in Cluster 1, Cluster 3 and Cluster 4 for 0.51 mm d−1, 0.2 mm d−1 and 0.23 mm d−1, respectively, with occurrence probabilities of 14.3%, 35.7% and 25%, respectively. Conversely, the projected Cluster 2 precipitation decrease is 0.01 mm d−1 with an occurrence probability of 25%. The differences in precipitation change are mainly contributed by dynamic effect due to different circulation changes across clusters. During extended summer, different circulation anomalies over western North Pacific (WNP) among clusters arise from the sea surface temperature anomaly (SSTA) warming patterns over the equatorial central-eastern Pacific, which explain the different precipitation increases over SC. During extended winter, a strong zonal SSTA gradient between the South China Sea and adjacent WNP is projected in Cluster 2, stimulating a zonally vertical cell with anomalous descent over SC and resulting in markedly decreased precipitation. A similar but much weaker zonal SSTA gradient and circulation anomaly are projected in Cluster 3. Distinct meridional SSTA gradients over the WNP are projected in the rest clusters, stimulating shifted descents with a weak effect on SC precipitation.
Uphill diffusions in single and multi-species systems
Authors: Colangeli Matteo , Giberti Claudio , Vernia Cecilia
Published: August 2023

Uphill diffusions constitute an intriguing phenomenon reported in a series of numerical simulations and experiments in which particles move from lower to higher density regions, at variance with the basic tenets of transport theory. In this paper we review several examples of uphill diffusions that appear in quite different frameworks. We highlight the role of the coupling with external reservoirs in the onset of particle currents with the ‘wrong’ sign, and also put forward a statistical mechanical explanation of the phenomenon for stochastic multi-species systems as well as for single-species models undergoing a phase transition.
New features of the surface wave propagation along an exponentially graded-index layer and nonlinear substrate with generalized Kerr-type nonlinear response
Authors: Savotchenko S E
Published: August 2023

New surface waves travelling along the interface between the medium with a generalization of the Kerr nonlinearity and an exponentially graded-index layer are found. The Kerr nonlinearity generalization is assumed to be an abruptly change in the values of Kerr nonlinear response parameters from one to another after the wave amplitude exceeds the threshold value of electric field. The differences between the localization features of surface waves in self-focusing and defocusing media are established. It is shown that the bulk of the surface wave energy is transferred in the optical domain formed near the interface in the case of contact between a graded-index medium and a self-focusing one, which can play the role of the core of the waveguide system. The opposite effect is observed in the case of contact between a graded-index and a defocusing medium, when the main fraction of the surface wave energy is transferred along the graded-index layer, and in the optical domain it is much lower than in a nonlinear substrate.
Renormalization group analysis of a self-organized critical system: intrinsic anisotropy vs random environment
Authors: Antonov N V , Kakin P I , Lebedev N M , Yu Luchin A
Published: August 2023

We study a self-organized critical system coupled to an isotropic random fluid environment. The former is described by a strongly anisotropic continuous (coarse-grained) model introduced by Hwa and Kardar (1989 Phys. Rev. Lett.
62 1813; 1992 Phys. Rev. A 45 7002); the latter is described by the stirred Navier–Stokes equation due to Forster et al (1977 Phys. Rev. A 16 732). The full problem of two coupled stochastic equations is represented as a field-theoretic model, which is shown to be multiplicatively renormalizable. The corresponding renormalization group (RG) equations possess a semi-infinite curve of fixed points in the four-dimensional space of the model parameters. The whole curve is infrared attractive for realistic values of parameters; its endpoint corresponds to the purely isotropic regime where the original Hwa–Kardar nonlinearity becomes irrelevant. There, one is left with a simple advection of a passive scalar field by the external environment. The main critical dimensions are calculated to leading (one-loop) order (first terms in the

ϵ
=
4
−
d

expansion); some of them are exact in all orders. These dimensions remain the same along that curve, which makes it reasonable to interpret it as a single universality class. However, the correction exponents do vary along the curve. It is therefore not clear whether the curve survives in all orders of the RG expansion or shrinks to a single point when the higher-order corrections are taken into account.
The ZX-calculus as a language for topological quantum computation
Authors: Ahmadi Fatimah Rita , Kissinger Aleks
Published: August 2023

Unitary fusion categories formalise the algebraic theory of topological quantum computation. These categories come naturally enriched in a subcategory of the category of Hilbert spaces, and by looking at this subcategory, one can identify a collection of generators for implementing quantum computation. We represent such generators for the Fibonacci and Ising models, namely the encoding of qubits and the associated braid group representations, with the ZX-calculus and show that in both cases, the Yang–Baxter equation is directly connected to an important rule in the complete ZX-calculus known as the P-rule, which enables one to interchange the phase gates defined with respect to complementary bases. In the Ising case, this reduces to a familiar rule relating two distinct Euler decompositions of the Hadamard gate as

π

/

2

Z- and X-phase gates, whereas in the Fibonacci case, we give a previously unconsidered exact solution of the P-rule involving the Golden ratio. We demonstrate the utility of these representations by giving graphical derivations of the single-qubit braid equations for Fibonacci anyons and the single- and two-qubit braid equations for Ising anyons. We furthermore present a fully graphical procedure for simulating and simplifying braids with the ZX-representation of Fibonacci anyons.
Side plasma flow and stagnation of a conical blunt body vehicle under an axial dipole magnetic field
Authors: Wang Chen , Tian Zhenguo , Li Shengdong , Hao Ying
Published: August 2023

The study of plasma flow under the thermal protection magnetic field of reentry vehicle is helpful to verify the magnetic control thermal protection technology and further understand its flow law. By solving hypersonic magnetohydrodynamics equations and combining with dipole magnetic field conditions, the plasma flow mechanism of radio attenuation measurement (RAM)-CII (RAM Experiment) spacecraft at 61 km altitude is analyzed and compared with orbital reentry experiment (OREX) spacecraft under the same conditions. The results show that the plasma flow of RAM-CII is more complex than that of OREX, and there are several regions with different Lorentz force directions near the aircraft, which play the role of plasma ejection and adsorption. Under the action of Lorentz force, the side flow of the aircraft will be separated and reattached, and the fluid stagnation zone will be generated. The results show that for different shapes of aircraft, the flow laws caused by magnetic thermal protection technology are different, and the side flow may be greatly affected.
Neoclassical models of charged particles
Authors: De Zela F
Published: August 2023

Classical electrodynamics (CED) has achieved great success in its domain of application, but despite this success, it has remained a theory that lacks complete self-consistency. It is worthwhile trying to make CED a self-consistent theory, because many important phenomena lie within its scope, and because modern field theories have been modelled on it. Alternative approaches to CED might help finding a definite formulation, and they might also lead to the prediction of new phenomena. Here we report two main results. The first one derives from standard CED. It is shown that the motion of a charged particle is ruled not only by the Lorentz equation, but also by equations that are formally identical to Maxwell equations. The latter hold for a velocity field and follow as a strict logical consequence of Hamilton’s action principle for a single particle. We construct a tensor with the velocity field in the same way as the electromagnetic tensor is constructed with the four potential. The two tensors are shown to be proportional to one another. As a consequence, and without leaving the realm of standard CED, one can envision new phenomena for a charged particle, which parallel those involving electromagnetic fields. The second result refers to a field-free approach to CED. This approach confirms the simultaneous validity of Maxwell-like and Lorentz equations as rulers of charged particle motion.
A bionic controllable strain membrane for cell stretching at air–liquid interface inspired by papercutting
Authors: Li Yuanrong , Xie Mingjun , Lv Shang , Sun Yuan , Li Zhuang , Gu Zeming , He Yong
Published: August 2023

Lung diseases associated with alveoli, such as acute respiratory distress syndrome, have posed a long-term threat to human health. However, an in vitro model capable of simulating different deformations of the alveoli and a suitable material for mimicking basement membrane are currently lacking. Here, we present an innovative biomimetic controllable strain membrane (BCSM) at an air–liquid interface (ALI) to reconstruct alveolar respiration. The BCSM consists of a high-precision three-dimensional printing melt-electrowritten polycaprolactone (PCL) mesh, coated with a hydrogel substrate—to simulate the important functions (such as stiffness, porosity, wettability, and ALI) of alveolar microenvironments, and seeded pulmonary epithelial cells and vascular endothelial cells on either side, respectively. Inspired by papercutting, the BCSM was fabricated in the plane while it operated in three dimensions. A series of the topological structure of the BCSM was designed to control various local-area strain, mimicking alveolar varied deformation. Lopinavir/ritonavir could reduce Lamin A expression under over-stretch condition, which might be effective in preventing ventilator-induced lung injury. The biomimetic lung-unit model with BCSM has broader application prospects in alveoli-related research in the future, such as in drug toxicology and metabolism.
Topology optimization for piezoresistive nanomechanical surface stress sensors in anisotropic 〈111〉 orientations
Authors: Zhuang Chao , Minami Kosuke , Shiba Kota , Yoshikawa Genki
Published: August 2023

Microelectromechanical systems (MEMS)-based piezoresistive nanomechanical sensors are compact sensing platforms widely employed in vapor sensing, environmental monitoring, and biosensing. Despite their extensive utility, their lower sensitivity relative to their optical readout counterparts has been a limiting factor, constraining the wider application of this technology. Prior research has suggested that alternative silicon orientations, such as 〈111〉 orientations in (110) wafers, can significantly improve the sensitivity of piezoresistive sensors. However, the complexity of optimizing two-dimensional stress distribution and handling anisotropic elasticity has made device design a formidable task, leaving this promising avenue largely unexplored. To address this challenge, we employ density-based topology optimization to generate a series of optimized designs for piezoresistive nanomechanical sensors manufactured along 〈111〉 orientations. The properties of the immobilization layer—the functional coating on the sensor—are parametrically varied to explore optimal designs. Our study reveals a transition in optimized designs from a double-cantilever configuration to a suspended platform configuration, dictated by the stiffness ratio between the immobilization layer and the silicon layer. This transition is attributed to the shift in the neutral plane and the prevailing stress relaxation mechanism. In addition, we scrutinize the effects of piezoresistor geometry and find that the optimized designs depend asymmetrically on the piezoresistor position, a characteristic stemming from the anisotropic elasticity in 〈111〉 orientations. These optimized designs, verified by finite element analysis (FEA), demonstrate a notable improvement in sensitivity of more than 20% when benchmarked against traditional rectangular designs and equivalent optimized designs in conventional orientations, thereby validating the effectiveness of the present model. This study provides crucial knowledge for the design of piezoresistive biosensors, facilitating more efficient geometric design in future sensor development.
Implementing a perioperative care of older people undergoing surgery (POPS) service: findings from a multi-site qualitative implementation study
Authors: Waring Justin , Martin Graham P , Hartley Peter , Partridge Judith S L , Dhesi Jugdeep K
Published: August 2023

Background

The Perioperative care for Older People undergoing Surgery (POPS) service model is increasingly being implemented across care providers in the English and Welsh National Health Services.

Objective

The study aimed to produce evidence regarding clinical leaders’ activities to implement POPS across different service contexts and to produce generalisable recommendations for future implementation.

Methods

A qualitative interview study was undertaken across six National Health Services hospitals with established POPS services. Interview participants were recruited on the basis of their direct involvement in the implementation and leadership of the service. Data collection involved semi-structured interviews with 26 people carried out between November 2022 and May 2023.

Results

The implementation of POPS is often hampered by a lack of managerial and financial support, and apprehension amongst surgeons and anaesthetist about new ways of working. POPS leaders address these through five interconnected activities, each targeted at a combination of implementation factors. (i) Securing management and financial support. (ii) Professional engagement. (iii) Evidence building as a resource for demonstrating the clinical and operational benefits of POPS. (iv) Communication and engagement activities to promote and legitimise POPS to stakeholder groups. (v) Designated and distributed leadership to promote and coordinate implementation activities and to spread the service to new pathways.

Conclusions

Through a combination of activities POPS can be effectively implemented across different organisational contexts. Some aspects of these activities can be guided by shared resources and learning across sites, but others require adaption to local contextual barriers and drivers.
Monkeypox virus cytologic findings: An institutional experience with an emerging threat
Authors: Viswanathan Kartik , Mansmann Katrina M , Workowski Kimberly , Guarner Jeannette , Heiman Kimberly M , Lubin Daniel J
Published: August 2023

Objectives

Mpox is a viral disease caused by monkeypox, a highly contagious orthopoxvirus that resulted in a global outbreak beginning in spring 2022. Diagnosis is confirmed via polymerase chain reaction (PCR) testing of swabs from mucocutaneous lesions. Rare reports have documented the histologic changes of mpox lesions, but the cytologic features have not been described. We present the cytology findings of samples taken from swabs of mucocutaneous mpox lesions in 3 different patients.

Methods

The patients were all male, aged 55, 43, and 37 years, all with mpox confirmed by PCR testing. Swabs from chest (cases 1 and 2) and tongue (case 3) lesions were directly sampled and submitted in Aptima (case 1) or PreservCyt solution (cases 2 and 3). Liquid-based preps were prepared and stained using the Papanicolaou method. Specimens were assessed for viral cytopathic changes.

Results

All cases showed nuclear cytopathic changes (enlarged nuclei with open chromatin and prominent red nucleoli), 2 cases demonstrated multinucleated keratinocytes, and 1 case showed potential Guarnieri bodies. The chromatin margination and nuclear molding typical of herpesviruses was not appreciated.

Conclusions

The cytopathic changes of monkeypox are not specific, but their recognition could prompt appropriate PCR testing. Monkeypox shows distinct cytologic changes compared with herpesviruses.
Relationship between drinking risk and preferences for helping resources among emerging adults living in disadvantaged communities in the Southeastern United States
Authors: Tucker Jalie A , Cheong JeeWon , Stinson Lesleigh A , Chandler Susan D
Published: August 2023

Compared to campus-based alcohol interventions for college students, services for emerging adult (EA) risky drinkers who reside off-campus in disadvantaged communities are not well established. This web survey assessed drinking practices, problems, and preferences for professional and lay helping resources spanning digital and in-person formats among community-dwelling EAs to guide services for them and determine whether drinking risk levels varied by preferences for help. Digital respondent-driven sampling recruited EA risky drinkers from disadvantaged communities (N = 356; M age = 23.6 years, 64.0% women, 77.4% employed, 64.9% residing in impoverished areas above the US average, 53.5% income < $20k/year). A web survey assessed participants’ drinking practices and problems, including alcohol use disorder symptoms, and help-seeking preferences for smartphone apps; online help; in-person help from doctors, clinics, teachers, and school programs; mutual help groups; and help from friends and family. Preferences were related to participant drinking risks using generalized linear modeling. Modeling results showed that risk levels were related to help-seeking preferences. EAs reporting more negative consequences preferred smartphone apps and help from friends, whereas EAs reporting fewer negative consequences and drinking days preferred professional in-person help (Ps < 0.05). Although >90% fulfilled alcohol use disorder diagnostic criteria, <4% had received an alcohol-related intervention. EAs who are riskier drinkers appear less likely to use professional resources in favor of informal and online resources that allow greater anonymity. Findings can guide services for this underserved population that are responsive to drinker risk levels.
Virtuous Outlaws: Affective Claims to Value in Professional Speechwriters’ Discourse
Authors: Mapes Gwynne
Published: August 2023

In this paper I investigate the unique ‘production format’ (Goffman 1981) of professional speechwriting; while the behind-the-scenes nature of this high-end language work (Thurlow 2020a) demands a marked erasure of authorship (see Mapes 2023, in press), this can simultaneously be used as a resource for claiming professional virtue and ingroup status. To demonstrate the largely reflexive (e.g. Giddens 1991) and affective (e.g. Weatherell 2013) underpinnings of this sort of discursive negotiation, I draw on my ethnographic fieldwork in the US American speechwriting community, including a 3-day professional speechwriting course; ‘language biography’ interviews (cf. Preston 2004); and a video-recorded virtual meeting. Following important scholarship in professional/workplace discourse, these data not only document the interesting ways in which speechwriters exercise their agency (e.g. White 2018), but also complicated entanglements with the ‘semiotic ideologies’ (Keane 2018) of contemporary life. Ultimately, certain kinds of words and work have value in the (linguistic) marketplace—and according to speechwriters, theirs certainly do.
Phylogeography of the American crocodile, Crocodylus acutus (Crocodylia: Crocodylidae) in Colombia: a conservation perspective
Authors: Moncada-jimenez Juan F , Hernandez-gonzalez Felipe , Prada-quiroga Carlos F , García-calderon Lina M , García Yessy , Hernandez Elkin , Lopez Aristides , Argel Arnold , Polo Juan Manuel , Farfan-ardila Nidia , Balaguera-Reina Sergio A
Published: August 2023

Crocodylus acutus is the most widely distributed crocodile in the Neotropics, playing a key role in the ecosystems it inhabits. However, unsustainable use and habitat degradation have depleted its populations across its range. In Colombia, it is classified as Endangered by local authorities, and a legislative framework for its protection has been created, implementing hunting bans and breeding programmes. Successful implementation of these programmes depends on the existence of baseline genetic information, which is currently insufficient for the species. We assess the genetic diversity, phylogeography, and demographic patterns of the American crocodile in Colombia based on three mitochondrial markers (cox1, cytb, and trnP/trnF/D-Loop) and propose actions for its management and conservation. We processed 33 American crocodile samples from both wild and captive populations and performed genetic variability, phylogenetic, phylogeographical, and neutrality tests, including previously reported sequences. We found evidence of high genetic variability in Colombia, the existence of clearly differentiated mitochondrial phylogenetic clades, and possible human-influenced or stochastic demographic variation events. We propose guidelines for the translocation of American crocodiles based on our findings and present evidence of possible dispersal events in the Caribbean and Magdalena regions. Finally, we suggest the implementation of management units and identify research priorities for future work.
Artificial intelligence-empowered cellular morphometric risk score improves prognostic stratification of cutaneous squamous cell carcinoma
Authors: Pérez-Baena Manuel J , Mao Jian-Hua , Pérez-Losada Jesús , Santos-Briz Ángel , Chang Hang , Cañueto Javier
Published: August 2023

Background

Risk stratification of cutaneous squamous cell carcinoma (cSCC) is essential for managing patients.

Objectives

To determine if artificial intelligence and machine learning might help to stratify patients with cSCC by risk using more than solely clinical and histopathological factors.

Methods

We retrieved a retrospective cohort of 104 patients whose cSCCs had been excised with clear margins. Clinical and histopathological risk factors were evaluated. Haematoxylin and eosin-stained slides were scanned and analysed by an algorithm based on the stacked predictive sparse decomposition technique. Cellular morphometric biomarkers (CMBs) were identified via machine learning and used to derive a cellular morphometric risk score (CMRS) that classified cSCCs into clusters of differential prognoses. Concordance analysis, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated and compared with results obtained with the Brigham and Women’s Hospital (BWH) staging system. The performance of the combination of the BWH staging system and the CMBs was also analysed.

Results

There were no differences among the CMRS groups in terms of clinical and histopathological risk factors and T-stage assignment, but there were significant differences in prognosis. Combining the CMRS with BWH staging systems increased distinctiveness and improved prognostic performance. C-indices were 0.91 local recurrence and 0.91 for nodal metastasis when combining the two approaches. The NPV was 94.41% and 96.00%, the PPV was 36.36% and 41.67%, and accuracy reached 86.75% and 89.16%, respectively, with the combined approach.

Conclusions

CMRS is helpful for cSCC risk stratification beyond classic clinical and histopathological risk features. Combining the information from the CMRS and the BWH staging system offers outstanding prognostic performance for patients with high-risk cSCC.
A comprehensive review of dermoscopy in melasma
Authors: Punchihewa Nisal , Rodrigues Michelle
Published: August 2023

Melasma is a common acquired hyperpigmentation disorder that predominantly affects females with skin of colour. It is difficult to treat and impacts on people’s quality of life, owing to its predilection for the face. In addition to helping make the correct diagnosis, dermoscopy can assist in the exclusion of differential diagnoses, to inform treatment decision-making and to recognize treatment-related adverse effects.
Abnormal interaction between cortical regions of obstructive sleep apnea hypopnea syndrome children
Authors: Shi Naikai , Pang Feng , Chen Jin , Lin Minmin , Liang Jiuxing
Published: August 2023

Obstructive sleep apnea hypopnea syndrome negatively affects the cognitive function of children. This study aims to find potential biomarkers for obstructive sleep apnea hypopnea syndrome in children by investigating the patterns of sleep electroencephalography networks. The participants included 16 mild obstructive sleep apnea hypopnea syndrome children, 12 severe obstructive sleep apnea hypopnea syndrome children, and 13 healthy controls. Effective brain networks were constructed using symbolic transfer entropy to assess cortical information interaction. The information flow pattern in the participants was evaluated using the parameters cross-within variation and the ratio of posterior-anterior information flow. Obstructive sleep apnea hypopnea syndrome children had a considerably higher symbolic transfer entropy in the full frequency band of N1, N2, and rapid eye movement (REM) stages (P < 0.05), and a significantly lower symbolic transfer entropy in full frequency band of N3 stage (P < 0.005), in comparison with the healthy controls. In addition, the cross-within variation of the β frequency band across all sleep stages were significantly lower in the obstructive sleep apnea hypopnea syndrome group than in the healthy controls (P < 0.05). What is more, the posterior-anterior information flowin the β frequency band of REM stage was significantly higher in mild obstructive sleep apnea hypopnea syndrome children than in the healthy controls (P < 0.05). These findings may serve as potential biomarkers for obstructive sleep apnea hypopnea syndrome in children and provide new insights into the pathophysiological mechanisms.
Neural synchrony underlies the positive effect of shared reading on children’s language ability
Authors: Zhai Yu , Xie Huixin , Zhao Hui , Wang Wenjing , Lu Chunming
Published: August 2023

Although it is well recognized that parent–child shared reading produces positive effects on children’s language ability, the underlying neurocognitive mechanisms are not well understood. Here, we addressed this issue by measuring brain activities from mother–child dyads simultaneously during a shared book reading task using functional near infrared spectroscopy hyperscanning. The behavioral results showed that the long-term experience of shared reading significantly predicted children’s language ability. Interestingly, the prediction was moderated by children’s age: for older children over 30 months, the more the shared reading experience, the better the language performance; for younger children below 30 months, however, no significant relationship was observed. The brain results showed significant interpersonal neural synchronization between mothers and children at the superior temporal cortex, which was closely associated with older children’s language ability through the mediation of long-term experience of shared reading. Finally, the results showed that the instantaneous quality of shared reading contributed to children’s language ability through enhancing interpersonal neural synchronization and increasing long-term experience. Based on these findings, we tentatively proposed a theoretical model for the relationship among interpersonal neural synchronization, shared reading and children’s language ability. These findings will facilitate our understanding on the role of shared reading in children’s language development.
Novel synergistic treatment for depression: involvement of GSK3β-regulated AMPA receptors in the prefrontal cortex of mice
Authors: Guo Lei , Wang Shuzhuo , Tian Haihua , Shang Mengyuan , Xu Jia , Wang Chuang
Published: August 2023

Previous evidence has suggested a vital role of glycogen synthase kinase 3β-mediated α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors trafficking in depression. Considering the antidepressant effect of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors activation in the prefrontal cortex, we hypothesized that glycogen synthase kinase 3β-induced alterations in α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors function in the prefrontal cortex participate in depression. Herein, we confirmed that the levels of phosphorylated glycogen synthase kinase 3β and GluA1, the latter being a subunit of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, were decreased in the prefrontal cortex of the chronic social defeat stress model mice presenting with depressive-like behaviors. We then found that a glycogen synthase kinase 3β (p.S9A) point mutation downregulated GluA1 and induced depressive-like behaviors in mice, whereas an agonist of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, PF-4778574 (2 mg/kg) did not reversed the molecular changes. On the other hand, the antidepressant effect of PF-4778574 was dose dependent, and the single administration of PF-4778574 at a lower dose (0.5 mg/kg) or of the glycogen synthase kinase 3β inhibitor SB216763 (5 and 10 mg/kg) did not evoke an antidepressant effect. In contrast, co-treatment with PF-4778574 (0.5 mg/kg) and SB216763 (10 mg/kg) led to antidepressant effects similar to those of PF-4778574 (2 mg/kg). Our results suggest that glycogen synthase kinase 3β-induced α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors dysfunction in the prefrontal cortex is one of the key mechanisms of depression, and the combination of a lower dose of PF-4778574 with SB216763 shows potential as a novel synergistic treatment for depression.
Recommendations for Setting a Criterion for Assessing Commutability of Secondary Calibrator Certified Reference Materials
Authors: Miller W Greg , Keller Thomas , Budd Jeffrey , Johansen Jesper V , Panteghini Mauro , Greenberg Neil , Delatour Vincent , Ceriotti Ferruccio , Deprez Liesbet , Rej Robert , Camara Johanna E , MacKenzie Finlay , Lyle Alicia N , van der Hagen Eline , Burns Chris , Fauskanger Pernille , Sandberg Sverre ,   for the IFCC Working Group on Commutability in Metrological Traceability
Published: August 2023

A secondary higher-order calibrator is required to be commutable with clinical samples to be suitable for use in the calibration hierarchy of an end-user clinical laboratory in vitro diagnostic medical device (IVD-MD). Commutability is a property of a reference material that means results for a reference material and for clinical samples have the same numeric relationship, within specified limits, across the measurement procedures for which the reference material is intended to be used. Procedures for assessing commutability have been described in the literature. This report provides recommendations for establishing a quantitative criterion to assess the commutability of a certified reference material (CRM).

The criterion is the maximum allowable noncommutability bias (MANCB) that allows a CRM to be used as a calibrator in a calibration hierarchy for an IVD-MD without exceeding the maximum allowable combined standard uncertainty for a clinical sample result (umaxCS). Consequently, the MANCB is derived as a fraction of the umaxCS for the measurand. The suitability of an MANCB for practical use in a commutability assessment is determined by estimating the number of measurements of clinical samples and CRMs required based on the precision performance and nonselectivity for the measurand of the measurement procedures in the assessment. Guidance is also provided for evaluating indeterminate commutability conclusions and how to report results of a commutability assessment.
Confirmation of Insertion, Deletion, and Deletion-Insertion Variants Detected by Next-Generation Sequencing
Authors: Choate Lauren A , Koleilat Alaa , Harris Kimberley , Vidal-Folch Noemi , Guenzel Adam , Newman Jessica , Peterson Brenda J , Peterson Sandra E , Rice Christopher S , Train Laura J , Hasadsri Linda , Marcou Cherisse A , Moyer Ann M , Baudhuin Linnea M
Published: August 2023

Background

Despite clinically demonstrated accuracy in next generation sequencing (NGS) data, many clinical laboratories continue to confirm variants with Sanger sequencing, which increases cost of testing and turnaround time. Several studies have assessed the accuracy of NGS in detecting single nucleotide variants; however, less has been reported about insertion, deletion, and deletion-insertion variants (indels).

Methods

We performed a retrospective analysis from 2015–2022 of indel results from a subset of NGS targeted gene panel tests offered through the Mayo Clinic Genomics Laboratories. We compared results from NGS and Sanger sequencing of indels observed in clinical runs and during the intra-assay validation of the tests.

Results

Results demonstrated 100% concordance between NGS and Sanger sequencing for over 490 indels (217 unique), ranging in size from 1 to 68 basepairs (bp). The majority of indels were deletions (77%) and 1 to 5 bp in length (90%). Variant frequencies ranged from 11.4% to 67.4% and 85.1% to 100% for heterozygous and homozygous variants, respectively, with a median depth of coverage of 2562×. A subset of indels (7%) were located in complex regions of the genome, and these were accurately detected by NGS. We also demonstrated 100% reproducibility of indel detection (n = 179) during intra-assay validation.

Conclusions

Together this data demonstrates that reportable indel variants up to 68 bp can be accurately assessed using NGS, even when they occur in complex regions. Depending on the complexity of the region or variant, Sanger sequence confirmation of indels is usually not necessary if the variants meet appropriate coverage and allele frequency thresholds.
Myenteric Plexus Immune Cell Infiltrations and Neurotransmitter Expression in Crohn’s Disease and Ulcerative Colitis
Authors: Wiese Jakob J , Manna Subhakankha , Kühl Anja A , Fascì Alberto , Elezkurtaj Sefer , Sonnenberg Elena , Bubeck Marvin , Atreya Raja , Becker Christoph , Weixler Benjamin , Siegmund Britta , Patankar Jay V , Prüß Magdalena S , Schumann Michael
Published: August 2023

Background and Aims

Pain is a cardinal symptom in inflammatory bowel disease [IBD]. An important structure in the transduction of pain signalling is the myenteric plexus [MP]. Nevertheless, IBD-associated infiltration of the MP by immune cells lacks in-depth characterisation. Herein, we decipher intra- and periganglionic immune cell infiltrations in Crohn´s disease [CD] and ulcerative colitis [UC] and provide a comparison with murine models of colitis.

Methods

Full wall specimens of surgical colon resections served to examine immune cell populations by either conventional immuno-histochemistry or immunofluorescence followed by either bright field or confocal microscopy. Results were compared with equivalent examinations in various murine models of intestinal inflammation.

Results

Whereas the MP morphology was not significantly altered in IBD, we identified intraganglionic IBD-specific B cell- and monocyte-dominant cell infiltrations in CD. In contrast, UC-MPs were infiltrated by CD8+ T cells and revealed a higher extent of ganglionic cell apoptosis. With regard to the murine models of intestinal inflammation, the chronic dextran sulphate sodium [DSS]-induced colitis model reflected CD [and to a lesser extent UC] best, as it also showed increased monocytic infiltration as well as a modest B cell and CD8+ T cell infiltration.

Conclusions

In CD, MPs were infiltrated by B cells and monocytes. In UC, mostly CD8+ cytotoxic T cells were found. The chronic DSS-induced colitis in the mouse model reflected best the MP-immune cell infiltrations representative for IBD.
Cardiac resynchronization therapy using conduction system pacing after double-switch surgery for congenitally corrected transposition of the great arteries: a case report
Authors: De Becker Benjamin , O’Neill Louisa , Pierard Sophie , Le Polain De Waroux Jean-Benoit
Published: August 2023

Background

Patients with congenitally corrected transposition of the great arteries (ccTGA) are at risk of developing conduction disease and complete atrio-ventricular block and this risk increases after corrective cardiac surgery. However, the optimum pacing modality remains controversial.

Case summary

Twelve years after a double-switch surgery with ventricular septal defect correction, a 16-year-old ccTGA female was referred with an indication for cardiac resynchronization therapy. In the absence of coronary sinus (CS) or direct access to the conduction system, several therapeutic options were considered. Finally, using a three-dimensional navigation system and customized sheaths, a left bundle branch area pacing (LBBAP) lead was successfully implanted. The implantation resulted in stable pacing parameters and positive haemodynamic changes. At 9-month follow-up, pacing parameters were stable and the patient reported a significant improvement in quality of life.

Discussion

Cardiac resynchronization therapy in adults with repaired congenital heart disease remains challenging, especially in the absence of CS or direct access to the conduction system. In such a situation, LBBAP appears as an attractive alternative pacing modality. However, pre-operative management is critical to the success of the implantation.
Expressway to Votes: Infrastructure Projects and Voter Persuasion
Authors: Akbulut-Yuksel Mevlude , Okoye Dozie , Turan Belgi
Published: August 2023

This paper provides causal evidence on how political parties can sway voters at scale in nascent electoral democracies. We collect novel data on expressway construction by the Justice and Development Party in Turkey and use province-by-year variation in construction to show that votes for the Justice and Development Party increased in response to the expressways. The estimates imply that the expressways increased the Justice and Development Party’s vote share by 4.8 percentage points—a third of the increase from 2002 to 2011. We provide evidence that the visibility and competence signalled by the expressway expansion, and not increased local economic growth, drove increased vote shares.
Leflutrozole in male obesity-associated hypogonadotropic hypogonadism: Ph 2b double-blind randomised controlled trial
Authors: Jones T Hugh , Dobs Adrian S , Randeva Harpal , Moore William , Parkin Jacqueline M
Published: August 2023

Objective

Assessment of the efficacy and safety/tolerability of the aromatase inhibitor leflutrozole to normalise testosterone in Obesity-associated Hypogonadotropic Hypogonadism (OHH).

Design

Placebo-controlled, double-blind, RCT, in 70 sites in Europe/USA.

Methods

Patient inclusion criteria: men with BMI of 30-50 kg/m2, morning total testosterone (TT) < 10.41 nmol/L, and two androgen deficiency symptoms (at least one of sexual dysfunction). Patients randomised to weekly leflutrozole (0.1/0.3/1.0 mg) or placebo for 24 weeks. Primary endpoint: normalisation of TT levels in ≥75% of patients after 24 weeks. Secondary endpoints (included): time to TT normalisation and change in LH/FSH. Safety was assessed through adverse events and laboratory monitoring.

Results and Conclusions

Of 2103 screened, 271 were randomised, 81 discontinued. Demographic characteristics were similar across groups. Mean BMI was 38.1 kg/m2 and TT 7.97 nmol/L. The primary endpoint was achieved in all leflutrozole-treated groups by 24 weeks with a dose-tiered response; mean TT 15.89; 17.78; 20.35 nmol/L, for leflutrozole 0.1 mg, 0.3 mg, and 1.0 mg groups respectively, vs 8.04 nmol/L for placebo. LH/FSH significantly increased in leflutrozole vs placebo groups. No improvements in body composition or sexual dysfunction were observed. Semen volume/total motile sperm count improved with leflutrozole vs placebo. Treatment-emergent adverse events, more common in leflutrozole-treated groups included, raised haematocrit, hypertension, increased PSA, and headache. Some reduction in lumbar bone density was observed with leflutrozole (mean −1.24%, −1.30%, −2.09%) and 0.66% for 0.1 mg, 0.3 mg, 1.0 mg, and placebo, respectively, without change at the hip. This RCT of leflutrozole in OHH demonstrated normalisation of TT in obese men. FSH/LH and semen parameter changes support that leflutrozole may preserve/improve testicular function.

Clinical Trial Registration number

NCT02730169.