bluuebunny/crossref_metadata_2025 huggingface dataset:
Antidepressant exposures associated with exploratory behavior among young children reported to United States poison control centers, 2000–2020
Authors: Francis Matilda , Spiller Henry A. , Badeti Jaahnavi , Casavant Marcel J. , Michaels Nichole L. , Zhu Motao , Smith Gary A.
Published: August 2022

Purpose

This study investigates characteristics and trends of antidepressant exposures among children <6 years old related to exploratory behavior reported to US poison control centers.

Methods

Using data from the National Poison Data System for 2000–2020, population‐based annual exposure rates by sex, antidepressant category, serious medical outcome, and health care facility admission were analyzed and odds ratios to assess associations of exposure type and antidepressant category with medical outcome and admission were calculated.

Results

There were 215 909 first‐ranked unintentional exploratory exposures involving antidepressants among children <6 years old during the study period, averaging 10 281 annually. Most cases were <3 years old (77.8%), involved a single substance (86.9%), and did not receive treatment at a health care facility (57.6%); however, 7.9% were admitted and 3.4% had serious medical outcomes, including 13 deaths. SSRIs were involved in 56.9% of all cases. Compared with SSRIs, bupropion (OR: 5.22, 95% CI: 4.68–5.82), TCAs (OR: 3.74, 95% CI: 3.44–4.07), SNRIs (OR: 2.39, 95% CI: 2.11–2.71), and lithium salts (OR: 2.00, 95% CI: 1.63–2.46) were more likely to be associated with a serious medical outcome. TCAs were the first‐ranked substance in 7 of the 13 deaths.

Conclusions

Although most unintentional antidepressant exposures related to pediatric exploratory behavior were inconsequential, an important minority of cases required admission to a HCF or had a serious medical outcome, including 13 deaths. Therefore, increased efforts to prevent these exposures among young children are needed, including public education and improved medication packaging.
A successful treatment of a lobar atelectasis in a patient with cystic fibrosis
Authors: Daccò Valeria , Sciarrabba Calogero Sathya , Corti Fabiola , Rosazza Chiara , Malfitano Anna , Borzani Irene , Colombo Carla
Published: August 2022

Lobar atelectasis may be a complication of pulmonary exacerbations in cystic fibrosis (CF). There are no established guidelines on the management of this condition in patients with CF. Therapeutic bronchoscopy with recombinant human deoxyribonuclease (rhDNase) instillation has been described to be successful in patients not responding to conservative measures. We describe a case of a young man with CF, with previously mild impaired lung function, presenting with cough, desaturation, and worsening dyspnea, persisting for over 6 weeks, despite conservative therapy. Thoracic imaging showed right lower lobe atelectasis, which was successfully treated with bronchoscopy and instillation of rhDNase. Long‐term resolution of the atelectasis was confirmed with chest magnetic resonance imaging follow‐up.
Pulmonary edema in a pediatric cancer patient after anesthetic induction
Authors: Mota Bárbara , Curval Ana Rita , Silva Sónia , Ferraz Catarina , Graça Maria Inês , da Silva Nuno Pereira , Azevedo Inês
Published: August 2022

Negative pressure pulmonary edema (NPPE) in the context of anesthesia is a rare condition, although pediatric patients are at higher risk. This case stands out for the severe respiratory clinic that quickly developed in a child with a cancer history whose radiological and clinical presentation suggested multiple differential diagnoses, including tumor recurrence with metastasis or pulmonary tuberculosis. NPPE is a well‐described, but a probably underrecognized clinical syndrome, that occurs after intense inspiratory effort against an obstructed airway. In clinical practice, when unexplained pulmonary edema takes place, NPPE should be considered in the differential diagnosis. NPPE usually has a favorable prognosis but pediatricians, radiologists, and anesthesiologists should be aware of this complication.
Magnetic Properties of Two‐Line Ferrihydrite Nanoparticles
Authors: Rani Chandni , Tiwari Surendra Deo
Published: August 2022

Two‐line ferrihydrite particles are synthesized. Structural characterization of the sample is done with an X‐ray diffractometer, transmission electron microscope, Fourier‐transform infrared spectroscope, and thermogravimetric analyzer. Average particle size is 2 nm. Temperature variation (10–300 K) of zero‐field‐cooled and field‐cooled susceptibility in 500 G applied magnetic field bifurcates at 50 K. The field‐cooled susceptibility below this temperature is almost temperature independent. Magnetization versus applied magnetic field (0–120 kG) data at 300 K are analyzed considering particle size distribution.
Approaches for Fabricating Tri‐ and Tetraphenylethene‐Based Blue Organic Light‐Emitting Diodes Using Donor–Acceptor and Non‐Donor–Acceptor Molecular Architectures
Authors: Harshini Deivendran , Devibala Panneerselvam , Angela Varghese Maria , Nagarajan Samuthira
Published: August 2022

Organic light‐emitting diodes (OLEDs) have exceeded expectations in terms of portability and affordability; still there is potential for advancement in terms of efficiency and color changeability. Research on flexible displays and OLED light emission is hampered by the low solid‐state efficiency and bandgap discrepancies of blue light emitters. However, aggregation‐induced emission (AIE) presents an opportunity to create efficient blue emitters. By suppressing the π‐π stacking interactions, triphenylethene (TriPE) and tetraphenylethene (TPE) molecule‐based AIE luminogens exhibit outstanding solid‐state emission and increased device efficiency. Additionally, the presence of TriPE and TPE donor units in the architecture of non‐donor–acceptor (non‐D–A)‐ and donor–acceptor (D–A)‐based architectures has increased chemical and thermal stability with high efficiency. This article emphasizes multiple device architectures and different light emissions (blue, red, and green) set forth by potential electron donating/accepting molecules possessing intriguing efficiency in the device fabrication. It also presents the substitution effect on TriPE and TPE donor units and the applicability of non‐D–A and D–A systems in OLEDs.
High‐Pressure Crystal Structures of Pb2CO4 and PbC2O5 with Tetrahedral [CO4] and Pyrocarbonate [C2O5] atomic groups
Authors: Banaev Maksim V. , Sagatov Nursultan E. , Sagatova Dinara N. , Gavryushkin Pavel N.
Published: August 2022

The search of the stable intermediate compounds in the system PbO−CO2 have been performed using crystal structure prediction technique in the pressure range of 0–50 GPa. Stable structures were found for the compositions Pb2CO4 and PbC2O5. The earlier known oxy‐carbonate Pb2CO4‐P212121 was shown to transform at 10 GPa into another oxy‐carbonate Pb2CO4‐Pnma and than at 22 GPa – into the sp3‐hybridized orthocarbonate with the same symmetry. PbC2O5 became thermodynamically stable at almost 10 GPa in the form of the pyrocarbonate structure P21/c. At 35–45 GPa, PbC2O5‐P21/c transforms into PbC2O5‐Fdd2 with the framework of [CO4] tetrahedra. Another energetically favorable, although dynamically unstable, pyrocarbonate structure PbC2O5‐P
was found in the narrow pressure interval around 10 GPa. We suggest that some analogue of this structure can appear in experiment. One structure, sp3‐hybridized Pb2CO4‐Pnma, is dynamically and thermally stable at ambient pressure, and therefore can be decompressed and extracted from the high‐pressure environment.
Novel Derivatives of 4,6‐Dihydroxy‐2‐Quinolone‐3‐Carboxamides as Potential PI3Kα Inhibitors
Authors: Sweidan Kamal , Elfadel Hussein , Sabbah Dima A. , Bardaweel Sanaa K. , Hajjo Rima , Anjum Shabana , Sinoj Jithna , Nair Vidhya A. , Abu‐Gharbieh Eman , El‐Huneidi Waseem
Published: August 2022

The phosphatidylinositol 3‐kinase/protein kinase B (PI3K/AKT) pathway is a crucial pathway in cancer pathogenesis. Novel derivatives of 4,6‐dihydroxy‐2‐quinolone‐3‐carboxamides were synthesized as potential PI3Kα inhibitors. Derivatives’ chemical identity was approved using 1H‐NMR, 13C‐NMR, FTIR, and MS. Cytotoxicity was evaluated on the breast (MCF‐7) and colon cancer (HCT‐116) cell lines using the CCK8 assay. Apoptosis was assessed by Annexin‐PI staining. Western blotting was employed to assess the expression of BcL2, Bax, and the phosphorylation status of AKT. Data revealed that compounds exhibited a dose‐response cytotoxic effect. Compounds 8 b and 8 f showed the lowest IC50 on all cell lines and highest apoptosis levels that were associated with lower BcL2/Bax ratios. Western blot results showed a significant inhibition of pAKT in the treated cells, which could be attributed to PI3Kα inhibitory effects of 8 b and 8 f. In conclusion, our findings indicate that 8 b and 8 f are drug‐like chemical compounds that possess promising anticancer effects.
Performance Enhancement of Crystal Silicon Solar Cell by a CsPbBr3–Cs4PbBr6 Perovskite Quantum Dot @ZnO/Ethylene Vinyl Acetate Copolymer Downshifting Composite Film
Authors: Song Jian , Ren Yifan , Gong Shijie , Zhao Liang , Xuan Wufan , Zhu Lei , Zhao Yulong , Qiang Yinghuai , Gao Lili , Huang Sheng
Published: August 2022

Crystal silicon solar cells being the most successful photovoltaic devices have prevailed in the energy market for decades. To further improve the device performance, photon management is necessary. Herein, a CsPbBr3–Cs4PbBr6 perovskite quantum dot@ZnO/ethylene vinyl acetate copolymer downshifting composite film is coated on the silicon solar cell. This downshifting composite film helps to convert high‐energy (UV‐blue) photons to relatively low‐energy photons with a wavelength at about 500 nm, which possess higher sensitivity in silicon solar cells. The effects of tetra‐n‐heptylammonium bromide and Zn(C2H5)2 on composition, optical and luminescence properties of perovskite quantum dots are thoroughly investigated, and a clean quantum dot solution with strong luminescent intensity can be obtained. The perovskite quantum dot@ZnO/ethylene vinyl acetate composite film absolutely improves the efficiency of silicon solar cells by 1.18%. The value is much higher than pure ethylene vinyl acetate (0.42%) and composite film without ZnO (0.57%). Moreover, ZnO inclusion can inhibit Cs and Pb leakage and maintain the device working stability, which is helpful for their commercial application in the future. This study further reveals that the enhancement lies in carrier relaxation energy loss reduction. Herein, a low‐cost downshifting composite film with excellent environmental stability for silicon solar cells applications is proposed.
The system‐process view of life from the perspective of systems science and its enlightenment to artificial life
Authors: Zhang Wangjun , Fan Dongping
Published: August 2022

The development of systems science has provided a new interdisciplinary approach to understanding the nature of life. General system theory, developed by Bertalanffy, understands life as open, dynamic and autonomous systems. The self‐organisation theory, represented by Prigogine, takes life as a self‐organising process‐structure that obtains sufficient negative entropy by exchanging material and energy with the environment. The complex adaptive system theory proposed by Holland and others understands life as adaptive process‐systems. Krakauer's information theory of individuality construes life as a process in which ordered information propagates forward with time. By highlighting the processual dimensions of the afore‐mentioned approaches, we propose the ‘system‐process view of life’, which underscores that life is not only a structural whole, but also a functional–processual whole. The system‐process view of life provides new inspirations for the replicator hypothesis of artificial life and the new basis for the discussion of the ontological status of artificial life.
Coupling Transition Metal Catalysts with Ir for Enhanced Electrochemical Water Splitting Activity
Authors: Yang Xin , Liu Yan , Guo Ruike , Xiao Jiafu
Published: August 2022

Developing advanced electrocatalysts is of great significance for boosting electrochemical water splitting to produce hydrogen. The electrocatalytic activity of a catalyst is associated with the surface/interface, geometric structure, and electronic properties. Coupling Ir with transition metal compounds is an effective strategy to improve their electrocatalytic performance. In this review, we summarize the recent progress of Ir coupled transition metal compound catalysts for the application in driving electrochemical water splitting. The significant role of Ir played in the promotion of electrocatalytic performance is firstly illustrated. Then, the applications of Ir‐based catalysts in the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) are comprehensively discussed, with an emphasis on correlating the structure‐function relationships. Lastly, the challenges and future directions for the fabrication of more advanced Ir coupled electrocatalysts are also presented.
The Cultural Theory and Model of Suicide for Youth
Authors: Chu Joyce , O’Neill Sam E. , Ng Juliana F. , Khoury Oula
Published: August 2022

This chapter identifies key guidelines and opportunities for the incorporation of cultural considerations into youth suicide prevention, assessment, and intervention. Cultural factors and principles from the Cultural Theory and Model of Suicide (Chu et al., 2010) are extended to ethnic, gender, and sexual minority youth, to identify cultural factors that are more salient or more strongly related to suicide risk for youth populations. Research supports a downward extension of the Cultural Theory and Model of Suicide for minority youth, with its three theoretical principles and four factors of cultural sanctions, idioms of distress, minority stress, and social discord. Specific youth-related risk factors within these four factors are specified, including academic stress, family rejection, intergenerational conflict, and experiences of peer rejection, victimization, and bullying due to the youth’s minority identities. Integration of these key cultural factors is important for culturally responsive suicide prevention and practice across diverse youth populations. Best practices for infusing cultural considerations and suggestions for future research are highlighted.
Black Youth Suicidal Behavior: What We Know and Where We Go from Here
Authors: Sheftall Arielle H. , Boyd Rhonda C.
Published: August 2022

Research concerning Black youth suicide and suicidal behavior is limited, yet the rates of these behaviors continue to rise in this population of youth. In children, 5–12 years, Black youth are two times more likely to die by suicide than their White peers, and suicide attempts among Black adolescents have increased by 73%. Understanding the risk factors associated with suicidal behavior in Black youth is imperative to create prevention efforts for Black youth. This chapter will discuss what is known concerning the topic of Black youth suicidal behavior and provide research, practice, and policy recommendations.
The Rise and Development of Digital Education
Authors: Weller Martin
Published: August 2022

Over the past 25 years, digital education has risen to prominence. It has a direct relationship with open education, which can be considered an umbrella term. In this chapter the rise of digital education is explored through five specific educational technologies. These technologies – the web, Learning Management System (LMS), blogs, social media, and Massive Open Online Courses (MOOCs) – all raise issues of control and ease of use. They also have a direct impact on different aspects of open education, which in turn helps inform their development. This chapter sets out the multiple interpretations of open education and their overlap with digital education. By then exploring five educational technologies, common themes are extracted which highlight this intersection of digital and open education.
Out-of-Time-Order correlators in driven conformal field theories
Authors: Das Suchetan , Ezhuthachan Bobby , Kundu Arnab , Porey Somnath , Roy Baishali , Sengupta K.
Published: August 2022

Abstract

We compute Out-of-Time-Order correlators (OTOCs) for conformal field theories (CFTs) subjected to either continuous or discrete periodic drive protocols. This is achieved by an appropriate analytic continuation of the stroboscopic time. After detailing the general structure, we perform explicit calculations in large-c CFTs where we find that OTOCs display an exponential, an oscillatory and a power-law behaviour in the heating phase, the non-heating phase and on the phase boundary, respectively. In contrast to this, for the Ising CFT representing an integrable model, OTOCs never display such exponential growth. This observation hints towards how OTOCs can demarcate between integrable and chaotic CFT models subjected to a periodic drive. We further explore properties of the light-cone which is characterized by the corresponding butterfly velocity as well as the Lyapunov exponent. Interestingly, as a consequence of the spatial inhomogeneity introduced by the drive, the butterfly velocity, in these systems, has an explicit dependence on the initial location of the operators. We chart out the dependence of the Lyapunov exponent and the butterfly velocities on the frequency and amplitude of the drive for both protocols and discuss the fixed point structure which differentiates such driven CFTs from their undriven counterparts.
Quantum corrections to the primordial tensor spectrum: open EFTs & Markovian decoupling of UV modes
Authors: Brahma Suddhasattwa , Berera Arjun , Calderón-Figueroa Jaime
Published: August 2022

Abstract

Perturbative quantum corrections to primordial power spectra are important for testing the robustness and the regime of validity of inflation as an effective field theory. Although this has been done extensively for the density power spectrum (and, to some extent, for the tensor spectrum) using loop corrections, we do so in an open quantum system approach to the problem. Specifically, we calculate the first-order corrections to the primordial gravitational wave spectrum due to (cubic) tensor interactions alone. We show that our results match expectations from standard loop corrections only in the strict Markovian limit, and therefore, establish a systematic way to relax this approximation in the future, as is generally necessary for gravitational systems.
Topological constraints in the LARGE-volume scenario
Authors: Junghans Daniel
Published: August 2022

Abstract

We elaborate on recent results regarding the self-consistency of de Sitter vacua in the LARGE-volume scenario of type IIB string theory. In particular, we analyze to what extent the control over warping, curvature and gs corrections depends on the topology and the orientifold/brane data of a compactification. We compute a general bound on the magnitude of these corrections which strongly constrains the D3 tadpole. The minimally required tadpole ranges from $$ \mathcal{O} $$
O
(500) to $$ \mathcal{O} $$
O
(106) or more and depends strongly on other data, in particular on the Euler number of the Calabi-Yau 3-fold, the triple-self-intersection and Euler numbers of the small divisor and the coefficient as appearing in the non-perturbative superpotential. We give arguments suggesting that satisfying these constraints is very challenging and perhaps impossible.
Hunting for vampires and other unlikely forms of parity violation at the Large Hadron Collider
Authors: Lester Christopher G. , Mastandrea Radha , Noel Daniel , Tombs Rupert
Published: August 2022

Abstract

Non-Standard-Model parity violation may be occurring in LHC collisions. Any such violation would go unseen, however, as searches for it are not currently performed. One barrier to searches for parity violation is the lack of model-independent methods sensitive to all of its forms. We remove this barrier by demonstrating an effective and model-independent way to search for parity-violating physics at the LHC. The method is data-driven and makes no reference to any particular parity-violating model. Instead, it inspects data to construct sensitive parity-odd event variables (using machine learning tools), and uses these variables to test for parity asymmetry in independent data. We demonstrate the efficacy of this method by testing it on data simulated from the Standard Model and from a non-standard parity-violating model. This result enables the possibility of investigating a variety of previously unexplored forms of parity violation in particle physics.

Data and software are shared at https://zenodo.org/record/6827724.
On the time dependence of holographic complexity for charged AdS black holes with scalar hair
Authors: Auzzi Roberto , Bolognesi Stefano , Rabinovici Eliezer , Schaposnik Massolo Fidel I. , Tallarita Gianni
Published: August 2022

Abstract

In the presence of a scalar hair perturbation, the Cauchy horizon of a Reissner-Nordström black hole disappears and is replaced by the rapid collapse of the Einstein-Rosen bridge, which leads to a Kasner singularity [1, 2]. We study the time-dependence of holographic complexity, both for the volume and for the action proposals, in a class of models with hairy black holes. Volume complexity can only probe a portion of the black hole interior that remains far away from the Kasner singularity. We provide numerical evidence that the Lloyd bound is satisfied by the volume complexity rate in all the parameter space that we explored. Action complexity can instead probe a portion of the spacetime closer to the singularity. In particular, the complexity rate diverges at the critical timetcfor which the Wheeler-DeWitt patch touches the singularity. After the critical time the action complexity rate approaches a constant. We find that the Kasner exponent does not directly affect the details of the divergence of the complexity rate att=tcand the late-time behaviour of the complexity. The Lloyd bound is violated by action complexity at finite time, because the complexity rate diverges att=tc. We find that the Lloyd bound is satisfied by the asymptotic action complexity rate in all the parameter space that we investigated.
Conformal blocks and bilocal vertex operator transition amplitudes
Authors: Vos Gideon
Published: August 2022

Abstract

We revisit the construction of the 2d conformal blocks of primary operator four-point functions as bilocal vertex operator correlators. We find an additional interpretation as a path integral over the reparametrizations of an intermediate cylinder. As a consequence we bridge the gap between the Kähler quantization of virasoro coadjoint orbits, SL(2, ℝ) Chern-Simons theory and the reparametrization formalism of 2d CFT that has made an appearance in recent literature.
Cdk5 regulates IP3R1-mediated Ca2+ dynamics and Ca2+-mediated cell proliferation
Authors: NavaneethaKrishnan Saranya , Law Vincent , Lee Jungkwon , Rosales Jesusa L. , Lee Ki-Young
Published: August 2022

Loss of cyclin-dependent kinase 5 (Cdk5) in the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) increases ER–mitochondria tethering and ER Ca2+ transfer to the mitochondria, subsequently increasing mitochondrial Ca2+ concentration ([Ca2+]mt). This suggests a role for Cdk5 in regulating intracellular Ca2+ dynamics, but how Cdk5 is involved in this process remains to be explored. Using ex vivo primary mouse embryonic fibroblasts (MEFs) isolated from Cdk5−/− mouse embryos, we show here that loss of Cdk5 causes an increase in cytosolic Ca2+concentration ([Ca2+]cyt), which is not due to reduced internal Ca2+ store capacity or increased Ca2+ influx from the extracellular milieu. Instead, by stimulation with ATP that mediates release of Ca2+ from internal stores, we determined that the rise in [Ca2+]cyt in Cdk5−/− MEFs is due to increased inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca2+ release from internal stores. Cdk5 interacts with the IP3R1 Ca2+ channel and phosphorylates it at Ser421. Such phosphorylation controls IP3R1-mediated Ca2+ release as loss of Cdk5, and thus, loss of IP3R1 Ser421 phosphorylation triggers an increase in IP3R1-mediated Ca2+ release in Cdk5−/− MEFs, resulting in elevated [Ca2+]cyt. Elevated [Ca2+]cyt in these cells further induces the production of reactive oxygen species (ROS), which upregulates the levels of Nrf2 and its targets, Prx1 and Prx2. Cdk5−/− MEFs, which have elevated [Ca2+]cyt, proliferate at a faster rate compared to wt, and Cdk5−/− embryos have increased body weight and size compared to their wt littermates. Taken together, we show that altered IP3R1-mediated Ca2+ dynamics due to Cdk5 loss correspond to accelerated cell proliferation that correlates with increased body weight and size in Cdk5−/− embryos.
Euphotic representations and rigid automorphic data
Authors: Jakob Konstantin , Yun Zhiwei
Published: August 2022

We propose a new method to construct rigid G-automorphic representations and rigid $${\widehat{G}}$$

G
^

-local systems for reductive groups G. The construction involves the notion of euphotic representations, and the proof for rigidity involves the geometry of certain Hessenberg varieties.
Diabetes precision medicine: plenty of potential, pitfalls and perils but not yet ready for prime time
Authors: Griffin Simon
Published: August 2022

Rapid advances in technology and data science have the potential to improve the precision of preventive and therapeutic interventions, and enable the right treatment to be recommended, at the right time, to the right person. There are well-described examples of successful precision medicine approaches for monogenic conditions such as specific diets for phenylketonuria, and sulfonylurea treatments for certain types of MODY. However, the majority of chronic diseases are polygenic, and it is unlikely that the research strategies used for monogenic diseases will deliver similar changes to practice for polygenic traits. Type 2 diabetes, for example, is a multifactorial, heterogeneous, polygenic palette of metabolic disorders. In this non-systematic review I highlight limitations of the evidence, and the challenges that need to be overcome prior to implementation of precision medicine in the prevention and management of type 2 diabetes. Most precision medicine approaches are spuriously precise, overly complex and too narrowly focused on predicting blood glucose levels with a limited set of characteristics of individuals rather than the whole person and their context. Overall, the evidence to date is insufficient to justify widespread implementation of precision medicine approaches into routine clinical practice for type 2 diabetes. We need to retain a degree of humility and healthy scepticism when evaluating novel strategies, and to demand that existing evidence thresholds are exceeded prior to implementation.

Graphical abstract
Quantum vs. Classical Algorithms for Solving the Heat Equation
Authors: Linden Noah , Montanaro Ashley , Shao Changpeng
Published: August 2022

Quantum computers are predicted to outperform classical ones for solving partial differential equations, perhaps exponentially. Here we consider a prototypical PDE—the heat equation in a rectangular region—and compare in detail the complexities of ten classical and quantum algorithms for solving it, in the sense of approximately computing the amount of heat in a given region. We find that, for spatial dimension$$d \ge 2$$d≥2, there is an at most quadratic quantum speedup in terms of the allowable error$$\epsilon $$ϵusing an approach based on applying amplitude estimation to an accelerated classical random walk. However, an alternative approach based on a quantum algorithm for linear equations is never faster than the best classical algorithms.
In vivo monitoring of Lactiplantibacillus plantarum in the nasal and vaginal mucosa using infrared fluorescence
Authors: Silva-Bea Sergio , Francisco-Tomé Mónica , Cabrera-Alvargonzález Jorge J. , Potel Carmen , Álvarez Maximiliano , Pérez Sonia , Regueiro Benito , Cabral Maria P.
Published: August 2022

Lactic acid bacteria (LAB) of the genus Lactiplantibacillus have been explored as potential mucosal vaccine vectors due to their ability to elicit an immune response against expressed foreign antigens and to their safety. However, tools for monitoring LAB distribution and persistence at the mucosal surfaces are needed. Here, we characterize Lactiplantibacillus plantarum bacteria expressing the infrared fluorescent protein IRFP713 for exploring their in vivo distribution in the mucosa and potential use as a mucosal vaccine vector. This bacterial species is commonly used as a vaginal probiotic and was recently found to have a niche in the human nose. Three different fluorescent L. plantarum strains were obtained using the nisin-inducible pNZRK-IRFP713 plasmid which contains the nisRK genes, showing stable and constitutive expression of IRFP713 in vitro. One of these strains was further monitored in BALB/c mice using near-infrared fluorescence, indicating successful colonization of the nasal and vaginal mucosae for up to 72 h. This study thus provides a tool for the in vivo spatiotemporal monitoring of lactiplantibacilli, allowing non-invasive bacterial detection in these mucosal sites.

Key points

• Stable and constitutive expression of the IRFP713 protein was obtained in different L. plantarum strains.

• IRFP713+ L. plantarum 3.12.1 was monitored in vivo using near-infrared fluorescence.

• Residence times observed after intranasal and vaginal inoculation were 24–72 h.

Graphical abstract
Cosmetic Revision Surgeries after Transfeminine Vaginoplasty
Authors: Mañero Ivan , Arno Anna I. , Herrero Roberto , Labanca Trinidad
Published: August 2022

Background

Vaginoplasty is the most frequent genital gender-affirming surgery. Although both functional and aesthetic outcomes after transfeminine vaginoplasty have improved over the years, cosmetic revision surgeries demand after transfeminine vaginoplasty appears to be increasing and requires updated knowledge.

Methods

All patients who underwent vulvar cosmetic revision surgeries at our institution following transfeminine vaginoplasty from January 2014 to April  2022 were studied. The prevalence, topography and surgical techniques of cosmetic revision surgeries after transfeminine genital gender-affirming surgery were examined using clinical charts review and statistical analysis.

Results

During the study period, 354 patients underwent gender-affirming vaginoplasty at our single institution (212 penile inversion vaginoplasty, 122 colovaginoplasty and 20 penile inversion vaginoplasty with scrotal skin graft patients). Forty out of these 354 patients (11.29%) required cosmetic revision surgery after transfeminine vaginoplasty; additionally, 44 patients with vaginoplasty performed at other centres also underwent vulvar cosmetic revision surgery at our clinic during the study period. From all performed cosmetic revision surgeries, most of them (31.42%) were labia corrections, followed by clitoris (23.26%) repair surgeries. Mons Venus (10.20%), urethral meatus (9.38%), spongiosus tissue remnants (8.57%) and introitus (6.53%) revisions followed in frequency. Corrections of peri-inguinal scars (5.30%), anterior commissure (2.84%) and inferior fourchette (2.42%) were less prevalent. No differences were found among the different studied vaginoplasty techniques regarding cosmetic revision surgery prevalence or topography following transfeminine vaginoplasty (p < 0.05).

Conclusions

Cosmetic revision surgeries after transfeminine vaginoplasty are frequent. In our large and long-term cohort study, labiaplasty followed by clitoroplasty were found as the most required cosmetic revision surgical procedures. Further multicentre, prospective and controlled studies are necessary to improve cosmetic outcomes and scientific evidence after transfeminine vaginoplasty.

Level of evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Percutaneous Thrombectomy in Patients with Occlusions of the Aortoiliac Segment: A Case Series
Authors: Sieren Malte Maria , Pfarr Julian , Aludin Schekeb , Mostafa Karim , Stahlberg Erik , Wegner Franz , Mogadas Sam , Rusch Rene , Horn Marco , Schäfer Philipp
Published: August 2022

Objective

Thrombectomy of the aortoiliac segment remains a challenge for surgical and endovascular revision. This study aimed to evaluate the concept of percutaneous thrombectomy in patients with aortoiliac segment occlusions.

Materials & Methods

Eighteen patients with aortoiliac occlusion who underwent percutaneous thrombectomy were retrospectively identified using the local picture archive and divided into the stent-graft (N = 10) and native vessels (N  =  8) groups. The procedure was performed by placing a 12–24 French sheath adjacent to the distal end of the occluded vessel segment. The occlusion was passed with a balloon catheter which was retracted after inflation, to deliver the thrombus into the sheath. Technical success (reperfusion of the vessel and no residual thrombus/stenosis < 30%), complications and primary arterial patency were assessed. Follow-up included computed tomography angiography and evaluation of the clinical situation via telephone.

Results

Technical success was achieved in 38% (7/18) of patients after percutaneous thrombectomy alone and in 100% after additional procedures. The most common complication was peripheral embolism (44%, 8/18), which was treated successfully in all cases and was linked to a mismatch between the sheath and target vessel of ≥ 1 mm (P < .01). There were no significant differences in the incidence of complications between the two groups. Primary patency was 72% (13/18) with no significant difference between groups (P  =  .94). Follow-up CT scans were available for 13/18 patients (72%), with a mean follow-up time of 270  ±  146 days. All patients were contacted via phone (follow-up time, 653  ±  264 days).

Conclusion

Percutaneous thrombectomy appears to be effective for revascularization of the aortoiliac segment, both in stent-grafts and in native vessels. The most common complication is peripheral embolism; however, the risk may be reduced by choosing an adequate sheath size.
Effect of fluconazole on the pharmacokinetics of a single dose of fedratinib in healthy adults
Authors: Chen Yizhe , Ogasawara Ken , Wood-Horrall Rebecca , Thomas Mark , Thomas Michael , He Bing , Liu Liangang , Xue Yongjun , Surapaneni Sekhar , Carayannopoulos Leonidas N. , Zhou Simon , Palmisano Maria , Krishna Gopal
Published: August 2022

Purpose

Fedratinib is an orally administered Janus kinase (JAK) 2–selective inhibitor for the treatment of adult patients with intermediate-2 or high-risk primary or secondary myelofibrosis. In vitro, fedratinib is predominantly metabolized by cytochrome P450 (CYP) 3A4 and to a lesser extent by CYP2C19. Coadministration of fedratinib with CYP3A4 inhibitors is predicted to increase systemic exposure to fedratinib. This study evaluated the effect of multiple doses of the dual CYP3A4 and CYP2C19 inhibitor, fluconazole, on the pharmacokinetics of a single dose of fedratinib.

Methods

In this non-randomized, fixed-sequence, open-label study, healthy adult participants first received a single oral dose of fedratinib 100 mg on day 1. Participants then received fluconazole 400 mg on day 10 and fluconazole 200 mg once daily on days 11–23, with a single oral dose of fedratinib 100 mg on day 18. Pharmacokinetic parameters were calculated for fedratinib administered with and without fluconazole.

Results

A total of 16 participants completed the study and were included in the pharmacokinetic population. Coadministration of fedratinib with fluconazole increased maximum observed plasma concentration (Cmax) and area under the plasma concentration–time curve from time 0 to the last quantifiable concentration (AUC0–t) of fedratinib by 21% and 56%, respectively, compared with fedratinib alone. Single oral doses of fedratinib 100 mg administered with or without fluconazole were well tolerated.

Conclusions

Systemic exposure after a single oral dose of fedratinib was increased by up to 56% when fedratinib was coadministered with fluconazole compared with fedratinib alone.

Trial registry: Clinicaltrials.gov

NCT04702464.
[18F]FDG-PET/CT radiomics for the identification of genetic clusters in pheochromocytomas and paragangliomas
Authors: Noortman Wyanne A. , Vriens Dennis , de Geus-Oei Lioe-Fee , Slump Cornelis H. , Aarntzen Erik H. , van Berkel Anouk , Timmers Henri J. L. M. , van Velden Floris H. P.
Published: August 2022

Objectives

Based on germline and somatic mutation profiles, pheochromocytomas and paragangliomas (PPGLs) can be classified into different clusters. We investigated the use of [18F]FDG-PET/CT radiomics, SUVmax and biochemical profile for the identification of the genetic clusters of PPGLs.

Methods

In this single-centre cohort, 40 PPGLs (13 cluster 1, 18 cluster 2, 9 sporadic) were delineated using a 41% adaptive threshold of SUVpeak ([18F]FDG-PET) and manually (low-dose CT; ldCT). Using PyRadiomics, 211 radiomic features were extracted. Stratified 5-fold cross-validation for the identification of the genetic cluster was performed using multinomial logistic regression with dimensionality reduction incorporated per fold. Classification performances of biochemistry, SUVmax and PET(/CT) radiomic models were compared and presented as mean (multiclass) test AUCs over the five folds. Results were validated using a sham experiment, randomly shuffling the outcome labels.

Results

The model with biochemistry only could identify the genetic cluster (multiclass AUC 0.60). The three-factor PET model had the best classification performance (multiclass AUC 0.88). A simplified model with only SUVmax performed almost similarly. Addition of ldCT features and biochemistry decreased the classification performances. All sham AUCs were approximately 0.50.

Conclusion

PET radiomics achieves a better identification of PPGLs compared to biochemistry, SUVmax, ldCT radiomics and combined approaches, especially for the differentiation of sporadic PPGLs. Nevertheless, a model with SUVmax alone might be preferred clinically, weighing model performances against laborious radiomic analysis. The limited added value of radiomics to the overall classification performance for PPGL should be validated in a larger external cohort.

Key Points

• Radiomics derived from [18F]FDG-PET/CT has the potential to improve the identification of the genetic clusters of pheochromocytomas and paragangliomas.

• A simplified model with SUVmaxonly might be preferred clinically, weighing model performances against the laborious radiomic analysis.

• Cluster 1 and 2 PPGLs generally present distinctive characteristics that can be captured using [18F]FDG-PET imaging. Sporadic PPGLs appear more heterogeneous, frequently resembling cluster 2 PPGLs and occasionally resembling cluster 1 PPGLs.
Morrey’s Conjecture for the Planar Volumetric-Isochoric Split: Least Rank-One Convex Energy Functions
Authors: Voss Jendrik , Martin Robert J. , Ghiba Ionel-Dumitrel , Neff Patrizio
Published: August 2022

We consider Morrey’s open question whether rank-one convexity already implies quasiconvexity in the planar case. For some specific families of energies, there are precise conditions known under which rank-one convexity even implies polyconvexity. We will extend some of these findings to the more general family of energies $$W{:}{\text {GL}}^+(n)\rightarrow \mathbb {R}$$

W
:

GL

+

(
n
)

→
R

with an additive volumetric-isochoric split, i.e. $$\begin{aligned} W(F)=W_{\mathrm{iso}}(F)+W_{\mathrm{vol}}(\det F)={\widetilde{W}}_{\mathrm{iso}}\bigg (\frac{F}{\sqrt{\det F}}\bigg )+W_{\mathrm{vol}}(\det F)\,, \end{aligned}$$

W

(
F
)

=

W
iso

(
F
)

+

W
vol

(
det
F
)

=

W
~

iso

(

F

det
F

)

+

W
vol

(
det
F
)

,

which is the natural finite extension of isotropic linear elasticity. Our approach is based on a condition for rank-one convexity which was recently derived from the classical two-dimensional criterion by Knowles and Sternberg and consists of a family of one-dimensional coupled differential inequalities. We identify a number of “least” rank-one convex energies and, in particular, show that for planar volumetric-isochorically split energies with a concave volumetric part, the question of whether rank-one convexity implies quasiconvexity can be reduced to the open question of whether the rank-one convex energy function $$\begin{aligned} W_{\mathrm{magic}}^{+}(F)=\frac{\lambda _{\mathrm{max}}}{\lambda _{\mathrm{min}}}-\log \frac{\lambda _{\mathrm{max}}}{\lambda _{\mathrm{min}}}+\log \det F=\frac{\lambda _{\mathrm{max}}}{\lambda _{\mathrm{min}}}+2\log \lambda _{\mathrm{min}} \end{aligned}$$

W

magic

+

(
F
)

=

λ
max

λ
min

-
log

λ
max

λ
min

+
log
det
F
=

λ
max

λ
min

+
2
log

λ
min

is quasiconvex. In addition, we demonstrate that under affine boundary conditions, $$W_{\mathrm{magic}}^+(F)$$

W

magic

+

(
F
)

allows for non-trivial inhomogeneous deformations with the same energy level as the homogeneous solution, and show a surprising connection to the work of Burkholder and Iwaniec in the field of complex analysis.
Getting to the root of the problem: new evidence for the use of plant root foods in Mesolithic hunter-gatherer subsistence in Europe
Authors: Bishop Rosie R. , Kubiak-Martens Lucy , Warren Graeme M. , Church Mike J.
Published: August 2022

This paper presents new evidence for the harvesting of edible plant roots and tubers at Northton, a Mesolithic hunter-gatherer site on Harris, in the Western Isles of Scotland, in the north-west corner of Europe. The excavations uncovered abundant root tuber remains of Ficaria verna Huds. (lesser celandine), an excellent high energy and carbohydrate-rich food source, and produced the first evidence for the use of tubers of Lathyrus linifolius (Reichard) Bässler (bitter-vetch) at a hunter-gatherer site in Europe. Here we report on the analysis of the charred root and tuber remains and other charred plant macrofossils from the site and consider the significance of these results within the wider context of European hunter-gatherer subsistence. The wide range of root and tuber taxa recovered from European hunter-gatherer sites and the importance of appropriate sampling on hunter-gatherer sites are highlighted.
Inhibition of beta-catenin shows therapeutic potential in head and neck squamous cell carcinoma in vitro
Authors: Maier Tobias , Stoiber Stefan , Gurnhofer Elisabeth , Haas Markus , Kenner Lukas , Heiduschka Gregor , Kadletz-Wanke Lorenz , Brkic Faris F.
Published: August 2022

Beta-catenin is known to be a vital component of the canonical Wnt signaling cascade, involved in the carcinogenesis of different solid tumors. We aimed to evaluate the effects of Beta-catenin inhibition in head and neck squamous cell carcinoma (HNSCC) in vitro. The small molecular compound MSAB was used to inhibit Wnt/Beta-catenin signaling in a human papillomavirus (HPV)-positive and HPV-negative cell line and its effects on cell proliferation, migration, colony formation, apoptosis, as well as radiosensitizing properties were assessed. Significant antineoplastic effects were observed in both cell lines. Interestingly, stronger anti-neoplastic and radiosensitizing effects were observed in the HPV-negative cell line, whereas stronger anti-migratory potential was detected in HPV-positive HNSCC cells. In conclusion, our findings suggest MSAB as a potential therapeutic agent for HNSCC. Further studies are warranted to unravel the mechanistic background of our findings.
Craniofacial superimposition: a review of focus distance estimation methods and an extension to profile view photographs
Authors: Stephan Carl N. , Healy Sean , Bultitude Hamish , Glen Chris
Published: August 2022

Craniofacial superimposition concerns the photographic overlay of skulls and faces, for skeletal identification. As a phased method that depends on photographic optics first and anatomical comparisons second, superimposition is strongly underpinned by the physics of light travel through glass lenses. So that the downstream (and dependent) anatomical evaluations are not thwarted or erroneous identification decisions risked, it is critical that the optical prerequisites for valid image comparisons are met. As focus distance sets the perspective, the focus distance used for skull photography must be matched to that used at face photography, so that anatomically comparable 1:1 images are obtained. In this paper, we review the pertinent camera optics that set these nonnegotiable fundamentals and review a recently proposed method for focus distance estimation. We go beyond the original method descriptions to explain the mathematical justification for the PerspectiveX algorithm and provide an extension to profile images. This enables the first scientifically grounded use of profile view (or partial profile view) photographs in craniofacial superimposition. Proof of concept is provided by multiple worked examples of the focus distance estimation for frontal and profile view images of three of the authors at known focus distances. This innovation (1) removes longstanding trial-and-error components of present-day superimposition methods, (2) provides the first systematic and complete optical basis for image comparison in craniofacial superimposition, and (3) will enable anatomical comparison standards to be established from a valid grassroots basis where complexities of camera vantage point are removed as interfering factors.
Delay in arrival: lineage-specific influence of haemosporidians on autumn migration of European robins
Authors: Ágh Nóra , Csörgő Tibor , Szöllősi Eszter
Published: August 2022

Haemosporidian blood parasites are widely used in evolutionary ecological research when exploring the effects of parasites on different life-history traits of their bird hosts. However, their roles in bird migration are less studied. If these parasites deteriorate the body condition of the birds strongly, they might negatively affect the whole migration phenology and the survival of the birds as well. In our study, we tested the relationships between infection for parasite genera (HaemoproteusorPlasmodium), the three most frequent parasite lineages and body condition (body mass, fat deposit), and the timing of autumn migration in the European Robin (Erithacus rubecula). We found that mean body mass and fat scores did not differ between parasitized and non-parasitized individuals, but infected juveniles arrived later than their non-infected counterparts. The difference in the arrival time of parasitized and non-parasitized birds was greater in the case ofHaemoproteusinfections. However, when we analysed the effects of the distinct parasite lineages separately, we found that prevalence of parasite lineages correlated with the body mass, fat storage, and timing of autumn migration of the birds in a different direction. Our results therefore emphasize the importance of testing the impacts of the different parasites individually, because possible lineage-specific effects on bird condition during migration might exist.