bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-time and high-transmission middle-infrared optical imaging system based on a pixel-wise metasurface micro-polarization array
Authors: Ma Lifeng , Du Shan , Chang Jun , Chen Weilin , Wu Chuhan , Shi Xinxin , Huang Yi , Zhong Yue , Mu Quanquan
Published: December 2022

Real-time polarization medium-wave infrared (MIR) optical imaging systems enable the acquisition of infrared and polarization information for a target. At present, real-time polarization MIR devices face the following problems: poor real-time performance, low transmission and high requirements for fabrication and integration. Herein, we aim to improve the performance of real-time polarization imaging systems in the MIR waveband and solve the above-mentioned defects. Therefore, we propose a MIR polarization imaging system to achieve real-time polarization-modulated imaging with high transmission as well as improved performance based on a pixel-wise metasurface micro-polarization array (PMMPA). The PMMPA element comprises several linear polarization (LP) filters with different polarization angles. The optimization results demonstrate that the transmittance of the center field of view for the LP filters is up to 77% at a wavelength of 4.0 μm and an extinction ratio of 88 dB. In addition, a near-diffraction-limited real-time MIR imaging optical system is designed with a field of view of 5° and an F-number of 2. The simulation results show that an MIR polarization imaging system with excellent real-time performance and high transmission is achieved by using the optimized PMMPA element. Therefore, the method is compatible with the available optical system design technologies and provides a way to realize real-time polarization imaging in MIR wavebands.
Effect of magnetic nanoparticles on magnetic field homogeneity
Authors: Guo Si-Lin , Yi Wen-Tong , Li Zhuang-Zhuang
Published: December 2022

The mechanism of magnetic nanoparticles (MNPs) affecting magnetic field uniformity is studied in this work. The spatial distribution of MNPs in liquid is simulated based on Monte Carlo method. The induced field of the single MNP is combined with the magnetic field distribution of magnetofluid. In the simulation, magnetic field uniformity is described by a statistical distribution. As the chemical shift (CS) and full width at half maximum (FWHM) of magnetic resonance (MR) spectrum can reflect the uniformity of magnetic field, the simulation is verified by spectrum experiment. Simulation and measurement results prove that the CS and FWHM of the MR spectrum are basically positively correlated with the concentration of MNPs and negatively correlated with the temperature. The research results can explain how MNPs play a role in MR by affecting the uniform magnetic field, which is of great significance in improving the temperature measurement accuracy of magnetic nanothermometers and the spatial resolution of magnetic particle imaging.
Design optimization of a silicon-germanium heterojunction negative capacitance gate-all-around tunneling field effect transistor based on a simulation study
Authors: Wei Weijie , Lü Weifeng , Han Ying , Zhang Caiyun , Chen Dengke
Published: December 2022

The steep sub-threshold swing of a tunneling field-effect transistor (TFET) makes it one of the best candidates for low-power nanometer devices. However, the low driving capability of TFETs prevents their application in integrated circuits. In this study, an innovative gate-all-around (GAA) TFET, which represents a negative capacitance GAA gate-to-source overlap TFET (NCGAA-SOL-TFET), is proposed to increase the driving current. The proposed NCGAA-SOL-TFET is developed based on technology computer-aided design (TCAD) simulations. The proposed structure can solve the problem of the insufficient driving capability of conventional TFETs and is suitable for sub-3-nm nodes. In addition, due to the negative capacitance effect, the surface potential of the channel can be amplified, thus enhancing the driving current. The gate-to-source overlap (SOL) technique is used for the first time in an NCGAA-TFET to increase the band-to-band tunneling rate and tunneling area at the silicon–germanium heterojunction. By optimizing the design of the proposed structure via adjusting the SOL length and the ferroelectric layer thickness, a sufficiently large on-state current of 17.20 μA can be achieved and the threshold voltage can be reduced to 0.31 V with a sub-threshold swing of 44.98 mV/decade. Finally, the proposed NCGAA-SOL-TFET can overcome the Boltzmann limit-related problem, achieving a driving current that is comparable to that of the traditional complementary metal–oxide semiconductor devices.
High-performance extended short-wavelength infrared PBn photodetectors based on InAs/GaSb/AlSb superlattices
Authors: Jiang Junkai , Chang Faran , Zhou Wenguang , Li Nong , Chen Weiqiang , Jiang Dongwei , Hao Hongyue , Wang Guowei , Wu Donghai , Xu Yingqiang , Niu Zhi-Chuan
Published: December 2022

High performance short-wavelength infrared PBn photodetectors based on InAs/GaSb/AlSb superlattices on GaSb substrate have been demonstrated. At 300 K, the device exhibits a 50% cut-off wavelength of ∼ 2.1 μm as predicted from the band structure calculation; the device responsivity peaks at 0.85 A/W, corresponding to a quantum efficiency (QE) of 56% for 2.0 μm-thick absorption region. The dark current density of 1.03 × 10−3 A/cm2 is obtained under 50 mV applied bias. The device exhibits a saturated dark current shot noise limited specific detectivity (D*) of 3.29 × 1010cm⋅Hz1/2/W (at a peak responsivity of 2.0 μm) under –50 mV applied bias.
Application of a Magnetic-field-induced Transition in Fe x to Solar and Stellar Coronal Magnetic Field Measurements
Authors: Chen Yajie , Li Wenxian , Tian Hui , Bai Xianyong , Hutton Roger , Brage Tomas
Published: December 2022

Magnetic fields play a key role in driving a broad range of dynamic phenomena in the atmospheres of the Sun and other stars. Routine and accurate measurements of the magnetic fields at all the atmospheric layers are of critical importance to understand these magnetic activities, but in the solar and stellar coronae such a measurement is still a challenge due to the weak field strength and the high temperature. Recently, a magnetic-field-induced transition (MIT) of Fe x at 257.26 Å has been proposed for the magnetic field measurements in the solar and stellar coronae. In this review, we present an overview of recent progresses in the application of this method in astrophysics. We start by introducing the theory underlying the MIT method and reviewing the existing atomic data critical for the spectral modeling of Fe x lines. We also discuss the laboratory measurements that verify the potential capability of the MIT technique as a probe for diagnosing the plasma magnetic fields. We then continue by investigating the suitability and accuracy of solar and stellar coronal magnetic field measurements based on the MIT method through forward modeling. Furthermore, we discuss the application of the MIT method to the existing spectroscopic observations obtained by the Extreme-ultraviolet Imaging Spectrometer onboard Hinode. This novel technique provides a possible way for routine measurements of the magnetic fields in the solar and stellar coronae, but still requires further efforts to improve its accuracy. Finally, the challenges and prospects for future research on this topic are discussed.
Erratum: Systematic uncertainties in integrated luminosity measurement at CEPC
Authors: Smiljanic I. , Bozovic Jelisavcic I. , Kacarevic G. , Vukasinovic N. , Vidakovic I. , Rekovic V.
Published: December 2022

The very forward region is one of the most challenging regions to instrument at a future
e+e− collider. At CEPC, machine-detector interface includes, among others, a calorimeter
dedicated for precision measurement of the integrated luminosity at a per mill level or
better. Here we review a feasibility of such precision, from the point of view of systematic
effects arising from luminometer mechanical precision and positioning, beam-related requirements
and physics background from two-photon processes. The impact of the beam energy spread and its
uncertainty on the integrated luminosity precision is also discussed, as well as the achievable
beam energy spread precision with the post-CDR CEPC beams.
Spring and latch dynamics can act as control pathways in ultrafast systems
Authors: Hyun N P , Olberding J P , De A , Divi S , Liang X , Thomas E , St. Pierre R , Steinhardt E , Jorge J , Longo S J , Cox S , Mendoza E , Sutton G P , Azizi E , Crosby A J , Bergbreiter S , Wood R J , Patek S N
Published: December 2022

Ultrafast movements propelled by springs and released by latches are thought limited to energetic adjustments prior to movement, and seemingly cannot adjust once movement begins. Even so, across the tree of life, ultrafast organisms navigate dynamic environments and generate a range of movements, suggesting unrecognized capabilities for control. We develop a framework of control pathways leveraging the non-linear dynamics of spring-propelled, latch-released systems. We analytically model spring dynamics and develop reduced-parameter models of latch dynamics to quantify how they can be tuned internally or through changing external environments. Using Lagrangian mechanics, we test feedforward and feedback control implementation via spring and latch dynamics. We establish through empirically-informed modeling that ultrafast movement can be controllably varied during latch release and spring propulsion. A deeper understanding of the interconnection between multiple control pathways, and the tunability of each control pathway, in ultrafast biomechanical systems presented here has the potential to expand the capabilities of synthetic ultra-fast systems and provides a new framework to understand the behaviors of fast organisms subject to perturbations and environmental non-idealities.
Popcorn Drude weights from quantum symmetry
Authors: Ilievski E
Published: December 2022

Integrable models provide emblematic examples of non-ergodic phenomena. One of their most distinguished properties are divergent zero-frequency conductivities signalled by finite Drude weights. Singular conductivities owe to long-lived quasiparticle excitations that propagate ballistically through the system without any diffraction. The case of the celebrated quantum Heisenberg chain, one of the best-studied many-body paradigms, turns out to be particularly mysterious. About a decade ago, it was found that the spin Drude weight in the critical phase of the model assumes an extraordinary, nowhere continuous, dependence on the anisotropy parameter in the shape of a ‘popcorn function’. This unprecedented discovery has been afterwards resolved at the level of the underlying deformed quantum symmetry algebra which helps explaining the erratic nature of the quasiparticle spectrum at commensurate values of interaction anisotropy. This work is devoted to the captivating phenomenon of discontinuous Drude weights, with the aim to give a broader perspective on the topic by revisiting and reconciling various perspectives from the previous studies. Moreover, it is argued that such an anomalous non-ergodic feature is not exclusive to the integrable spin chain but can be instead expected in a number of other integrable systems that arise from realizations of the quantum group

, specialized to unimodular values of the quantum deformation parameter q. Our discussion is framed in the context of gapless anisotropic quantum chains of higher spin and the sine-Gordon quantum field theory in two space-time dimensions.
Kidney Pathology of Tropical and Nontropical Infectious Diseases in the Pediatric Population
Authors: Williams Morgan , Reisler Jenna , James Tyler , Afrouzian Marjan
Published: December 2022

Objectives

To review kidney pathology of tropical and nontropical infectious diseases in the pediatric population.

Methods

We review 4 tropical and 2 nontropical infectious diseases that affect the kidneys of children in terms of their direct and indirect pathogenetic mechanism in inducing kidney damage.

Results

We demonstrate clinical manifestations, pathogenesis, kidney pathology, and laboratory diagnostic methods for (1) renal cryptococcosis, which represents involvement of a pure direct pathway; (2) schistosomiasis and dengue fever as examples of dual direct and indirect pathways; and (3) congenital syphilis, visceral leishmaniasis, and Chagas disease, which represent indirect pathways.

Conclusions

Infective agents affect the kidneys of children mainly through indirect mechanisms, such as through immunological mechanisms as part of an antigenic response. A direct mechanism of kidney injury, however, is less known within the medical community simply because the direct mechanism is rarely encountered in nontropical countries. In some infectious diseases, both indirect and direct pathways are responsible in inducing 2 sets of morphologically separate kidney lesions.
The gradient in gray matter thickness across auditory cortex and differential cortical thickness changes following perinatal deafness
Authors: Gordon Stephen G , Butler Blake E , Lomber Stephen G
Published: December 2022

In the absence of hearing during development, the brain adapts and repurposes what was destined to become auditory cortex. As cortical thickness is commonly used as a proxy to identify cortical regions that have undergone plastic changes, the purpose of this investigation was to compare cortical thickness patterns between hearing and deaf cats. In this study, normal hearing (n = 29) and deaf (n = 26) cats were scanned to examine cortical thickness in hearing controls, as well as differential changes in thickness as a consequence of deafness. In hearing cats, a gradient in cortical thickness was identified across auditory cortex in which it is thinner in more dorsal regions and thicker in more ventral regions. Compared with hearing controls, differential thickening and thinning was observed in specific regions of deaf auditory cortex. More dorsal regions were found to be bilaterally thicker in the deaf group, while more ventral regions in the left hemisphere were thinner. The location and nature of these changes creates a gradient along the dorsoventral axis, wherein dorsal auditory cortical fields are thicker, whereas more ventral fields are thinner in deaf animals compared with hearing controls.
A Phase 2A Trial of the Safety and Tolerability of Increased Dose Rifampicin and Adjunctive Linezolid, With or Without Aspirin, for Human Immunodeficiency Virus–Associated Tuberculous Meningitis: The LASER-TBM Trial
Authors: Davis Angharad G , Wasserman Sean , Stek Cari , Maxebengula Mpumi , Jason Liang C , Stegmann Stephani , Koekemoer Sonya , Jackson Amanda , Kadernani Yakub , Bremer Marise , Daroowala Remy , Aziz Saalikha , Goliath Rene , Lai Sai Louise , Sihoyiya Thandi , Denti Paolo , Lai Rachel P J , Crede Thomas , Naude Jonathan , Szymanski Patryk , Vallie Yakoob , Banderker Ismail Abbas , Moosa Muhammed S , Raubenheimer Peter , Candy Sally , Offiah Curtis , Wahl Gerda , Vorster Isak , Maartens Gary , Black John , Meintjes Graeme , Wilkinson Robert J
Published: December 2022

Background

Drug regimens that include intensified antibiotics alongside effective anti-inflammatory therapies may improve outcomes in tuberculous meningitis (TBM). Safety data on their use in combination and in the context of human immunodeficiency virus (HIV) are needed to inform clinical trial design.

Methods

We conducted a phase 2, open-label, parallel-design, randomized, controlled trial to assess the safety of high-dose rifampicin, linezolid, and high-dose aspirin in HIV-associated TBM. Participants were randomized (1.4:1:1) to 3 treatment arms (1, standard of care [SOC]; 2, SOC + additional rifampicin [up to 35 mg/kg/d] + linezolid 1200 mg/d reducing after 28 days to 600 mg/d; 3, as per arm 2 + aspirin 1000 mg/d) for 56 days, when the primary outcome of adverse events of special interest (AESI) or death was assessed.

Results

A total of 52 participants with HIV-associated TBM were randomized; 59% had mild disease (British Medical Research Council (MRC) grade 1) vs 39% (grade 2) vs 2% (grade 3). AESI or death occurred in 10 of 16 (63%; arm 3) vs 4 of 14 (29%; arm 2) vs 6 of 20 (30%; arm 1; P = .083). The cumulative proportion of AESI or death (Kaplan–Meier) demonstrated worse outcomes in arm 3 vs arm 1 (P = .04); however, only 1 event in arm 3 was attributable to aspirin and was mild. There was no difference in efficacy (modified Rankin scale) between arms.

Conclusions

High-dose rifampicin and adjunctive linezolid can safely be added to the standard of care in HIV-associated TBM. Larger studies are required to determine whether potential toxicity associated with these interventions, particularly high-dose aspirin, is outweighed by mortality or morbidity benefit.

Clinical Trials Registration

NCT03927313.
A case report of transcatheter repair of severe functional mitral regurgitation in cardiac amyloidosis
Authors: Fangmin Meng , Shaohua Lu , Lai Wei , Cuizhen Pan
Published: December 2022

Background

Transcatheter therapy has become an alternative for functional mitral regurgitation (FMR) in patients at high surgical risk. However, the intervention of FMR in cardiac amyloidosis (CA) with transcatheter edge-to-edge repair (TEER) is controversial due to the potential risk of left atrial pressure (LAP) elevation.

Case summary

An 83-year-old woman with repeated heart failure (HF) and severe mitral regurgitation (MR) was referred to our centre for TEER. Pre-procedural transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE) confirmed the degree of MR and a functional aetiology. A peculiar LAP increase in this patient occurred immediately after successful TEER clip implantation and her n-terminal prohormone of brain natriuretic peptide significantly increased post-operatively. The diagnosis of CA was suspected and was subsequently established through endomyocardial biopsy. Aggressive anti-HF therapy was initiated and the patient was discharged after her HF symptoms were relieved. At 6-month follow-up, the patient was still alive and no episode of acute HF was experienced.

Discussion

Severe functional MR in CA treated with TEER has the potential risk of increasing LAP. During the short-term follow-up, TEER appears beneficial for left heart function (reduction of MR) but harmful for right heart function (increase of LAP). CA patients with severe FMR should be carefully evaluated about the benefits and potential harm of TEER intervention.
Characterizing primary care patients with posttraumatic stress disorder using electronic medical records: a retrospective cross-sectional study
Authors: Singer Alexander , Kosowan Leanne , Muthumuni Dhasni , Katz Alan , Zafari Hasan , Zulkernine Farhana , Richardson J Don , Price Morgan , Williamson Tyler , Queenan John , Sareen Jitender
Published: December 2022

Background

Posttraumatic stress disorder (PTSD) has significant morbidity and economic costs. This study describes the prevalence and characteristics of patients with PTSD using primary care electronic medical record (EMR) data.

Methods

This retrospective cross-sectional study used EMR data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). This study included 1,574 primary care providers located in 7 Canadian provinces. There were 689,301 patients that visited a CPCSSN provider between 1 January 2017 and 31 December 2019. We describe associations between PTSD and patient characteristics using descriptive statistics, chi-square, and multiple logistic regression models.

Results

Among the 689,301 patients included, 8,817 (1.3%, 95% CI 1.2–1.3) had a diagnosis of PTSD. On multiple logistic regression analysis, patients with depression (OR 4.4, 95% CI 4.2–4.7, P < 0.001), alcohol abuse/dependence (OR 1.7, 95% CI 1.6–1.9, P < 0.001), and/or drug abuse/dependence (OR 2.6, 95% CI 2.5–2.8, P < 0.001) had significantly higher odds of PTSD compared with patients without those conditions. Patients residing in community areas considered the most material deprived (OR 2.1, 95% CI 1.5–2.1, P < 0.001) or the most socially deprived (OR 2.8, 95% CI 2.7–5.3, P < 0.001) had higher odds of being diagnosed with PTSD compared with patients in the least deprived areas.

Conclusions

The prevalence of PTSD in Canadian primary care is 1.3% (95% CI 1.25–1.31). Using EMR records we confirmed the co-occurrence of PTSD with other mental health conditions within primary care settings suggesting benefit for improved screening and evidence-based resources to manage PTSD.
The rock fragmentation and crack propagation under TBM tunneling based on particle flow code
Authors: Lan Donghao , Deng Hongjian , Gao Yanan , Wang Yunlong , Zhang Guangkai
Published: December 2022

The rock fragmentation and crack propagation of anisotropic rock induced by tunnel boring machine (TBM) tunneling is studied in this paper. First, a numerical model based on the 2D particle flow code (PFC2D) is established and calibrated to reveal the four stages of rock fragmentation. In Stage I (indentation depth 0–0.4 mm), the indentation force beneath the cutterhead increases and decreases dramatically with the accumulation and release of mechanical energy. Such a phenomenon indicates that a hydrostatic core (crushed zone) can be observed. In Stage II (indentation depth 0.4–1.1 mm), many median cracks propagate dramatically with the indentation force. Meanwhile, the hydrostatic core is pushed because the mechanical energy of the cutterhead is reaccumulated in the specimen. In Stage III (indentation depth 1.1–2.6 mm), lateral cracks begin to develop due to the further increase in indentation depth. In Stage IV (indentation depth 2.6–5 mm), the lateral cracks and median cracks continue to propagate, and rock chips can be found on the sides of the cutterhead. Then, with increasing confining pressure, lateral cracks begin to gradually develop and the maximum angle of lateral cracks is 70.5°. Furthermore, the magnitude of the intrusion velocity can seriously influence the evolution of the indentation force during Stages III and IV because of the accumulation and release of mechanical energy. The accumulation and release of mechanical energy are more obvious with a higher intrusion velocity of the cutterhead.
DNA/RNA helicase DHX36 is required for late stages of spermatogenesis
Authors: Zhang Kejia , Zhang Tianxin , Zhang Yujie , Yuan Jinyu , Tang Xinzhe , Zhang Chaobao , Yin Qianqian , Zhang Yonglian , Tong Ming-Han
Published: December 2022

Spermatogenesis is a highly complex developmental process that typically consists of mitosis, meiosis, and spermiogenesis. DNA/RNA helicase DHX36, a unique guanine-quadruplex (G4) resolvase, plays crucial roles in a variety of biological processes. We previously showed that DHX36 is highly expressed in male germ cells with the highest level in zygotene spermatocytes. Here, we deleted Dhx36 in advanced germ cells with Stra8-GFPCre and found that a Dhx36 deficiency in the differentiated spermatogonia leads to meiotic defects and abnormal spermiogenesis. These defects in late stages of spermatogenesis arise from dysregulated transcription of G4-harboring genes, which are required for meiosis. Thus, this study reveals that Dhx36 plays crucial roles in late stages of spermatogenesis.
TEAD1 regulates cell proliferation through a pocket-independent transcription repression mechanism
Authors: Li Feng , Negi Vinny , Yang Ping , Lee Jeongkyung , Ma Ke , Moulik Mousumi , Yechoor Vijay K
Published: December 2022

The Hippo-TEAD pathway regulates cellular proliferation and function. The existing paradigm is that TEAD co-activators, YAP and TAZ, and co-repressor, VGLL4, bind to the pocket region of TEAD1 to enable transcriptional activation or repressive function. Here we demonstrate a pocket-independent transcription repression mechanism whereby TEAD1 controls cell proliferation in both non-malignant mature differentiated cells and in malignant cell models. TEAD1 overexpression can repress tumor cell proliferation in distinct cancer cell lines. In pancreatic β cells, conditional knockout of TEAD1 led to a cell-autonomous increase in proliferation. Genome-wide analysis of TEAD1 functional targets via transcriptomic profiling and cistromic analysis revealed distinct modes of target genes, with one class of targets directly repressed by TEAD1. We further demonstrate that TEAD1 controls target gene transcription in a motif-dependent and orientation-independent manner. Mechanistically, we show that TEAD1 has a pocket region-independent, direct repressive function via interfering with RNA polymerase II (POLII) binding to target promoters. Our study reveals that TEAD1 target genes constitute a mutually restricted regulatory loop to control cell proliferation and uncovers a novel direct repression mechanism involved in its transcriptional control that could be leveraged in future studies to modulate cell proliferation in tumors and potentially enhance the proliferation of normal mature cells.
Single-cell CRISPR immune screens reveal immunological roles of tumor intrinsic factors
Authors: Hou Jiakai , Liang Shaoheng , Xu Chunyu , Wei Yanjun , Wang Yunfei , Tan Yukun , Sahni Nidhi , McGrail Daniel J , Bernatchez Chantale , Davies Michael , Li Yumei , Chen Rui , Yi S Stephen , Chen Yiwen , Yee Cassian , Chen Ken , Peng Weiyi
Published: December 2022

Genetic screens are widely exploited to develop novel therapeutic approaches for cancer treatment. With recent advances in single-cell technology, single-cell CRISPR screen (scCRISPR) platforms provide opportunities for target validation and mechanistic studies in a high-throughput manner. Here, we aim to establish scCRISPR platforms which are suitable for immune-related screens involving multiple cell types. We integrated two scCRISPR platforms, namely Perturb-seq and CROP-seq, with both in vitro and in vivo immune screens. By leveraging previously generated resources, we optimized experimental conditions and data analysis pipelines to achieve better consistency between results from high-throughput and individual validations. Furthermore, we evaluated the performance of scCRISPR immune screens in determining underlying mechanisms of tumor intrinsic immune regulation. Our results showed that scCRISPR platforms can simultaneously characterize gene expression profiles and perturbation effects present in individual cells in different immune screen conditions. Results from scCRISPR immune screens also predict transcriptional phenotype associated with clinical responses to cancer immunotherapy. More importantly, scCRISPR screen platforms reveal the interactive relationship between targeting tumor intrinsic factors and T cell-mediated antitumor immune response which cannot be easily assessed by bulk RNA-seq. Collectively, scCRISPR immune screens provide scalable and reliable platforms to elucidate molecular determinants of tumor immune resistance.
Clinical Implications and Treatment Strategies for ESR1 Fusions in Hormone Receptor-Positive Metastatic Breast Cancer: A Case Series
Authors: Brett Jamie O , Ritterhouse Lauren L , Newman Erik T , Irwin Kelly E , Dawson Megan , Ryan Lianne Y , Spring Laura M , Rivera Miguel N , Lennerz Jochen K , Dias-Santagata Dora , Ellisen Leif W , Bardia Aditya , Wander Seth A
Published: December 2022

In hormone receptor-positive metastatic breast cancer (HR+ MBC), endocrine resistance is commonly due to genetic alterations of ESR1, the gene encoding estrogen receptor alpha (ERα). While ESR1 point mutations (ESR1-MUT) cause acquired resistance to aromatase inhibition (AI) through constitutive activation, far less is known about the molecular functions and clinical consequences of ESR1 fusions (ESR1-FUS). This case series discusses 4 patients with HR+ MBC with ESR1-FUS in the context of the existing ESR1-FUS literature. We consider therapeutic strategies and raise the hypothesis that CDK4/6 inhibition (CDK4/6i) may be effective against ESR1-FUS with functional ligand-binding domain swaps. These cases highlight the importance of screening for ESR1-FUS in patients with HR+ MBC while continuing investigation of precision treatments for these genomic rearrangements.
Best practices in pain assessment and management for children
Authors: Trottier Evelyne D , Ali Samina , Doré-Bergeron Marie-Joëlle , Chauvin-Kimoff Laurel
Published: December 2022

Pain assessment and management are essential components of paediatric care. Developmentally appropriate pain assessment is an important first step in optimizing pain management. Self-reported pain should be prioritized. Alternatively, developmentally appropriate behavioural tools should be used. Acute pain management and prevention guidelines and strategies that combine physical, psychological, and pharmacological approaches should be accessible in all health care settings. Chronic pain is best managed using combined treatment modalities and counselling, with the primary goal of attaining functional improvement. The planning and implementation of pain management strategies for children should always be personalized and family-centred.
Les pratiques exemplaires pour l’évaluation et le traitement de la douleur chez les enfants
Authors: Trottier Evelyne D , Ali Samina , Doré-Bergeron Marie-Joëlle , Chauvin-Kimoff Laurel
Published: December 2022

L’évaluation et le traitement de la douleur sont des aspects essentiels des soins pédiatriques. L’évaluation de la douleur adaptée au développement représente une première étape importante pour en optimiser la prise en charge. L’autoévaluation de la douleur est à prioriser. Si c’est impossible, des outils appropriés d’évaluation du comportement, adaptés au développement, doivent être utilisés. Des directives et stratégies de prise en charge et de prévention de la douleur aiguë, qui combinent des approches physiques, psychologiques et pharmacologiques, doivent être accessibles dans tous les milieux de soins. Le meilleur traitement de la douleur chronique fait appel à une combinaison de modalités thérapeutiques et de counseling, dans l’objectif premier d’obtenir une amélioration fonctionnelle. La planification et la mise en œuvre de stratégies de prise en charge de la douleur chez les enfants doivent toujours être personnalisées et axées sur la famille.
Living with high potassium: Balance between nutrient acquisition and K-induced salt stress signaling
Authors: Pantha Pramod , Oh Dong-Ha , Longstreth David , Dassanayake Maheshi
Published: December 2022

High potassium (K) in the growth medium induces salinity stress in plants. However, the molecular mechanisms underlying plant responses to K-induced salt stress are virtually unknown. We examined Arabidopsis (Arabidopsis thaliana) and its extremophyte relative Schrenkiella parvula using a comparative multiomics approach to identify cellular processes affected by excess K and understand which deterministic regulatory pathways are active to avoid tissue damages while sustaining growth. Arabidopsis showed limited capacity to curb excess K accumulation and prevent nutrient depletion, contrasting to S. parvula which could limit excess K accumulation without restricting nutrient uptake. A targeted transcriptomic response in S. parvula promoted nitrogen uptake along with other key nutrients followed by uninterrupted N assimilation into primary metabolites during excess K-stress. This resulted in larger antioxidant and osmolyte pools and corresponded with sustained growth in S. parvula. Antithetically, Arabidopsis showed increased reactive oxygen species levels, reduced photosynthesis, and transcriptional responses indicative of a poor balance between stress signaling, subsequently leading to growth limitations. Our results indicate that the ability to regulate independent nutrient uptake and a coordinated transcriptomic response to avoid nonspecific stress signaling are two main deterministic steps toward building stress resilience to excess K+-induced salt stress.
Benefit of rituximab maintenance is associated with Follicular Lymphoma International Prognostic Index in patients with follicular lymphoma
Authors: Li Ru , Wang Tingyu , Lyv Rui , Wang Yi , Yu Ying , Yan Yuting , Sun Qi , Xiong Wenjie , Liu Wei , Sui Weiwei , Huang Wenyang , Wang Huijun , Li Chengwen , Wang Jun , Zou Dehui , An Gang , Wang Jianxiang , Qiu Lugui , Yi Shuhua
Published: December 2022

Rituximab maintenance (RM) prolongs the progression-free survival (PFS) of responding patients with follicular lymphoma (FL), but the maintenance efficacy in different Follicular Lymphoma International Prognostic Index (FLIPI) risk group is still confusing. We performed a retrospective analysis of the effect of RM treatments in patients with FL responding to induction therapy based on their FLIPI risk assessment carried out prior to treatment. We identified 93 patients between 2013 and 2019 who received RM every 3 months for ≥4 doses (RM group), and 60 patients who did not accept RM or received rituximab less than 4 doses (control group). After a median follow-up of 39 months, neither median overall survival (OS) nor PFS was reached for the entire population. The PFS was significantly prolonged in the RM group compared to the control group (median PFS NA vs 83.1 months, P = .00027). When the population was divided into the 3 FLIPI risk groups, the PFS differed significantly (4-year PFS rates, 97.5% vs 88.8% vs 72.3%, P = .01) according to group. There was no significant difference in PFS for FLIPI low-risk patients with RM compared to the control group (4-year PFS rates, 100% vs 93.8%, P = .23). However, the PFS of the RM group was significantly prolonged for FLIPI intermediate-risk (4-year PFS rates, 100% vs 70.3%, P = .00077) and high-risk patients (4-year PFS rates, 86.7% vs 57.1%, P = .023). These data suggest that standard RM significantly prolongs the PFS of patients assigned to intermediate- and high-risk FLIPI groups but not to low-risk FLIPI group, and pending larger-scale studies to validate.
A Single-Institution Cohort Study With Nevi of Special Site: Recurrence, Progression to Melanoma, and Patterns of Management
Authors: Elkeeb Dena M. , Hopkins Zachary H. , Bolender Caitlin M. , Moreno Christopher , Florell Scott R. , Bowen Anneli R. , Vitale Patricia , Zussman Jamie , Duffy Keith , Grossman Douglas , Secrest Aaron M. , Wada David A.
Published: December 2022

Nevi of specialized sites (NOSS) occur on the scalp, ears, flexural, acral, and genital areas and display atypical clinical and histologic features. We assessed NOSS recurrence and progression to melanoma, management patterns, and associations between histologic features and treatment recommendations. We queried all histologic diagnoses of NOSS (n = 275) from 2012 to 2017 from a large U.S. academic medical center with reference dermatopathology laboratory and matched these to clinical records. A blinded panel of dermatopathologists re-evaluated lesions, catalogued histologic findings, and gave management recommendation. Associations with dermatopathologist decision and concordance between new and original recommendations were assessed. Of 117 cases with follow-up, 2 locally recurred (1.46%) and none eventuated in melanoma. Clinical features were not associated with original treatment recommendations. After histopathologic review, large melanocytes [odds ratio ratio (ORR) = 8.00, 95% CI, 1.35–47.4] and junctional mitotic figures (ORR = 65.0, 6.5–650) predicted excision recommendation. Likewise, accumulation of many (>9) high-risk features was associated with excision recommendation. Panel review changed treatment recommendation in 27% of cases. Fair concordance existed between original and panel recommendations (κ = 0.29, 0.15–0.44). The low rate of recurrence and lack of melanoma occurrence suggest that despite an atypical clinical and histopathologic appearance, these nevi have limited potential for malignant transformation. Histopathologic findings seem to be principal drivers behind the recommendation for excision in this analysis. Variability existed in treatment recommendations; the panel's consensus recommendation tended to downgrade treatment. This highlights the importance of further outcomes-based studies to identify true high-risk features and refine management guidelines.
Histiocytoid Sweet Syndrome Presenting in Two Sisters With Deficiency of Deaminase Type 2
Authors: Hui Ong Eugene Liat , Cooray Samantha , Brogan Paul , Calonje Eduardo
Published: December 2022

Deficiency of adenosine deaminase type 2 (DADA2) is an autosomal recessive monogenic autoinflammatory syndrome that is classically characterised by polyarteritis nodosa, systemic vasculitis and stroke. The spectrum of disease manifestations has broadened to encompass a range of cutaneous, vascular and haematological manifestations. We report a novel association in two sisters with heterozygous p.R169G/p.M309l mutations in ADA2 with low serum ADA2 activity who both presented similarly with clinical and histological features consistent with histiocytoid Sweet syndrome.
A Case of a Rare Histologic Variant: Cavernous Hemangioma–Like Kaposi Sarcoma
Authors: Haller Courtney N. , Carrillo Brenda , Soldano Anthony C. , Keeling Brett H.
Published: December 2022

Kaposi sarcoma (KS) is an endothelial tumor associated with human herpesvirus 8. Cutaneous lesions can present with pink or purple patches, plaques, and nodules which can be ulcerated. The main subtypes of KS generally have similar histologic appearances, with spindle cells and expression of human herpesvirus 8 being characteristic features. However, various histologic variants have been reported. We present the case of a 55-year-old man with cutaneous KS with cavernous hemangioma-like histological features. Cavernous hemangioma–like KS is a rare morphologic type of KS, with only a handful of cases reported in the literature.
Perieccrine Coil Elastosis: An Unusual and Previously Unrecognized Aging-Related Phenomenon
Authors: Monteagudo Carlos , Álvarez Esther
Published: December 2022

Elastic fibers are present as a thin line around the normal secretory coil of eccrine and apocrine glands, although they are virtually imperceptible with hematoxylin-eosin staining. Skin aging is a consequence of intrinsic and extrinsic factors, and glycation and ultraviolet irradiation are involved in this process favoring elastosis. We report an unusual and prominent perieccrine elastosis on the left temple in the vicinity of a basal cell carcinoma in a 78-year old man with type 2 diabetes, dyslipidemia, and hypertension. Very thick multilamellar and tortuous elastic fibers surrounded the eccrine coils. This increased amount of elastic fibers was confirmed by orcein staining as well as amyloid-P and lysozyme immunostaining. Perieccrine coil elastosis is a very unusual phenomenon that to the best of our knowledge has not been reported. Similar to dermal actinic elastosis, the presence of perieccrine coil elastosis in a skin cancer microenvironment might hypothetically promote tumor growth because of the release of elastin-derived peptides.
Acquired Perforating Osteoma Cutis: A Rare Histopathological Diagnosis
Authors: Zipperer Kate , Munoz Ayezel , Kelly Erica , Goodwin Brandon
Published: December 2022

Perforating osteoma cutis is a benign proliferation of mature bone within the dermis and subcutaneous tissue of the skin with transepidermal elimination. Transepidermal elimination of bone is the hallmark of perforating osteoma cutis and is defined by the breaching of bone through the epidermis. Perforating osteoma cutis is exceptionally rare because only 6 cases have been recorded in the literature at the time of preparation of this report. In this report, we present the case of a 65-year-old female patient with a medical history of nonmelanoma skin cancer, hypertension, hyperlipidemia, and type II diabetes mellitus presented for evaluation of a skin lesion of the posterior lower left leg, which had been present for 1 year. Clinical and histopathologic findings were consistent with the diagnosis of acquired perforating osteoma cutis. Treatment with surgical removal by tangential biopsy has thus far proven to be both diagnostic and therapeutic because no recurrence has been noted as of 6 months.
An Unusual Case of a Scrotal Porocarcinoma and Review of the Literature
Authors: Hartsough Emily Mae , Moran Jakob , Devins Kyle , Wszolek Matthew , Cornejo Kristine M.
Published: December 2022

Porocarcinomas are rare tumors derived from the acrosyringium and eccrine ducts, which most commonly occur on the lower extremities or head and neck region in older adults. Microscopically, they invariably demonstrate continuity with the epithelium, showing downgrowth of broad anastomosing bands with more infiltrative intradermal cords and nests of pleomorphic tumor cells with ductal lumina; an associated poroma may also be seen. We report an unusual case of a porocarcinoma arising on the scrotum of a 55-year-old man. Because of the extraordinary location and the presence of keratinizing squamous differentiation, distinction from a squamous cell carcinoma was particularly challenging. Close examination revealed the presence of a co-existing poroma, and immunohistochemistry revealed loss of YAP1 with diffuse nuclear expression of NUT in both the porocarcinoma and poroma components. This finding is particularly suggestive of a YAP1::NUTM1 fusion which has been reported to be highly specific for poroid neoplasms. Distinction of porocarcinoma from its mimics is important due to the frequent aggressive behavior of this neoplasm.
Ponatinib-Associated Cutaneous Eruptions—A Case Series and Review of Clinicopathologic Findings
Authors: Weber Isaac , Gloss Catherine , Castillo Brianna , Smith Emily
Published: December 2022

Ponatinib is a third-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia and Philadelphia-positive acute lymphoblastic leukemia. Cutaneous toxicities are a commonly reported side effect of ponatinib treatment with “rash” being one of the most common. Specific subtypes are infrequently reported, but include hyperkeratotic, folliculocentric, ichthyosiform, and pityriasis rubra pilaris-like eruptions. Herein, we highlight the clinicopathologic features of 2 cases of ponatinib-induced pityriasis rubra pilaris-like eruptions. We also classify the clinical and histopathologic features of all previously reported ponatinib-associated eruptions in the literature and discuss treatment and potential diagnostic pitfalls.
The effect of subbranch for the quantification of local hemodynamic environment in the coronary artery: a computed tomography angiography–based computational fluid dynamic analysis
Authors: Shi Yibing , Zheng Jin , Yang Ning , Chen Yang , Sun Jingxi , Zhang Ying , Zhou Xuanxuan , Gao Yongguang , Li Suqing , Zhu Haijing , Acosta-Cabronero Julio , Xia Ping , Teng Zhongzhao
Published: December 2022

Background

Hemodynamic parameters derived from computed tomography angiography–based computational fluid dynamics (CFD) analysis have been widely used for clinical decision-making and researches to assess the vulnerability of atherosclerotic plaques and explain the initialization and development of atherosclerosis. Subbranches in the CFD model might affect the accuracy of hemodynamic parameters, but the effectiveness has been least quantified.

Methods

A coronary artery baseline model was generated with focal stenosis at the proximal left anterior descending artery. Nineteen comparing models were created by systematically removing various subbranches to examine the changes in hemodynamic parameters, including time-averaged pressure (TAP), time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and particle relative residence time (RRT). Changes in these parameters were assessed quantitatively around the stenosis and near the region where subbranches were removed.

Results

The removal of subbranches caused a significant change in outflow rate, and there was generally a decrease in all CFD parameters in the regions of interest with a decrease in outflow rate. The subbranch removal had a significant impact on the calculation of TAWSS, OSI, and RRT, whereas TAP was insensitive to the removal with approximately 0.25% variation in all 19 models. The local effect from removing branch segments generally became negligible after 5 diameters away from the cutting-off position, but the decrease could be affected by other factors, such as a large curvature.

Conclusion

The outflow rate is a dominant factor for the calculation of TAP, TAWSS, OSI, and RRT. Removal of subbranches has a minor effect on the TAP calculation, but its effect is considerable on the TAWSS, OSI, and RRT. The effect of subbranch removal is limited in a region with 5 local diameters.
The Influence of Iron and Ligand Type on Plutonium Uptake in Two Strains of Hydroponically Grown Corn (Zea Mays)
Authors: Phillips Stephanie Hoelbling , Donaher Sarah E. , Powell Brian A. , Tharayil Nishanth , Martinez Nicole E.
Published: December 2022

This work investigates the uptake and root-shoot transport of plutonium (Pu) and iron (Fe) in corn (Zea mays) to gain insight into the Pu uptake pathway. Plutonium has no known biological function in plants yet may feasibly enter plants through the uptake pathway used by Fe (an essential nutrient), as these two elements have similar chemical properties. A series of experiments was conducted in which two hydroponically grown corn strains (one normal and one deficient in the transporter protein for Fe) were exposed to varying concentrations of complexed Pu and Fe. Results suggest that while Fe did inhibit Pu uptake to a certain extent, Pu was able to use alternative uptake pathways. In a 10 ppb Pu:1 ppb Fe hydroponic solution, all shoots had detectable shoot Pu concentrations compared to only 22% of plants when the Fe concentration was raised to 10 ppb. While root Pu accumulation was reduced for the corn strain deficient in the Fe transporter protein at lower Pu media concentrations, there were no differences at higher Pu concentrations, signifying the existence of substitute transport routes. A comparison of citrate and deferoxamine B (DFOB) ligand influence found that Pu complexed with DFOB remained in the roots of the plant, while movement of Pu into the shoots of the plant was more prevalent with the Pu-citrate complex. This study advances understanding of the behavior and mobility of Pu in the terrestrial environment and specifically the interactions between Pu and an essential nutrient in a common crop species.
Intraoperative aberrometry: an update on applications and outcomes
Authors: Kaufman Aaron R. , Pineda Roberto
Published: December 2022

Purpose of review

There is now a large body of experience with intraoperative aberrometry. This review aims to synthesize available data regarding intraoperative aberrometry applications and outcomes.

Recent findings

The Optiwave Refractive Analysis (ORA) System utilizes Talbot-moiré interferometry and is the only commercially available intraoperative aberrometry device. There are few studies that include all-comers undergoing intraoperative aberrometry-assisted cataract surgery, as most studies examine routine patients only or atypical eyes only. In non-post-refractive cases, studies have consistently shown a small but statistically significant benefit in spherical equivalent refractive outcome for intraoperative aberrometry versus preoperative calculations. In studies examining axial length extremes, most studies have shown intraoperative aberrometry to perform similarly to preoperative calculations. Amongst post-refractive cases, post-myopic ablation cases appear to benefit the most from intraoperative aberrometry. For toric intraocular lenses (IOLs), intraoperative aberrometry may be used for refining IOL power (toricity and spherical equivalent) and alignment, and most studies show intraoperative aberrometry to achieve low postoperative residual astigmatism.

Intraoperative aberrometry can be utilized as an adjunct to preoperative planning and surgeon's judgment to optimize cataract surgery refractive outcomes. Non-post-refractive cases, post-myopic ablation eyes, and toric intraocular lenses may have the greatest demonstrated benefit in intraoperative aberrometry studies to date, but other eyes may also benefit from intraoperative aberrometry use.