bluuebunny/crossref_metadata_2025 huggingface dataset:
Precocious Puberty in a Boy With Bilateral Leydig Cell Tumors due to a Somatic Gain-of-Function LHCGR Variant
Authors: Flippo Chelsi , Kolli Vipula , Andrew Melissa , Berger Seth , Bhatti Tricia , Boyce Alison M , Casella Daniel , Collins Michael T , Délot Emmanuèle , Devaney Joseph , Hewitt Stephen M , Kolon Thomas , Mallappa Ashwini , White Perrin C , Merke Deborah P , Dauber Andrew
Published: August 2022

Context

Autosomal dominant and rarely de novo gain-of-function variants in the LHCGR gene are associated with precocious male puberty, while somatic LHCGR variants have been found in isolated Leydig cell adenomas and Leydig cell hyperplasia. Bilateral diffuse Leydig cell tumor formation in peripheral precocious male puberty has not been reported.

Case Description

We present a boy with gonadotropin-independent precocious puberty and rapid virilization beginning in infancy resistant to standard therapy. Treatment with abiraterone in addition to letrozole and bicalutamide proved effective. Bilateral diffuse Leydig cell tumors were identified at age 5 years.

Results

Whole-genome sequencing of tumor and blood samples was performed. The patient was confirmed to have bilateral, diffuse Leydig cell tumors harboring the somatic, gain-of-function p.Asp578His variant in the LHCGR gene. Digital droplet polymerase chain reaction of the LHCGR variant performed in tumor and blood samples detected low levels of this same variant in the blood.

Conclusion

We report a young boy with severe gonadotropin-independent precocious puberty beginning in infancy who developed bilateral diffuse Leydig cell tumors at age 5 years due to a somatic gain-of-function p.Asp578His variant in LHCGR. The gain-of-function nature of the LHCGR variant and the developmental timing of the somatic mutation likely play a role in the risk of tumor formation. Abiraterone (a CYP17A1 inhibitor), in combination with an antiandrogen, aromatase inhibitor, and glucocorticoid, appears to be an effective therapy for severe peripheral precocious puberty in boys.
Venous Sinus Stenting for Low Pressure Gradient Stenoses in Idiopathic Intracranial Hypertension
Authors: Inam Mehmet Enes , Martinez-Gutierrez Juan Carlos , Kole Matthew J. , Sanchez Francisco , Lekka Elvira , Truong Van Thi Thanh , Lopez-Rivera Victor , Sheriff Faheem G. , Zima Laura A. , Pedroza Claudia , Tang Rosa , Adesina Ore-Ofe , Engstrom Allison , Sheth Sunil A. , Chen Peng Roc
Published: August 2022

BACKGROUND:

Medically refractory idiopathic intracranial hypertension (IIH) is frequently treated with venous sinus stenosis stenting with high success rates. Patient selection has been driven almost exclusively by identification of supraphysiological venous pressure gradients across stenotic regions based on theoretical assessment of likelihood of response.

OBJECTIVE:

To explore the possibility of benefit in low venous pressure gradient patients.

METHODS:

Using a single-center, prospectively maintained registry of patients with IIH undergoing venous stenting, we defined treatment groups by gradient pressures of ≤4, 5 to 8, and >8 mmHg based on the most frequently previously published thresholds for stenting. Baseline demographics, clinical, and neuro-ophthalmological outcomes (including optical coherence tomography and Humphrey visual fields) were compared.

RESULTS:

Among 53 patients, the mean age was 32 years and 70% female with a mean body mass index was 36 kg/m2. Baseline characteristics were similar between groups. The mean change in lumbar puncture opening pressure at 6 months poststenting was similar between the 3 groups (≤4, 5-8, and >8 mmHg; 13.4, 12.9, and 12.4 cmH2O, P = .47). Papilledema improvement was observed across groups at 6 months (100, 93, and 86, P = .7) as were all clinical symptoms. The mean changes in optical coherence tomography retinal nerve fiber layer (−30, −54, and −104, P = .5) and mean deviation in Humphrey visual fields (60, 64, and 67, P = .5) at 6 weeks were not significantly different.

CONCLUSION:

Patients with IH with low venous pressure gradient venous sinus stenosis seem to benefit equally from venous stenting compared with their higher gradient counterparts. Re-evaluation of our restrictive criteria for this potentially vision sparing intervention is warranted. Future prospective confirmatory studies are needed.
Behaviour change techniques taxonomy v1: Feedback to inform the development of an ontology
Authors: Corker Elizabeth , Marques Marta M. , Johnston Marie , West Robert , Hastings Janna , Michie Susan
Published: August 2022

Background: To build cumulative evidence about what works in behaviour change interventions, efforts have been made to develop classification systems for specifying the content of interventions. The Behaviour Change Techniques (BCT) Taxonomy v1 (BCTTv1) is one of the most widely used classifications of behaviour change techniques across a variety of behaviours. The BCTTv1 was intentionally named version 1 to allow for further revisions to the taxonomy. This study aimed to gather data to inform the development of BCTTv1 into a more elaborated knowledge structure, an ontology. 

Methods: Feedback from users of BCTTv1 about limitations and proposed improvements was collected through the BCT website, a user survey, researchers and experts involved in the Human Behaviour Change Project, and a consultation. In addition, relevant published research reports and other classification systems of BCTs were analysed. These data were synthesised to produce recommendations to inform the development of an ontology of BCTs.

Results: A total of 282 comments from six sources were reviewed and synthesised into four categories of suggestions: additional BCTs, amendments to labels and definitions of specific BCTs, amendments to the groupings, and general improvements. Feedback suggested some lack of clarity regarding understanding and identifying techniques from labels, definitions, and examples; distinctions and relations between BCTs; and knowing what they would look like in practice. Three recommendations resulted from this analysis: to review the label and definition of each BCT, the 16 groupings of BCTs, and the examples illustrating BCTs.

Conclusions: This review of feedback about BCTTv1 identified the need to improve the precision and knowledge structure of the current taxonomy. A BCT ontology would enable the specification of relationships between BCTs, more precise definitions, and allow better interoperability with other ontologies. This ontology will be developed as part of the Human Behaviour Change Project.
El Batallón América. Un ejemplo de colaboración guerrillera en Colombia
Authors: Díaz-Maroto Isidro Aitor
Published: August 2022

En el presente artículo, realizaremos un recorrido tanto por la historia de la guerrilla colombiana Movimiento 19 de Abril (M-19) como por una de sus unidades armadas más significativa e interesantes: el Batallón América. Formado por unidades del citado M-19 y Movimiento Armado Quintín Lame (Colombia), Alfaro Vive Carajo (Ecuador), y del Movimiento Revolucionario Túpac Amaru (Perú), este Batallón es un ejemplo perfecto de la política de interrelaciones que el M-19 puso en marcha con guerrillas nacionales e internacionales. A través del estudio de las fuentes bibliográficas de la historia del M-19, construiremos una imagen primigenia acerca del impacto de este internacionalismo guerrillero, sus efectos en el devenir posterior de las guerrillas en él incluidas, la relevancia del Batallón América a la hora de constituir una estrategia de cooperación guerrillera al interior de Colombia, así como la constitución de una fuerza transnacional revolucionaria para toda Latinoamérica.
Personalized Ranking at a Mobile App Distribution Platform
Authors: Mao Shengjun , Dewan Sanjeev , Ho Yi-Jen (Ian)
Published: August 2022

Personalization is an emerging digital strategy to engage users across different business domains. It is defined as the capability to match content, products, and services to individual users based on the knowledge of their past behaviors and revealed preferences. It has shown its great potential across a variety of contexts, including search engines, recommender systems, targeted marketing, and more. In this study, we examine personalization on third-party mobile app platforms, which account for a $36 billion market in 2021. We develop a comprehensive structural framework for the personalized ranking of app impressions, leveraging revealed preferences embedded in consumer clickstream data. To improve platform revenues, the framework jointly accounts for consumer utility and cost per action margin. A series of policy experiments highlights the value of personalization to various extent. Remarkably, personalized rankings at the individual level outperform the current practice by 16.73%. This cost-efficient approach showcases how platforms can leverage routine consumer clickstream data to personalize the ranking of app impressions, thereby more effectively monetizing mobile app distribution.
Variations of the Bullwhip Effect Across Foreign Subsidiaries
Authors: Lee Seungrae , Park Seung Jae , Seshadri Sridhar
Published: August 2022

Problem definition: We investigate variations of the bullwhip effect across foreign subsidiaries and explore how it is affected by various features of foreign subsidiaries. Academic/practical relevance: During the era of global supply chain restructuring, researchers and executives of multinational firms should understand variations of the foreign subsidiary’s bullwhip effect, given that its reduction is a key strategy for coordinating supply chains. Methodology: Our work is based on a balanced panel data set of Korean-owned subsidiaries that provides distinguishable information on subsidiary purchases. It enables us to estimate an alternative measure for the bullwhip effect by the ratio of purchase volatility to demand volatility and compare it with the traditional measure of the ratio of production volatility to demand volatility. Results: Our alternative measure differs significantly from the traditional measure and better reflects the prevalence of the bullwhip effect across foreign subsidiaries. Using this new measure, we find that the bullwhip effect is strongly affected by country-specific factors and foreign subsidiary-specific factors. These findings support not only previous analytical findings on the bullwhip effect but also provide new remedies to reduce the bullwhip effect. Managerial implications: Our study advises managers of multinational firms. First, although locating foreign subsidiaries in developing countries tends to reduce production costs, it could instead increase the bullwhip effect, especially for politically unstable countries or those with lower import penetration. Second, we provide empirical evidence that relocating a subsidiary to a country close to its main suppliers or to one that incurs lower transportation costs will reduce the bullwhip effect. Finally, deploying expatriate managers and wholly owning the subsidiary are recommended strategies to reduce the bullwhip effect of foreign subsidiaries.

Funding: This work was supported by Yonsei University [Grants 2019-22-0006, 2020-22-0089, and 2021-22-0072] and Hankuk University of Foreign Studies [Grant 2022].

Supplemental Material: The online appendices are available at https://doi.org/10.1287/msom.2022.1137 .
Professional jargon
Authors: Allingham Sue
Published: August 2022

Our professional jargon slips so easily into our conversation that time to reflect on what we actually mean can often be forgotten. Or worse, the words are used with no real depth of understanding at all. There are many reasons for this and this is not about apportioning blame, but we have a professional responsibility, whatever our role or qualifications, to fully understand the what, why and how of our professional vocabulary.
Government consultation ‘a dangerous experiment’
Authors: Lloyd Eva
Published: August 2022

Do you have something to share, reflect on or provoke thinking around? Write to the editor: angelica.celinska@markallengroup.com
The powers of media literacy education
Authors: Fawkes Lauren
Published: August 2022

This article will explore the dazzling dream that media literacy education can offer for our early years children and the frightful fear that the online world creates for children's safeguarding. The article also challenges educators' knowledge of media literacy and their competence in supporting children's understanding of the nature of online content, the impact of material on others, and the consequences of material within the real world.
Supporting young children to think and talk about their learning
Authors: Mickelburgh Juliet
Published: August 2022

Young children spend a lot of time thinking and learning, and helping them to understand what thinking is and how it helps their learning will support them through childhood and beyond.
A new prime minister presents an opportunity to change the early years narrative
Authors: Leitch Neil
Published: August 2022

Neil Leitch looks at the current circumstances of the changes within the UK's Government, as well as looking back at the recent past and what this has meant for the early years sector, and how we can move forward.
Electric field enhancement by a hybrid dielectric-metal nanoantenna with a toroidal dipole contribution
Authors: Mu Haiwei , Wang Yu , Lv Jingwei , Yi Zao , Yang Lin , Chu Paul K. , Liu Chao
Published: August 2022

Plasmonic nanocavities enable extreme light–matter interactions by pushing light down to the nanoscale. The numerical simulation is carried out systematically on the slotted

Φ

-shaped Si disk system with the super-dipole mode based on the analysis of the scattering strength of electric and toroidal dipoles. New blocks are introduced to the zero-field strength region of a slotted Si disk system as a function of the field enhancement factors. The far-field scattering characteristics and near-field electromagnetic field distributions are investigated by a multipole decomposition analysis to elucidate the intrinsic causes of the field enhancement. In the hybrid metal-dielectric nanoantenna, the

Φ

-shaped Si structure is prepared by superimposing Au nanoantennas for further field enhancement. In addition, the effects of the placement of an electric dipole emitter on the Purcell factor are derived. The geometric volume of the system is increased, and the electric field strength is improved, leading to an electric field increase of

∼

30

. Coupling between the super-dipole mode of the dielectric nanostructure and plasmonic modes of the metallic nanoantenna produces an enhancement as large as 16 times. Our results reveal a greatly enhanced super-dipole mode by electromagnetic coupling in composite structures, which will play a significant role in enhanced nonlinear photonics, near-field enhancement spectroscopy, and strong photon–exciton coupling.
Nonlocal means filter based on cosine similarity applied in speckle reduction of digital holography
Authors: Xiao Jiaqi , Chen Li , Wen Kunhua , Hu Yihua
Published: August 2022

In the field of digital holography, the speckle caused by coherent light greatly disturbs the quality of the reconstruction. This paper presents an innovative method to efficiently reduce speckle noise with a nonlocal means filter based on cosine similarity that determines the weight of each traversal pixel to the target pixel by comparing the similarity between the target pixel neighborhood and the traversal pixel neighborhood. Experimental results with qualitative and quantitative analysis indicate that the proposed method significantly improves noise reduction performance while preserving the details of the original image. Compared with other general image-processing methods, this well-directed method is more in line with the characteristics of holographic speckle noise and has obvious advantages in various metrics.
Upconversion pumping of lasers via excited-state absorption: an analytical rate-equation formulation
Authors: Sennaroglu Alphan
Published: August 2022

Coupled power-gain equations were used to model lasers where optical pumping occurs as a result of a weak ground-state absorption followed by strong pump excited-state absorption (ESA). Inspired by the gain dynamics and energy-level structure of upconversion-pumped 2.3 µm

T
m

3
+

lasers and 3.4 µm

E
r

3
+

lasers, the model assumes that population in the lower laser level relaxes via a fast nonradiative decay to an intermediate storage level, which typically has a considerably slower decay rate than that of the upper laser level. After obtaining a description of the rate equation model, the continuous-wave regime was investigated by deriving analytical expressions for the power-dependent absorption, threshold pump power for lasing, output laser power, and laser slope efficiency. Results indicate that a slow decay rate of the lower level is necessary, so that sufficient population buildup can lead to enhanced nonlinear absorption via ESA. Furthermore, the asymptotic slope efficiency of the ESA pumped laser is similar to that of the ideal four-level laser, where the linear absorption is replaced by the effective nonlinear absorption.
3D-printed facet-attached optical elements for beam shaping in optical phased arrays
Authors: Singer Stefan , Xu Yilin , Skacel Sebastian Tobias , Bao Yiyang , Zwickel Heiner , Maier Pascal , Freter Lukas , Dietrich Philipp-Immanuel , Kaschel Mathias , Menzel Christoph , Randel Sebastian , Freude Wolfgang , Koos Christian
Published: August 2022

We demonstrate an optical phased-array equipped with a 3D-printed facet-attached element for shaping and deflection of the emitted beam. The beam shaper combines freeform refractive surfaces with total-internal-reflection mirrors and is in-situ printed to edge-emitting waveguide facets using high-resolution multi-photon lithography, thereby ensuring precise alignment with respect to on-chip waveguide structures. In a proof-of-concept experiment, we achieve a grating-lobe free steering range of

±

30
∘

and a full-width-half-maximum beam divergence of approximately

2
∘

. The concept opens an attractive alternative to currently used grating structures and is applicable to a wide range of integration platforms.
Weakly guiding graded-index ring-core fiber supporting 16-channel long distance mode division multiplexing systems based on OAM modes with low MIMO-DSP complexity
Authors: Zhang Xi , Chen Shi , Wang Jian
Published: August 2022

We propose a weakly guiding graded-index ring-core fiber (RCF) with trench-assisted structure. The simulation analysis indicates that such a special fiber design is able to support 8 orbital angular momentum (OAM) mode groups (MGs) with low inter-group crosstalk (< −25 dB/km) and low intra-group differential mode delay (DMD) (< 125 ps/km) for higher order OAM MGs with topological charge |l| = 4, 5, 6, 7. The designed RCF also shows favorable tolerance characteristics to ellipticity and bending. Moreover, stable and distinguished broadband performance of proposed RCF is verified over the whole C band ranging from 1530 nm to 1565 nm. This kind of fiber design could be employed in small-scale multiple-input multiple-output digital signal processing (MIMO-DSP) intra-group modes multiplexing transmission combined with MIMO-free inter-group mode multiplexing transmission. The simulated results of the designed RCF show its great potential of the 16-channel long-distance mode division multiplexing (MDM) transmission with low MIMO-DSP complexity.
Perovskite solar cells integrated with blue cut-off filters for mitigating light-induced degradation
Authors: Yoon Beomhee , Park Chul-Soon , Song Hyung-Jun , Kwak Jeonghun , Lee Sang-Shin , Lee Hyunho
Published: August 2022

The stability of methylammonium (MA)-based perovskite solar cells (PSCs) remains one of the most urgent issues that need to be addressed. Inherent weak binding forces between MAs and halides cause the perovskite structure to become unstable under exposure to various external environmental factors such as moisture, oxygen, ultraviolet radiation, and heat. In particular, the degradation of perovskite films under light exposure accelerates the deterioration of the device, mainly due to the migration of halide ions. In this study, we investigated the effect of light energy on the degradation of inverted PSCs by introducing red ( = 610–800 nm), green (500–590 nm), and blue (300–500 nm) light-pass filters. After 30 h, the inverted PSCs of blue-light-induced devices retained a power conversion efficiency (PCE) of 70%, while those of the green and red light-induced devices retained PCEs of 85% and 90%, respectively. Direct evidence of light-induced degradation was obtained by investigating morphological changes in the perovskite films and the amount of ion accumulation on the Ag electrode. This evidence highlights the varying effect of light with different energies on device degradation. Furthermore, to minimize light-induced device degradation, we designed two types of blue cut-off filters that can selectively block light ranging from  = 400 to 500 nm, comprising a multilayered inorganic metasurface. An optical simulation was used to optimize the performance of the designed filters. By investigating the changes in the photovoltaic parameters and the amount of ion accumulation on the Ag electrode, we confirmed that integrating blue cut-off filters into PSCs greatly improved the operational lifetime of the devices.
Bayesian optimization of nanophotonic electromagnetic shielding with very high visible transparency
Authors: Li Mingxuan , McCourt Michael J. , Galante Anthony J. , Leu Paul W.
Published: August 2022

Transparent electromagnetic interference (EMI) shielding is needed in many optoelectronic applications to protect electronic devices from surrounding radiation while allowing for high visible light transmission. However, very high transmission (over 92.5%), high EMI shielding efficiency (over 30 dB) structures have yet to be achieved in the literature. Bayesian optimization is used to optimize different nanophotonic structures for high EMI shielding efficiency (SE) and high visible light transmission (

T
¯

v
i
s

). Below 90% average visible light transmission, sandwich structures consisting of high index dielectric/silver/high index dielectric films are determined to be optimal, where they are able to achieve 43.1 dB SE and 90.0%

T
¯

v
i
s

. The high index of refraction dielectric layers reduce absorption losses in the silver and can be engineered to provide for antireflection through destructive interference. However, for optimal EMI shielding with

T
¯

v
i
s

above 90%, the reflection losses at the air/dielectric interfaces need to be further reduced. Optimized double sided nanocone sandwich structures are determined to be best where they can achieve 41.2 dB SE and 90.8%

T
¯

v
i
s

as well as 35.6 dB SE and 95.1%

T
¯

v
i
s

. K-means clustering is utilized to show the performance of characteristic near-Pareto optimal structures. Double sided nanocone structures are shown to exhibit omnidirectional visible transmission with SE = 35.6 dB and over 85%

T
¯

v
i
s

at incidence angles of 70

∘

.
Active–passive collaborative approach for XCO2 retrieval using spaceborne sensors
Authors: Cai Mengyang , Han Ge , Ma Xin , Pei Zhipeng , Gong Wei
Published: August 2022

We propose a novel, to the best of our knowledge, active–passive collaborative retrieval method for measuring XCO2 (APCRM-CO2). This method simultaneously uses observations from spectrometers and integrated path differential absorption laser detection and ranging (IPDA LIDAR), thus making its products have both the coverage advantages of passive detection and the high information content of active detection. The results of simulation experiments show that APCRM-CO2 can reduce the retrieval error by 15% to 70%. The minimum SNR for achieving 1 ppm is 24.7 dB. All these results are obtained without considering the LIDAR measured aerosol profile as input. Therefore, greater performance improvements on XCO2 retrievals are expected in the future for real data processing. The first satellite mission, DQ-2, carrying both a spectrometer and an IPDA LIDAR is planned to be launched by 2025. With the help of APCRM-CO2, its XCO2 products would better assist us with understanding the carbon cycle.
Boosting topological zero modes using elastomer waveguide arrays
Authors: Frank Angelina , Leykam Daniel , Smirnova Daria A. , Angelakis Dimitris G. , Ling Alexander
Published: August 2022

We employ the Su–Schrieffer–Heeger model in elastic polymer waveguide arrays to design and realize traveling topologically protected modes. The observed delocalization of the optical field for superluminal defect velocities agrees well with theoretical descriptions. We apply mechanical strain to modulate the lattices’ coupling coefficient. This work demonstrates a novel, to the best of our knowledge, platform for rapid prototyping of topological photonic devices and establishes strain-tuning as a viable design parameter for topological waveguide arrays.
Tribute to photosensitive glasses [Invited]
Authors: Borelli Nick F. , Schroeder Joseph F.
Published: August 2022

The ability to color glass is centuries old, using coloring agents such as Ag, Au, and Cu among, others. The subject of the paper is to show that not only color but other properties as well can be obtained by introducing the light exposure step into the process. The name given to this phenomenon is
photosensitive glasses
– that is, glasses that can be patterned and colored by use of light exposure post melting and forming. The scope of this article is to present some key highlights on developments at Corning in the framework of the International Year of Glass 2022, rather than a comprehensive review. Also included are examples of optical devices that derive from this process.
Near-field analysis of electromagnetic chirality in the Mie scattering by a dielectric sphere
Authors: Lee Hyoung-In
Published: August 2022

We revisit the Mie scattering in view of electromagnetic chirality, especially in the near field of a scattering sphere. To this goal, we take the simplest two-dielectric system where both an embedding medium and an embedded sphere are loss-free, non-magnetic, and dielectric. For a given linearly polarized incident wave, the net chirality should vanish when integrated over the whole space. The reactive chirality indicating the divergence-full spin angular momentum density shows an analogous behavior. Meanwhile, the electromagnetic chirality obtained in response to a circularly polarized incident wave exhibits distinct super-chiral behaviors. In addition, we examined key bilinear parameters for another incident wave, where two orthogonal linearly polarized waves are combined without a phase delay.
Caregivers’ perception of risk for malaria, helminth infection and malaria-helminth co-infection among children living in urban and rural settings of Senegal: A qualitative study
Authors: Afolabi Muhammed O. , Sougou Ndèye Mareme , Diaw Aminata , Sow Doudou , Manga Isaac A. , Mbaye Ibrahima , Greenwood Brian , Ndiaye Jean Louis A.
Published: August 2022

The parasites causing malaria, soil-transmitted helminthiasis and schistosomiasis frequently co-exist in children living in low-and middle-income countries, where existing vertical control programmes for the control of these diseases are not operating at optimal levels. This gap necessitates the development and implementation of strategic interventions to achieve effective control and eventual elimination of these co-infections. Central to the successful implementation of any intervention is its acceptance and uptake by caregivers whose perception about the risk for malaria-helminth co-infection has been little documented. Therefore, we conducted a qualitative study to understand the caregivers’ perspectives about the risk as well as the behavioural and social risk factors promoting malaria-helminth co-infection among pre-school and school-age children living in endemic rural and urban communities in Senegal. In June and December 2021, we conducted individual and group interviews, and participant observations, among 100 primary caregivers of children recruited from Saraya villages in southeast Senegal and among leaders and teachers of Koranic schools in Diourbel, western Senegal. Our findings showed that a majority of the study participants in the two settings demonstrated a high level of perception of risk for malaria and acceptable awareness about handwashing practices, but had misconceptions that malaria-helminth co-infection was due to a combination of excessive consumption of sugary food and mosquito bites. Our observations revealed many factors in the house structures, toilet practices and handwashing with ashes and sands, which the caregivers did not consider as risks for malaria-helminth co-infections. These findings underscore the need to promote caregivers’ awareness about the existence and risk of malaria-helminth co-infection in children. This approach would assist in addressing the caregivers’ misconceptions about the occurrence of the co-infection and could enhance their uptake of the strategic interventions targeted at achieving control and subsequent elimination of malaria and helminth co-infection.
The S-palmitoylome and DHHC-PAT interactome of Drosophila melanogaster S2R+ cells indicate a high degree of conservation to mammalian palmitoylomes
Authors: Porcellato Elena , González-Sánchez Juan Carlos , Ahlmann-Eltze Constantin , Elsakka Mahmoud Ali , Shapira Itamar , Fritsch Jürgen , Navarro Juan Antonio , Anders Simon , Russell Robert B. , Wieland Felix T. , Metzendorf Christoph
Published: August 2022

Protein S-palmitoylation, the addition of a long-chain fatty acid to target proteins, is among the most frequent reversible protein modifications in Metazoa, affecting subcellular protein localization, trafficking and protein-protein interactions. S-palmitoylated proteins are abundant in the neuronal system and are associated with neuronal diseases and cancer. Despite the importance of this post-translational modification, it has not been thoroughly studied in the model organism Drosophila melanogaster. Here we present the palmitoylome of Drosophila S2R+ cells, comprising 198 proteins, an estimated 3.5% of expressed genes in these cells. Comparison of orthologs between mammals and Drosophila suggests that S-palmitoylated proteins are more conserved between these distant phyla than non-S-palmitoylated proteins. To identify putative client proteins and interaction partners of the DHHC family of protein acyl-transferases (PATs) we established DHHC-BioID, a proximity biotinylation-based method. In S2R+ cells, ectopic expression of the DHHC-PAT dHip14-BioID in combination with Snap24 or an interaction-deficient Snap24-mutant as a negative control, resulted in biotinylation of Snap24 but not the Snap24-mutant. DHHC-BioID in S2R+ cells using 10 different DHHC-PATs as bait identified 520 putative DHHC-PAT interaction partners of which 48 were S-palmitoylated and are therefore putative DHHC-PAT client proteins. Comparison of putative client protein/DHHC-PAT combinations indicates that CG8314, CG5196, CG5880 and Patsas have a preference for transmembrane proteins, while S-palmitoylated proteins with the Hip14-interaction motif are most enriched by DHHC-BioID variants of approximated and dHip14. Finally, we show that BioID is active in larval and adult Drosophila and that dHip14-BioID rescues dHip14 mutant flies, indicating that DHHC-BioID is non-toxic. In summary we provide the first systematic analysis of a Drosophila palmitoylome. We show that DHHC-BioID is sensitive and specific enough to identify DHHC-PAT client proteins and provide DHHC-PAT assignment for ca. 25% of the S2R+ cell palmitoylome, providing a valuable resource. In addition, we establish DHHC-BioID as a useful concept for the identification of tissue-specific DHHC-PAT interactomes in Drosophila.
Genomic analysis of the rare British Lop pig and identification of distinctive genomic markers
Authors: Banos Georgios , Talenti Andrea , Chatziplis Dimitrios , Sánchez-Molano Enrique
Published: August 2022

Concentration of production on a few commercial pig breeds has led to the marginalization of many native, numerically small breeds, increasing their risk of endangerment. In the UK, one such rare breed is the British Lop, a lop-eared breed, of similar origin to the Welsh breed. The objective of the present study was to address the genomic status of the British Lop and its relationship with other breeds and identify a small set of genomic markers that uniquely characterize and distinguish British Lop animals. Results have shown that the British Lop is a relatively distinct population with reduced genomic diversity and effective size consistent with its status as a rare breed. Furthermore, we demonstrated the genetic closeness of the British Lop to phenotypically similar breeds such as Landrace and Welsh as well Large White, Middle White and Pietrain. Finally, a set of 75 Single Nucleotide Polymorphisms distributed across multiple chromosomes were identified and validated as markers that can consistently distinguish British Lops from other closely related breeds. Results may inform breeding and management strategies aiming to enhance diversity as well as the development of a breed purity test.
Isolation, cryo-laser scanning confocal microscope imaging and cryo-FIB milling of mouse glutamatergic synaptosomes
Authors: Gogoi Prerana , Shiozaki Momoko , Gouaux Eric
Published: August 2022

Ionotropic glutamate receptors (iGluRs) at postsynaptic terminals mediate the majority of fast excitatory neurotransmission in response to release of glutamate from the presynaptic terminal. Obtaining structural information on the molecular organization of iGluRs in their native environment, along with other signaling and scaffolding proteins in the postsynaptic density (PSD), and associated proteins on the presynaptic terminal, would enhance understanding of the molecular basis for excitatory synaptic transmission in normal and in disease states. Cryo-electron tomography (ET) studies of synaptosomes is one attractive vehicle by which to study iGluR-containing excitatory synapses. Here we describe a workflow for the preparation of glutamatergic synaptosomes for cryo-ET studies. We describe the utilization of fluorescent markers for the facile detection of the pre and postsynaptic terminals of glutamatergic synaptosomes using cryo-laser scanning confocal microscope (cryo-LSM). We further provide the details for preparation of lamellae, between ~100 to 200 nm thick, of glutamatergic synaptosomes using cryo-focused ion-beam (FIB) milling. We monitor the lamella preparation using a scanning electron microscope (SEM) and following lamella production, we identify regions for subsequent cryo-ET studies by confocal fluorescent imaging, exploiting the pre and postsynaptic fluorophores.
Psychological interventions to prevent relapse in anxiety and depression: A systematic review and meta-analysis
Authors: Krijnen-de Bruin Esther , Scholten Willemijn , Muntingh Anna , Maarsingh Otto , van Meijel Berno , van Straten Annemieke , Batelaan Neeltje
Published: August 2022

Objectives

The aim of this review is to establish the effectiveness of psychological relapse prevention interventions, as stand-alone interventions and in combination with maintenance antidepressant treatment (M-ADM) or antidepressant medication (ADM) discontinuation for patients with remitted anxiety disorders or major depressive disorders (MDD).

Methods

A systematic review and a meta-analysis were conducted. A literature search was conducted in PubMed, PsycINFO and Embase for randomised controlled trials (RCTs) comparing psychological relapse prevention interventions to treatment as usual (TAU), with the proportion of relapse/recurrence and/or time to relapse/recurrence as outcome measure.

Results

Thirty-six RCTs were included. During a 24-month period, psychological interventions significantly reduced risk of relapse/recurrence for patients with remitted MDD (RR 0.76, 95% CI: 0.68–0.86, p<0.001). This effect persisted with longer follow-up periods, although these results were less robust. Also, psychological interventions combined with M-ADM significantly reduced relapse during a 24-month period (RR 0.76, 95% CI: 0.62–0.94, p = 0.010), but this effect was not significant for longer follow-up periods. No meta-analysis could be performed on relapse prevention in anxiety disorders, as only two studies focused on relapse prevention in anxiety disorders.

Conclusions

In patients with remitted MDD, psychological relapse prevention interventions substantially reduce risk of relapse/recurrence. It is recommended to offer these interventions to remitted MDD patients. Studies on anxiety disorders are needed.

Systematic review registration number

PROSPERO 2018: CRD42018103142.
A high-throughput integrated biofilm-on-a-chip platform for the investigation of combinatory physicochemical responses to chemical and fluid shear stress
Authors: Nguyen Ann V. , Shourabi Arash Yahyazadeh , Yaghoobi Mohammad , Zhang Shiying , Simpson Kenneth W. , Abbaspourrad Alireza
Published: August 2022

Physicochemical conditions play a key role in the development of biofilm removal strategies. This study presents an integrated, double-layer, high-throughput microfluidic chip for real-time screening of the combined effect of antibiotic concentration and fluid shear stress (FSS) on biofilms. Biofilms of Escherichia coli LF82 and Pseudomonas aeruginosa were tested against gentamicin and streptomycin to examine the time dependent effects of concentration and FSS on the integrity of the biofilm. A MatLab image analysis method was developed to measure the bacterial surface coverage and total fluorescent intensity of the biofilms before and after each treatment. The chip consists of two layers. The top layer contains the concentration gradient generator (CGG) capable of diluting the input drug linearly into four concentrations. The bottom layer contains four expanding FSS chambers imposing three different FSSs on cultured biofilms. As a result, 12 combinatorial states of concentration and FSS can be investigated on the biofilm simultaneously. Our proof-of-concept study revealed that the reduction of E. coli biofilms was directly dependent upon both antibacterial dose and shear intensity, whereas the P. aeruginosa biofilms were not impacted as significantly. This confirmed that the effectiveness of biofilm removal is dependent on bacterial species and the environment. Our experimental system could be used to investigate the physicochemical responses of other biofilms or to assess the effectiveness of biofilm removal methods.
Data augmentation using image translation for underwater sonar image segmentation
Authors: Lee Eon-ho , Park Byungjae , Jeon Myung-Hwan , Jang Hyesu , Kim Ayoung , Lee Sejin
Published: August 2022

In underwater environment, the study of object recognition is an important basis for implementing an underwater unmanned vessel. For this purpose, abundant experimental data to train deep learning model is required. However, it is very difficult to obtain these data because the underwater experiment itself is very limited in terms of preparation time and resources. In this study, the image transformation model, Pix2Pix is utilized to generate data similar to experimental one obtained by our ROV named SPARUS between the pool and reservoir. These generated data are applied to train the other deep learning model, FCN for a pixel segmentation of images. The original sonar image and its mask image have to be prepared for all training data to train the image segmentation model and it takes a lot of effort to do it what if all training data are supposed to be real sonar images. Fortunately, this burden can be released here, for the pairs of mask image and synthesized sonar image are already consisted in the image transformation step. The validity of the proposed procedures is verified from the performance of the image segmentation result. In this study, when only real sonar images are used for training, the mean accuracy is 0.7525 and the mean IoU is 0.7275. When the both synthetic and real data is used for training, the mean accuracy is 0.81 and the mean IoU is 0.7225. Comparing the results, the performance of mean accuracy increase to 6%, performance of the mean IoU is similar value.
Economic burden of chronic pain in Alberta, Canada
Authors: Thanh Nguyen Xuan , Tanguay Robert L. , Manhas Kiran J. Pohar , Kania-Richmond Ania , Kashuba Sherri , Geyer Tracey , Pereira John X. , Wasylak Tracy
Published: August 2022

Background

Although chronic pain (CP) is common, little is known about its economic burden in Alberta, Canada.

Aims

To estimate incremental (as compared to the general population or people without CP) societal (healthcare and lost productivity) costs of CP in Alberta.

Methods

We applied the prevalence estimated from the Canadian Community Health Survey data to the population retrieved from the Statistics Canada to estimate the number of people with CP in Alberta in 2019. We analyzed the Alberta Health administrative databases to estimate the healthcare costs of person with CP. Finally, we multiplied the number of people with the cost per person.

Results

The prevalence of any CP was 20.1% and of activity-preventing CP was 14.5% among people aged > = 12 years. Incremental cost per person with CP per year was CA$2,217 for healthcare services (among people aged > = 12 years) and CA$8,412 for productivity losses (among people aged 18–64 years). Of the healthcare cost, prescription drugs accounted for the largest share (32.8%), followed by inpatient services (31.0%), outpatient services (13.1%), physician services (9.8%), other services (7.4%), and diagnostic imaging (5.8%). Provincially, total incremental cost of CP ranges from CA$1.2 to 1.7 billion for healthcare services (6% to 8% of total provincial health expenditure); and CA$3.4 to 4.7 billion for productivity losses. Considering costs for long-term care services, the total societal cost of CP in Alberta was CA$6.3 to 8.3 billion per year, reflecting 2.0% to 2.7% of Alberta’s GDP.

Conclusions

Interventions improving CP prevention and management to reduce this substantial economic burden are urgently needed.
Spatio-temporal variability of eDNA signal and its implication for fish monitoring in lakes
Authors: Hervé Alix , Domaizon Isabelle , Baudoin Jean-Marc , Dejean Tony , Gibert Pierre , Jean Pauline , Peroux Tiphaine , Raymond Jean-Claude , Valentini Alice , Vautier Marine , Logez Maxime
Published: August 2022

Environmental DNA (eDNA) metabarcoding is revolutionizing the monitoring of aquatic biodiversity. The use of eDNA has the potential to enable non-invasive, cost-effective, time-efficient and high-sensitivity monitoring of fish assemblages. Although the capacity of eDNA metabarcoding to describe fish assemblages is recognised, research efforts are still needed to better assess the spatial and temporal variability of the eDNA signal and to ultimately design an optimal sampling strategy for eDNA monitoring. In this context, we sampled three different lakes (a dam reservoir, a shallow eutrophic lake and a deep oligotrophic lake) every 6 weeks for 1 year. We performed four types of sampling for each lake (integrative sampling of sub-surface water along transects on the left shore, the right shore and above the deepest zone, and point sampling in deeper layers near the lake bottom) to explore the spatial variability of the eDNA signal at the lake scale over a period of 1 year. A metabarcoding approach was applied to analyse the 92 eDNA samples in order to obtain fish species inventories which were compared with traditional fish monitoring methods (standardized gillnet samplings). Several species known to be present in these lakes were only detected by eDNA, confirming the higher sensitivity of this technique in comparison with gillnetting. The eDNA signal varied spatially, with shoreline samples being richer in species than the other samples. Furthermore, deep-water samplings appeared to be non-relevant for regularly mixed lakes, where the eDNA signal was homogeneously distributed. These results also demonstrate a clear temporal variability of the eDNA signal that seems to be related to species phenology, with most of the species detected in spring during the spawning period on shores, but also a peak of detection in winter for salmonid and coregonid species during their reproduction period. These results contribute to our understanding of the spatio-temporal distribution of eDNA in lakes and allow us to provide methodological recommendations regarding where and when to sample eDNA for fish monitoring in lakes.
Changes in spending, utilization, and quality of care among Medicare accountable care organizations during the COVID-19 pandemic
Authors: Yan Brandon W. , Shashoua Maya , Figueroa Jose F.
Published: August 2022

The COVID pandemic disrupted health care spending and utilization, and the Medicare Shared Savings Program (MSSP), Medicare’s largest value-based payment model with 11.2 million assigned beneficiaries, was no exception. Despite COVID, the 513 accountable care organizations (ACO) in MSSP returned a program record $1.9 billion in net savings to Medicare in 2020. To understand the extent of COVID’s impact on MSSP cost and quality, we describe how ACO spending changed in 2020 and further analyze changes in measured quality and utilization. We found that non-COVID per capita spending in MSSP fell by 8.3 percent from $11,496 to $10,537 (95% confidence interval(CI),-1,223.8 to-695.4, p<0.001), driven by 14.6% and 7.5% reductions in per capita acute inpatient and outpatient spending, respectively. Utilization fell across inpatient, emergency, and outpatient settings. On quality metrics, preventive screening rates remained stable or improved, while control of diabetes and blood pressure worsened. Large reductions in non-COVID utilization helped ACOs succeed financially in 2020, but worsening chronic disease measures are concerning. The appropriateness of the benchmark methodology and exclusion of COVID-related spending, especially as the virus approaches endemicity, should be revisited to ensure bonus payments reflect advances in care delivery and health outcomes rather than COVID-related shifts in spending and utilization patterns.