bluuebunny/crossref_metadata_2025 huggingface dataset:
Environment, sustainability, and Hellenic studies
Authors: Post Ruben
Published: March 2023

This article reviews a selection of books published over the last decade that explore the relationship between humans and the environment in the ancient Greek world. These publications represent a new phase of the ecological turn in classical studies, in which ancient environmental studies has emerged as a distinct subdivision of the environmental humanities. Their contributions can roughly be divided into two groups according to their approaches and goals: one applies ecocritical analyses to Greek literature, presenting alternative ecologies to those that have produced contemporary environmental crises; the other applies historical methods to written and material evidence to illuminate the realities of ancient Greek human–environment relations. The three subsections of this review provide overviews of scholarship addressing sustainability and the conservation of natural resources; ecology and religion; and societal resilience in the face of ecological stress. I suggest productive avenues for further research in each area, arguing that interdisciplinary communication and collaboration are becoming increasingly important in this evidentially, methodologically and theoretically variegated field.
An agent-based model of COVID-19 pandemic and its variants using fuzzy subsets and real data applied in an island environment
Authors: Regis Sébastien , Manicom Olivier , Doncescu Andrei
Published: March 2023

In this paper, we present a model of the spread of the COVID-19 pandemic simulated by a multi-agent system (MAS) based on demographic data and medical knowledge. Demographic data are linked to the distribution of the population according to age and to an index of socioeconomic fragility with regard to the elderly. Medical knowledge are related to two risk factors: age and obesity. The contributions of this approach are as follows. Firstly, the two aggravating risk factors are introduced into the MAS using fuzzy sets. Secondly, the worsening of disease caused by these risk factors is modeled by fuzzy aggregation operators. The appearance of virus variants is also introduced into the simulation through a simplified modeling of their contagiousness. Using real data from inhabitants of an island in the Antilles (Guadeloupe, FWI), we model the rate of the population at risk which could be critical cases, if neither social distancing nor barrier gestures are respected by the entire population. The results show that hospital capacities are exceeded. The results show that hospital capacities are exceeded. The socioeconomic fragility index is used to assess mortality and also shows that the number of deaths can be significant.
A real-options analysis of climate change and international migration
Authors: Braun Marius
Published: March 2023

The potential impact of climate change on international migration patterns has recently received considerable attention, yet much of the empirical literature fails to find increases in international migration due to climate change. This paper attempts to resolve this “immobility paradox” by applying a real-options framework to the relationship between climate change and international migration. This framework suggests that individuals may postpone their migration response to climate change in the face of uncertainty and only migrate once impacts of climate change have exceeded certain thresholds. We test this prediction using semiparametric regression methods which allow us to empirically identify the threshold effects implied by the real-options framework. However, the findings are generally inconsistent with such threshold effects. Rather, the results suggest that in low-income countries, individuals’ migration response is hampered by the existence of liquidity constraints. These are likely to become more binding due to climate change-induced decreases in agricultural productivity.
Hypofractionated stereotactic radiotherapy for large vestibular schwannomas and the impact of pre-radiation debulking surgery on dosimetry and clinical outcomes
Authors: Mallory Matthew , Kauweloa Kevin , Staecker Hinrich , Camarata Paul , Chamoun Roukoz , Neeranjun Rishi , Badkul Rajeev , TenNapel Mindi , Shelton Shary , Wang Fen
Published: March 2023

Introduction:

This study was aimed to evaluate the outcomes of patients with large (>2 cm in great diameter) vestibular schwannomas (VSs) treated with hypofractionated stereotactic radiotherapy (HFSRT) compared to small (<2 cm) ones and the impact of debulking surgery prior to radiation for large VSs.

Methods:

Fifty-nine patients with VSs treated with HFSRT (25 Gy in 5 fractions) were evaluated by tumour size and surgical status. Patients were divided based on tumour size: small VSs (n = 42) and large VSs (n = 17). The large group was further divided into the groups of pre-treatment debulking surgery (n = 8) and no surgery (n = 9). Rates of tumour control, brainstem necrosis and neurologic dysfunction were assessed following treatment. Pre-surgical magnetic resonance imaging (MRI) were used to generate hypothetical HFSRT plans to compare the effect of debulking surgery on dosimetry. Normal tissue complication probability (NTCP) modelling was performed to compare toxicity probabilities with and without surgical debulking in large VSs.

Results:

There was no statistical difference of tumour control rate between small and large VSs with 100% for small tumours and 94·1% for large tumours (p = 0·12), respectively. In large VSs patient, the tumour control rate of HFSRT was 100% (8/8) for surgically debulked patients and 89% (8/9) for non-surgically debulked patients (p = 0·35). There were no patients who experienced brainstem necrosis or progression of facial and trigeminal nerve symptoms after HFSRT in the entire groups of patients. Surgical debulking large VSs did not change the maximum point dose of brainstem (p = 0·98), but significantly decreased volumes of VSs and changed the minimum dose to the hottest 0·5 cc of tumour (p = 0·016) as well as the volume receiving at least 23 Gy (p = 0·023). NTCP modelling revealed very low rates (average < 1%) of brainstem toxicity with or without surgical debulking, but there was a significant difference favoring surgery (p < 0·05).

Conclusions:

HFSRT is a safe and effective treatment for both small and large VSs and is a viable option for patients with large VSs who cannot undergo surgery, if NTCP of pre-debulking HFSRT dosimetry is lower.
Automated Calibration of a Snow‐On‐Sea‐Ice Model
Authors: Cabaj Alex , Kushner Paul J. , Petty Alek A.
Published: March 2023

Snow on Arctic sea ice has many, contrasting effects on ice thickness and extent. Furthermore, estimates of snow depth on Arctic sea ice are a key input for ice thickness estimates from satellite altimeters such as ICESat‐2. Models such as the NASA Eulerian Snow on Sea Ice Model (NESOSIM) have been recently utilized by the sea ice community to provide time‐varying basin‐wide estimates of snow depth and density on Arctic sea ice. NESOSIM is a two‐snow‐layer model with simple representations of snow accumulation, wind packing, loss due to blowing snow, and redistribution due to sea ice motion. Two free parameters in NESOSIM, which dictate the bulk effect of wind packing (densification) and blowing snow processes, lack direct observational constraints. We present an indirect calibration of these parameters using a Markov Chain Monte Carlo (MCMC) approach. NESOSIM output is calibrated to observations of snow depth from Operation IceBridge and CRREL‐Dartmouth buoys, and density from historical drifting stations. OIB measurements alone are found to more strictly constrain the blowing snow parameter, and including additional observations yields more physically reasonable density estimates. The MCMC‐calibrated model output is further used to estimate sea ice thickness and uncertainty from model parameter uncertainty using ICESat‐2 freeboard measurements. Despite visible differences in density, the change in ice thickness is minimal. We also find that the model is relatively insensitive to parameter variations, and hence, the snow model uncertainty contribution to ice thickness is small compared to the systematic uncertainty from snow in the current ICESat‐2 thickness product.
Bias‐Adjustment Methods for Future Subdaily Precipitation Extremes Consistent Across Durations
Authors: Van de Vyver Hans , Van Schaeybroeck Bert , De Cruz Lesley , Hamdi Rafiq , Termonia Piet
Published: March 2023

Model output from climate projections often requires bias‐adjustment to compensate for systematic model errors. A bias‐adjustment method for extreme precipitation intensity is proposed that preserves the scaling equation for different accumulation levels from hourly to daily, using intensity‐duration‐frequency (IDF) modeling. A validation is performed within a pseudo‐reality setting, based on hourly precipitation from 28 regional climate model projections of the EURO‐CORDEX ensemble over Belgium. The scaling‐based adjustment methods improve upon previous methods, an optimal method is identified, and, analytical quantile mapping methods must be avoided due to three identified problems. The ensemble mean of the adjusted extreme precipitation intensity obeys the above‐mentioned scale‐invariance property, which is consistent with observed extreme intensities. We thus show that IDF modeling provides added value in the context of bias‐adjustment, and, that the particular IDF model proposed balances well between accuracy and the preservation of desired properties such as scale invariance and consistency among rainfall durations.
Geometry‐Based Prediction of Solute Transport Process in Single 3D Rock Fractures Under Laminar Flow Regime
Authors: Zhou Jia‐Qing , Guo Li‐Guo , Jiao Jiu Jimmy , Luo Xin
Published: March 2023

Subsurface substance migration in the fractured rock aquifer is mainly controlled by fractures, and prediction of solute transport in fractures is important to many geophysical processes and engineering activities. This study explores the possibility of predicting transport process in single rock fractures from measurable physical properties. For this purpose, we conducted a large number of pore‐scale simulations of solute transport in single 3D rock fractures with different apertures and various degrees of roughness. The numerically‐obtained breakthrough curves under laminar flow regime were reproduced with high fidelity by the classic analytical solution within the framework of macroscopic advection‐dispersion theory. The fitted transport coefficients (hydrodynamic dispersion coefficient and transport velocity) were normalized by the parallel‐plate model's values, and were further parameterized by aperture b and roughness parameter σ/b in form of ωeb/ψ + λ(mσ/b − 1)/bn and 1 − α(σ/b)/βb, respectively. By incorporating these parameterized transport coefficients and the modified cubic law into the classic analytical solution, we proposed a new transport predictive model. This model was adaptively degenerated into the classic analytical solution of parallel‐plate model, and was proved to be capable of predicting macroscopic solute transport only relying on arithmetic‐mean mechanical aperture and its standard deviation, without solving the velocity and concentration fields. By the established model, we quantitatively revealed the impacts of aperture and roughness on the breakthrough curve under laminar flow regime. This study puts a step toward predicting solute transport process in fractured rock aquifers with measurable geometric properties.
An Interpretable Machine Learning Procedure Which Unravels Hidden Interplanetary Drivers of the Low Latitude Dayside Magnetopause
Authors: Li Sheng , Sun Yang‐Yi , Chen Chieh‐Hung
Published: March 2023

In this study, we propose an interpretable machine learning procedure to unravel the importance of multiple interplanetary parameters to the Earth's magnetopause standoff distance (MSD). We construct the interpretable procedure based on SHapley Additive exPlanations. A magnetopause crossings database from the Time History of Events and Macroscale Interactions during Substorms satellites and the multiple interplanetary parameters from OMNI during the period of 2007–2016 are utilized. The solar wind dynamic pressure and the interplanetary magnetic field (IMF) BZ are widely suggested as the important two interplanetary parameters that drive the MSD. However, the examination of the interpretable procedure suggests that the magnitude of the IMF is the second significant parameter after the dynamic pressure. Although the magnetic pressure, which is the function of the IMF magnitude was considered in previous studies, the importance of the IMF magnitude was underestimated. The interpretable procedure also reveals that the IMF magnitude and the BZ have different effects on the MSD. Their joint effect is the formation of the MSD sag near BZ = 5 nT. This is for the first time the interpretable concept is being applied to construct a machine‐learning magnetopause model.
Under What Conditions Does Transverse Macrodispersion Exist in Groundwater Flow?
Authors: Lester Daniel R. , Dentz Marco , Singh Prajwal , Bandopadhyay Aditya
Published: March 2023

In recent years there has been vigorous debate whether asymptotic transverse macrodispersion exists in steady three‐dimensional (3D) groundwater flows in the purely advective limit. This question is tied to the topology of 3D flow paths (termed the Lagrangian kinematics), specifically whether streamlines can undergo braiding motions or can wander freely in the transverse direction. In this study we determine which Darcy flows do admit asymptotic transverse macrodispersion for purely advective transport on the basis of the conductivity structure. We prove that porous media with smooth, locally isotropic hydraulic conductivity exhibit zero transverse macrodispersion under pure advection due to constraints on the Lagrangian kinematics of these flows, whereas either non‐smooth or locally anisotropic conductivity fields can generate transverse macrodispersion. This has implications for upscaling locally isotropic porous media to the block scale as this can result in a locally anisotropic conductivity, leading to non‐zero macrodispersion at the block scale that is spurious in that it does not arise for the fully resolved Darcy scale flow. We also show that conventional numerical methods for computation of particle trajectories do not explicitly preserve the kinematic constraints associated with locally isotropic Darcy flow, and propose a novel psuedo‐symplectic method that preserves these constraints. These results provide insights into the mechanisms that govern transverse macrodispersion in groundwater flow, and unify seemingly contradictory results in the literature in a consistent framework. These insights call into question the ability of smooth, locally isotropic conductivity fields to represent flow and transport in real heterogeneous porous media.
The molecular pathology of schizophrenia: an overview of existing knowledge and new directions for future research
Authors: Nakamura Takumi , Takata Atsushi
Published: March 2023

Despite enormous efforts employing various approaches, the molecular pathology in the schizophrenia brain remains elusive. On the other hand, the knowledge of the association between the disease risk and changes in the DNA sequences, in other words, our understanding of the genetic pathology of schizophrenia, has dramatically improved over the past two decades. As the consequence, now we can explain more than 20% of the liability to schizophrenia by considering all analyzable common genetic variants including those with weak or no statistically significant association. Also, a large-scale exome sequencing study identified single genes whose rare mutations substantially increase the risk for schizophrenia, of which six genes (SETD1A, CUL1, XPO7, GRIA3, GRIN2A, and RB1CC1) showed odds ratios larger than ten. Based on these findings together with the preceding discovery of copy number variants (CNVs) with similarly large effect sizes, multiple disease models with high etiological validity have been generated and analyzed. Studies of the brains of these models, as well as transcriptomic and epigenomic analyses of patient postmortem tissues, have provided new insights into the molecular pathology of schizophrenia. In this review, we overview the current knowledge acquired from these studies, their limitations, and directions for future research that may redefine schizophrenia based on biological alterations in the responsible organ rather than operationalized criteria.
L-2hydroxyglutaric acid rewires amino acid metabolism in colorectal cancer via the mTOR-ATF4 axis
Authors: Tabata Sho , Kojima Yasushi , Sakamoto Takeharu , Igarashi Kaori , Umetsu Ko , Ishikawa Takamasa , Hirayama Akiyoshi , Kajino-Sakamoto Rie , Sakamoto Naoya , Yasumoto Ken-ichi , Okano Keiichi , Suzuki Yasuyuki , Yachida Shinichi , Aoki Masahiro , Soga Tomoyoshi
Published: March 2023

Oncometabolites, such as D/L-2-hydroxyglutarate (2HG), have directly been implicated in carcinogenesis; however, the underlying molecular mechanisms remain poorly understood. Here, we showed that the levels of the L-enantiomer of 2HG (L2HG) were specifically increased in colorectal cancer (CRC) tissues and cell lines compared with the D-enantiomer of 2HG (D2HG). In addition, L2HG increased the expression of ATF4 and its target genes by activating the mTOR pathway, which subsequently provided amino acids and improved the survival of CRC cells under serum deprivation. Downregulating the expression of L-2-hydroxyglutarate dehydrogenase (L2HGDH) and oxoglutarate dehydrogenase (OGDH) increased L2HG levels in CRC, thereby activating mTOR-ATF4 signaling. Furthermore, L2HGDH overexpression reduced L2HG-mediated mTOR-ATF4 signaling under hypoxia, whereas L2HGDH knockdown promoted tumor growth and amino acid metabolism in vivo. Together, these results indicate that L2HG ameliorates nutritional stress by activating the mTOR-ATF4 axis and thus could be a potential therapeutic target for CRC.
Integrated analysis of next generation sequencing minimal residual disease (MRD) and PET scan in transplant eligible myeloma patients
Authors: Fonseca Rodrigo , Arribas Mariano , Wiedmeier-Nutor Julia E. , Kusne Yael N. , González Vélez Miguel , Kosiorek Heidi E. , Butterfield Richard J. , Kirsch Ilan R. , Mikhael Joseph R. , Stewart A. Keith , Reeder Craig , Larsen Jeremy , Bergsagel P. Leif , Fonseca Rafael
Published: March 2023

Minimal residual disease (MRD) assays allow response assessment in patients with multiple myeloma (MM), and negativity is associated with improved survival outcomes. The role of highly sensitive next generation sequencing (NGS) MRD in combination with functional imaging remains to be validated. We performed a retrospective analysis on MM patients who underwent frontline autologous stem cell transplant (ASCT). Patients were evaluated at day 100 post-ASCT with NGS-MRD and positron emission tomography (PET-CT). Patients with ≥ 2 MRD measurements were included in a secondary analysis for sequential measurements. 186 patients were included. At day 100, 45 (24.2%) patients achieved MRD negativity at a sensitivity threshold of 10−6. MRD negativity was the most predictive factor for longer time to next treatment (TTNT). Negativity rates did not differ according to MM subtype, R-ISS Stage nor cytogenetic risk. PET-CT and MRD had poor agreement, with high rates of PET-CT negativity in MRD-positive patients. Patients with sustained MRD negativity had longer TTNT, regardless of baseline risk characteristics. Our results show that the ability to measure deeper and sustainable responses distinguishes patients with better outcomes. Achieving MRD negativity was the strongest prognostic marker and could help guide therapy-related decisions and serve as a response marker for clinical trials.
Liver transplantation in metastatic colorectal cancer: are we ready for it?
Authors: Ros Javier , Salva Francesc , Dopazo Cristina , López Daniel , Saoudi Nadia , Baraibar Iosune , Charco Ramon , Tabernero Josep , Elez Elena
Published: March 2023

Colorectal cancer (CRC) is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Five-year overall survival remains modest among patients with metastatic CRC (mCRC) treated with conventional therapies however, liver transplantation in a highly selected population can improve clinical outcomes with an impressive 5-year overall survival of 83%. Despite liver transplantation appearing to be a promising therapeutical option for well-selected patients with mCRC with the liver-limited disease, these data come from small monocentric trials which included a heterogeneous population. Currently, several clinical trials are evaluating liver transplantation in this scenario, aiming for a more accurate patient selection by integrating liquid biopsy, tissue profiling, and nuclear medicine to the already known clinical biomarkers that eventually may lead to a survival improvement. In this paper, the clinical outcomes and inclusion criteria from the most relevant clinical trials and clinical series involving liver transplantation in patients with liver-limited disease colorectal cancer are reviewed as well as the trials currently recruiting.
The TRPM7 channel reprograms cellular glycolysis to drive tumorigenesis and angiogenesis
Authors: Wu Wanzhou , Wang Xuan , Liao Longsheng , Chen Jing , Wang Yue , Yao Meilian , Zhu Lingping , Li Jiayu , Wang Xuan , Chen Alex F. , Zhang Guogang , Zhang Zheng , Bai Yongping
Published: March 2023

Cancer or endothelial cells preferably catabolize glucose through aerobic glycolysis rather than oxidative phosphorylation. Intracellular ionic signaling has been shown to regulate glucose metabolism, but the underlying ion channel has yet to be identified. RNA-seq, metabolomics and genetic assay revealed that the TRPM7 channel regulated cellular glycolysis. Deletion of TRPM7 suppressed cancer cell glycolysis and reduced the xenograft tumor burden. Deficiency of endothelial TRPM7 inhibited postnatal retinal angiogenesis in mice. Mechanistically, TRPM7 transcriptionally regulated the solute carrier family 2 member 3 (SLC2A3, also known as GLUT3) via Ca2+ influx-induced calcineurin activation. Furthermore, CREB-regulated transcription coactivator 2 (CRTC2) and CREB act downstream of calcineurin to relay Ca2+ signal to SLC2A3 transcription. Expression of the constitutively active CRTC2 or CREB in TRPM7 knockout cell normalized glycolytic metabolism and cell growth. The TRPM7 channel represents a novel regulator of glycolytic reprogramming. Inhibition of the TRPM7-dependent glycolysis could be harnessed for cancer therapy.
USP7- and PRMT5-dependent G3BP2 stabilization drives de novo lipogenesis and tumorigenesis of HNSC
Authors: Wang Nan , Li Tianzi , Liu Wanyu , Lin Jinhua , Zhang Ke , Li Zhenhao , Huang Yanfei , Shi Yufei , Xu Meilan , Liu Xuekui
Published: March 2023

GTPase-activating protein-binding protein 2 (G3BP2) is a key stress granule-associated RNA-binding protein responsible for the formation of stress granules (SGs). Hyperactivation of G3BP2 is associated with various pathological conditions, especially cancers. Emerging evidence indicates that post-translational modifications (PTMs) play critical roles in gene transcription, integrate metabolism and immune surveillance. However, how PTMs directly regulate G3BP2 activity is lacking. Here, our analyses identify a novel mechanism that PRMT5-mediated G3BP2-R468me2 enhances the binding to deubiquitinase USP7, which ensures the deubiquitination and stabilization of G3BP2. Mechanistically, USP7- and PRMT5-dependent G3BP2 stabilization consequently guarantee robust ACLY activation, which thereby stimulating de novo lipogenesis and tumorigenesis. More importantly, USP7-induced G3BP2 deubiquitination is attenuated by PRMT5 depletion or inhibition. PRMT5-activity dependent methylation of G3BP2 is required for its deubiquitination and stabilization by USP7. Consistently, G3BP2, PRMT5 and G3BP2 R468me2 protein levels were found positively correlated in clinical patients and associated with poor prognosis. Altogether, these data suggest that PRMT5-USP7-G3BP2 regulatory axis serves as a lipid metabolism reprogramming mechanism in tumorigenesis, and unveil a promising therapeutic target in the metabolic treatment of head and neck squamous carcinoma.
Downregulation of KLF10 contributes to the regeneration of survived renal tubular cells in cisplatin-induced acute kidney injury via ZBTB7A-KLF10-PTEN axis
Authors: Zhang Yang , Bao Siyu , Wang Daxi , Lu Wei , Xu Sujuan , Zhou Weiran , Wang Xiaoyan , Xu Xialian , Ding Xiaoqiang , Zhao Shuan
Published: March 2023

Acute kidney injury (AKI) is a common clinical dysfunction with complicated pathophysiology and limited therapeutic methods. Renal tubular injury and the following regeneration process play a vital role in the course of AKI, but the underlining molecular mechanism remains unclear. In this study, network-based analysis of online transcriptional data of human kidney found that KLF10 was closely related to renal function, tubular injury and regeneration in various renal diseases. Three classical mouse models confirmed the downregulation of KLF10 in AKI and its correlation with tubular regeneration and AKI outcome. The 3D renal tubular model in vitro and fluorescent visualization system of cellular proliferation were constructed to show that KLF10 declined in survived cells but increased during tubular formation or conquering proliferative impediment. Furthermore, overexpression of KLF10 significantly inhibited, whereas knockdown of KLF10 extremely promoted the capacity of proliferation, injury repairing and lumen-formation of renal tubular cells. In mechanism, PTEN/AKT pathway were validated as the downstream of KLF10 and participated in its regulation of tubular regeneration. By adopting proteomic mass spectrum and dual-luciferase reporter assay, ZBTB7A were found to be the upstream transcription factor of KLF10. Our findings suggest that downregulation of KLF10 positively contributed to tubular regeneration in cisplatin induced acute kidney injury via ZBTB7A-KLF10-PTEN axis, which gives insight into the novel therapeutic and diagnostical target of AKI.
Iron supplementation enhances RSL3-induced ferroptosis to treat naïve and prevent castration-resistant prostate cancer
Authors: Maccarinelli Federica , Coltrini Daniela , Mussi Silvia , Bugatti Mattia , Turati Marta , Chiodelli Paola , Giacomini Arianna , De Cillis Floriana , Cattane Nadia , Cattaneo Annamaria , Ligresti Alessia , Asperti Michela , Poli Maura , Vermi William , Presta Marco , Ronca Roberto
Published: March 2023

Prostate cancer (PCa) is a leading cause of death in the male population commonly treated with androgen deprivation therapy that often relapses as androgen-independent and aggressive castration-resistant prostate cancer (CRPC). Ferroptosis is a recently described form of cell death that requires abundant cytosolic labile iron to promote membrane lipid peroxidation and which can be induced by agents that inhibit the glutathione peroxidase-4 activity such as RSL3. Exploiting in vitro and in vivo human and murine PCa models and the multistage transgenic TRAMP model of PCa we show that RSL3 induces ferroptosis in PCa cells and demonstrate for the first time that iron supplementation significantly increases the effect of RSL3 triggering lipid peroxidation, enhanced intracellular stress and leading to cancer cell death. Moreover, the combination with the second generation anti-androgen drug enzalutamide potentiates the effect of the RSL3 + iron combination leading to superior inhibition of PCa and preventing the onset of CRPC in the TRAMP mouse model. These data open new perspectives in the use of pro-ferroptotic approaches alone or in combination with enzalutamide for the treatment of PCa.
Implementation and scalability of shared care models for chronic eye disease: a realist assessment informed by health system stakeholders in Finland, the United Kingdom, and Australia
Authors: Ford Belinda , Angell Blake , Liu Hueiming , White Andrew , Keay Lisa
Published: March 2023

Background/Objectives

Several health systems have implemented innovative models of care which share the management of patients with chronic eye diseases between ophthalmologists and optometrists. These models have demonstrated positive outcomes for health systems including increased access for patients, service efficiency and cost-savings. This study aims to understand factors which support successful implementation and scalability of these models of care.

Subjects/Methods

Semi-structured interviews were conducted with 21 key health system stakeholders (clinicians, managers, administrators, policy-makers) in Finland, United Kingdom and Australia between October 2018 and February 2020. Data were analyzed using a realist framework to identify the contexts, mechanisms of action, and outcomes of sustained and emerging shared care schemes.

Results

Five key themes relating to successful implementation of shared care were identified as (1) clinician-led solutions, (2) redistributing teams, (3) building inter-disciplinary trust, (4) using evidence for buy-in, and (5) standardized care protocols. Scalability was found to be supported by (6) financial incentives, (7) integrated information systems, (8) local governance, and (9) a need for evidence of longer-term health and economic benefits.

Conclusions

The themes and program theories presented in this paper should be considered when testing and scaling shared eye care schemes to optimize benefits and promote sustainability.
A comparative study between 10-MHz and 15-MHz ultrasound probes for retinal evaluation in silicone-oil-filled globes
Authors: Albadawi Maha A. , Allam Riham S. H. M. , Khalil Noha M. M. , Eissa Iman M.
Published: March 2023

Purpose

To compare 10-MHz and 15-MHz B-scan probes regarding the detection and localization of retinal detachment (RD) in silicone-oil-filled eyes.

Methods

This cross-sectional observational study included 100 eyes (98 patients) -having media opacity precluding fundus examination- scheduled for silicone-oil removal. Patients were examined in the sitting-position using both frequencies one week preoperatively. Longitudinal and transverse scans were taken in primary-gaze, inferior, inferonasal, and inferotemporal positions to detect the presence/absence and extent of RD. Patients were sub-grouped according to axial lengths (AXLs), state of silicone emulsification, and globe filling. Agreement between sonographic and intraoperative observations was compared.

Results

No statistically significant differences were found between 15-MHz and intra-operative findings regarding RD detection (P = 0.752) and accurate localization of inferior, inferonasal, and inferotemporal RD (P = 0.279, 0.606, and 0.599). There were statistically significant differences between 10-MHz and intra-operative findings regarding RD detection and localization (P < 0.001). The 15-MHz probe was superior to 10-MHz probe regarding the accuracy of RD detection and localization (94% and 47%, respectively). The accuracy of 15-MHz probe was 88%, 83%, and 85% in detecting and localizing inferior, inferonasal, and inferotemporal RD compared to 45%, 60%, and 62% with 10-MHz probe. The 15-MHz probe showed better sensitivity while 10-MHz probe showed better accuracy in eyes with short AXLs. The 10-MHz probe showed better sensitivity in patients with sonographic emulsification while15-MHz probe had better sensitivity in detecting vitreoretinal-interface disorders.

Conclusion

The 15-MHz B-scan probe is more accurate in detecting and localizing recurrent RD in silicone-oil-filled globes with higher sensitivity in detecting vitreoretinal-interface disorders.
What do women with sexual interest in children tell us about the assumed cause of their sexual interest in children, (non-)disclosure, and professional help?—Results of a qualitative content analysis
Authors: Tozdan Safiye , Hübener Greta , Briken Peer , Schröder Johanna
Published: March 2023

Research on women with sexual interest in children is still rare, especially regarding women’s own theories about the cause of their sexual interest in children, their experiences with (non-)disclosure, and professional help. In the context of a broader online study, we provided 50 women with a sexual interest in children under the age of 14 years (mean age: 33.6, SD = 11.1) with open questions regarding their own theories about what causes their sexual interest in children, experiences with disclosure and non-disclosure, and experiences with and opinions about professional help. Analyses were conducted using an inductive qualitative content analysis method that aimed at ordering and structuring manifest and latent content by categorizing qualitative data. Results revealed that participants mainly think that past experiences caused their sexual interest in children (Σ = 16), e.g., abusive or non-abusive sexual experiences during childhood. Some participants think that their sexual interest in children is a disposition they were born with (Σ = 8). Disclose of sexual interest in children to another person was reported by 56.0% of the present sample and led to rather positive consequences (Σ = 24, e.g., acceptance or support). Those who did not disclose (44.0%) mainly did so due to fear of rejection and/or stigmatization (Σ = 24). A total of 30.0% already sought help due to their sexual interest in children and frequently reported negative experiences (Σ = 15). A frequent statement participants made on how to reach women with sexual interest in children in order to offer professional help was the destigmatization of sexual interest in children (Σ = 14). We recommend that women with sexual interest in children should be taken more seriously among research and in prevention measures.
Neuro-computational mechanisms and individual biases in action-outcome learning under moral conflict
Authors: Fornari Laura , Ioumpa Kalliopi , Nostro Alessandra D. , Evans Nathan J. , De Angelis Lorenzo , Speer Sebastian P. H. , Paracampo Riccardo , Gallo Selene , Spezio Michael , Keysers Christian , Gazzola Valeria
Published: March 2023

Learning to predict action outcomes in morally conflicting situations is essential for social decision-making but poorly understood. Here we tested which forms of Reinforcement Learning Theory capture how participants learn to choose between self-money and other-shocks, and how they adapt to changes in contingencies. We find choices were better described by a reinforcement learning model based on the current value of separately expected outcomes than by one based on the combined historical values of past outcomes. Participants track expected values of self-money and other-shocks separately, with the substantial individual difference in preference reflected in a valuation parameter balancing their relative weight. This valuation parameter also predicted choices in an independent costly helping task. The expectations of self-money and other-shocks were biased toward the favored outcome but fMRI revealed this bias to be reflected in the ventromedial prefrontal cortex while the pain-observation network represented pain prediction errors independently of individual preferences.
The crystal structure of a simian Foamy Virus receptor binding domain provides clues about entry into host cells
Authors: Fernández Ignacio , Dynesen Lasse Toftdal , Coquin Youna , Pederzoli Riccardo , Brun Delphine , Haouz Ahmed , Gessain Antoine , Rey Félix A. , Buseyne Florence , Backovic Marija
Published: March 2023

The surface envelope glycoprotein (Env) of all retroviruses mediates virus binding to cells and fusion of the viral and cellular membranes. A structure-function relationship for the HIV Env that belongs to the Orthoretrovirus subfamily has been well established. Structural information is however largely missing for the Env of Foamy viruses (FVs), the second retroviral subfamily. In this work we present the X-ray structure of the receptor binding domain (RBD) of a simian FV Env at 2.57 Å resolution, revealing two subdomains and an unprecedented fold. We have generated a model for the organization of the RBDs within the trimeric Env, which indicates that the upper subdomains form a cage-like structure at the apex of the Env, and identified residues K342, R343, R359 and R369 in the lower subdomain as key players for the interaction of the RBD and viral particles with heparan sulfate.
Serum/glucocorticoid-inducible kinase 1 deficiency induces NLRP3 inflammasome activation and autoinflammation of macrophages in a murine endolymphatic hydrops model
Authors: Zhang Dao-Gong , Yu Wen-Qian , Liu Jia-Hui , Kong Li-Gang , Zhang Na , Song Yong-Dong , Li Xiao-Fei , Fan Zhao-Min , Lyu Ya-Feng , Li Na , Wang Hai-Bo
Published: March 2023

Ménière’s disease, a multifactorial disorder of the inner ear, is characterized by severe vertigo episodes and hearing loss. Although the role of immune responses in Ménière’s disease has been proposed, the precise mechanisms remain undefined. Here, we show that downregulation of serum/glucocorticoid-inducible kinase 1 is associated with activation of NLRP3 inflammasome in vestibular-resident macrophage-like cells from Ménière’s disease patients. Serum/glucocorticoid-inducible kinase 1 depletion markedly enhances IL-1β production which leads to the damage of inner ear hair cells and vestibular nerve. Mechanistically, serum/glucocorticoid-inducible kinase 1 binds to the PYD domain of NLRP3 and phosphorylates it at Serine 5, thereby interfering inflammasome assembly. Sgk−/− mice show aggravated audiovestibular symptoms and enhanced inflammasome activation in lipopolysaccharide-induced endolymphatic hydrops model, which is ameliorated by blocking NLRP3. Pharmacological inhibition of serum/glucocorticoid-inducible kinase 1 increases the disease severity in vivo. Our studies demonstrate that serum/glucocorticoid-inducible kinase 1 functions as a physiologic inhibitor of NLRP3 inflammasome activation and maintains inner ear immune homeostasis, reciprocally participating in models of Ménière’s disease pathogenesis.
An intronic variant in TBX4 in a single family with variable and severe pulmonary manifestations
Authors: Flanagan Frances O. , Holtz Alexander M. , Vargas Sara O. , Genetti Casie A. , Schmitz-Abe Klaus , Casey Alicia , Kennedy John C. , Raby Benjamin A. , Mullen Mary P. , Fishman Martha P. , Agrawal Pankaj B.
Published: March 2023

A male infant presented at term with neonatal respiratory failure and pulmonary hypertension. His respiratory symptoms improved initially, but he exhibited a biphasic clinical course, re-presenting at 15 months of age with tachypnea, interstitial lung disease, and progressive pulmonary hypertension. We identified an intronic TBX4 gene variant in close proximity to the canonical donor splice site of exon 3 (hg 19; chr17:59543302; c.401 + 3 A > T), also carried by his father who had a typical TBX4-associated skeletal phenotype and mild pulmonary hypertension, and by his deceased sister who died shortly after birth of acinar dysplasia. Analysis of patient-derived cells demonstrated a significant reduction in TBX4 expression resulting from this intronic variant. Our study illustrates the variable expressivity in cardiopulmonary phenotype conferred by TBX4 mutation and the utility of genetic diagnostics in enabling accurate identification and classification of more subtly affected family members.
Microfluidics-free single-cell genomics with templated emulsification
Authors: Clark Iain C. , Fontanez Kristina M. , Meltzer Robert H. , Xue Yi , Hayford Corey , May-Zhang Aaron , D’Amato Chris , Osman Ahmad , Zhang Jesse Q. , Hettige Pabodha , Ishibashi Jacob S. A. , Delley Cyrille L. , Weisgerber Daniel W. , Replogle Joseph M. , Jost Marco , Phong Kiet T. , Kennedy Vanessa E. , Peretz Cheryl A. C. , Kim Esther A. , Song Siyou , Karlon William , Weissman Jonathan S. , Smith Catherine C. , Gartner Zev J. , Abate Adam R.
Published: March 2023

Current single-cell RNA-sequencing approaches have limitations that stem from the microfluidic devices or fluid handling steps required for sample processing. We develop a method that does not require specialized microfluidic devices, expertise or hardware. Our approach is based on particle-templated emulsification, which allows single-cell encapsulation and barcoding of cDNA in uniform droplet emulsions with only a vortexer. Particle-templated instant partition sequencing (PIP-seq) accommodates a wide range of emulsification formats, including microwell plates and large-volume conical tubes, enabling thousands of samples or millions of cells to be processed in minutes. We demonstrate that PIP-seq produces high-purity transcriptomes in mouse–human mixing studies, is compatible with multiomics measurements and can accurately characterize cell types in human breast tissue compared to a commercial microfluidic platform. Single-cell transcriptional profiling of mixed phenotype acute leukemia using PIP-seq reveals the emergence of heterogeneity within chemotherapy-resistant cell subsets that were hidden by standard immunophenotyping. PIP-seq is a simple, flexible and scalable next-generation workflow that extends single-cell sequencing to new applications.
High-resolution alignment of single-cell and spatial transcriptomes with CytoSPACE
Authors: Vahid Milad R. , Brown Erin L. , Steen Chloé B. , Zhang Wubing , Jeon Hyun Soo , Kang Minji , Gentles Andrew J. , Newman Aaron M.
Published: March 2023

Recent studies have emphasized the importance of single-cell spatial biology, yet available assays for spatial transcriptomics have limited gene recovery or low spatial resolution. Here we introduce CytoSPACE, an optimization method for mapping individual cells from a single-cell RNA sequencing atlas to spatial expression profiles. Across diverse platforms and tissue types, we show that CytoSPACE outperforms previous methods with respect to noise tolerance and accuracy, enabling tissue cartography at single-cell resolution.
Evolution of synchronous female bilateral breast cancers and response to treatment
Authors: Hamy Anne-Sophie , Abécassis Judith , Driouch Keltouma , Darrigues Lauren , Vandenbogaert Mathias , Laurent Cecile , Zaccarini Francois , Sadacca Benjamin , Delomenie Myriam , Laas Enora , Mariani Odette , Lam Thanh , Grandal Beatriz , Laé Marick , Bieche Ivan , Vacher Sophie , Pierga Jean-Yves , Brain Etienne , Vallot Celine , Hotton Judicael , Richer Wilfrid , Rocha Dario , Tariq Zakia , Becette Veronique , Meseure Didier , Lesage Laetitia , Vincent-Salomon Anne , Filmann Natalie , Furlanetto Jenny , Loibl Sibylle , Dumas Elise , Waterfall Joshua J. , Reyal Fabien
Published: March 2023

Synchronous bilateral breast cancer (sBBC) occurs after both breasts have been affected by the same germline genetics and environmental exposures. Little evidence exists regarding immune infiltration and response to treatment in sBBCs. Here we show that the impact of the subtype of breast cancer on levels of tumor infiltrating lymphocytes (TILs, n = 277) and on pathologic complete response (pCR) rates (n = 140) differed according to the concordant or discordant subtype of breast cancer of the contralateral tumor: luminal breast tumors with a discordant contralateral tumor had higher TIL levels and higher pCR rates than those with a concordant contralateral tumor. Tumor sequencing revealed that left and right tumors (n = 20) were independent regarding somatic mutations, copy number alterations and clonal phylogeny, whereas primary tumor and residual disease were closely related both from the somatic mutation and from the transcriptomic point of view. Our study indicates that tumor-intrinsic characteristics may have a role in the association of tumor immunity and pCR and demonstrates that the characteristics of the contralateral tumor are also associated with immune infiltration and response to treatment.
Grid-wise simulation acceleration of the electromagnetic fields of 2D optical devices using super-resolution
Authors: Seo Jangwon , Kim Insoo , Seok Junhee
Published: March 2023

The significance of simulation has been increasing in device design due to the cost of real test. The accuracy of the simulation increases as the resolution of the simulation increases. However, the high-resolution simulation is not suited for actual device design because the amount of computing exponentially increases as the resolution increases. In this study, we introduce a model that predicts high-resolution outcomes using low-resolution calculated values which successfully achieves high simulation accuracy with low computational cost. The fast residual learning super-resolution (FRSR) convolutional network model is a model that we introduced that can simulate electromagnetic fields of optical. Our model achieved high accuracy when using the super-resolution technique on a 2D slit array under specific circumstances and achieved an approximately 18 times faster execution time than the simulator. To reduce the model training time and enhance performance, the proposed model shows the best accuracy (R2: 0.9941) by restoring high-resolution images using residual learning and a post-upsampling method to reduce computation. It has the shortest training time among the models that use super-resolution (7000 s). This model addresses the issue of temporal limitations of high-resolution simulations of device module characteristics.
No impact of nitrogen fertilization on carbon sequestration in a temperate Pinus densiflora forest
Authors: Baek Gyeongwon , Lim Hyungwoo , Noh Nam Jin , Kim Choonsig
Published: March 2023

Carbon (C) sequestration capacity in forest ecosystems is generally constrained by soil nitrogen (N) availability. Consequently, N fertilization is seen as a promising tool for enhancing ecosystem-level C sequestration in N-limited forests. We examined the responses of ecosystem C (vegetation and soil) and soil N dynamics to 3 years of annual nitrogen-phosphorus-potassium (N3P4K1 = 11.3 g N, 15.0 g P, 3.7 g K m−2 year−1) or PK fertilization (P4K1), observed over 4 years in a 40-year-old Pinus densiflora forest with poor N nutrition in South Korea. PK fertilization without N was performed to test for PK limitation other than N. Neither tree growth nor soil C fluxes responded to annual NPK or PK fertilization despite an increase in soil mineral N fluxes following NPK fertilization. NPK fertilization increased the rate of N immobilization and 80% of the added N was recovered from mineral soil in the 0–5 cm layer, suggesting that relatively little of the added N was available to trees. These results indicate that N fertilization does not always enhance C sequestration even in forests with poor N nutrition and should therefore be applied with caution.
Type 2 diabetes prevalence, awareness, and risk factors in rural Mali: a cross-sectional study
Authors: Diawara Abdoulaye , Coulibaly Djibril Mamadou , Hussain Talib Yusuf Abbas , Cisse Cheickna , Li Jian , Wele Mamadou , Diakite Mahamadou , Traore Kassim , Doumbia Seydou O. , Shaffer Jeffrey G.
Published: March 2023

Diabetes is currently a crisis in sub-Saharan West Africa (SSWA) with dramatic implications for public health and national budgets prioritizing infectious diseases. There is limited recent literature about the prevalence, awareness, and risk factors for type 2 diabetes (T2D) in rural parts of SSWA. This study characterized T2D prevalence and risk factors for the rural Malian community of Nièna, which is situated in Mali’s second-largest province of Sikasso. Between December 2020 and July 2021, a cross-sectional study of 412 participants was conducted in the Nièna community using clinical questionnaires and rapid diagnostic tests. Among 412 participants, there were 143 (34.7%) and 269 (65.3%) males and females, respectively. The overall prevalence of T2D in Nièna was 7.5% (31/412), and prevalence rates were 8.6% (23/269) and 5.6% (8/143) for females and males, respectively. Age, family history of diabetes, hypertension, waist circumference, and fetal macrosomia were significantly associated with T2D (p = 0.007, p < 0.001, p = 0.003, p = 0.013, and p < 0.001, respectively). Notably, 61.3% (19/31) of T2D subjects were unaware of their diabetic status before the study. Field surveys have considerable utility in driving T2D awareness in rural African settings.