Systematic ocular phenotyping of 8,707 knockout mouse lines identifies genes associated with abnormal corneal phenotypes

PurposeCorneal dysmorphologies (CDs) are typically classified as either regressive degenerative corneal dystrophies (CDtrs) or defective growth and differentiation-driven corneal dysplasias (CDyps). Both eye disorders have multifactorial etiologies. While previous work has elucidated many aspects of CDs, such as presenting symptoms, epidemiology, and pathophysiology, the genetic mechanisms remain incompletely understood. The purpose of this study was to analyze phenotype data from 8,707 knockout mouse lines to identify new genes associated with the development of CDs in humans. Methods8,707 knockout mouse lines phenotyped by the International Mouse Phenotyping Consortium were queried for genes associated with statistically significant (P < 0.0001) abnormal cornea morphology to identify candidate CD genes. Corneal abnormalities were investigated by histopathology. A literature search was used to determine the proportion of candidate genes previously associated with CDs in mice and humans. Phenotypes of human orthologues of mouse candidate genes were compared with known human CD genes to identify protein-protein interactions and molecular pathways using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Protein Analysis Through Evolutionary Relationships (PANTHER), and Kyoto Encyclopedia of Genes and Genomes. ResultsAnalysis of data from 8,707 knockout mouse lines identified 213 candidate CD genes. Of these, 37 (17%) genes were previously known to be associated with CD, including 14 in the mouse, 16 in humans, and 7 in both. The remaining 176 (83%) genes have not been previously implicated in CD. We also searched publicly available RNAseq data and found that 131 of the total 213 (61.5%) were expressed in adult human corneal tissue. STRING analysis showed several interactions within and between candidate and established CD proteins. All cellular pathways of the established genes were found in the PANTHER analysis of the candidate genes. Several of the candidate genes were implicated in corneal disease, such as TGF-ss signaling. We also identified other possible underappreciated mechanisms relevant to the human cornea. ConclusionsWe identified 213 mouse genes that resulted in statistically significant abnormal corneal phenotypes in knockout mice, many of which have not previously been implicated in corneal pathology. Bioinformatic analyses implicated candidate genes in several signaling pathways which are potential therapeutic targets.Y

Comparison of clinical characteristics and outcomes in hospitalized adult patients infected with respiratory syncytial virus and influenza virus

Background Because patients infected with respiratory syncytial virus (RSV) have been reported to be older than patients infected with influenza virus, the more frequent incidence of complications in RSV-infected patients may be age-related. This study compared clinical characteristics and outcomes in hospitalized adults infected with RSV with findings in age- and sex-matched adults infected with influenza virus. Methods The medical records of hospitalized adult patients infected with RSV or influenza virus at two university hospitals from 2013 to 2022 were retrospectively analyzed. Virus infection was confirmed by real-time polymerase chain reaction. Each RSV-infected patient was matched by age and sex with two influenza virus-infected patients, and their clinical symptoms, laboratory parameters and hospital courses were compared. Results The study cohort consisted of 552 patients, 184 infected with RSV and 368 infected with influenza virus. Fever (71.2% vs. 79.9%, p = .022) and cough (70.1% vs. 80.4%, p = .007) were significantly less frequent in the RSV than in the influenza group, whereas white blood cell counts (9132/mm(3) vs. 7616/mm(3), p < .001) and C-reactive protein concentrations (10.25 vs. 8.88 mg/dL, p = .029) were significantly higher in the RSV group. The frequency of oxygen therapy was higher (60.3% vs. 48.6%, p = .010) and hospital stay was longer (8 vs. 6 days, p = .003) in RSV than in influenza virus-infected patients. Conclusions Clinical symptoms were less frequent, but disease was more severe, in hospitalized adult patients infected with RSV than in age- and sex-matched patients infected with influenza. Greater attention should be paid to diagnosing and preventing RSV infection in adults.N

Farmer Managed Natural Regeneration (FMNR) Adoption and Farmers' Perceptions on Conservation in the Tsavo Dispersal Area, Kenya: Insights from the KOICA-World Vision Climate Resilience Project

연구목적: 본 연구는 케냐 차보생태지역 주민을 대상으로 FMNR(Farmer Managed Natural Regeneration) 도입 여부와 이행 정도가 주민의 환경보전 및 산림복원에 대한 기대 인식, 그리고 환경보호 활동 참여에 미치는 영향을 분석한다. 이를 통해 FMNR의 지속가능한 구현과 주민들의 자발적 참여 및 연대를 위한 시사 점을 제시하고자 한다. 연구의 중요성: FMNR의 근본적 가치인 환경보전과 산림복원에 대한 인식이 실제 도입⋅이행 주체들에게 얼마나 내면화되고 개인적 가치관에 통합되었는 지를 확인함으로써 FMNR 확대 및 효과 극대화를 위한 방안을 논의한다는 점에서 의의가 있다. 연구방법론: 현지 가구 설문조사 데이터를 이용하여 FMNR 도입 및 이행 정도 가 환경보전 및 산림복원에 대한 기대 인식에 미치는 영향을 일반화된 순서형 로짓 모형(Generalized Ordered Logit)으로 분석한다. 또한, 환경보호 활동 참여 도에 미치는 영향을 다중선형회귀분석(Multiple OLS)을 통해 추정한다. 연구결과: FMNR을 도입한 가구일수록, 또 이행 정도가 높을수록 환경보전에 대한 인식이 더 긍정적이며 실제 환경보호 활동에도 더 적극적으로 참여하는 것으로 나타났다. 다만 FMNR을 도입하고 이행 정도가 높은 가구는 산림복원으로 기대할 수 있는 편익이 오히려 낮다고 인식하는 경향이 관찰되었다. 결론 및 시사점: FMNR이 성공적으로 정착 및 확산되기 위해서는 장기적인 수익 창출 체계를 제시하는 전략이 필요하다. 예컨데, 협동조합을 통한 임산물 공동판매, FMNR 기술 교육 및 이점 홍보, 소액 대출 등의 금융지원은 지역사회 구성원들이 실질적 혜택을 누릴 수 있는 방안을 마련함으로써 지속가능성을 제고할 수 있다.N

Quality of Life in Women With Gestational Diabetes Mellitus and Treatment Satisfaction Upon Intermittently Scanned Continuous Glucose Monitoring

Background: To assess the quality of life (QoL) and treatment satisfaction with intermittently-scanned continuous glucose monitoring (isCGM) in women with gestational diabetes mellitus (GDM). Methods: This prospective observational study included 189 women with GDM who completed the Korean version of the Audit of Diabetes-Dependent Quality of Life Questionnaire (K-ADDQoL). Among them, 25 women who utilized isCGM between gestational weeks 30 and 34 completed the Korean version of the Diabetes Treatment Satisfaction Questionnaire change version (K-DTSQc) to evaluate their satisfaction with isCGM during pregnancy. Results: GDM had a negative impact on the perceived QoL in 89.4% of the women. All 19 domains of the K-ADDQoL were adversely influenced by GDM, with the most significant impact on the freedom to eat (weighted impact score, −6.98 ± 2.49, P < 0.001) and the least impact on the sex life (−0.25 ± 0.80, P = 0.008). Younger women and those treated with insulin perceived themselves as being more affected in their QoL due to GDM. Women perceived to have less effect on their QoL attributed to GDM exhibited higher ΔHbA1c one year after delivery (ΔHbA1c, 0.3 ± 0.4% vs. 0.0 ± 0.4% in less affected vs. more affected women). The utilization of isCGM improved treatment satisfaction (overall satisfaction score, 10.36 ± 9.21, P < 0.001), independent of glycemic control during pregnancy. Conclusion: Although GDM negatively affects the perceived QoL during pregnancy, attentiveness to GDM management may have a positive impact on long-term glycemic control. Moreover, employing isCGM can enhance treatment satisfaction in women with GDM.N

Mechanistic Insights into the Role of Elements in Ni-Co-P Catalysts for Electrochemical Conversion of 5-Hydroxymethylfurfural to 2,5-Furandicarboxylic Acid

Ni phosphides and NiCo alloys are extensively explored for their remarkable efficiency in biomass alcohol oxidations, yet the underlying mechanisms remain inadequately understood. This study thoroughly elucidates the roles of Ni, Co, and P in improving the catalytic performance of Ni-Co-P catalysts for the electrochemical conversion of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA), a promising biomass-derived building block replacing terephthalic acid. Phosphorization of Ni results in the partial formation of Ni2P phase and significantly boosts the formation of the reactive NiOOH phase on the surface, which is the crucial catalytic phase for converting HMF into FDCA. The integration of Co into the heterojunction between Ni2P and NiOOH enhances the oxidation reactivity of 5-formyl-2-furancarboxylic acid (FFCA), a pivotal intermediate influencing FDCA productivity, by selectively stabilizing aldehydes, thereby promoting further oxidation rather than surface desorption. in situ/operando spectroscopic analyses consistently highlight the equal significance of the rapid generation of NiOOH and the robust adsorption of reactant molecules at the surface in achieving high catalytic performance. These insights into elemental contributions set a new standard for designing multi-component electrocatalysts for efficient biomass alcohol oxidation.Y

Enhancing Lithium-Mediated Nitrogen Reduction with Porous Polymer Fibers Featuring Lithium-Ion Affinity

The interaction between the electrolyte and working electrode surface affects the cascade of reactions involving Li deposition, N2, and proton carriers and consequently the NH3 production from Li-mediated nitrogen reduction reaction (Li-NRR). Efficient Li-NRR at low Li concentrations is particularly challenging because of low current density and uneven Li metal and lithium nitride plating. Here, the enhanced electrochemical production of NH3 for a low Li concentration of 0.5 m are demonstrated by employing 3D porous polymer fibers featuring Li+-affinity on Cu electrodes. Raman and IR spectroscopic analyses exhibit that the polymeric fibers composed of carboxyl and hydroxyl groups can form Li-binding complexes and decrease interactions with solvents and anions in the electrolyte. The electrochemical analyses support that this polymeric porous structure serves to retain Li+ near the electrode, expanding the active surface area and increasing current density. The Li-affinitive polymer fibers are effective even at a low Li salt concentration of 0.5 m to improve NH3 yield and Faradaic efficiency. This study underscores the importance of porous morphology, Li affinity, and its analytical methods in understanding Li-NRR.N

Unveiling Key Descriptors of Ionomer Materials for Enhanced Electrochemical CO2 Reduction

Polymeric ionomers near the catalyst surface of CO2 reduction reaction (CO2RR) electrodes affect their efficiency; however, their multifaceted properties complicate structure-activity relationship elucidation. Here, we synthesized polycarbazole-based anion-exchange (QPC) ionomers bearing varying functionalized side chains to explore this relationship. Comprehensive analysis in physicochemical properties, electrochemical activity, and operando ATR-SEIRAS revealed that functional group modification significantly influenced the intrinsic ionomer properties, thereby affecting the Ag catalyst properties, microenvironments of interfacial water structures, and reaction kinetics of the protonation step for CO2RR and the hydrogen evolution reaction (HER). Notably, the QPC-trimethyl phosphonium (TMP) ionomer induced favorable interfacial water structures, having a high proportion of strong H-bonded water with low Stark tuning slopes, which inhibit HER and promote CO2RR. A high CO Faradaic efficiency (>90%) was maintained using QPC-TMP in a membrane electrode assembly, even under varying CO2 concentrations (100-15%) and elevated temperatures (28-72 degrees C). These findings suggest that the catalytic environment can be optimized by fine-tuning the ionomer structure, contributing to the advancement of high-performance CO2RR ionomers.N

Excess Cations Alter *CO Intermediate Configuration and Product Selectivity of Cu in Acidic Electrochemical CO2 Reduction Reaction

Concentrated cations are often employed to promote electrochemical CO2 reduction reaction (CO2RR) selectivity in acidic electrolytes. Here, we investigate the influence of excess cations on the *CO adsorption configuration and the product distribution of the CO2RR. Operando attenuated total reflectance surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS) reveals that increasing the Cs+ concentration shifts the preference of the *CO intermediate on the Cu surface from the atop (*COatop) to the bridge (*CObridge) configuration. This transition leads to a sharp decline in C-C coupling and an increase in the hydrogen evolution reaction at high Cs+ concentrations (0.7 and 1.0 M) under acidic conditions. Time-resolved SEIRAS scans show that *COatop is kinetically dominant and the proportion of *CObridge increases gradually only at high cation concentrations. Density functional theory simulations confirm that Cs+ on the Cu surface can interact electrostatically with *CO and stabilize *CObridge over *COatop on the Cu surface. The evolution of *CObridge is also observed on Ag catalysts, indicating that the effect at high concentrations is not limited to Cu. Furthermore, polymeric binders on the Cu surface mitigate these detrimental effects on the CO2RR and restore C2H4 production by preventing the cation from altering the *CO adsorption sites on the catalyst surface. This study provides new insights into the effects of cations on catalyst performance, with implications for catalyst design and operation.Y

REALFRED: An Embodied Instruction Following Benchmark in Photo-Realistic Environments

Simulated virtual environments have been widely used to learn robotic agents that perform daily household tasks. These environments encourage research progress by far, but often provide limited object interactability, visual appearance different from real-world environments, or relatively smaller environment sizes. This prevents the learned models in the virtual scenes from being readily deployable. To bridge the gap between these learning environments and deploying (i.e., real) environments, we propose the ReALFRED benchmark that employs real-world scenes, objects, and room layouts to learn agents to complete household tasks by understanding free-form language instructions and interacting with objects in large, multi-room and 3D-captured scenes. Specifically, we extend the ALFRED benchmark with updates for larger environmental spaces with smaller visual domain gaps. With ReALFRED, we analyze previously crafted methods for the ALFRED benchmark and observe that they consistently yield lower performance in all metrics, encouraging the community to develop methods in more realistic environments. Our code and data are publicly available (Homepage: https://github.com/snumprlab/realfred).N

Genome-wide statistical evidence elucidates candidate factors of life expectancy in dogs

It is well-established that large and heavy dogs tend to live shorter lives. In this study, we aimed to determine whether traits other than body size are associated with the life expectancy of dogs. We compiled a dataset of 20 phenotypes, including body size, lifespan, snout ratio, and shedding, into a single matrix for 149 dog breeds using data from the American Kennel Club and other peer-reviewed sources. The analysis revealed that drooling might be associated with both the lifespan and body mass index of dogs. Furthermore, a genome-wide association study with adjusted phenotypes and statistical verification methods, such as Mendelian randomization. Additionally, conducting differential gene expression analysis with the salivary gland for the 2 cases, hypersalivation/less drooling vs various body sizes, we could observe the hypersalivation-related proteins. This genetic analysis suggests that body size and drooling might be candidate factors influencing lifespan. Consequently, we identified several candidate genes, including IGSF1, PACSIN2, PIK3R1, and MCCC2, as potential genetic factors influencing longevity-related phenotypes.Y