bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoparticle delivery of innate immune agonists combined with senescence-inducing agents promotes T cell control of pancreatic cancer
Authors: Chibaya Loretah , DeMarco Kelly D. , Lusi Christina F. , Kane Griffin I. , Brassil Meghan L. , Parikh Chaitanya N. , Murphy Katherine C. , Chowdhury Shreya R. , Li Junhui , Ma Boyang , Naylor Tiana E. , Cerrutti Julia , Mori Haruka , Diaz-Infante Miranda , Peura Jessica , Pitarresi Jason R. , Zhu Lihua Julie , Fitzgerald Katherine A. , Atukorale Prabhani U. , Ruscetti Marcus
Published: August 2024

Pancreatic ductal adenocarcinoma (PDAC) has quickly risen to become the third leading cause of cancer-related death in the United States. This is in part because of its fibrotic tumor microenvironment (TME) that contributes to poor vascularization and immune infiltration and subsequent chemo- and immunotherapy failure. Here, we investigated an immunotherapy approach combining delivery of stimulator of interferon genes (STING) and Toll-like receptor 4 (TLR4) innate immune agonists by lipid-based nanoparticle (NP) coencapsulation with senescence-inducing RAS-targeted therapies, which can remodel the immune suppressive PDAC TME through the senescence-associated secretory phenotype. Treatment of transplanted and autochthonous PDAC mouse models with these regimens led to enhanced uptake of NPs by multiple cell types in the PDAC TME, induction of type I interferon and other proinflammatory signaling pathways, increased antigen presentation by tumor cells and antigen-presenting cells, and subsequent activation of both innate and adaptive immune responses. This two-pronged approach produced potent T cell–driven and type I interferon–mediated tumor regression and long-term survival in preclinical PDAC models dependent on both tumor and host STING activation. STING and TLR4-mediated type I interferon signaling was also associated with enhanced natural killer and CD8
+
T cell immunity in human PDAC samples. Thus, combining localized immune agonist delivery with systemic tumor-targeted therapy can orchestrate a coordinated type I interferon–driven innate and adaptive immune response with durable antitumor efficacy against PDAC.
Activation and antitumor immunity of CD8
+
T cells are supported by the glucose transporter GLUT10 and disrupted by lactic acid
Authors: Liu Ying , Wang Feng , Peng Dongxue , Zhang Dan , Liu Luping , Wei Jun , Yuan Jian , Zhao Luyao , Jiang Huimin , Zhang Tingting , Li Yunxuan , Zhao Chenxi , He Shuhua , Wu Jie , Yan Yechao , Zhang Peitao , Guo Chunyi , Zhang Jiaming , Li Xia , Gao Huan , Li Ke
Published: August 2024

CD8
+
T cell activation leads to the rapid proliferation and differentiation of effector T cells (T
effs
), which mediate antitumor immunity. Although aerobic glycolysis is preferentially activated in CD8
+
T
effs
, the mechanisms that regulate CD8
+
T cell glucose uptake in the low-glucose and acidic tumor microenvironment (TME) remain poorly understood. Here, we report that the abundance of the glucose transporter GLUT10 is increased during CD8
+
T cell activation and antitumor immunity. Specifically, GLUT10 deficiency inhibited glucose uptake, glycolysis, and antitumor efficiency of tumor-infiltrating CD8
+
T cells. Supplementation with glucose alone was insufficient to rescue the antitumor function and glucose uptake of CD8
+
T cells in the TME. By analyzing tumor environmental metabolites, we found that high concentrations of lactic acid reduced the glucose uptake, activation, and antitumor effects of CD8
+
T cells by directly binding to GLUT10’s intracellular motif. Disrupting the interaction of lactic acid and GLUT10 by the mimic peptide PG10.3 facilitated CD8
+
T cell glucose utilization, proliferation, and antitumor functions. The combination of PG10.3 and GLUT1 inhibition or anti–programmed cell death 1 antibody treatment showed synergistic antitumor effects. Together, our data indicate that GLUT10 is selectively required for glucose uptake of CD8
+
T cells and identify that TME accumulated lactic acid inhibits CD8
+
T cell effector function by directly binding to GLUT10 and reducing its glucose transport capacity. Last, our study suggests disrupting lactate-GLUT10 binding as a promising therapeutic strategy to enhance CD8
+
T cell–mediated antitumor effects.
Osteomyelitis-relevant antibiotics at clinical concentrations show limited effectivity against acute and chronic intracellular
S. aureus
infections in osteocytes
Authors: Zelmer Anja R. , Yang Dongqing , Gunn Nicholas J. , Solomon L. Bogdan , Nelson Renjy , Kidd Stephen P. , Richter Katharina , Atkins Gerald J.
Published: August 2024

Osteomyelitis caused by
Staphylococcus aureus
can involve the persistent infection of osteocytes. We sought to determine if current clinically utilized antibiotics were capable of clearing an intracellular osteocyte
S. aureus
infection. Rifampicin, vancomycin, levofloxacin, ofloxacin, amoxicillin, oxacillin, doxycycline, linezolid, gentamicin, and tigecycline were assessed for their minimum inhibitory concentration (MIC) and minimum bactericidal concentrations against 12
S. aureus
strains, at pH 5.0 and 7.2 to mimic lysosomal and cytoplasmic environments, respectively. Those antibiotics whose bone estimated achievable concentration was commonly above their respective MIC for the strains tested were further assayed in a human osteocyte infection model under acute and chronic conditions. Osteocyte-like cells were treated at 1×, 4×, and 10× the MIC for 1 and 7 days following infection (acute model), or at 15 and 21 days of infection (chronic model). The intracellular effectivity of each antibiotic was measured in terms of CFU reduction, small colony variant formation, and bacterial mRNA expression change. Only rifampicin, levofloxacin, and linezolid reduced intracellular CFU numbers significantly in the acute model. Consistent with the transition to a non-culturable state, few if any CFU could be recovered from the chronic model. However, no treatment in either model reduced the quantity of bacterial mRNA or prevented non-culturable bacteria from returning to a culturable state. These findings indicate that
S. aureus
adapts phenotypically during intracellular infection of osteocytes, adopting a reversible quiescent state that is protected against antibiotics, even at 10× their MIC. Thus, new therapeutic approaches are necessary to cure
S. aureus
intracellular infections in osteomyelitis.
Respiratory syncytial virus infection provides protection against severe acute respiratory syndrome coronavirus challenge
Authors: Hartwig Stacey M. , Odle Abby , Wong Lok-Yin Roy , Meyerholz David K. , Perlman Stanley , Varga Steven M.
Published: August 2024

Respiratory infections are a major health burden worldwide. Respiratory syncytial virus (RSV) is among the leading causes of hospitalization in both young children and older adults. The onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and the public health response had a profound impact on the normal seasonal outbreaks of other respiratory viruses. However, little is known about how a prior respiratory virus infection impacts SARS-CoV-2 disease outcomes. In this study, we examine the impact of a previous RSV infection on the disease severity of a subsequent SARS-CoV-2 challenge in BALB/c mice. Mice infected with RSV, followed by a SARS-CoV-2 challenge, 30 days later, exhibited decreased weight loss and increased survival as compared to control groups. Our results suggest a prior RSV infection can provide protection against a subsequent SARS-CoV-2 infection.

IMPORTANCE

Severe acute respiratory syndrome coronavirus 2 and respiratory syncytial virus are respiratory viruses that are a major health burden worldwide. Severe acute respiratory syndrome coronavirus 2 and respiratory syncytial virus frequently have peak seasonal outbreaks during the winter months, and are capable of causing severe respiratory disease, often leading to hospitalization. The 2019 pandemic brought attention to the importance of understanding how co-circulating viruses can impact the disease severity of other respiratory viruses. It is known that many hospitalized patients are undergoing multiple viral infections at once, yet not much has been studied to understand the impact this has on other respiratory viruses or patients. How co-circulating viruses impact one another can provide critical knowledge for future interventions of hospitalized patients and potential vaccination strategies.
Host WD repeat-containing protein 5 inhibits protein kinase R-mediated integrated stress response during measles virus infection
Authors: BenDavid Ethan , Yang Chuyuan , Zhou Yuqin , Pfaller Christian K. , Samuel Charles E. , Ma Dzwokai
Published: August 2024

Some negative-sense RNA viruses, including measles virus (MeV), share the characteristic that during their infection cycle, cytoplasmic inclusion bodies (IBs) are formed where components of the viral replication machinery are concentrated. As a foci of viral replication, how IBs act to enhance the efficiency of infection by affecting virus-host interactions remains an important topic of investigation. We previously established that upon MeV infection, the epigenetic host protein, WD repeat-containing protein 5 (WDR5), translocates to cytoplasmic viral IBs and facilitates MeV replication. We now show that WDR5 is recruited to IBs by forming a complex with IB-associated MeV phosphoprotein via a conserved binding motif located on the surface of WDR5. Furthermore, we provide evidence that WDR5 promotes viral replication by suppressing a major innate immune response pathway, the double-stranded RNA-mediated activation of protein kinase R and integrated stress response.

IMPORTANCE

MeV is a pathogen that remains a global concern, with an estimated 9 million measles cases and 128,000 measles deaths in 2022 according to the World Health Organization. A large population of the world still has inadequate access to the effective vaccine against the exceptionally transmissible MeV. Measles disease is characterized by a high morbidity in children and in immunocompromised individuals. An important area of research for negative-sense RNA viruses, including MeV, is the characterization of the complex interactome between virus and host occurring at cytoplasmic IBs where viral replication occurs. Despite the progress made in understanding IB structures, little is known regarding the virus-host interactions within IBs and the role of these interactions in promoting viral replication and antagonizing host innate immunity. Herein we provide evidence suggesting a model by which MeV IBs utilize the host protein WDR5 to suppress the protein kinase R-integrated stress response pathway.
Breast milk induces the differentiation of monocytes into macrophages, promoting human cytomegalovirus infection
Authors: Cai Xiaodan , Padilla Nicole T. , Rosbe Kristina , Tugizov Sharof M.
Published: August 2024

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus found in human breast milk that is frequently transmitted from HCMV-seropositive mothers to their infants during the postnatal period. Despite extensive research, the mechanisms underlying HCMV transmission from breast milk and the anatomical location at which virus transfer takes place remain unclear. Breast milk contains many uniquely differentiated macrophages that undergo specific morphological and functional modifications in the mammary gland during lactation. Although the existence of permissive HCMV infection in differentiated macrophages has been well-described, the role of breast milk in this process remains unknown. Herein, we report that exposure of isolated peripheral blood monocytes to breast milk induces their differentiation into macrophages that exhibit an M2 phenotype (CD14
high
CD163
high
CD68
high
CD206
high
) and promotes a productive and sustained HCMV infection. We also found that breast milk triggers macrophage proliferation and thus sustains a unique population of proliferating, long-lived, and HCMV-susceptible macrophages that are capable of ongoing production of infectious virions. These results suggest a mechanism that explains chronic HCMV shedding into the breast milk of postpartum seropositive mothers. We also found that HCMV virions released from breast milk-induced macrophages generate a productive infection in primary infant tonsil epithelial cells. Collectively, our results suggest that breast milk may facilitate HCMV transmission from mother to infant via the oropharyngeal mucosa.

IMPORTANCE

While human cytomegalovirus (HCMV) is frequently detected in the breast milk of HCMV-seropositive women and is often transmitted to infants via breastfeeding, the mechanisms by which this transmission occurs remain unclear. In this study, we modeled HCMV transmission at the oropharyngeal mucosa. We treated human monocytes with breast milk to mimic the lactating mammary gland microenvironment. We found that monocytes differentiated into macrophages with an M2 phenotype, which were highly permissive for HCMV. We also discovered that breast milk induces macrophage proliferation. Thus, exposure to breast milk increased the number of HCMV-susceptible macrophages and supported high levels of infectious HCMV. We found that HCMV virions released from breast milk-induced macrophages could infect primary infant tonsil epithelial cells. Collectively, these findings reveal the dual role of breast milk that induces the differentiation and proliferation of macrophages in the mammary gland and thus facilitates mother-to-child HCMV transmission at the oropharyngeal mucosa.
Complete genome sequence of two isolates from long-term serial cultivation of
Escherichia coli
JCM 5491
Authors: Umekage So
Published: August 2024

Here, I report the complete genome sequences of two
Escherichia coli
JCM5491 mutants that were independently isolated from different lineages after approximately 9 years of long-term serial cultivation.
Draft genome sequences of
Butyrivibrio hungatei
DSM 14810 (JK 615
T
) and
Butyrivibrio fibrisolvens
DSM 3071 (D1
T
)
Authors: Berner Keely , Zoza-Veloz Michelle , Nolan Matt , Graham Danielle , Ivanova Natalia , Seshadri Rekha , Spring Stefan , Escobar Matthew
Published: August 2024

Here, we report the draft genome sequences of two
Butyrivibrio
-type strains isolated from rumen fluid. The genome sequence of
Butyrivibrio hungatei
DSM 14810 was 3.3 Mb with 3,093 predicted genes, while the
Butyrivibrio fibrisolvens
DSM 3071 genome sequence was 4.8 Mb with 4,132 predicted genes.
Genomic insight into the diversity of
Glaesserella parasuis
isolates from 19 countries
Authors: Gong Xiaowei , Cui Qingpo , Zhang Wanjiang , Shi Yuqian , Zhang Peng , Zhang Chaoyang , Hu Gongzheng , Sahin Orhan , Wang Lu , Shen Zhangqi , Fu Mengjiao
Published: August 2024

Glaesserella parasuis
is a commensal bacterial organism found in the upper respiratory tract of healthy pigs and the etiological agent of Glässer’s disease, which causes severe economic losses in the swine industry. This study aimed to better understand the epidemiological characteristics of this opportunistic pathogen. We investigated the prevalence and distribution of sequence types (STs), serovars, antimicrobial resistance genes (ARGs), and potential virulence factors (VFs) in 764
G
.
parasuis
isolates collected from diseased and healthy pigs from 19 countries, including China. Multilocus sequence typing showed a high degree of variation with 334 STs, of which 93 were not previously recognized. Phylogenetic analysis revealed two major clades distinguished by isolation year, source, country, and serovar. The dominant serovars of
G. parasuis
were serovars 4 (19.50%), 7 (15.97%), 5/12 (13.87%), and 13 (12.30%). Serovar 7 gradually became one of the dominant serovars in
G. parasuis
with more VFs and fewer ARGs. Serovars 4 and 5/12 were the most frequent serovars in diseased pigs, whereas serovars 2, 8, and 11 were predominant in healthy pigs. Serovars 7 and 13 possessed more VFs than the other serovars. This study provides novel insights into the global prevalence and epidemiology of
G. parasuis
and valuable clues for further investigation into the pathogenicity of
G. parasuis
, which will facilitate the development of effective vaccines.

IMPORTANCE

Glaesserella parasuis
is a clinically important gram-negative opportunistic pathogen, which causes serious financial losses in swine industry on a global scale. No vaccine is known that provides cross-protection against all 15 serovars; furthermore, the correlation between serovar and virulence is largely unknown. This study provides a large number of sequenced strains in 19 countries and compares the genomic diversity of
G. parasuis
between diseased and healthy pigs. We found a slight change in the dominant serovar of
G. parasuis
in the world, with serovar 7 gradually emerging as one of the predominant serovars. The observed higher average number of VFs in this particular serovar strain challenges the previously held notion that serovar 7 is non-virulent, indicating a more complex virulence landscape than previously understood. Our analysis indicating that six ARGs [
tet
(B),
sul2
,
aph(3')-Ia
,
aph (6)-Id
,
bla
ROB-1
, and
aph(3'')-Ib
] are likely to be transmitted horizontally in their entirety. By analyzing VFs, we provided an improved understanding of the virulence of
G. parasuis
, and these key findings suggest that vaccine development will be challenging.
Tomographic and topographic predictive factors of big bubble formation during deep anterior lamellar keratoplasty in keratoconus
Authors: Lucchino Luca , Visioli Giacomo , Scarinci Fabio , Colabelli Gisoldi Rossella A M , Komaiha Chiara , Marenco Marco , Pocobelli Giulio , Lambiase Alessandro , Pocobelli Augusto
Published: August 2024

Purpose

To identify preoperative predictors of big bubble (BB) formation during deep anterior lamellar keratoplasty (DALK) in patients with keratoconus (KC).

Methods

Design

Retrospective cohort study in an Italian tertiary centre.

Study population

Consecutive patients with KC undergoing DALK from January 2021 to July 2023.

Observation procedure

Tomographic and topographic data including K-max, K-mean, keratometric astigmatism, thinnest point, mean peripheral corneal thickness, difference between the mean peripheral corneal thickness and the thinnest point (peripheral-minimal corneal thickness), position (central/paracentral) and cone area (%), Amsler-Krumeich classification and anterior segment optical coherence tomography (AS-OCT) analysis to assess the severity stage.

Main outcome measures

Rate of BB formation and type; multivariate logistic regression analysis was used to analyse all preoperative parameters in patients with BB formation versus failure.

Results

Pneumatic dissection succeeded in 98 of 140 eyes (70.0%), with 94 type 1 bubbles (67.1%) and four type 2 bubbles (2.9%). BB formation succeeded more frequently in patients with lower K-max (p=0.032), lower K-mean (p=0.010), higher thinnest point (p=0.017), lower peripheral-minimal corneal thickness (p=0.009) and lower Amsler-Krumeich stages (p=0.021). According to the AS-OCT analysis, BB formation was more frequent in the lower stages (p<0.001). After the logistic regression (pseudo-R²=0.176, constant=3.21, 95% CI 1.14 to 5.29, p=0.002), AS-OCT classification was found to be the only factor that predicted BB formation (coefficient=−0.81, 95% CI −1.18 to −0.43, p<0.001).

Conclusions

AS-OCT classification is a reliable predictor for BB formation. Tomographic and topographic analyses indicated that a steeper and more ectatic cornea is more prone to BB failure.
Social Capital and Economic Development in a Large and Multi-Ethnic Developing Country: Evidence from Indonesia
Authors: SURYAHADI ASEP , RISHANTY ARNITA , SPARROW ROBERT
Published: August 2024

The role of social capital in economic development has been a subject of interest to both academics and practitioners of development for several decades. However, empirical evidence on social capital in the context of developing countries is still relatively scant. This study explores the effects of social capital on economic development in Indonesia, a large and multi-ethnic developing country. Using district-level data for 2006–2019, we find that the relationships between social capital and economic development are complex. There are both favorable and unfavorable effects of social capital on economic development, as well as nonlinear effects. Hence, we cannot draw unequivocal conclusions on the benefits or disadvantages of social capital for economic development. Nevertheless, this study finds that trust among people across different ethnic groups, participation in communal works and social activities, and trust in government are the most important forms of social capital needed to improve people’s welfare.
Which Nighttime Lights Data Better Represent India’s Economic Activities and Regional Inequality?
Authors: MATHEN CHRISTOPHER KURUVILLA , CHATTOPADHYAY SIDDHARTHA , SAHU SOHINI , MUKHERJEE ABHIJIT
Published: August 2024

This paper demonstrates how the estimation of economic activities and inequality for the Indian economy based on nighttime lights data from the Visible Infrared Imaging Radiometer Suite (VIIRS) satellite outperforms those obtained using traditional Defense Meteorological Satellite Program Operational Line-Scan System (DMSP-OLS) sources. In the extant literature, nighttime lights data have been frequently used as a proxy for economic activities, especially at granular geographical levels where gross domestic product data are otherwise unavailable. Since the traditional DMSP-OLS-based nighttime lights data suffer from measurement errors due to blurring and top coding, VIIRS-based nighttime lights data, which are devoid of such limitations, are gaining popularity. We show that at the subnational or district level in India, VIIRS satellite-based nighttime lights data are indeed a better proxy for economic activities and inequality. Our robust findings imply that all future scholarly works that employ nighttime lights data for the Indian economy should use VIIRS-based data for greater accuracy compared to other similar data sources.
Pauli–Villars and the ultraviolet completion of Einstein gravity
Authors: Mannheim Philip D.
Published: August 2024

Through use of the Pauli–Villars regulator procedure, we construct a second- plus fourth-order derivative theory of gravity that serves as an ultraviolet completion of standard second-order derivative quantum Einstein gravity that is ghost-free, unitary and power-counting renormalizable.
Dynamic Characteristics of Pressure-Balanced Metal Bellows in Fluid–Structure Interaction
Authors: Wei Yuhan , Ge Shaoxiang , Hu Feng , Xue Xin
Published: August 2024

As a flexible component in high-pressure vessels and pipeline systems, bellows experience significant fluid–structure interaction effects under high-speed internal fluids and external vibrations. Nevertheless, their dynamic response mechanisms coupled with fluid–structure interaction mentioned below have not yet been clarified so far. In this work, a novel pressure-balanced metal bellow (PBMB) for low-stiffness and high-pressure resistance is firstly proposed. Several fluid–structure interaction models were considered to study the dynamic response characteristics of the PBMB. An experimental platform associated with fluid–structure interaction was established to validate the effectiveness of its vibration attenuation performance. The results indicate that the PBMB has an obvious vibration attenuation effect in the range of 5–90[Formula: see text]Hz, and super-harmonic and sub-harmonic resonance phenomena occur in the range of 90–200[Formula: see text]Hz. Under constant fluid conditions, fluid density, viscosity, flow velocity, and pressure are positively correlated with the response amplitude of the PBMB. The response of the PBMB oscillates at the fluid entry point due to both pulsating flow velocity and pulsating pressure. After several cycles, the response caused by pulsating flow velocity gradually decays and stabilizes. Thus, the impact of pulsating frequency on the stability of the response of bellows is insignificant during the initial cycles.
Asymptotic behavior of stochastic p-Laplacian equations with dynamic boundary conditions
Authors: Gao Lili , Hong Mingli , Yang Lu
Published: August 2024

In this paper, we investigate the asymptotic behavior for the non-autonomous stochastic [Formula: see text]-Laplacian equations with dynamic boundary conditions via the stationary Wong–Zakai approximations given by the Wiener shift. We first establish the existence and uniqueness of pullback random attractor for the Wong–Zakai approximation equations in [Formula: see text]. Then we prove the upper semi-continuity of random attractors in [Formula: see text] and [Formula: see text] when the step size of approximations approaches zero.
The Dynamics of Urbanization and Its Effects on Rural Livelihoods: Evidence from Adama City and Adama Rural District, Ethiopia
Authors: DADI Wakitole , SIMIE Negussie , MULUGETA Messay
Published: August 2024

Rapid urbanization in cities brings about both opportunities and challenges for national development. This study focuses on investigating the dynamics of urbanization and its impact on livelihoods using land use/land cover change in Adama City, located in the Oromia Regional State. Various datasets from the U.S. Geological Survey (USGS), including Landsat Thematic Mapper (LTM), Landsat Enhanced Thematic Mapper Plus (ETH[Formula: see text]), and Operational Land Imager (OLI), were utilized. Geographic Information System (GIS) and remote sensing tools were employed to extract relevant information from these datasets for years from 1986 to 2022. In addition, findings pertain to the impact of urbanization on income diversification and the overall welfare of farm households near Adama City was aligned with the study. The findings reveal that built-up areas and agricultural land exhibit the most significant changes over the examined period. However, these changes occur in opposite directions. The built-up area has experienced a substantial increase of 60% from 1986 to 2022, while agricultural land has decreased by 40% during the same timeframe. The conversion of farmland to built-up areas negatively impacts farm households by reducing farming activities and increasing reliance on non-farm activities, resulting in lower consumption expenditures for rural households near urban areas compared to those farther from the urban center. The result underscores the need for policies that promote appropriate land management and a well-planned urbanization process to ensure sustainable urban development. Furthermore, it is vital to enhance understanding of the spatial and temporal dynamics of urban growth and its impacts on farm households residing near urban areas. By addressing these issues, sustainable food security and poverty reduction objectives can be better achieved in peri-urban areas of the region.
Comparison of Human-Drone Distancing Studies across In-Person and Online Modalities
Authors: Jelonek Karissa , Kunde Siya , Simms Nathan , Uriarte Gerson , Duncan Brittany
Published: August 2024

Human–robot proxemics behaviors can vary based on personal, robot, and environmental factors which, along with their deployment in public-facing interactions, calls for an in-depth exploration. This article explores the impact of altitude and safety modifications of small unmanned aerial vehicle (sUAV) on users’ comfortable interaction distance. By leveraging interaction techniques from literature like video, sound, and simulations, we explore personal space interactions in online studies (N = 376) with the sUAV and the Double telepresence robot. We then compare the findings with our in-person interaction data (N = 47). While in-person interactions are the ultimate goal, online methods can be used to reduce resources, allow larger sample sizes, and may lead to a more comprehensive sampling of population than would be expected from in-person studies. The lessons learned from this work are applicable broadly within the social robotics community, even outside those who are interested in proxemics interactions, to conduct future crowd-sourced experiments. The various modalities provided similar trends when compared with data from in-person studies. While the distances may not have been precise compared to those measured in the real world, these experiments are useful to detect patterns in human–robot interactions, and to conduct formative studies before committing resources to in-person testing.
The Economics of Electricity and Development: Planning for Growth and a Changing Climate
Authors: Meeks Robyn C. , Pokhrel Anil
Published: August 2024

Many low- and middle-income countries have made tremendous gains in electrification over the past few decades. These improvements in electricity access have enabled a growing body of empirical evidence on its impacts. This article complements prior reviews on the impacts of electrification by addressing several major remaining challenges faced by the electricity sector in developing countries—impediments to maximizing electricity services᾽ economic effects, obstacles to recovering utility costs, difficulties in forecasting future electricity demand, and uncertainty regarding the future adoption of climate-mitigating technologies—and the existing microeconomic causal evidence addressing those challenges. We describe how randomized experiments have complemented the quasi-experimental evidence and then highlight some remaining gaps in the existing literature. Specifically, we highlight climate adaptation within the electricity sector in developing countries, which remains a crucial gap in both the discussion on and financing of electrification for development. We use case studies of Nepal and Pakistan in South Asia—a region that both recently experienced great electrification gains and is among the most vulnerable to climate change—to illustrate the need for additional work on adaptation in the electricity sector. We conclude by linking to recent discussions on climate adaptation finance.
Layered double hydroxide-8HQ/CA composite coating with spin-coated bioactive glass for bioactivity and corrosion resistance of magnesium alloy WE43
Authors: Tan Jesslyn , Genasan Krishna , Kong Peggy , Birbilis Nick , Salema Arshad , Srinivasan Ganesh , Balan Poovarasi
Published: August 2024

Bioactive glass (BG) was spin-coated onto Layered double hydroxide /citric acid intercalated with 8-hydroxyquinoline (LDHCA8HQ) to develop a multi-functional coating with enhanced bioactivity and corrosion resistance. Mg-Fe LDH was prepared via electrodeposition of oxidized WE43 at -1.4 VSCE for 300s in an aqueous solution with pH 3.0, adjusted using 1.0 M nitric acid HNO3. The LDH coating was modified with citric acid (CA) and intercalated with 8-hydroxyquinoline (8HQ), following a previous method. A BG (45S5) solution was prepared and spin-coated onto the LDHCA8HQ sample at 2500 rpm for 30s, followed by drying at 200 ºC for 15 minutes, repeated three times, and then annealed at 250 ºC for 2 hours to obtain the final LDHCA8HQBG sample. The XRD analysis exhibits an amorphous glass-ceramic phase, indicating BG incorporation. The nanoindentation analysis with reduced elastic modulus and hardness demonstrates values closer to that of human bone and electrochemical testing confirms BG as an effective insulating layer. The surface morphology examination revealed the supported attachment of human bone marrow-derived stromal cells (hBMSCs), which maintained its ideal spindle shape. LDHCA8HQBG induced a higher proliferation rate and osteoinduction properties, comparable with commercial bone graft, suggesting its potential application in bone tissue engineering.
Path‐Tracking Control of Tilting Quadrotor UAV Based on Variable Structure Sliding Mode Control Method
Authors: Liu Qinghua , Zhang Ke , Pan Yunfan , Zhang Huan
Published: August 2024

Tilting quadcopter unmanned aerial vehicles have the ability to perform vertical takeoff and landing, hover in the air, and cruise at high speeds, They can complete various flight tasks. Due to the special flight mode of tilting quadcopter unmanned aerial vehicles, in transition mode, as the tilt angle changes, the control process of the drone becomes more complex, and the difficulty of control also increases significantly. This article takes the tilting quadcopter drone as the research object and analyzes its overall layout and flight principles in various flight modes. Analyze using the Newton–Euler method and dynamically model three flight modes. The flight process is controlled using inner and outer loop control methods, and a sliding mode manifold control law for a tilting quadcopter unmanned aerial vehicle is designed using the hyperbolic tangent‐sliding mode control method. Finally, MATLAB/Simulink was used to simulate the path‐tracking process of the tilting quadcopter unmanned aerial vehicles, proving the stability of the controller.
Biological Abnormalities of Hemostasis in Patients with Epistaxis or Menorrhagia in Yaoundé, Cameroon
Authors: Ndoumba Annick Mintya , Chendjou Kamela Aurélien , Wamba Colince , Azebaze Agueguia Franklin , Carolle Nsa’Amang Eyebe , Tagny Claude Tayou , Mbanya Dora
Published: August 2024

Introduction. In Cameroon, screening and diagnosis of minor hemorrhagic syndromes remain difficult and few research studies have been done to assess the magnitude of future bleeding risk and the burden of these disorders on quality of life. Epistaxis and menorrhagia are the two leading causes of bleeding disorders in the world population. Aim. The aim of this study was to investigate the biological abnormalities of hemostasis in patients with epistaxis and menorrhagia. Method. From January to December 2021, we conducted a cross‐sectional study in six hospitals with a gynecology and ENT department. We selected patients who presented epistasis or menorrhagia through clinical file and made them pass an interview and biological exams. Venous blood collected on EDTA tube allowed us to measure full blood count, thin blood smear, and blood grouping. PT, APPT, and fibrinogen assay were measured from citrate platelet‐poor plasma. This plasma stored at −20°C for a maximum of 3 months allowed us to measure vWF : Ag and vWF : CBA ELISA. The bleeding time was measured at the time of sampling. Result. In total, our study population consisted of 60 patients aged 01–45 years. Epistaxis (40%) and menorrhagia (29%) were the two main causes of bleeding complaints in our study, in addition to gingivorrhagia (15%) and prolonged bleeding after injury (03%). Almost 60% of the population had at least one abnormal hemostasis parameter. The main abnormalities found were low von Willebrand factor (30.19%), presence of macroplatelets (16.98%), prolonged bleeding time (15.09%), prolonged PT (15.09%), and low platelet count (¬07.55%). Conclusion. In Cameroon, bleeding disorders manifested by epistaxis and menorrhagia are mainly caused by abnormalities of primary hemostasis.
Supplementary Table S2 from Characterizing Relationships between T-cell Inflammation and Outcomes in Patients with High-Risk Neuroblastoma According to Mesenchymal and Adrenergic Signatures
Authors: Kaufman Maria E. , Vayani Omar R. , Moore Kelley , Chlenski Alexandre , Wu Tong , Lee Sang Mee , Desai Ami V. , He Chuan , Cohn Susan L. , Applebaum Mark A.
Published: August 2024

373 genes identified near single-stranded super-enhancers associated with adrenergic cell state.
Supplementary Table S1 from Characterizing Relationships between T-cell Inflammation and Outcomes in Patients with High-Risk Neuroblastoma According to Mesenchymal and Adrenergic Signatures
Authors: Kaufman Maria E. , Vayani Omar R. , Moore Kelley , Chlenski Alexandre , Wu Tong , Lee Sang Mee , Desai Ami V. , He Chuan , Cohn Susan L. , Applebaum Mark A.
Published: August 2024

159 genes identified near single-stranded super-enhancers associated with mesenchymal cell state.
Engineering Oncogenic Hotspot Mutations on SF3B1 via CRISPR-Directed PRECIS Mutagenesis
Authors: Fernandez Mike M. , Yu Lei , Jia Qiong , Wang Xuesong , Hart Kevyn L. , Jia Zhenyu , Lin Ren-Jang , Wang Lili
Published: August 2024

SF3B1 is the most recurrently mutated RNA splicing gene in cancer. However, research of its pathogenic role has been hindered by a lack of disease-relevant cell line models. Here, our study compared four genome engineering platforms to establish SF3B1 mutant cell lines: CRISPR-Cas9 editing, AAV homology-directed repair editing, base editing (ABEmax, ABE8e), and prime editing (PE2, PE3, PE5max). We showed that prime editing via PE5max achieved the most efficient SF3B1 K700E editing across a wide range of cell lines. Our approach was further refined by coupling prime editing with a fluorescent reporter that leverages a SF3B1 mutation-responsive synthetic intron to mark successfully edited cells. By applying this approach, called prime editing coupled intron-assisted selection (PRECIS), we introduced the K700E hotspot mutation into two chronic lymphocytic leukemia cell lines, HG-3 and MEC-1. We demonstrated that our PRECIS-engineered cells faithfully recapitulate known mutant SF3B1 phenotypes, including altered splicing, copy number variations, and cell-growth defect. Moreover, we discovered that the SF3B1 mutation can cause the loss of Y chromosome in chronic lymphocytic leukemia. Our results showcase that PRECIS is an efficient and generalizable method for engineering genetically faithful SF3B1 mutant models. Our approach provides new insights on the role of SF3B1 mutation in cancer and enables the generation of SF3B1 mutant cell lines in relevant cellular context.

Significance:

This study developed an approach that can reliably and efficiently engineer SF3B1 mutation into different cellular contexts, thereby revealing novel roles of SF3B1 mutation in driving aberrant splicing, clonal evolution, and genome instability.
Robust Differentiation of Human Pluripotent Stem Cells into Lymphatic Endothelial Cells Using Transcription Factors
Authors: Saha Sanjoy , Graham Francine , Knopp James , Patzke Christopher , Hanjaya-Putra Donny
Published: August 2024

Introduction: Generating new lymphatic vessels has been postulated as an innovative therapeutic strategy for various disease phenotypes, including neurodegenerative diseases, metabolic syndrome, cardiovascular disease, and lymphedema. Yet, compared to the blood vascular system, protocols to differentiate human induced pluripotent stem cells (hiPSCs) into lymphatic endothelial cells (LECs) are still lacking. Methods: Transcription factors, ETS2 and ETV2 are key regulators of embryonic vascular development, including lymphatic specification. While ETV2 has been shown to efficiently generate blood endothelial cells, little is known about ETS2 and its role in lymphatic differentiation. Here, we describe a method for rapid and efficient generation of LECs using transcription factors, ETS2 and ETV2. Results: This approach reproducibly differentiates four diverse hiPSCs into LECs with exceedingly high efficiency. Timely activation of ETS2 was critical, to enable its interaction with Prox1, a master lymphatic regulator. Differentiated LECs express key lymphatic markers, VEGFR3, LYVE-1, and Podoplanin, in comparable levels to mature LECs. The differentiated LECs are able to assemble into stable lymphatic vascular networks in vitro, and secrete key lymphangiocrine, reelin. Conclusion: Overall, our protocol has broad applications for basic study of lymphatic biology, as well as toward various approaches in lymphatic regeneration and personalized medicine.
Effects on Gait and Balance of VIM Gamma Knife Radiosurgery in Essential Tremor
Authors: Mira Valentin , Zwaard Babette , Boutin Emmanuelle , Guillaud Etienne , Cretol Axelle , Régis Jean , Azulay Jean-Philippe , Witjas Tatiana , Vaugoyeau Marianne
Published: August 2024

Introduction: Essential tremor (ET) is the most common movement disorder, characterized by an action tremor in the upper limbs. Neurosurgical techniques targeting the thalamic ventrointermediate nucleus (VIM) including thermocoagulation demonstrated a potential risk for gait and posture worsening. This study evaluates the potential effect of VIM Gamma Knife radiosurgery (GKR) in ET on gait and posture performances. Methods: We conducted a prospective study to quantitatively assess gait and balance in severe ET patients before and 1 year after unilateral GKR. Seventy-three patients were included in this series. Results: First, we confirmed the unilateral GKR efficacy in severe ET patients: global tremor score and impairments in activities of daily living improved, respectively, by 67% and 71.7%. The global gait and posture analysis found no significant differences before and 1 year after GKR. Three patients (4.1%) developed mild to moderate gait and posture impairment with proprioceptive ataxia. All of these AEs were induced by a hyper-response to radiosurgery. Conclusions: Gait and posture performances were not statistically significant at the population. Nevertheless, gait and posture worsened in 4% of patients after GKR, all in the setting of hyper-response. This study shows that GKR may be a safe neurosurgical alternative to improve ADL in a population of patients with TE.
Prognostic Value of the Pretransplant Fibrosis-4 Index on Non-Relapse and Overall Mortality following Unrelated Single-Unit Cord Blood Transplantation in Adults
Authors: Konuma Takaaki , Monna-Oiwa Maki , Kato Seiko , Isobe Masamichi , Takahashi Satoshi , Nannya Yasuhito
Published: August 2024

Introduction: The fibrosis-4 (FIB-4) index is a noninvasive marker of liver fibrosis. The FIB-4 index predicts poor outcomes in patients with hepatic and non-hepatic diseases. However, the association of the FIB-4 index with mortality and liver-related clinical outcomes following cord blood transplantation (CBT) is unclear. Methods: We retrospectively evaluated the impact of the pretransplant FIB-4 index on outcomes in 336 adults following single-unit unrelated CBT at our institution. Results: In multivariate analyses, when the FIB-4 index <1.3 group was used as the reference, non-relapse mortality was significantly higher in the FIB-4 index 1.3–2.67 (hazard ratio [HR], 2.51; 95% confidence interval [CI], 1.19–5.30) and FIB-4 index >2.67 (HR, 2.34; 95% CI, 1.12–4.90) groups. Overall mortality was significantly higher in the FIB-4 index >2.67 group (HR, 1.66; 95% CI, 1.00–2.73), but with only marginal significance in the FIB-4 index 1.3–2.67 group (HR, 1.59; 95% CI, 0.96–2.64). Hematopoietic recovery, acute and chronic graft-versus-host disease of the liver, and veno-occlusive disease/sinusoidal obstruction syndrome were not associated with the pretransplant FIB-4 index. Conclusion: The pretransplant FIB-4 index is accurate and useful in predicting mortality in adult patients undergoing single-unit unrelated CBT.
Universidade de São Paulo: epicentro de uma controvérsia transnacional
Authors: Consolim Marcia
Published: August 2024

Trata-se de analisar a controvérsia entre dois professores que ocuparam as cadeiras de sociologia I e II na Faculdade de Filosofia, Ciências e Letras da Universidade de São Paulo em seus primeiros anos de funcionamento. Essa controvérsia, que opôs sociologia e etnologia, teoria social e pesquisa empírica, enraizou-se em meios  intelectuais distintos: a sociologia, no Instituto de Educação da Universidade de São Paulo, e a etnologia, no Departamento de Cultura do Município de São Paulo. Assim, pretende-se mostrar que as transferências intelectuais dependem das afinidades eletivas estabelecidas entre grupos de intelectuais estrangeiros e brasileiros e que, no caso paulista, os intelectuais relativamente mais próximos aos grupos dirigentes se inclinam para a nova disciplina, etnologia, enquanto os relativamente mais dominados no campo do poder preferem a sociologia, já ensinada nas escolas normais. Para isso, utilizo análises documentais e textuais, bem como estudo de trajetórias e de redes de interdependência.
Comunhão universitária? Balanços e fraturas na história da Universidade de São Paulo
Authors: Consolim Marcia , Miceli Sergio
Published: August 2024

Trata-se de realizar uma análise das publicações coletivas voltadas a celebrar o aniversário da Universidade de São Paulo. Os dossiês escolhidos referem-se ao vigésimo, sexagésimo e septuagésimo aniversários dessa instituição. Pretende-se identificar padrões de avaliação, bem como percepções e juízos distintos sobre a excelência do ensino, pesquisa e extensão segundo as unidades e as áreas do conhecimento dessa instituição.
Analysis of the PARAGON-HF Study Results Using Win Ratio
Authors: Yoon Minjae , Kim Wonse , Kook Woong , Park Jin Joo , Greenberg Barry
Published: August 2024

BACKGROUND:

The PARAGON-HF study (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction) investigated the effect of sacubitril-valsartan in heart failure (HF) with preserved ejection fraction. The results, which were analyzed using conventional statistical methods, did not find a significant reduction in the primary composite end point of cardiovascular death and total hospitalization for HF. Recent clinical trials used win ratio statistics that enable the incorporation of multiple outcome aspects into the primary end point and can detect positive outcomes with fewer patients. In this study, we assessed the effect of sacubitril-valsartan on outcomes using the win ratio to analyze results from patients included in the PARAGON-HF study.

METHODS:

In the PARAGON-HF study, 4822 patients with HF with preserved ejection fraction were randomized either to sacubitril-valsartan or valsartan groups. In the present study, the primary outcome was a hierarchical composite of time to cardiovascular death, total number of hospitalization for HF, time to first hospitalization for HF, time to renal composite outcome, and change in the Kansas City Cardiomyopathy Questionnaire total symptom score at 8 months analyzed using a win ratio statistical model.

RESULTS:

Using this approach, we found that a greater number of patients who received sacubitril-valsartan experienced clinical benefits compared with those who received valsartan (win ratio, 1.13 [95% CI, 1.04–1.23];
P
=0.005). This clinical advantage was evident in patients regardless of whether the left ventricular ejection fraction was above or below the median, that is, the left ventricular ejection fraction of 57%, and regardless of sex (
P
interaction
=0.76 for the left ventricular ejection fraction and 0.73 for sex).

CONCLUSIONS:

Employing the innovative win ratio approach, sacubitril-valsartan demonstrated significant clinical benefits among patients with HF with preserved ejection fraction. Notably, this benefit was observed irrespective of left ventricular ejection fraction and sex.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01920711.