bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Whatever the GP says, is what I'll do’—A qualitative study of patient perspectives in accessing primary eye care for type 2 diabetes
Authors: Huang‐Lung Jessie , Rai Akshay , Duong Annita , Balakrishnan Apirami , Khan Abdullah , Husudo Jeremy , Gyawali Rajendra , Nazarian Joseph , Ford Belinda , Rhee Joel , Jalbert Isabelle , Keay Lisa
Published: October 2024

Introduction

To investigate the perspectives of people accessing a general medical practitioner (GP)‐optometry model of collaborative care that was established to increase access to diabetes eye care.

Methods

Qualitative study of patient barriers and facilitators to accessing primary diabetes eye care located in a metropolitan area in Australia. One‐on‐one interviews were recorded, transcribed and thematically analysed using a determinant framework on patient‐centred access to health care.

Results

Twenty‐four people with type 2 diabetes, including 15 males and 9 females, who accessed the service between September 2021 and June 2022 agreed to participate. Mean (SD) age of the participants was 52 (12) years and 50% had been diagnosed with diabetes for <2 years. Facilitators to accessing diabetes eye care included a referral from a GP or GP nurse, fee‐free consultations, availability of after‐hours appointments and short waiting times. Barriers to access included perceived out‐of‐pocket costs, competing responsibilities and lack of awareness of diabetic retinopathy screening recommendations.

Conclusion

Considering diabetic retinopathy may present asymptomatically, primary health practitioners (optometrists and GPs) are well positioned to raise patient awareness of the importance of routine eye examinations. In Australia, access to routine screening could be facilitated by fee‐free eye checks and personalised text message reminders implemented at a health system level.
Sentiment analysis of letters of recommendation for a U.S. pain medicine fellowship from 2020 to 2023
Authors: Cheng Christopher P. , Vasan Vikram , Patel Alopi M. , Shekane Paul R.
Published: October 2024

Objectives

Letters of recommendation (LORs) are an important part of pain medicine fellowship applications that may be subject to implicit bias by the letter's author. This study evaluated letters of recommendation for applications to pain medicine fellowships in the United States to characterize biases and differences among applicants over four application cycles.

Methods

This was a retrospective single‐site cohort study. De‐identified LORs were collected from 2020 to 2023 from one institution. The Valence Aware Dictionary and sEntiment Reasoner (VADER) natural language processing package scored positive LOR sentiment. In addition, the deep learning tool, Empath, scored LORs for 15 sentiments. Wilcoxon rank‐sum and one‐way ANOVA tests compared scores between applicant demographics: gender, race, medical school type, residency specialty, and chief resident status, as well as letter writers' academic position.

Results

Nine hundred and sixty‐four applications were studied over four application cycles. Program directors wrote fewer words (p = 0.020) and less positively (p < 0.001) compared to department chairs and letter writers with neither position. Department chairs wrote with less “negative emotion” compared to both program directors and writers with neither position (p < 0.001). Anesthesiologist applicants received more letters highlighting “achievement” (p < 0.001) while PM&R applicants submitted letters with less “negative emotion” (p < 0.001) compared to other specialties. Chief residents' letters scored higher in “leader” sentiment (p < 0.001) and lower in “negative emotion” (p < 0.001).

Discussion

Linguistic content did not favor certain genders or races over others. However, disparities in LORs do exist depending on an applicant's specialty and chief resident status, as well as the academic status of the letter writer.
8. Herpes zoster and post herpetic neuralgia
Authors: Adriaansen Elisabeth J. M. , Jacobs Julien G. , Vernooij Lisette M. , van Wijck Albert J. M. , Cohen Steven P. , Huygen Frank J. P. M. , Rijsdijk Mienke
Published: October 2024

Introduction

Patients suffering from postherpetic neuralgia (PHN) report unilateral chronic pain in one or more dermatomes after an acute herpes zoster (HZ) infection. The incidence of acute HZ ranges between three and five patients per 1000 person‐years. In one out of four patients, acute HZ‐related pain will transition into PHN. PHN can be very disabling for patients and reduce quality of life. Additionally, the treatment of PHN is characterized by high failure rates. The aim of this review is to give an update on the previous practical guideline published in 2011 and revised in 2015 (published in 2019) and to provide an overview of current interventional treatment options for HZ infection and PHN.

Methods

The literature on the diagnosis and treatment of HZ and PHN was systematically reviewed and summarized.

Results

The most important treatment for acute HZ‐related pain is antiviral therapy within 72 h of symptom onset. Additional symptomatic treatment options are analgesic drugs according to the WHO pain ladder, tricyclic antidepressants (eg, nortriptyline), and antiepileptic drugs (eg, gabapentin). If pain is not sufficiently reduced, interventional treatment such as an epidural injection with local anesthetics and corticosteroids or pulsed radiofrequency of the dorsal root ganglion (DRG) are options. Treatment for PHN is preferably transdermal capsaicin, lidocaine, or oral drugs such as antidepressants or antiepileptics.

Conclusions

Treatment of acute HZ‐related pain especially PHN is challenging. Besides the conventional treatment for PHN, interventional management is considered a new treatment option. PRF of DRG seems to be the most promising interventional management.
Effects of Amphotericin B‐Conjugated Functionalized Carbon Nanoparticles in the Treatment of Cutaneous Leishmaniasis
Authors: Heidari‐Kharaji Maryam , Guerra Suisha Suruwb , Puneiad Robinson Pavene
Published: October 2024

Leishmaniasis is a parasitic disease spread by the bite of an infected sandfly and caused by protozoan parasites of the genus Leishmania. Currently, there is no vaccine available for leishmaniasis in humans, and the existing chemotherapy methods face various clinical challenges. The majority of drugs are limited to a few toxic compounds, with some parasite strains developing resistance. Therefore, the discovery and development of a new anti‐leishmanial compound is crucial. One promising strategy involves the use of nanoparticle delivery systems to accelerate the effectiveness of existing treatments. In this study, Amphotericin B (AmB) was incorporated into functionalized carbon nanotube (f‐CNT) and evaluated for its efficacy against Leishmania major in vitro and in a BALB/c mice model. The increase in footpad thickness was measured, and real‐time PCR was used to quantify the parasite load post‐infection. Levels of nitric oxide and cytokines IL‐4 and IFN‐γ were also determined. We found that f‐CNT‐AmB significantly reduced the levels of promastigotes and amastigotes of the Leishmania parasite. The nanoparticle showed strong anti‐leishmanial activity with an IC50 of 0.00494 ± 0.00095 mg/mL for promastigotes and EC50 of 0.00294 ± 0.00065 mg/mL for amastigotes at 72 h post‐infection, without causing harm to mice macrophages. Treatment of infected BALB/c mice with f‐CNT‐AmB resulted in a significant decrease in cutaneous leishmania (CL) lesion size in the foot pad, as well as reduced Leishmania burden in both lymph nodes and spleen. The levels of nitric oxide and IFN‐γ significantly increased in the f‐CNT‐AmB treated groups. Also, our results showed that the level of IL‐4 significantly decreased after f‐CNT‐AmB treatment in comparison to other groups. In conclusion, our results demonstrate that AmB loaded into f‐CNT is significantly more effective than AmB alone in inhibiting parasite propagation and promoting a shift towards a Th1 response.
Root physiological and soil microbial mechanisms underlying responses to nitrogen deficiency and compensation in Indica and Japonica rice
Authors: Wang Runnan , Tang Guoping , Lu Yanyao , Zhang Dingshun , Cai Shuo , He Haohua , Zhang Hongcheng , Xiong Qiangqiang
Published: October 2024

Compensatory effects are common biological phenomena in nature. In this study, we investigated the changes in root nitrogen uptake, root morphological and physiological responses, and changes in the rhizosphere soil microbial communities of indica and japonica rice during a nitrogen deficiency‐sensitive period and an effective compensation period with double the nitrogen supply. We conducted a bucket experiment using Suxiu 867 (a japonica rice variety) and Yangxian You 918 (an indica rice variety). Treatments included CK (constant distribution of nitrogen fertilizer at each growth stage, represented by CK867 and CK918) and NDC (nitrogen deficiency in the tillering stage, double nitrogen application in the ear differentiation stage to compensate, represented by NDC867 and NDC918) variations. Both varieties presented the highest δ15N and 15N abundances and Ndff (refers to the proportion of nitrogen in a plant's body that comes directly from the fertilizer applied.) in rice under the NDC treatment. Metagenomic sequencing of rhizospheric soil showed that the dominant bacterial groups at the phylum level among each treatment were Actinobacteria, Proteobacteria, Chloroflexi, Acidobacteria, Gemmatimonadetes, and Nitrospirae. The rhizosphere of indica rice was more enriched with the microbial communities involved in nitrogen metabolism, which contributed to higher nitrogen utilization efficiency. A correlation‐based network was constructed and provides insights into the formation of nitrogen deficiency compensation effects and contributes to the enhancement of nitrogen uptake and utilization efficiency in rice production.
Pandemic‐induced job loss and mental health: Evidence from a moderated mediation model
Authors: Yao Rui , Zhang Jie
Published: October 2024

The strict anti‐contagion measures at the start of the COVID‐19 pandemic implemented by the US governments led to surges in the unemployment rate. Earlier studies have brought to light the association between job loss and mental disorders, as well as the link between financial hardship and mental health. Yet the mechanisms responsible for these relationships remain fragmentary and the specific role of pandemic‐induced job loss within this mechanism is unexplored. Addressing this gap, our study examines the mediating effect of financial hardship on the link between pandemic‐induced job loss and mental health during the COVID‐19 crisis and how income moderates this mediation. Findings show that respondents experienced elevated mental disorders primarily through the direct non‐financial aspect of pandemic‐induced job loss. Low‐income respondents suffered relatively more indirectly through financial hardship, while high‐income respondents were relatively more affected by the non‐financial aspects of job loss. Moreover, low‐income respondents showed higher resilience against mental disorders due to pandemic‐induced job loss. Our findings provide important implications for theory, policy, and practice in addressing the mental health impact of job loss during national crisis such as the COVID‐19 pandemic.
Natural variation at the cotton HIC locus increases trichome density and enhances resistance to aphids
Authors: Wang Yanan , Zhou Qi , Zhang Jilong , He Haiyan , Meng Zhigang , Wang Yuan , Guo Sandui , Zhang Rui , Liang Chengzhen
Published: October 2024

Plant trichomes are an excellent model for studying cell differentiation and development, providing crucial defenses against biotic and abiotic stresses. There is a well‐established inverse relationship between trichome density and aphid prevalence, indicating that higher trichome density leads to reduced aphid infestations. Here we present the cloning and characterization of a dominant quantitative trait locus, HIC (hirsute cotton), which significantly enhances cotton trichome density. This enhancement leads to markedly improved resistance against cotton aphids. The HIC encodes an HD‐ZIP IV transcriptional activator, crucial for trichome initiation. Overexpression of HIC leads to a substantial increase in trichome density, while knockdown of HIC results in a marked decrease in density, confirming its role in trichome regulation. We identified a variant in the HIC promoter (−810 bp A to C) that increases transcription of HIC and trichome density in hirsute cotton compared with Gossypium hirsutum cultivars with fewer or no trichomes. Interestingly, although the −810 variant in the HIC promoter is the same in G. barbadense and hirsute cotton, the presence of a copia‐like retrotransposon insertion in the coding region of HIC in G. barbadense causes premature transcription termination. Further analysis revealed that HIC positively regulates trichome density by directly targeting the EXPANSIN A2 gene, which is involved in cell wall development. Taken together, our results underscore the pivotal function of HIC as a primary regulator during the initial phases of trichome formation, and its prospective utility in enhancing aphid resistance in superior cotton cultivars via selective breeding.
Vascular limitations in blood pressure regulation with age in women: Insights from exercise and acute cardioselective β‐blockade
Authors: Studinski Matthew J. , Bowlus Christine , Pawelczyk James A. , Delgado Spicuzza Jocelyn M. , Gosalia Jigar , Mookerjee Swapan , Muller Matthew D. , Fragin Jason , Proctor David N.
Published: October 2024

Younger women rely on altering cardiac output () to regulate blood pressure (BP). In contrast, older women rely more on altering vascular tone. However, evidence suggests that the ability to alter systemic vascular conductance (SVC) is diminished in older women. In the present study, cardioselective β‐blockade was utilized to diminish the relative contribution of to BP regulation and thereby evaluate age‐related vascular limitations in women at rest and during large muscle dynamic exercise. Younger (n = 13, mean age 26.0 years) and older (n = 14, mean age 61.8 years) healthy women performed submaximal bouts of semi‐recumbent cycling exercise at varying intensities while receiving an intravenous infusion of esmolol, a β1‐antagonist, or saline control in a repeated‐measures crossover design. was attenuated during esmolol infusion, with greater reductions during exercise (moderate, –1.0 (95% CI, –1.6 to –0.5) L/min, P < 0.001; heavy, –2.0 (95% CI, –2.6 to –1.5) L/min, P < 0.001) than seated rest (–0.5 (95% CI, –1.1 to 0.0) L/min, P = 0.048), and this reduction was not significantly different between age groups (P = 0.122). Older women exhibited a greater attenuation in mean arterial pressure (MAP) during esmolol (–7 (95% CI, –9 to –4) mmHg, P < 0.001) relative to younger women (–2 (95% CI, –5 to 0) mmHg, P = 0.071). These changes coincided with a greater reduction of SVC in the younger women during esmolol (–15 (95% CI, –20 to –10) mL/min/mmHg, P < 0.001) compared to older women (–3 (95% CI, –9 to 2) mL/min/mmHg, P = 0.242). Together, these findings provide evidence that older, postmenopausal women have a diminished ability to adjust SVC in order to regulate MAP.
Generation on the Rise
Authors: Alburakeh Sarah
Published: October 2024

This inaugural Watch List spotlights 25 engineers who are starting business ventures, leading teams to success, advocating for engineering in the public eye, pursuing greatness in corporate settings, or discovering the next breakthroughs in research. Read on to discover more about this group’s accomplishments and learn why these individuals will be the ones to propel engineering into the future.
Fortifying the Pipeline
Authors: Poirier Louise
Published: October 2024

Since companies need workers immediately, waiting for someone to earn a four-year degree isn’t always a viable option. The effort to reduce time-to-talent is driving companies to increasingly pursue new strategies, such as a competency base with short training programs ranging from a week to six months, which helps recruit and train new talent that much faster.
Experimental Study on Flow and Thermal Transport in Additively Manufactured Lattices Based on Cube-Shaped Unit Cell
Authors: Singh Prashant , Aider Youssef , Phanikumar Mantha S. , Mahajan Roop L.
Published: October 2024

This paper presents the convective heat transfer coefficient of cubic lattices under both buoyancy-induced and forced convection. Additionally, it examines the effective thermal conductivity, permeability, and inertial coefficient of a cubic unit cell of porosity ∼0.87. The test specimens were additively manufactured using stainless steel 420 (with 40% bronze infiltration) using the binder jetting technique. In the buoyancy-driven convection experiments, three different aspect ratios (width/height) varying from 0.5 to 2 were tested across three different heating orientations, viz., bottom wall (0 deg), side wall (90 deg), and top wall (180 deg). The lattice with the lowest aspect ratio had the highest convective heat transfer coefficient in all three heating orientations. The forced convection heat transfer coefficient was determined for an additively manufactured part comprising 10 × 10 cubic unit cell array in the plane perpendicular to the flow and 20 unit cells in the streamwise direction. Additionally, the flow characteristics of the cubic lattice were characterized through permeability (K) and inertial coefficient (Cf), determined by conducting separate pressure drop experiments over a wide range of flow velocities. The thermal hydraulic performance (THP) of the cubic lattice was assessed by combining the periodic regime convective heat transfer coefficient with the pressure drop data obtained from the experimentally determined values of K and Cf. The comprehensive characterization of flow and thermal transport, including K and Cf, along with hsf, keff, presented in this paper, provides a robust foundation for their application in volume-averaged computations for detailed parametric study.
Insights Into Pool Boiling Heat Transfer on Minichannel Surfaces Through Point and Field Measurements
Authors: Dhanalakota Praveen , Rahaman Md Motiur , Mahapatra Pallab Sinha , Anand A. R. , Das Sarit Kumar , Pattamatta Arvind
Published: October 2024

In this study, saturated pool boiling experiments were conducted on copper minichannel and flat surfaces at atmospheric pressure using water as the working fluid. The heat transfer performance was assessed through point measurements with a heater block, cartridge heaters, and thermocouples, as well as field measurements using a thin-foil heater and infrared thermography. Two copper minichannel surfaces with square cross sections of 1 mm (minichannel-1) and 2 mm (minichannel-2) side lengths were tested and compared to a flat surface. Minichannel-1 and minichannel-2 enhanced the critical heat flux (CHF) by 17% and 45%, respectively, and improved the heat transfer coefficient by 24–40% and 51–75%, respectively, compared to the flat surface. Minichannel-2 exhibited the lowest and most uniform boiling surface temperature, making it the best performer among the three. There was no significant change in departure frequency among the surfaces, and no significant change in departure diameter for the flat surface and minichannel-1. However, minichannel-2 had lower departure diameters due to its deeper channels, which prevented bubble coalescence and maintained low departure diameters. Additionally, minichannel-2 delayed vapor film formation by breaking it with its deeper fins, thereby improving CHF and slightly enhancing bubble dynamics. The enhancement in boiling heat transfer is primarily attributed to the increased surface area provided by the minichannels, with a minor contribution from improved bubble dynamics. However, the dominant factor in enhancing pool boiling heat transfer on minichannel surfaces is the increase in surface area.
Variable Cycle Engine Concepts and Component Technologies—An Overview
Authors: Zenkner Sebastian , Carvalho Francisco , Brakmann Robin G. , Goinis Georgios
Published: October 2024

The variable cycle engine (VCE) is of interest for military and supersonic civil platforms due to its improved operational flexibility. However, the increase in design and control degrees-of-freedom results in a more complex engine architecture. Numerous different VCE concepts have been proposed and studied in literature. This paper provides an overview of VCE concepts and technology. A historical outline of important activities, investigated concepts, and technical advancements is given, and the main objectives and use cases of the technology are described. In addition, specific challenges and technical solutions for variable compressors and turbines are discussed in detail. Important VCE concepts are qualitatively evaluated, and their advantages and disadvantages are highlighted.
Optimal Part-Load Performance of Supercritical Carbon Dioxide Brayton Cycles During Inventory Control
Authors: Gupta Shrey Sahai , Kumar Pramod
Published: October 2024

Supercritical carbon dioxide (sCO2) cycles are gaining attention for their efficiency and low carbon footprint in power plants. This study focuses on optimizing the performance of a 5 MW simple recuperated sCO2 Brayton loop during inventory control, a recommended strategy for maximum part-load efficiencies. Variable speed operation of turbomachines is explored to enhance part-load efficiency across the operating range, contrasting with the baseline case of constant turbine and compressor speeds. The analysis, which is based on an analytical formulation and validated component models, reveals that part-load efficiency can be improved by variable speed operation of the turbomachines. Additionally, decoupled shaft systems are found to outperform coupled or single shaft systems. Further, part-load efficiency deterioration in case of constant speeds has been discussed in detail. A unique feature of this study is the modeling methodology; model for the compressor is derived by modifying an ideal gas compressor model to account for the behavior of a real gas compressor. Component matching is performed systematically to accurately estimate sCO2 cycle conditions. The results predicted by the model provide valuable insights on design of control strategy including inventory management for better response and improved efficiency while operating under part-load conditions.
Experimental Investigations on Carbon Segmented Seals With Smooth and Pocketed Pads
Authors: Jolly Pascal , Arghir Mihai , Kasahara Hidetoshi , Kimura Wataru
Published: October 2024

The present paper introduces experimental results for radial segmented seals operating at high rotating speed. These seals are made of three or more interlocking, carbon-graphite segments, in permanent contact with the rotor while also accommodating its dynamic displacements. Currently, many efforts are made to model these behaviors and for obtaining accurate leakage flowrate and friction torque predictions. A novel test rig fitted with a casing for measuring leakage and friction torque produced by two carbon segmented seals was developed. The tested seals were composed of three segments. Two types of segmented seals were tested: two seals with flat pads and one seal with pocketed pads. The seals were installed two by two in a casing and were simultaneously tested in a back to back arrangement. The process fluid was air, with a maximum inlet pressure of 0.3 MPa, while it was set to ambient at the outlet. The rotor diameter was 100 mm with a maximum rotating speed of 24,000 rpm. The main measurements were the inlet mass flowrate and friction torque produced by the two seals. Results show that the seal with pocketed pads produced higher leakage rates but lower friction torque compared to the smooth pads. This suggests that the seal with pocketed pads operated with segments completely lifted from the rotor surface. Mass flow rates measurements during run-up/coast-down tests revealed a hysteresis effect, which could be the consequence of segment tilt. The experimental results could also be useful to validate theoretical models.
Removing defects from sputter damage on InGaP surfaces using thermal atomic layer etching
Authors: Edel Ross , Alexander Ezra , Nam Taewook , Cavanagh Andrew S. , Van Voorhis Troy , George Steven M.
Published: October 2024

Thermal atomic layer etching (ALE) was utilized to remove sputter damage from InGaP samples. Removal of sputter damage from InGaP surfaces was measured using x-ray photoelectron spectroscopy (XPS). Damage was identified by the shifted doublets in the P 2p region of the XPS spectrum. Density functional theory identified the damage as corresponding to the undercoordinated atoms in the InGaP lattice. InGaP substrates were sputtered with Ar+ ions at 500 eV or 2 keV as a model system to simulate the exposure of InGaP to energetic species during plasma processing. The InGaP thermal ALE process used sequential exposures of hydrogen fluoride for fluorination and either trimethylaluminum or dimethylaluminum chloride for ligand exchange at 300 °C. The XPS spectra revealed that InGaP thermal ALE successfully removed damage from sputtering. The area of the shifted doublets in the P 2p region was progressively reduced versus the number of ALE cycles. After ALE, the resulting XPS spectra were equivalent to the spectrum of an InGaP sample with no sputter damage. A bulklike XPS spectrum showing minimal damage was recovered after 50 ALE cycles for a sample initially exposed to 500 eV sputtering. Sputtering at 2 keV required 100 ALE cycles to largely remove the surface defects. The etch depth consistent with 100 ALE cycles indicated a damaged material depth of ∼5–6 nm. In addition, Auger electron spectroscopy (AES) revealed that the Ar AES signal from implanted Ar in InGaP after sputtering was also progressively removed versus the number of ALE cycles.
A feasibility study on active sound reduction across an acoustic plenum window by cancelling source clusters on internal periphery of the window cavity
Authors: Chan P. Y. , Tang S. K. , Cheung Chi-Chung , Mui K. W. , Fu S. C.
Published: October 2024

The possibility of applying active control to reduce sound transmission across a practical plenum window is examined experimentally in the present study using measured transfer functions of all related sound transmission paths. As a result of the limited space within the window, the error microphones are located at the indoor window opening while the secondary cancelling sources are mounted along the periphery of the window void. Results show that the cancelling sources near the outdoor window opening corners and within the overlapping region of the window play more useful roles in the control. Also, the highest sound reduction is around 6 dB with six error microphones positioned either at the central region or along the periphery of the indoor window opening. However, the results with the central error microphones suggest the possibility of adopting a dual control system to enhance the low frequency performance. Control systems with fewer error microphones result in lower sound reduction. Besides, it is found that four cancelling sources, located around the outdoor opening of the window, will be enough to achieve meaningful active sound transmission reduction between 100 and 1000 Hz. Involving more cancelling sources does not result in better performance despite the added complexity.
Effect of ambisonic order on spatial release from masking
Authors: Culling John F. , Akrofi A. Ottopea , Dighton Samuel R.
Published: October 2024

In two experiments, spatial release from masking (SRM) was measured using an ambisonic reproduction system for a range of different ambisonic orders. The first experiment used ambisonic panning while the second experiment used impulse responses recorded from a sixth-order ambisonic microphone. Both experiments found a progressive increase in SRM with increasing ambisonic order for speech presented against a single speech-shaped-noise interferer. SRM increased progressively up to at least fourth order and continued to asymptotically improve at higher-ambisonic orders toward the level achieved with point sources. The second experiment found that this effect was robust for different acoustic environments.
Purkinje cell hyperexcitability and depressive-like behavior in mice lacking erg3 (ether-à-go-go–related gene) K
+
channel subunits
Authors: Schwarz Jürgen R. , Freitag Sandra , Pechmann Yvonne , Hermans-Borgmeyer Irm , Wagner Wolfgang , Hornig Sönke , Kneussel Matthias
Published: October 2024

Potassium channels stabilize the resting potential and neuronal excitability. Among them, erg (ether-à-go-go–related gene) K
+
channels represent a subfamily of voltage-gated channels, consisting of erg1, erg2, and erg3 subunits; however, their subunit-specific neuronal functions in vivo are barely understood. To find erg3- and erg1-mediated functions, we generated global
Kcnh7
(
erg3
) and conditional
Kcnh2
(
erg1
) knockout mice. We found that erg3 channels stabilize the resting potential and dampen spontaneous activity in cerebellar Purkinje cells (PCs) and hippocampal CA1 neurons, whereas erg1 channels have suprathreshold functions. Lack of erg3 subunits induced hyperexcitability with increased action potential firing in PCs, but not in CA1 neurons. Notably, erg3 depletion caused depressive-like behavior with reduced locomotor activity, strongly decreased digging behavior, and shorter latencies to fall off a rotating wheel, while learning and memory remained unchanged. Our data show that erg K
+
channels containing erg3 subunits mediate a neuronal subthreshold K
+
current that plays important roles in the regulation of locomotor behavior in vivo.
MerTK
+
macrophages promote melanoma progression and immunotherapy resistance through AhR-ALKAL1 activation
Authors: Wu Naming , Li Jun , Li Lu , Yang Liu , Dong Liyun , Shen Chen , Sha Shanshan , Fu Yangxue , Dong Enzhu , Zheng Fang , Tan Zheng , Tao Juan
Published: October 2024

Despite our increasing understanding of macrophage heterogeneity, drivers of macrophage phenotypic and functional polarization in the microenvironment are not fully elucidated. Here, our single-cell RNA sequencing data identify a subpopulation of macrophages expressing high levels of the phagocytic receptor MER proto-oncogene tyrosine kinase (MerTK
+
macrophages), which is closely associated with melanoma progression and immunotherapy resistance. Adoptive transfer of the MerTK
+
macrophages into recipient mice notably accelerated tumor growth regardless of macrophage depletion. Mechanistic studies further revealed that ALK And LTK Ligand 1 (ALKAL1), a target gene of aryl hydrocarbon receptor (AhR), facilitated MerTK phosphorylation, resulting in heightened phagocytic activity of MerTK
+
macrophages and their subsequent polarization toward an immunosuppressive phenotype. Specifically targeted delivery of AhR antagonist to tumor-associated macrophages with mannosylated micelles could suppress MerTK expression and improved the therapeutic efficacy of anti–programmed cell death ligand 1 therapy. Our findings shed light on the regulatory mechanism of MerTK
+
macrophages and provide strategies for improving the efficacy of melanoma immunotherapy.
Isolation and focal treatment of brain aneurysms using interfacial fluid trapping
Authors: Khoury Maria , Mekler Tirosh , Epshtein Mark , Kreinin Yevgeniy , Korneyev Dmitry , Abezgauz Ludmila , Anagnostakou Vania , Ramon Guy Z. , Sznitman Josué , Gounis Matthew , Korin Netanel
Published: October 2024

Current approaches for localized intravascular treatments rely on using solid implants, such as metallic coils for embolizing aneurysms, or on direct injection of a therapeutic agent that can disperse from the required site of action. Here, we present a fluid-based strategy for localizing intravascular therapeutics that leverages surface tension and immiscible fluid interactions, to allow confined and focal treatment at brain aneurysm sites. We first show, computationally and experimentally, that an immiscible phase can be robustly positioned at the neck of human aneurysm models to seal and isolate the aneurysm’s cavity for further treatment, including in wide-neck aneurysms. We then demonstrate localized delivery and confined treatment, by selective staining of cell nuclei within the aneurysm cavity as well as by hydrogel-based embolization in patient-specific aneurysm models. Altogether, our interfacial flow-driven strategy offers a potential approach for intravascular localized treatment of cardiovascular and other diseases.
Aridity drives the response of soil total and particulate organic carbon to drought in temperate grasslands and shrublands
Authors: Shi Baoku , Delgado-Baquerizo Manuel , Knapp Alan K. , Smith Melinda D. , Reed Sasha , Osborne Brooke , Carrillo Yolima , Maestre Fernando T. , Zhu Yu , Chen Anping , Wilkins Kate , Holdrege Martin C. , Kulmatiski Andrew , Picon-Cochard Catherine , Roscher Christiane , Power Sally , Byrne Kerry M. , Churchill Amber C. , Jentsch Anke , Henry Hugh A. L. , Beard Karen H. , Schuchardt Max A. , Eisenhauer Nico , Otfinowski Rafael , Hautier Yann , Shen Huitao , Wang Yonghui , Wang Zhongwu , Wang Chengliang , Cusack Daniela Francis , Petraglia Alessandro , Carbognani Michele , Forte T’ai G.W. , Flory S. , Hou Pengli , Zhang Tao , Gao Weifeng , Sun Wei
Published: October 2024

The increasing prevalence of drought events in grasslands and shrublands worldwide potentially has impacts on soil organic carbon (SOC). We leveraged the International Drought Experiment to study how SOC, including particulate organic carbon (POC) and mineral-associated organic carbon (MAOC) concentrations, responds to extreme drought treatments (1-in-100-year) for 1 to 5 years at 19 sites worldwide. In more mesic areas (aridity index > 0.65), SOC and POC concentrations decreased by 7.9% (±3.9) and 15.9% (±6.2) with drought, respectively, but there were no impacts on MAOC concentrations. However, drought had no impact on SOC, POC, or MAOC concentrations in drylands (aridity index < 0.65). The response of SOC to drought varied along an aridity gradient, concomitant with interannual precipitation variability and standing SOC concentration gradients. These findings highlight the differing response magnitudes of POC and MAOC concentrations to drought and the key regulating role of aridity.
Atom-glue stabilized Pt-based intermetallic nanoparticles
Authors: Huang Zhongliang , Wang Yingru , Xia Jing , Hu Shengnan , Chen Nanjun , Ding Tianyi , Zhan Changhong , Pao Chih-Wen , Hu Zhiwei , Huang Wei-Hsiang , Shi Tong , Meng Xiangmin , Xu Yong , Cao Liang , Huang Xiaoqing
Published: October 2024

Pt-based nanoparticles (NPs) have been widely used in catalysis. However, this suffers from aggregation and/or sintering at working conditions. We demonstrate a robust strategy for stabilizing PtCo NPs under high temperature with strong interaction between M–N–C and PtCo NPs with Pt–M–N coordination, namely, “atom glue.” Such atom glue for stabilizing Pt-based NPs can be extended to Zn, Mn, Fe, Ni, Co, and Cu, being a versatile strategy for stabilizing PtCo NPs, which substantially promotes the performance toward oxygen reduction reaction (ORR) and fuel cell. Impressively, the mass activity (MA) reaches 2.99 A mg
Pt
−1
for ORR over
g
-Zn–N–C/PtCo, and 79.3% of the initial MA is maintained after 90K cycles in fuel cell. This work provides a versatile strategy for stabilizing Pt-based NPs via atom glue, which is likely to spark widespread interest across various fields.
Additively manufactured micro-lattice dielectrics for multiaxial capacitive sensors
Authors: Berman Arielle , Hsiao Kaiwen , Root Samuel E. , Choi Hojung , Ilyn Daniel , Xu Chengyi , Stein Emily , Cutkosky Mark , DeSimone Joseph M. , Bao Zhenan
Published: October 2024

Soft sensors that can perceive multiaxial forces, such as normal and shear, are of interest for dexterous robotic manipulation and monitoring of human performance. Typical planar fabrication techniques have substantial design constraints that often prohibit the creation of functionally compelling and complex architectures. Moreover, they often require multiple-step operations for production. Here, we use an additive manufacturing process based on continuous liquid interface production to create high-resolution (30-micrometer) three-dimensional elastomeric polyurethane lattices for use as dielectric layers in capacitive sensors. We show that the capacitive responses and sensitivities are highly tunable through designs of lattice type, thickness, and material-void volume percentage. Microcomputed tomography and finite element simulation are used to elucidate the influence of lattice design on the deformation mechanism and concomitant sensing behavior. The advantage of three-dimensional printing is exhibited with examples of fully printed representative athletic equipment with integrated sensors.
High frequency of acquired virulence factors in carbapenemase-producing
Klebsiella pneumoniae
isolates from a large German university hospital, 2013–2021
Authors: Sattler Janko , Ernst Christoph M. , Zweigner Janine , Hamprecht Axel
Published: October 2024

Carbapenemase-producing
Klebsiella pneumoniae
(CP-Kp) isolates are a public health concern as they can cause severe hospital-acquired infections that are difficult to treat. It has recently been shown that CP-Kp can take up virulence factors from hypervirulent
K. pneumoniae
lineages. In this study, 109 clinical CP-Kp isolates from the University Hospital Cologne were examined for the presence of acquired virulence factors using whole-genome sequencing and phenotypic tests, and results were linked to clinical data. The virulence factor
iuc
was present in 18/109 of the CP-Kp isolates. Other acquired virulence factors, such as
ybt
,
cbt
,
iro
,
rmpA/rmpA2
,
peg-344
, and hypervirulence-associated capsule types were detected in various combinations among these isolates. The
iuc
-positive isolates produced OXA-232 (
n
= 7), OXA-48 (
n
= 6), OXA-48+NDM (
n
= 3), NDM, and KPC (each
n
= 1), and 7/18 isolates were resistant to ceftazidime-avibactam, colistin, and/or cefiderocol. Four isolates carried hybrid plasmids that harbored acquired virulence factors alongside the carbapenemase genes
bla
NDM-1/5
or
bla
OXA-48
. In 15/18 patients,
iuc
-positive CP-Kp were isolated from a clinically manifest infection site. Among these, four patients had osteomyelitis, and four patients died from pneumonia with OXA-232-producing ST231 isolates, three of them as part of an outbreak. In conclusion, acquired virulence factors are frequently detected in various combinations in carbapenemase-producing
K. pneumoniae
isolates in Germany, warranting continuous monitoring of infections caused by these strains.
A realistic approach for evaluating antimicrobial surfaces for dry surface exposure scenarios
Authors: Cheong Yi Enn , Weyandt Ralph , Dewald Wilma , Tolksdorf Timo , Müller Laura , Braun Armin
Published: October 2024

The severe acute respiratory syndrome coronavirus 2 pandemic has raised public awareness about the importance of hygiene, leading to an increased demand for antimicrobial surfaces to minimize microbial contamination on high-touch surfaces. This is particularly relevant in public and private transportation settings, where surfaces frequently touched by individuals pose a significant, yet preventable, risk of infection transmission. Typically, the antimicrobial activity of surfaces is tested using test methods of the International Standards Organization, American Society for Testing and Materials, or Japanese Industrial Standards, which involve complete submersion in liquid, elevated temperature (37°C), and prolonged (24 h) contact periods. However, these conditions do not accurately represent real-world scenarios where surfaces are exposed to air. In this study, we propose a modified test method designed to better reflect real-life conditions in the intended end-use setting. The modifications included using deionized water instead of nutrient broth while preparing bacterial inoculum, applying a small test inoculum to the surface and allowing it to dry, maintaining ambient temperature and relative humidity throughout the contact period, and reducing the contact period to 4 h. With this modified approach, the antimicrobial activity of 20 samples was reassessed. This screening revealed that out of 20 samples, only 2 samples were effective against all species, while 8 samples demonstrated partial effectiveness against selected species, and 10 samples showed no significant effect. These findings highlight the inadequacy of the current test standard and emphasize the urgent necessity for revised and adapted testing method to ensure a reliable and accurate evaluation.

IMPORTANCE

The recent severe acute respiratory syndrome coronavirus 2 pandemic has sparked increased demand for antimicrobial surfaces to mitigate the risk of fomites-transmitted infection in both indoors and confined spaces. Commonly, the antimicrobial activity of these surfaces is assessed using test standards established by national standards bodies, which do not distinguish between different application scenarios. While these test standards are suitable for surfaces intended for submerged application, they are inappropriate for antimicrobial surfaces designed for dry surface exposure. The usage of these standards can lead to an overestimation of antimicrobial efficacy. Thus, this study introduces a modified dry exposure test method aimed at better reflecting real-life conditions in the intended end-use setting. Our results revealed the subpar antimicrobial performance of numerous samples, highlighting the necessity to revise and tailor the universal test standard to real-world scenarios in order to ensure a reliable and accurate evaluation.
Antibiotic tolerance among clinical isolates: mechanisms, detection, prevalence, and significance
Authors: Deventer Ashley T. , Stevens Claire E. , Stewart Amy , Hobbs Joanne K.
Published: October 2024

Antibiotic treatment failures in the absence of resistance are not uncommon. Recently, attention has grown around the phenomenon of antibiotic tolerance, an underappreciated contributor to recalcitrant infections first detected in the 1970s. Tolerance describes the ability of a bacterial population to survive transient exposure to an otherwise lethal concentration of antibiotic without exhibiting resistance. With advances in genomics, we are gaining a better understanding of the molecular mechanisms behind tolerance, and several studies have sought to examine the clinical prevalence of tolerance. Attempts have also been made to assess the clinical significance of tolerance through
in vivo
infection models and prospective/retrospective clinical studies. Here, we review the data available on the molecular mechanisms, detection, prevalence, and clinical significance of genotypic tolerance that span ~50 years. We discuss the need for standardized methodology and interpretation criteria for tolerance detection and the impact that methodological inconsistencies have on our ability to accurately assess the scale of the problem. In terms of the clinical significance of tolerance, studies suggest that tolerance contributes to worse outcomes for patients (e.g., higher mortality, prolonged hospitalization), but historical data from animal models are varied. Furthermore, we lack the necessary information to effectively treat tolerant infections. Overall, while the tolerance field is gaining much-needed traction, the underlying clinical significance of tolerance that underpins all tolerance research is still far from clear and requires attention.
Oxford Nanopore’s 2024 sequencing technology for
Listeria monocytogenes
outbreak detection and source attribution: progress and clone-specific challenges
Authors: Biggel Michael , Cernela Nicole , Horlbog Jule Anna , Stephan Roger
Published: October 2024

Whole genome sequencing is an essential cornerstone of pathogen surveillance and outbreak detection. Established sequencing technologies are currently being challenged by Oxford Nanopore Technologies (ONT), which offers an accessible and cost-effective alternative enabling gap-free assemblies of chromosomes and plasmids. Limited accuracy has hindered its use for investigating pathogen transmission, but recent technology updates have brought significant improvements. To evaluate its readiness for outbreak detection, we selected 78
Listeria monocytogenes
isolates from diverse lineages or known epidemiological clusters for sequencing with ONT‘s V14 Rapid Barcoding Kit and R10.4.1 flow cells. The most accurate of several tested workflows generated assemblies with a median of one error (SNP or indel) per assembly. For 66 isolates, the cgMLST profiles from ONT-only assemblies were identical to those generated from Illumina data. Eight assemblies were of lower quality, with more than 20 erroneous sites each, primarily caused by methylations at the GAAGAC motif (5′-GAAG
6mA
C-3′/5′-GT
4mC
TTC-3′). This led to inaccurate clustering, failing to group isolates from a persistence-associated clone that carried the responsible restriction–modification system. Out of 50 methylation motifs detected among the 78 isolates, only the GAAGAC motif was linked to substantially increased error rates. Our study shows that most
L. monocytogenes
genomes assembled from ONT-only data are suitable for high-resolution genotyping, but further improvements of chemistries or basecallers are required for reliable routine use in outbreak and food safety investigations.
A Nanopore-sequenced high-quality genome of the
Bipolaris oryzae
strain Bo-1
Authors: Liu Meng , Yang Wei , Gu Xinyi , Xiao Yongxin , Yang Lei , Zhang Zhaowu , Wei Tong , Hsiang Tom , Zhang Yaling , Li Guotian
Published: October 2024

Brown spot disease of rice caused by
Bipolaris oryzae
results in severe yield losses. A high-quality genome was assembled using Nanopore sequencing data, resulting in a 36-Mb nuclear genome with 19 contigs and a mitogenome. This assembly provides valuable genetic resources for investigations of rice-
B. oryzae
interactions.
Complete genome sequence of
Escherichia coli
JCM 5491
Authors: Umekage So
Published: October 2024

Here, I report the complete genome sequence of
Escherichia coli
JCM5491, which is widely used in microbiological experiments.
Advancing microbiome research in Māori populations: insights from recent literature exploring the gut microbiomes of underrepresented and Indigenous peoples
Authors: Silk Ella T. , Bayer Simone B. , Foster Meika , Roy Nicole C. , Taylor Michael W. , Vatanen Tommi , Gearry Richard B.
Published: October 2024

The gut microbiome plays vital roles in human health, including mediating metabolism, immunity, and the gut-brain axis. Many ethnicities remain underrepresented in gut microbiome research, with significant variation between Indigenous and non-Indigenous peoples due to dietary, socioeconomic, health, and urbanization differences. Although research regarding the microbiomes of Indigenous peoples is increasing, Māori microbiome literature is lacking despite widespread inequities that Māori populations face. These inequities likely contribute to gut microbiome differences that exacerbate negative health outcomes. Characterizing the gut microbiomes of underrepresented populations is necessary to inform efforts to address health inequities. However, for microbiome research to be culturally responsible and meaningful, study design must improve to better protect the rights and interests of Indigenous peoples. Here, we discuss barriers to Indigenous participation in research and the role disparities may play in shaping the gut microbiomes of Indigenous peoples, with a particular focus on implications for Māori and areas for improvement.