bluuebunny/crossref_metadata_2025 huggingface dataset:
Shenqi Fuzheng injection facilitates skeletal muscle mitophagy mediated by the ubiquitination of HIF‐1α to ameliorate cancer‐associated fatigue
Authors: Guo Wei , Liu Shan , Xia Huan , Luo Jiamin , Chen Hanrui , Hu Leihao , Zheng Xinting , Xiao Zhiwei , Lin Lizhu
Published: June 2024

Cancer‐related fatigue (CRF) significantly impacts the quality of life of cancer patients. This study investigates the therapeutic potential of Shenqi Fuzheng injection (SFI) in managing CRF, focusing on its mechanistic action in skeletal muscle. We utilized a CRF mouse model to examine the effects of SFI on physical endurance, monitoring activity levels, swimming times and rest periods. Proteomic analysis of the gastrocnemius muscle was performed using isobaric tags and liquid chromatography–tandem mass spectrometry to map the muscle proteome changes post‐SFI treatment. Mitochondrial function in skeletal muscle was assessed via ATP bioluminescence assay. Furthermore, the regulatory role of the hypoxia inducible factor 1 subunit alpha (HIF‐1α) signalling pathway in mediating SFI's effects was explored through western blotting. In CRF‐induced C2C12 myoblasts, we evaluated cell viability (CCK‐8 assay), apoptosis (flow cytometry) and mitophagy (electron microscopy). The study also employed pulldown, luciferase and chromatin immunoprecipitation assays to elucidate the molecular mechanisms underlying SFI's action, particularly focusing on the transcriptional regulation of PINK1 through HIF‐1α binding at the PINK1 promoter region. Our findings reveal that SFI enhances physical mobility, reduces fatigue symptoms and exerts protective effects on skeletal muscles by mitigating mitochondrial damage and augmenting antioxidative responses. SFI promotes cell viability and induces mitophagy while decreasing apoptosis, primarily through the modulation of HIF‐1α, PINK1 and p62 proteins. These results underscore SFI's efficacy in enhancing mitochondrial autophagy, thereby offering a promising approach for ameliorating CRF. The study not only provides insight into SFI's potential therapeutic mechanisms but also establishes a foundation for further exploration of SFI interventions in CRF management.
Study of the mechanism by which Xiaoyan decoction combined with E7449 regulates tumorigenesis in lung adenocarcinoma
Authors: Zheng Xu , Han Yanyan , Gu Lili , Gao Shan , Lv Yan , Li Chong
Published: June 2024

TNKS is a new target for the treatment of lung adenocarcinoma, the synergistic effects of the TCM compound Xiaoyan decoction and the TNKS inhibitor E7449 in the intervention on TNKS were investigated, and the possible underlying mechanisms involved were clarified. Immunohistochemistry was used to analyse TNKS expression in tumour tissues. The impact of targeting TNKS on cell growth, invasion, apoptosis, key genes and signalling pathways was investigated in tumour cells by Western blotting, rescue experiments, colony formation assays, flow cytometry and label‐free experiments. Tumour xenografts with A549 cells were then transplanted for in vivo study. We found that TNKS high expression was closely related to the advanced tumour stage and tumour size in lung adenocarcinom. After TNKS was knocked down in vitro, the growth, proliferation, migration and invasion were markedly reduced in A549 and H1975 cells. We subsequently applied the Xiaoyan decoction and TNKS inhibitors to intervene in lung adenocarcinoma. Xiaoyan decoction and E7449 suppressed TNKS expression and inhibited adenocarcinoma cell proliferation, migration, invasion and apoptosis in vitro. Proteomic analysis revealed that E7449 treatment may be most closely associated with the classic Wnt/β‐catenin pathway, whereas Xiaoyan decoction treatment may be related to the WNT/PLAN pathway. Xenograft studies confirmed that E7449 or Xiaoyan decoction inhibited lung tumour growth in vivo and attenuated the Wnt signalling pathway in adenocarcinoma. These findings suggest that TNKS is a novel therapeutic target. TCM preparations and small molecule inhibitors are expected to constitute an effective combination strategy.
Autophagy is the main driver of radioresistance of HNSCC cells in mild hypoxia
Authors: Hill Rhianna M. , Li Chun , Hughes Jonathan R. , Rocha Sonia , Grundy Gabrielle J. , Parsons Jason L.
Published: June 2024

Hypoxia poses a significant challenge to the effectiveness of radiotherapy in head and neck squamous cell carcinoma (HNSCC) patients, and it is imperative to discover novel approaches to overcome this. In this study, we investigated the underlying mechanisms contributing to x‐ray radioresistance in HPV‐negative HNSCC cells under mild hypoxic conditions (1% oxygen) and explored the potential for autophagy modulation as a promising therapeutic strategy. Our findings show that HNSCC cells exposed to mild hypoxic conditions exhibit increased radioresistance, which is largely mediated by the hypoxia‐inducible factor (HIF) pathway. We demonstrate that siRNA knockdown of HIF‐1α and HIF‐1β leads to increased radiosensitivity in HNSCC cells under hypoxia. Hypoxia‐induced radioresistance was not attributed to differences in DNA double strand break repair kinetics, as these remain largely unchanged under normoxic and hypoxic conditions. Rather, we identify autophagy as a critical protective mechanism in HNSCC cells following irradiation under mild hypoxia conditions. Targeting key autophagy genes, such as BECLIN1 and BNIP3/3L, using siRNA sensitizes these cells to irradiation. Whilst autophagy's role in hypoxic radioresistance remains controversial, this study highlights the importance of autophagy modulation as a potential therapeutic approach to enhance the effectiveness of radiotherapy in HNSCC.
Senescence induces miR‐409 to down‐regulate CCL5 and impairs angiogenesis in endothelial progenitor cells
Authors: Chou Yen‐Hung , Lee Yi‐Nan , Su Cheng‐Huang , Lee Hsin‐I , Hsieh Chin‐Ling , Tien Ting‐Yi , Lin Chao‐Feng , Yeh Hung‐I , Wu Yih‐Jer
Published: June 2024

This study explores the impact of senescence on autocrine C‐C motif chemokine ligand 5 (CCL5) in human endothelial progenitor cell (EPCs), addressing the poorly understood decline in number and function of EPCs during ageing. We examined the effects of replication‐induced senescence on CCL5/CCL5 receptor (CCR5) signalling and angiogenic activity of EPCs in vitro and in vivo. We also explored microRNAs controlling CCL5 secretion in senescent EPCs, its impact on EPC angiogenic activity, and validated our findings in humans. CCL5 secretion and CCR5 levels in senescent EPCs were reduced, leading to attenuated angiogenic activity. CCL5 enhanced EPC proliferation via the CCR5/AKT/P70S6K axis and increased vascular endothelial growth factor (VEGF) secretion. Up‐regulation of miR‐409 in senescent EPCs resulted in decreased CCL5 secretion, inhibiting the angiogenic activity, though these negative effects were counteracted by the addition of CCL5 and VEGF. In a mouse hind limb ischemia model, CCL5 improved the angiogenic activity of senescent EPCs. Analysis involving 62 healthy donors revealed a negative association between CCL5 levels, age and Framingham Risk Score. These findings propose CCL5 as a potential biomarker for detection of EPC senescence and cardiovascular risk assessment, suggesting its therapeutic potential for age‐related cardiovascular disorders.
Reassessing the impact of health IT: Hidden costs and consequences of vendor heterogeneity
Authors: Lin Jianjing , Olson Mary K.
Published: June 2024

The government has invested more than $24.8 billion to incentivize the adoption of health information technology in hospitals; however, there is little evidence showing that these investments produced the expected efficiencies, such as cost savings and improved quality of care. We examine whether vendor heterogeneity can help explain this puzzle. Our results show that the effects of electronic medical record (EMR) adoption on hospital costs and quality vary substantially by vendor. Only certain EMR vendors lead to cost savings (ranging between 3.1% and 4.7%) or quality of care improvements (lowering rates of adverse drug events from 0.38 to 1.68 percentage points) for adopting hospitals, while the adoption of other EMR vendors leads to either cost increases, quality of care reductions, or no significant effects. Our results suggest that both quality improvement and cost savings may be improved by a more strategic choice of vendor. The variability in EMR effectiveness by vendor also implies that there was a hidden cost of the government's program to incentivize the adoption of EMRs in hospitals.
Half Banked: The Economic Impact of Cash Management in the Marijuana Industry
Authors: BERGER ELIZABETH A. , SEEGERT NATHAN
Published: June 2024

We investigate the economic value of cash management. In the legal marijuana industry, where only half of businesses have access to cash management services from a financial institution, we examine dispensary profitability using administrative and survey data. Our results show that businesses with cash management charge higher retail prices (8.3%), pay lower wholesale prices (7.3%), and have higher sales volume (19%). Together, these advantages create a 40% increase in profitability. These results support our model in which reputational capital and administrative costs drive profitability regardless of whether national banks, credit unions, or fintech provide the cash management functions.
Receiving screened donor human milk as part of a community‐based lactation support programme reduces parental symptoms of anxiety and depression
Authors: Brown Amy , Griffin Sam , Weaver Gillian , Shenker Natalie
Published: June 2024

Infant feeding decisions and maternal mental health are closely tied. Donor human milk (DHM) protects premature infant health and development and can reduce hospital stays. Recent qualitative research has highlighted that having the option for an infant to receive DHM can also support parental wellbeing through reducing concerns about infant health and supporting feeding preferences. However, no quantitative study has examined this relationship. In this study, anxiety and depression scores were measured before and after receiving DHM using the Hospital Anxiety and Depression Scale for 80 parents (77 mothers, 3 fathers) who had sought DHM from a community‐facing milk bank. Reasons for seeking DHM included maternal cancer, maternal and infant health complications, insufficient glandular tissue, and low milk supply. Open‐ended questions explored the experience of receiving milk. Milk bank records were used to match details of milk given (volume, duration, exclusivity, lactation support given) with survey responses. Both anxiety and depression scores significantly reduced after receiving milk. Although greater lactation support and longer duration of milk predicted a greater decrease in scores, in a regression analysis, only volume of milk given remained a significant predictor. Almost all parents agreed that being able to access DHM supported their wellbeing predominantly through reducing anxieties around infant health but also through feeding choices being respected and the support given at difficult times. The findings add important considerations to the literature considering when and for whom DHM should be used and the complex interplay between infant feeding and mental health.
Modeling of spatially embedded networks via regional spatial graph convolutional networks
Authors: Fan Xudong , Hackl Jürgen
Published: June 2024

Efficient representation of complex infrastructure systems is crucial for system‐level management tasks, such as edge prediction, component classification, and decision‐making. However, the complex interactions between the infrastructure systems and their spatial environments increased the complexity of network representation learning. This study introduces a novel geometric‐based multimodal deep learning model for spatially embedded network representation learning, namely the regional spatial graph convolutional network (RSGCN). The developed RSGCN model simultaneously learns from the node's multimodal spatial features. To evaluate the network representation performance, the introduced RSGCN model is used to embed different infrastructure networks into latent spaces and then reconstruct the networks. A synthetic network dataset, a California Highway Network, and a New Jersey Power Network were used as testbeds. The performance of the developed model is compared with two other state‐of‐the‐art geometric deep learning models, GraphSAGE and Spatial Graph Convolutional Network. The results demonstrate the importance of considering regional information and the effectiveness of using novel graph convolutional neural networks for a more accurate representation of complex infrastructure systems.
Classification and Treatment Strategies of Tibial Tubercle Fractures in Adults
Authors: Yao Xiang , Liu Hongyuan , Ma Yuxuan , Hu Minjie , Wang Chong , Miao Han , Liu ShengJie , Tang Jilei
Published: June 2024

Objectives

Tibial tubercle is a crucial player in maintaining the structural integrity and functional stability of the knee joint. Currently, there is no standardized protocol for the classification and treatment of tibial tubercle fractures in adults. This study analyzed the incidence and treatment strategies of tibial tubercle fractures in adults according to the four‐column and nine‐segment classification system.

Methods

Data of patients with proximal tibial fractures involving tibial tubercle fractures who were treated at our hospital from August 2007 to March 2023 were retrospectively reviewed. The fractures were classified using the AO/OTA classification and four‐column and nine‐segment classification systems, and the treatment protocol (surgically treated or conservatively treated) was recorded. The number and distribution proportion of patients were counted. A two‐sided t‐test was conducted to determine the significance of differences between the gender and sides.

Results

In total, 169 tibial tubercle fractures were found in 1484 proximal tibial fractures. According to the AO/OTA classification, seven of the 169 patients, (4.1%) were type A, 36 patients (21.3%) were type B, and 126 patients (74.6%) were type C. According to the four‐column and nine‐segment classification, type 1 cleavage without free fragments was the most common type of fracture (93/169, 55.0%), followed by type 2 dissociative segmental fragments (48/169, 28.4%) and type 3 comminuted fractures (28/169, 16.6%). Overall, 139 of the 169 proximal tibial fractures with tuberosity involvement were treated surgically. Among them, additional fixation of the tubercle fragment was performed in 52 fractures.

Conclusion

The incidence of tibial tubercle fractures involved in proximal tibial fractures was approximately 11.4% (169/1484) in adults, and approximately one‐third of the tubercle bone fragment required additional fixation (30.8%, 52/169). The injury types in the four‐column and nine‐segment classifications are helpful for accurately judging and making treatment‐related decisions for tibial tubercle fractures.
Interannual variation in provenance performance under drought in a Great Basin rangeland
Authors: Aoyama Lina , Silva Lucas , Copeland Stella M. , O'Connor Rory C. , Hallett Lauren M.
Published: June 2024

Rapid climate change poses a fundamental challenge to seed sourcing in restoration. While local provenancing is a common practice in restoration, local seeds may not survive or persist under future climate conditions. Alternative provenancing strategies, such as climate‐adjusted provenancing, that mix local seeds with non‐local seeds aim to increase the buffering capacity of restored populations. We hypothesized that seeds sourced from warmer and drier sites have higher seedling performance under drought than seeds sourced from cooler and wetter sites. We conducted a common garden experiment in a Great Basin rangeland where more frequent, severe drought events are expected to increase in the future. We sourced Bottlebrush squirreltail (Elymus elymoides [Raf.] Swezey) seeds from six locations along an aridity gradient and sowed them under three rainfall scenarios: ambient, moderate drought, and severe drought. We found strong interannual variation in seedling recruitment. In 1 year, some provenances from warmer/drier sites had high emergence and subsequent seedling survival under moderate drought. In another, emergence was low across provenances and rainfall treatments. Two provenances that survived 2 years of moderate drought had divergent seedling traits. Specifically, one had a high germination temperature optimum and high water‐use efficiency, such that it likely avoided freezing and resisted drought, while another had a low germination temperature optimum and low water‐use efficiency, such that it likely tolerated freezing and escaped drought. We highlight that understanding these differences in recruitment and stress coping strategies across provenances is important for creating climate‐adaptive seed mixes in anticipation of future climate conditions.
The Demands of the Disabled: Masculinity, Disability, and Citizenship in the Late Imperial Russian Military
Authors: Hearne Siobhán
Published: June 2024

In the years after 1905, catastrophic war, widespread political and social unrest, and rising demands from across all segments of the empire’s population forced the Russian imperial state to develop a rudimentary social contract with military personnel and implement a series of reforms to prevent the reoccurrence of military disaster and mass social unrest. These reforms entitled disabled veterans to some forms of state support that were denied to their civilian counterparts, including assistance finding work, pensions, and free prosthetic devices. These entitlements were part of a broader shift away from paternalistic approaches to social welfare provision toward the early germinations of a gendered and selective welfare state. Disability support was dependent on proximity to the military, which cemented the idea that civic inclusion—and by extension, Russian manhood—was something achieved only through military service. This article examines interactions between veterans with disabilities and representatives of the Russian imperial state to explore shifting conceptions of masculinity and the development of new political subjectivities in the aftermath of war. The Russian imperial military can be regarded as a test site within which masculine identities were negotiated and reconfigured amid the social, economic, and political transformations of the late imperial period.
A conversation with Nils Lid Hjort
Authors: Borgan Ørnulf , Glad Ingrid K.
Published: June 2024

Professor (now emeritus) Nils Lid Hjort has through more than four decades been one of the most original and productive statisticians in Norway, contributing to a wide range of topics such as survival analysis, Bayesian nonparametrics, empirical likelihood, density estimation, focused inference, model selection, and confidence distributions. This conversation, which took place at the University of Oslo in December 2023, sheds light on how Nils Hjort's curious and open mind, coupled with a deep understanding, has enabled him to seamlessly navigate between different fields of statistics and its applications. Our aim is to encourage the statistics community to always be on the lookout for unexpected connections in statistical science and to embrace unexpected encounters with fellow statisticians from around the world.
Randomised, split‐face study of a dermocosmetic cream containing Sphingobioma xenophaga extract and Neurosensine® in subjects with rosacea associated with erythema and sensitive skin
Authors: Berardesca Enzo , Cartigliani Claudia , Nioré Margot , Bonfigli Adriana , Canchy Ludivine , Kerob Delphine , Tan Jerry
Published: June 2024

Introduction

Rosacea is a chronic inflammatory skin condition associated with erythema, inflammation and skin sensitivity.

Objectives

To assess the benefit of a dermocosmetic cream (DC cream) containing Sphingobioma xenophaga extract and soothing agent in adult females with rosacea‐associated erythema and sensitive skin.

Materials and Methods

During phase 1, DC was applied twice daily on the randomized half‐face and compared to usual‐skincare (USC) for 28 days. During phase 2, DC was applied on the full face twice daily for 56 days. Clinical, instrumental and skin sensitivity assessments were performed at all visits; demodex density (standardized skin surface biopsy (SSSB) method) was performed at baseline and D28, quality of life (QoL) was assessed using the stigmatization questionnaire (SQ), Rosacea Quality of Life index (ROSAQoL) and Dermatology Life Quality Index (DLQI) at baseline and D84.

Results

At D28, a significant benefit of DC over USC was observed for erythema, tightness, burning and stinging (all p ≤ 0.05), erythema measured by chromameter (p < 0.01), corneometry and transepidermal water loss (p < 0.0001 and p < 0.05, respectively), skin sensitivity (p < 0.001) and significant reduction of mean demodex density (p < 0.05) on the DC side. At D84, DC significantly (all p < 0.05) improved clinical signs and symptoms on both sides of the face compared to baseline; SQ, ROSAQoL and DLQI scores improved by 40.4%, 25.0% and 55.7%, respectively compared to baseline. Tolerance was excellent.

Conclusion

DC significantly improved erythema, skin sensitivity, demodex count, QoL and feeling of stigmatization of subjects with rosacea and is very well tolerated.
The investigation and comparison of the efficacy and safety of stromal vascular fraction (SVF), platelet rich plasma (PRP), and 1064‐nm Q‐switched Nd:YAG laser in reducing nanofat treated infraorbital dark circles and wrinkles: A controlled blinded randomized clinical trial
Authors: Roohaninasab Masoumeh , Ahmadi Marzieh , Dehghani Abbas , Zare Sona , Goodarzi Azadeh , Nouri Maryam , Ebrahimi Zahra , Behrangi Elham , Nilforoushzadeh Mohammad Ali
Published: June 2024

Background

To evaluate the efficacy and safety of stromal vascular fraction (SVF), platelet rich plasma (PRP), and 1064‐nm Q‐switched Nd:YAG laser in reducing nanofat treated dark circles and wrinkles under the eyes.

Method

This study was a single‐blinded randomized clinical trial conducted on patients with suborbital darkening under the eyes that randomly divided into control and case groups. In the control group, 15 patients were treated with one session of nanofat injection only, and five patients of each intervention groups received one session of nanofat+SVF injection, nanofat+PRP injection, and nanofat injection+Nd:YAG laser, respectively. Assessments methods were (1) evaluation of the degree of darkness and repair under the eyes by a blinded dermatologist based on clinical photographs, (2) investigating patient satisfaction, (3) using biometric variables for color, thickness, and density of the skin (only 3 months after the treatment), and (4) recording the possible adverse effects.

Conclusion

In terms of the extent of reduction in the intensity of darkness under the eyes, the combined treatment of nanofat injection together with SVF, PRP, and Nd:YAG laser had a much greater therapeutic effect than nanofat injection alone. In all three groups of combined treatments, patients were 100% satisfied. In terms of biometric variables, amount of changes in colorimeter, complete and dermal thickness, complete and dermal density, between the different groups was statistically significant. The use of combined treatments including nanofat with SVF injection, PRP, and 1064 Q‐switched Nd:YAG laser may be more effective than nanofat alone, in reducing infraorbital dark circles and wrinkles.
Integrative taxonomy of the featherback fish genus Chitala (Osteoglossomorpha: Notopteridae) in Peninsular Malaysia
Authors: Ruzman Luqman Hakim , Jamaluddin Jamsari Amirul Firdaus , Muhammad‐Rasul Abdullah Halim , Sukmono Tedjo , Khaironizam Md. Zain , Lavoué Sébastien
Published: June 2024

The taxonomy of the freshwater featherback fish genus Chitala (Osteoglossomorpha: Notopteridae) remains unsettled because delimiting and naming Chitala species based solely on morphology led to different hypotheses. In this study, we aim to determine the number and identity of Chitala species present in Peninsular Malaysia by employing an integrative taxonomic approach that combines morphology and two mitochondrial markers: the cytochrome c oxidase subunit I (COI) and cytochrome b genes. A total of 60 specimens of Chitala were collected throughout Peninsular Malaysia. Initially, all specimens were sorted into three distinct categories based on their body marking patterns. A molecular phylogenetic analysis revealed that each of these groups was monophyletic, and an automated species partition method further recognized them as distinct species. These results support the presence of three Chitala species in Peninsular Malaysia, even though a multivariate morphometric analysis failed to fully differentiate each of these three species. Comparison with original species descriptions and genetic data from an additional 70 Chitala specimens from neighbouring regions allowed us to name these species as Chitala lopis, Chitala borneensis, and Chitala ornata. We also showed the presence of two undescribed species in Indonesia.
Geometric visualizations of single and entangled qubits
Authors: Chang Li-Heng Henry , Roccaforte Shea , Xu Ziyu , Cadden-Zimansky Paul
Published: June 2024

The Bloch Sphere visualization of the possible states of a single qubit serves as a useful pedagogical and conceptual tool, offering a one-to-one map between qubit states and points in a 3D space. However, understanding many important concepts of quantum mechanics, such as entanglement, requires developing intuitions about states with a minimum of two qubits, which map one-to-one to unvisualizable spaces of six dimensions and higher. In this paper, we circumvent this visualization issue by creating maps of subspaces of 1- and 2-qubit systems that quantitatively and qualitatively encode properties of these states in their geometries. For the 1-qubit case, the subspace approach allows one to visualize how mixed states relate to different choices of measurement in a basis-independent way and how to read off the entries in a density matrix representation of these states from lengths in a simple diagram. For the 2-qubit case, a toroidal map of 2-qubit states illuminates the non-trivial topology of the state space while allowing one to simultaneously read off, in distances and angles, the level of entanglement in the 2-qubit state and the mixed-state properties of its constituent qubits. By encoding states and their evolutions through quantum logic gates with little to no need of mathematical formalism, these maps may prove particularly useful for understanding fundamental concepts of quantum mechanics and quantum information at the introductory level.
Carbon nanotube fibers with dynamic strength up to 14 GPa
Authors: Zhang Xinshi , Lei Xudong , Jia Xiangzheng , Sun Tongzhao , Luo Jiajun , Xu Shichen , Li Lijun , Yan Dan , Shao Yuanlong , Yong Zhenzhong , Zhang Yongyi , Wu Xianqian , Gao Enlai , Jian Muqiang , Zhang Jin
Published: June 2024

High dynamic strength is of fundamental importance for fibrous materials that are used in high–strain rate environments. Carbon nanotube fibers are one of the most promising candidates. Using a strategy to optimize hierarchical structures, we fabricated carbon nanotube fibers with a dynamic strength of 14 gigapascals (GPa) and excellent energy absorption. The dynamic performance of the fibers is attributed to the simultaneous breakage of individual nanotubes and delocalization of impact energy that occurs during the high–strain rate loading process; these behaviors are due to improvements in interfacial interactions, nanotube alignment, and densification therein. This work presents an effective strategy to utilize the strength of individual carbon nanotubes at the macroscale and provides fresh mechanism insights.
JAKing up immunity
Authors: Gadina Massimo , O’Shea John J.
Published: June 2024

Janus kinase (JAK) inhibitors improve antitumor responses
Daniel C. Dennett (1942—2024)
Authors: Yuste Rafael , Levin Michael
Published: June 2024

Philosopher and science advocate
Reducing nuclear dangers
Authors: Bunn Matthew
Published: June 2024

Dark clouds loom on the nuclear horizon, with threats from all directions: Russia’s nuclear bombast in its war on Ukraine, China’s construction of hundreds of nuclear missile silos, North Korea’s missile testing, India and Pakistan’s ongoing nuclear competition, and Iran’s push toward nuclear weapons capability. In response, US policy-makers are discussing whether a further American nuclear arms buildup is needed. At the same time, evolving technologies, from hypersonic missiles to artificial intelligence, are straining military balances and may be making them more unstable. The risk of nuclear war has not been so high since the Cuban Missile Crisis.
As U.K. election nears, major parties reveal their science plans
Authors: Else Holly
Published: June 2024

All pledge support for research but would restrict immigration, dismaying researchers
B cells in perivascular and peribronchiolar granuloma-associated lymphoid tissue and B-cell signatures identify asymptomatic
Mycobacterium tuberculosis
lung infection in Diversity Outbred mice
Authors: Koyuncu Deniz , Tavolara Thomas , Gatti Daniel M. , Gower Adam C. , Ginese Melanie L. , Kramnik Igor , Yener Bülent , Sajjad Usama , Niazi Muhammad Khalid Khan , Gurcan Metin , Alsharaydeh Anas , Beamer Gillian
Published: June 2024

Because most humans resist
Mycobacterium tuberculosis
infection, there is a paucity of lung samples to study. To address this gap, we infected Diversity Outbred mice with
M. tuberculosis
and studied the lungs of mice in different disease states. After a low-dose aerosol infection, progressors succumbed to acute, inflammatory lung disease within 60 days, while controllers maintained asymptomatic infection for at least 60 days, and then developed chronic pulmonary tuberculosis (TB) lasting months to more than 1 year. Here, we identified features of asymptomatic
M. tuberculosis
infection by applying computational and statistical approaches to multimodal data sets. Cytokines and anti-
M
.
tuberculosis
cell wall antibodies discriminated progressors vs controllers with chronic pulmonary TB but could not classify mice with asymptomatic infection. However, a novel deep-learning neural network trained on lung granuloma images was able to accurately classify asymptomatically infected lungs vs acute pulmonary TB in progressors vs chronic pulmonary TB in controllers, and discrimination was based on perivascular and peribronchiolar lymphocytes. Because the discriminatory lesion was rich in lymphocytes and CD4 T cell-mediated immunity is required for resistance, we expected CD4 T-cell genes would be elevated in asymptomatic infection. However, the significantly different, highly expressed genes were from B-cell pathways (e.g.,
Bank1
,
Cd19
,
Cd79
,
Fcmr
,
Ms4a1
,
Pax5
, and
H2-Ob
), and CD20+ B cells were enriched in the perivascular and peribronchiolar regions of mice with asymptomatic
M. tuberculosis
infection. Together, these results indicate that genetically controlled B-cell responses are important for establishing asymptomatic
M. tuberculosis
lung infection.
Chemosensory systems interact to shape relevant traits for bacterial plant pathogenesis
Authors: Munar-Palmer Martí , Santamaría-Hernando Saray , Liedtke Janine , Ortega Davi R. , López-Torrejón Gema , Rodríguez-Herva José Juan , Briegel Ariane , López-Solanilla Emilia
Published: June 2024

Chemosensory systems allow bacteria to respond and adapt to environmental conditions. Many bacteria contain more than one chemosensory system, but knowledge of their specific roles in regulating different functions remains scarce. Here, we address this issue by analyzing the function of the F6, F8, and alternative (non-motility) cellular functions (ACF) chemosensory systems of the model plant pathogen
Pseudomonas syringae
pv. tomato. In this work, we assign PsPto chemoreceptors to each chemosensory system, and we visualize for the first time the F6 and F8 chemosensory systems of PsPto using cryo-electron tomography. We confirm that chemotaxis and swimming motility are controlled by the F6 system, and we demonstrate how different components from the F8 and ACF systems also modulate swimming motility. We also determine how the kinase and response regulators from the F6 and F8 chemosensory systems do not work together in the regulation of biofilm, whereas both components from the ACF system contribute together to regulate these traits. Furthermore, we show how the F6, F8, and ACF kinases interact with the ACF response regulator WspR, supporting crosstalk among chemosensory systems. Finally, we reveal how all chemosensory systems play a role in regulating virulence.

IMPORTANCE

Chemoperception through chemosensory systems is an essential feature for bacterial survival, as it allows bacterial interaction with its surrounding environment. In the case of plant pathogens, it is especially relevant to enter the host and achieve full virulence. Multiple chemosensory systems allow bacteria to display a wider plasticity in their response to external signals. Here, we perform a deep characterization of the F6, F8, and alternative (non-motility) cellular functions chemosensory systems in the model plant pathogen
Pseudomonas syringae
pv. tomato DC3000. These chemosensory systems regulate key virulence-related traits, like motility and biofilm formation. Furthermore, we unveil an unexpected crosstalk among these chemosensory systems at the level of the interaction between kinases and response regulators. This work shows novel results that contribute to the knowledge of chemosensory systems and their role in functions alternative to chemotaxis.
Complete genome sequence of three
Staphylococcus epidermidis
strains isolated from patients with skin diseases in Japan
Authors: Kawagishi Yu , Kimeu Teresia M. , Murase Kazunori , Yoshida Akemi , Minowa-Nozawa Atsuko , Nozawa Takashi , Tsuchido Yasuhiro , Noguchi Taro , Nagao Miki , Nakajima Saeko , Nakagawa Ichiro
Published: June 2024

Staphylococcus epidermidis
is a member of the human skin microbiota as a commensal organism but could be an important opportunistic pathogen for immunocompromised individuals. Here, we report the complete genome sequence of three
S
.
epidermidis
strains isolated from patients with skin diseases.
High-quality genome assembly and annotation of
Clonostachys chloroleuca
strain Cc878 using Oxford Nanopore long-read sequencing
Authors: Zhang Xin , Long Xinyuan , Xing Xiaoxing , Tai Jia , Wang Guanghui , Xu Ming , Liu Huiquan
Published: June 2024

As a noteworthy biocontrol fungus,
Clonostachys chloroleuca
currently lacks a high-quality reference genome. Here, we present the first high-quality genome assembly of
C. chloroleuca
strain Cc878 achieved through Oxford Nanopore Long-Read sequencing. The nuclear genome of Cc878 was assembled into four contigs, totaling 59.38 Mb.
BD Vaginal Panel assay results on the high-throughput BD COR system compared to the BD MAX system
Authors: Stonebraker Elizabeth , Greene Wallace , Taylor Stephanie N. , Cammarata Catherine L. , Bobenchik April , Lockamy Elizabeth
Published: June 2024

Molecular-based assays demonstrate excellent sensitivity for the detection of vaginitis causes. Here, the high-throughput BD Vaginal Panel for BD COR System (VP-COR) performance was compared to that of the predicate, BD MAX Vaginal Panel for BD MAX System (VP-MAX). Clinical or contrived samples were used to determine the agreement between VP-COR and VP-MAX. Acceptance criteria for VP-COR agreement were as follows: bacterial vaginosis (BV) required a positive percent agreement (PPA) point estimate of ≥95% and a negative percent agreement (NPA) point estimate of ≥98%;
Candida
group,
Candida glabrata
,
Candida krusei
, and
Trichomonas vaginalis
(TV) required a PPA and NPA point estimate of ≥95% [with lower bound of 95% confidence interval (95% CI) ≥90%]. PPA was 99.5% (95% CI: 97.5–100) and 97.9% (95% CI: 96.5–98.8) for BV contrived (
n
= 516) and BV clinical (
n
= 1,050) specimens, respectively. For the
Candida
group (clinical;
n
= 724),
C. glabrata
(contrived;
n
= 544),
C. krusei
(contrived;
n
= 522), and TV (clinical;
n
= 702), PPA was 99.4% (95% CI: 98.0–99.9), 100% (95% CI: 97.9–100), 100% (95% CI: 97.6–100), and 99.7% (95% CI: 98.3–100), respectively; the lowest lower bound CI value was 97.6%. NPA was >95% for BV contrived and BV clinical specimens. For the
Candida
group,
C. glabrata
,
C. krusei
, and TV, NPA was ≥98.9%; the lowest lower bound CI value was 97.3%. These results demonstrate the equivalent performance of the VP-COR assay when compared to VP-MAX.

IMPORTANCE

Vaginitis is common among women of reproductive age, resulting in around 10 million office visits a year. Diagnosis is often difficult due to its multiple causes—including bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis—as well as variation in symptom presentation. Typically, cases are identified with a combination of symptomology, medical history, physical examination, and office- or laboratory-based testing. These traditional techniques involve subjective elements and demonstrate varying sensitivity and specificity. Inaccurate or delayed diagnosis leads to continued symptoms, repeat visits, inappropriate treatment, and unnecessary costs. Alternatively, the use of molecular-based assays increases sensitivity for the detection of vaginitis causes. With the validation of the vaginal panel molecular assay on COR (a high-throughput platform), a workflow can be streamlined in high-demand laboratories while providing high sensitivity for vaginitis detection.
Supplemental Material: Coprecipitation of amorphous silica and gold nanoparticles contributes to gold hyperenrichment
Authors: McNab Rory R. , al. et
Published: June 2024

 Details of the experiment and analysis.  
Supplemental Material: Oceanic anoxic event 3 in Arctic Canada—Arc volcanism and ocean fertilization drove anoxia
Authors: Grasby Stephen , et al.
Published: June 2024

Geochemical data for samples used in this study.
Assessing the use of sodium-glucose cotransporter 2 inhibitor in patients with type 2 diabetes mellitus and chronic kidney disease in tertiary care: a SwissDiab Study
Authors: Hösli Pascale Sharon , Renström Frida , Laimer Markus , Cavelti-Weder Claudia , Gastaldi Giacomo , Lehmann Roger , Brändle Michael
Published: June 2024

Introduction

The overall aim of this study was to evaluate the implementation of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among patients in tertiary care with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).

Research design and methods

The cross-sectional analysis was based on outpatients in tertiary diabetes care enrolled in the Swiss Diabetes Registry with T2DM and a study visit January 1, 2020–March 31, 2021. Prevalence of CKD was ascertained as an estimated glomerular filtration rate <60 mL/min/1.73 m
2
and/or persistent albuminuria as defined by Kidney Disease Improving Global Outcomes, and the proportion of patients prescribed SGLT2i was determined. Documented reasons for non-treatment with SGLT2i were extracted by a retrospective review of the medical records.

Results

Of 368 patients with T2DM, 1.1% (n=4) were excluded due to missing data. Of the remaining 364 patients, 47.3% (n=172) had CKD of which 32.6% (n=56) were prescribed SGLT2i. The majority (75%) of these patients were on treatment already in 2018, before the renoprotective effects of SGLT2i were established. Among the 116 patients without SGLT2i, 19.0% had known contraindications, 9.5% stopped treatment due to adverse events, 5.2% had other reasons, and no underlying reason for non-treatment could be identified for 66.4%.

Conclusions

A divergence between recommended standard of care and implementation in daily clinical practice was observed. Although treatment should always consider patient-specific circumstances, the results highlight the need to reinforce current treatment recommendations to ensure patients benefit from the best available care.
Promising algorithms to perilous applications: a systematic review of risk stratification tools for predicting healthcare utilisation
Authors: Oddy Christopher , Zhang Joe , Morley Jessica , Ashrafian Hutan
Published: June 2024

Objectives

Risk stratification tools that predict healthcare utilisation are extensively integrated into primary care systems worldwide, forming a key component of anticipatory care pathways, where high-risk individuals are targeted by preventative interventions. Existing work broadly focuses on comparing model performance in retrospective cohorts with little attention paid to efficacy in reducing morbidity when deployed in different global contexts. We review the evidence supporting the use of such tools in real-world settings, from retrospective dataset performance to pathway evaluation.

Methods

A systematic search was undertaken to identify studies reporting the development, validation and deployment of models that predict healthcare utilisation in unselected primary care cohorts, comparable to their current real-world application.

Results

Among 3897 articles screened, 51 studies were identified evaluating 28 risk prediction models. Half underwent external validation yet only two were validated internationally. No association between validation context and model discrimination was observed. The majority of real-world evaluation studies reported no change, or indeed significant increases, in healthcare utilisation within targeted groups, with only one-third of reports demonstrating some benefit.

Discussion

While model discrimination appears satisfactorily robust to application context there is little evidence to suggest that accurate identification of high-risk individuals can be reliably translated to improvements in service delivery or morbidity.

Conclusions

The evidence does not support further integration of care pathways with costly population-level interventions based on risk prediction in unselected primary care cohorts. There is an urgent need to independently appraise the safety, efficacy and cost-effectiveness of risk prediction systems that are already widely deployed within primary care.
Anticipated and experienced stigma and discrimination in the workplace among individuals with major depressive disorder in 35 countries: qualitative framework analysis of a mixed-method cross-sectional study
Authors: Van Bortel Tine , Wickramasinghe Nuwan Darshana , Treacy Samantha , Khan Nashi , Ouali Uta , Sumathipala Athula , Svab Vesna , Nader Doaa , Kadri Nadia , Monteiro Maria Fatima , Knifton Lee , Quinn Neil , Van Audenhove Chantal , Lasalvia Antonio , Bonetto Chiara , Thornicroft Graham , van Weeghel Jaap , Brouwers Evelien
Published: June 2024

Objectives

Workplace stigmatisation and discrimination are significant barriers to accessing employment opportunities, reintegration and promotion in the workforce for people with mental illnesses in comparison to other disabilities. This paper presents qualitative evidence of anticipated and experienced workplace stigma and discrimination among individuals with major depressive disorder (MDD) in 35 countries, and how these experiences differ across countries based on their Human Development Index (HDI) level.

Design

Mixed-method cross-sectional survey.

Participants, setting and measures

The qualitative data were gathered as part of the combined European Union Anti-Stigma Programme European Network and global International Study of Discrimination and Stigma Outcomes for Depression studies examining stigma and discrimination among individuals with MDD across 35 countries. Anticipated and experienced stigma and discrimination were assessed using the Discrimination and Stigma Scale version 12 (DISC-12). This study used responses to the open-ended DISC-12 questions related to employment. Data were analysed using the framework analysis method.

Results

The framework analysis of qualitative data of 141 participants identified 6 key ‘frames’ exploring (1) participants reported experiences of workplace stigma and discrimination; (2) impact of experienced workplace stigma and discrimination; (3) anticipated workplace stigma and discrimination; (4) ways of coping; (5) positive work experiences and (6) contextualisation of workplace stigma and discrimination. In general, participants from very high HDI countries reported higher levels of anticipated and experienced discrimination than other HDI groups (eg, less understanding and support, being more avoided/shunned, stopping themselves from looking for work because of expectation and fear of discrimination). Furthermore, participants from medium/low HDI countries were more likely to report positive workplace experiences.

Conclusions

This study makes a significant contribution towards workplace stigma and discrimination among individuals with MDD, still an under-researched mental health diagnosis. These findings illuminate important relationships that may exist between countries/contexts and stigma and discrimination, identifying that individuals from very high HDI countries were more likely to report anticipated and experienced workplace discrimination.
10-year multimorbidity patterns among people with and without rheumatic and musculoskeletal diseases: an observational cohort study using linked electronic health records from Wales, UK
Authors: Jalali-najafabadi Farideh , Bailey Rowena , Lyons Jane , Akbari Ashley , Ba Dhafari Thamer , Azadbakht Narges , Rafferty James , Watkins Alan , Martin Glen Philip , Bowes John , Lyons Ronan A. , Barton Anne , Peek Niels
Published: June 2024

Objectives

To compare the patterns of multimorbidity between people with and without rheumatic and musculoskeletal diseases (RMDs) and to describe how these patterns change by age and sex over time, between 2010 and 2019.

Participants

103 426 people with RMDs and 2.9 million comparators registered in 395 Wales general practices (GPs). Each patient with an RMD aged 0–100 years between January 2010 and December 2019 registered in Clinical Practice Research Welsh practices was matched with up to five comparators without an RMD, based on age, gender and GP code.

Primary outcome measures

The prevalence of 29 Elixhauser-defined comorbidities in people with RMDs and comparators categorised by age, gender and GP practices. Conditional logistic regression models were fitted to calculate differences (OR, 95% CI) in associations with comorbidities between cohorts.

Results

The most prevalent comorbidities were cardiovascular risk factors, hypertension and diabetes. Having an RMD diagnosis was associated with a significantly higher odds for many conditions including deficiency anaemia (OR 1.39, 95% CI (1.32 to 1.46)), hypothyroidism (OR 1.34, 95% CI (1.19 to 1.50)), pulmonary circulation disorders (OR 1.39, 95% CI 1.12 to 1.73) diabetes (OR 1.17, 95% CI (1.11 to 1.23)) and fluid and electrolyte disorders (OR 1.27, 95% CI (1.17 to 1.38)). RMDs have a higher proportion of multimorbidity (two or more conditions in addition to the RMD) compared with non-RMD group (81% and 73%, respectively in 2019) and the mean number of comorbidities was higher in women from the age of 25 and 50 in men than in non-RMDs group.

Conclusion

People with RMDs are approximately 1.5 times as likely to have multimorbidity as the general population and provide a high-risk group for targeted intervention studies. The individuals with RMDs experience a greater load of coexisting health conditions, which tend to manifest at earlier ages. This phenomenon is particularly pronounced among women. Additionally, there is an under-reporting of comorbidities in individuals with RMDs.