bluuebunny/crossref_metadata_2025 huggingface dataset:
Piplartine attenuates aminoglycoside-induced TRPV1 activity and protects from hearing loss in mice
Authors: Zallocchi Marisa , Vijayakumar Sarath , Fleegel Jonathan , Batalkina Lyudmila , Brunette Katyarina E. , Shukal Dhaval , Chen Zhiyong , Devuyst Olivier , Liu Huizhan , He David Z. Z. , Imami Ali Sajid , Hamoud Abdul-Rizaq Ali , McCullumsmith Robert , Conda-Sheridan Martin , De Campos Luana Janaína , Zuo Jian
Published: August 2024

Hearing loss is a major health concern in our society, affecting more than 400 million people worldwide. Among the causes, aminoglycoside therapy can result in permanent hearing loss in 40% to 60% of patients receiving treatment, and despite these high numbers, no drug for preventing or treating this type of hearing loss has yet been approved by the US Food and Drug Administration. We have previously conducted high-throughput screenings of bioactive compounds, using zebrafish as our discovery platform, and identified piplartine as a potential therapeutic molecule. In the present study, we expanded this work and characterized piplartine’s physicochemical and therapeutic properties. We showed that piplartine had a wide therapeutic window and neither induced nephrotoxicity in vivo in zebrafish nor interfered with aminoglycoside antibacterial activity. In addition, a fluorescence-based assay demonstrated that piplartine did not inhibit cytochrome C activity in microsomes. Coadministration of piplartine protected from kanamycin-induced hair cell loss in zebrafish and protected hearing function, outer hair cells, and presynaptic ribbons in a mouse model of kanamycin ototoxicity. Last, we investigated piplartine’s mechanism of action by phospho-omics, immunoblotting, immunohistochemistry, and molecular dynamics experiments. We found an up-regulation of AKT1 signaling in the cochleas of mice cotreated with piplartine. Piplartine treatment normalized kanamycin-induced up-regulation of TRPV1 expression and modulated the gating properties of this receptor. Because aminoglycoside entrance to the inner ear is, in part, mediated by TRPV1, these results suggested that by regulating TRPV1 expression, piplartine blocked aminoglycoside’s entrance, thereby preventing the long-term deleterious effects of aminoglycoside accumulation in the inner ear compartment.
Neurotransmitter acetylcholine mediates the mummification of
Ophiocordyceps sinensis
-infected
Thitarodes xiaojinensis
larvae
Authors: Chai Wenmin , Mao Xianbing , Li Chunfeng , Zhu Liancai , He Zongyi , Wang Bochu
Published: August 2024

Parasites can manipulate host behavior to facilitate parasite transmission. One such host–pathogen interaction occurs between the fungus
Ophiocordyceps sinensis
and the ghost moth
Thitarodes xiaojinensis. O. sinensis
is involved in the mummification process of infected host larvae. However, the underlying molecular and chemical mechanism for this phenomenon is unknown. We characterized the small molecules regulating host behaviors and the altered metabolites in infected and mummified host larvae. Lipid-related metabolites, such as phosphatidylcholine, were identified in infected and mummified larvae. Decreased levels of the neurotransmitter acetylcholine (ACh) and elevated choline levels were observed in the brains of both the infected and mummified larvae. The aberrant activity of acetylcholinesterase (AChE) and relative mRNA expression of
ACE2
(acetylcholinesterase) may mediate the altered transformation between ACh and choline, leading to the brain dysfunction of mummified larvae. Caspofungin treatment inhibited the mummification of infected larvae and the activity of AChE. These findings indicate the importance of ACh in the mummification of host larvae after
O. sinensis
infection.

IMPORTANCE

Ophiocordyceps sinensis
-infected ghost moth larvae are manipulated to move to the soil surface with their heads up in death. A fruiting body then grows from the caterpillar’s head, eventually producing conidia for dispersal. However, the underlying molecular and chemical mechanism has not been characterized. In this study, we describe the metabolic profile of
Thitarodes xiaojinensis
host larvae after
O. sinensis
infection. Altered metabolites, particularly lipid-related metabolites, were identified in infected and mummified larvae, suggesting that lipids are important in
O. sinensis
-mediated behavioral manipulation of host larvae. Decreased levels of the neurotransmitter acetylcholine were observed in both infected and mummified larvae brains. This suggests that altered or reduced acetylcholine can mediate brain dysfunction and lead to aberrant behavior. These results reveal the critical role of acetylcholine in the mummification process of infected host larvae.
Inhibition of transient receptor potential vanilloid 1 reduces shedding and transmission during
Streptococcus pneumoniae
co-infection with influenza
Authors: Murakami Daichi , Kono Masamitsu , Sakatani Hideki , Iyo Takuro , Hijiya Masayoshi , Shiga Tatsuya , Kinoshita Tetsuya , Sumioka Takayoshi , Okada Yuka , Saika Shizuya , Koizumi Yusuke , Hotomi Muneki
Published: August 2024

Transmission is the first step for a microorganism to establish colonization in the respiratory tract and subsequent development of infectious disease.
Streptococcus pneumoniae
is a leading pathogen that colonizes the mucosal surfaces of the human upper respiratory tract and causes subsequent transmission and invasive infections especially in co-infection with influenza A virus. Host factors contributing to respiratory contagion are poorly understood. Transient receptor potential vanilloid (TRPV) channels have various roles in response to microoorganism. Inhibition of TRPV exacerbates invasive infection by
Streptococcus pneumoniae
, but it is unclear how TRPV channels influence pneumococcal transmission. Here, we describe the effect of inhibition of TRPV1 on pneumococcal transmission. We adopted a TRPV1-deficient infant mouse model of pneumococcal transmission during co-infection with influenza A virus. We also analyzed the expression of nasal mucin or pro-inflammatory cytokines. TRPV1 deficiency attenuated pneumococcal transmission and shedding during co-infection with influenza A virus. TRPV1 deficiency suppressed the expression of nasal mucin. In addition, there were increases in the expression of tumor necrosis factor-α and type I interferon, followed by the suppressed replication of influenza A virus in TRPV1-deficient mice. Inhibition of TRPV1 was shown to attenuate pneumococcal transmission by reducing shedding through the suppression of nasal mucin during co-infection with influenza A virus. Inhibition of TRPV1 suppressed nasal mucin by modulation of pro-inflammatory responses and regulation of replication of influenza A virus. TRPV1 could be a new target in preventive strategy against pneumococcal transmission.
Metabolic changes associated with polysaccharide utilization reduce susceptibility to some β-lactams in
Bacteroides thetaiotaomicron
Authors: Nilson Rachael , Penumutchu Swathi , Pagano Francesco S. , Belenky Peter
Published: August 2024

Antibiotic therapy alters bacterial abundance and metabolism in the gut microbiome, leading to dysbiosis and opportunistic infections.
Bacteroides thetaiotaomicron
(
Bth
) is both a commensal in the gut and an opportunistic pathogen in other body sites. Past work has shown that
Bth
responds to β-lactam treatment differently depending on the metabolic environment both
in vitro
and
in vivo
. Studies of other bacteria show that an increase in respiratory metabolism independent of growth rate promotes susceptibility to bactericidal antibiotics. We propose that
Bth
enters a protected state linked to an increase in polysaccharide utilization and a decrease in the use of simple sugars. Here, we apply antibiotic susceptibility testing, transcriptomic analysis, and genetic manipulation to characterize this polysaccharide-mediated tolerance (PM tolerance) phenotype. We found that a variety of mono- and disaccharides increased the susceptibility of
Bth
to several different β-lactams compared to polysaccharides. Transcriptomics indicated a metabolic shift from reductive to oxidative branches of the tricarboxylic acid cycle on polysaccharides. Accordingly, supplementation with intermediates of central carbon metabolism had varying effects on PM tolerance. Transcriptional analysis also showed a decrease in the expression of the electron transport chain (ETC) protein NQR and an increase in the ETC protein NUO, when given fiber versus glucose. Deletion of NQR increased
Bth
susceptibility while deletion of NUO and a third ETC protein NDH2 had no effect. This work confirms that carbon source utilization modulates antibiotic susceptibility in
Bth
and that anaerobic respiratory metabolism and the ETC play an essential role.

IMPORTANCE

Antibiotics are indispensable medications that revolutionized modern medicine. However, their effectiveness is challenged by a large array of resistance and tolerance mechanisms. Treatment with antibiotics also disrupts the gut microbiome which can adversely affect health.
Bacteroides
are prevalent in the gut microbiome and yet are frequently involved in anaerobic infections. Thus, understanding how antibiotics affect these bacteria is necessary to implement proper treatment. Recent work has investigated the role of metabolism in antibiotic susceptibility in distantly related bacteria such as
Escherichia coli
. Using antibiotic susceptibility testing, transcriptomics, and genetic manipulation, we demonstrate that polysaccharides reduce β-lactam susceptibility when compared to monosaccharides. This finding underscores the profound impact of metabolic adaptation on the therapeutic efficacy of antibiotics. In the long term, this work indicates that modulation of metabolism could make
Bacteroides
more susceptible during infections or protect them in the context of the microbiome.
Job satisfaction and psychosocial factors and their association with job performance in Iranian midwives: a cross-sectional study
Authors: Mashayekh-Amiri Sepideh , Mirghafourvand Mojgan
Published: August 2024

Background

The global shortage of midwives and their job performance can significantly affect the quality of care for mothers, newborns, and their families.

Objectives

This study aimed to determine the status of job satisfaction and psychosocial factors and their relationships with the job performance of midwives in Tabriz City, Iran.

Design

Cross-sectional study.

Setting

Urban health centres and public and private hospitals in Tabriz, Iran.

Participants

A total of 575 midwives were included in this study using census sampling from November 2022 to January 2023. Inclusion criteria were midwives with at least B.Sc. degrees and 6 months of work experience while midwives with a history of depression were excluded from the study. The occupational-social-demographic characteristics questionnaire, Copenhagen Psychosocial Questionnaire and Woman-Centred Care Scale Midwife Self-Report were used to collect data. The Pearson correlation test was used to investigate the relationship between job satisfaction and psychosocial factors in midwives’ job performance. In multivariate analysis, the general linear model (GLM) adjusting for occupational-social-demographic characteristics was also used.

Results

According to the Pearson correlation test, there was a significantly direct correlation between job satisfaction (r=0.21, p<0.001) and psychosocial factors (r=0.23, p<0.001) with job performance. Also, as suggested by the GLM, midwives’ job performance increases as job satisfaction (β=0.05, 95% CI 0.01 to 0.11, p=0.044) and psychosocial factors (β=0.13, 95% CI 0.04 to 0.23, p=0.007) increase.

Conclusions

There was a direct relationship between midwives’ job satisfaction and psychosocial factors and their job performance.
Protocol for a discrete choice experiment: understanding preferences for seeking health services for survivors of sexual violence in Uganda
Authors: Stark Lindsay , Mutumba M , Ssewamala Fred , Brathwaite Rachel , Brown Derek S , Atwebembere Raymond , Mwebembezi Abel
Published: August 2024

Introduction

Sexual violence is a significant public health concern with severe physical, social and psychological consequences, which can be mitigated by health service utilisation. However, in Uganda and much of sub-Saharan Africa, these services are significantly underused, with 9 out of 10 survivors not seeking care due to a range of psychological, cultural, economic and logistical factors. Thus, there is a strong need for research to improve health service utilisation for survivors of sexual violence.

Methods and analysis

The proposed study seeks to address the underutilization of health services for female survivors of sexual violence using a discrete choice experiment (DCE). The study will be conducted in the greater Masaka region of southwestern Uganda and target adult female survivors of sexual violence. We will first undertake qualitative interviews with 56 survivors of sexual violence to identify the key attributes and levels of the DCE. In order to ensure a sufficiently powered sample, 312 women who meet inclusion criteria will be interviewed. Our primary analysis will employ a mixed (random parameters) logit model. We will also model the role of individual-specific characteristics through latent class models.

Ethics and dissemination

The study protocol was reviewed and approved by the following ethics review boards in Uganda and the USA: the Uganda Virus Research Institute (UVRI), the Uganda National Council for Science and Technology (HS2364ES), Washington University in St Louis and the University of Michigan. Our methods conform to established guidelines for the protection of human subjects involved in research. Our dissemination plan targets a broad audience, ranging from policymakers and government agencies to healthcare providers, academic communities and survivors themselves.
Evaluating the impact of a ward environment with 20 single occupancy rooms and two four-bedded bays on patient and staff experiences and outcomes in an acute NHS Trust: a mixed-methods study protocol
Authors: Ataiyero Yetunde , Stimpson Emma , Hall Helen , Ashby Helen , Dube Alisen , Carter Vanda , Smith Hazel A , Ross Al , Copping Jacky , Morris Paul , Jones Sarahjane
Published: August 2024

Introduction

Traditionally, wards in acute care hospitals consist predominately of multioccupancy bays with some single rooms. There is an increasing global trend towards a higher proportion of single rooms in hospitals, with the UK National Health Service (NHS) advocating for single-room provision in all new hospital builds. There is limited evidence on the impact of a ward environment incorporating mostly single and some multioccupancy bays on patient care and organisational outcomes.

Methods and analyses

This study will assess the impact of a newly designed 28-bedded ward environment, with 20 single rooms and two four-bedded bays, on patient and staff experiences and outcomes in an acute NHS Trust in East England. The study is divided into two work packages (WP)—WP1 is a quantitative data extraction of routinely collected patient and staff data while WP2 is a mixed-methods process evaluation consisting of one-to-one, in-depth, semistructured interviews with staff, qualitative observations of work processes on the ward and a quantitative data evaluation of routinely collected process evaluation data from patients and staff.

Ethics and dissemination

Ethical approval was obtained from the UK Health Research Authority (IRAS ID: 334395). Study findings will be shared with key stakeholders, published in peer-reviewed high-impact journals and presented at relevant conferences.
Nurses’ perceptions of patient handoffs and predictors of patient handoff perceptions in tertiary care hospitals in Kelantan, Malaysia: a cross-sectional study
Authors: Mohd Nawawi Mohd Hanif , Ibrahim Mohd Ismail
Published: August 2024

Objectives

To study nurses’ perceptions of patient handoffs in tertiary care hospitals in Kelantan, Malaysia, and to identify predictors of these perceptions.

Design

Cross-sectional study.

Setting

Three tertiary care hospitals in Kelantan, Malaysia, February–March 2023.

Participants

The study’s inclusion criteria were nurses who were Malaysian citizens, working in shifts and possessing a minimum of 6 months of work experience. Nurses holding administrative positions and those unavailable during the study period were excluded from participation. A stratified proportionate random sampling method was employed, and a 100% response rate was achieved, with all 418 selected nurses participating in the study.

Outcome measures

Nurses’ perceptions of patient handoffs were assessed using the validated Hospital Patient Handoff Questionnaire. Predictors of these perceptions were identified through multiple linear regression analysis.

Results

The study revealed an overall positive perception of handoffs, with a mean score of 3.5 on a 1–5 scale. Receiving formal in-service training on handoff practices (regression coefficient 0.089, 95% CI: 0.016 to 0.161) and expressing satisfaction with the handoff process (regression coefficient 0.330, 95% CI: 0.234 to 0.425) were positively associated with nurses’ perceptions. Working in the paediatric department was associated with a lower perception of handoffs (regression coefficient −0.124, 95% CI: −0.195 to –0.053).

Conclusions

Formal in-service training, satisfaction and working in the paediatric department were significantly associated with nurses’ perceptions of patient handoffs in Kelantan. These findings suggest the need for tailored interventions to improve handoff processes and enhance patient safety. Further research could explore the effectiveness of specific training programmes targeting these identified predictors.
Reducing personal protective equipment waste in the emergency department of a large regional hospital: codesign informed by system science
Authors: Patrick Rebecca , Forrester Mike , Thanekar Urvi , Gunasiri Hasini , Ananthapavan Jaithri , Naebe Minoo , Naebe Maryam , Allender Steven
Published: August 2024

Background

This study aimed to bring together health workers from an emergency department (ED) and broader health system changemakers to cocreate a system-oriented understanding of the drivers of single-use personal protective equipment (PPE) waste, and recommend priority actions for government policy, and organisational change, to reduce PPE waste and transition towards a circular economy approach.

Methods

Participatory group model building was used with ED and PPE health service stakeholders to create a causal loop diagram of drivers of PPE waste and use this diagram to codesign actions to address this waste. The study setting was an ED of a large regional health service in Victoria, Australia. There were 25 participants including ED doctors, nurses and allied health staff (n=10), sustainability manager (n=1), waste management coordinator (n=1), infection prevention, (n=2) procurement leads, (n=1) external stakeholders (eg, Department of Health, and sustainability authority) (n=3), consumer representatives (n=2), and experts in materials and implementation science (n=2) life-cycle analysis (n=2) and health economics (n=1).

Results

A causal loop diagram was developed representing the drivers of PPE waste, and codeveloped solutions prioritised by feasibility and impact. Recommendations for priority actions were organised by theme, and at the level of change agent—system/policy level, healthcare organisations and academic organisation. Participants identified five key drivers of single-use PPE waste: (1) centralised state-level procurement processes limited hospital control over reusable or single-use PPE purchasing decisions; (2) lack of clarity of minimum PPE requirements for different clinical scenarios; (3) clinical capacity for cohorting infectious patients in ED; (4) waste management processes not capitalising on recyclable material; and (5) barriers to staff using optimal waste handling processes creating excessive ‘contaminated clinical waste.’ A comprehensive set of recommendations were made by staff to address these issues.

Conclusion

This study provides new insights into drivers and coproduced potential solutions to the reduction of PPE waste in a hospital ED.
Burden of unintentional drowning in Indonesia: insights from the Global Burden of Disease Study 2019
Authors: Cenderadewi Muthia , Devine Susan G , Peden Amy E , Franklin Richard Charles
Published: August 2024

Introduction

A high burden of unintentional fatal drowning has been reported in low- and middle-income countries. However, little is known about unintentional drowning in Indonesia.

Methods

This population-based retrospective cohort study analysed unintentional drowning data for Indonesia sourced from The Global Burden of Disease Study 2019. Estimates of trends, mortality rates, incidence rates, years lived with disability (YLDs) and disability adjusted life years were generated.

Results

A decline in unintentional drowning mortality rates was observed, with an average annual mortality rate of 2.58/100 000. Males were 1.81 (95% CI 1.79 to 1.84) times more likely than females to unintentionally drown. Average annual mortality rates were highest among the under-5 age group (9.67/100 000) and 70 and over (5.71/100 000 for males; 5.14/100 000 for females). Distributions of drowning deaths vary depending on region, with mortality rates higher in Papua, Kalimantan, Sulawesi, Maluku, Sumatra and Nusa Tenggara regions.

Discussion

While a decline in drowning mortality rates in Indonesia was identified between 2005 and 2019, mortality rates for unintentional drowning remained high among children under 5 years, the elderly population and those residing in Papua, Kalimantan, Sulawesi, Maluku, Sumatra and Nusa Tenggara, warranting further focused attention.

Conclusion

A downward trend in the rate of unintentional drowning deaths in Indonesia is observed from 2005 onwards, with risk variation based on age, gender and region. The findings highlight the importance of addressing drowning as a cause of premature mortality and health system burden in Indonesia, including through enhancing drowning data collection systems and identifying drowning risk factors.
Randomized, open-label, phase 2 study of nivolumab plus ipilimumab or nivolumab monotherapy in patients with advanced or metastatic solid tumors of high tumor mutational burden
Authors: Schenker Michael , Burotto Mauricio , Richardet Martin , Ciuleanu Tudor-Eliade , Gonçalves Anthony , Steeghs Neeltje , Schoffski Patrick , Ascierto Paolo A , Maio Michele , Lugowska Iwona , Lupinacci Lorena , Leary Alexandra , Delord Jean-Pierre , Grasselli Julieta , Tan David S P , Friedmann Jennifer , Vuky Jacqueline , Tschaika Marina , Konduru Somasekhar , Vemula Sai Vikram , Slepetis Ruta , Kollia Georgia , Pacius Misena , Duong Quyen , Huang Ning , Doshi Parul , Baden Jonathan , Di Nicola Massimo
Published: August 2024

Background

Checkpoint inhibitor therapy has demonstrated overall survival benefit in multiple tumor types. Tumor mutational burden (TMB) is a predictive biomarker for response to immunotherapies. This study evaluated the efficacy of nivolumab+ipilimumab in multiple tumor types based on TMB status evaluated using either tumor tissue (tTMB) or circulating tumor DNA in the blood (bTMB).

Patients and methods

Patients with metastatic or unresectable solid tumors with high (≥10 mutations per megabase) tTMB (tTMB-H) and/or bTMB (bTMB-H) who were refractory to standard therapies were randomized 2:1 to receive nivolumab+ipilimumab or nivolumab monotherapy in an open-label, phase 2 study (CheckMate 848;NCT03668119). tTMB and bTMB were determined by the Foundation Medicine FoundationOne®CDx test and bTMB Clinical Trial Assay, respectively. The dual primary endpoints were objective response rate (ORR) in patients with tTMB-H and/or bTMB-H tumors treated with nivolumab+ipilimumab.

Results

In total, 201 patients refractory to standard therapies were randomized: 135 had tTMB-H and 125 had bTMB-H; 82 patients had dual tTMB-H/bTMB-H. In patients with tTMB-H, ORR was 38.6% (95% CI 28.4% to 49.6%) with nivolumab+ipilimumab and 29.8% (95% CI 17.3% to 44.9%) with nivolumab monotherapy. In patients with bTMB-H, ORR was 22.5% (95% CI 13.9% to 33.2%) with nivolumab+ipilimumab and 15.6% (95% CI 6.5% to 29.5%) with nivolumab monotherapy. Early and durable responses to treatment with nivolumab+ipilimumab were seen in patients with tTMB-H or bTMB-H. The safety profile of nivolumab+ipilimumab was manageable, with no new safety signals.

Conclusions

Patients with metastatic or unresectable solid tumors with TMB-H, as determined by tissue biopsy or by blood sample when tissue biopsy is unavailable, who have no other treatment options, may benefit from nivolumab+ipilimumab.

Trial registration number

NCT03668119.
Relationship between cumulative silica exposure and silicosis: a systematic review and dose-response meta-analysis
Authors: Howlett Patrick , Gan Jeffrey , Lesosky Maia , Feary Johanna
Published: August 2024

Background

Silicosis, a chronic respiratory disease caused by crystalline silica exposure, is a persistent global lung health issue. No systematic review of the relationship between cumulative respirable crystalline silica (RCS) exposure and silicosis exists. UK exposure limits are currently under review. We therefore performed a systematic review and dose-response meta-analysis of this relationship.

Methods

Web of Science, Medline and Embase were searched on 24 February 2023. Studies of radiographic, autopsy or death certificate silicosis, with an estimated average follow-up of over 20 years since first employment, were included. Cumulative silicosis risk methods were compared. The relative risks (RR) of silicosis at increasing cumulative exposures were calculated and used to estimate the absolute risk reduction (ARR).

Results

Eight eligible studies, including 10 cohorts, contributed 8792 cases of silicosis among 65 977 participants. Substantial differences in cumulative risk estimates between methodologies exist. Using the same method, we observed higher cumulative silicosis risks among mining compared with non-mining cohorts. A reduction from 4 to 2 mg/m³-years in cumulative RCS exposure corresponded to substantial risk reductions among miners (RR 0.23 (95% CI 0.18 to 0.29, I2=92.9%) with an ARR of 323 (95% CI 298 to 344) per 1000) and non-miners (RR 0.55 (95% CI 0.36 to 0.83, I2=77.0%) with an ARR of 23 (95% CI 9 to 33) per 1000).

Conclusion

Despite significant heterogeneity, our findings support a reduction in permissible exposure limits from 0.1 mg/m3to 0.05 mg/m³, particularly among mining populations. Further research is needed among non-miners as only two studies were eligible.
Prairie soil improves wheat establishment and accelerates the developmental transition to flowering compared to agricultural soils
Authors: Petipas Renee H. , Peru Cassidy , Parks Janice M. , Friesen Maren L. , Jack Chandra N.
Published: August 2024

Less than 1% of native prairie lands remain in the United States. Located in eastern Washington, the rare habitat called Palouse prairie was largely converted to wheat monocropping. With this conversion came numerous physical, chemical, and biological changes to the soil that may ultimately contribute to reduced wheat yields. Here, we explored how wheat ( Tritcum aestivum L.) seedling establishment, plant size, and heading, signifying the developmental transition to flowering, were affected by being planted in prairie soil versus agricultural soils. We then sought to understand whether the observed effects were the result of changes to the soil microbiota due to agricultural intensification. We found that prairie soil enhanced both the probability of wheat seedling survival and heading compared to agricultural soil; however, wheat growth was largely unaffected by soil source. We did not detect effects on wheat developmental transitions or phenotype when inoculated with prairie microbes compared with agricultural microbes, but we did observe general antagonistic effects of microbes on plant size, regardless of soil source. This work indicates that agricultural intensification has affected soils in a way that changes early seedling establishment and the timing of heading for wheat, but these effects may not be caused by microbes, and instead may be caused by soil nutrient conditions.
Economic response of potato to nitrogen rate, timing of nitrogen application, cultivar, and irrigation
Authors: Khakbazan Mohammad , Mohr Ramona M. , Tomasiewicz Dale J. , Nelson Alison , Bizimungu Benoit
Published: August 2024

Three multiyear studies were conducted in Manitoba, Canada to evaluate the effect of nitrogen (N) fertilizer rate (ranging from 0 to 225 or 0 to 240 kg N ha−1) and its interactions with timing of N application (preplant, split application), cultivar (Russet Burbank (RB), Glacier Fryer (GF), Umatilla Russet (UR)), and moisture regime (irrigated, nonirrigated) on the yield and net revenue (NR) of potato ( Solanum tuberosum L.). Based on soil test N, all sites were expected to be N-responsive, with soil test N at most sites ranging from 24 to 45 kg NO3-N ha−1 to 60 cm and measuring 70 and 117 kg NO3-N ha−1 to 60 cm at the remaining two sites. Linear and quadratic coefficients of N and irrigation were significant for yield and NR. However, the NR curves for N inputs were relatively flat, and the NRs were only slightly less than the optimal NR within the vicinity of the optimum. Split N applications performed similarly to preplant N, and GF performed better than RB or UR; however, GF optimal economic N rates were about 55% higher than the optimal economic N rates of RB and UR cultivars. Optimal economic N rate for the best potato practices ranged from 157 to 216 kg N ha−1, depending on the studies; or averaging at about 188 kg N ha−1. Adoption of these best N management practices will improve profitability and N use efficiency in potato production and reduce negative environmental impacts.
Relationship of seeding rate to biological nitrogen fixation and seed production of red clover in Saskatchewan
Authors: Malamura Dan , Biligetu Bill , Prager Sean M.
Published: August 2024

In Saskatchewan, red clover ( Trifolium pratense L.) is often grown for seed production. However, there is no recognized or data supported seeding rate for seed production of red clover in Saskatchwan. The objectives of this study were to identify an optimal seeding rate for seed production and biological nitrogen fixation (BNF) and to examine their relationships under semi-arid conditions. This experiment was conducted under field conditions using six different seeding rates (0.5, 2.5, 4.5, 6.5, 8.5, and 10.5 kg ha−1) at Melfort and Clavet, SK in 2018 and 2019, and seed yield, biomass, plant density, and BNF were measured. In our study, red clover was able to compensate for the range of seeding rates between 2.5 and 10.5 kg ha−1 without seed yield loss and BNF reduction, whereas biomass production and BNF were higher at 4.5 kg ha−1 seeding rate than in 0.5 kg ha−1 at Melfort, but no seeding rate effects were found at Clavet. Regardless of location, biomass was always positively correlated with BNF. However, no association was found between seed yield and BNF. Our results suggest that 4.5 kg ha−1 is ideal for seed production, BNF and biomass production of red clover in Saskatchewan.
Euclidean quantum wormholes
Authors: Rahaman Farook , Choudhury Bikramarka S. , Islam Anikul
Published: August 2024

We study wormhole as the solution of the Wheeler–DeWitt (WdW) equation satisfying Hawking–Page wormhole boundary conditions in Friedmann–Robertson–Walker (FRW) cosmology. The quantum wormholes are formulated with arbitrary factor ordering of the Hamiltonian constraint operators with perfect fluid matter sources as well as minimally coupled scalar fields.
STABILITY AND BIFURCATION ANALYSIS OF A SIMPLE DELAYED p53-Mdm2 GENE NETWORK MODEL WITH DIFFUSION
Authors: YANG HONGLI , HUO RUIMIN , LIU NAN , YANG LIANGUI
Published: August 2024

p53 is a star protein in cancer biology, and its oscillatory dynamics have received much attention. However, most studies do not consider spatial effects. For this reason, we introduce the diffusion term in a classical p53-Mdm2 autoregulatory loop model. First, the equation is linearized at the positive equilibrium so that we can discuss the local asymptotic stability of this equilibrium. By taking the delay as a bifurcation parameter, the positive equilibrium transitions from stable to unstable and occurs a Hopf bifurcation. Second, we determine the stability of the bifurcating period solution by using a multiple time scales approach. Finally, the theoretical analysis is verified by the numerical simulations. Our study contributes to providing new insight in the controlling of p53 dynamics.
Report on the 46th European Conference on Information Retrieval (ECIR 2024)
Authors: McDonald Graham , Macdonald Craig , Ounis Iadh
Published: August 2024

The 46
th
European Conference on Information Retrieval (ECIR 2024) was held in Glasgow, Scotland, during 24
th
-28
th
March 2024. The conference brought together over four hundred researchers from the UK, Europe and abroad. ECIR 2024 was a fully in-person conference with a total of 417 attendees, the largest number of in-person attendees of any ECIR. The conference received over 700 submissions, not including submissions to the workshops (280 Full Paper and 184 Short paper submissions). ECIR 2024 introduced a number of novelties, including a new Findings track, an IR4Good track, a new innovation called the "Collab-athon" to foster collaborations within the community, and the Keith van Rijsbergen Award to recognise researchers who have made significant contributions in using theory to advance the field of information retrieval. This report details the conference programme and events.

Date
: 24--28 March 2024.

Website
: https://www.ecir2024.org.
Report on the 1st Workshop on Information Retrieval for Understudied Users (IR4U2 2024) at ECIR 2024
Authors: Pera Maria Soledad , Murgia Emiliana , Landoni Monica , Cena Federica , Mauro Noemi , Huibers Theo
Published: August 2024

In this report, we summarise the program and takeaways from the 1

st

edition of the Workshop on Information Retrieval for Understudied Users (IR4U2), co-located with the 46

th

European Conference on Information Retrieval (ECIR).

Date
: 24 March 2024.

Website
: https://ir4u2workshop.wixsite.com/ir4u2.
Bridging the Gap Between Information Seeking and Product Search Systems: Q&A Recommendation for E-Commerce
Authors: Kuzi Saar , Malmasi Shervin
Published: August 2024

Consumers on a shopping mission often leverage both product search and information seeking systems, such as web search engines and Question Answering (QA) systems, in an iterative process to improve their understanding of available products and reach a purchase decision. While product search is useful for shoppers to find the actual products meeting their requirements in the catalog, information seeking systems can be utilized to answer any questions they may have to refine those requirements. The recent success of Large Language Models (LLMs) has opened up an opportunity to bridge the gap between the two tasks to help customers achieve their goals quickly and effectively by integrating conversational QA within product search. In this paper, we propose to recommend users Question-Answer (Q&A) pairs that are relevant to their product search and can help them make a purchase decision. We discuss the different aspects of the problem including the requirements and characteristics of the Q&A pairs, their generation, and the optimization of the Q&A recommendation task. We highlight the challenges, open problems, and suggested solutions to encourage future research in this emerging area.
Cement and Alternatives in the Anthropocene
Authors: Miller Sabbie A. , Juenger Maria , Kurtis Kimberly E. , Weiss Jason
Published: August 2024

Globally, the production of concrete is responsible for 5% to 8% of anthropogenic CO2 emissions. Cement, a primary ingredient in concrete, forms a glue that holds concrete together when combined with water. Cement embodies approximately 90% of the greenhouse gas emissions associated with concrete production, and decarbonization methods focus primarily on cement production. But mitigation strategies can accrue throughout the concrete life cycle. Decarbonization strategies in cement manufacture, use, and disposal can be rapidly implemented to address the global challenge of equitably meeting societal needs and climate goals. This review describes (a) the development of our reliance on cement and concrete and the consequent environmental impacts, (b) pathways to decarbonization throughout the concrete value chain, and (c) alternative resources that can be leveraged to further reduce emissions while meeting global demands. We close by highlighting a research agenda to mitigate the climate damages from our continued dependence on cement.
Innovative Strategies to Study the Pathogenesis of Elusive Spirochetes and Difficulties Managing the Chronic Infections They Cause
Authors: Moustafa Mohamed Abdallah Mohamed , Schlachter Samantha , Parveen Nikhat
Published: August 2024

The major human spirochetal pathogens (Leptospira, Borrelia, and Treponema) are difficult to diagnose and lack vaccines to prevent infections. Infection by these spirochetes does not generate general protective immunity, allowing reinfection by different strains to occur. These stealth pathogens have uncommon physiology, pathogenesis, and clinical presentations and possess unique immune evasion mechanisms to facilitate their host adaptation and persistence. Collectively, host–spirochete interactions orchestrate systemic infections in a manner distinct from organ- and tissue-specific diseases caused by many bacterial pathogens. Difficulties in growing and genetic manipulation of infectious spirochetes have hindered the full understanding of their virulence factors despite decades to centuries of research. This article highlights the current understanding of the intricacies of spirochetal pathogenesis and diseases. Our comprehensive review of the progress versus gaps in knowledge lays a foundation for researchers to direct their studies toward the development of effective diagnostics and vaccines to protect patients from serious, chronic spirochetal diseases.
Ion-channel degeneracy and heterogeneities in the emergence of signature physiological characteristics of dentate gyrus granule cells
Authors: Kumari Sanjna , Narayanan Rishikesh
Published: August 2024

A recent study from our laboratory had demonstrated pronounced heterogeneities in a set of 17 electrophysiological measurements obtained from a large population of rat hippocampal granule cells. Here, we demonstrate the manifestation of ion-channel degeneracy in a heterogeneous population of morphologically realistic conductance-based granule cell models that were validated against these measurements and their cross-dependencies. Our analyses show that single neurons are complex entities whose functions emerge through intricate interactions among several functionally specialized subsystems.
Task-relevant visual feedback uncertainty attenuates visuomotor adaptation
Authors: Casasnovas Virginia , Amann Lukas K. , Haas Gianna L. , Gail Alexander
Published: August 2024

Motor adaptation is linked to the estimation of our actions. Whereas uncertainty of task-irrelevant visual feedback appears not to influence implicit adaptation for errors beyond a certain size, here we tested whether this is still the case for task-relevant feedback. We show that implicit adaptation is attenuated when task-relevant visual feedback is uncertain, suggesting a dependency on the assessment of not just sensory prediction errors but also target errors.
Sympathetic response following unannounced loss of balance during walking in young adults: laboratory study
Authors: Meir Gil , Katz Amos , Berdichevsky Yuliya , Reiner-Benaim Anat , Melzer Itshak
Published: August 2024

Up to date, the literature typically provides information about sympathetic nervous system activity and relatively static balance. We believe that exposing participants to a balance loss during walking, i.e., unexpected perturbation, provides a more ecologically valid situation to measure sympathetic nervous system response; this provides new and vital knowledge that can have a significant impact and understanding of how the SNS responds to a loss of balance in a real-life situation.
Superior performance by two new methods in identifying the online reaction time of reaching movements
Authors: Tanis Daniel , Kurtzer Isaac
Published: August 2024

Advancing our understanding of visual feedback control requires methods that accurately identify the onset of corrective action. We developed a modified regression approach and a template-based approach to identify the online reaction time of single-reaching movements. Both outperform previous methods when challenged by temporal jitter in the response onset and increased background noise.
The Effect of Endotoxin‐Induced Inflammation on the Activity of the Somatotropic Axis in Sheep
Authors: Wójcik Maciej , Zieba Dorota Anna , Bochenek Joanna , Krawczyńska Agata , Barszcz Marcin , Gajewska Alina , Antushevich Hanna , Herman Andrzej Przemysław
Published: August 2024

The hypothalamic‐pituitary‐somatotropic (HPS) axis controls many physiological and pathophysiological processes. The phenomenon of insensitivity to growth hormone resistance (GHres) was previously reported to be due to the development of inflammation. Therefore, the primary aim of the study was to determine the impact of inflammation caused by lipopolysaccharides (LPS) on the secretory activity of the HPS axis in sheep. The further goal was to determine the effect of inflammatory factors on individual components involved in intracellular signal transduction to GH via the GH receptor (GHR). The research was carried out on 24 seasonal sheep kept under a short‐day photoperiod, randomly divided into two groups. Before the experiment, the sheep estrous cycles were synchronized. The results of the current study in a sheep model showed that inflammation impairs the activity of the somatotropic axis. On the one hand, LPS injection stimulated (p < 0.01) GH secretion, and on the other hand, it reduced the liver’s sensitivity to this hormone by directly reducing (p < 0.01) GHR expression and activating the GHR inhibitory signal transduction mechanism. A symptom of such an inhibitory postreceptor signaling pathway may be due to an increase in SOCS3 expression (p < 0.01). The effect of various inhibition pathways is a significant reduction in the expression of the main transcription activator IGF1‐STAT5B (p < 0.05). The action of GHres in the liver resulted in the inhibition of IGF1 secretion, which in the long term may have negative consequences for growth and development. Our study suggests that disruption of the GH cell signaling pathway may be one of the important elements of the pathophysiology of inflammation. It can suppress growth and hepatic metabolism to spare energy expenditure.
Supplemental Table 4 from Personalized ctDNA for Monitoring Disease Status in Head and Neck Squamous Cell Carcinoma
Authors: Hanna Glenn J. , Dennis Michael J. , Scarfo Nicole , Mullin Michelle S. , Sethi Rosh K.V. , Sehgal Kartik , Annino Donald J. , Goguen Laura A. , Haddad Robert I. , Tishler Roy B. , Margalit Danielle N. , Uppaluri Ravindra , Schoenfeld Jonathan D. , Rettig Eleni M.
Published: August 2024

Supplemental Table 4. Summary of Test Performance Measures.
Supplemental Table 2 from Personalized ctDNA for Monitoring Disease Status in Head and Neck Squamous Cell Carcinoma
Authors: Hanna Glenn J. , Dennis Michael J. , Scarfo Nicole , Mullin Michelle S. , Sethi Rosh K.V. , Sehgal Kartik , Annino Donald J. , Goguen Laura A. , Haddad Robert I. , Tishler Roy B. , Margalit Danielle N. , Uppaluri Ravindra , Schoenfeld Jonathan D. , Rettig Eleni M.
Published: August 2024

Supplemental Table 2. Impact of clinical features on pre-treatment ctDNA values.
Figure 2 from Senescence Rewires Microenvironment Sensing to Facilitate Antitumor Immunity
Authors: Chen Hsuan-An , Ho Yu-Jui , Mezzadra Riccardo , Adrover Jose M. , Smolkin Ryan , Zhu Changyu , Woess Katharina , Bernstein Nicholas , Schmitt Georgia , Fong Linda , Luan Wei , Wuest Alexandra , Tian Sha , Li Xiang , Broderick Caroline , Hendrickson Ronald C. , Egeblad Mikala , Chen Zhenghao , Alonso-Curbelo Direna , Lowe Scott W.
Published: August 2024

Senescence triggers an immune evasion-to-immune recognition tumor switch. A, Representative images of CD45 and GFP staining marking immune cells and tumor cells, respectively, in p53-suppressed and p53-restored tumor (7 days after p53 restoration). Right, the quantification of the area of CD45+ staining calculated from 3 random fields per mouse. Each dot represents a mouse. B, Flow cytometry analysis of the global immune landscape in an orthotopic NSP liver tumor model. Immunophenotyping of senescent tumors is performed 9 days after Dox withdrawal, a time point when the senescent state is fully established, yet preceding the massive tumor regression. G-MDSC, granulocytic myeloid-derived suppressor cells; M-MDSC, monocytic myeloid-derived suppressor cells. Data are pooled from 2 independent experiments, with n = 7 in the proliferating group and n = 9 in the senescent group. Note that, as the absolute number of CD45+ cells increases in senescent NSP tumor lesions (A), so do the total numbers of the indicated cell types. C, Flow cytometry analysis of CD8 T cells. Data are pooled from 2 independent experiments, with n = 11 in the proliferating and n = 10 in the senescent groups. Experiments were performed 9 days after Dox withdrawal. D, Representative tissue clearing images of the orthotopic NSP liver tumors. T cells, neutrophils, and vasculature are labeled by CD3, MPO, and CD31 staining, respectively. Samples were collected 9 days after Dox withdrawal. E, Tumor size change measured by ultrasound upon p53 restoration in mice after depleting specific immune cell types using antibodies or drugs. F, Left, uniform manifold approximation and projection (UMAP) plot of CD8 T cells isolated from p53-suppressed proliferating (PRO) and p53-reactivated senescent (SEN) tumors. Right, gene set enrichment analysis of T-cell exhaustion marker genes in CD8+ T cells from proliferating (p53-suppressed) versus senescent (p53-reactivated) tumors. NES, normalized enrichment score; Pval, P value. G, UMAP plot of the expression of selected genes (Cd8a, Cd44, Tnfrsf9, Cd69, Tox, and Fasl) between CD8 T cells isolated from senescent (p53-reactivated) and proliferating (p53-suppressed) tumors. H, Representative immunofluorescence images of CD8 T cells and F4/80-positive macrophage staining in the orthotopic NSP liver tumor. Tumor samples were collected 9 days after Dox withdrawal. Data are presented as mean ± SEM. All scale bars, 100 μm. A two-tailed Student t test was used. *, P < 0.05; **, P < 0.01.
Supplementary Figure 8 from Molecular Pathways and Cellular Subsets Associated with Adverse Clinical Outcomes in Overlapping Immune-Related Myocarditis and Myositis
Authors: Siddiqui Bilal A. , Palaskas Nicolas L. , Basu Sreyashi , Dai Yibo , He Zhong , Yadav Shalini S. , Allison James P. , Sheth Rahul A. , Tummala Sudhakar , Buja Maximilian , Bhattacharjee Meenakshi B. , Iliescu Cezar , Rawther-Karedath Anishia , Deswal Anita , Wang Linghua , Sharma Padmanee , Subudhi Sumit K.
Published: August 2024

Single cell TCR sequencing (scRNASeq) from patient cardiac and skeletal muscle tissue
Supplementary Figure 16 from Molecular Pathways and Cellular Subsets Associated with Adverse Clinical Outcomes in Overlapping Immune-Related Myocarditis and Myositis
Authors: Siddiqui Bilal A. , Palaskas Nicolas L. , Basu Sreyashi , Dai Yibo , He Zhong , Yadav Shalini S. , Allison James P. , Sheth Rahul A. , Tummala Sudhakar , Buja Maximilian , Bhattacharjee Meenakshi B. , Iliescu Cezar , Rawther-Karedath Anishia , Deswal Anita , Wang Linghua , Sharma Padmanee , Subudhi Sumit K.
Published: August 2024

Cell-cell communication analysis from fibroblasts, endothelial cells, and myeloid cells to cytotoxic T cells in myocarditis