bluuebunny/crossref_metadata_2025 huggingface dataset:
An antibiotic preorganized for ribosomal binding overcomes antimicrobial resistance
Authors: Wu Kelvin J. Y. , Tresco Ben I. C. , Ramkissoon Antonio , Aleksandrova Elena V. , Syroegin Egor A. , See Dominic N. Y. , Liow Priscilla , Dittemore Georgia A. , Yu Meiyi , Testolin Giambattista , Mitcheltree Matthew J. , Liu Richard Y. , Svetlov Maxim S. , Polikanov Yury S. , Myers Andrew G.
Published: February 2024

We report the design conception, chemical synthesis, and microbiological evaluation of the bridged macrobicyclic antibiotic cresomycin (CRM), which overcomes evolutionarily diverse forms of antimicrobial resistance that render modern antibiotics ineffective. CRM exhibits in vitro and in vivo efficacy against both Gram-positive and Gram-negative bacteria, including multidrug-resistant strains of
Staphylococcus aureus
,
Escherichia coli
, and
Pseudomonas aeruginosa
. We show that CRM is highly preorganized for ribosomal binding by determining its density functional theory–calculated, solution-state, solid-state, and (wild-type) ribosome-bound structures, which all align identically within the macrobicyclic subunits. Lastly, we report two additional x-ray crystal structures of CRM in complex with bacterial ribosomes separately modified by the ribosomal RNA methylases, chloramphenicol-florfenicol resistance (Cfr) and erythromycin-resistance ribosomal RNA methylase (Erm), revealing concessive adjustments by the target and antibiotic that permit CRM to maintain binding where other antibiotics fail.
What’s at stake for science in ‘abortion pill’ case
Authors: Wadman Meredith
Published: February 2024

Supreme Court decision this summer could gut FDA’s authority over drugs
The unique salt bridge network in GlacPETase: a key to its stability
Authors: Qi Xiaoyan , Wu Yanfei , Zhang Shu-Ting , Yin Chao-Fan , Ji Mukan , Liu Yongqin , Xu Ying , Zhou Ning-Yi
Published: February 2024

The extensive accumulation of polyethylene terephthalate (PET) has become a critical environmental issue. PET hydrolases can break down PET into its building blocks. Recently, we identified a glacial PET hydrolase GlacPETase sharing less than 31% amino acid identity with any known PET hydrolases. In this study, the crystal structure of GlacPETase was determined at 1.8 Å resolution, revealing unique structural features including a distinctive N-terminal disulfide bond and a specific salt bridge network. Site-directed mutagenesis demonstrated that the disruption of the N-terminal disulfide bond did not reduce GlacPETase’s thermostability or its catalytic activity on PET. However, mutations in the salt bridges resulted in changes in melting temperature ranging from −8°C to +2°C and the activity on PET ranging from 17.5% to 145.5% compared to the wild type. Molecular dynamics simulations revealed that these salt bridges stabilized the GlacPETase’s structure by maintaining their surrounding structure. Phylogenetic analysis indicated that GlacPETase represented a distinct branch within PET hydrolases-like proteins, with the salt bridges and disulfide bonds in this branch being relatively conserved. This research contributed to the improvement of our comprehension of the structural mechanisms that dictate the thermostability of PET hydrolases, highlighting the diverse characteristics and adaptability observed within PET hydrolases.

IMPORTANCE

The pervasive problem of polyethylene terephthalate (PET) pollution in various terrestrial and marine environments is widely acknowledged and continues to escalate. PET hydrolases, such as GlacPETase in this study, offered a solution for breaking down PET. Its unique origin and less than 31% identity with any known PET hydrolases have driven us to resolve its structure. Here, we report the correlation between its unique structure and biochemical properties, focusing on an N-terminal disulfide bond and specific salt bridges. Through site-directed mutagenesis experiments and molecular dynamics simulations, the roles of the N-terminal disulfide bond and salt bridges were elucidated in GlacPETase. This research enhanced our understanding of the role of salt bridges in the thermostability of PET hydrolases, providing a valuable reference for the future engineering of PET hydrolases.
Nairovirus polymerase mutations associated with the establishment of persistent infection in human cells
Authors: Ohta Keisuke , Saka Naoki , Nishi Yuzuha , Nishio Machiko
Published: February 2024

Crimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne virus of the
Orthonairovirus
genus, persistently infects tick cells. It has been reported to establish persistent infection in non-human primates, but virological analysis has not yet been performed in human cells. Here, we investigated whether and how nairoviruses persistently infect human cells using Hazara orthonairovirus (HAZV), a surrogate model for CCHFV. We established a human cell line that was persistently infected with HAZV. Surprisingly, virions of persistently infected HAZV (HAZVpi) were not observed in the culture supernatants. There were five mutations (mut1, mut2, mut3, mut4, and mut5) in L protein of HAZVpi. Mutations in L protein of HAZVpi contribute to non-detection of virion in the supernatants. Lmut4 was found to cause low viral growth rate, despite its high polymerase activity. The low growth rate was restored by Lmut2, Lmut3, and Lmut5. The polymerase activity of Lmut1 was extremely low, and recombinant HAZV carrying Lmut1 (rHAZV/Lmut1) was not released into the supernatants. However, genomes of rHAZV/Lmut1 were retained in the infected cells. All mutations (Lmut1-5) found in L protein of HAZVpi were required for experimental reproduction of HAZVpi, and only Lmut1 and Lmut4 were insufficient. We demonstrated that point mutations in viral polymerase contribute to the establishment of persistent HAZV infection. Furthermore, innate immunity was found to be suppressed in HAZVpi-infected cells, which also potentially contributes to viral persistence. This is the first presentation of a possible mechanism behind how nairoviruses establish persistent infection in human cells.

IMPORTANCE

We investigated whether and how nairoviruses persistently infect human cells, using Hazara orthonairovirus (HAZV), a surrogate model for Crimean-Congo hemorrhagic fever virus. We established a human cell line that was persistently infected with HAZV. Five mutations were found in L protein of persistently infected HAZV (HAZVpi): mut1, mut2, mut3, mut4, and mut5. Among them, Lmut1 and Lmut4 restricted viral growth by low polymerase activity and low growth rate, respectively, leading to inhibition of viral overgrowth. The restriction of viral growth caused by Lmut1 and Lmut4 was compensated by other mutations, including Lmut2, Lmut3, and Lmut5. Each of the mutations found in L protein of HAZVpi was concluded to cooperatively modulate viral growth, which facilitates the establishment of persistent infection. Suppression of innate immunity also potentially contributes to virus persistence. This is the first presentation of a possible mechanism behind how nairoviruses establish persistent infection in human cells.
An intranasal influenza virus vector vaccine protects against
Helicobacter pylori
in mice
Authors: Nie Longyu , Huang Yu , Cheng Zhikui , Luo Hao , Zhan Yuxin , Dou Kaiwen , Ma Caijiao , Yu Chen , Luo Chuanjin , Liu Zhiqiang , Liu Shi , Zhu Ying
Published: February 2024

Helicobacter pylori
is a human pathogen that infects almost half of the population. Antibiotic resistance in
H. pylori
threatens health and increases the demand for prophylactic and therapeutic vaccines. Traditional oral vaccine research faces considerable challenges because of the epithelial barrier, potential enterotoxicity of adjuvants, and the challenging conditions of the gastric environment. We developed an intranasal influenza A virus (IAV) vector vaccine based on two live attenuated influenza viruses with modified acidic polymerase protein (PA) genes encoding the A subunit of
H. pylori
neutrophil-activating protein (NapA), named IAV-NapA, including influenza virus A/WSN/33 (WSN)-NapA and A/Puerto Rico/8/34 (PR8)-NapA. These recombinant influenza viruses were highly attenuated and exhibited strong immunogenicity in mice. Vaccination with IAV-NapA induced antigen-specific humoral and mucosal immune responses while stimulating robust Th1 and Th17 cell immune responses in mice. Our findings suggest that prophylactic and therapeutic vaccination with influenza virus vector vaccines significantly reduces colonization of
H. pylori
and inflammation in the stomach of mice.

IMPORTANCE

Helicobacter pylori
is the most common cause of chronic gastritis and leads to severe gastroduodenal pathology in some patients. Many studies have shown that Th1 and Th17 cellular and gastric mucosal immune responses are critical in reducing
H. pylori
load. IAV vector vaccines can stimulate these immune responses while overcoming potential adjuvant toxicity and antigen dosing issues. To date, no studies have demonstrated the role of live attenuated IAV vector vaccines in preventing and treating
H. pylori
infection. Our work indicates that vaccination with IAV-NapA induces antigen-specific humoral, cellular, and mucosal immunity, producing a protective and therapeutic effect against
H. pylori
infection in BALB/c mice. This undescribed
H. pylori
vaccination approach may provide valuable information for developing vaccines against
H. pylori
infection.
Draft genome sequence of
Exiguobacterium
sp. strain MMG028 isolated from a salt marsh
Authors: Farrell Morgan V. , Airkin Mina Y. , Ali Tatyana N. , Altoblani Zainalabdin S. , Bowman Chynna R. , Diaz Abigail Anne B. , Faurot Paul F. , Frausto Joshua E. , Haji Sazan F. , Hamad Basma A. , Lively James B. , Luistro Daniella Corene C. , Macias Yvette , Mathew Steffy , McKinley Kayla M. , Nasirimoseloo Somayeh , Tran Bradley P. , Trinh Amanda N. , Shikuma Nicholas J.
Published: February 2024

Here, we report the draft genome sequence of
Exiguobacterium
sp. strain MMG028, isolated from Rose Creek, San Diego, CA, USA, assembled and analyzed by undergraduate students participating in a marine microbial genomics course. A genomic comparison suggests that MMG028 is a novel species, providing a resource for future microbiology and biotechnology investigations.
IncA/C plasmid encoding
bla
CTX-M-55
in non-O1
Vibrio cholerae
isolates from the edible river fish
Mastacembelus
sp.
Authors: Yamaguchi Takahiro , Jinnai Michio , Nguyen Minh Doan Tran , Hoang Oanh Nguyen , Thi Hien Le , Ngo Thanh Phong , Hoang Hoai Phuong , Do Phuc Nguyen , Dang Van Chinh , Motooka Daisuke , Nakamura Shota , Kumeda Yuko , Hase Atsushi , Nakayama Tatsuya
Published: February 2024

Extended-spectrum β-lactamase-producing non-O1
Vibrio cholerae
was isolated from edible
Mastacembelus
sp. in Vietnam. The genome sequence was sequenced using DNBSEQ-G400 and MinION Mk1b. A plasmid of approximately 183-kb encoding
bla
CTX-M-55
and
bla
TEM-1
was detected.
From the outer space to the inner cell: deconvoluting the complexity of
Bacillus subtilis
disulfide stress responses by redox state and absolute abundance quantification of extracellular, membrane, and cytosolic proteins
Authors: Ferrero-Bordera Borja , Bartel Jürgen , van Dijl Jan Maarten , Becher Dörte , Maaß Sandra
Published: February 2024

Understanding cellular mechanisms of stress management relies on omics data as a valuable resource. However, the lack of absolute quantitative data on protein abundances remains a significant limitation, particularly when comparing protein abundances across different cell compartments. In this study, we aimed to gain deeper insights into the proteomic responses of the Gram-positive model bacterium
Bacillus subtilis
to disulfide stress. We determined proteome-wide absolute abundances, focusing on different sub-cellular locations (cytosol and membrane) as well as the extracellular medium, and combined these data with redox state determination. To quantify secreted proteins in the culture medium, we developed a simple and straightforward protocol for the absolute quantification of extracellular proteins in bacteria. We concentrated extracellular proteins, which are highly diluted in the medium, using StrataClean beads along with a set of standard proteins to determine the extent of the concentration step. The resulting data set provides new insights into protein abundances in different sub-cellular compartments and the extracellular medium, along with a comprehensive proteome-wide redox state determination. Our study offers a quantitative understanding of disulfide stress management, protein production, and secretion in
B. subtilis
.

IMPORTANCE

Stress responses play a crucial role in bacterial survival and adaptation. The ability to quantitatively measure protein abundances and redox states in different cellular compartments and the extracellular environment is essential for understanding stress management mechanisms. In this study, we addressed the knowledge gap regarding absolute quantification of extracellular proteins and compared protein concentrations in various sub-cellular locations and in the extracellular medium under disulfide stress conditions. Our findings provide valuable insights into the protein production and secretion dynamics of
B. subtilis
, shedding light on its stress response strategies. Furthermore, the developed protocol for absolute quantification of extracellular proteins in bacteria presents a practical and efficient approach for future studies in the field. Overall, this research contributes to the quantitative understanding of stress management mechanisms and protein dynamics in
B. subtilis
, which can be used to enhance bacterial stress tolerance and protein-based biotechnological applications.
High-dose intravenous immunoglobulin versus albumin 4% in paediatric toxic shock syndrome: a randomised controlled feasibility study
Authors: Portefaix Aurélie , Dhelens Carole , Recher Morgan , Cour-Andlauer Fleur , Naudin Jérôme , Mortamet Guillaume , Joram Nicolas , Tissières Pierre , Ginhoux Tiphanie , Kassai Behrouz , Boutitie Florent , Maucort-Boulch Delphine , Javouhey Etienne
Published: February 2024

Purpose

Toxic shock syndrome (TSS) is a rare disease responsible for significant morbidity and mortality. Intravenous immunoglobulin (IG) therapy in paediatric TSS could improve shock and organ failure, but more consistent efficacy and safety data are needed. Our objective was to determine whether a randomised clinical trial (RCT) assessing intravenous IG in TSS in children is feasible.

Methods

We performed a multicentre, feasibility, double-blind RCT assessing efficacy of high-dose intravenous IG versus albumin 4% (control group) within the first 12 hours of shock onset. Included patients were aged above 1 month and below 18 years with suspected TSS and septic shock. Feasibility was assessed by measuring inclusion rate, protocol compliance and missing data regarding death and the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) Score. Other secondary clinical outcomes were evaluated during hospital stay, at 60 day and 1 year.

Results

28 patients, admitted in 6 paediatric intensive care units during 36 consecutive months and followed for 1 year, received the allocated treatment: 13 in intravenous IG group, 15 in control group. The median age was 10.6 years and the sex ratio was 1. Inclusion rate was above 50%, protocol deviations were below 30% and missing data regarding death and PELOD-2 Score below 10%. No difference concerning secondary clinical outcomes between groups was observed, and more adverse events were reported in the control group.

Conclusion

It seems to be feasible to conduct an RCT assessing intravenous IG efficacy and safety in paediatric TSS but must be realised internationally, with choice of a clinically relevant endpoint and a specific design in order to be realistic.

Trial registration number

NCT02219165.
Metabolic control and incidence of hypoglycaemia, hospitalisation and complications among Saudi patients with type 2 diabetes initiating second-line therapy: an analysis of the Saudi Arabia data from the DISCOVER Observational Study programme
Authors: Al Rubeaan Khalid , Banah Faisal , Alruwaily Fayez G , Sheshah Eman , Alnaqeb Dhekra , AlQahtani Awad M , Ewais Diaa , Al Juhani Nassr , Hassan Abdul-Hameed , Youssef Amira M
Published: February 2024

Objectives

The aim of the global DISCOVERing Treatment Reality of Type 2 Diabetes in Real World Settings (DISCOVER) Study was to provide a comprehensive real world assessment of the treatment pattern changes for patients with type 2 diabetes. The aim of this analysis was to assess the metabolic control and the annual incidence of hypoglycaemia, hospitalisation and complications among Saudi patients with type 2 diabetes initiating second-line therapy.

Design

This study is part of the observational, longitudinal, prospective multinational DISCOVER Study.

Setting

Governmental and private health sectors from different regions within Saudi Arabia.

Participants

The study recruited 519 patients with type 2 diabetes aged ≥18 years who were switching to second-line therapy. Patients who were already using insulin/injectable agents, patients with type 1 diabetes, pregnant women, and patients undergoing dialysis or with a history of renal transplantation were excluded.

Primary and secondary outcome measures

Metabolic control among patients with type 2 diabetes mellitus; fear of hypoglycaemia; quality of life; and the incidence of complications, hypoglycaemic events and/or hospitalisations. Data were analysed using descriptive statistics.

Results

A total of 519 patients were recruited with a mean age of 52.4±11 years. Of these participants, 54.7% were male and 45.3% were female. The incidence of hypoglycaemia was 56.72/1000 patient-years. The Hypoglycemia Fear Survey II showed a significant increase in patient worry related to hypoglycaemia from 6.4±11.9 at baseline to (p=0.0446) at the 36-month follow-up. The incidence of hospitalisation was 30.81/1000 patient-years. There was a moderate improvement in glycaemic control, represented as an HbA1c reduction from 8.8% at baseline to 8.2% at the 36-month follow-up. The incidence of macroangiopathy was 24.51/1000 patient-years and the incidence of microvascular complications such as retinopathy and albuminuria was 47.00/1000 patient-years and 221.71/1000 patient-years, respectively. The mean score of fear of hypoglycaemia showed an increase with 13.0±21.5 at baseline to 16.1±22.2 at the 36-month follow-up. When assessing the patients’ quality of life, there was an improvement in the mental component score from 47.4±9.1 at baseline to 53.0±6.7 at the 36-month follow-up.

Conclusions

Treatment intensification decisions should be made individually, weighing the benefit of good glycaemic control against the risk of hypoglycaemia.

Trial registration number

NCT02322762 and NCT02226822.
Study protocol for a randomised controlled trial to determine the efficacy of an intensive seated postural intervention delivered with robotic and rigid trunk support systems
Authors: Santamaria Victor , Ai Xupeng , Chin Karen , Dutkowsky Joseph P , Gordon Andrew M , Agrawal Sunil K
Published: February 2024

Introduction

Children with cerebral palsy (CP) classified as gross motor function classification system (GMFCS) levels III–IV demonstrate impaired sitting and reaching control abilities that hamper their overall functional performance. Yet, efficacious interventions for improving sitting-related activities are scarce. We recently designed a motor learning-based intervention delivered with a robotic Trunk-Support-Trainer (TruST-intervention), in which we apply force field technology to individualise sitting balance support. We propose a randomised controlled trial to test the efficacy of the motor intervention delivered with robotic TruST compared with a static trunk support system.

Methods and analysis

We will recruit 82 participants with CP, GMFCS III–IV, and aged 6–17 years. Randomisation using concealed allocation to either the TruST-support or static trunk-support intervention will be conducted using opaque-sealed envelopes prepared by someone unrelated to the study. We will apply an intention-to-treat protocol. The interventions will consist of 2 hours/sessions, 3/week, for 4 weeks. Participants will start both interventions with pelvic strapping. In the TruST-intervention, postural task progression will be implemented by a progressive increase of the force field boundaries and then by removing the pelvic straps. In the static trunk support-intervention, we will progressively lower the trunk support and remove pelvic strapping. Outcomes will be assessed at baseline, training midpoint, 1-week postintervention, and 3-month follow-up. Primary outcomes will include the modified functional reach test, a kinematic evaluation of sitting workspace, and the Box and Block test. Secondary outcomes will include The Segmental Assessment of Trunk Control test, Seated Postural & Reaching Control test, Gross Motor Function Measure-Item Set, Canadian Occupational Performance Outcome, The Participation and Environment Measure and Youth, and postural and reaching kinematics.

Ethics and dissemination

The study was approved by the Columbia University Institutional Review Board (AAAS7804). This study is funded by the National Institutes of Health (1R01HD101903-01) and is registered at clinicaltrials.gov.

Trial registration number

NCT04897347; clinicaltrials.gov.
Study of How Adiposity in Pregnancy has an Effect on outcomeS (SHAPES): protocol for a prospective cohort study
Authors: Heslehurst Nicola , Vinogradov Raya , Nguyen Giang T , Bigirumurame Theophile , Teare Dawn , Hayes Louise , Lennie Susan C , Murtha Victoria , Tothill Rebecca , Smith Janine , Allotey John , Vale Luke
Published: February 2024

Introduction

Maternal obesity increases the risk of multiple maternal and infant pregnancy complications, such as gestational diabetes and pre-eclampsia. Current UK guidelines use body mass index (BMI) to identify which women require additional care due to increased risk of complications. However, BMI may not accurately predict which women will develop complications during pregnancy as it does not determine amount and distribution of adipose tissue. Some adiposity measures (eg, waist circumference, ultrasound measures of abdominal visceral fat) can better identify where body fat is stored, which may be useful in predicting those women who need additional care.

Methods and analysis

This prospective cohort study (SHAPES, Study of How Adiposity in Pregnancy has an Effect on outcomeS) aims to evaluate the prognostic performance of adiposity measures (either alone or in combination with other adiposity, sociodemographic or clinical measures) to estimate risk of adverse pregnancy outcomes. Pregnant women (n=1400) will be recruited at their first trimester ultrasound scan (11+2–14+1weeks’) at Newcastle upon Tyne National Health Service Foundation Trust, UK. Early pregnancy adiposity measures and clinical and sociodemographic data will be collected. Routine data on maternal and infant pregnancy outcomes will be collected from routine hospital records. Regression methods will be used to compare the different adiposity measures with BMI in terms of their ability to predict pregnancy complications. If no individual measure performs better than BMI, multivariable models will be developed and evaluated to identify the most parsimonious model. The apparent performance of the developed model will be summarised using calibration, discrimination and internal validation analyses.

Ethics and dissemination

Ethical favourable opinion has been obtained from the North East: Newcastle & North Tyneside 1 Research Ethics Committee (REC reference: 22/NE/0035). All participants provide informed consent to take part in SHAPES. Planned dissemination includes peer-reviewed publications and additional dissemination appropriate to target audiences, including policy briefs for policymakers, media/social-media coverage for public and conferences for research

Trial registration number

ISRCTN82185177.
Development of clinically meaningful quality indicators for contemporary lung cancer care, and piloting and evaluation in a retrospective cohort; experiences of the Embedding Research (and Evidence) in Cancer Healthcare (EnRICH) Program
Authors: Brown Bea , Galpin Kirsty , Simes John , Boyer Michael , Brown Chris , Chin Venessa , Young Jane
Published: February 2024

Objectives

Lung cancer continues to be the most common cause of cancer-related death and the leading cause of morbidity and burden of disease across Australia. There is an ongoing need to identify and reduce unwarranted clinical variation that may contribute to these poor outcomes for patients with lung cancer. An Australian national strategy acknowledges clinical quality outcome data as a critical component of a continuously improving healthcare system but there is a need to ensure clinical quality indicators adequately measure evidence-based contemporary care, including novel and emerging treatments. This study aimed to develop a suite of lung cancer-specific, evidence-based, clinically acceptable quality indicators to measure quality of care and outcomes, and an associated comparative feedback dashboard to provide performance data to clinicians and hospital administrators.

Design

A multistage modified Delphi process was undertaken with a Clinical Advisory Group of multidisciplinary lung cancer specialists, with patient representation, to update and prioritise potential indicators of lung cancer care derived from a targeted review of published literature and reports from national and international lung cancer quality registries. Quality indicators were piloted and evaluated with multidisciplinary teams in a retrospective observational cohort study using clinical audit data from the Embedding Research (and Evidence) in Cancer Healthcare Program, a prospective clinical cohort of over 2000 patients with lung cancer diagnosed from May 2016 to October 2021.

Setting and participants

Six tertiary specialist cancer centres in metropolitan and regional New South Wales, Australia.

Results

From an initial 37 potential quality indicators, a final set of 10 indicators spanning diagnostic, treatment, quality of life and survival domains was agreed.

Conclusions

These indicators build on and update previously available measures of lung cancer care and outcomes in use by national and international lung cancer clinical quality registries which, to our knowledge, have not been recently updated to reflect the changing lung cancer treatment paradigm.
Investigating experiences of people with advanced breast or lung cancer in their natural context: protocol for an experience sampling study
Authors: Geeraerts Joran , Pivodic Lara , De Nooijer Kim , Naert Eline , Crombez Geert , De Ridder Mark , Van den Block Lieve
Published: February 2024

Introduction

People with advanced cancer can experience a wide range of multidimensional symptoms or concerns, but little is known about when and how these fluctuate in daily life. Experience sampling methods (ESMs) involve repeated self-reports in people’s natural contexts aimed at uncovering everyday life experiences. ESM has limited recall bias and good ecological validity but might be burdensome to patients. This study aims to pretest and evaluate the feasibility and clinical utility of a validated ESM and use it to explore everyday experiences of people living with advanced breast or lung cancer.

Methods and analysis

In step 1, we will optimise our ESM method by pretesting it through usability interviews and a pilot ESM study. In step 2, we will evaluate and use the ESM method through an observational ESM study to investigate the daily experiences of people with advanced breast or lung cancer. Step 2 also includes interviews with healthcare professionals to determine the clinical utility of ESM in oncology. Participants will complete a digital questionnaire ten times per day, measuring momentary experiences in the physical, psychological, social, spiritual-existential domains and context. Multilevel regression models will analyse fluctuations and temporal relations among measured experiences and context. Analyses also include evaluation of compliance and participation rates. We will apply content analysis to the usability interviews and follow-up interviews of the pilot ESM study.

Ethics and dissemination

We obtained approval from the ethics committees of the University Hospitals of Brussels (BUN: 1432023000043) and Ghent (ONZ-2023-0136). Results will be published in open-access, peer-reviewed journals and presented at conferences. If ESM appears feasible in this population, it could offer new insights into the daily experiences and help optimise support for people with advanced cancer.
Rates of visual field change and functional progression in glaucoma following trabecular microbypass implantation of iStent technologies: a meta-analysis
Authors: Gillmann Kevin , Hornbeak Dana M
Published: February 2024

Background/aim

While intraocular pressure (IOP) remains the only modifiable risk factor for glaucoma progression, the ultimate goal of glaucoma management is to preserve patients’ functional vision and quality of life. To this end, minimally invasive glaucoma surgeries (MIGSs) aim to reduce IOP with minimal eye trauma. Commonly used MIGS devices include iStent technologies, which have well-documented IOP-reducing potential and favourable safety profiles. However, no study concluded on their effect on the rates of visual field (VF) changes. The aim of this meta-analysis is to determine the long-term effect of iStent technology implantation on glaucoma functional progression.

Methods

Electronic medical literature databases were searched to identify studies reporting on iStent technologies. Reports with follow-up durations <12 months, retention rates <75% and missing VF data were excluded. Fifteen studies reporting on 1115 eyes were identified. The overall weighted mean VF mean deviation (MD) progression, IOP reduction and follow-up duration were calculated.

Results

Weighted mean IOP at baseline was 19.0±3.1 mm Hg. At the end of a 37.9-month mean follow-up (range 12–96 months), a weighted mean 26.6% IOP reduction was achieved (range 15.2%–42.3%). Over the same duration, the weighted mean VF MD progression rate was −0.02±0.34 dBs/year, from a mean baseline of −5.76±5.68 dBs.

Conclusion

In this review, which examines functional stability of 1115 eyes, iStent technologies achieved a mean rate of progression of −0.024 dBs/year with serial standard automated perimetry, which is similar to that reported in non-glaucomatous eyes and slower than that reported in medically treated glaucoma.
Athletes who have already experienced an injury are more prone to adhere to an injury risk reduction approach than those who do not: an online survey of 7870 French athletics (track and field) athletes
Authors: Edouard Pascal , Sorg Marine , Martin Simon , Verhagen Evert , Ruffault Alexis
Published: February 2024

Objective

To compare the perception towards injury risk reduction approach between athletes who have already experienced an injury and those who have not.

Methods

We conducted a cross-sectional study using a one-time online survey asking athletics athletes licensed at the French Federation of Athletics (http://www.athle.fr) about their perceptions regarding injuries and injury risk reduction behaviours. We statistically compared athletes who already experienced an injury and those who did not.

Results

A total of 7870 athletes were included. 90% of athletes declared having experienced at least one injury. They (1) were proportionally more men than women, (2) had significantly more years of experience in athletics, (3) had a significant difference in disciplines (more hurdles, jumps and combined events and fewer sprint athletes), (4) had a significant difference in competition levels (more national and less departmental levels) and (5) reported significantly higher values or agreements in favour of injury risk reduction approach, compared with uninjured athletes. There were significantly more athletes declaring following injury risk reduction programmes among athletes who experienced at least one injury than those who did not.

Conclusions

Athletes who experienced at least one injury during their lifetime were more prone to adhere to injury risk reduction strategies than athletes who have never experienced an injury. Their entourage (coaches and health professionals) should use this fertile ground to implement injury risk reduction strategies. In addition, their experience should be disseminated to uninjured athletes to help them adhere to injury risk reduction without injury experience.
Clinical trial outcomes for SLE: what we have and what we need
Authors: Arnaud Laurent , Parodis Ioannis , Devilliers Hervé , Chasset Francois
Published: February 2024

The paradigm of drug approval in SLE currently relies on successful large phase III randomised controlled trials and a set of primary, secondary and additional end points. Taken together, these outcomes offer a nuanced understanding of the efficacy and safety of the investigational agent. In this review, we thoroughly examine the main outcomes used in SLE trials and highlight unmet requirements as well as potential venues for future trial design in SLE. Disease activity indices can be broadly categorised into global-specific and organ-specific indices, in particular for skin, joints and kidneys, but there is no universal consensus about their use in clinical trials. Because each of these instruments has its own intrinsic strengths and weaknesses, the assessment of treatment response has progressed from relying solely on one individual disease activity index to using composite responder definitions. Those are typically measured from the trial baseline to the end point assessment date and may be combined with the need to taper and maintain glucocorticoids (GCs) within prespecified ranges. Remission and low disease activity are two critical states in the perspective of ‘Treat-to-Target’ trials, but are not fully recognised by regulators. While significant progress has been made in clinical trial outcomes for SLE, there is a clear need for continued innovation. Addressing these challenges will require collaboration between researchers, clinicians, patients as well as with regulatory agencies to refine existing outcome measures, incorporate meaningful and ethnically diverse patient perspectives, foster relevant digital opportunities and explore new therapeutic avenues, including early use of investigational agents. By doing so, we can advance our ability to manage SLE effectively and safely and improve the lives of those living with this complex and impactful autoimmune disease.
Legionnaires’ disease in transportation, construction and other occupations in 39 US jurisdictions, 2014–2016
Authors: Harduar Morano Laurel , Morawski Bozena M , Herzig Carolyn T A , Edens Chris , Barskey Albert E , Luckhaupt Sara E
Published: February 2024

Background

Certain workers are at increased risk for acquiring Legionnaires’ disease compared with other workers. This study aims to identify occupations at increased risk for acquiring Legionnaires’ disease.

Methods

Using data from the US Centers for Disease Control and Prevention’s Supplemental Legionnaires’ Disease Surveillance System, this study identified Legionnaires’ disease confirmed patients ≥16 years of age in 39 states with reported symptom onset during 2014–2016. Age-adjusted and sex-adjusted incidence rate ratios (IRR) stratified by occupation group were calculated by comparing Legionnaires’ disease patients in an occupation group (eg, transportation) to those in all other occupation groups (eg, non-transportation).

Results

A total of 2553 patients had a known occupation group. The two occupations with the highest burden were transportation (N=287; IRR=2.11) and construction (N=269; IRR=1.82). Truck drivers comprised the majority (69.7%) of the transportation occupation group and construction labourers comprised almost half (49%) of the construction occupation group. The healthcare support occupation had the highest IRR (N=75; IRR=2.16).

Conclusion

Transportation and construction workers, who are generally not covered by guidance related to building water systems, have increased risk of Legionnaires’ disease compared with other workers. One hypothesised risk factor for truck drivers is the use of non-genuine windshield cleaner in their vehicles. A simple intervention is to use genuine windshield cleaner with bactericidal properties (ie, includes isopropanol/methanol) which can reduce the risk ofLegionellagrowth and transmission. To improve surveillance of Legionnaires’ disease and identification of similar exposures, the authors encourage the collection of occupation and industry information for all patients with Legionnaires’ disease.
Impact of ambient air pollution on lung function in preterm-born school-aged children
Authors: Watkins William John , Course Christopher William , Cousins Michael , Hart Kylie , Kotecha Sarah J , Kotecha Sailesh
Published: February 2024

Rationale

Increased outdoor air pollution worsens lung function in children. However, these associations are less well studied in preterm-born individuals.

Objectives

We assessed associations between ambient air pollutants and spirometry measures in preterm-born children.

Methods

The Respiratory Health Outcomes in Neonates study recruited preterm-born children aged 7–12 years who were born at ≤34 week's gestation. We associated four ambient air pollutants (particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5), PM10, nitrogen dioxide (NO2) and sulfur dioxide) at time of birth and spirometry assessment and averaged exposure between these two time points with spirometry measures, using linear regression analyses. Gestational age was banded into 23–28, 29–31 and 32–34 week's. Regression models estimated spirometry values against pollutant levels at birth and at the time of spirometry.

Measurements and main results

From 565 preterm-born children, 542 (96%) had satisfactory data. After adjustments for early and current life factors, significant detrimental associations were noted between PM10at birth and per cent predicted forced vital capacity (%FVC) for the 23–28 and 29–31 week's gestation groups and between current PM2.5and NO2exposure and %FVC for the 23–28 week's gestation group. No associations with spirometry were noted for the averaged pollution exposure between birth and spirometry. Predictive models showed 5.9% and 7.4% differences in %FVC between the highest and lowest current pollution exposures for PM2.5and NO2,respectively, in the 23–28 week group.

Conclusions

Birth and current exposures to road-traffic-associated pollutants detrimentally affected %FVC in preterm-born school-aged children, who already have compromised lung function.
Data-based equations for damage evaluation of reinforced concrete columns with square cross sections
Authors: Mokarram Vahid , Banan Mahmoud R. , Abazarnejad Meisam , Banan Mohammad R.
Published: February 2024

This study aims to develop simple equations for assessing the damage of reinforced concrete (RC) columns subjected to seismic loading. A fiber element model in OpenSees, validated against experimental data, was used to generate a large dataset of 56 548 data values for various RC columns. The Monte Carlo Hierarchical Adaptive Random Partitioning strategy was then applied to evaluate the sufficiency of the dataset and propose reliable equations for estimating the residual displacement ratio, damage index, and residual curvature of RC columns under given displacement demands. A relationship between these parameters and the structural performance levels was also established. Residual displacement is a practical measure that can be observed in the field after an earthquake. The proposed equations facilitate the determination of the performance level of the structure after an earthquake event. The findings of this paper can also be used in designing new structures within a performance-based seismic design context.
Diet is associated with age and habitat, not foraging range, in purple martins: implications for aerial insectivores as indicators
Authors: Dunoyer Julia N. , Lalla Kristen M. , Fraser Kevin C. , Elliott Kyle H.
Published: February 2024

Many aerial insects are declining, yet monitoring wildlife in airspace is challenging. Aerial insectivores, which are themselves a declining guild, may be useful indicators for aerial insects. However, their use as indicators may be complicated if they differentially sample prey depending on foraging range, as predicted by central place foraging theory. We measured diet composition of purple martins ( Progne subis (Linnaeus, 1758)) in Quebec by deoxyribonucleic acid (DNA) metabarcoding fecal samples collected from adults and nestlings and used GPS biologgers to measure foraging behaviour of the chick-rearing adults. Foraging range did not predict diet or diet diversity. The proportion of individuals with Diptera and Coleoptera detected in their diets was lower in developed and water habitats. Martins fed their nestlings soft-bodied insects (Diptera and Trichoptera) more often than they ate them themselves. As nestlings aged, they were fed more chitinous arthropods and less soft-bodied prey. As the proportion of different prey orders depended on habitat use and age, but not foraging distance, we argue that purple martin diet is a potential indicator of aerial insect community variation across space, but that interpretations may be complex as birds may sample different components of the aerial insect community during different life stages.
The small $$k_{\textrm{T}}$$region in Drell–Yan production at next-to-leading order with the parton branching method
Authors: Bubanja I. , Bermudez Martinez A. , Favart L. , Guzman F. , Hautmann F. , Jung H. , Lelek A. , Mendizabal M. , Moral Figueroa K. , Moureaux L. , Raicevic N. , Seidel M. , Taheri Monfared S.
Published: February 2024

The Parton Branching (PB) method describes the evolution of transverse momentum dependent (TMD) parton distributions, covering all kinematic regions from small to large transverse momenta $$k_{\textrm{T}}$$

k
T

. The small $$k_{\textrm{T}}$$

k
T

-region is very sensitive both to the contribution of the intrinsic motion of partons (intrinsic $$k_{\textrm{T}}$$

k
T

) and to the resummation of soft gluons taken into account by the PB TMD evolution equations. We study the role of soft-gluon emissions in TMD as well as integrated parton distributions. We perform a detailed investigation of the PB TMD methodology at next-to-leading order (NLO) in Drell–Yan (DY) production for low transverse momenta. We present the extraction of the nonperturbative “intrinsic-$$k_{\textrm{T}}$$

k
T

” distribution from recent measurements of DY transverse momentum distributions at the LHC across a wide range in DY masses, including a detailed treatment of statistical, correlated and uncorrelated uncertainties. We comment on the (in)dependence of intrinsic transverse momentum on DY mass and center-of-mass energy, and on the comparison with other approaches.
Quarkonia dissociation at finite magnetic field in the presence of momentum anisotropy
Authors: Nilima Indrani , Hasan Mujeeb , Singh B. K. , Jamal Mohammad Yousuf
Published: February 2024

In this study, we investigate the potential of heavy quarkonia within a magnetized hot QGP medium having finite momentum anisotropy. The phenomenon of inverse magnetic catalysis is introduced into the system, influencing the magnetic field-modified Debye mass and thereby altering the effective quark masses. Concurrently, the impact of momentum anisotropy in the medium is considered that influence the particle distribution in the medium. The thermal decay width and dissociation temperature of quarkonium states, specifically the 1S and 2S states of charmonium and bottomonium, are computed. Our results reveal that both momentum anisotropy and the inverse magnetic catalysis effects play a significant role in modifying the thermal decay width and dissociation temperature of these heavy quarkonia states.
Robots as Mental Well-being Coaches: Design and Ethical Recommendations
Authors: Axelsson Minja , Spitale Micol , Gunes Hatice
Published: February 2024

The last decade has shown a growing interest in robots as well-being coaches. However, insightful guidelines for the design of robots as coaches to promote mental well-being have not yet been proposed. This article details design and ethical recommendations based on a qualitative analysis drawing on a grounded theory approach, which was conducted with a three-step iterative design process which included user-centered design studies involving robotic well-being coaches, namely: (1) a user-centred design study conducted with 11 participants consisting of both prospective users who had participated in a Brief Solution-Focused Practice study with a human coach, as well as coaches of different disciplines, (2) semi-structured individual interview data gathered from 20 participants attending a Positive Psychology intervention study with the robotic well-being coach Pepper, and (3) a user-centred design study conducted with 3 participants of the Positive Psychology study as well as 2 relevant well-being coaches. After conducting a thematic analysis and a qualitative analysis, we collated the data gathered into convergent and divergent themes, and we distilled from those results a set of design guidelines and ethical considerations. Our findings can inform researchers and roboticists on the key aspects to take into account when designing robotic mental well-being coaches.
Optimizing with Attractor: A Tutorial
Authors: Li Weiqi
Published: February 2024

This tutorial presents a novel search system—the Attractor-Based Search System (ABSS)—that can solve the Traveling Salesman Problem very efficiently with optimality guarantee. From the perspective of dynamical systems, a heuristic local search algorithm for an NP-complete combinatorial problem is a discrete dynamical system. In a local search system, an attractor drives the search trajectories into the vicinity of a globally optimal point in the solution space, and the convergence of local search trajectories makes the search system become a global and deterministic system. The attractor contains a small set of the most promising solutions to the problem. The attractor can reduce the problem size exponentially, and thus make the exhaustive search feasible. Therefore, this new search paradigm is called optimizing with attractor. The ABSS consists of two search phases: local search phase and exhaustive search phase. The local search process is used to quickly construct the attractor in the solution space, and the exhaustive search process is used to completely search the attractor to identify the optimal solution. Therefore, the exact optimal solution can be found quickly by combining local search and exhaustive search. This tutorial introduces the concept of an attractor in a local search system, and describes the process of optimizing with the attractor, using the Traveling Salesman Problem as the study platform.
Tutorial on Matching-based Causal Analysis of Human Behaviors Using Smartphone Sensor Data
Authors: Jung Gyuwon , Park Sangjun , Ma Eun-Yeol , Kim Heeyoung , Lee Uichin
Published: February 2024

Smartphones can unobtrusively capture human behavior and contextual data such as user interaction and mobility. Thus far, smartphone sensor data have primarily been used to gain behavioral insights through correlation analysis. This article provides a tutorial on the causal analysis of human behavior using smartphone sensor data by reviewing well-known matching methods. The key steps of the causal inference pipeline employing matching methods are illustrated using a concrete scenario involving the identification of a causal relationship between phone usage and physical activity. Several practical considerations for conducting causal inferences about human behaviors using smartphone sensor data are also discussed.