bluuebunny/crossref_metadata_2025_split huggingface dataset:
Semantic search using protein large language models detects class II microcins in bacterial genomes
Authors: Kulikova Anastasiya V. , Parker Jennifer K. , Davies Bryan W. , Wilke Claus O. 
Published: September 2024

ABSTRACT

Class II microcins are antimicrobial peptides that have shown some potential as novel antibiotics. However, to date, only 10 class II microcins have been described, and the discovery of novel microcins has been hampered by their short length and high sequence divergence. Here, we ask if we can use numerical embeddings generated by protein large language models to detect microcins in bacterial genome assemblies and whether this method can outperform sequence-based methods such as BLAST. We find that embeddings detect known class II microcins much more reliably than does BLAST and that any two microcins tend to have a small distance in embedding space even though they typically are highly diverged at the sequence level. In data sets of
Escherichia coli
,
Klebsiella
spp., and
Enterobacter
spp. genomes, we further find novel putative microcins that were previously missed by sequence-based search methods.

IMPORTANCE
Antibiotic resistance is becoming an increasingly serious problem in modern medicine, but the development pipeline for conventional antibiotics is not promising. Therefore, alternative approaches to combat bacterial infections are urgently needed. One such approach may be to employ naturally occurring antibacterial peptides produced by bacteria to kill competing bacteria. A promising class of such peptides are class II microcins. However, only a small number of class II microcins have been discovered to date, and the discovery of further such microcins has been hampered by their high sequence divergence and short length, which can cause sequence-based search methods to fail. Here, we demonstrate that a more robust method for microcin discovery can be built on the basis of a protein large language model, and we use this method to identify several putative novel class II microcins.
Establishment and evaluation of a rapid method for the detection of bacterial pneumonia in hospitalized patients via multiplex PCR–capillary electrophoresis (MPCE)
Authors: Wang Jie , Zhao Pei , Zhao Mengchuan , Zhang Duoxiao , Chen Shan , Liu Ying , Gao Yuan , Tie Yanqing , Feng Zhishan 
Published: September 2024

ABSTRACT

Cost-effective molecular diagnostic techniques for bacterial pneumonia are limited. We designed primers for 13 bacteria, performed multiplex nucleic acid detection through fragment analysis to obtain pathogen identification results, and established a multiplex PCR–capillary electrophoresis (MPCE) method, which can simultaneously detect 13 pathogens associated with bacterial pneumonia. The sensitivity, specificity, and reproducibility of the MPCE assay were tested, and 420 clinical samples were used to assess the clinical detection ability of MPCE, with the culture method used as a reference. Samples with inconsistent results detected by the two methods were sent for Sanger sequencing. The minimum detection limit of MPCE for 13 bacteria was 6.0 × 10
3
cfu/mL~2.0 × 10
6
cfu/mL. No cross-reactivity was observed with other pathogens. The percentage of agreement for reproducibility analysis reached 100%. For the 420 sputum samples, when the culture method was used as the reference, the sensitivity of MPCE to 13 bacteria ranged from 80% to 100%. The specificity for 13 bacteria ranged from 67.1% to 100%. The percentage of agreement between the MPCE and the culture method ranged from 69.7% to 100%. There was no statistically significant difference (
P
> 0.05) in the detection of
Escherichia coli
,
Enterobacter cloacae complex
,
Staphylococcus aureus
, methicillin-resistant
S. aureus, Streptococcus pyogenes
,
Moraxella catarrhalis
, or
Legionella pneumophila
between the MPCE and the culture method. Clinical samples with negative cultures but positive MPCE results were validated by Sanger sequencing, and the results were consistent with those of MPCE. The MPCE method has high sensitivity and specificity for bacterial pneumonia, enabling the simultaneous and rapid detection of multiple pathogens. It is cost-effective and has potential for clinical application.

IMPORTANCE
This study successfully established a multiplex PCR–capillary electrophoresis detection system that can simultaneously detect 13 pathogens through a single detection method, significantly improving clinical efficiency. It is cost-effective and has potential for clinical application.
The First Discovery of Archean Dolerite Dikes in the Western Part of the Aldan Shield
Authors: Erofeeva K. G. , Larionova Yu. O. , Samsonov A. V. 
Published: September 2024

Abstract
Dolerite dikes were studied in the western part of the Aldan terrane, in the middle reaches of the Tokko River. These dolerite dikes form a swarm of submeridional trend about 1 km wide. The dolerites of the thickest dike preserve their primary textural and structural features and mineral composition: plagioclase + pigeonite + augite + titanomagnetite. Dolerite in the chilled margins and central parts of the dike are homogeneous in composition, corresponds to low-Mg tholeiites, has low contents of Ti and other HFSE, with weak enrichment in light REE and small negative Nb anomalies. Sm–Nd isotope data on magmatic minerals of dolerite from the central part of the dike yield a good linear regression in an isochron diagram that gives to an age of 2510 ± 64 Ma, which probably corresponds to the crystallization age of the basalt. Metadolerites in a thin dike retain plagioclase porphyritic structures, but the pyroxenes are completely replaced by amphibole and chlorite. The metadolerites are contrastingly different in low contents of MgO, Cr, and Ni and in higher contents of TiO2, Fe2O3, P2O5, Nb, and all REE. The differences in the composition of the dikes may be explained by the longterm (about 65%) crystallization differentiation of the initial melt and the emplacement of the residual melt from a shallow intermediate magma chamber via opening cracks. Such conditions probably may have existed in tectonically stable intraplate settings. The age of the dolerites of the dike swarm is comparable to that of the anorogenic granites of the Nelyuki complex (~2.4–2.5 Ga), which are widespread in the western part of Aldan granulite–gneiss terrane. Our data bridge some gaps in characteristics of intraplate anorogenic magmatism that occurred in the western Aldan Shield in the Late Archean and marked the final consolidation of a large block of Archean crust in the Chara–Olekma granite–greenstone area.
‘Going through the motions’; a rich account of the complexity of the anterior cruciate ligament reconstruction pathway, a UK qualitative study
Authors: Carter Hayley M , Beard David J , Leighton Paul , Moffatt Fiona , Smith Benjamin E , Webster Kate E , Logan Phillipa 
Published: September 2024

ObjectivesThis study aimed to understand the lived experiences of patients on the anterior cruciate ligament reconstruction (ACLR) pathway up to 3 months before, 3 months after and 1 year after surgery. Study objectives were to explore (1) patient experiences of preoperative and postoperative treatment, (2) views of/involvement in prehabilitation and (3) sources and consistency of healthcare advice.DesignSemi-structured interviews analysed using reflexive thematic analysis.SettingMidlands, England.ParticipantsPurposive sample of 18 participants aged 18–45. Three identified as female and 15 as male. Participants’ ethnic origin was white (n=14), Indian (n=2), British Asian (n=1) and Pakistani (n=1). 10 participants were awaiting ACLR, six were 3months postsurgery and two were 1 year postsurgery.ResultsParticipants gave a rich account of ACLR pathway experiences discussing negative impacts of the injury, difficulties with navigating the pathway and making decisions about surgery. Interacting with healthcare professionals and managing the variety of resources, advice and opinions were also highlighted as challenges. Participants reflected on their preoperative journey accounting a wide spectrum of expectations and realities of returning to work and physical activity postoperatively. Prehabilitation was perceived to offer an advantage to recovery, mental well-being, injury knowledge, postoperative rehabilitation and supports a faster return to physical activity. Five themes were identified:Injury experience, impact and support.Navigating the treatment pathway.Sense making in the preoperative period.Uncertainty, expectations and reality of the postsurgical period.Balancing resources, advice and opinions.ConclusionThis study has illuminated patient experiences of the National Health Service (NHS) ACLR pathway, novel to the evidence base.The results highlight the perceived shortcomings in patient support. They also demonstrate the difficulty patients face when navigating the NHS system, communicating with clinicians, making decisions about treatment and managing conflicting sources of healthcare advice. These problems are more prominent than previously recognised in the literature.RegistrationClinicalTrials.gov Identifier:NCT05529511.
Construction of a competency evaluation model for Clinical Research Coordinators in China: a study based on the Delphi method and questionnaire survey
Authors: Zhu Yanhong , Sun Xiang , Cai Maohang , Shi Jun , Li Xin 
Published: September 2024

PurposeAs the number of clinical trials in China continues to grow, the assessment of competency of Clinical Research Coordinators (CRCs), who play a crucial role in clinical trials, has become an important and challenging topic. This study aims to construct a competency model for CRCs tailored to the Chinese context, in order to promote the standardisation and regulated development of the CRC industry.Study design and settingThis study was conducted in China, engaging CRCs as the primary subjects. A competency evaluation model for CRCs was constructed through literature review, semi-structured interviews, Delphi expert consultation and the analytic hierarchy process. A questionnaire survey was distributed to a broad sample of CRCs across China to evaluate the model’s reliability and validity.ResultsThe final model encompasses 4 core competency dimensions and 37 indicators, tailored to assess the competencies of CRCs in China. The questionnaire yielded an effective response rate of 81.83%, with high internal consistency(Cronbach’s α>0.7). Factor analysis confirmed the model’s structure, indicating good reliability and validity.ConclusionThis study represents a pioneering effort in constructing a competency model specifically designed for Chinese CRCs, complemented by a robust and valid assessment scale. The findings bear significant implications for the recruitment, training, development and management of CRCs.
Road to Recovery: protocol for a mixed-methods prospective cohort study evaluating the impact of a new model of substance use care in a Canadian setting
Authors: Dennis Brittany B , Bowles Jeanette , Johnson Cheyenne , De Wolfe Travis , Mundel Erika , Fast Danya , Boyd Jade , Fleury Mathew , Bach Paxton , Fairbairn Nadia , Socías M Eugenia , Ti Lianping , Hayashi Kanna , DeBeck Kora , Milloy M J , Felicella Guy , Morgan Jeffrey , Eekhoudt Cameron R , McGrail Kimberlyn , Richardson Lindsey , Ryan Andrea , Mbuagbaw Lawrence , Guyatt Gordon , Nolan Seonaid 
Published: September 2024

IntroductionThe Road to Recovery (R2R) Initiative is an innovative model of substance use care that seeks to increase treatment capacity by creating approximately 100 new addiction treatment beds to provide on-demand addiction care in Vancouver, British Columbia, for patients with substance use disorders. The new model also coordinates the region’s existing clinical substance use services to support patients across a care continuum that includes traditional office-based addiction treatment and harm reduction services, early withdrawal management and more intensive abstinence-based treatment programming. To understand the impact of offering on-demand and coordinated substance use care, an observational cohort of individuals who access any R2R clinical service will be created to examine health and social outcomes over time.Methods and analysisThis prospective mixed-methods study will invite individuals from Vancouver, Canada, who access substance use treatment through the R2R model of care to (1) complete a baseline and 12-month follow-up quantitative questionnaire that solicits sociodemographic, substance use and previous addiction treatment data and (2) provide consent to the use of participants’ personal identifiers to access health records for chart review and for annual linkage to select health and administrative databases to allow for ongoing (virtual) community follow-up over 5 years. Additionally, a purposive sample of cohort participants will be invited to participate in baseline and 12-month follow-up qualitative interviews to share their experiences accessing R2R and identify challenges and opportunities associated with the implementation of R2R.Ethics and disseminationThe study was approved by the University of British Columbia Providence Health Care Research Ethics Board in September 2023. Results from the proposed study will be published in peer-reviewed journals, presented at national and international scientific conferences and disseminated through regular meetings with policymakers, individuals with lived and living experience, and other high-level stakeholders, academic presentations and lay media.
Loop quantum gravity effects on electromagnetic properties of charged leptons
Authors: Melo J. P. S. , Neves M. J. , Paixão J. M. A. , Helayël-Neto J. A. 
Published: September 2024

AbstractThe efforts in this contribution consist in reassessing a modified Dirac equation that incorporates a $$\gamma ^0 \gamma _5$$

γ
0

γ
5

-Lorentz-symmetry violating (LSV) term induced as a Loop Quantum Gravity (LQG) effect. Originally, this equation has been applied and considered as a good scenario for describing a number of investigations on the flight time of cosmic neutrinos, which suggests that the speed, in vacuum, in connection with the geometry that describes a granular space-time, takes the energy-dependent form, e.g., $$v(E) =1 \pm E/E_{\text {\tiny LSV}}$$

v

(
E
)

=
1
±
E
/

E

LSV

, with $$E_{\text {\tiny LSV}} \approx 6,5 \times 10^{17}$$

E

LSV

≈
6
,
5
×

10
17

GeV for neutrinos. Once LQG provides a viable way to understand this picture consistently, we pursue an analysis of this effective Dirac equation to inspect some of its properties. These include: the derivation of the modified fermionic propagator, attainment of the Gordon decomposition of the vector current with minimal electromagnetic coupling to obtain information on the form factors, examination of the non-relativistic limit of the equation, evaluation of the spin- and velocity-dependent corrections to the Coulomb potential due to LQG effects, and the modified Hamiltonian in the low-relativistic regime. The study of the form factors may open up paths to set up bounds on the LQG parameters from the precision measurements of electromagnetic attributes of the charged leptons, such as their respective electric and magnetic dipole moments.
Sarcopenia em pessoas idosas: concordância entre métodos preditores
Authors: Araújo Sílvia Ribeiro Santos , Miranda Rogério Mariano de , Silva Bruno Rodrigues 
Published: September 2024

Sarcopenia is a relevant clinical condition worldwide. Its prevalence ranges from 5% to 13% in the elderly aged 65 years and over. Over 80 years, this value can reach 50%, demonstrating the influence of age on the development of the disease. Its diagnosis is based on reduced muscle mass, associated with decreased strength and/or low muscle function. The gold standard for diagnosing the disease is Dual-energy X-ray absorptiometry, but it is inaccessible due to its high cost and diagnostic complexity. Thus, alternative methods for screening for sarcopenia, such as: sit and stand test (TSL), calf circumference (CP) and manual strength test (FPM), SARC-F questionnaire are applied. Defining methods suitable for the outpatient setting is essential for both screening and diagnosis of the disease. The present study aimed to analyze whether there is agreement between predictive methods used to estimate the existence of sarcopenia in the elderly. This is a cross-sectional study carried out with 27 healthy elderly people (23 women and 4 men). The predictive methods were measuring CP, FPM, TSL and Ishii Probability Score (ISHII). The agreement between the classifications was used the Kappa statistic. All predictive methods identified sarcopenic and non-sarcopenic individuals. There was no agreement in the combinations: CTS x FPM; TSL x FPM and; TSL x ISHII. As for the association between the CTS and TSL methods, there was a moderate agreement between the predicted values (k=0.43; p=0.006). Conclusion: Different predictive methods promote different sarcopenia diagnoses. A moderate agreement was observed for the combination between CTS and TSL predictors. It should be noted that the association between different tests is an option to be evaluated.
Low‐Level Tragus Stimulation Attenuates Blood Pressure in Young Individuals With Hypertension: Results From a Small‐Scale Single‐Blind Controlled Randomized Clinical Trial
Authors: Mbikyo Muisha B. , Wang Ai , Ma Qun , Miao Linlin , Cui Nan , Yang Yiqing , Fu Haoran , Sun Yingxian , Li Zhao 
Published: September 2024

Background
Hypertension is a significant risk factor for cardiovascular and chronic kidney diseases. Its management in young people remains limited. Device‐based therapies, such as low‐level tragus stimulation (LL‐TS), a noninvasive method that reduces sympathetic activity, have recently been explored for resistant hypertension.

Methods and Results

This trial involved patients with Grade 1 hypertension with no other medical history. LL‐TS (20 Hz, 1 mA, 1 h/day) was applied for 3 months on the tragus (Intervention group [IG]) or earlobe (Control group [CG]). Blood pressure and outcomes were assessed at the first, second, and third months. Among 40 patients, 21 were in IG and 19 in CG. Baseline systolic blood pressure was similar between IG (142.62±8.18 mm Hg) and CG (143.00±8.61 mm Hg),
P
=0.89. Post‐LL‐TS, systolic blood pressure showed significant reductions in IG compared with CG at the first (IG: 134.47±5.95 mm Hg, CG: 141.28±6.78 mm Hg,
P
=0.002), second (IG: 132.50±7.51 mm Hg, CG: 140.62±7.15 mm Hg,
P
=0.001), and third months (IG: 128.81±7.13 mm Hg, CG: 136.51±7.96 mm Hg,
P
=0.003). diastolic blood pressure also differed significantly: first month (IG: 85.34±5.81 mm Hg, CG: 89.74±6.32 mm Hg,
P
=0.03), second month (IG: 82.12±5.22 mm Hg, CG: 88.57±7.11 mm Hg,
P
=0.002), and third month (IG: 80.71±5.96 mm Hg, CG: 87.55±5.26 mm Hg,
P
=0.001). Heart rate was unchanged (
P
>0.05). Only 0.01% of IG subjects reported site irritation, with no serious adverse events.

Conclusions
LL‐TS led to significant blood pressure reductions in young patients with essential hypertension. Further larger trials are needed to confirm the safety and efficacy of LL‐TS.

Registration

URL:
https://www.chictr.org.cn/
; Unique identifier: ChiCTR2000038448.
Association of the Triglyceride‐Glucose Index With Resistant Hypertension and a Nomogram Model Construction
Authors: Yang Hai‐Tao , Liu Jing‐Kun , Liu Bang‐Quan , Yang Yi , Xie Xiang 
Published: September 2024

Background
Resistant hypertension (RH) remains one of the major risk factors for cardiovascular disease. This study aims to investigate the association between the triglyceride‐glucose (TyG) index and RH incidence in patients with hypertension and to construct a nomogram for predicting the occurrence of RH.

Methods and Results

A retrospective cohort study was conducted on 1635 patients initially diagnosed with hypertension at the Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University from August 2019 to August 2021. Patients were followed up for a median of 31 months, with 373 cases (22.81%) developing RH. Least absolute shrinkage and selection operator regression and multivariable Cox regression analysis identified the TyG index as the strongest predictor of RH (hazard ratio, 5.472 [95% CI, 4.028–7.433];
P
<0.001). Consistent results were also observed in subgroup analyses across different ages and sexes. In addition to the TyG index, other independent risk factors, including uric acid, age, and the apnea‐hypopnea index, were noted. A nomogram model was subsequently developed using these risk factors, and including the TyG index notably enhanced the diagnostic effectiveness of the model in predicting the occurrence of RH.

Conclusions
The TyG index appears to be a potential predictor of RH in patients with hypertension, indicating that insulin resistance might be an important factor in the development and progression of RH.
Ischemic Stroke in Adults With Congenital Heart Disease: Cumulative Incidence and Associated Factors
Authors: Angerbjörn Maria , Johansson Bengt , Eriksson Marie , Rinnström Daniel , Sandberg Camilla , Christersson Christina , Sörensson Peder , Trzebiatowska‐Krzynska Aleksandra , Mandalenakis Zacharias , Thilén Ulf , Pennlert Johanna 
Published: September 2024

Background
When more patients with congenital heart disease reach adult age, increased incidence of long‐term complications, including ischemic stroke, are expected. The aim of this study was to analyze cumulative incidence of ischemic stroke, associated factors, and case fatality in adult congenital heart disease.

Methods and Results
The study is based on Swedish national registers on congenital heart disease and stroke. Patients with congenital heart disease were followed between 2001 and 2018 for first‐ever ischemic stroke events (ischemic stroke due to patent foramen ovale excluded). Factors possibly associated with ischemic stroke were analyzed using Cox regression models. Out of 8914 adult patients with congenital heart disease, 108 suffered ischemic stroke over a mean period of 7.6±4.7 years. The mean age at ischemic stroke was 53.8 years, and the cumulative incidence was 0.15% at 1 year, 0.5% at 5 years, and 1.5% at 10 years. In multivariable analysis, age (hazard ratio [HR], 1.04 [95% CI, 1.03–1.06]), diabetes (HR, 2.9 [95% CI, 1.3–6.4]), ejection fraction <50% (HR, 1.9 [95% CI, 1.1–3.4]), atrial septal defect (HR, 3.0 [95% CI, 1.03–8.5]), and aortic valve lesions (HR, 4.8 [95% CI, 1.6–14.1]) were associated with increased risk. Among those with ischemic stroke, approximately half were on antithrombotic treatment (anticoagulants or antiplatelets) before admission. Case fatality was 6.5%.

Conclusions
The cumulative incidence of ischemic stroke was 1.5% after 10 years. In adult congenital heart disease, the type of heart lesion, diabetes, ejection fraction <50%, and age were important factors associated with ischemic stroke. Despite a relatively young age, mortality is a significant threat. At time of the ischemic stroke event, approximately half of the patients were on antithrombotic treatment.