bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining culture optimization and synthetic biology to improve production and detection of secondary metabolites in
Myxococcus xanthus
: application to myxoprincomide
Authors: Sourice Mathieu , Simmler Charlotte , Maresca Marc , Py Béatrice , Aubert Corinne 
Published: October 2024

ABSTRACT

Microbial secondary metabolites play crucial ecological roles in governing species interactions and contributing to their defense strategies. Their unique structures and potent bioactivities have been key in discovering antibiotics and anticancer drugs. Genome sequencing has undoubtedly revealed that myxobacteria constitute a huge reservoir of secondary metabolites as the well-known producers, actinomycetes. However, because most secondary metabolites are not produced in the laboratory context, the natural products from myxobacteria characterized to date represent only the tip of the iceberg. By combining the engineering of a dedicated
Myxococcus xanthus
DZ2 chassis strain with a two-step growth medium protocol, we provide a new approach called two-step Protocol for Resource Integration and Maximization–Biomolecules Overproduction and Optimal Screening Therapeutics (2PRIM-BOOST) for the production of non-ribosomal peptides synthetases (NRPS)/polyketides synthases (PKS) secondary metabolites from myxobacteria. We further show that the 2PRIM-BOOST strategy will facilitate the screening of secondary metabolites for biological activities of medical interest. As proof of concept, using a constitutive strong promoter, the myxoprincomide from
M. xanthus
DZ2 has been efficiently produced and its biosynthesis has been enhanced using the 2PRIM-BOOST approach, allowing the identification of new features of myxoprincomide. This strategy should allow the chances to produce and discover new NRPS, PKS, and mixed NRPS/PKS hybrid natural metabolites that are currently considered as cryptic and are the most represented in myxobacteria.

IMPORTANCE

Microbial secondary metabolites are important in species interactions and are also a prolific source of drugs. Myxobacteria are ubiquitous soil-dwelling bacteria constituting a huge reservoir of secondary metabolites. However, because most of these molecules are not produced in the laboratory context, one can estimate that only one-tenth have been characterized to date. Here, we developed a new strategy called two-step Protocol for Resource Integration and Maximization–Biomolecules Overproduction and Optimal Screening Therapeutics (2PRIM-BOOST) that combines the engineering of a dedicated
Myxococcus xanthus
chassis strain together with growth medium optimization. By combining these strategies with the insertion of a constitutive promoter upstream the biosynthetic gene cluster (BGC), the production of myxoprincomide, a characterized low-produced secondary metabolite, was successfully and significantly increased. The 2PRIM-BOOST enriches the toolbox used to produce previously cryptic metabolites, unveil their ecological role, and provide new molecules of medical interest.
Long Covid: a global health issue – a prospective, cohort study set in four continents
Authors: Pazukhina Ekaterina , Garcia-Gallo Esteban , Reyes Luis Felipe , Kildal Anders Benjamin , Jassat Waasila , Dryden Murray , Holter Jan Cato , Chatterjee Allegra , Gomez Kyle , Søraas Arne , Puntoni Matteo , Latronico Nicola , Bozza Fernando A , Edelstein Michael , Gonçalves Bronner P , Kartsonaki Christiana , Kruglova Oksana , Gaião Sérgio , Chow Yock Ping , Doshi Yash , Duque Vallejo Sara Isabel , Ibáñez-Prada Elsa D , Fuentes Yuli V , Hastie Claire , O'Hara Margaret E , Balan Valeria , Menkir Tigist , Merson Laura , Kelly Sadie , Citarella Barbara Wanjiru , Semple Malcolm G , Scott Janet T , Munblit Daniel , Sigfrid Louise ,   ISARIC Global Covid-19 follow up working group
Published: October 2024

IntroductionA proportion of people develop Long Covid after acute COVID-19, but with most studies concentrated in high-income countries (HICs), the global burden is largely unknown. Our study aims to characterise long-term COVID-19 sequelae in populations globally and compare the prevalence of reported symptoms in HICs and low-income and middle-income countries (LMICs).MethodsA prospective, observational study in 17 countries in Africa, Asia, Europe and South America, including adults with confirmed COVID-19 assessed at 2 to <6 and 6 to <12 months post-hospital discharge. A standardised case report form developed by International Severe Acute Respiratory and emerging Infection Consortium’s Global COVID-19 Follow-up working group evaluated the frequency of fever, persistent symptoms, breathlessness (MRC dyspnoea scale), fatigue and impact on daily activities.ResultsOf 11 860 participants (median age: 52 (IQR: 41–62) years; 52.1% females), 56.5% were from HICs and 43.5% were from LMICs. The proportion identified with Long Covid was significantly higher in HICs vs LMICs at both assessment time points (69.0% vs 45.3%, p<0.001; 69.7% vs 42.4%, p<0.001). Participants in HICs were more likely to report not feeling fully recovered (54.3% vs 18.0%, p<0.001; 56.8% vs 40.1%, p<0.001), fatigue (42.9% vs 27.9%, p<0.001; 41.6% vs 27.9%, p<0.001), new/persistent fever (19.6% vs 2.1%, p<0.001; 20.3% vs 2.0%, p<0.001) and have a higher prevalence of anxiety/depression and impact on usual activities compared with participants in LMICs at 2 to <6 and 6 to <12 months post-COVID-19 hospital discharge, respectively.ConclusionOur data show that Long Covid affects populations globally, manifesting similar symptomatology and impact on functioning in both HIC and LMICs. The prevalence was higher in HICs versus LMICs. Although we identified a lower prevalence, the impact of Long Covid may be greater in LMICs if there is a lack of support systems available in HICs. Further research into the aetiology of Long Covid and the burden in LMICs is critical to implement effective, accessible treatment and support strategies to improve COVID-19 outcomes for all.
Defining blood deserts and access to blood products for 660 million people: a geospatial analysis of eight states in Northern India
Authors: Kundu Shreenik , Munoz Valencia Alejandro , Virk Sargun Kaur , Kumar Nikathan , Gadgil Anita , Mammen Joy John , Roy Nobhojit , Raykar Nakul 
Published: October 2024

IntroductionBlood transfusion is crucial, but low-income and middle-income countries like India face a severe shortage of banked blood. This study focuses on the Empowered Action Group (EAG) states in India, where healthcare is limited, and health outcomes are poor. Our objective was to assess the blood banking infrastructure and access to blood products in these states.MethodsWe used e-Rakht Khosh, an online platform for blood availability data. We collected data on blood bank locations and stocks from 18 January to 9 February 2022 and used ArcGIS to determine the population residing within 30–60–90 min of a blood bank. Availability ratios were calculated by dividing available blood products by population in these catchment areas. Descriptive analysis characterised availability, and statistical tests evaluated differences across states and over the 4-week period.Results806 of 824 blood banks reported data on blood stocks. Our analysis showed that 25.72% of the EAG states’ population live within 30 min of a blood bank, while 61.45% and 92.46% live within 60 and 90 min, respectively.ConclusionBlood availability rates were low in the EAG states, with only 0.6 units per 1000 people. Additionally, only 61% of the population had access to blood-equipped facilities within an hour. These rates fell below the standards of the Lancet Commission on Global Surgery (15 units per 1000 population) and the WHO (10 donations per 1000 population). The study highlights the challenges in meeting demand for blood in emergencies due to inadequate blood banking infrastructure.
A cost-effectiveness analysis of sentinel lymph node biopsy compared with lymphadenectomy in intermediate- and high-risk endometrial carcinoma
Authors: Bjerre Trent Pernille , Eriksson Ane Gerda , Staff Anne Cathrine , Juul-Hansen Knut Erling , Burger Emily Annika , Wangen Knut Reidar 
Published: October 2024

BackgroundSentinel lymph node biopsy (SLN) is increasingly used for surgical staging of endometrial carcinoma.ObjectiveTo estimate the effect and cost-effectiveness of the implementation of an SLN algorithm for surgical staging in patients with intermediate- and high-risk endometrial carcinoma compared with lymphadenectomy.MethodsWe performed a model-based, cost-effectiveness analysis using primary data from a tertiary referral hospital that included 829 patients with endometrial carcinoma undergoing surgical staging. We quantified the health and economic outcomes from two time periods, before and after implementation of the SLN algorithm by robotic surgery. Costs were measured directly from the hospital’s financial department, while long-term health outcomes were estimated using self-reported lymphedema and health-related quality-of-life among survivors. Sensitivity analyses were conducted to evaluate uncertainty.ResultsWe projected that the SLN implementation period, predominately reflecting use of robotic SLN, simultaneously improved health outcomes (0.08 incremental quality-adjusted life-years) and lowered costs (US$1051) compared with the prior period involving robotic or open lymphadenectomy. SLN remained more beneficial and less costly across key sensitivity analyses—namely, varying the cost of the robotic platform, surgical equipment, number of yearly robotic procedures, percentage of robotic procedures versus percentage of laparotomies, length of stay, and lymphedema development. After 1000 simulations of the model, SLN implementation provided greater health benefits for lower costs (ie, cost saving) in 89% of simulations.ConclusionImplementation of an SLN algorithm in the staging of intermediate- and high-risk endometrial carcinoma improved health outcomes for lower costs compared with lymphadenectomy. Cost-effectiveness could further improve by continuing to increase the proportion of robotic procedures.
Lynch syndrome diagnostic testing pathways in endometrial cancers: a nationwide English registry-based study
Authors: Loong Lucy , Huntley Catherine , Pethick Joanna , McRonald Fiona , Santaniello Francesco , Shand Brian , Tulloch Oliver , Goel Shilpi , Lüchtenborg Margreet , Allen Sophie , Torr Bethany , Snape Katie , George Angela , Lalloo Fiona , Norbury Gail , Eccles Diana M , Tischkowitz Marc , Antoniou Antonis C , Pharoah Paul , Shaw Adam , Morris Eva , Burn John , Monahan Kevin , Hardy Steven , Turnbull Clare 
Published: October 2024

BackgroundFor female patients with Lynch syndrome (LS), endometrial cancer (EC) is often their first cancer diagnosis. A testing pathway of somatic tumour testing triage followed by germline mismatch repair (MMR) gene testing is an effective way of identifying the estimated 3% of EC caused by LS.MethodsA retrospective national population-based observational study was conducted using comprehensive national data collections of functional, somatic and germline MMR tests available via the English National Cancer Registration Dataset. For all EC diagnosed in 2019, the proportion tested, median time to test, yield of abnormal results and factors influencing testing pathway initiation were examined.ResultsThere was an immunohistochemistry (IHC) or microsatellite instability (MSI) test recorded for 17.8% (1408/7928) of patients diagnosed with EC in 2019. Proportions tested varied by Cancer Alliance and age. There was anMLH1promoter hypermethylation test recorded for 43.1% (149/346) of patients with MLH1 protein IHC loss or MSI. Of patients with EC eligible from tumour-testing, 25% (26/104) had a germline MMR test recorded. Median time from cancer diagnosis to germline MMR test was 315 days (IQR 222–486).ConclusionThis analysis highlights the regional variation in recorded testing, patient attrition, delays and missed opportunities to diagnose LS, providing an informative baseline for measuring the impact of the national guidance from the National Institute for Health and Care Excellence on universal reflex LS testing in EC, implemented in 2020.
Management of a fractured microcatheter during middle meningeal artery embolization
Authors: Webb Matthew , Luo Anqi , Al Saiegh Fadi , Birnbaum Lee , Gragnaniello Cristian , Mascitelli Justin R 
Published: October 2024

Middle meningeal artery embolization (MMAE) is an effective adjunctive treatment for chronic subdural hematomas and carries a low risk of significant complications.1 Here we describe the management of a retained and fractured microcatheter following liquid embolic MMAE. A patient with chronic recurrent subdural hematomas underwent bilateral MMAE with Onyx liquid embolic material (Medtronic). The Headway Duo (Microvention) microcatheter was placed in a small distal frontal branch of the middle meningeal artery to aid in reflux into the posterior middle meningeal artery branches. Following successful MMAE, the microcatheter became trapped within the Onyx cast and, on attempted removal, the microcatheter fractured, resulting in a retained fragment extending from the middle meningeal artery cast to the guide catheter in the common carotid artery.To retrieve the fractured microcatheter, a stent retriever was deployed and resheathed multiple times until the retained microcatheter became visibly entangled with the stent retriever. Next, the stent retriever was pulled back into the guide catheter and continuous aspiration was performed through the guide catheter, and the fragmented microcatheter was successfully removed in entirety. Final angiography demonstrated no further catheter fragments, vessel damage, extravasation, flow limitation, or thromboembolic complications.Methods to avoid the complication include using a detachable tip microcatheter, dual lumen balloon microcatheter, allowing less reflux, embolizing from a larger caliber branch, and a slower microcatheter pull. Additional methods for managing the complication include using a snare, leaving the retained microcatheter and putting the patient on aspirin, and carotid stenting to tack the fractured portion down (video 1).Video 1 Management of a fractured microcatheter during middle meningeal artery embolizationThis case demonstrates the successful use of a stent retriever and aspiration to retrieve a retained and fractured microcatheter following liquid embolic MMAE.
Nitrosamine and nicotine exposure after switching from filtered to unfiltered cigarette smoking: a cross-over clinical trial
Authors: Appolon Giovanni , Oren Eyal , Pulvers Kim , Romero Devan , Hoh Eunha , Dodder Nathan G , Wong Jade , Nynas Katelyn , Tracey LaRee , Lemus Hector , Novotny Thomas E 
Published: October 2024

BackgroundThe cellulose acetate filter is a plastic attachment on nearly all commercial cigarettes sold worldwide. It is the main component of discarded cigarette butts, and the most prevalent waste item collected during urban and beach cleanups. This waste leaches toxic chemicals, including nicotine, metals and tobacco-specific nitrosamines and contributes to environmental microplastic pollution. There is growing international interest in reducing plastic waste from single-use, non-essential products such as cellulose acetate cigarette filters. Public health and environmental advocates recommend a ban on the sale of filtered cigarettes to reduce environmental pollution caused by discarded cigarette butts and to discourage cigarette smoking.Research questionWhat potential health and behavioural implications might arise among people who smoke if filtered cigarettes are removed from the market.MethodsWe conducted a cross-over, randomised clinical trial of 29 people who smoke to evaluate changes in biomarkers for nicotine and tobacco-specific nitrosamine exposure when switching between filtered and unfiltered cigarette smoking.ResultsAlthough unfiltered smoking showed a higher trend in the geometric means of 4-[(methylnitrosamino])−1-[3-pyridyl]−1-butanol (NNAL) compared with filtered cigarettes, regression models for urinary cotinine and NNAL showed no significant differences when switching between filtered and unfiltered cigarettes.ConclusionThis proof-of-principle study suggests there is no increased risk to people who smoke when switching to unfiltered cigarette smoking. Although larger studies might provide more evidence regarding unfiltered cigarette smoking, banning the sale of filtered cigarettes may be an important policy intervention to both reduce hazardous tobacco waste and discourage smoking.
The $$v^{1/3}_{3}/v^{1/2}_{2}$$ ratio in PbAu collisions at $$\sqrt{s_{\textrm{NN}}} = $$ 17.3 GeV: a hint of a hydrodynamic behavior
Authors: Adamová D. , Agakishiev G. , Andronic A. , Antończyk D. , Appelshäuser H. , Belaga V. , Bielčíková J. , Braun-Munzinger P. , Busch O. , Cherlin A. , Damjanović S. , Dietel T. , Dietrich L. , Drees A. , Dubitzky W. , Esumi S. I. , Filimonov K. , Fomenko K. , Fraenkel Z. , Garabatos C. , Glässel P. , Hering G. , Holeczek J. , Kalisky M. , Krobath G. , Kushpil V. , Maas A. , Marín A. , Milošević J. , Miśkowiec D. , Panebrattsev Y. , Paulínyová Z. , Petchenova O. , Petráček V. , Radomski S. , Rak J. , Ravinovich I. , Rehak P. , Sako H. , Schmitz W. , Schuchmann S. , Sedykh S. , Shimansky S. , Stachel J. , Šumbera M. , Tilsner H. , Tserruya I. , Tsiledakis G. , Wessels J. P. , Wienold T. , Wurm J. P. , Yurevich S. , Yurevich V. ,   CERES/NA45 Collaboration
Published: October 2024

AbstractThe Fourier harmonics, $$v_2$$

v
2

and $$v_3$$

v
3

of negative pions are measured at center-of-mass energy per nucleon pair of $$\sqrt{s_{\textrm{NN}}}$$

s
NN

= 17.3 GeV around midrapidity by the CERES/NA45 experiment at the CERN SPS in 0–30% central PbAu collisions with a mean centrality of 5.5%. The analysis is performed in two centrality bins as a function of the transverse momentum $$\mathrm {p_{\textrm{T}}}$$

p
T

from 0.05 GeV/c to more than 2 GeV/c. This is the first measurement of the $$v^{1/3}_{3}/v^{1/2}_{2}$$

v
3

1
/
3

/

v
2

1
/
2

ratio as a function of transverse momentum at SPS energies, that reveals, independently of the hydrodynamic models, hydrodynamic behavior of the formed system. For $$\mathrm {p_{\textrm{T}}}$$

p
T

above 0.5 GeV/c, the ratio is nearly flat in accordance with the hydrodynamic prediction and as previously observed by the ATLAS and ALICE experiments at the much higher LHC energies. The results are also compared with the SMASH-vHLLE hybrid model predictions, as well as with the SMASH model applied alone.
The Correlation Between Visceral Fat Area to Skeletal Muscle Mass Ratio and Multiorgan Insulin Resistance in Chinese Population With Obesity
Authors: Zhang Yanju , Du Meiyang , Li Zhouhuiling , Wang Xincheng , Leng Mingxin , Huang Yaping , Li Libin , Zhang Shi , Li Chunjun 
Published: October 2024

Aims: Insulin resistance (IR) is an important risk factor for obesity and cardiometabolic diseases, and our previous findings have demonstrated that visceral fat area to skeletal muscle mass ratio (VSR) is significantly and positively associated with the risk of cardiometabolic diseases. Hence, this study aimed to investigate the relationship between VSR and multiorgan IR, provide a new approach to improve body composition, and set the basis for VSR to increase the incidence of cardiometabolic diseases.Materials and Methods: The study included 398 patients who underwent anthropometric and biochemical measurements, and body composition assessment. Spearman correlation analysis was used to investigate the correlation between VSR and homeostatic model assessment for insulin resistance (HOMA‐IR) as well as multiorgan IR, including homeostasis model assessment adiponectin (HOMA‐AD), adipose tissue insulin resistance (ADIPO‐IR), and hepatic insulin sensitivity (HISI). The new model that incorporated into the present study is made up of easily measured biochemical indicators and is used to predict IR. Logistic regression was used to analyze the odds ratio (OR) of VSR on the risk of multiorgan IR. The predictive value of VSR for HOMA‐IR and new model was evaluated using the receiver operating characteristic (ROC) curve.Results: VSR was significantly associated with HOMA‐IR, HOMA‐AD, ADIPO‐IR, 1/HISI, and new model (p < 0.001). With the increase of VSR, the OR increased significantly for HOMA‐IR and new model (p < 0.001). Then, multiorgan IR indicators were quantified, compared to the lowest quartile group, and increased VSR exacerbated the risk of IR in the highest quartile (ptrend < 0.001). The area under the curve for predicting IR using VSR for HOMA‐IR and new model was 0.88 for men, 0.85 for women and 0.73 for men, 0.76 for women, respectively.Conclusions: There was significant correlation between VSR and multiorgan IR, and the risk of multiorgan IR increased with increasing VSR.Trial Registration: Clinical Trial Registry identifier: ChiCTR2100044305.
2024 Guideline for the Primary Prevention of Stroke: A Guideline From the American Heart Association/American Stroke Association
Authors: Bushnell Cheryl , Kernan Walter N. , Sharrief Anjail Z. , Chaturvedi Seemant , Cole John W. , Cornwell William K. , Cosby-Gaither Christine , Doyle Sarah , Goldstein Larry B. , Lennon Olive , Levine Deborah A. , Love Mary , Miller Eliza , Nguyen-Huynh Mai , Rasmussen-Winkler Jennifer , Rexrode Kathryn M. , Rosendale Nicole , Sarma Satyam , Shimbo Daichi , Simpkins Alexis N. , Spatz Erica S. , Sun Lisa R. , Tangpricha Vin , Turnage Dawn , Velazquez Gabriela , Whelton Paul K. 
Published: October 2024

AIM:
The “2024 Guideline for the Primary Prevention of Stroke” replaces the 2014 “Guidelines for the Primary Prevention of Stroke.” This updated guideline is intended to be a resource for clinicians to use to guide various prevention strategies for individuals with no history of stroke.

METHODS:
A comprehensive search for literature published since the 2014 guideline; derived from research involving human participants published in English; and indexed in MEDLINE, PubMed, Cochrane Library, and other selected and relevant databases was conducted between May and November 2023. Other documents on related subject matter previously published by the American Heart Association were also reviewed.

STRUCTURE:
Ischemic and hemorrhagic strokes lead to significant disability but, most important, are preventable. The 2024 primary prevention of stroke guideline provides recommendations based on current evidence for strategies to prevent stroke throughout the life span. These recommendations align with the American Heart Association’s Life’s Essential 8 for optimizing cardiovascular and brain health, in addition to preventing incident stroke. We also have added sex-specific recommendations for screening and prevention of stroke, which are new compared with the 2014 guideline. Many recommendations for similar risk factor prevention were updated, new topics were reviewed, and recommendations were created when supported by sufficient-quality published data.