bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic characterization of recombinant
Clostridium beijerinckii
NCIMB 8052 expressing methylglyoxal synthase and glyoxal reductase from
Clostridium pasteurianum
ATCC 6013
Authors: Kumar Santosh , Agyeman-Duah Eric , Awaga-Cromwell Marian M. , Ujor Victor C. 
Published: September 2024

ABSTRACT

Bioconversion of abundant lactose-replete whey permeate to value-added chemicals holds promise for valorization of this expanding food processing waste. Efficient conversion of whey permeate-borne lactose requires adroit microbial engineering to direct carbon to the desired chemical. An engineered strain of
Clostridium beijerinckii
NCIMB 8052 (
C. beijerinckii
_mgsA+mgR) that produces 87% more butanol on lactose than the control strain was assessed for global transcriptomic changes. The results revealed broadly contrasting gene expression patterns in
C. beijerinckii
_mgsA+mgR relative to the control strain. These were characterized by widespread decreases in the abundance of mRNAs of Fe-S proteins in
C. beijerinckii
_mgsA+mgR, coupled with increased differential expression of lactose uptake and catabolic genes, iron uptake genes, two-component signal transduction and motility genes, and genes involved in the biosynthesis of vitamins B
5
and B
12
, aromatic amino acids (particularly tryptophan), arginine, and pyrimidines. Conversely, the mRNA patterns suggest that the L-aspartate-dependent
de novo
biosynthesis of NAD as well as biosynthesis of lysine and asparagine and metabolism of glycine and threonine were likely down-regulated. Furthermore, genes involved in cysteine and methionine biosynthesis and metabolism, including cysteine desulfurase—a central player in Fe-S cluster biosynthesis—equally showed reductions in mRNA abundance. Genes involved in biosynthesis of capsular polysaccharides and stress response also showed reduced mRNA abundance in
C. beijerinckii
_mgsA+mgR. The results suggest that remodeling of cellular and metabolic networks in
C. beijerinckii
_mgsA+mgR to counter anticipated effects of methylglyoxal production from heterologous expression of methylglyoxal synthase led to enhanced growth and butanol production in
C. beijerinckii
_mgsA+mgR.

IMPORTANCE

Biological production of commodity chemicals from abundant waste streams such as whey permeate represents an opportunity for decarbonizing chemical production. Whey permeate remains a vastly underutilized feedstock for bioproduction purposes. Thus, enhanced understanding of the cellular and metabolic repertoires of lactose-mediated production of chemicals such as butanol promises to identify new targets that can be fine tuned in recombinant and native microbial strains to engender stronger coupling of whey permeate-borne lactose to value-added chemicals. Our results highlight new genetic targets for future engineering of
C. beijerinckii
for improved butanol production on lactose and ultimately in whey permeate.
Bruck syndrome in pregnancy
Authors: Manohar Shravya , Jakes Adam , Watt-Coote Ingrid , Khalil Asma 
Published: September 2024

Bruck syndrome is a rare, autosomal-recessive condition associated with features of both arthrogryposis and osteogenesis imperfecta. It is characterised by congenital large joint contractures with pterygia and bone fragility, leading to fractures and deformities, along with a short stature caused by progressive skeletal deformities. There are fewer than 50 described cases of Bruck syndrome in the literature, with no reported cases in pregnancy. We describe a case of a successful pregnancy in a woman with Bruck syndrome.In pregnant women with Bruck syndrome, we recommend a multidisciplinary approach including input from obstetric and fetal medicine specialists, midwives, anaesthetists, geneticists, occupational therapists and physiotherapists.
Evaluating the impact of malaria rapid diagnostic tests on patient-important outcomes in sub-Saharan Africa: a systematic review of study methods to guide effective implementation
Authors: Otieno Jenifer Akoth , Were Lisa Malesi , Sagam Caleb Kimutai , Kariuki Simon , Ochodo Eleanor 
Published: September 2024

ObjectiveTo perform critical methodological assessments on designs, outcomes, quality and implementation limitations of studies evaluating the impact of malaria rapid diagnostic tests (mRDTs) on patient-important outcomes in sub-Saharan Africa.DesignA systematic review of study methods.Data sourcesMEDLINE, EMBASE, Cochrane Library, African Index Medicus and clinical trial registries were searched up to May 2022.Eligibility criteriaPrimary quantitative studies that compared mRDTs to alternative diagnostic tests for malaria on patient-important outcomes within sub-Sahara Africa.Data extraction and synthesisStudies were sought by an information specialist and two independent reviewers screened for eligible records and extracted data using a predesigned form using Covidence. Methodological quality was assessed using the National Institutes of Health tools. Descriptive statistics and thematic analysis guided by the Supporting the Use of Research Evidence framework were used for analysis. Findings were presented narratively, graphically and by quality ratings.ResultsOur search yielded 4717 studies, of which we included 24 quantitative studies; (15, 62.5%) experimental, (5, 20.8%) quasi-experimental and (4, 16.7%) observational studies. Most studies (17, 70.8%) were conducted within government-owned facilities. Of the 24 included studies, (21, 87.5%) measured the therapeutic impact of mRDTs. Prescription patterns were the most reported outcome (20, 83.3%). Only (13, 54.2%) of all studies reported statistically significant findings, in which (11, 45.8%) demonstrated mRDTs’ potential to reduce over-prescription of antimalarials. Most studies (17, 70.8%) were of good methodological quality; however, reporting sample size justification needs improvement. Implementation limitations reported were mostly about health system constraints, the unacceptability of the test by the patients and low trust among health providers.ConclusionImpact evaluations of mRDTs in sub-Saharan Africa are mostly randomised trials measuring mRDTs’ effect on therapeutic outcomes in real-life settings. Though their methodological quality remains good, process evaluations can be incorporated to assess how contextual concerns influence their interpretation and implementation.PROSPERO registration numberCRD42018083816.
Resection versus biopsy in patients with glioblastoma (RESBIOP study): study protocol for an international multicentre prospective cohort study (ENCRAM 2202)
Authors: Gerritsen Jasper Kees Wim , Young Jacob S , Krieg Sandro M , Jungk Christine , Ille Sebastian , Schucht Philippe , Nahed Brian V , Broekman Marike Lianne Daphne , Berger Mitchel , De Vleeschouwer Steven , Vincent Arnaud J P E 
Published: September 2024

IntroductionThere are no guidelines or prospective studies defining the optimal surgical treatment for glioblastomas in older patients (≥70 years), for those with a limited functioning performance at presentation (Karnofsky Performance Scale ≤70) or for those with tumours in certain locations (midline, multifocal). Therefore, the decision between resection and biopsy is varied, among neurosurgeons internationally and at times even within an institution. This study aims to compare the effects of maximal tumour resection versus tissue biopsy on survival, functional, neurological and quality of life outcomes in these patient subgroups. Furthermore, it evaluates which modality would maximise the potential to undergo adjuvant treatment.Methods and analysisThis study is an international, multicentre, prospective, two-arm cohort study of an observational nature. Consecutive patients with glioblastoma will be treated with resection or biopsy and matched with a 1:1 ratio. Primary endpoints are (1) overall survival and (2) proportion of patients that have received adjuvant treatment with chemotherapy and radiotherapy. Secondary endpoints are (1) proportion of patients with National Institute of Health Stroke Scale deterioration at 6 weeks, 3 months and 6 months after surgery; (2) progression-free survival (PFS); (3) quality of life at 6 weeks, 3 months and 6 months after surgery and (4) frequency and severity of serious adverse events. The total duration of the study is 5 years. Patient inclusion is 4 years; follow-up is 1 year.Ethics and disseminationThe study has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020-0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media.Trial registration numberNCT06146725.
Ten years trajectories of estimated glomerular filtration rate (eGFR) in a multiethnic cohort of people with type 1 diabetes and preserved renal function
Authors: Ayis Salma , Mangelis Anastasios , Fountoulakis Nikolaos , Collins Julian , Alobaid Thamer S , Gnudi Luigi , Hopkins David , Vas Prashanth , Thomas Stephen , Goubar Aicha , Karalliedde Janaka 
Published: September 2024

ObjectivesWe aim to evaluate estimated glomerular filtration rate (eGFR) patterns of progression in a multiethnic cohort of people with type I diabetes mellitus and with baseline eGFR ≥45 mL/min/1.73 m2.DesignObservational cohort.SettingPeople with a clinical diagnosis of type 1 diabetes, attending two university hospital-based outpatient diabetes clinics, in South London between 2004 and 2018.ParticipantsWe studied 1495 participants (52% females, 81% white, 12% African-Caribbean and 7% others).Primary and secondary outcome measuresClinical measures including weight and height, systolic blood pressure, diastolic blood pressure and laboratory results (such as serum creatinine, urine albumin to creatinine ratio (ACR), HbA1c were collected from electronic health records (EHRs) and eGFR was estimated by the Chronic Kidney Disease–Epidemiology Collaboration. Ethnicity was self-reported.ResultsFive predominantly linear patterns/groups of eGFR trajectories were identified. Group I (8.5%) had a fast eGFR decline (>3 mL/min/1.73 m2year). Group II (23%) stable eGFR, group III (29.8%), groups IV (26.3%) and V (12.4%) have preserved eGFR with no significant fall. Group I had the highest proportion (27.6%) of African-Caribbeans. Significant differences between group I and the other groups were observed in age, gender, HbA1C, systolic and diastolic blood pressure, body mass index, cholesterol and urine ACR, p<0.05 for all. At 10 years of follow-up, 33% of group I had eGFR <30 and 16.5%<15 (mL/min/1.73 m2).ConclusionsDistinct trajectories of eGFR were observed in people with type 1 diabetes. The group with the highest risk of eGFR decline had a greater proportion of African-Caribbeans compared with others and has higher prevalence of traditional modifiable risk factors for kidney disease.
Omission of sentinel lymph node biopsy in patients with clinically axillary lymph node-negative early breast cancer (OMSLNB): protocol for a prospective, non-inferiority, single-arm, phase II clinical trial in China
Authors: Li Xuan , Wang Lexin , Wang Yuanyuan , Ma Lingjun , Zheng Ran , Ding Jingjing , Gong Yichun , Yao Hao , Wang Jue , Zha Xiaoming 
Published: September 2024

IntroductionSentinel lymph node biopsy (SLNB) is a standard procedure for patients with clinically assessed negative axillary lymph nodes (cN0) during early-stage breast cancer (EBC). However, the majority of EBC patients have a negative pathological confirmation of the sentinel lymph node (SLN), and axillary surgery is inevitably associated with postoperative complications. Considering that SLNB has no therapeutic benefit, this trial aims to determine the safety of omitting SLNB in patients with cN0 early invasive breast cancer.Methods and analysisThe OMSLNB trial is a prospective, single-arm, non-inferiority, phase II, open-label study design involving female breast cancer patients with a tumor of ≤3 cm in diameter, who are considered axillary lymph-node-negative based on two or more radiological examinations, including axillary lymph node ultrasonography. Eligible patients will avoid axillary surgery but will undergo breast surgery, which is not limited to breast-conserving surgery. The trial begins in 2023 and is scheduled to end in 2027. The primary endpoint is 3 year invasive disease-free survival (iDFS). The secondary endpoints include the incidence of breast cancer-related lymphoedema, patient-reported outcomes, locoregional recurrence, local recurrence and regional recurrence. It is expected that the 3 year iDFS in patients undergoing SLNB is about 90%, combined with a non-inferiority cut-off of 5%, 80% power, 95% CIs, 0.05 test level, and 10% loss to follow-up rate, the planned enrollment is 311 patients. All enrolled patients will be included in the intention-to-treat analysis.Ethics and disseminationThis trial was approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (No.2023-SR-193). All participants must provide written informed consent to be eligible. The protocol will be described in a peer-reviewed manuscript, and the results will be published in scientific journals and/or at academic conferences.Trial registration numberNCT05935150.
Automatic retinal image analysis methods using colour fundus images for screening glaucomatous optic neuropathy
Authors: Shi Chuying , Lee Jack , Shi Di , Wang Gechun , Yuan Fei , Zee Benny Chung-Ying 
Published: September 2024

ObjectivesTrain an automatic retinal image analysis (ARIA) method to screen glaucomatous optic neuropathy (GON) on non-mydriatic retinal images labelled with the additional results of optical coherence tomography (OCT) and assess different models for the GON classification.MethodsAll the images were obtained from the hospital for training and 10-fold cross-validation. Two methods were used to improve the classification performance: (1) using images labelled with the additional results of OCT as the reference standard and (2) generating models using retinal features from the entire images, the region of interest (ROI) of the optic disc, and the ROI of the macula, and the combination of all the features.ResultsOverall, we collected 1338 images with paired OCT scans. In 10-fold validation, ARIA achieved sensitivities of 92.2 %, 92.7% and 85.7%, specificities of 88.8%, 86.7% and 80.2% and accuracies of 90.6%, 89.9% and 83.1% using the retinal features from the entire images, the ROI of the optic disc and the ROI of the macula, respectively. We found the model combining all the features has the best classification performance and obtained a sensitivity of 92.5%, a specificity of 92.1% and an accuracy of 92.4%, which is significantly different from other models (p<0.001).ConclusionWe used two methods to improve the classification performance and found the best model to detect glaucoma on colour fundus retinal images. It can become a cost-effective and relatively more accurate glaucoma screening tool than conventional methods.
Lifetime effects and cost-effectiveness of statin therapy for older people in the United Kingdom: a modelling study
Authors: Mihaylova Borislava , Wu Runguo , Zhou Junwen , Williams Claire , Schlackow Iryna , Emberson Jonathan , Reith Christina , Keech Anthony , Robson John , Parnell Richard , Armitage Jane , Gray Alastair , Simes John , Baigent Colin 
Published: September 2024

BackgroundCardiovascular disease (CVD) risk increases with age. Statins reduce cardiovascular risk but their effects are less certain at older ages. We assessed the long-term effects and cost-effectiveness of statin therapy for older people in the contemporary UK population using a recent meta-analysis of randomised evidence of statin effects in older people and a new validated CVD model.MethodsThe performance of the CVD microsimulation model, developed using the Cholesterol Treatment Trialists’ Collaboration (CTTC) and UK Biobank cohort, was assessed among participants ≥70 years old at (re)surveys in UK Biobank and the Whitehall II studies. The model projected participants’ cardiovascular risks, survival, quality-adjusted life years (QALYs) and healthcare costs (2021 UK£) with and without lifetime standard (35%–45% low-density lipoprotein cholesterol reduction) or higher intensity (≥45% reduction) statin therapy. CTTC individual participant data and other meta-analyses informed statins’ effects on cardiovascular risks, incident diabetes, myopathy and rhabdomyolysis. Sensitivity of findings to smaller CVD risk reductions and to hypothetical further adverse effects with statins were assessed.ResultsIn categories of men and women ≥70 years old without (15,019) and with (5,103) prior CVD, lifetime use of a standard statin increased QALYs by 0.24–0.70 and a higher intensity statin by a further 0.04–0.13 QALYs per person. Statin therapies were cost-effective with an incremental cost per QALY gained below £3502/QALY for standard and below £11778/QALY for higher intensity therapy and with high probability of being cost-effective. In sensitivity analyses, statins remained cost-effective although with larger uncertainty in cost-effectiveness among older people without prior CVD.ConclusionsBased on current evidence for the effects of statin therapy and modelling analysis, statin therapy improved health outcomes cost-effectively for men and women ≥70 years old.
Work Environment, Burnout, and Intent to Leave Current Job Among Cardiologists and Cardiology Health Care Workers: Results From the National Coping With COVID Survey
Authors: Mallick Sanjoyita , Douglas Pamela S. , Shroff Gautam R. , Karim Rehan , Sullivan Erin , Sinsky Christine , Nankivil Nancy , Shah Purva , Brown Roger , Linzer Mark 
Published: September 2024

Background
Little is known about factors contributing to burnout and intent to leave in cardiologists and other cardiology health care workers.

Methods and Results

The Coping With COVID survey assessed work conditions, burnout, and intent to leave among physicians, nurses, advanced practice providers, and other clinical staff (OCS) from April 2020 to December 2020. Single‐item measures assessed work conditions, burnout (emotional exhaustion), and intent to leave. Multilevel logistic regression examined work life variables' relationships to burnout among role types and feeling valued as a mediator. Open‐ended comments analyzed via grounded theory contributed to a conceptual model. Coping With COVID was completed by 1199 US cardiology health care workers (354 physician/520 nurses/198 advanced practice providers/127 OCS). Nurses were most likely to report burnout (59% nurses, 57% OCS, 46% advanced practice providers, 40% physicians,
P
<0.0001). Workload correlated with burnout in all groups (adjusted odds ratios [aORs], 4.1–17.4;
P
s<0.005), whereas anxiety/depression related to burnout in all except OCS (aORs, 3.9–8.3;
P
s≤0.001). Feeling valued was related to lower burnout in most groups. Intent to leave was common (23%–45%) and was lower in physicians and advanced practice providers who felt valued (aORs, 0.26 and 0.22, respectively;
P
s<0.05). Burnout was highest for nurses in practice 16 to 20 years, and intent to leave was highest for OCS in practice 16 to 20 years. Themes contributing to burnout included personal and patient safety, leadership, and financial issues.

Conclusions
Burnout was prevalent among cardiology health care workers and highest in nurses and OCS. Addressing factors associated with burnout in different role types may improve work life sustainability for all cardiology health care workers.
Temporal Trend in Hospitalization Among Patients With Congenital Heart Disease: A Danish Nationwide Study
Authors: Lim Chee Woon , Jensen Annette Schophuus , Marstein Camilla Margit , Bække Pernille Steen , Thuraiaiyah Jani , Lytzen Rebekka Miland Tøndering , Jøns Christian , Schmidt Michael Rahbek , Sondergaard Lars , Jørgensen Troels Højsgaard 
Published: September 2024

Background
The congenital heart disease (CHD) population is growing and aging. We aim to examine the impact by describing the temporal trend and causes of lifetime hospitalization burden among the CHD population.

Methods and Results

From the Danish National Patient Registry, 23 141 patients with CHD and their hospitalizations from 1977 to 2018 were identified, excluding patients with extracardiac malformation. Patients with CHD were categorized into major CHD and minor CHD, and each patient was matched with 10 controls by sex and year of birth. The rate of all‐cause hospitalization increased over time from 28.3 to 36.4 hospitalizations per 100 person‐years (PY) with rate difference (RD) per decade of 2.5 (95% CI, 2.0–3.1) hospitalizations per 100 PY for the patients with CHD, compared with the increase from 10.8 to 17.0 per 100 PY (RD per decade, 2.0 [95% CI, 1.8–2.2] per 100 PY) for the control group (RD for CHD versus control,
P
=0.08). The all‐cause hospitalization rate remained constant for the major CHDs (RD per decade, −0.2 [95% CI, −1.2 to 0.9] per 100 PY) but increased for the minor CHDs (RD per decade, 5.2 [95% CI, 4.3–6.0] per 100 PY). For all patients with CHD, the cardiovascular hospitalization rate remained constant over time (RD per decade, 0.2 [95% CI, −0.3 to 0.6] per 100 PY) whereas the noncardiovascular hospitalization rate increased (RD per decade, 2.1 [95% CI, 1.6–2.7] per 100 PY). The length of all‐cause hospital stays for all patients with CHD decreased from 2.7 (95% CI, 2.6–2.8) days per PY in 1977 to 1987 to 1.6 (95% CI, 1.6–1.7) days per PY in 2008 to 2018.

Conclusions
Compared with previous decades, patients with CHD have an increasing hospitalization rate, similar to the general population, but a decreasing length of hospital stay. The increase in hospitalization rate was driven by noncardiovascular hospitalizations, with the patients with minor CHD being the key contributor to the increasing rate.
Adverse Cardiovascular Effects of Nicotine Delivered by Chronic Electronic Cigarettes or Standard Cigarettes Captured by Cardiovascular Intrinsic Frequencies
Authors: Alavi Rashid , Dai Wangde , Mazandarani Sohrab P. , Arechavala Rebecca J. , Herman David A. , Kleinman Michael T. , Kloner Robert A. , Pahlevan Niema M. 
Published: September 2024

Background
Electronic cigarettes have gained popularity as a nicotine delivery system, which has been recommended by some as an aid to help people quit traditional smoking. The potential long‐term effects of vaping on the cardiovascular system, as well as how their effects compare with those from standard cigarettes, are not well understood. The intrinsic frequency (IF) method is a systems approach for analysis of left ventricle and arterial function. Recent clinical studies have demonstrated the diagnostic and prognostic value of IF. Here, we aim to determine whether the novel IF metrics derived from carotid pressure waveforms can detect effects of nicotine (delivered by chronic exposure to electronic cigarette vapor or traditional cigarette smoke) on the cardiovascular system.

Methods and Results
One hundred seventeen healthy adult male and female rats were exposed to purified air (control), electronic cigarette vapor without nicotine, electronic cigarette vapor with nicotine, and traditional nicotine‐rich cigarette smoke, after which hemodynamics were comprehensively evaluated. IF metrics were computed from invasive carotid pressure waveforms. Standard cigarettes significantly increased the first IF (indicating left ventricle contractile dysfunction). Electronic cigarettes with nicotine significantly reduced the second IF (indicating adverse effects on vascular function). No significant difference was seen in the IF metrics between controls and electronic cigarettes without nicotine. Exposure to electronic cigarettes with nicotine significantly increased the total IF variation (suggesting adverse effects on left ventricle‐arterial coupling and its optimal state), when compared with electronic cigarettes without nicotine.

Conclusions
Our IF results suggest that nicotine‐containing electronic cigarettes adversely affect vascular function and left ventricle‐arterial coupling, whereas standard cigarettes have an adverse effect on left ventricle function.