bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic changes in single yeast cells under various stress conditions
Authors: Su Yangqi , Xu Chen , Shea Jonathan , DeStephanis Darla , Su Zhengchang
Published: February 2023

Background

The stress response of Saccharomyces cerevisiae has been extensively studied in the past decade. However, with the advent of recent technology in single-cell transcriptome profiling, there is a new opportunity to expand and further understanding of the yeast stress response with greater resolution on a system level. To understand transcriptomic changes in baker’s yeast S. cerevisiae cells under stress conditions, we sequenced 117 yeast cells under three stress treatments (hypotonic condition, glucose starvation and amino acid starvation) using a full-length single-cell RNA-Seq method.

Results

We found that though single cells from the same treatment showed varying degrees of uniformity, technical noise and batch effects can confound results significantly. However, upon careful selection of samples to reduce technical artifacts and account for batch-effects, we were able to capture distinct transcriptomic signatures for different stress conditions as well as putative regulatory relationships between transcription factors and target genes.

Conclusion

Our results show that a full-length single-cell based transcriptomic analysis of the yeast may help paint a clearer picture of how the model organism responds to stress than do bulk cell population-based methods.
Transcriptomic profiling of the developing brain revealed cell-type and brain-region specificity in a mouse model of prenatal stress
Authors: Dong Yuhao , Weng Jie , Zhu Yueyan , Sun Daijing , He Wei , Chen Qi , Cheng Jin , Zhu Ying , Jiang Yan
Published: February 2023

Background

Prenatal stress (PS) is considered as a risk factor for many mental disorders. PS-induced transcriptomic alterations may contribute to the functional dysregulation during brain development. Here, we used RNA-seq to explore changes of gene expression in the mouse fetal brain after prenatal exposure to chronic unpredictable mild stress (CUMS).

Results

We compared the stressed brains to the controls and identified groups of significantly differentially expressed genes (DEGs). GO analysis on up-regulated DEGs revealed enrichment for the cell cycle pathways, while down-regulated DEGs were mostly enriched in the neuronal pathways related to synaptic transmission. We further performed cell-type enrichment analysis using published scRNA-seq data from the fetal mouse brain and revealed cell-type-specificity for up- and down-regulated DEGs, respectively. The up-regulated DEGs were highly enriched in the radial glia, while down-regulated DEGs were enriched in different types of neurons. Cell deconvolution analysis further showed altered cell fractions in the stressed brain, indicating accumulation of neuroblast and impaired neurogenesis. Moreover, we also observed distinct brain-region expression pattern when mapping DEGs onto the developing Allen brain atlas. The up-regulated DEGs were primarily enriched in the dorsal forebrain regions including the cortical plate and hippocampal formation. Surprisingly, down-regulated DEGs were found excluded from the cortical region, but highly expressed on various regions in the ventral forebrain, midbrain and hindbrain.

Conclusion

Taken together, we provided an unbiased data source for transcriptomic alterations of the whole fetal brain after chronic PS, and reported differential cell-type and brain-region vulnerability of the developing brain in response to environmental insults during the pregnancy.
Wellens’ syndrome following severe COVID-19 infection, an innocent coincidence or a deadly association: two case reports
Authors: Khattar Georges , Hallit Jennifer , El Chamieh Carolla , Bou Sanayeh Elie
Published: February 2023

Background

Coronavirus disease 2019 (COVID-19) has been associated with late-onset cardiovascular complications primarily due to a hypercoagulable state. Its association with Wellens’ syndrome, which reflects a stenosis in the proximal left anterior descending coronary artery, is not well established. We present two cases diagnosed with this syndrome following their COVID-19 acute phase despite taking adequate anticoagulation.

Case presentation

We present two patients with incidental electrocardiography (ECG) showing the typical Wellens’-related changes, with an underlying severe triple-vessel coronary artery disease a few weeks following a severe COVID-19 infection associated with high inflammatory markers. The stenotic lesions were diagnosed by cardiac catheterization, and both patients underwent Coronary Artery Bypass Grafting successfully. Notably, patients’ baseline ECGs were normal, and they were maintained on Rivaroxaban 10 mg following their viral illness.

Conclusion

Despite advances in the preventive measures for COVID-19 complications, its pathophysiologic impact on vasculature and atherosclerosis is still incompletely understood. Further clinical trials must be conducted to study this association between Wellens’ syndrome and this virus to prevent life-threatening complications.
Validation of Oura ring energy expenditure and steps in laboratory and free-living
Authors: Kristiansson Emilia , Fridolfsson Jonatan , Arvidsson Daniel , Holmäng Agneta , Börjesson Mats , Andersson-Hall Ulrika
Published: February 2023

Background

Commercial activity trackers are increasingly used in research and compared with research-based accelerometers are often less intrusive, cheaper, with improved storage and battery capacity, although typically less validated. The present study aimed to determine the validity of Oura Ring step-count and energy expenditure (EE) in both laboratory and free-living.

Methods

Oura Ring EE was compared against indirect calorimetry in the laboratory, followed by a 14-day free-living study with 32 participants wearing an Oura Ring and reference monitors (three accelerometers positioned at hip, thigh, and wrist, and pedometer) to evaluate Oura EE variables and step count.

Results

Strong correlations were shown for Oura versus indirect calorimetry in the laboratory (r = 0.93), and versus reference monitors for all variables in free-living (r ≥ 0.76). Significant (p < 0.05) mean differences for Oura versus reference methods were found for laboratory measured sitting (− 0.12 ± 0.28 MET), standing (− 0.27 ± 0.33 MET), fast walk (− 0.82 ± 1.92 MET) and very fast run (− 3.49 ± 3.94 MET), and for free-living step-count (2124 ± 4256 steps) and EE variables (MET: − 0.34-0.26; TEE: 362–494 kcal; AEE: − 487-259 kcal). In the laboratory, Oura tended to underestimate EE with increasing discrepancy as intensity increased.

Conclusion

This is the first study investigating the validity of Oura Ring EE against gold standard methods. Oura successfully identified major changes between activities and/or intensities but was less responsive to detailed deviations within activities. In free-living, Oura step-count and EE variables tightly correlated with reference monitors, though with systemic over- or underestimations indicating somewhat low intra-individual validity of the ring versus the reference monitors. However, the correlations between the devices were high, suggesting that the Oura can detect differences at group-level for active and total energy expenditure, as well as step count.
Association of statin use with outcomes of patients admitted with COVID-19: an analysis of electronic health records using superlearner
Authors: Rivera Adovich S. , Al-Heeti Omar , Petito Lucia C. , Feinstein Mathew J. , Achenbach Chad J. , Williams Janna , Taiwo Babafemi
Published: February 2023

Importance

Statin use prior to hospitalization for Coronavirus Disease 2019 (COVID-19) is hypothesized to improve inpatient outcomes including mortality, but prior findings from large observational studies have been inconsistent, due in part to confounding. Recent advances in statistics, including incorporation of machine learning techniques into augmented inverse probability weighting with targeted maximum likelihood estimation, address baseline covariate imbalance while maximizing statistical efficiency.

Objective

To estimate the association of antecedent statin use with progression to severe inpatient outcomes among patients admitted for COVD-19.

Design, setting and participants

We retrospectively analyzed electronic health records (EHR) from individuals ≥ 40-years-old who were admitted between March 2020 and September 2022 for ≥ 24 h and tested positive for SARS-CoV-2 infection in the 30 days before to 7 days after admission.

Exposure

Antecedent statin use—statin prescription ≥ 30 days prior to COVID-19 admission.

Main outcome

Composite end point of in-hospital death, intubation, and intensive care unit (ICU) admission.

Results

Of 15,524 eligible COVID-19 patients, 4412 (20%) were antecedent statin users. Compared with non-users, statin users were older (72.9 (SD: 12.6) versus 65.6 (SD: 14.5) years) and more likely to be male (54% vs. 51%), White (76% vs. 71%), and have ≥ 1 medical comorbidity (99% vs. 86%). Unadjusted analysis demonstrated that a lower proportion of antecedent users experienced the composite outcome (14.8% vs 19.3%), ICU admission (13.9% vs 18.3%), intubation (5.1% vs 8.3%) and inpatient deaths (4.4% vs 5.2%) compared with non-users. Risk differences adjusted for labs and demographics were estimated using augmented inverse probability weighting with targeted maximum likelihood estimation using Super Learner. Statin users still had lower rates of the composite outcome (adjusted risk difference: − 3.4%; 95% CI: − 4.6% to − 2.1%), ICU admissions (− 3.3%; − 4.5% to − 2.1%), and intubation (− 1.9%; − 2.8% to − 1.0%) but comparable inpatient deaths (0.6%; − 1.3% to 0.1%).

Conclusions and relevance

After controlling for confounding using doubly robust methods, antecedent statin use was associated with minimally lower risk of severe COVID-19-related outcomes, ICU admission and intubation, however, we were not able to corroborate a statin-associated mortality benefit.
Study protocol of a randomized controlled trial of fistula vs. graft arteriovenous vascular access in older adults with end-stage kidney disease on hemodialysis: the AV access trial
Authors: Murea Mariana , Gardezi Ali I. , Goldman Mathew P. , Hicks Caitlin W. , Lee Timmy , Middleton John P. , Shingarev Roman , Vachharajani Tushar J. , Woo Karen , Abdelnour Lama M. , Bennett Kyla M. , Geetha Duvuru , Kirksey Lee , Southerland Kevin W , Young Carlton J. , Brown William M. , Bahnson Judy , Chen Haiying , Allon Michael
Published: February 2023

Background

Treatment of end-stage kidney disease (ESKD) with hemodialysis requires surgical creation of an arteriovenous (AV) vascular access—fistula (AVF) or graft (AVG)—to avoid (or limit) the use of a central venous catheter (CVC). AVFs have long been considered the first-line vascular access option, with AVGs as second best. Recent studies have suggested that, in older adults, AVGs may be a better strategy than AVFs. Lacking evidence from well-powered randomized clinical trials, integration of these results into clinical decision making is challenging. The main objective of the AV Access Study is to compare, between the two types of AV access, clinical outcomes that are important to patients, physicians, and policy makers.

Methods

This is a prospective, multicenter, randomized controlled trial in adults ≥ 60 years old receiving chronic hemodialysis via a CVC. Eligible participants must have co-existing cardiovascular disease, peripheral arterial disease, and/or diabetes mellitus; and vascular anatomy suitable for placement of either type of AV access. Participants are randomized, in a 1:1 ratio, to a strategy of AVG or AVF creation. An estimated 262 participants will be recruited across 7 healthcare systems, with average follow-up of 2 years. Questionnaires will be administered at baseline and semi-annually. The primary outcome is the rate of CVC-free days per 100 patient-days. The primary safety outcome is the cumulative incidence of vascular access (CVC or AV access)-related severe infections—defined as access infections that lead to hospitalization or death. Secondary outcomes include access-related healthcare costs and patients’ experiences with vascular access care between the two treatment groups.

Discussion

In the absence of studies using robust and unbiased research methodology to address vascular access care for hemodialysis patients, clinical decisions are limited to inferences from observational studies. The goal of the AV Access Study is to generate evidence to optimize vascular access care, based on objective, age-specific criteria, while incorporating goals of care and patient preference for vascular access type in clinical decision-making.

Trial registration

: This study is being conducted in accordance with the tenets of the Helsinki Declaration, and has been approved by the central institutional review board (IRB) of Wake Forest University Health Sciences (approval number: 00069593) and local IRB of each participating clinical center; and was registered on Nov 27, 2020, at ClinicalTrials.gov (NCT04646226).
Case of Pierson syndrome presented with hyphema,vitrous haemorrhage and subsequent neovascular glaucoma
Authors: ALKhamees Abdullah , ALShemmari Mansoor
Published: February 2023

Background

Pierson syndrome is a rare autosomal recessive disorder that causes congenital nephrotic syndrome, neurodevelopmental abnormalities, and several ocular signs. The Pierson syndrome is caused by a mutation of the LAMB2 gene, that encodes laminin beta 2, which is expressed in the glomerular basement membrane, in neuromuscular junctions, and within ocular structures. First described by Pierson et al., the ocular signs of Pierson syndrome include microcoria, which is most characteristic sign, as well as iris abnormalities, cataract, glaucoma, and retinal detachment.

Case presentation

Herein, we report the case of a young female who, at 16 months, was diagnosed with congenital nephrotic syndrome, subsequently underwent a kidney transplant at age 4,did cataract surgery with IOL implantation in both eyes at age of 2 years and presented with ocular signs including high myopia, band keratopathy, t, nystagmus, retina, and optic nerve atrophy, she did not show nor did the family report any neurodevelopmental abnormalities. her genetic studies this missense variant c.970T< C p. (Cys324Arg) of LAMB2, later she developed spontaneous hyphema along with vitreous haemorrhage and increased intra ocular pressure in her left eye, she underwent cyclophotocouagulation to treat her high IOP.

Conclusion

LAMB 2 mutations can be associated with
multiple ocular signs that varies from mild to severe form, we are her to
report our case who did not present with the typical ocular sign of microcoria
for PS, did not have any neurodevelopmental  abnormality and
presented with hyphaemia 2ndry to iris neovascularisation with vitreous haemorrhage
with neovascular glaucoma.
A non-randomized, controlled, interventional study to investigate the effects of community pharmacists’ cognitive behavioral therapy–based interventions on medication adherence and relevant indicators in patients with depression
Authors: Shoji Masaki , Maeda Hatsuyo , Watanabe Fumiyuki , Tanuma Kazunori , Fujiwara Atsuko , Iwanaga Yusuke , Shimada Atsushi , Onda Mitsuko
Published: February 2023

Background

The prevalence of depression is increasing in Japan. Pharmacists play an important role in helping patients use medicines effectively. Several studies had investigated the impact of community pharmacists on patient adherence to antidepressant therapy, and their results indicated that further study was warranted.

Methods

This study was conducted from June 2019 to May 2020 using a cluster non-randomized, open-label, parallel-group design. Four community pharmacy stores in Osaka and Hyogo Prefectures, Japan, participated in the study, and enrolled patients with unipolar depression. In the intervention group (IG), patients received cognitive behavioral therapy (CBT)-based medication support, and their medication adherence and adverse drug reactions were monitored by telephone. In the control group (CG), the pharmacists engaged in routine interactions with the study participants. Before participating in this study, the intervention-group pharmacists attended a 5-hour training session on CBT-based medication support. The primary outcome of this study was medication adherence, assessed using the Drug Attitude Inventory (DAI)-10. Secondary outcomes included the changes from baseline at 6 months in the following variables: the Patient Health Questionnaire (PHQ)-9 total score, the EQ-5D-5 L (Euro-QOL 5 dimensions 5 levels) score, patient satisfaction, and the Pharmacists’ Confidence Scale about Medication Consultation for Depressive Patients (PCMCD) score.

Results

Four pharmacies (two in IG and two in CG) completed the intervention period. Results were obtained from 19 patients in the IG and 12 patients in the CG. In the IG, the mean DAI-10 score increased from 4.941 at baseline to 6.105, the mean PHQ-9 score decreased from 9.263 to 8.625, and the mean patient satisfaction score increased from 39.947 to 42.211. In the CG, the mean DAI-10 score decreased from 6.333 to 4.167, the mean PHQ-9 score increased from 9.333 to 12.923, and the mean patient satisfaction score decreased from 38.929 to 38.167.

Conclusion

CBT-based medication support provided by community pharmacists may improve patient medication adherence to antidepressant therapy and symptoms. Such support can be expected to facilitate better treatment of depressed patients and may also allow the duration of treatment to be shortened.

Trial registration

UMIN000037954, Date of first registration: 17/06/2019.
Impact of the COVID-19 pandemic on maternal mental health, early childhood development, and parental practices: a global scoping review
Authors: Penna Ana Luiza , de Aquino Camila Machado , Pinheiro Maria Suelly Nogueira , do Nascimento Rodrigo Leão Ferreira , Farias-Antúnez Simone , Araújo David Augusto Batista Sá , Mita Carol , Machado Marcia Maria Tavares , Castro Marcia C.
Published: February 2023

Background

In March 2020, the COVID-19 outbreak was declared a pandemic by the World Health Organization (WHO), generating stark economic and social repercussions that directly or indirectly affected families’ wellbeing and health status.

Aims

This review aims at mapping the existing evidence on the impact of the COVID-19 pandemic on maternal mental health, early childhood development, and parental practices, worldwide, to identify evidence gaps and better inform future delivery of care and health policy measures.

Methods

Following the protocol defined by PRISMA-ScR, this scoping review has searched for relevant studies published between January 2020 and June 2021, selecting evidence sources based on pre-established criteria. From a total of 2,308 articles, data were extracted from 537 publications from 35 countries on all three health domains.

Results

The combined stressors brought forth by the pandemic have exerted a heavy burden on the mental health of mothers and the development of young children, partly mediated by its impact on parental practices.

Conclusions

Despite remaining gaps, we have identified sufficient evidence pointing to an urgent need for more concerted global research efforts and rapid policy responses to timely address severe and pervasive negative impacts to the mental health of mothers and children at a key developmental stage.
Non-pharmaceutical interventions and risk of COVID-19 infection: survey of U.K. public from November 2020 – May 2021
Authors: Francis Nick A. , Becque Taeko , Willcox Merlin , Hay Alastair D. , Lown Mark , Clarke Richard , Stuart Beth , Yardley Lucy , Moore Michael , Houriet Joëlle , Little Paul
Published: February 2023

Introduction

Non-pharmaceutical interventions (NPIs), such as handwashing, social distancing and face mask wearing, have been widely promoted to reduce the spread of COVID-19. This study aimed to explore the relationship between self-reported use of NPIs and COVID-19 infection.

Methods

We conducted an online questionnaire study recruiting members of the UK public from November 2020 to May 2021. The association between self-reported COVID-19 illness and reported use of NPIs was explored using logistic regression and controlling for participant characteristics, month of questionnaire completion, and vaccine status. Participants who had been exposed to COVID-19 in their household in the previous 2 weeks were excluded.

Results

Twenty-seven thousand seven hundred fifty-eight participants were included and 2,814 (10.1%) reported having a COVID-19 infection. The odds of COVID-19 infection were reduced with use of a face covering in unadjusted (OR 0.17 (95% CI: 0.15 to 0.20) and adjusted (aOR 0.19, 95% CI 0.16 to 0.23) analyses. Social distancing (OR 0.27, 95% CI: 0.22 to 0.31; aOR 0.35, 95% CI 0.28 to 0.43) and handwashing when arriving home (OR 0.57, 95% CI 0.46 to 0.73; aOR 0.63, 95% CI: 0.48 to 0.83) also reduced the odds of COVID-19. Being in crowded places of 10–100 people (OR 1.89, 95% CI: 1.70 to 2.11; aOR 1.62, 95% CI: 1.42 to 1.85) and > 100 people (OR 2.33, 95% CI: 2.11 to 2.58; aOR 1.73, 95% CI: 1.53 to 1.97) were both associated with increased odds of COVID-19 infection. Handwashing before eating, avoiding touching the face, and cleaning things with virus on were all associated with increased odds of COVID-19 infections.

Conclusions

This large observational study found evidence for strong protective effects for individuals from use of face coverings, social distancing (including avoiding crowded places) and handwashing on arriving home on developing COVID-19 infection. We also found evidence for an increased risk associated with other behaviours, possibly from recall bias.
A clinical, radiological and isokinetic evaluation in patients with recurrent patellar dislocation undergoing MPFL reconstruction according to Avikainen: a prospective study evaluating early degenerative changes after a minimum 10-year follow-up period
Authors: Małecki Krzysztof , Niedzielski Kryspin , Korczyc-Stępnicka Agnieszka , Stelmach Wojciech , Beczkowski Jacek , Fabiś Jarosław , Fabiś-Strobin Anna
Published: February 2023

Background

The aim of the study was to conduct a comprehensive functional and radiological follow-up assessment in patients at least 10 years after adductor magnus MPFL reconstruction, and to assess the presence of early degenerative changes.

Methods

The mean age at the time of surgery was 16 years (range: 8 to 18 years, SD 2.5). The follow-up examination was performed at least 10 years following adductor magnus MPFL reconstruction (mean 11 years). Twenty-one patients (26 operated knees) attended the follow-up. The mean age at follow-up was 25.1 years (range 20–29 years).

Results

The significant improvement observed at 3 years, indicated by the Kujala and Lysholm scores, was maintained after 10 years of follow-up (p < 0.001). A single recurrence of dislocation was noted in three patients. A significant improvement in radiological parameters was noted. No significant difference in the incidence of chondromalacia, of any degree, was observed compared to controls.

Significantly higher quadriceps peak torque was noted for both angular velocities (60 and 180°/sec) compared to the preoperative readings (p < 0.001). Knee flexors were found to be significantly stronger at both 60 and 180°/sec at 10 years follow-up examination (p = 0.008 and p < 0.001 respectively).

Conclusion

The use of MPFL reconstruction according to Avikainen yields improvements in clinical and radiological results which are maintained throughout the observation period. No significantly greater articular cartilage degeneration was noted in patients after surgical treatment for recurrent patellar dislocation compared to healthy peers.

Trial registration

Registered on Clinical Trails.gov with ID: PMMHRI-BCO.67/2021-A.
Plantamajoside alleviates hypoxia-reoxygenation injury through integrin-linked kinase/c-Src/Akt and the mitochondrial apoptosis signaling pathways in H9c2 myocardial cells
Authors: Du Yuying , Li Jia , Cai Chao , Gong Fanying , Zhou Guoliang , Liu Fang , Wu Qiang , Liu Fuming
Published: February 2023

Myocardial ischemia–reperfusion injury(MIRI) is one of the common complications after myocardial infarction surgery, Oxidative stress is among the main mechanisms of myocardial ischemia–reperfusion injury. Plantamajoside (PMS), the main effective ingredient in the genus Plantain, has been reported to possess an antioxidation, anti-inflammatory and anti-apoptosis role. However, whether PMS can attenuate myocardial ischemia–reperfusion injury is not yet known. Herein, we explored the effects of PMS on hypoxia-reoxygenation (H/R) injury in H9c2 cardiomyocytes and the underling molecular mechanisms of the treatment. Network pharmacological analysis screened the top 31 key genes in the treatment of MIRI disease treated with PMS, and the result of molecular docking further illustrated the roles that the PMS play in the treatment of MIRI through its interference with integrin-linked kinase (ILK) target protein. PMS was not cytotoxic in the concentration range of 5–40 μM and increased cell survival after H/R injury in a concentration-dependent manner without affecting proliferation or growth. PMS significantly reduced the levels of lactate dehydrogenase, malonic dialdehyde, reactive oxygen species and cell apoptosis, and increased soperoxide dismutase activity compared with those of the H/R injury group. PMS promoted the protein and mRNA expression of ILK and Bcl-2, the protein expression of p-Akt, and reduced the protein and mRNA expression of Bax, Caspase-3, and Cytochrome c, the protein expression of p–c-Src. PMS has protective effects against H/R injury in H9c2 cells, and its protective mechanism may be related to reactive oxygen species clearance, activation of the ILK/c-Src/Akt pathway and inhibition of the mitochondrial apoptosis.
Mining of EHR for interface terminology concepts for annotating EHRs of COVID patients
Authors: Keloth Vipina K. , Zhou Shuxin , Lindemann Luke , Zheng Ling , Elhanan Gai , Einstein Andrew J. , Geller James , Perl Yehoshua
Published: February 2023

Background

Two years into the COVID-19 pandemic and with more than five million deaths worldwide, the healthcare establishment continues to struggle with every new wave of the pandemic resulting from a new coronavirus variant. Research has demonstrated that there are variations in the symptoms, and even in the order of symptom presentations, in COVID-19 patients infected by different SARS-CoV-2 variants (e.g., Alpha and Omicron). Textual data in the form of admission notes and physician notes in the Electronic Health Records (EHRs) is rich in information regarding the symptoms and their orders of presentation. Unstructured EHR data is often underutilized in research due to the lack of annotations that enable automatic extraction of useful information from the available extensive volumes of textual data.

Methods

We present the design of a COVID Interface Terminology (CIT), not just a generic COVID-19 terminology, but one serving a specific purpose of enabling automatic annotation of EHRs of COVID-19 patients. CIT was constructed by integrating existing COVID-related ontologies and mining additional fine granularity concepts from clinical notes. The iterative mining approach utilized the techniques of 'anchoring' and 'concatenation' to identify potential fine granularity concepts to be added to the CIT. We also tested the generalizability of our approach on a hold-out dataset and compared the annotation coverage to the coverage obtained for the dataset used to build the CIT.

Results

Our experiments demonstrate that this approach results in higher annotation coverage compared to existing ontologies such as SNOMED CT and Coronavirus Infectious Disease Ontology (CIDO). The final version of CIT achieved about 20% more coverage than SNOMED CT and 50% more coverage than CIDO. In the future, the concepts mined and added into CIT could be used as training data for machine learning models for mining even more concepts into CIT and further increasing the annotation coverage.

Conclusion

In this paper, we demonstrated the construction of a COVID interface terminology that can be utilized for automatically annotating EHRs of COVID-19 patients. The techniques presented can identify frequently documented fine granularity concepts that are missing in other ontologies thereby increasing the annotation coverage.
Patients’ and healthcare professionals’ perceived facilitators and barriers for shared decision-making for frail and elderly patients in perioperative care: a scoping review
Authors: Vogel Amyn , Guinemer Camille , Fürstenau Daniel
Published: February 2023

Background

Shared decision-making (SDM) in perioperative care, is an organizational approach to instituting sharing of information and decision-making around surgery. It aims at enabling patient autonomy and patient-centered care. Frail and elderly patients suffering from multiple health conditions and increased surgical vulnerability might particularly benefit from SDM. However, little is known about the facilitators and barriers to implementing SDM in perioperative care for the specific needs of frail and elderly patients.

Our objective is twofold: First, we aim at collecting, analyzing, categorizing, and communicating facilitators and barriers. Second, we aim at collecting and mapping conceptual approaches and methods employed in determining and analyzing these facilitators and barriers.

Methods

The search strategy focused on peer-reviewed studies. We employed a taxonomy which is based on the SPIDER framework and added the items general article information, stakeholder, barriers/facilitators, category, subcategory, and setting/contextual information. This taxonomy is based on preceding reviews. The scoping review is reported under the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews. Based on the databases MEDLINE, Embase, CINAHL, and Web of Science, we screened 984 articles, identified, and reviewed 13 original studies.

Results

Within this review, two primary facilitators concerning patients’ willingness to participate in SDM emerged: Patients want to be informed on their medical condition and procedures. Patients prefer sharing decisions with healthcare professionals, compared to decision-making solely by patients or decision-making solely by healthcare professionals. Communication issues and asymmetric power relationships between patients and clinical healthcare professionals are barriers to SDM. Regarding the methodological approaches, the evaluation of the conceptual approaches demonstrates that the selected articles lack employing a distinct theoretical framework. Second, the selected studies mainly used surveys and interviews, observational studies, like ethnographic or video-based studies are absent.

Conclusion

Diverging findings perceived by patients or clinical healthcare professionals were identified. These imply that SDM research related to elderly and frail patients should become more encompassing by employing research that incorporates theory-based qualitative analysis, and observational studies of SDM consultations for understanding practices by patients and clinical healthcare professionals. Observational studies are particularly relevant as these were not conducted.

Trial registration

https://osf.io/8fjnb/
Rare mutation-dominant compound EGFR-positive NSCLC is associated with enriched kinase domain-resided variants of uncertain significance and poor clinical outcomes
Authors: Zhao Weixin , Song Ailing , Xu Yang , Wu Qian , Liu Cuicui , Yin Jiani C. , Ou Qiuxiang , Wu Xue , Shao Yang , Zhao Xinmin
Published: February 2023

Background

Compound epidermal growth factor receptor (EGFR) mutations are less responsive to tyrosine kinase inhibitors (TKIs) than single EGFR mutations in non-small cell lung cancer (NSCLC). However, the detailed clinical characteristics and prognosis of various compound EGFR mutations remain to be elucidated.

Methods

We retrospectively studied the next-generation sequencing (NGS) data of treatment-naïve tumors from 1025 NSCLC patients with compound EGFR mutations, which were sub-categorized into different combinations of common mutations (19-Del and EGFR exon 21 p.L858R), rare mutations, and variants of uncertain significance (VUSs). Prognosis and drug resistance to first-line TKIs were analyzed in 174 and 95 patients, respectively.

Results

Compound EGFR mutations were enriched with EGFR exon 21 p.L858R and rare mutations, but not 19-Del (P < 0.001). The common + rare and rare + rare subtypes had fewer concurrent mutations in the PI3K pathway (P = 0.032), while the rare + rare and common + VUSs subtypes showed increased association with smoking- and temozolomide-related mutational signatures, respectively (P < 0.001). The rare mutation-dominant subtypes (rare + VUSs and rare + rare) had the worst clinical outcomes to first-line TKIs (P < 0.001), which was further confirmed using an external cohort (P = 0.0066). VUSs in the rare + VUSs subtype selectively reside in the EGFR kinase domain (P < 0.001), implying these tumors might select additional mutations to disrupt the regulation/function of the kinase domain.

Conclusions

Different subtypes of compound EGFR mutations displayed distinct clinical features and genetic architectures, and rare mutation-dominant compound EGFR mutations were associated with enriched kinase domain-resided VUSs and poor clinical outcomes. Our findings help better understand the oncogenesis of compound EGFR mutations and forecast prognostic outcomes of personalized treatments.
Targeted plasma proteomics reveals signatures discriminating COVID-19 from sepsis with pneumonia
Authors: Palma Medina Laura M. , Babačić Haris , Dzidic Majda , Parke Åsa , Garcia Marina , Maleki Kimia T. , Unge Christian , Lourda Magda , Kvedaraite Egle , Chen Puran , Muvva Jagadeeswara Rao , Cornillet Martin , Emgård Johanna , Moll Kirsten ,   Karolinska K. I./K. COVID-19 Study Group, Michaëlsson Jakob , Flodström-Tullberg Malin , Brighenti Susanna , Buggert Marcus , Mjösberg Jenny , Malmberg Karl-Johan , Sandberg Johan K. , Gredmark-Russ Sara , Rooyackers Olav , Svensson Mattias , Chambers Benedict J. , Eriksson Lars I. , Pernemalm Maria , Björkström Niklas K. , Aleman Soo , Ljunggren Hans-Gustaf , Klingström Jonas , Strålin Kristoffer , Norrby-Teglund Anna
Published: February 2023

Background

COVID-19 remains a major public health challenge, requiring the development of tools to improve diagnosis and inform therapeutic decisions. As dysregulated inflammation and coagulation responses have been implicated in the pathophysiology of COVID-19 and sepsis, we studied their plasma proteome profiles to delineate similarities from specific features.

Methods

We measured 276 plasma proteins involved in Inflammation, organ damage, immune response and coagulation in healthy controls, COVID-19 patients during acute and convalescence phase, and sepsis patients; the latter included (i) community-acquired pneumonia (CAP) caused by Influenza, (ii) bacterial CAP, (iii) non-pneumonia sepsis, and (iv) septic shock patients.

Results

We identified a core response to infection consisting of 42 proteins altered in both COVID-19 and sepsis, although higher levels of cytokine storm-associated proteins were evident in sepsis. Furthermore, microbiologic etiology and clinical endotypes were linked to unique signatures. Finally, through machine learning, we identified biomarkers, such as TRIM21, PTN and CASP8, that accurately differentiated COVID-19 from CAP-sepsis with higher accuracy than standard clinical markers.

Conclusions

This study extends the understanding of host responses underlying sepsis and COVID-19, indicating varying disease mechanisms with unique signatures. These diagnostic and severity signatures are candidates for the development of personalized management of COVID-19 and sepsis.
Risks of stroke, its subtypes and atrial fibrillation associated with glucagon-like peptide 1 receptor agonists versus sodium-glucose cotransporter 2 inhibitors: a real-world population-based cohort study in Hong Kong
Authors: Lui David Tak Wai , Tang Eric Ho Man , Wu Tingting , Au Ivan Chi Ho , Lee Chi Ho , Woo Yu Cho , Tan Kathryn Choon Beng , Wong Carlos King Ho
Published: February 2023

Background

There are limited data on head-to-head comparative risk of stroke between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). We compared risk of stroke with its subtypes and incident atrial fibrillation (AF) between them.

Methods

A population-based, retrospective cohort of patients with type 2 diabetes between 2008 and 2020 were identified from the electronic health records of Hong Kong Hospital Authority. Patients who received SGLT2i or GLP-1RA were matched pairwise by propensity score. Risks of stroke and AF were evaluated by hazard ratios (HRs) from the Cox proportional hazard regression models.

Results

A total of 5840 patients (2920 SGLT2i users; 2920 GLP-1RA users) were included (mean age 55.5 years, 56.1% men, mean HbA1c 8.9% and duration of diabetes 13.7 years). Upon median follow-up of 17 months, there were 111 (1.9%) events of stroke (SGLT2i: 62, 2.1%; GLP-1RA: 49 1.7%). SGLT2i users had comparable risk of all stroke as GLP-1RA users (HR 1.46, 95% CI 0.99–2.17, p = 0.058). SGLT2i users had higher risk of ischemic stroke (HR 1.53, 95% CI 1.01–2.33, p = 0.044) but similar risk of hemorrhagic stroke compared to GLP-1RA users. Although SGLT2i was associated with lower risk of incident AF (HR 0.43, 95% CI 0.23–0.79, p = 0.006), risk of cardioembolic stroke was similar.

Conclusions

Our real-world study demonstrated that GLP-1RA use was associated with lower risk of ischemic stroke, despite the association between SGLT2i use and lower risk of incident AF. There was no significant difference in hemorrhagic stroke risk. GLP-1RA may be the preferred agent for patients with type 2 diabetes at risk of ischemic stroke.
Effects of Fe2+ addition to sugarcane molasses on poly-γ-glutamic acid production in Bacillus licheniformis CGMCC NO. 23967
Authors: Guo Lifei , Lu Liang , Wang Huichao , Zhang Xiaoxing , Wang Genan , Zhao Tingbin , Zheng Guobao , Qiao Changsheng
Published: February 2023

Background

Poly-γ-glutamic acid (γ-PGA) is biodegradable, water-soluble, environment-friendly, and edible. Consequently, it has a variety of industrial applications. It is crucial to control production cost and increase output for industrial production γ-PGA.

Results

Here γ-PGA production from sugarcane molasses by Bacillus licheniformis CGMCC NO. 23967 was studied in shake-flasks and bioreactors, the results indicate that the yield of γ-PGA could reach 40.668 g/L in a 5L stirred tank fermenter. Further study found that γ-PGA production reached 70.436 g/L, γ-PGA production and cell growth increased by 73.20% and 55.44%, respectively, after FeSO4·7H2O was added. Therefore, we investigated the metabolomic and transcriptomic changes following FeSO4·7H2O addition. This addition resulted in increased abundance of intracellular metabolites, including amino acids, organic acids, and key TCA cycle intermediates, as well as upregulation of the glycolysis pathway and TCA cycle.

Conclusions

These results compare favorably with those obtained from glucose and other forms of biomass feedstock, confirming that sugarcane molasses can be used as an economical substrate without any pretreatment. The addition of FeSO4·7H2O to sugarcane molasses may increase the efficiency of γ-PGA production in intracellular.
A versatile multimodal chromatography strategy to rapidly purify protein nanostructures assembled in cell lysates
Authors: Winter Daniel L. , Lebhar Hélène , McCluskey Joshua B. , Glover Dominic J.
Published: February 2023

Background

Protein nanostructures produced through the self-assembly of individual subunits are attractive scaffolds to attach and position functional molecules for applications in biomaterials, metabolic engineering, tissue engineering, and a plethora of nanomaterials. However, the assembly of multicomponent protein nanomaterials is generally a laborious process that requires each protein component to be separately expressed and purified prior to assembly. Moreover, excess components not incorporated into the final assembly must be removed from the solution and thereby necessitate additional processing steps.

Results

We developed an efficient approach to purify functionalized protein nanostructures directly from bacterial lysates through a type of multimodal chromatography (MMC) that combines size-exclusion, hydrophilic interaction, and ion exchange to separate recombinant protein assemblies from excess free subunits and bacterial proteins. We employed the ultrastable filamentous protein gamma-prefoldin as a material scaffold that can be functionalized with a variety of protein domains through SpyTag/SpyCatcher conjugation chemistry. The purification of recombinant gamma-prefoldin filaments from bacterial lysates using MMC was tested across a wide range of salt concentrations and pH, demonstrating that the MMC resin is robust, however the optimal choice of salt species, salt concentration, and pH is likely dependent on the protein nanostructure to be purified. In addition, we show that pre-processing of the samples with tangential flow filtration to remove nucleotides and metabolites improves resin capacity, and that post-processing with Triton X-114 phase partitioning is useful to remove lipids and any remaining lipid-associated protein. Subsequently, functionalized protein filaments were purified from bacterial lysates using MMC and shown to be free of unincorporated subunits. The assembly and purification of protein filaments with varying amounts of functionalization was confirmed using polyacrylamide gel electrophoresis, Förster resonance energy transfer, and transmission electron microscopy. Finally, we compared our MMC workflow to anion exchange chromatography with the purification of encapsulin nanocompartments containing a fluorescent protein as a cargo, demonstrating the versatility of the protocol and that the purity of the assembly is comparable to more traditional procedures.

Conclusions

We envision that the use of MMC will increase the throughput of protein nanostructure prototyping as well as enable the upscaling of the bioproduction of protein nanodevices.

Graphic Abstract
When AHR signaling pathways meet viral infections
Authors: Hu Jieke , Ding Yuan , Liu Wen , Liu Shuzhen
Published: February 2023

Aryl hydrocarbon receptor (AHR) is a ligand-dependent transcriptional factor widely expressed among immune, epithelial, endothelial and stromal cells in barrier tissues. It can be activated by small molecules provided by pollutants, microorganisms, food, and metabolism. It has been demonstrated that AHR plays an important role in modulating the response to many microbial pathogens, and the abnormal expression of AHR signaling pathways may disrupt endocrine, cause immunotoxicity, and even lead to the occurrence of cancer. Most humans are infected with at least one known human cancer virus. While the initial infection with these viruses does not cause major disease, the metabolic activity of infected cells changes, thus affecting the activation of oncogenic signaling pathways. In the past few years, lots of studies have shown that viral infections can affect disease progression by regulating the transmission of multiple signaling pathways. This review aims to discuss the potential effects of virus infections on AHR signaling pathways so that we may find a new strategy to minimize the adverse effects of the AHR pathway on diseases.
Transcranial direct current stimulation to the left dorsolateral prefrontal cortex enhances early dexterity skills with the left non-dominant hand: a randomized controlled trial
Authors: Watanabe Akihiro , Sawamura Daisuke , Nakazono Hisato , Tokikuni Yukina , Miura Hiroshi , Sugawara Kazuhiro , Fuyama Kanako , Tohyama Harukazu , Yoshida Susumu , Sakai Shinya
Published: February 2023

Background

The left dorsolateral prefrontal cortex (DLPFC) is involved in early-phase manual dexterity skill acquisition when cognitive control processes, such as integration and complexity demands, are required. However, the effectiveness of left DLPFC transcranial direct current stimulation (tDCS) on early-phase motor learning and whether its effectiveness depends on the cognitive demand of the target task are unclear. This study aimed to investigate whether tDCS over the left DLPFC improves non-dominant hand dexterity performance and determine if its efficacy depends on the cognitive demand of the target task.

Methods

In this randomized, double-blind, sham-controlled trial, 70 healthy, right-handed, young adult participants were recruited. They were randomly allocated to the active tDCS (2 mA for 20 min) or sham groups and repeatedly performed the Purdue Pegboard Test (PPT) left-handed peg task and left-handed assembly task three times: pre-tDCS, during tDCS, and post tDCS.

Results

The final sample comprised 66 healthy young adults (mean age, 22.73 ± 1.57 years). There were significant interactions between group and time in both PPT tasks, indicating significantly higher performance of those in the active tDCS group than those in the sham group post tDCS (p < 0.001). Moreover, a greater benefit was observed in the left-handed assembly task performance than in the peg task performance (p < 0.001). No significant correlation between baseline performance and benefits from tDCS was observed in either task.

Conclusions

These results demonstrated that prefrontal tDCS significantly improved early-phase manual dexterity skill acquisition, and its benefits were greater for the task with high cognitive demands. These findings contribute to a deeper understanding of the underlying neurophysiological mechanisms of the left DLPFC in the modulation of early-phase dexterity skill acquisition.

Trial registration: This study was registered in the University Hospital Medical Information Network Clinical Trial Registry in Japan (UMIN000046868), Registered February 8, 2022 https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053467
Matrine alleviates depressive-like behaviors via modulating microbiota–gut–brain axis in CUMS-induced mice
Authors: Zhang Ming , Li Aoqiang , Yang Qifang , Li Jingyi , Zheng Lihua , Wang Guannan , Sun Ying , Huang Yanxin , Zhang Muqing , Song Zhenbo , Liu Lei
Published: February 2023

Background

The realization of the “microbiota–gut–brain” axis plays a critical role in neuropsychiatric disorders, particularly depression, is advancing rapidly. Matrine is a natural bioactive compound, which has been found to possess potential antidepressant effect. However, the underlying mechanisms of regulation of the “microbiota–gut–brain” axis in the treatment of depression by oral matrine remain elusive.

Methods

Its antidepressant effects were initially evaluated by behavioral tests and relative levels of monoamine neurotransmitters, and matrine has been observed to attenuate the depression-like behavior and increase neurotransmitter content in CUMS-induced mice. Subsequently, studies from the “gut” to “brain” were conducted, including detection of the composition of gut microbiota by 16S rRNA sequencing; the metabolomics detection of gut metabolites and the analysis of differential metabolic pathways; the assessment of relative levels of diamine oxidase, lipopolysaccharide, pro-inflammatory cytokines, and brain-derived neurotrophic factor (BDNF) by ELISA kits or immunofluorescence.

Results

Matrine could regulate the disturbance of gut microbiota and metabolites, restore intestinal permeability, and reduce intestinal inflammation, thereby reducing the levels of pro-inflammatory cytokines in peripheral blood circulation and brain regions, and ultimately increase the levels of BDNF in brain.

Conclusion

Matrine may ameliorate CUMS-induced depression in mice by modulating the “microbiota–gut–brain” axis.