bluuebunny/crossref_metadata_2025 huggingface dataset:
ICU Resource Limitations During Peak Seasonal Influenza: Results of a 2018 National Feasibility Study
Authors: Lane Christianne Joy , Bhatnagar Manas , Lutrick Karen , Maves Ryan C. , Weiner Debra , Rios Olvera Daisy , Uyeki Timothy M. , Cobb J. Perren , Brown Joan C. ,   for the Discovery Program Resilience and Emergency Preparedness (Discovery PREP)
Published: January 2022

OBJECTIVES:

Demonstrate the feasibility of weekly data collection and analysis of public health emergency (PHE) data. Assess fluctuations in, and challenges of, resource matching and potential effect on patient care for influenza in ICUs.

DESIGN:

Multicenter prospective noninterventional study testing effectiveness of leveraging the Discovery Critical Care Research Network Program for Resilience and Emergency Preparedness (Discovery-PREP) in performing PHE research. A 20-question internet survey was developed to prospectively assess ICU influenza-related resource stress. An informatics tool was designed to track responses; data were analyzed within 24 hours of weekly survey completion by the team biostatistician for timely reporting.

PARTICIPANTS:

Critical care and Emergency Medicine Discovery-PREP network investigators self-selected to participate in the voluntary query.

SETTING:

ICUs of 13 hospitals throughout the United States, 12 academic, and one community.

INTERVENTIONS:

ICU physicians were electronically surveyed weekly over 17 weeks during the influenza season (January 2018–April 2018). Responses were collected for 48 hours after each email query.

MEASUREMENTS AND MAIN RESULTS:

The average weekly response among the sites was 79% (range, 65–100%). Significant stress, defined as alterations in ICU staffing and/or resource allocation, occurred in up to 41% of sites during the national peak of influenza activity. These alterations included changes in staffing, not accepting external patient transfers, and canceling elective surgery. During this same period, up to 17% of the sites indicated that these changes might not have been sufficient to prevent potentially avoidable patient harm.

CONCLUSIONS:

This novel approach to querying ICU operational stress indicated that almost half of participating sites experienced critical care resource limitations during peak influenza season and required process and/or staffing changes to better balance resources with patient care demands. This weekly national reporting infrastructure could be adapted and expanded to better inform providers, hospital emergency management teams, and government leaders during PHEs.
A Prospective Observational Study Comparing Clinical Sepsis Criteria to Protein Biomarkers Reveals a Role for Vascular Dysfunction in Burn Sepsis
Authors: Burmeister David M. , Heard Tiffany C. , Chao Tony , Alcover Karl , Wagner Amanda , Chung Kevin K. , Akers Kevin S.
Published: January 2022

OBJECTIVES:

To compare the diagnostic value of clinical sepsis criteria to novel protein biomarkers in the burn patient.

DESIGN:

Prospective observational study.

SETTING:

American Burn Association verified Burn Center ICU.

PATIENTS:

Burn patients (n = 24) and healthy volunteers (n = 10).

INTERVENTIONS:

Enrolled burn patients (n = 24) were stratified based on whether or not they met a clinical definition of sepsis. Four separate clinical criteria for sepsis were analyzed for their diagnostic sensitivity and specificity, which were compared to a panel of protein biomarkers. The most significant protein biomarkers were further analyzed via the area under the receiver operating characteristic curves (AUROCs).

MEASUREMENTS AND MAIN RESULTS:

Of the clinical criteria, SEPSIS-2 criteria led to the highest AUROC (0.781; p < 0.001), followed by the quick Sequential Organ Failure Assessment score (AUROC = 0.670; p = 0.022). Multiplexing revealed a number of inflammatory proteins (complement C5) and matrix metalloproteinases (MMP1, MMP7) that were significantly elevated in septic samples compared with both healthy controls and nonseptic burn samples. Furthermore, three proteins associated with endothelial dysfunction and glycocalyx shedding revealed diagnostic potential. Specifically, syndecan-1, p-selectin, and galectin-1 were all significantly elevated in sepsis, and all resulted in an AUROC greater than 0.7; analyzing the sum of these three markers led to an AUROC of 0.808.

CONCLUSIONS:

These data reveal several potential biomarkers that may help with sepsis diagnosis in the burn patient. Furthermore, the role of endotheliopathy as a mechanistic etiology for sepsis after burns warrants further investigation.
Resuscitation fluids as drugs: targeting the endothelial glycocalyx
Authors: Wang Guangjian , Zhang Hongmin , Liu Dawei , Wang Xiaoting
Published: January 2022

Fluid resuscitation is an essential intervention in critically ill patients, and its ultimate goal is to restore tissue perfusion. Critical illnesses are often accompanied by glycocalyx degradation caused by inflammatory reactions, hypoperfusion, shock, and so forth, leading to disturbed microcirculatory perfusion and organ dysfunction. Therefore, maintaining or even restoring the glycocalyx integrity may be of high priority in the therapeutic strategy. Like drugs, however, different resuscitation fluids may have beneficial or harmful effects on the integrity of the glycocalyx. The purpose of this article is to review the effects of different resuscitation fluids on the glycocalyx. Many animal studies have shown that normal saline might be associated with glycocalyx degradation, but clinical studies have not confirmed this finding. Hydroxyethyl starch (HES), rather than other synthetic colloids, may restore the glycocalyx. However, the use of HES also leads to serious adverse events such as acute kidney injury and bleeding tendencies. Some studies have suggested that albumin may restore the glycocalyx, whereas others have suggested that balanced crystalloids might aggravate glycocalyx degradation. Notably, most studies did not correct the effects of the infusion rate or fluid volume; therefore, the results of using balanced crystalloids remain unclear. Moreover, mainly animal studies have suggested that plasma may protect and restore glycocalyx integrity, and this still requires confirmation by high-quality clinical studies.
Update on classification, diagnosis, and management of immunoglobulin G4-related disease
Authors: Chen Yu , Cai Shaozhe , Dong Lingli , Umehara Hisanori
Published: January 2022

Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized chronic fibro-inflammatory autoimmune disease, and its recognition has been constantly increasing worldwide over the last few years. A correct and timely recognition, as well as appropriate intervention, is crucial for the treatment of IgG4-RD. For certain subtypes of IgG4-RD, organ-specific criteria are formulated to make the diagnosis more accurate. New biomarkers have emerged in the recent years to aid the disease diagnosis, its prognosis prediction, as well as therapy response monitoring. Although recurrence is very common in IgG4-RD, glucocorticoid is still the first-line treatment for the majority of patients. The factors that affect the likelihood of disease relapse are multifaceted. The selection strategy of various steroid-sparing agents is still being explored. Besides, when patients have special sites involvement leading to severe clinical conditions, surgical operation or interventional therapy should also be considered. An update on classification, diagnosis, and management of IgG4-RD is provided in the current study to fully elucidate the recommended clinical practice of this mysterious disease.
Chemotherapy-Induced Arrhythmias
Authors: Essa Hani , Dobson Rebecca , Lip Gregory Y. H.
Published: January 2022

Cardio-oncology is a subspeciality within cardiology that has developed primarily as a consequence of the cardiovascular implications of cancer and its therapeutics. Arrhythmias are increasingly recognized as an adverse feature of many chemotherapeutic agents. This relationship is poorly defined and studied in the literature compared with other side effects of chemotherapy. In this review, we appraise the published literature on arrhythmogenic consequences of chemotherapeutic agents and summarize the available evidence. Atrial fibrillation (AF) and other supraventricular tachycardias are frequently observed in patients receiving chemotherapy. High rates of AF are seen with certain agents such as tyrosine kinase inhibitors eg, ibrutinib and the mechanism for this is poorly defined but likely related to off-target effects. The management of AF in cardio-oncology is similar to that of the noncancer patient with certain nuances. Mainly that bleeding and stroke risk stratification tools are not validated in the cancer population. In this patient cohort, treatment decisions are usually led by anecdotal evidence rather than an evidence base. This leads to treatment heterogeneity between clinicians. Furthermore, various drug interactions can limit the choice of therapy, particularly with respect to anticoagulant drugs. Many chemotherapeutic agents have been implicated in QT interval (A Measurement calculated from the start of the Q wave to the end of the T wave on the electrocardiogram approximating the time taken for ventricular relaxation.) of these, arsenic trioxide and several tyrosine kinase inhibitors are classic culprits. In patients receiving these agents, it is advisable to perform a baseline electrocardiogram and monitor the QT interval. If the (QT interval corrected for heart rate) increases by 60 milliseconds from baseline or is greater than 500 milliseconds, it is advisable to suspend treatment temporarily. Moving forward, further trials are required in the field of cardio-oncology to better understand the relationship between chemotherapeutic agents and arrhythmia.
OBJECTIVE AND QUANTITATIVE ESTIMATION OF THE OPTIMAL TIMING FOR EPIRETINAL MEMBRANE SURGERY ON THE BASIS OF METAMORPHOPSIA
Authors: Kanzaki Yuki , Doi Shinichiro , Matoba Ryo , Kanzaki Sayumi , Kimura Shuhei , Hosokawa Mio M. , Shiode Yusuke , Takasu Ippei , Morizane Yuki
Published: January 2022

Purpose:

To establish an objective and quantitative biomarker of metamorphopsia in epiretinal membranes (ERMs) and determine the optimal timing for ERM surgery.

Methods:

Retrospectively, 172 eyes with ERM were reviewed. Retinal folds because of tangential traction by ERM were visualized by en-face optical coherence tomography. The maximum depth of retinal folds (MDRF) within the parafovea was quantified. Metamorphopsia was quantified by M-CHARTS. The change in the distance between the retinal vessels after ERM surgery and the preoperative total depth of retinal folds between the vessels were quantified using en-face optical coherence tomography and optical coherence tomography angiography.

Results:

Significant correlations were observed between preoperative MDRF and M-CHARTS scores before and at 6 months after surgery (r = 0.617 and 0.460, respectively; P < 0.001) and change in the distance between the retinal vessels after ERM surgery and preoperative total depth of retinal folds between the vessels (r = 0.471; P = 0.013). The preoperative MDRF values at which M-CHARTS scores were 0.5 before and 6 months after the surgery were 69 µm and 118 µm, respectively.

Conclusion:

The MDRF is an objective and quantitative biomarker of metamorphopsia in ERM. To maintain patients' quality of vision, ERM surgery may be performed when the preoperative MDRF ranges between 69 µm and 118 µm.
CYP2C19 Genotyping Plus Therapeutic Drug Monitoring Dependent Voriconazole Treatment for Invasive Pulmonary Aspergillosis in a Patient with Liver Failure
Authors: Shen Chuan , Zhao Qian , Li Ziyue , Wang Wei , Zhao Yalin , Kong Lingya , Xie Jing , Zhao Caiyan
Published: January 2022

Invasive pulmonary aspergillosis (IPA) is a lethal infectious disease with high mortality in patients with liver failure. Early recognition of the risk factors prompting earlier diagnosis and treatment may improve the outcomes. Voriconazole is recommended as the first-line drug for IPA, but hepatotoxicity limits its use in the context of liver diseases. We report a case of a 63-year-old female who was admitted to the Third Affiliated Hospital of Hebei Medical University due to IPA after glucocorticoid therapy for liver failure. The polymorphism of cytochrome P450 (CYP) isoenzymes showed CYP2C19∗1/∗2 genotype associated with intermediate metabolism of voriconazole. However, the patient developed side effects such as skin rash, vomiting, hyperbilirubinemia, and alteration of consciousness, even if she received half of the recommended dosage for voriconazole. Therapeutic drug monitoring (TDM) was applied to guide the dosage adjustment of voriconazole in this patient, and consequently, the patient presented a favorable outcome. In conclusion, genotyping screening plus TDM dependent individualized treatment of voriconazole may improve the survival of liver failure patient with IPA.
Skin Cancer Back to Basics
Authors: Bai Heidi , Brickley Sylvana
Published: January 2022

Amelanotic melanoma is a rare subtype of cutaneous melanoma. Sun exposure is a known primary risk factor; however, the mechanism for amelanosis is poorly understood. Amelanotic melanoma is challenging to recognize clinically because of absence of pigment and its resemblance to a variety of benign and malignant neoplasms. Detection often occurs at late or metastatic stages, leading to poorer outcomes. Surgical excision is the current standard of care, with adjuvant therapies under investigation. This article discusses the clinical assessment and management of AM to improve early recognition and patient outcomes.
Hand Dermatitis in Response to Water Exposure
Authors: Holmes G. Alden , Furukawa Betsy J.
Published: January 2022

Teledermatology is a term to describe the provision of dermatologic medical services through telecommunication technology. This is a case of hand dermatitis in response to water exposure.
A decade of rising alcoholic liver disease hospital admissions and deaths in Irish hospitals, 2007–2016: a retrospective cross-sectional analysis
Authors: Armstrong Paul R. , Ring Éabha , MacNicholas Ross
Published: January 2022

Background

Alcoholic liver disease (ALD) is a major cause of both liver cirrhosis and hepatocellular carcinoma (HCC) in Ireland.

Aims

The aim of the study was to identify the epidemiological profile, temporal trends, development of complications and mortality arising from inpatient care episodes linked to ALD in Ireland from 2007 to 2016.

Methods

This was a national retrospective study that analysed data on patient discharges from hospitals across Ireland. The Hospital Inpatient Enquiry System was used to gather this data. The main outcome measures were the number of hospital discharges for patients with ALD or HCC, also expressed per 100 000 population, the mortality rate associated with ALD and the prevalence of complications associated with ALD.

Results

A total of 33 794 hospital discharges were examined. There was a 38% increase in hospital discharges and 300% increase in HCC coding for patients with ALD between 2006 and 2016. There were 73 hospital discharges with ALD per 100 000 population in 2016. That year, 40 482 bed days were required for inpatient management equating to 120 beds per day. Deaths from ALD rose by 29% over the 10-year period. Cirrhosis was diagnosed in 57% and 24% had ascites. Mortality was 9.8% rising to 16% with variceal bleeding and 42% with acute kidney injury. Only 31% were under the care of a gastroenterologist or hepatologist.

Conclusion

Ireland is seeing a rise in ALD-related hospital admissions and deaths, including HCC which increased three-fold. ALD is a preventable disease, and public health interventions are of proven benefit and required to reverse this trend.
Developing Nursing Care Guidelines for Patients With COVID-19
Authors: Stanton Elizabeth , Maxwell Marcia , Casados Shannon , Sweeney Michelle , Vannice Sandra , Smith Jeremy , Rider Ben
Published: January 2022

The COVID-19 pandemic has produced an abundance of new and evolving evidence related to providing care for this complex patient population. Keeping up with the rapid flow of published information can be challenging and time-consuming, even for those skilled at interpreting the literature. To help clinical nurses readily apply standardized, evidence-based recommendations in a rapidly changing healthcare environment, the Good Samaritan Medical Center Education Team created a nursing-specific guideline for care of patients with COVID-19.
Clear Cell Carcinoma (CCC) of the Cervix Is a Human Papillomavirus (HPV)-independent Tumor Associated With Poor Outcome
Authors: Stolnicu Simona , Karpathiou Georgia , Guerra Esther , Mateoiu Claudia , Reques Armando , Garcia Angel , Bart Joost , Felix Ana , Fanni Daniela , Gama Joao , Hardisson David , Bennett Jennifer A. , Parra-Herran Carlos , Oliva Esther , Abu-Rustum Nadeem , Soslow Robert A. , Park Kay J.
Published: January 2022

Cervical clear cell carcinoma (CCC) is a rare human papillomavirus–independent adenocarcinoma. While recent studies have focused on gastric-type endocervical adenocarcinoma (GTA), little is known about CCC. A total of 58 (CCCs) were collected from 14 international institutions and retrospectively analyzed using univariable and multivariable methods and compared with 36 gastric-type adenocarcinomas and 173 human papillomavirus–associated (HPVA) endocervical adenocarcinoma (ECA) regarding overall survival (OS) and recurrence-free survival (RFS). Most cases were FIGO stage I (72.4%), with Silva C pattern of invasion (77.6%), and the majority were treated with radical surgery (84.5%) and adjuvant therapy (55.2%). Lymphovascular invasion was present in 31%, while lymph node metastasis was seen in 24.1%; 10.3% were associated with abdominopelvic metastases at the time of diagnosis; 32.8% had recurrences, and 19% died of disease. We did not find statistically significant differences in OS and RFS between CCC and GTA at 5 and 10 years (P=0.313 and 0.508, respectively), but there were significant differences in both OS and RFS between CCC and HPVA ECA (P=0.003 and 0.032, respectively). Also, OS and RFS in stage I clear cell and GTA were similar (P=0.632 and 0.692, respectively). Multivariate analysis showed that OS is influenced by the presence of recurrence (P=0.009), while RFS is influenced by the FIGO stage (P=0.025). Cervical CCC has poorer outcomes than HPVA ECA and similar outcomes to human papillomavirus–independent GTA. Oncologic treatment significantly influences RFS in univariate analysis but is not an independent prognostic factor in multivariate analysis suggesting that alternative therapies should be investigated.
The problem of ‘Extinguished letters’ and the use of chemical reagents on manuscripts (1551–1553)
Authors: Cardinali Giacomo
Published: January 2022

The examination of unknown sources reveals that by the end of the fifteenth and the beginning of the sixteenth century, there was a widespread awareness in Italy of the damage produced by the passing of time on books and manuscripts. The expression used to describe such cases was
lettere svanite
or
caduche
, which indicated that the writing had faded and was almost unreadable, and, as such, hard to transcribe, indicating that the manuscript needed to be preserved from further damage. Already between 1550 and 1552, in Rome and Venice, some ecclesiastics of the Roman Curia attempted to brighten ancient writing, using vegetable distillate high in tannin. In two cases, it is possible to identify manuscripts processed with this method and to determine the preservation formula as well as an accurate description of each step of the method. The process, now brought back to light, anticipates the chemical experimentations by the Benedictines of St Maur and other techniques, widespread in the eighteenth century, and their basic chemical principle, namely the application of tannin. However, the earlier technique is paradoxically much more complicated than the one applied two centuries later.
The evolution of partner specificity in mutualisms
Authors: Carlson Christopher , Akçay Erol , Morsky Bryce
Published: January 2022

Mutualistic species vary in their level of partner specificity, which has important evolutionary, ecological, and management implications. Yet, the evolutionary mechanisms which underpin partner specificity are not fully understood. Most work on specialization focuses on the trade-off between generalism and specialism, where specialists receive more benefits from preferred partners at the expense of benefits from non-preferred partners, while generalists receive similar benefits from all partners. Because all mutualisms involve some degree of both cooperation and conflict between partners, we highlight that specialization to a mutualistic partner can be cooperative, increasing benefit to a focal species and a partner, or antagonistic, increasing resource extraction by a focal species from a partner. We devise an evolutionary game theoretic model to assess the evolutionary dynamics of cooperative specialization, antagonistic specialization, and generalism. Our model shows that cooperative specialization leads to bistability: stable equilibria with a specialist host and its preferred partner excluding all others. We also show that under cooperative specialization with spatial effects, generalists can thrive at the boundaries between differing specialist patches. Under antagonistic specialization, generalism is evolutionarily stable. We provide predictions for how a cooperation-antagonism continuum may determine the patterns of partner specificity that develop within mutualistic relationships.
Bayesian Estimation of real-time Epidemic Growth Rates using Gaussian Processes: local dynamics of SARS-CoV-2 in England
Authors: Guzmán-Rincón Laura M , Hill Edward M , Dyson Louise , Tildesley Michael J , Keeling Matt J
Published: January 2022

Quantitative assessments of the recent state of an epidemic and short-term projections into the near future are key public health tools that have substantial policy impacts, helping to determine if existing control measures are sufficient or need to be strengthened. Key to these quantitative assessments is the ability to rapidly and robustly measure the speed with which the epidemic is growing or decaying. Frequently, epidemiological trends are addressed in terms of the (time-varying) reproductive numberR. Here, we take a more parsimonious approach and calculate the exponential growth rate,r, using a Bayesian hierarchical model to fit a Gaussian process to the epidemiological data. We show how the method can be employed when only case data from positive tests are available, and the improvement gained by including the total number of tests as a measure of heterogeneous testing effort. Although the methods are generic, we apply them to SARS-CoV-2 cases and testing in England, making use of the available high-resolution spatio-temporal data to determine long-term patterns of national growth, highlight regional growth and spatial heterogeneity.
Effect of vitamin D on infection and inflammation in patients with cystic fibrosis: a systematic review and meta-analysis
Authors: Begum Nelufa , Tarique Abdullah Al , Blake Tamara , Vilcins Dwan , Islam Mohammad Zahirul , Islam Nazrul , Ware Robert S , Sly Peter
Published: January 2022

Background

Cystic fibrosis (CF) is a genetic disorder in which the respiratory system gets clogged with mucus leads to progressive lung damage. There is no known cure for CF but several treatments to manage symptoms and reduce complications. Vitamin D deficiency is common in CF associated with increased infection and inflammation. This systematic review and meta-analysis will evaluate the effectiveness of vitamin D treatment in reducing respiratory tract infection and inflammation in patients with CF.

Methods

Randomized and quasi-randomised studies in CF patients with control groups will be identified. The antibacterial activity of vitamin D supplementation will help in reducing respiratory tract infection and inflammation in CF. Overall effects of vitamin D in terms of infection and inflammatory markers such as C-reactive protein, inflammatory cytokine interleukin (IL)-6, IL-8, IL-17, IL-23, antimicrobial peptide (LL-37), lung function defined by forced expiratory volume in 1 second (FEV1) %, other assessed respiratory parameters will be calculated using random-effect models. Study quality will be assessed using RoB 2 – A revised Cochrane Risk of Bias tool for randomised trials. The overall quality of evidence for each outcome will be summarised according to the Grading of Recommendations Assessment, Development, and Evaluations (GRADE) framework.
Causal effects of motor control on gait kinematics after orthopedic surgery in cerebral palsy: a machine-learning approach
Authors: Steele Katherine M. , Schwartz Michael H.
Published: January 2022

Background

Altered motor control is common in cerebral palsy (CP). Understanding how altered motor control effects movement and treatment outcomes is important, but challenging due to complex interactions between impairments. While regression can be used to examine associations between impairments and gait, causal modeling provides a mathematical framework to specify assumed causal relationships, identify covariates that may introduce bias, and test model plausibility. The goal of this research was to quantify the causal effects of altered motor control and other impairments on gait, before and after single-event multi-level orthopedic surgery (SEMLS).

Methods

We evaluated the impact of SEMLS on change in Gait Deviation Index (ΔGDI) between gait analyses. We constructed our causal model with a Directed Acyclic Graph that included the assumed causal relationships between SEMLS, ΔGDI, baseline GDI (GDIpre), baseline neurologic and orthopedic impairments (Imppre), age, and surgical history. We identified the adjustment set to evaluate the causal effect of SEMLS on ΔGDI and the impact of Imppreon ΔGDI and GDIpre. We used Bayesian Additive Regression Trees (BART) and accumulated local effects to assess relative effects.

Results

We prospectively recruited a cohort of children with bilateral CP undergoing SEMLS (N=54, 35 males, age: 10.5±3.1 years) and identified a control cohort with bilateral CP who did not undergo SEMLS (N=55, 30 males, age: 10.0±3.4 years). There was a small positive causal effect of SEMLS on ΔGDI (1.68 GDI points). Altered motor control (i.e., dynamic and static motor control) and strength had strong effects on GDIpre, but minimal effects on ΔGDI. Spasticity and orthopedic impairments had minimal effects on GDIpreor ΔGDI.

Conclusions

Altered motor control and other baseline impairments did have a strong effect on GDIpre, indicating that these impairments do have a causal effect on a child’s gait pattern but minimal effect on expected changes in GDI after SEMLS. Heterogeneity in outcomes suggests there are other factors contributing to changes in gait. Identifying these factors and employing causal methods to examine the complex relationships between impairments and movement will be required to advance our understanding and care of children with CP.
Preliminary modeling estimates of the relative transmissibility and immune escape of the Omicron SARS-CoV-2 variant of concern in South Africa
Authors: Gozzi Nicolò , Chinazzi Matteo , Davis Jessica T. , Mu Kunpeng , Piontti Ana Pastore y , Vespignani Alessandro , Perra Nicola
Published: January 2022

We develop a stochastic, multi-strain, compartmental epidemic model to estimate the relative transmissibility and immune escape of the Omicron variant of concern (VOC) in South Africa. The model integrates population, non-pharmaceutical interventions, vaccines, and epidemiological data and it is calibrated in the period May 1st, 2021 – November 23rd, 2021. We explore a parameter space of relative transmissibility with respect to the Delta variant and immune escape for Omicron by assuming an initial seeding, from unknown origin, in the first week of October 2021. We identify a region of the parameter space where combinations of relative transmissibility and immune escape are compatible with the growth of the epidemic wave. We also find that changes in the generation time associated with Omicron infections strongly affect the results concerning its relative transmissibility. The presented results are informed by current knowledge of Omicron and subject to changes.
Guardian crypt-base-goblet-cells protect the human colonic stem cell niche by triggering cholinergic calcium signal-dependent MUC2 secretion and luminal flushing
Authors: Pelaez-Llaneza Nicolas , Jones Victoria , Kam Christy , Lee Alvin , Parris Alyson , Tattan Sean , Loader Martin , Champion Jordan , Russam George , Miller Ben , Juge Nathalie , Wharton Richard , Speakman Christopher , Kapur Sandeep , Hernon James , Stearns Adam , Shaik Irshad , Pal Anatu , Tsigka Alexia , Batsoulis Diogenis , Williams Mark
Published: January 2022

Mucus secreting goblet cells play a vital role in the maintenance of tissue homeostasis. Here we report the discovery of an enigmatic mechanism for the generation of calcium signals that couple cholinergic input to secretion of hydrated mucus in the human colonic stem cell niche. Mechanistic insights for this study were derived from native human colonic crypts and crypt-like organoids expressing MUC2-mNEON. Importantly, we demonstrate that the human colonic stem cell niche is also a cholinergic niche, and that activation of muscarinic receptors initiates calcium signals at the apical pole of intestinal stem cells and neighbouring crypt-base-goblet-cells. The calcium signal ‘trigger zone’ is defined by a microdomain of juxtaposed calcium stores expressing TPC1 and InsP3R3 calcium channels. Co-activation of TPC1 and InsP3R3 is required for generation of cholinergic calcium signals and downstream secretion of hydrated mucus, which culminates in the flushing of the colonic stem cell niche.
Mosquito Olfactory Response Ensemble: a curated database of behavioral and electrophysiological responses enables pattern discovery
Authors: Gupta Abhishek , Singh Swikriti S. , Mittal Aarush M. , Singh Pranjul , Goyal Shefali , Kannan Karthikeyan R. , Gupta Arjit K. , Gupta Nitin
Published: January 2022

Many experimental studies have examined behavioral and electrophysiological responses of mosquitoes to odors. However, the differences across studies in data collection, processing, and reporting make it difficult to perform large-scale analyses combining data from multiple studies. Here we extract and standardize data for 12 mosquito species, along with Drosophila melanogaster for comparison, from over 170 studies and curate the Mosquito Olfactory Response Ensemble (MORE), publicly available at https://neuralsystems.github.io/MORE. We demonstrate the ability of MORE in generating biological insights by finding patterns across studies. Our analyses reveal that ORs are tuned to specific ranges of several physicochemical properties of odorants; the empty-neuron recording technique for measuring OR responses is more sensitive than the Xenopus oocyte technique; there are systematic differences in the behavioral preferences reported by different types of assays; and odorants tend to become less attractive or more aversive at higher concentrations.
The crystal structure of TRPM2 MHR1/2 domain reveals a conserved Zn2+-binding domain essential for ligand binding and activity
Authors: Sander Simon , Gattkowski Ellen , Pick Jelena , Fliegert Ralf , Tidow Henning
Published: January 2022

Transient receptor potential melastatin 2 (TRPM2) is a Ca2+-permeable, non-selective cation channel involved in diverse physiological processes such as immune response, apoptosis and body temperature sensing. TRPM2 is activated by ADP-ribose (ADPR) and 2′-deoxy-ADPR in a Ca2+-dependent manner. While two species-specific binding sites exist for ADPR, a binding site for 2′-deoxy-ADPR is not known yet. Here, we report the crystal structure of the MHR1/2 domain of TRPM2 from zebrafish (Danio rerio) and show binding of both ligands to this domain. We identified a so-far unrecognized Zn2+-binding domain that was not resolved in previous cryo-EM structures and that is conserved in most TRPM channels. In combination with patch clamp experiments, we comprehensively characterize the effect of the Zn2+-binding domain on TRPM2 activation. Our results provide insight into a conserved structural element essential for channel activity.
Influence of sequencing depth on bacterial classification and abundance in bacterial communities
Authors: Sanchez Fernando Mejia , Jiménez Francisco Avilés , Tenorio Alfonso Méndez
Published: January 2022

Microbial diversity is the most abundant form of life. Next Generation Sequencing technologies provide the capacity to study complex bacterial communities, in which the depth and the bioinformatic tools can influence the results. In this work we explored two different protocols for bacterial classification and abundance evaluation, using 10 bacterial genomes in a simulated sample at different sequencing. Protocol A consisted of metagenome assembly with Megahit and Ray Meta and taxonomic classification with Kraken2 and Centrifuge. In protocol B only taxonomic classification. In both protocols, rarefaction, relative abundance and beta diversity were analyzed. In the protocol A, Megahit had a mean contig length of 1,128 and Ray Meta de 8,893 nucleotides. The number of species correctly classified in all depth assays were 6 out of 10 for protocol A, and 9 out of 10 using protocol B. The rarefaction analysis showed an overestimation of the number of species in almost all assays regardless of the protocol, and the beta diversity analysis results indicated significant differences in all comparisons. Protocol A was more efficient for diversity analysis, while protocol B estimated a more precise relative abundance. Our results do not allow us to suggest an optimal sequencing depth at specie level.
A Low-Cost, 3D-Printed Biosensor for Rapid Detection of Escherichia coli
Authors: Malhotra Samir , Pham Dang Song , Lau Michael P.H. , Nguyen Anh H. , Cao Hung
Published: January 2022

Detection of bacterial pathogens is significant in the fields of food safety, medicine, public health, etc. If bacterial pathogens are not treated promptly, antimicrobial resistance is possible and can lead to morbidity and mortality. Current bacterial detection methodologies rely on laboratory-based techniques that pose limitations such as long turnaround detection times, expensive costs, inadequate accuracy, and required trained specialists. Here, we describe a cost-effective and portable 3D-printed electrochemical biosensor that facilitates rapid detection of certain Escherichia coli (E. coli) strains (DH5α, BL21, TOP10, and JM109) within 15 minutes using 500 μL of sample and costs $2.50 per test. The sensor displayed an excellent limit of detection (LOD) of 53 cfu, limit of quantification (LOQ) of 270 cfu, and showed cross-reactivity with strains BL21 and JM109 due to shared epitopes. This advantageous diagnostic device is a potential candidate for high-frequency testing at point of care as well as applicable to various fields where pathogen detection is of interest.
Impact of membrane lipid polyunsaturation on dopamine D2 receptor ligand binding and signaling
Authors: Jobin Marie-Lise , De Smedt-Peyrusse Véronique , Ducrocq Fabien , Oummadi Asma , Baccouch Rim , Pedersen Maria Hauge , Medel-Lacruz Brian , Van Delft Pierre , Fouillen Laetitia , Mongrand Sébastien , Selent Jana , Tolentino-Cortez Tarson , Barreda-Gómez Gabriel , Grégoire Stéphane , Masson Elodie , Durroux Thierry , Javitch Jonathan A. , Guixà-González Ramon , Alves Isabel D. , Trifilieff Pierre
Published: January 2022

The heterogenous and dynamic constitution of the membrane fine-tunes signal transduction. In particular, the polyunsaturated fatty acid (PUFA) tails of phospholipids influence the biophysical properties of the membrane, production of second messengers, or membrane partitioning. Few evidence mostly originating from studies of rhodopsin suggest that PUFAs directly modulate the conformational dynamic of transmembrane proteins. However, whether such properties translate to other G protein-coupled receptors remains unclear. We focused on the dopamine D2 receptor (D2R), a main target of antipsychotics. Membrane enrichment in n-3, but not n-6, PUFAs potentiates ligand binding. Molecular dynamics simulations show that the D2R preferentially interacts with n-3 over n-6 PUFAs. Furthermore, even though this mildly affects signalling in heterologous systems, in vivo n-3 PUFA deficiency blunts the effects of D2R ligands. These results suggest that n-3 PUFAs act as allosteric modulators of the D2R and provide a putative mechanism for their potentiating effect on antipsychotic efficacy.
Cucumeropsis mannii seed oil (CMSO) ameliorates adipokines dysfunction and dyslipidemia in male Wistar rats exposed to Bisphenol-A
Authors: Aja P. M. , Chukwu D. A , Agu P.C. , Ani O. G. , Ekpono E. U. , Ogwoni H. A. , Awoke J. N. , Ogbu Patience N. , Aja L. , Nwite F. E. , Ukachi O. U. , Orji O. U. , Nweke P. C. , Egwu C. O. , Ekpono E. U. , Ewa G. O. , Igwenyi I. O. , Alum E. U. , Uti D. E. , Tusubira Deusdedit , Offor C. E. , Njoku A. , Maduagwuna E. K
Published: January 2022

Bisphenol-A (BPA) and its analog are extensively utilized in the production of plastics which are rather ubiquitous in our environment. At high temperatures, BPA is leached into water and food packed in plastic containers. This research investigated the ameliorative effects of CMSO on adipokines dysfunction and dyslipidemia in male Wistar rats exposed to Bisphenol-A. thirty-six (36) albino rats weighing 100 - 200 g were randomly assigned into six (6) different experimental groups of controls (1, 2, and 3) and the tests (4, 5, and 6). Group 1 was given only 1 ml of olive oil, group 2 received 100 mg/Kg body weight (b.w) of BPA, group 3 was given 7.5 ml/Kg b.w of CMSO, groups 4, 5, and 6 received 100 mg/Kg b.w of BPA and 7.5, 5 and 2.5 mg/Kg b.w of CMSO respectively. CMSO and BPA were concurrently administered via oral intubation for periods of 42 days. Lipid profile and adipokines levels were determined in plasma and adipose tissue. BPA in male rats significantly (p<0.05) elevated the levels of cholesterol, triglycerides, LDL-C, liptin, and coronary and atherogenic risk indices in plasma and adipose tissue with reductions in HDL-C and adiponectin levels. BPA plus CMSO in male rats significantly (p<0.05) decreased the levels of cholesterol, triglycerides, LDL-C, liptin, and coronary and atherogenic risk indices with an elevation of HDL-C and adiponectin levels in both plasma and adipose tissue. These results suggest that CMSO could be useful in the management of cardiovascular-related diseases induced by BPA.
Thiamine metabolism genes in diatoms are not regulated by thiamine despite the presence of predicted riboswitches
Authors: Pasquina Marcel Llavero , Geisler Katrin , Holzer Andre , Mehrshahi Payam , Mendoza-Ochoa Gonzalo I , Newsad Shelby , Davey Matthew P , Smith Alison G.
Published: January 2022

Thiamine pyrophosphate (TPP), an essential co-factor for all species, is biosynthesised through a metabolically expensive pathway regulated by TPP riboswitches in bacteria, fungi, plants and green algae. Diatoms are microalgae responsible for approximately 20% of global primary production. They have been predicted to contain TPP aptamers in the 3’UTR of some thiamine metabolism-related genes, but little is known about their function and regulation.

We used bioinformatics, antimetabolite growth assays, RT-qPCR, targeted mutagenesis and reporter constructs to test whether the predicted TPP riboswitches respond to thiamine supplementation in diatoms. Gene editing was used to investigate the functions of the genes with associated TPP riboswitches in Phaeodactylum tricornutum.

We found that thiamine-related genes with putative TPP aptamers are not responsive to thiamine or its precursor 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP), and the targeted mutation of the TPP aptamer in the HMP-P synthase (THIC) does not deregulate thiamine biosynthesis in P. tricornutum. Through genome editing we established that PtSSSP is necessary for thiamine uptake and that PtTHIC is essential for thiamine biosynthesis.

Our results highlight the importance of experimentally testing bioinformatic aptamer predictions and provide new insights into the thiamine metabolism shaping the structure of marine microbial communities with global biogeochemical importance.
Computational study of the furin cleavage domain of SARS-CoV-2: delta binds strongest of extant variants
Authors: Jawaid M. Zaki , Baidya A. , Jakovcevic S. , Lusk J. , Mahboubi-Ardakani R. , Solomon N. , Gonzalez G. , Arsuaga J. , Vazquez M. , Davis R.L. , Cox D.L.
Published: January 2022

We demonstrate that AlphaFold and AlphaFold Multimer, implemented within the ColabFold suite, can accurately predict the structures of the furin enzyme with known six residue inhibitory peptides. Noting the similarity of the peptide inhibitors to polybasic furin cleavage domain insertion region of the SARS-CoV-2, which begins at P681, we implement this approach to study the wild type furin cleavage domain for the virus and several mutants. We introduce mutationsin silicofor alpha, omicron, and delta variants, for several sequences which have been rarely observed, for sequences which have not yet been observed, for other coronaviruses (NL63, OC43, HUK1a, HUK1b, MERS, and 229E), and for the H5N1 flu. We show that interfacial hydrogen bonds between the furin cleavage domain and furin are a good measure of binding strength that correlate well with endpoint binding free energy estimates, and conclude that among all candidate viral sequences studied, delta is near the very top binding strength within statistical accuracy. However, the binding strength of several rare sequences match delta within statistical accuracy. We find that the furin S1 pocket is optimized for binding arginine as opposed to lysine. This residue, typically at sequence position five, contains the most hydrogen bonds to the furin, and hydrogen bond count for just this residue shows a strong positive correlation with the overall hydrogen bond count. We demonstrate that the root mean square backbone C-alpha fluctuation of the first residue in the furin cleavage domain has a strong negative correlation with the interfacial hydrogen bond count. We show by considering the variation with the number of basic residues that the maximum mean number of interfacial hydrogen bonds expected is 15.7 at 4 basic residues.
Zebrafish transposable elements show extensive diversification in age, genomic distribution, and developmental expression
Authors: Chang Ni-Chen , Rovira Quirze , Wells Jonathan , Feschotte Cédric , Vaquerizas Juan M.
Published: January 2022

There is considerable interest in understanding the effect of transposable elements (TEs) on embryonic development. Studies in humans and mice are limited by the difficulty of working with mammalian embryos and by the relative scarcity of active TEs in these organisms. The zebrafish is an outstanding model for the study of vertebrate development, and over half of its genome consists of diverse TEs. However, zebrafish TEs remain poorly characterized. Here we describe the demography and genomic distribution of zebrafish TEs and their expression throughout embryogenesis using bulk and single-cell RNA sequencing data. These results reveal a highly dynamic genomic ecosystem comprising nearly 2000 distinct TE families, which vary in copy number by four orders of magnitude and span a wide range of ages. Longer retroelements tend to be retained in intergenic regions, whereas short interspersed nuclear elements (SINEs) and DNA transposons are more frequently found nearby or within genes. Locus-specific mapping of TE expression reveals extensive TE transcription during development. Although two-thirds of TE transcripts are likely driven by nearby gene promoters, we still observe stage- and tissue-specific expression patterns in self-regulated TEs. Long terminal repeat (LTR) retroelements are most transcriptionally active immediately following zygotic genome activation, whereas DNA transposons are enriched among transcripts expressed in later stages of development. Single-cell analysis reveals several endogenous retroviruses expressed in specific somatic cell lineages. Overall, our study provides a valuable resource for using zebrafish as a model to study the impact of TEs on vertebrate development.
Fundamental analysis and the use of financial statement information to separate winners and losers in frontier markets: evidence from Vietnam
Authors: Ho Tuan , Nguyen Y Trong , Tran Hieu Truong Manh , Vo Dinh-Tri
Published: January 2022

Purpose

The pupose of the paper is to study the usefulness of Piotroski (2000)'s F-score in separating winners and losers in Vietnam.

Design/methodology/approach

The authors adopt a portfolio analysis and regression analysis on a sample of 501 of listed firms between 2009 and 2019 in Vietnam.

Findings

The authors find that a hedge strategy that buys high-F-score firms and sells low-F-score firms yield market-adjusted return of over 30 percent annually, which is statistically and economically significant. The hedge strategy based on F-score is not only profitable for value (high book-to-market [BM]) firms but also earn abnormal returns in a sample of growth (low BM) firms, suggesting that the usefulness of F-score strategy is not just a phenomenon in value firms as documented in previous literature.

Research limitations/implications

Whilst the authors' paper documents economically significant returns obtained from the F-score strategy, the authors do not examine what drives the abnormal returns.

Practical implications

The results provide supporting evidence for the use of financial statement analysis as a screening tool to improve the performance of value investment in Vietnam stock market and for the training of financial reporting and fundamental analysis in universities.

Originality/value

The authors' research is the first study examining the F-score strategy in Vietnam that provides insights about the usefulness of fundamental analysis in separating winners and losers in a frontier market and contributes to the literature on fundamental analysis and market efficiency in emerging and frontier markets.
Family firm versus non-family firm: the role of resource orchestration in fast-growing high-tech SMEs
Authors: Ljungkvist Torbjörn , Boers Börje , Andersén Jim
Published: January 2022

Purpose

This paper strives to understand the role of resource orchestration (RO) in the rapid growth of high-tech small and medium-sized enterprises (SMEs).

Design/methodology/approach

Based on a comparative case study, RO is compared between a high-tech family firm and a high-tech non-family firm. To capture the complexity of RO, this study applies a longitudinal approach using a large volume of archival and interview data gathered over ten years.

Findings

The configuration of family-firm paradoxical growth-oriented RO emphasizes RO based on collectivism and responsibility, although relying on large-scale conforming normative control. In contrast, the configuration of non-family-firm growth-oriented RO emphasizes administrative-based delegation and management-supported value creation.

Originality/value

By suggesting ownership-based RO configurations, this study provides insights into how ownership types, i.e. family firms and non-family firms, affect RO in firms operating in complex and dynamic environments. These configurations explain how and why RO is arranged in a growth context.