bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in Diagnosed Dry Eye Disease Incidence, 2001 to 2015: A Nationwide Population-Based Study in Taiwan
Authors: Lin I-Chan , Kuo Yu-Kai , Liu Hung-Yi , Chien Li-Nien
Published: January 2022

Purpose:

The purpose of this study was to estimate the longitudinal trend in the incidence of diagnosed dry eye disease (DED) from 2001 to 2015 in Taiwan.

Methods:

We obtained data from the Taiwan National Health Insurance Research Database that covers 99.9% of Taiwanese residents. The incident DED cases were identified according to diagnoses, drug codes, and procedure codes. We estimated age-specific and sex-specific incidence rates (IRs) between 2001 and 2015.

Results:

The annual age-adjusted IRs of DED increased from 0.97 per 1000 in 2001 to 2.52 per 1000 in 2015 among male population and from 2.06 in 2001 per 1000 to 4.91 in 2015 per 1000 among female population. From 2001 to 2015, the annual IRs increased starting from age 20 to 39 years to age 70 to 79 years in both the male and female population. The men in both 20 to 39 and 50 to 59 age groups showed 3-fold higher IRs in 2015 than in 2001. However, the IRs were consistently lower in men than in women from 2001 to 2015. Overall, the IR was highest, between 10.3 (95% confidence interval, 10.1–10.5) and 13.8 (13.5–14.1) per 1000 population, in the population with the highest socioeconomic status.

Conclusions:

The IRs of DED increased from 2001 to 2015 for all demographics, particularly in the 20 to 39 and 50 to 59 years aged male population. These findings highlight the disease burden of DED and are expected to grow substantially.
Initial Case Report of Cladorrhinum samala Mycotic Keratitis
Authors: Gupta Parakriti , Thakur Anchal , Rudramurthy Shivaprakash M. , Gupta Amit , Ghosh Anup , Kaur Harsimran
Published: January 2022

Purpose:

The purpose of this study was to report the first case of keratitis caused by Cladorrhinum samala and review of the literature.

Methods:

This was a case report and literature review.

Results:

A 35-year-old immunocompetent man presented with pain, redness, and watering in the right eye 7 days after trauma with some foreign body. He was diagnosed with infectious keratitis, and a thorough microbiological workup was performed. Corneal scrapings were subjected to a potassium hydroxide (KOH) examination, Gram staining, bacterial (blood agar and Robertson cooked meat broth), and fungal culture (Sabouraud dextrose agar and brain–heart infusion agar). The KOH mount revealed septate fungal hyphae with irregular margins. Yellow–white nonsporulating mycelial growth was noted on the Sabouraud dextrose agar, which was identified as C. samala by sequencing. The patient responded to 5% natamycin and 1% voriconazole eye drops, and there was a formation of a corneal opacity in a period of 3 weeks.

Conclusions:

We report the first case of keratitis by C. samala, highlighting the emergence of a rare dematiaceous fungi causing keratitis and the role of molecular modalities in the diagnosis of nonsporulating fungi in suspected cases.
Influence of Clinical Pharmacist's Interventions on Clinical Outcomes of Patients With Pneumonia in the Emergency Department of Tertiary Care Healthcare Setting
Authors: Shaat Maisaa Safwat , Gillani Syed Wasif , Mohiuddin Shabaz , Menon Vineetha , Azhar Anam , Jiaan Nada
Published: January 2022

The aims of the study were to evaluate the services of emergency medicine pharmacists in patient care and to assess the need to implement clinical pharmacy practice in emergency department. This study analyzed English language articles, which were identified and studied according to the inclusion criteria. The articles were identified from different databases from 1982 to 2020. Two hundred fifty articles were primarily searched for inclusion criteria and a preferred reporting items for systematic reviews and meta-analyses diagram was created to describe qualitative analysis. Quality assessment of the studies was done using the strengthening the reporting of observational studies in epidemiology checklist. A total of 9 studies were quality assessed and included for evidence synthesis. Four studies showed a significant reduction in readmission rate P < 0.0001 with an odds ratio (OR) of 1.6341 for the patients with the pharmacist care group. Patient's in-hospital mortality and appropriateness of medications had an OR of 3.2196 (P = 0.0353) and 0.1444 (P = 0.0001), respectively. The pooled OR (n = 1026) in 4 studies was 1.4534 (95% confidence interval = 0.2844–0.7292) in antibiotic guidelines for pharmacist interventions. In addition, evidence showed a statistically significant reduction in hospital revisits (P < 0.00001, OR = 2.05, 95% confidence interval = 1.76–2.39) with the pharmacist in the emergency department compared with no pharmacist. The meta-analysis concluded that clinical pharmacy interventions in the ambulatory setting had a positive impact on clinical outcomes related to disease management, medication optimization, ensuring patient safety, and providing quality of care. Studies identified did not evaluate the impact of pharmacists on cost-effectiveness, which is a useful direction for future study.
Impact of Rapidly Deployed COVID-19 Monoclonal Antibody Infusion Clinics on Rate of Hospitalization
Authors: Delasobera Bronson E. , Saggar Tara , Goodwin Jennifer N. , Joy Amanda , Henry Kiersten N. , Levin Bonnie , Hager David D. , McAlduff Joel , DeSale Sameer , Owens Xavier , Wortmann Glenn W. , Kumar Princy N.
Published: January 2022

Background

Providing monoclonal antibody therapy infusions requires challenging logistics, resources, and technology, hindering availability across the United States. Early identification and treatment of COVID-positive patients can reduce hospitalizations.

Objective

This study aimed to describe the referral, selection process, and deployment of outpatient monoclonal infusion clinics, as well as the impact of monoclonal antibody therapy in COVID-positive patients on the rate of emergency department (ED) visits and hospitalization.

Methods

This is a retrospective cohort study that used screening of all COVID-positive ambulatory patients using a unique scoring rubric embedded in the emergency medical response for appropriateness for therapy between November 2020 and January 2021. Participants included all outpatients testing positive for COVID-19 were screened, and those eligible were referred for treatment with bamlanivimab. Of the 443 patients referred for treatment, 252 patients were treated with bamlanivimab compared with 191 patients who declined treatment. Patients were treated either in 1 of the 2 outpatient infusion centers (74%) or the ED (26%.)

Results

Of 443 patients with positive COVID-19 diagnoses who were eligible for treatment based on a risk assessment rubric, 252 received bamlanivimab. There was a significant reduction in hospitalization of the treatment versus control group (6.7% vs 13.6%, P < 0.05). No significant differences were noted in risk score at screening, ED visits after infusion, days of symptom onset at screening or infusion, or death.

Conclusions and Relevance

The efficacy of monoclonal antibody therapy on reducing hospitalization was demonstrated. Rapid development of screening technology, scheduling and operational logistics, and physical space can overcome the challenges in the current environment.
Recurrent scleral-fixated intraocular lens dislocation with spontaneous repositioning produced by tilting and head movements
Authors: O'Riordan Matthew , Raman Vasant
Published: January 2022

Introduction:

An unusual case of a patient who could repeatedly reposition his dislocated sulcus poly(methyl methacrylate) intraocular lens (IOL) by head movements and tilting his body is reported.

Patient and clinical findings:

An 86-year-old man presented with a 3-year history of recurrent episodes of transient blurred vision and monocular diplopia in his left eye. 20 years previously, he had phacoemulsification cataract surgery complicated by posterior capsule tear, which was treated with anterior vitrectomy and a secondary scleral-fixated IOL. Over the previous 3 years, he had recurrent episodes of IOL dislocation. He could regain normal vision by tilting his head and trunk. The dislocated IOL was maneuvered into position by capturing the haptic into the residual capsular remnant by appropriate head movements. On examination, his corrected distance visual acuity (CDVA) was counting fingers, and the posterior chamber IOL was subluxated inferiorly. During presentation, he could not reposition it himself, warranting a surgical intervention.

Diagnosis, intervention and outcomes:

He underwent suturing of the IOL in the sulcus. The IOL was well-centered with a CDVA of 6/9.

Conclusions:

To the authors’ knowledge, this is the first case report of a patient who could repeatedly reposition a dislocated IOL through tilting and head movements.
Contribution of COVID Antigenic RDT to the Management Strategy of COVID-19 Pandemic in a Senegalese Company
Authors: Sagna Asséga Sylvain , Seydi Aïssatou Goundo , Gueye Modou Mbacké , Fall Mame Thioro Aïssatou , Mansuy Jean Michel
Published: January 2022

Objective:

To describe the contribution of the rapid antigen diagnostic testing (RDT) to the management strategy of the COVID-19 pandemic.

Methodologies:

The protein chain reaction (PCR) and the RDT have been performed on each COVID-19 suspected workers from December 2020 to September 2021.

Results:

A total of 286 people tested. A positivity rate of 38.1% was recorded. The average time to obtain PCR results was 8.3 days. 54.8% (n = 142) of the RDT were followed by a PCR for confirmation or invalidation and 100% of positive cases with Ag-RDT were confirmed by the PCR. We have noticed a 58.3% reduction of lost work days due to COVID-19, since the use of the Ag-RDT.

Conclusion:

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapid diagnostic tests are efficient. They have enabled early treatment of COVID-19 patients, helped hold back the spread of the disease in a high-risk professional environment, and reduced the impact of the pandemic on a vital sector in developing countries.
Measurement Properties of the Dizziness Handicap Inventory: A Systematic Review
Authors: Koppelaar-van Eijsden Hanna Maria , Schermer Tjard Roland , Bruintjes Tjasse Doewe
Published: January 2022

Objective:

To critically appraise and summarize the quality of the measurement properties of the Dizziness Handicap Inventory's (DHI) in adult patients with complaints of dizziness.

Databases Reviewed:

Pubmed, Embase, and CINAHL.

Methods:

The selected literature databases were systematically searched to identify studies investigating one or more measurement properties of the DHI. From the included studies, relevant data were extracted, their methodological quality was assessed, the results were synthesized and the evidence was graded and summarized according the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology.

Results:

The search strategy resulted in 768 eligible publications, 42 of which were included in the review. Overall, evidence on the DHI's content validity was either lacking or limited and of low quality. Moderate evidence was found for inconsistent structural validity, sufficient construct validity and borderline sufficient responsiveness. Based on the studies included, low evidence was found for sufficient reliability of the DHI total score. No evidence synthesis could be done for the DHI's internal consistency due to multidimensionality (i.e., lack of support of the original subscales) and for its measurement error due to a lack of published information on the minimal important change.

Conclusions:

The current evidence for a number of measurement properties of the DHI is suboptimal. Because of its widespread use and the current lack of a better alternative, researchers can use the DHI when assessing handicapping effects imposed by dizziness, but they should be aware of its limitations. Moreover, we recommend using the DHI total score only and also to consider adding an instrument with more favorable measurement properties when assessing self-perceived handicap in patients with dizziness.
Gastrointestinal hormones and regulation of gastric emptying
Authors: Mori Hideki , Verbeure Wout , Schol Jolien , Carbone Florencia , Tack Jan
Published: January 2022

Purpose of review

In this review, we evaluate recent findings related to the association between gastrointestinal hormones and regulation of gastric emptying.

Recent findings

Motilin and ghrelin, which act during fasting, promote gastric motility, whereas most of the hormones secreted after a meal inhibit gastric motility. Serotonin has different progastric or antigastric motility effects depending on the receptor subtype. Serotonin receptor agonists have been used clinically to treat dyspepsia symptoms but other hormone receptor agonists or antagonists are still under development. Glucagon-like peptide 1 agonists, which have gastric motility and appetite-suppressing effects are used as a treatment for obesity and diabetes.

Gastrointestinal hormones play an important role in the regulation of gastric motility. Various drugs have been developed to treat delayed gastric emptying by targeting gastrointestinal hormones or their receptors but few have been commercialized.
Tracheostomy Practices and Outcomes in Children During Respiratory Extracorporeal Membrane Oxygenation
Authors: Kohne Joseph G. , MacLaren Graeme , Rider Erica , Carr Benjamin D. , Mallory Palen , Gebremariam Acham , Friedman Matthew L. , Barbaro Ryan P.
Published: January 2022

OBJECTIVES:

Children receiving prolonged extracorporeal membrane oxygenation (ECMO) support may benefit from tracheostomy during ECMO by facilitating rehabilitation; however, the procedure carries risks, especially hemorrhagic complications. Knowledge of tracheostomy practices and outcomes of ECMO-supported children who undergo tracheostomy on ECMO may inform decision-making.

DESIGN:

Retrospective cohort study.

SETTING:

ECMO centers contributing to the Extracorporeal Life Support Organization registry.

PATIENTS:

Children from birth to 18 years who received ECMO support for greater than or equal to 7 days for respiratory failure from January 1, 2015, to December 31, 2019.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Three thousand six hundred eighty-five children received at least 7 days of ECMO support for respiratory failure. The median duration of ECMO support was 13.0 days (interquartile range [IQR], 9.3–19.9 d), and inhospital mortality was 38.7% (1,426/3,685). A tracheostomy was placed during ECMO support in 94/3,685 (2.6%). Of those who received a tracheostomy on ECMO, the procedure was performed at a median 13.2 days (IQR, 6.3–25.9 d) after initiation of ECMO. Surgical site bleeding was documented in 26% of children who received a tracheostomy (12% after tracheostomy placement). Among children who received a tracheostomy, the median duration of ECMO support was 24.2 days (IQR, 13.0–58.7 d); inhospital mortality was 30/94 (32%). Those that received a tracheostomy before 14 days on ECMO were older (median age, 15.8 yr [IQR, 4.7–15.5] vs 11.7 yr [IQR, 11.5–17.3 yr]; p =0.002) and more likely to have been supported on venovenous-ECMO (84% vs 52%; p = 0.001). Twenty-two percent (11/50) of those who received a tracheostomy before 14 days died in the hospital, compared with 19/44 (43%) of those who received a tracheostomy at 14 days or later (p = 0.03).

CONCLUSIONS:

Tracheostomies during ECMO were uncommon in children. One in four patients who received a tracheostomy on ECMO had surgical site bleeding. Children who had tracheostomies placed after 14 days were younger and had worse outcomes, potentially representing tracheostomy as a “secondary” strategy for prolonged ECMO support.
Platelets Derived Transthyretin Participate in The Development of Sepsis Associated Acute Kidney Injury by Inducing Oxidative Stress and Apoptosis of Renal Tubular Epithelial Cells
Authors: Lv Diyu , Zhang Ying , Wang Chunmei , Gu Yi , Zhang Yang , Li Xiuhua
Published: January 2022

The pathophysiology of sepsis-associated acute kidney injury (S-AKI) is not well elucidated. Platelets have been reported to play a critical role in the pathogenesis of AKI, but the true mechanism remains unknown. Herein, we established a mouse model of S-AKI by cecal ligation and puncture (CLP). Ticagrelor was given 24 h before and after CLP by gastric gavage. Platelets were isolated and analyzed by the label-free proteome approach to identify platelet-derived damage-associated molecular patterns (DAMPs). Our results demonstrated that, among all differentially expressed proteins (DEPs), platelet-derived transthyretin (TTR) exerted effects in S-AKI. To examine the direct effects of platelet TTR on human renal proximal tubule epithelial (HK2) cells damage, platelets were co-cultured with HK2 cells. The results indicated that platelet TTR can cause reactive oxygen species production and apoptosis in HK2 cells. Further research found that platelet TTR can also result in increased levels of mRNA and protein for protein kinase B (AKT), phosphatidylinositol 3-kinase (PI3K), and extracellular regulated protein kinase (ERK), as analyzed by real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. In conclusion, platelet-derived TTR may be one kind of DAMPs that plays an important role in the development of S-AKI.
Poor Practitioner Adherence to Clinical Tobacco Use Guidelines in Liver Transplant Recipients
Authors: Harrington Claire , Kosirog Megan , Campbell Patrick , Gregory Dyanna , Daud Amna , Levitsky Josh , Holl Jane L. , Lloyd-Jones Donald M. , VanWagner Lisa B.
Published: January 2022

Background.

Tobacco use is a modifiable risk factor for cardiovascular events (CVEs) in liver transplant recipients (LTRs), but there is a paucity of data about practitioner adherence to tobacco cessation guidelines for LTRs. We sought to assess adherence to these guidelines as a predictor of CVEs after liver transplant.

Methods.

We conducted a retrospective, observational, cohort study of adult LTRs from 2010 to 2016 at a large urban, tertiary care transplant network.

Results.

Of 572 LTRs (mean age‚ 56.9; 64.1% male), 325 (56.8%) were never, 191 (33.4%) were former, and 56 (9.8%) were current tobacco users before liver transplant. Most LTRs (59%) had their tobacco use assessed annually by transplant providers. Among current users, documented tobacco cessation interventions decreased over time‚ and <25% were offered pharmacologic treatment or referral to counseling. There was no difference in CVEs between tobacco users who received cessation interventions compared with those who did not.

Conclusions.

This single-center study suggests that although tobacco use cessation counseling and interventions were not associated with a decrease in CVEs, evidence-based interventions for tobacco use were under utilized in this high cardiac risk population. These findings underscore missed opportunities for transplant practitioners to provide tobacco use cessation interventions to LTRs, which potentially could reduce CVEs.
Loss of an apex predator in the wild induces physiological and behavioural changes in prey
Authors: Hammerschlag Neil , Fallows Chris , Meÿer Michael , Seakamela Simon Mduduzi , Orndorff Samantha , Kirkman Steve , Kotze Deon , Creel Scott
Published: January 2022

Predators can impact prey via predation or risk effects, which can initiate trophic cascades. Given widespread population declines of apex predators, understanding and predicting the associated ecological consequences is a priority. When predation risk is relatively unpredictable or uncontrollable by prey, the loss of predators is hypothesized to release prey from stress; however, there are few tests of this hypothesis in the wild. A well-studied predator–prey system between white sharks (Carcharodon carcharias) and Cape fur seals (Arctocephalus pusillus pusillus) in False Bay, South Africa, has previously demonstrated elevated faecal glucocorticoid metabolite concentrations (fGCMs) in seals exposed to high levels of predation risk from white sharks. A recent decline and disappearance of white sharks from the system has coincided with a pronounced decrease in seal fGCM concentrations. Seals have concurrently been rafting further from shore and over deeper water, a behaviour that would have previously rendered them vulnerable to attack. These results show rapid physiological and behavioural responses by seals to release from predation stress. To our knowledge, this represents the first demonstration in the wild of physiological changes in prey from predator decline, and such responses are likely to increase given the scale and pace of apex predator declines globally.
Tragedy of the commons in
Melipona
bees revisited
Authors: Oliveira Ricardo Caliari , Di Pietro Viviana , Quezada-Euán José Javier G. , Pech Jorge Ramirez , Moo-Valle Humberto , Wenseleers Tom
Published: January 2022

Melipona
stingless bees display a paradoxical overproduction of queens, which are later eliminated by nest-mate workers. Mechanistically, it was suggested that the monoterpenoid geraniol deposited into newly provisioned cells by adult bees would cause larvae to develop into queens in
Melipona beecheii
. This system could be evolutionarily stable if many of these new queens were to leave the nest and parasitize other genetically unrelated colonies nearby, as was shown to occur in a congeneric species
.
Here, we use microsatellite markers to test whether queen overproduction could be a strategy by which adult workers control the caste fate of the developing larvae to export copies of their own genes to the rest of the population via queen parasitism in
M. beecheii
. In addition, we re-examined whether artificially increasing the levels of geraniol indeed caused larvae to develop as queens rather than workers. Contrary to our prediction, we found no evidence for queen parasitism in
M. beecheii
and observed no effect of geraniol on the rearing of new queens. Together, these results support the original ‘tragedy of the commons' hypothesis for queen overproduction in
Melipona
bees, where individual larvae selfishly bias their development towards the queen pathway according to their best evolutionary interests.
Scared of the dark? Phototaxis as behavioural immunity in a host–parasite system
Authors: Horn Collin J. , Wasylenko Jacob A. , Luong Lien T.
Published: January 2022

Behavioural immunity describes suites of behaviours hosts use to minimize the risks of infection by parasites/pathogens. Research has focused primarily on the evasion and physical removal of infectious stages, as well as behavioural fever. However, other behaviours affect infection risk while carrying ecologically significant trade-offs. Phototaxis, in particular, has host fitness implications (e.g. altering feeding and thermoregulation) that also impact infection outcomes. In this study, we hypothesized that a fly host,
Drosophila nigrospiracula
, employs phototaxis as a form of behavioural immunity to reduce the risk of infection. First, we determined that the risk of infection is lower for flies exposed in the light relative to the dark using micro-arena experiments. Because
Drosophila
vary in ectoparasite resistance based on mating status we examined parasite-mediated phototaxis in mated and unmated females. We found that female flies spent more time in the light side of phototaxis chambers when mites were present than in the absence of mites. Mating marginally decreased female photophobia independently of mite exposure. Female flies moved to lighter, i.e. less infectious, environments when threatened with mites, suggesting phototaxis is a mechanism of behavioural immunity. We discuss how parasite-mediated phototaxis potentially trades-off with host nutrition and thermoregulation.
Functional insight into LOAD-associated microglial response genes
Authors: Jonas Lauren A. , Jain Tanya , Li Yue-Ming
Published: January 2022

Alzheimer's disease (AD) is characterized by the presence of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs), neuronal and synaptic loss and inflammation of the central nervous system (CNS). The majority of AD research has been dedicated to the understanding of two major AD hallmarks (i.e. Aβ and NFTs); however, recent genome-wide association studies (GWAS) data indicate neuroinflammation as having a critical role in late-onset AD (LOAD) development, thus unveiling a novel avenue for AD therapeutics. Recent evidence has provided much support to the innate immune system's involvement with AD progression; however, much remains to be uncovered regarding the role of glial cells, specifically microglia, in AD. Moreover, numerous variants in immune and/or microglia-related genes have been identified in whole-genome sequencing and GWAS analyses, including such genes as
TREM2
,
CD33
,
APOE
,
API1
,
MS4A
,
ABCA7
,
BIN1
,
CLU
,
CR1
,
INPP5D
,
PICALM
and
PLCG2
. In this review, we aim to provide an insight into the function of the major LOAD-associated microglia response genes.
Containing the spread of mumps on college campuses
Authors: Shah Mirai , Ferra Gabrielle , Fitzgerald Susan , Barreira Paul J. , Sabeti Pardis C. , Colubri Andrés
Published: January 2022

College campuses are vulnerable to infectious disease outbreaks, and there is an urgent need to develop better strategies to mitigate their size and duration, particularly as educational institutions around the world adapt to in-person instruction during the COVID-19 pandemic. Towards addressing this need, we applied a stochastic compartmental model to quantify the impact of university-level responses to contain a mumps outbreak at Harvard University in 2016. We used our model to determine which containment interventions were most effective and study alternative scenarios without and with earlier interventions. This model allows for stochastic variation in small populations, missing or unobserved case data and changes in disease transmission rates post-intervention. The results suggest that control measures implemented by the University's Health Services, including rapid isolation of suspected cases, were very effective at containing the outbreak. Without those measures, the outbreak could have been four times larger. More generally, we conclude that universities should apply (i) diagnostic protocols that address false negatives from molecular tests and (ii) strict quarantine policies to contain the spread of easily transmissible infectious diseases such as mumps among their students. This modelling approach could be applied to data from other outbreaks in college campuses and similar small population settings.
Trans-generational effect of protein restricted diet on adult body and wing size of
Drosophila melanogaster
Authors: Krittika Sudhakar , Yadav Pankaj
Published: January 2022

Protein restriction (PR) has established feasible trade-offs in
Drosophila melanogaster
to understand lifespan or ageing in a nutritionally challenged environment. However, the phenotypes of body size, weight and wing length respond according to factors such as flies' genotype, environmental exposure and parental diet, and hence their understanding is essential. Here, we demonstrate the effect of long-term PR diet on body size, weight, normal and dry wing length of flies subjected to PR50 and PR70 (50% and 70% protein content present in control food, respectively) for 20 generations from the pre-adult stage. We found that PR-fed flies have lower body weight, relative water content (in males), unaltered (PR50%) and higher (PR70%) relative fat content in males, smaller normal and dry body size when compared with control and generations 1 and 2. Interestingly, the wing size and pupal size of PR flies are smaller and showed significant effects on diet and generation. Thus, these traits are sex and generation dependent along with a diet interaction, which is capable of modulating these results variably. Taken together, the trans-generational effect of PR on fitness and fitness-related traits might be helpful to understand the underpinning mechanisms of evolution and ageing in fruit flies
D. melanogaster
.
Unbinding ligands from SARS-CoV-2 Mpro via umbrella sampling simulations
Authors: Tam Nguyen Minh , Nguyen Trung Hai , Ngan Vu Thi , Tung Nguyen Thanh , Ngo Son Tung
Published: January 2022

The umbrella sampling (US) simulation is demonstrated to be an efficient approach for determining the unbinding pathway and binding affinity to the SARS-CoV-2 Mpro of small molecule inhibitors. The accuracy of US is in the same range as the linear interaction energy (LIE) and fast pulling of ligand (FPL) methods. In detail, the correlation coefficient between US and experiments does not differ from FPL and is slightly smaller than LIE. The root mean square error of US simulations is smaller than that of LIE. Moreover, US is better than FPL and poorer than LIE in classifying SARS-CoV-2 Mpro inhibitors owing to the reciever operating characteristic–area under the curve analysis. Furthermore, the US simulations also provide detailed insights on unbinding pathways of ligands from the binding cleft of SARS-CoV-2 Mpro. The residues
Cys44
,
Thr45
,
Ser46
,
Leu141
,
Asn142
,
Gly143
,
Glu166
,
Leu167
,
Pro168
,
Ala191
,
Gln192
and
Ala193
probably play an important role in the ligand dissociation. Therefore, substitutions at these points may change the mechanism of binding of inhibitors to SARS-CoV-2 Mpro.
Factors affecting conspiracy theory endorsement in paranoia
Authors: Greenburgh A. G. , Liefgreen A. , Bell V. , Raihani N.
Published: January 2022

Paranoia and conspiracy thinking are known to be distinct but correlated constructs, but it is unknown whether certain types of conspiracy thinking are more common in paranoia than others. In a large (
n
= 1000), pre-registered online study we tested if endorsement of items on a new Components of Conspiracy Ideation Questionnaire varied according to whether harm was described as being (a) intentional and (b) self-referential. Our predictions were supported: paranoia was positively associated with endorsement of items on this questionnaire overall and more paranoid individuals were more likely to endorse items describing intentional and self-referential harm. Belief in any item on the Components of Conspiracy Ideation Questionnaire was associated with belief in others and items describing incidental harm and harm to others were found to be more believable overall. Individuals who endorsed conspiracy theory items on the questionnaire were more likely to state that people similar to them would as well, although this effect was not reduced in paranoia, counter to our expectations.
Multiple roles of ribosomal antimicrobial peptides in tackling global antimicrobial resistance
Authors: Luong Huy Xuan , Ngan Hoa Doan , Thi Phuong Hai Bui , Quoc Thang Nguyen , Tung Truong Thanh
Published: January 2022

In the last century, conventional antibiotics have played a significant role in global healthcare. Antibiotics support the body in controlling bacterial infection and simultaneously increase the tendency of drug resistance. Consequently, there is a severe concern regarding the regression of the antibiotic era. Despite the use of antibiotics, host defence systems are vital in fighting infectious diseases. In fact, the expression of ribosomal antimicrobial peptides (AMPs) has been crucial in the evolution of innate host defences and has been irreplaceable to date. Therefore, this valuable source is considered to have great potential in tackling the antimicrobial resistance (AMR) crisis. Furthermore, the possibility of bacterial resistance to AMPs has been intensively investigated. Here, we summarize all aspects related to the multiple applications of ribosomal AMPs and their derivatives in combating AMR.
Geometry evolution of mesoscopic mechanical structures during the rock fragmentation process induced by tunnel boring machine (TBM) cutters
Authors: Geng Qi , He Fei , Lu Zhiyong , Liu Xiaohui , Wang Xuebin , Ye Min
Published: January 2022

We investigated the geometric evolution of mesoscopic mechanical structures in rocks during the rock fragmentation process induced by tunnel boring machine cutters. Numerical models were built using a grain-based discrete element method to accurately represent the mesoscopic structures and macroscopic mechanical behaviours of rocks, and the relationship between the mesoscopic evolution and the macroscopic response of rock was determined. The major results are as follows. First, the crushing and re-compaction of the grains were found to mainly occur in the thin crushed zone immediately beneath the cutter tip. Second, the reduction in the bearing ability of the dense core during cutter indentation was due to the order increment of the contact topological structure at the mesoscopic scale. Third, the area percentages of low- and high-order meso-loops decreased and increased, respectively, during the indentation process, and the volume expansion of the dense core was mainly caused by an increase in the internal pore area of high-order meso-loops that have low internal solid fractions. Fourth, the low-order meso-loops primarily bore and transferred the indentation force. Finally, the distribution contour of the meso-loops was found to be an appropriate and intuitive approach for representing the evolution of cracks on a macroscopic scale.
Mussel memory: can bivalves learn to fear parasites?
Authors: Selbach Christian , Marchant Loïc , Mouritsen Kim N.
Published: January 2022

Fear plays a crucial role in predator–prey interactions and can have cascading impacts on the structure of whole ecosystems. Comparable fear effects have recently been described for hosts and their parasites but our understanding of the underlying mechanisms remains limited by the lack of empirical examples. Here, we experimentally tested if bivalvesMytilus eduliscan potentially ‘learn to fear’ the infective transmission stages (cercariae) of the trematodeHimasthla elongata, and if experienced mussels change their parasite-avoidance behaviour accordingly. Our results show that previous experience with parasites, but not established infections, lead to a reduced filtration activity in mussels in the presence of cercariae compared to parasite-naive conspecifics. This reduction in filtration activity resulted in lower infection rates in mussels. Since parasite avoidance comes at the cost of lower feeding rates, mussels likely benefit from the ability to adjust their defence behaviour when infection risks are high. Overall, these dynamic processes of avoidance behaviour can be expected to play a significant role in regulating the bivalves' ecosystem engineering function in coastal habitats.
Males of the parasitoid wasp,
Nasonia vitripennis
, can identify which fly hosts contain females
Authors: Prazapati Garima , Yadav Ankit , Ambili Anoop , Sharma Abhilasha , Raychoudhury Rhitoban
Published: January 2022

The reproductive success of a male is limited by the number of females it can mate with. Thus, males deploy elaborate strategies to maximize access to females. In
Nasonia
, which are parasitoids of cyclorrhaphous flies, such reproductive strategies are thought to be restricted to competition among males for access to females in the natal patch. This study investigates whether additional strategies are present, especially the capability to identify which fly hosts contain adult females inside. Behavioural assays revealed that only one out of the four species,
N. vitripennis,
can distinguish which hosts specifically have adult female wasps, indicating a species-specific reproductive strategy. Results of gas chromatography-mass spectrometry analyses and behavioural data suggest that female-signature cuticular hydrocarbons (CHCs) are used as chemical cues, possibly emanating from within the host puparium. Further assays indicated that
N. vitripennis
males can also detect differences in the intensities of female-signature CHCs, giving them the capability to seek out hosts with maximum number of females. This study uncovers a previously unknown reproductive strategy in one of the most widely studied parasitoid wasps.
Elephant seal foraging success is enhanced in Antarctic coastal polynyas
Authors: Arce Fernando , Hindell Mark A. , McMahon Clive R. , Wotherspoon Simon J. , Guinet Christophe , Harcourt Robert G. , Bestley Sophie
Published: January 2022

Antarctic polynyas are persistent open water areas which enable early and large seasonal phytoplankton blooms. This high primary productivity, boosted by iron supply from coastal glaciers, attracts organisms from all trophic levels to form a rich and diverse community. How the ecological benefit of polynya productivity is translated to the highest trophic levels remains poorly resolved. We studied 119 southern elephant seals feeding over the Antarctic shelf and demonstrated that: (i) 96% of seals foraging here used polynyas, with individuals spending on average 62% of their time there; (ii) the seals exhibited more area-restricted search behaviour when in polynyas; and (iii) these seals gained more energy (indicated by increased buoyancy from greater fat stores) when inside polynyas. This higher-quality foraging existed even when ice was not present in the study area, indicating that these are important and predictable foraging grounds year-round. Despite these energetic advantages from using polynyas, not all the seals used them extensively. Factors other than food supply may influence an individual's choice in their use of feeding grounds, such as exposure to predation or the probability of being able to return to distant sub-Antarctic breeding sites.
A Combinatorial Approach towards Adaptability of 22 Functional Cas12a Orthologs for Nucleic Acid Detection in Clinical Samples
Authors: Nguyen Long T. , Macaluso Nicolas C. , Jain Piyush K.
Published: January 2022

Reliable, efficient, and cheap detection of infectious diseases, especially in the wake of the SARS-CoV-2 pandemic, is of increasing importance. CRISPR/Cas systems have the capabilities to be optimized for this purpose. There is a broad diversity among Cas12a nucleases with immense detection capability, but only a few have been purified and studied biochemically. Here we present the investigation of 22 Cas12a orthologs, with a focus on their cis- and trans-cleavage activity, and thermal stability in combination with non-canonical crRNAs. We noticed that some non-canonical crRNA:Cas12a effector complexes outperformed its corresponding wild-type crRNA:Cas12a complex in trans-cleavage assays. In particular, TsCas12a, ErCas12a, and ArCas12a showed an increase in thermal stability in binary complex compared to its wild-type structure and apo form. Moreover, Cas12a was observed to have the ability to recruit segments of truncated crRNAs providing insights into crRNA:Cas12a catalytic complex with potential for further applications. We also discovered that ErCas12a, BsCas12a, BoCas12a, and TsCas12a possess robust trans-cleavage activity with a shorter PAM sequence requirement. Finally, we applied these effector complexes to discriminately detect SARS-CoV-2 and its B.1.1.7 lineage in clinical nasopharyngeal swabs, saliva samples, and tracheal aspirates. Our findings further expand the toolbox for next-generation CRISPR-based diagnostics.
Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time
Authors: Gentles Lauren E. , Kehoe Leanne , Crawford Katharine H.D. , Lacombe Kirsten , Dickerson Jane , Wolf Caitlin , Yuan Joanna , Schuler Susanna , Watson John T. , Nyanseor Sankan , Briggs-Hagen Melissa , Saydah Sharon , Midgley Claire M. , Pringle Kimberly , Chu Helen , Bloom Jesse D. , Englund Janet A.
Published: January 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits an antibody response that targets several viral proteins including spike (S) and nucleocapsid (N); S is the major target of neutralizing antibodies. Here, we assess levels of anti-N binding antibodies and anti-S neutralizing antibodies in unvaccinated children compared with unvaccinated older adults following infection. Specifically, we examine neutralization and anti-N binding by sera collected up to 52 weeks following SARS-CoV-2 infection in children and compare these to a cohort of adults, including older adults, most of whom had mild infections that did not require hospitalization. Neutralizing antibody titers were lower in children than adults early after infection, but by 6 months titers were similar between age groups. The neutralizing activity of the children’s sera decreased modestly from one to six months; a pattern that was not significantly different from that observed in adults. However, infection of children induced much lower levels of anti-N antibodies than in adults, and levels of these anti-N antibodies decreased more rapidly in children than in adults, including older adults. These results highlight age-related differences in the antibody responses to SARS-CoV-2 proteins and, as vaccines for children are introduced, may provide comparator data for the longevity of infection-elicited and vaccination-induced neutralizing antibody responses.
Brain Tumor Detection Using Deep Learning
Authors: Santos Dheiver , Santos Ewerton
Published: January 2022

A brain tumor is understood by the scientific community as the growth of abnormal cells in the brain, some of which can lead to cancer. The traditional method to detect brain tumors is nuclear magnetic resonance (MRI). Having the MRI images, information about the uncontrolled growth of tissue in the brain is identified. In several research articles, brain tumor detection is done through the application of Machine Learning and Deep Learning algorithms. When these systems are applied to MRI images, brain tumor prediction is done very quickly and greater accuracy helps to deliver treatment to patients. These predictions also help the radiologist to make quick decisions. In the proposed work, a set of Artificial Neural Networks (ANN) are applied in the detection of the presence of brain tumor, and its performance is analyzed through different metrics.
Breast Cancer Survival Prediction using Machine Learning and Gene Expression Profiles
Authors: Santos Dheiver
Published: January 2022

Breast cancer is one of the most common cancers with a high mortality rate among women. It is also the most frequent cause of cancer death in this population, with an estimated 684,996 deaths for that year (15.5% of cancer deaths in women) (IARC, 2020). In Brazil, breast cancer is also the most common type of cancer in women from all regions, after non-melanoma skin cancer. Therefore, an accurate and reliable system is needed for the early diagnosis of this cancer. Machine learning explores the study and construction of algorithms that can learn from their mistakes and make predictions about data. The results here are excellent with an accuracy and precision level of around 79%.
Empirical Calibration of a Simulation Model of Opioid Use Disorder
Authors: Madushani R. W. M. A. , Wang Jianing , Weitz Michelle , Linas Benjamin , White Laura F. , Chrysanthopoulou Stavroula
Published: January 2022

Simulation models of opioid use disorder (OUD) aim at evaluating the impact of different treatment strategies on population-level outcomes. Researching Effective Strategies to Prevent Opioid Death (RESPOND) is a dynamic population state-transition model that simulates Massachusetts (MA) OUD population synthesizing data from the MA Public Health Data Warehouse, published survey studies, and randomized trials. We implement an empirical calibration approach to fit RESPOND to multiple calibration targets, including yearly counts of fatal overdoses and detox admissions in 2013-2015, and 2015 OUD population counts in MA. We used capture-recapture analysis to estimate the OUD population and to quantify uncertainty around calibration targets.1 The empirical calibration approach involves Latin hypercube sampling for a parameter search of the multidimensional space, comprising demographics of “arrivals”, overdose rates, treatment transition rates, and substance use transition probabilities. The algorithm accepts proposed parameter values when the respective model outputs are “close” to the observed calibration targets based on uncertainty ranges of targets. Calibration provided an excellent fit to the model calibration targets. The flexibility of the algorithm also allowed us to identify certain “questionable” parts of the model structure and explore the underlying relationships between the model parameters in an efficient manner. The calibrated model also provided a good fit to validation targets: non-overdose related deaths, percentage of active OUDs, and all types of overdose counts (fatal and non-fatal). In addition, the resulting set of values for the calibrated parameters will inform the priors of a more comprehensive Bayesian calibration. The calibrated RESPOND model will be employed to improve shared decision-making for OUD.
One minute Multiple Pupillary Frequency Tagging test to assess visual field defects
Authors: Ajasse Suzon , Vignal-Clermont Catherine , Mohand-Said Saddek , Coen Cecilia , Romand Carole , Lorenceau Jean
Published: January 2022

Pupillary responses to light offer a convenient and objective way to quickly assess the functional health of the anterior afferent visual pathways. We here present a proof of concept of an innovative one minute pupillary test consisting in 9 visual sub-regions simultaneously modulated in luminance at 9 different temporal frequencies. The spectral power of the sustained pupillary responses evoked by this display over 45 seconds of passive fixation distinguishes patients with retinal and optic nerve diseases from healthy participants with remarkable sensitivity and specificity, at both global and local scales. Reliable and fast, this test could ease patient care and allow screening for, and following-up, chronic ophthalmic diseases whose prevalence worryingly increases worldwide.
mRNA-1273 Vaccine-elicited Neutralization of SARS-CoV-2 Omicron in Adolescents and Children
Authors: Girard Bethany , Tomassini Joanne E , Deng Weiping , Maglinao Maha , Zhou Honghong , Figueroa Amparo , Ghamloush Sabine Schnyder , Montefiori David C , Das Rituparna , Pajon Rolando
Published: January 2022

Background

The highly transmissible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron variant is a global concern. This study assessed the neutralization activity of two-dose regimens of mRNA-1273 vaccination against Omicron in adults, adolescents and children.

Methods

Neutralizing activity against the Omicron variant was evaluated in serum samples from adults (≥18 years) in the phase 3, Coronavirus Efficacy (COVE) and from adolescents (12-17 years) in the TeenCOVE trials following a two-dose regimen of 100 µg mRNA-1273 and from children (6-<12 years) in the KidCOVE trial administered two doses of 50 µg mRNA-1273. Neutralizing antibody geometric mean ID50 titers (GMT) were measured using a lentivirus-based pseudovirus neutralizing assay at day 1 and 4 weeks (day 57) following the second mRNA-1273 dose, compared with wild-type (D614G).

Results

At 4 weeks following a second dose of mRNA-1273 (100 µg), the GMT was reduced 28.8-fold compared with D614G in adults (≥18 years). In adolescents (12-17 years), the GMT was 11.8-fold lower than D614G, 4 weeks after a second dose of mRNA-1273 (100 µg), and compared with adults, were 1.5- and 3.8-fold higher for D614G and the Omicron variant, respectively. In children (6-<12 years), 4 weeks post-second dose of 50 µg mRNA-1273, Omicron GMTs were reduced 22.1-fold versus D614G and were 2.0-fold higher for D614G and 2.5-fold higher for Omicron compared with adults.

Conclusions

A two-dose regimen of 100 µg mRNA-1273 in adolescents and of 50 µg in children elicited neutralization responses against the Omicron variant that were reduced compared with the wild-type D614G, and numerically higher than those in adults.