bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ixodes ricinus
tick bacteriome alterations based on a climatically representative survey in Hungary
Authors: Tóth Adrienn Gréta , Farkas Róbert , Papp Márton , Kilim Oz , Yun Haeun , Makrai László , Maróti Gergely , Gyurkovszky Mónika , Krikó Eszter , Solymosi Norbert 
Published: November 2023

ABSTRACT

The microbial communities of disease vectors may represent a key feature in several biological functions and thus deserve special attention in light of climate change and the consequent need to develop novel control strategies. Nevertheless, vector-borne microbial networks are still poorly understood. Assessing vectors’ microbial interactions and climatic dependencies may contribute to better estimating pathogen transmission characteristics and public health risks. In a climatically representative country-wide survey,
Ixodes ricinus
ticks were collected from 17 locations in Hungary. Using shotgun metagenomic sequencing, the bacteriome composition was analyzed by investigating the relationship between the abundance of nymphs and females in various climatic environments. Bacterial composition on the genus level revealed a significant difference between the samples from females and nymphs. Within the core bacteriome, females and nymphs showed significant variation in the following genera:
Arsenophonus
,
Bacillus
,
Candidatus Midichloria
,
Rhodococcus
,
Sphingomonas
,
Staphylococcus
, and
Wolbachia
. Among females, according to temperature strata, the following were found differentiating:
Curtobacterium
,
Pseudomonas
, and
Sphingomonas
. There was no genus with a significant difference in precipitation categories for females.
Curtobacterium
showed significant variation between temperature and
Bacillus
and
Curtobacterium
for various precipitation levels in the nymphs. The composition of vector-borne bacteriome members showed significant alterations at sampling points with different climatic conditions and development stages of the tick hosts. Our findings not only pave the way toward understanding tick-borne bacterial networks and interdependencies but also shed light on the high potential for the presence of a possible biological tick control species, the tick parasitoid,
Ixodiphagus hookeri
based on related bacteriome patterns.

IMPORTANCE

Climate-sensitive disease vectors, such as ticks, respond to the environment with changes in their microbiome. These changes can affect the emergence or re-emergence of various vector-borne pathogens, such as the causative agent of Lyme borreliosis (LB) or tick-borne encephalitis. This aspect is particularly emphasized in light of climate change. The climatically representative assessment of microbiome differences in various developmental stages of the most common Central European tick species,
Ixodes ricinus
, deepens our understanding of the potential climatic factors behind microbial relative abundance and interaction changes. This knowledge can support the development of novel disease vector control strategies.
Identification and impact on
Pseudomonas aeruginosa
virulence of mutations conferring resistance to a phage cocktail for phage therapy
Authors: Forti Francesca , Bertoli Claudia , Cafora Marco , Gilardi Sara , Pistocchi Anna , Briani Federica 
Published: November 2023

ABSTRACT

Phage therapy represents a promising strategy for curing bacterial infections refractory to antibiotics. However, the success rate of phage therapy may be lowered by the emergence of bacterial resistance to the phages used for therapy. In this work, we studied the resistance to the CK4 cocktail, which is a mixture composed of four phages able to cure
Pseudomonas aeruginosa
infections in animal models. CK4-resistant mutants were easily isolated from cultures grown in either a standard laboratory medium or an artificial sputum medium mimicking the composition of the airway fluid of cystic fibrosis (CF) patients, who are highly susceptible to
P. aeruginosa
chronic lung infections. In both cases, CK4-resistant mutants resulted in being defective in lipopolysaccharide (LPS) biosynthesis. Accordingly, all CK4 phages were unable to infect
wzy
mutants lacking the O-antigen polymerase. A survey of the other 15
P
.
aeruginosa
phages isolated from different environmental sources showed that they all needed either
wzy
or the Type IV-pilus (T4P) biosynthetic gene
pilQ
for the infection. Overall, our data suggest that 16 out of the 19 analyzed
Pseudomonas
phages may use either the LPS or the T4P as a receptor. Interestingly, CK4-resistant mutants devoid of the O-antigen had strongly attenuated virulence in a zebrafish embryo infection model, and the lack of T4P also decreased virulence in zebrafish. With respect to isolates from patients with CF, phages not reproducing in the Δ
wzy
mutant had a wider host range than those requiring
pilQ
, suggesting that phages dependent on PAO1-type T4P may have limited therapeutic value for treating CF-related infections.

IMPORTANCE

In this work, we identified the putative receptors of 16
Pseudomonas
phages and evaluated how resistance to phages recognizing different bacterial receptors may affect the virulence. Our findings are relevant for the implementation of phage therapy of
Pseudomonas aeruginosa
infections, which are difficult to treat with antibiotics. Overall, our results highlight the need to modify natural phages to enlarge the repertoire of receptors exploited by therapeutic phages and suggest that phages using the PAO1-type T4P as receptor may have limited value for the therapy of the cystic fibrosis infection.
Susceptibility to caspofungin is regulated by temperature and is dependent on calcineurin in
Candida albicans
Authors: Zheng Lijun , Xu Yi , Wang Chen , Yang Feng , Dong Yubo , Guo Liangsheng 
Published: November 2023

ABSTRACT

Candida albican
s is a prevalent opportunistic human fungal pathogen. Echinocandins are first-line drugs for the treatment of invasive candidiasis. Molecular mechanisms of resistance to echinocandins have been extensively studied; however, the effect of physiological factors on antifungal efficacy of echinocandins is unexplored. Here, we found temperature-modulated susceptibility to caspofungin in medium-independent and strain background-independent manner in
C. albicans
. Deletions of protein kinase C (PKC) pathway and calcineurin-Crz1 signaling pathway genes conferred hypersensitivity to caspofungin, but only deletion or pharmacological inhibition of calcineurin subunits inverted the temperature effect on susceptibility to caspofungin. Furthermore, the enhanced growth at lower temperature was not due to altered expression of some established genes such as
FKS
,
CHS
, or
CHT
genes; PKC or calcineurin pathway genes; or
HSP90
. The expressions of other heat shock protein genes, including
HSP12
and
HSP70
, were higher at lower temperature. We posit that the temperature-modulated susceptibility to caspofungin is a non-canonical mechanism that is dependent on heat shock proteins and calcineurin.

IMPORTANCE

Echinocandins are the newest antifungal drugs and are first-line treatment option for life-threatening systemic infections. Due to lack of consensus regarding what temperature should be used when evaluating susceptibility of yeasts to echinocandins, typically either 30°C, 35°C, or 37°C is used. However, the impact of temperature on antifungal efficacy of echinocandins is unexplored. In the current study, we demonstrated that
Candida albicans
laboratory strain SC5314 was more susceptible to caspofungin at 37°C than at 30°C. We also found that calcineurin was required for temperature-modulated caspofungin susceptibility. Surprisingly, the altered caspofungin susceptibility was not due to differential expression of some canonical genes such as
FKS
,
CHS
, or
CHT
genes. The molecular mechanism of temperature-modulated caspofungin susceptibility is undetermined and deserves further investigations.
Identification of 10 genes on
Candida albicans
chromosome 5 that control surface exposure of the immunogenic cell wall epitope β-glucan and cell wall remodeling in caspofungin-adapted mutants
Authors: Sah Sudisht K. , Yadav Anshuman , Kruppa Michael D. , Rustchenko Elena 
Published: November 2023

ABSTRACT

Candida albicans
is part of normal microbiota; however, it can cause superficial and life-threatening infections in immune-compromised individuals. As the use of drugs from the echinocandin (ECN) class for the treatment of candidiasis is increasing, resistance against ECNs is also emerging. We identified 10 genes on
C. albicans
chromosome 5 (Ch5) that are simultaneously downregulated to decrease susceptibility to ECN caspofungin. Independent knock-out experiments demonstrated that these genes act overall to decrease the 1,3-
β
-glucan level in the cell wall, change levels of mannan and chitin, and affect expression of
FKS
genes. Importantly, 10 genes on Ch5 increase or decrease surface exposure of the immunogenic epitope 1,3-
β
-glucan. Our data indicate functions for previously uncharacterized orf19.970 and orf19.4149.1, of which orf19.970 has no human ortholog. Our data also indicate new functions for the genes
DUS4
,
RPS25B
,
UAP1
,
URA7
,
RPO26
,
HAS1
, and
CKS1
, whereas the function of
CHT2
as a negative regulator of ECN susceptibility has been previously established. Importantly, half of the above genes are essential; hence, indispensable processes are involved in the adaptation to ECNs. Our results suggest that a novel group of genes works in concert to control adaptation to ECNs and point to potential new drug targets.

IMPORTANCE

Candida
infections are often fatal in immuno-compromised individuals, resulting in many thousands of deaths per year. Caspofungin has proven to be an excellent anti-
Candida
drug and is now the frontline treatment for infections. However, as expected, the number of resistant cases is increasing; therefore, new treatment modalities are needed. We are determining metabolic pathways leading to decreased drug susceptibility in order to identify mechanisms facilitating evolution of clinical resistance. This study expands the understanding of genes that modulate drug susceptibility and reveals new targets for the development of novel antifungal drugs.
Association between dietary Intake, eating behavior, and childhood obesity among children and adolescents in Ethiopia
Authors: Biadgilign Sibhatu , Mgutshini Tennyson , Gebremichael Bereket , Berhanu Lioul , Cook Courtney , Deribew Amare , Gebre Betemariam , Memiah Peter 
Published: November 2023

IntroductionThe upsurge of overweight/obesity (OW/OB) among children and adolescents is as a result of complex interactions between lifestyle behaviours and socioeconomic factors. The objective of this study was to determine socioeconomic and sociodemographic factors, dietary intake and eating behaviours of children and adolescents in Ethiopia and their association with OW/OB.MethodsA cross-sectional study was conducted among 632 children and adolescents-parent dyads. To identify overweight/obese among children and adolescents, body mass index-for-age Z-scores by sex and age relative to WHO 2007 reference was calculated using WHO AnthroPlus software. A multivariable logistic regression model fitted to determine the adjusted associations between the outcome and the predictors selected from the bivariate analyses. Data analysis was carried out using STATA V.15.0.ResultsThe proportion of participants with low, medium and high dietary diversity scores was 7.28%, 22.5%, and 70.2%, respectively. Participants aged 13–18 years were less likely to be overweight or obese [adjusted OR (aOR) = 0.40; 95%CI: 0.26, 0.64] to those aged 5–12 years. Children in a family with the richest or highest socioeconomic status (SES) were more likely to be overweight or obese than those in families with the poorest or lowest status. Children and adolescents who consumed soft drinks (sugar-sweetened beverages) four or more times per week [aOR = 3.24; 95%CI: 1.13, 7.95] were more likely to be overweight or obese to those who did not consume soft drinks.ConclusionsThe study identified factors such as younger age (<12 years), high SES and consumption of soft drinks as key contributors to overweight and obesity among children and adolescents. Therefore, interventions targeting behavioural prevention and reduction of overweight and obesity among children and adolescents should be cognizant of the above factors during implementation in order to achieve desired outcomes, further guided by exploratory qualitative studies to identify public perceptions and attitudes affecting dietary practices.
Our evolving understanding of placebo effects: implications for research and practice in neuropsychiatry
Authors: Burke Matthew 
Published: November 2023

Dr. Matthew Burke is a Cognitive Neurologist in the Neuropsychiatry Program and Department of Psychiatry at Sunnybrook Health Sciences Center. He is currently the Director of Sunnybrook’s Traumatic Brain Injury Clinic and he also sees patients with functional neurological disorders, headache disorders, and other neuropsychiatric conditions. Before starting at Sunnybrook, Dr. Burke completed medical school and his neurology residency training at the University of Toronto, where he was the Chief Neurology Resident in his last year of training. He then completed a two-year Sidney R. Baer, Jr. Foundation fellowship in Cognitive Neurology and Neuropsychiatry at Beth Israel Deaconess Medical Center and Harvard Medical School.Dr. Burke’s clinical research fellowship provided specialized training in non-invasive brain stimulation and brain network mapping. His research applies these novel techniques to investigate the complex and poorly understood brain disorders at the interface between neurology and psychiatry. He also has research interests in the neurobiology of placebo effects and is an active collaborator with the Harvard Program in Placebo Studies. Finally, concurrent with his fellowship, Dr. Burke completed the Harvard Catalyst Clinical Translational Research Academy. This is a NIH-funded program that provides advanced training in methods of clinical investigation.Dr. Burke’s research to date has resulted in multiple peer-reviewed publications, media attention on platforms such as CNN and BBC, and recent recognition with the American Neuropsychiatric Association’s 2019 Young Investigator Award and the American Headache Society’s 2018 Frontiers in Headache Research Award.AbstractPlacebo effects are the beneficial therapeutic effects derived from the context surrounding the administration of a treatment rather than the treatment itself. Recent research has shifted our understanding of placebo effects from a mystical unempirical entity to a biologically-based phenomenon capable of meaningfully modulating brain regions and neurotransmitter systems. In this presentation, Dr. Burke will begin by summarizing the evidence underlying the principles and neurobiology of placebo effects. He will then discuss clinical factors that contribute to placebo effects and how placebo effects could be harnessed in the management of neuropsychiatric disorders. Finally, Dr. Burke will interrogate how our evolving understanding of placebo effects may impact the way we design, appraise and interpret research studies in neuropsychiatry and across medicine.
Should we be preparing to give new dementia treatments to our patients?
Authors: Howard Robert 
Published: November 2023

Professor Robert Howard. I spend half my week working with older people with mental health disorders and dementia and my research aims to develop and evaluate better treatments for my patients. Through the conduct of independent clinical trials - from earliest proof of efficacy concept through to phase III - we can provide powerful evidence of what works and what doesn’t. Within the Department we have potential PhD supervisors with interests in dementia, depression, psychosis and anxiety disorders in older people. We’ve experts in epidemiology, PET and MR imaging, wet lab science and old fashioned clinical studies. Please come and talk to me if you think you might have an interesting idea but need to find someone to help you to develop it into your own supervised research project.AbstractAlmost a generation has passed since the cholinesterase inhibitors and memantine were licensed for the treatment of Alzheimer’s disease and, after what has felt like an endless series of treatment failures, the amyloid antibodies aducanumab and lecanemab have recently shown efficacy in phase 3 trials and received accelerated approval by the US FDA. We are standing on the threshold of a new era of treatments for neurodegenerative disorders and there is understandable excitement about the prospect of intervening to slow progression of disease.Treatment with amyloid antibodies is invasive and not without risks of serious side-effects, including, rarely, death. The administration and safety monitoring of these drugs will require completely new clinical services and access to trained staff and imaging facilities that are not currently available within the NHS. The financial implications of this, even if the drug is provided for free, would be enormous.Unfortunately, treatment benefits demonstrated within the phase 3 trials appear to be modest. In absolute terms, they are about 50% of what is generally considered to represent the minimum clinically important treatment difference and the trials were not designed to definitively demonstrate that the course of neurodegeneration had been modified.There also appears to be little or no clear association between the amount of amyloid cleared from the brain and measured benefits in cognition and function, casting doubt on the role of amyloid as a driver of neurodegeneration. Despite such concerns, many have expressed enthusiasm for these treatments. An argument has been made that, in the presence of disease course modification, absolute differences between drug and placebo after 18 months of treatment do not fairly represent the full benefits of treatment. I will review the results of the amyloid antibody trials, the status of the evidence for disease course modification and the apparent clinical effectiveness of treatment with lecamemab.
10 Distressing dreams, cognitive decline, and risk of dementia: a prospective study of three population-based cohorts
Authors: Otaiku Abidemi I 
Published: November 2023

Objectives/AimsDistressing dreams are associated with faster cognitive decline and increased dementia risk in people with Parkinson’s disease (PD). Whether distressing dreams might be associated with cognitive decline and dementia in people without PD is unknown. This study investigated the association between self-reported distressing dream frequency and the risk of cognitive decline and incident dementia in community- dwelling men and women without cognitive impairment or PD.MethodsRisk of cognitive decline was evaluated in 605 middle-aged adults (mean age = 50 years) from the Midlife in the United States study, who were cognitively normal at baseline, and were followed-up for a mean of 9 years. Cognitive decline was defined as having an annual rate of decline in global cognitive function (measured using five cognitive tests) ≥ 1 standard deviation faster than the mean decline rate from baseline to follow-up. Risk of incident all-cause dementia was evaluated in 2600 older adults (mean age = 83 years) pooled from the Osteoporotic Fractures in Men Study and the Study of Osteoporotic Fractures, who were dementia-free at baseline, and were followed-up for up a mean of 4.5 years. Incident dementia was based on doctor- diagnosis. Frequency of distressing dreams was assessed in all cohorts at baseline (January 2002 – March 2012) using item 5h of the Pittsburgh Sleep Quality Index. The association between self-reported distressing dream frequency (‘never’, ‘less than weekly’, ‘weekly’) and later cognitive outcomes, was evaluated using multivariable logistic regression in the middle-aged and pooled older adult cohorts.ResultsAfter adjustment for all covariates, a higher frequency of distressing dreams was linearly and statistically significantly associated with higher risk of cognitive decline amongst middle-aged adults (P for trend = 0.016), and higher risk of incident all-cause dementia amongst older adults (P for trend <0.001). Compared with middle-aged adults who reported having no distressing dreams at baseline, those who reported having weekly distressing dreams had a 4-fold risk of experiencing cognitive decline (odds ratio [OR] = 3.99; 95% CI: 1.07, 14.85). Amongst older adults, the difference in dementia risk was 2.2-fold (aOR = 2.21; 95% CI: 1.35, 3.62). In sex-stratified analyses, the associations between distressing dreams and both cognitive outcomes were only statistically significant amongst men.ConclusionsDistressing dreams predict cognitive decline and all-cause dementia in middle-aged and older adults without cognitive impairment or PD - especially amongst men. These findings may help to identify individuals at risk of dementia and could facilitate early prevention strategies.
11 The experience of hearing life altering medical news? Perspectives from health professionals
Authors: Dilley Mike , Rose Anita , Bindemann Neil 
Published: November 2023

Introduction and ObjectivesBeing diagnosed with a neurological condition can lead to an adverse effect on a person’s wellbeing. Wellbeing is unique to individuals as is the experience of neurological change regardless of condition. Therefore, we could hypothesize it is likely that the same diagnosis will affect people differently. Furthermore, it is argued that giving a life-altering diagnosis is a traumatic experience not only for the person receiving the news but also for the person giving the news. Such hypotheses suggest the need of a person-centred care approach when breaking bad news.To explore this further several healthcare professionals (HCPs) who had received a diagnosis of a neurological condition were interviewed about their experience. Being HCPs meant they also could reflect on their experience of breaking bad news making this study unique.MethodHCPs, diagnosed with a neurological condition, were invited to a ‘roundtable’ held on zoom. A qualitative interview approach was utilised, and the transcript was analysed for themes.ResultsThemes elicited included. False Optimism: Hope, Language, Honesty, Shared Responsibility, Preparation, Empower, Safe, Realistic, Time, Individualistic, Engaged, Empathy. These themes occurred in both the experience of receiving and in giving bad news.ConclusionThis acknowledges the significance of learning from those who have lived experiences of life-altering diagnoses. This knowledge will be invaluable in supporting both the HCP in giving news and the individual receiving the news, and can help with the creation of simple guidance when having to impart life-altering medical news such as:Establish an appropriate settingCheck the patient’s perception of the situation prompting the news regarding the illness or test resultsDetermine the amount of information known or how much information is desiredKnow the medical facts and their implication, before initiating the conversationExplore the emotions raised during the interviewRespond with empathyEstablish a strategy for support