bluuebunny/crossref_metadata_2025 huggingface dataset:
Low salinity activates a virulence program in the generalist marine pathogen
Photobacterium damselae
subsp.
damselae
Authors: Barca Alba V. , Vences Ana , Terceti Mateus S. , do Vale Ana , Osorio Carlos R.
Published: June 2023

Facultative marine bacterial pathogens sense environmental signals so that the expression of virulence factors is upregulated on entry into hosts and downregulated during the free-living lifestyle in the environment. In this study, we utilized transcriptome sequencing to compare the transcriptional profiles of
Photobacterium damselae
subsp.
damselae
, a generalist pathogen that causes disease in diverse marine animals and fatal infections in humans at NaCl concentrations that mimic the free-living lifestyle or host internal milieu, respectively. We here show that NaCl concentration constitutes a major regulatory signal that shapes the transcriptome and uncover 1,808 differentially expressed genes (888 upregulated and 920 downregulated in response to low-salt conditions). Growth at 3% NaCl, a salinity that mimics the free-living lifestyle, upregulated genes involved in energy production, nitrogen metabolism, transport of compatible solutes, utilization of trehalose and fructose, and carbohydrate and amino acid metabolism with strong upregulation of the arginine deiminase system (ADS). In addition, we observed a marked increase in resistance to antibiotics at 3% NaCl. On the contrary, the low salinity conditions (1% NaCl) that mimic those encountered in the host triggered a virulence gene expression profile that maximized the production of the type 2 secretion system (T2SS)-dependent cytotoxins damselysin, phobalysin P, and a putative PirAB-like toxin, observations that were corroborated by the analysis of the secretome. Low salinity also upregulated the expression of iron-acquisition systems, efflux pumps, and other functions related to stress response and virulence. The results of this study greatly expand our knowledge of the salinity-responsive adaptations of a generalist and versatile marine pathogen.

IMPORTANCE

Pathogenic
Vibrionaceae
species experience continuous shifts of NaCl concentration in their life cycles. However, the impact of salinity changes in gene regulation has been studied in a small number of
Vibrio
species. In this study, we analyzed the transcriptional response of
Photobacterium damselae
subsp.
damselae
(
Pdd
), a generalist and facultative pathogen, to changes in salinity, and demonstrate that growth at 1% NaCl in comparison to 3% NaCl triggers a virulence program of gene expression, with a major impact in the T2SS-dependent secretome. The decrease in NaCl concentration encountered by bacteria on entry into a host is proposed to constitute a regulatory signal that upregulates a genetic program involved in host invasion and tissue damage, nutrient scavenging (notably iron), and stress responses. This study will surely inspire new research on
Pdd
pathobiology, as well as on other important pathogens of the family
Vibrionaceae
and related taxa whose salinity regulons still await investigation.
Functional Characterization of Small Alarmone Synthetase and Small Alarmone Hydrolase Proteins from Treponema denticola
Authors: Wang Miao , Tang Nga-Yeung , Xie Shujie , Watt Rory M.
Published: June 2023

The spirochete bacterium
Treponema denticola
is a common component of the oral microbiota. However, it may play important pathological roles in multispecies oral infectious diseases such as periodontitis: a severe and destructive form of gum disease, which is a major cause of tooth loss in adults.
One-year survival and outcomes of infants born at 22 and 23 weeks of gestation in Sweden 2004–2007, 2014–2016 and 2017–2019
Authors: Farooqi Aijaz , Hakansson Stellan , Serenius Fredrik , Kallen Karin , Björklund Lars , Normann Erik , Domellöf Magnus , Ådén Ulrika , Abrahamsson Thomas , Elfvin Anders , Sävman Karin , Bergström Petra Um , Stephansson Olof , Ley David , Hellstrom-Westas Lena , Norman Mikael
Published: June 2023

Objective

To explore associations between perinatal activity and survival in infants born at 22 and 23 weeks of gestation in Sweden.

Design/Setting

Data on all births at 22 and 23 weeks’ gestational age (GA) were prospectively collected in 2004–2007 (T1) or obtained from national registers in 2014–2016 (T2) and 2017–2019 (T3). Infants were assigned perinatal activity scores based on 3 key obstetric and 4 neonatal interventions.

Main outcome

One-year survival and survival without major neonatal morbidities (MNM): intraventricular haemorrhage grade 3–4, cystic periventricular leucomalacia, surgical necrotising enterocolitis, retinopathy of prematurity stage 3–5 or severe bronchopulmonary dysplasia. The association of GA-specific perinatal activity score and 1-year survival was also determined.

Results

977 infants (567 live births and 410 stillbirths) were included: 323 born in T1, 347 in T2 and 307 in T3. Among live-born infants, survival at 22 weeks was 5/49 (10%) in T1 and rose significantly to 29/74 (39%) in T2 and 31/80 (39%) in T3. Survival was not significantly different between epochs at 23 weeks (53%, 61% and 67%). Among survivors, the proportions without MNM in T1, T2 and T3 were 20%, 17% and 19% for 22 weeks and 17%, 25% and 25% for 23 weeks’ infants (p>0.05 for all comparisons). Each 5-point increment in GA-specific perinatal activity score increased the odds for survival in first 12 hours of life (adjusted OR (aOR) 1.4; 95% CI 1.3 to 1.6) in addition to 1-year survival (aOR 1.2; 95% CI 1.1 to 1.3), and among live-born infants it was associated with increased survival without MNM (aOR 1.3; 95% CI 1.1 to 1.4).

Conclusion

Increased perinatal activity was associated with reduced mortality and increased chances of survival without MNM in infants born at 22 and 23 weeks of GA.
Visual function after ultrathin Descemet’s stripping automated endothelial keratoplasty or Descemet’s membrane endothelial keratoplasty combined with cataract surgery: a randomised controlled clinical trial
Authors: Madsen Morten Brok Molbech , Ivarsen Anders , Hjortdal Jesper
Published: June 2023

Aims

To compare best-corrected visual acuity (BCVA), contrast sensitivity and endothelial cell density (ECD) after ultrathin Descemet’s stripping automated endothelial keratoplasty (UT-DSAEK) and Descemet’s membrane endothelial keratoplasty (DMEK).

Methods

A randomised, single-blinded, single-centre design was used. 72 patients with Fuchs’ endothelial dystrophy and cataract were randomised to UT-DSAEK or DMEK combined with phacoemulsification and lens implantation. 27 patients with cataract were included in a control group and treated with phacoemulsification and lens implantation. The primary outcome was BCVA at 12 months.

Results

Compared with UT-DSAEK, DMEK resulted in better BCVA with mean differences of 6.1 early treatment diabetic retinopathy study (ETDRS) (p=0.001) after 3 months, 7.4 ETDRS (p<0.001) after 6 months and 5.7 ETDRS (p<0.001) after 12 months. The control group obtained significantly better BCVA with a mean difference of 5.2 ETDRS (p<0.001) compared with DMEK 12 months postoperatively. Compared with UT-DSAEK, contrast sensitivity was significantly better 3 months after DMEK with a mean difference of 0.10 LogCS (p=0.03). However, our study found no effect after 12 months (p=0.08). ECD was significantly lower after UT-DSAEK compared with DMEK with mean differences of 332 cells/mm2(p<0.01) after 3 months, 296 cells/mm2(p<0.01) after 6 months and 227 cells/mm2(p=0.03) after 12 months.

Conclusions

Compared with UT-DSAEK, DMEK resulted in better BCVA 3, 6 and 12 months postoperatively. Twelve months postoperatively, DMEK had a higher ECD than UT-DSAEK; however, no difference in contrast sensitivity was found.

Trial registration number

NCT04417959
Associations between antipsychotics and the risk of incident cardiovascular diseases in individuals with schizophrenia: a nested case–control study
Authors: Peng Peng , Li Jiqing , Chen Yujiao , Li Mingzhuo , Ma Feifei , Ji Shuang , Sun Shihua , Tang Fang
Published: June 2023

Background

The association between antipsychotics and cardiovascular diseases (CVDs) remains significant yet unestablished, especially in Chinese populations.

Objective

To investigate the risk of CVDs associated with antipsychotics among Chinese individuals with schizophrenia.

Methods

We conducted a nested case–control study on individuals diagnosed with schizophrenia in Shandong, China. The case group included individuals diagnosed with incident CVDs between 2012 and 2020. Each case was randomly matched with up to three controls. We used weighted logistic regression models to assess the risk of CVDs associated with antipsychotics and restricted cubic spline analysis to explore the dose–response relationship.

Findings

In total, 2493 cases and 7478 matched controls were included in the analysis. Compared with non-users, any antipsychotics use was associated with higher risk of any CVDs (weighted OR=1.54, 95% CI 1.32 to 1.79), with the risk mainly driven by ischaemic heart diseases (weighted OR=2.26, 95% CI 1.71 to 2.99). Treatments with haloperidol, aripiprazole, quetiapine, olanzapine, risperidone, sulpiride and chlorpromazine were associated with increased risk of CVDs. A non-linear dose–response relationship between dosage of antipsychotics and risk of CVDs was observed, with a sharp increase in risk in the beginning and then flattening out with higher doses.

Conclusions

Use of antipsychotics was associated with increased risk of incident CVDs among individuals with schizophrenia, and the risk varied substantially among different antipsychotics and specific CVDs.

Clinical implications

Clinicians should consider the cardiovascular risk of antipsychotics and choose the appropriate type and dose of drugs in the treatment of schizophrenia.
New living evidence resource of human and non-human studies for early intervention and research prioritisation in anxiety, depression and psychosis
Authors: Cipriani Andrea , Seedat Soraya , Milligan Lea , Salanti Georgia , Macleod Malcolm , Hastings Janna , Thomas James , Michie Susan , Furukawa Toshi A , Gilbert David , Soares-Weiser Karla , Moreno Carmen , Leucht Stefan , Egger Matthias , Mansoori Parisa , Barker James M , Siafis Spyridon , Ostinelli Edoardo Giuseppe , McCutcheon Robert , Wright Simonne , Simpson Matilda , Elugbadebo Olufisayo , Chiocchia Virginia , Tonia Thomy , Elgarf Rania , Kurtulmus Ayse , Sena Emily , Simple Ouma , Boyce Niall , Chung Sophie , Sharma Anjuli , Wolpert Miranda , Potts Jennifer , Elliott Julian H
Published: June 2023

In anxiety, depression and psychosis, there has been frustratingly slow progress in developing novel therapies that make a substantial difference in practice, as well as in predicting which treatments will work for whom and in what contexts. To intervene early in the process and deliver optimal care to patients, we need to understand the underlying mechanisms of mental health conditions, develop safe and effective interventions that target these mechanisms, and improve our capabilities in timely diagnosis and reliable prediction of symptom trajectories. Better synthesis of existing evidence is one way to reduce waste and improve efficiency in research towards these ends. Living systematic reviews produce rigorous, up-to-date and informative evidence summaries that are particularly important where research is emerging rapidly, current evidence is uncertain and new findings might change policy or practice. Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis (GALENOS) aims to tackle the challenges of mental health science research by cataloguing and evaluating the full spectrum of relevant scientific research including both human and preclinical studies. GALENOS will also allow the mental health community—including patients, carers, clinicians, researchers and funders—to better identify the research questions that most urgently need to be answered. By creating open-access datasets and outputs in a state-of-the-art online resource, GALENOS will help identify promising signals early in the research process. This will accelerate translation from discovery science into effective new interventions for anxiety, depression and psychosis, ready to be translated in clinical practice across the world.
Is proactive telephone-based breastfeeding peer support a cost-effective intervention? A within-trial cost-effectiveness analysis of the ‘Ringing Up about Breastfeeding earlY’ (RUBY) randomised controlled trial
Authors: McLardie-Hore Fiona E , Forster Della A , McLachlan H L , Shafiei Touran , Amir Lisa H , Davey Mary-Ann , Grimes Heather , Gold Lisa
Published: June 2023

Objective

The ‘Ringing Up about Breastfeeding earlY’ (RUBY) randomised controlled trial showed increased breastfeeding at 6 months in participants who received the proactive telephone-based peer support breastfeeding intervention compared with participants allocated to receive standard care and supports. The present study aimed to evaluate if the intervention was cost-effective.

Design

A within-trial cost-effectiveness analysis.

Setting

Three metropolitan maternity services in Melbourne, Victoria, Australia.

Participants

First time mothers intending to breastfeed their infant (1152) and peer volunteers (246).

Intervention

The intervention comprised proactive telephone-based support from a peer volunteer from early postpartum up to 6 months. Participants were allocated to usual care (n=578) or the intervention (n=574).

Main outcome measures

Costs during a 6-month follow-up period including individual healthcare, breastfeeding support and intervention costs in all participants, and an incremental cost-effectiveness ratio.

Results

Costs per mother supported were valued at $263.75 (or $90.33 excluding costs of donated volunteer time). There was no difference between the two arms in costs for infant and mothers in healthcare and breastfeeding support costs. These figures result in an incremental cost-effectiveness ratio of $4146 ($1393 if volunteer time excluded) per additional mother breast feeding at 6 months.

Conclusion

Considering the significant improvement in breastfeeding outcomes, this intervention is potentially cost-effective. These findings, along with the high value placed on the intervention by women and peer volunteers provides robust evidence to upscale the implementation of this intervention.

Trial registration number

ACTRN12612001024831.
Long-term impacts of an urban sanitation intervention on enteric pathogens in children in Maputo city, Mozambique: study protocol for a cross-sectional follow-up to the Maputo Sanitation (MapSan) trial 5 years postintervention
Authors: Holcomb David A , Monteiro Vanessa , Capone Drew , António Virgílio , Chiluvane Márcia , Cumbane Victória , Ismael Nália , Knee Jackie , Kowalsky Erin , Lai Amanda , Linden Yarrow , Mataveia Elly , Nala Rassul , Rao Gouthami , Ribeiro Jorge , Cumming Oliver , Viegas Edna , Brown Joe
Published: June 2023

Introduction

We previously assessed the effect of an onsite sanitation intervention in informal neighbourhoods of urban Maputo, Mozambique on enteric pathogen detection in children after 2 years of follow-up (Maputo Sanitation (MapSan) trial, ClinicalTrials.gov:NCT02362932). We found significant reductions inShigellaandTrichurisprevalence but only among children born after the intervention was delivered. In this study, we assess the health impacts of the sanitation intervention after 5 years among children born into study households postintervention.

Methods and analysis

We are conducting a cross-sectional household study of enteric pathogen detection in child stool and the environment at compounds (household clusters sharing sanitation and outdoor living space) that received the pour-flush toilet and septic tank intervention at least 5 years prior or meet the original criteria for trial control sites. We are enrolling at least 400 children (ages 29 days to 60 months) in each treatment arm. Our primary outcome is the prevalence of 22 bacterial, protozoan, and soil transmitted helminth enteric pathogens in child stool using the pooled prevalence ratio across the outcome set to assess the overall intervention effect. Secondary outcomes include the individual pathogen detection prevalence and gene copy density of 27 enteric pathogens (including viruses); mean height-for-age, weight-for-age, and weight-for-height z-scores; prevalence of stunting, underweight, and wasting; and the 7-day period prevalence of caregiver-reported diarrhoea. All analyses are adjusted for prespecified covariates and examined for effect measure modification by age. Environmental samples from study households and the public domain are assessed for pathogens and faecal indicators to explore environmental exposures and monitor disease transmission.

Ethics and dissemination

Study protocols have been reviewed and approved by human subjects review boards at the Ministry of Health, Republic of Mozambique and the University of North Carolina at Chapel Hill. Deidentified study data will be deposited athttps://osf.io/e7pvk/.

Trial registration number

ISRCTN86084138.
Cohort profile: the BABY1000 pilot prospective longitudinal birth cohort study based in Sydney, Australia
Authors: Grech Allison Marie , Kizirian Nathalie , Lal Ravin , Zankl Angelika , Birkner Karin , Nasir Reeja , Muirhead Roslyn , Sau-Harvey Rachelle , Haghighi Marjan Mosalman , Collins Clare , Holmes Andrew , Skilton Michael , Simpson Stephen , Gordon Adrienne
Published: June 2023

Purpose

The health of parents prior to conception, a woman’s health during pregnancy and the infant’s environment across their first months and years collectively have profound effects on the child’s health across the lifespan. Since there are very few cohort studies in early pregnancy, gaps remain in our understanding of the mechanisms underpinning these relationships, and how health may be optimised. ‘BABY1000’, a pilot prospective longitudinal birth cohort study, aims to (1) identify factors before and during pregnancy and early life that impact longer-term health and (2) assess the feasibility and acceptability of study design to inform future research.

Participants

Participants were based in Sydney, Australia. Women were recruited at preconception or 12 weeks’ gestation, and data were collected from them throughout pregnancy and postpartum, their children until the age of 2 years, and dietary information from a partner (if able) at the last study visit. The pilot aimed to recruit 250 women. However, recruitment ceased earlier than planned secondary to limitations from the COVID-19 pandemic and the final number of subjects was 225.

Findings to date

Biosamples, clinical measurements and sociodemographic/psychosocial measures were collected using validated tools and questionnaires. Data analysis and 24-month follow-up assessments for children are ongoing. Key early findings presented include participant demographics and dietary adequacy during pregnancy. The COVID-19 pandemic and associated public health and research restrictions affected recruitment of participants, follow-up assessments and data completeness.

Future plans

The BABY1000 study will provide further insight into the developmental origins of health and disease and inform design and implementation of future cohort and intervention studies in the field. Since the BABY1000 pilot was conducted across the COVID-19 pandemic, it also provides unique insight into the early impacts of the pandemic on families, which may have effects on health across the lifespan.
Impact of fatigue as the primary determinant of functional limitations among patients with post-COVID-19 syndrome: a cross-sectional observational study
Authors: Walker Sarah , Goodfellow Henry , Pookarnjanamorakot Patra , Murray Elizabeth , Bindman Julia , Blandford Ann , Bradbury Katherine , Cooper Belinda , Hamilton Fiona L , Hurst John R , Hylton Hannah , Linke Stuart , Pfeffer Paul , Ricketts William , Robson Chris , Stevenson Fiona A , Sunkersing David , Wang Jiunn , Gomes Manuel , Henley William , Collaboration Living With Covid Recovery
Published: June 2023

Objectives

To describe self-reported characteristics and symptoms of treatment-seeking patients with post-COVID-19 syndrome (PCS). To assess the impact of symptoms on health-related quality of life (HRQoL) and patients’ ability to work and undertake activities of daily living.

Design

Cross-sectional single-arm service evaluation of real-time user data.

Setting

31 post-COVID-19 clinics in the UK.

Participants

3754 adults diagnosed with PCS in primary or secondary care deemed suitable for rehabilitation.

Intervention

Patients using the Living With Covid Recovery digital health intervention registered between 30 November 2020 and 23 March 2022.

Primary and secondary outcome measures

The primary outcome was the baseline Work and Social Adjustment Scale (WSAS). WSAS measures the functional limitations of the patient; scores of ≥20 indicate moderately severe limitations. Other symptoms explored included fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue), depression (Patient Health Questionnaire–Eight Item Depression Scale), anxiety (Generalised Anxiety Disorder Scale, Seven-Item), breathlessness (Medical Research Council Dyspnoea Scale and Dyspnoea-12), cognitive impairment (Perceived Deficits Questionnaire, Five-Item Version) and HRQoL (EQ-5D). Symptoms and demographic characteristics associated with more severe functional limitations were identified using logistic regression analysis.

Results

3541 (94%) patients were of working age (18-65); mean age (SD) 48 (12) years; 1282 (71%) were female and 89% were white. 51% reported losing ≥1 days from work in the previous 4 weeks; 20% reported being unable to work at all. Mean WSAS score at baseline was 21 (SD 10) with 53% scoring ≥20. Factors associated with WSAS scores of ≥20 were high levels of fatigue, depression and cognitive impairment. Fatigue was found to be the main symptom contributing to a high WSAS score.

Conclusion

A high proportion of this PCS treatment-seeking population was of working age with over half reporting moderately severe or worse functional limitation. There were substantial impacts on ability to work and activities of daily living in people with PCS. Clinical care and rehabilitation should address the management of fatigue as the dominant symptom explaining variation in functionality.
Health literacy among adolescents and young adults in the Eastern Mediterranean region: a scoping review
Authors: Sarhan Mohammed B A , Fujiya Rika , Kiriya Junko , Htay Zin Wai , Nakajima Kayono , Fuse Rie , Wakabayashi Nao , Jimba Masamine
Published: June 2023

Objectives

For adolescents and young adults, most health literacy research has been conducted in Western countries, but few studies have been conducted in the Eastern Mediterranean region (EMR). This review aimed to explore the existing health literacy research in the EMR in addition to the levels of health literacy and its associated factors among adolescents and young adults.

Methods

The search, conducted using the PubMed/MEDLINE, EBSCOhost/CINAHL plus, Web of Science and J-STAGE databases, was initially performed on 16 June 2022 and later updated on 1 October 2022. Studies that targeted 10–25 years old persons, conducted in any of the EMR countries and that used the health literacy concept and/or described its levels or predictors were included in the review. Content analysis was used for data extraction and analysis. Data related to the study methods, participants, outcome variables and health literacy were extracted.

Results

The review included 82 studies, most of which were conducted in Iran and Turkey and adopted a cross-sectional design. Half of the studies showed that more than half of adolescents and young adults had low or moderate health literacy. Nine studies applied university-based or school-based health education interventions to improve health literacy, which was also predicted by demographic and socioeconomic factors and internet usage. Little attention was paid to assessing the health literacy of vulnerable people, such as refugees and those with a disability and exposed to violence. Finally, various health literacy topics were investigated, including nutrition, non-communicable diseases, media and depression.

Conclusion

Health literacy levels were low-to-moderate in adolescents and young adults in the EMR. To promote health literacy, it is recommended to use school-based health education and attempt to reach adolescents and young adults through social media platforms. More attention should be paid to refugees, people with disabilities and those exposed to violence.
Home-based cardiac rehabilitation: development, implementation and outcome evaluation in patients with coronary artery diseases in Lahore, Pakistan – a mixed-methods study protocol
Authors: Yaqoob Adnan , Barolia Rubina , Ladak Laila , Hanif Asif , Khan Aamir Hameed , Sahar Wajeeha
Published: June 2023

Introduction

Cardiac rehabilitation (CR) is an important strategy to bring cardiac patients back to a normal life after a cardiac event. The benefits of CR as part of secondary prevention are widely known among people who have undergone myocardial infarction or revascularisation. As evidenced by several systematic reviews and meta-analyses, home-based CR (HBCR) has similar or greater effects on health-related quality of life, health outcomes, physical activity, anxiety and unplanned visits to the emergency department as compared with centre-based CR. The purpose of this study is to develop a contextual HBCR intervention and evaluate its effects on quality of life, health behaviours, bio-physiological parameters and emergency hospital visits of patients with coronary artery diseases in Lahore, Pakistan.

Methods and analysis

This study will employ a mixed-method exploratory sequential research design. The researchers will invite 15–20 cardiac patients and 12–15 healthcare providers for semi-structured interviews in the qualitative phase of the study. Once the intervention is developed and validated through the qualitative phase, the outcomes will be evaluated through a single-blinded randomised control trial in the quantitative phase. A total of 118 patients with acute coronary syndrome will be recruited through a screening checklist and randomly allocated into the control and intervention groups (59 patients in each group). The inductive coding approach will be used for the thematic analysis of qualitative data, whereas the quantitative data will be analysed through descriptive and inferential statistics using SPSS to see the difference within the groups, between groups and between three intervals.

Ethics and dissemination

The Ethical Review Committee of Aga Khan University and Mayo Hospital Lahore under the registration number 2023-8282-24191 and No/75749MH have approved this study protocol, respectively. The results of this study will be disseminated to participating patients (in the Urdu language), healthcare professionals and the public by publishing the manuscript in an open-access peer-reviewed journal and presenting it at different conferences.

Trial registration number

Australian New Zealand Clinical Trial Registry (ACTRN12623000049673p).
Observational study of survival outcomes of people referred for ‘fast-track’ end-of-life care funding in a district general hospital: too little too late?
Authors: Morrison Jo , Choudhary Cherry , Beazley Ryan , Richards James , Davis Charlie
Published: June 2023

Background

End-of-life care requires support for people to die where they feel safe and well-cared for. End-of-life care may require funding to support dying outside of hospital. In England, funding is procured through Continuing Healthcare Fast-Track funding, requiring assessment to determine eligibility. Anecdotal evidence suggested that Fast-Track funding applications were deferred where clinicians thought this inappropriate due to limited life-expectancy.

Aim

To evaluate overall survival after Fast-Track funding application.

Design

Prospective evaluation of Fast-Track funding application outcomes and survival.

Setting/participants

All people in 2021 who had a Fast-Track funding application from a medium-sized district general hospital in Southwest England.

Results

439 people were referred for Fast-Track funding with a median age of 80 years (range 31–100 years). 413/439 (94.1%) died during follow-up, with a median survival of 15 days (range 0–436 days). Median survival for people with Fast-Track funding approved or deferred was 18 days and 25 days, respectively (p=0.0013). 129 people (29.4%) died before discharge (median survival 4 days) and only 7.5% were still alive 90 days after referral for Fast-Track funding.

Conclusions

Fast-Track funding applications were deferred for those with very limited life-expectancy, with minimal clinical difference in survival (7 days) compared with those who had applications approved. This is likely to delay discharge to the preferred place of death and reduce quality of end-of-life care. A blanket acceptance of Fast-Track funding applications, with review for those still alive after 60 days, may improve end-of-life care and be more efficient for the healthcare system.
The Phenotypic variability of 16p11.2 distal BP2–BP3 deletion in a transgenerational family and in neurodevelopmentally ascertained samples
Authors: Woodbury-Smith Marc , D’Abate Lia , Stavropoulos Dimitri J , Howe Jennifer , Drmic Irene , Hoang Ny , Zarrei Mehdi , Trost Brett , Iaboni Alana , Anagnostou Evdokia , Scherer Stephen W
Published: June 2023

Background

We present genomic and phenotypic findings of a transgenerational family consisting of three male offspring, each with a maternally inherited distal 220 kb deletion at locus 16p11.2 (BP2–BP3). Genomic analysis of all family members was prompted by a diagnosis of autism spectrum disorder (ASD) in the eldest child, who also presented with a low body mass index.

Methods

All male offspring underwent extensive neuropsychiatric evaluation. Both parents were also assessed for social functioning and cognition. The family underwent whole-genome sequencing. Further data curation was undertaken from samples ascertained for neurodevelopmental disorders and congenital abnormalities.

Results

On medical examination, both the second and third-born male offspring presented with obesity. The second-born male offspring met research diagnostic criteria for ASD at 8 years of age and presented with mild attention deficits. The third-born male offspring was only noted as having motor deficits and received a diagnosis of developmental coordination disorder. Other than the 16p11.2 distal deletion, no additional contributing variants of clinical significance were observed. The mother was clinically evaluated and noted as having a broader autism phenotype.

Conclusion

In this family, the phenotypes observed are most likely caused by the 16p11.2 distal deletion. The lack of other overt pathogenic mutations identified by genomic sequencing reinforces the variable expressivity that should be heeded in a clinical setting. Importantly, distal 16p11.2 deletions can present with a highly variable phenotype even within a single family. Our additional data curation provides further evidence on the variable clinical presentation among those with pathogenetic 16p11.2 (BP2–BP3) mutations.
Towards compact laser-driven accelerators: exploring the potential of advanced double-layer targets
Authors: Maffini Alessandro , Mirani Francesco , Galbiati Marta , Ambrogioni Kevin , Gatti Francesco , Galli De Magistris Maria Sole , Vavassori Davide , Orecchia Davide , Dellasega David , Russo Valeria , Zavelani-Rossi Margherita , Passoni Matteo
Published: June 2023

The interest in compact, cost-effective, and versatile accelerators is increasing for many applications of great societal relevance, ranging from nuclear medicine to agriculture, pollution control, and cultural heritage conservation. For instance, Particle Induced X-ray Emission (PIXE) is a non-destructive material characterization technique applied to environmental analysis that requires MeV-energy ions. In this context, superintense laser-driven ion sources represent a promising alternative to conventional accelerators. In particular, the optimization of the laser-target coupling by acting on target properties results in an enhancement of ion current and energy with reduced requirements on the laser system. Among the advanced target concepts that have been explored, one appealing option is given by double-layer targets (DLTs), where a very low-density layer, which acts as an enhanced laser absorber, is grown to a thin solid foil. Here we present some of the most recent results concerning the production with deposition techniques of advanced DLTs for laser-driven particle acceleration. We assess the potential of these targets for laser-driven ion acceleration with particle-in-cell simulations, as well as their application to PIXE analysis of aerosol samples with Monte Carlo simulations. Our investigation reports that MeV protons, accelerated with a ∼20 TW compact laser and optimized DLTs, can allow performing PIXE with comparable performances to conventional sources. We conclude that compact DLT-based laser-driven accelerators can be relevant for environmental monitoring.
GENERAL THEORY FOR SIGNIFICANCE OF CULLING IN TWO-WAY DISEASE TRANSMISSION BETWEEN HUMANS AND ANIMALS
Authors: BUGALIA SARITA , TRIPATHI JAI PRAKASH , ABBAS SYED , WANG HAO
Published: June 2023

An epidemic model is proposed to comprehend the disease dynamics between humans and animals and back to humans with a culling intervention strategy. The proposed model is separated into two cases with two different culling rates: (1) at a per-capita constant rate and (2) constant population being culled. The global asymptotic stability of equilibria is determined in terms of the basic reproduction numbers. Further, we find that the culling rate (2) considered in the model could change the dynamics by having multiple positive equilibria. Sensitivity analysis recommends developing a strategy that promotes animals’ natural and disease-related death rates. By ranking the efficacies of various intervention strategies, we obtain that vaccination in the human population, isolation and public awareness are the largely effective control interventions. Our general theory raises concerns about both human and animal populations becoming reservoirs of the disease and affecting each other dynamically.
Simple weight modules for Yangian Y (𝔰𝔩2)
Authors: Tan Yilan , Xia Limeng , Zhou Yikun
Published: June 2023

Let [Formula: see text] be a finite-dimensional simple Lie algebra over [Formula: see text]. A [Formula: see text]-module is said to be weight if it is a weight [Formula: see text]-module. We give a complete classification of simple weight modules for [Formula: see text] which admits a one-dimensional weight space. We prove that there are four classes of such modules: finite, highest weight, lowest weight and dense modules. Different from the classical [Formula: see text]-representation theory, we show that there exists a class of [Formula: see text] irreducible modules which have uniformly two-dimensional weight spaces.
Enabling Timely and Persistent Deletion in LSM-Engines
Authors: Sarkar Subhadeep , Papon Tarikul Islam , Staratzis Dimitris , Zhu Zichen , Athanassoulis Manos
Published: June 2023

Data-intensive applications have fueled the evolution of
log-structured merge (LSM)
based key-value engines that employ the
out-of-place
paradigm to support high ingestion rates with low read/write interference. These benefits, however, come at the cost of
treating deletes as second-class citizens
. A delete operation inserts a
tombstone
that invalidates older instances of the deleted key. State-of-the-art LSM-engines do not provide guarantees as to how fast a tombstone will propagate to
persist the deletion
. Further, LSM-engines only support deletion on the sort key. To delete on another attribute (e.g., timestamp), the entire tree is read and re-written, leading to undesired latency spikes and increasing the overall operational cost of a database. Efficient and persistent deletion is key to support: (i) streaming systems operating on a window of data, (ii) privacy with latency guarantees on data deletion, and (iii)
en masse
cloud deployment of data systems.

Further, we document that LSM-based key-value engines perform suboptimally in the presence of deletes in a workload. Tombstone-driven logical deletes, by design, are unable to purge the deleted entries in a timely manner, and retaining the invalidated entries perpetually affects the overall performance of LSM-engines in terms of space amplification, write amplification, and read performance. Moreover, the potentially unbounded latency for persistent deletes brings in critical privacy concerns in light of the data privacy protection regulations, such as the
right to be forgotten
in EU’s GDPR, the
right to delete
in California’s CCPA and CPRA, and
deletion right
in Virginia’s VCDPA. Toward this, we introduce the delete design space for LSM-trees and highlight the performance implications of the different classes of delete operations.

To address these challenges, in this article, we build a new key-value storage engine,

Lethe
+

, that uses a very small amount of additional metadata, a set of new delete-aware compaction policies, and a new physical data layout that weaves the sort and the delete key order. We show that

Lethe
+

supports any user-defined threshold for the delete persistence latency offering
higher read throughput
(1.17× -1.4×) and
lower space amplification
(2.1× -9.8×), with a modest increase in write amplification (between 4% and 25%) that can be further amortized to less than 1%. In addition,

Lethe
+

supports efficient range deletes on a
secondary delete key
by dropping entire data pages without sacrificing read performance or employing a costly full tree merge.
Technical Perspective: When is it safe to run a transactional workload under Read Committed?
Authors: Fekete Alan D.
Published: June 2023

A data management platform provides many capabilities to assist the data owner, application coder, or end-user. For example, it should support an expressive query language, schema definition, and sophisticated access control. Another way many platforms add value is through a transaction mechanism, which allows the application programmer to indicate that a stretch of code, including multiple accesses to data, represents a single real-world activity and so all these steps should happen as if a single step, despite really being interleaved with other programs, or perhaps cancelled after partial execution. If the platform perfectly hides interleaving of different activities, the execution is called serializable, and this is a great aid to protecting data quality. Any integrity constraint over the data (whether explicitly declared in schema or not) which is preserved by each transaction running alone, is also valid at the end of any serializable execution of several transactions.
Technical Perspective: Accurate Summary-based Cardinality Estimation Through the Lens of Cardinality Estimation Graphs
Authors: Suciu Dan
Published: June 2023

Query engines are really good at choosing an efficient query plan. Users don't need to worry about how they write their query, since the optimizer makes all the right choices for executing the query, while taking into account all aspects of data, such as its size, the characteristics of the storage device, the distribution pattern, the availability of indexes, and so on. The query optimizer always makes the best choice, no matter how complex the query is, or how contrived it was written. Or, this is what we expect today from a modern query optimizer. Unfortunately, reality is not as nice.
A Glance at Biogenesis and Functionality of MicroRNAs and Their Role in the Neuropathogenesis of Parkinson’s Disease
Authors: Szelągowski Adam , Kozakiewicz Mariusz
Published: June 2023

MicroRNAs (miRNAs) are short, noncoding RNA transcripts. Mammalian miRNA coding sequences are located in introns and exons of genes encoding various proteins. As the central nervous system is the largest source of miRNA transcripts in living organisms, miRNA molecules are an integral part of the regulation of epigenetic activity in physiological and pathological processes. Their activity depends on many proteins that act as processors, transporters, and chaperones. Many variants of Parkinson’s disease have been directly linked to specific gene mutations which in pathological conditions are cumulated resulting in the progression of neurogenerative changes. These mutations can often coexist with specific miRNA dysregulation. Dysregulation of different extracellular miRNAs has been confirmed in many studies on the PD patients. It seems reasonable to conduct further research on the role of miRNAs in the pathogenesis of Parkinson’s disease and their potential use in future therapies and diagnosis of the disease. This review presents the current state of knowledge about the biogenesis and functionality of miRNAs in the human genome and their role in the neuropathogenesis of Parkinson’s disease (PD)—one of the most common neurodegenerative disorders. The article also describes the process of miRNA formation which can occur in two ways—the canonical and noncanonical one. However, the main focus was on miRNA’s use in in vitro and in vivo studies in the context of pathophysiology, diagnosis, and treatment of PD. Some issues, especially those regarding the usefulness of miRNAs in PD’s diagnostics and especially its treatment, require further research. More standardization efforts and clinical trials on miRNAs are needed.
Univocal Discrimination of α Particles Produced by 11B(p, α)2α Fusions in Laser-Matter Experiments by Advanced Thomson Spectrometry
Authors: Salvadori Martina , Scisciò Massimiliano , Di Giorgio Giorgio , Cipriani Mattia , Andreoli Pier Luigi , Cristofari Giuseppe , De Angelis Riccardo , Giulietti Danilo , Consoli Fabrizio , Margarone Daniele
Published: June 2023

The energy problem is an open issue becoming increasingly pressing. The possibility to use nuclear fusion as an alternative energy source is thus acquiring progressively more importance and many investors are pushing to achieve the goal of an electric plant based on fusion. The most studied reaction is the deuterium-tritium one, but this poses several technical issues related to the handling of the radioactive fuel and neutron generation. In this frame, the aneutronic 11B(p, α)2α fusion reaction has attracted the interest of many researchers. Despite a fusion reactor based on pB is still a long-term goal, the study of this reaction is important both for astrophysics research and for its possible employment in schemes of high brightness source of α particles for applications, as for instance in medicine. Nevertheless, the univocal identification of the produced alphas is a well-known challenging task when the reaction is triggered by high-intensity lasers. Indeed, due to the multifaceted emission typical of laser-matter interactions, the signal coming from alphas is often superimposed to that generated by protons and by other ions, and in many cases, it is therefore hardly recognizable. In this work, we analysed the possibility of employing a Thomson spectrometer (TS) with an adequate differential filtering system for the exclusion from the α-particle trace, the contribution of all other ionic species. Moreover, for the energy ranges where the filtering method cannot be successfully applied, we investigated the feasibility of integrating in the TS assembly a particle detector for time-of-flight (TOF) measurements.
Supplementary Table S3 from The Impact of Germline Alterations in Appendiceal Adenocarcinoma
Authors: Foote Michael B. , Walch Henry , Kemel Yelena , Vakiani Efsevia , Johannet Paul , Sheehan Margaret , Chatila Walid , Chung Sebastian , Nash Garrett M. , Maio Anna , Shia Jinru , Mandelker Diana , Berger Michael , Schultz Nikolaus , Diaz Luis A. , Cercek Andrea , Stadler Zsofia K.
Published: June 2023

Clinicopathologic Features of the Appendix-Specific Survival Analysis Cohort
Supplementary Table S5 from Plasma 25-Hydroxyvitamin D Levels and Survival in Stage III Colon Cancer: Findings from CALGB/SWOG 80702 (Alliance)
Authors: Wang Qiao-Li , Ma Chao , Yuan Chen , Shi Qian , Wolpin Brian M. , Zhang Yin , Fuchs Charles S. , Meyer Jeffrey , Zemla Tyler , Cheng En , Kumthekar Priya , Guthrie Katherine A. , Couture Felix , Kuebler Philip , Kumar Pankaj , Tan Benjamin , Krishnamurthi Smitha , Goldberg Richard M. , Venook Alan , Blanke Charles , Shields Anthony F. , O'Reilly Eileen M. , Meyerhardt Jeffrey A. , Ng Kimmie
Published: June 2023

Table S5. Hazard ratio of cancer-specific mortality by plasma 25-hydroxyvitamin D levels in plasma biomarker companion study and by predicted vitamin D scores in diet and lifestyle companion study
Supplementary Table S4 from Plasma 25-Hydroxyvitamin D Levels and Survival in Stage III Colon Cancer: Findings from CALGB/SWOG 80702 (Alliance)
Authors: Wang Qiao-Li , Ma Chao , Yuan Chen , Shi Qian , Wolpin Brian M. , Zhang Yin , Fuchs Charles S. , Meyer Jeffrey , Zemla Tyler , Cheng En , Kumthekar Priya , Guthrie Katherine A. , Couture Felix , Kuebler Philip , Kumar Pankaj , Tan Benjamin , Krishnamurthi Smitha , Goldberg Richard M. , Venook Alan , Blanke Charles , Shields Anthony F. , O'Reilly Eileen M. , Meyerhardt Jeffrey A. , Ng Kimmie
Published: June 2023

Table S4. Hazard ratio of disease-free survival, overall survival, time to recurrence by quartiles of predicted vitamin D score
Supplementary Figure S1 from Plasma 25-Hydroxyvitamin D Levels and Survival in Stage III Colon Cancer: Findings from CALGB/SWOG 80702 (Alliance)
Authors: Wang Qiao-Li , Ma Chao , Yuan Chen , Shi Qian , Wolpin Brian M. , Zhang Yin , Fuchs Charles S. , Meyer Jeffrey , Zemla Tyler , Cheng En , Kumthekar Priya , Guthrie Katherine A. , Couture Felix , Kuebler Philip , Kumar Pankaj , Tan Benjamin , Krishnamurthi Smitha , Goldberg Richard M. , Venook Alan , Blanke Charles , Shields Anthony F. , O'Reilly Eileen M. , Meyerhardt Jeffrey A. , Ng Kimmie
Published: June 2023

Figure S1. Diagram for study cohort derivation
Supplementary Methods from Proteogenomic Analysis of Salivary Adenoid Cystic Carcinomas Defines Molecular Subtypes and Identifies Therapeutic Targets
Authors: Ferrarotto Renata , Mitani Yoshitsugu , McGrail Daniel J. , Li Kaiyi , Karpinets Tatiana V. , Bell Diana , Frank Steven J. , Song Xingzhi , Kupferman Michael E. , Liu Bin , Lee J. Jack , Glisson Bonnie S. , Zhang Jianhua , Aster Jon C. , Lin Shiaw-Yih , Futreal P. Andrew , Heymach John V. , El-Naggar Adel K.
Published: June 2023

Supplementary Methods from Proteogenomic Analysis of Salivary Adenoid Cystic Carcinomas Defines Molecular Subtypes and Identifies Therapeutic Targets