bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of an integrated multilevel early child development intervention on caregiver knowledge and behavior: a quasi-experimental evaluation of the Malezi program in Tanzania
Authors: Antelman Gretchen , Ferla Josephine , Gill Michelle M. , Hoffman Heather J. , Komba Teopista , Abubakar Amina , Remes Pieter , Jahanpour Ola , Mariki Martha , Mang’enya Mary A. , van de Ven Roland
Published: January 2023

Background

The quality of caregiving and the parent-child relationship is critical for early child development (ECD) and has been shown to be modifiable. This study evaluated an ECD project in Tanzania, assessing the effectiveness of radio messaging (RM) alone and a combined radio messaging/video job aids/ECD (RMV-ECD) intervention.

Methods

This two-arm pre-post evaluation study enrolled a cohort of caregivers of children 0–24 months in four districts of Tabora region, following them for 9 months. ECD radio messages were broadcast on popular stations at least 10 times/day reaching all study districts. In two districts, community health workers (CHW), trained in UNICEF’s Care for Child Development package, used ECD videos in home- and facility-based sessions with caregivers. We used McNemar’s testing (pre-post pairs) within intervention group to describe how the intervention was associated with change in five outcomes: ECD knowledge, early stimulation, father engagement, responsive care, and environment safety. Logistic regression was used to describe the relative benefits of the combined intervention package (RMV-ECD) compared to radio messaging (RM).

Results

In the RMV-ECD arm, all outcomes at endline except environment safety significantly improved after the intervention with the largest change seen in ECD knowledge (35.8% increase, p < .0001) and the smallest in father engagement (6.7%, p = .015). In the RM arm, ECD knowledge (5.7%, p = .031) and environment safety (18.1%, p = <.0001) improved. High measures of parenting stress were associated with lower likelihood of having good ECD knowledge (AOR 0.50, 95%CI: 0.35, 0.71), father engagement (AOR 0.72, 95%CI: 0.52, 0.99) and responsive care (AOR 0.31, 95%CI: 0.18, 0.54).

Conclusions

An intervention that includes mass media, educational video content and CHWs who counsel caregivers in their homes and health facilities was associated with significant improvements in ECD parenting knowledge and behaviors but a relationship with responsive care could not be established. The less costly mass media-only intervention was associated with improved parenting knowledge and household environment safety. Parenting interventions targeting young children could be improved by incorporating more messaging and caregiver coaching in managing parental stress.

Trial registration

NCT05244161 (17/02/2022); retrospectively registered with the US National Institutes of Health ClinicalTrials.gov.
The burden of lower respiratory infections and their underlying etiologies in the Middle East and North Africa region, 1990–2019: results from the Global Burden of Disease Study 2019
Authors: Ashrafi-Asgarabad Ahad , Bokaie Saied , Razmyar Jamshid , Akbarein Hesameddin , Nejadghaderi Seyed Aria , Carson-Chahhoud Kristin , Sullman Mark J. M. , Kaufman Jay S. , Safiri Saeid
Published: January 2023

Background

Lower respiratory infections (LRIs) cause substantial mortality and morbidity. The present study reported and analysed the burden of LRIs in the Middle East and North Africa (MENA) region between 1990 and 2019, by age, sex, etiology, and socio-demographic index (SDI).

Methods

The data used in this study were sourced from the Global Burden of Disease (GBD) study 2019. The annual incidence, deaths, and disability-adjusted life-years (DALYs) due to LRIs were presented as counts and age-standardised rates per 100,000 population, along with their 95% uncertainty intervals (UIs). The average annual percent changes (AAPC) in the age-standardised incidence, death and DALYs rates were calculated using Joinpoint software and correlations (Pearson’s correlation coefficient) between the AAPCs and SDIs were calculated using Stata software.

Results

In 2019, there were 34.1 million (95% UI 31.7–36.8) incident cases of LRIs in MENA, with an age-standardised rate of 6510.2 (95% UI 6063.6–6997.8) per 100,000 population. The number of regional DALYs was 4.7 million (95% UI 3.9–5.4), with an age-standardised rate of 888.5 (95% UI 761.1–1019.9) per 100,000 population, which has decreased since 1990. Furthermore, Egypt [8150.8 (95% UI 7535.8–8783.5)] and Afghanistan [61.9 (95% UI 52.1–72.6)] had the highest age-standardised incidence and death rates, respectively. In 2019, the regional incidence and DALY rates were highest in the 1–4 age group, in both females and males. In terms of deaths, pneumococcus and H. influenza type B were the most and least common types of LRIs, respectively. From 1990 to 2019, the burden of LRIs generally decreased with increasing SDI. There were significant positive correlations between SDI and the AAPCs for the age-standardised incidence, death and DALY rates (p < 0.05). Over the 1990–2019 period, the regional incidence, deaths and DALYs attributable to LRIs decreased with AAPCs of − 1.19% (− 1.25 to − 1.13), − 2.47% (− 2.65 to − 2.28) and − 4.21% (− 4.43 to − 3.99), respectively.

Conclusions

The LRI-associated burden in the MENA region decreased between 1990 and 2019. SDI had a significant positive correlation with the AAPC and pneumococcus was the most common underlying cause of LRIs. Afghanistan, Yemen and Egypt had the largest burdens in 2019. Further studies are needed to investigate the effectiveness of healthcare interventions and programs to control LRIs and their risk factors.
Patient characteristics and procedural variables are associated with length of stay and hospital cost among unilateral primary total hip arthroplasty patients: a single-center retrospective cohort study
Authors: Li Guoqing , Yu Fei , Liu Su , Weng Jian , Qi Tiantian , Qin Haotian , Chen Yixiao , Wang Fangxi , Xiong Ao , Wang Deli , Gao Liang , Zeng Hui
Published: January 2023

Background

Total hip arthroplasty (THA) is a successful treatment for many hip diseases. Length of stay (LOS) and hospital cost are crucial parameters to quantify the medical efficacy and quality of unilateral primary THA patients. Clinical variables associated with LOS and hospital costs haven’t been investigated thoroughly.

Methods

The present study retrospectively explored the contributors of LOS and hospital costs among a total of 452 unilateral primary THA patients from January 2019 to January 2020. All patients received conventional in-house rehabilitation services within our institute prior to discharge. Outcome parameters included LOS and hospital cost while clinical variables included patient characteristics and procedural variables. Multivariable linear regression analysis was performed to assess the association between outcome parameters and clinical variables by controlling confounding factors. Moreover, we analyzed patients in two groups according to their diagnosis with femur neck fracture (FNF) (confine THA) or non-FNF (elective THA) separately.

Results

Among all 452 eligible participants (266 females and 186 males; age 57.05 ± 15.99 year-old), 145 (32.08%) patients diagnosed with FNF and 307 (67.92%) diagnosed with non-FNF were analyzed separately. Multivariable linear regression analysis revealed that clinical variables including surgery duration, transfusion, and comorbidity (stroke) among the elective THA patients while the approach and comorbidities (stoke, diabetes mellitus, coronary heart disease) among the confine THA patients were associated with a prolonged LOS (P < 0.05). Variables including the American Society of Anesthesiologists classification (ASA), duration, blood loss, and transfusion among the elective THA while the approach, duration, blood loss, transfusion, catheter, and comorbidities (stoke and coronary heart disease) among the confine THA were associated with higher hospital cost (P < 0.05). The results revealed that variables were associated with LOS and hospital cost at different degrees among both elective and confine THA.

Conclusions

Specific clinical variables of the patient characteristics and procedural variables are associated the LOS and hospital cost, which may be different between the elective and confine THA patients. The findings may indicate that evaluation and identification of detailed perioperative factors are beneficial in managing perioperative preparation, adjusting patients’ anticipation, decreasing LOS, and reducing hospital cost.
What do consumer and providers view as important for integrated care? A qualitative study
Authors: Carrigan Ann , Roberts Natalie , Clay-Williams Robyn , Hibbert Peter , Austin Elizabeth , Pulido Diana Fajardo , Meulenbroeks Isabelle , Nguyen Hoa Mi , Sarkies Mitchell , Hatem Sarah , Maka Katherine , Loy Graeme , Braithwaite Jeffrey
Published: January 2023

Background

Integrated care is a model recognised internationally, however, there is limited evidence about its usability in the community. This study aimed to elicit community and provider views about integrated care and how implementation could meet their healthcare needs in a new hospital.

Methods

Using a qualitative approach, consumer and provider views on the strengths, barriers and enablers for integrated care were collected via a series of online workshops and supplementary interviews.

Results

A total of 22 consumers and 49 providers participated in 11 focus groups; all perceived integrated care to be an accessible and efficient model that offers a high level of care which enhanced staff and patient well-being. Providers expressed concerns about longer waiting times and safety risks associated with communication gaps and insufficient staff. Enablers include supporting consumers in navigating the integrated care process, co-ordinating and integrating primary care into the model as well as centralising patient electronic medical records.

Discussion

Primary, tertiary and community linkages are key for integrated care. Successful interoperability of services and networks requires an investment in resources and infrastructure to build the capability for providers to seamlessly access information at all points along the patient pathway.

Conclusion

Integrated care is perceived by consumers and providers to be a flexible and patient-focused model of healthcare that offers benefits for a hospital of the future.
Separating the effects of early and later life adiposity on colorectal cancer risk: a Mendelian randomization study
Authors: Papadimitriou Nikos , Bull Caroline J. , Jenab Mazda , Hughes David J. , Bell Joshua A. , Sanderson Eleanor , Timpson Nicholas J. , Smith George Davey , Albanes Demetrius , Campbell Peter T. , Küry Sébastien , Le Marchand Loic , Ulrich Cornelia M. , Visvanathan Kala , Figueiredo Jane C. , Newcomb Polly A. , Pai Rish K. , Peters Ulrike , Tsilidis Kostas K. , Boer Jolanda M. A. , Vincent Emma E. , Mariosa Daniela , Gunter Marc J. , Richardson Tom G. , Murphy Neil
Published: January 2023

Background

Observational studies have linked childhood obesity with elevated risk of colorectal cancer; however, it is unclear if this association is causal or independent from the effects of obesity in adulthood on colorectal cancer risk.

Methods

We conducted Mendelian randomization (MR) analyses to investigate potential causal relationships between self-perceived body size (thinner, plumper, or about average) in early life (age 10) and measured body mass index in adulthood (mean age 56.5) with risk of colorectal cancer. The total and independent effects of body size exposures were estimated using univariable and multivariable MR, respectively. Summary data were obtained from a genome-wide association study of 453,169 participants in UK Biobank for body size and from a genome-wide association study meta-analysis of three colorectal cancer consortia of 125,478 participants.

Results

Genetically predicted early life body size was estimated to increase odds of colorectal cancer (odds ratio [OR] per category change: 1.12, 95% confidence interval [CI]: 0.98–1.27), with stronger results for colon cancer (OR: 1.16, 95% CI: 1.00–1.35), and distal colon cancer (OR: 1.25, 95% CI: 1.04–1.51). After accounting for adult body size using multivariable MR, effect estimates for early life body size were attenuated towards the null for colorectal cancer (OR: 0.97, 95% CI: 0.77–1.22) and colon cancer (OR: 0.97, 95% CI: 0.76–1.25), while the estimate for distal colon cancer was of similar magnitude but more imprecise (OR: 1.27, 95% CI: 0.90–1.77). Genetically predicted adult life body size was estimated to increase odds of colorectal (OR: 1.27, 95% CI: 1.03, 1.57), colon (OR: 1.32, 95% CI: 1.05, 1.67), and proximal colon (OR: 1.57, 95% CI: 1.21, 2.05).

Conclusions

Our findings suggest that the positive association between early life body size and colorectal cancer risk is likely due to large body size retainment into adulthood.
Identification of a novel porcine Teschovirus 2 strain as causative agent of encephalomyelitis in suckling piglets with high mortality in China
Authors: Liang Wenqi , Wu Xiangdong , Ding Zhen , Zhong Shengwei , Qian Xinjie , Ye Pei , Liu Hao , Chen Zheng , Zhang Jinhua , Cao Huabin , Hu Guoliang , Luo Junrong , Li Zuohua , Ding Nengshui , Hu Ruiming
Published: January 2023

Background

Porcine Teschovirus (PTV), also named Teschovirus A, is prevalent in pig populations, mainly causing neurological symptoms, diarrhea, pneumonia, and reproductive failure, however the morbidity and mortality are usually low in pig farms.

Case presentation

In this study, we reported a PTV outbreak investigation in one large-scale pig farm in China with severe symptoms including diarrhea, lethargy, locomotor ataxia, nystagmus, paralysis of the hind limbs, and coma in piglets. More importantly, the mortality reached 38% in suckling pigs, which is remarkably high in PTV history. A novel PTV strain, named HeNZ1, was isolated from cerebral samples of one suckling pig and the genome sequence was obtained by NGS sequencing. Phylogenetic and evolutionary divergence analyses revealed that HeNZ1 belongs to PTV genotype 2. Surprisingly, the VP1 coding region of HeNZ1 shares the highest sequence similarity with European PTV-2 strains, instead of China domestic PTV-2 strains, implying it may not derive from China local PTV-2 strains. Multiple sequence alignment and B cell epitope prediction of PTV VP1 and VP2 protein revealed 10 B cell epitopes, 5 mutant clusters and 36 unique mutation sites, of which 19 unique mutation sites are located in B cell epitopes and exposed on the surface of VP1 or VP2, implying significant antigenic drift potential of HeNZ1.

Conclusion

These results indicate that HeNZ1 is a highly virulent PTV-2 strain, which capable of causing severe neurological symptoms and high mortality in piglets. Bioinformatic analysis suggest that HeNZ1 is genetically and antigenically different from other Chinese PTV-2 strains. Overall, current case expanded our understanding of PTV-2 clinical spectrum and revealed the emergence of a highly virulent PTV-2 strain with substantial genetic diversity and antigenic drift potential in VP1 and VP2.
Gene’s expression underpinning the divergent predictive value of [18F]F-fluorodeoxyglucose and prostate-specific membrane antigen positron emission tomography in primary prostate cancer: a bioinformatic and experimental study
Authors: Bauckneht Matteo , Marini Cecilia , Cossu Vanessa , Campi Cristina , Riondato Mattia , Bruno Silvia , Orengo Anna Maria , Vitale Francesca , Carta Sonia , Chiola Silvia , Chiesa Sabrina , Miceli Alberto , D’Amico Francesca , Fornarini Giuseppe , Terrone Carlo , Piana Michele , Morbelli Silvia , Signori Alessio , Barboro Paola , Sambuceti Gianmario
Published: January 2023

Background

Positron Emission Tomography (PET) imaging with Prostate-Specific Membrane Antigen (PSMA) and Fluorodeoxyglucose (FDG) represent promising biomarkers for risk-stratification of Prostate Cancer (PCa). We verified whether the expression of genes encoding for PSMA and enzymes regulating FDG cellular uptake are independent and additive prognosticators in PCa.

Methods

mRNA expression of genes involved in glucose metabolism and PSMA regulation obtained from primary PCa specimens were retrieved from open-source databases and analyzed using an integrative bioinformatics approach. Machine Learning (ML) techniques were used to create predictive Progression-Free Survival (PFS) models. Cellular models of primary PCa with different aggressiveness were used to compare [18F]F-PSMA-1007 and [18F]F-FDG uptake kinetics in vitro. Confocal microscopy, immunofluorescence staining, and quantification analyses were performed to assess the intracellular and cellular membrane PSMA expression.

Results

ML analyses identified a predictive functional network involving four glucose metabolism-related genes: ALDOB, CTH, PARP2, and SLC2A4. By contrast, FOLH1 expression (encoding for PSMA) did not provide any additive predictive value to the model. At a cellular level, the increase in proliferation rate and migratory potential by primary PCa cells was associated with enhanced FDG uptake and decreased PSMA retention (paralleled by the preferential intracellular localization).

Conclusions

The overexpression of a functional network involving four glucose metabolism-related genes identifies a higher risk of disease progression since the earliest phases of PCa, in agreement with the acknowledged prognostic value of FDG PET imaging. By contrast, the prognostic value of PSMA PET imaging is independent of the expression of its encoding gene FOLH1. Instead, it is influenced by the protein docking to the cell membrane, regulating its accessibility to tracer binding.
Delayed NLRP3 inflammasome inhibition ameliorates subacute stroke progression in mice
Authors: Bellut Maximilian , Bieber Michael , Kraft Peter , Weber Alexander N. R. , Stoll Guido , Schuhmann Michael K.
Published: January 2023

Background

Ischemic stroke immediately evokes a strong neuro-inflammatory response within the vascular compartment, which contributes to primary infarct development under vessel occlusion as well as further infarct growth despite recanalization, referred to as ischemia/reperfusion injury. Later, in the subacute phase of stroke (beyond day 1 after recanalization), further inflammatory processes within the brain parenchyma follow. Whether this second wave of parenchymal inflammation contributes to an additional/secondary increase in infarct volumes and bears the potential to be pharmacologically targeted remains elusive. We addressed the role of the NLR-family pyrin domain-containing protein 3 (NLRP3) inflammasome in the subacute phase of ischemic stroke.

Methods

Focal cerebral ischemia was induced in C57Bl/6 mice by a 30-min transient middle cerebral artery occlusion (tMCAO). Animals were treated with the NLRP3 inhibitor MCC950 therapeutically 24 h after or prophylactically before tMCAO. Stroke outcome, including infarct size and functional deficits as well as the local inflammatory response, was assessed on day 7 after tMCAO.

Results

Infarct sizes on day 7 after tMCAO decreased about 35% after delayed and about 60% after prophylactic NLRP3 inhibition compared to vehicle. Functionally, pharmacological inhibition of NLRP3 mitigated the local inflammatory response in the ischemic brain as indicated by reduction of infiltrating immune cells and reactive astrogliosis.

Conclusions

Our results demonstrate that the NLRP3 inflammasome continues to drive neuroinflammation within the subacute stroke phase. NLRP3 inflammasome inhibition leads to a better long-term outcome—even when administered with a delay of 1 day after stroke induction, indicating ongoing inflammation-driven infarct progression. These findings may pave the way for eagerly awaited delayed treatment options in ischemic stroke.
A novel nutrition-related nomogram for the survival prediction of colorectal cancer-results from a multicenter study
Authors: Ruan Guo-Tian , Song Meng-Meng , Zhang Kang-Ping , Xie Hai-Lun , Zhang Qi , Zhang Xi , Tang Meng , Zhang Xiao-Wei , Ge Yi-Zhong , Yang Ming , Zhu Li-Chen , Shi Han-Ping
Published: January 2023

Background

Precisely predicting the short- and long-term survival of patients with cancer is important. The tumor-node-metastasis (TNM) stage can accurately predict the long-term, but not short-term, survival of cancer. Nutritional status can affect the individual status and short-term outcomes of patients with cancer. Our hypothesis was that incorporating TNM stage and nutrition-related factors into one nomogram improves the survival prediction for patients with colorectal cancer (CRC).

Method

This multicenter prospective primary cohort included 1373 patients with CRC, and the internal validation cohort enrolled 409 patients with CRC. Least absolute shrinkage and selection operator regression analyses were used to select prognostic indicators and develop a nomogram. The concordance (C)-index, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to assess the prognostic discriminative ability of the nomogram, TNM stage, Patient-Generated Subjective Global Assessment (PGSGA), and TNM stage + PGSGA models. The overall survival (OS) curve of risk group stratification was calculated based on the nomogram risk score.

Results

TNM stage, radical resection, reduced food intake, activities and function declined, and albumin were selected to develop the nomogram. The C-index and calibration plots of the nomogram showed good discrimination and consistency for CRC. Additionally, the ROC curves and DCA of the nomogram showed better survival prediction abilities in CRC than the other models. The stratification curves of the different risk groups of the different TNM categories were significantly different.

Conclusion

The novel nomogram showed good short- and long-term outcomes of OS in patients with CRC. This model provides a personalized and convenient prognostic prediction tool for clinical applications.
Predisposing factors for allogeneic blood transfusion in patients with ankylosing spondylitis undergoing primary unilateral total hip arthroplasty: a retrospective study
Authors: Bian Tao , Zhang Liang , Man Siliang , Li Hongchao , Dou Yong , Zhou Yixin
Published: January 2023

Background

The transfusion rate is relatively high in patients with ankylosing spondylitis (AS) undergoing total hip arthroplasty (THA). However, relevant studies focusing on the predisposing factors for transfusion with a large sample size are lacking. This study aimed to investigate the incidence of and risk factors for allogeneic blood transfusion in patients with AS undergoing primary unilateral THA.

Methods

This retrospective study included 331 patients with AS who underwent primary unilateral THA between 2011 and 2021. Relevant parameters were collected through a chart review. Multivariate logistic regression analysis was conducted to identify possible factors associated with perioperative allogeneic blood transfusion.

Results

A total of 113 (34.1%) patients received perioperative allogeneic blood transfusions. Factors related to receiving an allogeneic blood transfusion included prolonged operative duration (odds ratio [OR] per 10 min = 1.139, P = 0.047), increased estimated intraoperative blood loss (OR per 100 mL = 1.348, P < 0.001), and increased postoperative drainage volume (OR per 100 mL = 1.235, P = 0.024). A higher body mass index (BMI) (OR = 0.914, P = 0.012), perioperative tranexamic acid (TXA) use (OR = 0.166, P < 0.001), and a higher preoperative hemoglobin level (OR per 1 g/dL = 0.744, P = 0.004) decreased the risk of transfusion.

Conclusions

In patients with AS undergoing THA, prolonged operative duration, increased estimated intraoperative blood loss, and increased postoperative drainage volume were found to be risk factors for transfusion, whereas a higher BMI, perioperative TXA use, and a higher preoperative hemoglobin level were protective factors. These results may aid in developing a better perioperative management strategy, ultimately reducing the need for transfusion.
APOE effects on regional tau in preclinical Alzheimer’s disease
Authors: Young Christina B. , Johns Emily , Kennedy Gabriel , Belloy Michael E. , Insel Philip S. , Greicius Michael D. , Sperling Reisa A. , Johnson Keith A. , Poston Kathleen L. , Mormino Elizabeth C. ,   for the Alzheimer’s Disease Neuroimaging Initiative,   the A4 Study Team
Published: January 2023

Background

APOE variants are strongly associated with abnormal amyloid aggregation and additional direct effects of APOE on tau aggregation are reported in animal and human cell models. The degree to which these effects are present in humans when individuals are clinically unimpaired (CU) but have abnormal amyloid (Aβ+) remains unclear.

Methods

We analyzed data from CU individuals in the Anti-Amyloid Treatment in Asymptomatic AD (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies. Amyloid PET data were available for 4486 participants (3163 Aβ-, 1323 Aβ+) and tau PET data were available for a subset of 447 participants (55 Aβ-, 392 Aβ+). Linear models examined APOE (number of e2 and e4 alleles) associations with global amyloid and regional tau burden in medial temporal lobe (entorhinal, amygdala) and early neocortical regions (inferior temporal, inferior parietal, precuneus). Consistency of APOE4 effects on regional tau were examined in 220 Aβ + CU and mild cognitive impairment (MCI) participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI).

Results

APOE2 and APOE4 were associated with lower and higher amyloid positivity rates, respectively. Among Aβ+ CU, e2 and e4 were associated with reduced (−12 centiloids per allele) and greater (+15 centiloids per allele) continuous amyloid burden, respectively. APOE2 was associated with reduced regional tau in all regions (-0.05 to -0.09 SUVR per allele), whereas APOE4 was associated with greater regional tau (+0.02 to +0.07 SUVR per allele). APOE differences were confirmed by contrasting e3/e3 with e2/e3 and e3/e4. Mediation analyses among Aβ+ s showed that direct effects of e2 on regional tau were present in medial temporal lobe and early neocortical regions, beyond an indirect pathway mediated by continuous amyloid burden. For e4, direct effects on regional tau were only significant in medial temporal lobe. The magnitude of protective e2 effects on regional tau was consistent across brain regions, whereas detrimental e4 effects were greatest in medial temporal lobe. APOE4 patterns were confirmed in Aβ+ ADNI participants.

Conclusions

APOE influences early regional tau PET burden, above and beyond effects related to cross-sectional amyloid PET burden. Therapeutic strategies targeting underlying mechanisms related to APOE may modify tau accumulation among Aβ+ individuals.
Randomized controlled trial evaluating a virtual parenting intervention for young children at risk of obesity: study protocol for Parenting Addressing Early Years Intervention with Coaching Visits in Toronto (PARENT) trial
Authors: Rae Sarah , Maguire Jonathon , Aglipay Mary , Barwick Melanie , Danavan Karoon , Haines Jess , Jenkins Jennifer , Klaassen Marie , Moretti Myla E. , Ong Frank , Persaud Nav , Porepa Michelle , Straus Sharon , Tavares Erika , Willan Andrew , Birken Catherine
Published: January 2023

Background

The prevalence of overweight (15%) and obesity (6%) in children under 5 years of age in Canada are high, and young children with overweight and obesity are at increased risk of the development of chronic disease(s) in adulthood. Prior research has demonstrated very few published trials on effective obesity prevention interventions in young children at risk of obesity, within primary healthcare settings. The aim of this study is to determine if 18–48-month-old children at risk for obesity, who are randomized to receive the Parents Together program (i.e., intervention group), have reduced body mass index z-score (zBMI), compared to those not receiving the intervention, at a 12-month follow-up. Secondary clinical outcomes between the intervention and control groups will be compared at 12 months.

Methods

A pragmatic, parallel group, 1:1, superiority, randomized control trial (RCT) through the TARGetKids! Practice Based Research Network will be conducted. Young children (ages 18–48 months) who are at increased risk for childhood obesity will be invited to participate. Parents who are enrolled in the intervention group will participate in eight weekly group sessions and 4–5 coaching visits, facilitated by a trained public health nurse. Children and parents who are enrolled in the control group will receive the usual health care. The primary outcome will be compared between intervention arms using an analysis of covariance (ANCOVA). Feasibility and acceptability will be assessed by parent focus groups and interviews, and fidelity to the intervention will be measured using nurse-completed checklists. A cost-effectiveness analysis (CEA) will be conducted.

Discussion

This study will aim to reflect the social, cultural, and geographic diversity of children in primary care in Toronto, Ontario, represented by an innovative collaboration among applied child health researchers, community health researchers, and primary care providers (i.e., pediatricians and family physicians in three different models of primary care). Clinical and implementation outcomes will be used to inform future research to test this intervention in a larger number, and diverse practices across diverse geographic settings in Ontario.

Trial registration

ClinicalTrials.gov NCT03219697. Registered on June 27, 2017.
Family wellbeing in general practice: a study protocol for a cluster-randomised trial of the web-based resilience programme on early child development
Authors: Overbeck Gritt , Kragstrup Jakob , Gørtz Mette , Rasmussen Ida Scheel , Graungaard Anette Hauskov , Siersma Volkert , de Voss Sarah , Ertmann Ruth Kirk , Shahrzad Sinead , Appel Clara Lundmark , Wilson Philip
Published: January 2023

Background

Social, emotional and behavioural problems in early childhood are associated with increased risk for a wide range of poor outcomes associated with substantial cost and impact on society as a whole. Some of these problems are rooted in the early mother-infant relationship and might be prevented. In Denmark, primary health care has a central role in preventive care during pregnancy and the first years of the child’s life and general practice provides opportunities to promote a healthy mother-infant relationship in early parenthood.

Objective

In the context of standardised antenatal and child development assessments focused on psychosocial wellbeing, we examine the impact of a complex intervention designed to improve maternal mentalisation skills, involving training of general practice clinicians and signposting towards a web-based resource. Joint main outcomes are child socio-emotional and language development at age 30 months measured by parentally reported questionnaires (Communicative Development Inventory and Strengths and Difficulties Questionnaire).

Methods

The study is a cluster-randomised controlled trial based in general practices in the Capital Region and the Zealand Region of Denmark. Seventy practices were included. Practices were randomised by a computer algorithm in a ratio of 1:1 to intervention or control groups. Each practice was asked to recruit up to 30 women consecutively at their first scheduled antenatal assessment. Clinicians in both groups received one day of training in preventive antenatal and child development consultations with added focus on parental psychosocial well-being, social support, and parent–child interaction. These preventive consultations delivered in both trial arms require enhanced data recording about psychosocial factors. In intervention clinics, clinicians were asked to signpost a web page at three scheduled antenatal consultations and at four scheduled consultations when the child is 5 weeks, 5 months, 1 and 2 years.

Discussion

We hypothesise that the intervention will increase mothers’ ability to be sensitive to their child’s mental state to an extent that improves the child’s language and mental state at 30 months of age measured by parent-reported questionnaires.

Trial registration

ClinicalTrials.gov NCT04129359. Registered on Oct 16 2019.
Cell phenotype changes and oxidative stress response in Vibrio spp. induced into viable but non-culturable (VBNC) state
Authors: Prosdocimi Erica M. , Arioli Stefania , Mapelli Francesca , Zeaiter Zahraa , Fusi Marco , Daffonchio Daniele , Borin Sara , Crotti Elena
Published: January 2023

Purpose

Aquatic bacteria of the genus Vibrio include animal and human pathogens. The occurrence of Vibrio-related diseases has been associated with the current climate change-driven increase of sea surface temperature. Vibrio spp. can enter into the viable but non-culturable (VBNC) state, as a consequence of starvation in seawater at low temperatures. In such physiological state, Vibrio cells are no longer culturable on standard media agar plates but can resuscitate if incubated at 30 °C prior to plating, retaining virulence. Since limited information is available on regards to this topic, in this work, we characterized the phenotypic changes of four Vibrio spp. strains (one laboratory strain and three environmental isolates) in cold seawater microcosms, investigating the relationship between resuscitation and a hydrogen peroxide-induced oxidative stress.

Methods

Cell phenotypic changes and the effect of hydrogen peroxide and/or catalase addition to the medium were studied on VBNC and resuscitated cells by flow cytometry in microcosm experiments, paralleled by culturability experiments by plating.

Results

The cells of all the Vibrio strains changed their phenotype upon the induction of the VBNC state resulting in cell dwarfing and decrease in DNA quantity, losing the ability to grow on solid media. These features were partially or totally reverted when the cells were treated for resuscitation. Hydrogen peroxide at concentrations as low as 0.007 mM prevented resuscitation and a prolonged exposure to hydrogen peroxide at concentrations far under those inhibiting the growth of log-phase cells permanently damaged VBNC cells, which could not be resuscitated. However, the potential of culturability of VBNC cells could be preserved, at least for a part of the population, by plating the cells in the presence of catalase. The study also showed that during the resuscitation process, the cells gradually increased their resistance to hydrogen peroxide.

Conclusions

The timing and mode of induction of the VBNC state, as well as cell resuscitation and response to hydrogen peroxide, differed among Vibrio strains, indicating that induction and resuscitation from dormancy could vary in the context of species belonging to a single genus.
Single-cell DNA methylation sequencing by combinatorial indexing and enzymatic DNA methylation conversion
Authors: Chatterton Zac , Lamichhane Praves , Ahmadi Rastegar Diba , Fitzpatrick Lauren , Lebhar Hélène , Marquis Christopher , Halliday Glenda , Kwok John B.
Published: January 2023

Background

DNA methylation is a critical molecular mark involved in cellular differentiation and cell-specific processes. Single-cell whole genome DNA methylation profiling methods hold great potential to resolve the DNA methylation profiles of individual cell-types. Here we present a method that couples single-cell combinatorial indexing (sci) with enzymatic conversion (sciEM) of unmethylated cytosines.

Results

The sciEM method facilitates DNA methylation profiling of single-cells that is highly correlated with single-cell bisulfite-based workflows (r2 > 0.99) whilst improving sequencing alignment rates, reducing adapter contamination and over-estimation of DNA methylation levels (CpG and non-CpG). As proof-of-concept we perform sciEM analysis of the temporal lobe, motor cortex, hippocampus and cerebellum of the human brain to resolve single-cell DNA methylation of all major cell-types.

Conclusion

To our knowledge sciEM represents the first non-bisulfite single-cell DNA methylation sequencing approach with single-base resolution.
Multi-sensor tracking with partly overlapping FoV using detection field of probability modeling and the GLMB filter
Authors: Liu Weifeng , Liu Qiliang , Chen Yimei , Cui Hailong
Published: January 2023

In this paper, we consider multi-sensor with partly overlapping field of view (FoV) in the labeled random finite set (L-RFS) framework. This is different from most existing multi-sensor tracking algorithms, where the sensors are assumed to have the same FoV. We describe the partly overlapping FoV by modeling probability field of detection for individual sensors in whole observation area and can be seen as the same range of FoV. We consider all these using generalized labeled multi-Bernoulli filter in labeled RFS framework. Besides, we also propose a measurement-driven target birth model. Finally, the effectiveness of the proposed algorithm is verified by experiments.
A meta-analysis on the effects of probiotics on the performance of pre-weaning dairy calves
Authors: Wang Liyun , Sun Honghong , Gao Haixu , Xia Yaohui , Zan Linsen , Zhao Chunping
Published: January 2023

Background

Probiotics have been used in livestock production for many years, but information on their benefits during the early life of calves is inconsistent. This study aimed to assess the effects of probiotics on the performance of pre-weaning dairy calves and identify the factors influencing their effect sizes.

Results

Forty-nine studies were selected for meta-analysis based on the inclusion and exclusion criteria. The study qualities were evaluated using a predefined risk assessment tool following GRADE guidelines. Meta-analysis results showed that probiotics increased the growth performance (body weight by 1.988 kg and average daily gain by 40.689 g/d), decreased digestibility and feed efficiency (feed conversion rate by 0.073), altered rumen parameter (decreased acetate by 2.815 mmol/L and increased butyrate by 0.788 mmol/L), altered blood parameter (decreased AST by 4.188 U/L, increased BHBA by 0.029 mmol/L and IgG by 0.698 g/L), increased faecal parameter (faecal bacteria counts by 0.680 log10 CFU/g), based on the strict criteria (PSMD < 0.05, I2 < 50%). Additionally, probiotics increased digestibility and feed efficiency (starter dry matter intake by 0.034 kg/d and total dry matter intake by 0.020 kg/d), altered blood parameter (increased IgA by 0.313 g/L, IgM by 0.262 g/L, and total antioxidant capacity by 0.441 U/mL, decreased MDA by 0.404 nmol/mL), decreased faecal parameter (faecal score by 0.052), based on the loose criteria (PSMD < 0.05, I2 > 50%).

Regression and sub-group analyses showed that probiotic strains, supplementation dosage, and methods significantly affected the performance of calves. The probiotics supplied with more than 9.5 log10 CFU/d significantly increased IgA and IgM contents (PSMD < 0.05). Additionally, the compound probiotics significantly increased TDMI, IgA, and IgM (PSMD ≤ 0.001). Furthermore, probiotics supplemented in liquid (whole milk or milk replacer) significantly increased TDMI and decreased faecal score (PSMD < 0.05), while in whole milk, they significantly increased body weight, IgA, and IgM (PSMD < 0.001).

Conclusions

Probiotics could improve the growth performance, feed intake and efficiency, rumen fermentation, immune and antioxidant capacity, and health of pre-weaning calves. However, the effect sizes were related to the dosage, composition, and supplementation methods of probiotics.
Variability of radiotherapy volume delineation: PSMA PET/MRI and MRI based clinical target volume and lymph node target volume for high-risk prostate cancer
Authors: Liu Lin-Lin , Zhu Lei-Lei , Lu Zhen-Guo , Sun Jun-Die , Zhao Jun , Wang Hai-Feng , Xiang Zuo-Lin
Published: January 2023

Purpose

A comparative retrospective study to assess the impact of PSMA Ligand PET/MRI ([68 Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 PET/MRI) as a new method of target delineation compared to conventional imaging on whole-pelvis radiotherapy for high-risk prostate cancer (PCa).

Patients and methods

Forty-nine patients with primary high-risk PCa completed the whole-pelvis radiotherapy plan based on PSMA PET/MRI and MRI. The primary endpoint compared the size and overlap of clinical target volume (CTV) and nodal gross tumour volume (GTVn) based on PSMA PET/MRI and MRI. The diagnostic performance of two methods for pelvic lymph node metastasis (PLNM) was evaluated.

Results

In the radiotherapy planning for high-risk PCa patients, there was a significant correlation between MRI-CTV and PET/MRI-CTV (P = 0.005), as well as between MRI-GTVn and PET/MRI-GTVn (P < 0.001). There are non-significant differences in the CTV and GTVn based on MRI and PET/MRI images (P = 0.660, P = 0.650, respectively). The conformity index (CI), lesion coverage factor (LCF) and Dice similarity coefficient (DSC) of CTVs were 0.999, 0.953 and 0.954. The CI, LCF and DSC of GTVns were 0.927, 0.284, and 0.32. Based on pathological lymph node analysis of 463 lymph nodes from 37 patients, the sensitivity, specificity of PET/MRI in the diagnosis of PLNM were 77.78% and 99.76%, respectively, which were higher than those of MRI (P = 0.011). Eight high-risk PCa patients who finished PSMA PET/MRI changed their N or M stage.

Conclusion

The CTV delineated based on PET/MRI and MRI differ little. The GTVn delineated based on PET/MRI encompasses metastatic pelvic lymph nodes more accurately than MRI and avoids covering pelvic lymph nodes without metastasis. We emphasize the utility of PET/MRI fusion images in GTVn delineation in whole pelvic radiotherapy for PCa. The use of PSMA PET/MRI aids in the realization of more individual and precise radiotherapy for PCa.
Prognostic impact of 18F-FDG PET/CT in pathologic stage II invasive ductal carcinoma of the breast: re-illuminating the value of PET/CT in intermediate-risk breast cancer
Authors: Park Hye Lim , Lee Sea-Won , Hong Ji Hyung , Lee Jieun , Lee Ahwon , Kwon Soo Jin , Park Sonya Youngju , Yoo Ie Ryung
Published: January 2023

Background

The aim of this study is to investigate the impact of18F-FDG PET/CT on prognosis of stage II invasive ductal carcinoma (IDC) of the breast primarily treated with surgery.

Methods

The clinical records of 297 consecutive IDC with preoperative PET/CT and pathologically staged II in surgery from 2013 to 2017 were retrospectively reviewed. The maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), tumor-to-liver ratio (TLR), and metabolic tumor volume (MTV) were measured. Association of clinicopathologic factors (age, T stage, N stage, AJCC pathologic stage of IIA or IIB, pathologic prognostic stage, grade, hormonal receptor status, HER2 status, Ki-67, and adjuvant therapy) and PET parameters with DFS was assessed using the Cox proportional hazards model.

Results

There were 35 recurrences and 10 deaths at a median follow-up of 49 months (range 0.8 ~ 87.3). All PET parameters were significantly associated with DFS in univariate analysis but in multivariate analysis, SUVpeak was the only factor significantly associated with DFS (hazard ratio 2.58, 95% confidence interval 1.29–5.15,P = 0.007). In cohorts with higher values of SUVpeak or TLR, patients who received adjuvant chemotherapy had significantly superior DFS.

Conclusion

Metabolic parameters derived from preoperative PET/CT was significantly associated with recurrence in stage II IDC primarily treated with surgery. PET/CT can be a powerful prognostic tool in conjunction with novel staging systems and current biomarkers for patients undergoing contemporary therapy. Our results urge to reconsider the currently underestimated value of PET/CT confined to diagnostic aspect and to newly recognize its prognostic impact in these intermediate-risk breast cancer.
Reproducibility of each retinal layer thickness measurement in epiretinal membrane patients with ectopic inner foveal layers
Authors: Jung Il , Na Yong-Jin , Lee Sung-Chul , Lee Min-Woo
Published: January 2023

Background

To identify the reliability of each retinal layer thickness measurement in epiretinal membrane (ERM) patients with ectopic inner foveal layers (EIFLs).

Methods

Subjects were divided into two groups: ERM patients with EIFLs (Group 1) and without EIFLs (Group 2). The retinal layer thickness was measured twice, and intraclass correlation coefficient (ICC) and coefficient of variation (CV) values were calculated.

Results

In Group 1, the CVs of the nerve fiber layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), and outer nuclear layer (ONL) were 22.39%, 13.12%, 13.37%, 13.21%, 15.09%, and 11.94%, while the ICCs were 0.431, 0.550, 0.440, 0.286, 0.279, and 0.503, respectively. In Group 2, the CVs were 18.20%, 10.59%, 10.65%, 13.27%, 14.75%, and 10.37%, while the ICCs were 0.788, 0.834, 0.830, 0.715, 0.226, and 0.439, respectively. The average central macular thickness (CMT) was significantly correlated with the CVs of NFL (coefficient = 0.317; P < 0.001), GCL (coefficient = 0.328; P < 0.001), and IPL (coefficient = 0.186; P = 0.042) in Group 1.

Conclusions

The reproducibility of the inner retinal layer thickness measurements in ERM patients with EIFLs was low compared to those without EIFLs. The reproducibility of the outer retinal layer thickness measurements, including OPL and ONL, was poor regardless of the presence of EIFLs in ERM patients. Additionally, the thicker the CMT in patients with EIFLs, the lower the reproducibility of the inner retinal layer thickness measurements.