bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of five supervised feature selection algorithms leading to top features and gene signatures from multi-omics data in cancer
Authors: Bhadra Tapas , Mallik Saurav , Hasan Neaj , Zhao Zhongming
Published: April 2022

Background

As many complex omics data have been generated during the last two decades, dimensionality reduction problem has been a challenging issue in better mining such data. The omics data typically consists of many features. Accordingly, many feature selection algorithms have been developed. The performance of those feature selection methods often varies by specific data, making the discovery and interpretation of results challenging.

Methods and results

In this study, we performed a comprehensive comparative study of five widely used supervised feature selection methods (mRMR, INMIFS, DFS, SVM-RFE-CBR and VWMRmR) for multi-omics datasets. Specifically, we used five representative datasets: gene expression (Exp), exon expression (ExpExon), DNA methylation (hMethyl27), copy number variation (Gistic2), and pathway activity dataset (Paradigm IPLs) from a multi-omics study of acute myeloid leukemia (LAML) from The Cancer Genome Atlas (TCGA). The different feature subsets selected by the aforesaid five different feature selection algorithms are assessed using three evaluation criteria: (1) classification accuracy (Acc), (2) representation entropy (RE) and (3) redundancy rate (RR). Four different classifiers, viz., C4.5, NaiveBayes, KNN, and AdaBoost, were used to measure the classification accuary (Acc) for each selected feature subset. The VWMRmR algorithm obtains the best Acc for three datasets (ExpExon, hMethyl27 and Paradigm IPLs). The VWMRmR algorithm offers the best RR (obtained using normalized mutual information) for three datasets (Exp, Gistic2 and Paradigm IPLs), while it gives the best RR (obtained using Pearson correlation coefficient) for two datasets (Gistic2 and Paradigm IPLs). It also obtains the best RE for three datasets (Exp, Gistic2 and Paradigm IPLs). Overall, the VWMRmR algorithm yields best performance for all three evaluation criteria for majority of the datasets. In addition, we identified signature genes using supervised learning collected from the overlapped top feature set among five feature selection methods. We obtained a 7-gene signature (ZMIZ1, ENG, FGFR1, PAWR, KRT17, MPOandLAT2) for EXP, a 9-gene signature for ExpExon, a 7-gene signature for hMethyl27, one single-gene signature (PIK3CG) for Gistic2 and a 3-gene signature for Paradigm IPLs.

Conclusion

We performed a comprehensive comparison of the performance evaluation of five well-known feature selection methods for mining features from various high-dimensional datasets. We identified signature genes using supervised learning for the specific omic data for the disease. The study will help incorporate higher order dependencies among features.
TCR-L: an analysis tool for evaluating the association between the T-cell receptor repertoire and clinical phenotypes
Authors: Liu Meiling , Goo Juna , Liu Yang , Sun Wei , Wu Michael C. , Hsu Li , He Qianchuan
Published: April 2022

Background

T cell receptors (TCRs) play critical roles in adaptive immune responses, and recent advances in genome technology have made it possible to examine the T cell receptor (TCR) repertoire at the individual sequence level. The analysis of the TCR repertoire with respect to clinical phenotypes can yield novel insights into the etiology and progression of immune-mediated diseases. However, methods for association analysis of the TCR repertoire have not been well developed.

Methods

We introduce an analysis tool, TCR-L, for evaluating the association between the TCR repertoire and disease outcomes. Our approach is developed under a mixed effect modeling, where the fixed effect represents features that can be explicitly extracted from TCR sequences while the random effect represents features that are hidden in TCR sequences and are difficult to be extracted. Statistical tests are developed to examine the two types of effects independently, and then the p values are combined.

Results

Simulation studies demonstrate that (1) the proposed approach can control the type I error well; and (2) the power of the proposed approach is greater than approaches that consider fixed effect only or random effect only. The analysis of real data from a skin cutaneous melanoma study identifies an association between the TCR repertoire and the short/long-term survival of patients.

Conclusion

The TCR-L can accommodate features that can be extracted as well as features that are hidden in TCR sequences. TCR-L provides a powerful approach for identifying association between TCR repertoire and disease outcomes.
Nutritional and genetic variation in a core set of Ethiopian Tef (Eragrostis tef) varieties
Authors: Ereful Nelzo C. , Jones Huw , Fradgley Nick , Boyd Lesley , Cherie Hirut Assaye , Milner Matthew J.
Published: April 2022

Background

Tef (Eragrostis tef) is a tropical cereal domesticated and grown in the Ethiopian highlands, where it has been a staple food of Ethiopians for many centuries. Food insecurity and nutrient deficiencies are major problems in the country, so breeding for enhanced nutritional traits, such as Zn content, could help to alleviate problems with malnutrition.

Results

To understand the breeding potential of nutritional traits in tef a core set of 24 varieties were sequenced and their mineral content, levels of phytate and protein, as well as a number of nutritionally valuable phenolic compounds measured in grain. Significant variation in all these traits was found between varieties. Genome wide sequencing of the 24 tef varieties revealed 3,193,582 unique SNPs and 897,272 unique INDELs relative to the tef reference var. Dabbi. Sequence analysis of two key transporter families involved in the uptake and transport of Zn by the plant led to the identification of 32 Zinc Iron Permease (ZIP) transporters and 14 Heavy Metal Associated (HMA) transporters in tef. Further analysis identified numerous variants, of which 14.6% of EtZIP and 12.4% of EtHMA variants were non-synonymous changes. Analysis of a key enzyme in flavanol synthesis, flavonoid 3′-hydroxylase (F3’H), identified a T-G variant in the tef homologue Et_s3159-0.29-1.mrna1 that was associated with the differences observed in kaempferol glycoside and quercetin glycoside levels.

Conclusion

Wide genetic and phenotypic variation was found in 24 Ethiopian tef varieties which would allow for breeding gains in many nutritional traits of importance to human health.
Genome-wide association mapping and genomic prediction for kernel color traits in intermediate wheatgrass (Thinopyrum intermedium)
Authors: Bajgain Prabin , Li Catherine , Anderson James A.
Published: April 2022

Background

Intermediate wheatgrass (IWG) is a novel perennial grain crop currently undergoing domestication. It offers important ecosystem benefits while producing grain suitable for human consumption. Several aspects of plant biology and genetic control are yet to be studied in this new crop. To understand trait behavior and genetic characterization of kernel color in IWG breeding germplasm from the University of Minnesota was evaluated for the CIELAB components (L*, a*, b*) and visual differences. Trait values were used in a genome-wide association scan to reveal genomic regions controlling IWG’s kernel color. The usability of genomic prediction in predicting kernel color traits was also evaluated using a four-fold cross validation method.

Results

A wide phenotypic variation was observed for all four kernel color traits with pairwise trait correlations ranging from − 0.85 to 0.27. Medium to high estimates of broad sense trait heritabilities were observed and ranged from 0.41 to 0.78. A genome-wide association scan with single SNP markers detected 20 significant marker-trait associations in 9 chromosomes and 23 associations in 10 chromosomes using multi-allelic haplotype blocks. Four of the 20 significant SNP markers and six of the 23 significant haplotype blocks were common between two or more traits. Evaluation of genomic prediction of kernel color traits revealed the visual score to have highest mean predictive ability (r2 = 0.53); r2 for the CIELAB traits ranged from 0.29–0.33. A search for candidate genes led to detection of seven IWG genes in strong alignment with MYB36 transcription factors from other cereal crops of the Triticeae tribe. Three of these seven IWG genes had moderate similarities with R-A1, R-B1, and R-D1, the three genes that control grain color in wheat.

Conclusions

We characterized the distribution of kernel color in IWG for the first time, which revealed a broad phenotypic diversity in an elite breeding germplasm. Identification of genetic loci controlling the trait and a proof-of-concept that genomic selection might be useful in selecting genotypes of interest could help accelerate the breeding of this novel crop towards specific end-use.
Efficacy and safety of glecaprevir and pibrentasvir in Japanese patients with hepatitis C virus infection aged 75 years or older
Authors: Komaki Yuri , Ozono Yoshinori , Nakamura Kenichi , Iwakiri Hisayoshi , Hasuike Satoru , Sueta Mitsue , Miike Tadashi , Yamamoto Shojiro , Uto Hirofumi , Kusumoto Kazunori , Ochiai Toshimasa , Kato Junya , Komada Naoto , Kuroki Kazuo , Eto Toshiharu , Shigehira Masafumi , Hirono Shuichi , Nagata Kenji , Kawakami Hiroshi
Published: April 2022

Background

It is estimated that approximately 50% of patients with hepatitis C virus (HCV) infection in Japan are currently over 75 years old. However, patients aged ≥ 75 years are typically underrepresented in clinical trials of direct-acting antivirals. This study aimed to evaluate the efficacy and safety of glecaprevir and pibrentasvir (G/P) treatment in Japanese patients with HCV infection aged ≥ 75 years.

Methods

This multicenter, retrospective study included 271 Japanese patients with HCV infection from 12 centers in Miyazaki Prefecture, Japan. Demographic, clinical, virological, and adverse events (AEs) data obtained during and after G/P treatment were collected from medical records. The patients were divided into two groups: younger (n = 199, aged < 75 years) and older (n = 72, aged ≥ 75 years). Virological data and AEs were analyzed according to the age group.

Results

In intention-to-treat (ITT) and per-protocol analyses, the overall sustained virological response 12 (SVR12) rates were 93% and 98.8%, respectively. Two patients in the older group and 14 patients in the younger group dropped out before SVR12 assessment. Although patients in the older group tended to have liver cirrhosis, 95.8% in the older group and 92% in the younger group achieved SVR12 in the ITT analysis (P = 0.404). In total, 48 (17.7%) patients experienced treatment-related AEs. Common AEs during treatment included pruritus, headache, and fatigue. The AEs were not significantly different between the two groups.

Conclusions

Compared with younger patients, older patients showed similar virological response and tolerance to G/P treatment.
Determinants of technology adoption and continued use among cognitively impaired older adults: a qualitative study
Authors: Dequanter Samantha , Fobelets Maaike , Steenhout Iris , Gagnon Marie-Pierre , Bourbonnais Anne , Rahimi Samira , Buyl Ronald , Gorus Ellen
Published: April 2022

Background

Technology offers opportunities to support older adults with mild cognitive impairments to remain independent and socially connected, but is often not used. Although determinants of technology use among older adults in general are well studied, much less is known about how these factors impact technology use behaviour in cognitively impaired older adults. This study aimed to bridge this gap in research by examining the factors underlying technology use in community-dwelling older adults with mild cognitive impairments.

Methods

We applied a generic qualitative design and used 16 semi-structured interviews to collect data from Belgian (Flemish) community-dwelling older adults diagnosed with Mild Cognitive Impairment or dementia and informal caregivers. To get data from different perspectives, a focus group with professional caregivers was added. We used thematic analysis with an inductive approach to identify and select themes from the data.

Results

We identified two themes: introduction of technology and determinants of technology adoption and continued use. Successful technology adoption in cognitively impaired older adults is need-driven and subject to individual, technological and contextual characteristics. Specific for older adults with cognitive impairments are the importance of disease awareness and cognitive ability for adoption and continued use, respectively. Although social support can be a valuable alternative to technology, it is an important facilitator of continued technology use in these older adults. Similarly, integration of technologies in daily routines can buffer discontinuation of technologies.

Conclusions

Future research is encouraged to validate our findings in a postpandemic era and to further develop a novel theoretical framework for technology acceptance among older adults with cognitive impairments. Moreover, identification of crucial determinants as well as strategies to remove use barriers are also important future research tasks. Clinical practice should focus on improving disease awareness to facilitate technology adoption and policies should invest in training and support of professional caregivers and in reimbursement strategies to facilitate implementation of technology in practice.
Suicidal ideation and its related factors among older adults: a population-based study in Southwestern Iran
Authors: Shiraly Ramin , Mahdaviazad Hamideh , Zohrabi Roya , Griffiths Mark D.
Published: April 2022

Objectives

Suicidal ideation is a major risk factor for suicide and can negatively affect self-care and health behaviors among the older adults. There are limited data on the prevalence and risk factors of suicidal ideation among the older population during the COVID-19 pandemic. The aim of the present study was to examine the prevalence and risk factors of suicidal ideations among Iranian older adults during the COVID-19 pandemic.

Methods

A total of 803 older community adults in Shiraz (Southwestern Iran) were surveyed to determine potential factors influencing suicidal ideation, including demographic factors, physical health status, access to healthcare, current depression status, fear of COVID-19, perceived social support, and social engagement. Data were collected utilizing face-to-face interviews between November and December 2020. Multivariate logistic regression analysis was used to identify independent variables associated with suicidal ideations.

Results

Among the 803 participants, 69 reported suicidal ideations (8.6%). Individuals with suicidal ideations were more likely to have greater fear of COVID-19. However, based on the results of multivariate logistic regression analysis, current depression (OR: 2.07, CI 95%: 1.18–3.65), not being married (OR: 1.82, CI 95%: 1.06–3.13), inability to pay for medical bills (OR: 2.16, CI 95%: 1.23–3.79), low perceived social support (OR: 2.03, CI95%: 1.11–3.71), and having limited social network (OR:1.77, CI 95%: 1.02–3.10) appeared to be more powerful influencing factors.

Conclusion

Suicidal ideation appears to be relatively common among Iranian older adults during the COVID-19 pandemic. A lack of longitudinal data makes it difficult to establish an association between suicidal ideations and the COVID-19 pandemic. Systematic monitoring of suicidal ideation is recommended among high-risk groups, particularly the older population.
Cognitive decline and poor social relationship in older adults during COVID-19 pandemic: can information and communications technology (ICT) use helps?
Authors: Li Yaya , Godai Kayo , Kido Michiko , Komori Susumu , Shima Ryoichi , Kamide Kei , Kabayama Mai
Published: April 2022

Background

To answer whether older adults' cognitive function benefits from ICT use, we (1) examined the relationship between ICT use and cognitive decline during the COVID-19 pandemic and (2) explored the potential role of ICT use in mitigating the relationship between loneliness, social isolation, and cognitive decline among community-dwelling older adults.

Methods

From February to March 2021, a mail survey was distributed to 1,400 older adults aged 70–89 years old. Responded participants were 1,003 (71.6% response rate). Subjective cognitive decline (SCD) was the independent variable. ICT use was assessed based on ICT use history and current ICT use activities. Loneliness was based on the Japanese version of the Three-Item Loneliness Scale. Social isolation was a total score of six items. Covariate-adjusted logistic regressions were performed and stratified by age groups (70–79 and ≥ 80 years).

Results

During the COVID-19 epidemic, the proportion of people aged ≥ 80 years who reported cognitive decline was twice that of 70s. Non-ICT use was independently associated with a higher risk of cognitive decline in participants aged ≥ 80 years. Furthermore, the significant associations between cognitive decline and interaction items (non-ICT use by loneliness or social isolation) were observed in the ≥ 80 age group. No association was found in the 70–79 age group.

Conclusions

Non-ICT users with high loneliness or social isolation scores were more likely to experience cognitive decline for adults age ≥ 80 years. For older adults who were vulnerable to poor social relationships, ICT use is potentially an efficient intervention. Further longitudinal investigations are needed.
The impact of a history of child abuse on cognitive performance: a cross-sectional study in older patients with a depressive, anxiety, or somatic symptom disorder
Authors: Tjoelker F. M. , Jeuring H. W. , Aprahamian I. , Naarding P. , Marijnissen R. M. , Hendriks G. J. , Rhebergen D. , Lugtenburg A. , Lammers M. W. , van den Brink R. H. S. , Oude Voshaar R. C.
Published: April 2022

Background

Child abuse is a major global burden with an enduring negative impact on mental and physical health. A history of child abuse is consistently associated with worse cognitive performance among adults; data in older age groups are inconclusive. Since affective symptoms and cognitive functioning are interrelated among older persons, a synergistic effect can be assumed in patients with affective symptoms who also have suffered from child abuse. This study examines the association between a history of child abuse and cognitive performance in such patients.

Methods

Cross-sectional data were collected from the ‘Routine Outcome Monitoring for Geriatric Psychiatry & Science’ project, including 179 older adults (age 60–88 years) with either a unipolar depressive, any anxiety, or somatic symptom disorder referred to specialized geriatric mental health care. A history of physical, sexual, and psychological abuse, and emotional neglect was assessed with a structured interview. Cognitive functioning was measured with three paper and pencils tests (10-words verbal memory test, Stroop Colour-Word test, Digit Span) and four tests from the computerized Cogstate Test Battery (Detection Test, Identification Test, One Card Learning Test, One Back Test). The association between a history of child abuse and cognitive performance was examined by multiple linear regression analyses adjusted for covariates.

Results

Principal component analyses of nine cognitive parameters revealed four cognitive domains, i.e., visual-verbal memory, psychomotor speed, working memory and interference control. A history of child abuse was not associated with any of these cognitive domains. However, when looking at the specific types of child abuse separately, a history of physical abuse and emotional neglect were associated with poorer interference control. A history of physical abuse was additionally associated with better visual-verbal memory.

Conclusions

The association between a history of child abuse and cognitive performance differs between the different types of abuse. A history of physical abuse might particularly be a key determinant of cognitive performance in older adults with a depressive, anxiety, or somatic symptom disorder. Future studies on the impact of these disorders on the onset of dementia should take child abuse into account.

Trial registration

ROM-GPS is registered at the Dutch Trial Register (NL6704 at www.trialregister.nl).
Respiratory virus detection in the upper respiratory tract of asymptomatic, community-dwelling older people
Authors: Yasuda Ikkoh , Suzuki Motoi , Maeda Haruka , Terada Mayumi , Sando Eiichiro , Ng Chris Fook Sheng , Otomaru Hirono , Yoshida Lay-Myint , Morimoto Konosuke
Published: April 2022

Background

The prevalence of virus positivity in the upper respiratory tract of asymptomatic community-dwelling older people remains elusive. Our objective was to investigate the prevalence of respiratory virus PCR positivity in asymptomatic community-dwelling older people using saliva samples and nasopharyngeal and oropharyngeal swabs.

Methods

We analyzed 504 community-dwelling adults aged ≥ 65 years who were ambulatory and enrolled in a cross-sectional study conducted from February to December 2018 in Nagasaki city, Japan. Fourteen respiratory viruses were identified in saliva, nasopharyngeal and oropharyngeal samples using multiplex PCR assays.

Results

The prevalences of PCR positivity for rhinovirus, influenza A, enterovirus and any respiratory virus were 12.9% (95% CI: 10.1–16.1%), 7.1% (95% CI: 5.1–9.8%), 6.9% (95% CI: 4.9–9.5%) and 25.2% (95% CI: 21.5–29.2%), respectively. Rhinovirus was detected in 21.5% of subjects, influenza A in 38.9% of subjects, enterovirus in 51.4% of subjects and any virus in 32.3% of subjects using only saliva sampling.

Conclusions

The prevalences of several respiratory viruses were higher than the percentages reported previously in pharyngeal samples from younger adults. Saliva sampling is a potentially useful method for respiratory virus detection in asymptomatic populations.
Contribution of portable obstetric ultrasound service innovation in averting maternal and neonatal morbidities and mortalities at semi-urban health centers of Ethiopia: a retrospective facility-based study
Authors: Abawollo Hailemariam Segni , Tsegaye Zergu Tafesse , Desta Binyam Fekadu , Beshir Ismael Ali , Mengesha Birhan Tenaw , Guteta Asfaw Adugna , Heyi Atrie Fekadu , Mamo Tsega Teferi , Gebremedhin Zenawork Kassa , Damte Heran Demissie , Zelealem Meseret , Argaw Mesele Damte
Published: April 2022

Background

The maternal and neonatal mortalities in Ethiopia are high. To achieve the Sustainable Development Goals, innovations in ultrasound scanning and surveillance activities have been implemented at health centers for over 2 years. This study aims to estimate the contribution of obstetric ultrasound services on averted maternal and neonatal morbidities and mortalities in Ethiopia.

Methods

A retrospective facility-based cross-sectional study design was conducted in 25 selected health centers. Data were extracted from prenatal ultrasound registers. SPSS version 25 was used for analysis. To claim statistically significant relationship among sartorial variables, a chi-square test was analyzed and P < 0.05 was the cut-off point.

Results

Over the 2 years, 12,975 pregnant women were scanned and 52.8% of them were residing in rural areas. Abnormal ultrasound was reported in 12.7% and 98.4% of them were referred for confirmation of diagnosis and treatment. The ultrasound service has contributed to the prevention of 1,970 maternal and 19.05 neonatal morbidities and mortalities per 100,000 and 1,000 live births respectively. The averted morbidities and mortalities showed a statistically significant difference among women residing in rural and semi-urban areas, X,2 df (10) = 24.07, P = 0. 007 and X,2 df (5) = 20.87. P = 0.00, 1 respectively.

Conclusion

After availing the appropriate ultrasound machines with essential supplies and capacitating mid-level providers, significant number of high-risk pregnant women were identified on time and managed or referred to health facilities with safe delivery services. Therefore, scaling-up limited obstetric ultrasound services in similar setups will contribute to achieving the Sustainable Development Goals by 2030. It is recommended to enhance community awareness for improved utilization of ultrasound services by pregnant women before the 24th week of gestational age.
Prevalence and psychosocial factors associated with serious injuries among in-school adolescents in eight sub-Saharan African countries
Authors: Aboagye Richard Gyan , Mireku Dickson Okoree , Nsiah John Jackson , Ahinkorah Bright Opoku , Frimpong James Boadu , Hagan John Elvis , Abodey Eric , Seidu Abdul- Aziz
Published: April 2022

Background

Injury is one of the major causes of death and illness among children and adolescents worldwide. We sought to investigate the prevalence of serious injury and its associated factors among in-school adolescents in eight countries in sub-Saharan Africa.

Methods

A sample of 14,967 in-school adolescents was drawn from the Global School-based Student Health Surveys conducted from 2012 to 2017 in eight sub-Saharan African countries. Data were collected using self-administered structured questionnaires. The prevalence of serious injuries was calculated using proportions while multivariable binary logistic regression analysis was carried out to determine the factors associated with serious injuries.

Results

Approximately 45% of in-school adolescents had experienced serious injuries during the past 12 months to the survey in the eight sub-Saharan African countries, with variations from 32.3% in Mauritius to 68.2% in Liberia. Adolescents who experienced bullying [aOR = 2.37, CI = 2.10, 2.68], those who engaged in physical fight [aOR = 2.14, CI = [1.87, 2.44], those who experienced an attack [aOR = 1.96, CI = [1.73, 2.22], those who felt anxious [aOR = 1.47, CI = 1.22,1.77], those who attempted suicide [aOR = 1.38, CI = 1.14, 1.65], truants [aOR = 1.33, CI = [1.17,1.51], current tobacco users [aOR = 1.42, CI = [1.01, 2.01] and current marijuana users [aOR = 1.78, CI = 1.08, 2.93] had higher odds of experiencing serious injuries. However, those whose parents or guardians respected their privacy had lower odds of experiencing serious injuries [aOR =0.78, CI = [0.68, 0.88] compared to those whose parents or guardians did not respect their privacy.

Conclusion

A relatively high prevalence of serious injuries among in-school adolescents was identified in the eight sub-Saharan African countries studied. Programs and interventions that target the reduction of injuries in educational institutions should take a keen interest in the factors identified in this study. To deal with injury victims, first aid services should be provided in school settings.
Subsequent ipsi- and contralateral femoral fractures after intramedullary nailing of a trochanteric or subtrochanteric fracture: a cohort study on 2012 patients
Authors: Grønhaug Kirsten Marie Larsen , Dybvik Eva , Gjertsen Jan-Erik , Samuelsson Kristian , Östman Bengt
Published: April 2022

Background

The literature is inconclusive as to whether an intramedullary nail changes the distribution of a subsequent ipsi- or contralateral fracture of the femur. We have compared the incidence, localisation, and fracture pattern of subsequent femoral fractures after intramedullary nailing of trochanteric or subtrochanteric fractures in patients without previous implants in either femur at the time of surgery.

Methods

Retrospective analysis was performed of a two-centre cohort of 2012 patients treated with a short or long intramedullary nail for the management of trochanteric or subtrochanteric fracture between January 2005 and December 2018. Subsequent presentations with ipsi- and contralateral femoral fractures were documented. Only patients with no previous femoral surgery performed, other than the index nailing were followed. Odds ratios (ORs) for subsequent femoral fracture were calculated using robust variance estimates in logistic regression.

Results

The mean age of the cohort was 82.4 years and 72.1% were female. The total number of patients presenting with subsequent femoral fractures was 299 (14.9%). The number of patients presenting with subsequent ipsilateral and contralateral femoral fractures was 51 (2.5%) and 248 (12.3%) respectively (OR 5.0; CI 3.7–6.9). Twenty-six (8.7%) of all subsequent femoral fractures occured in the ipsilateral shaft, 14 (4.7%) in the ipsilateral metaphyseal area, one (0.33%) in the contralateral shaft, and three (1.0%) in the contralateral metaphysis (OR 10; CI 3.6–29).

Conclusion

An intramedullary nail significantly changes the fracture pattern in the event of a second low-energy trauma, reducing the risk of subsequent proximal ipsilateral femoral fractures and increasing the risk of subsequent ipsilateral femoral fractures in the shaft and distal metaphyseal area compared with the native contralateral femur.
Prospective evaluation of social risks, physical function, and cognitive function in prediction of non-elective rehospitalization and post-discharge mortality
Authors: Clancy Heather A. , Zhu Zheng , Gordon Nancy P. , Kipnis Patricia , Liu Vincent X. , Escobar Gabriel J.
Published: April 2022

Background

Increasing evidence suggests that social factors and problems with physical and cognitive function may contribute to patients’ rehospitalization risk. Understanding a patient’s readmission risk may help healthcare providers develop tailored treatment and post-discharge care plans to reduce readmission and mortality. This study aimed to evaluate whether including patient-reported data on social factors; cognitive status; and physical function improves on a predictive model based on electronic health record (EHR) data alone.

Methods

We conducted a prospective study of 1,547 hospitalized adult patients in 3 Kaiser Permanente Northern California hospitals. The main outcomes were non-elective rehospitalization or death within 30 days post-discharge. Exposures included patient-reported social factors and cognitive and physical function (obtained in a pre-discharge interview) and EHR–derived data for comorbidity burden, acute physiology, care directives, prior utilization, and hospital length of stay. We performed bivariate comparisons using Chi-square, t-tests, and Wilcoxon rank-sum tests and assessed correlations between continuous variables using Spearman’s rho statistic. For all models, the results reported were obtained after fivefold cross validation.

Results

The 1,547 adult patients interviewed were younger (age, p = 0.03) and sicker (COPS2, p < 0.0001) than the rest of the hospitalized population. Of the 6 patient-reported social factors measured, 3 (not living with a spouse/partner, transportation difficulties, health or disability-related limitations in daily activities) were significantly associated (p < 0.05) with the main outcomes, while 3 (living situation concerns, problems with food availability, financial problems) were not. Patient-reported cognitive (p = 0.027) and physical function (p = 0.01) were significantly lower in patients with the main outcomes. None of the patient-reported variables, singly or in combination, improved predictive performance of a model that included acute physiology and longitudinal comorbidity burden (area under the receiver operator characteristic curve was 0.716 for both the EHR model and maximal performance of a random forest model including all predictors).

Conclusions

In this insured population, incorporating patient-reported social factors and measures of cognitive and physical function did not improve performance of an EHR-based model predicting 30-day non-elective rehospitalization or mortality. While incorporating patient-reported social and functional status data did not improve ability to predict these outcomes, such data may still be important for improving patient outcomes.
Importation and distribution of unregistered medicines in the public sector: similarities, differences, and shared challenges among Southern African Development Community (SADC) countries
Authors: Nyika Admire , Ngara Bernard , Mutingwende Isaac , Gwaza Luther
Published: April 2022

Background

The purpose of the study was to assess the requirements for approval of the importation of unregistered medicines for use in the public sector in the Southern African Development Community (SADC) countries.

Methods

The study reviewed the legal provisions and requirements to be fulfilled when importing unregistered medicines for the public sector in SADC countries relative to two comparators drawn from countries with stringent regulatory systems through extant document analysis. The relative implementation index score was calculated and used to measure the level of implementing legal provisions and requirements to be fulfilled. Analysis was performed using the STATA software package.

Results

Approximately 13 out of 16 SADC countries had a relative implementation index below 50%. The aggregated implementation index across all SADC countries was 44%, ranging from 4 to 54%, while the two comparators had a relative implementation index of 81% and 85%, respectively.

Conclusion

Implementing the minimum requirements for importing unregistered medicines for the public sector was deficient compared to the jurisdictions with stringent regulatory systems, and wide implementation gaps also existed within the SADC region.
Impact of prenatal tobacco smoking on infant telomere length trajectory and ADHD symptoms at 18 months: a longitudinal cohort study
Authors: Howell Meghan P. , Jones Christopher W. , Herman Cade A. , Mayne Celia V. , Fernandez Camilo , Theall Katherine P. , Esteves Kyle C. , Drury Stacy S.
Published: April 2022

Background

Prenatal maternal tobacco smoking is a predictor of child attention-deficit/hyperactivity disorder (ADHD) and is associated with offspring telomere length (TL). In this study, we examine the relationship between maternal prenatal smoking, infant TL, and maternal report of early childhood symptoms of ADHD.

Methods

One-hundred and eighty-one mother-infant dyads were followed prospectively for the infant’s first 18 months of life. Prenatal smoking was assessed from maternal report and medical records. TL was measured from infant buccal swab DNA obtained across the first 18 months of life. ADHD symptoms were obtained from maternal report on the Child Behavior Check List. Multiple regression models tested the relation between prenatal smoking and both ADHD symptoms and infant TL. Additional analyses tested whether the change in infant TL influenced the relation between prenatal smoking and ADHD symptoms.

Results

Sixteen percent of mothers reported prenatal smoking. Infant TL at 4, 12, and 18 months of age were correlated. Consistent with previous cross-sectional studies linking shorter offspring TL to maternal prenatal smoking, maternal prenatal smoking predicted greater telomere shortening from four to 18 months of infant age (β = − 5.797, 95% CI [-10.207, -1.386]; p = 0.010). Maternal depression was positively associated with both prenatal smoking (odds ratio (OR): 4.614, 95% CI [1.733, 12.282]; p = 0.002) and child ADHD symptoms (β = 4.713, 95% CI [2.073, 7.354]; p = 0.0006). To prevent confounding, analyses examined the relation between TL, ADHD symptoms, and prenatal smoking only in non-depressed mothers. In non-depressed mothers, infant TL attrition across the first 18 months moderated the relation between smoking and child ADHD.

Conclusions

The findings extend previous studies linking prenatal smoking to shorter infant TL by providing data demonstrating the effect on TL trajectory. The relation between prenatal smoking and early infant ADHD symptoms was moderated by the change in TL. The findings provide novel initial evidence suggesting that TL dynamics are one mechanistic pathway influencing the relation between maternal prenatal smoking and ADHD.
Responses in randomised groups of healthy, adult Labrador retrievers fed grain-free diets with high legume inclusion for 30 days display commonalities with dogs with suspected dilated cardiomyopathy
Authors: Bakke Anne Marie , Wood Joshua , Salt Carina , Allaway David , Gilham Matt , Kuhlman Gail , Bierer Tiffany , Butterwick Richard , O’Flynn Ciaran
Published: April 2022

Early responses in healthy adult dogs fed grain-free diets with high inclusion of split peas (20%) and lentils (40%) that may lead to canine diet-induced dilated cardiomyopathy (DCM) were investigated. To help understand the clinical relevance of the findings, a survey of electronic health records (EHR) was conducted of dogs with and without suspected DCM for comparison. Control and Test diets were fed to Labrador retriever dogs for 30 days (n = 5 and 6, respectively). Blood and urine samples collected at baseline and days 3, 14 and 28/30 were analyzed for hematology, clinical biochemistry and taurine concentrations. The EHRs of dogs at Banfield® Pet Hospitals in the 2-year period 2018-2019 were surveyed, revealing 420 dogs diagnosed with DCM, which were compared with 420 breed, gender and age-matched healthy control dogs. Compared to baseline values, feeding the Test diet for 28 days caused progressive, significant (p < 0.001) decreases in red blood cell counts (RBC), hematocrit and total hemoglobin by 7.7, 8.3 and 6.3%, respectively, and a 41.8% increase in plasma inorganic phosphate. Commonalities in these parameters were observed in clinical DCM cases. Regarding taurine status, Test dogs transiently increased whole-blood (23.4%) and plasma (47.7%) concentrations on day 14, while taurine:creatinine ratio in fresh urine and taurine in pooled urine were reduced by 77 and 78%, respectively, on day 28/30. Thus grain-free, legume-rich Test diets caused reduced RBC and hyperphosphatemia, findings also indicated in dogs with suspected DCM. Changes in taurine metabolism were indicated. The data will aid in generating hypotheses for future studies.
Mechanisms underlying the blood pressure lowering effects of dapagliflozin, exenatide, and their combination in people with type 2 diabetes: a secondary analysis of a randomized trial
Authors: van Ruiten Charlotte C. , Smits Mark M. , Kok Megan D. , Serné Erik H. , van Raalte Daniël H. , Kramer Mark H. H. , Nieuwdorp Max , IJzerman Richard G.
Published: April 2022

Background

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) lower blood pressure (BP). When SGLT2i and GLP-1RA are combined, synergistic effects on BP have been observed. The mechanisms underlying these BP reductions are incompletely understood. The aim of this study was to assess the mechanisms underlying the BP reduction with the SGLT2i dapagliflozin, GLP-1RA exenatide, and dapagliflozin-exenatide compared with placebo in people with obesity and type 2 diabetes.

Methods

Sixty-six people with type 2 diabetes were randomized to 16 weeks of dapagliflozin 10 mg/day, exenatide 10 µg twice daily, dapagliflozin-exenatide, or placebo treatment. The effect of treatments on estimates of: (1) plasma volume (calculated by Strauss formula, bioimpedance spectroscopy, hematocrit, (2) autonomic nervous system activity (heart rate variability), (3) arterial stiffness (pulse wave applanometry), (4) systemic hemodynamic parameters including peripheral vascular resistance, cardiac output and stroke volume (all derived from non-invasively systemic hemodynamic monitoring), and (5) natriuresis (24-hour urine collection) were assessed after 10 days and 16 weeks of treatment.

Results

After 10 days, dapagliflozin reduced systolic BP (SBP) by − 4.7 mmHg, and reduced plasma volume. After 16 weeks, dapagliflozin reduced SBP by − 4.4 mmHg, and reduced sympathetic nervous system (SNS) activity. Exenatide had no effect on SBP, but reduced parasympathetic nervous system activity after 10 days and 16 weeks. After 10 days, dapagliflozin-exenatide reduced SBP by − 4.2 mmHg, and reduced plasma volume. After 16 weeks, dapagliflozin-exenatide reduced SBP by − 6.8 mmHg, and the reduction in plasma volume was still observed, but SNS activity was unaffected.

Conclusions

The dapagliflozin-induced plasma volume contraction may contribute to the initial SBP reduction, while a reduction in SNS activity may contribute to the persistent SBP reduction. Dapagliflozin-exenatide resulted in the largest decrease in SBP. The effect on plasma volume was comparable to dapagliflozin monotherapy, and SNS activity was not reduced, therefore other mechanisms are likely to contribute to the blood pressure lowering effect of this combination, which need further investigation.

Trial registration Clinicaltrials.gov, NCT03361098.
Sodium and potassium intakes and adiposity among Iranian pre-adolescents and adolescents: a cross-sectional study
Authors: Golpour-Hamedani Sahar , Rafie Nahid , Pourmasoumi Makan , Morteza Safavi Sayyed , Mohammadifard Noushin
Published: April 2022

Background

High sodium and low potassium intakes are associated with the early development of chronic diseases (e.g., hypertension, obesity). Taking into account the limited data on sodium and potassium intakes by 24-h excretion in urine in pre-adolescents and adolescents, we wished to determine baseline salt intake in Iranian subjects aged 11–18 years.

Methods

This was an observational study involving 374 pre-adolescents and adolescents (154 boys and 220 girls). Sodium and potassium intakes were ascertained by measuring sodium and potassium excretion in urine over 24 h. Creatinine level was used to validate the completeness of the urine collections. The association between sodium and potassium intake and adiposity was determined based on body fat percentage.

Results

The mean 24-h urine sodium concentration was 3130 ± 2200 mg/day, equal to 7.961 ± 5.596 g/day salt intake. Approximately half of the study participants exceeded the upper limit of Na intake. The mean potassium intake was estimated 1480 ± 1050 mg/day. There was a positive association between urinary sodium excretion and adiposity in crude (OR 1.79; 95% CI: 1.08—2.74) and full adjusted model (OR: 3.15; 95% CI: 2.28–4.63). Also, in subsample analysis, there was a positive correlation between urinary sodium and adiposity in both pre-adolescents (OR: 2.71; 95% CI: 2.29—3.93) and adolescents (OR: 3.55; 95% CI: 2.17—4.74). However, no significant association was found between 24-h urinary potassium and adiposity.

Conclusion

Sodium intake, as estimated by 24-h urinary excretion, was higher than recommended and it was positively associated with adiposity. Also, this study reported low compliance of potassium intake recommendations in 11–18 years’ Iranian pre-adolescents and adolescents. Health promotion interventions are needed in order to broaden public awareness of high sodium intake and potassium inadequacy to reduce chronic diseases.
The shifting role of the cerebellum in executive, emotional and social processing across the lifespan
Authors: Beuriat Pierre-Aurélien , Cristofori Irene , Gordon Barry , Grafman Jordan
Published: April 2022

The cerebellum’s anatomical and functional organization and network interactions between the cerebellum and the cerebral cortex and subcortical structures are dynamic across the lifespan. Executive, emotional and social (EES) functions have likewise evolved during human development from contributing to primitive behaviors during infancy and childhood to being able to modulate complex actions in adults. In this review, we address how the importance of the cerebellum in the processing of EES functions might change across development. This evolution is driven by the macroscopic and microscopic modifications of the cerebellum that are occurring during development including its increasing connectivity with distant supra-tentorial cortical and sub-cortical regions. As a result of anatomical and functional changes, neuroimaging and clinical data indicate that the importance of the role of the cerebellum in human EES-related networks shifts from being crucial in newborns and young children to being only supportive later in life. In early life, given the immaturity of cortically mediated EES functions, EES functions and motor control and perception are more closely interrelated. At that time, the cerebellum due to its important role in motor control and sequencing makes EES functions more reliant on these computational properties that compute spatial distance, motor intent, and assist in the execution of sequences of behavior related to their developing EES expression. As the cortical brain matures, EES functions and decisions become less dependent upon these aspects of motor behavior and more dependent upon high-order cognitive and social conceptual processes. At that time, the cerebellum assumes a supportive role in these EES-related behaviors by computing their motor and sequential features. We suspect that this evolving role of the cerebellum has complicated the interpretation of its contribution to EES computational demands.
Reconstructing virtual large slides can improve the accuracy and consistency of tumor bed evaluation for breast cancer after neoadjuvant therapy
Authors: Han Dandan , Liao Jun , Zhang Meng , Qin Chenchen , Han Mengxue , Wu Chun , Li Jinze , Yao Jianhua , Liu Yueping
Published: April 2022

Background

To explore whether the “WSI Stitcher”, a program we developed for reconstructing virtual large slide through whole slide imaging fragments stitching, can improve the efficiency and consistency of pathologists in evaluating the tumor bed after neoadjuvant treatment of breast cancer compared with the conventional methods through stack splicing of physical slides.

Methods

This study analyzed the advantages of using software-assisted methods to evaluate the tumor bed after neoadjuvant treatment of breast cancer. This new method is to use “WSI Stitcher” to stitch all the WSI fragments together to reconstruct a virtual large slide and evaluate the tumor bed with the help of the built-in ruler and tumor proportion calculation functions.

Results

Compared with the conventional method, the evaluation time of the software-assisted method was shortened by 35%(P < 0.001). In the process of tumor bed assessment after neoadjuvant treatment of breast cancer, the software-assisted method has higher intraclass correlation coefficient when measuring the length (0.994 versus 0.934), width (0.992 versus 0.927), percentage of residual tumor cells (0.947 versus 0.878), percentage of carcinoma in situ (0.983 versus 0.881) and RCB index(0.997 versus 0.772). The software-assisted method has higher kappa values when evaluating tumor staging(0.901 versus 0.687) and RCB grading (0.963 versus 0.857).

Conclusion

The “WSI Stitcher” is an effective tool to help pathologists with the assessment of breast cancer after neoadjuvant treatment.