bluuebunny/crossref_metadata_2025 huggingface dataset:
Micro-MRI improves the accuracy of clinical diagnosis in cerebral small vessel disease
Authors: Ishikawa Hidehiro , Niwa Atsushi , Kato Shinya , Ii Yuichiro , Shindo Akihiro , Matsuura Keita , Nishiguchi Yamato , Tamura Asako , Taniguchi Akira , Maeda Masayuki , Hashizume Yoshio , Tomimoto Hidekazu
Published: April 2021

Even with postmortem pathological examination, only limited information is provided of the foci of in vivo clinical information. Cerebral small vessel disease, which is associated with ageing, dementia and stroke, highlights the difficulty in arriving at a definitive diagnosis of the lesions detected on in vivo radiological examination. We performed a radiological−pathological comparative study using ex vivo MRI to examine small cerebral lesions. Four patients with small vessel disease lesions detected on in vivo MRI were studied. Exact pathological findings of in vivo MRI-detected lesions were revealed. The ischaemic lesion after 17 days from onset showed positivity for peroxiredoxin, cluster of differentiation 204 and glial fibrillary acidic protein, indicating sterile inflammation and neuroprotective reaction. Cortical microinfarcts beneath the cortical superficial siderosis were associated with inflammation from the superficial layer in a patient with cerebral amyloid angiopathy; in this patient, a bilinear track-like appearance of the cortical superficial siderosis on the ex vivo MRI was compatible with iron deposition on the pia matter and within cortical layers II–III. An in vivo MRI-detected cerebral microbleed was revealed to be heterogeneous. An in vivo MRI-detected cerebral microbleed was revealed to be a venous angioma. Furthermore, a neuropathologically confirmed embolic cerebral microbleed was firstly detected using this method. Our results suggest that in vivo MRI-detected lobar cerebral microbleeds can be caused by non-cerebral amyloid angiopathy aetiologies, such as microembolism and venous angioma. Venous angioma and embolic microbleeds may mimic cerebral amyloid angiopathy markers on in vivo MRI. To clarify the clinical importance of these lesions, we should investigate their rate and frequency in a large cohort of healthy individuals and patients with cardiac risk factors. Thus, we provide evidence that ex vivo micro-MRI improves the clinical diagnosis of small vessel diseases.
Determination of Organophosphorus Pesticides Using Solid-Phase Extraction Followed by Gas Chromatography–Mass Spectrometry
Authors: Sun Peng , Zheng Shusheng , Yan Rui , Lian Yongfu
Published: April 2021

In this study, a method was developed for determination of three organophosphorus pesticides (OPPs) using graphene aerogel solid-phase extraction (SPE) combined with gas chromatography–mass spectrometry (GC–MS). The experimental results showed that the target analytes could be extracted on packed SPE cartridges and then eluted with tetrahydrofuran. The final sample solution was analyzed by GC–MS, which demonstrated good linearity between 0.5 and 500 μg L−1 with a correlation coefficient (r) of 0.9991–0.9998. The limits of detection (S/N = 3) and the limits of quantification (S/N = 10) for the three OPPs ranged from 0.38 to 0.82 μg L−1 and 1.32 to 2.75 μg L−1, respectively. The accuracy of the proposed method was evaluated by measuring the recovery of the spiked samples, which ranged from 91.2 to 103.7%, with relative standard deviations of 2.1–7.2%. This method was successfully applied for the determination of the target analytes in water samples taken from tap, wetlands and canal water.
Ultra-sensitive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antigen Detection for the Diagnosis of Coronavirus Disease 2019 (COVID-19) in Upper Respiratory Samples
Authors: Wang Hannah , Hogan Catherine A , Verghese Michelle , Solis Daniel , Sibai Mamdouh , Huang ChunHong , Zehnder James , Sahoo Malaya K , Pinsky Benjamin A
Published: April 2021

An ultra-sensitive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid antigen assay (S-PLEX, MesoScale Diagnostics) was evaluated in 250 retrospective and 200 prospective upper respiratory specimens. In samples with cycle threshold <35, there was 95%–98% positive and 93%–96% negative percent agreement with reverse transcription-polymerase chain reaction. S-PLEX may provide a high-throughput alternative to nucleic acid-based testing for coronavirus disease 2019 (COVID-19) diagnosis.
The Effect of In-Person Primary and Secondary School Instruction on County-Level Severe Acute Respiratory Syndrome Coronavirus 2 Spread in Indiana
Authors: Bosslet Gabriel T , Pollak Micah , Jang Jeong Hoon , Roll Rebekah , Sperling Mark , Khan Babar
Published: April 2021

Background

Our goal was to determine the county-level effect of in-person primary and secondary school reopening on daily cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Indiana.

Methods

In this county-level, population-based study, we used a panel data regression analysis of the proportion of in-person learning to evaluate an association with community-wide daily new SARS-CoV-2 cases. The study period was 12 July 2020–6 October 2020. We included 73 of 92 (79.3%) Indiana counties in the analysis, accounting for 85.7% of school corporations and 90.6% of student enrollment statewide. The primary exposure was the proportion of students returning to in-person instruction. The primary outcome was the daily new SARS-CoV-2 cases per 100 000 residents at the county level.

Results

There is a statistically significant relationship between the proportion of students attending K-12 schools in-person and the county level daily cases of SARS-CoV-2 28 days later. For all ages, the coefficient of interest (β) is estimated at 3.36 (95% confidence interval, 1.91 to 4.81; P < .001). This coefficient represents the effect of a change in the proportion of students attending in-person on new daily cases 28 days later. For example, a 10 percentage point increase in K-12 students attending school in-person is associated with a daily increase in SARS-CoV-2 cases in the county equal to 0.336 cases/100 000 residents of all ages.

Conclusions

In-person primary and secondary school is associated with a statistically significant but proportionally small increase in the spread of SARS-CoV-2 cases.
Post-translational modifications in proteins: resources, tools and prediction methods
Authors: Ramazi Shahin , Zahiri Javad
Published: April 2021

Posttranslational modifications (PTMs) refer to amino acid side chain modification in some proteins after their biosynthesis. There are more than 400 different types of PTMs affecting many aspects of protein functions. Such modifications happen as crucial molecular regulatory mechanisms to regulate diverse cellular processes. These processes have a significant impact on the structure and function of proteins. Disruption in PTMs can lead to the dysfunction of vital biological processes and hence to various diseases. High-throughput experimental methods for discovery of PTMs are very laborious and time-consuming. Therefore, there is an urgent need for computational methods and powerful tools to predict PTMs. There are vast amounts of PTMs data, which are publicly accessible through many online databases. In this survey, we comprehensively reviewed the major online databases and related tools. The current challenges of computational methods were reviewed in detail as well.
Selective perimeter lockdowns in Madrid: a way to bend the COVID-19 curve?
Authors: Fontán-Vela Mario , Gullón Pedro , Padilla-Bernáldez Javier
Published: April 2021

Lockdowns have been widespread used to limit social interaction and bend the epidemic curve. However, their intensity and geographical delimitation have been variable across different countries. Madrid (Spain) implemented perimeter lockdowns in September with the purpose of bending the COVID-19 curve. In this article, we compared, using join point regressions, the evolution of COVID-19 cases in those areas where this intervention was implemented and those where it was not. According to our analysis, the decrease in the epidemic curve started before the impact of the perimeter lockdown could be reflected.
‘I was scared I will end up in another abortion’: a mixed-methods study assessing the impact of COVID-19 pandemic and lockdown on the antenatal care of pregnant women in Puducherry, South India
Authors: Ulaganeethi Revathi , Dorairajan Gowri , Ramaswamy Gomathi , Thekkur Pruthu , Olickal Jeby Jose , Rajkumari Nonika , Kumar Saya Ganesh
Published: April 2021

Background

As a mitigation measure for COVID-19 pandemic, lockdown was implemented in India for a period of 2 months (24 March–31 May 2020). Disruption in antenatal care (ANC) provisions during lockdown is expected due to diversion of public health facilities on pandemic.

Objective

To assess the proportion of pregnant women who had not completed the ideal number of antenatal visits, availability of iron–folic acid (IFA) supplements and challenges in availing health services during the period of lockdown.

Methods

A concurrent mixed-methods study was conducted among pregnant women in Puducherry, India. Information on obstetric characteristics and details regarding antenatal visits were collected through telephonic interviews. In-depth interviews were conducted to understand the perceived challenges in availing health services during the lockdown period.

Results

Out of 150 pregnant women, 62 [41.3%; 95% confidence interval (CI) 33.6–49.3] did not complete the ideal number of visits and 61 (40.7%, 95% CI 32.7–49.0) developed health problems. Out of 44 women who received medical care for health problems, 11 (25%) used teleconsultation. Of all the women, 13 (8.7%, 95% CI 4.9–14.0) had not taken the IFA supplements as prescribed by the health provider. Economic hardship, restricted mobility, lack of information about the health system changes and psychological stress due to the fear of COVID were the challenges in accessing care.

Conclusions

Two out of five pregnant women did not complete the ideal number of visits and developed health problems during the lockdown period.
Upper airway cough syndrome may be the main cause of chronic cough in Japan: a cohort study
Authors: Yasuda Kimihiko
Published: April 2021

Background

Upper airway cough syndrome (UACS) is generally considered a common cause of chronic cough but remains poorly recognised in Japan.

Objective

This study aimed to assess whether UACS was a common cause of chronic cough in Japan, as is true in other countries. Interview and examination items were evaluated for their potential use in UACS diagnosis.

Methods

All patients with chronic cough were preliminarily diagnosed with bronchial asthma, UACS, gastroesophageal reflux disease, or postinfectious prolonged cough, based on interviews and examinations. Treatment centred on nasal steroids was administered to the UACS group and standard treatment to the other groups. The observation period lasted 4 weeks. The subjective cough score at first diagnosis was set at 10, and the final diagnosis was made based on the treatment administered at the time the cough score had decreased to ≤2. The associations between the presence or absence of UACS and interview and examination items were statistically evaluated.

Results

Among 230 patients with chronic cough, 146 were diagnosed with UACS-only. Multivariate logistic regression revealed that the assessment items ‘awareness of mucus accumulating in the back of the throat’, ‘presence of abnormal echography findings’, ‘absence of associated coughing when exercising’ and ‘presence of coughing persisting after onset’ were significantly correlated with the presence or absence of UACS (p < 0.05).

Conclusions

UACS may be the most common cause of chronic cough in Japan and may be effectively treated with nasal corticosteroids. Diagnosing UACS might be possible by selecting appropriate interview and examination items.
Isolation, identification and some characteristics of two lytic bacteriophages against Salmonella enterica serovar Paratyphi B and S. enterica serovar Typhimurium from various food sources
Authors: Sabzali Somaieh , Bouzari Majid
Published: April 2021

Salmonellosis is an important worldwide food-borne disease. Increasing resistance to Salmonella spp. has been reported in recent years, and now the prevalence of multidrug-resistant Salmonella spp. is a worldwide problem. This necessitates alternative approaches like phage therapy. This study aimed to isolate bacteriophages specific for Salmonella enterica serovar Paratyphi B and S. enterica serovar Typhimurium isolated from different sources (chicken meat, beef and eggshells). The antibiotic resistance profiles of the bacteria were determined by phenotypic and genotypic methods. The prevalence of extended-spectrum β-lactamase genes was examined by polymerase chain reaction. In total, 75% of the isolated Salmonella strains were resistant to tetracycline, whereas 70% of them were resistant to azithromycin. All of the isolates from beef were resistant to nalidixic acid. The most common extended-spectrum β-lactamase genes among the isolates were blaSHV (15%) followed by blaTEM (10%) and blaCTX (5%). Two specific bacteriophages were isolated and characterized. The host range for vB_SparS-ui was Salmonella Paratyphi B, S. enterica serovar Paratyphi A and S. enterica, while that for vB_StyS-sam phage was Salmonella Typhimurium and S. enterica serovar Enteritidis. The characteristics of the isolated phages indicate that they are proper candidates to be used to control some foodstuff contaminations and also phage therapy of infected animals.
Inactivation of the Neurospora crassa gene encoding the mitochondrial protein import receptor MOM19 by the technique of "sheltered RIP".
Authors: Harkness T A , Metzenberg R L , Schneider H , Lill R , Neupert W , Nargang F E
Published: April 2021

We have used a technique referred to as "sheltered RIP" (repeat induced point mutation) to create mutants of the mom-19 gene of Neurospora crassa, which encodes an import receptor for nuclear encoded mitochondrial precursor proteins. Sheltered RIP permits the isolation of a mutant gene in one nucleus, even if that gene is essential for the survival of the organism, by sheltering the nucleus carrying the mutant gene in a heterokaryon with an unaffected nucleus. Furthermore, the nucleus harboring the RIPed gene contains a selectable marker so that it is possible to shift nuclear ratios in the heterokaryons to a state in which the nucleus containing the RIPed gene predominates in cultures grown under selective conditions. This results in a condition where the target gene product should be present at very suboptimal levels and allows the study of the mutant phenotype. One allele of mom-19 generated by this method contains 44 transitions resulting in 18 amino acid substitutions. When the heterokaryon containing this allele was grown under conditions favoring the RIPed nucleus, no MOM19 protein was detectable in the mitochondria of the strain. Homokaryotic strains containing the RIPed allele exhibit a complex and extremely slow growth phenotype suggesting that the product of the mom-19 gene is important in N. crassa.
Genetic analysis of male reproductive contributions in Chamaelirium luteum (L.) gray (Liliaceae).
Authors: Smouse P E , Meagher T R
Published: April 2021

Genealogical analysis is a powerful tool for analysis of reproductive performance in both natural and captive populations, but assignment of paternity has always been a stumbling block for this sort of work. Statistical methods for determining paternity have undergone several phases of development, ranging from straightforward genetic exclusion to assignment of paternity based on genetic likelihood criteria. In the present study, we present a genetic likelihood-based iterative procedure for fractional allocation of paternity within a progeny pool and apply this method to a population of Chamaelirium luteum, a dioecious member of the Liliaceae. Results from this analysis clearly demonstrate that different males make unequal contributions to the overall progeny pool, with many males contributing essentially nothing to the next generation. Furthermore, the distribution of paternal success among males shows a highly significant departure from (Poisson) randomness. The results from the present analysis were compared with earlier results obtained from the same data set, using likelihood-based categorical paternity assignments. The general biological pattern revealed by the two analyses is the same, but the estimates of reproductive success are only modestly (though significantly) correlated. The iterative procedure makes more complete use of the data and generates a more sharply resolved distribution of male reproductive success.
Possible role of natural selection in the formation of tandem-repetitive noncoding DNA.
Authors: Stephan W , Cho S
Published: April 2021

A simulation model of sequence-dependent amplification, unequal crossing over and mutation is analyzed. This model predicts the spontaneous formation of tandem-repetitive patterns of noncoding DNA from arbitrary sequences for a wide range of parameter values. Natural selection is found to play an essential role in this self-organizing process. Natural selection which is modeled as a mechanism for controlling the length of a nucleotide string but not the sequence itself favors the formation of tandem-repetitive structures. Two measures of sequence heterogeneity, inter-repeat variability and repeat length, are analyzed in detail. For fixed mutation rate, both inter-repeat variability and repeat length are found to increase with decreasing rates of (unequal) crossing over. The results are compared with data on micro-, mini- and satellite DNAs. The properties of minisatellites and satellite DNAs resemble the simulated structures very closely. This suggests that unequal crossing over is a dominant long-range ordering force which keeps these arrays homogeneous even in regions of very low recombination rates, such as at satellite DNA loci. Our analysis also indicates that in regions of low rates of (unequal) crossing over, inter-repeat variability is maintained at a low level at the expense of much larger repeat units (multimeric repeats), which are characteristic of satellite DNA. In contrast, the microsatellite data do not fit the proposed model well, suggesting that unequal crossing over does not act on these very short tandem arrays.
Drosophila genetics in the classroom.
Authors: Sofer W , Tompkins L
Published: April 2021

Drosophila has long been useful for demonstrating the principles of classical Mendelian genetics in the classroom. In recent years, the organism has also helped students understand biochemical and behavioral genetics. In this connection, this article describes the development of a set of integrated laboratory exercises and descriptive materials--a laboratory module--in biochemical genetics for use by high-school students. The module focuses on the Adh gene and its product, the alcohol dehydrogenase enzyme. Among other activities, students using the module get to measure alcohol tolerance and to assay alcohol dehydrogenase activity in Adh-negative and -positive flies. To effectively present the module in the classroom, teachers attend a month-long Dissemination Institute in the summer. During this period, they learn about other research activities that can be adapted for classroom use. One such activity that has proved popular with teachers and students utilizes Drosophila to introduce some of the concepts of behavioral genetics to the high-school student. By establishing closer interactions between high-school educators and research scientists, the gulf between the two communities can begin to be bridged. It is anticipated that the result of a closer relationship will be that the excitement and creativity of science will be more effectively conveyed to students.
The SPT10 and SPT21 genes of Saccharomyces cerevisiae.
Authors: Natsoulis G , Winston F , Boeke J D
Published: April 2021

Mutations in the SPT10 and SPT21 genes were originally isolated as suppressors of Ty and LTR (delta) insertion mutations in Saccharomyces cerevisiae, and the genes were shown to be required for normal transcription at a number of loci in yeast. Now we have cloned, sequenced, mapped and mutagenized SPT10 and SPT21. Since the spt10 mutation used to clone SPT10 resulted in very poor transformation efficiency, a novel method making use of the kar1-1 mutation was used. Neither SPT gene is essential for growth, and constructed null alleles cause phenotypes similar to those caused by spontaneous mutations in the genes. spt10 null alleles are strong suppressor mutations and cause extremely slow growth. Certain spt10 spontaneous alleles are good suppressors but have a normal growth rate, suggesting that the SPT10 protein may have two distinct functions. An amino acid sequence motif that is similar to the Zn-finger motif was found in SPT10. Mutation of the second Cys residue in this motif resulted in loss of complementation of the suppression phenotype but a normal growth rate. Thus, this motif may reside in a part of the SPT10 protein that is important for transcriptional regulation but not for normal growth. Both the SPT10 and SPT21 proteins are relatively tolerant of large deletions; in both cases deletions of the C-terminus resulted in at least partially functional proteins; also, a large internal deletion in SPT21 was phenotypically wild type.
Association of Pulmonary Function With Cognitive Decline in Older Adults: A Nationwide Longitudinal Study in China
Authors: Shang Xianwen , Scott David , Chan Roseanne Kimberley , Zhang Lei , He Mingguang
Published: April 2021

This study aimed to examine whether pulmonary function and cognition are independently associated at multiple time points. We included 8264 participants (49.9% women) aged 50–94 years at baseline from the China Health and Retirement Longitudinal Study in our analysis. Participants were enrolled in 2011 and followed up in 2013 and 2015. Cognitive function was assessed through a face-to-face interview in each survey. Pulmonary function was assessed via peak expiratory flow. Pulmonary function and cognitive function decreased significantly with age in both genders. Individuals in quintile 5 of pulmonary function had a relative increase in immediate memory (β [95% CI]: 0.19 [0.09, 0.30]) and delayed memory (0.16 [0.04, 0.28]) during follow-up compared with those in quintile 1. In the repeated-measures analysis, each standard deviation increment of pulmonary function was associated with a 0.44 (95% CI: 0.34, 0.53), 0.12 (0.09, 0.15), 0.12 (0.08, 0.16), 0.08 (0.06, 0.11), and 0.10 (0.07, 0.14) higher increase in global cognitive score, immediate memory, delayed memory, orientation, and subtraction calculation, respectively. The inverse association between pulmonary function and cognitive decline during follow-up was more evident in women (p for interaction = .0333), low-educated individuals (p for interaction = .0002), or never smokers (p for interaction = .0412). In conclusion, higher baseline pulmonary function was independently associated with a lower rate of cognitive decline in older adults. The positive association between pulmonary function and cognition was stronger in women, lower-educated individuals, or never smokers.
Cardiometabolic Conditions and All-Cause Dementia Among American Indian and Alaska Native People
Authors: Goins R Turner , Winchester Blythe , Jiang Luohua , Grau Laura , Reid Maggie , Corrada Maria M , Manson Spero M , O’Connell Joan
Published: April 2021

Background

Diabetes, hypertension, and cardiovascular disease (CVD) are modifiable lifestyle-related cardiometabolic conditions associated with dementia. Yet, little is known regarding these associations among American Indian and Alaska Native (AI/AN) people. Thus, we examined the association of diabetes, hypertension, and CVD with all-cause dementia among AI/ANs aged 65 years and older.

Method

This was a cross-sectional analysis of the Indian Health Service Improving Health Care Delivery Data Project. Our study population was a 1:1 matched sample of 4 074 AI/ANs aged 65 years and older and Indian Health Service active users during fiscal year 2013. We employed International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes for all-cause dementia, hypertension, and CVD. Diabetes was measured with a validated algorithm to identify adults with diabetes that uses diagnoses, laboratory test results, and medication criteria.

Results

Multivariable analyses revealed that diabetes and CVD were associated with increased odds of all-cause dementia and hypertension was not. Cardiovascular disease types associated with all-cause dementia differed with cerebrovascular disease having the strongest association. Analyses stratified by gender revealed that diabetes and CVD were associated with increased odds of all-cause dementia for women and only CVD was associated with all-cause dementia for men.

Conclusions

Training and support of primary care clinicians, addressing cultural considerations, and ensuring inclusion of AI/ANs in research are steps that could help meet AI/AN people’s needs. Our findings underscore to the importance of improved management and control of diabetes and CVD, which may lead to the prevention of dementia among older AI/ANs.
Sarcopenia and Neuroscience: Learning to Communicate
Authors: Clark Brian C , Carson Richard G
Published: April 2021

In the 1990s and early 2000s, the common definition for sarcopenia was age-related loss of skeletal muscle, and low levels of muscle mass were central to sarcopenia diagnosis. In more recent consensus definitions, however, low muscle strength displaces low muscle mass as a defining feature of sarcopenia. The change stems from growing evidence that muscle weakness is a better predictor of adverse health outcomes (eg, mobility limitations) than muscle mass. This evidence accompanies an emerging recognition that central neural mechanisms are critical determinants of age-related changes in strength and mobility that can occur independently of variations in muscle mass. However, strikingly little practical attention is typically given to the potential role of the central nervous system in the etiology or remediation of sarcopenia (ie, low muscle function). In this article, we provide an overview of some mechanisms that mediate neural regulation of muscle contraction and control, and highlight the specific contributions of neural hypoexcitability, dopaminergic dysfunction, and degradation of functional and structural brain connectivity in relation to sarcopenia. We aim to enhance the lines of communication between the domains of sarcopenia and neuroscience. We believe that appreciation of the neural regulation of muscle contraction and control is fundamental to understanding sarcopenia and to developing targeted therapeutic strategies for its treatment.
Racial Disparities in Cognitive Function Among Middle-Aged and Older Adults: The Roles of Cumulative Stress Exposures Across the Life Course
Authors: Chen Ruijia , Weuve Jennifer , Misra Supriya , Cuevas Adolfo , Kubzansky Laura D , Williams David R
Published: April 2021

Background

Racial disparities in cognitive function are well documented, but factors driving these disparities remain underexplored. This study aims to quantify the extent to which cumulative stress exposures across the life course explain Black–White disparities in executive function and episodic memory in middle-aged and older adults.

Method

Data were drawn from the 2004–2006 wave of the Midlife Development in the United States Study (MIDUS 2) and the MIDUS Refresher study (N = 5,947; 5,262 White and 685 Black). Cumulative stress exposures were assessed by 10 stressor domains (ie, childhood stress, stressful life events in adulthood, financial stress, work psychological stress, work physical stress, work–family conflicts, neighborhood disorder, relationship stress, perceived inequality, and perceived discrimination). Cognitive function was assessed using the Brief Test of Adult Cognition by Telephone. Marginal structural models were used to quantify the proportion of the effect of race/ethnicity status on cognitive function mediated through cumulative stress exposures.

Results

After adjusting for age, sex, and sample, on average, Black participants had lower levels of executive function (difference: −0.83 SD units, 95% CI: −0.91, −0.75) and episodic memory (difference: −0.53 SD units, 95% CI: −0.60, −0.45) scores than White participants. Cumulative stress exposures accounted for 8.4% of the disparity in executive function and 13.2% of the disparity in episodic memory.

Conclusions

Cumulative stress exposures across the life course explained modest proportions of Black–White disparities in cognitive function in this large cross-sectional study.
The health and well-being impacts of a work integration social enterprise from a systems perspective
Authors: Joyce Andrew , Elmes Aurora , Campbell Perri , Moussa Batool , Suchowerska Roksolana , Barraket Jo , Carey Gemma
Published: April 2021

Recent research has drawn upon the social determinants of health (SDH) framework to attempt to systematize the relationship between social enterprise and health. In this article, we adopt a realist evaluation approach to conceptualize social enterprises, and work integration social enterprises in particular, as ‘complex interventions’ that necessarily produce differential health outcomes for their beneficiaries, communities and staff. Drawing upon the findings from four social enterprises involving a range of methods including 93 semi-structured interviews with employees, managers and enterprise partners, together with participant observation, we demonstrate that these health outcomes are influenced by a limitless mix of complex and dynamic interactions between systems, settings, spaces, relationships and organizational and personal factors that cannot be distilled by questions of causality and attribution found in controlled trial designs. Given the increased policy focus on the potential of social enterprises to affect the SDH, this article seeks to respond to evidence gaps about the mechanisms and contexts through which social enterprises promote or constrain health outcomes, and thereby provide greater clarity about how research evidence can be used to support the social enterprise sector and policy development more broadly.
Snord116 Post-transcriptionally Increases Nhlh2 mRNA Stability: Implications for Human Prader-Willi Syndrome
Authors: Kocher Matthew A , Huang Fenix W , Le Erin , Good Deborah J
Published: April 2021

The smallest genomic region causing Prader-Willi Syndrome (PWS) deletes the non-coding RNA SNORD116 cluster; however, the function of SNORD116 remains a mystery. Previous work in the field revealed the tantalizing possibility that expression of NHLH2, a gene previously implicated in both obesity and hypogonadism, was downregulated in PWS patients and differentiated stem cells. In silico RNA: RNA modeling identified several potential interaction domains between SNORD116 and NHLH2 mRNA. One of these interaction domains was highly conserved in most vertebrate NHLH2 mRNAs examined. A construct containing the Nhlh2 mRNA, including its 3’-UTR, linked to a c-myc tag was transfected into a hypothalamic neuron cell line in the presence and absence of exogenously-expressed Snord116. Nhlh2 mRNA expression was upregulated in the presence of Snord116 dependent on the length and type of 3’UTR used on the construct. Furthermore, use of actinomycin D to stop new transcription in N29/2 cells demonstrated that the upregulation occurred through increased stability of the Nhlh2 mRNA in the 45 minutes immediately following transcription. In silico modeling also revealed that a single nucleotide variant (SNV) in the NHLH2 mRNA could reduce the predicted interaction strength of the NHLH2:SNORD116 diad. Indeed, use of an Nhlh2 mRNA construct containing this SNV significantly reduces the ability of Snord116 to increase Nhlh2 mRNA levels. For the first time, these data identify a motif and mechanism for SNORD116-mediated regulation of NHLH2, clarifying the mechanism by which deletion of the SNORD116 snoRNAs locus leads to PWS phenotypes.
Ancient and modern mitogenomes from Central Argentina: new insights into population continuity, temporal depth and migration in South America
Authors: García Angelina , Nores Rodrigo , Motti Josefina M B , Pauro Maia , Luisi Pierre , Bravi Claudio M , Fabra Mariana , Gosling Anna L , Kardailsky Olga , Boocock James , Solé-Morata Neus , Matisoo-Smith Elizabeth A , Comas David , Demarchi Darío A
Published: April 2021

The inverted triangle shape of South America places Argentina territory as a geographical crossroads between the two principal peopling streams that followed either the Pacific or the Atlantic coasts, which could have then merged in Central Argentina (CA). Although the genetic diversity from this region is therefore crucial to decipher past population movements in South America, its characterization has been overlooked so far. We report 92 modern and 22 ancient mitogenomes spanning a temporal range of 5000 years, which were compared with a large set of previously reported data. Leveraging this dataset representative of the mitochondrial diversity of the subcontinent, we investigate the maternal history of CA populations within a wider geographical context. We describe a large number of novel clades within the mitochondrial DNA tree, thus providing new phylogenetic interpretations for South America. We also identify several local clades of great temporal depth with continuity until the present time, which stem directly from the founder haplotypes, suggesting that they originated in the region and expanded from there. Moreover, the presence of lineages characteristic of other South American regions reveals the existence of gene flow to CA. Finally, we report some lineages with discontinuous distribution across the Americas, which suggest the persistence of relic lineages likely linked to the first population arrivals. The present study represents to date the most exhaustive attempt to elaborate a Native American genetic map from modern and ancient complete mitochondrial genomes in Argentina and provides relevant information about the general process of settlement in South America.
Comparison between robot-assisted thoracoscopic surgery and video-assisted thoracoscopic surgery for mediastinal and hilar lymph node dissection in lung cancer surgery
Authors: Haruki Tomohiro , Takagi Yuzo , Kubouchi Yasuaki , Kidokoro Yoshiteru , Nakanishi Atsuyuki , Nozaka Yuji , Oshima Yuki , Matsui Shinji , Nakamura Hiroshige
Published: April 2021

OBJECTIVES

Lymph node dissection (LND) with robot-assisted thoracoscopic surgery (RATS) in lung cancer surgery has not been fully evaluated. The aim of this study was to compare LND surgical results between video-assisted thoracoscopic surgery (VATS) and RATS.

METHODS

We retrospectively compared perioperative parameters, including the incidence of LND-associated complications (chylothorax, recurrent and/or phrenic nerve paralysis and bronchopleural fistula), lymph node (LN) counts and postoperative locoregional recurrence, among 390 patients with primary lung cancer who underwent lobectomy and mediastinal LND by RATS (n = 104) or VATS (n = 286) at our institution.

RESULTS

The median total dissected LN numbers significantly differed between the RATS and the VATS groups (RATS: 18, VATS: 15; P < 0.001). They also significantly differed in right upper zone and hilar (#2R + #4R + #10L) (RATS: 12, VATS: 10; P = 0.002), left lower paratracheal and hilar (#4L + #10L) (RATS: 4, VATS: 3; P = 0.019), aortopulmonary zone (#5 + #6) (RATS: 3, VATS: 2; P = 0.001) and interlobar and lobar (#11 + #12) LNs (RATS: 7, VATS: 6; P = 0.041). The groups did not significantly differ in overall nodal upstaging (P = 0.64), total blood loss (P = 0.69) or incidence of LND-associated complications (P = 0.77).

CONCLUSIONS

In this comparison, it was suggested that more LNs could be dissected using RATS than VATS, especially in bilateral superior mediastinum and hilar regions. Accumulation of more cases and longer observation periods are needed to verify whether RATS can provide the acceptable quality of LND and local control of lung cancer.
The Ross–Konno operation for neonates and infants with severe aortic incompetence following treatment for critical aortic stenosis
Authors: Hebala Muhammed , Rao Vinay , Jaber Osama , Congiu Stefano , Bentham Jamie , Thomson John , van Doorn Carin
Published: April 2021

OBJECTIVES

Aortic valve stenosis in neonates and infants is associated with congestive cardiac failure, and balloon or surgical valvuloplasty provides relief of stenosis. Occasionally severe aortic insufficiency necessitates urgent aortic valve replacement. We reviewed our experience with the Ross–Konno procedure in patients <1 year.

METHODS

Between October 2013 and May 2020, 36 patients underwent balloon (34) or surgical (2) aortic valvuloplasty for aortic stenosis. Six patients subsequently underwent a Ross–Konno procedure. The median age at operation was 55 (27–116) days and weight was 4.25 (2.5–12) kg. All patients were in severe cardiac failure and had a small aortic annulus with Z-score −3.1 (−1 to −4.4).

RESULTS

There were no early or late deaths. At the latest follow-up at 39 (13–60) months, ventricular function had improved in all patients and no patient was on anti-failure medication. On echocardiography, there wasno more than trivial aortic regurgitation and no left ventricular outflow tract obstruction. One patient required right ventricle to pulmonary artery conduit replacement and one patient had homograft stenting.

CONCLUSIONS

Despite the severe preoperative haemodynamic compromise, the urgent Ross–Konno procedure was associated with excellent operative survival and recovery of ventricular function. The need for reintervention to the pulmonary conduit remains a cause for concern.
Total aortic arch replacement using the J-graft open stent graft for distal aortic arch aneurysm: report from two centres in Japan
Authors: Tsutsumi Koji , Ishida Osamu , Yamanaka Nozomu , Hayashi Kanako , Hashizume Kenichi
Published: April 2021

OBJECTIVES

The open-style stent graft technique has been changing the strategy for true distal arch aneurysms extending to the descending aorta. Our mid-term results of surgical repair using a J-graft open stent graft are presented.

METHODS

Between May 2015 and June 2020, 69 patients with a distal arch aneurysm (53 males, median age 74 years) underwent total arch replacement combined with J-graft open stent deployment. All 59 surviving patients were followed for a median follow-up period of 1.8 (0.6–3.6) years.

RESULTS

Antegrade deployment was successfully performed in all patients without any difficulties. The deployed device was securely fixed at the target area, and it initiated thrombus formation. The diameter of the excluded aneurysm was decreased in 54 patients (91.5%) during the follow-up period. There were no type I endoleaks, but there were 3 type II endoleaks; 2 of the 3 type II endoleaks disappeared during the follow-up period. Additional endovascular operations were performed in 3 patients. There were 10 in-hospital deaths (14.5%), and the incidences of stroke, spinal cord injury and distal embolism were 11.6%, 5.8% and 2.9%, respectively. The 1- and 3-year survival rates were 84.8% and 79.4%, respectively, and the 1- and 3-year freedom from reintervention rates were 97.2% and 81.3%, respectively.

CONCLUSIONS

The J-graft open stent graft was easy to deploy, and it could shift the distal anastomosis to a more proximal side. The mid-term performance of this device was good. It has the potential to provide one-stage repair.
Does anatomical location-based metastatic lymph node density affect prognosis in lung cancer patients?
Authors: Aksoy Yunus , Çıtak Necati , Obuz Çiğdem , Metin Muzaffer , Sayar Adnan
Published: April 2021

OBJECTIVES

The newly proposed N subclassification (new-N) was compared with the combined anatomical location and ratio of the number of metastatic lymph nodes to the total number of resected lymph nodes (anatomic-LNR) in terms of prognosis in resected lung cancer patients.

METHODS

Between 2005 and 2018, 961 patients who underwent lung cancer resection were catergorized into the pN1-single (N1a; n = 281), pN1-multiple (N1b; n = 182), pN2-single with skip metastasis (N2a1; n = 116), pN2-single with N1 metastasis (N2a2; n = 222) and pN2-multiple (N2b; n = 160) groups based on new-N. The optimal cut-off points for survival in pN1 and pN2 patients were determined using the best sensitivity and specificity scores, calculated using receiver operating characteristic analysis.

RESULTS

The difference in survival between N1a and N1b patients was statistically significant (P = 0.001), but there was no significant difference in the survival rates of N1b and N2a1 (P = 0.52). The survival curves for N2a1 and N2a2 patients almost overlapped (P = 0.143). N2a2 patients showed a better survival rate than N2b patients, with no significant difference (P = 0.132). The cut-off points for LNR were 0.10 and 0.25 for pN1 and pN2 patients, respectively, according to receiver operating characteristic analysis for survival. Based on receiver operating characteristic analysis, pN patients were categorized into the N1-lowLNR (n = 232), N1-highLNR (n = 231), N2-lowLNR (n = 266) and N2-highLNR (n = 232) groups. The 5-year survival rate was 62.9%, 49.8%, 41.1% and 27.1% for N1-lowLNR, N1-highLNR, N2-lowLNR and N2-highLNR, respectively (P < 0.001).

CONCLUSIONS

LowLNR is associated with better survival than highLNR in resected lung cancer patients. Anatomic-LNR shows a high discriminatory power for prognosis.
How does childhood maltreatment influence cardiovascular disease? A sequential causal mediation analysis
Authors: Soares Ana G , Howe Laura D , Heron Jon , Hammerton Gemma , Rich-Edwards Janet , Magnus Maria C , Halligan Sarah L , Fraser Abigail
Published: April 2021

Background

Childhood maltreatment has been consistently associated with cardiovascular disease (CVD). However, the mechanisms of this relationship are not yet fully understood. We explored the relative contribution of anxiety/depression, smoking, body mass index (BMI) and inflammation (C-reactive protein, CRP) to the association between childhood maltreatment and CVD in men and women aged 40–69 years in the UK.

Methods

We used data from 40 596 men and 59 511 women from UK Biobank. To estimate the indirect effects of childhood maltreatment (physical, sexual and emotional abuse, and emotional and physical neglect) on incident CVD via each of the mediators, we applied a sequential mediation approach.

Results

All forms of maltreatment were associated with increased CVD risk [hazard ratios (HRs) ranging from 1.09 to 1.27]. Together, anxiety/depression, smoking, BMI and inflammation (indexed by CRP) mediated 26–90% of the association between childhood maltreatment and CVD, and the contribution of these mediators differed by type of maltreatment and sex. Anxiety/depression mediated the largest proportion of the association of sexual abuse, emotional abuse and emotional neglect with CVD (accounting for 16–43% of the total effect), especially in women. In men, BMI contributed the most to the indirect effect of associations of physical abuse and physical neglect with CVD; in women, anxiety/depression and BMI had similar contributions.

Conclusions

These findings add to the understanding of how childhood maltreatment affects CVD risk and identify modifiable mediating factors that could potentially reduce the burden of CVD in people exposed to maltreatment in early life.
Trivial multiple zeta values in Tate algebras
Authors: Gezmiş O , Pellarin F
Published: April 2021

We study trivial multiple zeta values in Tate algebras. These are particular examples of the multiple zeta values in Tate algebras introduced by the second author. If the number of variables involved is “not large” in a way that is made precise in the paper, we can endow the set of trivial multiple zeta values with a structure of module over a non-commutative polynomial ring with coefficients in the rational fraction field over ${\mathbb{F}}_q$. We determine the structure of this module in terms of generators and we show how in many cases, this is sufficient for the detection of linear relations between Thakur’s multiple zeta values.
Limited Flavivirus Cross-Reactive Antibody Responses Elicited by a Zika Virus Deoxyribonucleic Acid Vaccine Candidate in Humans
Authors: Burgomaster Katherine E , Foreman Bryant M , Aleshnick Maya A , Larman Bridget C , Gordon David N , Maciejewski Sonia , Morabito Kaitlyn M , Ledgerwood Julie E , Gaudinski Martin R , Chen Grace L , Mascola John R , Debbink Kari , Dowd Kimberly A , Graham Barney S , Pierson Theodore C
Published: April 2021

Zika virus (ZIKV) deoxyribonucleic acid vaccine VRC5283 encoding viral structural genes has been shown to be immunogenic in humans. Recognizing that antigenically related flaviviruses cocirculate in regions with ZIKV activity, we explored the degree of antibody cross-reactivity elicited by this vaccine candidate using genetically diverse flaviviruses. The antibody response of vaccinated individuals with no evidence of prior flavivirus infection or vaccine experience had a limited capacity to bind heterologous viruses. In contrast, vaccine-elicited antibodies from individuals with prior flavivirus experience had a greater capacity to bind, but not neutralize, distantly related flaviviruses. These findings suggest that prior flavivirus exposure shapes the humoral immune response to vaccination.
Effect of long-term feeding of graded levels of deoxynivalenol on performance, nutrient utilization, and organ health of grower-finisher pigs (35 to 120 kg)
Authors: Wellington Michael O , Bosompem Michael A , Rodrigues Lucas A , Columbus Daniel A
Published: April 2021

The objective of this study was to evaluate the effect of long-term feeding of graded levels of deoxynivalenol (DON) on performance, nutrient utilization, and organ health of grower-finisher pigs. A total of 240 mixed-sex grower-finisher pigs (35.9 ± 1.1 kg initial body weight, BW) were randomly assigned to 1 of 4 dietary treatments (6 pigs/pen; 10 pens/treatment) for 77 d. Diets consisted of a control diet without DON (CONT) and diets containing 1, 3, or 5 ppm DON (DON1, DON3, or DON5). Nitrogen-balance was determined in 1 pig/pen during weeks 6 and 12 of the study. Growth performance measures were taken weekly for average daily feed intake (ADFI), average daily gain (ADG), and gain:feed (GF) until day 77. Blood samples were collected on days 0, 14, 42, 56, and 84 from 1 pig/pen for analysis of indicators of liver and kidney function. On day 7, ADG and ADFI for pigs fed DON3 and DON5 diets were lower (P < 0.05) compared with DON1- and CONT-fed pigs. Overall, ADG and ADFI (days 0 to 77) were lower in DON3- and DON5-fed pigs compared with CONT and DON1 pigs (P < 0.05), with no difference in GF (P > 0.05). Final BW was reduced in DON3- and DON5-fed pigs (P < 0.05) compared with CONT and DON1, which were not different (P > 0.05). No significant (P > 0.05) treatment effects were observed on carcass characteristics. In the grower-phase, protein deposition (PD) was reduced in DON3 and DON5 pigs compared with CONT and DON1 pigs (P < 0.05). In the finisher phase, PD was not affected by dietary treatment (P > 0.05). There was no effect of dietary treatment on the majority of selected serum chemistry (P > 0.05). In summary, pigs exposed to diets containing > 1 ppm DON had reduced growth performance with little or no effect on nitrogen utilization, organ health, or carcass characteristics, suggesting that the negative effects of DON may be largely due to depressed feed intake.