bluuebunny/crossref_metadata_2025 huggingface dataset:
The association between kidney function, cognitive function, and structural brain abnormalities in community-dwelling individuals aged 50+ is mediated by age and biomarkers of cardiovascular disease
Authors: Nowak Natalia , De Looze Celine , O’Halloran Aisling , Kenny Rose Anne , Sexton Donal J
Published: April 2023

Aims

Cognitive impairment has been associated with kidney function and chronic kidney disease. Whether this association is due to accelerated cardiovascular disease (CVD) or an independent specific kidney function effect related to toxins is unclear. We investigated the impact of an array of clinical factors, inflammatory biomarkers, and cardiovascular biomarkers on the association between kidney function, cognitive function, and structural brain abnormalities.

Methods and results

We used data from the first and third waves of the TILDA Study, a population-representative prospective cohort of Irish adults aged 50 years and over, based on stratified random sampling (n = 3774). The MRI sub-study included participants who consented to MRI brain imaging in addition to the health assessment. Multivariable linear and mixed-effect longitudinal regression models were fitted separately for each kidney marker/estimated glomerular filtration rate (eGFR) equation after adjusting for baseline age and demographics, clinical vascular risk factors, and biomarkers. Unadjusted analyses showed an association between low eGFR, cognitive dysfunction, and cognitive decline (P < 0.001 for all kidney markers). Kidney function markers were also associated with white matter disease [OR = 3.32 (95% CI: 1.11, 9.98)], total grey matter volume (β = -0.17, 95% CI -0.27 to -0.07), and regional grey matter volumes within areas particularly susceptible to hypoxia (P < 0.001 for all). All the associations decreased after adjusting for age and were also diminished after adjusting for CVD biomarkers. Age and CVD-biomarker score were significant mediators of the adjusted associations between eGFR and cognitive status. These results remained consistent for cross-sectional and longitudinal outcomes and specific cognitive domains.

Conclusion

Decreased kidney function was associated with cerebrovascular disease. The association appeared to be mediated predominantly by age and the combination of CVD markers [namely N-terminal pro-B-type natriuretic peptide (NT-proBNP) and Growth Differentiation Factor 15 (GDF15)], supporting the idea that shared biological pathways underline both diseases. Further mechanistic studies of the specific molecular mechanisms that lead to both kidney and cognitive decline are warranted.
Childbirth fear in the USA during the COVID-19 pandemic: key predictors and associated birth outcomes
Authors: Thayer Z M , Geisel-Zamora S A , Uwizeye G , Gildner T E
Published: April 2023

Background and objectives

Childbirth fear, which has been argued to have an adaptive basis, exists on a spectrum. Pathologically high levels of childbirth fear is a clinical condition called tokophobia. As a chronic stressor in pregnancy, tokophobia could impact birth outcomes. Many factors associated with tokophobia, including inadequate labor support, were exacerbated by the COVID-19 pandemic.

Methodology

We used longitudinally collected data from a convenience sample of 1775 pregnant persons in the USA to evaluate the association between general and COVID-19 pandemic-related factors and tokophobia using the fear of birth scale. We also assessed associations between tokophobia, low birth weight and preterm birth when adjusting for cesarean section and other covariates among a subset of participants (N = 993).

Results

Tokophobia was highly prevalent (62%). Mothers who self-identified as Black (odds ratio (OR) = 1.90), had lower income (OR = 1.39), had less education (OR = 1.37), had a high-risk pregnancy (OR = 1.65) or had prenatal depression (OR = 4.95) had significantly higher odds of tokophobia. Concerns about how COVID-19 could negatively affect maternal and infant health and birth experience were also associated with tokophobia (ORs from 1.51 to 1.79). Tokophobia was significantly associated with increased odds of giving birth preterm (OR = 1.93).

Conclusions and implications

Tokophobia increases the odds of preterm birth and is more prevalent among individuals who are Black, have a lower income, and have less education. Tokophobia may, therefore, be an underappreciated contributor to inequities in US birth outcomes. The COVID-19 pandemic likely compounded these effects.
Control of light-dependent behaviour in cyanobacteria by the second messenger cyclic di-GMP
Authors: Enomoto Gen , Wallner Thomas , Wilde Annegret
Published: April 2023

Nucleotide-derived signalling molecules control a wide range of cellular processes in all organisms. The bacteria-specific cyclic dinucleotide c-di-GMP plays a crucial role in regulating motility-to-sessility transitions, cell cycle progression, and virulence. Cyanobacteria are phototrophic prokaryotes that perform oxygenic photosynthesis and are widespread microorganisms that colonize almost all habitats on Earth. In contrast to photosynthetic processes that are well understood, the behavioural responses of cyanobacteria have rarely been studied in detail. Analyses of cyanobacterial genomes have revealed that they encode a large number of proteins that are potentially involved in the synthesis and degradation of c-di-GMP. Recent studies have demonstrated that c-di-GMP coordinates many different aspects of the cyanobacterial lifestyle, mostly in a light-dependent manner. In this review, we focus on the current knowledge of light-regulated c-di-GMP signalling systems in cyanobacteria. Specifically, we highlight the progress made in understanding the most prominent behavioural responses of the model cyanobacterial strains Thermosynechococcus vulcanus and Synechocystis sp. PCC 6803. We discuss why and how cyanobacteria extract crucial information from their light environment to regulate ecophysiologically important cellular responses. Finally, we emphasize the questions that remain to be addressed.
Impact of Mild Behavioral Impairment on Longitudinal Changes in Cognition
Authors: Rouse Hillary J , Ismail Zahinoor , Andel Ross , Molinari Victor A , Schinka John A , Small Brent J
Published: April 2023

Background

To examine cross-sectional differences and longitudinal changes in cognitive performance based on the presence of mild behavioral impairment (MBI) among older adults who are cognitively healthy or have mild cognitive impairment (MCI).

Methods

Secondary data analysis of participants (n = 17 291) who were cognitively healthy (n = 11 771) or diagnosed with MCI (n = 5 520) from the National Alzheimer’s Coordinating Center database. Overall, 24.7% of the sample met the criteria for MBI. Cognition was examined through a neuropsychological battery that assessed attention, episodic memory, executive function, language, visuospatial ability, and processing speed.

Results

Older adults with MBI, regardless of whether they were cognitively healthy or diagnosed with MCI, performed significantly worse at baseline on tasks for attention, episodic memory, executive function, language, and processing speed and exhibited greater longitudinal declines on tasks of attention, episodic memory, language, and processing speed. Cognitively healthy older adults with MBI performed significantly worse than those who were cognitively healthy without MBI on tasks of visuospatial ability at baseline and on tasks of processing speed across time. Older adults with MCI and MBI performed significantly worse than those with only MCI on executive function at baseline and visuospatial ability and processing speed tasks across time.

Conclusions

This study found evidence that MBI is related to poorer cognitive performance cross-sectionally and longitudinally. Additionally, those with MBI and MCI performed worse across multiple tasks of cognition both cross-sectionally and across time. These results provide support for MBI being uniquely associated with different aspects of cognition.
Do Individuals Aged 50 or Older View Cognitive Conditions Differently Than Physical Conditions? Evidence From a Pooled Analysis of Illness Perceptions in Type 2 Diabetes and Mild Cognitive Impairment
Authors: Kim Hyejin , Lingler Jennifer H , Bender Catherine M , Albert Steven M , Sereika Susan M
Published: April 2023

Background and Objectives

Type 2 diabetes (T2DM) and mild cognitive impairment (MCI) are common late-life physical and cognitive health conditions. Illness perceptions, an individual’s personal beliefs about the conditions, should be explored in the context of disease characteristics (physical or cognitive). This secondary analysis explored illness perceptions with a priori hypotheses about control (perceived controllability) and coherence (perceived understanding) dimensions among persons with T2DM and MCI, treating each as an exemplar of late-life physical and cognitive health conditions. We also explored whether age, education, and comorbid conditions moderate the relationships between T2DM or MCI condition groups and illness perceptions.

Research Design and Methods

This cross-sectional, descriptive study examined baseline data collected from 146 T2DM to 90 MCI participants in 2 independent studies. The 9-item Brief Illness Perception Questionnaire was used to identify the similarities and differences in illness perceptions among persons with T2DM and MCI. We performed hierarchical linear regression controlling for identified covariates.

Results

We found that T2DM and MCI participants had significantly different illness perceptions, including perceptions of personal control (b = −0.943, p = .009), treatment control (b = −1.619, p < .001), and coherence (b = −1.265, p = .001), after controlling for covariates. The results suggest that persons with MCI were likely to believe that their condition is less controllable (through their own strategies or medical treatment) and less understandable compared with their T2DM counterparts. Such associations remained statistically significant when the interactions were added to the models.

Discussion and Implications

As T2DM and MCI are prevalent late-life conditions, health care professionals should consider individuals’ subjective perceptions about their conditions in the context of disease characteristics when counseling secondary prevention strategies for disease management. Further research on illness perceptions in other conditions is needed to ensure the replicability of our findings.
Chromosome-level genome assembly of Salvia miltiorrhiza with orange roots uncovers the role of Sm2OGD3 in catalyzing 15,16-dehydrogenation of tanshinones
Authors: Pan Xian , Chang Yujie , Li Caili , Qiu Xiaoxiao , Cui Xinyun , Meng Fanqi , Zhang Sixuan , Li Xian’en , Lu Shanfa
Published: April 2023

Salvia miltiorrhiza is well known for its clinical practice in treating heart and cardiovascular diseases. Its roots, used for traditional Chinese medicine materials, are usually brick-red due to accumulation of red pigments, such as tanshinone IIA and tanshinone I. Here we report a S. miltiorrhiza line (shh) with orange roots. Compared with the red roots of normal S. miltiorrhiza plants, the contents of tanshinones with a single bond at C-15,16 were increased, whereas those with a double bond at C-15,16 were significantly decreased in shh. We assembled a high-quality chromosome-level genome of shh. Phylogenomic analysis showed that the relationship between two S. miltiorrhiza lines with red roots was closer than the relationship with shh. It indicates that shh could not be the mutant of an extant S. miltiorrhiza line with red roots. Comparative genomic and transcriptomic analyses showed that a 1.0 kb DNA fragment was deleted in shh Sm2OGD3m. Complementation assay showed that overexpression of intact Sm2OGD3 in shh hairy roots recovered furan D-ring tanshinone accumulation. Consistently, in vitro protein assay showed that Sm2OGD3 catalyzed the conversion of cyptotanshinone, 15,16-dihydrotanshinone I and 1,2,15,16-tetrahydrotanshinone I into tanshinone IIA, tanshinone I and 1,2-dihydrotanshinone I, respectively. Thus, Sm2OGD3 functions as tanshinone 15,16-dehydrogenase and is a key enzyme in tanshinone biosynthesis. The results provide novel insights into the metabolic network of medicinally important tanshinone compounds.
Control of ovule development in Vitis vinifera by VvMADS28 and interacting genes
Authors: Zhang Songlin , Wang Li , Yao Jin , Wu Na , Ahmad Bilal , van Nocker Steve , Wu Jiuyun , Abudureheman Riziwangguli , Li Zhi , Wang Xiping
Published: April 2023

Seedless grapes are increasingly popular throughout the world, and the development of seedless varieties is a major breeding goal. In this study, we demonstrate an essential role for the grapevine MADS-box gene VvMADS28 in morphogenesis of the ovule. We found that VvMADS28 mRNA accumulated in the ovules of a seeded cultivar, ‘Red Globe’, throughout the course of ovule and seed development, especially within the integument/seed coat. In contrast, in the seedless cultivar ‘Thompson Seedless’, VvMADS28 was expressed only weakly in ovules, and this was associated with increased levels of histone H3 lysine 27 trimethylation (H3K27me3) within the VvMADS28 promoter region. RNAi-mediated transient suppression of VvMADS28 expression in ‘Red Globe’ led to reduced seed size associated with inhibition of episperm and endosperm cell development. Heterologous overexpression of VvMADS28 in transgenic tomatoes interfered with sepal development and resulted in smaller fruit but did not obviously affect seed size. Assays in yeast cells showed that VvMADS28 is subject to regulation by the transcription factor VvERF98, and that VvMADS28 could interact with the Type I/ Mβ MADS-domain protein VvMADS5. Moreover, through DNA-affinity purification-sequencing (DAP-seq), we found that VvMADS28 protein specifically binds to the promoter of the grapevine WUSCHEL (VvWUS) gene, suggesting that maintenance of the VvMADS28–VvMADS5 dimer and VvWUS expression homeostasis influences seed development. Taken together, our results provide insight into regulatory mechanisms of ovule and seed development associated with VvMADS28.
Nicotiana benthamiana XYLEM CYSTEINE PROTEASEgenes facilitate tracheary element formation in interfamily grafting
Authors: Huang Chaokun , Kurotani Ken-ichi , Tabata Ryo , Mitsuda Nobutaka , Sugita Ryohei , Tanoi Keitaro , Notaguchi Michitaka
Published: April 2023

Grafting is a plant propagation technique widely used in agriculture. A recent discovery of the capability of interfamily grafting in Nicotiana has expanded the potential combinations of grafting. In this study, we showed that xylem connection is essential for the achievement of interfamily grafting and investigated the molecular basis of xylem formation at the graft junction. Transcriptome and gene network analyses revealed gene modules for tracheary element (TE) formation during grafting that include genes associated with xylem cell differentiation and immune response. The reliability of the drawn network was validated by examining the role of the Nicotiana benthamiana XYLEM CYSTEINE PROTEASE (NbXCP) genes in TE formation during interfamily grafting. Promoter activities of NbXCP1 and NbXCP2 genes were found in differentiating TE cells in the stem and callus tissues at the graft junction. Analysis of a Nbxcp1;Nbxcp2 loss-of-function mutant indicated that NbXCPs control the timing of de novo TE formation at the graft junction. Moreover, grafts of the NbXCP1 overexpressor increased the scion growth rate as well as the fruit size. Thus, we identified gene modules for TE formation at the graft boundary and demonstrated potential ways to enhance Nicotiana interfamily grafting.
Stability of fixed points in an approximate solution of the spring-mass running model
Authors: Wróblewska Zofia , Kowalczyk Piotr , Płociniczak Łukasz
Published: April 2023

We consider a classical spring-mass model of human running which is built upon an inverted elastic pendulum. Based on previous results concerning asymptotic solutions for large spring constant (or small angle of attack), we introduce an analytical approximation of a reduced mapping. Although approximate solutions already exist in the literature, our results have some benefits over them. They give us an advantage of being able to explicitly control the error of the approximation in terms of the small parameter, which has a physical meaning—the inverse of the square-root of the spring constant. Our approximation also shows how the solutions are asymptotically related to the magnitude of attack angle $\alpha $. The model itself consists of two sets of differential equations—one set describes the motion of the centre of mass of a runner in contact with the ground (support phase), and the second set describes the phase of no contact with the ground (flight phase). By appropriately concatenating asymptotic solutions for the two phases we are able to reduce the dynamics to a one-dimensional apex to apex return map. We find sufficient conditions for this map to have a unique stable fixed point. By numerical continuation of fixed points with respect to energy, we find a transcritical bifurcation in our model system.
Disseminating child abuse clinical decision support among commercial electronic health records: Effects on clinical practice
Authors: Feldstein David A , Barata Isabel , McGinn Thomas , Heineman Emily , Ross Joshua , Kaplan Dana , Bullaro Francesca , Khan Sundas , Kuehnel Nicholas , Berger Rachel P
Published: April 2023

Objectives

The use of electronic health record (EHR)-embedded child abuse clinical decision support (CA-CDS) may help decrease morbidity from child maltreatment. We previously reported on the development of CA-CDS in Epic and Allscripts. The objective of this study was to implement CA-CDS into Epic and Allscripts and determine its effects on identification, evaluation, and reporting of suspected child maltreatment.

Materials and Methods

After a preimplementation period, CA-CDS was implemented at University of Wisconsin (Epic) and Northwell Health (Allscripts). Providers were surveyed before the go-live and 4 months later. Outcomes included the proportion of children who triggered the CA-CDS system, had a positive Child Abuse Screen (CAS) and/or were reported to Child Protective Services (CPS).

Results

At University of Wisconsin (UW), 3.5% of children in the implementation period triggered the system. The CAS was positive in 1.8% of children. The proportion of children reported to CPS increased from 0.6% to 0.9%. There was rapid uptake of the abuse order set.

At Northwell Health (NW), 1.9% of children in the implementation period triggered the system. The CAS was positive in 1% of children. The child abuse order set was rarely used. Preimplementation, providers at both sites were similar in desire to have CA-CDS system and perception of CDS in general. After implementation, UW providers had a positive perception of the CA-CDS system, while NW providers had a negative perception.

Discussion

CA-CDS was able to be implemented in 2 different EHRs with differing effects on clinical care and provider feedback. At UW, the site with higher uptake of the CA-CDS system, the proportion of children who triggered the system and the rate of positive CAS was similar to previous studies and there was an increase in the proportion of cases of suspected abuse identified as measured by reports to CPS. Our data demonstrate how local environment, end-users’ opinions, and limitations in the EHR platform can impact the success of implementation.

Conclusions

When disseminating CA-CDS into different hospital systems and different EHRs, it is critical to recognize how limitations in the functionality of the EHR can impact the success of implementation. The importance of collecting, interpreting, and responding to provider feedback is of critical importance particularly with CDS related to child maltreatment.
Anti-money-laundering oversight and banks’ reporting of suspicious transactions: some empirical evidence
Authors: Gara Mario , Manaresi Francesco , Marchetti Domenico J , Marinucci Marco
Published: April 2023

We investigate the relation between anti-money-laundering (AML) inspections and banks’ ability and effort to identify and report suspicious transactions. We do so by using detailed data from the Bank of Italy and the Italian Financial Intelligence Unit, which include information on (i) authorities’ on-site inspections and enforcement actions, (ii) quantity and quality of suspicious transactions reports filed by banks before and after inspections, and (iii) reports’ investigative follow-ups. We document an increase in banks’ reporting after an inspection. Crucially, the increase is not concentrated among low-quality reports, but is spread to reports which are relevant from both a financial and an investigative point of view. We thus overall observe a rise in the information conveyed by AML reports after the authorities’ intervention. On the mechanism of the effect, we provide some suggestive evidence that inspections induce an increase of both banks’ reporting effort as well as screening skills (JEL G28, K23, L51, M21).
The difficulty of using prescription drug monitoring program among office-based physicians in the USA: a challenge to mitigate controlled substance prescriptions
Authors: Alshehri Khalid , Palm David , Wehbi Nizar K , Jung Tak Hyo , ElRayes Wael
Published: April 2023

Objectives

To address the usability challenge of Prescription Drug Monitoring Program (PDMP) among office-based physicians in the USA imposed by the difficulty barrier for the system usage, we sought: (1) to estimate the association between the PDMP difficulty of use and reducing or eliminating controlled substance prescriptions; and (2) to test the mediating effect of the frequency of PDMP check in the association between the PDMP difficulty of use and the reduction of controlled substance prescriptions.

Methods

We conducted a cross-sectional study using nationally representative data from the 2019 National Electronic Health Records Survey with a weighted sample of 214 889 office-based physicians. Weighted bivariate chi-square tests and multivariate logistic regressions with a confidence interval of 95% were performed. Bootstrap technique was used to conduct the causal mediation analysis.

Key findings

A PDMP that is easier to use was significantly associated with a higher reduction or elimination of controlled substance prescriptions (OR = 1.68; 95% CI: 1.01, 2.77). Easier PDMP use was also significantly associated with more frequent PDMP check prior to prescribing a controlled substance to a patient for the first time (OR = 6.39; 95% CI: 3.36, 12.15). About third (29.79%) of the observed association between PDMP difficulty of use and reducing or eliminating controlled substance prescriptions was mediated through the frequency of PDMP check.

Conclusion

The difficulty of PDMP limits the system’s usability which undermines the process of mitigating controlled substance prescriptions. Future efforts are needed to re-assess and regulate facilitators for difficult PDMP usage to maximise the success of this system and reach the goals behind its implementation.
Totally intramyocardial bullet in a clinically stable patient: a successfully managed case from a low income country
Authors: Fekadu Desalegn , Bezabih Abebe , Tesfaye Mahlet , Hayato Abdella , Muluneh Natnael , Kejela Segni
Published: April 2023

Intra-cardiac retained bullets rare entities in clinical practice owing to the high mortality associated with it. We present a case of a 26-year-old male patient presented 24 days after sustaining a bullet injury to the left side of the chest. Intra-operatively totally myocardial bullet was found within the right ventricle and extracted successfully.
A rare case of duodenal angiodysplasia—a case report
Authors: Razzak Saad Abdul , Awan Faisal Nazir , Murphy Amy Edward , Mustafa Hamid , Mehmood Umer , Ashraf Jawad
Published: April 2023

Gastrointestinal bleeding can be manifested as a variety of symptoms and, often, it is difficult to classify as upper or lower gastrointestinal bleeding on mere symptomatology. This is a case report of a similar kind of patient who initially was diagnosed with fresh per rectum bleeding, subsequently diagnosed as bleeding angiodysplasia in duodenal diverticulum by a series of investigations and management including urgent oesophageal-gastroduodenoscopy (OGD), laparotomy, followed by computerized tomography-angiogram. As diagnosis was established after laparotomy, the patient was kept intubated and IR selective embolization was performed. Keeping this case report in view, it can be suggested that bleeding vascular malformation in any part duodenum should be considered as a cause of massive upper GI bleeding. Furthermore, if operative intervention is indicated, it should be preceded by OGD, not only for a therapeutic purpose but also as an adjunct for guidance for the operative plan.
Panel Conditioning in A Probability-based Longitudinal study: A Comparison of Respondents with Different Levels of Survey Experience
Authors: Kraemer Fabienne , Silber Henning , Struminskaya Bella , Sand Matthias , Bosnjak Michael , Koßmann Joanna , Weiß Bernd
Published: April 2023

Learning effects due to repeated interviewing, also known as panel conditioning, are a major threat to response quality in later waves of a panel study. To date, research has not provided a clear picture regarding the circumstances, mechanisms, and dimensions of potential panel conditioning effects. In particular, the effects of conditioning frequency, that is, different levels of experience within a panel, on response quality are underexplored. Against this background, we investigated the effects of panel conditioning by using data from the GESIS Panel, a German mixed-mode probability-based panel study. Using two refreshment samples, we compared three panel cohorts with differing levels of experience on several response quality indicators related to the mechanisms of reflection, satisficing, and social desirability. Overall, we find evidence for both negative (i.e., disadvantageous for response quality) and positive (i.e., advantageous for response quality) panel conditioning. Highly experienced respondents were more likely to satisfice by speeding through the questionnaire. They also had a higher probability of refusing to answer sensitive questions than less experienced panel members. However, more experienced respondents were also more likely to optimize the response process by needing less time compared to panelists with lower experience levels (when controlling for speeding). In contrast, we did not find significant differences with respect to the number of “don’t know” responses, nondifferentiation, the selection of first response categories and mid-responses, and the number of nontriggered filter questions. Of the observed differences, speeding showed the highest magnitude with an average increase of 6.0 percentage points for highly experienced panel members compared to low experienced panelists.
Development of a new travellers’ diarrhoea clinical severity classification and its utility in confirming rifamycin-SV efficacy
Authors: DuPont Herbert L , Almenoff June S , Jamindar Mansi S , Bortey Enoch , Steffen Robert
Published: April 2023

Background

travellers’ diarrhoea (TD) is frequently reported with incidence up to 40% in high-risk destinations. Previous studies showed that the number of loose stools alone is inadequate to holistically predict the severity of TD. To improve the prediction of prognosis and to optimize treatments, a simple risk-based clinical severity classification has been developed.

Methods

pooled baseline data of signs and symptoms and number of loose stools from 1098 subjects enrolled in two double-blind Phase 3 trials of rifamycin-SV were analyzed with correlation, multiple correspondence analyses, prognostic factor criteria, and Contal and O’Quigley method to generate a TD severity classification (mild, moderate and severe). The relative importance of this classification on resolution of TD was assessed by Cox proportional model hazard model on the time to last unformed stool (TLUS).

Results

the analysis showed that TLUS were longer for the severe [hazard ratio (HR) 0.24; P < 0.001; n = 173] and moderate (HR 0.54; P = 0.0272; n = 912) vs mild. Additionally, when the treatment assigned in the studies was investigated in the severity classification, the results yielded that rifamycin-SV significantly shortened TLUS vs placebo for all subjects (HR 1.9; P = 0.0006), severe (HR 5.9; P = 0.0232) and moderate (HR 1.7; P = 0.0078) groups and was as equally efficacious as ciprofloxacin for all subjects, moderate and severe groups (HRs: 0.962, 0.9, 1.2; all P = NS, respectively). When reassessed by this classification, rifamycin-SV showed consistent efficacy with the Phase 3 studies.

Conclusions

this newly developed TD clinical severity classification demonstrated strong prognostic value and clinical utility by combining patients’ multiple signs and symptoms of enteric infection and number of loose stools to provide a holistic assessment of TD. By expanding on the current classification by incorporating patient reported outcomes in addition to TLUS, a classification like the one developed, may help optimize patient selection for future clinical studies.
The importance of the trisomy 21 local cutoff value evaluation for prenatal screening in the second trimester of pregnancy
Authors: Yiming Chen , Chen Yijie , Sun Long , Li Liyao , Ning Wenwen
Published: April 2023

Objective

The aim of this work was to compare different local cutoff values (LCV) and inline cutoff values (ICV) in pregnant women in the second trimester at high risk for carrying fetuses with trisomy 21.

Methods

This retrospective cohort study analyzed prenatal screening outcomes in pregnant women (n = 311,561). The receiver operating characteristic curve was used to evaluate the diagnostic significance of the trisomy 21 risk value, alpha-fetoprotein, and free beta human chorionic gonadotropin multiple of the median for predicting trisomy 21 risk. The cutoff value corresponding to the maximal Youden index was taken as the LCV. The screening efficiency of both cutoff values was compared.

Results

The LCV cutoff value was lower than the ICV cutoff value (1/643 vs 1/270). The sensitivity increased by 19.80%, the positive predictive value decreased by 0.20%, and the false-positive rate increased by 6.50%.

Conclusion

The LCV should be used to determine trisomy 21 risk, which can increase the detection rate of trisomy 21 in the second trimester.
Role of rituximab in the treatment of systemic sclerosis: A literature review
Authors: Yoshifuji Hajime , Yomono Keina , Yamano Yasuhiko , Kondoh Yasuhiro , Yasuoka Hidekata
Published: April 2023

This literature review aimed to evaluate the effectiveness of rituximab (RTX) in patients with systemic sclerosis (SSc). PubMed was searched for articles, published through 31 March 2022, on any controlled studies using RTX in the treatment of SSc. Of 85 identified articles, 9 were selected by title/abstract screening and full text examination. All nine articles reported outcomes of forced vital capacity (%FVC), and seven reported those of modified Rodnan skin scores (mRSS). The results showed that among the seven controlled studies evaluating skin lesions in patients with SSc, four showed a significant improvement of mRSS by RTX when compared with a control group, whereas three showed no significant effect. Among the nine controlled studies evaluating lung lesions, five showed a significant improvement of %FVC compared with a control group, whereas four showed no significant effect. In conclusion, RTX may be effective in the treatment of skin and lung lesions in patients with SSc. The profiles of SSc patients for whom RTX was indicated were unclear, although patients with diffuse cutaneous SSc and those positive for anti-topoisomerase I antibody were considered potential targets. Additional studies are needed to assess the long-term effectiveness of RTX in the treatment of patients with SSc.
Describing and explaining consciousness
Authors: Grinde Bjørn
Published: April 2023

Consciousness is a property of advanced brains and as such a biological feature. Explaining biological features is somewhat different from explaining physical phenomena; in the former case, the key is to first define its functional role (the reason why it was selected) and then to outline the evolutionary trajectory leading to its presence. In the case of consciousness, there are reasonable models for both. Further research is required to substantiate these models, but they offer, arguably, the best explanatory framework.
Host Expression Profiling From Diagnostic Coronavirus Disease 2019 Swabs Associates Upper Respiratory Tract Immune Responses With Radiologic Lung Pathology and Clinical Severity
Authors: Kozak Robert A , Salvant Elsa , Chang Veronica , Oikonomou Anastasia , Biondi Mia J , Feld Jordan J , Armstrong Susan , Wasif Sumaiyah , Mubareka Samira , Nirmalarajah Kuganya , Seth Arun , Amemiya Yutaka , Wang Chao , Tsui Hubert
Published: April 2023

Background

COVID-19 presents with a breadth of symptomatology including a spectrum of clinical severity requiring intensive care unit (ICU) admission. We investigated the mucosal host gene response at the time of gold standard COVID-19 diagnosis using clinical surplus RNA from upper respiratory tract swabs.

Methods

Host response was evaluated by RNA-sequencing, and transcriptomic profiles of 44 unvaccinated patients including outpatients and in-patients with varying levels of oxygen supplementation were included. Additionally, chest X-rays were reviewed and scored for patients in each group.

Results

Host transcriptomics revealed significant changes in the immune and inflammatory response. Patients destined for the ICU were distinguished by the significant upregulation of immune response pathways and inflammatory chemokines, including cxcl2 which has been linked to monocyte subsets associated with COVID-19 related lung damage. In order to temporally associate gene expression profiles in the upper respiratory tract at diagnosis of COVID-19 with lower respiratory tract sequalae, we correlated our findings with chest radiography scoring, showing nasopharygeal or mid-turbinate sampling can be a relevant surrogate for downstream COVID-19 pneumonia/ICU severity.

Conclusions

This study demonstrates the potential and relevance for ongoing study of the mucosal site of infection of SARS-CoV-2 using a single sampling that remains standard of care in hospital settings. We highlight also the archival value of high quality clinical surplus specimens, especially with rapidly evolving COVID-19 variants and changing public health/vaccination measures.
Respiratory Syncytial Virus–Related Complications and Healthcare Costs Among a Medicare-Insured Population in the United States
Authors: DeMartino Jessica K , Lafeuille Marie-Hélène , Emond Bruno , Rossi Carmine , Wang Jingru , Liu Stephanie , Lefebvre Patrick , Krishnarajah Girishanthy
Published: April 2023

Background

Literature describing respiratory syncytial virus (RSV)–related complications in older adults in the United States is scarce. This study described risk factors of RSV-related complications and healthcare costs of Medicare-insured patients aged ≥60 years with medically attended RSV.

Methods

100% Medicare Research Identifiable Files (1 January 2007–31 December 2019) were used to identify adults aged ≥60 years with RSV (index: first diagnosis date). Predictors of ≥1 RSV-related complication (ie, pneumonia, acute respiratory failure, congestive heart failure, hypoxia/dyspnea, non-RSV lower/upper respiratory tract infections, or chronic respiratory disease) during the up to 6-month post–RSV diagnosis period were identified. Patients with all aforementioned diagnoses during the 6 months pre-index could not be evaluated for a complication and were therefore ineligible for analyses. Differences between 6-month pre- and post-index total all-cause and respiratory/infection-related healthcare costs were assessed.

Results

Overall, 175 392 patients with RSV were identified. Post–RSV diagnosis, 47.9% had ≥1 RSV-related complication, with mean time-to-event of 1.0 month. The most common complications were pneumonia (24.0%), chronic respiratory disease (23.6%), and hypoxia or dyspnea (22.0%). Baseline predictors of ≥1 RSV-related complication included having previous diagnoses for complication/comorbidity listed in the Methods, hypoxemia, chemotherapy, chest radiograph, stem cell transplant, and anti-asthmatic and bronchodilator use. Total all-cause and respiratory/infection-related healthcare costs were $7797 and $8863 higher, respectively, post-index versus pre-index (both P < .001).

Conclusions

In this real-world study, almost half of patients with medically attended RSV experienced an RSV-related complication within 1 month post–RSV diagnosis, and costs significantly increased post-diagnosis. Having a complication/comorbidity pre-RSV predicted a higher risk of developing a different complication post–RSV infection.
Selective inhibition of somatostatin-positive dentate hilar interneurons induces age-related cellular changes and cognitive dysfunction
Authors: Lyu Jinrui , Nagarajan Rajasekar , Kambali Maltesh , Wang Muxiao , Rudolph Uwe
Published: April 2023

The cellular basis of age-related impairments of hippocampal function is not fully understood. In order to evaluate the role of somatostatin-positive (Sst+) interneurons in the dentate gyrus (DG) hilus in this process, we chemogenetically inhibited Sst+ interneurons in the DG hilus. Chronic chemogenetic inhibition (CCI) of these neurons resulted in increased c-Fos staining in the DG hilus, a decrease in the percentage of GAD67- and of Sst-expressing interneurons in the DG, and increased microglial activation in DG, CA3, and CA1. Total dendritic length and spine density were reduced in DG and CA1, suggesting reduced dendritic complexity. Behaviorally, the recognition index in an object recognition task and the percentage of spontaneous alternations in the Y-maze were decreased, while in both initial and reversal learning in the Morris water maze, the latencies to find the hidden platform were increased, suggesting cognitive dysfunction. Our findings establish a causal role for a reduced function of Sst+ interneurons in the DG hilus for cognitive decline and suggest that this reduced function may contribute to age-related impairments of learning and memory. Furthermore, our CCI mice may represent a cellularly defined model of hippocampal aging.
Investigation of the frequencies of various B cell populations in non-responder healthcare workers in comparison with responders to hepatitis B virus vaccination
Authors: Karimi Sara , Mehdipour Fereshteh , Sarvari Jamal , Ataollahi Mohammad Reza , Ramezani Amin , Meri Seppo , Kalantar Kurosh
Published: April 2023

Background

Hepatitis B is a major global health problem. More than 90% of hepatitis B-vaccinated immunocompetent adults become fully immune. The main purpose of vaccination is immunization. Whether non-responders have a lower percentage of total or antigen-specific memory B cells in comparison with responders is still controversial. We aimed to assess and compare the frequency of various B cell subpopulations in non-responders and responders.

Methods

Fourteen responders and 14 non-responders of hospital healthcare workers were enrolled in this study. We used flow cytometry to evaluate various CD19+ B cell subpopulations using fluorescent-labeled antibodies against CD19, CD10, CD21, CD27 and IgM and ELISA to evaluate total anti-HBs antibodies.

Results

We found no significant differences in the frequency of various B cell subpopulations between the non-responder and responder groups. Furthermore, the frequency of the isotype-switched memory B cell population was significantly higher in the atypical memory B cell subset compared with the classical memory B cell subset in the responder and total groups (p=0.010 and 0.003, respectively).

Conclusions

Responders and non-responders to HBsAg vaccine had comparable memory B cell populations. Whether anti-HBs Ab production has a correlation with the level of class switching in B lymphocytes in healthy vaccinated individuals needs further investigation.
Semi-infectious particles contribute substantially to influenza virus within-host dynamics when infection is dominated by spatial structure
Authors: Farrell Alex , Phan Tin , Brooke Christopher B , Koelle Katia , Ke Ruian
Published: April 2023

Influenza is an ribonucleic acid virus with a genome that comprises eight segments. Experiments show that the vast majority of virions fail to express one or more gene segments and thus cannot cause a productive infection on their own. These particles, called semi-infectious particles (SIPs), can induce virion production through complementation when multiple SIPs are present in an infected cell. Previous within-host influenza models did not explicitly consider SIPs and largely ignore the potential effects of coinfection during virus infection. Here, we constructed and analyzed two distinct models explicitly keeping track of SIPs and coinfection: one without spatial structure and the other implicitly considering spatial structure. While the model without spatial structure fails to reproduce key aspects of within-host influenza virus dynamics, we found that the model implicitly considering the spatial structure of the infection process makes predictions that are consistent with biological observations, highlighting the crucial role that spatial structure plays during an influenza infection. This model predicts two phases of viral growth prior to the viral peak: a first phase driven by fully infectious particles at the initiation of infection followed by a second phase largely driven by coinfections of fully infectious particles and SIPs. Fitting this model to two sets of data, we show that SIPs can contribute substantially to viral load during infection. Overall, the model provides a new interpretation of the in vivo exponential viral growth observed in experiments and a mechanistic explanation for why the production of large numbers of SIPs does not strongly impede viral growth. Being simple and predictive, our model framework serves as a useful tool to understand coinfection dynamics in spatially structured acute viral infections.
Neck Disability Index as a Prognostic Factor for Outcomes Following Cervical Disc Replacement
Authors: Hartman Timothy J. , Nie James W. , MacGregor Keith R. , Oyetayo Omolabake O. , Zheng Eileen , Singh Kern
Published: April 2023

Study Design:

Retrospective review

Objective:

We aim to elucidate the potential relationship between neck disability index (NDI) and outcomes following cervical disk replacement (CDR).

Summary of Background Data:

The use of preoperative disability scores as predictors of outcomes following spine surgery has previously been studied, yet no literature has been published regarding its use in CDR.

Methods:

A retrospective database of a single orthopedic spine surgeon was searched for single-level CDR patients with preoperative NDI scores, excluding those with trauma, infection, or malignancy. Patients were separated into 2 cohorts by NDI score: Mild-Moderately Disabled (MD) (NDI<50) and Severely Disabled (NDI≥50). Patient-reported outcome measures were collected and compared within and between groups up to 1 year postoperatively and included Patient-reported Outcome Measurement Information System Physical Function, 12-Item Short Form (SF-12) Physical Component Score and Mental Component Score, visual analog scale (VAS) neck and arm pain, and NDI. MCID achievement rates were compared between the groups.

Results:

All PROM scores significantly improved for both cohorts at one or more postoperative time points compared with preoperative baseline (P≤0.049, all), with the exception of SF-12 Mental Component Score, which only significantly improved in the MD cohort at 2 postoperative points (P≤0.007, both). Between groups, the MD cohort reported significantly superior scores at one or more time points for all studied patient-reported outcome measures (P≤0.047, all). MCID achievement rate did not significantly vary for any outcome at any time between cohorts.

Conclusion:

Regardless of preoperative disability, both groups reported improvement in physical function, pain, and disability scores following CDR. While not finding significance, patients with severe disability preoperatively consistently demonstrated higher minimal clinically important difference achievement in NDI. These data do not promote the use of NDI as a prognostic factor for outcomes following CDR. Further study with larger patient populations may be useful to clarify this potential relationship.
Human hair follicle-derived mesenchymal stem cells promote tendon repair in a rabbit Achilles tendinopathy model
Authors: Ma Yingyu , Lin Zhiwei , Chen Xiaoyi , Zhao Xin , Sun Yi , Wang Ji , Mou Xiaozhou , Zou Hai , Chen Jinyang
Published: April 2023

Background:

Hair follicles are easily accessible and contain stem cells with different developmental origins, including mesenchymal stem cells (MSCs), that consequently reveal the potential of human hair follicle (hHF)-derived MSCs in repair and regeneration. However, the role of hHF-MSCs in Achilles tendinopathy (AT) remains unclear. The present study investigated the effects of hHF-MSCs on Achilles tendon repair in rabbits.

Methods:

First, we extracted and characterized hHF-MSCs. Then, a rabbit tendinopathy model was constructed to analyze the ability of hHF-MSCs to promote repair in vivo. Anatomical observation and pathological and biomechanical analyses were performed to determine the effect of hHF-MSCs on AT, and quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical staining were performed to explore the molecular mechanisms through which hHF-MSCs affects AT. Furthermore, statistical analyses were performed using independent sample t test, one-way analysis of variance (ANOVA), and one-way repeated measures multivariate ANOVA as appropriate.

Results:

Flow cytometry, a trilineage-induced differentiation test, confirmed that hHF-derived stem cells were derived from MSCs. The effect of hHF-MSCs on AT revealed that the Achilles tendon was anatomically healthy, as well as the maximum load carried by the Achilles tendon and hydroxyproline proteomic levels were increased. Moreover, collagen I and III were upregulated in rabbit AT treated with hHF-MSCs (compared with AT group; P < 0.05). Analysis of the molecular mechanisms revealed that hHF-MSCs promoted collagen fiber regeneration, possibly through Tenascin-C (TNC) upregulation and matrix metalloproteinase (MMP)-9 downregulation.

Conclusions:

hHF-MSCs can be a treatment modality to promote AT repair in rabbits by upregulating collagen I and III. Further analysis revealed that treatment of AT using hHF-MSCs promoted the regeneration of collagen fiber, possibly because of upregulation of TNC and downregulation of MMP-9, thus suggesting that hHF-MSCs are more promising for AT.