bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of sex and estrous cycle on sleep and cataplexy in narcoleptic mice
Authors: Arthaud Sébastien , Villalba Manon , Blondet Camille , Morel Anne-Laure , Peyron Christelle
Published: April 2022

Narcolepsy type 1 (NT1) is a rare neurology disorder caused by the loss of orexin/hypocretin neurons. NT1 is characterized by excessive daytime sleepiness, sleep and wake fragmentation, and cataplexy. These symptoms have been equally described in both women and men, although influences of gender and hormonal cycles have been poorly studied. Unfortunately, most studies with NT1 preclinical mouse models, use only male mice to limit potential variations due to the hormonal cycle. Therefore, whether gender and/or hormonal cycles impact the expression of narcoleptic symptoms remains to be determined. To address this question, we analyzed vigilance states and cataplexy in 20 female and 17 male adult orexin knock-out narcoleptic mice, with half of the females being recorded over multiple days. Mice had access to chocolate to encourage the occurrence of cataplectic episodes. A vaginal smear was performed daily in female mice to establish the state of the estrous cycle (EC) of the previous recorded night. We found that vigilance states were more fragmented in males than females, and that females had less paradoxical sleep (p = 0.0315) but more cataplexy (p = 0.0375). Interestingly, sleep and wake features were unchanged across the female EC, but the total amount of cataplexy was doubled during estrus compared to other stages of the cycle (p = 0.001), due to a large increase in the number of cataplexy episodes (p = 0.0002). Altogether these data highlight sex differences in the expression of narcolepsy symptoms in orexin knock-out mice. Notably, cataplexy occurrence was greatly influenced by estrous cycle. Whether it is due to hormonal changes would need to be further explored.
A review of converting woody biomass waste into useful and eco-friendly road materials
Authors: Zhang Xue , Li Hui , Harvey John T , Butt Ali A , Jia Ming , Liu Jiawen
Published: April 2022

Because of abundant reserves and renewable and environmentally friendly properties, the utilization of woody biomass waste in road engineering can alleviate the shortage of fossil fuels and carbon emissions so as to mitigate global climate change and achieve sustainable development of road engineering. This paper synthesizes the state of the art about the strategies of applying five kinds of resources derived from waste woody biomass, including biochar, bio-oil, lignin, wood ash and nanocellulose to road construction. Based on the characteristics analysis of the five materials, it can be concluded that biochar can comprehensively improve the road performance of asphalt and its mixtures, and has the potential of runoff purification; bio-oil can soften asphalt and improve its low-temperature performance, but has negative effects on high-temperature performance; lignin increases the asphalt ageing resistance and can be used as a regenerant, and will improve the overall performance of asphalt mixtures if combined with other modifiers; wood ash can increase subgrade bearing capacity and bring significant environmental benefits; nanocellulose improves the strength of cement mortar, but there is a lack of research on its effects on performance of pavement materials and the interaction mechanism; the lifecycle environmental and economic assessment of woody biomass-modified road materials is not comprehensive. Moreover, prospects were also summarized to show the opportunities for future study, such as the establishment of a database for biomass. This review provides useful insights for the utilization of woody biomass as road materials to achieve waste management and sustainable development.

Highlights

• Reveal the characteristics of five kinds of materials derived from woody biomass wastes for use as road materials.

• The effects of biochar, bio-oil, lignin, wood ash and nanocellulose on road material performance are summarized.

• The use of woody biomass such as biochar and bio-oil in road materials contributes to reducing carbon emissions.

• Existing problems and future research prospects about the woody biomass waste used in the road structure are put forward.
Lessons Learned as Thomas Jefferson University’s Rural Physician Shortage Area Program (PSAP) Approaches the Half-Century Mark
Authors: Rabinowitz Howard K. , Motley Robert J. , Markham Fred W. , Love Gillian A.
Published: April 2022

To help increase the supply and retention of rural family physicians, Thomas Jefferson University initiated the Physician Shortage Area Program (PSAP) in 1974. The program selectively admits medical school applicants who both grew up in a rural area and plan to practice in a rural area. During medical school, PSAP students have ongoing mentoring and rural clinical experiences.

As the program now approaches the half-century mark, this commentary summarizes several important lessons learned. First, outcomes research is critical, and program leaders have been able to publish 15 papers and a book about the PSAP and its outcomes. Second, these studies have shown that the program has been highly successful, with PSAP graduates 8.5–9.9 times more likely to enter rural family medicine than their peers, and that the PSAP contributed 12% of all rural family physicians in Pennsylvania. Other similar medical school rural programs have had comparable success, with more than half of all graduates combined (including PSAP graduates) practicing rural. Third, long-term retention has a multiplicative impact. Long-term retention of PSAP graduates in rural family medicine was greater than 70% after 20–25 years. Fourth, research has shown that the admissions component accounted for approximately three-quarters of the PSAP’s success. Three factors available at the time of matriculation (rural background, plans for rural practice, and plans for family medicine) identified almost 80% of all Jefferson graduates in rural practice 3 decades later. Having a peer group with similar backgrounds, mentoring, and the rural curriculum were also very important. Fifth, wanting to live rural appears key to the rural practice decision. Finally, given that medical school programs like the PSAP produce substantial increases in the supply and retention of rural physicians while requiring modest resources, medical schools can have a critical role in addressing the rural physician shortage.
Beneficial Role of Microbial Transglutaminase in the Pathogenetic Mechanisms of Coeliac Disease
Authors: Treppiccione Lucia , Picarelli Antonio , Rossi Mauro
Published: April 2022

Coeliac disease (CD) is caused by immunological intolerance to wheat gluten and related proteins of rye and barley. Consequently, gluten‐free (GF) products have been developed but technological implementation is required to improve their intrinsic rheological properties. One alternative for increasing the functional properties of GF foodstuff is the incorporation of microbial transglutaminase (mTG), which allows for the cross‐linking of proteins that can substitute for the gluten network in the bakery industry. mTG has been, however, suggested to mimic tissue transglutaminase and to be immunogenic in CD patients. Recently, both mTG and gliadin were found to be transported to the endoplasmic reticulum of enterocytes, suggesting cross‐presentation and potential interaction with immune cells in CD. Although pathogenetic activity of mTG has not been found to date, these data naturally raise concerns among clinicians and patients about the use of mTG as a food additive. On the contrary, different studies have shown that treatment with mTG was effective in reducing the inflammatory immune response of gluten in CD. In this article, we take advantage of recent advances in gut physiology and CD pathogenesis to revise the literature data on mTG. An updated and unbiased overview of the role of mTG in this pathology allowed us to definitively highlight the beneficial use of this food additive by CD patients.
Impact of Surfactant Protein-A on Immunomodulatory Properties of Murine and Human Breast Milk
Authors: Meyer Cydney M. , Khan Amir M. , Alcorn Joseph L.
Published: April 2022

Objectives:

Human milk reduces the incidence of necrotizing enterocolitis (NEC). Prior studies have demonstrated that exogenous surfactant protein-A (SP-A) modulates intestinal inflammation, reduces NEC-like pathology in SP-A-deficient (SPAKO) pups, and may contribute to breast milk’s immunomodulatory potential. We hypothesize that SP-A is present in milk and impacts inflammatory responses in the terminal ileum of neonatal mice.

Methods:

Human milk was collected at postpartum days 1–3 and 28. Mouse milk was collected at postpartum days 1–10. SP-A was detected in milk through immunoprecipitation and western blot analysis. The impact of murine wild-type (WT) milk on SPAKO pup ileum was evaluated in a model of intestinal inflammation via cross-rearing experiments. Terminal ileum was evaluated for inflammatory cytokine and toll-like receptor 4 (TLR4) mRNA expression via quantitative real-time RT-PCR.

Results:

SP-A was detected in human milk and wild type (WT) mouse milk, but not in SPAKO mouse milk. Expression of TLR4, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α was decreased in SPAKO pups reared with WT dams compared to SPAKO pups reared with SPAKO dams, with a peak effect at day of life 14. When inflammation was induced using a lipopolysaccharide-induced model of inflammation, expression of TLR4, IL-1β, IL-6, CXCL-1, and TNF-α was significantly lower in SPAKO pups reared with WT dams compared to SPAKO pups reared with SPAKO dams.

Conclusions:

SP-A is present in human and murine milk and plays a role in lowering inflammation in murine pup terminal ileum. Both baseline inflammation and induced inflammatory responses are reduced via exposure to SP-A in milk with the effect amplified in inflammatory conditions.
Analysis of Neurogastrointestinal and Motility Disorders From the National Pediatric Database (Kid’s Inpatient Database): Exploring Demographic Access and Outcomes
Authors: Patel Dhiren , Al-Hammadi Noor , Xu Evan , Hinyard Leslie , Attard Thomas
Published: April 2022

Objectives:

Pediatric neurogastroenterology and motility (PNGM) disorders impose a significant impact on health-related quality of life and cost of health care in children and adolescents. The detailed understanding of its burden across demographic groups is unknown. The objective of our study is to characterize the demographic and hospitalization trends of patients undergoing PNGM tests.

Methods:

We used Healthcare Cost and Utilization Project (HCUP) Inpatient Database (KID) for years 2003–2016 to perform a trend analysis in US hospitalizations for International Classification of Diseases (ICD)-9 and -10 Clinical Modification (CM)–identified PNGM studies in patients (<18 years of age) with elective admission and a length of stay (LOS) <3 days. The hospitalization rates were analyzed by year, hospital region, facility type, and patient sociodemographic characteristics. Multivariable logistic regression was used to examine factors influencing the receipt of motility studies.

Results:

There was an overall increase trend in hospitalizations, rates of PNGM studies, and median hospital charges from 2003 to 2016. Patients with private insurance and living in the high-income zip codes were more likely to receive a PNGM study compared with those with governmental insurance and lower income area. Although the race was not found to influence the receipt of the study, a major difference in the LOS was noted across the regions.

Conclusions:

There are income- and insurance-based differences in the rates of inpatient PNGM studies. PNGM studies significantly add to health care burden. Standardization of PNGM practices across the country may decrease the LOS and associated expenses. Future analysis should include ambulatory PNGM services to understand combined inpatient and outpatient trends.
Restless Leg Syndrome in Hemodialysis Patients
Authors: Matar Sajeda G. , El-Nahas Zeinab S. , Aladwan Hala , Hasanin Menna , Elsayed Sarah M. , Nourelden Anas Z. , Benmelouka Amira Y. , Ragab Khaled M.
Published: April 2022

Background:

Restless legs syndrome (RLS) is a clinical entity characterized by sensory-motor manifestations commonly observed in end-stage renal illness. Evidence suggests that RLS is a multifactorial phenomenon that can be influenced by many critical factors, including genetic predisposition, dietary patterns, and deficiency in some vitamins. Iron metabolism disorders and metabolic derangements have been generally accepted as predisposing elements in RLS. Furthermore, both pharmacological and neuroimaging studies demonstrated dopamine deficiency and dopamine receptors decrease in basal ganglia during RLS.

Review Summary:

A literature search was done in three databases (PubMed, Google Scholar, and Cochrane) to identify the pertinent articles discussing the epidemiology, pathogenesis, and management of RLS in hemodialysis patients. RLS can affect the morbidity and mortality of patients treated with dialysis. It also has significant impacts on the quality of life since it can lead to insomnia, increased fatigue, mental health troubles, and other movement problems. Appropriate measures should be considered in this particular population so to prevent and treat RLS. Many drugs and other nonpharmacological methods have been investigated to attenuate the disease’s severity. No treatment, however, could offer long-term effects.

Conclusion:

Further efforts are still required to improve the understanding of RLS pathogenic trends to find more specific and efficient therapies. A wide range of treatment options is available. However, it can be individualized according to the patients’ several factors.
The Bridged Digital Artery Perforator Flap as an Alternative Reconstructive Option for Dorsal Digital or Toe Soft Tissue Defects
Authors: Kostopoulos Epameinondas , Konofaos Petros , Mitchel Matthew , Kotsakis Ioannis , Georgopoulos Gerasimos , Diamantopoulos Antonios , Korfiati Georgia , Champsas Gregorios , Casoli Vincent
Published: April 2022

Background

Dorsal digital soft tissue defects are considered among the most challenging to reconstruct. Numerous treatment options are proposed, including advancement flaps, antegrade, retrograde flow flaps, adipofascial flaps, and digital artery perforator flaps. However, the optimal treatment remains controversial. The concept of the “bridge principle,” consisting of the indirect transfer of the flap to the defect area through a muscular bridge, has recently introduced by authors for medial canthal reconstruction. The aim of the study was to examine the feasibility of its application in digital reconstruction for dorsal defects and the development of a new flap. The utilization of the dorsal subcutaneous adipofascial digital or toe tissue as a “bridge” led to description and development of bridged digital artery perforator flaps as an alternative treatment of such defects.

Methods

From November 2017 to September 2019, a series of 14 patients (mean age of 57.1 years) suffered from dorsal digital or toe soft tissue defects of different dimensions and sustained reconstruction with this new technique.

Results

Twelve digits and 2 toes have been concerned. The mean size of the defects was 1.3 × 1.1 cm. All flaps survived without a sign of venous congestion. No functional digital or toe problems were observed during the follow-up period (mean of 11.6 months). Minor wound dehiscence presented in 2 cases (2 of 14 [14.3%]) and a transient skin swelling around the flap in 1.

Conclusions

A new concept was introduced to resolve a challenging problem. Initial outcomes are very encouraging. These flaps could be a valuable and reliable reconstructive option.
Ferret Lung Transplantation Models Differential Lymphoid Aggregate Morphology Between Restrictive and Obstructive Forms of Chronic Lung Allograft Dysfunction
Authors: Lynch Thomas J. , Ahlers Bethany A. , Swatek Anthony M. , Ievlev Vitaly , Pai Albert C. , Brooks Leonard , Tang Yinghua , Evans Idil A. , Meyerholz David K. , Engelhardt John F. , Parekh Kalpaj R.
Published: April 2022

Background.

Long-term survival after lung transplantation remains limited by chronic lung allograft dysfunction (CLAD). CLAD has 2 histologic phenotypes, namely obliterative bronchiolitis (OB) and restrictive alveolar fibroelastosis (AFE), which have distinct clinical presentations, pathologies, and outcomes. Understanding of OB versus AFE pathogenesis would improve with better animal models.

Methods.

We utilized a ferret orthotopic single-lung transplantation model to characterize allograft fibrosis as a histologic measure of CLAD. Native lobes and “No CLAD” allografts lacking aberrant histology were used as controls. We used morphometric analysis to evaluate the size and abundance of B-cell aggregates and tertiary lymphoid organs (TLOs) and their cell composition. Quantitative RNA expression of 47 target genes was performed simultaneously using a custom QuantiGene Plex Assay.

Results.

Ferret lung allografts develop the full spectrum of human CLAD histology including OB and AFE subtypes. While both OB and AFE allografts developed TLOs, TLO size and number were greater with AFE histology. More activated germinal center cells marked by B-cell lymphoma 6 Transcription Repressor, (B-cell lymphoma 6) expression and fewer cells expressing forkhead box P3 correlated with AFE, congruent with greater diffuse immunoglobulin, plasma cell abundance, and complement 4d staining. Furthermore, forkhead box P3 RNA induction was significant in OB allografts specifically. RNA expression changes were seen in native lobes of animals with AFE but not OB when compared with No CLAD native lobes.

Conclusions.

The orthotopic ferret single-lung transplant model provides unique opportunities to better understand factors that dispose allografts to OB versus AFE. This will help develop potential immunomodulatory therapies and antifibrotic approaches for lung transplant patients.
Hostile media perception affects news bias, but not news sharing intentions
Authors: Lo Iacono Sergio , Daniel Dores Cruz Terence
Published: April 2022

Hostile media perception (HMP) theory suggests that partisans perceive neutral coverage of news by outlets opposite to their political leaning as biased against their side. We conducted two pre-registered online experiments to assess the effect of HMP on news bias and news sharing intentions regarding two salient and controversial topics in the US: police conduct (Study 1,
N
= 817) and COVID-19 norms (Study 2,
N
= 819). Results show that partisans perceive neutral coverage of news by outlets opposite to their political leaning as biased, even when we account for their prior beliefs regarding the media outlet and news content. However, HMP seems to be limited in its consequences, as it has little impact on partisans' willingness to share news from outlets of opposite political leaning, even though the news is perceived as biased.
The impact of news media on Bitcoin prices: modelling data driven discourses in the crypto-economy with natural language processing
Authors: Coulter Kelly Ann
Published: April 2022

This paper examines the relationship between events reported in international news via categorical discourses and Bitcoin price. Natural language processing was adopted in this study to model data-driven discourses in the crypto-economy, specifically the Bitcoin market. Using topic modelling, namely Latent Dirichlet Allocation, a text analysis of cryptocurrency articles (
N
= 4218) published from 60 countries in international news media identified key topics associated with cryptocurrency in the international news media from 2018 to 2020. This study provides empirical evidence that across the corpora of international news articles, 18 key topics were framed around the following categorical macro discourses: crypto-related crime, financial governance, and economy and markets. Analysis shows that the identified discourses may have had a ‘social signal’ effect on movements in the crypto-financial markets, particularly on Bitcoin's price volatility. Results show these specific discourses proved to have a negative effect on Bitcoin's market price, within 24 h of when the crypto news articles were published. Further, the study found that in some cases, the source of the news may have amplified the volatility effect, particularly in terms of geographical region, relative to broader market conditions.
Life-history traits predict responses of wild bees to climate variation
Authors: Pardee Gabriella L. , Griffin Sean R. , Stemkovski Michael , Harrison Tina , Portman Zachary M. , Kazenel Melanie R. , Lynn Joshua S. , Inouye David W. , Irwin Rebecca E.
Published: April 2022

Life-history traits, which are physical traits or behaviours that affect growth, survivorship and reproduction, could play an important role in how well organisms respond to environmental change. By looking for trait-based responses within groups, we can gain a mechanistic understanding of why environmental change might favour or penalize certain species over others. We monitored the abundance of at least 154 bee species for 8 consecutive years in a subalpine region of the Rocky Mountains to ask whether bees respond differently to changes in abiotic conditions based on their life-history traits. We found that comb-building cavity nesters and larger bodied bees declined in relative abundance with increasing temperatures, while smaller, soil-nesting bees increased. Further, bees with narrower diet breadths increased in relative abundance with decreased rainfall. Finally, reduced snowpack was associated with reduced relative abundance of bees that overwintered as prepupae whereas bees that overwintered as adults increased in relative abundance, suggesting that overwintering conditions might affect body size, lipid content and overwintering survival. Taken together, our results show how climate change may reshape bee pollinator communities, with bees with certain traits increasing in abundance and others declining, potentially leading to novel plant–pollinator interactions and changes in plant reproduction.
Volatile social environments can favour investments in quality over quantity of social relationships
Authors: Aubier Thomas G. , Kokko Hanna
Published: April 2022

Cooperation does not occur in a vacuum: interactions develop over time in social groups that undergo demographic changes. Intuition suggests that stable social environments favour developing few but strong reciprocal relationships (a ‘focused' strategy), while volatile social environments favour the opposite: more but weaker social relationships (a ‘diversifying' strategy). We model reciprocal investments under a quality–quantity trade-off for social relationships. We find that volatility, counterintuitively, can favour a focused strategy. This result becomes explicable through applying the theory of antagonistic pleiotropy, originally developed for senescence, to social life. Diversifying strategies show superior performance later in life, but with costs paid at young ages, while the social network is slowly being built. Under volatile environments, many individuals die before reaching sufficiently old ages to reap the benefits. Social strategies that do well early in life are then favoured: a focused strategy leads individuals to form their first few social bonds quickly and to make strong use of existing bonds. Our model highlights the importance of pleiotropy and population age structure for the evolution of cooperative strategies and other social traits, and shows that it is not sufficient to reflect on the fate of survivors only, when evaluating the benefits of social strategies.
A global analysis of aerial displays in passerines revealed an effect of habitat, mating system and migratory traits
Authors: Mikula Peter , Toszogyova Anna , Albrecht Tomáš
Published: April 2022

Aerial displaying is a flamboyant part of the sexual behaviour of several volant animal groups, including birds. Nevertheless, little attention has been focused on identifying correlates of large-scale diversity in this trait. In this study, we scored the presence and absence of aerial displays in males of 1732 species of passerine birds (Passeriformes) and employed Bayesian phylogenetically informed mixed models to test for associations between aerial displays and a set of life-history and environmental predictors. Our multi-variate models revealed that species with males that perform aerial displays inhabited open rather than closed (forested) habitats. These species also exhibited higher levels of polygyny, had more elongated wings, migrated over longer distances and bred at higher latitudes. When we included species where the sexual function of displays has not been explicitly described but is likely to occur, we found that aerial displaying was also associated with smaller body size and increased male plumage coloration. Our results suggest that both sexual selection and natural selection have been important sources of selection on aerial displays in passerines.
The Contributions of Rare Inherited and Polygenic Risk to ASD in Multiplex Families
Authors: Chang Timothy S , Cirnigliaro Matilde , Arteaga Stephanie A , Pérez-Cano Laura , Ruzzo Elizabeth K , Gordon Aaron , Bicks Lucy , Jung Jae-Yoon , Lowe Jennifer K , Wall Dennis P , Geschwind Daniel H
Published: April 2022

Autism Spectrum Disorder (ASD) has a complex genetic architecture involving contributions fromde novoand inherited variation. Few studies have been designed to address the role of rare inherited variation, or its interaction with polygenic risk in ASD. Here, we performed whole genome sequencing of the largest cohort of multiplex families to date, consisting of 4,551 individuals in 1,004 families having 2 or more affected children with ASD. Using this study design, we identify seven novel risk genes supported primarily by rare inherited variation, finding support for a total of 74 genes in our cohort and a total of 152 genes after combining with other studies. Probands demonstrated an increased burden of mutations in 2 or more known risk genes (KARGs) — in three families both probands inherited protein truncating variants in two KARGs. We also find that polygenic risk is over transmitted from unaffected parents to affected children with rare inherited variants, consistent with combinatorial effects in the offspring, which may explain the reduced penetrance of these rare variants in parents. We also observe that in addition to social dysfunction, language delay is associated with ASD polygenic risk over-transmission. These results are consistent with an additive complex genetic risk architecture of ASD involving rare and common variation and further suggest that language delay is a core biological feature of ASD.
Immediate effect of osteopathic techniques on human resting muscle tone in healthy subjects using myotonometry: A factorial randomized trial
Authors: Bohlen Lucas , Schwarze Jonah , Richter Jannik , Gietl Bernadette , Lazarov Christian , Kopyakova Anna , Brandl Andreas , Schmidt Tobias
Published: April 2022

Background

Musculoskeletal disorders (MSDs) are highly prevalent, burdensome, and putatively associated with an altered human resting muscle tone (HRMT). Osteopathic manipulative treatment (OMT) is commonly and effectively applied to treat MSDs and reputedly influences the HRMT. Arguably, OMT may modulate alterations in HRMT underlying MSDs. However, there is sparse evidence even for the effect of OMT on HRMT in healthy subjects.

Methods

A 3x3 factorial randomised trial was performed to investigate the immediate-term effect of myofascial release (MRT), muscle energy (MET), and soft tissue techniques (STT) on the HRMT of the corrugator supercilii (CS), superficial masseter (SM), and upper trapezius muscles (UT) in healthy subjects in Hamburg, Germany. Participants were randomised into three groups (1:1:1 allocation ratio) receiving treatment, according to different muscle-technique pairings, over the course of three sessions with one-week washout periods. Primarily, we assessed the effect of osteopathic techniques on muscle tone (F), biomechanical (S, D), and viscoelastic properties (R, C) from baseline to follow-up (main effect) and tested if specific muscle-technique pairs modulate the effect pre- to post-intervention (interaction effect) using the MyotonPRO (at rest). Data were analysed using descriptive (mean, standard deviation, quantiles, and simple effect) and inductive statistics (Bayesian ANOVA).

Results

59 healthy participants were randomised into three groups and two subjects dropped out from one group (n=20; n=20; n=19 and n=17, respectively). The CS produced frequent measurement errors and was excluded from analysis. The main effect changed significantly for F (-0.163 [0.060]; p=0.008), S (-3.060 [1.563]; p=0.048), R (0.594 [0.141]; p<0.001), and C (0.038 [0.017]; p=0.028) but not for D (0.011 [0.017]; p=0.527). The interaction effect did not change significantly (p>0.05). No adverse events were reported.

Conclusion

OMT modified the HRMT in healthy subjects which may inform future research on MSDs. In detail, MRT, MET, and STT reduced the muscle tone (F), decreased biomechanical (S not D), and increased viscoelastic properties (R and C) of the SM and UT (CS was not measurable) at immediate term. However, the effect on HRMT was not modulated by muscle–technique interaction.

Trial registration

German Clinical Trial Register (DRKS00020393).
Altered gene expression profiles impair the nervous system development in individuals with 15q13.3 microdeletion
Authors: Körner Marek B. , Velluva Akhil , Bundalian Linnaeus , Radtke Maximilian , Lin Chen-Ching , Zacher Pia , Bartolomaeus Tobias , Kirstein Anna , Mrestani Achmed , Scholz Nicole , Platzer Konrad , Teichmann Anne-Christin , Hentschel Julia , Langenhan Tobias , Lemke Johannes R. , Garten Antje , Jamra Rami Abou , Le Duc Diana
Published: April 2022

Background

The 15q13.3 microdeletion has pleiotropic effects ranging from apparently healthy to severely affected individuals. The underlying basis of the variable phenotype remains elusive.

Methods

We analyzed gene expression using blood from 3 individuals with 15q13.3 microdeletion and brain cortex tissue from 10 mice Df[h15q13]/+. We assessed differentially expressed genes (DEGs), protein-protein interaction (PPI) functional modules, and gene expression in brain developmental stages.

Results

The deleted genes’ haploinsufficiency was not transcriptionally compensated, suggesting a dosage effect may contribute to the pathomechanism. DEGs shared between tested individuals and a corresponding mouse model show a significant overlap including genes involved in monogenic neurodevelopmental disorders. Yet, network-wide dysregulatory effects suggest the phenotype is not caused by a singular critical gene. A significant proportion of blood DEGs, silenced in adult brain, have maximum expression during the prenatal brain development. Based on DEGs and their PPI partners we identified altered functional modules related to developmental processes, including nervous system development.

Conclusions

We show that the 15q13.3 microdeletion has a ubiquitous impact on the transcriptome pattern, especially dysregulation of genes involved in brain development. The high phenotypic variability seen in 15q13.3 microdeletion could stem from an increased vulnerability during brain development, instead of a specific pathomechanism.
Sotrovimab drives SARS-CoV-2 Omicron variant evolution in immunocompromised patients
Authors: Destras G. , Bal A. , Simon B. , Lina B. , Josset L.
Published: April 2022

After monoclonal antibody sotrovimab implementation, Rockett et al have warned on March 9th about two resistant mutations in the spike at position 337 and 340 occurring within the first week in four immunocompromised patients infected by a Delta variant and resulting in viable infection up to 25 days. As sotrovimab is currently the only effective treatment against BA.1 lineage of Omicron variant, we investigated the presence of these mutations in our 22,908 Omicron sequences performed from December 2021 to March 2022.

Among 25 Omicron sequences with S:337 and S:340 substitutions, 9 were reported in six patients who had available clinical data and a follow up. All were immunicompromised, and presented a rapid selection of these mutations after sotrovimab monotherapy infusion.

With these findings, we underscore that although these mutations are rare, they have been exclusively reported in immunocompromised patients treated with sotrovimab. We urge to consider monoclonal antibody as monotherapy in immunocompromised patients as a risk for escape mutants selection.
Protocol for the pilot study of group video yogic breathing app in breast cancer survivors
Authors: Balasubramanian Sundaravadivel , Harper Jennifer , Sterba Katherine R. , Viswanathan Ramakrishnan , Eldredge-Hindy Harriet
Published: April 2022

Introduction

Breast cancer remains a leading cause of cancer deaths; however, recent improvements in treatment have improved survivorship. As a result of this improvement, more individuals are living with the long-term side effects of cancer treatment. Therefore, methods that incorporate lifestyle and mind-body approaches are becoming increasingly used in the patient treatment pathway.

Methods

In this study, PranaScience Institute will develop and test a group video mobile application for Yogic Breathing (YB). YB is shown to reduce symptomatic conditions associated with several conditions including breast cancer. For this initial feasibility study, PranaScience will collaborate with the Medical University of South Carolina to implement the study app-based program in breast cancer survivors. This research is aimed to understand if the YB could be delivered via an app, if participants are able to practice it satisfactorily, and if there is any symptom relief by the YB practice. In the control group, participants will be directed to the Attention Control (AC) feature of the app, which guides users to focus on a mindfulness activity not involving YB. Participants will be randomly assigned to the YB or AC study plan (N=20 per group). Breast cancer survivors who have completed radiation therapy within last 6 months will be recruited for this study and provided access to the app for a 12-week program. The study app will record total practice times. Virtual visits by a study yoga instructor during group video sessions will measure participant compliance with proper technique. Feasibility will be examined by evaluating intervention delivery factors and resource needs. Acceptability of using the mobile study app to support symptom management will be evaluated using a satisfaction and system usability scale. Behavioral survey measures will help guide effect sizes and power calculations for the next larger-scale study. Biomarkers in the saliva (tumor suppressors, cytokines), and fingernails (cortisol, differential proteomics) will be measured at baseline and end of study at 12 weeks.

Discussion

All findings from this pilot study will be synthesized to refine the mobile study app in preparation for large-scale evaluation in Phase II involving all-study site participants with cancer. ClinicalTrials.gov Identifier NCT05161260.
Attitude towards gender inequitable norms and associated factors among male youths in Arba Minch town, Southern Ethiopia
Authors: Basa Muluken Bafa , Samuel Barkot , Shegaze Mulugeta , Gebru Zeleke , Boda Belay , Glagn Mustefa
Published: April 2022

Background

Gender inequitable norms are common cultural traditions across the world, which characterized women as someone who deserves less basic life support and fundamental human rights than men. The unfairness of such practices has demolished women’s quality of life. Studies are limited to measuring some factors in Ethiopia. The information obtained from this study will help to take an evidence-based approach to reduce gender inequitable norms.

Objective

To assess attitude towards gender inequitable norms and associated factors among male youths from August 16 th – 30 th , 2020 at Arba Minch town, Southern Ethiopia.

Methods

A community-based cross-sectional study was conducted among 423 male youths. Gender-Equitable Men Scale was used to measure the attitudes towards gender inequitable norms. The study participants were selected using a simple random sampling technique by allocating a proportion to each kebeles. Both bivariable and multivariable logistic regression analyses were performed to identify associated factors. The level of statistical significance was set at a p-value of less than 0.05 in multivariable logistic regression.

Results

The overall prevalence of favorable attitude towards gender inequitable norms among male youths was 47.3% with 95% CI (42%, 52%). No formal education, lower household income, not participating in youth clubs, poor knowledge, and having a prior history of physical violence during childhood were factors significantly associated with a favorable attitude towards gender inequitable norms.

Conclusion and recommendation

Almost half of the participants had a favorable attitude towards gender inequitable norms. Proactive measures need to be taken to curb the problem by taking integrated interventions for youths like enrolling in school, enhancing participation in a youth club, prevent childhood physical violence, increasing household income, and creating awareness on gender inequitable norms to change traditional beliefs that undermine women.
RATING: Medical-knowledge-guided rheumatoid arthritis assessment from multimodal ultrasound images via deep learning
Authors: Zhou Zhanping , Zhao Chenyang , Qiao Hui , Wang Ming , Guo Yuchen , Wang Qian , Zhang Rui , Wu Huaiyu , Dong Fajin , Qi Zhenhong , Li Jianchu , Tian Xinping , Zeng Xiaofeng , Jiang Yuxin , Xu Feng , Dai Qionghai , Yang Meng
Published: April 2022

Ultrasound (US) examination has been commonly utilized in clinical practice for assessing the rheumatoid arthritis (RA) activity, which is hampered by low intra-observer and inter-observer agreement as well as considerable time and expense to train experienced radiologists. Here, we present the Rheumatoid ArthriTIs kNowledge Guided (RAT ING) model that scores RA activity and generates interpretable features to assist radiologists’ decision-making. The RATING model achieved an accuracy of 86.1% (95% confidence interval (CI)=82.5%–90.1%) in the clinical trial setting, and achieved an accuracy of 85.0% (95% CI=80.5%–89.1%) on the US images collected from an external medical center. An AI-assisted reader study demonstrated that the RATING model improved the average accuracy of ten radiologists from 41.4% to 64.0%. Automated AI models for the assessment of RA may facilitate US RA examination and provide support for clinical decision-making.
Prevalence and risk factors of Schistosomiasis among school aged children in Al- Fashir, North Darfur state, Sudan: a cross sectional study
Authors: Elzain Ishraga Adam , Abdalla Hamid Suliman , Idris Abeer Babiker , Ahmed Nagla Mohamed , Jomaa Salah , Hassan Mohamed A.
Published: April 2022

Objective

Schistosomiasis represents a significant health problem in Sudan. School aged children who live in areas with poor sanitation are often at risk because they tend to spend time swimming or bathing in water containing infectious cercariae. Therefore, this study aimed to investigate schistosomiasis in terms of prevalence of the infection, and its risk factors among school aged children at Al- Fashir, the capital city of North Darfur state in Sudan.

Results

In this study, S. haematobium was detected in 6.1% of the school age children at Al- Fashir. Also, hematuria was detected in 85.7% of infected patients, and there was significant correlation between hematuria and presence of S. haematobium eggs (P. value= 0.001). Regarding the risk factor, the low prevalence rate of S. haematobium was observed in populations who depend on faucets as water sources and live in Nifasha and Zamzam camps.
Dynamics of anti-Spike IgG antibody titer after the third BNT162b2 COVID-19 vaccination in the Japanese health care workers
Authors: Ikezaki Hiroaki , Nomura Hideyuki , Shimono Nobuyuki
Published: April 2022

Introduction

Many countries are administering a third dose of some coronavirus disease 2019 (COVID-19) vaccines, but the evaluation of vaccine-induced immunity is insufficient. This study aimed to evaluate anti-spike immunoglobulin G (IgG) titers in the health care workers after the third BNT162b2 vaccination.

Methods

Dynamics of anti-spike IgG titers were assessed two months following the third BNT162b2 vaccination in 52 participants. All participants received the primary series of vaccination with BNT162b2 and received the third dose eight months after the second vaccination. Associations between anti-spike IgG titer, baseline characteristics, and adverse reactions were also evaluated.

Results

The geometric mean titer of anti-spike IgG one month after the third vaccination was 17400 AU/ml, which increased to approximately 30 times immediately before the third vaccination and approximately twice that one month after the second vaccination. In addition, participants with anti-spike IgG titers less than 10000 AU/ml after the second vaccination tended to have higher increases in ant-spike IgG titers before and after the third vaccination.

The decline rate of anti-spike IgG was significantly slower after the third vaccination as 35.7% than that after the second vaccination as 59.1%. The anti-spike IgG titer was significantly negatively associated with age (r = -0.31). Participants who had a headache at the vaccination showed significantly higher anti-spike IgG titer than those without a headache.

Conclusions

The anti-spike IgG induced by primary immunization with BNT162b2 waned over time. The third dose of BNT162b2 substantially increased the anti-spike IgG with a slower decline rate.
Poor Working Relationship between Doctors and Hospital Managers: A Systematic Review
Authors: Ogbeivor Collins , Ogbeivor Precious E
Published: April 2022

What This Study Adds

We conducted a systematic review on the effect of tension between doctors and hospital managers on the quality of care provided in hospital or healthcare centres; 15 (qualitative, quantitative and mixed) primary papers were reviewed.

This qualitative systematic study found considerable evidence of organisational factors that contributes to poor working relationships between doctors and managers

Abstract

Background: The problem of poor relationships between doctors and hospital managers is a common feature of many healthcare systems worldwide, including the United Kingdom's NHS. Despite the significant impact that a poor working relationship between doctors and managers could have on the quality of care, there is limited research in this area.

Objectives: To investigate the organisational factors, contributing to the poor working relationship between doctors and hospital managers with a view to recommend potential solutions to address them.

Methods: We performed a systematic literature review; a comprehensive search of AMED, MEDLINE, CINAHL, Plus with Full Text, SportDiscus and EBSCO EBooks from January 2000 to July 2019 and updated in March 2022, and no further article was found that meets the selection criteria. Mixed methods, qualitative studies and quantitative studies published in English language in peer reviewed journals between January 2000 and March 2022 were included. Study selection, data extraction and appraisal of study were undertaken by the authors. Quality criteria were selected from CASP Checklist.

Results: A total of 49,340 citations were retrieved and screened for eligibility, 41 articles were assessed as full text and 15 met the inclusion criteria. These include 2 mixed method studies, 8 qualitative studies, and 5 quantitative studies. A thematic analysis was undertaken, and narrative summaries used to synthesise the findings.

Conclusion: The findings of this systematic review show strong evidence of poor collaboration and lack of effective communication that contribute to poor working relationships between physicians and hospital administrators. The results from this review may guide the development of a hospital plan that involves both doctors and managers in the decision making process regarding the quality of patient care, which could potentially enhance the relationship between the two groups as it would build trust between them.
A Systematic Review of Long-term Antidepressant Outcomes in Comorbid Depression and Type 2 Diabetes
Authors: Jeffery Annie , Buckman Joshua E. J. , Francis Emma , Walters Kate , Wong Ian C. K. , Osborn David , Hayes Joseph F.
Published: April 2022

Background

Depression is a common and chronic comorbidity affecting approximately one in four people with type 2 diabetes (T2DM), and often lasting several years. Past systematic reviews have been unable to identify evidence for long-term (12+ months) antidepressant treatment outcomes in comorbid depression and type 2 diabetes. These reviews are >10years old, included only randomised controlled trials or had limited search strategies. We aimed to systematically review observational studies for long-term outcomes of antidepressant treatment in adults with comorbid depression and T2DM, including broader, up-to-date searches.

Methods and findings

This review was pre-registered on PROSPERO (CRD42020182788). We searched seven databases using terms related to depression, T2DM and antidepressant medication. From 14,389 reports retrieved, 63 were screened at full text stage and 0 met inclusion criteria. The reasons for exclusion at full text stage were: Studies did not meet inclusion criteria for antidepressant treatment (n = 50); studies did not meet inclusion criteria for T2DM (n = 36); studies did not meet inclusion criteria for depression (n = 29); studies did not include follow-up time (n = 25); studies did not meet inclusion criteria for observational study (n = 14); studies did not include any measurable outcomes (n = 5); studies did not include a suitable comparison (n = 3).

Conclusions

We found no evidence concerning long-term outcomes of antidepressant treatment in individuals with comorbid depression and T2DM. Insufficient ascertainment of antidepressant prescription, case identification, and short follow-up times are the primary reasons for this. Research is urgently required to determine long-term outcomes associated with antidepressant treatment in this patient group.
Systematic comparison of Mendelian randomization studies and randomized controlled trials using electronic databases
Authors: Sobczyk Maria K. , Zheng Jie , Smith George Davey , Gaunt Tom R.
Published: April 2022

Mendelian Randomization (MR) uses genetic instrumental variables to make causal inferences. Whilst sometimes referred to as “nature’s randomized trial”, it has distinct assumptions that make comparisons between the results of MR studies with those of actual randomized controlled trials (RCTs) invaluable. To scope the potential for (semi-)-automated triangulation of MR and RCT evidence, we minedClinicalTrials.Gov, PubMed and EpigraphDB databases and carried out a series of 26 manual literature comparisons among 54 MR and 77 RCT publications. We found that only 11% of completed RCTs identified inClinicalTrials.Govsubmitted their results to the database. Similarly low coverage was revealed for Semantic Medline (SemMedDB) semantic triples derived from MR and RCT publications –25% and 12%, respectively. Among intervention types that can be mimicked by MR, only trials of pharmaceutical interventions could be automatically matched to MR results due to insufficient annotation with MeSH ontology. A manual survey of the literature highlighted the potential for triangulation across a number of exposure/outcome pairs if these challenges can be addressed. We conclude that careful triangulation of MR with RCT evidence should involve consideration of similarity of phenotypes across study designs, intervention intensity and duration, study population demography and health status, comparator group, intervention goal and quality of evidence.