bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing Risk Factors for Necrotizing Enterocolitis
Authors: Dickison Linda , Gonzalez-Shalaby Carmela
Published: April 2022

Background:

Development of necrotizing enterocolitis is multifactorial, with contributing factors that are unique to the preterm infant in the neonatal intensive care unit (NICU). The use of probiotics may reduce these risk factors.

Purpose:

To evaluate evidence of biologic plausibility for probiotic supplementation to mitigate key risk factors implicated in the development of disease and show recent evidence of safety and effectiveness.

Data Sources:

A literature survey of electronic databases, including PubMed, Cochrane Database of Systematic Reviews, and CINAHL, was conducted.

Study Selection:

Selection terms included “necrotizing enterocolitis,” “probiotics,” and “prematurity.” Reviews that were included were full text, in English, and published in the last 5 years. Ten systematic reviews of randomized controlled trials were extracted from 749 records. Excluded were studies that used adjuncts to probiotics, such as lactoferrin or prebiotics, and studies of probiotics given antenatally.

Data Extraction:

Two independent reviewers extracted data to AMSTAR 2, a critical appraisal tool for systematic reviews of randomized or nonrandomized studies of healthcare interventions.

Results:

All the reviews found statistically significant reductions in necrotizing enterocolitis rates after supplementation with probiotics. None of the reviews reported adverse effects.

Implication for Practice and Research:

Probiotic supplementation with specific strains reduces risk for necrotizing enterocolitis. To advance probiotic use in the NICU, additional high-quality trials are needed to focus on specific strains or combinations of strains and to evaluate dosing and duration of treatment.

Video Abstract available at
https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx.
Histopathological and immunological spectrum in response evaluation of talimogene laherparepvec treatment and correlation with durable response in patients with cutaneous melanoma
Authors: Mulder Evalyn E.A.P. , Damman Jeffrey , Verver Daniëlle , van der Veldt Astrid A.M. , Tas Sam , Khemai-Mehraban Tamana , Heezen Kim C. , Wouters Roxane A. , Verhoef Cornelis , Verjans Georges M.G.M. , Langerak Anton W. , Grünhagen Dirk J. , Mooyaart Antien L.
Published: April 2022

Talimogene laherparepvec (T-VEC) is an intralesional oncolytic virotherapy for patients with irresectable stage III–IVM1a cutaneous melanoma. Although this treatment is considered to mainly act through T cell-mediated mechanisms, prominent numbers of plasma cells after T-VEC treatment have been described. The aim was to investigate how often these plasma cells were present, whether they were relevant in the response to treatment, and if these or other histopathological features were associated with durable response to treatment. Histopathological (granulomas, perineural inflammation, etc.) and immunological features [e.g. B cells/plasma cells (CD20/CD138) and T cells (CD3,CD4,CD8)] were scored and correlated with durable tumor response [i.e. complete response (CR) persisting beyond 6 months after treatment]. Plasmacellular infiltrate was examined with next-generation sequencing and immunohistochemistry (IgG, IgM, IgA, and IgD). Plasma cells were present in all T-VEC injected biopsies from 25 patients with melanoma taken at 3–5 months after starting treatment. In patients with a durable response (n = 12), angiocentric features and granulomas were more frequently identified compared with patients without a (durable) response (n = 13); 75% versus 29% for angiocentric features (P = 0.015) and 58% versus 15% for granulomas (P = 0.041). There was a class switch of IgM to IgG with skewing to certain dominant Ig heavy chain clonotypes. An angiocentric granulomatous pattern in T-VEC injected melanoma lesions was associated with a durable CR (>6 months). Plasma cells are probably a relevant feature in the mechanism of response but were not associated with durable response.
Recurrent SARS-CoV-2 Infection and Impaired Immunologic Response in a Pediatric Oncologic Patient While Treated With Radiochemotherapy
Authors: Eichholz Thomas , Arendt Anne-Marie , Holzer Ursula , Seitz Christian , Rabsteyn Armin , Ganzenmueller Tina , Klein Reinhild , Walz Juliane , Lang Peter
Published: April 2022

Immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pediatric patients with malignant disease may be affected by tumor therapy. Here, we report the case of a child with rhabdomyosarcoma and recurrent SARS-CoV-2 infection. Immunologic responses, analyzed by T-cell activity and anti-viral IgG levels, were impaired and not durable as a result of intensive radiochemotherapy.
Congenital Syphilis and the Prozone Phenomenon: Case Report
Authors: Catueno Samanta , Tsou Po-Yang , Wang Yu-Hsun , Becker Emily , Fergie Jaime
Published: April 2022

Congenital syphilis represents an important public health challenge in the United States, and its prevalence has been increasing for the past 10 years because of many factors. The diagnosis can be difficult given its various and nonspecific clinical manifestations in newborns, and the possibility of false negative results during prenatal care. The prozone phenomenon, caused by an excess of antibody, which interferes with the regular screening tests, is a cause of false negative tests. This could delay the diagnosis and increase morbidity and mortality in the newborn. We present a case of congenital syphilis in a 3-month-old infant whose mother had prenatal care and negative tests for syphilis, which contributed to the late diagnosis. In the face of clinical findings suggestive of congenital syphilis and negative maternal syphilis tests healthcare providers should consider the possibility of maternal false negative test caused by the prozone phenomenon.
Factors Related to Psychological Distress in Multiparous Women in the First Trimester: A Cross-Sectional Study
Authors: WANG Shu-Wei , CHEN Jyu-Lin , CHEN Yi-Hsuan , WANG Ruey-Hsia
Published: April 2022

Background

The birth rate in Taiwan has declined rapidly; thus, encouraging women to give birth is an important issue in the country. Pregnant women may experience psychological distress, which may negatively impact the health of children and mothers. Prenatal psychological distress is more common in multiparous women than in primiparous women. In addition, compared with that in the second and third trimesters, psychological distress in the first trimester is relatively high. Understanding psychological distress and the associated factors for multiparous women in the first trimester is important to providing early interventions and preventing subsequent maternal and child health problems.

Purpose

This study was designed to examine the important predictive factors related to depression, anxiety, and stress among Taiwanese multiparous women in the first trimester.

Methods

A cross-sectional design was used. In all, 216 multiparous women at 16 weeks of pregnancy were recruited from three hospitals in Taiwan. Self-reported questionnaires were used to gather data on demographic characteristics, the parenting stress of motherhood, spousal support, and psychological distress. A multiple logistic regression analysis was conducted to examine the factors associated with psychological distress.

Results

The prevalence of depression, anxiety, and stress in multiparous women was found to be 31.9%, 42.6%, and 11.1%, respectively. The multiple logistic regression analysis indicated that the stress related to parent–child interaction was a significant predictor of depression and anxiety, the stress related to child-rearing was a significant predictor of anxiety, and low spousal instrumental support was a significant predictor of stress. The model respectively explained 30%, 27%, and 23% of the variance in depression, anxiety, and stress.

Conclusions/Implications for Practice

Reducing the stress related to parent–child interaction and child-rearing and encouraging spousal instrumental support should be considered during prenatal care when designing interventions to reduce the psychological distress of multiparous women in their first trimester.
Supporting business educators and students against COVID-19 trauma using trauma-focused cognitive behavioral therapy
Authors: Edeh Nathaniel Ifeanyi , Ugwoke Ernest O. , Anaele Eunice N. , Madusaba Babalulu M. , Naboth-Odums Augustine , Isiwu Evelyn A. , Olinya Timothy O. , Enyi Chinwe , David Adeleye Olaide , Yumma Dorcas Cathreine , Yeldim Tongshinen Peter , Odunukwe Maryann Chiamaka , Victor Sandra Nkoliko , Abubakar Ahmed
Published: April 2022

Background:

The outbreak of COVID-19 manifests in peoples’ mental health and psychological dispositions and may also result to acute distress, depression, anxiety and post-traumatic stress disorder (PTSD) on victims. The objective of this study was to support business educators’ and students’ mental health against coronavirus trauma using trauma-focused cognitive behavioral therapy (TF-CBT).

Methods:

The participants (n = 74 – educators and students) who indicated PTSD symptoms based on the self-reporting questionnaire they filled, were randomly assigned to treatment and waitlist control groups. The TF-CBT manual was used for the intervention. The intervention was a 14-week treatment with 2 weeks follow-up meeting. Using repeated measures of Analysis of Variance, we determined the level of improvement of each participant in the treatment group against Coronavirus trauma at the end of the intervention.

Results:

The study established that gender has no significant difference in determining the effects of Coronavirus trauma on participants. Through intervention, the PTSDs and depression arising from Coronavirus event were significantly reduced in the treatment group. Again, there was a significant improvement in the participants’ general mental health at the end of the intervention. Hence, we established the implication for research and practice in line with the outcome of the study. The study advocates that TF-CBT should be employed by educational institutions in Nigeria to cushion the traumatic effects of coronavirus and future disasters on both workers and students.

Conclusion:

We conclude that mental health problems remain a serious challenge among business educators and students in this COVID-19 pandemic era. The study established that low educational qualifications, PTSD symptoms and negative coping strategies are the factors aggravating the general low mental health of the study participants. Finally, we advocate that the educational institutions in Nigeria should adopt TF-CBT interventions to support staff and students’ mental health against adverse effects of COVID-19.
Prevalence and Risk Factors for Endocrine Disorders in Childhood Brain Tumors From a Single Tertiary Center in Malaysia
Authors: Ng Yean Joo , Jalaludin Muhammad Yazid , Foo Jen Chun , Qaddoumi Ibrahim , Rajagopal Revathi
Published: April 2022

Patients with childhood brain tumors are at risk of endocrine disorders. The prevalence of endocrine disorders varies across the world but is unknown in Malaysia. This study’s objectives were to determine the prevalence of endocrine disorders among children with brain tumors in Malaysia and to identify endocrinopathy-associated risk factors. We retrospectively reviewed the clinical data of pediatric patients with brain tumors diagnosed and treated at the University Malaya Medical Center from 1 January 2001 to 31 December 2015, with a follow-up period until the age of 18 years old or at least 3 years from the initial diagnosis. A total of 106 patients were included; 71 patients (66%) were screened for endocrine disorders, and 61% of these had endocrine disorders at a median follow-up of 4 years. Hypothyroidism, short stature, and adrenocortical insufficiency were present in one-third of the patients, followed by central diabetes insipidus (21%), growth hormone deficiency (10%), delayed puberty (9%), and precocious puberty (4%). Radiation therapy and surgical intervention were risk factors for endocrine disorders, but hydrocephalus, supratentorial tumors, and malignant tumors were not. Most endocrinopathies developed within the first 2 years of brain tumor diagnosis. Therefore, standard endocrine-monitoring guidelines aiming for early diagnosis and therapy are essential.
Long-term Results of Splenectomy in Transfusion-dependent Thalassemia
Authors: Akca Tugberk , Ozdemir Gul N. , Aycicek Ali , Ozkaya Guven
Published: April 2022

Splenectomy is indicated in transfusion-dependent thalassemia (TDT) only in certain situations. This study aimed to present the effectiveness, complications, and long-term follow-up results of splenectomy in children with TDT. We performed a 30-year single-institution analysis of cases of splenectomy for TDT between 1987 and 2017 and their follow-up until 2021. A total of 39 children (female/male: 24/15) were included. The mean age at splenectomy was 11.2±3.2 years, and their mean follow-up duration after splenectomy was 21.5±6.4 years. Response was defined according to the patient’s annual transfusion requirement in the first year postsplenectomy and on the last follow-up year. Complete response was not seen in any of the cases; partial response was observed in 32.3% and no response in 67.6%. Thrombocytosis was seen in 87% of the patients. The platelet counts of 7 (17.9%) patients were >1000 (109/L), and aspirin prophylaxis was given to 22 (56.4%) patients. Complications were thrombosis in 2 (5.1%) patients, infections in 11 (28.2%) patients, and pulmonary hypertension in 4 (10.2%) patients. Our study showed that after splenectomy, the need for transfusion only partially decreased in a small number of TDT patients. We think splenectomy can be delayed with appropriate chelation therapy up to higher annual transfusion requirement values.
School Closures in the United States and Severe Respiratory Illnesses in Children: A Normalized Nationwide Sample
Authors: Rogerson Colin M. , Lin Anna , Klein Margaret J. , Zee-Cheng Janine , McCluskey Casey K. , Scanlon Matthew C. , Rotta Alexandre T. , Remy Kenneth E. , Shein Steven L. , Carroll Christopher L.
Published: April 2022

OBJECTIVES:

To determine the association between nationwide school closures and prevalence of common admission diagnoses in the pediatric critical care unit.

DESIGN:

Retrospective cohort study.

SETTING:

National database evaluation using the Virtual Pediatric Systems LLC database.

PATIENTS:

All patients admitted to the PICU in 81 contributing hospitals in the United States.

MEASUREMENTS AND MAIN RESULTS:

Diagnosis categories were determined for all 110,418 patients admitted during the 20-week study period in each year (2018, 2019, and 2020). Admission data were normalized relative to statewide school closure dates for each patient using geographic data. The “before school closure” epoch was defined as 8 weeks prior to school closure, and the “after school closure” epoch was defined as 12 weeks following school closure. For each diagnosis, admission ratios for each study day were calculated by dividing 2020 admissions by 2018–2019 admissions. The 10 most common diagnosis categories were examined. Significant changes in admission ratios were identified for bronchiolitis, pneumonia, and asthma. These changes occurred at 2, 8, and 35 days following school closure, respectively. PICU admissions decreased by 82% for bronchiolitis, 76% for pneumonia, and 76% for asthma. Nonrespiratory diseases such as diabetic ketoacidosis, status epilepticus, traumatic injury, and poisoning/ingestion did not show significant changes following school closure.

CONCLUSIONS:

School closures are associated with a dramatic reduction in the prevalence of severe respiratory disease requiring PICU admission. School closure may be an effective tool to mitigate future pandemics but should be balanced with potential academic, economic, mental health, and social consequences.
The Expression of HPV E6/E7 mRNA In Situ Hybridization in HPV Typing-negative Cervical Cancer
Authors: Xu Yating , Sun Yonghong , Chang Hui , Cai Jingjing , Cao Chengcheng , Zhang Baogang , Zhang Youzhong , Liu Yuzhen
Published: April 2022

High-risk human papillomavirus (HPV) persistent infection is the major tumorigenesis factor for cervical cancer (CC). However, the incidence of HPV-negative CC is 5% to 30% with different HPV detection methods. High-risk HPV E6/E7 mRNA in situ hybridization (RISH) can detect HPV-driven tumors. Our study aimed to explore whether HPV typing-negative CC was caused by HPV infection. The tissues of CC patients with HPV typing results, collected from cervical biopsies, conization, or hysterectomies, were submitted to RISH using RNAscope chromogenicin. Immunohistochemistry was performed to evaluate the expression of p16INK4a and Ki-67. A total of 308 women with HPV typing results were enrolled, and 30 (9.74%) cases of HPV typing were negative. In HPV typing-negative CCs, 28/30 (93.3%) were positive for RISH, which contained 22/22 (100%) squamous cell carcinomas and 6/8 (75%) adenocarcinomas. RISH was positive in 278/278 (100%) HPV typing-positive CCs, which included 232/232 (100%) squamous cell carcinomas and 46/46 (100%) adenocarcinomas. Positive RISH in HPV typing-negative CC was significantly lower than in the HPV typing-positive group (P=0.002, 95% confidence interval: 0.848–1.027). However, this significant difference only existed in adenocarcinoma. No significant differences were seen in the expression of p16INK4a and Ki-67 (all P>0.05). HPV typing may cause misdiagnosis in 9.74% of CC patients, and HPV E6/E7 mRNA can detect HPV in CC with HPV typing-negative patients. This approach could provide a novel option to accurately detect high-risk HPVs in cervical tumors and help to eliminate the percentage of misdiagnosed HPV-related cases.
Characterisation of the symbionts in the Mediterranean fruit fly gut
Authors: Darrington Mike , Leftwich Philip T. , Holmes Neil A. , Friend Lucy A. , Clarke Naomi V. E. , Worsley Sarah F. , Margaritopolous John T. , Hogenhout Saskia A. , Hutchings Matthew I. , Chapman Tracey
Published: April 2022

Symbioses between bacteria and their insect hosts can range from loose associations through to obligate interdependence. While fundamental evolutionary insights have been gained from the in-depth study of obligate mutualisms, there is increasing interest in the evolutionary potential of flexible symbiotic associations between hosts and their gut microbiomes. Understanding relationships between microbes and hosts also offers the potential for exploitation for insect control. Here, we investigate the gut microbiome of a global agricultural pest, the Mediterranean fruit fly (Ceratitis capitata). We used 16S rRNA profiling to compare the gut microbiomes of laboratory and wild strains raised on different diets and from flies collected from various natural plant hosts. The results showed that medfly guts harbour a simple microbiome that is primarily determined by the larval diet. However, regardless of the laboratory diet or natural plant host on which flies were raised,

Klebsiella

spp. dominated medfly microbiomes and were resistant to removal by antibiotic treatment. We sequenced the genome of the dominant putative

Klebsiella

spp. (‘Medkleb’) isolated from the gut of the Toliman wild-type strain. Genome-wide ANI analysis placed Medkleb within the K. oxytoca / michiganensis group. Species level taxonomy for Medkleb was resolved using a mutli-locus phylogenetic approach - and molecular, sequence and phenotypic analyses all supported its identity as

K. michiganensis

. Medkleb has a genome size (5825435 bp) which is 1.6 standard deviations smaller than the mean genome size of free-living

Klebsiella

spp. Medkleb also lacks some genes involved in environmental sensing. Moreover, the Medkleb genome contains at least two recently acquired unique genomic islands as well as genes that encode pectinolytic enzymes capable of degrading plant cell walls. This may be advantageous given that the medfly diet includes unripe fruits containing high proportions of pectin. The results suggest that the medfly harbours a commensal gut bacterium that may have developed a mutualistic association with its host and provide nutritional benefits.
Ultrafast and interpretable single-cell 3D genome analysis with Fast-Higashi
Authors: Zhang Ruochi , Zhou Tianming , Ma Jian
Published: April 2022

Single-cell Hi-C (scHi-C) technologies can probe three-dimensional (3D) genome structures in single cells and their cell-to-cell variability. However, existing scHi-C analysis methods are hindered by the data quality and the complex 3D genome patterns. The lack of computational scalability and interpretability poses further challenges for large-scale scHi-C analysis. Here, we introduce Fast-Higashi, an ultrafast and interpretable method based on tensor decomposition that can jointly identify cell identities and chromatin meta-interactions. Fast-Higashi is able to simultaneously model multiple tensors with unmatched features of different sizes. A new partial random walk with restart (Partial RWR) algorithm in Fast-Higashi efficiently mitigates data sparseness. Extensive evaluations on real scHi-C datasets demonstrate the advantage of Fast-Higashi over existing methods for embedding, leading to improved delineation of rare cell types and better reconstruction of developmental trajectories. Fast-Higashi can directly infer chromatin meta-interactions, identify 3D genome features that define distinct cell types, and help elucidate cell type-specific connections between genome structure and function. Moreover, Fast-Higashi can be generalized to incorporate other single-cell omics data. Fast-Higashi provides a highly efficient and interpretable scHi-C analysis solution that is applicable to a broad range of biological contexts.
The yeast claudin Dcv1 is important for demarcating the front domain of pheromone-responding yeast cells
Authors: Sukumar Madhushalini , DeFlorio Reagan , Pai Chih-Yu , Stone David E.
Published: April 2022

Cell polarization in response to chemical gradients is important in development and homeostasis across eukaryota. Chemosensing cells orient toward or away from gradient sources by polarizing along a front-rear axis. Using the chemotropic mating response of the budding yeast S. cerevisiae as a model of environmentally-induced cell polarization, we found that Dcv1, a claudin homolog, is a determinant of front-rear polarity. Although Dcv1 localized uniformly on the plasma membrane (PM)† of vegetative cells, it was confined to the rear of cells responding to pheromone, away from the pheromone receptor and mating projection. Deletion of DCV1 conferred mislocalization of sensory, polarity, and trafficking proteins, as well as the PM lipids ergosterol, phosphatidylinositol-4,5-bisphosphate (PIP2), and phosphatidylserine (PS). These phenotypes correlated with defects in pheromone-gradient tracking and cell fusion. We propose that the novel claudin-like and rear-domain protein, Dcv1, demarcates the mating-specific front domain primarily by restricting PM lipid distribution. Consistent with this hypothesis, a mutation that blocks ergosterol biosynthesis partially phenocopies dcv1Δ.

Summary statement

The yeast claudin Dcv1 facilitates the proper localization of plasma membrane lipids and proteins that are required for front-rear polarity, efficient chemotropism, and cell fusion.
Men in menopause? Experimental verification of the mate choice theory withDrosophila melanogastershows both sexes can undergo menopause
Authors: Purohith Divya , Chaudhary Mitali , Gomes Alyssa , Rajapakse Nina , Das Aditi , Dhanvanthry Neha , Brown Michelle , Mukherjee Manan , Singh Rama S.
Published: April 2022

Various hypotheses regarding the origin of menopause have been proposed, and although the kin-selection-based theory appears promising, it involves population genetic processes that are insufficient to compensate for loss of fitness. The grandmother hypothesis and its variation the live long hypothesis are untenable; the former requires “climbing a steep fitness hill”, as grandmothers share only 25% of their genes with their grandchildren, compared to 50% with their direct offspring, while the latter proposes a prolongation of the post-menopausal lifespan through selection, which is impossible in a population of non-reproducing females. The mate choice theory explains menopause as the result of asymmetric mating involving younger females and older males that leads to an accumulation of infertility mutations and the evolution of menopause in older females. In this study, we investigated the mate choice theory using an infertility mutation accumulation experiment withDrosophila melanogasterthat involved mating between individuals of different age groups. After 70 generations of asymmetric mating, the results showed that younger females who were paired with older males showed declining fertility in old age. The same trend was noted with younger males when mated with older females; the fertility of the males declined in old age. These results support the mate choice theory and indicate that menopause is not a life history trait of females but of the sex of the younger mate. Mate choice theory treats the evolution of menopause and post-menopausal lifespan as independent traits that are driven by the mate choices exercised by older males. Menopause may be an atypical process because the evolutionary mechanism (age-restricted asymmetric mating) involved is rarely observed.
COVID-19 Infection and Transmission Includes Complex Sequence Diversity
Authors: Chan Ernest R. , Jones Lucas D. , Linger Marlin , Kovach Jeffrey D. , Torres-Teran Maria M. , Wertz Audric , Donskey Curtis J. , Zimmerman Peter A.
Published: April 2022

SARS-CoV-2 whole genome sequencing has played an important role in documenting the emergence of polymorphisms in the viral genome and its continuing evolution during the COVID-19 pandemic. Here we present data from over 360 patients to characterize the complex sequence diversity of individual infections identified during multiple variant surges (e.g., Alpha and Delta; requiring ≥ 80% genome coverage and ≥100X read depth). Across our survey, we observed significantly increasing SARS-CoV-2 sequence diversity during the pandemic and frequent occurrence of multiple biallelic sequence polymorphisms in all infections. This sequence polymorphism shows that SARS-CoV-2 infections are heterogeneous mixtures. Convention for reporting microbial pathogens guides investigators to report a majority consensus sequence. In our study, we found that this approach would under-report at least 79% of the observed sequence variation. As we find that this sequence heterogeneity is efficiently transmitted from donors to recipients, our findings illustrate that infection complexity must be monitored and reported more completely to understand SARS-CoV-2 infection and transmission dynamics involving both immunocompetent and immunocompromised patients. Many of the nucleotide changes that would not be reported in a majority consensus sequence have now been observed as lineage defining SNPs in Omicron BA.1 and/or BA.2 variants. This suggests that minority alleles in earlier SARS-CoV-2 infections may play an important role in the continuing evolution of new variants of concern.

AUTHOR SUMMARY

Evolution of the virus causing COVID-19 (SARS-CoV-2) has been associated with significant transmission surges. With evolution of SARS-CoV-2, evidence has accumulated regarding increased transmissibility of lineages, varying severity of illness, evasion of vaccines and diagnostic tests. Continuous tracking of SARS-CoV-2 lineage evolution distills very large and complex viral sequence data sets down to consensus sequences that report the majority nucleotide at each of over 29,000 positions in the SARS-CoV-2 genome. We observe that this eliminates considerable sequence variation and leads to a significant underestimation of SARS-CoV-2 infection diversity and transmission complexity. Additionally, concentration on the majority consensus sequence diverts attention from genetic variation that may contribute significantly to the continuing evolution of the COVID-19 pandemic.
Predictors of COVID-19 vaccine uptake: An online longitudinal study of US Veterans and non-Veterans
Authors: Thorpe Alistair , Fagerlin Angela , Drews Frank A. , Shoemaker Holly , Brecha Federica S. , Scherer Laura D.
Published: April 2022

Background

To effectively promote vaccine uptake, it is important to understand which people are most and least inclined to be vaccinated and why.

Purpose

To identify predictors of COVID-19 vaccine uptake and reasons for non-vaccination.

Design

A longitudinal English-language survey study.

Setting

Online in December-2020, January-2021, and March-2021. Participants. 930 US respondents (63% Veterans).

Measurements

Surveys included questions about respondents’ behaviors, well-being, healthcare experiences, and attitudes regarding the pandemic.

Results

The proportion of respondents who received ≥1-dose of a COVID-19 vaccine increased from 18% in January to 67% in March. Older age predicted vaccine uptake in January (OR=2.02[95%CI=1.14–3.78], p<.001) and March (10.92[6.76–18.05], p<.001). In January, additional predictors of vaccine uptake were higher numeracy (1.48[1.20–1.86], p<.001), COVID-19 risk perceptions (1.35[1.03–1.78], p=.029), and believing it is important that adults get the COVID-19 vaccine (1.66[1.05–2.66], p=.033). In March, additional predictors of vaccine uptake were believing it is important that adults get the COVID-19 vaccine (1.63[1.15–2.34], p=.006), previous (January) COVID-19 vaccine intentions (1.37[1.10–1.72], p=.006), and belief in science (0.84[0.72–0.99], p=.041). Concerns about side effects and the vaccine development process were the most common reasons for non-vaccination. Unvaccinated respondents with no interest in getting a COVID-19 vaccine were younger (0.27[0.09–0.77], p=.016), held negative views about COVID-19 vaccines for adults (0.15[0.08–0.26], p<.001), had lower trust in healthcare (0.59[0.36–0.95], p=.032), and preferred to watch and wait in clinically ambiguous medical situations (0.66[0.48–0.89], p=.007).

Limitations

Reliance on the accuracy and consistency of self-reported data.

Conclusion

These findings offer important insights regarding key predictors of vaccine uptake during the early stages of the COVID-19 vaccine rollout in the US, which can help guide health communications and public outreach. Evidence that attitudes and intentions towards COVID-19 vaccines are important predictors of uptake provides validation for studies which have used these measures and reinforces the need to develop effective strategies for addressing concerns about vaccine safety and development which continue to be at the forefront of vaccine hesitancy.

Registration

The pre-registration document associated with this manuscript is available at: https://aspredicted.org/MKS_HRZ.
High-dimensional and spatial analysis reveals immune landscape dependent progression in cutaneous squamous cell carcinoma
Authors: Ferguson A.L. , Sharman A.R. , Allen R.O. , Ye T. , Lee J.H. , Low H. , Ch’ng S. , Palme C.E. , Ashford B. , Ranson M. , Clark J.R. , Patrick E. , Gupta R. , Palendira U.
Published: April 2022

Purpose

The tumour immune microenvironment impacts the biological behaviour of the tumour but its effect on clinical outcomes in head and neck cutaneous squamous cell carcinomas (HNcSCC) is largely unknown.

Experimental Design

We compared the immune milieu of high-risk HNcSCC that never progressed to metastasis with those that metastasised using multi-parameter imaging mass cytometry. The cohort included both immunosuppressed patients (IS) and patients with an absence of clinical immune-suppression (ACIS). Spatial analyses were used to identify cellular interactions that were associated with tumour behaviour.

Results

Non-progressing primary HNcSCC were characterised by higher CD8+ and CD4+ T cell responses, including numerically increased Regulatory T cells. By contrast, primary lesions from HNcSCC patients who progressed were largely devoid of T cells with lower numbers of innate immune cells and increased expression of checkpoint receptors and in the metastatic lesions were characterised by an accumulation of B cells. Spatial analysis reveals multiple cellular interactions associated with non-progressing primary tumours that were distinct in primary tumours of disease progressing patients. Cellular regional analysis of the tumour microenvironment also shows squamous cell-enriched tumour regions associated with primary non-progressing tumours.

Conclusions

Effective responses from both CD8+ and CD4+ T cells in the tumour microenvironment are essential for immune control of primary HNcSCC. Our findings indicate that the early events that shape the immune responses in primary tumours dictate progression and disease outcomes in HNcSCC.

Translational Relevance

The ability to predict metastatic tumour progression at the time of initial diagnosis of primary HNcSCC could tailor personalised medical care including disease surveillance strategies and identifying patients who will benefit most from adjuvant therapy.

One Sentence Summary

The immune landscape of high-risk cutaneous squamous cell carcinoma differs in tumours that never progress compared to those that progress to metastasis.
The baseline immunological and hygienic status of pigs impact disease severity of African swine fever
Authors: Radulovic Emilia , Mehinagic Kemal , Wüthrich Tsering , Hilty Markus , Posthaus Horst , Summerfield Artur , Ruggli Nicolas , Benarafa Charaf
Published: April 2022

African Swine Fever virus (ASFV) is a large double-enveloped DNA virus of the Asfarviridae family that causes a lethal hemorrhagic disease in domestic pigs and wild boars. Since 2007, a highly virulent genotype II strain has emerged and spread in Europe and South-East Asia, where millions of animals succumbed to the disease. Field- and laboratory-attenuated strains of ASFV cause highly variable clinical disease severity and survival, and mechanisms remain unclear. We hypothesized that the immunological and hygienic status of pigs is a determinant of ASF disease course. Here we compared the immunological profile at baseline and in response to ASFV infection in specific pathogen-free (SPF) and farm-raised Large White domestic pigs. At steady state, SPF pigs showed lower white blood cell counts and a lower basal inflammatory and antiviral transcriptomic profile compared to farm pigs associated with profound differences in gut microbiome composition. After inoculation with a highly virulent ASFV genotype II strain (Armenia 2008), severe clinical signs, viremia and pro-inflammatory cytokines appeared sooner in SPF pigs, indicating a reduced capacity to control early virus replication. In contrast, during infection with an attenuated field isolate (Estonia 2014), SPF pigs presented a milder and shorter clinical disease with full recovery, whereas farm pigs presented severe protracted disease with 50% lethality. Interestingly, farm pigs showed higher production of inflammatory cytokines, whereas SPF pigs produced more anti-inflammatory IL-1ra early after infection, and presented a stronger expansion of leukocytes in the recovery phase. Altogether, our data indicate that the hygiene-dependent innate immune status has a double-edge sword impact on immune responses in ASF pathogenesis. While the higher baseline innate immune activity helps the host in reducing initial virus replication, it promotes immunopathological cytokine responses, and delays lymphocyte proliferation after infection with an attenuated strain. Such effects should be considered for live vaccine development and vigilance.
Bleaching-resistant, near-continuous single-molecule fluorescence and FRET based on fluorogenic and transient DNA binding
Authors: Kümmerlin Mirjam , Mazumder Abhishek , Kapanidis Achillefs N.
Published: April 2022

Photobleaching of fluorescent probes limits the observation span of typical single-molecule fluorescence measurements and hinders observation of dynamics at long timescales. Here, we present a general strategy to circumvent photobleaching by replenishing fluorescent probes via transient binding of fluorogenic DNAs to complementary DNA strands attached to a target molecule. Our strategy allows observation of near-continuous single-molecule fluorescence for more than an hour, a timescale two orders of magnitude longer than the typical photobleaching time of single fluorophores under our conditions. Using two orthogonal sequences, we show that our method is adaptable to Förster Resonance Energy Transfer (FRET) and that can be used to study the conformational dynamics of dynamic structures, such as DNA Holliday junctions, for extended periods. By adjusting the temporal resolution and observation span, our approach should enable capturing the conformational dynamics of proteins and nucleic acids over a wide range of timescales.
scAEGAN: Unification of Single-Cell Genomics Data by Adversarial Learning of Latent Space Correspondences
Authors: Khan Sumeer Ahmad , Lehmann Robert , Martinez-de-Morentin Xabier , Ruiz Albert Malillo , Lagani Vincenzo , Kiani Narsis A. , Gomez-Cabrero David , Tegner Jesper
Published: April 2022

Recent progress in Single-Cell Genomics have produced different library protocols and techniques for profiling of one or more data modalities in individual cells. Machine learning methods have separately addressed specific integration challenges (libraries, samples, paired-unpaired data modalities). We formulate an unifying data-driven methodology addressing all these challenges. To this end, we design a hybrid architecture using an autoencoder (AE) network together with adversarial learning by a cycleGAN (cGAN) network, jointly referred to as scAEGAN. The AE learns a low-dimensional embedding of each condition, whereas the cGAN learns a non-linear mapping between the AE representations. The core insight is that the AE respects each sample’s uniqueness, whereas the cGAN exploits the distributional data similarity in the latent space. We evaluate scAEGAN using simulated data and real datasets of a single-modality (scRNA-seq), different library preparations (Fluidigm C1, CelSeq, CelSeq2, SmartSeq), and several data modalities such as paired scRNA-seq and scATAC-seq. We find that scAEGAN outperforms Seurat3 in library integration, is more robust against data sparsity, and beats Seurat 4 in integrating paired data from the same cell. Furthermore, in predicting one data modality from another, scAEGAN outperforms Babel. We conclude scAEGAN surpasses current state-of-the-art methods across several seemingly different integration challenges.
More than just hitchhikers: a survey of bacterial communities associated with diatoms originating from marine reptiles
Authors: Filek Klara , Lebbe Liesbeth , Willems Anne , Chaerle Peter , Vyverman Wim , Žižek Marta , Bosak Sunčica
Published: April 2022

Diatoms and bacteria are known for being the first colonizers of submerged surfaces including the skin of marine reptiles. Sea turtle carapace and skin harbour diverse prokaryotic and eukaryotic microbial taxa, including several epizoic diatoms. However, the importance of diatom-bacteria associations is hardly investigated in biofilms associated with animal hosts. This study provides a detailed inventory of diatoms, bacteria, and diatom-associated bacteria originating from several loggerhead sea turtles using a combination of metabarcoding and culturing approaches. Carapace and skin samples rbcL and 16S rRNA amplicon sequencing showed a high diversity of diatoms and bacteria, respectively. Cultures of putative epizoic and non-epizoic diatom strains contained from 18 to 101 bacterial amplicon sequence variants (ASVs) and their bacterial assemblages strongly reflected those of their source host. Diatom strains allowed for enrichment and isolation of rare-in-source bacterial families such as Marinobacteraceae, Alteromonadaceae, and Alcanivoracaceae. When accounting for phylogenetic relationships between bacterial ASVs, we observed related diatom genera might retain related microbial taxa in culture, regardless of the source environment. These data provide deeper insights into several levels of sea turtle epizoic diatom and bacterial communities, and reveal the potential of epizoic biofilms as a source of novel microbes and possibly important diatom-bacteria associations.
Structural Basis of MicroRNA Biogenesis by Dicer-1 and Its Partner Protein Loqs-PB
Authors: Jouravleva Karina , Golovenko Dmitrij , Demo Gabriel , Dutcher Robert C. , Tanaka Hall Traci M. , Zamore Phillip D. , Korostelev Andrei A.
Published: April 2022

In animals and plants, Dicer enzymes collaborate with double-stranded RNA-binding proteins to convert precursor-microRNAs (pre-miRNAs) into miRNA duplexes. We report six cryo-EM structures of Drosophila Dicer-1 and its partner Loqs-PB. The structures show Dicer-1•Loqs-PB (1) before binding pre-miRNA, (2) after binding and in a catalytically competent state, (3) after nicking one arm of the pre-miRNA, (4) following complete dicing and initial product release. Our reconstructions suggest that pre-miRNA binds a rare, open conformation of the Dicer-1•Loqs-PB heterodimer, enabling conformational proofreading. The Dicer-1 dsRBD and three Loqs-PB dsRBD domains form a tight belt around the pre-miRNA, distorting the RNA helix to place the scissile phosphodiester bonds in the RNase III active sites. Pre-mRNA cleavage shifts the RNA- binding domains and tightens Dicer-1, promoting product release. Our data suggest a model for how the Dicer-1•Loqs-PB complex effects a complete cycle of pre-miRNA recognition, stepwise endonuclease cleavage, and sequential product release.
Canal number and configuration are predictors of external root morphology
Authors: Gellis Jason J.
Published: April 2022

Within tooth roots canals can vary in shape and configuration, and it is not uncommon for a single root to contain multiple canals. Externally, root morphology also varies, though the range of variation, and its relation to canals remains little explored. This investigation of modern human post-canine teeth uses data from computerized tomography scans of a global sample of 945 modern humans to identify the most frequent phenotypes of root and canal morphologies, and investigate how canal number, shape, and configuration relate to external root morphology. Results (1) include descriptions and definitions of root and canal morphologies, counts, and configurations; (2) indicate that certain canal counts, morphologies, and configurations can predict external morphologies; and (3) that this pattern varies in individual teeth and roots in the maxilla and mandible.
The transcriptional regulator Sin3A balances IL-17A and Foxp3 expression in primary CD4 T cells
Authors: Perucho Laura , Icardi Laura , Di Simone Elisabetta , Basso Veronica , Zornoza Amaia Vilas , Lozano Teresa , Prosper Felipe , Lasarte Juan José , Mondino Anna
Published: April 2022

The Sin3 transcriptional regulator homolog A (Sin3A) is the core member of a multi-protein chromatin-modifying complex known to control gene transcription via epigenetic mechanisms. Its inactivation in developing thymocytes halts T cell maturation. We and others had previously shown that Sin3A controls STAT3 transcriptional activity. Given the role of STAT3 in the differentiation of T helper 17 cells critical in inflammatory disorders and against opportunistic infections, we asked whether Sin3A could also contribute to their differentiation. To this aim, we exploited CD4-Cre and CD4-CreERT2deleter strains for conditional and inducible Sin3A deletion in CD4 cell subsets. We report that Sin3A inactivation in vivo arrested thymocyte development at the double positive stage, hindering the characterization of mature T cells. At difference, tamoxifen-inducible Sin3A deletion proved permissive for in vitro proliferation of T cells in Th17 skewing conditions and the acquisition of memory markers. Transcriptional profiling indicated that while Sin3A inactivation imprinted T cells with a mTORC1 signaling gene signature, Sin3A deficient cells lacked the expression of IL-17A, the signature Th17 cytokine. This reflected a defective induction of Il17a, and also of the Il23R and Il22 genes, which occurred in spite of proper upregulation of the lineage defining transcription factor RORγt. We found that Sin3A inactivation was paralleled by increased STAT3 phosphorylation and nuclear representation, and by higher fractions of IL-2 and FoxP3 expressing cells. Such events proved causally linked as inhibiting Foxp3 partially rescued IL-17A expression, and neutralizing IL-2 simultaneously lowered the representation of FoxP3+cells, while rescuing IL- 17A+ ones. Thus, together our data underline a previously unappreciated role for Sin3A in Th17 differentiation and the shaping of their immunoregulatory potential.

Statement

This study identifies a new role for the transcriptional regulator Sin3A in the shaping of Th17 cell differentiation. Data indicate that by controlling IL-2 expression, and mTORC1 signaling, it balances IL-17A and Foxp3 levels, shaping Th17 inflammatory potentials.
A motor-based approach to induce chromosome-specific mis-segregations in human cells
Authors: Truong My Anh , Cané-Gasull Paula , de Vries Sippe G. , Nijenhuis Wilco , Wardenaar René , Kapitein Lukas C. , Foijer Floris , Lens Susanne M.A.
Published: April 2022

Various cancer types exhibit highly characteristic and recurrent aneuploidy patterns. The origin of these cancer type-specific karyotypes, and the extent to which they contribute to cancer progression, remains to be elucidated, partly because introducing or eliminating specific chromosomes in human cells still poses a challenge. Here, we describe a novel strategy to mis-segregate specific chromosomes at will in different human cell types. We employed Tet repressor (TetR) or nuclease dead Cas9 (dCas9) to link a plant-derived microtubule minus-end-directed kinesin (Physcomitrella patens Kinesin14VIb) to integrated Tet operon repeats and chromosome-specific endogenous repeats, respectively. By live- and fixed-cell imaging, we observed poleward movement of the targeted loci during (pro)metaphase. Kinesin14VIb-mediated pulling forces on the targeted chromosome were often counteracted by forces from kinetochore-attached microtubules. This tug of war resulted in chromosome-specific segregation errors during anaphase, and revealed that spindle forces can heavily stretch chromosomal arms. Using chromosome-specific FISH and single-cell whole genome sequencing, we established that motor-induced mis-segregations result in specific arm-level, and to a lesser extent, whole chromosome aneuploidies, after a single cell division. Our kinesin-based strategy to manipulate individual mitotic chromosomes opens up the possibility to investigate the immediate cellular responses to specific (arm level) aneuploidies in different cell types; an important step towards understanding how recurrent aneuploidy patterns arise in different cancer types.