bluuebunny/crossref_metadata_2025 huggingface dataset:
Interventions to Reduce Hospital and Emergency Department Utilization Among People With Alcohol and Substance Use Disorders
Authors: Gardner Rebekah L. , Baier Rosa R. , Cooper Emily L. , Clements Erin E. , Belanger Emmanuelle
Published: December 2021

Background:

Substance use disorders (SUDs), prevalent worldwide, are associated with significant morbidity and health care utilization.

Objectives:

To identify interventions addressing hospital and emergency department utilization among people with substance use, to summarize findings for those seeking to implement such interventions, and to articulate gaps that can be addressed by future research.

Research Design:

A scoping review of the literature. We searched PubMed, PsycInfo, and Google Scholar for any articles published from January 2010 to June 2020. The main search terms included the target population of adults with substance use or SUDs, the outcomes of hospital and emergency department utilization, and interventions aimed at improving these outcomes in the target population.

Subjects:

Adults with substance use or SUDs, including alcohol use.

Measures:

Hospital and emergency department utilization.

Results:

Our initial search identified 1807 titles, from which 44 articles were included in the review. Most interventions were implemented in the United States (n=35). Half focused on people using any substance (n=22) and a quarter on opioids (n=12). The tested approaches varied and included postdischarge services, medications, legislation, and counseling, among others. The majority of study designs were retrospective cohort studies (n=31).

Conclusions:

Overall, we found few studies assessing interventions to reduce health care utilization among people with SUDs. The studies that we did identify differed across multiple domains and included few randomized trials. Study heterogeneity limits our ability to compare interventions or to recommend one specific approach to reducing health care utilization among this high-risk population.
Prevalence and Characteristics of Avoidant/Restrictive Food Intake Disorder in Pediatric Neurogastroenterology Patients
Authors: Murray Helen Burton , Rao Fatima U. , Baker Corey , Silvernale Casey J. , Staller Kyle , Harshman Stephanie G. , Thomas Jennifer J. , Kuo Braden , Zar‐Kessler Claire
Published: December 2021

Recent reports document avoidant/restrictive food intake disorder (ARFID) symptoms among 13–40% of adults presenting to neurogastroenterology clinics, but ARFID in pediatrics is understudied. We conducted a retrospective review of charts from 129 consecutive referrals (ages 6–18 years; 57% female) for pediatric neurogastroenterology examination, from January 2016 through December 2018. Eleven cases (8%) met the full criteria for ARFID by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition and 19 cases (15%) had clinically significant avoidant/ restrictive eating behaviors with insufficient information for a definitive ARFID diagnosis. Of patients with ARFID symptoms (n = 30), 20 (67%) cited fear of gastrointestinal symptoms as motivation for their avoidant/ restrictive eating. Compared to patients without ARFID symptoms, patients with ARFID symptoms were older (P < .001), more likely to be female (51% vs 79%, P = 0.014), and more frequently presented with eating/weight‐related complaints (15% vs 33%, P = 0.026). This pilot retrospective study showed ARFID symptoms present in 23% of pediatric neurogastroenterology patients; further research is needed to understand risk and maintenance factors of ARFID in the neurogastroenterology setting.
“First Five” Quality Improvement Program Increases Adherence and Continuity with Well-child Care
Authors: Bunik Maya , Galloway Kelly , Maughlin Mike , Hyman Daniel
Published: December 2021

Introduction:

The American Academy of Pediatrics Bright Futures recommends routine well-child care as optimal care for children. This quality improvement project aimed to increase adherence to the “First Five” visits after newborn follow-up at 2, 4, 6, 9, and 12 months—by 25% (50% or higher) and continuity with providers by 20% (64% or higher) between 2013 and 2016.

Methods:

Retrospective data collection identified a quality gap, in which only 25% had the required well-child visits by the first year. We interviewed parents/caregivers of 12- to 15-month-old children for their perspectives on access to care, scheduling, and the medical home concept. Plan-Do-Study-Act cycles targeted modification of electronic medical record templates, scheduling, staff and parental education, standardization of work processes, and birth to 1-year age-specific incentives. We then piloted interventions in one of our clinic’s pod/subgroup. Process and outcome measures were analyzed using descriptive statistics, a run chart, and a 2-sample % Defective Test.

Results:

Parent/caregiver interviews revealed that only 6% knew what a medical home was, and only 40% “almost always saw the same provider for care.” At baseline in 2012, we documented completion of all 5 visits in only 25% of the children; <10% of those children had consecutive visits with the same provider. After multiple Plan-Do-Study-Act cycles and pilot, our “First Five” well-child care adherence rose to 78%, and continuity increased to 74% in 2018 (P < 0.001 for adherence, P < 0.001 for continuity).

Conclusion:

A multifaceted, evidence-based approach improved both well-child care adherence and provider continuity.
Surgical Accuracy of Positioning the Maxilla in Patients With Skeletal Class II Malocclusion Using Computer-Aided Design and Computer-Aided Manufacturing-Assisted Orthognathic Surgery
Authors: Alqussair Ali , Baek Seung-Hak , Kim Tae-Seup , Ha Sugn-Ho , Choi Jin-Young
Published: December 2021

Objective:

To evaluate the surgical accuracy of positioning the maxilla in patients with skeletal class II malocclusion using computer-aided design and computer-aided manufacturing (CAD/ CAM)-assisted orthognathic surgery.

Materials and Methods:

The samples consisted of 10 patients with skeletal class II malocclusion, whose cone-beam computed tomographys taken before and immediately after surgery were available and who underwent bimaxillary orthognathic surgery by a single surgeon using Le Fort I osteotomy and bilateral sagittal split ramus osteotomy at the Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital, Seoul, South Korea between January 2018 and December 2019. After virtual surgical planning was performed using the FACEGIDE system (Korea), surgical cutting guides, intermediate splints, and custom-made titanium mini-plates were fabricated using CAD/CAM technique. Using 8 landmarks (anterior nasal spine, point A, #16, #13, contact point between #11 and #21, #23, #26, posterior nasal spine), the mean differences between the virtually planned (Virtual) and actual postsurgical position of the maxilla (Actual) in the three-dimensional coordinates (ΔActual-Virtual) and their mean absolute deviations were investigated.

Results:

The mean differences of 8 landmarks were 0.42 mm left side movement in the transverse coordinate, 0.15 mm forward movement in the sagittal coordinate and 0.10 mm downward movement in the vertical coordinate. Their mean absolute deviations were 0.98, 0.67, and 0.62 mm in the sagittal, vertical, and transverse coordinates, respectively.

Conclusions:

Since the mean difference was less than 0.5 mm and the range of error was less than 1.0 mm, CAD/CAM-assisted orthognathic surgery might have a high degree of surgical accuracy and clinical relevance in the positioning of the maxilla.
Surgical Treatment of Cherubism With the Use of ThreeDimensional Virtual Planning and CAD-CAM Resection Guides: A Case Report and Systematic Literature Review
Authors: Järvinen Sanna , Suojanen Juho , Suomalainen Anni , Stoor Patricia
Published: December 2021

We report the use of a three-dimensional virtual surgical planning technique including both fusion and superimposition to obtain harmony and symmetry of the face in an 18-year-old woman suffering from cherubism. The treatment contained several threedimensional techniques that allowed precise planning and a predictable surgical outcome. The reduction plasty was successful, and the postoperative healing was uneventful. No relapse of the disease occurred after the surgical treatment and the sensation of the mentalis area recovered. The patient was satisfied with the aesthetic result and no additional surgery was needed. The surgical planning techniques described, and the CAD/CAM patient-specific resection guides seems to be safe and reliable in a one-step surgical treatment of cherubism patients after the disease has clearly ceased based on radiological findings. A systematic review of the literature on surgical correction of deformities due to cherubism was conducted. The systematic review of the existing literature was performed on the available studies from PubMed and Ovid Medline published before June 9, 2020. The search term was ‘‘Cherubism.’’ The inclusion criteria were: 1) full article published in English and 2) the patient had surgical treatment. We excluded the cases that included only minor surgery as biopsy or only treatment of unerupted teeth. The database identified 638 citations of which 50 met the eligibility criteria. The systematic review revealed no earlier use of surgical 3D planning in the treatment of cherubism.
Uncovering a Long-term Graft Survival Advantage Afforded by Infant Renal Transplants—An Organ Procurement and Transplantation Network Database Analysis
Authors: Tancredi Daniel , Butani Lavjay
Published: December 2021

Background.

Renal transplants (Tx) are performed infrequently in infants, due to concerns related to poor outcomes. The aim of our study was to compare graft failure rates in infant (<1 y) renal Tx recipients compared with older children.

Methods.

Retrospective cohort study of pediatric renal Tx recipients from 2000 to 2015, using the Organ Procurement and Transplant Network database. A log-linear event history regression model for time to graft failure, adjusting for age group and important confounders, was used to estimate post-Tx graft failure probabilities.

Results.

In 2696 Tx followed for a median of 6.1 y, 704 failures were observed. Significant predictors of graft failure were year of Tx (for each year after 2000, rates were 8.6% lower), Black race-ethnicity (63% higher compared with Whites), and number of HLA matches. For infants (n = 27), estimated graft failure percentage (95% confidence interval) within the first 1-, 2-, and 5-y post-Tx were 10.4 (0.1–21.1), 11.9 (1.2–22.6), and 16.4 (4.9–27.9). For the 1- to 11-y-olds (n = 1429), these were 3.8 (3.0–4.6), 6.3 (5.4–7.3), and 13.6 (12.2–15.0), respectively, and for the 12+ y olds (n = 1240), they were 3.8 (3.1–4.5), 8.1 (7.2–9.0), and 19.9 (18.1–21.7), respectively (P < 0.001 for 5-y graft failure rate across age groups).

Conclusions.

Infant renal Tx recipients experience a higher graft failure rate in the first year, compared with older cohorts, but over longer intervals, cumulative failure rates are comparable or even lower. To minimize early graft losses such Tx should be performed in experienced centers.
Personality profile and therapeutic response to lithium carbonate and sodium valproate in mania with psychotic features
Authors: Akbarzadeh Farzad , Zolfaghari Maryam , Fayyazi Bordbar Mohammad Reza , Dadgar Moghaddam Maliheh , Ziaee Maliheh , Eslamzadeh Mahboubeh , Mokhber Naghmeh
Published: December 2021

Bipolar disorder is one of the major psychiatric disorders. Therefore, determining the factors that predict mood stabilizer response is important. This study aimed to investigate the relationship between personality profile and the response to lithium carbonate and sodium valproate in patients with psychotic mania. In this study, 50 patients with bipolar I disorder (manic episode with psychotic features) were randomly assigned to receive lithium carbonate (up to a serum level of 0.8-1.5 mEq/L) or sodium valproate (20 mg/kg). After stabilization of acute manic phase, Temperament and Character Inventory was completed by the patients themselves. Fifty subjects completed this study. The mean age ± SD of participants in the sodium valproate group and lithium carbonate group was 32.99 ± 9.94 and 30.73±7.94 years, respectively. The responders to sodium valproate had significantly higher scores in novelty seeking, harm avoidance (P = 0.003 and 0.004, respectively) and lower scores in persistence (P = 0.006) than the non-responders, but the responders to lithium carbonate did not have significantly different personality profiles. The results of the present study revealed that the personality profiles in the inpatients with psychotic mania are related to the responses to sodium valproate, but are irrelevant to the responses to lithium carbonate.
Myelin sheath and cyanobacterial thylakoids as concentric multilamellar structures with similar bioenergetic properties
Authors: Morelli Alessandro Maria , Chiantore Mariachiara , Ravera Silvia , Scholkmann Felix , Panfoli Isabella
Published: December 2021

There is a surprisingly high morphological similarity between multilamellar concentric thylakoids in cyanobacteria and the myelin sheath that wraps the nerve axons. Thylakoids are multilamellar structures, which express photosystems I and II, cytochromes and ATP synthase necessary for the light-dependent reaction of photosynthesis. Myelin is a multilamellar structure that surrounds many axons in the nervous system and has long been believed to act simply as an insulator. However, it has been shown that myelin has a trophic role, conveying nutrients to the axons and producing ATP through oxidative phosphorylation. Therefore, it is tempting to presume that both membranous structures, although distant in the evolution tree, share not only a morphological but also a functional similarity, acting in feeding ATP synthesized by the ATP synthase to the centre of the multilamellar structure. Therefore, both molecular structures may represent a convergent evolution of life on Earth to fulfill fundamentally similar functions.
Long-term gut microbiome dynamics inDrosophila melanogasterreveal environment-specific associations between bacterial taxa at the family level
Authors: Mazzucco Rupert , Schlötterer Christian
Published: December 2021

The influence of the microbiome on its host is well-documented, but the interplay of its members is not yet well-understood. Even for simple microbiomes, the interaction among members of the microbiome is difficult to study. Longitudinal studies provide a promising approach to studying such interactions through the temporal covariation of different taxonomic units. By contrast to most longitudinal studies, which span only a single host generation, we here present apost hocanalysis of a whole-genome dataset of 81 samples that follows microbiome composition for up to 180 host generations, which cover nearly 10 years. The microbiome diversity remained rather stable in replicatedDrosophila melanogasterpopulations exposed to two different temperature regimes. The composition changed, however, systematically across replicates of the two temperature regimes. Significant associations between families, mostly specific to one temperature regime, indicate functional interdependence of different microbiome components. These associations also involve moderately abundant families, which emphasizes their functional importance, and highlights the importance of looking beyond the common constituents of theDrosophilamicrobiome.
Paenibacillus tianjinensis sp. nov., isolated from corridor air
Authors: Liu Hongxiang , Lu Lijing , Wang Sijin , Yu Meng , Cao Xiaoyun , Tang Sufang , Bai Haijiao , Ma Shihong , Liu Ruina , Liu Rui , Jiang Xiaoying , Yao Su , Shao Jianqiang
Published: December 2021

A Gram-stain-positive, facultatively anaerobic, non-motile, endospore-forming and rod-shaped bacterium, occurring singly or in pairs, designated TB2019T, was isolated from environmental monitoring samples of corridor air collected at the Tianjin Institute for Drug Control, Tianjin Province (PR China). The isolate was able to grow at 15–40 °C (optimum growth at 37 °C), pH 6.0–8.0 (pH 7.0) and in the presence of 0–2% (w/v) NaCl (0% NaCl). Comparison of 16S rRNA gene sequences indicated that TB2019T was most closely related to

Paenibacillus typhae

CGMCC 1.11012T (98.63%),

Paenibacillus albidus

Q4-3T (98.19%),

Paenibacillus borealis

DSM 13188T (97.55%),

Paenibacillus helianthi

P26ET (97.33%) and

Paenibacillus odorifer

DSM 15391T (97.19%). The digital DNA–DNA hybridization and the average nucleotide identity values between TB2019T and the five type strains mentioned above ranged from 20.7 to 25.0% and 75.2 to 81.3%, respectively, and the genomic DNA G+C content was 49.52 mol%. The diagnostic cell-wall sugar was ribose, and the diagnostic amino acid was meso-diaminopimelic acid. The polar lipids of TB2019T included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, three unidentified aminophospholipids and one unidentified phospholipid. MK-7 was the predominant menaquinone, and anteiso-C15:0 (30.6%) was the major fatty acid. Based on the polyphasic taxonomic data, strain TB2019T represents a novel species of the genus

Paenibacillus

, for which the name Paenibacillus tianjinensis sp. nov. is proposed. The type strain is TB2019T (=CICC 25065T=JCM 34610T).
Genomic diversity of antimicrobial resistance in non-typhoidal Salmonella in Victoria, Australia
Authors: Sia Cheryll M. , Baines Sarah L. , Valcanis Mary , Lee Darren Y. J. , Gonçalves da Silva Anders , Ballard Susan A. , Easton Marion , Seemann Torsten , Howden Benjamin P. , Ingle Danielle J. , Williamson Deborah A.
Published: December 2021

Non-typhoidal

Salmonella

(NTS) is the second most common cause of foodborne bacterial gastroenteritis in Australia with antimicrobial resistance (AMR) increasing in recent years. Whole-genome sequencing (WGS) provides opportunities for in silico detection of AMR determinants. The objectives of this study were two-fold: (1) establish the utility of WGS analyses for inferring phenotypic resistance in NTS, and (2) explore clinically relevant genotypic AMR profiles to third generation cephalosporins (3GC) in NTS lineages. The concordance of 2490 NTS isolates with matched WGS and phenotypic susceptibility data against 13 clinically relevant antimicrobials was explored. In silico serovar prediction and typing was performed on assembled reads and interrogated for known AMR determinants. The surrounding genomic context, plasmid determinants and co-occurring AMR patterns were further investigated for multidrug resistant serovars harbouring bla
CMY-2, bla
CTX-M-55 or bla
CTX-M-65. Our data demonstrated a high correlation between WGS and phenotypic susceptibility testing. Phenotypic-genotypic concordance was observed between 2440/2490 (98.0 %) isolates, with overall sensitivity and specificity rates >98 % and positive and negative predictive values >97 %. The most common AMR determinants were bla
TEM-1, sul2, tet(A), strA-strB and floR. Phenotypic resistance to cefotaxime and azithromycin was low and observed in 6.2 % (151/2486) and 0.9 % (16/1834) of the isolates, respectively. Several multi-drug resistant NTS lineages were resistant to 3GC due to different genetic mechanisms including bla
CMY-2, bla
CTX-M-55 or bla
CTX-M-65. This study shows WGS can enhance existing AMR surveillance in NTS datasets routinely produced in public health laboratories to identify emerging AMR in NTS. These approaches will be critical for developing capacity to detect emerging public health threats such as resistance to 3GC.
A Phenome Wide Association Study of Severe COVID-19 Genetic Risk Variants
Authors: Regan Jessica A. , Abdulrahim Jawan , Bihlmeyer Nathan , Haynes Carol , Kwee Lydia Coulter , Patel Manesh , Shah Svati H.
Published: December 2021

Background

Genetic loci associated with risk of severe COVID-19 infection have been identified and individuals with complicated COVID-19 infections often have multiple comorbidities.

Objective

Identify known and unidentified comorbidities associated with genetic loci linked to risk of severe COVID-19 infection.

Methods

A Phenome Wide Association Study (PheWAS) was conducted in 247,448 unrelated, white individuals from the UK Biobank to test the association of 1,402 unique phenotypes with ten genome-wide significant severe-COVID risk single nucleotide polymorphisms (SNP) identified from prior studies. A validation PheWAS was conducted in 2,247 white individuals from the CATHGEN.

Results

Four of the ten tested genetic loci showed significant phenotypic associations in UK Biobank after FDR adjustment. Vascular dementia significantly associated with rs7271165 near TMEM65 on 8q24.13 in individuals with the C risk allele (OR 5.66 [95% CI 2.21-11.85], q=0.049). We identified 40 novel phenotype associations with rs657152 on 9q34.2 coinciding with the ABO gene with individuals with the A COVID risk allele having higher odds of heart failure (OR 1.09 [95% CI 1.03-1.14], q=0.004), diabetes mellitus (OR 1.05 [95% CI 1.02-1.07], q=0.004) and hypercholesterolemia (OR 1.04 [95% CI 1.02-1.06], q=6.3×10−5). Eight phenotypes associated with rs1819040 near KANSL1 on 17q21.31 in individuals with the A risk allele including atrial fibrillation and flutter (OR 1.07 [95% CI 1.04-1.10], q=0.0084) and pulmonary fibrosis (OR 0.80 [95% CI 0.71-0.89], q=0.035). Ten novel phenotypic associations were identified in association with rs74956615 on 19p13.2 near the TYK2 gene including individuals with the A COVID risk allele having lower odds of psoriatic arthropathy (OR 0.31 [95% CI 0.20-0.47], q=4.5×10−5), rheumatoid arthritis (OR 0.83 [95% CI 0.64-0.83], p=1.4×10−6) and thyrotoxicosis with or without goiter (OR 0.77 [95% CI 0.68-0.87], p-6.9×10−5). Two associations for rs1819040 (KANSL1) and seven associations for rs74956615 (TYK2) validated in CATHGEN.

Conclusions

Using a broad PheWAS approach in a large discovery and validation cohort, we have identified novel phenotypic associations with risk alleles for severe COVID-19 infection. Interestingly, the ABO locus was associated with comorbidities that are also risk factors for severe COVID-19 infection, suggesting that this locus has pleiotropic effects and provides a potential mechanism for this association. The 19p13 locus was associated with lower risk of autoimmune disease, these findings may have broad implications for the importance of multiple comorbidities across both infectious and non-infectious diseases and may provide insight in the molecular function of the genes near these genetic risk loci.
Genetic insights into smoking behaviours in 10,558 men of African ancestry from continental Africa and the UK
Authors: Piga Noemi-Nicole , Boua Palwende Romuald , Soremekun Chisom , Shrine Nick , Coley Kayesha , Brandenburg Jean-Tristan , Tobin Martin D. , Ramsay Michèle , Fatumo Segun , Choudhury Ananyo , Batini Chiara
Published: December 2021

Smoking is a leading risk factor for many of the top ten causes of death worldwide. Of the 1 billion smokers globally, 80% live in low- and middle-income countries, where the number of deaths due to tobacco use is expected to double in the next decade according to the World Health Organization. Genetic studies have helped to identify biological pathways for smoking behaviours, but have mostly focussed on individuals of European ancestry or living in either North America or Europe.

Here we present a genome-wide association study of two smoking behaviour traits in 10,558 men of African ancestry living in five African countries and the UK. Eight independent variants were associated with either smoking initiation or cessation at p-value < 5 × 10−6. Of these, four were monomorphic or rare in European populations. Gene prioritization strategy highlighted five genes, including SEMA6D, previously described as associated with several smoking behaviour traits. These results confirm the importance of genetic epidemiological studies in underrepresented populations.
Confirmation of multi-parallel quantitative real-time PCR as the gold standard for detecting soil-transmitted helminths in stool
Authors: Papaiakovou Marina , Pilotte Nils , Dunn Julia , Littlewood David TJ , Cimino Rubén O , Krolewiecki Alejandro , Williams Steven A , Mejia Rojelio
Published: December 2021

Due to its simplicity and cost-effectiveness, microscopy has seen extensive field-use as the diagnostic standard for the detection of soil-transmitted helminths (STH) in stool samples. However, the sensitivity of microscopy-based detection is inadequate in reduced-transmission settings where worm burden is oftentimes low. Equally problematic, eggs of closely related species oftentimes have indistinguishable morphologies, leading to species misidentification. In light of these shortcomings, the purpose of this study was to demonstrate multi-parallel quantitative real-time PCR (qPCR) as the new “gold standard” for STH detection. Accordingly, stool samples from non-endemic participants were spiked with limited numbers of eggs or larvae (1 to 40) of five different species of STH. DNA extracts were tested using two unique multi-parallel real-time PCR-based diagnostic methods. These methods employed different target sequences (ribosomal internal transcribed spacer, or highly repetitive non-coding regions), to evaluate the detection of DNA from as little as one egg per sample. There was a statistically significant kendall correlation between egg/larvae counts and qPCR from both methods for Trichuris trichiura (0.86 and 0.872 for NHM and Baylor assays) and a strong correlation (0.602 and 0.631 for NHM and Baylor assays, respectively) for Ascaris lumbricoides. Less strong but still significant was the Kendall Tau-b value for A. duodenale (0.408 for both) and for S. stercoralis (0.483 and 0.653, respectively). In addition, using field stool samples from rural Argentina both assays had fair to moderate kappa agreement (0.329-0.454), except for Strongyloides stercoralis (0.121) that both assays had slight agreement. In spite of the small cohort of samples, both qPCR assays, targeting of two independent genomic regions, provided reproducible results and we believe that, low cost multi-parallel quantitative real-time PCR-based diagnostics should supplant microscopy as the new gold standard for stool-based detection of soil transmitted helminths in public-health and community settings.
The protein organization of a red blood cell
Authors: Sae-Lee Wisath , McCafferty Caitlyn L. , Verbeke Eric J. , Havugimana Pierre C. , Papoulas Ophelia , McWhite Claire D. , Houser John R. , Vanuytsel Kim , Murphy George J. , Drew Kevin , Emili Andrew , Taylor David W. , Marcotte Edward M.
Published: December 2021

Red blood cells (RBCs, erythrocytes) are the simplest primary human cells, lacking nuclei and major organelles, and instead employing about a thousand proteins to dynamically control cellular function and morphology in response to physiological cues. In this study, we defined a canonical RBC proteome and interactome using quantitative mass spectrometry and machine learning. Our data reveal an RBC interactome dominated by protein homeostasis, redox biology, cytoskeletal dynamics, and carbon metabolism. We validated protein complexes through electron microscopy and chemical crosslinking, and with these data, built 3D structural models of the ankyrin/Band 3/Band 4.2 complex that bridges the spectrin cytoskeleton to the RBC membrane. The model suggests spring-link compression of ankyrin may contribute to the characteristic RBC cell shape and flexibility. Taken together, our study provides an in-depth view of the global protein organization of human RBCs and serves as a comprehensive resource for future research.
The population genetics of adaptation through copy-number variation in a fungal plant pathogen
Authors: Stalder Luzia , Oggenfuss Ursula , Mohd-Assaad Norfarhan , Croll Daniel
Published: December 2021

Microbial pathogens can rapidly adapt to changing environments such as the application of pesticides or host resistance. Copy number variations (CNV) are a major source of adaptive genetic variation for recent adaptation. Here, we analyze how a major fungal pathogen of barley,Rhynchosporium commune, has adapted to host environment, fungicide and temperature challenges. We screen the genomes of 126 isolates sampled across a worldwide set of populations and identify a total of 7’879 gene duplications and 116 gene deletions. Most gene duplications result from segmental chromosomal duplications. We find that genes showing recent gains or losses are enriched in functions related to host exploitation (i.e.effectors and cell wall degrading enzymes). We perform a phylogeny-informed genome-wide association study (GWAS) and identify 191 copy-number variants associated with different pathogenesis and temperature related traits, including a large segmental duplication ofCYP51Athat has contributed to the emergence of azole resistance. Additionally, we use a genome-wide SNP dataset to replicate the GWAS and contrast it with the CNV-focused analysis. We find that frequencies of adaptive CNV alleles show high variation among populations for traits under strong selection such as fungicide resistance. In contrast, adaptive CNV alleles underpinning temperature adaptation tend to be near fixation. Finally, we show that transposable elements are important drivers of recent gene copy-number variation. Loci showing signatures of recent positive selection are enriched in miniature inverted repeat transposons. Our findings show how extensive segmental duplications create the raw material for recent adaptation in global populations of a fungal pathogen.
Myosin phosphatase target subunit 1governs integrity of the embryonic gut epithelium to circumvent atresia development in medaka,Oryzias latipes
Authors: Kobayashi Daisuke , Matsuo Kazuhiko , Kimura Tetsuaki , Ansai Satoshi , Yokoi Hayato , Takashima Shigeo , Kitagawa Tadao , Kage Takahiro , Narita Takanori , Jindo Tomoko , Kinoshita Masato , Naruse Kiyoshi , Nakajima Yoshiro , Shigeta Masaki , Sakaki Shinichiro , Inoue Satoshi , Saba Rie , Yamada Kei , Yokoyama Takahiko , Ishikawa Yuji , Araki Kazuo , Saga Yumiko , Takeda Hiroyuki , Yashiro Kenta
Published: December 2021

Background

Intestinal atresia (IA) is a congenital gut obstruction caused by the absence of gut opening. Genetic factors are assumed to be critical for the development of IA, in addition to accidental vascular insufficiency or mechanical strangulation. However, the molecular mechanism underlying IA remains poorly understood.

Results

In this study, to better understand such a mechanism, we isolated a mutant ofOryzias latipes(the Japanese rice fish known as medaka) generated by N-ethyl-N-nitrosourea mutagenesis, in which IA develops during embryogenesis. Positional cloning identified a nonsense mutation in themyosin phosphatase target subunit 1(mypt1) gene. Consistent with known Mypt1 function, the active form of myosin regulatory light chain (MRLC), which is essential for actomyosin contraction, and F-actin were ectopically accumulated in the intestinal epithelium of mutant embryos, whereas cell motility, proliferation and cell death were not substantially affected. Corresponding to the accumulation site of F-actin/active MRLC, the intestinal epithelium architecture was disordered. Importantly, blebbistatin, a non-muscle myosin inhibitor, attenuated the development of IA in the mutant.

Conclusions

Cytoskeletal contraction governed bymypt1regulates the integrity of the embryonic intestinal epithelium. This study provides new insight into our understanding of the mechanism of IA development in humans.

Bullet Points

Medakamypt1mutants display intestinal atresia.

The level of phosphorylated myosin regulatory light chain was higher inmypt1mutant embryos than inwild-typeembryos.

The levels of F-actin appeared elevated in the intestinal epithelium ofmypt1mutants.

Blebbistatin, an inhibitor of non-muscle myosin II, rescued intestinal atresia inmypt1mutant embryos.
LONG-TERM OUTCOMES OF ENDOSCOPIC ULTRASOUND-GUIDED RADIOFREQUENCY ABLATION (EUS-RFA) FOR ADVANCED PANCREATIC AND PERIAMPULLARY ADENOCARCINOMA
Authors: Thosani Nirav , Cen Putao , Rowe Julie , Guha Sushovan , Bailey-Lundberg Jennifer , Bhakta Dimpal , Patil Prithvi , Rashtak Shahrooz , Davee Roy Tomas , Ramireddy Srinivas , Wray Curtis J.
Published: December 2021

Background

Long term prognosis for pancreatic adenocarcinoma (PDAC) remains especially poor with an overall 5-year survival rate less than 9%. Endoscopic ultrasound (EUS) guided RFA (EUS-RFA) is an emerging technology and limited data exist regarding long-term outcomes of EUS-RFA for PDAC. In addition to thermal-induced coagulative necrosis and tissue damage, radiofrequency ablation (RFA) has potential to stimulate the host’s antitumor immunity. The aim of this study is to report long-term outcomes of EUS-RFA for unresectable PDAC.

Methods

Retrospective chart review of adult patients with an established diagnosis of locally-advanced or metastatic PDAC undergoing EUS-RFA between October 2016 to March 2018 with long term follow up (>30 months). Patients included in the review underwent a total of 1-4 RFA sessions using the Habib EUS-RFA radiofrequency catheter. All patients were concurrently undergoing standard of care chemotherapy.

Results

10 patients (median age 62 years, male 70%) underwent EUS-RFA (Table 1). Location of the primary PDAC was in the head (4), neck (2), body (2), and tail (2). A total of 22 RFA sessions were performed with a range of 1-4 RFA sessions per patient. RFA was technically successful in all RFA sessions (100%). There were no major adverse events (bleeding, perforation, infection, pancreatitis) in immediate (up to 72 hours) and short-term follow up (4 week). Mild worsening of existing abdominal pain was noted during post-procedure observation in 12/22 (55%) of RFA treatments. Follow-up imaging after RFA treatment was available in 8/10 patients. Tumor progression was noted in 2 patients, whereas tumor regression was noted in 6 patients (>50% reduction in size in 3 patients). Median survival for the cohort was 20.5 months (95% CI, 9.93 to 42.2 months). Currently, 2 patients remain alive at 53 and 73 months follow-up since initial diagnosis. One patient had 3 cm PDAC with encasement of the portal confluence, abutment of the celiac axis, common hepatic and superior mesenteric artery. This patient had significant reduction in tumor size and underwent standard pancreaticoduodenectomy.

Conclusion

In our experience, EUS-RFA was safe, well-tolerated and could be concurrently performed with standard of care chemotherapy. In this select cohort, median survival (20.5 months) was improved when compared to published survival based upon SEER database and clinical trials. Future prospective trials are needed to understand the role of EUS-RFA in overall management of PDAC.
Social and labor stressors influencing disability in Adult Attention Deficit/Hyperactivity
Authors: Abramov Dimitri Marques , Baruzzi Marjorie Mastellaro , Alvim Renata Joviano , Peixoto Ana Carolina Moda Nunes , de Souza Mannarino Victor , Pacheco Loureiro Caroline Barros , Ferreira Danilla , Almeida Iara , Pinheiro Ingrid , Valentim Rosângela Marques
Published: December 2021

Attention Deficit/Hyperactivity Disorder (ADHD) is a controversial issue. If ADH represents a mental disorder, it must be the cause of a primary dysfunctionality and maladaptation from childhood to adult life. We will look for evidence to substantiate this discussion. We conducted an online survey about economic and academic performances and maladaptation, following a screening for ADHD using Adult Self Report Scale (ASRS). The subjects were naive. There were 2173 participants, of which 28.06% were ADH(+). Even regarding only subjects with extreme ASRS scores (<1.0 and >2.5), ADH(+) and (−) groups did not shown difference in functionality. We grouped subjects by professional career. The highest ADH(+) prevalence was found in publicity, where almost no difference in subjective suffering between the groups was observed. Our results indicate that ADH(+) people can show equivalent functionality and adaptability than ADH(−) ones when they live in their preferred labor/social niches, arguing that ADHD can be a different cognitive style with dysfunctionality and mental suffering could be secondary to social stress.
Immunogenicity and reactogenicity after booster dose with AZD1222 via intradermal route among adult who had received CoronaVac
Authors: Nantanee Rapisa , Aikphaibul Puneyavee , Jaru-Ampornpan Peera , Sodsai Pimpayao , Himananto Orawan , Theerawit Tuangtip , Sophonphan Jiratchaya , Tovichayathamrong Punyot , Manothummetha Kasama , Laohasereekul Tysdi , Hiransuthikul Narin , Hirankarn Nattiya , Puthanakit Thanyawee
Published: December 2021

Background

Currently, booster dose is needed after 2 doses of inactivated COVID-19 vaccine. With limited resource and shortage of COVID-19 vaccine, intradermal(ID) administration might be a potential dose-sparing strategy.

Objective

To determine antibody response and reactogenicity of ID ChAdOx1 nCoV-19 vaccine(AZD1222,Oxford/AstraZeneca) as a booster dose after completion of 2-dose CoronaVac(SV) in healthy adult.

Methods

This is a prospective cohort study of adult aged 18-59 years who received 2-dose SV at 14-35 days apart for more than 2 months. Participants received ID AZD1222 at fractional low dose(1×1010 viral particles,0.1ml). Antibody responses were evaluated by surrogate virus neutralization test(sVNT) against wild type and delta variant and anti-spike-receptor-binding-domain immunoglobulin G(anti-S-RBD IgG) at prior, day14 or 28, and day90 post booster. Solicited reactogenicity was collected during 7 days post-booster. Primary endpoint was the differences of sVNT against delta strain ≥80%inhibition at day14 and 90 compared with the parallel cohort study of 0.5-ml intramuscular(IM) route.

Results

From August2021, 100 adults with median(IQR) age of 46(41-52) years participated. At baseline, geometric means(GMs) of sVNT against delta strain prior to booster were 22.4%inhibition(95%CI 18.7-26.9) and of anti-S-RBD IgG were 109.3(95.4-125.1)BAU/ml. GMs of sVNT against delta strain were 92.9%inhibition(95%CI 87.7-98.3) at day14 and 73.1%inhibition(66.7-80.2) at day90 post ID booster. The differences of proportion of participants with sVNT to delta strain≥80%inhibition in ID recipients versus IM were +4.2%(95%CI-2.0to10.5) at day14, and -37.3%(−54.2to−20.3) at day90. Anti-S-RBD IgG GMs were 2037.1(95%CI1770.9-2343.2) at day14 and 744.6(650.1-852.9) BAU/ml at day90, respectively. Geometric mean ratios(GMRs) of anti-S-RBD IgG were 0.99(0.83-1.20) at day14, and 0.82(0.66-1.02) at day90. Only 18% reported feverish, compared with 37% of IM(p=0.003). Only 18% reported feverish, compared with 37% of IM(p=0.003). Common reactogenicity was erythema(55%) at injection site while 7% reported blister.

Conclusion

Low-dose ID AZD1222 booster enhanced lower neutralizing antibodies at 3 months compared with IM route. Less systemic reactogenicity occurred, but higher local reactogenicity.

Highlights

Intradermal AZD1222 booster vaccine gave comparable short-term immunogenicity but lower 90-day immunogenicity with conventional intramuscular vaccine.

Lower systemic but higher local reactogenicity was found in intradermal AZD1222 booster vaccine.

Blister and pruritus could be seen after intradermal AZD1222 booster vaccine.
Proposing Response Evaluation Criteria in Solid Tumors Based on Genomic Profiling or Genomic RECIST: A Retrospective Study on the Liquid Biopsy Results of 29 Cancer Patients
Authors: Yar Myint Khin Zay , Shimabuku Masamori , Kashihara Kenichi , Horio Ruriko , Kaneda Munehisa , Shimizu Yoko , Taguchi Junichi
Published: December 2021

Tumor response and disease progression are assessed using imaging technologies. However, these technologies fail to detect tumor responses at the molecular level and clonal evolution. A potential surrogate for such parameters is using circulating tumor DNA (ctDNA). This study aimed to examine the quantity and composition of the ctDNA results of 29 cancer patients before and after dendritic cell (DC) immunotherapy and develop criteria to evaluate the molecular response to treatment based on these results. We categorized the patients into four categories based on percent changes in the total ctDNA compared with the baseline ctDNA titers, and this response assessment was termed genomic response evaluation criteria in solid tumors or gRECIST. Even those who are clinically evaluated as having a good response might harbor unfavorable tumor responses at the molecular level. Newly formed ctDNA levels can be the most prognostic parameter in tumor progression or the treatment response, while ctDNA clearance and the decline or rise in existing ctDNA did not change significantly in genomic response categories (gRECIST). More research is needed to support the clinical use of ctDNA in precision oncology and personalized cancer treatment.
Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects on brain
Authors: Kember Rachel L. , Vickers-Smith Rachel , Xu Heng , Toikumo Sylvanus , Niarchou Maria , Zhou Hang , Hartwell Emily , Crist Richard C. , Rentsch Christopher T. ,   VA Million Veteran Program, Davis Lea K. , Justice Amy C. , Sanchez-Roige Sandra , Kampman Kyle M. , Gelernter Joel , Kranzler Henry R.
Published: December 2021

Despite an estimated twin heritability of ∼50%, genome-wide association studies (GWAS) of opioid use disorder (OUD) have revealed few genome-wide significant (GWS) loci, with replicated findings only in European-ancestry individuals. To identify novel loci, including those in non-European ancestries, and improve our understanding of the biology of OUD, we conducted a cross-ancestry meta-analysis using the Million Veteran Program (MVP). OUD cases in MVP had at least 1 International Classification of Diseases (ICD)-9 or ICD-10 code for opioid abuse or dependence (N=31,473). Opioid-exposed controls (N=394,471) had one or more outpatient opioid prescription fills. We conducted GWAS for each major ancestral group in MVP: African Americans (AAs; N=88,498), European Americans (EAs; N=302,585), and Hispanic Americans (HAs; N=34,861), followed by a cross-ancestry meta-analysis. Ten loci were GWS in the cross-ancestry meta-analysis, 8 of them novel. In addition to the known coding variant rs1799971 in OPRM1, which was the lead SNP genome-wide (p=6.78×10−10), and a recently reported exonic variant in FURIN, we identified intronic variants in RABEPK, FBXW4, NCAM1, and KCNN1. Ancestry-specific analyses identified an additional novel locus for each of the 3 ancestry groups. A supplementary meta-analysis within EAs that included MVP and other samples identified a locus in TSNARE1, which was also GWS in the cross-ancestry meta-analysis of all datasets. Gene-based association analyses identified 1 gene in AAs (CHRM2) and 3 in EAs (OPRM1, DRD2, and FTO). Significant genetic correlations (rg’s) were identified for 127 traits, including positive correlations with schizophrenia, problematic alcohol use, and major depressive disorder. The most significantly enriched cell type group was the central nervous system with gene-expression enrichment identified in brain regions previously associated with substance use disorders. With a case sample 50% larger than that of the previous largest GWAS, we identified 14 loci for OUD, including 12 novel loci, some of which were ancestry-specific. These findings increase our understanding of the biological pathways involved in OUD, which can inform preventive, diagnostic, and therapeutic efforts and thereby help to address the opioid epidemic.
Comparisons of the risk of myopericarditis between COVID-19 patients and individuals receiving COVID-19 vaccines: a population-based study
Authors: Chou Oscar Hou In , Zhou Jiandong , Lee Teddy Tai Loy , Kot Thompson , Lee Sharen , Wai Abraham Ka Chung , Wong Wing Tak , Zhang Qingpeng , Cheng Shuk Han , Liu Tong , Vassiliou Vassilios S , Cheung Bernard Man Yung , Tse Gary
Published: December 2021

Background

Both COVID-19 infection and COVID-19 vaccines have been associated with the development of myopericarditis. The objective of this study is to 1) analyze the rates of myopericarditis after COVID-19 infection and COVID-19 vaccination in Hong Kong and 2) compare to the background rates, and 3) compare the rates of myopericarditis after COVID-19 vaccination to those reported in other countries.

Methods

This was a population-based cohort study from Hong Kong, China. Patients with positive RT-PCR test for COVID-19 between 1st January 2020 and 30th June 2021 or individuals who received COVID-19 vaccination until 31st August were included. The main exposures were COVID-19 positivity or COVID-19 vaccination. The primary outcome was myopericarditis.

Results

This study included 11441 COVID-19 patients from Hong Kong, of whom four suffered from myopericarditis (rate per million: 350; 95% confidence interval [CI]: 140-900). The rate was higher than the pre-COVID-19 background rate in 2020 (rate per million: 61, 95% CI: 55-67) with a rate ratio of 5.73 (95% CI: 2.23-14.73. Compared to background rates, the rate of myopericarditis among vaccinated subjects in Hong Kong was substantially lower (rate per million: 8.6; 95% CI: 6.4-11.6) with a rate ratio of 0.14 (95% CI: 0.10-0.19). The rates of myocarditis after vaccination in Hong Kong are comparable to those vaccinated in the United States, Israel, and the United Kingdom.

Conclusions

COVID-19 infection is associated with a higher rate of myopericarditis whereas COVID-19 vaccination is associated with a lower rate of myopericarditis compared to the background.
Development of an explicit and implicit knowledge identification tool for the analysis of the decision-making process of traditional Asian medicine doctors
Authors: Park Musun , Kim Min Hee , Park So-young , Kang Minseo , Choi Inhwa , Kim Chang-Eop
Published: December 2021

Background and objectives

While pattern identification (PI) is an essential process for diagnosis and treatment in traditional Asian medicine (TAM), it is difficult to objectify since it relies heavily on implicit knowledge. Here, we propose a machine learning-based analysis tool to objectify and evaluate the clinical decision-making process of PI in terms of explicit and implicit knowledge.

Methods

Clinical data for the development of the analysis tool were collected using a questionnaire administered to allergic rhinitis (AR) patients and the diagnosis and prescription results of TAM doctors based on the completed AR questionnaires. Explicit knowledge and implicit knowledge were defined based on the explicit and implicit importance scores of the AR questionnaire, which were obtained through doctors’ explicit scoring and feature evaluations of machine learning models, respectively. The analysis tool consists of eight evaluation indicators used to compare, analyze and visualize the explicit and implicit knowledge of TAM doctors.

Results

The analysis results for 8 doctors showed that our tool could successfully identify explicit and implicit knowledge in the PI process. We also conducted a postquestionnaire study with the doctors who participated to evaluate the applicability of our tool.

Conclusions

This study proposed a tool to evaluate and compare decision-making processes of TAM doctors in terms of their explicit and implicit knowledge. We identified the differences between doctors’ own explicit and implicit knowledge and the differences among TAM doctors. The proposed tool would be helpful for the clinical standardization of TAM, doctors’ own clinical practice, and intern/resident training.