bluuebunny/crossref_metadata_2025 huggingface dataset:
Good sleep is a mood buffer for young women during menses
Authors: Shuster Alessandra E , Simon Katharine C , Zhang Jing , Sattari Negin , Pena Andres , Alzueta Elisabet , de Zambotti Massimiliano , Baker Fiona C , Mednick Sara C
Published: March 2023

Study Objectives

We sought to elucidate the interaction between sleep and mood considering menstrual cycle phase (menses and non-menses portions of the cycle) in 72 healthy young women (18–33 years) with natural, regular menstrual cycles and without menstrual-associated disorders. This work fills a gap in literature of examining mood in context of sleep and menstrual cycle jointly, rather than individually.

Methods

Daily subjective measures of sleep and mood, and date of menses were remotely, digitally collected over a 2-month period. Each morning, participants rated their sleep on the previous night, and each evening participants rated the extent of positive and negative mood for that day. Objective sleep was tracked with a wearable (ŌURA ring) during month 2 of the study. Time-lag cross-correlation and mixed linear models were used to analyze the significance and directionality of the sleep–mood relationship, and how the interaction between menstrual cycle status and sleep impacted mood levels.

Results

We found that menstrual status alone did not impact mood. However, subjective sleep quality and menstrual status interacted to impact positive mood (p < .05). After a night of perceived poor sleep quality, participants reported lower positive mood during menses compared to non-menses portions of the cycle, while after a night of perceived good sleep quality participants reported equivalent levels of positive mood across the cycle.

Conclusions

We suggest that the perception of good sleep quality acts as a mood equalizer, with good sleep providing a protective buffer to positive mood across the menstrual cycle.
Science-led regulatory strategies in nonclinical development of new medicines
Authors: Roberts Ruth , Jones David
Published: March 2023

The development of a pharmaceutical is a stepwise process involving an evaluation of both animal and human efficacy and safety information. Regulations around drug development exist to protect people and the environment from harm and should create a level playing field for business, allowing well-run companies to thrive. However, adherence to good science should guide decisions rather than rigorously following guidelines, and there is almost always more than one way to get to the ultimate goal.
Genomic epidemiology of human adenovirus F40 and F41 in coastal Kenya: A retrospective hospital-based surveillance study (2013–2022)
Authors: Lambisia Arnold W , Makori Timothy O , Mutunga Martin , Cheruiyot Robinson , Murunga Nickson , Quick Joshua , Githinji George , Nokes D James , Houldcroft Charlotte J , Agoti Charles N
Published: March 2023

Human enteric adenovirus species F (HAdV-F) is a leading cause of childhood diarrhoeal deaths. The genomic analysis would be key to understanding transmission dynamics, potential drivers of disease severity, and vaccine development. However, currently, there are limited HAdV-F genomic data globally. Here, we sequenced and analysed HAdV-F from stool samples collected in coastal Kenya between 2013 and 2022. The samples were collected at Kilifi County Hospital in coastal Kenya from children <13 years of age who reported a history of three or more loose stools in the previous 24 hours. The genomes were analysed together with the data from the rest of the world by phylogenetic analysis and mutational profiling. Types and lineages were assigned based on phylogenetic clustering consistent with the previously described criteria and nomenclature. Participant clinical and demographic data were linked to genotypic data. Of ninety-one cases identified using real-time Polymerase Chain Reaction, eighty-eight near-complete genomes were assembled, and these were classified into HAdV-F40 (n = 41) and HAdV-F41 (n = 47). These types co-circulated throughout the study period. Three and four distinct lineages were observed for HAdV-F40 (Lineages 1–3) and HAdV-F41 (Lineages 1, 2A, 3A, 3C, and 3D). Types F40 and F41 coinfections were observed in five samples and F41 and B7 in one sample. Two children with F40 and 41 coinfections were also infected with rotavirus and had moderate and severe diseases as defined using the Vesikari Scoring System, respectively. Intratypic recombination was found in four HAdV-F40 sequences occurring between Lineages 1 and 3. None of the HAdV-F41 cases had jaundice. This study provides evidence of extensive genetic diversity, coinfections, and recombination within HAdV-F40 in a rural coastal Kenya that will inform public health policy, vaccine development that includes the locally circulating lineages, and molecular diagnostic assay development. We recommend future comprehensive studies elucidating on HAdV-F genetic diversity and immunity for rational vaccine development.
Identifying and addressing common contributors to nonadherence with ophthalmic medical therapy
Authors: Hovanesian John , Singh I Paul , Bauskar Aditi , Vantipalli Srilatha , Ozden Rabia Gurses , Goldstein Michael H.
Published: March 2023

Purpose of review

To discuss common reasons for nonadherence and review existing and emerging options to reduce nonadherence with ocular medical therapy and optimize therapeutic outcomes.

Recent findings

Nonadherence can arise from patient-related issues (e.g. physical, cognitive) and healthcare-related issues (e.g. cost, access to care). Multiple strategies have been developed and evaluated to overcome these barriers to adherence. Identifying nonadherence and its cause(s) facilitates the development of strategies to overcome it.

Many common causes of nonadherence can be mitigated through a variety of strategies presented.
Public Perceptions of Mobility and Exercise in the Hospital and Intensive Care Unit
Authors: Toonstra Amy , Chelstrom Sydney , Ciesynski Emily , Hixson Brandon , Jensen Mackenzie
Published: March 2023

Introduction:

The purpose of this study was to evaluate the public's perception of exercise and early mobility for individuals in hospital and intensive care unit (ICU) through use of a validated survey.

Review of Literature:

Limited research has been performed to assess the general public's views on the importance, safety, and role of exercise and mobility for patients in hospital and ICU. Identification of public perceptions will be important in addressing patient education and engagement needs in the acute care setting.

Subjects:

A total of 186 respondents with median (interquartile range) age 43 (23-61). Inclusion criteria were 18 years or older and able to read English.

Methods:

A prospective, descriptive design was used. A survey was adapted from a validated survey for ICU providers regarding perceived barriers to mobility and was adapted for administration to the public. Content validity was established by 6 content experts. The survey had 11 items and used a 5-point Likert scale to evaluate the public's beliefs surrounding benefits of exercise and mobility in hospital and ICU. Demographic information was collected. Cronbach's α measured internal consistency and Spearman's ρ calculated correlation of responses and demographics.

Results:

Internal consistency was acceptable at 0.75. Survey responses were neutral toward benefits of mobilization and exercise for patients in the ICU and positive toward hospitalized patients. There were no correlations between demographics and responses.

Discussion and Conclusion:

The small cohort of the public responded with a positive attitude toward mobilization and exercise for patients in the hospital, and a neutral attitude toward mobilization in the ICU. Increased education to patients regarding the benefits of exercise and mobility in the ICU may be important for improving patient knowledge and engagement in physical therapy.
Identification of Patient Safety Threats in a Post-Intensive Care Clinic
Authors: Karlic Kevin J. , Valley Thomas S. , Cagino Leigh M. , Prescott Hallie C. , Iwashyna Theodore J. , Mohammad Rima A. , Pitcher Mari , Haezebrouck Evan , McSparron Jakob I.
Published: March 2023

The extent to which postintensive care unit (ICU) clinics may improve patient safety for those discharged after receiving intensive care remains unclear. This observational cohort study conducted at an academic, tertiary care medical center used qualitative survey data analyzed via conventional content analysis to describe patient safety threats encountered in the post-ICU clinic. For 83 included patients, safety threats were identified for 60 patients resulting in 96 separate safety threats. These were categorized into 7 themes: medication errors (27%); inadequate medical follow-up (25%); inadequate patient support (16%); high-risk behaviors (5%); medical complications (5%); equipment/supplies failures (4%); and other (18%). Of the 96 safety threats, 41% were preventable, 27% ameliorable, and 32% were neither preventable nor ameliorable. Nearly 3 out of 4 patients within a post-ICU clinic had an identifiable safety threat. Medication errors and delayed medical follow-up were the most common safety threats identified; most were either preventable or ameliorable.
The VASCERN-VASCA Working Group Diagnostic and Management Pathways for Venous Malformations
Authors: Dompmartin Anne , Baselga Eulalia , Boon Laurence M. , Diociaiuti Andrea , Dvorakova Veronika , El Hachem May , Gasparella Paolo , Haxhija Emir , Ghaffarpour Nader , Kyrklund Kristiina , Irvine Alan D. , Kapp Friedrich G. , Rößler Jochen , Salminen Päivi , van den Bosch Caroline , van der Vleuten Carine , Schultze Kool Leo , Vikkula Miikka
Published: March 2023

Objective(s):

To elaborate expert consensus patient pathways to guide patients and physicians toward efficient diagnostics and management of patients with venous malformations.

Methods:

VASCERN-VASCA (https://vascern.eu/) is a European network of multidisciplinary centers for Vascular Anomalies. The Nominal Group Technique was used to establish the pathways. Two facilitators were identified: one to propose initial discussion points and draw the pathways, and another to chair the discussion. A dermatologist (AD) was chosen as first facilitator due to her specific clinical and research experience. The draft was subsequently discussed within VASCERN-VASCA monthly virtual meetings and annual face-to-face meetings.

Results:

The Pathway starts from the clinical suspicion of a venous type malformation (VM) and lists the clinical characteristics to look for to support this suspicion. Strategies for subsequent imaging and histopathology are suggested. These aim to inform on the diagnosis and to separate the patients into 4 subtypes: (1) sporadic single VMs or (2) multifocal, (3) familial, multifocal, and (4) combined and/or syndromic VMs. The management of each type is detailed in subsequent pages of the pathway, which are color coded to identify sections on (1) clinical evaluations, (2) investigations, (3) treatments, and (4) associated genes. Actions relevant to all types are marked in separate boxes, including when imaging is recommended. When definite diagnoses have been reached, the pathway also points toward disease-specific additional investigations and recommendations for follow up. Options for management are discussed for each subtype, including conservative and invasive treatments, as well as novel molecular therapies.

Conclusion:

The collaborative efforts of VASCERN-VASCA, a network of the 9 Expert Centers, has led to a consensus Diagnostic and Management Pathways for VMs to assist clinicians and patients. It also emphasizes the role of multidisciplinary expert centers in the management of VM patients. This pathway will become available on the VASCERN website (http://vascern.eu/).
Feasibility of a universal suicidality tool for adolescents
Authors: Abaddi Rebecca , Pickens LaVetta , Burns Jade , Adams Mackenzie , Shade George H. , Bradley Wayne W. , Duffy Elizabeth A.
Published: March 2023

Background:

The suicide rate among adolescents has been increasing rapidly over the past several years.

Local problem:

Adequate screening for suicide risk in this population, particularly youth of color, is lacking.

Methods:

The Ask Suicide-Screening Questions (ASQ) tool was implemented at two adolescent-focused health clinics in a large U.S. city.

Interventions:

This project followed the Ottawa Model of Research Use. Participating clinicians were surveyed before and after receiving an educational module on suicide risk screening, the ASQ tool, and clinical pathways. Clinicians were also asked about the feasibility and acceptability of the ASQ tool in their practice. An electronic medical records software was used to gather data on patients newly screened for suicide risk using the ASQ tool.

Results:

Among eligible patients, 40.2% were screened using the ASQ tool during the 4-month duration of the project. Most clinicians reported that using the tool was feasible within their practice (66%) and 100% endorsed its acceptability (i.e., reporting that they were comfortable screening for suicide and that the ASQ was easy to use).

Conclusions:

The ASQ may be a promising screening tool for clinicians to use to address the mental health needs of at-risk youth. This project supports the universal acceptability and feasibility of its use in inner-city primary care clinics.
Current Practices in Brazil on Diagnosis and Management of Women With Vulvodynia
Authors: Bardin Marcela G. , Giraldo Paulo C. , Fante Júlia F. , Carvalho de Araujo Camila , Cyr Marie-Pierre , Marques Andrea A.
Published: March 2023

Objective

Vulvodynia (VVD) is a frequent and harrowing condition for which diagnosis and management remain insufficient. Our study aimed to describe and compare vulvovaginal signs and symptoms of Brazilian women with VVD and controls and describe previous medical assessment, past treatments, and vulvar pain relief among women with VVD.

Methods

This cross-sectional descriptive study included Brazilian women with (n = 151) and without VVD (n = 106). All women were assessed for vaginal infection, vulvar pain intensity by means of a cotton swab test based on a numerical rate scale, and answered the Female Sexual Function Index questionnaire and a structured instrument about current vulvar symptoms. Previous treatments were assessed in the VVD group, and vulvar pain relief achieved with previous treatments was qualified through a 4-point Likert scale.

Results

Volunteers were mainly White, with mean age of 30 years. Vulvovaginal signs and symptoms were significantly more frequent in women with VVD (p < .05), and vulvar pain duration was 5.8 (±4) years. More than 50% consulted with three or more physicians, and 49% remained without a conclusive diagnosis. Previous diagnosis and treatment of vulvovaginal infection were often reported by women with VVD. Most of the tried prescriptions were self-reported as providing only low vulvar pain relief.

Conclusions

Prolonged duration of vulvar pain, multiple visits to health care professionals, and poor relief of pain are common aspects in the clinical history of women with VVD. In addition to pain, vulvar fissure, edema, erythema, vaginal discharge, and foul odor are common and should be considered to avoid misdiagnosis. Appropriate treatments to VVD are still poorly reported.
Factors Affecting Completion of Human Papillomavirus Vaccination Series by Gender in a Predominantly Hispanic Border Town Community
Authors: Calderón-Mora Jessica , Lara Hatty , Hernandez Blanca , Molokwu Jennifer
Published: March 2023

Objectives

The human papillomavirus (HPV) vaccine is recommended for females and males aged 9 to 45. Nationally, the HPV vaccination rates are lower for males than females; however, this has not been studied in a US-Mexico border community. Our study aims to report the HPV vaccination completion by gender and determine which sociodemographic factors influence vaccination.

Methods

This cross-sectional study was conducted among uninsured and underinsured individuals aged between 9 and 26 years served through a community-based HPV vaccine program in El Paso, TX. Data collected included demographic information, psychosocial variables, and vaccine administration data. Descriptive statistics were used to summarize demographic data. Unadjusted t test/Fisher exact test and multivariable relative risk regression were run on significant variables to determine the association with vaccine completion by gender.

Results

Most participants were female (63.4%), and an overall vaccine series completion was 30.67%. We found no significant difference in HPV vaccine completion rates by gender. Males who resided in the United States for more than a decade were 31% more likely to complete the vaccine series, and females who had 9 to 13 years of education had lower odds of vaccine completion. Knowledge significantly increased after the intervention for both genders (p = .002). There was no significant change in psychosocial variables from the preintervention to the immediate postintervention survey.

Conclusions

Our multicomponent, culturally tailored intervention may equally impact male and female participants and encourages all genders to complete their HPV vaccine series. Additional studies with a larger male sample are needed.
Contributions of ARID5B, IKZF1, PIP4K2A, and GATA3 Gene Polymorphisms to Childhood Acute Lymphoblastic Leukemia in a Chinese Population
Authors: Liu Xiaorong , Xiao Min , Xing Zhihao , Jiang Hanfang , Zhu Chunqing , Zhang Xingliang , Li Weiqiong , Wang Zijie , Wu Feng , Chen Yunsheng
Published: March 2023

Various studies have shown that single nucleotide polymorphisms in the AT-rich interaction domain 5B (ARID5B), IKAROS family zinc finger 1 (IKZF1), phosphatidylinositol-5-phosphate 4-kinase type 2 alpha (PIP4K2A), and GATA binding protein 3 (GATA3) genes may be associated with the susceptibility and prognosis of childhood acute lymphoblastic leukemia (ALL). The present study aimed to investigate the association of ARID5B rs10821936, IKZF1 rs4132601, PIP4K2A rs7088318, and GATA3 rs3824662 gene polymorphisms with the susceptibility and prognosis of childhood ALL in China. We found that the C allele of rs10821936 (ARID5B) and the A allele of rs3824662 (GATA3) were associated with an increased risk of childhood ALL in the Chinese population. There was no significant difference in frequencies of rs4132601 (IKZF1) and rs7088318 (PIP4K2A) genotypes and alleles between the childhood ALL and control groups. We observed that CC genotype of rs10821936 (ARID5B) was associated with increased rates of high-risk and moderate-risk childhood ALL. The rs10821936 (ARID5B) could serve as a potential biomarker for assessing the risk of childhood ALL in Chinese children.
An Interview With Jeanette Ives Erickson, DNP, RN, NEA-BC, FAAN
Authors: Lal M. Maureen
Published: March 2023

At the end of 2022, American Nurses Credentialing Center Magnet Recognition Program® bid farewell to Jeanette Ives Erickson, DNP, RN, NEA-BC, FAAN, as she stepped down as Chair of the Commission on Magnet® (COM). Dr Ives Erickson, the Chief Nurse Emerita and the Distinguished Paul M. Erickson Chair in Nursing at Massachusetts General Hospital (MGH), joined the COM in 2015 as the chief nurse representative. She served a 2nd term as the American Academy of Nursing representative and Commission Chair. As her tenure closed, Dr Ives Erickson shared her thoughts on the nursing profession, changes and challenges in the healthcare environment, and the enduring value of American Nurses Credentialing Center Magnet Recognition Program.
Nurse Practitioners Are Stepping Up to Meet Access to Primary Care Services Across the United States
Authors: Kapu April , Pitts Courtney J.
Published: March 2023

This month's column highlights the need for access to primary care services across the United States and how nurse practitioners (NPs) have risen to meet this need. The authors discuss the modernization of licensure laws that will remove unnecessary barriers to full and direct access to NP healthcare services.
Ordering Eyeglasses Using 3D Head Scan Technology versus Established Online and Storefront Clinic Methods
Authors: Fontaine Nicolas , Hanssens Jean-Marie , Nguyen Marina , Bérubé Odile
Published: March 2023

SIGNIFICANCE

This study investigates how a new smartphone scanning technology compares with established online and storefront vendors in providing remote measurement and adjustment of prescription eyeglasses.

PURPOSE

This study aimed to evaluate a new technology for ordering prescription eyeglasses online.

METHODS

Thirty participants with 2.00 to 2.75 D of presbyopia (aged 49 to 74 years) were asked to order eyeglasses with progressive addition lenses from four vendors: one online vendor using a new head scan technology (Topology, San Francisco, CA), two established Web site–based vendors (vendors A and B), and one storefront vendor: Université de Montréal's Vision Clinic (UMVC). The resulting measurements were compared with those of opticians. Participant-reported preferences on visual and physical comfort of eyeglasses were collected after 15-minute trials of eyeglasses from each vendor.

RESULTS

Pupillary half-distance measured with Topology matched optician measurements, but online vendors A and B diverged (mean difference, − 0.80 mm [Z = −2.79; P = .005]). Topology and vendor B segment addition heights were similar to optician measurements, but vendor A diverged (mean, −1.40 mm [Z = −2.58; P = .01]). The personalization parameter values obtained with Topology were different from optician measurements for pantoscopic angle (−5.30° [Z = −4.12; P < .001]) and face wrap angle (+1.25° [Z = −2.94; P = .003]). The UMVC eyeglasses scored best for adjustment (8.71/10 [Z = −5.53; P < .001]), with Topology coming second (7.23/10). Topology scores were equivalent to UMVC scores for all eight items of patient-reported preferences (nonparametric Friedman analysis of variance, P < .05).

CONCLUSIONS

Basic lens centration measurements obtained with Topology compare well with those of opticians, but some aspects of the methodology for measuring personalization parameters could be improved. In comparison with two established online vendors, resulting measurements with Topology are more consistent. Initial wearer satisfaction with Topology eyeglasses was also better.
TERT Immunohistochemistry as a Surrogate Marker for TERT Promoter Mutations in Infiltrating Gliomas
Authors: Dono Antonio , Moosvi Ali M. , Goli Puneetha S. , Bellman Allison C. , Aung Phyu P. , Esquenazi Yoshua , Ballester Leomar Y.
Published: March 2023

Genomic alterations are critical for the diagnosis, prognostication, and treatment of patients with infiltrating gliomas. Telomerase reverse transcriptase promoter (TERTp) mutations are among such crucial alterations. Although DNA sequencing is the preferred method for identifying TERTp mutations, it has limitations related to cost and accessibility. We tested telomerase reverse transcriptase (TERT) immunohistochemistry (IHC) as a surrogate for TERTp mutations in infiltrating gliomas. Thirty-one infiltrating gliomas were assessed by IHC using an anti-TERT Y182 antibody. IHC results were analyzed by a board-certified neuropathologist. Tumors were analyzed by targeted next-generation sequencing. A literature review of the use of TERT antibodies as a surrogate for TERTp mutations was performed. Eighteen gliomas harbored TERTp mutations. Overall, TERT IHC demonstrated a sensitivity of 61.1% and a specificity of 69.2% for identifying TERTp mutations. Among the 19 IDH1/IDH2-wild-type gliomas, 16 (84%) harbored TERTp mutations, and TERT IHC had a sensitivity of 62.5% and a specificity of 33.3%. Among the 12 IDH1/IDH2-mutant gliomas, 2 (17%) harbored TERTp mutations, and TERT IHC had a sensitivity of 50% and a specificity of 80%. TERT IHC had low positive and negative likelihood values in the identification of TERTp mutations. The literature review included 5 studies with 645 patients and 4 different TERT antibodies. The results consistently showed poor sensitivity and specificity of TERT IHC for identifying TERTp mutations. TERT IHC is a suboptimal surrogate marker for TERTp mutations in infiltrating gliomas. The need remains for cost-effective, efficient, and accessible alternatives to next-generation sequencing for the evaluation of TERTp mutations in gliomas.
Microbiome and Diet in Colon Cancer Development and Treatment
Authors: Kato Ikuko , Sun Jun
Published: March 2023

Diet plays critical roles in defining our immune responses, microbiome, and progression of human diseases. With recent progress in sequencing and bioinformatic techniques, increasing evidence indicates the importance of diet-microbial interactions in cancer development and therapeutic outcome. Here, we focus on the epidemiological studies on diet-bacterial interactions in the colon cancer. We also review the progress of mechanistic studies using the experimental models. Finally, we discuss the limits and future directions in the research of microbiome and diet in cancer development and therapeutic outcome. Now, it is clear that microbes can influence the efficacy of cancer therapies. These research results open new possibilities for the diagnosis, prevention, and treatment of cancer. However, there are still big gaps to apply these new findings to the clinical practice.
Radiation Therapy and the Microbiome; More Than a Gut Feeling
Authors: Amit Uri , Facciabene Andrea , Ben-Josef Edgar
Published: March 2023

It is increasingly recognized that heterogeneities in tumor response and severity of adverse effects in irradiated patients can be attributed to the tumor microenvironment and host-related factors. Among the latter, a growing body of literature in recent years has demonstrated the role of the patient's microbiome in modulating both tumor and normal tissue response to radiotherapy (RT). Upon contact with the environment after birth, the infant's gastrointestinal tract is rapidly colonized by microbiota, which is low in diversity and predominantly characterized by 2 dominant species, Actinobacteria and Proteobacteria. With time, intestinal microbiota diversity increases, and colonization of Firmicutes and Bacteroidetes becomes dominant. By the time a child reaches 3 years, the gut microbiota composition has been reshaped and is relatively similar to that of an adult. The microbiome colonizing the different body organs comprises various species and abundances, which may impact human health. Although the adult microbiome composition is thought to remain stable in health, microbiome diversity and composition respond to different environmental and pathological conditions, including pharmaceutical interventions and RT. Our review focuses on how the gut microbiota modulates normal tissue toxicity and tumor control. Readers who want to learn more about how RT shapes gut microbiome diversity and composition are referred to several excellent recently published reviews.
Psychometric Properties of the BAASIS: A Meta-analysis of Individual Participant Data
Authors: Denhaerynck Kris , Dobbels Fabienne , Košťálová Barbora , De Geest Sabina ,   on behalf of the BAASIS Consortium
Published: March 2023

Background.

Nonadherence to immunosuppressives, a risk factor for poor posttransplant outcomes, can be assessed by self-report using the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS). Available in written and interview versions, and previously validated on content, the BAASIS is widely used in research and clinical practice. The aim of this study was to investigate its psychometric properties.

Methods.

Using a literature search and our BAASIS database, this meta-analysis identified completed studies in adult transplant recipients whose data were usable to examine the BAASIS’ reliability and 3 validity aspects: (1) relationships with other variables (electronic monitoring, other self-report scales, tacrolimus blood-level variability, collateral report, depressive symptoms, psycho-behavioral constructs, and interventions); (2) response processes; and (3) internal structure. Testing used random-effects logistic regressions.

Results.

Our sample included 12 109 graft recipients from 26 studies. Of these 26, a total of 20 provided individual participant data. Evidence of the BAASIS’ stability over time supports its reliability. Validity testing of relationships with other variables showed that BAASIS-assessed nonadherence was significantly associated with the selected variables: electronically monitored nonadherence (P < 0.03), other self- and collaterally-reported nonadherence (P < 0.001), higher variability in tacrolimus concentrations (P = 0.02), higher barriers (P < 0.001), lower self-efficacy (P < 0.001), lower intention (P < 0.001), and higher worries (P = 0.02). Nonadherence also decreased after regimen change interventions (P = 0.03). Response process evaluation indicated good readability and slightly higher nonadherence with the written version. Structurally, items on taking and timing shared variability.

Conclusions.

The BAASIS shows good validity and reliability as a self-report instrument to assess medication nonadherence in transplantation.
Capnocytophaga catalasegens sp. nov., isolated from feline oral cavities
Authors: Suzuki Michio , Imaoka Koichi , Kimura Masanobu , Morikawa Shigeru , Maeda Ken
Published: March 2023

Three bacterial strains, KC07075, KC07079 and KC07084T, were isolated from the oral cavity of cats in 2007 in Japan. These strains were Gram-negative rods, exhibited gliding motility, grew in air with 5 % CO2, and showed oxidase activity, but not catalase activity. The 16S rRNA gene sequences of the three strains were 100 % identical. The 16S rRNA gene sequence of strain KC07084T showed 92.1 and 91.9% identity to the type strains of

Capnocytophaga canis

and

Capnocytophaga felis

, respectively, and showed 89.3–91.6% identity to other

Capnocytophaga

species. The major cellular fatty acids of strain KC07084T were iso-C15 : 0 (58.4 %) and summed feature 11 (13.1 %). The G+C content of DNA from strain KC07084T was 33.7 mol%, and the genome size was 2.92 Mbp. Strains KC07075, KC07079 and KC07084T showed digital DNA–DNA hybridization values (dDDH) values of 99.9 % and average nucleotide identity (ANI) values of 99.98 % with each other, strain KC07084T had dDDH values of 18.7–28.2 % and ANI values of 67.12–72.30 % to the type strains of other

Capnocytophaga

species. All known species of the genus

Capnocytophaga

inhabiting the oral cavity of dogs and cats have catalase activity, but the three strains, including type strain KC07084T, lacked catalase activity. These results of the phylogenetic analysis of the 16S rRNA gene sequence, biochemical characteristics, and dDDH and ANI values suggest that strain KC07084T represents a novel species. We propose the name Capnocytophaga catalasegens sp. nov., with KC07084T as the type strain (=JCM 32682T=DSM 107252T).
Amycolatopsis iheyensis sp. nov., isolated from soil on Iheya Island, Japan
Authors: Ngamcharungchit Chananan , Kanto Hiroki , Také Akira , Intra Bungonsiri , Matsumoto Atsuko , Panbangred Watanalai , Inahashi Yuki
Published: March 2023

A novel actinomycete, designated strain OK19-0408T, was isolated from soil collected on Iheya island, Okinawa prefecture, Japan. Using the polyphasic taxonomic approach, comparing 16S rRNA gene sequences, the new isolate was found to be most closely related to

Amycolatopsis vancoresmycina

JCM12675T (98.71 %). Phylogenetic analyses using 16S rRNA sequences indicated that strain OK19-0408T was clustered with

Amycolatopsis australiensis

JCM15587T. However, digital DNA–DNA hybridization analyses indicated a low relatedness, in the range of 33.9–34.7 %, between strain OK19-0408T and these closely related strains. Strain OK19-0408T contained meso-diaminopimelic acid and whole-cell sugars consisting of arabinose and galactose. The acyl type of the peptidoglycan was acetyl and mycolic acids were absent in strain OK19-0408T. The major menaquinone was MK-9(H4) and hydroxy-phosphatidylethanolamine was detected as the predominant phospholipid. The predominant cellular fatty acid was iso-C16 : 0. The DNA G+C content of the genomic DNA was 71.5 mol%. Based on the polyphasic approach, strain OK19-0408T represents a novel species of the genus

Amycolatopsis

, for which the name Amycolatopsis iheyensis sp. nov. is proposed. The type strain of the type species is OK19-0408T (=NBRC115671T=TBRC16040T).
Estimating the Impact of Pre-Exposure Prophylaxis (PrEP) on Mortality in COVID-19 Patients: A Causal Inference Approach
Authors: Subramanian Ajan , Huang Yong , Pinto Melissa D. , Downs Charles A. , Rahmani Amir M.
Published: March 2023

Traditional machine learning (ML) approaches learn to recognize patterns in the data but fail to go beyond observing associations. Such data-driven methods can lack generalizability when the data is outside the independent and identically distributed (i.i.d) setting. Using causal inference can aid data-driven techniques to go beyond learning spurious associations and frame the data-generating process in a causal lens. We can combine domain expertise and traditional ML techniques to answer causal questions on the data. Hypothetical questions on alternate realities can also be answered with such a framework. In this paper, we estimate the causal effect of Pre-Exposure Prophylaxis (PrEP) on mortality in COVID-19 patients from an observational dataset of over 120,000 patients. With the help of medical experts, we hypothesize a causal graph that identifies the causal and non-causal associations, including the list of potential confounding variables. We use estimation techniques such as linear regression, matching, and machine learning (meta-learners) to estimate the causal effect. On average, our estimates show that taking PrEP can result in a 2.1% decrease in the death rate or a total of around 2,540 patients’ lives saved in the studied population.
mRNA challenge predicts brain cancer immunogenicity and response to checkpoint inhibitors
Authors: Castillo Paul , Ogando-Rivas Elizabeth , Geffrard Hilary , Pepe Alfonso , Liu Ruixuan , Nguyen Duy T , Pedro Diego I , Zhang Dingpeng , DeVries Anna , Qdaisat Sadeem , Karachi Aida , Rahman Maryam , Weidert Frances , Milner Rowan , Huang Jianping , Silver Natalie L. , Ligon John , Li Derek , Lee Ji-Hyun , Carrera-Justiz Sheila , Mitchell Duane A , Mendez-Gomez Hector , Sawyer W Gregory , Sayour Elias J
Published: March 2023

To prospectively determine whether brain tumors will respond to immune checkpoint inhibitors (ICIs), we developed a novel mRNA vaccine as a viral mimic to elucidate cytokine release from brain cancer cells in vitro. Our results indicate that cytokine signatures following mRNA challenge differ substantially from ICI responsive versus non-responsive murine tumors. These findings allow for creation of a diagnostic assay to quickly assess brain tumor immunogenicity, allowing for informed treatment with ICI or lack thereof in poorly immunogenic settings.
Telomemore enables single-cell analysis of cell cycle and chromatin condensation
Authors: Yakovenko Iryna , Mihai Ionut S , Selinger Martin , Rosenbaum William , Dernstedt Andy , Groning Remigius , Trygg Johan , Carroll Laura , Forsell Mattias , Henriksson Johan
Published: March 2023

Single-cell RNA-seq methods can be used to delineate cell types and states at unprecedented resolution but do little to explain why certain genes are expressed. Single-cell ATAC-seq and multiome (ATAC+RNA) have emerged to give a complementary view of the cell state. It is however unclear what additional information can be extracted from ATAC-seq data besides transcription factor binding sites. Here we show that ATAC-seq telomere-like reads, mostly originating from the subtelomere, cannot be used to infer telomere length, but can be used as a biomarker for chromatin condensation. Using long-read sequencing, we further show that modern hyperactive Tn5 does not duplicate 9bp of its target sequence, contrary to common belief. We provide a new tool, Telomemore, which can quantify non-aligning subtelomeric reads. By analyzing several public datasets, and generating new multiome fibroblast and B cell atlases, we show how this new readout can aid single-cell data interpretation. We show how drivers of condensation processes can be inferred, and how it complements common RNA-seq-based cell cycle inference, which fails for monocytes. Telomemore-based analysis of the condensation state is thus a valuable complement to the single-cell analysis toolbox.
PGM3 inhibition Shows cooperative Effects With Erastin inducing Pancreatic cancer cell death via activation of the Unfolded Protein Response
Authors: Zerbato Barbara , Gobbi Maximilian , Ludwig Tobias , Brancato Virginia , Pessina Alex , Brambilla Luca , Wegner Andre , Chiaradonna Ferdinando
Published: March 2023

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Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a poor patient prognosis. Remarkably, PDAC is one of the most aggressive and deadly tumor types and is notorious for its resistance to all types of treatment. PDAC resistance is frequently associated with a wide metabolic rewiring and in particular of the glycolytic branch named Hexosamine Biosynthetic Pathway (HBP). Here we show the effect of the combined treatment between an HBP’s Phosphoglucomutase 3 (PGM3) enzyme inhibitor, named FR054, and erastin (ERA), a recognized ferroptosis inducer, on PDAC cell growth and survival. Noteworthy, the combined treatment applied to PDAC cell lines induces a significant decrease in cell proliferation and a concurrent enhancement of cell death. Furthermore, we show that this combined treatment induces Unfolded Protein Response (UPR), NFE2 Like BZIP Transcription Factor 2 (NRF2) activation, a change in cellular redox state, a greater sensitivity to oxidative stress, a major dependence on glutamine metabolism, and finally ferroptosis cell death. Our study discloses that HBP inhibition enhances, through UPR activation, the ERA effect and therefore might be a novel anticancer mechanism to be exploited as PDAC therapy.
GREMI: an Explainable Multi-omics Integration Framework for Enhanced Disease Prediction and Module Identification
Authors: Liang Hong , Luo Haoran , Sang Zhiling , Jia Miao , Jiang Xiaohan , Wang Zheng , Yao Xiaohui , Cong Shan
Published: March 2023

Multi-omics integration has demonstrated promising performance in complex disease prediction. However, existing research typically focuses on maximizing prediction accuracy, while often neglecting the essential task of discovering meaningful biomarkers. This issue is particularly important in biomedicine, as molecules often interact rather than function individually to influence disease outcomes. To this end, we propose a two-phase framework named GREMI to assist multi-omics classification and explanation. In the prediction phase, we propose to improve prediction performance by employing a graph attention architecture on sample-wise co-functional networks to incorporate biomolecular interaction information for enhanced feature representation, followed by the integration of a joint-late mixed strategy and the true-class-probability block to adaptively evaluate classification confidence at both feature and omics levels. In the interpretation phase, we propose a multi-view approach to explain disease outcomes from the interaction module perspective, providing a more intuitive understanding and biomedical rationale. We incorporate Monte Carlo tree search (MCTS) to explore local-view subgraphs and pinpoint modules that highly contribute to disease characterization from the global-view. Extensive experiments demonstrate that the proposed framework outperforms state-of-the-art methods in seven different classification tasks, and our model effectively addresses data mutual interference when the number of omics types increases. We further illustrate the functional- and disease-relevance of the identified modules, as well as validate the classification performance of discovered modules using an independent cohort. Code and data are available athttps://github.com/Yaolab-fantastic/GREMI.
Inferring compound heterozygosity from large-scale exome sequencing data
Authors: Guo Michael H. , Francioli Laurent C. , Stenton Sarah L. , Goodrich Julia K. , Watts Nicholas A. , Singer-Berk Moriel , Groopman Emily , Darnowsky Philip W. , Solomonson Matthew , Baxter Samantha ,   gnomAD Project Consortium, Tiao Grace , Neale Benjamin M. , Hirschhorn Joel N. , Rehm Heidi L. , Daly Mark J. , O’Donnell-Luria Anne , Karczewski Konrad J. , MacArthur Daniel G. , Samocha Kaitlin E.
Published: March 2023

Recessive diseases arise when both the maternal and the paternal copies of a gene are impacted by a damaging genetic variant in the affected individual. When a patient carries two different potentially causal variants in a gene for a given disorder, accurate diagnosis requires determining that these two variants occur on different copies of the chromosome (i.e., are intrans) rather than on the same copy (i.e. incis). However, current approaches for determining phase, beyond parental testing, are limited in clinical settings. We developed a strategy for inferring phase for rare variant pairs within genes, leveraging genotypes observed in exome sequencing data from the Genome Aggregation Database (gnomAD v2, n=125,748). When applied to trio data where phase can be determined by transmission, our approach estimates phase with 95.7% accuracy and remains accurate even for very rare variants (allele frequency < 1×10−4). We also correctly phase 95.9% of variant pairs in a set of 293 patients with Mendelian conditions carrying presumed causal compound heterozygous variants. We provide a public resource of phasing estimates from gnomAD, including phasing estimates for coding variants across the genome and counts per gene of rare variants intrans, that can aid interpretation of rare co-occurring variants in the context of recessive disease.
High throughput detection of variation in single-cell whole transcriptome through streamlined scFAST-seq
Authors: Sang Guoqin , Chen Jiaxin , Zhao Meng , Shi Huanhuan , Han Jinhuan , Sun Jiacheng , Guan Ying , Ma Xingyong , Zhang Guangxin , Gong Yuyan , Zhao Yi , Jiao Shaozhuo
Published: March 2023

High-throughput single-cell full-length RNA sequencing is a powerful tool to explore the entire transcriptome, including non-polyadenylated transcripts. We developed asinglecellFull-length RNA SequenceTranscriptomesequencing method (scFAST-seq), which combines semi-random primers with high reverse transcription efficiency, template switching and convenient rRNA removal methods, allowing the construction of full-length RNA libraries of up to 12,000 cells within 8 hours. Compared to regular 3’ scRNA-seq, scFAST-seq has similar sensitivity to mRNA detection, sequencing cost and experimental workflow. Moreover, scFAST-seq has clear advantages in detecting non-polyadenylated transcripts, covering longer transcript length, and identifying more splice junctions. In addition, scFAST-seq can more accurately predict the direction of cell differentiation by calculating RNA velocity. Furthermore, we demonstrated that scFAST-seq combined with target region enrichment can simultaneously identify somatic mutations and cellular status of individual tumor cells, which is valuable information for precision medicine.
Phased chromosome-scale genome assembly of an asexual, allopolyploid root-knot nematode reveals complex subgenomic structure
Authors: Winter Michael R , Taranto Adam P , Yimer Henok Zemene , Blundell Alison Coomer , Siddique Shahid , Williamson Valerie M , Lunt David H
Published: March 2023

We present the chromosome-scale genome of the allopolyploid root-knot nematodeMeloidogyne javanica. We show that theM. javanicagenome is predominantly allotetraploid, comprising two subgenomes, A and B, that most likely originated from hybridisation of two ancestral parental species. The assembly is annotated using full-length non-chimeric transcripts, comparison to reference databases, andab initioprediction techniques, and the subgenomes are phased using ancestral k-mer spectral analysis. Subgenome B appears to show greater fission of chromosomal contigs, and while there is substantial synteny between subgenomes, we also identify regions lacking synteny that may have diverged in the ancestral genomes prior to or following hybridisation. Indels are common both between alleles within a subgenome, and between the A and B subgenomes, suggesting theM. javanicagenome exists in a dynamic hypo-tetraploidy where copy number can vary along the chromosome. This annotated and phased genome assembly forms a significant resource for understanding the origins and genetics of these globally important plant pathogens.

Author Summary

Root-knot nematodes represent one of the most significant crop parasites globally. Despite their agricultural importance, only rudimentary genomic resources have been published to date, leaving a gap in the understanding of genetic mechanisms driving genome evolution and crop virulence. Here, we have used modern genomic and bioinformatic approaches to create a chromosome-scale reference genome to investigate the origins and genomic constitution of the root-knot nematode speciesMeloidogyne javanica. This species reproduces by ameiotic parthenogenesis and has an allopolyploid genome and is among the most damaging plant parasitic nematodes with a large and evolving plant host range.

Utilising modern long-range DNA sequencing and bioinformatics approaches, we successfully phased the genome into its constituent subgenomes, a first for this agriculturally important clade. While we find the genomic landscape is mostly syntenic between subgenomes, we identified regions of minimal similarity, and highlight structural divergence between subgenomes. We demonstrate that this species was originally tetraploid, but insertions and deletions have been the major force in generating diversity, resulting in a hypo-tetraploid genome with local variations in ploidy.
Establishment and validation of a High-throughput Micro-Neutralization assay for Respiratory Syncytial Virus (subtypes A and B)
Authors: Bonifazi Carolina , Trombetta Claudia Maria , Barneschi Irene , Latanza Simona , Leopoldi Sara , Benincasa Linda , Leonardi Margherita , Semplici Claudia , Piu Pietro , Marchi Serena , Montomoli Emanuele , Manenti Alessandro
Published: March 2023

The validation of a bioanalytical method allows us to determine its validity for a designated purpose and to guarantee the reliability of its analytical results. The virus neutralization assay has proved to be suitable for the detection and quantization of specific serum neutralizing antibodies against respiratory syncytial virus subtypes A and B. Respiratory syncytial virus is a negative-sense RNA virus and is responsible for the majority of acute lower respiratory tract infections in infants and older adults worldwide. Owing to its widespread infection, the WHO considers it a target for the development of preventive vaccines. Despite the high impact of its infections, however, no vaccine candidate is currently available.

The aim of this paper is to provide a detailed validation process for the micro-neutralization assay and to demonstrate that this method can effectively support the efficacy assessment of candidate vaccines and the definition of correlates of protection.