bluuebunny/crossref_metadata_2025 huggingface dataset:
Tendon Healing in a Mouse Model of Loeys-Dietz Syndrome: Controlled Study Using a Patellar Tendon Transection Model
Authors: Cottrill Ethan J. , Bowen Caitlin J. , Pennington Zach A. , Murray Jason A. , Rajkovic Christian J. , Dietz Harry C. , Sponseller Paul D.
Published: April 2022

Background:

Loeys-Dietz syndrome (LDS) is a rare autosomal-dominant connective tissue disorder caused by genetic mutations in the transforming growth factor-β (TGFβ) signaling pathway. In addition to vascular malformations, patients with LDS commonly present with bone and tendon abnormalities, including joint laxity. While TGFβ signaling dysregulation has been implicated in many of these clinical manifestations, the degree to which it influences the tendinopathy and tendon healing issues in LDS has not been determined.

Methods:

Wound healing after patellar tendon transection was compared between wild-type (WT) and Tgfbr2-mutant (LDS) mice (7 mice per group). In all mice, the right patellar tendon was transected at midsubstance, while the left was untouched to serve as a control. Mice were euthanized 6 weeks after surgery. Tendon specimens were harvested for histopathologic grading according to a previously validated scoring metric, and gene expression levels of Mmp2, Tgfb2, and other TGFβ-signaling genes were assayed. Between-group comparisons were made using 1-way analysis of variance with post hoc Tukey honestly significant difference testing.

Results:

Expression levels of assayed genes were similar between LDS and WT tendons at baseline; however, at 6 weeks after patellar tendon transection, LDS tendons showed sustained elevations in Mmp2 and Tgfb2 compared with baseline values; these elevations were not seen in normal tendons undergoing the same treatments. Histologically, untreated LDS tendons had significantly greater cellularity and cell rounding compared with untreated WT tendons, and both WT and LDS tendons had significantly worse histologic scores after surgery.

Conclusion:

We present the first mechanistic insight into the effect of LDS on tendons and tendon healing. The morphologic differences between LDS and WT tendons at baseline may help explain the increased risk of tendon/ligament dysfunction in patients with LDS, and the differential healing response to injury in LDS may account for the delayed healing and weaker repair tissue.

Level of Evidence:

Level V.
Exploring Systemic Influences on Data-Informed Learning: Document Review of Policies, Procedures, and Legislation from Canada and the United States
Authors: Wiljer David , Williams Spencer , Charow Rebecca , Campbell Craig , Davis Dave , Younus Sarah , Mylopoulos Maria , Okrainec Allan , Silver Ivan , Tavares Walter , Sockalingam Sanjeev
Published: April 2022

Introduction:

Despite the support for and benefits of data-driven learning, physician engagement is variable. This study explores systemic influences of physician use of data for performance improvement in continuing professional development (CPD) by analyzing and interpreting data sources from organizational and institutional documents.

Methods:

The document analysis is the third phase of a mixed-methods explanatory sequential study examining cultural factors that influence data-informed learning. A gray literature search was conducted for organizations both in Canada and the United States. The analysis contains nonparticipant observations from professional learning bodies and medical specialty organizations with established roles within the CPD community known to lead and influence change in CPD.

Results:

Sixty-two documents were collected from 20 Canadian and American organizations. The content analysis identified the following: (1) a need to advocate for data-informed self-assessment and team-based learning strategies; (2) privacy and confidentiality concerns intersect at the point of patient data collection and physician-generated outcomes and need to be acknowledged; (3) a nuanced data strategy approach for each medical specialty is needed.

Discussion:

This analysis broadens our understanding of system-level factors that influence the extent to which health information custodians and physicians are motivated to engage with data for learning.
Outcomes Analyses of Pediatric Acute Liver Failure Subjects Listed for Liver Transplantation
Authors: Kulkarni Sakil S. , Goss Charles W. , Khan Adeel S. , Nadler Michelle L. , Stoll Janis M. , Doyle Maria B. , Turmelle Yumirle P. , Rudnick David A.
Published: April 2022

Background:

We characterized recent outcomes in US pediatric acute liver failure (PALF) subjects listed for liver transplantation (LT) using the Scientific Registry of Transplant Recipients (SRTR) database.

Methods:

Pediatric subjects listed for LT from 2002 to 2015 were assigned to the “PALF” group based on status 1/1A listing, INR >2, no hepatic artery thrombosis, and no primary graft nonfunction (N = 397). Subjects were assigned to the “non‐PALF” group if listed with any status other than 1/1A (N = 4509).

Results:

The PALF group had more infants <3 months of age and males at listing for LT compared to the non‐PALF group. Two‐thirds of PALF subjects had an indeterminate etiology. LT waitlist survival was significantly worse in the PALF group compared to the non‐PALF group. Likelihood of removal from the LT waitlist for being “too sick” was higher, while that of removal for “spontaneous recovery” was lower in PALF subjects. Post‐LT short‐term (30 days) and long‐term (60 months) outcomes were also significantly worse in PALF versus non‐PALF subjects. PALF subjects who underwent living‐donor‐liver‐transplant (LDLT) had similar LT waitlist times and post‐LT survival compared to those undergoing deceased‐donor‐liver‐transplant (DDLT). Over the study period, we observed a decreased number of liver transplants, and increase in LT waitlist‐ and short‐term post‐LT‐survival in PALF subjects.

Conclusion:

LT waitlist and post‐LT outcomes are worse in PALF subjects compared to non‐PALF subjects. PALF subjects who undergo LDLT have similar waitlist times and post‐LT outcomes compared to those undergoing DDLT.
Risk of Post‐Resection Recurrence in Pediatric Crohn Disease
Authors: Gray Ashley , Boyle Brendan , Michel Hilary K. , Wright Molly , Dotson Jennifer L. , Maltz Ross M.
Published: April 2022

Background:

Ileocecectomy related to stricturing, fistula formation, or medically refractory disease is commonly required in patients with Crohn disease (CD). Limited research exists in endoscopic recurrence (ER) in pediatric inflammatory bowel disease (IBD). In this study, we sought to determine ER rates and the impact of therapy duration before surgery in pediatric patients with CD.

Methods:

This was a single‐center retrospective review of patients with CD between the ages of 2 to 20 years who required ileocecectomy between January 2015 and December 2019 at Nationwide Children's Hospital. Follow‐up endoscopies, laboratory values, medications, and sPCDAI scores were recorded at 6, 12, 24, and 36 months post‐resection wherever available. Modified Rutgeert scores (mRS) were independently assigned to post‐resection colonoscopy images by 3 trained investigators. Post‐resection outcomes were compared between patients on CD therapy >30 days before resection (late surgery) to those started on CD therapy <30 days before resection (early surgery).

Results:

A total of 48 patients underwent ileocecectomy, with a mean age at time of resection of 17 years (+/−2.3). In total, 88% of patients had a post‐resection endoscopy and 57% had an endoscopy within 12 months of resection. Twenty‐nine percentage had ER with a mRS ≥i2. There was no statistical difference in endoscopic and clinical outcomes after resection between the early and late surgery groups.

Conclusions:

Post‐resection endoscopic recurrence after ileocecectomy was found in 29% of our center's pediatric CD population based on mRS. Post‐resection outcomes were not affected by therapy duration before resection.
Changes in Glucose Breath Test in Cystic Fibrosis Patients Treated With 1 Month of Lumacaftor/Ivacaftor
Authors: Gabel Megan E. , Wang Hongyue , Gelfond Daniel , Roach Christine , Rowe Steven M. , Clancy John P. , Sagel Scott D. , Borowitz Drucy ,   on behalf of the PROSPECT GIFT Sub-study Investigators of the Cystic Fibrosis Foundation Therapeutics Development Network
Published: April 2022

Background:

Alteration of the airway microbiota is a hallmark of cystic fibrosis (CF) pulmonary disease. Dysfunction of cystic fibrosis transmembrane regulator (CFTR) in the intestine also promotes changes in local microbiota such as small intestinal bacterial overgrowth (SIBO), which is common in CF. We evaluated whether therapy with the CFTR modulator combination lumacaftor/ivacaftor (luma/iva) has a beneficial impact on SIBO as measured by breath testing (BT).

Methods:

A multicenter longitudinal study of CFTR-dependent disease profiling (NCT02477319) included a prospective evaluation for SIBO by BT. Tidal breath samples were collected after fasting and 15, 30, 45, 60, 90, and 120 minutes after ingestion of glucose, before and 1 month after subjects initiated luma + iva.

Results:

Forty-two subjects enrolled in the sub-study (mean age = 23.3 years; 51% female; 9.5% Latinx); 38 completed a hydrogen BT at both time points, of which 73.7% had a positive BT before luma/iva (baseline) and 65.8% had a positive test after luma/iva (P = 0.44); shifts from negative to positive were also seen. Use of azithromycin (63.1%) and inhaled antibiotics (60.5%) were not associated with positive BT. Acid-blocking medications were taken by 73% of those with a negative BT at baseline and by 35% with a positive baseline BT (P = 0.04).

Conclusion:

We found a high rate of positive hydrogen breath tests in individuals with CF, confirming that SIBO is common. One month of luma/iva did not significantly change the proportion of those with positive breath hydrogen measurements.
Patient and Caregivers’ Perspectives on Biosimilar Use in Pediatric Inflammatory Bowel Disease
Authors: Yossef Lina , Wright Molly , Benedict Jason , Morris Grant A. , McNicol Megan , Boyle Brendan , Dotson Jennifer L. , Michel Hilary K. , Maltz Ross M.
Published: April 2022

Background:

Studies assessing adult inflammatory bowel disease (IBD) patient perspectives on biosimilar use revealed that most were unfamiliar with biosimilars and had a negative perception. The objective of this study was to evaluate the perspectives of pediatric patients with IBD and their caregivers regarding biosimilar use and non-medical switches.

Methods:

A survey was given to a cross section of patients with IBD ages 11–21 years receiving the intravenous anti-tumor necrosis factor originator and caregivers of patients with IBD ages 3–21 years receiving the originator. Recruitment occurred via mail, during clinic visits, and infusions. Fisher exact tests were used to test for statistically significant differences.

Results:

Response rate amongst caregivers was 49% (n = 98) and among patients was 35% (n = 67). Sixty-four percent of caregivers and 79% of patients had never heard of biosimilars. There was increased discomfort surrounding the use of biosimilars and switching to a biosimilar amongst caregivers who had previously heard of biosimilars compared to caregivers who had not previously heard of biosimilars (P < 0.05). Similar concerns were not seen in patient respondents. The length of time on the originator had no effect on patient or caregiver concerns related to biosimilar efficacy, adverse effects, or switches.

Conclusion:

The majority of pediatric patients and caregivers had never heard of biosimilars. Caregivers that had heard of biosimilars before the study were more likely to have a negative perception of them. This study highlights the importance of providing thorough and accurate education to pediatric patients and families regarding the safety and efficacy of biosimilars.
EURO-MUSCULUS/USPRM Dynamic Ultrasound Protocols for Wrist and Hand
Authors: Mezian Kamal , Ricci Vincenzo , Güvener Orhan , Jačisko Jakub , Novotný Tomáš , Kara Murat , Ata Ayşe Merve , Wu Wei-Ting , Chang Ke-Vin , Stecco Carla , Pirri Carmelo , Leblebicioğlu Gürsel , Özçakar Levent
Published: April 2022

In this dynamic protocol, ultrasound evaluation of the wrist and hand is described using various maneuvers for relevant conditions. Scanning videos are coupled with real-time patient examination videos. The authors believe that this practical guide - prepared by the international consensus of several experts - will help musculoskeletal physicians perform a better and uniform/standard examination approach.
Development and Usability Testing of the Agency for Healthcare Research and Quality Common Formats to Capture Diagnostic Safety Events
Authors: Bradford Andrea , Shahid Umber , Schiff Gordon D. , Graber Mark L. , Marinez Abigail , DiStabile Paula , Timashenka Andrea , Jalal Hamid , Brady P. Jeffrey , Singh Hardeep
Published: April 2022

Objectives

A lack of consensus around definitions and reporting standards for diagnostic errors limits the extent to which healthcare organizations can aggregate, analyze, share, and learn from these events. In response to this problem, the Agency for Healthcare Research and Quality (AHRQ) began the development of the Common Formats for Event Reporting for Diagnostic Safety Events (CFER-DS). We conducted a usability assessment of the draft CFER-DS to inform future revision and implementation.

Methods

We recruited a purposive sample of quality and safety personnel working in 8 U.S. healthcare organizations. Participants were invited to use the CFER-DS to simulate reporting for a minimum of 5 cases of diagnostic safety events and then provide written and verbal qualitative feedback. Analysis focused on participants’ perceptions of content validity, ease of use, and potential for implementation.

Results

Estimated completion time was 30 to 90 minutes per event. Participants shared generally positive feedback about content coverage and item clarity but identified reporter burden as a potential concern. Participants also identified opportunities to clarify several conceptual definitions, ensure applicability across different care settings, and develop guidance to operationalize use of CFER-DS. Findings led to refinement of content and supplementary materials to facilitate implementation.

Conclusions

Standardized definitions of diagnostic safety events and reporting standards for contextual information and contributing factors can help capture and analyze diagnostic safety events. In addition to usability testing, additional feedback from the field will ensure that AHRQ’s CFER-DS is useful to a broad range of users for learning and safety improvement.
How informal healthcare providers improve uptake of HIV testing: qualitative results from a randomized controlled trial
Authors: Ponticiello Matthew , Mwanga-Amumpaire Juliet , Tushemereirwe Patricia , Nuwagaba Gabriel , Nansera Denis , King Rachel , Muyindike Winnie , Sundararajan Radhika
Published: April 2022

Objective:

Uganda is HIV-endemic with a prevalence of 5.7%. Lack of epidemic control has been attributed to low engagement with HIV testing. Collaborating with informal healthcare providers, such as traditional healers, has been proposed as a strategy to increase testing uptake. We explored acceptability and implementation of an HIV testing program where traditional healers delivered point-of-care testing and counseling to adults of unknown serostatus (clinicaltrials.gov NCT#03718871).

Methods:

This study was conducted in rural, southwestern Uganda. We interviewed participating traditional healers (N = 17) and a purposive sample of trial participants (N = 107). Healers were practicing within 10 km of Mbarara township, and 18+ years old. Participants were 18+ years old; sexually active; had received care from participating healers; self-reported not receiving an HIV test in prior 12 months; and not previously diagnosed with HIV infection. Interviews explored perceptions of a healer-delivered HIV testing model and were analyzed following a content-analysis approach.

Results:

Most participants were female individuals (N = 68, 55%). Healer-delivered HIV testing overcame structural barriers, such as underlying poverty and rural locations that limited use, as transportation was costly and often prohibitive. Additionally, healers were located in villages and communities, which made services more accessible compared with facility-based testing. Participants also considered healers trustworthy and ‘confidential’. These qualities explain some preference for healer-delivered HIV testing, in contrast to ‘stigmatizing’ biomedical settings.

Conclusion:

Traditional healer-delivered HIV testing was considered more confidential and easily accessible compared with clinic-based testing. Offering services through traditional healers may improve uptake of HIV testing services in rural, medically pluralistic communities.
Coordination of inflammatory responses in children with perinatally acquired HIV infection
Authors: Weinberg Adriana , Giganti Mark J. , Sirois Patricia A. , Montepiedra Grace , Canniff Jennifer , Agwu Allison , Boivin Michael J. , Kapetanovic Suad , Abzug Mark J. ,   for the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) network
Published: April 2022

Objective:

We investigated dynamics of inflammatory biomarkers in children with perinatally acquired HIV (PHIV) who started antiretrovirals at age less than 3 years and achieved sustained virologic control (HIV plasma RNA <400 copies/ml).

Design:

This was a retrospective analysis of inflammatory biomarkers in children enrolled in a randomized trial of early (<3 years of age) PI-based versus NNRTI-based regimens (P1060), who achieved sustained virologic control and participated in a neurodevelopmental follow-up study (P1104s) between ages 5 and 11 years.

Methods:

We measured 20 inflammatory biomarkers using ELISA or chemiluminescence at onset of sustained virologic control (Tc) and at P1104s entry (Te).

Results:

The 213 participants had median ages of 1.2, 1.9, and 7 years at antiretroviral initiation, Tc, and Te, respectively, with 138 on protease inhibitor-based and 74 on NNRTI-based regimens at Tc. Eighteen markers decreased and two increased from Tc to Te (Te-Tc). Biomarker subsets, particularly cytokines, the chemokine IP-10, and adhesion molecules sICAM-1 and sVCAM-1, correlated at Tc, Te, and Te-Tc. At Tc, higher biomarker levels were associated with younger age, female sex, HIV plasma RNA at least 750 000 copies/ml, lower nadir CD4+%, lower nadir weight z scores, and NNRTI-based treatment. Greater Te-Tc biomarker declines were associated with younger age, male sex, higher Tc biomarker levels, lower nadir CD4+%, and NNRTI-based treatment. Duration of controlled viremia and nadir height z scores showed mixed associations.

Conclusion:

Biomarker expression showed substantial coordination. Most markers decreased after virologic control. Demographic and clinical variables associated with biomarker patterns were identified. Mechanistic studies of these biomarker patterns are needed to inform interventions to control inflammation.
Cytomegalovirus viremia and risk of disease progression and death in HIV-positive patients starting antiretroviral therapy
Authors: Levi Laura I. , Sharma Shweta , Schleiss Mark R. , Furrer Hansjakob , Nixon Daniel E. , Blackstad Mark , Hernandez-Alvarado Nelmary , Dwyer Dominic E. , Borges Alvaro H. , Lane H. Clifford , Lundgren Jens , Neaton James D. , Molina Jean-Michel
Published: April 2022

Objective:

To assess the prevalence of CMV viremia in HIV-positive patients starting antiretroviral therapy (ART) and to evaluate its impact on clinical outcomes.

Design:

Retrospective analysis of four clinical trials (INSIGHT FIRST, SMART, START, and ANRS REFLATE TB).

Methods:

Stored plasma samples from participants were used to measure CMV viremia at baseline prior to initiating ART and at visits through one year of follow-up after ART initiation. CMV viremia was measured centrally using a quantitative PCR assay. Within FIRST, associations of CMV viremia at baseline and through eight months of ART were examined with a composite clinical outcome of AIDS, serious non-AIDS events, or death using Cox proportional hazards regression.

Results:

Samples from a total of 3176 participants, 1169 from FIRST, 137 from ANRS REFLATE TB, 54 from SMART, and 1816 from START were available with baseline CMV viremia prevalence of 17%, 26%, 0% and 1%, respectively. Pooled across trials, baseline CMV viremia was associated with low CD4+ T-cell counts and high HIV RNA levels. In FIRST, CMV viremia was detected in only 5% of participants between baseline and month 8. After adjustment for CD4+ T-cell count and HIV RNA levels, hazard ratios (HR) for risk of clinical outcomes was 1.15 (0.86–1.54) and 2.58 (1.68 – 3.98) in FIRST participants with baseline and follow-up CMV viremia, respectively.

Conclusion:

Baseline CMV viremia in HIV-positive patients starting ART is associated with advanced infection and only persistent CMV viremia after ART initiation is associated with a higher risk of morbidity and mortality.
Decentralized Distributed Multi-institutional PET Image Segmentation Using a Federated Deep Learning Framework
Authors: Shiri Isaac , Vafaei Sadr Alireza , Amini Mehdi , Salimi Yazdan , Sanaat Amirhossein , Akhavanallaf Azadeh , Razeghi Behrooz , Ferdowsi Sohrab , Saberi Abdollah , Arabi Hossein , Becker Minerva , Voloshynovskiy Slava , Gündüz Deniz , Rahmim Arman , Zaidi Habib
Published: April 2022

Purpose

The generalizability and trustworthiness of deep learning (DL)–based algorithms depend on the size and heterogeneity of training datasets. However, because of patient privacy concerns and ethical and legal issues, sharing medical images between different centers is restricted. Our objective is to build a federated DL-based framework for PET image segmentation utilizing a multicentric dataset and to compare its performance with the centralized DL approach.

Methods

PET images from 405 head and neck cancer patients from 9 different centers formed the basis of this study. All tumors were segmented manually. PET images converted to SUV maps were resampled to isotropic voxels (3 × 3 × 3 mm3) and then normalized. PET image subvolumes (12 × 12 × 12 cm3) consisting of whole tumors and background were analyzed. Data from each center were divided into train/validation (80% of patients) and test sets (20% of patients). The modified R2U-Net was used as core DL model. A parallel federated DL model was developed and compared with the centralized approach where the data sets are pooled to one server. Segmentation metrics, including Dice similarity and Jaccard coefficients, percent relative errors (RE%) of SUVpeak, SUVmean, SUVmedian, SUVmax, metabolic tumor volume, and total lesion glycolysis were computed and compared with manual delineations.

Results

The performance of the centralized versus federated DL methods was nearly identical for segmentation metrics: Dice (0.84 ± 0.06 vs 0.84 ± 0.05) and Jaccard (0.73 ± 0.08 vs 0.73 ± 0.07). For quantitative PET parameters, we obtained comparable RE% for SUVmean (6.43% ± 4.72% vs 6.61% ± 5.42%), metabolic tumor volume (12.2% ± 16.2% vs 12.1% ± 15.89%), and total lesion glycolysis (6.93% ± 9.6% vs 7.07% ± 9.85%) and negligible RE% for SUVmax and SUVpeak. No significant differences in performance (P > 0.05) between the 2 frameworks (centralized vs federated) were observed.

Conclusion

The developed federated DL model achieved comparable quantitative performance with respect to the centralized DL model. Federated DL models could provide robust and generalizable segmentation, while addressing patient privacy and legal and ethical issues in clinical data sharing.
Urinary Bladder Matrix Improves Irradiated Wound Healing in a Murine Model
Authors: Yao Jingxin , Vangsness Kella L. , Khim Phillip , Raghuram Anjali C. , Park Sun Young , Yu Roy , Wang Jin , Jiao Wan , Wong Alex K.
Published: April 2022

Radiation skin damage is associated with chronic wounds and poor healing. Existing localized treatment modalities have limited benefit. Therefore, there has been increased interest in biologically based solutions. In this study, we aimed to determine the effect of topical urinary bladder matrix (UBM) on chronic irradiated skin wounds using an established murine model. Our findings demonstrated that topical urinary bladder matrix significantly accelerated the healing of irradiated wounds on day 7 (P = 0.0216), day 14 (P = 0.0140), and day 21 (P = 0.0393). Histologically, urinary bladder matrix treatment was associated with higher-quality reorganization and reepithelialization of wounds, an increased density of myofibroblasts (P = 0.0004), and increased collagen deposition (P < 0.0001). In addition, quantitative real-time polymerase chain reaction data demonstrated decreased expression of profibrotic mediators (P = 0.0049). We conclude that urinary bladder matrix may be a useful, noninvasive, adjunctive therapy for the treatment of chronic irradiated skin wounds.
A fungal symbiont converts provisioned cellulose into edible yield for its leafcutter ant farmers
Authors: Conlon Benjamin H. , O'Tuama David , Michelsen Anders , Crumière Antonin J. J. , Shik Jonathan Z.
Published: April 2022

While ants are dominant consumers in terrestrial habitats, only the leafcutters practice herbivory. Leafcutters do this by provisioning a fungal cultivar (
Leucoagaricus gongylophorus
) with freshly cut plant fragments and harnessing its metabolic machinery to convert plant mulch into edible fungal tissue (hyphae and swollen hyphal cells called gongylidia). The cultivar is known to degrade cellulose, but whether it assimilates this ubiquitous but recalcitrant molecule into its nutritional reward structures is unknown. We use
in vitro
experiments with isotopically labelled cellulose to show that fungal cultures from an
Atta colombica
leafcutter colony convert cellulose-derived carbon into gongylidia, even when potential bacterial symbionts are excluded. A laboratory feeding experiment showed that cellulose assimilation also occurs
in vivo
in
A. colombica
colonies. Analyses of publicly available transcriptomic data further identified a complete, constitutively expressed, cellulose-degradation pathway in the fungal cultivar. Confirming leafcutters use cellulose as a food source sheds light on the eco-evolutionary success of these important herbivores.
How to behave when marooned: the behavioural component of the island syndrome remains underexplored
Authors: Gavriilidi Ioanna , De Meester Gilles , Van Damme Raoul , Baeckens Simon
Published: April 2022

Animals on islands typically depart from their mainland relatives in assorted aspects of their biology. Because they seem to occur in concert, and to some extent evolve convergently in disparate taxa, these changes are referred to as the ‘island syndrome’. While morphological, physiological and life-history components of the island syndrome have received considerable attention, much less is known about how insularity affects behaviour. In this paper, we argue why changes in personality traits and cognitive abilities can be expected to form part of the island syndrome. We provide an overview of studies that have compared personality traits and cognitive abilities between island and mainland populations, or among islands. Overall, the pickings are remarkably slim. There is evidence that animals on islands tend to be bolder than on the mainland, but effects on other personality traits go either way. The evidence for effects of insularity on cognitive abilities or style is highly circumstantial and very mixed. Finally, we consider the ecological drivers that may induce such changes, and the mechanisms through which they might occur. We conclude that our knowledge of the behavioural and cognitive responses to island environments remains limited, and we encourage behavioural biologists to make more use of these ‘natural laboratories for evolution’.
Pedobacter fastidiosus sp. nov., isolated from glacial habitats of maritime Antarctica
Authors: Švec Pavel , Králová Stanislava , Staňková Eva , Holochová Pavla , Sedlář Karel , Koudelková Sylva , Krsek Daniel , Grzesiak Jakub , Šedo Ondrej , Váczi Peter , Urvashi  , Gupta Vipin , Sood Utkarsh , Lal Rup , Korpole Suresh , Sedláček Ivo
Published: April 2022

Strains P8930T and 478 were isolated from Antarctic glaciers located on James Ross Island and King George Island, respectively. They comprised Gram-stain-negative short rod-shaped cells forming pink pigmented colonies and exhibited identical 16S rRNA gene sequences and highly similar MALDI TOF mass spectra, and hence were assigned as representatives of the same species. Phylogenetic analysis based on 16S rRNA gene sequences assigned both isolates to the genus

Pedobacter

and showed

Pedobacter frigidisoli

and

Pedobacter terrae

to be their closest phylogenetic neighbours, with 97.4 and 97.2 % 16S rRNA gene sequence similarities, respectively. These low similarity values were below the threshold similarity value of 98.7%, confirming the delineation of a new bacterial species. Further genomic characterization included whole-genome sequencing accompanied by average nucleotide identity (ANI) and digital DNA–DNA hybridization calculations, and characterization of the genome features. The ANI values between P8930T and

P. frigidisoli

RP-3-11T and

P. terrae

DSM 17933T were 79.7 and 77.6 %, respectively, and the value between

P. frigidisoli

RP-3-11T and

P. terrae

DSM 17933T was 77.7 %, clearly demonstrating the phylogenetic distance and the novelty of strain P8930T. Further characterization included analysis of cellular fatty acids, quinones and polar lipids, and comprehensive biotyping. All the obtained results proved the separation of strains P8930T and 478 from the other validly named

Pedobacter

species, and confirmed that they represent a new species for which the name Pedobacter fastidiosus sp. nov. is proposed. The type strain is P8930T (=CCM 8938T=LMG 32098T).
Campylobacter bilis sp. nov., isolated from chickens with spotty liver disease
Authors: Phung Canh , Scott Peter C. , Dekiwadia Chaitali , Moore Robert J. , Van Thi Thu Hao
Published: April 2022

A novel species of

Campylobacter

was isolated from bile samples of chickens with spotty liver disease in Australia, making it the second novel species isolated from chickens with the disease, after

Campylobacter hepaticus

was isolated and described in 2016. Six independently derived isolates were obtained. They were Gram-stain-negative, microaerobic, catalase-positive, oxidase-positive and urease-negative. Unlike most other species of the genus

Campylobacter

, more than half of the tested strains of this novel species hydrolysed hippurate and most of them could not reduce nitrate. Distinct from

C. hepaticus

, many of the isolates were sensitive to 2,3,5-triphenyltetrazolium chloride (0.04%) and metronidazole (4 mg ml−1), and all strains were sensitive to nalidixic acid. Phylogenetic analysis using 16S rRNA and hsp60 gene sequences demonstrated that the strains formed a robust clade that was clearly distinct from recognized

Campylobacter

species. Whole genome sequence analysis of the strains showed that the average nucleotide identity and the genome blast distance phylogeny values compared to other

Campylobacter

species were less than 86 and 66%, respectively, which are below the cut-off values generally recognized for isolates of the same species. The genome of the novel species has a DNA G+C content of 30.6 mol%, while that of

C. hepaticus

is 27.9 mol%. Electron microscopy showed that the cells were spiral-shaped, with bipolar unsheathed flagella. The protein spectra generated from matrix-assisted laser desorption/ionization time of flight analysis demonstrated that they are different from the most closely related

Campylobacter

species. These data indicate that the isolates belong to a novel

Campylobacter

species, for which the name Campylobacter bilis sp. nov. is proposed. The type strain is VicNov18T (=ATCC TSD-231T=NCTC 14611T).
Early in vivo transcriptome of Trichoplusia ni ascovirus core genes
Authors: Zaghloul Heba A. H. , Hice Robert , Arensburger Peter , Federici Brian A.
Published: April 2022

Ascoviruses are large double-stranded DNA insect viruses that destroy the nucleus and transform each cell into 20 or more viral vesicles for replication. In the present study we used RNA-sequencing to compare the expression of Trichoplusia ni ascovirus 6a1 (TnAV-6a1) core genes during the first week of infection, with emphasis on the first 48 h, comparing transcript levels in major somatic tissues (epidermis, tracheal matrix and fat body), the sites infected initially, with those of the haemolymph, where viral vesicles circulate and most replication occurs. By 48 h post-infection (p.i.), only 26 genes were expressed in somatic tissues at ≥5 log2 reads per kilobase per million, whereas in the haemolymph 48 genes were expressed at a similar level by the same time. Early and high expression of TnAV caspase-2-like gene occurred in all tissues, implying it is required for replication, but that it is probably not associated with apoptosis induction, which occurs in infections of Spodoptera frugiperda ascovirus 1 a (SfAV-1a), the ascovirus type species. Other highly expressed viral genes at 48 h p.i. in viral vesicles included a dynein-like beta chain and lipid-modifying enzymes, suggesting their importance to vesicle formation and growth as well as virion synthesis. Finally, as occurs in SfAV expression, we found bicistronic and tricistronic mRNA messages produced by TnAV.
Household transmission of SARS-CoV-2 from adult index cases living with and without HIV in South Africa, 2020-2021: a case-ascertained, prospective observational household transmission study
Authors: Kleynhans Jackie , Walaza Sibongile , Martinson Neil A. , Neti Mzimasi , Gottberg Anne von , Bhiman Jinal N. , Toi Dylan , Amoako Daniel G. , Buys Amelia , Ndlangisa Kedibone , Wolter Nicole , Genade Leisha , Maloma Lucia , Chewparsad Juanita , Lebina Limakatso , de Gouveia Linda , Kotane Retshidisitswe , Tempia Stefano , Cohen Cheryl
Published: April 2022

Background

In South Africa 19% of the adult population aged 15-49 years are living with HIV (LWH). Few data on the influence of HIV on SARS-CoV-2 household transmission are available.

Methods

We performed a case-ascertained, prospective household transmission study of symptomatic index SARS-CoV-2 cases LWH and HIV-uninfected adults and their contacts in South Africa. Households were followed up thrice weekly for 6 weeks to collect nasal swabs for SARS-CoV-2 testing. We estimated household cumulative infection risk (HCIR), duration of SARS-CoV-2 positivity (at cycle threshold value<30 as proxy for high viral load), and assessed associated factors.

Results

We recruited 131 index cases and 457 household contacts. HCIR was 59% (220/373); not differing by index HIV status (60% [50/83] in cases LWH vs 58% [173/293] in HIV-uninfected cases, OR 1.0, 95%CI 0.4-2.3). HCIR increased with index case age (35-59 years: aOR 3.4 95%CI 1.5-7.8 and ≥60 years: aOR 3.1, 95%CI 1.0-10.1) compared to 18-34 years, and contacts’ age, 13-17 years (aOR 7.1, 95%CI 1.5-33.9) and 18-34 years (aOR 4.4, 95%CI 1.0-18.4) compared to <5 years. Mean positivity duration at high viral load was 7 days (range 2-28), with longer positivity in cases LWH (aHR 0.3, 95%CI 0.1-0.7).

Conclusions

HIV-infection was not associated with higher HCIR, but cases LWH had longer positivity duration at high viral load. Adults aged >35 years were more likely to transmit, and individuals aged 13-34 to acquire SARS-CoV-2 in the household. Health services must maintain HIV testing with initiation of antiretroviral therapy for those HIV-infected.

In this case-ascertained, prospective household transmission study, household cumulative infection risk was 59% from symptomatic SARS-CoV-2 index cases, not differing based on index HIV status. Index cases living with HIV were positive for SARS-CoV-2 for longer at higher viral loads.
Data and care integration for post-acute intensive care program of stroke patients: effectiveness assessment using a disease-matched comparator cohort
Authors: Vela Emili , Plaza Aina , Carot-Sans Gerard , Contel Joan C. , Salvat-Plana Mercè , Fabà Marta , Giralt Andrea , Ribera Aida , Santaeugènia Sebastià , Piera-Jiménez Jordi ,   the REDOM group
Published: April 2022

Purpose

To assess the effectiveness of an integrated care program for post-acute care of stroke patients, the return home program (RHP program), deployed in Barcelona (North-East Spain) between 2016 and 2017 in a context of health and social care information systems integration.

Design

The health outcomes and resource use of the RHP program participants were compared with a population-based matched control group built from central healthcare records of routine care data.

Findings

The study included 92 stroke patients attended within the RHP program and their matched-controls. Patients in the intervention group received domiciliary care service, home rehabilitation, and telecare significantly earlier than the matched-controls. Within the first two years after the stroke episode, recipients of the RHP program were less frequently institutionalized in a long-term care facility (5% vs. 15%). The use of primary care services, non-emergency transport, and telecare services were more frequent in the RHP group.

Originality

Our analysis shows that an integrated care program can effectively promote and accelerate delivery of key domiciliary care services, reducing institutionalization of stroke patients in the mid-term. The integration of health and social care information allows not only a better coordination among professionals but also to monitor health and resource use outcomes of care delivery
A protocol for a multicentre observational study across an integrated care system to understand the effect of living with frailty on access to video consultations
Authors: Shorthose Matthew , Watts Nick , Carter Ben , Evans Bekah , Jeynes Samuel , Wensley Sue , Braude Philip
Published: April 2022

Risks for digital exclusion include older age, disability, and deprivation. No literature exists examining frailty as an additional possible risk factor. Many studies have shown frailty to be a more accurate predictor of adverse outcome in healthcare than age alone. Understanding risk factors for digital exclusion may help healthcare services appropriately tailor interventions. The Healthier Together integrated care system (HTICS) in Bristol is developing video consultations for clinics. The aim of this prospective observational cross-sectional study is to identify whether living with frailty is a risk factor of digital exclusion from video consultation. Data will be collected using a structured survey including patients from three sites across the Heal secondary care services at North Bristol Trust, and then two subsequent sites will be included across HTICS. Data will be collected on known risk factors for digital exclusion, frailty using the Clinical Frailty Scale, and will cover four domains for digital exclusion as defined by NHS Digital: access, skill, motivation, and confidence. Data will be presented with descriptive statistics. The association between frailty and outcomes will be analysed with a multivariable logistic regression.

Key Study Contacts

Study Summary

Funding and Support in Kind

Role of Study Sponsor and Funder

The pilot at North Bristol Trust (NBT) is overseen by Neuromusculoskeletal (NMSK) Division governance. NBT NMSK Division takes responsibility for ensuring that the design of the study meets appropriate standards and that arrangements are in place to ensure appropriate conduct and reporting. Governance oversight for Hospital at Home was registered with NBT NMSK, and for primary care with Horfield Health Centre.

Roles and Responsibilities

Study Flow Chart
Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure
Authors: Rasooly Danielle , Peloso Gina M , Pereira Alexandre C , Dashti Hesam , Giambartolomei Claudia , Wheeler Eleanor , Aung Nay , Ferolito Brian R , Pietzner Maik , Farber-Eger Eric H , Wells Quinn Stanton , Kosik Nicole M , Gaziano Liam , Posner Daniel C , Bento A Patrícia , Hui Qin , Liu Chang , Aragam Krishna , Wang Zeyuan , Charest Brian , Huffman Jennifer E , Wilson Peter W.F. , Phillips Lawrence S , Whittaker John , Munroe Patricia B , Petersen Steffen E , Cho Kelly , Leach Andrew R , Magariños María Paula , Gaziano John Michael ,   VA Million Veteran Program, Langenberg Claudia , Sun Yan V , Joseph Jacob , Casas Juan P
Published: April 2022

We conduct a large-scale meta-analysis of heart failure genome-wide association studies (GWAS) consisting of over 90,000 heart failure cases and more than 1 million control individuals of European ancestry to uncover novel genetic determinants for heart failure. Using the GWAS results and blood protein quantitative loci, we perform Mendelian randomization and colocalization analyses on human proteins to provide putative causal evidence for the role of druggable proteins in the genesis of heart failure. We identify 39 genome-wide significant heart failure risk variants, of which 18 are previously unreported. Using a combination of Mendelian randomization proteomics and genetic cis-only colocalization analyses, we identify 10 additional putatively causal genes for heart failure. Findings from GWAS and Mendelian randomization-proteomics identify seven (CAMK2D,PRKD1,PRKD3,MAPK3,TNFSF12,APOC3andNAE1) proteins as potential targets for interventions to be used in primary prevention of heart failure.
Effectiveness and waning of protection with different SARS-CoV-2 primary and booster vaccines during the Delta pandemic wave in 2021 in Hungary (HUN-VE 3 study)
Authors: Vokó Zoltán , Kiss Zoltán , Surján György , Surján Orsolya , Barcza Zsófia , Wittmann István , Molnár Gergő Attila , Nagy Dávid , Müller Veronika , Bogos Krisztina , Nagy Péter , Kenessey István , Wéber András , Polivka Lőrinc , Pálosi Mihály , Szlávik János , Rokszin György , Müller Cecília , Szekanecz Zoltán , Kásler Miklós
Published: April 2022

Background

In late 2021, the pandemic wave was dominated by the Delta SARS-CoV-2 variant in Hungary. Booster vaccines were offered starting from August 2021.

Methods

The nationwide HUN-VE 3 study examined the effectiveness and durability of primary immunization and single booster vaccinations on SARS-CoV-2-related infection, hospitalization and mortality during the Delta wave.

Results

The study population included 8,087,988 individuals aged 18–100 years at the beginning of the pandemic. During the Delta wave, after adjusting for age, sex, calendar day, and chronic diseases, vaccine effectiveness (VE) of primary vaccination against registered SARS-CoV-2 infection was between 11% to 77% and 18% to 79% 14–120 days after primary immunization in the 16–64 and 65–100 years age cohort respectively, while it decreased to close to zero in the younger age group and around 40% or somewhat less in the elderly after 6 months for almost all vaccine types. In the population aged 65–100 years, we found high, 88.1%–92.5% adjusted effectiveness against Covid-19 infection after the Pfizer-BioNTech, and 92.2%–95.6% after the Moderna booster dose, while Sinopharm and Janssen booster doses provided 26.5%–75.3% and 72.9%–100.0% adjusted VE, respectively. Adjusted VE against Covid-19 related hospitalization was high within 14–120 days for Pfizer-BioNTech: 76.6%, Moderna: 83.8%, Sputnik-V: 78.3%, AstraZeneca: 73.8%, while modest for Sinopharm: 45.7% and Janssen: 26.4%. The waning of protection against Covid-19 related hospitalization was modest and booster vaccination with mRNA vaccines or the Janssen vaccine increased adjusted VE up to almost 100%, while the Sinopharm booster dose proved to be less effective. VE against Covid-19 related death after primary immunization was high or moderate: for Pfizer-BioNTech: 81.5%, Moderna: 93.2%, Sputnik-V: 100.0%, AstraZeneca: 84.8%, Sinopharm: 58.6%, Janssen: 53.3%). VE against this outcome also showed moderate decline over time, while booster vaccines restored effectiveness up to almost 100%, except for the Sinopharm booster.

Conclusions

The HUN-VE 3 study demonstrated waning VE with all vaccine types for all examined outcomes during the Delta wave and confirmed the outstanding benefit of booster vaccination with the mRNA or Janssen vaccines. This is the first study to provide comparable effectiveness results for six different booster types during the Delta pandemic wave.
Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study
Authors: Zhao Jian , Stewart Isobel D , Baird Denis , Mason Dan , Wright John , Zheng Jie , Gaunt Tom R , Evans David M , Freathy Rachel M , Langenberg Claudia , Warrington Nicole M , Lawlor Deborah A , Borges Maria Carolina
Published: April 2022

Amino acids are key to protein synthesis, energy metabolism, cell signaling and gene expression; however, the contribution of specific maternal amino acids to fetal growth is unclear. We explored the effect of maternal circulating amino acids on fetal growth, proxied by birthweight, using two-sample Mendelian randomization and summary data from a genome-wide association study (GWAS) of serum amino acids levels (sample 1, n = 86,507) and a maternal GWAS of offspring birthweight, adjusting for fetal genotype effects (sample 2, n = 406,063 with maternal and/or fetal genotype effect estimates). A total of 106 independent single nucleotide polymorphisms (SNPs) robustly associated with 19 amino acids (p < 4.9 × 10−10) were used as genetic instrumental variables. Our results provide evidence that maternal circulating glutamine (59 g offspring birthweight increase per SD increase in maternal amino acid level, 95% CI: 7, 110) and serine (27 g, 95% CI: 9, 46) raise, while leucine (−59 g, 95% CI: -106, -11) and phenylalanine (−25 g, 95% CI: -47, -4) lower offspring birthweight. Our findings strengthen evidence for key roles of maternal circulating amino acids in healthy fetal growth.
In Silico transcriptional analysis of asymptomatic and severe COVID-19 patients reveals the susceptibility of severe patients to other comorbidities and non-viral pathological conditions
Authors: Sen Poonam , Kaur Harpreet
Published: April 2022

COVID-19 is a severe respiratory disease caused by SARS-CoV-2, a novel human coronavirus. The host response to SARS-CoV-2 infection is not clearly understood. Patients infected with SARS-CoV-2 exhibit heterogeneous intensity of symptoms, i.e., asymptomatic, mild, and severe. Moreover, effects on organs also vary from person to person. These heterogeneous responses pose pragmatic hurdles for implementing appropriate therapy and management of COVID-19 patients. Post-COVID complications pose another major challenge in managing the health of these patients. Thus, understanding the impact of disease severity at the molecular level is vital to delineate the precise host response and management. In the current study, we performed a comprehensive transcriptomics analysis of publicly available seven asymptomatic and eight severe COVID-19 patients. Exploratory data analysis using Principal Component Analysis (PCA) showed the distinct clusters of asymptomatic and severe patients. Subsequently, the differential gene expression analysis using DESeq2 identified 1,224 significantly upregulated genes (logFC>= 1.5, p-adjusted value <0.05) and 268 significantly downregulated genes (logFC<= -1.5, p-adjusted value <0.05) in severe samples in comparison to asymptomatic samples. Eventually, Gene Set Enrichment Analysis (GSEA) of upregulated genes revealed significant enrichment of terms, i.e., anti-viral and anti-inflammatory pathways, secondary infections, Iron homeostasis, anemia, cardiac-related, etc. Gene set enrichment analysis of downregulated genes indicates lipid metabolism, adaptive immune response, translation, recurrent respiratory infections, heme-biosynthetic pathways, etc. In summary, severe COVID-19 patients are more susceptible to other health issues/concerns, non-viral pathogenic infections, atherosclerosis, autoinflammatory diseases, anemia, male infertility, etc. And eventually, these findings provide insight into the precise therapeutic management of severe COVID-19 patients and efficient disease management.