bluuebunny/crossref_metadata_2025 huggingface dataset:
Physician practices in evaluation and treatment of patients with generalized joint hypermobility and bleeding
Authors: Kendel Nicole E. , O’Brien Sarah H. , Laukaitis Christina M. , Kumar Manjusha , Levy Howard P. , Jesudas Rohith
Published: June 2021

The association between bleeding and joint hypermobility may not be as diagnostically obvious in patients with milder connective tissue disorders. We surveyed members of the Hemostasis and Thrombosis Research Society regarding their knowledge, evaluation, and management practices in patients with generalized hypermobility spectrum disorder/hypermobile Ehlers–Danlos syndrome (hEDS) and bleeding symptoms. The objectives of this study were to (1) evaluate hematologists’ diagnosis and management practices for patients with bleeding symptoms and generalized hypermobility spectrum disorder/hEDS and (2) determine future education and research priorities regarding bleeding symptoms within this population. Evaluate hematologists’ diagnosis and management practices for patients with bleeding symptoms and generalized hypermobility spectrum disorder/hEDS. Determine future education and research priorities regarding bleeding symptoms within this population. A web-based survey was sent to Hemostasis and Thrombosis Research Society physician members. Physician demographics, preferred evaluation for hEDS, management of bleeding episodes, and referral patterns were collected and descriptive statistics were performed. Only two-thirds of respondents reported evaluating for hypermobility, despite all respondents being aware of the association with bleeding. There were significant variations in referral patterns for genetic counseling, diagnostic evaluation, and management of nonhematologic symptoms. There were also significant variations in reported medical homes for this patient population. Research prioritization included understanding the evolution of bleeding symptoms with age in this population as well as the development of functional tests to identify the molecular mechanism of bleeding and the development of novel hemostatic agents for this population. Results from 33 respondents show differing physician practices regarding the evaluation and management of bleeding in hypermobile patients. Many physicians suggested further research priorities to include studying the natural history of the disease and development of functional diagnostic testing as well as targeted therapeutic options in this patient population.
Acceptability of Nurse-Driven HIV Screening for Key Populations in Emergency Departments
Authors: Leblanc Judith , Côté José , Auger Patricia , Rouleau Geneviève , Bastide Théophile , Piquet Hélène , Fromentin Hélène , Jegou Carole , Duchêne Gaëlle , Verbrugghe Rachel , Lancien Cécile , Simon Tabassome , Crémieux Anne-Claude ,   for the DICI-VIH (Dépistage Infirmier CIblé du VIH) group
Published: June 2021

Background

Optimizing care continuum entry interventions is key to ending the HIV epidemic. Offering HIV screening to key populations in emergency departments (EDs) is a strategy that has been demonstrated to be effective. Analyzing patient and provider perceptions of such screening can help identify implementation facilitators and barriers.

Objectives

The aim of this study was to investigate the acceptability of offering nurse-driven HIV screening to key populations based on data collected from patients, nurses, and other service providers.

Methods

This convergent mixed-methods study was a substudy of a cluster-randomized two-period crossover trial conducted in eight EDs to evaluate the effectiveness of the screening strategy. During the DICI-VIH (Dépistage Infirmier CIblé du VIH) trial, questionnaires were distributed to patients aged 18–64 years. Based on their responses, nurses offered screening to members of key populations.

Over 5 days during the intervention period in four EDs, 218 patients were secondarily questioned about the acceptability of screening. Nurses completed 271 questionnaires pre- and posttrial regarding acceptability in all eight EDs. Descriptive analyses were conducted on these quantitative data. Convenience and purposeful sampling was used to recruit 53 providers to be interviewed posttrial. Two coders conducted a directed qualitative content analysis of the interview transcripts independently.

Results

The vast majority of patients (95%) were comfortable with questions asked to determine membership in key populations and agreed (89%) that screening should be offered to key populations in EDs. Nurses mostly agreed that offering screening to key populations was well accepted by patients (62.2% pretrial and 71.4% posttrial), was easy to implement, and fell within the nursing sphere of competence. Pretrial, 73% of the nurses felt that such screening could be implemented in EDs. Posttrial, the proportion was 41%. Three themes emerged from the interviews: preference for targeted screening and a written questionnaire to identify key populations, facilitators of long-term implementation, and implementation barriers. Nurses were favorable to such screening provided specific conditions were met regarding training, support, collective involvement, and flexibility of application to overcome organizational and individual barriers.

Discussion

Screening for key populations was perceived as acceptable and beneficial by patients and providers. Addressing the identified facilitators and barriers would help increase screening implementation in EDs.
Isolated Anterior Interosseous Neuropathy Affecting Only the Flexor Digitorum Profundus to the Index Finger After Shoulder Arthroscopy
Authors: Carrier Jonathan , Colorado Berdale
Published: June 2021

Anterior interosseous nerve neuropathy is an uncommon neuropathy with multiple potential etiologies. We present a rare case of anterior interosseous nerve neuropathy affecting only the flexor digitorum profundus to the index finger and occurring after shoulder arthroscopy. This unique presentation used a combination of both electrodiagnostic testing and neuromuscular ultrasound to obtain an accurate diagnosis and highlights the importance of these complementary tests in the evaluation of nerve disorders. To our knowledge, anterior interosseous nerve neuropathy after shoulder arthroscopy affecting only the flexor digitorum profundus to the index finger has not been previously described in the literature.
Virtually Possible
Authors: Huang Laura Y. , McKenty Nathan , Alvarez Armando , Gober Joslyn , Irwin Robert , Molinares Diana , Price Chane , Sherman Andrew , Tiu Timothy , Gater David R.
Published: June 2021

The novel coronavirus 2019 pandemic has led to new dilemmas in medical education because of an initial shortage of personal protective equipment, uncertainty regarding disease transmission and treatments, travel restrictions, and social distancing guidelines. These new problems further compound the already existing problem of limited medical student exposure to the field of physical medicine and rehabilitation, particularly for students in medical schools lacking a department of physical medicine and rehabilitation, approximately 50% of medical schools. A virtual medical student physical medicine and rehabilitation rotation was created to mitigate coronavirus 2019–related limitations and impact on medical education. Using audiovisual technology, students had the opportunity to participate in clinical inpatient and outpatient care, live-streamed procedures, and virtual didactics, develop and showcase their clinical knowledge and reasoning skills, and become familiar with the culture of the physical medicine and rehabilitation residency program. Adaptive educational approaches, including integration of the flipped classroom model, success, pitfalls, and areas for improvement will be described and discussed. Providing nontraditional methods for physical medicine and rehabilitation education and exposure to medical students is crucial to maintain and promote growth of the field in this unprecedented and increasingly virtual era.
Depression and HIV viral nonsuppression among people engaged in HIV care in an urban clinic, 2014–2019
Authors: Lesko Catherine R. , Hutton Heidi E. , Fojo Anthony T. , Shen Nicola M. , Moore Richard D. , Chander Geetanjali
Published: June 2021

Objective:

The aim of this study was to describe the risk of viral nonsuppression across the depression care cascade.

Design:

A clinical cohort study.

Methods:

We used depressive symptoms (PHQ-8 ≥ 10) self-reported on computer-assisted surveys, clinical diagnoses of depression in the medical record in the prior year and pharmacologic (any prescription for an antidepressant) and psychologic treatments for depression (attendance at at least two mental health visits in the prior year) to classify patients into groups: no history of depression; prior depression diagnosis; current indication for depression treatment (symptoms or clinical diagnosis); and treated depression (stratified by presence of persistent symptoms). We associated position in the depression care cascade with viral nonsuppression (>200 copies/ml) 7 days before to 6 months after the index self-report of depressive symptoms.

Results:

History of depression [adjusted risk difference (aRD) relative to no history = 5.9%, 95% confidence interval (95% CI): 1.5–10.3] and current depression (symptoms or diagnosis) in the absence of treatment (aRD relative to no current depression or depression treatment = 4.8%, 95% CI: 1.8–7.8) were associated with a higher risk of viral nonsuppression than no history of depression. Depression treatment mitigated this association (aRD = −0.4%, 95% CI: −2.5 to 1.7).

Conclusion:

The relationship between depression care cascade and viral suppression is complex. Untreated depression and clinically unrecognized depressive symptoms were both related to viral nonsuppression. Treated depression was not associated with viral nonsuppression; however, a high proportion of treated patients still had depressive symptoms. Depression treatment should be titrated if patients’ symptoms are not responsive and patients with a history of depression should be monitored for ART adherence.
Brief Report: Are Serious Falls Associated With Subsequent Fragility Fractures Among Veterans Living With HIV?
Authors: Womack Julie A. , Murphy Terrence E. , Ramsey Christine , Bathulapalli Harini , Leo-Summers Linda , Smith Alexandria C. , Bates Jonathan , Jarad Samah , Gill Thomas M. , Hsieh Evelyn , Rodriguez-Barradas Maria C. , Tien Phyllis C. , Yin Michael T. , Brandt Cynthia , Justice Amy C.
Published: June 2021

Background:

The extensive research on falls and fragility fractures among persons living with HIV (PWH) has not explored the association between serious falls and subsequent fragility fracture. We explored this association.

Setting:

Veterans Aging Cohort Study.

Methods:

This analysis included 304,951 6-month person- intervals over a 15-year period (2001–2015) contributed by 26,373 PWH who were 50+ years of age (mean age 55 years) and taking antiretroviral therapy (ART). Serious falls (those falls significant enough to result in a visit to a health care provider) were identified by the external cause of injury codes and a machine learning algorithm applied to radiology reports. Fragility fractures were identified using ICD9 codes and included hip fracture, vertebral fractures, and upper arm fracture and were modeled with multivariable logistic regression with generalized estimating equations.

Results:

After adjustment, serious falls in the previous year were associated with increased risk of fragility fracture [odds ratio (OR) 2.10; 95% confidence interval (CI): 1.83 to 2.41]. The use of integrase inhibitors was the only ART risk factor (OR 1.17; 95% CI: 1.03 to 1.33). Other risk factors included the diagnosis of alcohol use disorder (OR 1.49; 95% CI: 1.31 to 1.70) and having a prescription for an opioid in the previous 6 months (OR 1.40; 95% CI: 1.27 to 1.53).

Conclusions:

Serious falls within the past year are strongly associated with fragility fractures among PWH on ART—largely a middle-aged population—much as they are among older adults in the general population.
Performance Analysis of Three Commercial Kits Designed for RNA Quantification of HIV-1 Group O Variants
Authors: Alessandri-Gradt Elodie , Unal Guillemette , Baron Adeline , Leoz Marie , Gueudin Marie , Plantier Jean-Christophe ,   the RES-O Network
Published: June 2021

Background:

The genetic divergence of HIV-1 group O is high relative to pandemic group M, which could impact detection and quantification of plasma RNA. Recent commercial kits for RNA quantification seem to show good performances in HIV-1/O, but discrepancies are still observed. Here, we compare the performances of 3 commercial assays for the RNA quantification of HIV-1/O.

Methods:

We studied the RNA quantification of 117 clinical samples using Abbott RealTime HIV-1, Cepheid Xpert HIV-1 Viral Load, or Roche Cobas TaqMan HIV-1 v2. First, we conducted a qualitative description, and second, we focused on a quantitative analysis of the results above 40 cp/mL. The degree of agreement between methods and the strength of the correlation of viral load determination were estimated using Bland–Altman plot and Passing–Bablok regression with the Spearman coefficient, respectively.

Results:

Our 2-by-2 analysis showed that the Abbott and Cepheid assays were very close in terms of correlation and dispersion of points, whereas Roche presented higher values in the highest range of quantification (>5 log10). The Cepheid assay combined better correlation with the consensus value and a lower dispersion of values, leading to an overall better performance of quantification. The quantification was still impacted by intragroup genetic diversity with, here, 1 strain (YBF26).

Conclusions:

Using a new approach to compare the performances of RNA quantification between more than 2 techniques, we demonstrated that Cepheid could be the most suitable assay for HIV-1/O quantification, although the results from all assays remained strain dependent.
Brief Report: Impact of the COVID-19 Pandemic on Virological Suppression in People Living With HIV Attending a Large Italian HIV Clinic
Authors: Giacomelli Andrea , Bonazzetti Cecilia , Conti Federico , Pezzati Laura , Oreni Letizia , Micheli Valeria , Mancon Alessandro , Vimercati Stefania , Albrecht Maria , Passerini Matteo , Cossu Maria Vittoria , Capetti Amedeo Ferdinando , Meraviglia Paola , Antinori Spinello , Rizzardini Giuliano , Galli Massimo , Ridolfo Anna Lisa
Published: June 2021

Background:

We assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on HIV suppression rates in people living with HIV (PLWH) attending a large Italian HIV clinic.

Setting:

The HIV outpatient clinic of the Infectious Diseases Department of Luigi Sacco Hospital, Milan, Italy, which serves more than 5000 PLWH per year.

Methods:

A before and after quasi-experimental study design was used to make a retrospective assessment of the monthly trend of HIV-RNA determinations of ≥50 among the PLWH attending our clinic, with “before” being the period from January 1, 2016 to February 20, 2020, and “after” being the period from February 21, 2020 to December 31, 2020 (the COVID-19 period). Interrupted time series analysis was used to evaluate any changes in the trend.

Results:

During the study period, 70,349 HIV-RNA viral load determinations were made, and the percentage of HIV-RNA viral load determinations of <50 copies/mL increased from 88.4% in 2016 to 93.2% in 2020 (P < 0.0001). There was a significant monthly trend toward a decrease in the number of HIV-RNA determinations of ≥50 copies/mL before the pandemic (β −0.084; standard error 0.015; P < 0.001), and this did not significantly change after it started (β −0.039, standard error 0.161; P = 0.811).

Conclusions:

A high prevalence of viral suppression was maintained among the PLWH referring to our clinic, despite the structural barriers raised by the COVID-19 pandemic. The use of simplified methods of delivering care (such as teleconsultations and multiple antiretroviral treatment prescriptions) may have contributed to preserving this continuum.
Safety and Pharmacokinetics of Once-Daily Multiple-Dose Administration of Islatravir in Adults Without HIV
Authors: Matthews Randolph P. , Jackson Rudd Deanne , Zhang Saijuan , Fillgrove Kerry L. , Sterling Laura M. , Grobler Jay A. , Vargo Ryan C. , Stoch S. Aubrey , Iwamoto Marian
Published: June 2021

Background:

Islatravir (MK-8591) is a novel nucleoside analog in development for the treatment and prevention of HIV-1 infection. Islatravir has potent antiviral activity and a long intracellular half-life.

Setting:

A 3-panel, randomized, double-blind, placebo-controlled, multiple-dose study in 36 adults without HIV evaluated the safety, tolerability, and pharmacokinetics of islatravir after daily administration.

Methods:

Islatravir or placebo was administered orally once daily for 42 days (5 mg) or 28 days (0.25 mg; 0.75 mg). Blood samples were taken at prespecified time points for pharmacokinetic analysis of islatravir (plasma) and islatravir-triphosphate (ISL-TP; peripheral blood mononuclear cells [PBMCs]). Rectal and vaginal tissue samples were also collected in a subset of participants. Safety and tolerability were evaluated throughout.

Results:

The pharmacokinetics of islatravir were approximately dose proportional, with concentrations approaching a steady state between days 14 and 21 in plasma and by day 28 for ISL-TP in PBMCs. Plasma exposure accumulation was 1.5-fold to 1.8-fold, and ISL-TP exposure accumulation was ∼10-fold. The apparent terminal half-life of ISL-TP was 177–209 hours. The ISL-TP pharmacokinetic trough threshold—the minimal concentration required for efficacy—of 0.05 pmol/106 cells was achieved after a single administration at all dose levels. Rectal and vaginal tissue also exhibited potentially therapeutic concentrations. Islatravir was generally well tolerated at all doses.

Conclusions:

ISL-TP levels in PBMCs were above the threshold projected for antiviral efficacy against wild-type HIV after a single 0.25-mg dose. Multiple once-daily dosing of islatravir in adults without HIV was generally well tolerated up to doses of 5 mg administered for up to 6 weeks.
Unpacking a Telemedical Takeover: Recommendations for Improving the Sustainability and Usage of Telemedicine Post-COVID-19
Authors: Kaundinya Trisha , Agrawal Rishi
Published: June 2021

Telemedicine technology and regulation have been steadily growing over the last 2 decades. Prior to the coronavirus disease-2019 (COVID-19) pandemic, the availability of telemedicine in health systems and coverage of telemedicine were variable. Sudden and improved access to telemedicine was propelled by the COVID-19 pandemic, during which governments, insurers, and health systems ramped up telemedical utilization with short-term exceptions and waivers. As in-person care opportunities open back up, the presence of telemedicine is not receding and thus its widespread adoption needs to be facilitated outside pandemic-specific conditions. Long-term funding for telemedicine acquisition, centralized electronic health records, extended waivers related to telemedicine coverage and use, a Medicaid expansion that involves parity in telemedicine and in-person care, a nationalized licensure system, and an assessment of what types of care settings can and cannot utilize telemedicine are necessary recommendations to improve the sustainability of telemedicine after the pandemic.
Follicular Thyroid Adenoma Showing Avid Uptake on 68Ga-DOTA-FAPI-04 PET/CT
Authors: Ou Lei , Wu Junhao , Wu Ji , Mou Chunru , Zhang Chunyin
Published: June 2021

We describe the case of a 48-year-old man suspected to have recurrent colon carcinoma who underwent 68Ga-DOTA-FAPI-04 PET/CT, revealing the presence of an incidentaloma with intense FAPI uptake in the left thyroid lobe. Based on PET/CT findings, malignancy was suspected. Biopsy confirmed the diagnosis of follicular thyroid adenoma with fibrosis and calcification. This case emphasizes the need to increase awareness of this benign lesion in the differential diagnosis of incidental thyroid nodules with high FAPI activity.
Glomangiopericytoma Uptake With 99mTc-MIBI, 18F-FDG, and 11C-Choline
Authors: Nguyen Ba Duong
Published: June 2021

The author presents 3 incidental cases of glomangiopericytoma exhibiting avidity of 99mTc-MIBI, 18F-FDG, and 11C-choline, respectively, during SPECT/CT evaluation of hyperparathyroidism, and PET/CT monitoring of metastatic melanoma and biochemical recurrence of prostate cancer. All the 3 cases show similar functional and anatomic features of tracer-avid lesion in the right nasal cavity from histologically proven glomangiopericytoma.
Unusual Variant of Breast Cancer Presenting With Pituitary Symptoms Detected on 68Ga-DOTATATE PET/CT
Authors: Dev Indraja D. , Puranik Ameya D. , Rangarajan Venkatesh , Purandare Nilendu C. , Agrawal Archi , Shah Sneha , Sahay Ayushi
Published: June 2021

Carcinoma of breast with neuroendocrine differentiation is an extremely rare entity, especially in male population. Although the “garden variety” of male breast cancers is often metastatic at presentation, with an aggressive course, there is hardly any literature about neuroendocrine variants. We report a case of a 57-year-old man who had pituitary symptoms, which on 68Ga-DOTANOC PET/CT imaging turned out to be a metastatic lesion, with somatostatin expressing primary in breast and other sites, with histopathological confirmation of neuroendocrine differentiation in breast cancer.
Colon Transit Scintigraphy in Schaaf-Yang Syndrome
Authors: Infante Jose R. , Baena Alvaro , Martinez Andres , Rayo Juan I. , Serrano Justo
Published: June 2021

Schaaf-Yang syndrome is a genetic disorder characterized by delayed psychomotor development, hypotonia, intellectual disability, feeding difficulties, and variable dysmorphic facial features. It is an extremely rare disorder with over 250 cases reported in the medical literature. This condition has been determined to be inherited by an autosomal dominant pattern. We present colon transit scintigraphy of a 6-year-old boy with history of chronic constipation with poor response to medical treatment, clinical characteristics, and gene mutations consistent with this syndrome. After oral administration of 111In-DTPA, planar and SPECT/CT images showed rapid proximal colonic transit and anorectal retention.
Prostate-Specific Membrane Antigen Expression in Metastatic Angiosarcoma Detected on 18F-PMSA PET/CT
Authors: Marafi Fahad , Esmail Abdulredha , Usmani Sharjeel
Published: June 2021

18F-PSMA is a promising tracer for both staging and detection of biochemical recurrence in prostate cancer. PSMA is also expressed in the endothelium of tumor-associated neovasculature of various solid malignancies possibly due to tumor-associated angiogenic factors and endothelial cell sprouting. We report a case of a 59-year-old man with known case of prostate cancer underwent 18F-PSMA for restaging. 18F-PSMA PET/CT shows multiple lytic bone lesions with high PSMA expression. Histopathological evaluation showed metastatic angiosarcoma. 18F-PSMA expression in the angiosarcoma can be potentially guided to radionuclide legend therapy.
Changes of Ocular Surface Before and After Treatment of Blepharoptosis With Combined Fascial Sheath Suspension and Frontal Muscle Flap Suspension
Authors: Li Yan , Wang Huixing , Bai Ping
Published: June 2021

Objective:

To explore the ocular surface changes after ptosis surgery in patients with severe congenital blepharoptosis.

Methods:

The patients were divided into group A and group B, Group A received conjoint fascial sheath suspension, and group B received frontal muscle flap suspension. The ocular surface changes were followed upon the 7th day and in the 1st and 3rd month after operation, which included Schirmer test (ST), break-up time (BUT), tear meniscus height (TMH). For normal distribution variables, t test was used before and after operation, and the Wilcoxon test was used for variables with abnormal distribution.

Results:

Compared to preoperative status, the ST and TMH were not significantly changed after surgery (P > 0.05), but BUT higher on the 7th day and in the 1st and 3rd month after operation (P < 0.05). The fluorescence staining (FL) score was higher in the 3rd month than that in the 1st month (P < 0.05), but was not significantly different between the 7th and in the 1st month after operation (P > 0.05). The ST, TMH, and BUT after surgery were not significantly different between groups of A and B (P > 0.05), but the FL score lower in the 3rd month than on the 7th day and in the 1st month after operation (P < 0.05).

Conclusions:

The ST, BUT, and TMH were not significantly changed after surgery between groups of A and B, but the FL score was lower in group A than that in group B in early postoperative time.
Three-Dimensional Facial Soft Tissue Changes After Orthognathic Surgery in Cleft Patients Using Artificial Intelligence-Assisted Landmark Autodigitization
Authors: Seo Jihee , Yang Il-Hyung , Choi Jin-Young , Lee Jong-Ho , Baek Seung-Hak
Published: June 2021

The purpose of this study was to investigate three-dimensional facial soft tissue changes after bimaxillary orthognathic surgery (BOGS) in patients with cleft lip and palate. The samples consisted of 34 Korean young adult patients with skeletal class III malocclusion who underwent BOGS for maxillary advancement/posterior impaction and mandibular setback. They were divided into cleft-class III (C-CIII) group (n = 18) and noncleft-class III (NC-CIII) group (n = 16). Three-dimensional computed tomography images were taken 1 month before (T1) and 3 months after (T2) surgery. After 34 hard/soft tissue landmarks were automatically identified using software, the amount and direction of change in landmarks and the amount of change in 16 soft tissue variables during T1-T2 were calculated. Then, statistical analysis was performed. Compared to NC-CIII group, C-CIII group showed more posteriorly-positioned hard/soft tissue landmarks, larger alar width, alar base width and philtrum width, and more obtuse nasal tip angle at both T1 and T2 stages. C-CIII group exhibited higher soft-to-hard tissue movement ratios at the bottom of the nose (ΔSn/ΔANS, 1.08 versus 0.81) and the upper part of the upper lip (ΔPoint A’/ΔPoint A, 1.08 versus 0.91), but a lower ratio at the lower part of the upper lip (ΔLs’/ΔIs, 0.72 versus 1.01) than NC-CIII group. The number of hard-soft tissue landmarks with high correlation (>0.90) was smaller in C-CIII group than in NC-CIII group (2 versus 6). Scar tissues and abnormal muscles in the nose and upper lip might elicit different responses in the nasolabial soft tissues to BOGS between C-CIII and NC-CIII patients.
Midline Mandibular Cleft Treatment
Authors: Dadaci Mehmet , Ismayilzade Majid , Yildirim Mehmet Emin Cem , Ince Bilsev
Published: June 2021

Tessier 30 cleft is a more rare anomaly comparing the other clefts and has variable clinical presentations. According to the literature, there were only 66 cases with Tessier 30 cleft reported since 2007. Furthermore, because of the rarity and variable clinical presentation of this condition, there is no consensus on the mode of management and timing of surgical procedures. In this case, we demonstrated the earlier treatment method of a newborn case with Tessier 30 cleft.
Hypothermic Machine Perfusion as a National Standard Preservation Method for Deceased Donor Kidneys
Authors: Brat Aukje , de Vries Kirsten M. , van Heurn Ernst W. E. , Huurman Volkert A. L. , de Jongh Wim , Leuvenink Henri G. D. , van Zuilen Arjan D. , Haase-Kromwijk Bernadette J. J. M. , de Jonge Jeroen , Berger Stefan P. , Hofker Sijbrand H.
Published: June 2021

Background.

Recently, continuous nonoxygenated hypothermic machine perfusion (HMP) has been implemented as standard preservation method for deceased donor kidneys in the Netherlands. This study was designed to assess the effect of the implementation of HMP on early outcomes after transplantation.

Methods.

Kidneys donated in the Netherlands in 2016 and 2017 were intended to be preserved by HMP. A historical cohort (2010–2014) preserved by static cold storage was chosen as the control group. Primary outcome was delayed graft function (DGF). Additional analyses were performed on safety, graft function, and survival up until 2 y after transplantation.

Results.

Data were collected on 2493 kidneys. Analyses showed significantly more donation after circulatory death, preemptive transplantation, and retransplants in the project cohort. Of the 681 kidneys that were transplanted during the project, 81% were preserved by HMP. No kidneys were discarded due to HMP-related complications. DGF occurred in 38.2% of the project cohort versus 43.7% of the historical cohort (P < 0.001), with a significantly shorter duration within the project cohort (7 versus 9 d, P = 0.003). Multivariate regression analysis showed an odds ratio of 0.69 (95% confidence interval, 0.553-0.855) for the risk of DGF when using HMP compared with cold storage (P = 0.001). There was no significant difference in kidney function, graft survival, and recipient survival up until 2 y posttransplantation.

Conclusions.

This study showed that HMP as a standard preservation method for deceased donor kidneys is safe and feasible. HMP was associated with a significant reduction of DGF.
Prognostic Impact of Early Recovering Acute Kidney Injury Following Liver Transplantation: A Multicenter Retrospective Study
Authors: Dewitte Antoine , Defaye Mylène , Dahmi Anissa , Ouattara Alexandre , Joannes-Boyau Olivier , Chermak Faiza , Chiche Laurence , Laurent Christophe , Battelier Mathieu , Sigaut Stéphanie , Khoy-Ear Linda , Grigoresco Bénédicte , Cauchy François , Francoz Claire , Paugam Burtz Catherine , Janny Sylvie , Weiss Emmanuel
Published: June 2021

Background.

Acute kidney injury (AKI) is a common complication after liver transplantation (LT), but the specific impact of rapidly resolving AKI is not elucidated. This study investigates the factors associated with early recovery from AKI and its association with post-LT outcomes.

Methods.

Retrospective analysis of 441 liver transplant recipients with end-stage liver disease without pretransplant renal impairment. AKI was defined according to Kidney Disease Improving Global Outcomes criteria and early renal recovery by its disappearance within 7 d post-LT.

Results.

One hundred forty-six patients (32%) developed a post-LT AKI, of whom 99 (69%) recovered early and 45 (31%) did not. Factors associated with early recovery were Kidney Disease Improving Global Outcomes stage 1 (odds ratio [OR],14.11; 95% confidence interval [CI], 5.59-40.22; P < 0.0001), minimum prothrombin time >50 % (OR, 4.50; 95% CI, 1.67-13.46; P = 0.003) and aspartate aminotransferase peak value <1000 U/L (OR, 4.07; 95% CI, 1.64-10.75; P = 0.002) within 48 h post-LT. Patients with early recovery had a renal prognosis similar to that of patients without AKI with no difference in estimated glomerular filtration rate between day 7 and 1 y. Their relative risk of developing chronic kidney disease was 0.88 (95% CI, 0.55-1.41; P = 0.6) with survival identical to patients without AKI and better than patients without early recovery (P < 0.0001).

Conclusions.

Most patients with post-LT AKI recover early and have a similar renal prognosis and survival to those without post-LT AKI. Factors associated with early renal recovery are related to the stage of AKI, the extent of liver injury, and the early graft function. Patients at risk of not recovering may benefit the most from perioperative protective strategies, particularly those aimed at minimizing the adverse effects of calcineurin inhibitors.
Brachybacterium subflavum sp. nov., a novel actinobacterium isolated from the foregut of grass carp
Authors: Ming Hong , Cheng Li-jiao , Yi Bing-fang , Xia Ting-ting , Niu Ming-ming , Zhao Zi-yu , Liu Bing-bing , Nie Guo-xing , Cui Cai-xia
Published: June 2021

A novel actinobacterium, designated CFH 10395T, was isolated from the foregut of grass carp (Ctenopharyngodon idella), which had been fed with ginseng extract supplement. The taxonomic position was investigated by a polyphasic approach. Cells of CFH 10395Twere Gram-staining-positive, aerobic, ovoid-shaped, non-spore-forming and non-motile. On the basis of the results of 16S rRNA gene sequence analysis, CFH 10395Twas most closely related toBrachybacterium endophyticumKCTC 49087T,Brachybacterium squillarumJCM 16464TandBrachybacterium paraconglomeratumJCM 17781T(97.85%, 97.51 and 97.29% similarity, respectively). CFH 10395Tgrew at 4–37 °C, pH 5.0–9.0 and in the presence of up to 10.0 % NaCl (w/v). The dominant menaquinone was MK-7. The whole-cell sugars were rhamnose, glucose, mannose and galactose.meso-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The major fatty acids were anteiso-C15 : 0, anteiso-C17 : 0and iso-C16 : 0. The genome size was 3.99 Mbp with a DNA G+C content of 71.9 mol%. On the basis of the results of phylogenetic analysis, physiological properties, chemotaxonomic characteristics, low average nucleotide identity (ANI) and digital DDH (dDDH) results [ANI calculated using MUMmer (ANIm) <87 %, ANI calculated usingblast(ANIb) <83 % and dDDH <23 %], it is concluded that CFH 10395Trepresents a novel species of the genusBrachybacterium, for which the nameBrachybacterium subflavumsp. nov., is proposed. The type strain is CFH 10395T(=CGMCC 1.13804T=KCTC 49235T).
Investigating the effect of sexual behaviour on oropharyngeal cancer risk: a methodological assessment of Mendelian randomization
Authors: Gormley Mark , Dudding Tom , Kachuri Linda , Burrows Kimberley , Chong Amanda HW , Martin Richard M , Thomas Steven , Tyrrell Jessica , Ness Andrew R , Brennan Paul , Munafò Marcus R , Pring Miranda , Boccia Stefania , Olshan Andrew F , Diergaarde Brenda , Hung Rayjean J , Liu Geoffrey , Tajara Eloiza , Severino Patricia , Toporcov Tatiana N , Lacko Martin , Waterboer Tim , Brenner Nicole , Smith George Davey , Vincent Emma E , Richmond Rebecca C
Published: June 2021

Human papilloma virus infection is known to influence oropharyngeal cancer (OPC) risk, likely via sexual transmission. However, sexual behaviour has been correlated with other risk factors including smoking and alcohol, meaning independent effects are difficult to establish. Here we evaluate aspects of sexual behaviour in relation to the risk of OPC (2,641 cases and 6,585 controls), using genetic variants associated with age at first sex (AFS) and number of sexual partners (NSP) to perform Mendelian randomization (MR) analyses. While univariable MR showed a causal effect of both later AFS and increasing NSP on OPC, results attenuated in the multivariable models (AFS IVW OR 0.7, 95%CI 0.4, 1.2,p=0.21; NSP IVW OR 0.9, 95%CI 0.5 1.7,p=0.76). We also found evidence for correlated pleiotropy in the genetic instruments for sexual behaviour, emphasising the need for multivariable approaches when performing MR of complex behavioural traits and the triangulation of evidence.
Sound level context modulates neural activity in the human brainstem
Authors: Herrmann Björn , Yasmin Sonia , Araz Kurdo , Purcell David W. , Johnsrude Ingrid S.
Published: June 2021

Optimal perception requires adaptation to sounds in the environment. Adaptation involves representing the acoustic stimulation history in neural response patterns, for example, by altering response magnitude or latency as sound-level context change. Neurons in the auditory brainstem of rodents are sensitive to acoustic stimulation history and sound-level context (often referred to as sensitivity to stimulus statistics), but the degree to which the human brainstem exhibits such neural adaptation is unclear. In six electroencephalography experiments with over 125 participants, we demonstrate that the response latency of the human brainstem is sensitive to the history of acoustic stimulation over a few tens of milliseconds. We further show that human brainstem responses adapt to sound-level context in, at least, the last 44 ms, but that neural sensitivity to sound-level context decreases when the time window over which acoustic stimuli need to be integrated becomes wider. Our study thus provides evidence of adaptation to sound-level context in the human brainstem and of the timescale over which sound-level information affects neural responses to sound. The research delivers an important link to studies on neural adaptation in non-human animals.
Identification of antigenic epitopes on the F and G glycoproteins of bovine respiratory syncytial virus and in vitro assessment of their synthetic peptide vaccine potential
Authors: Lemon J. , Douglas A. , Power U. , McMenamy MJ.
Published: June 2021

Globally, bovine respiratory disease (BRD) remains the principal reason for mortality of calves over one month of age despite the availability of various vaccines on the UK market. Bovine respiratory syncytial virus (BRSV) was first discovered in the 1970s and is now considered a principal pathogen implicated in the disease complex. Outbreaks occur annually and re-infections are common even in the presence of maternal antibodies. Difficulties have arisen from using both live-attenuated and inactivated vaccines and recent efforts have focused on the development of sub-unit vaccines that are suitable for use in neonatal calves with maternally-derived circulating antibodies. This study was undertaken to identify antigenic epitopes on two of the surface glycoproteins of BRSV, the fusion (F) and attachment (G) proteins, the major surface viral antigens, for inclusion into a novel subunit peptide vaccine. Sequencing and antigenicity prediction of the F and G genes of BRSV revealed 21 areas of potential antigenicity; of which genuine peptide/antisera binding occurred with 4 peptides. Identification of the antigenic components of a vaccine is an important first step in the development of novel BRSV vaccines and this data, therefore, provides the basis for the generation of such vaccines.
The developmental transcriptome of Parhyale hawaiensis: microRNAs and mRNAs show different expression dynamics during the maternal-zygotic transition
Authors: Calvo Llilians , Birgaoanu Maria , Pettini Tom , Ronshaugen Matthew , Griffiths-Jones Sam
Published: June 2021

Parhyale hawaiensis has emerged as the crustacean model of choice due to its tractability, ease of imaging, sequenced genome, and development of CRISPR/Cas9 genome editing tools. However, transcriptomic datasets spanning embryonic development are lacking, and there is almost no annotation of non-protein-coding RNAs, including microRNAs. We have sequenced microRNAs, together with mRNAs and long non-coding RNAs, in Parhyale using paired size-selected RNA-seq libraries at seven time-points covering important transitions in embryonic development. Focussing on microRNAs, we annotate 175 loci in Parhyale, 85 of which have no known homologs. We use these data to annotate the microRNome of 37 crustacean genomes, and suggest a core crustacean microRNA set of around 61 sequence families. We examine the dynamic expression of microRNAs and mRNAs during the maternal-zygotic transition. Our data suggest that zygotic genome activation occurs in two waves in Parhyale with microRNAs transcribed almost exclusively in the second wave. Contrary to findings in other arthropods, we do not predict a general role for microRNAs in clearing maternal transcripts. These data significantly expand the available transcriptomics resources for Parhyale, and facilitate its use as a model organism for the study of small RNAs in processes ranging from embryonic development to regeneration.
PV-specific loss of the transcriptional coactivator PGC-1α slows down the evolution of epileptic activity in an acute ictogenic model
Authors: Parrish R. Ryley , Mackenzie-Gray-Scott Connie , Walsh Darren , Racca Claudia , Cowell Rita M. , Trevelyan Andrew J.
Published: June 2021

The transcriptional coactivator, PGC-1α (peroxisome proliferator activated receptor gamma coactivator 1α), plays a key role coordinating energy requirement within cells. Its importance is reflected in the growing number of psychiatric and neurological conditions that have been associated with reduced PGC-1α levels. In cortical networks, PGC-1α is required for the induction of parvalbumin (PV) expression in interneurons, and PGC-1α deficiency affects synchronous GABAergic release. It is unknown, however, how this affects cortical excitability. We show here that knocking down PGC-1α specifically in the PV-expressing cells (PGC-1αPV-/-), blocks the activity-dependent regulation of the synaptic proteins, SYT2 and CPLX1. More surprisingly, this cell-class specific knock-out of PGC-1α appears to have a novel anti-epileptic effect, as assayed in brain slices bathed in 0 Mg2+ media. The rate of pre-ictal discharges developed approximately equivalently in wild-type and PGC-1αPV-/- brain slices, but the intensity of these discharges was lower in PGC-1αPV-/- slices, as evident from the reduced power in the gamma range and reduced firing rates in both PV interneurons and pyramidal cells during these discharges. Reflecting this reduced intensity in the pre-ictal discharges, the PGC-1αPV-/- brain slices experienced many more discharges before transitioning into a seizure-like event. Consequently, there was a large increase in the latency to the first seizure-like event in brain slices lacking PGC-1α in PV interneurons. We conclude that knocking down PGC-1α limits the range of PV interneuron firing, and this slows the pathophysiological escalation during ictogenesis.
Single cell multi-omics analysis of chromothriptic medulloblastoma highlights genomic and transcriptomic consequences of genome instability
Authors: Parra R. Gonzalo , Przybilla Moritz J , Simovic Milena , Susak Hana , Ratnaparkhe Manasi , Wong John KL , Körber Verena , Mallm Philipp , Sill Martin , Kolb Thorsten , Kumar Rithu , Casiraghi Nicola , Norali Ghasemi David R , Maaß Kendra Korinna , Pajtler Kristian W , Jauch Anna , Korshunov Andrey , Höfer Thomas , Zapatka Marc , Pfister Stefan M , Stegle Oliver , Ernst Aurélie
Published: June 2021

Chromothripsis is a form of genome instability, whereby a presumably single catastrophic event generates extensive genomic rearrangements of one or few chromosome(s). However, little is known about the heterogeneity of chromothripsis across different clones from the same tumor, as well as changes in response to treatment. We analyzed single-cell genomic and transcriptomic alterations linked with chromothripsis in human p53-deficient medulloblastoma (n=7). We reconstructed the order of somatic events, identified early alterations likely linked to chromothripsis and depicted the contribution of chromothripsis to malignancy. We characterized subclonal variation of chromothripsis and its effects on double-minute chromosomes, cancer drivers and putatively druggable targets. Furthermore, we highlighted the causative role and the fitness consequences of specific rearrangements in neural progenitors.

Graphical Abstract
Functional divergence of the bag of marbles gene in the Drosophila melanogaster species group
Authors: Bubnell Jaclyn E. , Ulbing Cynthia K.S. , Begne Paula Fernandez , Aquadro Charles F.
Published: June 2021

In Drosophila melanogaster, a key germline stem cell (GSC) differentiation factor, bag of marbles (bam) shows rapid bursts of amino acid fixations between sibling species D. melanogaster and D. simulans, but not in the outgroup species D. ananassae. Here, we test the null hypothesis that bam’s differentiation function is conserved between D. melanogaster and four additional Drosophila species in the melanogaster species group spanning approximately 30 million years of divergence. Surprisingly, we demonstrate that bam is not necessary for oogenesis or spermatogenesis in D. teissieri nor is bam necessary for spermatogenesis in D. ananassae. Remarkably bam function may change on a relatively short time scale. We further report tests of neutral sequence evolution at bam in additional species of Drosophila and find a positive, but not perfect, correlation between evidence for positive selection at bam and its essential role in GSC regulation and fertility for both males and females. Further characterization of bam function in more divergent lineages will be necessary to distinguish between bam’s critical gametogenesis role being newly derived in D. melanogaster, D. simulans, D. yakuba, and D. ananassae females or it being basal to the genus and subsequently lost in numerous lineages.
ETV2 primes hematoendothelial gene enhancers prior to hematoendothelial fate commitment
Authors: Steimle Jeffrey D. , Kim Chul , Nadadur Rangarajan D. , Wang Zhezhen , Hoffmann Andrew D. , Hanson Erika , Kweon Junghun , Sinha Tanvi , Choi Kyunghee , Black Brian L. , Cunningham John M. , Ikegami Kohta , Moskowitz Ivan P.
Published: June 2021

The lineage-determining transcription factor ETV2 is necessary and sufficient for hematoendothelial fate commitment. We investigated how ETV2-driven gene regulatory networks promote hematoendothelial fate commitment. We resolved the sequential determination steps of hematoendothelial versus cardiac differentiation from mouse embryonic stem cells.Etv2was strongly induced and bound to the enhancers of hematoendothelial genes in a common cardiomyocyte-hematoendothelial mesoderm progenitor. However, onlyEtv2itself andTal1, not other ETV2-bound genes, were induced. Despite ETV2 genomic binding andEtv2andTal1expression, cardiomyogenic fate potential was maintained. A second wave of ETV2-bound target genes was up-regulated during the transition from the common cardiomyocyte-hematoendothelial progenitor to the committed hematoendothelial population. A third wave of ETV-bound genes were subsequently expressed in the committed hematoendothelial population for sub-lineage differentiation. The shift from ETV2 binding to productive transcription, not ETV2 binding to target gene enhancers, drove hematoendothelial fate commitment. This work identifies mechanistic phases of ETV2-dependent gene expression that distinguish hematoendothelial specification, commitment, and differentiation.

HIGHLIGHTS

The hematoendothelial master TF ETV2 is expressed in a multipotent mesoderm progenitor.

ETV2 binds to target genes in the mesoderm progenitor without target gene activation.

ETV2 binding in the mesoderm progenitor does not diminish alternative cardiac fate potential.

ETV2-bound target genes are activated upon hematoendothelial fate commitment.

GRAPHICAL ABSTRACT
Simulation study evaluating the ability of two statistical approaches to identify variance quantitative trait loci Arabidopsis and maize
Authors: Murphy Matthew D. , Fernandes Samuel B. , Morota Gota , Lipka Alexander E.
Published: June 2021

Genomic loci that control the variance of agronomically important traits are increasingly important due to the profusion of unpredictable environments arising from climate change. The ability to identify such variance quantitative trait loci (vQTL) in association studies will be critical for future breeding efforts. Two statistical approaches that have already been used to detect vQTL are the Brown-Forsythe test (BFT) and the double generalized linear model (DGLM). To ensure that they are deployed to variance genome-wide association studies as effectively as possible, it is critical to study the factors that influence their ability to identify vQTL. We used genome-wide marker data in maize (Zea maysL.) andArabidopsis thalianato simulate traits controlled by variance quantitative trait nucleotides (vQTNs) and then quantified true and false positive detection rates of the BFT and DGLM. We observed that the DGLM yielded similar or higher true positive vQTN detection rates than the BFT, regardless of the effect size or minor allele frequency (MAF) of the vQTNs. Low true positive detection rates were noted for QTNs with low MAFs (~0.10), especially when tested on subsets ofn= 500 individuals. We recommend that larger data sets than those used in our study (i.e.,n> 2,532) be considered to overcome these low observed true positive detection rates. Such an undertaking should maximize the potential of the BFT and DGLM to highlight which vQTLs should be considered for further study.