Publications by authors named "Michael Weber"

1,070 Publications

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Low muscle volume of the anal sphincter complex: A novel prognostic factor in children with anorectal malformations?

J Pediatr Surg 2021 Oct 29. Epub 2021 Oct 29.

Division of Pediatric Surgery, Department of Surgery, Medical University of Vienna, MUV, Austria.

Background/purpose: The anal sphincter complex (ASC) plays a key role in continence and is often dysfunctional in infants born with anorectal malformations (ARM). The ASC is well depicted by magnetic resonance (MR) imaging but volumetric reference data are lacking in infants. Thus, we tested the feasibility of MR based ASC volumetry, collected reference data, and compared them with cases of favorableprognosis and unfavorable prognosis (as defined by the type of ARM).

Methods: We determined ASC volume on T2 weighted MR images of seventy six infants (ARM n = 33; controls n = 43) by manual segmentation. Inter operator agreement was assessed by intraclass correlation coefficient. Linear regression was used to establish weight dependent reference data. Observed to expected ASC volumes of patients with unfavorable and favorable prognosis were compared (unpaired t test).

Results: ASC volumetry was feasible in all cases. Patients with ARM had low 'observed to expected' ASC volume ( 18.1%; p = 0.006). 'Observed to expected' ASC volume differed significantly between patients with favorableand unfavorable prognosis (p < 0.001).

Conclusion: We confirmed the feasibility of MRI based ASC volumetry and provided initial reference data for infants. Although ASC volumes were lowest in infants with ARM of unfavorable prognosis for fecal continence, the value of ASC volume as prognostic parameter remains to be determined.
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http://dx.doi.org/10.1016/j.jpedsurg.2021.10.017DOI Listing
October 2021

Decadal-scale onset and termination of Antarctic ice-mass loss during the last deglaciation.

Nat Commun 2021 Nov 18;12(1):6683. Epub 2021 Nov 18.

Earth and Sustainability Science Research Centre, School of Biological Earth and Environmental Sciences, University of New South Wales, Sydney, NSW, Australia.

Emerging ice-sheet modeling suggests once initiated, retreat of the Antarctic Ice Sheet (AIS) can continue for centuries. Unfortunately, the short observational record cannot resolve the tipping points, rate of change, and timescale of responses. Iceberg-rafted debris data from Iceberg Alley identify eight retreat phases after the Last Glacial Maximum that each destabilized the AIS within a decade, contributing to global sea-level rise for centuries to a millennium, which subsequently re-stabilized equally rapidly. This dynamic response of the AIS is supported by (i) a West Antarctic blue ice record of ice-elevation drawdown >600 m during three such retreat events related to globally recognized deglacial meltwater pulses, (ii) step-wise retreat up to 400 km across the Ross Sea shelf, (iii) independent ice sheet modeling, and (iv) tipping point analysis. Our findings are consistent with a growing body of evidence suggesting the recent acceleration of AIS mass loss may mark the beginning of a prolonged period of ice sheet retreat and substantial global sea level rise.
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http://dx.doi.org/10.1038/s41467-021-27053-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602255PMC
November 2021

Are humanized IgE reporter systems potential game changers in serological diagnosis of human parasitic infection?

Parasitol Res 2021 Nov 12. Epub 2021 Nov 12.

Biomedical Research Centre Seltersberg (BFS), Institute for Parasitology, Justus Liebig University Giessen, Giessen, Germany.

Immunoglobulin E (IgE) is thought to have evolved to protect mammalian hosts against parasitic infections or toxins and plays a central role in the pathogenesis, diagnosis, and therapy of IgE-mediated allergy. Despite the prominence of IgE responses in most parasitic infections, and in stark contrast to its use in the diagnosis of allergy, this isotype is almost completely unexploited for parasite diagnosis. Here, we discuss the perceived or real limitations of IgE-based diagnosis in parasitology and suggest that the recent creation of a new generation of very sensitive cellular IgE-based reporters may represent a powerful new diagnostic platform, but needs to be based on a very careful choice of diagnostic allergens.
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http://dx.doi.org/10.1007/s00436-021-07352-zDOI Listing
November 2021

Multidisciplinarity Is Critical to Unlock the Full Potential of Modern Light Microscopy.

Front Cell Dev Biol 2021 21;9:739015. Epub 2021 Oct 21.

Morgridge Institute for Research, Madison, WI, United States.

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http://dx.doi.org/10.3389/fcell.2021.739015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567166PMC
October 2021

Photoactivatable Fluorescent Dyes with Hydrophilic Caging Groups and Their Use in Multicolor Nanoscopy.

J Am Chem Soc 2021 Nov 29;143(44):18388-18393. Epub 2021 Oct 29.

Department of Optical Nanoscopy, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.

We propose a series of fluorescent dyes with hydrophilic carbamate caging groups that undergo rapid photoactivation under UV (≤400 nm) irradiation but do not undergo spurious two-photon activation with high-intensity (visible or infrared) light of about twice the wavelength. The caged fluorescent dyes and labels derived therefrom display high water solubility and convert upon photoactivation into validated super-resolution and live-cell-compatible fluorophores. In combination with popular fluorescent markers, multiple (up to six)-color images can be obtained with stimulated emission depletion nanoscopy. Moreover, individual fluorophores can be localized with precision <3 nm (standard deviation) using MINSTED and MINFLUX techniques.
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http://dx.doi.org/10.1021/jacs.1c09999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587603PMC
November 2021

Effects of vibegron on ambulatory blood pressure in patients with overactive bladder: results from a double-blind, placebo-controlled trial.

Blood Press Monit 2021 Oct 25. Epub 2021 Oct 25.

State University of New York Downstate College of Medicine, Brooklyn, New York, USA Urovant Sciences, Irvine, California, USA Apex Biostatistics, Inc, Apex, North Carolina, USA Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, Connecticut, USA.

Objectives: To characterize the blood pressure (BP) profile of the new β3-adrenergic receptor agonist, vibegron, in patients with overactive bladder.

Methods: Patients were randomized to once-daily vibegron 75 mg or placebo for 28 days and underwent ambulatory BP monitoring. The primary endpoint was change from baseline (CFB) to day 28 in mean daytime ambulatory systolic BP (SBP). Secondary endpoints were CFB in mean 24-h SBP and in mean daytime and mean 24-h ambulatory diastolic BP (DBP) and heart rate (HR). Safety was assessed through adverse event reporting.

Results: Of 214 patients randomized, 96 receiving vibegron and 101 receiving placebo had evaluable baseline and day 28 measurements. Overall, 39.6 and 30.7% of patients receiving vibegron and placebo, respectively, had preexisting hypertension. The least squares mean difference (LSMD; 90% confidence interval) between vibegron and placebo in CFB in mean daytime SBP was 0.8 (-0.9, 2.5) mmHg. LSMD in CFB in mean daytime DBP and HR was 0.0 mmHg and 0.9 bpm, respectively. No significant differences between treatments were seen in CFB in mean 24-h SBP (LSMD, 0.6 mmHg), DBP (-0.2 mmHg) or HR (1.0 bpm). The most common treatment-emergent adverse event was hypertension, with rates comparable between groups [vibegron: n = 5 (4.7%); placebo: n = 4 (3.7%)]. One patient receiving vibegron took a prohibited medication (phentermine) known to increase BP.

Conclusions: Once-daily vibegron had no statistically significant or clinically relevant effects on BP or HR.
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http://dx.doi.org/10.1097/MBP.0000000000000572DOI Listing
October 2021

Temporal muscle thickness as a prognostic marker in newly diagnosed glioblastoma patients: translational imaging analysis of the CENTRIC EORTC 26071-22072 and CORE trials.

Clin Cancer Res 2021 Oct 19. Epub 2021 Oct 19.

Department of Internal Medicine 1, Medical University of Vienna

Purpose: To investigate the prognostic relevance of temporal muscle thickness (TMT) as a surrogate parameter of skeletal muscle status in patients with newly diagnosed glioblastoma.

Methods: We assessed TMT in cranial magnetic resonance images (MRI) of 755 patients enrolled in the CENTRIC EORTC 26071-22072 study (n=508) and CORE study (n=247). We used predefined sex-specific TMT cutoff values to categorize "patients at risk of sarcopenia" and "patients with normal muscle status" at baseline. Furthermore, we categorized patients according to the extent of TMT loss over time. Associations with progression-free survival (PFS) and overall survival (OS) were evaluated using the Cox model adjusted for other exploratory variables.

Results: Patients at risk of sarcopenia (CENTRIC; n=158/508, 31.1%; CORE; n=87/247, 35.2%) at baseline had significantly higher risk of progression and death than patients with normal muscle status in both study cohorts (CENTRIC: PFS=HR 0.16, 95% CI: 0.12, 0.21, p<0.001; OS=HR 0.341, 95% CI: 0.27, 0.44, p < 0.001; CORE: PFS=HR 0.29, 95% CI: 0.21, 0.39, p<0.001; OS=HR 0.365, 95% CI: 0.27, 0.49, p<0.001). Similar results were obtained in multivariate Cox models adjusted for other important prognostic parameters. The extent of TMT loss over time showed a significant inverse correlation with median OS times in patients at risk for sarcopenia (CENTRIC: p<0.001, CORE: p=0.005), but not in patients with normal baseline muscle mass (CENTRIC: p=0.538, CORE: p=0.28).

Conclusion: TMT identifies ambulatory patients with newly diagnosed glioblastoma at risk for progressive sarcopenia and adverse outcomes. Early intervention may prevent skeletal muscle loss and improve patient outcome.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-1987DOI Listing
October 2021

Clinical Early-Onset Sepsis Is Equally Valid to Culture-Proven Sepsis in Predicting Outcome in Infants after Preterm Rupture of Membranes.

J Clin Med 2021 Sep 30;10(19). Epub 2021 Sep 30.

Department of Obstetrics and Gynecology, Medical University of Vienna, 1090 Vienna, Austria.

Background: Culture-proven sepsis is the gold standard in early-onset neonatal sepsis diagnosis. Infants born ≤29 weeks gestation after preterm rupture of membranes in the years 2009-2015 were included in a retrospective cohort study performed at a level III fetal-maternal unit. The study aimed to compare culture-proven sepsis, clinical sepsis and positive laboratory biomarkers ≤72 h as predictors of mortality before discharge and the combined outcome of mortality or severe short-term morbidity (severe cerebral morbidity, bronchopulmonary dysplasia and retinopathy).

Results: Of the 354 patients included, culture-proven sepsis, clinical sepsis and laboratory biomarkers were positive in 2.3%, 8.5% and 9.6%, respectively. The mortality rate was 37.5% for patients with culture-proven sepsis (3/8), 33.3% for patients with clinical sepsis (10/30) and 8.8% for patients with positive laboratory biomarkers (3/34), respectively. Mortality or severe morbidity occurred in 75.0% of patients with culture-proven sepsis (6/8), 80.0% of patients with clinical sepsis (24/30) and 44.1% of patients with positive laboratory biomarkers (15/34), respectively.

Conclusion: In preterm infants after preterm rupture of membranes, clinical sepsis was almost four times more common and at least equally valuable in predicting mortality and mortality or severe morbidity compared to culture-proven sepsis.
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http://dx.doi.org/10.3390/jcm10194539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509355PMC
September 2021

Measurement of Blood Pressure in Clinical Practice.

Am J Med Sci 2021 Oct 7. Epub 2021 Oct 7.

Division of Translational Neurosciences and Population Studies, Department of Neurology, Medical University of South Carolina, Charleston, SC, USA.

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http://dx.doi.org/10.1016/j.amjms.2021.09.010DOI Listing
October 2021

The meningioma surface factor: a novel approach to quantify shape irregularity on preoperative imaging and its correlation with WHO grade.

J Neurosurg 2021 Oct 8:1-7. Epub 2021 Oct 8.

1Department of Neurosurgery, University Hospital St. Poelten, Karl Landsteiner University of Health Sciences, Krems.

Objective: Atypical and anaplastic meningiomas account for 20% of all meningiomas. An irregular tumor shape on preoperative MRI has been associated with WHO grade II-III histology. However, this subjective allocation does not allow quantification or comparison. An objective parameter of irregularity could substantially influence resection strategy toward a more aggressive approach. Therefore, the aim of this study was to objectively quantify the level of irregularity on preoperative MRI and predict histology based on WHO grade using this novel approach.

Methods: A retrospective study on meningiomas resected between January 2010 and December 2018 was conducted at two neurosurgical centers. This novel approach relies on the theory that a regularly shaped tumor has a smaller surface area than an irregularly shaped tumor with the same volume. A factor was generated using the surface area of a corresponding sphere as a reference, because for a given volume a sphere represents the shape with the smallest surface area possible. Consequently, the surface factor (SF) was calculated by dividing the surface area of a sphere with the same volume as the tumor with the surface area of the tumor. The resulting value of the SF ranges from > 0 to 1. Finally, the SF of each meningioma was then correlated with the corresponding histopathological grading.

Results: A total of 126 patients were included in this study; 60.3% had a WHO grade I, 34.9% a WHO grade II, and 4.8% a WHO grade III meningioma. Calculation of the SF demonstrated a significant difference in SFs between WHO grade I (SF 0.851) and WHO grade II-III meningiomas (SF 0.788) (p < 0.001). Multivariate analysis identified SF as an independent prognostic factor for WHO grade (OR 0.000009, 95% CI 0.000-0.159; p = 0.020).

Conclusions: The SF is a proposed mathematical model for a quantitative and objective measurement of meningioma shape, instead of the present subjective assessment. This study revealed significant differences between the SFs of WHO grade I and WHO grade II-III meningiomas and demonstrated that SF is an independent prognostic factor for WHO grade.
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http://dx.doi.org/10.3171/2021.5.JNS204223DOI Listing
October 2021

Renal and Salivary Gland Functions after Three Cycles of PSMA-617 Therapy Every Four Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer.

Curr Oncol 2021 09 23;28(5):3692-3704. Epub 2021 Sep 23.

Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, 1090 Vienna, Austria.

Background: [Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT) could affect kidney and salivary gland functions in metastatic castration-resistant prostate cancer (mCRPC) patients.

Methods: We retrospectively analyzed clinical, renal, and salivary scintigraphy data and salivary [Ga]Ga-PSMA-11 ligand PET scan measures such as metabolic volume and SUVmax values of 27 mCRPC men (mean age 71 ± 7 years) before and 4 weeks after receiving three cycles of PSMA-RLT every 4 weeks. Twenty-two patients additionally obtained renal and salivary scintigraphy prior to each cycle. A one-way ANOVA, post-hoc Scheffé test and Cochran's Q test were applied to assess organ toxicity.

Results: In total, 54 PSMA PET scans, 98 kidney, and 98 salivary scintigraphy results were evaluated. There were no significant differences for the ejection fraction, peak time, and residual activity after 5 min for both parotid and submandibular glands prior to each cycle and 4 weeks after the last cycle. Similarly, no significant differences in serum creatinine and renal scintigraphy parameters were observed prior to each cycle and 4 weeks after the last treatment. Despite there being no changes in the metabolic volume of both submandibular glands, SUVmax values dropped significantly ( < 0.05).

Conclusion: Results evidenced no alterations in renal function and only minimal impairment of salivary function of mCRPC patients who acquired an intense PSMA-RLT regimen every 4 weeks.
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http://dx.doi.org/10.3390/curroncol28050315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482282PMC
September 2021

SmartCards as Analogous Tools to Operate Tablet Computers for Elderly-A Feasibility Study.

Healthcare (Basel) 2021 Sep 10;9(9). Epub 2021 Sep 10.

Institute of Psychology, Martin Luther University Halle-Wittenberg, Social Psychology, 06099 Halle (Saale), Germany.

Background: Older adults sometimes shy away from using modern digital communication devices due to lacking experience and fear of failure. Within the present project, SmartCards were developed as analogous means to operate tablet computers for older adults with little previous computer experience. We investigated whether the SmartCards-Tablet-System would (a) increase use of digital communication and (b) affect loneliness, autonomy, cognitive ability and wellbeing of the users.

Methods: The suitability and acceptance of the system was evaluated during a three month trial period with seniors in retirement homes, seniors with home assistance care and a waiting control group.

Results: Acceptance, duration of use and frequency of use were high in both experimental groups. Cognitive ability significantly improved after three months' use in both experimental groups. Effects on loneliness, autonomy and wellbeing could not be observed.

Discussion: Our results indicate that seniors are very much able and curious to use modern digital devices if the interface and hardware are adjusted to their needs and capabilities without being stigmatizing. The use of modern communication services and the World Wide Web can promote contact of seniors with their (younger) relatives.
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http://dx.doi.org/10.3390/healthcare9091198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466033PMC
September 2021

Time to return to work after elective lumbar spine surgery.

J Neurosurg Spine 2021 Sep 24:1-9. Epub 2021 Sep 24.

1Combined Neurosurgical and Orthopedic Spine Service, Department of Orthopedic Surgery, University of British Columbia, Vancouver, British Columbia.

Objective: Time to return to work (RTW) after elective lumbar spine surgery is variable and dependent on many factors including patient, work-related, and surgical factors. The primary objective of this study was to describe the time and rate of RTW after elective lumbar spine surgery. Secondary objectives were to determine predictors of early RTW (< 90 days) and no RTW in this population.

Methods: A retrospective analysis of prospectively collected data from the multicenter Canadian Spine Outcomes and Research Network (CSORN) surgical registry was performed to identify patients who were employed and underwent elective 1- or 2-level discectomy, laminectomy, and/or fusion procedures between January 2015 and December 2019. The percentage of patients who returned to work and the time to RTW postoperatively were calculated. Predictors of early RTW and not returning to work were determined using a multivariable Cox regression model and a multivariable logistic regression model, respectively.

Results: Of the 1805 employed patients included in this analysis, 71% returned to work at a median of 61 days. The median RTW after a discectomy, laminectomy, or fusion procedure was 51, 46, and 90 days, respectively. Predictors of early RTW included male gender, higher education level (high school or above), higher preoperative Physical Component Summary score, working preoperatively, a nonfusion procedure, and surgery in a western Canadian province (p < 0.05). Patients who were working preoperatively were twice as likely to RTW within 90 days (HR 1.984, 95% CI 1.680-2.344, p < 0.001) than those who were employed but not working. Predictors of not returning to work included symptoms lasting more than 2 years, an increased number of comorbidities, an education level below high school, and an active workers' compensation claim (p < 0.05). There were fourfold odds of not returning to work for patients who had not been working preoperatively (OR 4.076, 95% CI 3.087-5.383, p < 0.001).

Conclusions: In the Canadian population, 71% of a preoperatively employed segment returned to work after 1- or 2-level lumbar spine surgery. Most patients who undergo a nonfusion procedure RTW after 6 to 8 weeks, whereas patients undergoing a fusion procedure RTW at 12 weeks. Working preoperatively significantly increased the likelihood of early RTW.
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http://dx.doi.org/10.3171/2021.2.SPINE202051DOI Listing
September 2021

CXCR4 PET/MRI for follow-up of gastric mucosa-associated lymphoid tissue lymphoma after first-line H. pylori eradication.

Blood 2021 Sep 15. Epub 2021 Sep 15.

Medical University of Vienna, Vienna, Austria.

Post-treatment evaluation of gastric mucosa-associated lymphoid tissue (MALT) lymphoma currently relies on esophagogastroduodenoscopy with histological assessment of biopsies. Overexpression of the G-protein-coupled C-X-C chemokine receptor type 4 (CXCR4) has been previously observed in MALT lymphoma. The aim of this prospective study was to evaluate PET with the novel CXCR4 tracer [68Ga]Pentixafor as a potential alternative to follow-up biopsies for assessment of residual disease (non-complete remission (CR)) after first-line H. pylori (HP) eradication. Forty-six post-HP eradication [68Ga]Pentixafor-PET/MRI examinations of 26 gastric MALT lymphoma patients, and 20 [68Ga]Pentixafor-PET/MRI examinations of 20 control group patients without lymphoma, were analyzed. In the MALT lymphoma group, time-matched gastric biopsies were used as reference standard, and showed CR in six cases. Pooled examination-based accuracy, sensitivity, specificity, and positive and negative predictive value of [68Ga]Pentixafor-PET for detection of residual gastric MALT lymphoma at follow-up, were 97.0%, 95.0%, 100.0%, 100.0%, and 92.9%, respectively. Maximum and mean PET standardized uptake values showed moderate correlation with immunohistochemistry-based CXCR4+ cell counts, with correlation coefficients of r=0.51 and r=0.52 (P=0.008 and P=0.006). In conclusion, CXCR4 imaging with [68Ga]Pentixafor-PET may represent a promising test for assessment of residual gastric MALT lymphomas after HP eradication.
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http://dx.doi.org/10.1182/blood.2021013239DOI Listing
September 2021

Effect of Heart Rate on the Outcome of Renal Denervation in Patients With Uncontrolled Hypertension.

J Am Coll Cardiol 2021 Sep;78(10):1028-1038

Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg/Saar, Germany. Electronic address: https://twitter.com/FelixMahfoud.

Background: Sham-controlled trials demonstrated safety and efficacy of renal denervation (RDN) to lower blood pressure (BP). Association of baseline heart rate with BP reduction after RDN is incompletely understood.

Objectives: The purpose of this analysis was to evaluate the impact of baseline heart rate on BP reduction without antihypertensive medications in the SPYRAL HTN-OFF MED (Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications) Pivotal trial.

Methods: Patients removed from any antihypertensive medications were enrolled with office systolic blood pressure (SBP) ≥150 and <180 mm Hg and randomized 1:1 to RDN or sham control. Patients were separated according to baseline office heart rate <70 or ≥70 beats/min. BP changes from baseline to 3 months between treatment arms were adjusted for baseline SBP using analysis of covariance.

Results: Scatter plots of 3-month changes in 24-hour and office SBP illustrate a wide range of changes in SBP for different baseline heart rates. Treatment difference at 3 months between RDN and sham control with baseline office heart rate ≥70 beats/min for 24-hour SBP was -6.2 mm Hg (95% CI: -9.0 to -3.5 mm Hg) (P < 0.001) and for baseline office heart rate <70 beats/min it was -0.1 mm Hg (-3.8 to 3.6 mm Hg) (P = 0.97) with an interaction P value of 0.008. Results were similar for changes in office, daytime, and nighttime SBP at 3 months, with a greater reduction in SBP with baseline office heart rate ≥70 beats/min.

Conclusions: Reduction in mean office, 24-hour, daytime, and nighttime SBP for RDN at 3 months was greater with baseline office heart rate ≥70 than <70 beats/min, suggesting an association between baseline heart rate and BP reduction after RDN. (SPYRAL PIVOTAL-SPYRAL HTN-OFF MED Study; NCT02439749).
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http://dx.doi.org/10.1016/j.jacc.2021.06.044DOI Listing
September 2021

Long-Term Results up to 12 Months After Catheter-Based Alcohol-Mediated Renal Denervation for Treatment of Resistant Hypertension.

Circ Cardiovasc Interv 2021 09 2;14(9):e010075. Epub 2021 Sep 2.

Division of Cardiology, Department of Cardiovascular Diseases, Cliniques Universitaires Saint-Luc and Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium (J.-P.L., A.P.).

[Figure: see text].
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.010075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452324PMC
September 2021

Minimally Invasive vs. Open Surgery for Lumbar Spinal Stenosis in Patients with Diabetes - A Canadian Spine Outcomes and Research Network Study.

Global Spine J 2021 Aug 31:21925682211042576. Epub 2021 Aug 31.

Canada East Spine Centre, Saint John, NB, Canada.

Study Design: Retrospective cohort.

Objectives: To compare outcomes of minimally invasive surgery (MIS) vs open surgery (OPEN) for lumbar spinal stenosis (LSS) in patients with diabetes.

Methods: Patients with diabetes who underwent spinal decompression alone or with fusion for LSS within the Canadian Spine Outcomes and Research Network (CSORN) database were included. MIS vs OPEN outcomes were compared for 2 cohorts: (1) patients with diabetes who underwent decompression alone (N = 116; MIS n = 58 and OPEN n = 58), (2) patients with diabetes who underwent decompression with fusion (N = 108; MIS n = 54 and OPEN n = 54). Modified Oswestry Disability Index (mODI) and back and leg pain were compared at baseline, 6-18 weeks, and 1-year post-operation. The number of patients meeting minimum clinically important difference (MCID) or minimum pain/disability at 1-year was compared.

Results: MIS approaches had less blood loss (decompression alone difference 100 mL, = .002; with fusion difference 244 mL, < .001) and shorter length of stay (LOS) (decompression alone difference 1.2 days, = .008; with fusion difference 1.2 days, = .026). MIS compared to OPEN decompression with fusion had less patients experiencing adverse events (AEs) (difference 13 patients, = .007). The MIS decompression with fusion group had lower 1-year mODI (difference 14.5, 95% CI [7.5, 21.0], < .001) and back pain (difference 1.6, 95% CI [.6, 2.7], = .002) compared to OPEN. More patients in the MIS decompression with fusion group exceeded MCID at 1-year for mODI (MIS 75.9% vs OPEN 53.7%, = .028) and back pain (MIS 85.2% vs OPEN 70.4%, = .017).

Conclusions: MIS approaches were associated with more favorable outcomes for patients with diabetes undergoing decompression with fusion for LSS.
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http://dx.doi.org/10.1177/21925682211042576DOI Listing
August 2021

Light Sheet Microscopy of Fast Cardiac Dynamics in Zebrafish Embryos.

J Vis Exp 2021 08 13(174). Epub 2021 Aug 13.

Morgridge Institute for Research, Madison, WI.

Embryonic cardiac research has greatly benefited from advances in fast in vivo light sheet fluorescence microscopy (LSFM). Combined with the rapid external development, tractable genetics, and translucency of the zebrafish, Danio rerio, LSFM has delivered insights into cardiac form and function at high spatial and temporal resolution without significant phototoxicity or photobleaching. Imaging of beating hearts challenges existing sample preparation and microscopy techniques. One needs to maintain a healthy sample in a constricted field of view and acquire ultrafast images to resolve the heartbeat. Here we describe optimized tools and solutions to study the zebrafish heart in vivo. We demonstrate the applications of bright transgenic lines for labeling the cardiac constituents and present novel gentle embedding and immobilization techniques that avoid developmental defects and changes in heart rate. We also propose a data acquisition and analysis pipeline adapted to cardiac imaging. The entire workflow presented here focuses on zebrafish embryonic heart imaging but can also be applied to various other samples and experiments.
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http://dx.doi.org/10.3791/62741DOI Listing
August 2021

Extrinsic interactions in the microenvironment in vivo activate an antiapoptotic multidrug-resistant phenotype in CLL.

Blood Adv 2021 09;5(17):3497-3510

Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA.

The Bcl-2 inhibitor venetoclax has yielded exceptional clinical responses in chronic lymphocytic leukemia (CLL). However, de novo resistance can result in failure to achieve negative minimal residual disease and predicts poor treatment outcomes. Consequently, additional proapoptotic drugs, such as inhibitors of Mcl-1 and Bcl-xL, are in development. By profiling antiapoptotic proteins using flow cytometry, we find that leukemic B cells that recently emigrated from the lymph node (CD69+/CXCR4Low) in vivo are enriched for cell clusters simultaneously overexpressing multiple antiapoptotic proteins (Mcl-1High/Bcl-xLHigh/Bcl-2High) in both treated and treatment-naive CLL patients. These cells exhibited antiapoptotic resistance to multiple BH-domain antagonists, including inhibitors of Bcl-2, Mcl-1, and Bcl-xL, when tested as single agents in a flow cytometry-based functional assay. Antiapoptotic multidrug resistance declines ex vivo, consistent with resistance being generated in vivo by extrinsic microenvironmental interactions. Surviving "persister" cells in patients undergoing venetoclax treatment are enriched for CLL cells displaying the functional and molecular properties of microenvironmentally induced multidrug resistance. Overcoming this resistance required simultaneous inhibition of multiple antiapoptotic proteins, with potential for unwanted toxicities. Using a drug screen performed using patient peripheral blood mononuclear cells cultured in an ex vivo microenvironment model, we identify novel venetoclax drug combinations that induce selective cytotoxicity in multidrug-resistant CLL cells. Thus, we demonstrate that antiapoptotic multidrug-resistant CLL cells exist in patients de novo and show that these cells persist during proapoptotic treatment, such as venetoclax. We validate clinically actionable approaches to selectively deplete this reservoir in patients.
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http://dx.doi.org/10.1182/bloodadvances.2020003944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525241PMC
September 2021

High-resolution ultrasound demonstrates in vivo effects of wrist movement on the median nerve along the forearm.

Muscle Nerve 2021 Nov 1;64(5):585-589. Epub 2021 Sep 1.

Neuromuscular Imaging and High-Resolution Sonography, Neuromuscular Imaging Vienna, Vienna, Austria.

Introduction/aims: High-resolution ultrasound (HRUS) is the imaging method of choice to visualize peripheral nerve size, structure, and biomechanical performance. The purpose of this study was to show and quantify the effects of active and passive wrist alignment on median nerve (MN) cross-sectional area (CSA) along the forearm in a healthy population.

Methods: Sixteen healthy volunteers underwent HRUS of their dominant forearm (n = 16, 10 males, 6 females, 18-55 y of age). Median nerve's CSA was assessed at four defined areas on the forearm in relation to active and passive wrist alignment.

Results: Changes in wrist alignment were significantly associated with MN CSA (P < .001), regardless if the wrist was moved actively or passively. MN CSA was lowest during passive extension of the wrist joint and highest during passive flexion of the wrist joint (range: 4.5-23.2 mm ).

Discussion: The elasticity of nerve tissue, the loose connective tissue between the fascicles, and the paraneurium allow peripheral nerves to adapt to longitudinal strain. HRUS enables the demonstration of significant median nerve CSA changes along the forearm during active and passive wrist movement in healthy volunteers.
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http://dx.doi.org/10.1002/mus.27403DOI Listing
November 2021

National adverse event profile after lumbar spine surgery for lumbar degenerative disorders and comparison of complication rates between hospitals: a CSORN registry study.

J Neurosurg Spine 2021 Aug 20:1-6. Epub 2021 Aug 20.

1Department of Surgery, Vancouver General Hospital/University of British Columbia, Vancouver, British Columbia.

Objective: Previous works investigating rates of adverse events (AEs) in spine surgery have been retrospective, with data collection from administrative databases, and often from single centers. To date, there have been no prospective reports capturing AEs in spine surgery on a national level, with comparison among centers.

Methods: The Spine Adverse Events Severity system was used to define the incidence and severity of AEs after spine surgery by using data from the Canadian Spine Outcomes and Research Network (CSORN) prospective registry. Patient data were collected prospectively and during hospital admission for those undergoing elective spine surgery for degenerative conditions. The Spine Adverse Events Severity system defined minor and major AEs as grades 1-2 and 3-6, respectively.

Results: There were 3533 patients enrolled in this cohort. There were 85 (2.4%) individual patients with at least one major AE and 680 (19.2%) individual patients with at least one minor AE. There were 25 individual patients with 28 major intraoperative AEs and 260 patients with 275 minor intraoperative AEs. Postoperatively there were 61 patients with a total of 80 major AEs. Of the 487 patients with minor AEs postoperatively there were 698 total AEs. The average enrollment was 321 patients (range 47-1237 patients) per site. The rate of major AEs was consistent among sites (mean 2.9% ± 2.4%, range 0%-9.1%). However, the rate of minor AEs varied widely among sites-from 7.9% to 42.5%, with a mean of 18.8% ± 9.7%. The rate of minor AEs varied depending on how they were reported, with surgeon reporting associated with the lowest rates (p < 0.01).

Conclusions: The rate of major AEs after lumbar spine surgery is consistent among different sites but the rate of minor AEs appears to vary substantially. The method by which AEs are reported impacts the rate of minor AEs. These data have implications for the detection and reporting of AEs and the design of strategies aimed at mitigating complications.
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http://dx.doi.org/10.3171/2021.2.SPINE202150DOI Listing
August 2021

The World Hypertension League becomes a partner of the Journal of Human Hypertension.

J Hum Hypertens 2021 09;35(9):821-822

Professor of Medicine, Downstate Medical Center, State University of New York, Brooklyn, NY, USA.

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http://dx.doi.org/10.1038/s41371-021-00581-wDOI Listing
September 2021

Evaluation of the 'H2NOE Water Schools' programme to promote water consumption in elementary schoolchildren: a non-randomised controlled cluster trial.

Public Health Nutr 2021 Aug 13:1-11. Epub 2021 Aug 13.

Department for Evidence-based Medicine and Evaluation, Danube University Krems, Dr. Karl-Dorrek-Straße 30, 3500Krems, Austria.

Objective: This study evaluated a simple environmental intervention called 'Water Schools' in Lower Austria providing free refillable water bottles and educational material.

Design: Non-randomised controlled cluster trial with three measurements: at baseline (T0), after the intervention at 9 months (T1) and after 1-year follow-up (T2).

Setting: Half-day elementary schools in Lower Austria (Austria).

Participants: Third-grade pupils from twenty-two schools in the intervention group (IG) and thirty-two schools in the control group (CG) participated in the study. Data were analysed for 569 to 598 pupils in the IG and for 545 to 613 in the CG, depending on the time of measurement.

Results: The consumption of tap water increased in the IG from baseline to T1 and then decreased again at T2, but this was similar in the CG (no statistically significant difference in the time trend between the IG and CG). Similar results were seen for tap water consumption in the mornings. The proportion of children who only drank tap water on school mornings increased significantly from baseline to T1 in the IG compared to the CG (P = 0·020). No difference in the changes over time occurred between the groups for the proportion of pupils drinking approximately one bottle of tap water during school mornings.

Conclusions: Not only the children in the IG but also those in the CG drank more tap water after 1 school year than at the beginning. The measurement of drinking habits in the CG may have been intervention enough to bring about changes or to initiate projects.
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http://dx.doi.org/10.1017/S1368980021003438DOI Listing
August 2021

Competition for light induces metal accumulation in a metal hyperaccumulating plant.

Oecologia 2021 Sep 9;197(1):157-165. Epub 2021 Aug 9.

Institute of Evolution and Ecology, University of Tübingen, Tübingen, Germany.

Plants can respond to competition with a myriad of physiological or morphological changes. Competition has also been shown to affect the foraging decisions of plants belowground. However, a completely unexplored idea is that competition might also affect plants' foraging for specific elements required to inhibit the growth of their competitors. In this study, we examined the effect of simulated competition on root foraging and accumulation of heavy metals in the metal hyperaccumulating perennial plant Arabidopsis halleri, whose metal accumulation has been shown to provide allelopathic ability. A. halleri plants originating from both metalliferous and non-metalliferous soils were grown in a "split-root" setup with one root in a high-metal pot and the other in a low-metal one. The plants were then assigned to either simulated light competition or no-competition (control) treatments, using vertical green or clear plastic filters, respectively. While simulated light competition did not induce greater root allocation into the high-metal pots, it did result in enhanced metal accumulation by A. halleri, particularly in the less metal-tolerant plants, originating from non-metalliferous soils. Interestingly, this accumulation response was particularly enhanced for zinc rather than cadmium. These results provide support to the idea that the accumulation of metals by hyperaccumulating plants can be facultative and change according to their demand following competition.
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http://dx.doi.org/10.1007/s00442-021-05001-xDOI Listing
September 2021

One view or two views for wide-angle tomosynthesis with synthetic mammography in the assessment setting?

Eur Radiol 2021 Jul 29. Epub 2021 Jul 29.

Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna/General Hospital Vienna, Waehringer Guertel 18-20, Vienna, Austria.

Objectives: To evaluate the diagnostic performance in the assessment setting of three protocols: one-view wide-angle digital breast tomosynthesis (WA-DBT) with synthetic mammography (SM), two-view WA-DBT/SM, and two-view digital mammography (DM).

Methods: Included in this retrospective study were patients who underwent bilateral two-view DM and WA-DBT. SM were reconstructed from the WA-DBT data. The standard of reference was histology and/or 2 years follow-up. Included were 205 women with 179 lesions (89 malignant, 90 benign). Four blinded readers randomly evaluated images to assess density, lesion type, and level of suspicion according to BI-RADS. Three protocols were evaluated: two-view DM, one-view (mediolateral oblique) WA-DBT/SM, and two-view WA-DBT/SM. Detection rate, sensitivity, specificity, and accuracy were calculated and compared using multivariate analysis. Reading time was assessed.

Results: The detection rate was higher with two-view WA-DBT/SM (p = 0.063). Sensitivity was higher for two-view WA-DBT/SM compared to two-view DM (p = 0.001) and one-view WA-DBT/SM (p = 0.058). No significant differences in specificity were found. Accuracy was higher with both one-view WA-DBT/SM and two-view WA-DBT/SM compared to DM (p = 0.003 and > 0.001, respectively). Accuracy did not differ between one- and two-view WA-DBT/SM. Two-view WA-DBT/SM performed better for masses and asymmetries. Reading times were significantly longer when WA-DBT was evaluated.

Conclusions: One-view and two-view WA-DBT/SM can achieve a higher diagnostic performance compared to two-view DM. The detection rate and sensitivity were highest with two-view WA-DBT/SM. Two-view WA-DBT/SM appears to be the most appropriate tool for the assessment of breast lesions.

Key Points: • Detection rate with two-view wide-angle digital breast tomosynthesis (WA-DBT) is significantly higher than with two-view digital mammography in the assessment setting. • Diagnostic accuracy of one-view and two-view WA-DBT with synthetic mammography (SM) in the assessment setting is higher than that of two-view digital mammography. • Compared to one-view WA-DBT with SM, two-view WA-DBT with SM seems to be the most appropriate tool for the assessment of breast lesions.
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http://dx.doi.org/10.1007/s00330-021-08079-2DOI Listing
July 2021

Correlation Between the Spinal Instability Neoplastic Score (SINS) and Patient Reported Outcomes.

Global Spine J 2021 Jul 26:21925682211033591. Epub 2021 Jul 26.

Research Department, AO Spine International, Davos, Switzerland.

Study Design: International multicenter prospective observational cohort study on patients undergoing radiation +/- surgical intervention for the treatment of symptomatic spinal metastases.

Objectives: To investigate the association between the total Spinal Instability Neoplastic Score (SINS), individual SINS components and PROs.

Methods: Data regarding patient demographics, diagnostics, treatment, and PROs (SF-36, SOSGOQ, EQ-5D) was collected at baseline, 6 weeks, and 12 weeks post-treatment. The SINS was assessed using routine diagnostic imaging. The association between SINS, PRO at baseline and change in PROs was examined with the Spearmans rank test.

Results: A total of 307 patients, including 174 patients who underwent surgery+/- radiotherapy and 133 patients who underwent radiotherapy were eligible for analyses. In the surgery+/- radiotherapy group, 18 (10.3%) patients with SINS score between 0-6, 118 (67.8%) with a SINS between 7-12 and 38 (21.8%) with a SINS between 13-18, as compared to 55 (41.4%) SINS 0-6, 71(53.4%) SINS 7-12 and 7 (5.2%) SINS 13-18 in the radiotherapy alone group. At baseline, the total SINS and the presence of mechanical pain was significantly associated with the SOSGOQ pain domain (r = -0.519, < 0.001) and the NRS pain score (r = 0.445, < 0.001) for all patients. The presence of mechanical pain demonstrated to be moderately associated with a positive change in PROs at 12 weeks post-treatment.

Conclusion: Spinal instability, as defined by the SINS, was significantly correlated with PROs at baseline and change in PROs post-treatment. Mechanical pain, as a single SINS component, showed the highest correlations with PROs.
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http://dx.doi.org/10.1177/21925682211033591DOI Listing
July 2021

A Composite Lactide-Mineral 3D-Printed Scaffold for Bone Repair and Regeneration.

Front Cell Dev Biol 2021 9;9:654518. Epub 2021 Jul 9.

Department of Surgery, Division of Orthopaedic Surgery, McGill University, Montreal, QC, Canada.

Orthopedic tumor resection, trauma, or degenerative disease surgeries can result in large bone defects and often require bone grafting. However, standard autologous bone grafting has been associated with donor site morbidity and/or limited quantity. As an alternate, allografts with or without metallic or polyether-etherketone have been used as grafting substitutes. However, these may have drawbacks as well, including stress shielding, pseudarthrosis, disease-transmission, and infection. There is therefore a need for alternative bone substitutes, such as the use of mechanically compliant three-dimensional (3D)-printed scaffolds. Several off-the-shelf materials are available for low-cost fused deposition 3D printing such as polylactic acid (PLA) and polycaprolactone (PCL). We have previously described the feasibility of 3D-printed PLA scaffolds to support cell activity and extracellular matrix deposition. In this study, we investigate two medical-grade filaments consistent with specifications found in American Society for Testing and Materials (ASTM) standard for semi-crystalline polylactide polymers for surgical implants, a pure polymer (100M) and a copolymeric material (7415) for their cytocompatibility and suitability in bone tissue engineering. Moreover, we assessed the impact on osteo-inductive properties with the addition of beta-tricalcium phosphate (β-TCP) minerals and assessed their mechanical properties. 100M and 7415 scaffolds with the additive β-TCP demonstrated superior mesenchymal stem cells (MSCs) differentiation detected increased alkaline phosphatase activity (6-fold and 1.5-fold, respectively) and mineralized matrix deposition (14-fold and 5-fold, respectively) . Furthermore, we evaluated compatibility, biosafety and bone repair potential in a rat femur window defect model. 100M implants displayed a positive biosafety profile and showed significantly enhanced new bone formation compared to 100M implants evidenced by μCT (39 versus 25% bone volume/tissue volume ratio) and histological analysis 6 weeks post-implantation. These scaffolds are encouraging composite biomaterials for repairing bone applications with a great potential for clinical translation. Further analyses are required with appropriate evaluation in a larger critical-sized defect animal model with long-term follow-up.
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http://dx.doi.org/10.3389/fcell.2021.654518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299729PMC
July 2021

Home blood pressure monitoring: methodology, clinical relevance and practical application: a 2021 position paper by the Working Group on Blood Pressure Monitoring and Cardiovascular Variability of the European Society of Hypertension.

J Hypertens 2021 09;39(9):1742-1767

Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan.

The present paper provides an update of previous recommendations on Home Blood Pressure Monitoring from the European Society of Hypertension (ESH) Working Group on Blood Pressure Monitoring and Cardiovascular Variability sequentially published in years 2000, 2008 and 2010. This update has taken into account new evidence in this field, including a recent statement by the American Heart association, as well as technological developments, which have occurred over the past 20 years. The present document has been developed by the same ESH Working Group with inputs from an international team of experts, and has been endorsed by the ESH.
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http://dx.doi.org/10.1097/HJH.0000000000002922DOI Listing
September 2021

A re-examination of the SPYRAL HTN-OFF MED Pivotal trial with respect to the underlying model assumptions.

Contemp Clin Trials Commun 2021 Sep 29;23:100818. Epub 2021 Jun 29.

Piedmont Heart Institute, 95 Collier Road NW, Atlanta, GA, 30309, USA.

Background: The SPYRAL HTN-OFF MED Pivotal trial demonstrated that RDN was efficacious compared to a sham control. The underlying model was an extension of the analysis of covariance (ANCOVA) model, adjusted for baseline blood pressure (BP), and allowed borrowing of information from the previously reported feasibility study using a novel Bayesian method. Fundamental to the estimation of a treatment effect for efficacy are a multitude of statistical modelling assumptions, including the role of outliers, linearity of the association between baseline BP and outcome, and parallelism of the treatment effect difference over the baseline BP range. In this report, we examine the validity of these assumptions to verify the robustness of the treatment effect measured.

Methods: We examined the requisite modelling assumptions of the ANCOVA model fitted to the SPYRAL HTN-OFF MED Pivotal trial using Bayesian methods. To address outliers, we fit a robust regression model (with heavy tailed errors) to the data with diffuse weakly informative prior distributions on the parameters. To address linearity, we replaced the linear baseline term by a natural spline term with 4 degrees of freedom. To address parallelism, we refit the ANCOVA model with an interaction term for treatment arm and baseline BP.

Results: ANCOVA models were fitted to the trial data (pooled across the feasibility and pivotal cohorts) using Bayesian methodology with diffuse (non-informative) prior distributions. The modelling assumptions inherent to the ANCOVA models were shown to be broadly satisfied. A robust ANCOVA model yielded a posterior treatment effect of -4.1 mmHg (95% credible interval: -6.3 to -1.9) indicating the influence of outlier values was small. There was moderate evidence of an interaction term effect between baseline BP and treatment, but no evidence of gross violation of linearity in baseline BP.

Conclusion: The posterior treatment effect estimate is shown to be robust to underlying model assumptions, thus further supporting the evidence of RDN to be an efficacious treatment for resistant hypertension.
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http://dx.doi.org/10.1016/j.conctc.2021.100818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256182PMC
September 2021
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