bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal Patterns and Adoption of Germline and Somatic BRCA Testing in Ovarian Cancer
Authors: Huepenbecker Sarah P. , Wright Jason D. , Downer Mary K. , Incerti Devin , Luhn Patricia , Dolado Ignacio , Bastiere-Truchot Lydie , Lin Yvonne G. , Chan John K. , Meyer Larissa A.
Published: October 2022

OBJECTIVE:

To describe the testing rate, patient characteristics, temporal trends, timing, and results of germline and somatic BRCA testing in patients with ovarian cancer using real-world data.

METHODS:

We included a cross-sectional subset of adult patients diagnosed with ovarian cancer between January 1, 2011, and November 30, 2018, who received frontline treatment and were followed for at least 1 year in a real-world database. The primary outcome was receipt of BRCA testing, classified by biosample source as germline (blood or saliva) or somatic (tissue). Lines of therapy (frontline, second line, third line) were derived based on dates of surgery and chemotherapy. Descriptive statistics were analyzed.

RESULTS:

Among 2,557 patients, 72.2% (n=1,846) had at least one documented BRCA test. Among tested patients, 62.5% (n=1,154) had only germline testing, 10.6% (n=197) had only somatic testing, and 19.9% (n=368) had both. Most patients had testing before (9.7%, n=276) or during (48.6%, n=1,521) frontline therapy, with 17.6% (n=273) tested during second-line and 12.7% (n=129) tested during third-line therapy. Patients who received BRCA testing, compared with patients without testing, were younger (mean age 63 years vs 66 years, P<.001) and were more likely to be treated at an academic practice (10.4% vs 7.0%, P=.01), with differences by Eastern Cooperative Oncology Group performance score (P<.001), stage of disease (P<.001), histology (P<.001), geography (P<.001), and type of frontline therapy (P<.001), but no differences based on race or ethnicity. The proportion of patients who received BRCA testing within 1 year of diagnosis increased from 24.6% of patients in 2011 to 75.6% of patients in 2018.

CONCLUSION:

In a large cohort of patients with ovarian cancer, significant practice disparities existed in testing for actionable BRCA mutations. Despite increased testing over time, many patients did not receive testing, suggesting missed opportunities to identify patients appropriate for targeted therapy and genetic counseling.
Association of Driving Distance to Maternity Hospitals and Maternal and Perinatal Outcomes
Authors: Minion Sarah C. , Krans Elizabeth E. , Brooks Maria M. , Mendez Dara D. , Haggerty Catherine L.
Published: October 2022

OBJECTIVE:

To assess whether there are associations between driving distance from the patient residence to the delivery hospital and adverse maternal and perinatal health outcomes.

METHODS:

We performed a retrospective cohort study using 2011–2015 Pennsylvania birth records of live births at 20 weeks of gestation or more, excluding inpatient hospital transfers or implausible distances. The shortest driving distance from patient residence to the delivery hospital was calculated in ArcGIS and was evaluated in association with a composite of adverse maternal outcomes (blood transfusion, unplanned operation, ruptured uterus, unplanned hysterectomy, or intensive care unit admission) and neonatal intensive care unit (NICU) admission. Multivariable-adjusted Poisson models were used to estimate relative risks with 95% CIs with a referent difference of 1 km distance to the delivery hospital.

RESULTS:

A total 662,245 birth records were included, and the median driving distance to the hospital was 11.3 km (interquartile range 5.4–21.6 km). The overall rate of the composite maternal outcome was 0.6% and of NICU admission was 8.4%. Compared with the referent distance, increasing driving distance was significantly associated with increased adjusted risks of the maternal composite outcome (adjusted relative risk [aRR] 1.22, 95% CI 1.07–1.36 for 60 km; aRR 1.36, 95% CI 1.19–1.53 for 70 km; and 1.53, 95% CI 1.31–1.75 for 80 km) and NICU admission (aRR 1.70, 95% CI 1.65–1.76 for 60 km; aRR 1.96, 95% CI 1.90–2.02 for 70 km; and aRR 2.25, 95% CI 2.18–2.33 for 80 km).

CONCLUSION:

Longer distances to the delivery hospital were associated with greater risk of adverse maternal outcomes and NICU admission. Whether these finding reflect health care delivery deficits or simply serve as a marker of social deprivation requires further study.
Peptide Mimotope-Enabled Quantification of Natalizumab Arm Exchange During Multiple Sclerosis Treatment
Authors: Page Lesley J. , Lagunas-Acosta Jacqueline , Heussen Raphaela , Castellana Edward T. , Messmer Bradley T.
Published: October 2022

Background:

Natalizumab, a therapeutic antibody used to treat multiple sclerosis, undergoes in vivo Fab arm exchange to form a monovalent bispecific antibody. Although highly efficacious, the immunosuppressive activity of natalizumab has been associated with JC polyomavirus-driven progressive multifocal leukoencephalopathy (PML). Development of assays that can distinguish between and quantify bivalent (unexchanged) and monovalent (exchanged) forms of natalizumab in clinical samples may be useful for optimizing extended interval dosing and reducing the risk of PML.

Methods:

In vitro natalizumab arm exchange was conducted, along with peptide mimotope and anti-idiotype surface capture chemistry, to enable the development of enzyme-linked immunosorbent assays.

Results:

An assay using a unique peptide VeritopeTM was developed, which can exclusively bind to bivalent natalizumab. In combination with enzyme-linked immunosorbent assays that quantifies total natalizumab, the assay system allows quantification of both natalizumab forms.

Conclusions:

In this article, a novel assay for the quantification of unexchanged and exchanged natalizumab variants in clinical samples was developed. This assay will enable investigations into the clinical significance of the relationship of PK/PD with the monovalent-to-bivalent ratio, as it relates to the efficacy of the drug and risk of PML.
The Influence of HEV-Filtering Contact Lenses on Behavioral Indices of Glare
Authors: Renzi-Hammond Lisa M. , Buch John , Xu Jie , Hammond Billy R.
Published: October 2022

Objectives:

We assessed the effects of a HEV-filtering contact lens on positive dysphotopsia (halos and starbursts) and a behavioral index of scatter measured using two-point light thresholds. These effects were assessed by direct comparison to a clear (i.e., non-HEV filtering) contact lens tested in the fellow eye.

Methods:

Sixty-one subjects were randomized and fit with study lenses and 58 subjects completed the study. A double-masked contralateral design was used. Subjects were randomized to test lens-OD, control lens-OS, or vice versa. Participants were exposed to a point source of broadband simulated sunlight (a 403-nm condition was also tested) that created the appearance of halos/starbursts. The degree of dysphotopsia was measured as the diameter of broadband and violet-induced halos, and broadband light-induced starbursts. Two-point thresholds were assessed as the minimum resolvable distance between two pinpoints of light.

Results:

The HEV-filtering lens was statistically superior (P<0.0001) to the clear lens in all the conditions tested. The HEV-filtering lens significantly reduced halo diameter by 30%, starburst diameter by 23%, and resolvable distance in the two-point condition by 18% (white) and 30% (violet).

Conclusions:

HEV-filtering contact lenses can reduce some deleterious effects of bright broadband light by decreasing light scatter, halos, and starbursts.
SARS-CoV-2 Sequelae and Postdischarge Health Care Visits Over 5 Months Follow-up Among Children Hospitalized for COVID-19 or MIS-C
Authors: Doshi Jalpa A. , Sheils Natalie E. , Buresh John , Quinicot Elijah , Islam Nazmul , Chen Yong , Asch David A. , Werner Rachel M. , Swami Sanjeev
Published: October 2022

Although post-acute sequelae of COVID-19 among adult survivors has gained significant attention, data in children hospitalized for severe acute respiratory syndrome coronavirus 2 is limited. This study of commercially insured US children shows that those hospitalized with COVID-19 or multisystem inflammatory syndrome in children have a substantial burden of severe acute respiratory syndrome coronavirus 2 sequelae and associated health care visits postdischarge.
Recurrent ESBL Escherichia coli Urosepsis in a Pediatric Renal Transplant Patient Treated With Antibiotics and Bacteriophage Therapy
Authors: Gainey Andrew B. , Daniels Robert , Burch Anna-Kathryn , Hawn Jason , Fackler Joseph , Biswas Biswajit , Brownstein Michael J.
Published: October 2022

Introduction:

Treating recurrent multidrug resistant (MDR) urosepsis in pediatric transplant recipients can be challenging. Particularly when antibiotics fail to prevent future occurrence and the nidus is seemingly undiscoverable. While there is an increasing amount of data on phage therapy, to our knowledge, there are no published cases involving pediatric renal transplant recipients. Therefore, we present a challenging clinical case in which phage therapy was used in a pediatric renal transplant recipient who developed recurrent MDR urosepsis with an unclear source.

Case Presentation:

Our patient was a 17-year-old female who initially developed urosepsis caused by extended-spectrum β-lactamase (ESBL) Escherichia coli, while being treated with an immunosuppressant regimen because of kidney rejection secondary to poor immunosuppression therapy compliance. She was admitted to our hospital intermittently for 4 months with 4 episodes of urosepsis caused by ESBL E. coli. She received multiple courses of antibiotics (mainly ertapenem) and underwent a fecal material transplant to eradicate her ESBL E. coli colonized gastrointestinal tract. Because of recurrent development of urosepsis after antibiotic treatment, she later underwent treatment with a phage cocktail consisting of 2 isolate-specific phages. After a prolonged antibiotic course and subsequent 3-week intravenous phage treatment, she had no ESBL E. coli in her urinary cultures for 4 years post-treatment.

Discussion:

This case highlights the challenges of treating recurrent ESBL E. coli infections in a pediatric renal transplant patient and provides evidence that phage therapy may prove useful in such cases.
Effect of a new phacoemulsification and aspiration handpiece on anterior chamber stability
Authors: Suzuki Hisaharu , Igarashi Tsutomu , Takahashi Hiroshi
Published: October 2022

Purpose:

To evaluate the responsiveness of 3 phacoemulsification and aspiration (PEA) systems and a new handpiece to occlusion break by measuring anterior chamber depth (ACD) and intraocular pressure (IOP).

Setting:

Zengyo Suzuki Eye Clinic, Kanagawa, Japan.

Design:

Experimental study.

Methods:

ACD change during intentional occlusion breaks was observed and evaluated using the slit side view (SSV) method and IOP measurement with the Centurion Vision System (Group 1), Centurion Vision System with Active Sentry (Group 2), Infiniti Vision System (Group 3), and Constellation Vision System (Group 4). 5 eyes were included per group. Occlusion breaks were triggered at IOP of 30 mm Hg, vacuum limits of 550 mm Hg, and aspiration rate of 40 mL/min. ACD change ratio, surge duration, and surge volume were analyzed from videos of SSV and IOP measurement.

Results:

The smallest ACD change was observed in Group 2 with SSV. ACD change ratios in Groups 1 to 4 were 17.5% ± 3.9%, 7.3% ± 1.2%, 35.7% ± 9.5%, and 74.1 ± 7.7%, respectively. Surge duration and surge volume were calculated only for Groups 1 and 2 and were significantly lower in Group 2 than in Group 1 (0.32 ± 0.03 vs 1.17 ± 0.07 seconds; 18.91 ± 4.70 vs 45.70 ± 0.83 μL). In these 2 groups, ACD change ratio correlated with surge volume.

Conclusions:

This study evaluated the responsiveness of 3 PEA systems and a new handpiece to occlusion breaks by measuring IOP and ACD. The Active Sentry system was useful for maintaining the ACD even during occlusion breaks.
Comparative Analysis of Robotics-Assisted and Manual Insertions of Cochlear Implant Electrode Arrays
Authors: Claussen Alexander D. , Shibata Seiji B. , Kaufmann Christopher R. , Henslee Allan , Hansen Marlan R.
Published: October 2022

Hypothesis

Robotics-assisted cochlear implant (CI) insertions will result in reduced intracochlear trauma when compared with manual, across multiple users.

Background

Whether intracochlear trauma and translocations are two factors that may contribute to significant variability in CI outcomes remains to be seen. To address this issue, we have developed a robotics-assisted insertion system designed to aid the surgeon in inserting electrode arrays with consistent speeds and reduced variability. This study evaluated the effect of robotics-assisted insertions on the intracochlear trauma as compared with manual insertions in cadaveric cochleae in a simulated operative environment.

Methods

Twelve neurotologists performed bilateral electrode insertions into cochleae of full cadaveric heads using both the robotics-assisted system and manual hand insertion. Lateral wall electrodes from three different manufacturers (n = 24) were used and randomized between surgeons. Insertion angle of the electrode and trauma scoring were evaluated using high-resolution three-dimensional x-ray microscopy and compared between robotics-assisted and manual insertions.

Results

Three-dimensional x-ray microscopy provided excellent resolution to characterize the in situ trauma and insertion angle. Robotics-assisted insertions significantly decreased insertional intracochlear trauma as measured by reduced trauma scores compared with manual insertions (average: 1.3 versus 2.2, device versus manual, respectively; p < 0.05). There was no significant difference between insertion angles observed for manual and robotics-assisted techniques (311 ± 131° versus 307 ± 96°, device versus manual, respectively).

Conclusions

Robotics-assisted insertion systems enable standardized electrode insertions across individual surgeons and experience levels. Clinical trials are necessary to investigate whether insertion techniques that reduce insertional variability and the likelihood of intracochlear trauma also improve CI auditory outcomes.
Prediction of Severe Esophageal Varices in Patients With Cirrhosis Based on Levitt’s CO Breath Test
Authors: Feng Chu-Wu , Kang Ling-Ling , Zhang Hou-De
Published: October 2022

Goals:

This study investigated the feasibility of using erythrocyte (RBC) lifespan determined by Levitt’s CO breath test (LCOBT) to predict esophageal varices needing treatment (VNT) in patients with cirrhosis.

Background:

Esophageal varix bleeding is a common fatal complication of cirrhosis and portal hypertension. The gold standard for identifying VNT is esophagogastroduodenoscopy (EGD), an invasive procedure with low patient compliance. VNT screening based on Baveno VI criteria has mediocre specificity.

Study:

RBC lifespan was determined by LCOBT in 53 cirrhotic patients (13 without varices, 11 mild/moderate varices, and 29 severe varices). Correlation of varix severity with RBC lifespan and other variables was analyzed. Rates of shortened RBC lifespan and thrombocytopenia (Baveno VI criteria) were compared.

Results:

RBC lifespan correlated inversely with severity of varices (r=−0.793, P<0.001). Mean RBC lifespans were 129±31, 96±21, and 59±21 days for Nonvarix, Mild/Moderate, and Severe groups. Shortened RBC lifespan (<75 d) was observed in 79.3% (23/29) of patients with severe varices, a frequency similar or identical to thrombocytopenia rates [original Baveno VI criteria, 86.2% (25/29), P=0.487; expanded criteria, 79.3% (23/29), P>0.999]. Among 24 patients without severe varices, shortened RBC lifespan was observed in 1 patient whereas thrombocytopenia was detected in 13 and 8 patients based on the original (P<0.001) and expanded criteria (P=0.010), respectively.

Conclusions:

RBC lifespan correlates inversely with varix severity in patients with cirrhosis. LCOBT may enable specific screening for VNT.
Eating Habits and Eating Disorder Associated Behavior in Bipolar Disorder
Authors: Hirte Teresa S. , Fellendorf Frederike T. , Unterrainer Human-Friedrich , Dalkner Nina , Bengesser Susanne A. , Birner Armin , Platzer Martina , Queissner Robert , Holasek Sandra , Schwerdtfeger Andreas , Reininghaus Eva Z.
Published: October 2022

A relevant comorbidity of bipolar disorder (BD) is eating disorders (EDs). Crossed vulnerability factors as eating disorder–specific symptoms (EDSSs) may trigger the onset of both disorders in either direction. The Structured Inventory for Anorexic and Bulimic Eating Disorders for Self-Report was used to examine the occurrence of EDs in euthymic/subsyndromal individuals with BD (n = 86) and healthy controls (n = 86) matched for age and sex. Furthermore, we explored EDSSs with the subscales “general psychopathology and social integration,” “bulimic symptoms,” “body image and slimness ideal,” “sexuality and body weight,” “counteract,” and “atypical binge.” Higher rates of all EDSSs were reported in BD. Younger individuals with BD showed higher expression in “bulimic symptoms,” “body image and slimness ideal,” and “atypical binge” subscales. No participants fulfilled ED diagnosis. The findings show a link between EDSS and BD. Clinicians should pay attention to a multimodal intervention, considering risk factors, investigating eating habits and ED associated behaviors.
Multimodal analgesia is superior to opiates alone after tibial fracture in patients with substance abuse history
Authors: Lenk Erica , Strecker Sara E. , Nolan William
Published: October 2022

Objectives: To evaluate the effectiveness of multimodal analgesia in patients with a tibial shaft fracture.

Design: Retrospective review.

Setting: Large, urban, academic center.

Patients: One hundred thirty-eight patients were evaluated before implementation of multimodal analgesia. Thirty-four patients were evaluated after implementation. All patients were treated operatively with internal fixation for their tibial shaft fracture. Patients with polytrauma were excluded.

Intervention: Multimodal analgesia.

Main Outcome Measures: Pain levels at rest and with movement were assessed. Morphine milligram equivalents (MMEs) dosed per patient were calculated each day. Length of stay was also documented.

Results: After implementation of a multimodal analgesic program, there was a statistically significant decrease in pain score at rest (4.7–4.0, P = 0.034) and with movement (5.8–4.8, P = 0.007). MMEs dosed in the multimodal analgesic program correlated with pain score (R2 = 0.5), whereas before implementation of the program, MMEs dosed were not dependent on pain score (R2 = 0.007). Patients with a history of substance abuse had the most profound effect from this paradigm change. For those with a history of substance abuse, treatment of pain using a multimodal approach reduces MMEs dosed and length of stay (5.7–3.1 days, P = 0.016).

Conclusions: Multimodal analgesia improves patient pain scores both at rest and during movement. In patients with a history of substance abuse, multimodal analgesia not only decreases pain but also decreases length of stay and MMEs dosed to levels consistent with someone who does not have a substance abuse history.

Level of Evidence: Therapeutic Level III.
Direct versus indirect posterior malleolar fixation in the treatment of trimalleolar ankle fractures: Is there a difference in outcomes?
Authors: Saad Bishoy N. , Rampertaap Yajesh , Menken Luke G. , Whitlock Keith G. , Crook Bryan S. , Baker Rafael L. , Keller David M. , Liporace Frank A. , Gage Mark J. , Yoon Richard S.
Published: October 2022

Purpose:

The purpose of this study was to examine the differences in functional outcomes between direct and indirect surgical fixation methods of the posterior malleolus in the setting of trimalleolar fractures and identify any variables affecting patient outcomes.

Methods:

Primary outcomes were evaluated by PROMIS scores for short-term outcomes regarding total pain (TP) and total function (TF) comparing 40 patients with direct fixation with 77 with indirect fixation. Continuous variables were analyzed using t tests for parametric variables and the Mann–Whitney U test for nonparametric variables. Categorical variables were analyzed using a χ2 test. Univariate and multivariate linear regression models were performed to analyze factors that affect outcomes of TP and TF.

Results:

There was no difference in TP or TF between groups (P = 0.65 vs. P = 0.19). On univariate linear regression for TP, BMI, incidence of complication, tobacco use, and open injury showed significance in increasing pain levels with open injuries providing the greatest effect (coef = 11.8). On multivariate analysis, BMI, incidence of complication, open injury, and tourniquet time all significantly increased pain. For TF, univariate analysis showed age, BMI, incidence of complication, and diabetes to decrease function, and use of external fixator and tourniquet time increased function. In the multivariate model, increased BMI, open injuries, and increasing tourniquet time all decreased TF while use of an external fixator increased TF.

Conclusion:

This study showed no difference in TP and TF using the PROMIS outcome scores when comparing direct fixation versus indirect fixation under univariate and multivariate models.

Level of Evidence:

Therapeutic III.
Routine Perioperative Esmolol After Infant Tetralogy of Fallot Repair: Single-Center Retrospective Study of Hemodynamics
Authors: Affolter Jeremy T. , Well Andrew , Gottlieb Erin A. , Fraser Charles D.
Published: October 2022

OBJECTIVES:

Currently, surgical repair of tetralogy of Fallot (TOF) is associated with an 1.1% 30-day mortality rate. Those with junctional ectopic tachycardia (JET) and restrictive right ventricular physiology have poorer outcomes. Routine postoperative adrenergic or inodilator therapy has been reported, while beta-blockade following cardiopulmonary bypass has not. This study evaluated routine perioperative treatment with esmolol in infants undergoing TOF repair.

DESIGN:

Retrospective chart review of the perioperative course following TOF repair.

SETTING:

Single-center case series describing perioperative management of TOF in a cardiac ICU.

PATIENTS:

This study reviewed all patients less than 18 months old who underwent TOF repair, excluding cases of TOF with absent pulmonary valve or atrioventricular septal defect, at our institution from June 2018 to April 2021.

INTERVENTIONS:

This review investigates the hemodynamic effects of esmolol following cardiopulmonary bypass for TOF repair.

MEASUREMENTS AND MAIN RESULTS:

Preoperative clinical characteristics and perioperative course were extracted from the medical record. Descriptive statistics were used. Twenty-six patients receiving perioperative esmolol after TOF repair were identified and included. Postoperative hemodynamic parameters were within a narrow range with minimal vasoactive support in most patients. Three of 26 patients experienced JET, and one of 26 of whom had a brief cardiac arrest. Median and interquartile range (IQR) for hospital and postoperative length of stay was 7 days (IQR, 6–9 d) and 6 days (IQR, 5–8 d), respectively. There were no 30-day or 1-year mortalities.

CONCLUSIONS:

In this infant cohort, our experience is that the routine use of postoperative esmolol is associated with good cardiac output with minimal requirement for vasoactive support in most patients. We believe optimal postoperative management of infant TOF repair requires a meticulous multidisciplinary approach, which in our experience is enhanced with routine postoperative esmolol treatment.
Balancing Clinician Workload Through Strategic Patient Panel Designs
Authors: Huang Yu-Li , Berg Bjorn P. , Horn Jennifer L. , Nagaraju Darshan , Rushlow David R.
Published: October 2022

Background and Objectives:

Clinician workload is a key contributor to burnout and well-being as well as overtime and staff shortages, particularly in the primary care setting. Appointment volume is primarily driven by the size of patient panels assigned to clinicians. Thus, finding the most appropriate panel size for each clinician is essential to optimization of patient care.

Methods:

One year of appointment and panel data from the Department of Family Medicine were used to model the optimal panel size. The data consisted of 82 881 patients and 105 clinicians. This optimization-based modeling approach determines the panel size that maximizes clinician capacity while distributing heterogeneous appointment types among clinician groups with respect to their panel management time (PMT), which is the percent of clinic work.

Results:

The differences between consecutive PMT physician groups in total annual appointment volumes per clinician for the current practice range from 176 to 348. The optimization-based approach for the same PMT physician group results in having a range from 211 to 232 appointments, a relative reduction in variability of 88%. Similar workload balance gains are also observed for advanced practice clinicians and resident groups. These results show that the proposed approach significantly improves both patient and appointment workloads distributed among clinician groups.

Conclusion:

Appropriate panel size has valuable implications for clinician well-being, patients' timely access to care, clinic and health system productivity, and the quality of care delivered. Results demonstrate substantial improvements with respect to balancing appointment workload across clinician types through strategic use of an optimization-based approach.
Using the Electronic Medical Record to Increase Laboratory Test Monitoring in Ocular Inflammation Patients: A Quality Improvement Study
Authors: Tipton Caroline W. , Burkholder Bryn M. , Chaon Benjamin C. , Berkenstock Meghan K.
Published: October 2022

Background and Objectives:

Treatment of chronic, noninfectious ocular inflammation includes corticosteroids, disease-modifying antirheumatic medications, and biologics. To mitigate adverse effects associated with the use of these medications, routine laboratory test monitoring is recommended throughout treatment. We evaluated the effectiveness of an alert added to the electronic medical record (EMR) to aid in laboratory test monitoring for patients prescribed these high-risk medications.

Methods:

A prospective, interventional study assessed the effect of the alert within the EMR on laboratory test ordering at the Division of Ocular Immunology at the Wilmer Eye Institute. The primary outcome measure was the change in number of ordered laboratory tests at 3, 6, and 12 months after the alert activation compared with pre-intervention levels and overall through the study period. The laboratory tests that were monitored included complete blood count, comprehensive metabolic panel, dual-energy x-ray absorptiometry (DXA) scanning, fasting lipid panel, and interferon gamma release assays.

Results:

The laboratory test orders for 153 patients on high risk medications were analyzed. Only the frequency of ordering the DXA and interferon gamma release assays increased significantly, compared with baseline, throughout the study. Conversely, there was a significant decrease in the frequency of ordering of fasting lipid profiles and hemoglobin A1c at each time point and for complete blood count and comprehensive metabolic panel at the 6-month time point.

Conclusion:

An EMR alert results in increased laboratory test ordering initially for tests drawn on a yearly basis, but the effect on more frequently ordered tests wanes with time if the alert can be silenced by the provider. Nonetheless, it provides a novel mechanism to increase laboratory ordering in patients on high-risk medications that can be adapted for use in other EMR software. Future studies are needed to assess whether physician laboratory test ordering behavior is altered throughout the study period with the use of a non-silencable alert.
Chryseobacterium oryzae sp. nov. and Chryseobacterium suipulveris sp. nov., isolated from Andong sikhye and pigpen dust, respectively
Authors: Heo Jun , Won Miyoung , Lee Daseul , Kim Jeong-Seon , Han Byeong-Hak , Kim Soo-Jin , Hong Seung-Beom , Kwon Soon-Wo
Published: October 2022

Two Gram-stain-negative, aerobic, mesophilic, rod-shaped bacteria, ADR-1T and SC2-2T, were isolated from Andong sikhye and dust in a pigpen, respectively. The phylogenetic tree on the basis of 16S rRNA gene sequences showed that strains ADR-1T and SC2-2T were members of the genus

Chryseobacterium

and revealed the highest sequence similarities to

Chryseobacterium binzhouense

LM2T (97.6 %) and

Chryseobacterium koreense

Chj707T (94.9 %), respectively. Phylogenomic treeing using 92 core genes clearly indicated that strain ADR-1T clustered with

Chryseobacterium echinoideorum

CC-CZW010T,

Chryseobacterium binzhouense

LM2T and

Chryseobacterium taihuense

CGMCC 1.10941T, and strain SC2-2T formed a compact cluster with

Chryseobacterium koreense

CCUG 49689T. The digital DNA–DNA hybridization (dDDH) and orthologous average nucleotide identity (ANI) values of strain ADR-1T with the closely related species of the genus

Chryseobacterium

were ≤24.4 % and ≤80.7 %, and those of strain SC2-2T were ≤24.0 % and ≤77.8 %, respectively, which are well below the cut-off values of species discrimination (>70 % dDDH and >95–96 % ANI). The only respiratory quinone in both strains was menaquinone 6. The polar lipid profile of strain ADR-1T comprised phosphatidylethanolamine, four unidentified aminolipids and three unidentified lipids, while strain SC2-2T contained phosphatidylethanolamine, two unidentified aminolipids, one unidentified aminophospholipid and five unidentified polar lipids. The major fatty acids (>10 %) of strain ADR-1T were iso-C15 : 0, summed feature 9 (iso-C17 : 1
 ω9c and/or C16 : 0 10-methyl), iso-C17 : 0 3-OH and summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c), and those of strain SC2-2T were iso-C15 : 0 and anteiso-C15 : 0. On the basis of the results of phenotypic and phylogenetic analyses, strains ADR-1T and SC2-2T represent two distinct novel species in the genus

Chryseobacterium

, for which the names Chryseobacterium oryzae sp. nov. (type strain ADR-1T=KACC 19311T=NBRC 113104T) and Chryseobacterium suipulveris sp. nov. (type strain SC2-2T=KACC 19313T=NBRC 113106T) are proposed.
Feasibility of Conducting Comparative Effectiveness Research and Validation of a Clinical Disease Activity Score for Chronic Nonbacterial Osteomyelitis
Authors: Wu Eveline Y. , Oliver Melissa , Scheck Joshua , Lapidus Sivia , Akca Ummusen Kaya , Yasin Shima , Stern Sara M. , Insalaco Antonella , Pardeo Manuela , Simonini Gabriele , Marrani Edoardo , Wang Xing , Huang Bin , Kovalick Leonard K. , Rosenwasser Natalie , Casselman Gabriel , Liau Adriel , Shao Yurong , Yang Claire , Mosa Doaa Mosad , Tucker Lori , Girschick Hermann , Laxer Ronald M. , Akikusa Jonathan D. , Hedrich Christian , Onel Karen , Dedeoglu Fatma , Twilt Marinka , Ferguson Polly J. , Ozen Seza , Zhao Yongdong
Published: October 2022

Introduction

Prospective comparative effectiveness research in chronic nonbacterial osteomyelitis (CNO) is lacking.

Objectives

Study objectives were to: 1) determine the use and safety of each consensus treatment plan (CTP) regimen for CNO, 2) the feasibility of usingchronic nonbacterialosteomyelitis international registry (CHOIR) data for comparative effectiveness research, and 3) develop and validate a CNO clinical disease activity score (CDAS) using CHOIR.

Methods

Consenting children or young adults with CNO were enrolled into CHOIR. Demographic, clinical, and imaging data were prospectively collected. The CNO CDAS was developed through a Delphi survey and nominal group technique. External validation surveys were administered to CHOIR participants.

Results

140 (76%) CHOIR participants enrolled between August 2018 and September 2020 received at least one CTP regimen. Baseline characteristics from the three groups were well matched. Patient pain, patient global assessment, and clinical CNO lesion count were key variables included in the CNO CDAS. The CDAS showed a strong correlation with patient/parent report of difficulty using a limb, back, or jaw and patient/parent report of disease severity, but a weak correlation with patient/parent report of fatigue, sadness, and worry. The change in CDAS was significant in patients reporting disease worsening or improvement. The CDAS significantly decreased after initiating second-line treatments from median 12 (8-15.5) to 5 (3-12). While second-line treatments were well tolerated, psoriasis was the most common adverse event.

Conclusion

The CNO CDAS was developed and validated for disease monitoring and assessment of treatment effectiveness. CHOIR provided a comprehensive framework for future comparative effectiveness research.

Key messages

Thechronic nonbacterialosteomyelitis international registry (CHOIR) provides comprehensive prospective data for comparison of treatment effectiveness

The clinical disease activity score (CDAS) has content and construct validity to assess CNO
Mucosal-associated invariant T (MAIT) cell responses in Salmonella enterica serovar Typhi strain Ty21a oral vaccine recipients
Authors: Trivedi Shubhanshi , Cheng Olivia , Brintz Ben J , Charles Richelle C. , Leung Daniel T
Published: October 2022

Background

Mucosal–associated invariant T (MAIT) cells are unconventional innate-like T cells abundant in mucosal tissue of humans, and associated with protective responses to microbial infections. MAIT cells have capacity for rapid effector function, including the secretion of cytokines and cytotoxic molecules. However, limited information is available regarding the activity of MAIT cells in mucosal vaccine-mediated immune responses in humans.

Methods

We enrolled healthy adults who received a course of oral live-attenuated S. Typhi strain Ty21a vaccine and collected peripheral blood samples pre-vaccination, and at 7 days and one month post-vaccination. We used flow cytometry, cell migration assays, and tetramer decay assay to assess MAIT cell responses.

Results

We show that following vaccination, circulating MAIT cells are decreased in frequency but have increased activation markers. Post-vaccine timepoints had higher levels of MAIT cells expressing gut-homing marker integrin α4β7 and chemokine receptor CCR9, suggesting the potential of MAIT cells to migrate to mucosal sites. While we found higher frequencies of TNF-α expression on MAIT cells post-vaccination, we did not find significant differences in expression of other effector molecules, TCR avidity, or cell migration.

Conclusions

We show how MAIT cell immune responses are modulated post-vaccination against S.Typhi. This study contributes to our understanding of MAIT cells’ potential role in oral vaccination against bacterial mucosal pathogens.
Potential use of Immunodaat® (Botanical extract of Elderberry -Sambucus Nigra L.) in the management of Post Covid-19 symptoms- a comparative, multi-centric, randomized, clinical study
Authors: Deshpande Shailesh , Mundhe Narendra , Deshpande Vaishali , Tamoli Sanjay , Mahadik Swapnali , Pawar Vinay
Published: October 2022

Background

Immunodaat™, a proprietary botanical extract, contains standardized extract of Elderberry (Sambucus Nigra L.). Elderberry is used as an immunity enhancer for prevention and management of various respiratory diseases and as an anti-oxidant.

Objectives

The present study evaluated the effect of Immunodaat™, in Post Covid-19 recovery.

Methods

An open labeled, comparative, randomized, multi-centric, prospective clinical study was conducted on 74 subjects who had post COVID-19 symptoms recovery from mild-moderate COVID-19 within the last 15 days. Subjects were divided equally, with 37 subjects in trial and control groups each, where subjects in trial group were given Immunodaat™ capsules in a dose of 250 mg Capsules twice daily along with the standard care for COVID-19 for consecutive 30 days while subjects in control group were given only the standard care for Post Covid. Subjects were evaluated for post clinical recovery signs and symptoms (like cough, fatigue, Myalgia, Joint pain, confusion, altered mood, anxiety, insomnia etc.) and lab parameters. Subjects were evaluated for quality of life using WHO QOL BREF.

Results

Continuous 30 days administration of Immunodaat™ showed a significant difference in reducing physical as well as mental symptoms when compared to the control group. Also, a significant improvement in quality of life was observed on WHO QOL BREF scale with the use of Immunodaat compared to the control group. Overall quality of life, energy levels and stamina levels improved with the use of Immunodaat™.

Subjects showed excellent tolerability and did not have any adverse effect with the use of Immunodaat™.

Conclusion

The study concludes that use of Immunodaat™ over 30 days aided to normalize the physical and mental symptoms that occurred due to Post COVID and long COVID. Immunodaat™ can be considered as a safe and effective natural ingredient in the management of Post COVID-19 or long COVID condition.
Orthogonal tRNA Expression using Endogenous Machinery in Cell-Free Systems
Authors: Seki Kosuke , Galindo Joey L. , Jewett Michael C.
Published: October 2022

A wide variety of non-canonical amino acids (ncAAs) can be incorporated into proteins through the coordinated action of a stop codon suppressing tRNA and aminoacyl-tRNA synthetase. However, methods to discover and characterize suppressor tRNAs are generally lacking. In this work, we show that cell-free systems can express functional suppressor tRNAs using endogenous machinery and characterize their activity. This method is compatible with widely used orthogonal tRNAs, such as the Methanocaldococus jannaschii tyrosyl tRNA, the Methanosarcina barkeri pyrrolysyl tRNA, the Methanomethylophilus Alvus pyrrolysyl tRNA, and an engineered Int pyrroysyl tRNA. Modifying the workflow to evaluate TAA suppression revealed that the M. jannaschii and M. alvus are highly functional TAA suppressors in cell-free systems. Finally, we show that we can express two distinct tRNAs simultaneously, enabling the incorporation of multiple, distinct ncAAs. In total, our work shows that cell-free systems are useful platforms to express and characterize tRNAs.
Non-patient related SARS-CoV-2 exposure to colleagues and household members impose the highest infection risk for hospital employees with and without patient contact in a German university hospital: follow-up of the prospective Co-HCW Seroprevalence study
Authors: Bahrs Christina , Weis Sebastian , Kesselmeier Miriam , Ankert Juliane , Hagel Stefan , Beier Stephanie , Maschmann Jens , Stallmach Andreas , Steiner Andrea , Bauer Michael , Behringer Wilhelm , Baier Michael , Richert Cora , Zepf Florian , Walter Martin , Scherag André , Kiehntopf Michael , Löffler Bettina , Pletz Mathias W.
Published: October 2022

Background

The Co-HCW study is a prospective, longitudinal single center observational study on the SARS-CoV-2 seroprevalence and infection status in staff members of Jena University Hospital (JUH) in Jena, Germany.

Material and Methods

This follow-up study covers the observation period from 19th May 2020 to 22nd June 2021. At each out of three voluntary study visits, participants filled out a questionnaire on individual SARS-CoV-2 exposure. In addition, serum samples to assess specific SARS-CoV-2 antibodies were collected. Participants with antibodies against nucleocapsid and/or spike protein without previous vaccination and/or a reported positive SARS-CoV-2 PCR test were regarded as participants with detected SARS-CoV-2 infection. Multivariable logistic regression modeling was applied to identify potential risk factors for infected compared to non-infected participants.

Results

Out of 660 participants that were included during the first study visit, 406 participants (61.5%) were eligible for final analysis as they did not change the COVID-19 risk area (high-risk n=76; intermediate-risk n=198; low-risk n=132) during the study. Forty-four participants (10.8%, 95% confidence interval (95%CI) 8.0%-14.3%) had evidence of a current or past SARS-CoV-2 infection detected by serology (n=40) and/or PCR (n=28). No association of any SARS-CoV-2 infection with the COVID-19 risk group according to working place could be detected. But exposure to a SARS-CoV-2 positive household member (adjusted OR (AOR) 4.46, 95%CI 2.06-9.65) or colleague (AOR 2.30, 95%CI 1.10-4.79) significantly increased the risk of a SARS-CoV-2 infection.

Conclusion

Our results demonstrate that non-patient-related SARS-CoV-2 exposure imposed the highest infection risk in hospital staff members of JUH.
Rapid isolation of respiring skeletal muscle mitochondria using nitrogen cavitation
Authors: Younis Awais Z. , Lavery Gareth G. , Christian Mark , Doig Craig L.
Published: October 2022

Background

Methods of isolating mitochondria commonly utilize mechanical force and shear stress to homogenize tissue followed by purification by multiple rounds of ultracentrifugation. Existing protocols can be time-consuming with some physically impairing integrity of the sensitive mitochondrial double membrane.

Methods

Here, we describe a method for the recovery of intact, respiring mitochondria from murine skeletal muscle tissue and cell lines using nitrogen cavitation in combination with differential centrifugation.

Results

This protocol results in high yield, pure and respiring mitochondria without the need for purification gradients or ultracentrifugation. The protocol takes under an hour and requires limited specialised equipment. Our methodology is successful in extracting mitochondria of both cell extracts and skeletal muscle tissue. This represents an improved yield in comparison to many of the existing methods. Western blotting and electron microscopy demonstrate an enrichment of mitochondria with their ultrastructure well-preserved and an absence of contamination from cytoplasmic or nuclear fractions. Using respirometry analysis we show that mitochondria extracted from the murine skeletal muscle cell lines and tibialis anterior have an appropriate respiratory control ratio. These measures are indicative of healthy coupled mitochondria.

Conclusion

Our method successfully demonstrates the rapid isolation of functional mitochondria and will benefit researchers studying mitochondrial bioenergetics as well as providing greater throughput and application for time-sensitive assays.
Opposing regulation of METTL11A by its family members METTL11B and METTL13
Authors: Parker Haley V. , Schaner Tooley Christine E.
Published: October 2022

N-terminal protein methylation (Nα-methylation) is a post-translational modification (PTM) that influences a variety of biological processes by regulating protein stability, protein-DNA interactions, and protein-protein interactions. Although significant progress has been made in understanding the biological roles of this PTM, we still do not completely understand how the methyltransferases that place it are regulated. A common mode of methyltransferase regulation is through complex formation with close family members, and we have previously shown that the Nα-trimethylase METTL11A (NRMT1/NTMT1) is activated through binding of its close homolog METTL11B (NRMT2/NTMT2). It has also recently been reported that METTL11A co-fractionates with a third METTL family member METTL13, which methylates both the N-terminus and lysine 55 (K55) of eukaryotic elongation factor 1 alpha (eEF1A). Here we confirm a regulatory interaction between METTL11A and METTL13 and show that, while METTL11B is an activator of METTL11A, METTL13 inhibits METTL11A activity. This is the first example of a methyltransferase being opposingly regulated by different family members. Similarly, we find that METTL11A promotes the K55 methylation activity of METTL13 but inhibits its Nα-methylation activity. We also find that catalytic activity is not needed for these regulatory effects, demonstrating new, non-catalytic functions for METTL11A and METTL13. Finally, we show METTL11A, METTL11B, and METTL13 can complex together, and when all three are present, the regulatory effects of METTL13 take precedence over those of METTL11B. These findings provide a better understanding of the regulation of Nα-methylation, and suggest a model where these methyltransferases can serve in both catalytic and non-catalytic roles.
Conceptualizing disability accommodation device acceptance by workgroups through a sociomaterial lens
Authors: Kulkarni Mukta , Baldridge David , Swift Michele
Published: October 2022

Purpose

The provision of accommodation devices is said to aid organizational inclusion of employees with a disability. However, devices that are meant to enable might only partially facilitate productivity, independence, and social inclusion if these devices are not accepted by the user's workgroup. The authors outline a conceptual model of accommodation device acceptance through a sociomaterial lens to suggest conditions influencing workgroup device acceptance.

Design/methodology/approach

To build the model, the authors draw upon the sociomateriality and disability literature to frame accommodation devices as experienced in ongoing interactions, representing the goals, feelings, and interpretations of specific workgroups. The authors also unpack attributes of devices—instrumentality, aesthetics, and symbolism—and propose how each of these can pattern social conduct to influence device acceptance. The authors then draw upon the disability literature to identify attributes of workgroups that can be expected to amplify or diminish the effect of device attributes on device acceptance in that workgroup.

Findings

The conceptualization, which the authors illustrate with examples particular to visual impairment, presents implications for who and what serves as a gatekeeper to accommodation device acceptance and thereby workgroup inclusion.

Originality/value

Prior research has focused on conditions under which devices are requested by users or made available by organizations, undergirded by the assumption that devices are well-specified once provided and that they operate relatively predictably when used in various workgroups. The authors focus instead on what happens after the device is provided and highlight the complex and dynamic interaction between an accommodation device and the workgroup, which influences device and user acceptance.
Conducting techno-economic analyses of early-stage designs for net-zero water and energy affordable homes
Authors: Wurthmann Kurt
Published: October 2022

Purpose

This study aims to provide and illustrate the application of a framework for conducting techno-economic analyses (TEA) of early-stage designs for net-zero water and energy, single-family homes that meet affordable housing criteria in diverse locations.

Design/methodology/approach

The framework is developed and applied in a case example of a TEA of four designs for achieving net zero-water and energy in an affordable home in Saint Lucie County, Florida.

Findings

Homes built and sold at current market prices, using combinations of well versus rainwater harvesting (RWH) systems and grid-tied versus hybrid solar photovoltaic (PV) systems, can meet affordable housing criteria for moderate-income families, when 30-year fixed-rate mortgages are at 2%–3%. As rates rise to 6%, unless battery costs drop by 40% and 60%, respectively, homes using hybrid solar PV systems combined with well versus RWH systems cease to meet affordable housing criteria. For studied water and electricity usage and 6% interest rates, only well and grid-tied solar PV systems provide water and electricity at costs below current public supply prices.

Originality/value

This article provides a highly adaptable framework for conducting TEAs in diverse locations for designs of individual net-zero water and energy affordable homes and whole subdivisions of such homes. The framework includes a new technique for sizing storage tanks for residential RWH systems and provides a foundation for future research at the intersection of affordable housing development and residential net-zero water and energy systems design.