bluuebunny/crossref_metadata_2025 huggingface dataset:
Doubling Intensive Care Unit Capacity by Surging Onto Medical-Surgical Units During the COVID-19 Pandemic
Authors: O'Donoghue Sharon C. , Donovan Barbara , Anderson Joanna , Foley Jane , Gillis Jean , Maloof Kimberly , Milano Andrea , Whitlock John , DeSanto-Madeya Susan
Published: October 2021

Introduction

The ability of an organization to accommodate a large influx of patients during a prolonged period is dependent on surge capacity. The aim of this article is to describe the surge experience with space, supplies, and staff training in response to COVID-19 and provide guidance to other organizations.

Background

A hospital's response to a large-scale event is greatly impacted by the ability to surge and, depending on the type of threat, to maintain a sustained response. To identify surge capacity, an organization must first consider the type of event to appropriately plan resources.

Preparation Process

An epidemic surge drill, conducted in 2012, served as a guide in planning for the COVID-19 pandemic. The principles of crisis standards of care and a hospital incident command structure were used to clearly define roles, open lines of communication, and inform our surge plan. Preparation began by collaborating with multidisciplinary groups to acquire the most appropriate space, as well as adequate supplies, and identify and train staff.

Implementation

Teams were formed to identify the necessary resources to expand the intensive care unit (ICU) environment quickly and efficiently. Educational training was developed for redeployed staff.

Outcomes

Beth Israel Deaconess Medical Center experienced the largest surge of ICU patients within a hospital system in the state of Massachusetts. The ICU capacity was expanded by 93% from 77 to 149 beds, and the surge was maintained for approximately 9 weeks. Shadowing experiences before the actual surge were extremely valuable.

Conclusions

Planning for the surge of critically ill patients required a thoughtful, collaborative approach. Ongoing staff support and communication from nursing leadership were necessary to ensure safe, effective care for critically ill patients in a new and dynamic environment.
Nicorandil Decreases Renal Injury in Patients With Coronary Heart Disease Complicated With Type I Cardiorenal Syndrome
Authors: Du Xiaozhi , Ma Zhiyong , Li Li , Zhong Xuezhen
Published: October 2021

Cardiorenal syndrome (CRS) is a group of disorders in which heart or kidney dysfunction worsens each other. This study aimed to explore the improvement effect of nicorandil on cardiorenal injury in patients with type I CRS. Patients with coronary heart disease complicated with type I CRS were enrolled. Based on the conventional treatment, the patients were prospectively randomized into a conventional treatment group and a nicorandil group, which was treated with 24 mg/d nicorandil intravenously for 1 week. Fasting peripheral venous blood serum and urine were collected before and at the end of treatment. An automatic biochemical analyzer and enzyme linked immunosorbent assay were used to detect B-type brain natriuretic peptide (BNP), serum creatinine (Scr) and cystatin C (Cys-C), renal injury index–kidney injury molecule-1 (KIM-1), neutrophil gelatinase–associated lipocalin (NGAL), and interleukin-18 (IL-18) levels. The left ventricular ejection fraction was measured by echocardiography. All measurements were not significantly different between the nicorandil and conventional treatment groups before treatment (all P > 0.05), and BNP, Scr, Cys-C, NGAL, KIM-1, and IL-18 were decreased in the 2 groups at the end of treatment (all P < 0.05). Compared with the conventional treatment group, BNP, Scr, Cys-C, NGAL, KIM-1, and IL-18 were more significantly decreased in the nicorandil group (all P < 0.05) and left ventricular ejection fraction was more significantly increased (P < 0.05). Therefore, nicorandil could significantly improve the cardiac and renal function of patients with type I CRS. This may prove to be a new therapeutic tool for improving the prognosis and rehabilitation of type I CRS.
CUL5-Mediated Visfatin (NAMPT) Degradation Blocks Endothelial Proliferation and Angiogenesis via the MAPK/PI3K-AKT Signaling
Authors: Shi Zanhua , Yao Jiamei , Ma Xinhua , Xu Daomiao , Ming Guangfeng
Published: October 2021

Endothelial dysfunction participates in the pathogenesis of various cardiovascular disorders, and dysregulated angiogenesis involves the vascular endothelial growth factor (VEGF)–matrix metalloproteinases (MMP) system. Nicotinamide phosphoribosyltransferase (NAMPT) is known to enhance endothelial function and angiogenesis. The study found that NAMPT overexpression protected human coronary artery endothelial cells (HCAECs) from H2O2-induced injury through promoting cell viability, inhibiting cell apoptosis, enhancing cell motility, and promoting tube formation. Through analyses based on 2 Protein–Protein Interaction databases, Mentha and BioGrid, we identified CUL5 as a protein that may interact with NAMPT, which was then validated by Co-IP experiments. Through interacting with NAMPT, CUL5 inhibited NAMPT expression. In contrast to NAMPT, CUL5 overexpression further aggravated H2O2-induced HCAEC dysfunction. In the meantime, CUL5 overexpression reduced, whereas NAMPT overexpression increased the phosphorylation of p38 and Akt and the protein levels of VEGF and MMP2. More importantly, NAMPT overexpression partially reversed the effects of CUL5 overexpression on H2O2-stimulated HCAECs and the MAPK/phosphatidylinositol 3-kinase-Akt/VEGF/MMP signaling. In conclusion, CUL5 interacts with NAMPT in H2O2-stimulated HCAECs, suppressing cell viability, promoting cell apoptosis, and inhibiting cell mobility and tube formation. NAMPT overexpression protects against H2O2-induced HCAEC dysfunction by promoting cell viability, inhibiting cell apoptosis, and enhancing cell mobility and tube formation.
The Role of Progestogens in Menopausal Hormone Therapy
Authors: Liu James H.
Published: October 2021

Progestogens are steroid compounds that have the ability to induce secretory transformation in the endometrium and are utilized in menopausal hormone therapy to prevent endometrial hyperplasia and endometrial cancer. Progestogens can be derived from 21-carbon or 19-carbon steroid cytoskeletons and thus have different properties and metabolic effects beyond the progestational effects on the endometrium. This limited review will focus on the available progestogens utilized in combination hormone therapy including progesterone, medroxyprogesterone acetate, norethindrone, norethindrone acetate, levonorgestrel, and drospirenone. The impact of progestogens on a variety of target tissues including the endometrium, breast, cardiovascular system, brain, and bone, will be reviewed. Last, the current clinical regimens that can be utilized by clinicians will be discussed.
The “Brookhaven Brassie” and the Response to the Three Mile Island Accident
Authors: Studer Nicholas M.
Published: October 2021

In the mid-1970s, American civil defense authorities became increasingly concerned with the potential threat of fission reactor accidents. Research from the Defense Civil Preparedness Agency began to be aimed not just at the ever-present threat of nuclear warfare but also peacetime emergencies as part of a “dual use” philosophy. The Brookhaven National Laboratory received funding to create a prototype radioiodine air sampling system, with multiple publications detailing the creation of the air sampler itself and a special CD V-700 survey meter that accompanied it. In late March 1979, the system found its first operational employment at the reactor accident at Three Mile Island in Pennsylvania. Despite successful use and further study, the BNL Air Sampler was not widely fielded by the federal government. However, lessons learned from its employment and development may be applicable to contemporary radiological emergency response.
Inpatient and Outpatient Differences in Pediatric Patients with Laboratory-confirmed COVID-19
Authors: Spaulding Alicen B. , Watson David , Norton Laura
Published: October 2021

Among 30,286 pediatric inpatient and outpatient encounters with laboratory-confirmed COVID-19 seen at one of 40 US healthcare organizations, 1586 (5.2%) were inpatient. Encounter types varied by age and sex; the proportion of Black/African American inpatients was significantly higher than outpatients, and Hispanic/Latinx children made up nearly one-fourth of patients.
Optic Nerve Head Vessel Density Changes from Graves’ Disease without TED to TED Dysthyroid Optic Neuropathy: Does Optic Nerve Head Ischemia Play a Role?
Authors: Abdolalizadeh Parya , Kashkouli Mohsen Bahmani , Moradpasandi Farideh , Falavarjani Khalil Ghasemi , Mirshahi Reza , Akbarian Shadi
Published: October 2021

Purpose:

To compare the retinal peripapillary capillary (RPC) vessel density (VD) between 5 groups of patients on the spectrum of thyroid eye disease (TED).

Method:

This is a prospective comparative study looking at 5 groups of patients who were consecutively included from January 2018 to March 2021. They were composed of: Healthy volunteers (39 eyes and 20 subjects), patients with Graves’ disease without TED (26 eyes and 13 patients), mild TED (28 eyes and 14 patients), moderate-severe TED (30 eyes and 17 patients), and TED with dysthyroid optic neuropathy (DON) (21 eyes and 12 patients). Ocular and periocular examination, visual field indices, RPC-VD (with optical coherence tomography angiography), and retinal nerve fiber layer, and macular ganglion cell complex thickness were recorded.

Result:

An initial insignificant (0.5 < p < 0.9) rise in the peripapillary-VD (pp-VD) and whole image-VD (wi-VD) from the healthy subject to the Graves’ disease without TED was followed by a significant (p = 0.001) fall in RPC-VD in different severity grades of the TED. Paired comparison between the 5 groups showed that the statistically significant fall from the Graves’ disease group occurred in the moderate-severe and DON groups (0.001 ≤ p ≤ 0.04). No variable significantly affected the VD (0.08 ≤ p ≤ 0.9). A lower wi-VD and pp-VD were significantly (0.001 ≤ p ≤ 0.009) correlated with the impaired optic nerve functional and structural tests. The sensitivity and specificity of wi-VD (81% and 76%) and pp-VD (69% and 71%) for detecting the DON were statistically significant (p < 0.001).

Conclusion:

Despite an insignificant rise in the wi- and pp-VD from the healthy volunteers to the patients with Graves’ disease without TED, VD showed a declining trend in the course of patients with TED, which was statistically significant in the moderate-severe TED and DON groups.
Prevalence of pseudophakia: U.S. population–based study
Authors: Erie Ellen A. , Hodge David O. , Mahr Michael A.
Published: October 2021

Purpose:

To determine the current prevalence and trends of pseudophakia in a well-defined U.S. population, calculating values for Olmsted County, Minnesota, from 1988 through 2018.

Setting:

Mayo Clinic, Rochester, Minnesota.

Design:

Population-based cohort study.

Methods:

Rochester Epidemiology Project (REP) databases were used to identify all cases of pseudophakia in Olmsted County, Minnesota, between January 1, 1988, and December 31, 2018. Age- and sex-specific prevalence rates were calculated in 1988, 1998, 2008, and 2018 using REP census population estimates and mortality counts. Poisson regression analysis was used to assess changes in prevalence over time. Mortality rates were estimated by Kaplan-Meier analysis.

Results:

In 2018, 10 024 county residents were pseudophakic in at least 1 eye, for a total population prevalence of 6.5%. The prevalence increased 67% in the last 10 years and 590% in the last 30 years (P < .001). By 2018, 51% of residents aged 75 years and 88% of residents aged 85 years and older were pseudophakic in at least 1 eye, 53% of residents with pseudophakia aged 65 years and older were bilaterally pseudophakic, and 29% of residents with pseudophakia had lived with pseudophakia for more than 10 years. The prevalence was higher among women than men and increased with age (P < .001). Overall, pseudophakia had a lower all-cause mortality compared with the general Minnesota population (P < .001).

Conclusions:

In 2018, most residents aged 75 years and older were pseudophakic in at least 1 eye. These numbers underscore the changing visual status of older adults and the large number of adults who benefit from cataract surgery.
Characterization of Androgen Receptor Complex Associated Protein (ARCAP) in hepatocellular carcinoma and liver
Authors: Chang Tai-Jay , Hsia Cheng-Yuan , Chau Gar-Yang , Hsiao Liang-Tsai , Huang Kuang-Tzu , King Kung-Liang , Lui Wing-Yiu , Li Anna F.-Y. , Wang Chia-Lin , Tsai Pin-Hsing , Chien Yueh , Lin Ta-Hsien
Published: October 2021

Background:

Hepatocellular carcinoma (HCC) ranks many tasks in clinical oncology due to possibly developing a general tumor in men and, usually lead to malignant to death within years. Researches had reported about major factors for being HCC was male sex and HCC associated with cirrhosis in childhood was found more common in males than females. In certain mouse strains as studied, breeding with testosterone significantly increases the development of HCC. Furthermore, castration of male mice diminished the frequency of the development of liver tumors. Meanwhile male hepatitis B virus transgenic mice have a greater occurrence of HCC than females.

Methods:

We apply degenerate priming PCR to observe the expression of various steroid receptors in livers. Yeast-two hybrid screening to search a novel RNA fragment helps to find a new full-length gene by RACE experiment. RT-PCR is applied to detect various expressions in tissues and cell lines. In situ hybridization detects DNA in Chromosome mapping. GFP-constructs transfection proves the gene localization in cells. Immunoprecipitation pulldown assay verifies protein interaction. Gene transfection followed with luciferase assay demonstrates the interaction of genes within cellular signaling. Genomic alignment analysis for observing sequences data perform from NCBI database website (http://www.ncbi.nim.nih.gov/genebank/).

Results:

The androgen receptor (AR) expression level is found at the highest level among the steroid receptors families detected in liver tumors. By yeast-two hybrid screening, we cloned an Androgen Receptor Complex Associated Protein (ARCAP), of 95 Kd in molecular weight and its cDNA. ARCAP locates at Chromosome 1. Our findings indicate ARCAP is highly expressed in hepatoma cell lines and liver tumors and their adjacent tumors as observed. Yeast two-hybrid assay and in vitro immunoprecipitation assays demonstrated an interaction between AR and ARCAP.

Conclusion:

We aim to search for different types and levels of steroid receptors expressed within human HCCs and in the adjacent liver tissues. To verify possible molecular mechanisms by which AR might affect hepatoma cells, we had characterized a novel protein ARCAP which functions as a coregulator to interact with AR within liver. The ligand-dependent AR with its cofactor, ARCAP, can induce a signal cascade by transactivation.
End-of-Life Healthcare Service Needs Among Children With Neurological Conditions: A Latent Class Analysis
Authors: Lindley Lisa C. , Svynarenko Radion , Mooney-Doyle Kim , Mendola Annette , Naumann Wendy C. , Fortney Christine A.
Published: October 2021

BACKGROUND: At the end of life, children with neurological conditions have complex healthcare needs that can be met by providing care of their life-limiting conditions concurrently with hospice care (ie, concurrent care). Given the limited literature on concurrent care for children with neurologic conditions, this investigation aimed to identify patterns of nonhospice, healthcare service needs and to assess characteristics of children within each group. METHODS: A nationally representative sample children with neurological conditions enrolled in concurrent hospice care was used. Latent class analysis and descriptive statistics were calculated to identify patterns of healthcare needs and characteristics of children within the groups. A subgroup analysis of infants was conducted. RESULTS: Among the 1601 children, the most common types of services were inpatient hospitals, durable medical equipment, and home health. Two classes of service needs were identified: moderate intensity (58%) and high intensity (42%). Children in the moderate-intensity group were predominantly between 1 and 5 years old, male, White, and non-Hispanic. The most common neurological condition was central nervous system degeneration. They also had significant comorbidities, mental/behavioral health conditions, and technology dependence. They commonly resided in urban areas in the South. Children in the high-intensity group had a wide range of neurological conditions and high acuity. The subgroup analysis of infants indicated a different neurological profile. CONCLUSIONS: Two distinct classes of nonhospice, healthcare service needs emerged among children with neurological conditions at the end of life. The groups had unique demographic profiles.
Potential Factors for Poor Reproducibility of In Vitro Hemolysis Testing
Authors: von Petersdorff-Campen Kai , Fischer Peter , Bogdanova Anna , Schmid Daners Marianne
Published: October 2021

In vitro testing of hemolysis is essential for the validation and development of ventricular assist devices. However, as many factors influence hemolysis, such tests’ inter- and intralaboratory reproducibility is poor. In this work, CentriMag blood pumps were used to conduct a hemolysis study according to ASTM F1841 with blood from 23 bovine donors. Complementary blood analysis, including cell count, plasma composition, and viscosity, was performed to identify factors relevant to the variability of hemolysis testing results. Three strategies were tested to improve reproducibility: albumin supplementation, maintaining glucose concentration, and replacement of plasma with plasma-like buffer. Differences in red blood cell stability among donors were responsible for the largest portion of the total variance. Hematocrit varied widely among donors, and its adjustment to a standard value led to the artificial introduction of between-donor differences, especially in viscosity. It seems likely, that a more careful selection of donors with similar characteristics or repeated blood collection from the same donor could improve reproducibility. However, no direct correlations were found between the susceptibility to hemolysis and individual donor or blood characteristics in this study. The addition of albumin and glucose had a negligible effect while washing blood samples with artificial plasma significantly reduced mean hemolysis, although not its variation. The findings contribute to the understanding of variability in hemolysis experiments and give reason to question the common standard operating procedures, such as hemodilution or maintaining glucose concentration. To confirm the factors identified here, additional studies isolating the effects of individual factors are necessary.
Transcatheter aortic valve replacement via a transsubclavian approach in a patient with severe aortic stenosis who had previously undergone kidney transplantation
Authors: Oh Seok , Kim Ju Han , Hyun Dae Young , Cho Kyung Hoon , Kim Min Chul , Sim Doo Sun , Hong Young Joon , Ahn Youngkeun , Jeong Myung Ho , Lee Kyo Seon
Published: October 2021

Rationale:

Although the transfemoral approach is the gold standard for transcatheter aortic valve replacement (TAVR), it is not feasible in a considerable number of patients. We report a case of successful transsubclavian TAVR (TS-TAVR) in a patient with severe aortic stenosis (AS) who was ineligible for transfemoral TAVR because she was a kidney transplant recipient.

Patient concerns:

A 72-year-old Korean woman, who had previously undergone kidney transplantation in the right iliac fossa for end-stage kidney disease, was admitted to our center with dyspnea. Upon auscultation, grade IV systolic murmurs were detected in both upper sternal borders and the left lower sternal border, suggestive of valvular heart disease.

Diagnosis:

Two-dimensional transthoracic echocardiography revealed heavy calcification of the aortic valve with a high peak velocity (4.54 m/s) and mean pressure gradient (48.49 mm Hg), indicative of severe AS.

Interventions:

TS-TAVR was performed by a heart team comprised of interventional cardiologists, cardiac surgeons, and anesthesiologists. A self-expandable valve prosthesis (CoreValveTM Evolut RTM, Medtronic Inc., Minneapolis, MN) was successfully deployed via the left subclavian artery.

Outcomes:

Post-TAVR 2-dimensional transthoracic echocardiography demonstrated a well-functioning valve with mild paravalvular leakage. The peak velocity had declined from 4.54 m/s to 2.22 to 2.24 m/s, and the mean pressure gradient had declined from 48.49 to 8.57–9.61 mmHg. The patient was discharged successfully and uneventfully.

Lessons:

Because kidney transplant recipients with severe AS are considered poor candidates for transfemoral TAVR, TS-TAVR is a suitable alternative to consider.
Association of total cholesterol and atherosclerotic cardiovascular disease in patients with follicular thyroid cancer
Authors: Huang Guoding , Lu Hongquan , Li Meigui , Lv Qiongxiu , Chen Qizhu
Published: October 2021

The association between serum total cholesterol (TC) level and incident atherosclerotic cardiovascular disease (ASCVD) in patients with follicular thyroid cancer postthyroidectomy is unknown.

This was a retrospective study and patients (n = 384) were divided into low and high TC groups according to the median TC level. Incidence of composite ASCVD (myocardial infarction, ischemic stroke, and cardiovascular death) was compared between these 2 groups and factors contributing to the association of TC and ASCVD were evaluated.

Patients in the high TC group were older and more likely to have diabetes and have higher C-reactive protein level. After thyroidectomy, serum levels of free triiodothyronine and free thyroxine were lower while thyroid-stimulating hormone level was higher in the high TC group. 31.6% and 39.7% of patients developed hypothyroidism in the low and high TC groups (P < .05) postthyroidectomy. The incidence rate of composite ASCVD was higher in the high TC versus low TC groups, with incidence rate ratio of 1.69 (95% confidence interval [CI]: 1.07–2.69), which was mainly driven by a higher incidence rate of myocardial infarction in the high TC group (incidence rate ratio: 2.11 and 95% CI: 1.10–4.20). In unadjusted model, higher TC was associated with 73% higher risk of composite ASCVD. After adjustment for hypothyroidism, the association of higher TC and composite ASCVD was attenuated into insignificance, with hazard ratio of 0.92 and 95% CI: 0.81 to 1.34.

Increased TC level was associated with composite ASCVD, which might be attributed to hypothyroidism postthyroidectomy. The use of levothyroxine might help to prevent hypercholestemia and reduce the incidence of ASCVD.
Hepatic inflammatory pseudotumor-like follicular dendritic cell tumor with hepatic lymphoma history
Authors: Li Jiang , Tao Hai-su , Chen Dong , Huang Zhi-yong , Zhang Er-lei
Published: October 2021

Rationale:

Hepatic inflammatory pseudotumor (IPT)-like follicular dendritic cell (FDC) sarcoma is a very rare disease. Till now, only 19 cases were reported in the English literature. However, the coexistence of IPT-like sarcoma and non-Hodgkin lymphoma (NHL) in the same patient has never been reported. In this report, we presented a case of hepatic IPT-like FDC with hepatic NHL history of which both were successfully resected.

Patient concerns:

We reported a case of a 47-year-old male patient who presented with right upper abdominal discomfort. Nineteen years ago, he underwent liver resection of segment VII for hepatic NHL (B-cell lymphoma). He had a history of chronic hepatitis B virus infection. Serum alpha fetoprotein level was normal. However, imaging studies revealed a well-circumscribed, solid mass in the right hepatic lobe, he came back to the clinic because he was worried about a recurrence of the B-cell lymphoma.

Diagnoses:

Based on the patient's past medical history and magnetic resonance imaging results, and he was diagnosed as hepatocellular carcinoma or hepatic NHL preoperatively.

Interventions:

Right hemi-hepatectomy was performed on this patient.

Outcomes:

Histological report showed features of a mixture of chronic inflammatory cells and variable amounts of spindle cells. Also, immuno-histo-chemical studies demonstrated that all the tumor cells showed strong nuclear in situ labeling for EBV-encoded small RNAs and strongly positive stainings with CD21 and CD35. The patient tolerated the surgery well, recovered smoothly and he was discharged on postoperative day 7 (day 7). The patient is still disease free after a follow-up of over 50 months.

Conclusions:

To our knowledge, this is the first report demonstrating hepatic IPT-like FDC sarcoma in a patient with primary hepatic NHL history. In regards to treatment, complete surgical resection should be performed and would acquire excellent long-term outcomes.
Workplace Predictors of Quality and Safe Patient Care Delivery Among Nurses Using Machine Learning Techniques
Authors: Havaei Farinaz , Ji Xuejun Ryan , Boamah Sheila A.
Published: October 2021

Background:

Working in unhealthy environments is associated with negative nurse and patient outcomes. Previous body of evidence in this area is limited as it investigated only a few factors within nurses' workplaces.

Purpose:

The purpose of this study was to identify the most important workplace factors predicting nurses' provision of quality and safe patient care using a 13-factor measure of workplace conditions.

Methods:

A cross-sectional correlational survey study involving 4029 direct care nurses in British Columbia was conducted using random forest data analytics methods.

Results:

Nurses' reports of healthier workplaces, particularly workload management, psychological protection, physical safety and engagement, were associated with higher ratings of quality and safe patient care.

Conclusion:

These workplace conditions are perceived to impact patient care through influencing nurses' mental health. To ensure a high standard of patient care, data-driven policies and interventions promoting overall nurse mental health and well-being are urgently required.
Weight-bearing status may influence rates of radiographic healing following reamed, intramedullary fixation of diaphyseal femur fractures
Authors: Flanagan Christopher D. , Joseph Noah M. , Copp Jonathan , Romeo Nicholas , Alfonso Nicholas , Hirschfeld Adam
Published: October 2021

Objective:

To investigate the effect of weight-bearing status on radiographic healing of diaphyseal femur fractures.

Design:

Retrospective 1:1 matched cohort study.

Setting:

Single-level 1 trauma center.

Participants:

One-hundred forty-four (N = 154) patients matched 1:1 in non-weight bearing (NWB) and weight-bearing as tolerated (WBAT) groups.

Intervention:

Non-weight bearing following reamed, statically locked intramedullary fixation of diaphyseal femur fracture, generally due to concurrent lower extremity fracture.

Main Outcome Measurement:

Postoperative radiographic healing using modified Radiographic Union Scale for Tibia fractures (mRUST) scores.

Results:

Groups were well matched on age, sex, race, prevalence of tobacco and alcohol use, diabetes mellitus status, Injury Severity Score, fracture pattern and shaft location, vascular injury, open fracture prevalence, and operative characteristics. Radiographic follow-up was similar between groups (231 vs 228 days, P = .914). At 6 to 8 weeks status post intramedullary fixation, the median mRUST score in the NWB group (9) was lower than that of the WBAT group (10) (mean: 8.4 vs 9.7, P = .004). At 12 to 16 weeks, the median mRUST in the NWB group (10) was again lower than the WBAT group (12) (mean: 9.9 vs 11.7, P = .003). The median number of days to 3 cortices of bridging callous was 85 in the WBAT group, compared with 122 in the NWB group (P = .029). Median time to mRUST scores of 12 (111 vs 162 days, P = .008), 13 (218 vs 278 days, P = .023), and 14 (255 vs 320 days, P = .028) were all longer in the NWB group compared with the WBAT group.

Conclusions:

Non-weight bearing after intramedullary fixation of diaphyseal femur fractures delays radiographic healing, with median time to 3 cortices of bridging callous increased from 85 days in WBAT groups to 122 days in NWB groups. These results provide clinicians with an understanding of the expected postoperative course, as well as further support the need to expeditiously advance weight-bearing status.

Level of Evidence: IV
Description and Functional Outcomes of a Novel Interdisciplinary Rehabilitation Program for Hospitalized Patients With COVID-19
Authors: Patel Nija , Steinberg Chelsea , Patel Ruchi , Chomali Cheryl , Doulatani Gargi , Lindsay Leroy , Jaywant Abhishek
Published: October 2021

Objectives

The aims of the study were to describe an interdisciplinary inpatient rehabilitation program for patients recovering from COVID-19 and to evaluate functional outcomes.

Design

This is an analysis of retrospective data captured from the electronic health record of COVID-19 patients admitted to the rehabilitation unit (N = 106). Rehabilitation approaches are described narratively. Functional gain was evaluated using the Activity Measure for Postacute Care 6 Clicks, basic mobility and daily activities.

Results

Interdisciplinary approaches were implemented to address the medical, physical, communication, cognitive, and psychosocial needs of COVID-19 patients. COVID-19 patients exhibited significant improvements in basic mobility (Activity Measure for Postacute Care for basic mobility, P < 0.001, Cohen d = 1.35) and daily activities (Activity Measure for Postacute Care for daily activities, P < 0.001, Cohen d = 1.06) from admission to discharge. There was an increase in ambulatory distance as well as the percentage of the patients who were able to breathe on room air. At discharge, fewer patients required supplemental oxygen on exertion. Eighty percent of the patients were discharged home after an average length of stay of 17 days. Greater functional improvement was associated with younger age, longer intubation duration, and participation in psychotherapy, but not a history of delirium during hospitalization.

Conclusions

Early rehabilitation is associated with improved mobility and independence in activities of daily living after COVID-19.
The Hirsch Index and Self-Citation in Academic Physiatry Among Graduate Medical Education Program Directors
Authors: Pfirrman Scott J. , Yheulon Christopher G. , Parziale John R.
Published: October 2021

The Hirsch Index is a measure of academic productivity which captures both the quantity and quality of an author’s output. A well-accepted bibliometric, the Hirsch Index still may be influenced by self-citation, which has been assessed in other medical and surgical specialties. This study aims to evaluate research output and self-citation in physiatry, establishing a benchmark for the field, in addition to identifying differences between physical medicine and rehabilitation subspecialties. This study identified physical medicine and rehabilitation residency and fellowship program directors and analyzed the number of publications, citations, self-citations, and h-indices. A total of 169 program directors were identified, and the mean number ± SD of publications, citations, and Hirsch Index for the cohort were 16.7 ± 29.5, 348 ± 753, and 5.7 ± 6.7, respectively. When self-citation was excluded, less than 2% of program directors (3 of 169) had changes in Hirsch Index greater than one integer, and none greater than two integers. The Hirsch Index remained unchanged for 90% (152 of 169). Spinal cord injury fellowship directors had significantly higher mean number of publications (28, P = 0.04), mean number of citations (672, P = 0.03), and Hirsch Index (9.2, P < 0.01; 95% confidence interval). Overall, self-citation is infrequent in physical medicine and rehabilitation, and spinal cord injury directors had more robust academic profiles.
Role of Adjuvant Therapy in Esophageal Cancer Patients After Neoadjuvant Therapy and Esophagectomy
Authors: Lee Yung , Samarasinghe Yasith , Lee Michael H. , Thiru Luxmy , Shargall Yaron , Finley Christian , Hanna Wael , Levine Oren , Juergens Rosalyn , Agzarian John
Published: October 2021

Objective:

The aim of this study was to analyze esophageal cancer patients who previously underwent neoadjuvant therapy followed by a curative resection to determine whether additional adjuvant therapy is associated with improved survival outcomes.

Summary Background Data:

Neoadjuvant therapy followed by surgery is the standard of care for locally advanced esophageal cancer, whereas adjuvant therapy is typically employed for patients with residual disease. However, the role of adjuvant therapy after a curative resection is still uncertain.

Methods:

MEDLINE, EMBASE, and CENTRAL databases were searched for studies comparing patients with esophageal cancer who underwent neoadjuvant therapy and curative resection with and without adjuvant therapy. Primary outcome was overall survival (OS), and random effects meta-analysis was conducted where appropriate. Grading of recommendations, assessment, development, and evaluation was used to assess the certainty of evidence.

Results:

Ten studies involving 6462 patients were included. When compared to patients who received neoadjuvant therapy and esophagectomy alone, adjuvant therapy groups experienced a significant decrease in mortality by 48% at 1 year (Risk Ratio (RR) 0.52, 95% confidence interval [CI] 0.41–0.65,P< 0.001,moderate certainty). This reduction in mortality was carried through to 5-year follow-up (RR 0.91, 95% CI 0.86–0.96,P< 0.001,moderate certainty). The difference between the adjuvant therapy and the control group was uncertain regarding the secondary outcomes.

Conclusion:

Adjuvant therapy after neoadjuvant treatment and esophagectomy with negative resection margins provide an improved OS at 1 and 5 years with moderate to high certainty of evidence, but the benefit for disease-free survival and locoregional/distal recurrence remain uncertain due to limited reporting of these outcomes.
Reduced sialidase activity of influenza A(H3N2) neuraminidase associated with positively charged amino acid substitutions
Authors: Hussain Saira , Daniels Rodney S. , Wharton Stephen A. , Howell Steven , Halai Chandrika , Kunzelmann Simone , Whittaker Lynne , McCauley John W.
Published: October 2021

Neuraminidase (NA) inhibitors (NAI), oseltamivir and zanamivir, are the main antiviral medications for influenza and monitoring of susceptibility to these antivirals is routinely done by determining 50 % inhibitory concentrations (IC50) with MUNANA substrate. During 2010–2019, levels of A(H3N2) viruses presenting reduced NAI inhibition (RI) were low (~0.75 %) but varied year-on-year. The highest proportions of viruses showing RI were observed during the 2013–2014, 2016–2017 and 2017–2018 Northern Hemisphere seasons. The majority of RI viruses were found to contain positively charged NA amino acid substitutions of N329K, K/S329R, S331R or S334R, being notably higher during the 2016–2017 season. Sialidase activity kinetics were determined for viruses of RI phenotype and contemporary wild-type (WT) viruses showing close genetic relatedness and displaying normal inhibition (NI). RI phenotypes resulted from reduced sialidase activity compared to relevant WT viruses. Those containing S329R or N329K or S331R showed markedly higher Km for the substrate and Ki values for NAIs, while those with S334R showed smaller effects. Substitutions at N329 and S331 disrupt a glycosylation sequon (NDS), confirmed to be utilised by mass spectrometry. However, gain of positive charge at all three positions was the major factor influencing the kinetic effects, not loss of glycosylation. Because of the altered enzyme characteristics NAs carrying these substitutions cannot be assessed reliably for susceptibility to NAIs using standard MUNANA-based assays due to reductions in the affinity of the enzyme for its substrate and the concentration of the substrate usually used.
2-Alkyl-4-quinolone quorum sensing molecules are biomarkers for culture-independent Pseudomonas aeruginosa burden in adults with cystic fibrosis
Authors: Zain Nur Masirah M. , Webb Karmel , Stewart Iain , Halliday Nigel , Barrett David A. , Nash Edward F. , Whitehouse Joanna L. , Honeybourne David , Smyth Alan R. , Forrester Douglas L. , Knox Alan J. , Williams Paul , Fogarty Andrew , Cámara Miguel , Bruce Kenneth D. , Barr Helen L.
Published: October 2021

Introduction.

Pseudomonas aeruginosa

produces quorum sensing signalling molecules including 2-alkyl-4-quinolones (AQs), which regulate virulence factor production in the cystic fibrosis (CF) airways.

Hypothesis/Gap statement. Culture can lead to condition-dependent artefacts which may limit the potential insights and applications of AQs as minimally-invasive biomarkers of bacterial load.

Aim. We aimed to use culture-independent methods to explore the correlations between AQ levels and live

P. aeruginosa

load in adults with CF.

Methodology. Seventy-five sputum samples at clinical stability and 48 paired sputum samples obtained at the beginning and end of IV antibiotics for a pulmonary exacerbation in adults with CF were processed using a viable cell separation technique followed by quantitative

P. aeruginosa

polymerase chain reaction (qPCR). Live

P. aeruginosa

qPCR load was compared with the concentrations of three AQs (HHQ, NHQ and HQNO) detected in sputum, plasma and urine.

Results. At clinical stability and the beginning of IV antibiotics for pulmonary exacerbation, HHQ, NHQ and HQNO measured in sputum, plasma and urine were consistently positively correlated with live

P. aeruginosa

qPCR load in sputum, compared to culture. Following systemic antibiotics live

P. aeruginosa

qPCR load decreased significantly (P<0.001) and was correlated with a reduction in plasma NHQ (plasma: r=0.463, P=0.003).

Conclusion. In adults with CF, AQ concentrations correlated more strongly with live

P. aeruginosa

bacterial load measured by qPCR compared to traditional culture. Prospective studies are required to assess the potential of systemic AQs as biomarkers of

P. aeruginosa

bacterial burden.
Rotational Activity Around an Obstacle in 2D Cardiac Tissue in Presence of Cellular Heterogeneity
Authors: Konovalov Pavel , Mangileva Daria , Dokuchaev Arsenii , Solovyova Olga , Panfilov Alexander V.
Published: October 2021

Waves of electrical excitation rotating around an obstacle is one of the important mechanisms of dangerous cardiac arrhythmias occurring in the heart damaged by post-infarction scar. Such a scar also has a border zone around it, which has electrophysiological properties different from the rest of normal myocardial tissue. Spatial patterns of wave rotation in the presence of such tissue heterogeneity are poorly studied. In this paper we perform a comprehensive numerical study of various regimes of rotation of a wave in a plane layer of the ventricular tissue around an obstacle surrounded by a gray zone. We use a TP06 cellular ionic model which reproduces the electrophysiological properties of cardiomyocytes in the left ventricle of human heart. We vary the extent of obstacle and gray zone and study the pattern of wave rotation and its period. We observed different regimes of wave rotation that can be subdivided into several classes: (1) functional rotation and (2) scar rotation regimes, which were identified in the previous studies, and new (3) gray zone rotation regime: where the wave instead of rotation around the obstacle, rotates around the gray zone (an area of tissue heterogeneity) itself. For each class, the period of rotation is determined by different factors, which we discuss and quantify. We also found that due to regional pathological remodeling of myocardial tissue, we can obtain additional regimes associated with dynamical instabilities of two types which may affect or not affect the period of rotation.
A cell-based screen identifies HDAC inhibitors as activators of RIG-I signaling
Authors: Fraile-Bethencourt Eugenia , Foss Marie H , Nelson Dylan , Malhotra Sanjay V , Anand Sudarshan
Published: October 2021

Enhancing the immune microenvironment in cancer by targeting the nucleic acid sensors is becoming a potent therapeutic strategy. Among the nucleic acid sensors, activation of the RNA sensor Retinoic Acid-inducible Gene (RIG-I) using small hairpin RNAs has been shown to elicit powerful innate and adaptive immune responses. Given the challenges inherent in pharmacokinetics and delivery of RNA based agonists, we set out to discover small molecule agonists of RIG-I using a cell-based assay. To this end, we established and validated a robust high throughput screening assay based on a commercially available HEK293 reporter cell line with a luciferase reporter downstream of tandem interferon stimulated gene 54 (ISG54) promoter elements. We first confirmed that the luminescence in this cell line is dependent on RIG-I and the interferon receptor using a hairpin RNA RIG-I agonist. We established a 96-well and a 384-well format HTS based on this cell line and performed a proof-of-concept screen using an FDA approved drug library of 1200 compounds. Surprisingly, we found two HDAC inhibitors Entinostat, Mocetinostat and the PLK1 inhibitor Volasertib significantly enhanced ISG-luciferase activity. This luminescence was substantially diminished in the null reporter cell line indicating the increase in signaling was dependent on RIG-I expression. Combination treatment of tumor cell lines with Entinostat increased RIG-I induced cell death in a mammary carcinoma cell line that is resistant to either Entinostat or RIG-I agonist alone. Taken together, our data indicates an unexpected role for HDAC1,-3 inhibitors in enhancing RIG-I signaling and highlight potential opportunities for therapeutic combinations.
SVAT: Secure Outsourcing of Variant Annotation and Genotype Aggregation
Authors: Kim Miran , Wang Su , Jiang Xiaoqian , Harmanci Arif
Published: October 2021

Background

Sequencing of thousands of samples provides genetic variants with allele frequencies spanning a very large spectrum and gives invaluable insight for genetic determinants of diseases. Protecting the genetic privacy of participants is challenging as only a few rare variants can easily re-identify an individual among millions. In certain cases, there are policy barriers against sharing genetic data from indigenous populations and stigmatizing conditions.

Results

We present SVAT, a method for secure outsourcing of variant annotation and aggregation, which are two basic steps in variant interpretation and detection of causal variants. SVAT uses homomorphic encryption to encrypt the data at the client-side. The data always stays encrypted while it is stored, in-transit, and most importantly while it is analyzed. SVAT makes use of a vectorized data representation to convert annotation and aggregation into efficient vectorized operations in a single framework. Also, SVAT utilizes a secure re-encryption approach so that multiple disparate genotype datasets can be combined for federated aggregation and secure computation of allele frequencies on the aggregated dataset.

Conclusions

Overall, SVAT provides a secure, flexible, and practical framework for privacy-aware outsourcing of annotation, filtering, and aggregation of genetic variants. SVAT is publicly available for download from https://github.com/harmancilab/SVAT
Nanoparticle Shape Governs Immunomodulation of MUC1 Antigen to Develop Anti-cancer Vaccine
Authors: Toraskar Suraj , Chaudhary Preeti Madhukar , Kikkeri Raghavendra
Published: October 2021

T-cell-dependent immunomodulation of carbohydrate antigens under benign conditions is the most promising approach for carbohydrate-based vaccine development. However, to achieve such adaptive immune responses, well-defined multifunctional nanocarriers loaded with immunogenic materials must be explored. Current efforts to use gold nanoparticles (AuNPs) as antigen carriers in vaccine development have conveniently introduced considerable diversity. Here, we show that the shape of AuNPs markedly influences carbohydrate-based antigen processing in murine dendritic cells (mDCs) and subsequent T-cell activation. In the study, CpG-adjuvant coated sphere-, rod-, and star-shaped AuNPs were conjugated to the tripodal Tn-glycopeptide antigen to study their DC uptake and the activation of T-cells in the DCs/T-cell co-culture assay. Our results showed that sphere- and star-shaped AuNPs displayed relatively weak receptor-mediated uptake but induced a high level of T helper-1 (Th1) biasing immune responses compared with rod-shaped AuNPs, showing that receptor-mediated uptake and cytokine secretion of nanostructures are two independent mechanisms. Significantly, the shapes of AuNPs and antigen/adjuvant conjugation synergistically work together to modulate the effective anti-Tn-glycopeptide immunoglobulin (IgG) antibody response after in vivo administration of the AuNPs. These results show that by varying the shape parameter, one can alter the immunomodulation, leading to the development of carbohydrate vaccines.
Genome-wide functional screens enable the prediction of high activity CRISPR-Cas9 and -Cas12a guides in Yarrowia lipolytica
Authors: Baisya Dipankar , Ramesh Adithya , Schwartz Cory , Lonardi Stefano , Wheeldon Ian
Published: October 2021

Genome-wide functional genetic screens have been successful in discovering genotype-phenotype relationships and in engineering new phenotypes. While broadly applied in mammalian cell lines and in E. coli, use in non-conventional microorganisms has been limited, in part, due to the inability to accurately design high activity CRISPR guides in such species. Here, we develop an experimental-computational approach to sgRNA design that is specific to an organism of choice, in this case the oleaginous yeast Yarrowia lipolytica. A negative selection screen in the absence of non-homologous end-joining, the dominant DNA repair mechanism, was used to generate single guide RNA (sgRNA) activity profiles for both SpCas9 and LbCas12a. This genome-wide data served as input to a deep learning algorithm, DeepGuide, that is able to accurately predict guide activity. DeepGuide uses unsupervised learning to obtain a compressed representation of the genome, followed by supervised learning to map sgRNA sequence, genomic context, and epigenetic features with guide activity. Experimental validation, both genome-wide and with a subset of selected genes, confirms DeepGuide’s ability to accurately predict high activity sgRNAs. DeepGuide provides an organism specific predictor of CRISPR guide activity that could be broadly applied to fungal species, prokaryotes, and other non-conventional organisms.