bluuebunny/crossref_metadata_2025 huggingface dataset:
Surveillance Imaging vs Symptomatic Recurrence Detection and Survival in Stage II-III Breast Cancer (AFT-01)
Authors: Schumacher Jessica R , Neuman Heather B , Yu Menggang , Vanness David J , Si Yajuan , Burnside Elizabeth S , Ruddy Kathryn J , Partridge Ann H , Schrag Deborah , Edge Stephen B , Zhang Ying , Jacobs Elizabeth A , Havlena Jeffrey , Francescatti Amanda B , Winchester David P , McKellar Daniel P , Spears Patricia A , Kozower Benjamin D , Chang George J , Greenberg Caprice C ,   for the Alliance ACS-CRP CCDR Breast Cancer Surveillance Working Group, Ballman Karla , Gavin Patrick , Green Bettye , Perlmutter Jane , Berger Elizabeth , Punglia Rinaa , Chen Ronald , Brys Nicole , Adesoye Taiwo
Published: August 2022

Background

Guidelines for follow-up after locoregional breast cancer treatment recommend imaging for distant metastases only in the presence of patient signs and/or symptoms. However, guidelines have not been updated to reflect advances in imaging, systemic therapy, or the understanding of biological subtype. We assessed the association between mode of distant recurrence detection and survival.

Methods

In this observational study, a stage-stratified random sample of women with stage II-III breast cancer in 2006-2007 and followed through 2016 was selected, including up to 10 women from each of 1217 Commission on Cancer facilities (n = 10 076). The explanatory variable was mode of recurrence detection (asymptomatic imaging vs signs and/or symptoms). The outcome was time from initial cancer diagnosis to death. Registrars abstracted scan type, intent (cancer-related vs not, asymptomatic surveillance vs not), and recurrence. Data were merged with each patient’s National Cancer Database record.

Results

Surveillance imaging detected 23.3% (284 of 1220) of distant recurrences (76.7%, 936 of 1220 by signs and/or symptoms). Based on propensity-weighted multivariable Cox proportional hazards models, patients with asymptomatic imaging compared with sign and/or symptom detected recurrences had a lower risk of death if estrogen receptor (ER) and progesterone receptor (PR) negative, HER2 negative (triple negative; hazard ratio [HR] = 0.73, 95% confidence interval [CI] = 0.54 to 0.99), or HER2 positive (HR = 0.51, 95% CI = 0.33 to 0.80). No association was observed for ER- or PR-positive, HER2-negative (HR = 1.14, 95% CI = 0.91 to 1.44) cancers.

Conclusions

Recurrence detection by asymptomatic imaging compared with signs and/or symptoms was associated with lower risk of death for triple-negative and HER2-positive, but not ER- or PR-positive, HER2-negative cancers. A randomized trial is warranted to evaluate imaging surveillance for metastases results in these subgroups.
Typical ephemeral plant—Erodium oxyrhinchum: growth response to snow change in temperate desert, Northwest China
Authors: Yin Jin-Fei , Zhou Xiao-Bing , Wu Nan , Zhang Yuanming
Published: August 2022

Snow-cover changes in temperate desert ecosystems influence plant diversity, richness and distribution. The growth and distribution of herbaceous plants in these ecosystems are closely related to snow-cover depth, the most important water resource during the growth period due to water shortage during the dry season. However, the response to snow-cover change in winter remains unclear. The present investigation was undertaken to examine the influence of snow-cover change on the root growth of herbaceous species. The growth of desert typical ephemeral species, Erodium oxyrhinchum, was examined in Gurbantunggut Desert with four snow-cover depth treatments in winter. The four treatments were snow removal (−S), ambient snow, double snow (+S) and triple snow (+2S). The snow depth addition increased the abundance and growth rate of herbaceous plants. It also enhanced the biomass (including total and individual biomass) of these plants. The leaf area of E. oxyrhinchum increased significantly with snow addition, and the leaf dry matter content had an opposite trend. The study showed that the aboveground section of the plant was more sensitive to snow change than the underground. Snow change also influenced the root morphology. Snow removal resulted in the emergence of more lateral roots, whereas snow addition promoted the elongation of the main root for water and nutrient absorption. These results explain how changes in winter snow-cover depth alter plant growth, community structure and ecosystem function during the growing period in temperate desert ecosystems.
Surgical treatment of hepatic xanthogranuloma arising from a giant hepatic cyst causing gastrointestinal obstruction: a case report
Authors: Kohata Akihiro , Inoue Masashi , Nomimura Ken , Matsubara Kazuki , Kochi Masatoshi , Hotta Ryuichi , Miyamoto Kazuaki , Toyota Kazuhiro , Sadamoto Seiji , Takahashi Tadateru
Published: August 2022

Hepatic cysts are benign liver lesions and are often asymptomatic. Large hepatic cysts may cause jaundice and portal hypertension; however, they rarely cause gastrointestinal obstruction. Symptomatic cysts require treatment, and when malignancy is suspected, cyst puncture for pathological examination of the fluid may pose a risk of dissemination. Herein, we describe a case of xanthogranuloma arising from a large hepatic cyst that was causing duodenal obstruction. Thus, cyst puncture was performed for emergency decompression. Cytological examination of the puncture fluid revealed no malignant findings. Hence, laparoscopic deroofing was performed to treat the hepatic cyst. As the cyst and duodenal wall were firmly adherent, the cyst wall was left behind without dissection from the duodenum. A two-stage approach of cyst puncture followed by surgery may be an option for patients requiring urgent treatment for potentially malignant hepatic cysts.
Incidental discovery of goblet cell carcinoid, a rare appendiceal malignancy case report
Authors: Barbash Daniel , Trivedi Aakash A , Yang James Y , Nguyen Richard B , Huribal John C , Zuberi Jamshed , Elsawy Osama , Wessner Scott
Published: August 2022

Goblet cell carcinoid (GCC) tumor is a rare appendiceal carcinoma that has had several names throughout its history. Often found incidentally on pathology following an appendectomy, treatment includes a right hemicolectomy and possible adjuvant chemotherapy. Survival rate has been shown to be correlated with the histological features. Here, we report a 45-year-old African American male who presented with signs and symptoms consistent with acute appendicitis, but was ultimately diagnosed with GCC. After undergoing a right hemicolectomy, he continues to undergo long-term surveillance with his oncologist. Due to the rarity of this tumor, we describe the history of GCC and our recommendations for surgical and long-term management.
Subaltern subjectivity and embodiment in human rights practices
Authors: Abdelkarim Shaimaa
Published: August 2022

This article problematises the representation of subaltern resistance in practices of human rights. It critiques the normative framing of the subaltern by those practices, a framing which it argues contributes to their subjugation. Against such framing, the article follows the 2011 Egyptian uprising through the film Rags & Tatters, offering a practice of freedom beyond human rights and through self-recollection.
Effects of Neural Mobilization on Sensory Dysfunction and Peripheral Nerve Degeneration in Rats With Painful Diabetic Neuropathy
Authors: Zhu Guan-Cheng , Chen Yu-Wen , Tsai Kun-Ling , Wang Jhi-Joung , Hung Ching-Hsia , Schmid Annina B
Published: August 2022

Objective

This study aims to evaluate the effectiveness of neural mobilization (NM) in the management of sensory dysfunction and nerve degeneration related to experimental painful diabetic neuropathy (PDN).

Methods

This is a pre-clinical animal study performed in the streptozocin-induced diabetic rat model. Three groups were included: a treatment group of rats with PDN receiving NM under anesthesia (PDN-NM, n = 10), a sham treatment group of rats with PDN that received only anesthesia (PDN-Sham, n = 9), and a vehicle control group with nondiabetic animals (Vehicle, n = 10). Rats in the PDN-NM and PDN-Sham groups received 1 treatment session on days 10, 12, and 14 after streptozocin injection, with a 48-hour rest period between sessions. Behavioral tests were performed using von Frey and Plantar tests. Evaluation for peripheral nerve degeneration was performed through measuring protein gene product 9.5-positive intra-epidermal nerve fiber density in hind-paw skin biopsies. All measurements were performed by a blinded investigator.

Results

The behavioral tests showed that a single NM session could reduce hyperalgesia, which was maintained for 48 hours. The second treatment session further improved this treatment effect, and the third session maintained it. These results suggest that it requires multiple treatment sessions to produce and maintain hypoalgesic effects. Skin biopsy analysis showed that the protein gene product 9.5-positive intra-epidermal nerve fiber density was higher on the experimental side of the PDN-NM group compared with the PDN-Sham group, suggesting NM may mitigate the degeneration of peripheral nerves.

Conclusion

This study demonstrated that NM may be an effective method to manage experimentally induced PDN, potentially through mitigation of nerve degeneration. Further studies are needed to develop standardized protocols for clinical use.

Impact

These findings provide neurophysiological evidence for the use of NM in PDN and can form the basis for the development of physical therapy-based programs in clinics.
Mitochondria-targeting polydopamine-coated nanodrugs for effective photothermal- and chemo-synergistic therapies against lung cancer
Authors: Meng Ziyu , Wang Binchao , Liu Yiqiang , Wan Yejian , Liu Qianshi , Xu Huasheng , Liang Renchuan , Shi Ying , Tu Peng , Wu Hong , Xu Chuan
Published: August 2022

Targeting mitochondria via nano platform emerged as an attractive anti-tumor pathway due to the central regulation role in cellar apoptosis and drug resistance. Here, a mitochondria-targeting nanoparticle (TOS-PDA-PEG-TPP) was designed to precisely deliver polydopamine (PDA) as the photothermal agent and alpha-tocopherol succinate (α-TOS) as the chemotherapeutic drug to the mitochondria of the tumor cells, which inhibits the tumor growth through chemo- and photothermal- synergistic therapies. TOS-PDA-PEG-TPP was constructed by coating PDA on the surface of TOS NPs self-assembled by α-TOS, followed by grafting PEG and triphenylphosphonium (TPP) on their surface to prolong the blood circulation time and target delivery of TOS and PDA to the mitochondria of tumor cells. In vitro studies showed that TOS-PDA-PEG-TPP could be efficiently internalized by tumor cells and accumulated at mitochondria, resulting in cellular apoptosis and synergistic inhibition of tumor cell proliferation. In vivo studies demonstrated that TOS-PDA-PEG-TPP could be efficiently localized at tumor sites and significantly restrain the tumor growth under NIR irradiation without apparent toxicity or deleterious effects. Conclusively, the combination strategy adopted for functional nanodrugs construction aimed at target-delivering therapeutic agents with different action mechanisms to the same intracellular organelles can be extended to other nanodrugs-dependent therapeutic systems.
Tar Spot of Corn: A Diagnostic and Methods Guide
Authors: Solórzano José E. , Cruz C. D. , Arenz Brett E. , Malvick Dean K. , Kleczewski Nathan M.
Published: August 2022

Tar spot of corn is an emerging plant disease in the continental United States and Canada caused by the fungal pathogen Phyllachora maydis Maubl. Tar spot has been known to occur in Mexico, the Caribbean, and Central and South America since the early to mid-1900s. In 2015, it was reported for the first time in the continental United States. Since that time, tar spot has spread across corn-producing areas in the United States with epidemics as recent as 2021 resulting in significant yield losses. Although tar spot has been known to affect corn for over a century in the Americas, the biology of the pathogen, etiology, and epidemiology of the disease are not well understood. Additionally, symptoms and signs of tar spot resemble other foliar diseases and abiotic disorders of corn, which may lead to misdiagnosis. In this paper, we provide a brief description of current knowledge about tar spot of corn, including pathogen taxonomy, host range, symptoms and signs, specimen storage, pathogenicity testing, diagnostic protocols, and geographic distribution. This information will be useful to diagnosticians, researchers, and other professionals working with this disease.
Three-year Retention Rates With Office-based Treatment of Buprenorphine for Opioid Use Disorder in a Private Family Medicine Practice
Authors: Cope Kevin , DeMicco James , Salib Justina , Michael Mina , Yakoub Peter , Daoud Kirollos , Cope Rebecca
Published: August 2022

Objective

Although primary care settings have benefits for implementing office-based opioid treatment (OBOT) programs with buprenorphine, few studies have examined the impact on patient retention beyond 12 months. The objective of this study is to assess long-term outcomes of buprenorphine treatment for opioid use disorder (OUD) integrated into comprehensive primary care treatment at a family medicine practice.

Methods

A retrospective chart review of patients diagnosed with OUD who received treatment with buprenorphine between December 2006 and January 2018 was conducted at private family medicine practice in semirural Upstate New York. Patients were seen continuously by the same provider. The primary outcome was retention in OBOT at 3 years.

Results

The primary outcome was met by 47.4% of included patients (N = 152). Mean retention in care for all patients was 24.3 months. More than three quarters of patients (77%) had a least one psychiatric comorbidity managed by the practice, most commonly depression (59.9%). Self-reported history of intravenous drug use at baseline was associated with a higher likelihood of patient dropout at year 1 (odds ratio, 2.99; 95% confidence interval, 1.39–6.44; P = 0.004) and year 2 (odds ratio, 2.46; 95% confidence interval, 1.15–5.28; P = 0.019), with no difference observed at year 3.

Conclusions

Office-based opioid treatment with buprenorphine in a family medicine practice setting resulted in high retention rates, emphasizing the importance of continuity of care and integration of primary care within the OUD treatment model. Further research is needed on barriers to implementation of OBOT among family medicine providers.
Addiction Services for Veterans: Opportunities in Acute Care
Authors: Shah Meghna N. , Starks Helene , Wander Pandora L. , Saxon Andrew J.
Published: August 2022

Objective

This study aimed to estimate the proportion of total hospital discharges that involved a primary or secondary substance-related diagnosis code (SubDx) on inpatient medicine, psychiatry, and surgery services as part of a needs assessment for inpatient addiction consultation at our large, academic-affiliated Veterans Affairs (VA) hospital.

Methods

We first calculated the percentage of total and service-specific discharges with a primary or secondary substance-related International Classification of Disease, Tenth Revision, code on all inpatient services (medicine, psychiatry, and surgery) in Fiscal Year 2017, 2018, and 2019, using facility-level data. Second, we calculated the proportion of total discharges that involved alcohol- and opioid-related diagnoses.

Results

Over the 3 years studied, 29% of total discharges had a SubDx (4469 of 15,575). The proportion of total discharges that involved a SubDx was 23% (1246 of 5449) in 2017, 31% (1664 of 5332) in 2018, and 33% in 2019 (1559 of 4794), a statistically significant increase (P < 0.001). As a percentage of service-specific discharges, 65% of discharges from psychiatry (1446 of 2217) had a SubDx, compared with 25% from medicine (2469 of 9713), and 15% from surgery (554 of 3645). Medicine services had the most discharges with SubDx, with a year-over-year increase in the number of discharges with SubDx. The percentage of total discharges that involved alcohol- and opioid-related diagnoses was 14% and 4%, respectively.

Conclusions

Substance-related diagnoses are prevalent at our hospital and are increasing over time. The largest number of discharges with SubDx was found on medicine services. Alcohol-related diagnoses were nearly 4 times more prevalent than opioid-related diagnoses. We found focused need around alcohol use and alcohol withdrawal.
Will the new treatment recommendations for asthma increase adverse events?
Authors: Dalin Dagmar A. , Koch Nicoline E. , Hilberg Ole
Published: August 2022

The Global Initiative for Asthma has since 2019 recommended as-needed inhaled steroids (ICS)/formoterol either alone or in combination with ICS/long-acting β2-agonists (LABA) maintenance for mild to moderate asthma. This might give patients more adverse effects by using LABA instead of short-acting β2-agonists (SABA) and by using ICS as needed where the patient might not be able to wash their mouth after use. The objective of this study is through a literature review to investigate whether the new recommendations increase the incidence of adverse events. We included 15 randomized clinical trials. They showed no increase in adverse events with as-needed ICS/formoterol only compared with either as-needed SABA only or maintenance ICS and SABA as-needed, and even a small tendency to less adverse events. When comparing as-needed and maintenance ICS/formoterol with as-needed SABA and maintenance ICS/LABA a small increase was seen for some adverse events, especially candidiasis (1.4 vs. 0.7%) and dysphonia (1.5 vs. 1.0%). In conclusion, the new treatment with as-needed ICS/formoterol only is at least as safe as the previously recommended treatment, regarding adverse effects. ICS/formoterol used as needed and maintenance might give an increased risk of candidiasis and dysphonia, though the absolute risk remains low.
Association Between Working Hours and Poor Glycemic Control in Patients With Diabetes
Authors: Seo Eunhye , Lee Yesung , Lee Woncheol
Published: August 2022

Objective

This study aimed to evaluate the relationship between working hours and glycemic control.

Methods

Study was performed among Korean participants who underwent at least two health screening examinations between 2012 and 2018. The study included 2169 participants who were older than 40 years and undergoing treatment for diabetes at baseline. A hemoglobin A1c level >9% at the follow-up visit was defined as poor glycemic control. The weekly working hours were divided into three groups for analysis.

Results

Compared with participants with 45–54 weekly working hours, multivariate-adjusted hazard ratios (95% confidence intervals) for incident poor glycemic control among participants with ≥55 and 35–44 working hours were 1.40 (1.01–1.96) and 1.51 (1.09–2.09), respectively.

Conclusions

Standard working hours and long working hours were independent risk factors for poor diabetes control in patients with diabetes.
The Effects of Visual Field Loss from Stroke on Performance in a Driving Simulator
Authors: Bro Tomas , Andersson Jan
Published: August 2022

SIGNIFICANCE

Visual field loss is a common consequence of stroke and often precludes driving. However, legal visual requirements for drivers' licenses are largely without scientific basis.

PURPOSE

This study aimed to examine the effects of different types of homonymous visual field loss after stroke on simulated driving.

METHODS

Data on performance and safety from a traffic simulator test for 153 participants with withdrawn drivers' licenses due to visual field loss from stroke were retrospectively compared with data from 83 healthy individuals without visual deficits in a cross-sectional study. The 93 individuals in the stroke group who regained their driving licenses after a successful simulator test were then followed in a national accident database.

RESULTS

Sixty-five percent of the stroke participants passed the simulator test (95% confidence interval, 57 to 72%). Younger patients were more successful than older. However, classification by neither type of homonymous visual field loss nor side of visual field loss was predictive of driver safety. Participants with hemianopia had their lateral lane position dislocated to the nonaffected side of the visual field. None of the participants with a regained license were involved in motor vehicle accidents 3 to 6 years after the test.

CONCLUSIONS

In this large cohort, driver safety could not be predicted from the type of homonymous visual field loss. Even individuals with severe visual field loss might be safe drivers. Therefore, it seems reasonable to provide an opportunity for individualized assessments of practical fitness to drive in circumstances of licensing issues. This study demonstrates the potential of using a standardized driving simulator test for such assessments of fitness to drive.
Relationships among Clinical Factors and Patient-reported Outcome Measures in Adults with Convergence Insufficiency
Authors: Lorenzana Ingryd J. , Leske David A. , Hatt Sarah R. , Dean Trevano W. , Jenewein Erin C. , Dagi Linda R. , Beal Casey J. , Pang Yi , Retnasothie Dashaini V. , Esposito Christina A. , Erzurum S. A. , Aldrich Amy E. , Crouch Eric R. , Li Zhuokai , Kraker Raymond T. , Holmes Jonathan M. , Cotter Susan A.
Published: August 2022

SIGNIFICANCE

When exploring relationships among clinical measures and patient-reported outcome measures in adults with convergence insufficiency, worse symptoms (Convergence Insufficiency Symptom Survey [CISS] score) seemed to be correlated with worse reading function domain score (Adult Strabismus-20 quality-of-life questionnaire). After treatment, improved symptoms were associated with improved reading function quality of life.

PURPOSE

This study aimed to explore relationships between clinical measures and patient-reported outcome measures in adults undergoing treatment for symptomatic convergence insufficiency.

METHODS

In a prospective multicenter observational study, we evaluated adults with symptomatic convergence insufficiency (i.e., clinical measures of near exodeviation, receded near point of convergence, reduced near positive fusional vergence; CISS score ≥21). Fifty-seven participants treated with vision therapy/exercises (n = 35) or base-in prism (n = 22) were analyzed. Spearman correlation coefficients (R) were used to assess associations among the three clinical measures and patient-reported outcome measures (CISS, Diplopia Questionnaire, four Adult Strabismus-20 quality-of-life domains) before treatment (baseline) and after 10 weeks and 1 year. Associations were interpreted to be present when the lower limit of the 95% confidence interval (CI) was moderate to strong (R ≥ 0.4).

RESULTS

Among multiple exploratory analyses, the only moderate to strong baseline correlation was between worse CISS and worse Adult Strabismus-20 reading function scores (R = 0.62; 95% CI, 0.43 to 0.76). Regarding change in measures with treatment, the only moderate to strong correlations were between improved CISS and improved Adult Strabismus-20 reading function scores for prism at 10 weeks (R = 0.78; 95% CI, 0.52 to 0.91) and 1 year (R = 0.85; 95% CI, 0.65 to 0.94) and for vision therapy/exercises at 1 year (R = 0.78; 95% CI, 0.57 to 0.89).

CONCLUSIONS

In exploratory analyses, we found positive correlations between CISS symptom scores and reading function quality-of-life scores. The absence of correlations between symptoms and individual clinical measures is consistent with clinical experience that, in convergence insufficiency, symptoms and clinical findings can be discordant.
The Developmental Eye Movement Test Does Not Detect Oculomotor Problems: Evidence from Children with Nystagmus
Authors: Tanke Nouk , Barsingerhorn Annemiek D. , Goossens Jeroen , Boonstra F. Nienke
Published: August 2022

SIGNIFICANCE

The Developmental Eye Movement (DEM) test, a test purported to assess oculomotor skills, does not detect eye movement disorder in nystagmus syndromes. The test should not be used for the clinical evaluation of oculomotor disorders.

PURPOSE

The DEM test ratio compares a horizontal number naming subtest with a vertical one to identify oculomotor problems independent of a child's visual-verbal naming skills. Here, we tested the construct validity of this method by comparing scores of children with and without pathologic nystagmus. Such a nystagmus disturbs normal fixation and saccadic behavior because of the presence of involuntary rhythmic oscillations of the eyes. Therefore, if the ratio is indeed a comprehensive measure of oculomotor problems, children with nystagmus should show an increased ratio score.

METHODS

The DEM test performances of normally sighted children (n = 94), children with ocular visual impairments (VIo; n = 33), and children with cerebral visual impairment (n = 30) were analyzed using linear regression. Part of the children with VIo and cerebral visual impairment had either fusion maldevelopment nystagmus syndrome (n = 8) or infantile nystagmus syndrome (n = 20), whereas the others showed no pathologic nystagmus.

RESULTS

The times needed for the horizontal and vertical subtests were significantly different between children with normal vision, VIo, and cerebral visual impairment (P < .001). However, the presence of nystagmus did not add significantly to the horizontal and vertical times (P > .20), nor did it have an effect on the ratio (P > .10).

CONCLUSIONS

The DEM test ratio is not sensitive to fixation and saccade abnormalities associated with nystagmus, indicating that it does not have general construct validity to detect true eye movement disorders. Although not suitable for the evaluation of oculomotor disorders, the subtests do have clinical relevance in the diagnosis of cerebral visual impairment.
Identifying Operational Challenges and Solutions During the COVID-19 Response Among US Public Health Laboratories
Authors: Potter Christina , Kaushal Natasha , Wroblewski Kelly , Becker Scott , Nuzzo Jennifer B.
Published: August 2022

Context:

The ability to diagnose and screen for infection is an important component of the US COVID-19 response and is facilitated by public health laboratories (PHLs). Anecdotal media reports and limited case studies have described some of the challenges faced by PHLs during the pandemic, particularly initial challenges related to developing and deploying tests to PHLs, but there has not been a systematic evaluation of the experience of PHLs during the pandemic.

Objective:

To document challenges and lessons learned experienced by local and state PHLs during the COVID-19 pandemic to support generation of best practices for current and future similar emergencies.

Design, Setting, and Participants:

From February to June 2021, researchers conducted 24 interviews with 68 leaders and staff representing 28 local and state PHLs across 27 states. Thematic analysis of interview content documented operational challenges and any identified solutions or preventive measures used or proposed.

Main Outcome Measures:

Analysis identified the following themes regarding challenges faced among PHLs: strategic decision making and determining the mandate of the PHL; political interference by jurisdictional leadership; federal mismanagement of the emergency; regulatory challenges; managing partnerships with other laboratories; acquisition of appropriate supplies; insufficient information systems; acquiring and retaining workforce; and difficulty accessing sufficient funding.

Results:

Within the identified themes, key informants provided further elaboration regarding how PHLs experienced, evaded, or solved these challenges. In addition, PHLs described how challenges evolved throughout the course of the COVID-19 pandemic and made proposals regarding how challenges could be prevented or further addressed in the future by laboratories or other decision makers and stakeholders.

Conclusions:

While fellow laboratories and political leadership may gain inspiration from creative solutions employed by PHLs, recognition of long-standing gaps related to funding, laboratory workforce, and consideration of laboratory needs in preparedness policies must be addressed for future large-scale outbreaks.
Quality Improvement Initiative Increasing Early Discharges From an Acute Care Cardiology Unit for Cardiac Surgery and Cardiology Patients–Associated With Reduced Hospital Length of Stay
Authors: Colyer Jessica , Ring Lisa , Gallagher Sarah , Mullenholz Mary , Robison Jan , Rigney-Radford Kathleen , Harahsheh Ashraf S.
Published: August 2022

Introduction:

Discharging patients from the acute care setting is complex and requires orchestration of many clinical and technical processes. Focusing on timely discharges improves throughput by off-loading ICUs and coordinating safe outpatient transitions. Our data review demonstrated most discharges occurred later in the day. We sought to improve our discharge times for cardiology and cardiovascular surgery (CVS) patients in our 26-bed inpatient acute care cardiology unit (ACCU). We aimed to increase the number of discharges between 6 am and 12 pm for cardiology and CVS patients on ACCU from 5 to 10 patients per month over 6 months and sustain.

Methods:

We performed a simplified Failure Mode Effect Analysis on the discharge process and identified improvement opportunities. Our key drivers centered around education, documentation, and planning. Our interventions included: staff education, communication of discharge expectations, daily quality board rounds, hospital-wide collaboration emphasizing conditional discharges, and hospital information technology (IT) improvements. We utilized statistical process control charts to analyze the data.

Results:

Discharges between 6 am, and 12 pm increased from a baseline of 5 (8%) to 12 (18%) patients per month with a centerline shift. Our process measures demonstrated appropriate conditional discharge usage linked to earlier discharges. Upgrades to our EMR, documentation further increased our timely discharges. Our efforts resulted in a 22% reduction in hospital length of stay from 11.2 to 8.7 days without increased readmission rates suggesting that improved efficiency did not impact care quality.

Conclusion:

We successfully show how multidisciplinary collaboration and systems-based improvement can increase the number of safe, early discharges.
The Imperfect Science of Publicly Reported Hospital Rating Systems: Lessons From Credit Rating Agencies
Authors: Yuce Tarik K. , Barnard Cynthia , Hobson Leah , Bilimoria Karl Y.
Published: August 2022

The number of publicly available hospital quality rating systems has substantially increased over the past 2 decades. These rating systems are meant to provide patients, clinicians, and payers with relevant information to select and pay differentially for better quality of care. However, there is evidence of inconsistency, unreliability, and bias in current hospital quality rating systems. Financial ratings are similarly intended to enable investors to identify stronger companies (as investment targets), and these rating systems could provide insight into strategies to improve hospital quality ratings. We evaluate the credit rating methodologies of Standard & Poor's, Moody's, and Fitch Group and propose principles to improve hospital quality rating systems through better standardized measures and the use of external audits of source data. Emulating key features of credit rating systems may advance the delivery of meaningful hospital quality ratings.
A Meta-Analysis of Sleep Disorders and Nonalcoholic Fatty Liver Disease
Authors: Yu Lebing , Lin Chenli , Chen Xinhe , Teng Yuxin , Zhou Shuang , Liang Yinji
Published: August 2022

Nonalcoholic fatty liver disease is a type of metabolic disease, and recent research indicates that it may be associated with sleep disorders. We conducted a meta-analysis of current studies to estimate the associations between nonalcoholic fatty liver disease and sleep situation, including sleep duration, daytime sleepiness, and sleep disorder. This study follows the checklist of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Articles in the recent 10 years were searched from five databases. Eighteen articles, which met the eligibility criteria, were included in this meta-analysis. The results show that patients with nonalcoholic fatty liver disease have a shorter sleep duration and higher Epworth Sleepiness Scale score. Patients with short sleep duration (≤6 hours per night) or with obstructive sleep apnea have a higher risk of nonalcoholic fatty liver disease. In conclusion, there is a significant association between nonalcoholic fatty liver disease and sleep disorders in the included studies. In addition, patients with nonalcoholic fatty liver disease may have more severe daytime sleepiness and shorter sleep duration. More attention should be paid to the sleep situation of nonalcoholic fatty liver disease patients to potentially slow the disease progression.
Computational modelling of the crushing of carbon fibre-reinforced polymer composites
Authors: Falzon Brian G.
Published: August 2022

The use of lightweight carbon fibre-reinforced polymer (CFRP) composites in transportation vehicles has necessitated the need to guarantee that these new materials and their structures are able to deliver a sufficient level of crashworthiness to ensure passenger safety. Unlike their metallic counterparts, which absorb energy primarily through plastic deformation, CFRPs absorb energy through a complex interaction of damage mechanisms involving matrix (polymer) cracking, fibre/matrix debonding, fibre pull-out/kinking/fracture, delamination and inter/intralaminar friction. CFRP is primarily deployed as a laminate and can potentially deliver a higher specific energy absorption than metals. Translating this capability to a structural scale requires careful design and is dependent on geometry, fibre architecture, laminate stacking sequence and damage initiation strategies for optimal uniform crushing. Consequently, the design of crashworthy CFRP structures currently entails extensive physical testing which is expensive and time consuming. This paper reports on progress and challenges in the development of a finite-element computational capability for simulating the crushing of composites for crashworthiness assessments, with the aim of reducing the burden of physical testing. It addresses the ‘tyranny of scales’ in modelling structures constructed of CFRP composites. Intrinsic to this capability is the acquisition of reliable material data for the damage model, in particular interlaminar and intralaminar fracture toughness values. While quasi-static values can be obtained with a reasonable level of confidence, results achieved through dynamic testing are still the subject of debate and the relationship between fracture toughness and strain rate has yet to be satisfactorily resolved.

This article is part of the theme issue ‘Nanocracks in nature and industry’.
Adhesion and wear of diamond: formation of nanocracks and adhesive craters of torn out material
Authors: Borodich Feodor M. , Galanov Boris A. , Grigoriev Oleg N.
Published: August 2022

Mechanical transformation of rough diamonds into brilliant ones is usually achieved by polishing using microsized abrasive diamond particles. It is shown that in addition to formation of periodic pattern of ‘partial’ Hertzian cone cracks on the diamond surface, nano-sized domains (50–150 nm in diameter) of crumbled material are observed. Because these domains are located in the centres of the regions (250–500 nm in diameter) partially surrounded by the Hertzian cone cracks, where the stresses are close to the stress field of hydrostatic compression, the material removal cannot be explained by creation of tensile or shear cracks. It is argued that the creation of these domains of crumbled material is due to adhesive interactions between sliding diamond particles and the diamond surface. Employing a two-term law of friction, the scheme of ultimate equilibrium between the particle and the surface is presented. The distributions of contact stresses are calculated for two approaches: (i) the extended Johnson–Kendall–Roberts model and (ii) the ‘soft’ model of adhesive contact. Thus, adhesion between the sliding diamond particle and the surface leads to creation of periodic pattern of the crumbling domains with the steps 500–1000 nm and adhesive tearing out of the material from the domains.

This article is part of the theme issue ‘Nanocracks in nature and industry’.
COGNITION AND INFLUENCING FACTORS OF HOSPICE CARE AMONG NURSING UNDERGRADUATES
Authors: Zhang Rui-ting
Published: August 2022

Objective

To investigate the current cognition of hospice care among nursing undergraduates, and analyze the influencing factors affecting their cognition, so as to provide suggestions for improving the cognition of hospice care among nursing undergraduates.

Methods

290 nursing undergraduates were selected for an online questionnaire survey. The questionnaire includes general information, hospice care knowledge, and hospice care attitude.

Results

The mean score of the hospice care knowledge questionnaire is 9.68±4.73, and the mean score of the attitude questionnaire is 62.59±7.29. The influencing factors of hospice care cognition of nursing undergraduates are gender, age, religious belief, the only child, internship experience, grade, source of death experience, death talk at home, and access to hospice care knowledge.

Conclusion

Nursing undergraduates’ lack of knowledge of hospice care, and hospice care attitude is more positive, suggesting that nursing undergraduates should strengthen hospice care education according to the influencing factors, call for government support, in order to further improve nursing undergraduates’ hospice care cognition status.
High throughput steady-state enzyme kinetics measured in a parallel droplet generation and absorbance detection platform
Authors: Neun Stefanie , van Vliet Liisa , Hollfelder Florian , Gielen Fabrice
Published: August 2022

Microfluidic water-in-oil emulsion droplets are becoming a mainstay of experimental biology, where they replace the classical test tube. In most applications (e.g. in ultrahigh throughput directed evolution) the droplet content is identical for all compartmentalized assay reactions. When emulsion droplets are used for kinetics or other functional assays, though, concentration dependencies (e.g. of initial rates for Michaelis-Menten plots) are required. Droplet-on-demand systems satisfy this need but extracting large amounts of data is challenging. Here we introduce a multiplexed droplet absorbance detector which, coupled to semi-automated droplet generation, forms a tubing-based droplet-on-demand system able to generate and extract quantitative datasets from defined concentration gradients across multiple series of droplets for multiple time points. The emergence of product is detected by reading the absorbance of the droplet sets at multiple, adjustable time points (reversing the flow direction after each detection, so that the droplets pass a line scan camera multiple times). Detection multiplexing allows absorbance values at twelve distinct positions to be measured and enzyme kinetics are recorded for label-free concentration gradients (composed of about 60 droplets each, covering as many concentrations). With a throughput of around 8640 data points per hour, a 10-fold improvement compared to the previously reported single point detection method is achieved. In a single experiment, twelve full datasets of high-resolution and high accuracy Michaelis-Menten kinetics were determined to demonstrate the potential for enzyme characterization for glycosidase substrates covering a range in enzymatic hydrolysis of seven orders of magnitude in kcat/KM. The straightforward set-up, high throughput, excellent data quality, wide dynamic range that allows coverage of diverse activities suggest that this system may serve as a miniaturized spectrophotometer to for detailed analysis of study clones emerging from large-scale combinatorial experiments.

Abstract Figure
JBrowse 2: A modular genome browser with views of synteny and structural variation
Authors: Diesh Colin , Stevens Garrett J , Xie Peter , De Jesus Martinez Teresa , Hershberg Elliot A. , Leung Angel , Guo Emma , Dider Shihab , Zhang Junjun , Bridge Caroline , Hogue Gregory , Duncan Andrew , Morgan Matthew , Flores Tia , Bimber Benjamin N. , Haw Robin , Cain Scott , Buels Robert M. , Stein Lincoln D. , Holmes Ian H.
Published: August 2022

We present JBrowse 2, a general-purpose genome annotation browser offering enhanced visualization of complex structural variation and evolutionary relationships. JBrowse 2 retains the core features of the open-source JavaScript genome browser JBrowse while adding new views for synteny, dotplots, breakpoints, gene fusions, and whole-genome overviews. The software readily allows users to share sessions, open multiple genomes or views, and navigate quickly between these views. It can be embedded in a web page, used as a standalone desktop application, or run from Jupyter notebooks or R sessions. Using a plugin framework, developers can create new data adapters, track types, and visualizations. These improvements are enabled by a ground-up redesign of the JBrowse architecture using modern web technology. We describe application functionality, use cases, performance benchmarks, and implementation notes for web administrators and developers.
Fat Extract Modulates Calcium Signaling and Protects Against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity
Authors: Yang Yiqi , Xu Mingming , Kan Tianyou , Wang Yao , Zhang Shuhong , Deng Mingwu , Zhang Wenjie , Li Hanjun , Yu Zhifeng
Published: August 2022

Osteoclasts are cells which are primarily involved in bone remodeling and osteolytic bone diseases. Hyperactive osteoclastogenesis leads to pathological bone loss and microarchitectural deterioration, particularly in postmenopausal osteoporosis. However, given the limitations of current first-line osteoclast inhibitors, there is an urgent need for a novel antiresorptive agent with higher efficiency and fewer side effects. Cell-free fat extract (CEFFE) is the liquid fraction obtained from human adipose tissues, which are enriched with a variety of cytokines and growth factors. This study aims to explore its pharmaceutical effect on hyperactive osteoclast formation in vivo and in vitro. CEFFE exhibits excellent potentials to attenuate osteoclast-associated bone loss in an ovariectomy (OVX) mouse model and to inhibit RANKL-induced osteoclastogenesis in primary bone marrow-derived monocytes. Furthermore, the cationic protein fraction of CEFFE (CEFFE-Cation) is identified as the main inhibitory component in osteoclast formation assay. Excessive reactive oxygen species (ROS) production is the main cause of osteoclast overactivation. According to LC-MS/MS analysis, the CEFFE-Cation fraction mainly consists of various antioxidant enzymes, extracellular matrix, and secreted cytokines, which endow it with a superior antioxidant capacity. Ca2+ signaling contributes to osteoclast maturation. In addition to scavenging ROS, CEFFE-Cation is also capable of mitigating Ca2+ oscillation, calcineurin activation, and subsequent NFATc1 nuclear translocation during osteoclastogenesis. Overall, this study elucidates the promising translational potential of CEFFE as a next-generation personalized antiresorptive agent for osteolytic bone disease treatment.
Constraints and trade-offs shape the evolution of T cell search strategies
Authors: Wortel Inge M N , Textor Johannes
Published: August 2022

Two decades of in vivo imaging have revealed how diverse the shapes and motion patterns of migrating T cells can be. This finding has sparked the notion of “search strategies”: T cells may have evolved ways to search for antigen efficiently and might even adapt their motion to the task at hand. Mathematical models have indeed confirmed that observed T-cell migration patterns resemble a theoretical optimum in several contexts; for example, frequent turning, stop-and-go motion, or alternating short and long motile runs have all been interpreted as deliberately tuned behaviours, optimising the cell’s chance of finding antigen. But the same behaviours could also arise simply because T cells can’t follow a straight, regular path through the tight spaces they navigate. Even if T cells can be shown to follow a theoretically optimal pattern, the question remains: has that pattern truly been evolved for this particular searching task, or does it merely reflect how the cell’s migration machinery and surroundings constrain motion paths?

We here examine to what extent cells can evolve search strategies when faced with realistic constraints. Using a cellular Potts model (CPM), where motion arises from interactions between intracellular dynamics, cell shape, and a constraining environment, we simulate an evolutionary process in which cells “optimise” a simple task: explore as much area as possible. We find that cells evolve several motility characteristics previously attributed to search optimisation, even though these features were not beneficial for the task given here. Our results stress that “optimal” search strategies do not always stem from evolutionary adaptation: instead, they may be the inevitable side effects of interactions between cell shape, intracellular actin dynamics, and the diverse environments T cells face in vivo.
DLC3/Cv-c function in testis development in humans and Drosophila: implication for variants of sex development
Authors: Sotillos Sol , von der Decken Isabel , Mercadé Ivan Domenech , Srinivasan Sriraksha , Vanni Stefano , Nef Serge , Biason-Lauber Anna , Gutiérrez Daniel Rodríguez , Hombría James C-G
Published: August 2022

Identifying genes affecting gonad development is essential to understand the mechanisms causing Variants/Differences in Sex Development. Recently, a DLC3 mutation was associated with male gonadal dysgenesis in 46,XY DSD patients. We show that Cv-c, the Drosophila ortholog of DLC3, is also required to maintain testis integrity during fly development. We found that Cv-c and human DLC3 can perform the same function in fly embryos, as flies with wild type but not mutated DLC3 rescue gonadal dysgenesis, suggesting a functional conservation. Expression of different Cv-c protein variants demonstrated that the StART domain mediates the Cv-c function in the male gonad, independently from the GAP domain activity. This work demonstrates a role for DLC3/Cv-c in male gonadogenesis and highlights a novel StART-mediated function required for gonadal mesoderm-germ cell interaction during testis development.

Significance Statement

Associating rare human genetic variants to specific conditions is complex. An amino acid change in the StART domain of the RhoGAP DLC3 protein has been found in female DSD patients with a 46,XY male karyotype. We present a second DSD patient with a mutation in the same region and show that the Cv-c/DLC3 homolog is also required in Drosophila testis. In cv-c mutant embryos the testis mesodermal cells display various defects: the testes are unable to retain the germ cells due to their abnormal ensheathment by mesodermal cells and the mesodermal sheet of cells surrounding the testis is discontinuous resulting in the liberation of the germ cells outside the gonad. Defects can be rescued by gonadal expression of Cv-c or DLC3 but not by the patients’ DLC3 protein variant. Testis development requires the StART lipid binding domain but not the GAP domain, revealing a novel function of this RhoGAP family.