bluuebunny/crossref_metadata_2025 huggingface dataset:
The Safety of Drivers
Authors: Kao Feng-Hsia , Kuo Chien-Chih
Published: October 2020

Objectives:

The aim of this study was to understand the relationship between employees’ perception of work load, group interactional quality, and their effects on employee's psychological strain (need for recovery after work and fatigue) and job accidents.

Methods:

Questionnaire was used to collect data form 401 employees in the transport service industry in Taiwan.

Results:

(1) Workload was positively related with need for recovery after work; (2) group interaction quality was negatively related with need for recovery after work; (3) need for recovery after work was positively related with fatigue; (4) fatigue was positively related with job accidents.

Conclusions:

The findings highlight the importance for organizations to provide adequate work design and build a supportive working environment, which may ultimately contribute to decreased psychological strain and fewer job accidents.
Spring-Loaded Dynamic Foot: An Act of Product Development in Economically Developing Country
Authors: Divya Dharshni M. , Rout Bapina Kumar
Published: October 2020

Introduction

There is a need for a new prosthetic foot in economically developing countries that is technically simple yet functionally more equivalent to the dynamic response foot.

Objectives

The aim of this study is to develop and clinically evaluate a new prosthetic foot with a simple technical design that is as energy efficient as a dynamic response foot.

Study Design

This study is a crossover repeated measures study design comparing the new prosthetic foot to the participant's conventional high-end or low-end prosthetic foot.

Methods

Twenty-meter and 2-minute walk tests were performed to measure gait speed, and energy expenditure was estimated using the physiological cost index (PCI) for both the conventional prosthetic foot and the new spring-loaded dynamic (SLD) foot.

Results

The gait speed with the SLD foot was on average 0.27 m/s faster than conventional low-end foot (P < 0.0001), but −0.18 m/s slower than conventional high-end prosthetic foot (P < 0.0001). The PCI was similar across all three prosthetic feet technologies (P = 0.276).

Conclusions

The mobility function of the SLD foot was nearer to the dynamic response foot as compared with the low-end prosthetic foot. Given its technical simplicity and cost-effectiveness, the SLD foot may be considered as a true alternative to the existing dynamic response foot in economically developing countries. This article describes a new design of prosthetic foot that is simple in design, cost-effective, and made from readily available local material, yet shows clinical features that are nearer to the dynamic response foot. With further immaculate clinical and mechanical testing, it can be integrated to prosthetic users in developing countries.
How Do Orthoses Impact Ease of Donning, Handwriting, Typewriting, and Transmission of Manual Torque? A Study of Three Prefabricated Wrist-Hand Orthoses
Authors: Ferrari Ana Lya M. , Medola Fausto O. , Sandnes Frode E.
Published: October 2020

Introduction

Many upper-limb injuries have work-related causes such as continued use of computers, typing activities, mouse manipulation, and repetitive movements performed for long periods. This study evaluated the performance of wrist-hand orthoses in manual tasks and in transmission of torque measurement during canned glass opening.

Methods

Thirty healthy participants performed donning, typing, and handwriting tasks and transmission of manual torque. The procedures were performed in four conditions: with three different orthoses and with no orthosis as a control.

Results

The results showed a significant difference in the time of manual writing (P < 0.001) and in the number of words per minute (P < 0.001) in the typing task with and without orthoses. The perceived difficulty in performing typing (P < 0.001) and manual writing (P < 0.001) was lower with no orthoses and higher for canvas orthosis and the two neoprene orthoses. Transmission of manual torque also decreased with the orthoses compared with using no orthosis (P < 0.001). Among the orthoses, the canvas fabric orthosis yielded a lower performance compared with the two different neoprene fabric orthoses for all the tasks.

Conclusions

There are effects of the materials used and the orthosis design when performing handwriting typing tasks and twisting tasks (transmission of manual torque), as well as the correctness of how users donned the orthosis.
Breastfeeding Monitoring Improves Maternal Self-Efficacy and Satisfaction
Authors: Ahmed Azza H. , Roumani Ali M.
Published: October 2020

Purpose:

The purpose of this study was to determine the effects of an interactive web-based breastfeeding monitoring system on breastfeeding self-efficacy and satisfaction among mothers of full-term infants at 1, 2, and 3 months after hospital discharge.

Study Design:

We conducted a secondary data analysis of our two-arm, repeated-measures randomized controlled trial that took place in three Midwestern hospitals. Participants were assigned to either control or intervention groups using random numbers. Of the 141 mother–baby dyads enrolled and randomized, 35 dropped out of the study, leaving 57 mothers in the control group and 49 in the intervention group. Mothers in both groups received care based on the hospital protocol, but mothers in the intervention group were also given access to an interactive web-based breastfeeding monitoring system prior to discharge. Participants were asked to enter breastfeeding data, receive educational messages for 30 days, and complete the Breastfeeding Self-Efficacy Scale (BFSE) at 1, 2, and 3 months and the Maternal Breastfeeding Evaluation Scale (MBFES) at 3 months. Mothers received feedback in case of breastfeeding problems.

Results:

A significant difference between groups in BFSE at the 2 and 3 months (p = 0.04; p = 0.04) with medium effect size (0.52, 0.53) was found. There was a significant difference between groups in the total score of MBFES (p = 0.02, effect size 0.53). Mean scores were 122.2, SD = 17.68 for intervention and 112.8, SD = 18.03 for control group. The MBFES scores were positively correlated to BFSE scores among intervention group at all time points (r = .714, n = 45, p < .00; r = .611, n = 41, p < .00; r = .637, n = 39, p < .00).

Clinical Implications:

Interactive web-based breastfeeding monitoring improved maternal breastfeeding self-efficacy and satisfaction and may be a promising innovation to promote maternal breastfeeding self-efficacy and satisfaction.
Central nervous system disease with JC virus infection in adults with congenital HIV
Authors: McEntire Caleb R.S. , Fong Kathryn T. , Jia Dan Tong , Cooper Ellen R. , Cervantes-Arslanian Anna M. , Mateen Farrah J. , Anand Pria , Thakur Kiran T.
Published: October 2020

Objective:

The aim of this study was to describe the natural history of individuals with congenital HIV who develop JC virus (JCV) infection of the central nervous system (CNS).

Methods:

We retrospectively evaluated individuals with congenital HIV who met criteria for progressive multifocal leukoencephalopathy (PML) or JCV granule cell neuronopathy (JCV GCN) at three major healthcare centres in the northeast USA. Data on adherence to combined antiretroviral therapy (cART), neurologic symptoms, serum markers of immunity and HIV infection, cerebrospinal fluid (CSF) analyses, radiographic features, modified Rankin Scale (mRS) scores and survival were collected from the electronic medical record up to a censoring date of 1 August 2020.

Results:

Among 10 adults with congenitally acquired HIV, nine were diagnosed with definitive PML and one was diagnosed with probable JCV GCN. Individuals presented at the time of their PML or JCV GCN diagnosis with a mean mRS of 2.0 (standard deviation 1.0). A premorbid mRS was documented for six patients and was zero in all cases. The most common risk factor was confirmed cART nonadherence in nine individuals. Five individuals with PML and one with JCV GCN died, with a latency from symptom onset to death of approximately 3 months for three individuals, and approximately 2 years for the remaining two.

Conclusion:

Youth-adulthood transition is a high-risk point for dropping off from medical care. The study of this timepoint in people living with HIV could help inform effective care in these individuals.
Bone Scintigraphy in Pembrolizumab-Induced Inflammatory Arthritis
Authors: Imai Masamichi , Kosaka Yuki , Tachi Masato , Mori Kazuaki , Maruno Hirotaka
Published: October 2020

We present a novel report on the use of bone scintigraphy in pembrolizumab-induced inflammatory arthritis. A 70-year-old man with lung cancer complained about arthralgia after 7 courses of the pembrolizumab therapy. 99mTc-HMDP bone scintigraphy revealed symmetrically strong uptakes in the major distal joints of the upper and lower extremities, thereby clearly identifying them as the affected joints. The pattern of uptakes was not consistent with that of other pathophysiologies including bone metastases, hypertrophic osteoarthropathy, and rheumatoid arthritis. 99mTc-HMDP bone scintigraphy is more practical and cost-effective compared with PET to reveal the affected joints in pembrolizumab-induced inflammatory arthritis.
Quality and Safety in Health Care, Part LXXXII
Authors: Harolds Jay A.
Published: October 2020

Reports from the Institute of Medicine regarding the number of errors in medicine leading to fatalities prompted a major review of medical practices and a move to make medical systems high reliability organizations. Many of the concepts used today to improve performance in health care are borrowed from what has been learned from successes and accidents in other industries, especially in the aviation, space, and nuclear power programs. An emphasis on excellent leadership and communication, the knowledge that there needs to be an emphasis on system failures rather than human failures, and having a safety culture that encourages everyone to be mindful of potential errors and report errors are critical to achieve high reliability.
Altered FDG Biodistribution in Subcutaneous White Fat on PET/CT Following l-Asparaginase Chemotherapy
Authors: Young Colin R. , Kulon Michal E. , Boustani Anne Marie , Pucar Darko
Published: October 2020

A 13-year-old boy with mediastinal T-cell lymphoblastic lymphoma demonstrated an altered biodistribution with diffuse activity in subcutaneous white adipose tissue and decreased visceral activity on interim posttreatment FDG PET/CT. This altered biodistribution was attributed to administration of the chemotherapeutic enzymel-asparaginase 3 hours preceding the PET/CT, altering adipocytes amino acid and glucose metabolism. Treatment response assessment was adversely affected by the altered biodistribution, emphasizing the importance of maximizing the time between chemotherapy and PET/CT during successive oncologic treatment cycles. Because adipocytes protect leukemic cells in culture froml-asparaginase, we hypothesize that white adipose tissue–altered biodistribution may be related tol-asparaginase resistance.
Elevated 68Ga-FAPI Accumulation in a Recurrent Angiomyolipoma
Authors: Qin Chunxia , Gai Yongkang , Liu Qingyao , Shao Fuqiang , Lan Xiaoli
Published: October 2020

68Ga-FAPI (68Ga-labeled fibroblast activation protein inhibitor) PET imaging has been recently introduced for the diagnosis and staging in various malignant tumors. However, the reports about the utility of FAPI imaging in benign tumor are relatively rare. Here we report a case of pathologically proven recurrent angiomyolipoma in the left retroperitoneal area with low 18F-FDG uptake but diffuse heterogeneous intense 68Ga-FAPI uptake together with suspected lung metastases in a 53-year-old woman. Our case illustrates FAPI imaging could be helpful not only for detecting various malignant tumors but also for benign tumor like this case due to fibrotic activity in the disease.
Recurrent Malignant Pheochromocytoma With Unusual Peritoneal Carcinomatosis Detected on 131I-MIBG SPECT/CT
Authors: Wang Hui , Cheng Junjun , Ou Xiaohong
Published: October 2020

The most common sites of metastasis for pheochromocytoma are the lymph nodes, bones, lungs, and liver. Peritoneal metastasis or implantation is very rare. We present a case of recurrent malignant pheochromocytoma with unusual multiple peritoneal carcinomatosis on 131I-MIBG SPECT/CT after laparoscopic adrenalectomy.
Tooth Development Following Mandibular Distraction Osteogenesis in Neonates With Pierre Robin Sequence
Authors: Shuman Irene , Cardo Vito A.
Published: October 2020

Background:

Mandibular distraction osteogenesis is a widely utilized surgical procedure in the pediatric population for the treatment of mandibular retrognathia. Patients with congenital abnormalities may display severe mandibular hypoplasia and associated functional problems. Distraction osteogenesis is effective in alleviating airway obstruction for these patients and is performed early in life, often during the neonatal period and during infancy. However, problems in tooth development may arise as a surgical complication.

Evidence Review:

A systematic search was conducted in PubMed and EMBASE to identify retrospective studies describing long term outcomes of mandibular distraction osteogenesis on tooth development. Each article was reviewed and relevant data were extracted, collected, and examined according to the type of dental injury, specific tooth effected, and frequency of occurrence.

Results:

Tooth injuries include positional change (35%), shape alteration/fracture (24%), missing tooth (15%), root injury/malformation (14%), follicle/bud perforation (9%), delayed eruption (2%), and dentigerous cyst (1%). The most commonly affected tooth is the permanent first molar, followed by the primary second molar. The least common tooth affected is the third molar.

Conclusions:

Although tooth injuries exist following mandibular distraction osteogenesis in the pediatric population, the risk of pathology and major complications remain relatively low. Technological advancements in presurgical planning can be expected to continue reducing the risk of adverse effects to primary and permanent tooth development.
Early Elective Surgery After Colon Cancer Diagnosis has Higher Risk of Readmission and Death
Authors: Gleason Frank , Chu Daniel I. , Kennedy Gregory D. , Kenzik Kelly M.
Published: October 2020

Objective:

We hypothesized colon resection within 30 days of diagnosis of cancer would have higher rates of readmission and cancer specific mortality, unless there was demonstrated evidence of preoperative workup.

Summary Background Data:

Few studies have examined if negative consequences exist with expedited elective surgery after diagnosis of colon cancer. Surgery in a shorter time frame may result in a lack of appropriate preoperative care.

Methods:

Retrospective analysis of 25,407 patients in the Surveillance Epidemiology and End Results registry who underwent elective surgical resection for colon cancer from 2010 to 2015. Cohort stratified by age (66–75 vs >75 years). Primary outcomes of interest were 30-day readmission and 5-year colon cancer specific mortality. Relationships between timing of surgery and outcomes were assessed.

Results:

On unadjusted analysis, surgery before 20 days of diagnosis was associated with higher risk of 30-day readmission and colon cancer specific mortality in both age groups. Among those age 66 to 75 years old, adjusting for patient factors and preoperative workup eliminated the risk of 30-day readmission (risk ratio 1.5–0.9 for 0–10 days, risk ratio 1.3–0.9 for 11–20 days). However, the risk for colon cancer specific mortality, although reduced, persisted (hazard ratio 2.2–1.3 for 0–10 days, hazard ratio 2.0–1.2 for 11–20 days). In the cohort older than 75 years, adjusting for patient level factors and preoperative workup eliminated risk of surgery 20 days postop or sooner.

Conclusions:

The risk associated with short time to surgery (within 30 days) may be mitigated if full oncologic workups are provided.
Complications and Failure to Rescue After Inpatient Pediatric Surgery
Authors: Portuondo Jorge I. , Shah Sohail R. , Raval Mehul V. , Pan I-wen E. , Zhu Huirong , Fallon Sara C. , Harris Alex H. S. , Singh Hardeep , Massarweh Nader N.
Published: October 2020

Objective:

To describe the frequency and patterns of postoperative complications and FTR after inpatient pediatric surgical procedures and to evaluate the association between number of complications and FTR.

Summary and Background:

FTR, or a postoperative death after a complication, is currently a nationally endorsed quality measure for adults. Although it is a contributing factor to variation in mortality, relatively little is known about FTR after pediatric surgery.

Methods:

Cohort study of 200,554 patients within the National Surgical Quality Improvement Program-Pediatric database (2012–2016) who underwent a high (≥ 1%) or low (< 1%) mortality risk inpatient surgical procedures. Patients were stratified based on number of postoperative complications (0, 1, 2, or ≥3) and further categorized as having undergone either a low- or high-risk procedure. The association between the number of postoperative complications and FTR was evaluated with multivariable logistic regression.

Results:

Among patients who underwent a low- (89.4%) or high-risk (10.6%) procedures, 14.0% and 12.5% had at least 1 postoperative complication, respectively. FTR rates after low- and high-risk procedures demonstrated step-wise increases as the number of complications accrued (eg, low-risk— 9.2% in patients with ≥3 complications; high-risk—36.9% in patients with ≥ 3 complications). Relative to patients who had no complications, there was a dose-response relationship between mortality and the number of complications after low-risk [1 complication – odds ratio (OR) 3.34 (95% CI 2.62–4.27); 2 – OR 10.15 (95% CI 7.40–13.92); ≥3-27.48 (95% CI 19.06-39.62)] and high-risk operations [1 – OR 3.29 (2.61–4.16); 2–7.24 (5.14–10.19); ≥3–20.73 (12.62–34.04)].

Conclusions:

There is a dose-response relationship between the number of postoperative complications after inpatient surgery and FTR, ever after common, “minor” surgical procedures. These findings suggest FTR may be a potential quality measure for pediatric surgical care.
Policies Restricting Overlapping Surgeries Negatively Impact Access to Care, Clinical Efficiency, and Hospital Revenue
Authors: Brandon Cameron , Ghenbot Yohannes , Buch Vivek , Contreras-Hernandez Enrique , Tooker John , Dimentberg Ryan , Richardson Andrew G. , Lucas Timothy H.
Published: October 2020

Objective:

To model the financial impact of policies governing the scheduling of overlapping surgeries, and to identify optimal solutions that maximize operating efficiency that satisfy the fiduciary duty to patients.

Background:

Hospitals depend on procedural revenue to maintain financial health as the recent pandemic has revealed. Proposed policies governing the scheduling of overlapping surgeries may dramatically impact hospital revenue. To date, the potential financial impact has not been modeled.

Methods:

A linear forecasting model based on a logic matrix decision tree enabled an analysis of surgeon productivity annualized over a fiscal year. The model applies procedural and operational variables to policy constraints limiting surgical scheduling. Model outputs included case and financial metrics modeled over 1000-surgeon-year simulations. case metrics included annual case volume, case mix, operating room (OR) utilization, surgeon utilization, idle time, and staff overtime hours. Financial outputs included annual revenue, expenses, and contribution margin.

Results:

The model was validated against surgical data. case and financial metrics decreased as a function of increasingly restrictive scheduling scenarios, with the greatest contribution margin loses ($1,650,000 per surgeon-year) realized with the introduction of policies mandating that a second patient could not enter the OR until the critical portion of the first surgery was completed. We identify an optimal scheduling scenario that maximizes surgeon efficiency, minimizes OR idle time and revenue loses, and satisfies ethical obligations to patients.

Conclusions:

Hospitals may expect significant financial loses with the introduction of policies restricting OR scheduling. We identify an optimal solution that maximizes efficiency while satisfying ethical duty to patients. This forecast is immediately relevant to any hospital system that depends upon procedural revenue.
Prospective Phase II Trials Validate the Effect of Neoadjuvant Chemotherapy on Pattern of Recurrence in Pancreatic Adenocarcinoma
Authors: Chawla Akhil , Qadan Motaz , Castillo Carlos Fernandez-del , Wo Jennifer Y. , Allen Jill N. , Clark Jeffrey W. , Murphy Janet E. , Catalano Onofrio A. , Ryan David P. , Ting David T. , Deshpande Vikram , Weekes Colin D. , Parikh Aparna , Lillemoe Keith D. , Hong Theodore S. , Ferrone Cristina R.
Published: October 2020

Objective:

The objective of this study was to characterize the patterns of first recurrence after curative-intent resection for pancreatic adenocarcinoma (PDAC).

Summary of Background Data:

We evaluated the first site of recurrence after neoadjuvant treatment as locoregional (LR) or distant metastasis (DM). To validate our findings, we evaluated the pattern from 2 phase II clinical trials evaluating neoadjuvant chemotherapy (NAC) in PDAC.

Methods:

We identified site of first recurrence from a retrospective cohort of patients from 2011 to 2017 treated with NAC followed by chemoradiation and then an operation or an operation first followed by adjuvant therapy, and 2 separate prospective cohorts of patients derived from 2 phase II clinical trials evaluating patients treated with NAC in borderline-resectable and locally advanced PDAC

Results:

In the retrospective cohorts, 160 out of 285 patients (56.1%) recurred after a median disease-free survival (mDFS) of 17.2 months. The pattern of recurrence was DM in 81.9% of patients, versus LR in 11.1%. This pattern was consistent in patients treated with upfront resection and adjuvant chemotherapy (DM 83.0%, LR 16.9%) regardless of margin-involvement (DM 80.1%, LR 19.4%). The use of NAC did not alter pattern of recurrence; 81.7% had DM and 18.3% had LR. This pattern also remained consistent regardless of margin-involvement (DM 94.1%, LR 5.9%). In the Phase II borderline-resectable trial (NCI# 01591733) cohort of 32 patients, the mDFS was 34.2 months. Pattern of recurrence remained predominantly DM (88.9%) versus LR (11.1%). In the Phase II locally-advanced trial (NCI# 01821729) cohort of 34 patients, the mDFS was 30.7 months. Although there was a higher rate of local recurrence in this cohort, pattern of first recurrence remained predominantly DM (66.6%) versus LR (33.3%) and remained consistent independent of margin-status.

Conclusions:

The pattern of recurrence in PDAC is predominantly DM rather than LR, and is consistent regardless of the use of NAC and margin involvement.
Acute Toxicity and Triphasic Waves—The Example of Cefepime
Authors: Husari Khalil S. , Ritzl Eva K. , Kaplan Peter W.
Published: October 2020

Purpose:

Triphasic waves (TWs) have been associated with a host of medication toxicities, and cefepime has emerged recently as a frequently encountered offending agent. This investigation aims to evaluate cefepime-induced encephalopathy and to report the associated clinical, EEG expression with TWs, and the radiologic findings.

Methods:

A retrospective multicenter observational study examining adult patients with cefepime-induced encephalopathy with generalized periodic discharges on either routine or continuous EEG between January 2014 and January 2020. Clinical, electrographic, and radiologic data were collected. Patients in whom cefepime was not the sole causative factor for their encephalopathy were excluded.

Results:

Twenty-seven patients with cefepime-induced encephalopathy marked by generalized periodic discharges with triphasic morphology were identified at both centers, whereas no patients were presenting with generalized periodic discharges without TWs. Patients had a median age of 63 years (interquartile range, 56–73). Fifty-six percent of the cohort (15 patients) were <65 years of age. Eighteen patients (67%) had either acute or chronic kidney impairment (either acute kidney injury or chronic kidney disease or both), whereas 81% had preexisting white matter disease on brain imaging. Of these, 14 patients (51%) were classified as either moderate or severe. In the majority of the patients, TWs were either state-dependent or stimulus-sensitive, and in one third of them presented only as stimulus-induced pattern. All patients improved with discontinuation of cefepime.

Conclusions:

Cefepime toxicity should be considered in the differential diagnosis in encephalopathic patients with TWs. The presence of preexisting white matter disease in these patients should heighten the degree of suspicion, especially in younger patients and patients without renal dysfunction.
Reprogramming of human cells to pluripotency induces CENP-A chromatin depletion
Authors: Milagre Inês , Pereira Carolina , Oliveira Raquel A. , Jansen Lars E. T.
Published: October 2020

Pluripotent stem cells (PSCs) are central to development as they are the precursors of all cell types in the embryo. Therefore, maintaining a stable karyotype is essential, both for their physiological role as well as for their use in regenerative medicine. Karyotype abnormalities in PSCs in culture are common but the underlying causes remain unknown. To gain insight, we explore the composition of the centromere and kinetochore in human embryonic and induced PSCs. Centromere function depends on CENP-A nucleosome-defined chromatin. We show that while PSCs maintain abundant pools of CENP-A, CENP-C and CENP-T, these essential centromere components are strongly reduced at stem cell centromeres. Outer kinetochore recruitment is also impaired to a lesser extent, indicating an overall weaker kinetochore while the inner centromere protein Aurora B remains unaffected. We further show that, similar to differentiated human cells, CENP-A chromatin assembly in PSCs requires transition into G1 phase. Finally, reprogramming experiments indicate that reduction of centromeric CENP-A levels is an early event during dedifferentiation, coinciding with global chromatin remodelling. Our characterization of centromeres in human stem cells suggests a possible link between impaired centromere function and stem cell aneuploidies.
Slc39a5-mediated zinc homeostasis plays an essential role in venous angiogenesis in zebrafish
Authors: Xia Zhidan , Bi Xinying , Lian Jia , Dai Wei , He Xuyan , Zhao Lu , Min Junxia , Wang Fudi
Published: October 2020

Angiogenesis is a precise process mediated by a variety of signals and the environmental niche. Although the essential trace element zinc and its homeostasis are essential for maintaining proper cellular functions, whether zinc plays a role in angiogenesis is currently unknown. Using zebrafish embryos as a model system, we found that zinc treatment significantly increased the expression of the
slc39a5
gene, which encodes the zinc transporter Slc39a5. Moreover, knocking down
slc39a5
expression using either a morpholino or CRISPR/Cas9-mediated gene editing led to cardiac ischaemia and an accumulation of red blood cells in the caudal vein plexus (CVP), as well as delayed venous sprouting and fewer vascular loops in the CVP region during early development. Further analysis revealed significantly reduced proliferation and delayed cell migration in the caudal vein of
slc39a5
morphants. At the mechanistic level, we found increased levels of systemic zinc in
slc39a5
-deficient embryos, and chelating zinc restored CVP development. In addition, we found that zinc overload in wild-type embryos leads to impaired CVP formation. Taken together, these results indicate that Slc39a5 plays a critical role in endothelial sprouting and migration in venous angiogenesis by regulating zinc homeostasis.
Synthesis and evaluation of protein-based biopolymer in production of silver nanoparticles as bioactive compound versus carbohydrates-based biopolymers
Authors: Basta Altaf H. , Lotfy Vivian F. , Mahmoud Khaled , Abdelwahed Nayera A. M.
Published: October 2020

This overall process deals with evaluating the performance of silver nanoparticles, synthesized from sodium caseinate (SC) as green biological active agent, in comparison with widely produced from carboxymethyl cellulose, other carbohydrates (oxidized nanocellulose fibres (OC) and starch (St)). The TGA, FTIR and TEM, as well as its antimicrobial activities toward pathogenic Gram-positive and Gram-negative bacteria in addition to the yeast strain
Candida albicans
NRRL Y-477 were examined. In addition, with regard to their anti-tumour activity, the evaluation was studied via many cancer cell lines against RPE1 (normal retina cell line). The results revealed that the SC–Ag(I) and CMC–Ag(I) complexes were formed in six- and five-membered chelate rings, respectively, as nanoparticles, while linear chelation structure was formed in case of OC–Ag(I) and St–Ag(I) complexes. The complexation of SC with Ag(I) ions was recommended as promising stable and antimicrobial agent, with lower free Ag(I) ions and particle size than other Ag-complexes. Moreover, it provided anti-tumour activity of most tested cell lines (
in vitro
), with the following sequence HCT116 > PC3 > HePG 2 > MCF-7 > A549 with IC
50
and IC
90
values of 25.8 and 54.73 µg ml
−1
, 45.1 and 66.7 µg ml
−1
, 64.3 and 110.7 µgml
−1
, 71.4 and 114.8 µgml
−1
and 80.1 and 127.7 µgml
−1
, respectively. The promising effect of SC–Ag complex was also clear from its selective index versus RPE1 (normal retina cell line).
AbnormalTP53predicts risk of progression in patients with Barrett’s esophagus regardless of a diagnosis of dysplasia
Authors: Redston Mark , Noffsinger Amy , Kim Anthony , Akarca Fahire G , Stapleton Diane , Nowden Laurel , Lash Richard , Bass Adam J , Stachler Matthew D
Published: October 2020

Barrett’s esophagus is the precursor to esophageal adenocarcinomas, which are deadly cancers with a rapidly rising incidence. A major challenge is identifying the small group with Barrett’s esophagus who will progress to advanced disease from the many who will not. Assessment of p53 status has promise as a predictive biomarker, but analytic limitations and lack of validation in large, definitive studies have precluded its use. In this study, criteria for abnormal immunohistochemical expression of p53 were developed in non-dysplastic Barrett’s biopsies and validated with sequencing to assessTP53mutations. The utility of p53 expression as a biomarker for progression of Barrett’s esophagus was tested retrospectively in 561 Barrett’s patients with or without known progression. The findings were prospectively validated in a clinical practice setting in 1487 Barrett’s patients. Abnormal p53 expression highly correlated withTP53mutation status (90.6% agreement) and strongly associated with neoplastic progression in the retrospective cohorts, regardless of histologic diagnosis (P<0.001). In patients with non-dysplastic Barrett’s esophagus at baseline, 89/179 (49.7%) of those with subsequent progression to high grade dysplasia/cancer and 3/179 (1.7%) of non-progressors had abnormal p53 (sensitivity: 49.7,% specificity: 98.3%, Odds ratio: 58 (95% CI 17.9-188.5, P<0.0001) for identifying progressors). In the prospective validation cohort, p53 immunohistochemistry predicted progression among non-dysplastic Barrett’s, indefinite for dysplasia, and low-grade dysplasia (P<0.001). p53 immunohistochemistry can successfully identify Barrett’s esophagus patients at high risk of progression, including in patients without evidence of dysplasia. p53 immunohistochemistry is inexpensive, easily integrated into routine practice, and should be considered in biopsies from all Barrett’s patients without high grade dysplasia or cancer.
Hepatic resection versus transarterial chemoembolization for the intermediate stage hepatocellular carcinoma: A cohort study
Authors: Lu Linbin , Zheng Peichan , Wu Zhixian , Chen Xiong
Published: October 2020

Background

The selection criterion for hepatic resection(HR) in intermediate-stage(IM) hepatocellular carcinoma(HCC) is still controversial. We used real-world data to evaluate the overall survival (OS) treated with HR or TACE.

Methods

In all, 942 patients with IM-HCC were categorized in HR and TACE groups. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score- matched (PSM) analyses. The smooth curve was performed through the generalized additive model. The interaction test was performed to evaluate the HR impact on OS concerning risk factors. Also, we used multiple imputation to deal with the missing data.

Results

Totally, 23.0% (n=225) of patients received HR. At a median overall survival of 23.7 months, HR was associated with the improved OS on multivariate analysis (hazard ratio, 0.45; 95%CI: 0.35, 0.58; after PSM: 0.56; 95%CI: 0.41, 0.77). Landmark analyses limited to long-term survivors of ≥ 6 months, ≥ 1, and ≥ 2 years demonstrated better OS with HR in all subsets (all P<0.05). After PSM analysis, however, HR increased 20% risk of death (HR, 1.20; 95%CI: 0.67, 2.15) in the subgroup of LDH ≤192 U/L (P for interaction = 0.037). Furthermore, the significant interaction was robust between the LDH and the HR with respect to 1-, 3-, and 5-year observed survival rate (all P<0.05).

Conclusion

Hepatic resection was superior to TACE for intermediate-stage HCC in the range of LDH level > 192 U/L. Moreover, TACE might be suitable for patients with LDH level ≤ 192 U/L.

Synopsis

Hepatectomy was superior to TACE for BCLC-B HCC.

Hepatectomy increased 20% risk of death for LDH < 192 U/L after matching.

A significant interaction was robust between LDH and with respect to hepatectomy the 1-, 3-, and 5-year observed survival rate.
Graph theory analysis of induced neural plasticity post-Acceptance and Commitment Therapy for chronic pain
Authors: Meier Sarah K. , Ray Kimberly L. , Waller Noah C. , Gendron Barry C. , Aytur Semra A. , Robin Donald A.
Published: October 2020

Chronic musculoskeletal pain affects the lives of over 50 million individuals in the United States, at a cost of more than $550 billion each year. Chronic pain leads to functional brain changes within those suffering from the condition. Not only does the primary pain network transform as the condition changes from acute to persistent pain, a state of hyper-connectivity also exists between the default mode, frontoparietal, and salience networks. Graph theory analysis has recently been used to investigate treatment-driven brain network changes. For example, current research suggests that Acceptance and Commitment Therapy (ACT) may reduce the chronic pain associated hyper-connectivity between the default mode, frontoparietal, and salience networks, as well as within the salience network. This study extended previous work by examining the associations between the three networks above and a meta-analytically derived pain network. Results indicate decreased connectivity within the pain network (including left putamen, right insula, left insula, and right thalamus) in addition to triple network connectivity changes after the four-week Acceptance and Commitment therapy intervention.
Sex differences in the genetic regulation of the blood transcriptome response to glucocorticoid receptor activation
Authors: Moore Sarah R. , Halldorsdottir Thorhildur , Martins Jade , Lucae Susanne , Müller-Myhsok Bertram , Müller Nikola S. , Piechaczek Charlotte , Feldmann Lisa , Freisleder Franz Joseph , Greimel Ellen , Schulte-Körne Gerd , Binder Elisabeth B. , Arloth Janine
Published: October 2020

Substantial sex differences have been reported in the physiological response to stress at multiple levels, including the release of the stress hormone, cortisol. Here, we explore the genomic variants in 93 females and 196 males regulating the initial transcriptional response to cortisol via glucocorticoid receptor (GR) activation. Gene expression levels in peripheral blood were obtained before and after GR-stimulation with the selective GR agonist dexamethasone to identify differential expression following GR-activation. Sex stratified analyses revealed that while the transcripts responsive to GR-stimulation were mostly overlapping between males and females, the quantitative trait loci (eQTLs) regulation differential transcription to GR-stimulation were distinct. Sex-stratified eQTL SNPs (eSNPs) were located in different functional genomic elements and sex-stratified transcripts were enriched within postmortem brain transcriptional profiles associated with Major Depressive Disorder (MDD) specifically in males and females in the cingulate cortex. Female eSNPs were enriched among SNPs linked to MDD in genome wide association studies. Finally, transcriptional sensitive genetic profile scores derived from sex-stratified eSNPS regulating differential transcription to GR-stimulation were predictive of depression status and depressive symptoms in a sex-concordant manner in a child and adolescent cohort (n = 584). These results suggest potential of eQTLs regulating differential transcription to GR-stimulation as biomarkers of sex-specific biological risk for stress-related psychiatric disorders.
A placebo-controlled double blind trial of hydroxychloroquine in mild-to-moderate COVID-19
Authors: Dubée Vincent , Roy Pierre-Marie , Vielle Bruno , Parot-Schinkel Elsa , Blanchet Odile , Darsonval Astrid , Lefeuvre Caroline , Abbara Chadi , Boucher Sophie , Devaud Edouard , Robineau Olivier , Rispal Patrick , Guimard Thomas , d’Anglejean Emma , Diamantis Sylvain , Custaud Marc-Antoine , Pellier Isabelle , Mercat Alain ,   for the HYCOVID study group
Published: October 2020

Background

The efficacy of hydroxychloroquine in coronavirus disease 2019 (COVID-19) remains controversial.

Methods

We conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: age ≥75 years, age between 60 and 74 years, and presence of at least one comorbidity, or need for supplemental oxygen (≤3 L/min). Eligible patients were randomized in a 1:1 ratio to receive either 800mg hydroxychloroquine on Day 0 followed by 400mg per day for 8 days or a placebo. The primary endpoint was a composite of death or tracheal intubation within 14 days following randomization. Secondary endpoints included mortality and clinical evolution at Day 14 and 28, viral shedding at Day 5 and 10.

Results

The trial was stopped after 250 patients were included due to a slowdown of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years and 151 patients required oxygen therapy. The primary endpoint occurred in nine patients in the hydroxychloroquine group and eight patients in the placebo group (relative risk 1.12; 95% confidence interval 0.45– 2.80; P=0.82). No difference was observed between the two groups in any of the secondary endpoints.

Conclusion

In this trial involving mainly older patients with mild-to-moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo.
Assessment of Total Parenteral Nutrition administration among Intensive Care Unit patients at Omdurman Military Hospital, Sudan
Authors: Khalafallah Bashir Bothina Essameldin , Ahmed Abdallah Mudawi Mohammed , Abd El-Raheem Ghada Omer Hamad , Ali Nassir Elkhansaa Hamad
Published: October 2020

Total parenteral nutrition is one of the important types of nutrition among patients with intestinal failure. This research was intended to assess total parenteral nutrition administration of the intensive care unit patients at the Military hospital, Sudan. A cross-sectional hospital-based study assessed the patients records in the period between April 2014-November 2015, data were analyzed through chi-square test, it was considered significant when p≤ 0.05. Twenty patients who received total parenteral nutrition were assessed, 60% were males, while 40% were females. The most frequent indication for total parenteral nutrition was laparotomy (35% of patients). The duration of total parenteral nutrition was assessed, 70% of patients had duration between 1-20 days. Regarding total parenteral nutrition complications, the most frequent complication was hypokalemia (45% of patients), refeeding syndrome occurred in 10 % of patients. A statistically significant association was found between total parenteral nutrition duration when assessed with age and indication (p= 0.005 and 0.000 respectively). Patients suffering from electrolytes imbalance need more care to avoid the development of refeeding syndrome, as well as high level of hygiene is strictly required to overcome septic complications. There is a need to consider specialized care team composed of nurses, clinical pharmacists and nutritionists.
Evaluation of Eye-tracking for a Decision Support Application
Authors: Visweswaran Shyam , King Andrew J , Tajgardoon Mohammadamin , Calzoni Luca , Clermont Gilles , Hochheiser Harry , Cooper Gregory F
Published: October 2020

Eye-tracking is used widely to investigate attention and cognitive processes while performing tasks in electronic medical record (EMR) systems. We explored a novel application of eye tracking to collect training data for a machine learning-based clinical decision support tool that predicts which patient data are likely to be relevant for a clinical task. Specifically, we investigated in a laboratory setting the accuracy of eye tracking compared to manual annotation for inferring which patient data in the EMR are judged to be relevant by physicians. We evaluated several methods for processing gaze points that were recorded using a low-cost eye tracking device. Our results show that eye-tracking achieves accuracy and precision of 69% and 53% respectively compared to manual annotation and are promising for machine learning. The methods for processing gaze points and scripts that we developed offer a first step in developing novel uses for eye-tracking for clinical decision support.

LAY SUMMARY

In the context of electronic medical record systems, eye-tracking is used extensively to explore attention and cognitive processes. We investigated a novel application of eye tracking to collect training data for machine learning-based clinical decision support. We evaluated several methods for processing gaze points that were recorded using a low-cost eye tracking device. The methods for processing gaze points and scripts that we developed offer a first step in developing novel uses for eye-tracking for clinical decision support.
Use of dried blood spot samples for SARS-CoV-2 antibody detection using the Roche Elecsys ® high throughput immunoassay
Authors: Mulchandani Ranya , Brown Ben , Brooks Tim , Semper Amanda , Machin Nicholas , Linley Ezra , Borrow Ray ,   EDSAB-HOME Study Investigators, Wyllie David
Published: October 2020

Background

Dried blood spot samples (DBS) provide an alternative sample type to venous blood samples for antibody testing. DBS are used by NHS for diagnosing HCV and by PHE for large scale HIV and Hepatitis C serosurveillance; the applicability of DBS based approaches to SARS-CoV-2 antibody detection is uncertain.

Objective

To compare antibody detection in dried blood spot eluates using the Roche Elecsys ® immunoassay (index test) with antibody detection in paired plasma samples, using the same assay (reference test).

Setting

One Police and one Fire & Rescue facility in England.

Participants

195 participants within a larger sample COVID-19 serodiagnostics study of keyworkers, EDSAB-HOME.

Outcome Measures

Sensitivity and specificity of DBS (the index test) relative to plasma (the reference test), at an experimental cut-off; quality of DBS sample collected; estimates of relative sensitivity of DBS vs. plasma immunoassay in a larger population.

Results

18/195 (9.2%) participants tested positive using plasma samples. DBS sample quality varied markedly by phlebotomist, and low sample volume significantly reduced immunoassay signals. Using a cut-off of ten median absolute deviations above the immunoassay result with negative samples, sensitivity and specificity of DBS were 89.0% (95% CI 67.2, 96.9%) and 100.0% (95% CI 97.9, 100%) respectively compared with using plasma. The limit of detection for DBS is about 30 times higher than for plasma.

Conclusion

DBS use for SARS-CoV-2 serology, though feasible, is insensitive relative to immunoassays on plasma. Sample quality impacts on assay performance. Alternatives, including the collection of capillary blood samples, should be considered for screening programs.
City-level SARS-CoV-2 sewage surveillance
Authors: Yaniv Karin , Shagan Marilou , Kramarsky-Winter Esti , Weil Merav , Indenbaum Victoria , Elul Michal , Erster Oran , Brown Alin Sela , Mendelson Ella , Mannasse Batya , Shirazi Rachel , Lakkakula Satish , Miron Oren , Rinott Ehud , Baibich Ricardo Gilead , Bigler Iris , Malul Matan , Rishti Rotem , Brenner Asher , Lewis Yair E. , Friedler Eran , Gilboa Yael , Sabach Sara , Alfiya Yuval , Cheruti Uta , Davidovitch Nadav , Bilenko Natalya , Moran-Gilad Jacob , Berchenko Yakir , Bar-Or Itay , Kushmaro Ariel
Published: October 2020

The COVID-19 pandemic created a global crisis impacting not only healthcare systems, but also world economies and society. Recent data have indicated that fecal shedding of SARS-CoV-2 is common, and that viral RNA can be detected in wastewater. This suggests that wastewater monitoring is a potentially efficient tool for both epidemiological surveillance, and early warning for SARS-CoV-2 circulation at the population level. In this study we sampled an urban wastewater infrastructure in the city of Ashkelon, Israel, during the end of the first COVID-19 wave in May 2020 when the number of infections seemed to be waning. We were able to show varying presence of SARS-CoV-2 RNA in wastewater from several locations in the city during two sampling periods. This was expressed as a new index, Normalized Viral Load (NVL), which can be used in different area scales to define levels of virus activity such as red (high) or green (no), and to follow morbidity in the population at tested area. Our index showed the rise in viral load between the two sampling periods (one week apart) and indicated an increase in morbidity that was evident a month later in the population. Thus, this methodology may provide an early indication for SARS-CoV-2 infection outbreak in a population before an outbreak is clinically apparent.

HIGHLIGHTS

Detecting the presence of SARS-CoV-2 virus RNA in urban wastewater

The city sewer system may provide an early indication for SARS-CoV-2 infection and may be used as early warning for SARS-CoV-2 outbreaks

NVL index defines various infected urban zones from red (high) to green (low)

Graphical abstract
What predicts adherence to COVID-19 government guidelines? Longitudinal analyses of 51,000 UK adults
Authors: Wright Liam , Steptoe Andrew , Fancourt Daisy
Published: October 2020

In the absence of a vaccine, governments have focused on social distancing, self-isolation, and increased hygiene procedures to reduce the transmission of SARS-CoV-2 (COVID-19). Compliance with these measures requires voluntary cooperation from citizens. Yet, compliance is not complete, and existing studies provide limited understanding of what factors influence compliance; in particular modifiable factors. We use weekly panel data from 51,000 adults across the first three months of lockdown in the UK to identify factors that are related to compliance with COVID-19 guidelines. We find evidence that increased confidence in government to tackle the pandemic is longitudinally related to higher compliance, but little evidence that factors such as mental health and wellbeing, worries about future adversities, and social isolation and loneliness are related to changes in compliance. Our results suggest that to effectively manage the pandemic, governments should ensure that confidence is maintained, something which has not occurred in all countries.