bluuebunny/crossref_metadata_2025 huggingface dataset:
Unusual Manifestations of Vulval Paget Disease
Authors: Shah Varsha I. , Bergin Lindsay , Rowlands Gareth L. , McCluggage W. Glenn
Published: September 2021

Vulval extramammary Paget disease (vEMPD) is an uncommon epithelial malignancy that may arise within the vulva (primary vEMPD) or represent vulval skin involvement by a noncutaneous carcinoma (secondary vEMPD). Primary vEMPD is most often an in situ carcinoma arising within the epidermis but may be associated with dermal invasion (invasive vEMPD) or represent intraepidermal spread of an adenocarcinoma originating in vulval skin adnexa or anogenital mammary-like glands. The latter, termed mammary gland-like adenocarcinoma (MGLA), exhibits morphologic, immunohistochemical, and molecular features of various breast carcinomas but, as far as we are aware, the metaplastic variant of MGLA has not been reported on the vulva. We report 2 cases of metaplastic MGLA of the vulva with associated Paget disease and postulate that some cases of vulval MGLA may arise from Paget disease rather than originating in mammary-like glands. We also report a unique case of secondary vEMPD resulting from spread of urothelial carcinoma in situ that subsequently progressed to invasive urothelial carcinoma within the vulva.
Neurosurgical Advances for Malignant Gliomas
Authors: Dastagirzada Yosef , Suryadevara Carter , Weiss Hannah , Orringer Daniel
Published: September 2021

The intersection of biology and technology has led to many advancements for the field of neurosurgery. Molecular developments have led to the identification of specific mutations, allowing for more accurate discussions in regard to prognosis and treatment effect. Even amid the progress from basic science benchwork, malignant gliomas continue to have a bleak natural history in lieu of the resistance to chemotherapy and the diffuse nature of the disease, leaving room for further research to discover more effective treatment modalities. Novel imaging methods, including the emerging field of radiogenomics, involve the merging of molecular and radiographic data, enabling earlier, detailed molecular diagnoses and improved surveillance of this pathology. Furthermore, surgical advancements have led to safer and more extensive resections. This review aims to delineate the various advancements in the many facets that are used daily in the care of our glioma population, specifically pertaining to its biology, imaging modalities, and perioperative adjuncts used in the operating room.
Examination of the Allostatic Load Construct and Its Longitudinal Association With Health Outcomes in the Boston Puerto Rican Health Study
Authors: López-Cepero Andrea , McClain Amanda C. , Rosal Milagros C. , Tucker Katherine L. , Mattei Josiemer
Published: September 2021

Objective

Despite evidence on allostatic load (AL) as a model explaining associations between stress and disease, there is no consensus on its operationalization. This study aimed to contrast various AL constructs and their longitudinal associations with disease and disability.

Methods

Baseline and 5-year follow-up data from 738 adults participating in the Boston Puerto Rican Health Study were used. Five AL scores were created by summing the presence of 21 dysregulated multisystem physiological parameters using the following: a) z scores, b) population-based quartile cutoffs, c) clinical-based cutoffs, d) 10 preselected clinical-based cutoffs (AL-reduced), and e) 12 clinical-based cutoffs selected a posteriori based on association with disease (AL-select). Adjusted logistic regression models examined associations between each AL score at baseline and 5-year incident type 2 diabetes (T2D), cardiovascular disease (CVD), activities (or instrumental activities) of daily living (ADL; IADL) for physical impairment, and cognitive impairment.

Results

AL-quartile was associated with greater odds of T2D (odds ratio [OR] = 1.20; 95% confidence interval [CI] = 1.07–1.35) and CVD (OR = 1.14; 95% CI = 1.06–1.22). AL-reduced was associated with higher odds of IADL (OR = 1.21; 95% CI = 1.07–1.37) and AL-clinical with CVD (OR = 1.14; 95% CI = 1.07–1.21), IADL (OR = 1.11; 95% CI = 1.04–1.19), and ADL (OR = 1.15; 95% CI = 1.04–1.26). AL-select showed associations with T2D (OR = 1.35; 95% CI = 1.14–1.61), CVD (OR = 1.21; 95% CI = 1.11–1.32), IADL (OR = 1.15; 95% CI = 1.04–1.26), and ADL (OR = 1.24; 95% CI = 1.08–1.41). No associations were found with AL z-score.

Conclusions

AL scores computed with clinical-based cutoffs performed robustly in our sample of mainland Puerto Ricans, whereas z scores did not predict disease and disability. AL-select was the most consistent predictor, supporting its use as a disease-predicting model. Future assessment of AL-select in other populations may help operationalize AL.
Evaluation of In-Hospital Venous Thromboembolism Prevention and Management System Using Hospital-Level Metrics: A Nationwide Cross-Sectional Survey in China
Authors: Zhen Kaiyuan , Dong Fen , Fang Fang , Gao Qian , Zhang Zhu , Xia Lei , Wang Wei , Yang Peiran , Jia Cunbo , Liu Peng , Zhai Zhenguo , Wang Chen ,   On behalf of Chinese Prevention Strategy for Venous Thromboembolism (CHIPS-VTE) study group
Published: September 2021

Background

Countries in the world have taken actions to prevent venous thromboembolism (VTE) in hospitals. We have conducted a study in China to assess the establishment of hospital-based systems for VTE prevention and management.

Methods

A nationwide hospital survey was conducted in China to collect hospital-level metrics on their system for VTE prevention between 2019 and 2020. We analyzed hospital-level metrics potentially influencing the implementation of thromboprophylaxis using a multivariable regression model. Characteristics of the hospital, organizational structure, quality control, and staff training were analyzed.

Results

Among 435 hospitals responding to the survey, 328 (75.4%) were able to implement thromboprophylaxis. They performed VTE and bleeding risk assessments and had prophylactic interventions. Institutional VTE steering committee and unit-based working group were set up in 317 (72.9%) and 339 (77.9%) hospitals, respectively. More than 80% of the hospitals performed quality control and staff training. In contrast, digitalization of risk assessment was only accomplished in 196 (45.1%) hospitals. Proportions of the aforementioned metrics were consistently higher in tertiary hospitals than secondary hospitals (P < 0.01) except for quality control. There were geographical disparities in the establishment of VTE steering committees (P = 0.0004). In multivariable analysis, VTE steering committee was an independent factor for the implementation of thromboprophylaxis (odds ratio, 2.22, 95% confidence interval, 1.17–4.23). Working group, quality control, and training on VTE were also positively associated with the implementation of thromboprophylaxis.

Conclusions

In-hospital VTE prevention has been undertaken in China, but system establishment remains suboptimal. Implementation of VTE prevention programs was associated with a decrease in thrombolytic events. Hospitals with VTE steering committees performed better on implementing preventive strategies. Suboptimal adoption of information digitization was identified, and the implementation of computer supporting techniques would be expected to improve the implementation of thromoboprophylaxis.
Responding to COVID-19 Through Interhospital Resource Coordination: A Mixed-Methods Evaluation
Authors: Usher Michael G. , Tignanelli Christopher J. , Hilliard Brian , Kaltenborn Zachary P. , Lupei Monica I. , Simon Gyorgy , Shah Surbhi , Kirsch Jonathan D. , Melton Genevieve B. , Ingraham Nicholas E. , Olson Andrew P.J. , Baum Karyn D.
Published: September 2021

Objectives

The COVID-19 pandemic stressed hospital operations, requiring rapid innovations to address rise in demand and specialized COVID-19 services while maintaining access to hospital-based care and facilitating expertise. We aimed to describe a novel hospital system approach to managing the COVID-19 pandemic, including multihospital coordination capability and transfer of COVID-19 patients to a single, dedicated hospital.

Methods

We included patients who tested positive for SARS-CoV-2 by polymerase chain reaction admitted to a 12-hospital network including a dedicated COVID-19 hospital. Our primary outcome was adherence to local guidelines, including admission risk stratification, anticoagulation, and dexamethasone treatment assessed by differences-in-differences analysis after guideline dissemination. We evaluated outcomes and health care worker satisfaction. Finally, we assessed barriers to safe transfer including transfer across different electronic health record systems.

Results

During the study, the system admitted a total of 1209 patients. Of these, 56.3% underwent transfer, supported by a physician-led System Operations Center. Patients who were transferred were older (P = 0.001) and had similar risk-adjusted mortality rates. Guideline adherence after dissemination was higher among patients who underwent transfer: admission risk stratification (P < 0.001), anticoagulation (P < 0.001), and dexamethasone administration (P = 0.003). Transfer across electronic health record systems was a perceived barrier to safety and reduced quality. Providers positively viewed our transfer approach.

Conclusions

With standardized communication, interhospital transfers can be a safe and effective method of cohorting COVID-19 patients, are well received by health care providers, and have the potential to improve care quality.
Role of Intravenous Immunoglobulin in Necrotizing Autoimmune Myopathy
Authors: Kocoloski Amanda , Martinez Silvia , Moghadam-Kia Siamak , Lacomis David , Oddis Chester V. , Ascherman Dana P. , Aggarwal Rohit
Published: September 2021

Background/Objective

Immune-mediated necrotizing myopathy (IMNM) is a subtype of myositis that is associated with a refractory phenotype and poorer prognosis. The aim of the study was to provide single large center experience of outcomes of intravenous immunoglobulin (IVIg) for patients with IMNM using longitudinally collected data.

Methods

This case series longitudinally evaluated 4 of the 6 myositis core set measures at baseline and at 3 and 6 months after IVIg on 20 adult IMNM patients from 2014 to 2019 at the University of Pittsburgh. We assessed patients for improvement in core set measures, prednisone dose, adverse effects, and by the “limited” ACR/EULAR 2016 myositis response criteria. The mean differences in CK and manual muscle testing (MMT-8) were compared using a paired t test. A clinically significant response was defined as a >10% absolute improvement in the MMT-8 and a >50% absolute reduction in serum CK at 6 months of IVIg.

Results

Intravenous immunoglobulin treatment was associated with marked improvement in IMNM patients, with 85% of patient meeting clinically significant response. The median (interquartile range) relative percent improvement in CK level was 96% (85%–98%) and in MMT was 29% (14%–36%) at 6 months.

There was a significant reduction in the mean (SD) dose of prednisone at 6 months and had minimal adverse effects. In addition, with IVIg, most (13/14) patients had at least minimal improvement as per ACR/EULAR 2016 myositis response criteria.

Conclusions

Based on objective, meaningful improvement in MMT-8 and CK as well as marked reduction in prednisone doses with acceptable tolerability, early implementation of IVIg should be considered in adult IMNM.
Laparoscopic Totally Extraperitoneal (TEP) Groin Hernia Repair in Patients After Contralateral TEP Groin Hernia Repair
Authors: Zuiki Toru , Ohki Jun , Miyahara Go , Kobayashi Fuyumi , Lefor Alan K.
Published: September 2021

Background:

The totally extraperitoneal (TEP) repair for groin hernia is considered difficult in patients with a healed surgical scar in the lower abdomen. We reported the feasibility of repair in those patients and found that the most frequent previous procedure in patients for whom the procedure was changed intraoperatively was a contralateral TEP after TEP repair. We now report an expanded patient cohort with a suggested unified treatment strategy.

Materials and Methods:

From 2006 to 2020, 443 patients underwent laparoscopic TEP groin hernia repair. A contralateral TEP after TEP repair was performed in 35 patients. The conversion rate after TEP was compared with that after other operations. Patients were divided into completed contralateral TEP after TEP repair (N=28) and changed procedure groups (N=7). Clinical characteristics were compared including age, body mass index, location and type of hernia, and interval after previous surgery. Multivariate analysis was performed to evaluate risk factors for conversion of the TEP procedure.

Results:

Patients undergoing contralateral TEP after TEP repair were significantly overrepresented among patients for whom the procedure was changed compared with other previous operations (P<0.01), with an odds ratio of 19.91. Comparing completed TEP after TEP repair and changed procedure groups, there were no significant differences regarding age (mean: 67 vs. 69 y old), body mass index (22.4 vs. 22.5 kg/m2), type of hernia (indirect or direct), or duration after previous TEP repair (median: 642 vs. 470 d) and identified no significant risk factors.

Conclusions:

The contralateral TEP after TEP repair for groin hernia is feasible. However, dense adhesions may be present if balloon dissection was performed at the previous TEP repair, and it is necessary to carefully dissect being ready to convert to other procedures such as TAPP repair or an anterior approach.
Is There an Impact of the Duration of Antibiotic Therapy on the Outcome of Nonsurgical Treatment of Complicated Diverticulitis?
Authors: Khaoudy Iman , Sabbagh Charles , Brac Baptiste , Regimbeau Jean-Marc
Published: September 2021

Background:

Patients treated nonsurgically for complicated diverticulitis are managed by antibiotics. However, there are no recommendations concerning their duration. We aimed to determine the impact of the duration of antibiotic therapy on the risk of failure of nonsurgical treatment of complicated acute diverticulitis.

Patients and Methods:

This was a single-center retrospective study of patients with computer tomography (CT)-diagnosed complicated diverticulitis between January 2015 and April 2020. Treatment failure was defined as early recurrence and/or a persistent abscess by control CT.

Results:

In total, 148 patients fulfilled the inclusion criteria [87 men (58.8%), mean age 55±15 y]. The diverticulitis was classified as Hinchey I in 41.9%, Hinchey II in 9.5%, and pericolic free air in 48.6% of cases. The median abscess size was 2.9±1.7 cm. The median duration of antibiotic treatment was 10±4.2 days. The median follow-up was 64±60 months. The rate of failure was 12.8%. In univariate analysis, treatment >10 days (P=0.015) and an abscess >3 cm (P=0.032) were associated with a risk of treatment failure. In multivariate analysis, only the diameter of the abscess remained associated with a risk of failure (odds ratio: 1.6, 95% confidence interval: 1.09-2.4, P=0.01).

Conclusion:

This study suggests that there is no need to extend the duration of antibiotic treatment beyond 10 days in nonsurgically treated complicated acute diverticulitis.
Laparoscopic Remnant Cholecystectomy With CBD Exploration: A Tertiary Center Experience
Authors: Sahoo Manash R. , Panigrahi Sanhita , Sethi Mahesh K. , Kumar Bodda A.
Published: September 2021

Background:

After partial cholecystectomy, the remnant gallbladder can become symptomatic requiring surgical intervention. This study aims at assessing feasibility and safety of laparoscopic remnant cholecystectomy with common bile duct (CBD) exploration in patients having remnant gallbladder stones with choledocholithiasis.

Materials and Methods:

This retrospective observational study includes data obtained over a period of 10 years, from 2010 to 2020, in 2 tertiary care centers performing advanced laparoscopic surgery. Patients with remnant gallbladder stones with choledocholithiasis were include in this study. All of them underwent laparoscopic remnant cholecystectomy with CBD exploration. Demographic, perioperative and follow up data were collected and analyzed.

Results:

A total of 18 patients with a mean age of 47 years, male to female ratio of 1:3.5, with cholecystectomy done 10 months to 15 years back, were diagnosed with remnant gallbladder stones with choledocholithiasis during the period of 2010 to 2020. Five patients had undergone endoscopic retrograde cholangiopancreatography stenting of CBD 3 months to 2 years back. All of them underwent laparoscopic remnant cholecystectomy with CBD exploration. Trans cystic approach for CBD exploration was performed in 11 patients. In 7 patients, transductal CBD exploration was done, out of which, 1 patient needed T-tube placement. Median hospital stay was for 3 days. Morbidity rate was 5.56% at 30 days after operation. There was no recurrence of symptoms or mortality after a median follow up of 24 months (range: 5 to 60 mo).

Conclusion:

Concurrent laparoscopic remnant cholecystectomy with CBD exploration is feasible, safe, and reproducible when performed in centers with experience in advanced laparoscopic surgery.
Long-term Outcome of Per-oral Endoscopic Myotomy Performed in the Endoscopy Unit With Trainees
Authors: Abdelfatah Mohamed M. , Calderon Lucie F. , Koldhekar Amol , Kapil Neil , Noll Alan , Shah Rush , Mekaroonkamol Parit , Patel Vaishali , Dacha Sunil , Philips George , Shahnavaz Nikrad , Keilin Steve , Willingham Field F. , Christie Jennifer , Cai Qiang
Published: September 2021

Introduction:

Per-oral endoscopic myotomy (POEM) has been widely adopted for the treatment of achalasia as it provides a precise, tailored myotomy in a minimally invasive endoscopic procedure. Several short-term studies and a few long-term studies have confirmed that POEM is a safe and effective treatment for achalasia. However, the long-term outcome of POEM performed by trainees is unknown.

Materials and Methods:

We conducted a retrospective study of all patients who underwent POEM for achalasia at our tertiary care center during December 2012 and January 2019. All procedures performed with trainees were included. The primary outcome was the clinical response to POEM, defined as an Eckardt score of <3 after POEM. Trainees were trained in performing mucosotomy and submucosal dissection, creating a submucosal tunnel, identifying gastroesophageal junction, and performing myotomy and closure of mucosal incision in a step-by-step fashion. Trainees’ performance was evaluated by the mentor based on several key points in each step.

Results:

A total of 153 consecutive patients with a median age of 57±18 years were analyzed in this study. Of the total patients, 69 (45%) were male. The median length of follow-up after POEM was 32 months (range: 7 to 77 mo). A clinically significant response to POEM was achieved in 95% of patients at year 1, 84% at year 2, 80% at year 3, 79% at year 4, 78% at year 5, and 78% at year 6 and above. All trainees obtained competence within 6 cases for each step and could perform the procedure alone after 20 supervised cases.

Conclusions:

Overall, 78% of patients maintained positive clinical response at 6 years following POEM procedure. The recurrence rate of symptoms following POEM was 22% at a 6-year follow-up. This long-term outcome of POEM performed with trainees was comparable to those without trainees in other studies. To our knowledge, this is the longest follow-up and the largest number of patients after the POEM procedure performed with trainees.
Methane flux measurements along a floodplain soil moisture gradient in the Okavango Delta, Botswana
Authors: Gondwe M. J. , Helfter C. , Murray-Hudson M. , Levy P. E. , Mosimanyana E. , Makati A. , Mfundisi K. B. , Skiba U. M.
Published: September 2021

Data-poor tropical wetlands constitute an important source of atmospheric CH4in the world. We studied CH4fluxes using closed chambers along a soil moisture gradient in a tropical seasonal swamp in the Okavango Delta, Botswana, the sixth largest tropical wetland in the world. The objective of the study was to assess net CH4fluxes and controlling environmental factors in the Delta's seasonal floodplains. Net CH4emissions from seasonal floodplains in the wetland were estimated at 0.072 ± 0.016 Tg a−1. Microbial CH4oxidation of approximately 2.817 × 10−3 ± 0.307 × 10−3 Tg a−1in adjacent dry soils of the occasional floodplains accounted for the sink of 4% of the total soil CH4emissions from seasonal floodplains. The observed microbial CH4sink in the Delta's dry soils is, therefore, comparable to the global average sink of 4–6%. Soil water content (SWC) and soil organic matter were the main environmental factors controlling CH4fluxes in both the seasonal and occasional floodplains. The optimum SWC for soil CH4emissions and oxidation in the Delta were estimated at 50% and 15%, respectively. Electrical conductivity and pH were poorly correlated (r2 ≤ 0.11,p < 0.05) with CH4fluxes in the seasonal floodplain at Nxaraga.

This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part1)'.
Atmospheric methane removal: a research agenda
Authors: Jackson Robert B. , Abernethy Sam , Canadell Josep G. , Cargnello Matteo , Davis Steven J. , Féron Sarah , Fuss Sabine , Heyer Alexander J. , Hong Chaopeng , Jones Chris D. , Damon Matthews H. , O'Connor Fiona M. , Pisciotta Maxwell , Rhoda Hannah M. , de Richter Renaud , Solomon Edward I. , Wilcox Jennifer L. , Zickfeld Kirsten
Published: September 2021

Atmospheric methane removal (e.g.in situmethane oxidation to carbon dioxide) may be needed to offset continued methane release and limit the global warming contribution of this potent greenhouse gas. Because mitigating most anthropogenic emissions of methane is uncertain this century, and sudden methane releases from the Arctic or elsewhere cannot be excluded, technologies for methane removal or oxidation may be required. Carbon dioxide removal has an increasingly well-established research agenda and technological foundation. No similar framework exists for methane removal. We believe that a research agenda for negative methane emissions—‘removal' or atmospheric methane oxidation—is needed. We outline some considerations for such an agenda here, including a proposed Methane Removal Model Intercomparison Project (MR-MIP).

This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 1)'.
Atmospheric methane and nitrous oxide: challenges alongthe path to Net Zero
Authors: Nisbet Euan G. , Dlugokencky Edward J. , Fisher Rebecca E. , France James L. , Lowry David , Manning Martin R. , Michel Sylvia E. , Warwick Nicola J.
Published: September 2021

The causes of methane's renewed rise since 2007, accelerated growth from 2014 and record rise in 2020, concurrent with an isotopic shift to values more depleted in13C, remain poorly understood. This rise is the dominant departure from greenhouse gas scenarios that limit global heating to less than 2°C. Thus a comprehensive understanding of methane sources and sinks, their trends and inter-annual variations are becoming more urgent. Efforts to quantify both sources and sinks and understand latitudinal and seasonal variations will improve our understanding of the methane cycle and its anthropogenic component. Nationally declared emissions inventories under the UN Framework Convention on Climate Change (UNFCCC) and promised contributions to emissions reductions under the UNFCCC Paris Agreement need to be verified independently by top-down observation. Furthermore, indirect effects on natural emissions, such as changes in aquatic ecosystems, also need to be quantified. Nitrous oxide is even more poorly understood. Despite this, options for mitigating methane and nitrous oxide emissions are improving rapidly, both in cutting emissions from gas, oil and coal extraction and use, and also from agricultural and waste sources. Reductions in methane and nitrous oxide emission are arguably among the most attractive immediate options for climate action.

This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 1)'.
Cellulomonas aurantiaca Kim et al. 2020 is a later heterotypic synonym of Cellulomonas algicola Yamamura et al. 2019
Authors: Wu Yong , Gao Yuxin , Fang Jiasong , Wei Yuli
Published: September 2021

Cellulomonas algicola

KZ-21T was compared with

Cellulomonas aurantiaca

THG-SMD2.3T to examine the taxonomic relationship between the two type strains. The 16S rRNA gene sequence of

Cellulomonas algicola

KZ-21T shared complete similarity (100.0 %) with that of

Cellulomonas aurantiaca

THG-SMD2.3T. The results of phylogenetic analyses based on 16S rRNA gene sequences indicated that the two strains formed a tight cluster within the genus

Cellulomonas

. Genome comparison between the two strains revealed an average nucleotide identity of 99.2 % and a digital DNA–DNA hybridization estimate of 93.7±1.8 %, strongly indicating that the two strains belong to a single species. In addition, neither strain displayed any striking differences in metabolic, physiological or chemotaxonomic features. Therefore, we propose

Cellulomonas aurantiaca

as a later heterotypic synonym of

Cellulomonas algicola

.
Clinical Annotations for Prostate Cancer Research: Defining Data Elements, Creating a Reproducible Analytical Pipeline, and Assessing Data Quality
Authors: Keegan Niamh M. , Vasselman Samantha E. , Barnett Ethan S. , Nweji Barbara , Carbone Emily A. , Blum Alexander , Morris Michael J. , Rathkopf Dana E. , Slovin Susan F. , Danila Daniel C. , Autio Karen A. , Kantoff Philip W. , Abida Wassim , Stopsack Konrad H.
Published: September 2021

Background

Routine clinical data from clinical charts are indispensable for retrospective and prospective observational studies and clinical trials. Their reproducibility is often not assessed.

Objective

To develop a prostate cancer-specific database with a defined source hierarchy for clinical annotations in conjunction with molecular profiling and to evaluate data reproducibility.

Design, setting, and participants

For men with prostate cancer and clinical-grade paired tumor–normal sequencing, we performed team-based retrospective data collection from the electronic medical record at a comprehensive cancer center. We developed an open-source R package for data processing. We assessed reproducibility using blinded repeat annotation by a reference medical oncologist.

Outcome measurements and statistical analysis

We evaluated completeness of data elements, reproducibility of team-based annotation compared to the reference, and impact of measurement error on bias in survival analyses.

Results and limitations

Data elements on demographics, diagnosis and staging, disease state at the time of procuring a genomically characterized sample, and clinical outcomes were piloted and then abstracted for 2,261 patients (with 2,631 samples). Completeness of data elements was generally high. Comparing to the repeat annotation by a medical oncologist blinded to the database (100 patients/samples), reproducibility of annotations was high to very high; T stage, metastasis date, and presence and date of castration resistance had lower reproducibility. Impact of measurement error on estimates for strong prognostic factors was modest.

Conclusions

With a prostate cancer-specific data dictionary and quality control measures, manual clinical annotations by a multidisciplinary team can be scalable and reproducible. The data dictionary and the R package for reproducible data processing are freely available to increase data quality in clinical prostate cancer research.

Patient summary

Information in the medical record is the backbone for clinical research on prostate cancer. The tools provided in this study can increase quality and efficiency of this research.
Trends in Cognitive Function Pre- and Post- Stroke: Finding from the China Health and Retirement Longitudinal Study
Authors: Hua Jianian , Dong Jianye , Shen Yueping
Published: September 2021

Introduction

The magnitude of changes in cognitive function after stroke among the Chinese population is not clear. We aimed to learn the trajectories of cognitive function before and after incident stroke among Chinese participants.

Methods

Data were obtained from a nationally representative study. A total of 13311 Chinese participants aged 45 years or older and without a history of stroke were assessed at baseline between June 2011 and March 2012 and in at least one cognitive test between Wave 2 to Wave 4. Cognitive function was assessed by a global cognition score, which included episodic memory, visuospatial abilities, and executive function. A linear mixed model was developed to explore the repeated measurements.

Results

During the seven-year follow-up, we observed 610 (4.6%) participants experienced the first stroke. The baseline mean (SD) age was 58.6 (9.2) years. 47.3% of them were male. There was no difference in the baseline cognitive function and decline rate of pre-stroke cognition between stroke survivors and stroke-free participants after adjusting for covariates. Among the stroke survivors, the acute decline was -0.123, -0.169, and -0.135 SD/y in cognitive domains of episodic memory, visuospatial ability, and global cognition, respectively. The executive function did not decline acutely after stroke. In the years following stroke, the decline rate of executive function was 0.056 SD/y faster than the rate before stroke. The decline rate of episodic memory, visuospatial ability, and global cognition did not accelerate after stroke.

Conclusion

Before stroke onset, the cognitive function of Chinese stroke survivors was similar to that of stroke-free participants. Incident stroke was associated with acute decline in global cognition, episodic memory, and visuospatial abilities, and accelerated decline in orientation, attention, and calculation abilities. The cognitive trajectories revealed by our study highlights the need to care for the cognitive decline among Chinese stroke survivors.
Intravenous Immunoglobulin (IVIG) in Treating Non-ventilated COVID-19 Patients with Moderate to Severe Hypoxia is Pharmacoeconomically Favorable When Appropriately Targeted
Authors: Poremba Matthew , Dehner Matthew , Perreiter Alexandra , Semma Ashley , Mills Kimberly , Sakoulas George
Published: September 2021

Background

Prior studies have shown that intravenous immunoglobulin (IVIG) can improve outcomes in patients with COVID-19, but the high costs of IVIG leave questions as to its pharmacoeconomic value.

Methods

The hospital costs of 2 IVIG vs. non-IVIG COVID-19 patient groups were compared. The first cohort was a case-control analysis of 10 non-ventilated moderately to severely hypoxic COVID-19 patients who received IVIG (Privigen) matched 1:2 with 20 control patients of similar age, body mass index (BMI), degree of hypoxemia, and co-morbidities. The second cohort consisted of patients enrolled in a previously published randomized open-label prospective study of 14 COVID-19 patients receiving standard of care (SOC) versus 13 patients who received SOC plus IVIG (Octagam 10%).

Results

Among the first case control population, mean total direct costs including IVIG for the treatment group was $21,982 per IVIG-treated case versus $42,431 per case for matched non-IVIG receiving controls, representing a net cost reduction of $20,449 (48%) per case. For the second (randomized) group, mean total direct costs including IVIG for the treatment group was $28,268 per case versus $62,707 per case for untreated controls, representing a net cost reduction of $34,439 (55%) per case. 24% of the non-IVIG patients had hospital costs exceeded $80,000, as compared to none of the IVIG patient host (p=0.016, Fisher exact test).

Conclusion

When allocated to the appropriate patient type (moderate to severe illness without end-organ comorbidities and age <70 years), IVIG can significantly reduce hospital costs in COVID-19 care. More importantly, it may reduce the demand on scare critical care resources during the COVID-19 pandemic.
A Neuromuscular Model of Human Locomotion Combines Spinal Reflex Circuits with Voluntary Movements
Authors: Ramadan Rachid , Geyer Hartmut , Jeka John , Schöner Gregor , Reimann Hendrik
Published: September 2021

Existing models of human walking use low-level reflexes or neural oscillators to generate movement. While appropriate to generate the stable, rhythmic movement patterns of steady-state walking, these models lack the ability to change their movement patterns or spontaneously generate new movements in the specific, goal-directed way characteristic of voluntary movements. Here we present a neuromuscular model of human locomotion that bridges this gap and combines the ability to execute goal directed movements with the generation of stable, rhythmic movement patterns that are required for robust locomotion. The model represents goals for voluntary movements of the swing leg on the task level of swing leg joint kinematics. Smooth movements plans towards the goal configuration are generated on the task level and transformed into descending motor commands that execute the planned movements, using internal models. The movement goals and plans are updated in real time based on sensory feedback and task constraints. On the spinal level, the descending commands during the swing phase are integrated with a generic stretch reflex for each muscle. Stance leg control solely relies on dedicated spinal reflex pathways. Spinal reflexes stimulate Hill-type muscles that actuate a biomechanical model with eight internal joints and six free-body degrees of freedom. The model is able to generate voluntary, goal-directed reaching movements with the swing leg and combine multiple movements in a rhythmic sequence. During walking, the swing leg is moved in a goal-directed manner to a target that is updated in real-time based on sensory feedback to maintain upright balance, while the stance leg is stabilized by low-level reflexes and a behavioral organization switching between swing and stance control for each leg. With this combination of reflex-based stance leg and voluntary, goal-directed control of the swing leg, the model controller generates rhythmic, stable walking patterns in which the swing leg movement can be flexibly updated in real-time to step over or around obstacles.
High prevalence of somatic PIK3CA and TP53 pathogenic variants in the normal mammary gland tissue of sporadic breast cancer patients revealed by duplex sequencing
Authors: Kostecka Anna , Nowikiewicz Tomasz , Olszewski Paweł , Koczkowska Magdalena , Horbacz Monika , Heinzl Monika , Andreou Maria , Salazar Renato , Mair Theresa , Madanecki Piotr , Gucwa Magdalena , Davies Hanna , Skokowski Jarosław , Buckley Patrick G. , Pęksa Rafał , Śrutek Ewa , Szylberg Łukasz , Hartman Johan , Jankowski Michał , Zegarski Wojciech , Tiemann-Boege Irene , Dumanski Jan P. , Piotrowski Arkadiusz
Published: September 2021

The mammary gland undergoes hormonally stimulated cycles of proliferation, lactation and involution. We hypothesized that these factors increase the mutational burden in glandular tissue and may explain high cancer incidence rate in the general population and recurrent disease. Hence, we investigated the DNA sequence variants in the normal mammary gland, tumor and peripheral blood from 52 reportedly sporadic breast cancer patients, including breast-conserving surgery cases. Targeted resequencing of 542 cancer associated genes revealed mosaic somatic pathogenic variants of: PIK3CA, TP53, AKT1, MAP3K1, CDH1, RB1, NCOR1, MED12, CBFB, TBX3 and TSHR in the normal mammary gland, at considerable allelic frequencies (9×10−2 to 5.2×10−1) indicating clonal expansion. Further evaluation of the frequently damaged PIK3CA and TP53 genes by ultra-sensitive duplex sequencing demonstrated a diversified picture of multiple low level-mosaic (in 10−2 to 10−4 alleles) hotspot pathogenic variants. Our results raise a question about the oncogenic potential in non-tumor mammary gland tissue of breast-conserving surgery patients.
virusMED: an atlas of hotspots of viral proteins
Authors: Zhang HuiHui , Chen Pei , Ma Haojie , Woińska Magdalena , Liu Dejian , Cooper David R. , Peng Guo , Peng Yousong , Deng Lei , Minor Wladek , Zheng Heping
Published: September 2021

Metal binding sites, antigen epitopes and drug binding sites are the hotspots in viral proteins that control how viruses interact with their hosts. virusMED (virus
Metal binding sites, Epitopes and Drug binding sites) is a rich internet application based on a database of atomic interactions around hotspots in 7041 experimentally determined viral protein structures. 25306 hotspots from 805 virus strains from 75 virus families were characterized, including influenza, HIV-1 and SARS-CoV-2 viruses. Just as Google Maps organizes and annotates points of interest, virusMED presents the positions of individual hotspots on each viral protein and creates an atlas upon which newly characterized functional sites can be placed as they are being discovered. virusMED contains an extensive set of annotation tags about the virus species and strains, viral hosts, viral proteins, metal ions, specific antibodies and FDA-approved drugs, which permits rapid screening of hotspots on viral proteins tailored to a particular research problem. The virusMED portal (https://virusmed.biocloud.top) can serve as a window to a valuable resource for many areas of virus research and play a critical role in the rational design of new preventative and therapeutic agents targeting viral infections.
Crystal structures of human coronavirus NL63 main protease at different pH values
Authors: Gao Hongxia , Zhang Yuting , Jiang Haihai , Hu Xiaohui , Zhang Yuting , Zhou Xuelan , Zhong Fanglin , Lin Cheng , Li Jian , Luo Jun , Zhang Jin
Published: September 2021

Human coronavirus NL63 (HCoV-NL63), which belongs to the genus Alphacoronavirus, mainly infects children and the immunocompromized and is responsible for a series of clinical manifestations, including cough, fever, rhinorrhoea, bronchiolitis and croup. HCoV-NL63, which was first isolated from a seven-month-old child in 2004, has led to infections worldwide and accounts for 10% of all respiratory illnesses caused by etiological agents. However, effective antivirals against HCoV-NL63 infection are currently unavailable. The HCoV-NL63 main protease (Mpro), also called 3C-like protease (3CLpro), plays a vital role in mediating viral replication and transcription by catalyzing the cleavage of replicase polyproteins (pp1a and pp1ab) into functional subunits. Moreover, Mpro is highly conserved among all coronaviruses, thus making it a prominent drug target for antiviral therapy. Here, four crystal structures of HCoV-NL63 Mpro in the apo form at different pH values are reported at resolutions of up to 1.78 Å. Comparison with Mpro from other human betacoronaviruses such as SARS-CoV-2 and SARS-CoV reveals common and distinct structural features in different genera and extends knowledge of the diversity, function and evolution of coronaviruses.
Metalloprotein catalysis: structural and mechanistic insights into oxidoreductases from neutron protein crystallography
Authors: Schröder Gabriela C. , Meilleur Flora
Published: September 2021

Metalloproteins catalyze a range of reactions, with enhanced chemical functionality due to their metal cofactor. The reaction mechanisms of metalloproteins have been experimentally characterized by spectroscopy, macromolecular crystallography and cryo-electron microscopy. An important caveat in structural studies of metalloproteins remains the artefacts that can be introduced by radiation damage. Photoreduction, radiolysis and ionization deriving from the electromagnetic beam used to probe the structure complicate structural and mechanistic interpretation. Neutron protein diffraction remains the only structural probe that leaves protein samples devoid of radiation damage, even when data are collected at room temperature. Additionally, neutron protein crystallography provides information on the positions of light atoms such as hydrogen and deuterium, allowing the characterization of protonation states and hydrogen-bonding networks. Neutron protein crystallography has further been used in conjunction with experimental and computational techniques to gain insight into the structures and reaction mechanisms of several transition-state metal oxidoreductases with iron, copper and manganese cofactors. Here, the contribution of neutron protein crystallography towards elucidating the reaction mechanism of metalloproteins is reviewed.
Consumer empowerment in corporate social responsibility: the effect of participatory CSR on company admiration and word-of-mouth communications
Authors: Park Hyojung , Kim Soo-Yeon
Published: September 2021

Purpose

This study conceptualizes participatory corporate social responsibility (CSR) as a consumer empowerment strategy and examines the effect of participatory CSR on consumer responses in a social media setting.

Design/methodology/approach

This study uses a 2 (type of CSR campaign) × 4 (tone of consumer comments) between-subjects experimental design. The sample comprises college students and nonstudent participants recruited from Amazon Mechanical Turk.

Findings

Data indicate that the participatory CSR program leads to higher levels of perceived self-efficacy and social worth, which subsequently results in stronger intentions to spread positive word of mouth about the company’s CSR efforts. The findings suggest that participatory CSR has the power to boost a company’s reputation as an “admired” company through consumer empowerment.

Originality/value

This study advances the scholarship of CSR by explicating participatory CSR communication as a consumer empowerment strategy and providing empirical evidence for the effect of participatory CSR on public responses. The overall findings support the notion that CSR communication as an important function of public relations can generate public engagement with the organization and further co-create meaning with publics for mutual benefit.
Predicting intention of business students to behave ethically in the Indian context: from the perspective of Theory of Planned Behaviour
Authors: Marmat Geeta
Published: September 2021

Purpose

The purpose of this paper is to understand business students' intention to behave ethically in general, and in particularly in the business context of a developing country, India.

Design/methodology/approach

The paper surveyed 250 final semester MBA students from different business schools in Indore city of Madhya Pradesh in India. The study employed the most popular behavioural theory, the Theory of Planned Behaviour (TPB) to understand the intention of business students to behave ethically. Structural equation modelling was used to analyse direct effects of the constructs on behavioural intention, and the overall model.

Findings

Findings revealed that attitude, subjective norm and perceived behavioural control are positively related and have strong influence on ethical behavioural intention of business students. All constructs together explain 67 percent variance in intention. Attitude alone contributes 46 percent in explaining variance in ethical behavioural intention.

Research limitations/implications

Business ethics field can benefit from this study as it provides an empirical explanation of the contribution of each factor that is, attitude, subjective norms and perceived behavioural control, in ethical behavioural intention of business students. This is directly beneficial for business schools and for education policymakers as the information can help policymakers to understand the potential of existing business ethics education. This study is limited to a data set of 250 business students in the context of a single country which cannot be generalized. So, there is need for research of this type in a more collaborative international context.

Originality/value

To the best of my knowledge, this is the first study in the Indian context to predict the intention of business students to behave ethically, using the TPB model. This study contributes valuable knowledge to the domain of business ethics, behavioural studies as well the field of business education, and suggests to explore ways to strengthen the three constructs attitude, subjective norm and perceived behavioural control, as these constructs were found to have a strong influence in forming ethical behavioural intention of business students of business schools in India.
Multiphysics simulation of single pulse laser powder bed fusion: comparison of front capturing and front tracking methods
Authors: Mayi Yaasin Abraham , Queva Alexis , Dal Morgan , Guillemot Gildas , Metton Charlotte , Moriconi Clara , Peyre Patrice , Bellet Michel
Published: September 2021

Purpose

During thermal laser processes, heat transfer and fluid flow in the melt pool are primary driven by complex physical phenomena that take place at liquid/vapor interface. Hence, the choice and setting of front description methods must be done carefully. Therefore, the purpose of this paper is to investigate to what extent front description methods may bias physical representativeness of numerical models of laser powder bed fusion (LPBF) process at melt pool scale.

Design/methodology/approach

Two multiphysical LPBF models are confronted: a Level-Set (LS) front capturing model based on a C++ code and a front tracking model, developed with COMSOL Multiphysics® and based on Arbitrary Lagrangian–Eulerian (ALE) method. To do so, two minimal test cases of increasing complexity are defined. They are simplified to the largest degree, but they integrate multiphysics phenomena that are still relevant to LPBF process.

Findings

LS and ALE methods provide very similar descriptions of thermo-hydrodynamic phenomena that occur during LPBF, providing LS interface thickness is correctly calibrated and laser heat source is implemented with a modified continuum surface force formulation. With these calibrations, thermal predictions are identical. However, the velocity field in the LS model is systematically underestimated compared to the ALE approach, but the consequences on the predicted melt pool dimensions are minor.

Originality/value

This study fulfils the need for comprehensive methodology bases for modeling and calibrating multiphysical models of LPBF at melt pool scale. This paper also provides with reference data that may be used by any researcher willing to verify their own numerical method.