bluuebunny/crossref_metadata_2025 huggingface dataset:
Being Happy and Becoming Happier as Independent Predictors of Physical Health and Mortality
Authors: Willroth Emily C. , Ong Anthony D. , Graham Eileen K. , Mroczek Daniel K.
Published: June 2020

Objective

The present study tested preregistered predictions regarding the prospective associations between level and change in subjective well-being (SWB) and physical health.

Methods

In two large longitudinal panel studies conducted in the United States (N = 3294) and Japan (N = 657), we used multilevel growth curve models to estimate level and change in components of SWB (i.e., life satisfaction, positive affect, and negative affect). Next, we used random intercepts and slopes to predict subsequent self-reported general health and number of chronic health conditions (in the United States and Japan) and mortality risk (in the United States).

Results

Greater life satisfaction, higher positive affect, and lower negative affect were associated with better health (0.22 < |β values| < 0.46) and longer survival. Above and beyond SWB level, longitudinal increases in life satisfaction and positive affect and longitudinal decreases in negative affect were associated with better health (0.06 < |β values| < 0.20). Moreover, all three SWB components independently predicted health, and life satisfaction and negative affect independently predicted survival. The preregistration and analysis scripts are available at osf.io/mz9gy.

Conclusions

The present findings suggest that being happy and becoming happier across time are independently associated with better physical health in the United States and Japan.
Postoperative Psychological Disorders Among Heart Transplant Recipients: A Meta-Analysis and Meta-Regression
Authors: Loh Alvona Z.H. , Tan Julia S.Y. , Tam John K.C. , Zhang Melvyn W. , Ho Cyrus S.H. , Ho Roger C.
Published: June 2020

Objective

This meta-analysis evaluates the pooled prevalence of depression, anxiety, adjustment disorder, and posttraumatic stress disorder (PTSD) among heart transplant recipients globally and determines underlying moderators.

Methods

The authors searched PubMed, Embase, PsychINFO, BIOSIS, Science Direct, and Cochrane CENTRAL databases from inception to March 1, 2019, and 1321 records and 42 full-text articles were selected and reviewed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We calculated the pooled prevalence proportion of depression, anxiety, adjustment disorder, and PTSD using random-effects models. Meta-regression was performed to identify important moderators that contribute to heterogeneity.

Results

Twenty studies met the inclusion criteria and comprised 2169 patients. The pooled prevalence of depression was 21.6% (95% confidence interval [CI] = 16.8%–27.3%), anxiety 11.1% (95% CI = 3.8%–28.5%), adjustment disorder 11.0% (95% CI = 3.1%–32.1%), and PTSD 13.5% (95% CI = 8%–21.8%). There was significant heterogeneity. Meta-regression was conducted to account for the heterogeneity of the prevalence proportion. Predisposing factors, for example, New York Heart Association classes II and III/IV, steroid treatment, and acute rejection of transplant (<3 months), were associated with high prevalence of depression. Protective factors, for example, age and higher ejection fraction after transplant of patients, were associated with low prevalence of depression. Female sex, single status, and number of months since transplant were associated with high prevalence of anxiety. Single status was associated with high prevalence of both adjustment disorder and transplant-related PTSD.

Conclusions

The prevalence of psychiatric conditions, particularly depression, is high in heart transplant recipients. The identified protective and risk factors may guide psychological interventions in heart transplant recipients.
Perforator-Based Flaps for Defect Reconstruction of the Posterior Trunk
Authors: Hernekamp Jochen-Frederick , Cordts Tomke , Kremer Thomas , Kneser Ulrich
Published: June 2020

Introduction

Full-thickness soft tissue defects of the back remain challenging clinical problems for reconstructive surgeons. Among a vast variety of local flap options, perforator-based local flaps gain increasing popularity lately. Because mostly heterogeneous patient cohort comparison of different perforator flaps is difficult and decision-making algorithms are lacking.

Methods

Patients, who received a local perforator-based soft tissue reconstruction between 2012 and 2019, were evaluated retrospectively. Patients' data were evaluated in terms of flap type and dimension, wound size and cause, surgery time, postoperative complications, and hospitalization. A focus was set on decision making concerning reconstructive techniques and flap choice for defect closure.

Results

Thirty-six patients (17 women, 19 men) were included, who received 40 perforator-based local flaps to reconstruct extended defects of the posterior trunk. Mean patient age was 56.3 years and mean hospitalization was 29 days. Average time of flap surgery was 179.7 minutes. Mean flap size was 160.8 cm2 and average defect size was 110 cm2. Defects occurred because of tumor resection (50%), orthopedic/trauma surgery (16.7%), or pressure sores (33.3%). Twenty-eight propeller flaps (PPFs, 70%) and 12 perforator-based VY-advancement flaps (P-VYF, 30%) were transferred. In 4 patients, a bilateral approach using more than one flap was necessary. Revision surgery was required in 9 patients (25%) because of postoperative hematoma (n = 3), postoperative wound infection (n = 3), partial flap necrosis (1× P-VYF) and 2 flap losses (2× PPFs).

Conclusions

Pedicled perforator flaps are a reliable option for soft tissue reconstruction of complex wounds of the posterior trunk. A flexible surgical strategy is mandatory, and the individual perforator anatomy has to be considered. In most cases, P-VYFs or PPFs are reliably possible and allow sufficient defect reconstruction. However, skin incisions should always be performed in a way that classic random pattern flaps are still possible. Even in large defects combined, local perforator flaps may lead to sustainable soft tissue reconstructions without functional donor site deficits.
The Protective Effect of Platelet Rich Plasma Against Cisplatin-Induced Ototoxicity
Authors: Yurtsever Kum Nurcan , Baklaci Deniz , Guler Ismail , Kuzucu Ihsan , Kum Rauf Oguzhan , Ozhamam Esra Ucaryilmaz , Ozcan Muge , Dere Huseyin
Published: June 2020

Cisplatin, a pharmacological agent widely used for treating many cancers, may cause serious side effects including ototoxicity, nephrotoxicity, and peripheral neuropathy. The present study aimed to investigate whether platelet-rich plasma (PRP) protects against cisplatin ototoxicity. Eight rats (16 ears) were divided into 2 groups: control group (4 rats, 8 ears) that received intratympanic saline and study group (4 rats, 8 ears) that received intratympanic PRP. Cisplatin (10 mg/day intraperitoneally) or vehicle was administered 2 times per day to the animals. Auditory brainstem responses were recorded preoperatively and postoperatively on day 4 and at week 3. The authors compared the morphological appearances of spiral ganglion cells and the organ of Corti and the density of spiral ganglion cells between treatment groups. The number of outer hair cells in the organ of Corti significantly decreased in the control group compared with that in the PRP group. Although no statistically significant difference was observed between the groups regarding ABR thresholds on day 4 (P = 0.083, a statistically significant difference was observed between groups at week 3 (P = 0.038). Our results suggest that PRP can prevent cisplatin-induced ototoxicity.
Reconstruction of Full Thickness Scalp Defects in Extremely Elderly Patients Using Dermal Regeneration Templates
Authors: Bernstein Jaime L. , Premaratne Ishani D. , Levy Adam S. , Kuhel William I. , Kutler David I. , Spector Jason A.
Published: June 2020

The reconstruction of full thickness scalp defects following oncologic resection poses a unique challenge that is further magnified in “extremely elderly” patients, defined as those in at least their ninth decade of life, who are often unsuitable candidates for complex reconstruction. A “simpler” option is two-stage reconstruction: placement of Integra dermal regenerative template (Integra Life Science, Plainsboro, NJ) followed by a split thickness skin graft (STSG). This case series illustrates the success of this technique in the extremely elderly. A retrospective analysis of patients > 80 years at the time of surgery who underwent full thickness scalp reconstruction following tumor extirpation in a two-stage approach under the care of single surgeon from January 2010 to June 2019 was conducted. Variables reviewed were medical history, surgical treatment response, time to split thickness skin graft, follow up, and success of wound coverage. Fourteen patients, with a mean age of 87 years (range: 80 to 101, median: 87), met inclusion criteria. Split thickness skin grafts were placed after an average of 18 days. Twelve patients had successful two-stage reconstruction with 100% take. One patient developed a hematoma under a portion of the template that neither required reoperation nor delayed split thickness skin graft placement. A second suffered from insufficient vascularization of the template with delay to split thickness skin graft and incomplete wound closure. This two-stage approach is a successful primary reconstructive option for definitive management of full thickness scalp defects following oncologic resection in extremely elderly patients.
Poor Clinical Outcomes and Immunoevasive Contexture in Intratumoral IL-10-Producing Macrophages Enriched Gastric Cancer Patients
Authors: Zhang Hongyu , Li Ruochen , Cao Yifan , Gu Yun , Lin Chao , Liu Xin , Lv Kunpeng , He Xudong , Fang Hanji , Jin Kaifeng , Fei Yuchao , Chen Yifan , Wang Jieti , Liu Hao , Li He , Zhang Heng , He Hongyong , Zhang Weijuan
Published: June 2020

Objective:

To investigate the clinical significance of IL-10+ tumor-associated macrophages (TAMs) in gastric cancer.

Background:

Due to the plasticity and diversity of TAMs, it is necessary to phenotypically and functionally classify subsets of TAMs to better understand the critical role of TAMs in cancer progression. TAMs expressing interleukin-10 (IL-10) have been found to facilitate immune evasion in many malignancies, but the role of IL-10+ TAMs in gastric cancer remains obscure.

Methods:

Four hundred and sixty-eight tumor tissue microarray specimens, 52 fresh tumor tissue samples of gastric cancer patients from Zhongshan Hospital, and data of 298 gastric cancer patients from the Cancer Genome Atlas (TCGA) were analyzed. IL-10+ TAM level and immune contexture were examined by CIBERSORT, immunohistochemistry, and flow cytometry. Clinical outcomes were analyzed by Kaplan–Meier curves and Cox model.

Results:

Gastric cancer patients with high IL-10+ TAM infiltration exhibited poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy. IL-10+ TAM infiltration yielded an immunoevasive tumor microenvironment featured by regulatory T cell infiltration and CD8+ T cell dysfunction. The combinational analysis of IL-10+ TAM and CD8+ T cell infiltration stratified patients into distinct risk groups with different clinical outcomes. Moreover, IL-10+ TAM infiltration was correlated with tumor-intrinsic characteristics including EBV status, PD-L1 expression, and genome stability in gastric cancer.

Conclusions:

This study revealed that IL-10+ TAMs might drive an immunoevasive microenvironment and determine poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy, indicating IL-10+ TAMs could be applied as a potential target for immunotherapeutic approach in gastric cancer.
Is Local Endoscopic Resection a Viable Therapeutic Option for Early Clinical Stage T1a and T1b Esophageal Adenocarcinoma?
Authors: Kamarajah Sivesh K. , Phillips Alexander W. , Hanna George B. , Low Donald E. , Markar Sheraz R.
Published: June 2020

Objective:

The aim of this study was to evaluate the outcome of endoscopic resection (ER) versus esophagectomy in node-negative cT1a and cT1b esophageal adenocarcinoma.

Summary of Background Data:

The role of ER in the management of subsets of clinical T1N0 esophageal adenocarcinoma is controversial.

Methods:

Data from the National Cancer Database (2010–2015) were used to identify patients with clinical T1aN0 (n = 2545) and T1bN0 (n = 1281) esophageal adenocarcinoma that received either ER (cT1a, n = 1581; cT1b, n = 335) or esophagectomy (cT1a, n = 964; cT1b, n = 946). Propensity score matching and Cox analyses were used to account for treatment selection bias.

Results:

ER for cT1a and cT1b disease was performed more commonly over time. The rates of node-positive disease in patients with cT1a and cT1b esophageal adenocarcinoma were 4% and 15%, respectively. In the matched cohort for cT1a cancers, ER had similar survival to esophagectomy [hazard ratio (HR): 0.85, 95% confidence interval (CI): 0.70–1.04, P = 0.1]. The corresponding 5-year survival for ER and esophagectomy were 70% and 74% (P = 0.1), respectively. For cT1b cancers, there was no statistically significant difference in overall survival between the treatment groups (HR: 0.87, 95% CI: 0.66–1.14, P = 0.3). The corresponding 5-year survival for ER and esophagectomy were 53% versus 61% (P = 0.3), respectively.

Conclusions:

This study demonstrates ER has comparable long-term outcomes for clinical T1aN0 and T1bN0 esophageal adenocarcinoma. However, 15% of patients with cT1b esophageal cancer were found to have positive nodal disease. Future research should seek to identify the subset of T1b cancers at high risk of nodal metastasis and thus would benefit from esophagectomy with lymphadenectomy.
Comparison of Perioperative Outcomes in Heart Failure Patients With Reduced Versus Preserved Ejection Fraction After Noncardiac Surgery
Authors: Huang Yolanda Ya-Chin , Chen Ling , Wright Jason D.
Published: June 2020

Objective:

To compare outcome after noncardiac surgery between HF patients with reduced versus preserved ejection fraction.

Summary of Background Data:

HF patients who undergo major noncardiac surgery have higher risks of morbidity and mortality compared to the general population. However, it is unclear whether HF subtypes confer different risk.

Methods:

This retrospective study included HF patients, 45 years or older, who underwent noncardiac surgery from January 1, 2010 to September 30, 2015 in the Nationwide Readmissions Database. Multivariable logistic regression models were used to provide adjusted rates of postoperative outcomes. Hospital-level clustering and Nationwide Readmissions Database sampling weights were applied to all models.

Results:

Of the weighted 296,057 HF patients [HF with reduced ejection fraction (HFrEF) 48.1%; HF with preserved ejection fraction (HFpEF) 51.9%] who underwent noncardiac surgery, 41.1% had cardiopulmonary complications, 55.7% had noncardiopulmonary complications and 5.4% died during hospitalization. Thirty-day readmission rates for the weighted 232,852 HF patients was 21.5%. The adjusted odds ratios of cardiopulmonary and noncardiopulmonary complications, in-hospital mortality and 30-day readmission for HFrEF compared to HFpEF patients were 1.01 [95% confidence interval (CI), 0.99–1.04], 1.05 (95% CI, 1.02–1.07), 1.27 (95% CI, 1.21–1.34), and 1.08 (95% CI, 1.05–1.12), respectively.

Conclusions:

HFrEF patients have increased risks of noncardiopulmonary complications, mortality, and readmission after noncardiac surgery. These findings suggest that targeted perioperative care for HF subtypes may be crucial for the growing population of HF patients undergoing noncardiac surgery. Despite cardiopulmonary complications not being statistically different between HF subtypes, given the high occurrence rate, any intervention to decrease the rate would be clinically meaningful.
The Fistula Risk Score Catalog
Authors: Trudeau Maxwell T. , Casciani Fabio , Ecker Brett L. , Maggino Laura , Seykora Thomas F. , Puri Priya , McMillan Matthew T. , Miller Benjamin , Pratt Wande B. , Asbun Horacio J. , Ball Chad G. , Bassi Claudio , Behrman Stephen W. , Berger Adam C. , Bloomston Mark P. , Callery Mark P. , Castillo Carlos Fernandez-del , Christein John D. , Dillhoff Mary E. , Dickson Euan J. , Dixon Elijah , Fisher William E. , House Michael G. , Hughes Steven J. , Kent Tara S. , Malleo Giuseppe , Salem Ronald R. , Wolfgang Christopher L. , Zureikat Amer H. , Vollmer Charles M.
Published: June 2020

Objective:

This study aims to present a full spectrum of individual patient presentations of pancreatic fistula risk, and to define the utility of mitigation strategies amongst some of the most prevalent, and vulnerable scenarios surgeons encounter.

Background:

The FRS has been utilized to identify technical strategies associated with reduced CR-POPF incidence across various risk strata. However, risk-stratification using the FRS has never been investigated with greater granularity. By deriving all possible combinations of FRS elements, individualized risk assessment could be utilized for precision medicine purposes.

Methods:

FRS profiles and outcomes of 5533 PDs were accrued from 17 international institutions (2003–2019). The FRS was used to derive 80 unique combinations of patient “scenarios.” Risk-matched analyses were conducted using a Bonferroni adjustment to identify scenarios with increased vulnerability for CR-POPF occurrence. Subsequently, these scenarios were analyzed using multivariable regression to explore optimal mitigation approaches.

Results:

The overall CR-POPF rate was 13.6%. All 80 possible scenarios were encountered, with the most frequent being scenario #1 (8.1%) – the only negligible-risk scenario (CR-POPF rate = 0.7%). The moderate-risk zone had the most scenarios (50), patients (N = 3246), CR-POPFs (65.2%), and greatest non-zero discrepancy in CR-POPF rates between scenarios (18-fold). In the risk-matched analysis, 2 scenarios (#59 and 60) displayed increased vulnerability for CR-POPF relative to the moderate-risk zone (both P < 0.001). Multivariable analysis revealed factors associated with CR-POPF in these scenarios: pancreaticogastrostomy reconstruction [odds ratio (OR) 4.67], omission of drain placement (OR 5.51), and prophylactic octreotide (OR 3.09). When comparing the utilization of best practice strategies to patients who did not have these conjointly utilized, there was a significant decrease in CR-POPF (10.7% vs 35.5%, P < 0.001; OR 0.20, 95% confidence interval 0.12–0.33).

Conclusion:

Through this data, a comprehensive fistula risk catalog has been created and the most clinically-impactful scenarios have been discerned. Focusing on individual scenarios provides a practical way to approach precision medicine, allowing for more directed and efficient management of CR-POPF.
Skin Picking Successfully Treated With Atomoxetine in Comorbid Skin Picking and Attention-Deficit/Hyperactivity Disorder: A Case Report
Authors: Yurteri Nihal , Sarıgedik Enes
Published: June 2020

“Skin picking disorder” (SPD: also known as neurotic excoriation, psychogenic excoriation, or dermatillomania) is classified in the “obsessive-compulsive and related disorders” category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and characterized by unintentional, repetitive skin picking behaviors. Atomoxetine is a selective noradrenaline reuptake inhibitor used in the treatment of attention-deficit/hyperactivity disorder (ADHD). In this case report, we present a 9-year-old girl with the comorbid diagnosis of ADHD and SPD treated successfully with atomoxetine. To our knowledge, this is the first report of skin picking treated with atomoxetine in a patient with ADHD. We discussed possible explanations of mechanisms. Further studies are required on the effectiveness of atomoxetine for the treatment of SPD in the presence and absence of comorbid ADHD.
Expanding Access to Continuous EEG Monitoring in Neonatal Intensive Care Units
Authors: Fitzgerald Mark P. , Massey Shavonne L. , Fung France W. , Puopolo Karen M. , Posencheg Michael , Allen-Napoli Linda , Malcolm Marissa , Abend Nicholas S.
Published: June 2020

Purpose:

Neonatal seizures are common and difficult to identify clinically because the majority are subclinical and correct identification of electroclinical seizures based on semiology is unreliable. Therefore, continuous EEG monitoring (CEEG) is critical for seizure identification in neonates and is recommended as the gold standard method in American Clinical Neurophysiology Society guidelines. Despite these recommendations, barriers to implementing widespread CEEG exist.

Methods:

To expand access to CEEG for at-risk neonates, a framework for providing remote CEEG was established at two network hospital neonatal intensive care units. Utilization and clinical impact were tracked as a quality improvement study.

Results:

In a 27-month period from June 2017 through September 2019, 76 neonates underwent CEEG between the two network neonatal intensive care units. Electrographic seizures occurred in about one quarter of records (18/76; 24%), though their incidence varied by CEEG indication. Care notes indicated that CEEG impacted clinical care in three quarters of cases (57/76; 75%). Continuous EEG impacted decisions to treat with anti-seizure medications in approximately one half of patients (impact: 28/57 [49%]; no impact 29/57 [51%]), and CEEG impacted prognostic discussions in approximately two thirds of patients (impact: 39/57 [68%]; no impact 18/57 [32%]).

Conclusions:

Establishment of a remote CEEG program for neonates is feasible, effective at identifying seizures, and improves the quality of care provided to neonates hospitalized at these network hospitals.
Streptococcus downii sp. nov., isolated from the oral cavity of a teenager with Down syndrome
Authors: Martínez-Lamas Lucía , Limeres-Posse Jacobo , Diz-Dios Pedro , Álvarez-Fernández Maximiliano
Published: June 2020

A new α-haemolytic streptococcal strain has been isolated from the dental plaque of a teenager with Down syndrome. Genetic and taxonomic analyses place this

Streptococcus

within the oralis group. It is a Gram-stain-positive, non-motile, non-spore-forming spherical alpha-haemolytic coccus arranged in chains, and it ferments a large number of monosaccharides and disaccharides, as well as polymeric carbohydrates. It differs biochemically from closely related species of

Streptococcus

due to its production of α-galactosidase, β-galactosidase and N-acetyl-β-d-glucosaminidase and by the absence of arginine dihydrolase deiminase and IgA1-protease. It grows in a temperature range of 25 to 40 °C (optimal growth temperature at 37 °C) and in a pH range of 4.5 to 8 (optimal pH at 7.0). A phylogenetic analysis based on its 16S and 23S rRNA gene sequences placed it close to

Streptococcus dentisani

CECT 7747T. The ANIb and ANIm values were 93.19 and 93.61 %, respectively, both below the accepted threshold to designate it as a new species of bacteria. A phylogenetic tree based on its core genome placed it close to

Streptococcus oralis

subsp.

dentisani

strain CECT 7747T with a distance in the expanded core phylogeny of 0.1298. The in silico DNA–DNA hybridization value was 52.2 % with respect to the closest species,

S. oralis

subsp.

dentisani

CECT 7747T. Based on these data, a new species of bacteria within the genus

Streptococcus

, family

Streptococcaceae

and order

Lactobacillales

is described, for which the name of Streptococcus downii sp. nov. is proposed (type strain CECT 9732T=CCUG 73139T).
In silico multi-epitope vaccine against covid19 showing effective interaction with HLA-B*15:03
Authors: Faiza Muniba , Abdullah Tariq , Calderon-Tantalean Jose Franklin , Upadhyay Manish Ravindranath , Abdelmoneim Abdelrahman H. , Akram Fareeha , Thakur Bhupender Singh , Abdulaziz Ibrahim , Ononamadu Chimaobi James , Ghoraba Dina Abdelazim , Munawar Saba , Faruque MD Fakhrul Islam , Kigen Collins , Sharma Abhishek , Kumar Ashwani , Khalid Aqsa , Gharip Ali , Gupta Ankit , Manikumar Manne , Chaudhary Uma
Published: June 2020

The recent outbreak of severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 (SARS-CoV-2) causing coronavirus disease (covid19) has posed a great threat to human health. Previous outbreaks of SARS-CoV and Middle East respiratory Syndrome CoV (MERS-CoV) from the same CoV family had posed similar threat to human health and economic growth. To date, not even a single drug specific to any of these CoVs has been developed nor any anti-viral vaccine is available for the treatment of diseases caused by CoVs. Subunits present in spike glycoproteins of SARS-CoV and SARS-CoV-2 are involved in binding to human ACE2 Receptor which is the primary method of viral invasion. As it has been observed in the previous studies that there are very minor differences in the spike glycoproteins of SARS-CoV and SARS-CoV-2. SARS-CoV-2 has an additional furin cleavage site that makes it different from SARS-CoV (Walls et al., 2020). In this study, we have analyzed spike glycoproteins of SARS-CoV-2 and SARS-CoV phylogenetically and subjected them to selection pressure analysis. Selection pressure analysis has revealed some important sites in SARS-CoV-2 and SARS-CoV spike glycoproteins that might be involved in their pathogenicity. Further, we have developed a potential multi-epitope vaccine candidate against SARS-CoV-2 by analyzing its interactions with HLA-B*15:03 subtype. This vaccine consists of multiple T-helper (TH) cells, B-cells, and Cytotoxic T-cells (CTL) epitopes joined by linkers and an adjuvant to increase its immunogenicity. Conservation of selected epitopes in SARS, MERS, and human hosts, suggests that the designed vaccine could provide cross-protection. The vaccine is designed in silico by following a reverse vaccinology method acknowledging its antigenicity, immunogenicity, toxicity, and allergenicity. The vaccine candidate that we have designed as a result of this work shows promising result indicating its potential capability of simulating an immune response.
Functional connectivity within and betweenn-back modulated regions: An adult lifespan PPI investigation
Authors: Pongpipat Ekarin E. , Kennedy Kristen M. , Foster Chris M. , Boylan Maria A. , Rodrigue Karen M.
Published: June 2020

Working memory (WM) and its BOLD-related parametric modulation under load decrease with age. Functional connectivity (FC) generally increases with WM load; however, how aging impacts connectivity and whether this is load-dependent, region-dependent, or associated with cognitive performance is unclear. This study examines these questions in 170 healthy adults (Mage= 52.99 ± 19.18) who completed fMRI scanning during ann-back task (0-, 2-, 3-, and 4-back). FC was estimated utilizing a modified generalized psychophysiological interaction approach with seeds from fronto-parietal (FP) and default mode (DM) regions that modulated ton-back difficulty. FC analyses focused on both connectivity during WM engagement (task vs control) and connectivity in response to increased WM load (linear slope across conditions). Each analysis utilized within- and between-region FC, predicted by age (linear or quadratic), and its associations with in- and out-of-scanner task performance. Engaging in WM either generally (task vs control) or as a function of difficulty strengthened integration within- and between-FP and DM regions. Notably, these task-sensitive functional connections were robust to the effects of age. Stronger negative FC between FP and DM regions was also associated with better WM performance in an age-dependent manner, occurring selectively in middle- and older-adults. These results suggest that FC is critical for engaging in cognitively demanding tasks, and its lack of sensitivity to healthy aging may provide a means to maintain cognition across the adult lifespan. Thus, this study highlights the contribution of maintenance in brain function to support working memory processing with aging.

Impact Statement

The literature examining functional connectivity (FC) during working memory (WM) in healthy adults is mixed in both age effects and its relationship to performance. This study contributes to the literature by examining a large, adult lifespan sample, increased levels of WM load, and additional investigation of connections within and between fronto-parietal and default mode regions. Results revealed age-invariant strengthened FC during WM, suggesting that healthy aging may be resilient to FC changes. Additionally, negative FC between regions was associated with better WM performance in middle-aged and older adults, highlighting the important of FC maintenance to support successful WM ability.
Self-reported taste and smell disorders in patients with COVID-19:distinct features in China
Authors: Song Jia , Deng Yi-ke , Wang Hai , Wang Zhi-Chao , Liao Bo , Ma Jin , He Chao , Pan Li , Liu Yang , Alobid Isam , Wang De-Yun , Zeng Ming , Mullol Joaquim , Liu Zheng
Published: June 2020

Objectives

We aimed to explore the frequencies of nasal symptoms in patients with COVID-19, including loss of smell and taste, as well as their presentation as the first symptom of the disease and their association with the severity of COVID-19.

Methods

In this retrospective study, 1,206 laboratory-confirmed COVID-19 patients were included and followed-up by telephone call one month after discharged from Tongji Hospital, Wuhan. Demographic data, laboratory values, comorbidities, symptoms, and numerical rating scale scores (0-10) of nasal symptoms were extracted from the hospital medical records, and confirmed or reevaluated by the telephone follow-up.

Results

From COVID-19 patients (N = 1,172) completing follow-up, 199 (17%) subjects had severe COVID-19 and 342 (29.2%) reported nasal symptoms. The most common nasal symptom was loss of taste (20.6%, median score = 6), while 11.4% had loss of smell (median score = 5). The incidence of nasal symptom including loss of smell and loss of taste as the first onset symptom was <1% in COVID-19 patients. Loss of smell or taste scores showed no correlation with the scores of other nasal symptoms. Loss of taste scores, but not loss of smell scores, were significantly increased in severe vs. non-severe COVID-19 patients. Interleukin (IL)-6 and lactose dehydrogenase (LDH) serum levels positively correlated with loss of taste scores. About 80% of COVID-19 patients recovered from smell and taste dysfunction in 2 weeks.

Conclusion

In the Wuhan COVID-19 cohort, only 1 out of 10 hospital admitted patients had loss of smell while 1 out 5 reported loss of taste which was associated to severity of COVID-19. Most patients recovered smell and taste dysfunctions in 2 weeks.
Growth pattern Learning for Unsupervised Extraction of Cancer Kinetics
Authors: Axenie Cristian , Kurz Daria
Published: June 2020

Neoplastic processes are described by complex and heterogeneous dynamics. The interaction of neoplastic cells with their environment describes tumor growth and is critical for the initiation of cancer invasion. Despite the large spectrum of tumor growth models, there is no clear guidance on how to choose the most appropriate model for a particular cancer and how this will impact its subsequent use in therapy planning. Such models need parametrization that is dependent on tumor biology and hardly generalize to other tumor types and their variability. Moreover, the datasets are small in size due to the limited or expensive measurement methods. Alleviating the limitations that incomplete biological descriptions, the diversity of tumor types, and the small size of the data bring to mechanistic models, we introduce Growth pattern Learning for Unsupervised Extraction of Cancer Kinetics (GLUECK) a novel, data-driven model based on a neural network capable of unsupervised learning of cancer growth curves. Employing mechanisms of competition, cooperation, and correlation in neural networks, GLUECK learns the temporal evolution of the input data along with the underlying distribution of the input space. We demonstrate the superior accuracy of GLUECK, against four typically used tumor growth models, in extracting growth curves from a four clinical tumor datasets. Our experiments show that, without any modification, GLUECK can learn the underlying growth curves being versatile between and within tumor types.
Inhaled corticosteroids downregulate the SARS-CoV-2 receptor ACE2 in COPD through suppression of type I interferon
Authors: Finney Lydia J , Glanville Nicholas , Farne Hugo , Aniscenko Julia , Fenwick Peter , Kemp Samuel V , Trujillo-Torralbo Maria-Belen , Calderazzo Maria Adelaide , Wedzicha Jadwiga A , Mallia Patrick , Bartlett Nathan W , Johnston Sebastian L , Singanayagam Aran
Published: June 2020

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a new rapidly spreading infectious disease. Early reports of hospitalised COVID-19 cases have shown relatively low frequency of chronic lung diseases such as chronic obstructive pulmonary disease (COPD) but increased risk of adverse outcome. The mechanisms of altered susceptibility to viral acquisition and/or severe disease in at-risk groups are poorly understood. Inhaled corticosteroids (ICS) are widely used in the treatment of COPD but the extent to which these therapies protect or expose patients with a COPD to risk of increased COVID-19 severity is unknown. Here, using a combination of human and animalin vitroandin vivodisease models, we show that ICS administration attenuates pulmonary expression of the SARS-CoV-2 viral entry receptor angiotensin-converting enzyme (ACE)-2. This effect was mechanistically driven by suppression of type I interferon as exogenous interferon-β reversed ACE2 downregulation by ICS. Mice deficient in the type I interferon-α/β receptor (Ifnar1−/−) also had reduced expression of ACE2. Collectively, these data suggest that use of ICS therapies in COPD reduces expression of the SARS-CoV-2 entry receptor ACE2 and this effect may thus contribute to altered susceptibility to COVID-19 in patients with COPD.
Unsupervised manifold alignment for single-cell multi-omics data
Authors: Singh Ritambhara , Demetci Pinar , Bonora Giancarlo , Ramani Vijay , Lee Choli , Fang He , Duan Zhijun , Deng Xinxian , Shendure Jay , Disteche Christine , Noble William Stafford
Published: June 2020

Integrating single-cell measurements that capture different properties of the genome is vital to extending our understanding of genome biology. This task is challenging due to the lack of a shared axis across datasets obtained from different types of single-cell experiments. For most such datasets, we lack corresponding information among the cells (samples) and the measurements (features). In this scenario, unsupervised algorithms that are capable of aligning single-cell experiments are critical to learning anin silicoco-assay that can help draw correspondences among the cells. Maximum mean discrepancy-based manifold alignment (MMD-MA) is such an unsupervised algorithm. Without requiring correspondence information, it can align single-cell datasets from different modalities in a common shared latent space, showing promising results on simulations and a small-scale single-cell experiment with 61 cells. However, it is essential to explore the applicability of this method to larger single-cell experiments with thousands of cells so that it can be of practical interest to the community. In this paper, we apply MMD-MA to two recent datasets that measure transcriptome and chromatin accessibility in ~2000 single cells. To scale the runtime of MMD-MA to a more substantial number of cells, we extend the original implementation to run on GPUs. We also introduce a method to automatically select one of the user-defined parameters, thus reducing the hyperparameter search space. We demonstrate that the proposed extensions allow MMD-MA to accurately align state-of-the-art single-cell experiments.
Accurate determination of meat mass fractions using DNA measurements for quantifying meat adulteration
Authors: Temisak Sasithon , Thangsunan Pattanapong , Boonil Jiranun , Yenchum Watiporn , Hongthong Kanjana , Yata Teerapong , Rios-Solis Leonardo , Morris Phattaraporn
Published: June 2020

The problem in meat adulteration and food fraud emphasised the requirement of developing accurate analytical approaches for the quantitative detection in helping the control of meat adulteration. In this study, the droplet digital Polymerase Chain Reaction (ddPCR) assays to quantify the ratios of pork DNA to the total amount of meat DNA were developed by challenging against DNA extracted from a range of gravimetrically prepared matrices of pork in beef. A single copy nuclear DNA gene,β-actin, was employed as a target gene, accompanied withmyostatingene as a cross species target for mammal and poultry meat background in order to quantifying approach. All the developed assays, singleplex, duplex and triplex did not show significant difference in quantification of pork content in beef background and demonstrated a good and comparable performance to the mass fractions. The singleplex assay provided more biases than the other two assays when performing with a low concentration of target species. The duplex assay provided a simultaneous quantification of pork andmyostatin, whereas the triplex assay was able to detect pork, beef andmyostatinwith a decrease of technical error, cost and running time. All proposed methods allowed us to quantify pork addition in beef with a limit of quantification (LOQ) estimated at 0.1% (w/w) and a limit of detection (LOD) down to 0.01% (w/w). The developed triplex assay was also tested with commercial processed foods and showed the ability to determine not only the presence of particular pork or beef but also the quantitative purpose directly without standard curves. Hence, the developed ddPCR assays demonstrated a good trueness and precision of the methods in quantifying pork or beef content for meat adulteration. It is expected that these developed approaches can be applied to help regulators to confidently enforce food labelling obligations.
The bacterial effector HopZ1a acetylates MKK7 to suppress plant immunity
Authors: Rufián José S. , Rueda-Blanco Javier , López-Márquez Diego , Macho Alberto P. , Beuzón Carmen R. , Ruiz-Albert Javier
Published: June 2020

ThePseudomonas syringaetype III secretion system translocates effector proteins into the host cell cytosol, suppressing plant basal immunity triggered upon recognition of pathogen-associated molecular patterns (PAMPs), and effector-triggered immunity. Effector HopZ1a suppresses local and systemic immunity triggered by PAMPs and effectors, through target acetylation. HopZ1a has been shown to target several plant proteins, but none fully substantiates HopZ1a-associated immune suppression. Here, we investigateArabidopsis thalianamitogen-activated protein kinase kinases (MKKs) as potential targets, focusing on AtMKK7, a positive regulator of local and systemic immunity. We analyse HopZ1a interference with AtMKK7 by translocation of HopZ1a from bacteria inoculated into Arabidopsis expressing MKK7 from an inducible promoter. Reciprocal phenotypes are analysed on plants expressing a construct quenching MKK7 native expression. We analyse HopZ1a-MKK7 interaction by three independent methods, and the relevance of acetylation byin vitrokinase andin plantafunctional assays. We demonstrate AtMKK7 contribution to immune signalling showing MKK7-dependent flg22-induced ROS burst, MAPK activation, and callose accumulation, plus AvrRpt2-triggered MKK7-dependent signalling. Further, we demonstrate HopZ1a suppression of all MKK7-dependent responses, HopZ1a-MKK7 interaction in planta, and HopZ1a acetylation of MKK7 in a lysine required for full kinase activity. We demonstrate that HopZ1a targets AtMKK7 to suppress local and systemic plant immunity.
The Growth Rate Hypothesis as a predictive framework for microevolutionary adaptation to selection for high population growth: an experimental test under phosphorus rich and phosphorus poor conditions
Authors: Lemmen Kimberley D. , Zhou Libin , Papakostas Spiros , Declerck Steven A.J.
Published: June 2020

The growth rate hypothesis, a central concept of Ecological Stoichiometry, explains the frequently observed positive association between somatic growth rate and somatic phosphorus content (Psom) in organisms across a broad range of taxa. Here, we explore its potential in predicting intraspecific microevolutionary adaptation. For this, we subjected zooplankton populations to selection for fast population growth (PGR) in either a P-rich (HP) or P-poor (LP) food environment. With common garden transplant experiments we demonstrate evolution in HP populations towards increased PGR concomitant with an increase in Psom. In contrast we show that LP populations evolved higher PGR independently of Psom. We conclude that the GRH hypothesis has considerable value for predicting microevolutionary change, but that its application may be contingent on stoichiometric context. Our results highlight the potential of cryptic evolution in determining the performance response of field populations to elemental limitation of their food resources.
Moderating role of CEO compensation in lean innovation strategies of Chinese listed family firms
Authors: Zulfiqar Muhammad , Hussain Khalid , Yousaf Muhammad Usman , Sohail Nadeem , Ghafoor Sadeen
Published: June 2020

Purpose

The purpose of this paper is to examine the impact of Chinese listed family firms on lean innovation strategies. Additionally, the authors also examined the moderating role of CEO compensation on the family ownership and lean innovation strategies relationship.

Design/methodology/approach

Data is obtained from CSMAR database about Chinese family firms listed at Shenzhen Stock Exchange and Shanghai Stock Exchange. Panel data comprising of firm year observations from 2007 to 2016 is analyzed using STATA.

Findings

Family firms are proactive towards research and development investment (innovation input) as well as towards patent applications (innovation output). Moreover, family firms show propensity towards patent applications and towards converting their R&D investment into granted patent applications. CEO compensation negatively moderates the nexus between family firms and lean innovation which seriously needs to be addressed to reduce agency costs.

Research limitations/implications

The study has focused on Chinese market only. The study is useful for policy makers to address the serious concerns identified in the conclusion section, i.e. effectiveness of CEO compensation in addressing the lean innovation strategies in emerging economy like that of China.

Originality/value

Given the usually considered conservative approach of family firms towards innovation, this is the first study which has tested the moderating role of CEO compensation on family firms and lean innovation relationship in an emerging economy. This study is unique because it provides a detailed analysis of lean innovation process by splitting the process into different stages. The negative moderating impact of CEO compensation raises new concerns to resolve agency conflicts.
Digital transformation of industrial firms: an innovation diffusion perspective
Authors: Steiber Annika , Alänge Sverker , Ghosh Swapan , Goncalves Dulce
Published: June 2020

Purpose

The digitization process has increased the pressure on large firms to transform. However, current frameworks on digital transformation are not well explaining what factors contribute to, or hinder, a firm's digital transformation. Innovation diffusion theories could complement existing frameworks, and for this reason, the purpose of this paper is to expand the existing body of knowledge on what contributes to, or hinders, an industrial firm's digital transformation by applying a validated framework based on innovation diffusion theories on two pioneer cases: General Electric and Siemens EHR/Health Services.

Design/methodology/approach

The framework used in this paper is based on several years' empirical studies and iterative literature reviews on innovation diffusion theories. Further, each use case is based on literature reviews and unique empirical data, collected by the authors of this paper as a result of taking active part of respective company's multi-years transformation.

Findings

Common drivers of, and clear inhibitors to the two firms' transformation, were identified. The innovation diffusion framework was found to work very well in identifying those factors.

Research limitations/implications

The implications are that researchers better can analyze/explain a digital transformation of a firm, and business managers can better plan or improve their firms' transformation processes.

Originality/value

The theoretical contributions of this paper are two: first, complement existing frameworks with a validated framework for innovation diffusion; second, provide an extension of our body of knowledge on factors that contributes to, or hinders, industrial firm's digital transformation.
Cost of lung cancer in East Azerbaijan province, in Iran, in 2017
Authors: Mir Habibeh , Seyednejad Farshad , Jalilian Habib , Nosratnejad Shirin , Yousefi Mahmood
Published: June 2020

Purpose

Costs estimation is essential and important to resource allocation and prioritizing different interventions in the health system. The purpose of this paper is to estimate the costs of lung cancer in Iran, in 2017.

Design/methodology/approach

This was a prevalence-based cost of illness study with a bottom-up approach costing conducted from October 2016 to April 2017. The sample included 645 patients who referred to Imam Reza hospital, Tabriz, Iran, in 2017. Follow-up interviews were every two months. Hospitalization costs extracted from the patient’s record and outpatient costs, nondirect medical costs and indirect costs collected using questionnaire. SPSS software version 22 was used for the data analysis.

Findings

Mean direct medical costs, nondirect medical costs and indirect costs amounted to 36,637.02 ± 23,515.13 PPP (2016) (251,313,217.83 Rials), 2,025.25 ± 3,303.72 PPP (2016) (16,613,202.53 Rials) and 48,348.55 ± 34,371.84 PPP (2016) (396,599,494.56 Rials), respectively. There was a significant and negative correlation between direct medical costs, direct nonmedical costs, indirect costs and age at diagnosis, and there was a significant and positive correlation between the length of hospital stay and direct medical cost.

Originality/value

As the cost of lung cancer is substantial and there have been little studies in this area, the objective of this study is to investigate the cost of lung cancer and present ways to tackle this.