bluuebunny/crossref_metadata_2025 huggingface dataset:
Network Analysis of the CSF Proteome Characterizes Convergent Pathways of Cellular Dysfunction in ALS
Authors: Thompson Alexander G. , Gray Elizabeth , Charles Philip D. , Hu Michele T. M. , Talbot Kevin , Fischer Roman , Kessler Benedikt M. , Turner Martin R.
Published: March 2021

Background

Amyotrophic lateral sclerosis is a clinical syndrome with complex biological determinants, but which in most cases is characterized by TDP-43 pathology. The identification in CSF of a protein signature of TDP-43 network dysfunction would have the potential to inform the identification of new biomarkers and therapeutic targets.

Methods

We compared CSF proteomic data from patients with ALS (n = 41), Parkinson’s disease (n = 19) and healthy control participants (n = 20). Weighted correlation network analysis was used to identify modules within the CSF protein network and combined with gene ontology enrichment analysis to functionally annotate module proteins. Analysis of module eigenproteins and differential correlation analysis of the CSF protein network was used to compare ALS and Parkinson’s disease protein co-correlation with healthy controls. In order to monitor temporal changes in the CSF proteome, we performed longitudinal analysis of the CSF proteome in a subset of ALS patients.

Results

Weighted correlation network analysis identified 10 modules, including those enriched for terms involved in gene expression including nucleic acid binding, RNA metabolism and translation; humoral immune system function, including complement pathways; membrane proteins, axonal outgrowth and adherence; and glutamatergic synapses. Immune system module eigenproteins were increased in ALS, whilst axonal module eigenproteins were decreased in ALS. The 19 altered protein correlations in ALS were enriched for gene expression (OR 3.05, p = 0.017) and membrane protein modules (OR 17.48, p = 0.011), including intramodular hub proteins previously identified as TDP-43 interactors. Proteins decreasing over longitudinal analysis ALS were enriched in glutamatergic synapse and axonal outgrowth modules. Protein correlation network disruptions in Parkinson’s disease showed no module enrichment.

Conclusions

Alterations in the co-correlation network in CSF samples identified a set of pathways known to be associated with TDP-43 dysfunction in the pathogenesis of ALS, with important implications for therapeutic targeting and biomarker development.
The Effects of a High-Protein Dairy Milk Beverage With or Without Progressive Resistance Training on Fat-Free Mass, Skeletal Muscle Strength and Power, and Functional Performance in Healthy Active Older Adults: A 12-Week Randomized Controlled Trial
Authors: Huschtscha Zoya , Parr Alexandra , Porter Judi , Costa Ricardo J. S.
Published: March 2021

The study aimed to investigate the independent and combined effects of consuming a high-protein dairy milk beverage, twice daily, with or without a progressive resistance training (PRT) program on outcomes of age-related sarcopenia, in healthy active older (≥50 years) adults. In this 12-week, 2 × 2 factorial study, participants were randomly allocated into one of four groups: dairy milk beverage (DM), exercise and dairy milk beverage (EX+DM), exercise alone (EX), and control (CON). The EX group underwent a 12-week whole-body PRT schedule (three sessions/week) and a high-protein dairy milk beverage (DM) was consumed twice daily (30 g protein/day). At weeks 0, 6, and 12, body composition (iDXA), strength [one-repetition maximum (1RM): leg press, chest press, lateral (lat) pull-down, and handgrip], power (countermovement jump), cardiorespiratory fitness (VO2), and physical performance (gait speed) were measured. Before measurements, blood samples were collected to determine the immune (i.e., leukocyte trafficking and inflammatory cytokines) and hormonal (i.e., insulin, cortisol, IGF-1, testosterone, and estradiol) profiles. Participants (n= 37) completed the study within the controlled experimental conditions. Protein intake increased in the EX+DM [mean ± SD, 1.2 ± 0.2 to 1.8 ± 0.4 g/kg body mass (BM) per day−1] and DM (1.3 ± 0.5 to 1.8 ± 0.6 g kg−1BM day−1) groups during the intervention. Absolute fat-free mass increased in the EX+DM [mean (95% confidence interval) = 0.65 (0.25–1.0) kg] and EX [0.49 (−0.44 to 1.40) kg] groups (P< 0.001) compared to DM [−0.54 (−1.6 to 0.05) kg]. Relative fat mass decreased (group*time,P= 0.018) in DM [−1.8% (−3.3 to −0.35%)] and EX+DM [−1.3% (−2.3 to −0.31%)], which was a greater reduction than that in the CON [0.10% (−0.80 to 1.0%)] group (P < 0.01). Relative maximal strength increased in both the EX and EX+DM (≥35%,P< 0.05) groups, but not in the DM and CON groups. The change in 1RM strength outcomes was higher in EX+DM compared to all other groups (53–78%,P< 0.01). There was an increase in resting plasma IL-10 concentration in EX+DM (88%), compared to all the other groups (P= 0.016). No other differences in systemic inflammatory cytokines were observed. There were no significant changes in all hormone concentrations measured among all groups. In conclusion, a high-protein dairy milk beverage providing additional protein did not further enhance the effects of PRT on outcomes of fat-free mass, power, or physical performance. However, there was a significant augmentative effect for high-protein dairy milk consumption on changes to maximal strength outcomes during PRT in healthy active older adults.
Molecular Subtypes and CD4+ Memory T Cell-Based Signature Associated With Clinical Outcomes in Gastric Cancer
Authors: Ning Zhi-Kun , Hu Ce-Gui , Huang Chao , Liu Jiang , Zhou Tai-Cheng , Zong Zhen
Published: March 2021

Background

CD4+ memory T cells are an important component of the tumor microenvironment (TME) and affect tumor occurrence and progression. Nevertheless, there has been no systematic analysis of the effect of CD4+ memory T cells in gastric cancer (GC).

Methods

Three datasets obtained from microarray and the corresponding clinical data of GC patients were retrieved and downloaded from the Gene Expression Omnibus (GEO) database. We uploaded the normalize gene expression data with standard annotation to the CIBERSORT web portal for evaluating the proportion of immune cells in the GC samples. The WGCNA was performed to identify the modules the CD4+ memory T cell related module (CD4+ MTRM) which was most significantly associated with CD4+ memory T cell. Univariate Cox analysis was used to screen prognostic CD4+ memory T cell-related genes (CD4+ MTRGs) in CD4+ MTRM. LASSO analysis and multivariate Cox analysis were then performed to construct a prognostic gene signature whose effect was evaluated by Kaplan-Meier curves and receiver operating characteristic (ROC), Harrell’s concordance index (C-index), and decision curve analyses (DCA). A prognostic nomogram was finally established based on the CD4+ MTRGs.

Result

We observed that a high abundance of CD4+ memory T cells was associated with better survival in GC patients. CD4+ MTRM was used to stratify GC patients into three clusters by unsupervised clustering analysis and ten CD4+ MTRGs were identified. Overall survival, five immune checkpoint genes and 17 types of immunocytes were observed to be significantly different among the three clusters. A ten-CD4+ MTRG signature was constructed to predict GC patient prognosis. The ten-CD4+ MTRG signature could divide GC patients into high- and low-risk groups with distinct OS rates. Multivariate Cox analysis suggested that the ten-CD4+ MTRG signature was an independent risk factor in GC. A nomogram incorporating this signature and clinical variables was established, and the C-index was 0.73 (95% CI: 0.697–0.763). Calibration curves and DCA presented high credibility for the OS nomogram.

Conclusion

We identified three molecule subtypes, ten CD4+ MTRGs, and generated a prognostic nomogram that reliably predicts OS in GC. These findings have implications for precise prognosis prediction and individualized targeted therapy.
Inhibition of HSP90 as a Strategy to Radiosensitize Glioblastoma: Targeting the DNA Damage Response and Beyond
Authors: Orth Michael , Albrecht Valerie , Seidl Karin , Kinzel Linda , Unger Kristian , Hess Julia , Kreutzer Lisa , Sun Na , Stegen Benjamin , Nieto Alexander , Maas Jessica , Winssinger Nicolas , Friedl Anna A. , Walch Axel K. , Belka Claus , Zitzelsberger Horst , Niyazi Maximilian , Lauber Kirsten
Published: March 2021

Radiotherapy is an essential component of multi-modality treatment of glioblastoma (GBM). However, treatment failure and recurrence are frequent and give rise to the dismal prognosis of this aggressive type of primary brain tumor. A high level of inherent treatment resistance is considered to be the major underlying reason, stemming from constantly activated DNA damage response (DDR) mechanisms as a consequence of oncogene overexpression, persistent replicative stress, and other so far unknown reasons. The molecular chaperone heat shock protein 90 (HSP90) plays an important role in the establishment and maintenance of treatment resistance, since it crucially assists the folding and stabilization of various DDR regulators. Accordingly, inhibition of HSP90 represents a multi-target strategy to interfere with DDR function and to sensitize cancer cells to radiotherapy. Using NW457, a pochoxime-based HSP90 inhibitor with favorable brain pharmacokinetic profile, we show here that HSP90 inhibition at low concentrations with per se limited cytotoxicity leads to downregulation of various DNA damage response factors on the protein level, distinct transcriptomic alterations, impaired DNA damage repair, and reduced clonogenic survival in response to ionizing irradiation in glioblastoma cells in vitro. In vivo, HSP90 inhibition by NW457 improved the therapeutic outcome of fractionated CBCT-based irradiation in an orthotopic, syngeneic GBM mouse model, both in terms of tumor progression and survival. Nevertheless, in view of the promising in vitro results the in vivo efficacy was not as strong as expected, although apart from the radiosensitizing effects HSP90 inhibition also reduced irradiation-induced GBM cell migration and tumor invasiveness. Hence, our findings identify the combination of HSP90 inhibition and radiotherapy in principle as a promising strategy for GBM treatment whose performance needs to be further optimized by improved inhibitor substances, better formulations and/or administration routes, and fine-tuned treatment sequences.
Development and Validation of a Prognostic Signature Based on Immune Genes in Cervical Cancer
Authors: Chen Yu , Lin Hao , Pi Ya-Nan , Chen Xi-Xi , Zhou Hu , Tian Yuan , Zhao Wei-Dong , Xia Bai-Rong
Published: March 2021

Background

Cervical cancer is one of the most common types of gynecological malignancies worldwide. This study aims to develop an immune signature to predict survival in cervical cancer.

Method

The gene expression data of 296 patients with cervical cancer from The Cancer Genome Atlas database (TCGA) and immune-related genes from the Immunology Database and Analysis Portal (ImmPort) database were included in this study. The immune signature was developed based on prognostic genes. The validation dataset was downloaded from the Gene Expression Omnibus (GEO) database.

Result

The immune signature namely immune-based prognostic score (IPRS) was developed with 229 genes. Multivariate analysis revealed that the IPRS was an independent prognostic factor for overall survival (OS) and progression-free survival (PFS) in patients with cervical cancer. Patients were stratified into high IPRS and low IPRS groups, and those in the high IPRS group were associated with better survival, which was validated in the validation set. A nomogram with IPRS and stage was constructed to predict mortality in cervical cancer.

Conclusions

We developed a robust prognostic signature IPRS that could be used to predict patients’ survival outcome.
YBX3 Mediates the Metastasis of Nasopharyngeal Carcinoma via PI3K/AKT Signaling
Authors: Fan Xiaoqin , Xie Xina , Yang Ming , Wang Yujie , Wu Hanwei , Deng Tingting , Weng Xin , Wen Weiping , Nie Guohui
Published: March 2021

The metastasis of nasopharyngeal carcinoma (NPC) is a complex process associated with oncogenic dysfunction, the deciphering of which remains a challenge and requires more in-depth studies. Y-box protein 3 (YBX3) is a DNA/RNA binding protein associated with gene transcription, DNA repair, and the progression of various diseases. However, whether and how YBX3 affects the metastasis of NPC remains unknown. Thus, in this study, we aimed to investigate the role of YBX3 in the metastasis of NPC and determine its underlying mechanism. Interestingly, it was found that the expression of YBX3, which was associated with NPC metastasis, was upregulated in the clinical NPC tissues and cell lines. Moreover, we found that knockdown of YBX3 expression by lentivirus shRNA significantly suppressed NPC cells migration in vitro and metastasis in vivo. Mechanistically, RNA sequencing results suggested that the genes regulated by YBX3 were significantly enriched in cell adhesion molecules, cAMP signaling pathway, calcium signaling pathway, focal adhesion, PI3K/AKT signaling pathway, Ras signaling pathway, Rap1 signaling pathway, NF-κB signaling pathway, and Chemokine signaling pathway. Of these, PI3K/AKT signaling pathway contained the most genes. Accordingly, YBX3 knockdown decreased the activation of PI3K/AKT signaling pathway, thereby inhibit epithelial-to-mesenchymal transition (EMT) and MMP1. These results have demonstrated that YBX3 are involved in the metastasis of NPC through regulating PI3K/AKT signaling pathway, and serve as a potential therapeutic target for patients with NPC.
Case Report: Paratesticular Rhabdomyosarcoma
Authors: Zhu Yiyi , Zhu Ziwei , Xiao Yunyuan , Zhu Zaisheng
Published: March 2021

Paratesticular rhabdomyosarcoma (RMS) accounts for only 7% of all the RMS cases. Due to the limited available data, there is no consensus on the diagnosis and management of the paratesticular tumors. Here, we interrogated two paratesticular RMS cases in 25 and 27-year-old men presenting with painless and rapidly growing mass in the scrotum. Whereas the data showed no upregulation of tumor markers such as β-human chorionic gonadotropin (β-HCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH), scrotal ultrasonography and magnetic resonance imaging indicated the existence of paratesticular and inguinal lesions respectively. There was local recurrence in one patient who underwent radical orchiectomy for the sarcoma one year ago. In addition, the CT scans showed no occurrence of distant metastasis. The two patients underwent radical inguinal orchiectomy or resection of the recurrent tumors with nerve-sparing retroperitoneal lymph node dissection. Histologic examination revealed embryonal RMS (eRMS) without lymph node metastasis. We highlight the importance of multi-disciplinary participation for paratesticular RMS detection and preoperative ultrasound-guided needle biopsy (UNB) for rapid confirmatory diagnosis. Complete surgical resection coupled with chemotherapy and radiotherapy is the main treatment option for the paratesticular RMS. In addition, sperm cryopreservation treatment and endocrine follow-up could increase the overall survival and quality of life of the patients.
A Clinicogenetic Prognostic Classifier for Prediction of Recurrence and Survival in Asian Breast Cancer Patients
Authors: Chen Ting-Hao , Wei Jun-Ru , Lei Jason , Chiu Jian-Ying , Shih Kuan-Hui
Published: March 2021

Background

Several prognostic factors affect the recurrence of breast cancer in patients who undergo mastectomy. Assays of the expression profiles of multiple genes increase the probability of overexpression of certain genes and thus can potentially characterize the risk of metastasis.

Methods

We propose a 20-gene classifier for predicting patients with high/low risk of recurrence within 5 years. Gene expression levels from a quantitative PCR assay were used to screen 473 luminal breast cancer patients treated at Taiwan Hospital (positive for estrogen and progesterone receptors, negative for human epidermal growth factor receptor 2). Gene expression scores, along with clinical information (age, tumor stage, and nodal stage), were evaluated for risk prediction. The classifier could correctly predict patients with and without relapse (logistic regression, P<0.05).

Results

A Cox proportional hazards regression analysis showed that the 20-gene panel was prognostic with hazard ratios of 5.63 (95% confidence interval 2.77-11.5, univariate) and 5.56 (2.62-11.8, multivariate) for the “genetic” model, and of 8.02 (3.52-18.3, univariate) and 19.8 (5.96-65.87, multivariate) for the “clinicogenetic” model during a 5-year follow-up.

Conclusions

The proposed 20-gene classifier can successfully separate the patients into two risk groups, and the two risk group had significantly different relapse rate and prognosis. This 20-gene classifier can provide better estimation of prognosis, which can help physicians to make better personalized treatment plans.
Early-Onset Sepsis in Neonates - A Population-Based Study in South-West Norway From 1996 to 2018
Authors: Vatne Anlaug , Klingenberg Claus , Rettedal Siren , Øymar Knut
Published: March 2021

Background: The epidemiology of early-onset sepsis (EOS) may change over time. Longitudinal surveillance of causative pathogens, antibiotic susceptibility patterns and antibiotic therapy is important for optimal therapy strategies.

Objectives: To describe the incidence of culture-confirmed EOS, causative pathogens, antibiotic susceptibility patterns and antibiotic therapy over a 23-year period.

Methods: Retrospective population-based study from a single-center neonatal intensive care unit at Stavanger University Hospital, Norway, covering a population in South-West Norway, during the 23-year period 1996–2018.

Results: Of 104,377 live born infants, 101 infants (0.97/1,000) had culture-confirmed EOS; 89 with Gram positive and 12 with Gram-negative bacteria. The EOS-attributable mortality was 6/101 (5.8%). For the three most prevalent pathogens the incidences were; Group B streptococcus (GBS) 0.57/1,000, Escherichia coli 0.11/1,000 and viridans group streptococci (VGS) 0.10/1,000. GBS was the most common pathogen (59/93; 63%) in infants with gestational age (GA) ≥ 28 weeks. In contrast, among extremely preterm infants (GA <28 weeks) the incidence of E. coli infection was higher than for GBS infection. The second most common bacterial pathogens causing EOS among term infants were VGS. There was no change in the incidence of EOS for the entire study period, but from 2000 to 2018 there was a mean decline in EOS by 6% per year (95% CI 1%−10%) (p = 0.019). The incidences of GBS and E. coli did not change during the study period. The initial empirical antibiotic regimen for EOS was in all cases a combination of benzylpenicillin or ampicillin and an aminoglycoside, but in 21/101 (21%) of cases a broad-spectrum antibiotic was either added or substituted this regimen. In 2/101 (2%) EOS cases, the pathogens were nonsusceptible to the empirical antibiotic regimen. All E. coli isolates were susceptible to aminoglycosides.

Conclusion: GBS was the most common causative pathogens in EOS, but E. coli dominated in infants with GA <28 weeks. There was no change in the incidence of EOS during the entire study period. The current empiric regimen with benzylpenicillin and gentamicin provides a very high coverage for EOS in our setting.
A New Therapeutic Candidate for Cardiovascular Diseases: Berberine
Authors: Cai Yun , Xin Qiqi , Lu Jinjin , Miao Yu , Lin Qian , Cong Weihong , Chen Keji
Published: March 2021

Cardiovascular diseases (CVD) are the leading cause of death in the world. However, due to the limited effectiveness and potential adverse effects of current treatments, the long-term prognosis of CVD patients is still discouraging. In recent years, several studies have found that berberine (BBR) has broad application prospects in the prevention and treatment of CVD. Due to its effectiveness and safety for gastroenteritis and diarrhea caused by bacterial infections, BBR has been widely used in China and other Asian countries since the middle of the last century. The development of pharmacology also provides evidence for the multi-targets of BBR in treating CVD. Researches on CVD, such as arrhythmia, atherosclerosis, dyslipidemia, hypertension, ischemic heart disease, myocarditis and cardiomyopathy, heart failure, etc., revealed the cardiovascular protective mechanisms of BBR. This review systematically summarizes the pharmacological research progress of BBR in the treatment of CVD in recent years, confirming that BBR is a promising therapeutic option for CVD.
Combining the Fecal Immunochemical Test with a Logistic Regression Model for Screening Colorectal Neoplasia
Authors: Liu Feiyuan , Long Qiaoyun , He Hui , Dong Shaowei , Zhao Li , Zou Chang , Wu Weiqing
Published: March 2021

Background: The fecal immunochemical test (FIT) is a widely used strategy for colorectal cancer (CRC) screening with moderate sensitivity. To further increase the sensitivity of FIT in identifying colorectal neoplasia, in this study, we established a classifier model by combining FIT result and other demographic and clinical features.

Methods: A total of 4,477 participants were examined with FIT and those who tested positive (over 100 ng/ml) were followed up by a colonoscopy examination. Demographic and clinical information of participants including four domains (basic information, clinical history, diet habits and life styles) that consist of 15 features were retrieved from questionnaire surveys. A mean decrease accuracy (MDA) score was used to select features that are mostly related to CRC. Five different algorithms including logistic regression (LR), classification and regression tree (CART), support vector machine (SVM), artificial neural network (ANN) and random forest (RF) were used to generate a classifier model, through a 10X cross validation process. Area under curve (AUC) and normalized mean squared error (NMSE) were used in the evaluation of the performance of the model.

Results: The top six features that are mostly related to CRC include age, gender, history of intestinal adenoma or polyposis, smoking history, gastrointestinal discomfort symptom and fruit eating habit were selected. LR algorithm was used in the generation of the model. An AUC score of 0.92 and an NMSE score of 0.076 were obtained by the final classifier model in separating normal individuals from participants with colorectal neoplasia.

Conclusion: Our results provide a new “Funnel” strategy in colorectal neoplasia screening via adding a classifier model filtering step between FIT and colonoscopy examination. This strategy minimizes the need of colonoscopy examination while increases the sensitivity of FIT-based CRC screening.
Transformation of the Peregrine Breather Into Gray Solitons on a Vertically Sheared Current
Authors: Hsu H. C. , Abid M. , Chen Y. Y. , Kharif C.
Published: March 2021

In this Brief Research Report, we show, within the framework of the nonlinear Schrödinger equation in deep water and in the presence of vorticity (vor-NLS), that the Peregrine breather traveling at the free surface of a shear current of slowly varying vorticity may transform into gray solitons.
Autonomic Nervous System Response to Psychosocial Stress in Anorexia Nervosa: A Cross-Sectional and Controlled Study
Authors: Schmalbach Ileana , Herhaus Benedict , Pässler Sebastian , Runst Sarah , Berth Hendrik , Wolff Silvia , Schmalbach Bjarne , Petrowski Katja
Published: March 2021

To foster understanding in the psychopathology of patients with anorexia nervosa (PAN) at the psychological and physiological level, standardized experimental studies on reliable biomarkers are needed, especially due to the lack of disorder-specific samples. To this end, the autonomic nervous system (ANS) response to a psychosocial stressor was investigated in n = 19 PAN (BMI: 18.7 ± 3.3 kg/m2), age, and gender-matched to n = 19 healthy controls (HC; BMI: 24.23 ± 3.0 kg/m2). For this purpose, heart rate (HR) and heart rate variability (HRV) parameters were assessed in a cross-sectional study design under two experimental conditions: (1) rest and (2) stress (Trier Social Stress Test). In addition, psychological indicators of stress were assessed. An 2 × 2 × 8 ANOVA demonstrated similar HR and HRV patterns (except LF-HRV) between PAN and HC at rest. Under stress, PAN (vs. HC) demonstrated a blunted HR [condition*time*group: F(2.91, 104.98) = 9.326, p = 0.000, η2 = 0.206] and an attenuated HRV response (reduced SNS/PNS reactivity). Significant effects of stress appraisal (SA) and BMI on HRV-reactivity were revealed. SA on SDNN = Condition*time*SA = F(4.12, 140.15) = 2.676, p = 0.033, η2 = 0.073. BMI on LF/HF-Ratio = Condition*time*BMI = F(3.53, 60.16) = 3.339, p = 0.019, η2 = 0.164. Psychological indices suggested higher levels of chronic and appraised stress in PAN relative to HC. Additional analyses demonstrated that ED-symptoms are highly correlated with the latter constructs, as well as with psychological burden, but not with weight. Further, it was shown that abnormalities in reactivity persisted despite normalized ANS activity. Overall, we suggested that besides weight recovery, improvement in stress appraisal could be beneficial for cardiac health. In this light, a combination of therapy (e.g., development and activation of coping skills, cognitive reappraisal) and biofeedback training may improve treatment outcomes and regulate stress reactivity.
Successful Implementation and Development of a Phase II Cardiac Rehabilitation Program: A China-Wide Cross-Sectional Study Tracking In-service Training Clinical Staff
Authors: Gong Xun , Zhang Wenliang , Ripley-Gonzalez Jeffrey W. , Liu Yuan , Dun Yaoshan , Zheng Fan , Qiu Ling , Liu Suixin
Published: March 2021

Background: Despite the benefits of cardiac rehabilitation (CR), phase II CR remains highly unavailable; the factors influential to the successful implementation and development of phase II CR programs have not been fully explored.

Methods: A cross-sectional survey was completed by 168 nationwide clinical staff. Parameters associated with the successful implementation and development of phase II CR and the factors associated with the quality of CR were explored by multivariable logistic regression.

Results: One hundred and eighteen of 168 respondents' institutions had successfully developed phase II CR programs, 41 of which delivered high-quality CR. Independent factors associated with successful implementation and development of CR were leadership support from hospital administrators, support from resident physicians, staff perception in CR increasing medical risk, and department type (cardiology vs. rehabilitation department). Independent factors associated with CR quality were the availability of “professional CR providers” and staff perceptions of CR improving physician–patient relationships. The medical system factors did not affect the development and quality of CR, including hospital level, funding type, academic type, general/specialized hospital, located city, medical insurance, the existence of a CR outpatient clinic and independent space, the availability of professional CR providers, staff structure, and the availability of regular training and standard procedure.

Conclusions: The development and quality of a phase II CR program may benefit from factors including support from administrators and resident physicians, adequately training more CR providers, without viewing medical system factors as a major issue.
Cost-Effectiveness of Peer-Delivered HIV Self-Tests for MSM in Uganda
Authors: Okoboi Stephen , Castelnuovo Barbara , Van Geertruyden Jean-Pierre , Lazarus Oucul , Vu Lung , Kalibala Sam , Kamara Yvonne , Ochanda Perez N. , King Rachel , Mujugira Andrew
Published: March 2021

Introduction: Distribution of HIV self-testing (HIVST) kits through MSM peer networks is a novel and effective strategy to increase HIV testing coverage in this high-risk population. No study has evaluated the cost or cost effectiveness of peer distribution of HIVST strategies among MSM in sub-Saharan Africa.

Methods: From June to August 2018, we conducted a pilot study of secondary MSM peer HIVST kit distribution at The AIDS Support Organization at Entebbe and Masaka. We used an ingredients approach to estimate the cost of MSM peer HIVST kit distribution relative to standard-of-care (SOC) hotspot testing using programme expenditure data reported in US dollars. The provider perspective was used to estimate incremental cost-effective ratios per HIV infection averted using the difference in HIV annual transmission rates between MSM with HIV who knew their status and were not virologically suppressed and MSM with HIV who did not know their status.

Results: We enrolled 297 participants of whom 150 received MSM peer HIVST kit distribution (intervention group) and 147 received TASO standard of care HIV testing (control group). Provider cost for the intervention was $2,276 compared with $1,827 for SOC during the 3-month study period. Overall, the intervention resulted in higher HIV positivity yield (4.9 vs. 1.4%) and averted more HIV infections per quarter (0.364 vs. 0.104) compared with SOC. The cost per person tested was higher for the intervention compared to SOC ($15.90 vs. $12.40). Importantly, the cost per new HIV diagnosis ($325 vs. $914) and cost per transmission averted ($6,253 vs. $ 17,567) were lower for the intervention approach relative to SOC. The incremental cost per HIV transmission averted by the self-testing program was $1,727. The incremental cost to providers per additional HIV-positive person identified by the intervention was $147.30.

Conclusion: The intervention strategy was cost-effective, and identified more undiagnosed HIV infections than SOC hotspot testing at a cost-effectiveness threshold of US $2,129. Secondary distribution of HIVST kits through peers should further be evaluated with longer duration aimed at diagnosing 95% of all persons with HIV by 2030; the first UNAIDS 95-95-95 target.
Leveling Up Injury Recovery: Video Games for Good!
Authors: Cochran Sean , Hout Michael C.
Published: March 2021

Have you ever heard that video games are not good for you, or that playing them is simply a waste of time? It is a common misconception that video games only provide entertainment and hold little or no other value. One important piece of technology can provide entertainment, can be used in educational settings, and is now even being incorporated into medical practice: virtual reality. Virtual reality refers to computer-generated reality that is in some ways similar to the reality we experience every day. This virtual world is used to “trick” our brains into feeling like we are somewhere else [1], but importantly, doctors are now also using VR as a tool to help people with mobility problems. Imagine injuring your foot or leg so badly that you are unable to walk properly. Now imagine getting better through the use of VR!
Thoracoscopic Ablation of Critically Located Liver Tumors: A Safety and Efficacy Cohort Study
Authors: Cillo Umberto , Finotti Michele , Di Renzo Chiara , Vitale Alessandro , Zanus Giacomo , Gringeri Enrico , Bertacco Alessandra , Polacco Marina , D'Amico Francesco
Published: March 2021

Background: Liver resection represents the first curative treatment to treat primary and secondary hepatic tumors. Thoracoscopic liver ablation is a viable and minimally invasive alternative treatment, especially for patients with previous multiple abdominal surgeries. The aim of the study was to evaluate the safety and efficacy of thoracoscopic ablation for liver tumors.

Methods: Retrospective analysis of a prospective database of patients with liver tumors, treated with thoracoscopic trans-diagrammatic ablation (MWA or RFA) at our institution from 2012 to 2018. The primary endpoint was post-operative mortality at 30 days, while secondary endpoints were morbidity and efficacy of ablation (i.e., response rate evaluated according to mRECIST criteria, and overall patient survival). Patient demographics, operational characteristics, and complications were recorded.

Results: A total of 13 nodules were treated in 10 patients with a median age of 65.5 years. Post-operative mortality was 0%, and overall morbidity was 40% (Clavien-Dindo I complications 30%, II 0%, III 10%, IV 0%). Complete radiological response was obtained in 83.3% of nodules at 3 months. After a median follow-up of 20.95 months, the local tumor progression rate was 30%, with an intra-segmental-recurrence of 30%, and an intra-hepatic-recurrence of 30%. The overall 1-, 2-, and 3-years survival rates were 80%, 58%, and 58%.

Conclusion: Thoracoscopic trans-diaphragmatic ablation proved to be a safe and effective way to treat liver tumors when abdominal approach is not feasible. Considering the low morbidity, it is a viable option to treat patients with recurrent disease and/or previous multiple abdominal surgeries.
Historical Trends in Incidence of Breast Cancer in Shanghai, Hong Kong and Los Angeles, 1973–2012: A Joinpoint and Age-Period-Cohort Analysis
Authors: Luan Hang-Hang , Luo Li-Sha , Lu Zhi-Yan
Published: March 2021

Objectives: This study aimed to estimate the long-term trends of breast cancer incidence in Shanghai, Hong Kong, and Los Angeles (LA).

Methods: Data were obtained from Cancer Incidence in Five Continents (CI5plus) database. The average annual percent change (AAPC) was conducted by joinpoint regression analysis, and the age, period and cohort effects were estimated by age-period-cohort (APC) analysis.

Results: The age-standardized incidence rates (ASIRs) in LA were higher than Shanghai and Hong Kong. During 1988–2012, the ASIRs significantly decreased in white women in LA (AAPC = −0.6%, 95% CI: −0.9% to −0.4%) while increased in Shanghai (2.5%: 2.1%–2.9%) and Hong Kong (2.2%: 2.0%–2.5%). The APC analysis revealed significantly increased effects of age and period, and decreased effect of birth cohort.

Conclusion: Although age and cohort effects were relatively strong, the period effect may be the key factor affecting trends of incidence, which may be caused by increasing exposures to carcinogens and risk factors. Therefore, more effective measures should be carried out promptly to protect high-risk populations such as elder women, to avoid exposures to risk factors of breast cancer.
Three-Axis Pneumatic Haptic Display for the Mechanical and Thermal Stimulation of a Human Finger Pad
Authors: Lee Eun-Hyuk , Kim Sang-Hoon , Yun Kwang-Seok
Published: March 2021

Haptic displays have been developed to provide operators with rich tactile information using simple structures. In this study, a three-axis tactile actuator capable of thermal display was developed to deliver tactile senses more realistically and intuitively. The proposed haptic display uses pneumatic pressure to provide shear and normal tactile pressure through an inflation of the balloons inherent in the device. The device provides a lateral displacement of ±1.5 mm for shear haptic feedback and a vertical inflation of the balloon of up to 3.7 mm for normal haptic feedback. It is designed to deliver thermal feedback to the operator through the attachment of a heater to the finger stage of the device, in addition to mechanical haptic feedback. A custom-designed control module is employed to generate appropriate haptic feedback by computing signals from sensors or control computers. This control module has a manual gain control function to compensate for the force exerted on the device by the user’s fingers. Experimental results showed that it could improve the positional accuracy and linearity of the device and minimize hysteresis phenomena. The temperature of the device could be controlled by a pulse-width modulation signal from room temperature to 90 °C. Psychophysical experiments show that cognitive accuracy is affected by gain, and temperature is not significantly affected.
The Genetic Diversity and Structure of Tomato Landraces from the Campania Region (Southern Italy) Uncovers a Distinct Population Identity
Authors: Caramante Martina , Rouphael Youssef , Corrado Giandomenico
Published: March 2021

Italy is one of the main producers and processors of tomato and it is considered a secondary center of diversity. In some areas, such as the Campania region (Southern Italy), a range of traditional tomato landraces is still cultivated. The distinction of this heritage germplasm is often based only on folk taxonomy and a more comprehensive definition and understanding of its genetic identity is needed. In this work, we compared a set of 15 local landraces (representative of traditional fruit types) to 15 widely used contemporary varieties, using 14 fluorescent Simple Sequence Repeat (SSR) markers. Each of the accessions possessed a unique molecular profile and overall landraces had a genetic diversity comparable to that of the contemporary varieties. The genetic diversity, multivariate, and population structure analysis separated all the genotypes according to the pre-defined groups, indicating a very reduced admixture and the presence of a differentiated (regional) population of landraces. Our work provides solid evidence for implementing conservation actions and paves the way for the creation of a premium regional brand that goes beyond the individual landrace names of the Campania region known throughout the world.
Demographic Processes Allow Echinochloa crus-galli to Compensate Seed Losses by Seed Predation
Authors: Pannwitt Heike , Westerman Paula R. , De Mol Friederike , Gerowitt Bärbel
Published: March 2021

The effect of weed management that targets the seed stage on subsequent life stages is largely unknown. Post-dispersal seed predation reduces the number of seeds from the soil surface before the seeds contribute to the seedbank. Density-dependent processes can mitigate the effect of seed predation in subsequent life stages. In this study, we tested if (i) targeting the seed stage affects the subsequent seedling stage; (ii) if density-dependent mortality in subsequent life stages partly compensates seedling abundance; and (iii) if the magnitude of final seed production depends on seed predation. We fully parameterized a model for the summer-annual weed Echinochloa crus-galli (L.) P. Beauv. Field data from three maize fields in north-eastern Germany were obtained, in the presence or absence of seed predation and different population levels of the weed species. Seeds of E. crus-galli were applied in autumn and the number of seedlings, adult plants, and seed production per m2 was determined the following season. Seed predation reduced the number of seedlings. Density-dependent mortality during the seedling stage increased fecundity with decreasing seedling density, and, thus, compensated for lower numbers of seedlings. The final level of seed production per m2 did not depend on seed predation and initial population densities, but differed among fields. We conclude, solely targeting the seed stage can scarcely limit the population growth of E. crus-galli.
A Workspace-Analysis-Based Genetic Algorithm for Solving Inverse Kinematics of a Multi-Fingered Anthropomorphic Hand
Authors: Lee Chun-Tse , Chang Jen-Yuan (James)
Published: March 2021

Although the solution of inverse kinematics for a serial redundant manipulator has been widely researched, many algorithms still seem limited in dealing with complex geometries, including multi-finger anthropomorphic hands. In this paper, the inverse kinematic problems of multiple fingers are an aggregate problem when the target points of fingers are given. The fingers are concatenated to the same wrist and the objective is to find a solution for the wrist and two fingers simultaneously. To achieve this goal, a modified immigration genetic algorithm based on workspace analysis is developed and validated. To reduce unnecessary computation of the immigration genetic algorithm, which arises from an inappropriate inverse kinematic request, a database of the two fingers’ workspace is generated using the Monte Carlo method to examine the feasibility of inverse kinematic request. Furthermore, the estimation algorithm provides an optimal set of wrist angles for the immigration genetic algorithm to complete the remaining computation. The results reveal that the algorithm can be terminated immediately even when the inverse kinematic request is out of the workspace. In addition, a distribution of population in each generation illustrates that the optimized wrist angles provide a better initial condition, which significantly improves the convergence of the immigration genetic algorithm.
Sensor-Guided Assembly of Segmented Structures with Industrial Robots
Authors: Peng Yuan-Chih , Chen Shuyang , Jivani Devavrat , Wason John , Lawler William , Saunders Glenn , J. Radke Richard , Trinkle Jeff , Nath Shridhar , T. Wen John
Published: March 2021

This paper presents a robotic assembly methodology for the manufacturing of large segmented composite structures. The approach addresses three key steps in the assembly process: panel localization and pick-up, panel transport, and panel placement. Multiple stationary and robot-mounted cameras provide information for localization and alignment. A robot wrist-mounted force/torque sensor enables gentle but secure panel pick-up and placement. Human-assisted path planning ensures reliable collision-free motion of the robot with a large load in a tight space. A finite state machine governs the process flow and user interface. It allows process interruption and return to the previous known state in case of error condition or when secondary operations are needed. For performance verification, a high resolution motion capture system provides the ground truth reference. An experimental testbed integrating an industrial robot, vision and force sensors, and representative laminated composite panels demonstrates the feasibility of the proposed assembly process. Experimental results show sub-millimeter placement accuracy with shorter cycle times, lower contact force, and reduced panel oscillation than manual operations. This work demonstrates the versatility of sensor guided robotic assembly operation in a complex end-to-end tasks using the open source Robot Operating System (ROS) software framework.
Physics of Failure (PoF) Based Lifetime Prediction of Power Electronics at the Printed Circuit Board Level
Authors: Wileman Andrew , Perinpanayagam Suresh , Aslam Sohaib
Published: March 2021

This paper presents the use of physics of failure (PoF) methodology to infer fast and accurate lifetime predictions for power electronics at the printed circuit board (PCB) level in early design stages. It is shown that the ability to accurately model silicon–metal layers, semiconductor packaging, printed circuit boards (PCBs), and assemblies allows, for instance, the prediction of solder fatigue failure due to thermal, mechanical, and manufacturing conditions. The technique allows a life-cycle prognosis of the PCB, taking into account the environmental stresses it will encounter during the period of operation. Primarily, it involves converting an electronic computer aided design (eCAD) circuit layout into computational fluid dynamic (CFD) and finite element analysis (FEA) models with accurate geometries. From this, stressors, such as thermal cycling, mechanical shock, natural frequency, and harmonic and random vibrations, are applied to understand PCB degradation, and semiconductor and capacitor wear, and accordingly provide a method for high-fidelity power PCB modelling, which can be subsequently used to facilitate virtual testing and digital twinning for aircraft systems and sub-systems.
Application of Quality Function Deployment for Product Design Concept Selection
Authors: Shvetsova Olga A. , Park Sung Chul , Lee Jang Hee
Published: March 2021

For business-to-business (B2B) companies, selecting new product concepts is vital to new product development (NPD), since it significantly contributes to the ultimate success and reputation of the product in terms of quality and function. The research problem is defining the best solution of new product’s design concept selection within high competition and resources’ limitation by mathematical approaches. The main objective of this study is developing an integrated analytical approach, combining quality function deployment (QFD) and analytic hierarchy process (AHP) approach, and data envelopment analysis (DEA) to enhance the effectiveness of design product decisions. The proposed approach focuses on mathematical methods to comprehensively evaluate and strategically select the best new product concept while considering the features of the B2B product and the available information during concept selection. The best new concept is selected by the combined scores derived from the concept competitiveness (quality function deployment—analytic hierarchy process) and the design development efficiency (data envelopment analysis). Finally, the design alternatives are classified into four categories by quadrant analysis for design concept management. The benefit of this approach—combining three mathematical models together for the best concept’s solution.
Effects of Pulsed Electric Fields on Yeast with Prions and the Structure of Amyloid Fibrils
Authors: Jurgelevičiūtė Justina , Bičkovas Nedas , Sakalauskas Andrius , Novickij Vitalij , Smirnovas Vytautas , Lastauskienė Eglė
Published: March 2021

Prions are misfolded, self-replicating, and transmissible proteins capable of causing different conditions that affect the brain and nervous system in humans and animals. Yeasts are the perfect model to study prion formation, dissemination, and the structure of protein aggregates. Yeast prions are related to stress resistance, cell fitness, and viability. Applying a pulsed electric field (PEF) as a factor capable of disintegrating the amyloid aggregates arises from the fact that the amyloid aggregates form via noncovalent bonds and stabilize via electrostatic interactions. In this research, we applied 2–26 kV/cm PEF delivered in sequences of 5 pulses of 1 ms duration to the Saccharomyces cerevisiae cell without prions and containing strong and weak variants of the [PSI+] prion (prion form of Sup35 translation termination factor). We determined that prions significantly increase cell survivability and resistance to PEF treatment. The application of PEF to the purified Sup35NM fibrils showed that the electric field causes significant reductions in the length of fibrils and the full disintegration of fibrils to Sup35 oligomers can be achieved in higher fields.
A Fast, Hybrid, Time-Domain Discontinuous Galerkin-Physical Optics Method for Composite Electromagnetic Scattering Analysis
Authors: Ma Ceyi , Wen Yinghong , Zhang Jinbao
Published: March 2021

To accelerate the solution of transient electromagnetic scattering from composite scatters, a novel hybrid discontinuous Galerkin time domain (DGTD) and time-domain physical optics (TDPO) method is proposed. The DGTD method is used to solve the accurate scattering field of the multi-scale objects region, and a hybrid explicit-implicit time integration method is also used to improve the efficiency of multi-scale problems in the time domain. Meanwhile, the TDPO method is used to accelerate the speed of surface current integration in an electrically large region. In addition, the DGTDPO method considers the mutual coupling between two regions, and effectively reduces the number of numerical calculations for the other space of the composite target, thereby significantly reducing the computer memory consumption. Numerical results certified the high efficiency and accuracy of the hybrid DGTDPO. According to the results, in comparison with the DGTD algorithm in the entire computational domain, the DGTDPO method can reduce computing time and memory by 90% and 70% respectively. Meanwhile, the normalized root mean square deviation (NRMSD) of the time-domain, high-frequency approximation method is over 0.2, and that of the DGTDPO method is only 0.0971. That is, compared with the approximation methods, the hybrid method improves the accuracy by more than 64%.