bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternate recurrent coronary artery spasm and stress cardiomyopathy: a case report
Authors: Jin Yunpeng , Li Qiming , Guo Xiaogang
Published: November 2020

Background

Coronary artery spasm (CAS) and stress cardiomyopathy (SC) have different characteristic clinical manifestations in the case of suspicious myocardial infarction with nonobstructive coronary arteries. Established recurrence rates of both conditions have been reported, however, alternate recurrent CAS and SC in the same individual have not been described.

Case presentation

A 59-year-old man suffered from atypical chest pain in the first episode, acute heart attack in the second and third episodes (totally 3 times over a period of approximately 5 years). During the first episode, he visited our hospital with mild paroxysmal chest pain without obvious inducement for approximately 2 years. He was underdiagnosed at that time without other obvious findings except the poor R wave progression in V1–3 leads revealed in electrocardiogram. At 4 months after the first episode, he suffered from a heart attack (the second episode) and was diagnosed with SC based on the coronary angiography (CAG) and left ventriculography findings of nonobstructive coronary arteries combined with a classic apical ballooning shape. At 31 months after the second episode, he suffered another heart attack (the third episode) and was diagnosed with CAS based on the CAG results of recoverable severe multivessel stenoses. During the episodes, partial reversible nature of apical hypokinesis was observed in echocardiogram. In retrospect, the patient suffered silent CAS in the first episode, SC in the second episode, and severe multivessel CAS in the third episode.

Conclusion

The unusual presentations observed in this case have not been reported. This case suggests that cardiologists should be aware of the possibility of alternate recurrent CAS and SC in the same individual. Provocative tests for spasm and cardiac magnetic resonance imaging might help gain more insights into this issue.
Recruitment and retention of participants from socioeconomically deprived communities: lessons from the Awareness and Beliefs About Cancer (ABACus3) Randomised Controlled Trial
Authors: Kolovou Vasiliki , Moriarty Yvonne , Gilbert Stephanie , Quinn-Scoggins Harriet , Townson Julia , Padgett Louise , Owen Sioned , Buckle Peter , Edwards Adrian , Hepburn Julie , Lau Mandy , Matthews Maura , Mitchell Caroline , Neal Richard , Playle Rebecca , Robling Mike , Smits Stephanie , Trubey Rob , Wood Fiona , Brain Kate
Published: November 2020

Background

Recruitment of research participants poses challenges in socioeconomically deprived areas. The Awareness and Beliefs About Cancer (ABACus) phase 3 Randomised Control Trial recruited adult participants from socioeconomically deprived areas using a combined healthcare/community engagement model. We report the strategies used to successfully recruit and retain our trial participant sample.

Methods

Community and healthcare settings in areas of high socioeconomic deprivation were identified by lay advisors who recruited participants opportunistically or by appointment. Follow-up was done by telephone or post at 2-weeks and 6-months after recruitment, and all participants were offered financial incentives. Qualitative interviews were conducted with lay advisors regarding their experience and reflections.

Results

The lay advisors identified and contacted 107 potential recruitment venues across South and West Yorkshire and South East Wales of which 41.1% (n = 42) were opened for recruitment. A total of 234 participants were recruited, with 91% (n = 212) retention at 2-weeks and 85% (n = 199) at 6-months. Community settings yielded 75% (n = 176) of participants. Participants had a mean age of 61.3 years and 63.3% (n = 148) were female, with 66% (n = 154) resident in the most deprived geographical areas. Lay advisors described recruitment as intensive, although engaging participants was easier in community settings.

Conclusions

The ABACus3 trial achieved recruitment and high retention with a population that is often “hard to reach” or entirely missed in health research. Strategies were specifically tailored to engage the venues and adult residents of highly deprived areas. Future studies recruiting adults living in the most deprived areas might benefit from community recruitment and from collaborating with local gatekeepers who are key to engagement.

This study adheres to CONSORT guidelines.

Trial registration

Retrospectively registered with ISRCTN (http://www.isrctn.com/ISRCTN16872545) on 12.01.2018.
Non-invasive predictors of prognosis of Asian patients with histopathologically-confirmed lean nonalcoholic fatty liver disease
Authors: Iritani Soichi , Akuta Norio , Kawamura Yusuke , Kajiwara Akira , Kasuya Kayoko , Fujiyama Shunichiro , Sezaki Hitomi , Hosaka Tetsuya , Kobayashi Masahiro , Kobayashi Mariko , Saito Satoshi , Suzuki Fumitaka , Arase Yasuji , Ikeda Kenji , Suzuki Yoshiyuki , Kumada Hiromitsu
Published: November 2020

Background

The prognostic factors of morbidity and mortality in patients with lean NAFLD (body mass index < 25.0 kg/m2) are unknown.

Methods

In this retrospective study, 446 Japanese patients with histopathologically-confirmed NAFLD (lean NAFLD, n = 170) were followed for liver events, cardiovascular events, type 2 diabetes mellitus, and non-liver malignancies. The median observation period was 4.6 years. We also investigated the predictors of severe fibrosis (stage 3–4) and mortality in lean NAFLD patients.

Results

Glycolipid metabolic markers, liver function tests, NAFLD fibrosis score (NFS), and histological scoring were significantly lower in lean NAFLD patients than in non-lean NAFLD. The incidence of liver cancer was higher while that of T2DM was lower in lean NAFLD. Kaplan–Meier analysis showed no significant difference in overall survival between the lean and non-lean NAFLD. Multivariate analysis of data of lean NAFLD identified NFS ≥ − 1.455 as significant independent predictor of severe fibrosis, while history of liver cancer and NFS ≥ − 1.455 were predictors of overall survival.

Conclusions

Although patients with lean NAFLD have better histopathological and biochemical profile compared to patients with non-lean NAFLD, the prognosis is not different between the two groups. Lean NAFLD patients with NFS ≥ − 1.455 or history of liver cancer should be monitored carefully during follow-up.
Identification of ALDH3A2 as a novel prognostic biomarker in gastric adenocarcinoma using integrated bioinformatics analysis
Authors: Yin Zhenhua , Wu Dejun , Shi Jianping , Wei Xiyi , Jin Nuyun , Lu Xiaolan , Ren Xiaohan
Published: November 2020

Background

Extensive research has revealed that genes play a pivotal role in tumor development and growth. However, the underlying involvement of gene expression in gastric carcinoma (GC) remains to be investigated further.

Methods

In this study, we identified overlapping differentially expressed genes (DEGs) by comparing tumor tissue with adjacent normal tissue using the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) database.

Results

Our analysis identified 79 up-regulated and ten down-regulated genes. Functional enrichment analysis and prognosis analysis were conducted on the identified genes, and the fatty aldehyde dehydrogenase (FALDH) gene, ALDH3A2, was chosen for more detailed analysis. We performed Gene Set Enrichment Analysis (GSEA) and immunocorrelation analysis (infiltration, copy number alterations, and checkpoints) to elucidate the mechanisms of action of ALDH3A2 in depth. The immunohistochemical (IHC) result based on 140 paraffin-embedded human GC samples indicated that ALDH3A2 was over-expressed in low-grade GC cases and the OS of patients with low expression of ALDH3A2 was significantly shorter than those with high ALDH3A2 expression. In vitro results indicated that the expression of ALDH3A2 was negatively correlated with PDCD1, PDCD1LG2, and CTLA-4.

Conclusion

We conclude that ALDH3A2 might be useful as a potential reference value for the relief and immunotherapy of GC, and also as an independent predictive marker for the prognosis of GC.
The DLC-1 tumor suppressor is involved in regulating immunomodulation of human mesenchymal stromal /stem cells through interacting with the Notch1 protein
Authors: Na Tao , Zhang Kehua , Yuan Bao-Zhu
Published: November 2020

Background

Immunomodulatory activities of human mesenchymal stromal /stem cells (hMSCs) has been widely recognized as the most critical function of hMSCs for exerting its therapeutic effects. However, the detailed mechanisms responsible for regulating the immunomodulation of hMSCs still remain largely unknown. Previous studies revealed that the Notch1 protein exerted a pro-immunomodulatory function probably through interacting with the protein(s) subjective to proteasome-mediated protein degradation. The DLC-1 protein represents a well characterized tumor suppressor subjective to proteasome-mediated degradation. However, the detailed signaling pathway of Notch1 and the involvement of DLC-1 in regulating the immunomodulation of hMSCs have not been studied before.

Methods

The transfection with cDNA or siRNA into hMSCs assisted by co-culture of hMSCs with peripheral blood mononuclear cells and small molecule inhibitors of signaling proteins, followed by immunoprecipitation, Western blotting, RT-PCR, and flowcytometry, were employed to characterize the Notch1 signaling, to identify DLC-1 as a candidate proteasome-targeted protein, and to characterize DLC-1 signaling pathway and its interaction with the Notch1 signaling, in the regulation of immunomodulation of hMSCs, specifically, the inhibition of pro-inflammatory CD4+-Th1 lymphocytes, and the release of immunomodulatory molecule IDO1.

Statistical analysis

One-way ANOVA was utilized as a statistical tool to analyze the data presented as means ± SEM of at least three separate experiments.

Results

The present study revealed that the Notch1-Hey1 axis, but not the Notch1-Hes1 axis, was likely responsible for mediating the pro-immunomodulatory function of the Notch1 signaling. The DLC-1 protein was found subjective to proteasome-mediated protein degradation mediated by the DDB1 and FBXW5 E3 ligases and served as an inhibitor of the immunomodulation of hMSCs through inhibiting Rock1, but not Rock2, downstream the DLC-1 signaling. The Notch1 signaling in the Notch1-Hey1 pathway and the DLC-1 signaling in the DLC-1-Rock1-FBXW5 pathway exhibited a mutual exclusion interaction in the regulation of immunomodulation of hMSCs.

Conclusions

The present study uncovers a novel function of DLC-1 tumor suppressor in regulating the immunomodulation of hMSCs. It also proposes a novel mutual exclusion mechanism between the DLC-1 signaling and the Notch1 signaling that is possibly responsible for fine-tuning the immunomodulation of hMSCs with different clinical implications in hMSCs therapy.
Borderline personality disorder and prior suicide attempts define a severity gradient among hospitalized adolescent suicide attempters
Authors: Aouidad Aveline , Cohen David , Mirkovic Bojan , Pellerin Hugues , Garny de La Rivière Sébastien , Consoli Angèle , Gérardin Priscille , Guilé Jean-Marc
Published: November 2020

Background

Borderline personality disorder (BPD) and history of prior suicide attempt (SA) have been shown to be high predictors for subsequent suicide. However, no previous study has examined how both factors interact to modify clinical and suicide severity among adolescents.

Methods

This study presents a comprehensive assessment of 302 adolescents (265 girls, mean age = 14.7 years) hospitalized after a SA. To test clinical interactions between BPD and history of prior SA, the sample was divided into single attempters without BPD (non-BPD-SA, N = 80), single attempters with BPD (BPD-SA, N = 127) and multiple attempters with BPD (BPD-MA, N = 95).

Results

Univariate analyses revealed a severity gradient among the 3 groups with an additive effect of BPD on the clinical and suicide severity already conferred by a history of SA. This gradient encompassed categorical (anxiety and conduct disorders and non-suicidal-self-injury [NSSI]) and dimensional comorbidities (substance use and depression severity) and suicide characteristics (age at first SA).

According to regression analyses, the BPD-MA group that was associated with the most severe clinical presentation also showed specific features: the first SA at a younger age and a higher prevalence of non-suicidal self-injury (NSSI) and anxiety disorders. The BPD-MA group was not associated with higher impulsivity or frequency of negative life events.

Conclusions

Based on these findings and to improve youth suicide prevention, future studies should systematically consider BPD and the efficacy of reinforcing early interventions for anxiety disorders and NSSI.
Clients’ satisfaction with preventive services for malaria during pregnancy in Anambra state, Nigeria
Authors: Obagha Emmanuel Chijioke , Ajayi IkeOluwakpo , Abdullahi Gobir A. , Umeokonkwo Chukwuma David
Published: November 2020

Background

Burden of Malaria in pregnancy (MIP) is still high despite availability of proven cost-effective interventions. Considerable progress has been made on improving antenatal attendance, but MIP preventive services utilization remains low. Factors responsible for this include dissatisfaction with the services provided. We assessed clients’ satisfaction with preventative services for malaria during pregnancy delivered at antenatal clinics (ANC) in Anambra State Nigeria.

Method

We conducted a cross-sectional study among 284 pregnant women attending ANC using multistage sampling technique. Pre-tested semi-structured interviewer-administered questionnaire was used to collect information on socio-demographics, knowledge of malaria in pregnancy services and satisfaction with services. Responses to questions on satisfaction was on a 5-point Likert scale. A cut off of ≥75% of composite score was used to classify respondents as satisfied. For knowledge, every correct answer was scored 1 and incorrect 0; ≥75% of the composite score was graded as good knowledge. Chi square and logistic regression were used to test for association between client satisfaction and independent variables.

Results

The mean age of participants is 28 years±4.4 years. Overall, 62.2% were satisfied with quality of preventive services for malaria during pregnancy. However, 64.8 and 57.8% were dissatisfied with cost of healthcare and interpersonal relationship with the health workers (HWs). Majority of the respondents (88.73%) had poor knowledge of malaria preventive services during pregnancy. Type of facility (Adjusted odds ratio [aOR] = 2.11; 95%CI: 1.20–3.71) and knowledge (aOR: 0.41; 95%CI: 0.18–0.90) were independently associated with satisfaction with interpersonal relationship. Type of facility (aOR: 0.47; 95%CI: 0.27–0.80) and employment status (aOR: 3.07; 95%CI: 1.39–6.74) were also independently associated with satisfaction with cost of healthcare.

Conclusion

A fair proportion of respondents were satisfied with the preventive services for malaria during pregnancy provided even though most were dissatisfied with the cost of assessing care and interpersonal relationship with health workers. Uninterrupted availability of long lasting insecticide treated bed nets and intermittent preventive treatment for malaria at all health facilities, subsidized cost of malaria-related commodities, and incentives for good customer satisfaction ratings may remediate the described barriers to seeking preventative care for malaria during pregnancy.
Iranian general populations' and health care providers' preferences for benefits and harms of statin therapy for primary prevention of cardiovascular disease
Authors: Saadati Hassan , Baradaran Hamid Reza , Danaei Goodarz , Ostovar Afshin , Hadaegh Farzad , Janani Leila , Steyerberg Ewout W. , Khalili Davood
Published: November 2020

Background

The use of statins for primary prevention of cardiovascular diseases is associated with different benefit and harm outcomes. The aime of this study is how important these outcomes are for people and what people's preferences are.

Methods

We conducted a preference-eliciting survey incorporating a best–worst scaling (BWS) instrument in Iran from June to November 2019. The relative importance of 13 statins-related outcomes was assessed on a sample of 1085 participants, including 913 general population (486 women) and 172 healthcare providers from the population covered by urban and rural primary health care centers. The participants made trade-off decisions and selected the most and least worrisome outcomes concurrently from 13 choice sets; each contains four outcomes generated using the balanced incomplete block design.

Results

According to the mean (SD) BWS scores, which can be (+ 4) in maximum and (− 4) in minimum, in the general population, the most worrisome outcomes were severe stroke (3.37 (0.8)), severe myocardial infarction (2.71(0.7)), and cancer (2.69 (1.33)). While myopathy (− 3. 03 (1.03)), nausea/headache (− 2.69 (0.94)), and treatment discontinuation due to side effects (− 2.24 (1.14)) were the least worrisome outcomes. Preferences were similar between rural and urban areas and among health care providers and the general population with overlapping uncertainty intervals.

Conclusion

The rank of health outcomes may be similar in various socio-cultural contexts. The preferences for benefits and harms of statin therapy are essential to assess benefit-harm balance when recommending statins for primary prevention of cardiovascular diseases.
Leadership styles and leadership outcomes in nursing homes: a cross-sectional analysis
Authors: Poels Joris , Verschueren Marc , Milisen Koen , Vlaeyen Ellen
Published: November 2020

Background

Although leadership is considered as a key factor in health care, leadership styles and outcomes in nursing homes often remain a black box. Therefore, this study explored leadership styles and leadership outcomes of head nurses and directors of nursing (DoN) in nursing homes based on well-defined leadership concepts.

Methods

A multicenter cross-sectional analysis was conducted on baseline data of an ongoing cohort study comprising a convenience sample of nursing home staff (n = 302). Leadership styles and leadership outcomes of head nurses and DoN were measured through the rater form of the Multifactor Leadership Questionnaire 5X (MLQ-5X). Based on the Full Range of Leadership Model, the MLQ-5X visualizes transformational (relation and change focused), transactional (task-focused) and passive-avoidant (absence of leadership) leadership styles. Scores of head nurses and DoN for leadership styles and outcomes were compared with European Reference Scores (ERS) using two-sided one-sample t-tests.

Results

Compared with ERS, head nurses and DoN scored significantly lower (p < 0.001) on transformational and transactional leadership styles and significantly higher (p < 0.001) on passive-avoidant leadership styles. All leadership outcomes were significantly lower (p < 0.001) for head nurses. Similar results, however not statistically significant, were found concerning leadership outcomes of DoN.

Conclusions

Results indicate that passive-avoidant leadership styles are excessively present in contrast to transformational leadership styles in nursing homes. This highlights an urgent need to invest in leadership development. Therefore, future research should focus on interventions for the development of transformational leadership.
Assessment of immunization data quality of routine reports in Ho municipality of Volta region, Ghana
Authors: Ziema Sorengmen Amos , Asem Livingstone
Published: November 2020

Background

Immunization has been an important public health intervention for preventing and reducing child morbidity and mortality over the years and coverage has increased in the past decades. However, the validity of the data from immunization coverages is usually disputed. Immunization data from health facilities show poor concordance between tallied registers and monthly reports as they are reported to higher levels of the health system. The study assessed the quality of data from routine immunization of some health facilities in the Ho central municipality in the Volta region of Ghana.

Methods

A descriptive cross-sectional study was used to review routine immunization data in tallied registers and reports submitted to the Municipal Health Directorate (MHD) from January to December, 2015. Simple random sampling was used to select three health facilities in Ho central municipality. The World Health Organization (WHO) Data Quality Self-assessment (DQS) tool was the main instrument used to present and analyze data for accuracy and discrepancy level between the tallied registers and reports. A template was created in Microsoft excel which automatically presented accuracy and discrepancy levels when data was entered. Ethical approval for the study was obtained from Ghana Health Service Ethics Review Committee.

Results

The result showed discrepancies between recounted tallies at the facilities and reports submitted to the MHD. Accuracy ratios of 102, 64 and 94% for Bacillus Calmette Guerin (BCG), Pentavalent (Penta) vaccine dose 3 and Measles 2 respectively indicating underreporting for BCG and over reporting for the rest were obtained. There was 460 over reported data to the municipal level representing accuracy ratio of 80% and discrepancy level of 20%.

Conclusions

Immunization data was characterized by underreporting and overreporting, hence not accurate and lacked quality. Immunization data quality should be a priority among health staff at health facilities.
Modified base-binding EVE and DCD domains: striking diversity of genomic contexts in prokaryotes and predicted involvement in a variety of cellular processes
Authors: Bell Ryan T. , Wolf Yuri I. , Koonin Eugene V.
Published: November 2020

Background

DNA and RNA of all cellular life forms and many viruses contain an expansive repertoire of modified bases. The modified bases play diverse biological roles that include both regulation of transcription and translation, and protection against restriction endonucleases and antibiotics. Modified bases are often recognized by dedicated protein domains. However, the elaborate networks of interactions and processes mediated by modified bases are far from being completely understood.

Results

We present a comprehensive census and classification of EVE domains that belong to the PUA/ASCH domain superfamily and bind various modified bases in DNA and RNA. We employ the “guilt by association” approach to make functional inferences from comparative analysis of bacterial and archaeal genomes, based on the distribution and associations of EVE domains in (predicted) operons and functional networks of genes. Prokaryotes encode two classes of EVE domain proteins, slow-evolving and fast-evolving ones. Slow-evolving EVE domains in α-proteobacteria are embedded in conserved operons, potentially involved in coupling between translation and respiration, cytochrome c biogenesis in particular, via binding 5-methylcytosine in tRNAs. In β- and γ-proteobacteria, the conserved associations implicate the EVE domains in the coordination of cell division, biofilm formation, and global transcriptional regulation by non-coding 6S small RNAs, which are potentially modified and bound by the EVE domains. In eukaryotes, the EVE domain-containing THYN1-like proteins have been reported to inhibit PCD and regulate the cell cycle, potentially, via binding 5-methylcytosine and its derivatives in DNA and/or RNA. We hypothesize that the link between PCD and cytochrome c was inherited from the α-proteobacterial and proto-mitochondrial endosymbiont and, unexpectedly, could involve modified base recognition by EVE domains. Fast-evolving EVE domains are typically embedded in defense contexts, including toxin-antitoxin modules and type IV restriction systems, suggesting roles in the recognition of modified bases in invading DNA molecules and targeting them for restriction. We additionally identified EVE-like prokaryotic Development and Cell Death (DCD) domains that are also implicated in defense functions including PCD. This function was inherited by eukaryotes, but in animals, the DCD proteins apparently were displaced by the extended Tudor family proteins, whose partnership with Piwi-related Argonautes became the centerpiece of the Piwi-interacting RNA (piRNA) system.

Conclusions

Recognition of modified bases in DNA and RNA by EVE-like domains appears to be an important, but until now, under-appreciated, common denominator in a variety of processes including PCD, cell cycle control, antivirus immunity, stress response, and germline development in animals.
Impact of Covid-19 in pregnancy on mother’s psychological status and infant’s neurobehavioral development: a longitudinal cohort study in China
Authors: Wang Yuanyuan , Chen Lian , Wu Tianchen , Shi Huifeng , Li Qin , Jiang Hai , Zheng Danni , Wang Xiaoli , Wei Yuan , Zhao Yangyu , Qiao Jie
Published: November 2020

Background

Evidence concerning the long-term impact of Covid-19 in pregnancy on mother’s psychological disorder and infant’s developmental delay is unknown.

Methods

This study is a longitudinal single-arm cohort study conducted in China between May 1 and July 31, 2020. Seventy-two pregnant patients with Covid-19 participated in follow-up surveys until 3 months after giving birth (57 cases) or having abortion (15 cases). We collected data from medical records regarding Covid-19, delivery or abortion, testing results of maternal and neonatal specimens, and questionnaires of quarantine, mother–baby separation, feeding, and measuring of mothers’ mental disorders and infants’ neurobehavioral disorders.

Results

All cases infected in the first trimester and 1/3 of cases infected in the second trimester had an abortion to terminate the pregnancy. 22.2% of pregnant patients were suffering from post-traumatic stress disorder or depression at 3 months after delivery or induced abortion. Among 57 live births, only one neonate was positive of nucleic acid testing for throat swab, but negative in repeated tests subsequently. The median duration of mother–baby separation was 35 days (interquartile range 16 to 52 days). After the termination of maternal quarantine, 49.1% of mothers chose to prolong the mother–baby separation (median 8 days; IQR 5 to 23 days). The breastfeeding rate was 8.8% at 1 week after birth, 19.3% at the age of 1 month, and 36.8% at the age of 3 months, respectively. The proportion of “monitoring” and “risk” in the social–emotional developmental domain at the age of 3 months was 22.7% and 63.6%, respectively. After the adjustment of preterm, neonatal sex, admitted to NICU, and the mother’s Covid-19 condition, the negative associations were significantly identified (p < 0.05) between mother–baby separation days and three developmental domains: communication, gross motor, and personal–social.

Conclusions

There is no definite evidence on vertical transmission of SARS-CoV-2. In addition to control infection risk, researchers and healthcare providers should pay more attention to maternal mental health and infant’s feeding, closeness with parents, and early development.
Autophagy regulation using luteolin: new insight into its anti-tumor activity
Authors: Ashrafizadeh Milad , Ahmadi Zahra , Farkhondeh Tahereh , Samarghandian Saeed
Published: November 2020

Application of novel methods in cancer therapy is important in terms of management and treatment of the life-threatening disorder. It appears that autophagy is a potential target in cancer therapy, as a variety of drugs targeting autophagy have shown great potential in reducing the viability and proliferation of cancer cells. Autophagy is primarily a catabolic process which provides energy during starvation. Besides, this process contributes to the degradation of aged or potentially toxic components and organelles. On the other hand, the source of a variety of naturally occurring anti-tumor drugs are flavonoids which have high anti-tumor activity. Luteolin is a polyphenolic flavone with the great pharmacological effects such as anti-diabetic, hepatoprotective, antioxidant, anti-inflammation, and anti-tumor. At the present review, we demonstrate how luteolin affects on autophagy process to induce anti-tumor activity.
The pathological features and prognoses of intraductal papillary mucinous neoplasm and mucinous cystic neoplasm after surgical resection: a single institution series
Authors: Li Yuqiong , Zhu Zhongfei , Peng Lisi , Jin Zhendong , Sun Liqi , Song Bin
Published: November 2020

Background

Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) represent the tumors with malignant transformation potential. The objective of the study was to verify their pathological characteristics, prognoses, and recurrence factors.

Methods

Two hundred eighteen IPMNs and 27 MCNs resected at a single institution were included. The demographic, preoperative, histopathological, and follow-up data of the patients were recorded and analyzed. Overall survival (OS) and disease-free survival (DFS) were defined as the interval from the date of initial surgery to death or the last follow-up (OS) and to diagnosis of recurrence or death at follow-up (DFS).

Results

Of the 218 IPMN and 27 MCN patients, 93 (42.7%) and 8 (29.6%) cases were malignant, respectively. IPMNs occurred in older patients compared with MCN patients (median 63 years vs 54 years, P < 0.0001), and MCNs occurred exclusively in females (100%). Of the overall study cohort, the pathological specimens presented peripheral invasion in 37 (15.1%) patients and incisal margin invasion was observed in 46 (18.8%) patients. After a median follow-up of 34 months, 37 (14.9%) patients relapsed. The 5-year OS and DFS rates of IPMNs were 97.5% and 80.6%; and the OS and DFS rates of MCNs were 95.7% and 87.0%, respectively. There were four independent risk factors associated with recurrence: pathological diagnoses with malignancy (odds ratio, OR = 3.65), presence of oncocytic type for IPMN (OR = 1.69), peripheral invasion (OR = 12.87), and incisal margin invasion (OR = 1.99).

Conclusions

IPMNs and MCNs are indolent tumors with favorable prognoses after surgical resection in terms of their relatively high OS and DFS rate. Patients with malignant pathological-related diagnoses should accept strict tumor surveillance in view of their higher risk of recurrence.
Eukaryotic translation initiation factors as promising targets in cancer therapy
Authors: Hao Peiqi , Yu Jiaojiao , Ward Richard , Liu Yin , Hao Qiao , An Su , Xu Tianrui
Published: November 2020

The regulation of the translation of messenger RNA (mRNA) in eukaryotic cells is critical for gene expression, and occurs principally at the initiation phase which is mainly regulated by eukaryotic initiation factors (eIFs). eIFs are fundamental for the translation of mRNA and as such act as the primary targets of several signaling pathways to regulate gene expression. Mis-regulated mRNA expression is a common feature of tumorigenesis and the abnormal activity of eIF complexes triggered by upstream signaling pathways is detected in many tumors, leading to the selective translation of mRNA encoding proteins involved in tumorigenesis, metastasis, or resistance to anti-cancer drugs, and making eIFs a promising therapeutic target for various types of cancers. Here, we briefly outline our current understanding of the biology of eIFs, mainly focusing on the effects of several signaling pathways upon their functions and discuss their contributions to the initiation and progression of tumor growth. An overview of the progress in developing agents targeting the components of translation machinery for cancer treatment is also provided.
The biology of tardigrade disordered proteins in extreme stress tolerance
Authors: Hesgrove Cherie , Boothby Thomas C.
Published: November 2020

Disordered proteins have long been known to help mediate tolerance to different abiotic stresses including freezing, osmotic stress, high temperatures, and desiccation in a diverse set of organisms. Recently, three novel families of intrinsically disordered proteins were identified in tardigrades, microscopic animals capable of surviving a battery of environmental extremes. These three families include the Cytoplasmic-, Secreted-, and Mitochondrial- Abundant Heat Soluble (CAHS, SAHS, and MAHS) proteins, which are collectively termed Tardigrade Disordered Proteins (TDPs). At the level of sequence conservation TDPs are unique to tardigrades, and beyond their high degree of disorder the CAHS, SAHS, and MAHS families do not resemble one another. All three families are either highly expressed constitutively, or significantly enriched in response to desiccation. In vivo, ex vivo, and in vitro experiments indicate functional roles for members of each TDP family in mitigating cellular perturbations induced by various abiotic stresses. What is currently lacking is a comprehensive and holistic understanding of the fundamental mechanisms by which TDPs function, and the properties of TDPs that allow them to function via those mechanisms. A quantitative and systematic approach is needed to identify precisely what cellular damage TDPs work to prevent, what sequence features are important for these functions, and how those sequence features contribute to the underlying mechanisms of protection. Such an approach will inform us not only about these fascinating proteins, but will also provide insights into how the sequence of a disordered protein can dictate its functional, structural, and dynamic properties.

Graphical abstract
Process evaluation of an implementation trial to improve the triage, treatment and transfer of stroke patients in emergency departments (T3 trial): a qualitative study
Authors: McInnes Elizabeth , Dale Simeon , Craig Louise , Phillips Rosemary , Fasugba Oyebola , Schadewaldt Verena , Cheung N. Wah , Cadilhac Dominique A. , Grimshaw Jeremy M. , Levi Chris , Considine Julie , McElduff Patrick , Gerraty Richard , Fitzgerald Mark , Ward Jeanette , D’Este Catherine , Middleton Sandy
Published: November 2020

Background

The implementation of evidence-based protocols for stroke management in the emergency department (ED) for the appropriate triage, administration of tissue plasminogen activator to eligible patients, management of fever, hyperglycaemia and swallowing, and prompt transfer to a stroke unit were evaluated in an Australian cluster-randomised trial (T3 trial) conducted at 26 emergency departments. There was no reduction in 90-day death or dependency nor improved processes of ED care. We conducted an a priori planned process influential factors that impacted upon protocol uptake.

Methods

Qualitative face-to-face interviews were conducted with purposively selected ED and stroke clinicians from two high- and two low-performing intervention sites about their views on factors that influenced protocol uptake. All Trial State Co-ordinators (n = 3) who supported the implementation at the 13 intervention sites were also interviewed. Data were analysed thematically using normalisation process theory as a sensitising framework to understand key findings, and compared and contrasted between interviewee groups.

Results

Twenty-five ED and stroke clinicians, and three Trial State Co-ordinators were interviewed. Three major themes represented key influences on evidence uptake: (i) Readiness to change: reflected strategies to mobilise and engage clinical teams to foster cognitive participation and collective action; (ii) Fidelity to the protocols: reflected that beliefs about the evidence underpinning the protocols impeded the development of a shared understanding about the applicability of the protocols in the ED context (coherence); and (iii) Boundaries of care: reflected that appraisal (reflexive monitoring) by ED and stroke teams about their respective boundaries of clinical practice impeded uptake of the protocols.

Conclusions

Despite initial high ‘buy-in’ from clinicians, a theoretically informed and comprehensive implementation strategy was unable to overcome system and clinician level barriers. Initiatives to drive change and integrate protocols rested largely with senior nurses who had to overcome contextual factors that fell outside their control, including low medical engagement, beliefs about the supporting evidence and perceptions of professional boundaries. To maximise uptake of evidence and adherence to intervention fidelity in complex clinical settings such as ED cost-effective strategies are needed to overcome these barriers.

Trial registration

Australian New Zealand Clinical Trials Registry (ACTRN12614000939695).
Reprogramming the tumour microenvironment by radiotherapy: implications for radiotherapy and immunotherapy combinations
Authors: Colton Madyson , Cheadle Eleanor J. , Honeychurch Jamie , Illidge Tim M.
Published: November 2020

Radiotherapy (RT) is a highly effective anti-cancer therapy delivered to around 50–60% of patients. It is part of therapy for around 40% of cancer patients who are cured of their disease. Until recently, the focus of this anti-tumour efficacy has been on the direct tumour cytotoxicity and RT-induced DNA damage. Recently, the immunomodulatory effects of RT on the tumour microenvironment have increasingly been recognized. There is now intense interest in potentially using RT to induce an anti-tumour immune response, which has led to rethinking into how the efficacy of RT could be further enhanced. Following the breakthrough of immune check point inhibitors (ICIs), a new era of immuno-oncology (IO) agents has emerged and established immunotherapy as a routine part of cancer treatment. Despite ICI improving outcomes in many cancer types, overall durable responses occur in only a minority of patients. The immunostimulatory effects of RT make combinations with ICI attractive to potentially amplify anti-tumour immunity resulting in increased tumour responses and improved outcomes. In contrast, tumours with profoundly immunosuppressive tumour microenvironments, dominated by myeloid-derived cell populations, remain a greater clinical challenge and RT may potentially further enhance the immunosuppression. To harness the full potential of RT and IO agent combinations, further insights are required to enhance our understanding of the role these immunosuppressive myeloid populations play, how RT influences these populations and how they may be therapeutically manipulated in combination with RT to improve outcomes further. These are exciting times with increasing numbers of IO targets being discovered and IO agents undergoing clinical evaluation. Multidisciplinary research collaborations will be required to establish the optimal parameters for delivering RT (target volume, dose and fractionation) in combination with IO agents, including scheduling to achieve maximal therapeutic efficacy.
Preparing humanitarians to address ethical problems
Authors: McGowan Catherine R. , Baxter Louisa , DuBois Marc , Sheather Julian , Khondaker Ruma , Cummings Rachael , Watkins Kevin
Published: November 2020

Infectious disease outbreaks represent potentially catastrophic threats to those affected by humanitarian crises. High transmissibility, crowded living conditions, widespread co-morbidities, and a lack of intensive care capacity may amplify the effects of the outbreak on already vulnerable populations and present humanitarian actors with intense ethical problems. We argue that there are significant and troubling gaps in ethical awareness at the level of humanitarian praxis. Though some ethical guidance does exist most of it is directed at public health experts and fails to speak to the day-to-day ethical challenges confronted by frontline humanitarians. In responding to infectious disease outbreaks humanitarian workers are likely to grapple with complex dilemmas opening the door to moral distress and burnout.
Comparison of the 2018 and 2003 International Society of Nephrology/Renal Pathology Society classification in terms of renal prognosis in patients of lupus nephritis: a retrospective cohort study
Authors: Umeda Ryosuke , Ogata Soshiro , Hara Shigeo , Takahashi Kazuo , Inaguma Daijo , Hasegawa Midori , Yasuoka Hidetaka , Yuzawa Yukio , Hayashi Hiroki , Tsuboi Naotake
Published: November 2020

Background

Although the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification was proposed recently, until now, no reports have been made comparing the association of renal prognosis between the 2018 revised ISN/RPS classification and the 2003 ISN/RPS classification. The present study aimed to assess the usefulness, especially of activity and chronicity assessment, of the 2018 revised ISN/RPS classification for lupus nephritis (LN) in terms of renal prognosis compared to the classification in 2003.

Methods

We retrospectively collected medical records of 170 LN patients from the database of renal biopsy at Fujita Health University from January 2003 to April 2019. Each renal biopsy specimen was reevaluated according to both the 2003 ISN/RPS classification and the 2018 revised ISN/RPS classification. Renal endpoint was defined as a 30% decline of estimated glomerular filtration rate (eGFR).

Results

A total of 129 patients were class III/IV±V (class III, 44 patients; class IV, 35 patients; class III/IV+V, 50 patients). The mean age was 42 years, 88% were female, and the median observation period was 50.5 months. Renal prognosis was significantly different among the classes and significantly poor in the patients with higher modified National Institute of Health (mNIH) chronicity index (C index, ≥ 4) by a log-rank test (p = 0.05 and p = 0.02, respectively). By Cox proportional hazard models, only the C index was significantly associated with renal outcome (hazard ratio 1.32, 95% CI 1.11–1.56, p ≤ 0.01), while the classes, the 2003 activity and chronicity subdivision, and the mNIH activity index had no significant association with renal outcome. Each component of the C index was significantly associated with renal outcome in different models.

Conclusion

This study demonstrates that the 2018 revised ISN/RPS classification was more useful in terms of association with renal prognosis compared to the 2003 ISN/RPS classification.
Can pre-trained convolutional neural networks be directly used as a feature extractor for video-based neonatal sleep and wake classification?
Authors: Awais Muhammad , Long Xi , Yin Bin , Chen Chen , Akbarzadeh Saeed , Abbasi Saadullah Farooq , Irfan Muhammad , Lu Chunmei , Wang Xinhua , Wang Laishuan , Chen Wei
Published: November 2020

Objective

In this paper, we propose to evaluate the use of pre-trained convolutional neural networks (CNNs) as a features extractor followed by the Principal Component Analysis (PCA) to find the best discriminant features to perform classification using support vector machine (SVM) algorithm for neonatal sleep and wake states using Fluke® facial video frames. Using pre-trained CNNs as a feature extractor would hugely reduce the effort of collecting new neonatal data for training a neural network which could be computationally expensive. The features are extracted after fully connected layers (FCL’s), where we compare several pre-trained CNNs, e.g., VGG16, VGG19, InceptionV3, GoogLeNet, ResNet, and AlexNet.

Results

From around 2-h Fluke® video recording of seven neonates, we achieved a modest classification performance with an accuracy, sensitivity, and specificity of 65.3%, 69.8%, 61.0%, respectively with AlexNet using Fluke® (RGB) video frames. This indicates that using a pre-trained model as a feature extractor could not fully suffice for highly reliable sleep and wake classification in neonates. Therefore, in future work a dedicated neural network trained on neonatal data or a transfer learning approach is required.
A PUF-based cryptographic security solution for IoT systems on chip
Authors: Balan Alexandra , Balan Titus , Cirstea Marcian , Sandu Florin
Published: November 2020

The integration of multicore processors and peripherals from multiple intellectual property core providers as hardware components of IoT multiprocessor systems-on-chip (SoC) represents a source of security vulnerabilities for the in-chip communication.
This paper describes the concept and the practical results of a SoC security implementation that is illustrative for IoT applications. The mechanism employed in this approach uses physically unclonable functions (PUF) and symmetric cryptography in order to encrypt the transferred messages within the SoC between the microprocessor and its peripherals. The mechanism is experimentally validated at FPGA level, the paper describing also an implementation scenario for an IoT ARM based device.
Porcine hemothropic mycoplasmas infection associated with productive impact in intensive pig production
Authors: Petri Fernando Antônio Moreira , Sonalio Karina , de Souza Almeida Henrique Meiroz , Ferraz Maria Eugênia Silveira , Storino Gabriel Yuri , de Souza Mauro Rodrigo , André Marcos Rogério , de Oliveira Luis Guilherme
Published: November 2020

Background

So far, three porcine hemoplasmas (PH) have been identified, namely Mycoplasma suis, Mycoplasma parvum, and Mycoplasma haemosuis. The first one is the main agent associated with porcine hemoplasmosis, a possible cause of economic losses in pig production. Thus, this work aimed to detect and quantify PH 16S rRNA in finishing pigs and to associate its load estimate with average daily weight gain (ADWG). For this purpose, whole blood samples from 318 pigs were collected at an age of 75 days (d0) when the pigs entered the finishing phase and 105 days later (d105). To calculate ADWG, the animals were weighed at the abovementioned dates. Then, DNA from blood samples were submitted to a qPCR targeting the 16S rRNA gene for PH. Spearman correlation test was performed to investigate potential associations between ADWG and the quantification values. Lastly, the molecular characterization of PH was done by sequencing the 23S rDNA gene.

Results

Out of the 318 samples, 190 (59.74%) were positive on d0, and 304 (95.6%) were positive on d105. A significant correlation was observed (p < 0.05), albeit with a low coefficient value (0.18), when comparing ADWG with quantification values on d105. The phylogenetic analysis based on the 23S rDNA gene showed that four sequences were closely related to M. parvum, and one sequence was positioned in the M. suis cluster.

Conclusion

Two PH, M. suis and M. parvum, were detected in a Brazilian pig farm. Moreover, increasing occurrence through time was observed, which may have affected the productive performance of positive animals, mainly at the end of the finishing phase, when antimicrobials are removed.