bluuebunny/crossref_metadata_2025 huggingface dataset:
Older working adults in the HEAF study are more likely to report loneliness after two years of follow-up if they have negative perceptions of their work quality
Authors: Bevilacqua Gregorio , D’Angelo Stefania , Ntani Georgia , Syddall Holly Emma , Harris Elizabeth Clare , Linaker Cathy , Stevens Martin , Cooper Cyrus , Walker-Bone Karen
Published: March 2021

Background

Loneliness is an important public health issue associated with mortality and morbidity. Often researched amongst older people, less is known about risk factors for loneliness among adults aged 50–64 years who are in work. We investigated (a) if exit from the workforce increases the odds of loneliness; (b) whether adverse psychosocial work factors are associated with increased odds of loneliness over 2 years of follow-up; and (c) whether the association is stronger among subjects still working compared with those who have exited the workforce.

Methods

Data came from the Health and Employment After Fifty (HEAF) study, a large population cohort who provided questionnaire information about work and health at baseline and 2 annual follow-ups. Logistic regression was used to explore the association between psychosocial risk factors and loneliness at follow-up 2, with adjustment for loneliness at baseline, sex, age, self-rated health, living alone, and mental health diagnosis.

Results

Of the initial 8134 participants, 4521 were working at baseline and provided data for this analysis. Of those, 507 (11.2%) were defined as lonely at 2 years’ follow-up. Exiting the workforce was not significantly associated with loneliness (OR = 1.1, 95%CI: 0.7–1.7). However, negative psychosocial work factors predicted loneliness at follow-up. After mutual adjustment, lack of choice at work (OR: 1.5, 95%CI: 1.1–1.9), often lying awake worrying about work (OR: 1.4, 95%CI: 1.0–1.9) and perceived not coping with physical demands of the job (OR: 1.3, 95%CI: 1.0–1.7) were independent predictors, with associations robust to adjustment for demographic factors and health. Associations were only slightly altered when we restricted the sample to those who remained in work until the end of follow-up.

Conclusions

Loneliness amongst middle-aged working adults is not predicted by permanent work exit but is predicted by individuals’ perceptions about their work. Provision of good-quality work, matched to the capacity of the older worker, could prevent loneliness.
Mind the gap: what explains the rural-nonrural inequality in diarrhoea among under-five children in low and medium-income countries? A decomposition analysis
Authors: Fagbamigbe A. F. , Oyinlola F. F. , Morakinyo O. M. , Adebowale A. S. , Fagbamigbe O. S. , Uthman A. O.
Published: March 2021

Background

Diarrhoea poses serious health problems among under-five children (U5C) in Low-and Medium-Income Countries (LMIC) with a higher prevalence in rural areas. A gap exists in knowledge on factors driving rural-non-rural inequalities in diarrhoea development among U5C in LMIC. This study investigates the magnitude of rural-non-rural inequalities in diarrhoea and the roles of individual-level and neighbourhood-level factors in explaining these inequalities.

Methods

Data of 796,150 U5C, from 63,378 neighbourhoods across 57 LMIC from the most recent Demographic and Health Survey (2010–2018) was analysed. The outcome variable was the recent experience of diarrhoea while independent variables consist of the individual- and neighbourhood-level factors. Data were analysed using multivariable Fairlie decomposition at p < 0.05 in Stata Version 16 while visualization was implemented in R Statistical Package.

Results

Two-thirds (68.0%) of the children are from rural areas. The overall prevalence of diarrhoea was 14.2, 14.6% vs 13.4% among rural and non-rural children respectively (p < 0.001). From the analysis, the following 20 countries showed a statistically significant pro-rural inequalities with higher odds of diarrhoea in rural areas than in nonrural areas at 5% alpha level: Albania (OR = 1.769; p = 0.001), Benin (OR = 1.209; p = 0.002), Burundi (OR = 1.399; p < 0.001), Cambodia (OR = 1.201; p < 0.031), Cameroon (OR = 1.377; p < 0.001), Comoros (OR = 1.266; p = 0.029), Egypt (OR = 1.331; p < 0.001), Honduras (OR = 1.127; p = 0.027), India (OR = 1.059; p < 0.001), Indonesia (OR = 1.219; p < 0.001), Liberia (OR = 1.158; p = 0.017), Mali (OR = 1.240; p = 0.001), Myanmar (OR = 1.422; p = 0.004), Namibia (OR = 1.451; p < 0.001), Nigeria (OR = 1.492; p < 0.001), Rwanda (OR = 1.261; p = 0.010), South Africa (OR = 1.420; p = 0.002), Togo (OR = 1.729; p < 0.001), Uganda (OR = 1.214; p < 0.001), and Yemen (OR = 1.249; p < 0.001); and pro-non-rural inequalities in 9 countries. Variations exist in factors associated with pro-rural inequalities across the 20 countries. Overall main contributors to pro-rural inequality were neighbourhood socioeconomic status, household wealth status, media access, toilet types, maternal age and education.

Conclusions

The gaps in the odds of diarrhoea among rural children than nonrural children were explained by individual-level and neighbourhood-level factors. Sustainable intervention measures that are tailored to country-specific needs could offer a better approach to closing rural-non-rural gaps in having diarrhoea among U5C in LMIC.
Association of the presence and its types of lamina fractures with posterior dural tear and neurological deficits in traumatic thoracic and lumbar burst fractures
Authors: Shi Xuchao , Xiang Shate , Dai Bo , He Zhennian
Published: March 2021

Introduction

The appropriate and optimal treatment for thoracic and lumbar (TL) burst fractures remains a topic of debate. Characterization of vertical laminar fractures (coronal cross-sectional imaging) is presented in this study to determine the severity and treatment options in TL burst fractures.

Methods

A retrospective evaluation of 341 consecutive patients with TL burst fractures was divided into Group I (whole), Group II (partial), and Group III (intact) based on the vertical laminar fracture morphology from coronal images on computed tomography (CT) scans. The presence of preoperative neurological status was reviewed, and several radiological parameters were measured. In addition, the incidence of dural tears was calculated in patients that underwent a decompression with posterior approach.

Results

In total, 270 lumbar and 71 thoracic burst fractures were analyzed. Compared with the intact group, the two other groups had significantly shorter central canal distance, wider interpedicular distance, and smaller spinal canal area, in particular, Group III. The incidences of preoperative neurological deficits in Groups I to III were 63.0, 22.2, and 6.3%, respectively. The incidences of dural tears in Groups I to III were 25.6, 6.3, and 0%, respectively.

Conclusion

The morphology of vertical laminar fractures observed across the coronal plane was important. Patients with “whole”, “partial” and “intact” laminar fractures indicated different severity of TL burst fractures. Due to the high probability of dural tears, decompression is recommended as a primary intervention for patients with “whole” laminar fractures. However, for patients without vertical laminar fractures, minimally invasive technique might be a better choice to avoid approach-related complications.
Oro-facial malignancy in north of Iraq: a retrospective study of biopsied cases
Authors: Fuoad Sura Ali Ahmed , Mohammad Dena Nadhim , Hamied Marwa Abdul-Salam , Garib Balkees Taha
Published: March 2021

Background

Identifying the prevalence of orofacial malignancies is essential to provide health-care programs and services for a specific population. This study aimed to specify the prevalence, clinical and histopathological features of oral malignancies in Sulaimani for over 12 years.

Methods

All archived reports for orofacial specimens from 2008 to 2019 were collected from three major centers in Sulaimani governorate. The demographic data, date, type of surgery, lesion's site, and diagnosis were recorded. The ICD-10 coding was specified for each case. A Chi-square test was used to assess differences between genders. A one-way ANOVA test was applied to analyze the differences in mean age distributions among different sites of oral malignancies and oral squamous cell carcinoma histopathological grades.P < 0.05 was considered significant.

Results

Orofacial malignant lesions account for 14.53% of the total sample. Patients' mean age was (55.46 ± 18.48) years, and they were predominantly males (M: F ratio = 1.15:1). The tongue was the frequently affected site (14.8%). A Chi-square test showed no significant difference between genders concerning age (P = 0.118), years of registration (P = 0.28), and site (P = 0.29). The C06 (represents; cheek mucosa C06.0, the vestibule of mouth C06.1, retromolar area C06.2, and other unspecified parts of mouth C06.8) was the most frequent topographical ICD-code (18.1%). Carcinoma was a frequent malignancy (63.2%). OSCC was the most common lesion (56.4%). It commonly affects males, and the tongue was the frequent site (24.1%) followed by lip (17.8%).

Conclusions

There is a slight increase in the registered oral malignancies in Sulaimani city over 12 years; they were predominated in males, in 61–70 years old patients, and being oral squamous cell carcinoma types.
Accurate diagnosis of colorectal cancer based on histopathology images using artificial intelligence
Authors: Wang K. S. , Yu G. , Xu C. , Meng X. H. , Zhou J. , Zheng C. , Deng Z. , Shang L. , Liu R. , Su S. , Zhou X. , Li Q. , Li J. , Wang J. , Ma K. , Qi J. , Hu Z. , Tang P. , Deng J. , Qiu X. , Li B. Y. , Shen W. D. , Quan R. P. , Yang J. T. , Huang L. Y. , Xiao Y. , Yang Z. C. , Li Z. , Wang S. C. , Ren H. , Liang C. , Guo W. , Li Y. , Xiao H. , Gu Y. , Yun J. P. , Huang D. , Song Z. , Fan X. , Chen L. , Yan X. , Li Z. , Huang Z. C. , Huang J. , Luttrell J. , Zhang C. Y. , Zhou W. , Zhang K. , Yi C. , Wu C. , Shen H. , Wang Y. P. , Xiao H. M. , Deng H. W.
Published: March 2021

Background

Accurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients’ treatment. The current heavy workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on daily image analyses.

Methods

Based on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC diagnosis using weakly labeled pathological whole-slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, > 14,680 WSIs, from > 9631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, the USA, and Germany.

Results

Our innovative AI tool consistently and nearly perfectly agreed with (average Kappa statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multicenters. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.988 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells.

Conclusions

This first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. It will drastically alleviate the heavy clinical burden of daily pathology diagnosis and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.
Oral probiotic activities and biosafety of Lactobacillus gasseri HHuMIN D
Authors: Mann Soyon , Park Myeong Soo , Johnston Tony V. , Ji Geun Eog , Hwang Keum Taek , Ku Seockmo
Published: March 2021

Background

Lactobacillus spp. have been researched worldwide and are used in probiotics, but due to difficulties with laboratory cultivation of and experimentation on oral microorganisms, there are few reports of Lactobacillus spp. being isolated from the oral cavity and tested against oral pathogens. This research sought to isolate and determine the safety and inhibitory capabilities of a Lactobacillus culture taken from the human body.

Results

One organism was isolated, named “L. gasseri HHuMIN D”, and evaluated for safety. A 5% dilution of L. gasseri HHuMIN D culture supernatant exhibited 88.8% inhibition against halitosis-producing anaerobic microorganisms and the organism itself exhibited powerful inhibitory effects on the growth of 11 oral bacteria. Hydrogen peroxide production reached 802 μmol/L after 12 h and gradually diminished until 24 h, it efficiently aggregated with P. catoniae and S. sanguinis, and it completely suppressed S. mutans-manufactured artificial dental plaque. L. gasseri HHuMIN D’s KB cell adhesion capacity was 4.41 cells per cell, and the cell adhesion of F. nucleatum and S. mutans diminished strongly in protection and displacement assays.

Conclusion

These results suggest that L. gasseri HHuMIN D is a safe, bioactive, lactobacterial food ingredient, starter culture, and/or probiotic microorganism for human oral health.
The role of opioids in cancer response to immunotherapy
Authors: Botticelli Andrea , Cirillo Alessio , Pomati Giulia , Cerbelli Bruna , Scagnoli Simone , Roberto Michela , Gelibter Alain , Mammone Giulia , Calandrella Maria Letizia , Cerbelli Edoardo , Di Pietro Francesca Romana , De Galitiis Federica , Lanzetta Gaetano , Cortesi Enrico , Mezi Silvia , Marchetti Paolo
Published: March 2021

Background

The response to immunotherapy can be impaired by several factors including external intervention such as drug interactions with immune system. We aimed to examine the immunomodulatory action of opioids, since immune cells express opioid receptors able to negatively influence their activities.

Methods

This observational, multicenter, retrospective study, recruited patients with different metastatic solid tumors, who have received immunotherapy between September 2014 and September 2019. Immunotherapy was administered according to the standard schedule approved for each primary tumor and line of treatment. The concomitant intake of antibiotics, antifungals, corticosteroids and opioids were evaluated in all included patients. The relationship between tumor response to immunotherapy and the oncological outcomes were evaluated. A multivariate Cox-proportional hazard model was used to identify independent prognostic factors for survival.

Results

One hundred ninety-three patients were recruited. Overall, progression-free survival (PFS) and overall survival (OS) were significantly shorter in those patients taking opioids than in those who didn’t (median PFS, 3 months vs. 19 months, HR 1.70, 95% CI 1.37–2.09, p < 0.0001; median OS, 4 months vs. 35 months, HR 1.60, 95% CI 1.26–2.02, p < 0.0001). In addition, PFS and OS were significantly impaired in those patients taking corticosteroids, antibiotics or antifungals, in those patients with an ECOG PS ≥ 1 and in patients with a high tumor burden. Using the multivariate analyses, opioids and ECOG PS were independent prognostic factors for PFS, whereas only ECOG PS resulted to be an independent prognostic factor for OS, with trend toward significance for opioids as well as tumor burden.

Discussion

Our study suggests that the concomitant administration of drugs as well as some clinical features could negatively predict the outcomes of cancer patients receiving immunotherapy. In particular, opioids use during immunotherapy is associated with early progression, potentially representing a predictive factor for PFS and negatively influencing OS as well.

Conclusions

A possible negative drug interaction able to impair the immune response to anti-PD-1/PD-L1 agents has been highlighted. Our findings suggest the need to further explore the impact of opioids on immune system modulation and their role in restoring the response to immunotherapy treatment, thereby improving patients' outcomes.
Prediction of hepatocellular carcinoma risk in patients with chronic liver disease from dynamic modular networks
Authors: Chen Yinying , Yang Wei , Chen Qilong , Liu Qiong , Liu Jun , Zhang Yingying , Li Bing , Li Dongfeng , Nan Jingyi , Li Xiaodong , Wu Huikun , Xiang Xinghua , Peng Yehui , Wang Jie , Su Shibing , Wang Zhong
Published: March 2021

Background

Discovering potential predictive risks in the super precarcinomatous phase of hepatocellular carcinoma (HCC) without any clinical manifestations is impossible under normal paradigm but critical to control this complex disease.

Methods

In this study, we utilized a proposed sequential allosteric modules (AMs)-based approach and quantitatively calculated the topological structural variations of these AMs.

Results

We found the total of 13 oncogenic allosteric modules (OAMs) among chronic hepatitis B (CHB), cirrhosis and HCC network used SimiNEF. We obtained the 11 highly correlated gene pairs involving 15 genes (r > 0.8, P < 0.001) from the 12 OAMs (the out-of-bag (OOB) classification error rate < 0.5) partial consistent with those in independent clinical microarray data, then a three-gene set (cyp1a2-cyp2c19-il6) was optimized to distinguish HCC from non-tumor liver tissues using random forests with an average area under the curve (AUC) of 0.973. Furthermore, we found significant inhibitory effect on the tumor growth of Bel-7402, Hep 3B and Huh7 cell lines in zebrafish treated with the compounds affected those three genes.

Conclusions

These findings indicated that the sequential AMs-based approach could detect HCC risk in the patients with chronic liver disease and might be applied to any time-dependent risk of cancer.
A circular RNA derived from PLXNB2 as a valuable predictor of the prognosis of patients with acute myeloid leukaemia
Authors: Lin Leilei , Wang Yu , Bian Sicheng , Sun Lili , Guo Zhibo , Kong Desheng , Zhao Linlin , Guo Dan , Li Qi , Wu Min , Wang Yuhuang , Wang Yuying , Li Yinghua
Published: March 2021

Background

As a common haematological malignancy, acute myeloid leukaemia (AML), particularly with extramedullary infiltration (EMI), often results in a high mortality rate and poor prognosis. Circular RNAs (circRNAs) regulate biological and pathogenic processes, suggesting a potential role in AML. We have previously described the overall alterations in circRNAs and their regulatory networks between patients with AML presenting with and without EMI. This study aims to find new prognostic and therapeutic targets potentially associated with AML.

Methods

qRT-PCR was performed on samples from 40 patients with AML and 15 healthy controls. The possibility of using circPLXNB2 (circRNA derived from PLXNB2) as a diagnostic and prognostic biomarker for AML was analysed with multiple statistical methods. In vitro, the function of circPLXNB2 was studied by lentivirus transfection, CCK-8 assays, flow cytometry, and Transwell experiments. Western blotting and qRT-PCR were performed to detect the expression of related proteins and genes. The distribution of circPLXNB2 in cells was observed using RNA fluorescence in situ hybridization (RNA-FISH). We also investigated the role of circPLXNB2 by establishing AML xenograft models in NOD/SCID mice.

Results

By analysing the results of qRT-PCR detection of clinical samples, the expression of the circPLXNB2 and PLXNB2 mRNAs were significantly increased in patients with AML, more specifically in patients with AML presenting with EMI. High circPLXNB2 expression was associated with an obviously shorter overall survival and leukaemia-free survival of patients with AML. The circPLXNB2 expression was positively correlated with PLXNB2 mRNA expression, as evidenced by Pearson’s correlation analysis. RNA-FISH revealed that circPLXNB2 is mainly located in the nucleus. In vitro and in vivo, circPLXNB2 promoted cell proliferation and migration and inhibited apoptosis. Notably, circPLXNB2 also increased the expression of PLXNB2, BCL2 and cyclin D1, and reduced the expression of BAX.

Conclusion

In summary, we validated the high expression of circPLXNB2 and PLXNB2 in patients with AML. Elevated circPLXNB2 levels were associated with poor clinical outcomes in patients with AML. Importantly, circPLXNB2 accelerated tumour growth and progression, possibly by regulating PLXNB2 expression. Our study highlights the potential of circPLXNB2 as a new prognostic predictor and therapeutic target for AML in the future.
Homegarden agroecosystems managed by Salar people on Qinghai-Tibet Plateau
Authors: Zhu Mingjing , Luo Binsheng , La Ben , Chen Ruijie , Liu Fenggui , Long Chunlin
Published: March 2021

Background

Salar is a Turkic-speaking Islamic ethnic group in China living mainly in Xunhua Salar Autonomous County (Xunhua or Xunhua County), Qinghai-Tibet Plateau. Salar people are skilled in horticulture and their homegarden (HG) management. They are regarded as the first people on the Qinghai-Tibet Plateau to practice horticulture, especially manage their HGs, traditional farming systems, and supplementary food production systems. Traditional knowledge of Salar people associated with their HGs always contributes significantly to the local livelihood, food security, ornamental value, and biodiversity conservation. The cultivation of different plants in HGs for self-sufficiency has a long tradition in China’s rural areas, especially in some mountainous areas. However, Salar traditional HGs have not been described. The present paper aims to report the features of Salar HGs mostly based on agrobiodiversity and its ecosystem services.

Methods

The methods used in this work included semi-structured interviews and participatory observation. A total of 60 households in three townships, 9 villages were surveyed. There are 4–12 family members in each household, aged from 20 to 86 years old. The homestead size is between 200 and 1200 m2. Plant species cultivated in Salar HGs were identified according to Flora of China. Based on a comprehensive survey of Salar HGs and related to background data, we identified and characterized the most important services and functions provided by Salar HGs.

Results

According to primary production systems, there are 4 different types of Salar HGs, including ornamental focus, product focus, dual-purpose and multi-purpose. In total, 108 (excluding weeds and bonsai) plant species were recorded in Salar HGs, within 43 plant families. The most important and frequently used plants are Rosa chinensis, Armeniaca vulgar, Prunus salicina, and Ziziphus jujuba. About 4 to 32 plant species were recorded in each homegarden. We found that the Salar HGs, as a typical agroecosyste, prossess multiple servcices and functions that directly benefit households according to the field investigation.

Conclusion

This paper reveals the floristic diversity of Salar HGs. It presents useful information in the homegarden agroecosystem of Salar people, such as HG types and species diversity in Salar HGs. Ecosystem functions and services research suggested that the Salar HG agroecosystem provides agroecosystem services mainly related to supply and culture services. Salar HGs are important as food supplement resources, aesthetics symbol, and cultural spaces.
Treatment of intrathoracic anastomotic leak after esophagectomy with the sump drainage tube
Authors: Yin Qifan , Zhou Shaohui , Song Yongbin , Xun Xuejiao , Liu Nana , Liu Lijun
Published: March 2021

Background

Intrathoracic esophagogastric anastomotic leak is one of the deadliest complications after esophagectomy. In recent years, we have implemented new method for the treatment of intrathoracic esophagogastric anastomotic leak with the nasogastric placement of sump drainage tube through fistula into abscess cavity. The aim of this study is to compare the efficacy of the new method and conventional therapies for intrathoracic anastomotic leak after esophagectomy.

Method

Esophagectomy and esophagogastric anastomotic procedures were performed in 875 patients at our institution from January 2008 to December 2019. Of these patients, 43(4.9%) patients developed intrathoracic anastomotic leaks postoperatively were enrolled into our study and their clinical data were retrospectively assessed. 20 (47%) patients from January 2008 to December 2012 received conventional treatments (group 1) known as the traditional “three-tube method”, and 23 (53%) patients from January 2013 to December 2019 received new treatments (group 2), consisted of conventional therapies and the nasogastric placement of sump drainage tube through fistula into abscess cavity.

Results

The presence of intrathoracic anastomotic leak was proven by contrast esophagography in 43 patients (4.9%). Among them, The average duration of chest tube was 47 days in group 1 and 28 days in group 2. The average length of leak treatment was 52 days in group 1 and 35 days in group 2. The average length of postoperative hospital stay was 56 days in group 1 and 39 days in group 2, respectively. 7(35%) patients among 20 patients died from intrathoracic anastomotic leak in group 1; and 3(13%) patients among 23 patients died from intrathoracic anastomotic leak in group 2. Compared with the conventional treatments (group 1), The average duration of chest tube was significantly decreased in the new treatments (group 2) (P < 0.01), as well as the length of leak treatment (P < 0.05) and the length of postoperative hospital stay (P < 0.01). However, there was no significant difference in the mortality rate (P = 0.148 > 0.05).

Conclusion

In conclusion, Our results showed this method of the nasogastric placement of sump drainage tube through fistula appears to be an safe, effective, technically feasible treatment option for intrathoracic esophagogastric anastomotic leak. The efficacy and feasibility could be further investigated with a well-designed and large-scale RCT research.
SGTA associates with intracellular aggregates in neurodegenerative diseases
Authors: Kubota Shun , Doi Hiroshi , Koyano Shigeru , Tanaka Kenichi , Komiya Hiroyasu , Katsumoto Atsuko , Ikeda Shingo , Hashiguchi Shunta , Nakamura Haruko , Fukai Ryoko , Takahashi Keita , Kunii Misako , Tada Mikiko , Takeuchi Hideyuki , Tanaka Fumiaki
Published: March 2021

Intracellular aggregates are a common pathological hallmark of neurodegenerative diseases such as polyglutamine (polyQ) diseases, amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and multiple system atrophy (MSA). Aggregates are mainly formed by aberrant disease-specific proteins and are accompanied by accumulation of other aggregate-interacting proteins. Although aggregate-interacting proteins have been considered to modulate the formation of aggregates and to be involved in molecular mechanisms of disease progression, the components of aggregate-interacting proteins remain unknown. In this study, we showed that small glutamine-rich tetratricopeptide repeat-containing protein alfa (SGTA) is an aggregate-interacting protein in neurodegenerative diseases. Immunohistochemistry showed that SGTA interacted with intracellular aggregates in Huntington disease (HD) cell models and neurons of HD model mice. We also revealed that SGTA colocalized with intracellular aggregates in postmortem brains of patients with polyQ diseases including spinocerebellar ataxia (SCA)1, SCA2, SCA3, and dentatorubral–pallidoluysian atrophy. In addition, SGTA colocalized with glial cytoplasmic inclusions in the brains of MSA patients, whereas no accumulation of SGTA was observed in neurons of PD and ALS patients. In vitro study showed that SGTA bound to polyQ aggregates through its C-terminal domain and SGTA overexpression reduced intracellular aggregates. These results suggest that SGTA may play a role in the formation of aggregates and may act as potential modifier of molecular pathological mechanisms of polyQ diseases and MSA.
Emerging agents and regimens for AML
Authors: Liu Hongtao
Published: March 2021

Until recently, acute myeloid leukemia (AML) patients used to have limited treatment options, depending solely on cytarabine + anthracycline (7 + 3) intensive chemotherapy and hypomethylating agents. Allogeneic stem cell transplantation (Allo-SCT) played an important role to improve the survival of eligible AML patients in the past several decades. The exploration of the genomic and molecular landscape of AML, identification of mutations associated with the pathogenesis of AML, and the understanding of the mechanisms of resistance to treatment from excellent translational research helped to expand the treatment options of AML quickly in the past few years, resulting in noteworthy breakthroughs and FDA approvals of new therapeutic treatments in AML patients. Targeted therapies and combinations of different classes of therapeutic agents to overcome treatment resistance further expanded the treatment options and improved survival. Immunotherapy, including antibody-based treatment, inhibition of immune negative regulators, and possible CAR T cells might further expand the therapeutic armamentarium for AML. This review is intended to summarize the recent developments in the treatment of AML.
Small-molecule HDAC and Akt inhibitors suppress tumor growth and enhance immunotherapy in multiple myeloma
Authors: Hirano Mitsuhito , Imai Yoichi , Kaito Yuta , Murayama Takahiko , Sato Kota , Ishida Tadao , Yamamoto Junichi , Ito Takumi , Futami Muneyoshi , Ri Masaki , Yasui Hiroshi , Denda Tamami , Tanaka Yukihisa , Ota Yasunori , Nojima Masanori , Kamikubo Yasuhiko , Gotoh Noriko , Iida Shinsuke , Handa Hiroshi , Tojo Arinobu
Published: March 2021

Background

Multiple myeloma (MM) is an incurable disease. The acquisition of resistance to drugs, including immunomodulatory drugs (IMiDs), has a negative effect on its prognosis. Cereblon (CRBN) is a key mediator of the bioactivities of IMiDs such as lenalidomide. Moreover, genetic alteration of CRBN is frequently detected in IMiD-resistant patients and is considered to contribute to IMiD resistance. Thus, overcoming resistance to drugs, including IMiDs, is expected to improve clinical outcomes. Here, we examined potential mechanisms of a histone deacetylase (HDAC) inhibitor and Akt inhibitor in relapsed/refractory MM patients.

Methods

We established lenalidomide-resistant cells by knocking down CRBN with RNAi-mediated downregulation or knocking out CRBN using CRISPR-Cas9 in MM cells. Additionally, we derived multi-drug (bortezomib, doxorubicin, or dexamethasone)-resistant cell lines and primary cells from relapsed/refractory MM patients. The effects of HDAC and Akt inhibitors on these drug-resistant MM cells were then observed with a particular focus on whether HDAC inhibitors enhance immunotherapy efficacy. We also investigated the effect of lenalidomide on CRBN-deficient cells.

Results

The HDAC inhibitor suppressed the growth of drug-resistant MM cell lines and enhanced the antibody-dependent cellular cytotoxicity (ADCC) of therapeutic antibodies by upregulating natural killer group 2D (NKG2D) ligands in MM cells. CRBN-deficient cells showed lenalidomide-induced upregulation of phosphorylated glycogen synthase kinase-3 (p-GSK-3) and c-Myc phosphorylation. Moreover, HDAC and Akt inhibitors downregulated c-Myc by blocking GSK-3 phosphorylation. HDAC and Akt inhibitors also exhibited synergistic cytotoxic and c-Myc-suppressive effects. The dual HDAC and PI3K inhibitor, CUDC-907, exhibited cytotoxic and immunotherapy-enhancing effects in MM cells, including multi-drug-resistant lines and primary cells from lenalidomide-resistant patients.

Conclusions

The combination of an HDAC and an Akt inhibitor represents a promising approach for the treatment of relapsed/refractory MM.
Research on cluster overlap and non-overlap region for 5G-IoV networks with NOMA
Authors: Gu Jinyuan , Zhang Guoan , Lv Haibin , Duan Wei
Published: March 2021

As a multi hop self-organizing network, wireless sensor network has the ability to cooperatively sense, collect and process the information of the sensed objects. The applications of WCN in 5G-based Internet of Vehicles (5G-IoV), using information fusion and intelligent information processing technologies, can obtain more reliable and accurate detection parameters, which has been widely concerned. However, the massive connectivity and information exchange in 5G-IoV pose great challenges to the bandwidth efficiency. In order to overcome these issues in 5G-IoV networks, a performance enhanced scheme based on non-orthogonal multiple access (NOMA) is proposed. In the proposed scheme, different vehicle locations are respectively discussed, i.e., whether in the overlap region of cluster head vehicles (CHVs). In particular, different to conventional works, each receiving node only decodes the desired signal to avoid performance loss provided from the poor channel quality limitation. On the other hand, all CHVs decode-and-forward new superposition coded signals with new power allocation factors, while that the maximum ratio combining is utilized at receivers to further improve the ergodic sum-rate (SR) and probability of conflict. The closed-form expressions of ergodic SR for our proposed scheme are analyzed under the independent Rayleigh fading channels. Numerical results corroborating our theoretical analysis show that the superposition coded signal transmission scheme applied to the proposed NOMA-IoV improves the ergodic SR performance significantly compared with the existing works, especially for the high signal-to-noise region.
Homoclinic orbits of sub-linear Hamiltonian systems with perturbed terms
Authors: Lv Haiyan , Chen Guanwei
Published: March 2021

By using variational methods, we obtain the existence of homoclinic orbits for perturbed Hamiltonian systems with sub-linear terms. To the best of our knowledge, there is no published result focusing on the perturbed and sub-linear Hamiltonian systems.
A hepatitis stochastic epidemic model with acute and chronic stages
Authors: Khan Amir , Hussain Ghulam , Yusuf Abdullahi , Usman Auwalu Hamisu , Humphries Usa Wannasingha
Published: March 2021

The article is based on the study of hepatitis transmission dynamics using a stochastic epidemic model. We discuss the stochastic perturbations of our proposed model by considering the effect of environmental fluctuation and distribute the transmission rate in the form of white noise. Taking into account the Lyapunov function theory, the uniqueness and existence of the global positive solution are proven. Some sufficient conditions for the extinction and persistence in the mean are established. The numerical simulations are given to verify the main theoretical findings.
Machine learning-based ability to classify psychosis and early stages of disease through parenting and attachment-related variables is associated with social cognition
Authors: Antonucci Linda A. , Raio Alessandra , Pergola Giulio , Gelao Barbara , Papalino Marco , Rampino Antonio , Andriola Ileana , Blasi Giuseppe , Bertolino Alessandro
Published: March 2021

Background

Recent views posited that negative parenting and attachment insecurity can be considered as general environmental factors of vulnerability for psychosis, specifically for individuals diagnosed with psychosis (PSY). Furthermore, evidence highlighted a tight relationship between attachment style and social cognition abilities, a key PSY behavioral phenotype. The aim of this study is to generate a machine learning algorithm based on the perceived quality of parenting and attachment style-related features to discriminate between PSY and healthy controls (HC) and to investigate its ability to track PSY early stages and risk conditions, as well as its association with social cognition performance.

Methods

Perceived maternal and paternal parenting, as well as attachment anxiety and avoidance scores, were trained to separate 71 HC from 34 PSY (20 individuals diagnosed with schizophrenia + 14 diagnosed with bipolar disorder with psychotic manifestations) using support vector classification and repeated nested cross-validation. We then validated this model on independent datasets including individuals at the early stages of disease (ESD, i.e. first episode of psychosis or depression, or at-risk mental state for psychosis) and with familial high risk for PSY (FHR, i.e. having a first-degree relative suffering from psychosis). Then, we performed factorial analyses to test the group x classification rate interaction on emotion perception, social inference and managing of emotions abilities.

Results

The perceived parenting and attachment-based machine learning model discriminated PSY from HC with a Balanced Accuracy (BAC) of 72.2%. Slightly lower classification performance was measured in the ESD sample (HC-ESD BAC = 63.5%), while the model could not discriminate between FHR and HC (BAC = 44.2%). We observed a significant group x classification interaction in PSY and HC from the discovery sample on emotion perception and on the ability to manage emotions (bothp = 0.02). The interaction on managing of emotion abilities was replicated in the ESD and HC validation sample (p = 0.03).

Conclusion

Our results suggest that parenting and attachment-related variables bear significant classification power when applied to both PSY and its early stages and are associated with variability in emotion processing. These variables could therefore be useful in psychosis early recognition programs aimed at softening the psychosis-associated disability.
Large deviations of extreme eigenvalues of generalized sample covariance matrices
Authors: Maillard Antoine
Published: March 2021

We present an analytical technique to compute the probability of rare events in which the largest eigenvalue of a random matrix is atypically large (i.e., the right tail of its large deviations). The results also transfer to the left tail of the large deviations of the smallest eigenvalue. The technique improves upon past methods by not requiring the explicit law of the eigenvalues, and we apply it to a large class of random matrices that were previously out of reach. In particular, we solve an open problem related to the performance of principal components analysis on highly correlated data, and open the way towards analyzing the high-dimensional landscapes of complex inference models. We probe our results using an importance sampling approach, effectively simulating events with probability as small as

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Urinary Phthalate Biomarkers and Bone Mineral Density in Postmenopausal Women
Authors: Reeves Katherine W , Vieyra Gabriela , Grimes Nydjie P , Meliker Jaymie , Jackson Rebecca D , Wactawski-Wende Jean , Wallace Robert , Zoeller R Thomas , Bigelow Carol , Hankinson Susan E , Manson JoAnn E , Cauley Jane A , Calafat Antonia M
Published: March 2021

Context

Phthalates are endocrine-disrupting chemicals that could disrupt normal physiologic function, triggering detrimental impacts on bone.

Objective

We evaluated associations between urinary phthalate biomarkers and BMD in postmenopausal women participating in the prospective Women’s Health Initiative (WHI).

Methods

We included WHI participants enrolled in the BMD substudy and selected for a nested case-control study of phthalates and breast cancer (N = 1255). We measured 13 phthalate biomarkers and creatinine in 2 to 3 urine samples per participant collected over 3 years, when all participants were cancer free. Total hip and femoral neck BMD were measured at baseline and year 3, concurrent with urine collection, via dual-energy x-ray absorptiometry. We fit multivariable generalized estimating equation models and linear mixed-effects models to estimate cross-sectional and longitudinal associations, respectively, with stratification on postmenopausal hormone therapy (HT) use.

Results

In cross-sectional analyses, mono-3-carboxypropyl phthalate and the sum of di-isobutyl phthalate metabolites were inversely associated with total hip BMD among HT nonusers, but not among HT users. Longitudinal analyses showed greater declines in total hip BMD among HT nonusers and with highest concentrations of mono-3-carboxyoctyl phthalate (–1.80%; 95% CI, –2.81% to –0.78%) or monocarboxynonyl phthalate (–1.84%; 95% CI, –2.80% to –0.89%); similar associations were observed with femoral neck BMD. Among HT users, phthalate biomarkers were not associated with total hip or femoral neck BMD change.

Conclusion

Certain phthalate biomarkers are associated with greater percentage decreases in total hip and femoral neck BMD. These findings suggest that phthalate exposure may have clinically important effects on BMD, and potentially fracture risk.
Impact of Adrenal Function on Hemostasis/Endothelial Function in Patients Undergoing Surgery
Authors: Fischli Stefan , von Wyl Viktor , Wuillemin Walter , von Känel Roland , Schütz Philipp , Christ-Crain Mirjam , Studer Fabian , Brander Lukas , Schüpfer Guido , Metzger Jürg , Henzen Christoph
Published: March 2021

Context

Glucocorticoids regulate hemostatic and endothelial function, and they are critical for adaptive functions during surgery. No data regarding the impact of adrenal function on hemostasis and endothelial function in the perioperative setting are available.

Objective

We assessed the association of adrenal response to adrenocorticotropic hormone (ACTH) and markers of endothelial/hemostatic function in surgical patients.

Methods

This prospective observational study, conducted at a tertiary care hospital, included 60 patients (35 male/25 female) undergoing abdominal surgery. Adrenal function was evaluated by low-dose ACTH stimulation test on the day before, during, and the day after surgery. According to their stimulated cortisol level (cutoff ≥ 500 nmol/L), patients were classified as having normal hypothalamic-pituitary-adrenal (HPA)-axis function (nHPA) or deficient HPA-axis function (dHPA). Parameters of endothelial function (soluble vascular cell adhesion molecule-1, thrombomodulin) and hemostasis (fibrinogen, von Willebrand factor antigen, factor VIII [FVIII]) were measured during surgery.

Results

Twenty-one patients had dHPA and 39 had nHPA. Compared with nHPA, patients with dHPA had significantly lower peak cortisol before (median 568 vs 425 nmol/L, P < 0.001) and during (693 vs 544 nmol/L, P < 0.001) surgery and lower postoperative hemoglobin levels (116 g/L vs 105 g/L, P = 0.049). FVIII was significantly reduced in patients with dHPA in uni- and multivariable analyses; other factors displayed no significant differences. Coagulation factors/endothelial markers changed progressively in relation to stimulated cortisol levels and showed a turning point at cortisol levels between 500 and 600 nmol/L.

Conclusions

Patients with dHPA undergoing abdominal surgery demonstrate impaired hemostasis which can translate into excessive blood loss.
Pollen protein and lipid content influence resilience to insecticides in honey bees (Apis mellifera)
Authors: Crone Makaylee K. , Grozinger Christina M.
Published: March 2021

In honey bees (Apis mellifera), there is growing evidence that the impacts of multiple stressors can be mitigated by quality nutrition. Pollen, which is the primary source of protein and lipids in bee diets, is particularly critical for generating more resilient phenotypes. Here, we evaluated the relationship between pollen protein to lipid (P:L) ratio and honey bee insecticide resilience. We hypothesized that pollen diets richer in lipids would lead to increased survival in bees exposed to insecticides, as pollen-derived lipids have previously been shown to improve bee resilience to pathogens and parasites. Furthermore, lipid metabolic processes are altered in bees exposed to insecticides. We fed age-matched bees pollen diets of different P:L ratios by altering a base pollen by either adding protein (casein powder) or lipid (canola oil) and simulating chronic insecticide exposure by feeding bees an organophosphate (chlorpyrifos). We also tested pollen diets of naturally different P:L ratios to determine whether the results were consistent. Linear regression analysis revealed that mean survival time for bees fed altered diets was best explained by protein concentration (P=0.04, adjusted R2=0.92), and that mean survival time for bees fed natural diets was best explained by the P:L ratio (P=0.008, adjusted R2=0.93). Our results indicate that higher dietary P:L ratios have a negative effect on bee physiology when combined with insecticide exposure, while lower P:L ratios have a positive effect. These results suggest that protein and lipid intake differentially influence insecticide response in bees, laying the groundwork for future studies of metabolic processes and development of improved diets.
Feasibility and safety of percutaneous computed tomography guided radiofrequency ablation of lymph nodes in oligometastatic patients: a single center’s experience
Authors: Filippiadis Dimitrios , Charalampopoulos George , Tsochatzis Athanasios , Reppas Lazaros , Mazioti Argyro , Kelekis Alexis , Kelekis Nikolaos
Published: March 2021

Objectives:

To retrospectively evaluate feasibility and safety of CT-guided percutaneous radiofrequency ablation (RFA) of metastatic lymph nodes (LN) in terms of achieving local tumor control.

Methods:

Institutional database research identified 16 patients with 24 metastatic LNs who underwent percutaneous CT-guided radiofrequency ablation. Mean patient age was 66.6 ± 15.70 years (range 40–87) and male/female ratio was 8/8. Contrast-enhanced CT or MRI was used for post-ablation follow-up. Patient and tumor characteristics and RFA technique were evaluated. Technical and clinical success on per tumor and per patient basis as well as complication rates were recorded.

Results:

Mean size of the treated nodes was 1.78 ± 0.83 cm. The mean number of tumors per patient was 1.5 ± 0.63. The mean procedure time was 56.29 ± 24.27 min including local anesthesia, electrode(s) placement, ablation and post-procedural CT evaluation. Median length of hospital stay was 1.13 ± 0.34 days. On a per lesion basis, the overall complete response post-ablation according to the mRECIST criteria applied was 75% (18/24) of evaluable tumors. Repeat treatment of an index tumor was performed on two patients (three lesions) with complete response achieved in 87.5% (21/24) of evaluable tumors following a second RFA. On a per patient basis, disease progression was noted in 10/16 patients at a mean of 13.9 ± 6.03 months post the ablation procedure.

Conclusion:

CT-guided percutaneous RFA for oligometastatic LNs is a safe and feasible therapy.

Advances in knowledge:

With this percutaneous therapeutic option, metastatic LNs can be eradicated with a very low complication rate.
Empowering Democracy Through Internetization
Authors: Passaris Constantine E.
Published: March 2021

This policy brief explores the challenges and opportunities congruent with the advent of internetization on the democratic landscape. Internetization is a new word that I have coined to describe our contemporary empowerment through global outreach and electronic connectivity.  There is no denying that the 21st century has precipitated profound structural change and empowered democracy through digital capacity and electronic connectivity. This paper analyzes the impact of internetization on e-democracy, social media, civics education, non-governmental organizations and global outreach. It also addresses the consequences of internetization on cybersecurity threats, election tampering and the contemporary challenges associated with electronic voting. This policy brief concludes with a set of recommendations embracing a new governance architecture, adapting the machinery of governance to electronic capacity and a strategic list of public policy initiatives directed to enhance the role of internetization on the democratic landscape.