bluuebunny/crossref_metadata_2025 huggingface dataset:
Benign juvenile idiopathic epilepsy in captive Iberian lynx (Lynx pardinus) in the ex situ conservation program (2005–2019)
Authors: Mínguez Juan J. , El Bouyafrouri Yasmin , Godoy José A. , Rivas Antonio , Fernández Jesús , Asensio Victoria , Serra Rodrigo , Perez-Aspa María J. , Lorenzo Valentina
Published: April 2021

Background

Benign juvenile idiopathic epilepsy has been described in humans but rarely in animals. The objectives of the study were to describe the clinical signs, clinical data, imaging findings, genetic examinations, treatment, long-term outcome and prognosis in Iberian lynx with juvenile epilepsy. Medical records, video recordings and diagnostic data from 2005 to 2019 were reviewed.

Results

Twenty lynx cubs with early onset of epileptic seizures (ES) from the conservation program were included. The average age at seizure onset was 75 days. Isolated and cluster ES were recorded. Focal ES, focal ES evolving into generalized ES with a stereotypical pattern and generalized ES were observed. All the cubs were normal between episodes, had a normal neurological examination and unremarkable investigations. Phenobarbital was used as a first line antiepileptic drug (AED). ES halted 10 days (0–34) after starting treatment in eight out of twenty cubs (40%). Treatment was discontinued in this group after a mean of 578 days and no further ES were reported (mean follow-up longer than 5 years). Eleven animals (55%) continued on AED treatment for a mean of 1306 days (70–3466). An adult-onset was observed for one lynx (5%). Polytherapy was necessary in seven lynxes (35%). The inheritance pattern observed was compatible with an autosomal recessive condition. Based on this assumption, mating between two identified carriers has been avoided since 2012, which may have contributed to the subsequent decrease in prevalence, with no further cases detected in 2018 and 2019.

Conclusions

Lynx pardinus may have an early onset self-limiting ES syndrome characteristic of benign juvenile idiopathic epilepsy. Information obtained from this study strongly suggests a genetic basis for the here presented epilepsy.
Construction of a long noncoding RNA-based competing endogenous RNA network and prognostic signatures of left- and right-side colon cancer
Authors: Li Ke-zhi , Yin Yi-xin , Tang Yan-ping , Long Long , Xie Ming-zhi , Li Ji-lin , Ding Ke , Hu Bang-li
Published: April 2021

Background

Cancers located on the right and left sides of the colon have distinct clinical and molecular characteristics. This study aimed to explore the regulatory mechanisms of location-specific long noncoding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) in colon cancer and identify potential prognostic biomarkers.

Method

Differentially expressed lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs) between right- and left-side colon cancers were identified by comparing RNA sequencing profiles. Functional enrichment analysis was performed for the DEGs, and a ceRNA network was constructed. Associations between DELs and patient survival were examined, and a DEL-based signature was constructed to examine the prognostic value of these differences. Clinical colon cancer tissues and Gene Expression Omnibus (GEO) datasets were used to validate the results.

Results

We identified 376 DELs, 35 DEMs, and 805 DEGs between right- and left-side colon cancers. The functional enrichment analysis revealed the functions and pathway involvement of DEGs. A ceRNA network was constructed based on 95 DEL–DEM–DEG interactions. Three DELs (LINC01555, AC015712, and FZD10-AS1) were associated with the overall survival of patients with colon cancer, and a prognostic signature was established based on these three DELs. High risk scores for this signature indicated poor survival, suggesting that the signature has prognostic value for colon cancer. Examination of clinical colon cancer tissues and GEO dataset analysis confirmed the results.

Conclusion

The ceRNA regulatory network suggests roles for location-specific lncRNAs in colon cancer and allowed the development of an lncRNA-based prognostic signature, which could be used to assess prognosis and determine treatment strategies in patients with colon cancer.
MicroRNA-665 facilitates cell proliferation and represses apoptosis through modulating Wnt5a/β-Catenin and Caspase-3 signaling pathways by targeting TRIM8 in LUSC
Authors: Chen Tian-Jun , Zheng Qi , Gao Fei , Yang Tian , Ren Hui , Li Yang , Chen Ming-Wei
Published: April 2021

Background

MicroRNAs (miRNAs) are involved in the oncogenesis, development and transformation of lung squamous cell carcinoma (LUSC). miR-665 is clinically significant and acts as a pivotal function in some cancers. Nevertheless, the effects and the potential mechanisms of miR-665 in human LUSC are still unknown.

Methods

To analyse the clinical significant of miR-665 in human LUSC, quantitative real-time PCR (qRT-PCR) was use to measure miR-665 expression in LUSC specimen tissues and cell lines. Tripartite motif 8 (TRIM8) was verified a target of miR-665 by performing bioinformatic prediction and luciferase reporter assay. The expression levels of TRIM8 were examined through qRT-PCR and Western blotting in LUSC specimen tissues. CCK8 assay was fulfilled for analyzing the function in LUSC cell proliferation. Flow cytometry was used to detect cell and apoptosis. TRIM8 silencing and overexpression further verified the biological effects as those caused by miR-665.

Results

Here we reported that miR-665 expression was upregulated in LUSC specimen tissues and cell lines. High miR-665 levels were related to differentiation, tumor size and TNM stage. miR-665 mimics facilitated LUSC cell growth and cell cycle G1-S transition and repressed apoptosis. miR-665 inhibitor suppressed cell proliferation and G1-S transition and promoted apoptosis. miR-665 expression was negatively correlated with TRIM8 mRNA expression in LUSC. Luciferase reporter assay confirmed that TRIM8 was a direct target gene of miR-665. miR-665 mimics downregulated the TRIM8 levels, and miR-665 inhibitor upregulated the TRIM8 levels in LUSC cells. Particularly, silencing TRIM8 led to the similar effects of miR-665 mimics in LUSC cells. Overexpression of TRIM8 inhibited LUSC cell proliferation in vitro and in vivo. Furthermore, miR-665 promoted LUSC cell proliferation through facilitating the Wnt5a/β-catenin signaling pathway and restrained apoptosis via inhibiting Caspase-3 signaling pathway, whereas TRIM8 suppressed cell growth by repressing the Wnt5a/β-catenin signaling pathway and induced apoptosis through activating Caspase-3 signaling pathway.

Conclusions

The current study demonstrates that miR-665 facilitates LUSC cell proliferation and cell cycle transition by regulation of the Wnt5a/β-Catenin signaling pathway and represses cell apoptosis via modulation of Caspase-3 signaling pathway by directly targeting TRIM8. These findings suggest that miR-665 might be a potential new target for LUSC therapy.
Alkaline phosphatase downregulation promotes lung adenocarcinoma metastasis via the c-Myc/RhoA axis
Authors: Lou Zhefeng , Lin Weiwei , Zhao Huirong , Jiao Xueli , Wang Cong , Zhao He , Liu Lu , Liu Yu , Xie Qipeng , Huang Xing , Huang Haishan , Zhao Lingling
Published: April 2021

Background

Lung adenocarcinoma (LUAD) metastasis significantly reduces patient survival; hence inhibiting the metastatic ability of lung cancer cells will greatly prolong patient survival. Alkaline phosphatase (ALPL), a homodimeric cell surface phosphohydrolase, is reported to play a controversial role in prostate cancer and ovarian cancer cell migration; however, the function of ALPL in LUAD and the related mechanisms remain unclear.

Methods

TCGA database was used to analysis the expression of ALPL, and further verification was performed in a cohort of 36 LUAD samples by qPCR and western blot. Soft-agar assay, transwell assay and lung metastasis assay were employed to detect the function of ALPL in LUAD progression. The qPCR, luciferase promoter reporter assay and western blot were used to clarify the molecular mechanisms of ALPL in promoting metastasis in LUAD.

Results

ALPL was downregulated in LUAD, and the disease-free survival rate of patients with low ALPL was significantly reduced. Further studies showed that overexpression of ALPL in LUAD cell lines did not significantly affect cell proliferation, but it did significantly attenuate lung metastasis in a mouse model. ALPL downregulation in LUAD led to a decrease in the amount of phosphorylated (p)-ERK. Because p-ERK promotes the classical c-Myc degradation pathway, the decrease in p-ERK led to the accumulation of c-Myc and therefore to an increase in RhoA transcription, which enhanced LUAD cell metastasis.

Conclusion

ALPL specially inhibits the metastasis of LUAD cells by affecting the p-ERK/c-Myc/RhoA axis, providing a theoretical basis for the targeted therapy of clinical LUAD.
The biological function and clinical significance of STIL in osteosarcoma
Authors: Ji Shu-fan , Wen Sheng-Lian , Sun Yu , Huang Pi-wei , Wu Hao , He Mao-lin
Published: April 2021

Background

SCL/TAL1 interrupting locus (STIL) is associated with the progression of several tumors; however, the biological role of STIL in osteosarcoma remains poorly understood.

Methods

In this study, the clinical significance of STIL in osteosarcoma was analyzed by gene chip data recorded in public databases. STIL expression was silenced in osteosarcoma cell lines to observe the effects on proliferation, apoptosis, invasion, and migration. Differentially expressed genes (DEGs) in the osteosarcoma chip were analyzed using The Limma package, and STIL co-expressed genes were obtained via the Pearson correlation coefficient. The potential molecular mechanism of STIL in osteosarcoma was further explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.

Results

Osteosarcoma was associated with higher STIL expression compared to the control samples, and the standardized mean difference (SMD) was 1.52. STIL also had a good ability to distinguish osteosarcoma from non-osteosarcoma samples [area under the curve (AUC) = 0.96]. After silencing STIL, osteosarcoma cell proliferation decreased, apoptosis increased, and the migratory and invasion ability decreased. A total of 294 STIL differentially co-expressed genes were screened, and a bioinformatics analysis found that differentially co-expressed genes were primarily enriched in the cell signaling pathways. The protein-protein interaction (PPI) network indicated that the hub differentially co-expressed genes of STIL were CDK1, CCNB2, CDC20, CCNA2, BUB1, and AURKB.

Conclusions

STIL is associated with osteosarcoma proliferation and invasion, and may be promote the progression of osteosarcoma by regulating the expression of CDK1, CCNB2, CDC20, CCNA2, BUB1 and AURKB.
Allelic diversity of merozoite surface protein genes (msp1 and msp2) and clinical manifestations of Plasmodium falciparum malaria cases in Aceh, Indonesia
Authors: Jamil Kurnia Fitri , Pratama Nandha Rizki , Marantina Sylvia Sance , Harapan Harapan , Kurniawan Muhammad Riza , Zanaria Tjut Mariam , Hutagalung Jontari , Rozi Ismail Ekoprayitno , Asih Puji Budi Setia , Supargiyono  , Syafruddin Din
Published: April 2021

Background

The malaria control programme in Indonesia has successfully brought down malaria incidence in many parts in Indonesia, including Aceh Province. Clinical manifestation of reported malaria cases in Aceh varied widely from asymptomatic, mild uncomplicated to severe and fatal complications. The present study aims to explore the allelic diversity of merozoite surface protein 1 gene (msp1) and msp2 among the Plasmodium falciparum isolates in Aceh Province and to determine their potential correlation with the severity of malaria clinical manifestation.

Methods

Screening of over 500 malaria cases admitted to the hospitals in 11 districts hospital within Aceh Province during 2013–2015, identified 90 cases of P. falciparum mono-infection without any co-morbidity. The subjects were clinically phenotyped and parasite DNA was extracted and polymerase chain reaction (PCR) amplified for the msp1 and msp2 allelic subfamilies.

Results

Analysis of clinical manifestation revealed that fever-chill is the most frequent symptom. Based on WHO criteria showed 19 cases were classified as severe and 71 as mild malaria. Analysis of msp1 gene revealed the presence of K1 allele subfamily in 34 subjects, MAD20 in 42 subjects, RO33 in 1 subject, and mixed allelic of K1 + MAD20 in 5 subjects, K1 + RO33 in 4 subjects, and MAD20 + RO33 in 4 subjects. Analysis of msp2 gene revealed 34 subjects carried the FC27 allelic subfamily, 37 subjects carried the 3D7 and 19 subjects carried the mixed FC27 + 3D7. Analysis of multiplicity of infection revealed that msp1 alleles is slightly higher than msp2 with the mean of MOI were 2.69 and 2.27, respectively. Statistical analysis to determine the association between each clinical manifestation and msp1 and msp2 alleles revealed that liver function abnormal value was associated with the msp2 mixed alleles (odds ratio (OR):0.13; 95%CI: 0.03–0.53). Mixed msp1 of K1 + RO33 was associated with severe malaria (OR: 28.50; 95%CI: 1.59–1532.30).

Conclusion

This study found a strong association between severe malaria in Aceh with subjects carrying the msp1 mixed alleles of K1 and RO33. The liver function abnormal value associated with the msp2 mixed allelic subfamilies. Further study in different geographic areas is recommended.
Are malaria transmission-blocking vaccines acceptable to high burden communities? Results from a mixed methods study in Bo, Sierra Leone
Authors: McCoy Kaci D. , Weldon Caroline T. , Ansumana Rashid , Lamin Joseph M. , Stenger David A. , Ryan Sadie J. , Bardosh Kevin , Jacobsen Kathryn H. , Dinglasan Rhoel R.
Published: April 2021

Background

Malaria transmission-blocking vaccines (TBVs) could help break the cycle of malaria transmission by conferring community rather than individual protection. When introducing new intervention strategies, uptake is dependent on acceptability, not just efficacy. In this exploratory study on acceptability of TBVs in Sierra Leone, it was hypothesized that TBVs would be largely acceptable to adults and health workers in areas with relatively few ongoing malaria interventions, and that (i) knowledge of malaria and vaccines, (ii) health behaviours associated with malaria and vaccines, and (iii) attitudes towards different vaccines types could lead to greater TBV acceptability.

Methods

This study used a mixed methods approach in Bo, Sierra Leone, to understand community knowledge, attitudes, and practices related to malaria and vaccination in general. This included: (i) a population-based cross-sectional survey (n=615 adults), (ii) 6 focus group discussions with parents, and (iii) 20 key informant interviews. The concept of a TBV was explained to participants before they were asked about their willingness to accept this vaccine modality as part of an integrated malaria elimination programme.

Results

This study found that most adults would be willing to receive a TBV vaccine. Respondents noted mostly positive past experiences with adult and childhood vaccinations for other infectious diseases and high levels of engagement in other malaria prevention behaviors such as bed nets. Perceived barriers to TBV acceptance were largely focused on general community-level distribution of a vaccine, including personal fears of vaccination and possible costs. After an explanation of the TBV mechanism, nearly all focus group and interview participants believed that community members would accept the vaccine as part of an integrated malaria control approach. Both parents and health workers offered insight on how to successfully roll-out a future TBV vaccination programme.

Conclusions

The willingness of community members in Bo, Sierra Leone to accept a TBV as part of an integrated anti-malarial strategy suggests that the atypical mechanism of TBV action might not be an obstacle to future clinical trials. This study’s findings suggests that perceived general barriers to vaccination implementation, such as perceived personal fears and vaccine cost, must be addressed in future clinical and implementation research studies.
Interaction between major dietary patterns and cardiorespiratory fitness on metabolic syndrome in Iranian adults: a cross-sectional study
Authors: Shahinfar Hossein , Ghanbari Mahtab , Jalilpiran Yahya , Payande Nastaran , Shahavandi Mahshid , Babaei Nadia , Djafarian Kurosh , Clark Cain C. C. , Shab-Bidar Sakineh
Published: April 2021

Background

Several researches have been conducted on the associations between diet and cardiorespiratory fitness (CRF) and major cardiovascular risk factors. However, there is no report about the interaction between major dietary patterns and CRF on metabolic syndrome (MetS) and its components. To investigate the combined association of major dietary patterns and CRF on MetS and its components.

Methods

This cross-sectional study was conducted on 270 apparently healthy adults living in Tehran, Iran. Dietary intake was evaluated using a validated food frequency questionnaire (FFQ). CRF was assessed using a graded exercise treadmill test. Socio-economic status, anthropometric measures, biochemical parameters, and blood pressure were evaluated according to standard methods. Major dietary patterns were identified by factor analysis.

Results

Three major identified dietary patterns were (healthy, mixed, and western). Significant positive association was found between mixed dietary pattern and metabolic syndrome (OR = 2.68, 95% CI (1.92,7.78), P = 0.04). There were not relations between tertiles of identified dietary patterns and remained outcomes. Those who had higher adherence to mixed pattern with also higher CRF showed a significant decrease for diastolic blood pressure (P < 0.01). Also we found that there was no significant interaction between any of dietary patterns and CRF on odds of MetS.

Conclusions

Overall, adherence to mixed dietary pattern in this population was associated with increasing odds of MetS. However, nor CRF neither the combination of dietary patterns and CRF was related to the odds of MetS among Iranian adults. More studies are needed to clarify these associations and to consider interpersonal determinants.
Prevalence of plasma lipid disorders with an emphasis on LDL cholesterol in selected countries in the Asia-Pacific region
Authors: Lee Zhen-Vin , Llanes Elmer Jasper , Sukmawan Renan , Thongtang Nuntakorn , Ho Huynh Quang Tri , Barter Philip ,   on behalf of the Cardiovascular RISk Prevention (CRISP) in Asia Network
Published: April 2021

Cardiovascular disease (CVD) is a major cause of mortality and morbidity within the Asia-Pacific region, with the prevalence of CVD risk factors such as plasma lipid disorders increasing in many Asian countries. As members of the Cardiovascular RISk Prevention (CRISP) in Asia network, the authors have focused on plasma lipid disorders in the six countries within which they have clinical experience: Indonesia, Malaysia, Philippines, Thailand, Vietnam, and Australia. Based on country-specific national surveys, the prevalence of abnormal levels of total cholesterol, low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), and triglycerides (TG) are reported. An important caveat is that countries have used different thresholds to define plasma lipid disorders, making direct comparisons difficult. The prevalence of abnormal lipid levels was as follows: high total cholesterol (30.2–47.7%, thresholds: 190–213 mg/dL); high LDL-C (33.2–47.5%; thresholds: 130–135 mg/dL); low/abnormal HDL-C (22.9–72.0%; thresholds: 39–50 mg/dL); and high/abnormal TG (13.9–38.7%; thresholds: 150–177 mg/dL). Similarities and differences between country-specific guidelines for the management of plasma lipid disorders are highlighted. Based on the authors’ clinical experience, some of the possible reasons for suboptimal management of plasma lipid disorders in each country are described. Issues common to several countries include physician reluctance to prescribe high-dose and/or high-intensity statins and poor understanding of disease, treatments, and side effects among patients. Treatment costs and geographical constraints have also hampered disease management in Indonesia and the Philippines. Understanding the factors governing the prevalence of plasma lipid disorders helps enhance strategies to reduce the burden of CVD in the Asia-Pacific region.
Dual activity of PD-L1 targeted Doxorubicin immunoliposomes promoted an enhanced efficacy of the antitumor immune response in melanoma murine model
Authors: Merino María , Lozano Teresa , Casares Noelia , Lana Hugo , Troconiz Iñaki F. , ten Hagen Timo L. M. , Kochan Grazyna , Berraondo Pedro , Zalba Sara , Garrido María J.
Published: April 2021

Background

The immunomodulation of the antitumor response driven by immunocheckpoint inhibitors (ICIs) such as PD-L1 (Programmed Death Ligand-1) monoclonal antibody (α-PD-L1) have shown relevant clinical outcomes in a subset of patients. This fact has led to the search for rational combinations with other therapeutic agents such as Doxorubicin (Dox), which cytotoxicity involves an immune activation that may enhance ICI response. Therefore, this study aims to evaluate the combination of chemotherapy and ICI by developing Dox Immunoliposomes functionalized with monovalent-variable fragments (Fab’) of α-PD-L1.

Results

Immunoliposomes were assayed in vitro and in vivo in a B16 OVA melanoma murine cell line over-expressing PD-L1. Here, immune system activation in tumor, spleen and lymph nodes, together with the antitumor efficacy were evaluated. Results showed that immunoliposomes bound specifically to PD-L1+ cells, yielding higher cell interaction and Dox internalization, and decreasing up to 30-fold the IC50, compared to conventional liposomes. This mechanism supported a higher in vivo response. Indeed, immunoliposomes promoted full tumor regression in 20% of mice and increased in 1 month the survival rate. This formulation was the only treatment able to induce significant (p < 0.01) increase of activated tumor specific cytotoxic T lymphocytes at the tumor site.

Conclusion

PD-L1 targeted liposomes encapsulating Dox have proved to be a rational combination able to enhance the modulation of the immune system by blocking PD-L1 and selectively internalizing Dox, thus successfully providing a dual activity offered by both, chemo and immune therapeutic strategies.

Graphic Abstract
‘I perceive it to be less harmful, I have no idea if it is or not:’ a qualitative exploration of the harm perceptions of IQOS among adult users
Authors: East Katherine A. , Tompkins Charlotte N. E. , McNeill Ann , Hitchman Sara C.
Published: April 2021

Background

Harm perceptions of tobacco and nicotine products can influence their use and could be targeted by policies to change behaviour. IQOS was introduced to the UK in 2016, and there is little independent qualitative research on IQOS harm perceptions. This study explored the perceived health harms of IQOS to users and those exposed to the emissions, what shapes these perceptions, and what participants wanted to know about the harms of IQOS.

Methods

Qualitative interviews in London, UK, with 30 adult current and former IQOS users who currently smoked or quit smoking in the last 2 years.

Results

IQOS was perceived as less harmful than smoking but not risk-free, although there was great uncertainty. Influences on harm perceptions were consolidated into six themes: (1) dominance of manufacturer claims influenced perceptions that IQOS is less harmful than smoking to users and those around them, although mistrust of the tobacco industry heightened scepticism about harms; (2) limited independent and long-term research led to uncertainty about harms, although some participants trusted IQOS would not be marketed if it were very harmful. Participants wanted more independent and long-term studies into harm; (3) appearance of HEETS (tobacco sticks) packaging conveyed reduced harm because packets were ‘pretty’, without graphic/specific warnings, although written warnings conveyed some harm. Participants wanted more information on HEETS packets about harms; (4) process of heating and HEETS contents—heating, compared with burning, tobacco was perceived to produce fewer harmful chemicals, while tobacco, nicotine, and chemicals in HEETS were perceived to cause some harm. Participants wanted clarification about the harms of heating tobacco and HEETS ingredients; (5) improvements in physical health and personal appearance reduced perceptions of harm; (6) differences in sensory experiences (taste, sight, smell) when using IQOS over smoking reduced perceptions of harm, while ‘black’ deposits inside IQOS led to perceptions of some harm. Reduced volume and smell of IQOS emissions also reduced perceptions of harm to non-users exposed to the emissions.

Conclusions

IQOS was perceived as less harmful than smoking but not risk-free, although there was great uncertainty. Participants wanted clarification about IQOS harms from independent sources in accessible forms, specifically related to HEETS ingredients, heating tobacco, and emissions to others.
Translation and validation of the Japanese version of the measure of moral distress for healthcare professionals
Authors: Fujii Tomoko , Katayama Shinshu , Miyazaki Kikuko , Nashiki Hiroshi , Niitsu Takehiro , Takei Tetsuhiro , Utsunomiya Akemi , Dodek Peter , Hamric Ann , Nakayama Takeo
Published: April 2021

Objectives

Moral distress occurs when professionals cannot carry out what they believe to be ethically appropriate actions because of constraints or barriers. We aimed to assess the validity and reliability of the Japanese translation of the Measure of Moral Distress for Healthcare Professionals (MMD-HP).

Methods

We translated the questionnaire into Japanese according to the instructions of EORTC Quality of Life group translation manual. All physicians and nurses who were directly involved in patient care at nine departments of four tertiary hospitals in Japan were invited to a survey to assess the construct validity, reliability and factor structure. Construct validity was assessed with the relation to the intention to leave the clinical position, and internal consistency was assessed with Cronbach’s alpha. Confirmatory factor analysis was conducted.

Results

308 responses were eligible for the analysis. The mean total score of MMD-HP (range, 0–432) was 98.2 (SD, 59.9). The score was higher in those who have or had the intention to leave their clinical role due to moral distress than in those who do not or did not have the intention of leaving (mean 113.7 [SD, 61.3] vs. 86.1 [56.6], t-test p < 0.001). The confirmatory factor analysis and Cronbach’s alpha confirmed the validity (chi-square, 661.9; CMIN/df, 2.14; GFI, 0.86; CFI, 0.88; CFI/TLI, 1.02; RMSEA, 0.061 [90%CI, 0.055–0.067]) and reliability (0.91 [95%CI, 0.89–0.92]) of the instrument.

Conclusions

The translated Japanese version of the MMD-HP is a reliable and valid instrument to assess moral distress among physicians and nurses.
Pre-colectomy location and TNM staging of colon cancer by the computed tomography colonography: a diagnostic performance study
Authors: Zhou Yadong , Han Zhiwei , Dou Fafu , Yan Tao
Published: April 2021

Background

The Chinese Society of Clinical Oncology guidelines 2018 and the recent update of that (version 2020) recommends accurate examination before major treatment for decision(s) in cases of colon cancer. Also, the difficulty in the identification of the lesion during colectomy may lead to resection of a wrong segment of the colon or a more extensive resection than planned. Accurate pre-colectomy local staging of colon cancer is required to make decisions for treatment of colon cancer. The objective of the study was to evaluate the diagnostic performance of the computed tomography colonography (CTC) for pre-colectomy tumor location and tumor, node, and metastasis (TNM) staging of colon cancer.

Methods

Data of preoperative colonoscopies, CTC, surgeries, and surgical pathology of a total of 269 patients diagnosed with colon cancer by colonoscopy and biopsy and underwent pre-colectomy location and TNM staging by CTC were collected and analyzed. The consistency between the radiological and the surgery/surgical-pathological for location and TN stages of colon tumor were estimated with the weighted kappa or kappa coefficient (κ) at 95% confidence interval (CI).

Results

CTC detected 261 (93%) and colonoscopy detected 201 (72%) correct locations of tumors. Sensitivity and accuracy of CTC for detection of location of colon tumors were 100% and 92.58% (κ = 0.89; 95% Cl: 0.83–0.95). 72.48% sensitivity, 90.64% specificity, and 83.57% accuracy were reported for CTC in differentiation of tumors confined to the colon wall (T1/T2) from advanced tumors (T3/T4) (κ = 0.69, 95% Cl: 0.51–0.75). 81.01% sensitivity, 89.11% specificity, and 83.93% accuracy of CTC was reported for differentiation of tumors between low–intermediate risk and high risk (κ = 0.68, 95% Cl: 0.53–0.75). 69.31% sensitivity, 66.15% specificity, and 67.14% accuracy of CTC were reported for N staging of tumors (κ = 0.41, 95% Cl: 0.59–0.69).

Conclusions

CTC has high diagnostic parameters for pre-colectomy location and T staging of colon tumors except patients of colon cancer who received neoadjuvant chemotherapy.

Level of Evidence

III.

Technical Efficacy Stage

2.
Adolescents’ sedentary time, affect, and contextual factors: An ecological momentary assessment study
Authors: Kracht Chelsea L. , Beyl Robbie A. , Maher Jaclyn P. , Katzmarzyk Peter T. , Staiano Amanda E.
Published: April 2021

Background

Few adolescents achieve sufficient levels of physical activity, and many are spending most of their time in sedentary behavior. Affective response following sedentary time may influence motivation to remain sedentary. Ecological Momentary Assessment (EMA) is a real-time data capture methodology that can be used to identify factors influencing sedentary time, such as the context of the home setting, and resulting affective state within a free-living setting. The purpose of this study was to evaluate the relationship between context at home and adolescent sedentary time, and the relationship of sedentary time and subsequent affect.

Methods

Adolescents (n = 284; 10–16 y) participated in an EMA study that used random, interval-based sampling methods. Adolescents each received 22 unannounced surveys over 7-days through a smartphone application. One survey was randomly sent within each 2-h time-period. These time-periods occurred between 4:00 pm-8:00 pm on weekdays and 8:00 am-8:00 pm on the weekend. This 15-question survey included a series of questions on context (indoors/outdoors, alone/not alone) and positive affect. Adolescents concurrently wore an accelerometer at the hip, and the 30-min bout of accelerometry data prior to each survey was used in analyses. Mixed-effect location scale models were used to examine the association between context at home and sedentary time (stage 1) and the adjusted sedentary time and positive affect (stage 2), with each model adjusted for covariates.

Results

Adolescents were 12.6 ± 1.9 y of age on average, about half were White (58%), and engaged in high levels of sedentary behavior during the 30 min prior to the survey (21.4 ± 6.8 min). Most surveys occurred when adolescents were with others (59%) and indoors (88%). In Stage 1, both being alone and being indoors at home were positively associated with sedentary time (p <  0.001 for both). In Stage 2, adjusted sedentary time was not related to positive affect. Age was negatively related to positive affect (p <  0.001).

Conclusions

Both contextual factors, being alone and indoors at home, were related to additional time spent sedentary compared to being with someone or outdoors. After adjustment, sedentary time was not related to subsequent positive affect, indicating other factors may be related to adolescent’s positive affect in home settings.
New-onset focal seizure as a presenting feature of HIV infection: a case report and mini review to the challenge in resource-limited settings
Authors: Ayele Biniyam A. , Getu Zemichael , Samuel Amen
Published: April 2021

Background

The frequency of new-onset HIV-associated seizure in the HIV-infected patient is estimated to be between 2 and 11%. Identifying the underlying etiology of new-onset seizure will have a vital impact on the mortality and morbidity of patients living with HIV infection.

Case presentation

We report a 34-year old newly diagnosed HIV+ male patient presented with abnormal body movement (ABM) involving his right hemibody associated with loss of consciousness lasting few minutes of two weeks duration. The ABM occurred frequently (> five times per week) and associated with frothy and excessive salivation. He reported headache following each spells. Brain magnetic resonance imaging (MRI) showed bilateral frontal T2 and FLAIR hyperintensity and T1 hypointensity; post contrast study showed bilateral small ring enhancing lesion with perilesional oedema, the biggest one on the left hemisphere, with a 10 mm diameter; considering patient advanced immunosuppression and underlying HIV infection, the brain MRI findings were consistent with cerebral toxoplasmosis. Bipolar montage electroencephalography (EEG) study showed generalized background slowing, prominent in the left fronto-centeral region. Patient was managed with combination antiretroviral therapy, anti-toxoplasmosis medication, and anticonvulsant. On follow up, the frequency of seizure attack has significantly reduced.

Conclusion

Considering the high prevalence of HIV infection and associated seizure among people living with HIV in sub-Saharan Africa, this case fairly highlights on the importance of utilizing advanced imaging techniques such as MRI and EEG in identifying the underlying causes of HIV-associated seizures.
The role of SOCS proteins in the development of virus- induced hepatocellular carcinoma
Authors: Xie Jinyan , Wang Mingshu , Cheng Anchun , Jia Renyong , Zhu Dekang , Liu Mafeng , Chen Shun , Zhao XinXin , Yang Qiao , Wu Ying , Zhang Shaqiu , Luo Qihui , Wang Yin , Xu Zhiwen , Chen Zhengli , Zhu Ling , Liu Yunya , Yu Yanling , Zhang Ling , Chen Xiaoyue
Published: April 2021

Background

Liver cancer has become one of the most common cancers and has a high mortality rate. Hepatocellular carcinoma is one of the most common liver cancers, and its occurrence and development process are associated with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections.

Main body

The serious consequences of chronic hepatitis virus infections are related to the viral invasion strategy. Furthermore, the viral escape mechanism has evolved during long-term struggles with the host. Studies have increasingly shown that suppressor of cytokine signaling (SOCS) proteins participate in the viral escape process. SOCS proteins play an important role in regulating cytokine signaling, particularly the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. Cytokines stimulate the expression of SOCS proteins, in turn, SOCS proteins inhibit cytokine signaling by blocking the JAK-STAT signaling pathway, thereby achieving homeostasis. By utilizing SOCS proteins, chronic hepatitis virus infection may destroy the host’s antiviral responses to achieve persistent infection.

Conclusions

This review provides recent knowledge regarding the role of SOCS proteins during chronic hepatitis virus infection and provides some new ideas for the future treatment of chronic hepatitis.
Self-assembled raccoon dog parvovirus VP2 protein confers immunity against RDPV disease in raccoon dogs: in vitro and in vivo studies
Authors: Xia Linya , Luo Guoliang , Wu Mingjie , Wang Lei , Zhang Ning , Wu Congmei , Yin Yuhe
Published: April 2021

Background

Raccoon dog parvovirus (RDPV) causes acute infectious diseases in raccoon dogs and may cause death in severe cases. The current treatment strategy relies on the extensive usage of classical inactivated vaccine which is marred by large doses, short immunization cycles and safety concerns.

Methods

The present study aimed at optimization of RDPV VP2 gene, subcloning the gene into plasmid pET30a, and its subsequent transfer to Escherichia coli with trigger factor 16 for co-expression. The protein thus expressed was purified with ammonium sulfate precipitation, hydrophobic chromatography, and endotoxin extraction procedures. VLPs were examined by transmission electron microscopy, dynamic light scattering, and the efficacy of VLPs vaccine was tested in vivo.

Results

Results indicated that RDPV VP2 protein could be expressed soluble. Transmission electron microscopy and dynamic light scattering results indicated that RDPV VP2 self-assembled into VLPs. Hemagglutination inhibition antibody titers elicited by Al(OH)3 adjuvanted RDPV VLPs were comparable with RDPV inactivated vaccines, and the viral loads in the blood of the struck raccoon dogs were greatly reduced. Hematoxylin and eosin and Immunohistochemical results indicated that RDPV VLPs vaccine could protect raccoon dogs against RDPV infections.

Conclusions

These results suggest that RDPV VLPs can become a potential vaccine candidate for RDPV therapy.
Prevalence and genotype distribution of human papillomavirus in Czech non-vaccinated heterosexual couples
Authors: Jaworek Hana , Koudelakova Vladimira , Oborna Ivana , Zborilova Blazena , Brezinova Jana , Ruzickova Dagmar , Vrbkova Jana , Kourilova Pavla , Hajduch Marian
Published: April 2021

Background

Data about the genotype-specific human papillomavirus (HPV) prevalence in the Czech Republic is limited. We aimed to evaluate the prevalence and concordance of genotype-specific HPV infection detected in semen samples, penile swabs and cervical swabs from non-vaccinated heterosexual couples without HPV-associated disease.

Methods

Semen samples and penile swabs were collected from male partners and cervical swabs were collected from female partners of heterosexual couples treated for infertility (n = 195). Presence of HPV DNA in semen samples and cervical swabs was analyzed using the cobas® HPV Test and PapilloCheck®. Only the PapilloCheck® test was used to detect HPV in penile swabs. The genotype-specific prevalence and concordance of HPV infection not targeted by vaccine were evaluated using Fisher exact test.

Results

Both partners were infected with any HPV type in 13.8% (27/195) of couples and, of these couples, 55.6% (15/27) harbored at least one mutual genotype. High-risk HPV (hrHPV) genotypes were detected in 12.3% (24/195) of semen samples, 31.3% (61/195) of penile swabs, and 19.5% (38/195) of cervical swabs (P < 0.001). The most prevalent hrHPV genotype were HPV53 (2.56%; 5/195) in semen samples, HPV16 (6.67%, 13/195) in penile swabs and HPV39 (3.59%, 7/195) in cervical swabs. Low-risk (lrHPV) genotypes were detected in 5.13% (10/195) of semen samples, 15.9% (31/195) of penile swabs, and 4.10% (8/195) of cervical swabs (P < 0.001). Male sexual partners of HPV-positive women were more likely to be infected with at least one of the same HPV types than female sexual partners of HPV-positive men (34.9% vs. 17.9%, P = 0.055).

Conclusions

This study showed that the detection of HPV infection differ by anatomic site and gender. Regardless the anatomic site, high prevalence of HPV genital infection was found in both Czech men and women.
Mulberry leaf extract improves glycaemic response and insulaemic response to sucrose in healthy subjects: results of a randomized, double blind, placebo-controlled study
Authors: Thondre Pariyarath Sangeetha , Lightowler Helen , Ahlstrom Lis , Gallagher Andrew
Published: April 2021

Background

There are many benefits of maintaining healthy blood glucose levels, and studies have shown that lifestyle changes such as changes to diet can successfully restore normoglycaemia in participants with dysglycaemia. Significant health-related lifestyle changes are often difficult to implement and functional ingredients that can reduce glycaemic and insulaemic responses may help at risk populations. The aim of this study was to investigate whether a mulberry leaf extract could lower the glycaemic and insulinaemic responses to 75 g sucrose in healthy individuals.

Methods

A double-blind, randomised, placebo-controlled, crossover design trial was conducted by the Oxford Brookes Centre for Nutrition and Health. Thirty-eight participants were recruited into the trial and, after an overnight fast, were given 75 g sucrose + white mulberry leaf extract, or 75 g sucrose alone. Capillary blood samples were collected at 15-min intervals in the first hour and at 30-min intervals over the second hour to determine glucose and plasma insulin levels. Data analysis was conducted using a paired samples T test or a Wilcoxon signed rank test.

Results

The addition of mulberry leaf extract to sucrose resulted in a significantly lower glycaemic response and insulinaemic response compared to a matched placebo (sucrose alone). The change in blood glucose measurements were significantly lower at 15 min (p < 0.001), 30 min (p < 0.001), 45 min (p = 0.008), and 120 min (p < 0.001) and plasma insulin measurements were significantly lower at 15 min (p < 0.001), 30 min (p < 0.001), 45 min (p < 0.001), 60 min (p = 0.001) and 120 min (p < 0.001). The glucose iAUC (− 42%, p = 0.001), insulin iAUC (− 40%, p < 0.001), peak glucose (− 40.0%, p < 0.001) and peak insulin (− 41%, p < 0.001) from baseline were significantly lower for white mulberry leaf extract compared with the placebo. White mulberry leaf extract was well tolerated and there were no reported adverse events.

Conclusions

Mulberry leaf extract can be used as part of lifestyle changes that may lead to healthy blood glucose levels.

Trial registration: ISRCTN99601810 (23 October 2020, retrospectively registered)
The impact of chronic co-exposure to different heavy metals on small fibers of peripheral nerves. A study of metal industry workers
Authors: Koszewicz Magdalena , Markowska Katarzyna , Waliszewska-Prosol Marta , Poreba Rafał , Gac Paweł , Szymanska-Chabowska Anna , Mazur Grzegorz , Wieczorek Malgorzata , Ejma Maria , Slotwinski Krzysztof , Budrewicz Slawomir
Published: April 2021

Background

Chronic exposure to heavy metals affects various organs, among them the brain and peripheral nerves. Polyneuropathy is mainly length-dependent with predominantly sensory symptoms. There have been few studies on small fiber neuropathy due to heavy metal intoxication.

Methods

We investigated 41 metal industry workers, mean age 51.3 ± 10.5 years, with at least 5 years’ professional exposure to heavy metals, and 36 age- and sex-matched healthy controls. We performed neurological examinations, and assessed blood levels of cadmium, lead, and zinc protoporphyrin, urine levels of arsenic, standard, sensory and motor electrophysiological tests in the ulnar and peroneal nerves, sympathetic skin responses from the palm and foot, and quantitative sensation testing from dermatomes C8 and S1.

Discussion

The results of standard conduction tests of all nerves significantly differed between groups. The latency of sympathetic skin responses achieved from the foot was also statistically significantly prolonged in the study group. Significant differences were seen in both C8 and S1 regions for temperature and pain thresholds, and for vibratory threshold only in the S1 region, while the dispersions of low and high temperatures were important exclusively in the C8 region.

Conclusions

We can conclude that co-exposure to many heavy metals results in explicit impairment of peripheral nerves. The lesion is more pronounced within small fibers and is predominantly connected with greater impairment of temperature-dependent pain thresholds. The evaluation of small fiber function should be considered in the early diagnosis of toxic polyneuropathy or in low-dose exposure to heavy metals.
Hypoproteinemia predicts disease severity and mortality in COVID-19: a call for action
Authors: Ali Amira Mohammed , Kunugi Hiroshi
Published: April 2021

Proteins represent the major building blocks of body tissues, and they regulate signaling involved in most cellular activities. Coronavirus disease 2019 (COVID-19) infection has been associated with high fatality, especially among older adults. The main cause of death is pulmonary tissue damage and multiple organ failure. The disease is associated with a hypercatabolic state that entails excessive protein loss. This review commentary sheds the light on hypoproteinemia in symptomatic/hospitalized COVID-19 with a special emphasis on its pathophysiology, screening, as well as its contribution to disease severity and adverse effects.
Experimental comparison of two methods to study barley responses to partial submergence
Authors: Miricescu Alexandra , Byrne Tomás , Doorly Catherine M. , Ng Carl K. Y. , Barth Susanne , Graciet Emmanuelle
Published: April 2021

Background

Crop yield is dependent on climate conditions, which are becoming both more variable and extreme in some areas of the world as a consequence of global climate change. Increased precipitation and flooding events are the cause of important yield losses due to waterlogging or (partial) submergence of crops in the field. Our ability to screen efficiently and quickly for varieties that have increased tolerance to waterlogging or (partial) submergence is important. Barley, a staple crop worldwide, is particularly sensitive to waterlogging. Screening for waterlogging tolerant barley varieties has been ongoing for many years, but methods used to screen vary greatly, from the type of soil used to the time at which the treatment is applied. This variation makes it difficult to cross-compare results.

Results

Here, we have devised a scoring system to assess barley tolerance to waterlogging and compare two different methods when partial submergence is applied with either water or a starch solution at an early developmental stage, which is particularly sensitive to waterlogging or partial submergence. The use of a starch solution has been previously shown to result in more reducing soil conditions and has been used to screen for waterlogging tolerance.

Conclusions

Our results show that the two methods provide similar results to qualitatively rank varieties as tolerant or sensitive, while also affecting plants differently, in that application of a starch solution results in stronger and earlier symptoms than applying partial submergence with water.
BMSC seeding in different scaffold incorporation with hyperbaric oxygen treats seawater-immersed bony defect
Authors: Zhang Gan , Chen Xiaosong , Cheng Xunsheng , Ma Wuxiu , Chen Congcong
Published: April 2021

Introduction

The experiment was undertaken to estimate the effect of BMSC seeding in different scaffold incorporation with HBO on the repair of a seawater-immersed bone defect. And future compared n-HA/PLGA with β-TCP/PLGA as a scaffold in treatment effect of the seawater-immersed bone defect.

Methods

Sixty New Zealand White rabbits with standard seawater defect in radius were randomly divided into group A (implant with nothing), group B (implanted with autogenous bone), group C (implanted with n-HA/PLGA/BMSCs), and group D (implanted with β-TCP/PLGA/BMSCs). After the implant, each rabbit receives HBO treatment at 2.4 ATA 100% oxygen for 120 min/day for 2 weeks. Radiograph, histological, and biomechanical examinations were used to analyze osteogenesis.

Result

X-ray analysis shows that n-HA/PLGA/BMSCs and β-TCP/PLGA/BMSCs could accelerate the new bone formation, and the new bone formation in group C was larger than that in group D or group A and close to group B (P < 0.05). After 12 weeks, in group A, the defect without scaffold shows a loose connect tissue filled in the areas. The medullary canal in group B was recanalized. Defects in groups C and D show a larger number of woven bone formation. The new woven bone formation in defect areas in group C was larger than that in group D. The mechanical examination revealed ultimate strength at 12 weeks was group D > group C > group B > group A (P < 0.05).

Conclusion

Scaffolds of n-HA/PLGA and β-TCP/PLGA incorporation with HBO and BMSCs were effective to treat seawater-immersed bone defect, and n-HA/PLGA was more excellent than β-TCP/PLGA.