bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome sequencing reveals high-salt diet-induced abnormal liver metabolic pathways in mice
Authors: Li Yanping , Lyu Yufei , Huang Jing , Huang Kun , Yu Jiufei
Published: August 2021

Background

Although salt plays an important role in maintaining the normal physiological metabolism of the human body, many abnormalities in the liver caused by a high-salt diet, especially with normal pathological results, are not well characterized.

Methods

Eight-week-old female C57BL/6 mice were randomly divided into a normal group and a high salt group. These groups were then fed with normal or sodium-rich chow (containing 6% NaCl) for 6 weeks. Liver injury was evaluated, and the influences of a high-salt diet on the liver were analyzed by transcriptome sequencing at the end of week 6.

Results

We found that although no liver parenchymal injury could be found after high-salt feeding, many metabolic abnormalities had formed based on transcriptome sequencing results. GO and KEGG enrichment analyses of differentially expressed genes revealed that at least 15 enzymatic activities and the metabolism of multiple substances were affected by a high-salt diet. Moreover, a variety of signaling and metabolic pathways, as well as numerous biological functions, were involved in liver dysfunction due to a high-salt diet. This included some known pathways and many novel ones, such as retinol metabolism, linoleic acid metabolism, steroid hormone biosynthesis, and signaling pathways.

Conclusions

A high-salt diet can induce serious abnormal liver metabolic activities in mice at the transcriptional level, although substantial physical damage may not yet be visible. This study, to our knowledge, was the first to reveal the impact of a high-salt diet on the liver at the omics level, and provides theoretical support for potential clinical risk evaluation, pathogenic mechanisms, and drug design for combating liver dysfunction. This study also provides a serious candidate direction for further research on the physiological impacts of high-salt diets.
Blepharochalasis: clinical and epidemiological characteristics, surgical strategy and prognosis-- a retrospective cohort study with 93 cases
Authors: Zhou Jinqiong , Ding Jingwen , Li Dongmei
Published: August 2021

Background

Blepharochalasis is a rare eyelid disorder but eventually leading to destructive eyelid deformation. Until now the clinical and epidemiological data are unavailable. This study aimed to report the manifestations, epidemiological characteristics and surgical strategy of a large series of blepharochalasis patients with long-term follow-up. The prognosis of different clinical deformities was also investigated.

Methods

This was a retrospective cohort study, including consecutive patients diagnosed with blepharochalasis in a single center. Blepharoplasty and other surgical approaches were performed according to manifestations, after a 2-year quiescent period with no recurrent attacks and exacerbation of lesions. Prognosis after surgery was recorded.

Results

A total of 93 patients, with a mean age of 30.77 ± 14.04 (range: 9.00–70.00) years were included. Of all those 93 patients, 72.04% were females (67,P = 0.02). The mean follow-up was 5.29 ± 2.07 (range: 3–10) years before surgery, and 2.07 (range:1.54–4.22)years follow-up after surgery. The mean age of onset of blepharochalasis symptoms was 10.09 ± 3.32 (range: 5–16) years, and 83.87% patients got symptoms in puberty. With an average of 5 times per year, the mean duration of each acute attack was 28.12 ± 1.01 (rang: 2–192) hours. The mean duration from the onset of acute attack to the quiescent stage lasted for 7.33 ± 2.05 (range: 4–10) years. Most of the cases (88, 94.62%) had more than one manifestation at the end of the last follow-up before surgery. Ptosis (48.39%) was the most common deformity. Followed by lacrimal gland prolapse (44.09%), canthal angle deformity (29.04%), lower eyelid retraction (17.20%). After surgery, the functional and cosmetically acceptable results were achieved in all patients except for overcorrection in 5 (11.90%) patients with ptosis. The lacrimal gland prolapse recurred in two (4.00%) patients at 29 and 36 months after surgery.

Conclusions

Blepharochalasis is rare but mostly occurred in adolescent females. The process from the onset to the stable stage usually lasted for about 7 years, which might be associated with the onset of puberty. Surgical management of clinical manifestations after at least 2-year follow-up period of quiescence would be appropriate in order to observe a great plastic effect, low overcorrection and recurrence rate.
Thai version of the dry eye-related quality-of-life score questionnaire: preliminary assessment for psychometric properties
Authors: Tansanguan Sasiwimon , Tananuvat Napaporn , Wongpakaran Nahathai , Wongpakaran Tinakon , Ausayakhun Somsanguan
Published: August 2021

Background

This study aimed to develop a Thai version of the Dry Eye–Related Quality-of-Life Score (DEQS-Th) questionnaire and evaluate its validity, reliability, and feasibility among Thai participants.

Methods

The DEQS-Th, a 15-item self-report measuring dry eye and its impact on quality of life (QOL) was developed based on the DEQS. The questionnaire was divided into two subscales: Bothersome Ocular Symptoms (six questions), and Impact on Daily Life (nine questions). It employed a 5-point Likert scale, addressing on both the frequency and the degree of symptoms. Backward and forward and cultural adaptation process translation methods were employed. Thirty healthy participants were enrolled to evaluate the feasibility of the DEQS-Th in terms of difficulty and convenience. Reliability was assessed using internal consistency determined by Cronbach’s alpha, with values > 0.7 considered acceptable. Convergent validity was determined by the correlation between DEQS-Th and overall health status. Confirmatory factor analysis was conducted for its factor structure.

Results

The participants’ mean age was 38.6 ± 12.9 years, and 23 (76.7%) were females. The mean time to complete the questionnaire was 9.3 ± 2.7 min. The Cronbach’s alpha of the ocular symptoms subscale, impact on QOL subscale, and summary score on frequency and degree were 0.80 and 0.70, 0.89 and 0.89, and 0.90 and 0.89, respectively. The overall health status significantly correlated with the summary score (r = 0.564, p = .001), subscale ocular symptoms (r = 0.594, p = .001), and impact on QOL scores (r = 0.626, p < .001) of the DEQS-Th, respectively. A one-factor model fitted the data the best for both the ocular symptoms subscale (CFI = 1.000, TLI = 1.000, RMSEA = 0.000) and the impact on QOL subscale (CFI = 0.998, TLI = 0.997, RMSEA = 0.053).

Conclusion

When tested among normal participants, the DEQS-Th is a valid and reliable measurement for dry eye symptoms and impact on QOL.
Prevalence and associated metabolic factors for thyroid nodules: a cross-sectional study in Southwest of China with more than 120 thousand populations
Authors: Xu Li , Zeng Fanling , Wang Yutong , Bai Ye , Shan Xuefeng , Kong Lingxi
Published: August 2021

Objective

To explore the prevalence and its associated metabolic factors of thyroid nodules (TNs) among subjects who participated in the physical examinations in Chongqing, China.

Methods

The participants from the Health Management Center of JinShan Hospital of Chongqing Medical University, between September 2015 and May 2020, were included in this study. All of the participants underwent thyroid ultrasonography, anthropometric measurements, and serum examinations. Differences in the TNs prevalence were compared with the chi-square test or Wilcoxon rang-sum test. Multivariable logistic regression analyses were used to estimate the metabolic factors associated with TNs and multiple thyroid nodules (MTNs).

Results

Of the included 121,702 participants, 41,547 had TNs, and 20,899 had MTNs, with the prevalence of 34.1 and 17.0 %, respectively. Women had a significantly higher prevalence of TNs than men (40.6 % vs. 29.8 %; χ2 = 1517.33, P < 0.001), and TNs prevalence was gradually increased with age (P for trend < 0.001). Female gender, advanced age, and metabolic factors including central obesity, hypertension, diabetes and fatty liver were positively associated with TNs; BMI, hyperlipoidemia and hyperuricemia were not independent risk factors of TNs. While female gender, advanced age, central obesity, hypertension and diabetes were independent risk factors of MTNs.

Conclusions

The prevalence of thyroid nodules was relatively high. The associated factors identified in this study could help the clinicians to detect the high-risk patients and make targeted screening strategies for the preventing of the occurrence of TNs.
Vulvar Crohn’s disease in an adolescent diagnosed after unsuccessful surgical treatment
Authors: Kim Suhra , Won Young Bin , Seo Seok Kyo , Cho SiHyun , Choi Young Sik , Lee Byung Seok , Yun Bo Hyon
Published: August 2021

Background

This case report presents a case of Vulvar Crohn’s disease (VCD) in an adolescent, that is an uncommon manifestation of Crohn’s disease (CD) without gastrointestinal symptoms. Before treating CD itself with proper medication, vulvar abscess continued to recur without improvement.

Case presentation

We report the case of an 18-year-old woman with VCD. After treatment with azathioprine 50 mg daily and mesalazine 1 g three times daily, vulvar lesions resolved after 6 weeks. We collected electronic medical data on patient characteristics, and evaluated findings of physical examinations, pelvic MRI, and biopsy specimen obtained from gastroduodenoscopy/colonoscopy.

Conclusions

VCD is a rare manifestation of CD that may be misdiagnosed in the absence of gastrointestinal symptoms leading to delayed treatment. If a patient has an unexplained vulvar inflammatory lesion and with repeated failed surgical treatment, gynecologists should consider the possibility of a VCD.
Analysis of basal serum TSH, FT3, and FT4 levels based on age, sampling time in women with infertility
Authors: Zhang Yuchao , Wu Wenbin , Liu Yanli , Wang Xingling , Guan Yichun , Jia Liting
Published: August 2021

Background

To analyze the characteristics of basal thyroid hormone levels in infertile women consulting for assisted reproductive technology (ART) treatment.

Methods

This was a retrospective study. Serum TSH, FT3 and FT4 levels of women seeking ART consultation were tested routinely. Analyses were performed based on age and sampling time. One-way ANOVA or Kruskal-Wallis rank sum test was used to compare the continuous data among the groups, and the chi-square test or Fisher’s exact test was used to compare categorical data where appropriate.

Results

A total of 6426 women were initially included in the study. After exclusion criteria were applied, the remaining 4126 women were categorized into different groups. The prevalence of subclinical hypothyroidism significantly decreased with age and sampling time, from 21.09 to 11.91% and from 28.57 to 10.67%, respectively (P < 0.001, respectively). Mean serum TSH, FT3, and FT4 levels decreased significantly with age (P = 0.017, < 0.001, < 0.001, respectively). In the context of sampling time, TSH levels from early in the morning were significantly higher (P < 0.001), while FT4 and FT3 levels were similar in different groups (P = 0.258, 0.300, respectively).

Conclusions

The prevalence of subclinical hypothyroidism significantly decreased with increasing age and sampling time, as did the serum TSH levels. Even though, the establishment of reference interval of TSH level based on age or sampling time was not recommended. Full consideration of age and sampling time should be carefully taken before initiation of treatment.
Are investigators’ access to trial data and rights to publish restricted and are potential trial participants informed about this? A comparison of trial protocols and informed consent materials
Authors: Paludan-Müller Asger S. , Ogden Michelle C. , Marquardsen Mikkel , Jørgensen Karsten J. , Gøtzsche Peter C.
Published: August 2021

Objectives

To determine to which degree industry partners in randomised clinical trials own the data and can constrain publication rights of academic investigators.

Methods

Cohort study of trial protocols, publication agreements and other documents obtained through Freedom of Information requests, for a sample of 42 trials with industry involvement approved by ethics committees in Denmark. The main outcome measures used were: proportion of trials where data was owned by the industry partner, where the investigators right to publish were constrained and if this was mentioned in informed consent documents, and where the industry partner could review data while the trial was ongoing and stop the trial early.

Results

The industry partner owned all data in 20 trials (48%) and in 16 trials (38%) it was unclear. Publication constraints were described for 30 trials (71%) and this was not communicated to trial participants in informed consent documents in any of the trials. In eight trials (19%) the industry partner could review data during the trial, for 20 trials (48%) it was unclear. The industry partner could stop the trial early without any specific reason in 23 trials (55%).

Conclusions

Publication constraints are common, and data is often owned by industry partners. This is rarely communicated to trial participants. Such constraints might contribute to problems with selective outcome reporting. Patients should be fully informed about these aspects of trial conduct.
Apomixis and genetic background affect distinct traits in Hieracium pilosella L. grown under competition
Authors: Sailer Christian , Tiberi Simone , Schmid Bernhard , Stöcklin Jürg , Grossniklaus Ueli
Published: August 2021

Background

Apomixis, the asexual reproduction through seeds, occurs in over 40 plant families and avoids the hidden cost of sex. Apomictic plants are thought to have an advantage in sparse populations and when colonizing new areas but may have a disadvantage in changing environments because they propagate via fixed genotypes.

In this study, we separated the influences of different genetic backgrounds (potentially reflecting local adaptation) from those of the mode of reproduction, i.e., sexual vs. apomictic, on nine fitness-related traits in Hieracium pilosella L. We aimed to test whether apomixis per se may provide a fitness advantage in different competitive environments in a common garden setting.

Results

To separate the effects of genetic background from those of reproductive mode, we generated five families of apomictic and sexual full siblings by crossing two paternal with four maternal parents. Under competition, apomictic plants showed reproductive assurance (probability of seeding, fertility), while offspring of sexual plants with the same genetic background had a higher germination rate. Sexual plants grew better (biomass) than apomictic plants in the presence of grass as a competitor but apomictic plants spread further vegetatively (maximum stolon length) when their competitors were sexual plants of the same species. Furthermore, genetic background as represented by the five full-sibling families influenced maximum stolon length, the number of seeds, and total fitness. Under competition with grass, genetic background influenced fecundity, the number of seeds, and germination rate.

Conclusions

Our results suggest that both the mode of reproduction as well as the genetic background affect the success of H. pilosella in competitive environments. Total fitness, the most relevant trait for adaptation, was only affected by the genetic background. However, we also show for the first time that apomixis per se has effects on fitness-related traits that are not confounded by—and thus independent of—the genetic background.
Prevalence and in vitro antifungal susceptibility of commensal yeasts in the external ear canal of cats
Authors: Niae Sara , Yurayart Chompoonek , Thengchaisri Naris , Sattasathuchana Panpicha
Published: August 2021

Background

Lifestyle factors such as hair length, the frequency of ear cleaning and bathing, age, cat rearing, and sex may contribute to opportunistic yeast infections in the external ear canal of cats. This study aimed to determine the prevalence of commensal yeast organisms in cats’ external ear canals, evaluate their predisposing lifestyle factors, and test the susceptibility of Malassezia pachydermatis to antifungal agents.

Results

A total of 53 cats (33 male and 20 female) seronegative for feline leukemia virus and feline immunodeficiency virus were enrolled in this study. Their mean age (± standard deviation) was 6.04 (± 3.49) years. Fungal cultures and polymerase chain reaction tests were performed to identify the yeast species derived from the external ear canal. The association between lifestyle factors and the presence of M. pachydermatis was evaluated using Fisher’s exact test. The susceptibility of M. pachydermatis to antifungal agents was also analyzed. M. pachydermatis was the most frequently recovered yeast species, with a prevalence of 50.94 % (95 % confidence interval [CI]: 36.84–64.94 %). There was an association between hair length and a positive culture for M. pachydermatis (p = 0.0001). The odds of a negative culture for M. pachydermatis among short-haired cats was 11.67 (95 % CI, 3.22–42.24) times higher than that among long-haired cats (p = 0.0002). There was also an association between the frequency of ear cleaning and the presence of M. pachydermatis (p = 0.007). The odds of a negative culture for M. pachydermatis in cats that were receiving ear cleaning at intervals of ≤ 2 weeks was 5.78 (95 % CI, 1.67–19.94) times greater than that of cats receiving ear cleaning at intervals greater than 2 weeks or never (p = 0.0055). Ranges of minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations for itraconazole, ketoconazole, miconazole, and terbinafine against M. pachydermatis were ≤ 0.063–4 and ≤ 0.063–≥32, ≤ 0.063–8 and 0.125–≥32, ≤ 0.063–≥32 and 0.5–≥32, and ≤ 0.016–1 and 0.125–8 µg/ml, respectively.

Conclusions

M. pachydermatis was the most commonly identified yeast organism in the external ear canal of healthy cats. Hair length and the frequency of ear cleaning played a role in the colonization of M. pachydermatis. The M. pachydermatis isolates had various MIC levels for common fungicides.
Pan-cancer analysis of the oncogenic role of discs large homolog associated protein 5 (DLGAP5) in human tumors
Authors: Tang Neng , Dou Xiaolin , You Xing , Shi Qiman , Ke Mujing , Liu Guodong
Published: August 2021

Background

In recent years, there have been many studies on the relationship between DLGAP5 and different types of cancers, yet there is no pan-cancer analysis of DLGAP5. Therefore, this study aims to analyze the roles of DLGAP5 in human tumors.

Methods

Firstly, we evaluated the expression level of DLGAP5 in 33 types of tumors throughout the datasets of TCGA (Cancer Genome Atlas) and GEO (Gene Expression Synthesis). Secondly, we used the GEPIA2 and Kaplan-Meier plotter to conduct Survival prognosis analysis. Additionally, cBioPortal web was utilized to analyze the genetic alteration of DLGAP5, after which we selected hepatocellular carcinoma (HCC) cell lines to define the function of DLGAP5. Last but not least, we performed immune infiltration analysis and DLGAP5-related gene enrichment analysis.

Results

DLGAP5 is highly expressed in most type of cancers, and there is a significant correlation between the expression of DLGAP5 and the prognosis of cancer patients. We have observed that DLGAP5 promotes the proliferation and invasion of hepatocellular carcinoma (HCC) cell lines. We also found that DLGAP5 expression was related with the CD8+ T-cell infiltration status in kidney renal clear cell carcinoma, uveal melanoma, and thymoma, and cancer-associated fibroblast infiltration was observed in breast invasive carcinoma, kidney renal papillary cell carcinoma and testicular germ cell tumors. In addition, enrichment analysis revealed that cell cycle- and oocyte meiosis-associated functions were involved in the functional mechanism of DLGAP5.

Conclusions

Taken together, our unpresented pan-cancer analysis of DLGAP5 provides a relatively integrative understanding of the oncogenic role of DLGAP5 in various tumors. DLGAP5 may prompt HCC cellular proliferation, invasion and metastasis. All of these provides solid basement and will promote more advanced understanding the role of DLGAP5 in tumorigenesis and development from the perspective of clinical tumor samples and cells.
Maternal mortality reduction: a need to focus actions on the prevention of hypertensive disorders of pregnancy
Authors: Belizán José M. , Gibbons Luz , Cormick Gabriela
Published: August 2021

Maternal mortality (MM) reflects one of the most striking global health inequalities. Global figures of MM fell significantly from 1990 to 2017. The reduction was largely due to a 70% fall in haemorrhages, and a limited (18.2%) improvement in hypertensive disorders of pregnancy (HDP). If this trend continues, by 2021 HDP will be the main cause of global MM.

MM reductions due to haemorrhage is reassuring, however MM due to HDP show a more complex situation as early detection of HDP requires regular contact of pregnant women with the health system. In order to reduce MM due to HDP, population wide preventive actions such as low dose aspirin and adequate calcium intake are required, especially in areas where women have little contact with the health systems.

Calcium supplementation for women with low calcium intake has reduced the risk of pre-eclampsia, with further reductions starting daily supplementation with 500 mg of calcium preconceptionally, however adherence to supplementation is limited.

To reduce global inequities in calcium intake and consequently in the HDP, food fortification seem to be an attractive strategy to achieve an increase of calcium intake.
The neuroprotective effect of pretreatment with carbon dots from Crinis Carbonisatus (carbonized human hair) against cerebral ischemia reperfusion injury
Authors: Zhang Yue , Wang Suna , Lu Fang , Zhang Meiling , Kong Hui , Cheng Jinjun , Luo Juan , Zhao Yan , Qu Huihua
Published: August 2021

Background

Cerebral infarction and cerebral hemorrhage, also known as “stroke”, is one of the leading cause of death. At present, there is no real specific medicine for stroke. Crinis Carbonisatus (named Xue-yu-tan in Chinese), produced from carbonized hair of healthy human, and has been widely applied to relieve pain and treat epilepsy, stroke and other diseases in China for thousands of years.

Results

In this work, a new species of carbon dots derived from Crinis Carbonisatus (CrCi-CDs) were separated and identified. And the neuroprotective effect of carbon dots from CrCi were evaluated using the middle cerebral artery occlusion (MCAO) model. Neurological deficit score and infarction volume was assessed, evans blue content of ischemic hemispheres was measured, the concentrations of inflammatory factors, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) in the cortex were measured, and the levels of neurotransmitters in the brain were determined. Preconditioning of CrCi-CDs significantly reduced ischemic lesion volume and blood–brain-barrier (BBB) permeability, improved neurologic deficits, decreased the level of TNF-α and IL-6 in MCAO rats, inhibited excitatory neurotransmitters aspartate (Asp) and glutamate (Glu), and increased the level of 5-hydroxytryptamine (5-HT). The RNA-Sequencing results reveal that further potential mechanisms behind the activities may be related to the anti-inflammation effects and inhibition of neuroexcitatory toxicity.

Conclusion

CrCi-CDs performs neuroprotective effect on cerebral ischemia and reperfusion injury, and the mechanisms may correlate with its anti-inflammatory action, which suggested that CrCi-CDs have potential value in clinical therapy on the acute apoplexy cases in combination with thrombolytic drugs.

Graphic abstract
Anxiety, trauma and well-being in health-care professionals during COVID-19 first wave in Spain: the moderating role of personal protection equipment availability
Authors: Bajo Miriam , Gallego Pilar , Stavraki Maria , Lamprinakos Grigorios , Luna Pablo , Díaz Darío
Published: August 2021

Background

The effect of COVID-19 on Health-Care Professionals’ mental health has received increased attention in the last year’s literature. However, previous studies essentially evaluated psychopathological symptoms and not the presence of positive mental health. Therefore, the first objective of the present research is to evaluate health-care professionals’ mental illness (i.e., anxiety and traumatic intensity) and positive mental health (i.e., well-being) using the Complete State Model of Health. Our second objective is to study the effect of Personal Protection Equipment availability on professionals’ mental health.

Methods

Two-hundred and thirty-two health-care professionals working in Spain in the first line of COVID-19 patient care participated in the study. To measure anxiety, traumatic intensity and well-being participants completed the State Trait Anxiety Inventory, the Davidson Trauma Scale, and the Mental Health Continuum-Short Form. Pearson correlations were used to examine the relationships between all scales. In order to test the two continua model of mental health, we used parallel analysis and exploratory factor analysis. To analyze anxiety, traumatic intensity, and well-being differences between health-care professionals with and without Personal Protection Equipment availability we conducted different ANOVAS. To test our hypothesis regarding the moderating role of Personal Protection Equipment availability in the effect of mental illness on positive mental health, data were subjected to a hierarchical regression analysis.

Results

As in previous studies, health-care professionals showed high levels of anxiety and traumatic intensity. They also presented low levels of well-being indicators. According to our hypothesis, results of parallel analysis and exploratory factorial analysis indicated that the measures of mental illness and positive mental health loaded on separate but correlated factors. Finally, Personal Protection Equipment availability moderated the effects of state anxiety and traumatic intensity on professionals’ well-being.

Conclusions

Health-care professionals’ mental illness and positive mental health reflect distinct continua, rather than the extreme ends of a single spectrum. Therefore, it is essential to measure both psychopathology and the presence of positive health to comprehensively evaluate professionals’ mental health. Finally, our results indicated that Personal Protection Equipment availability is essential not only for professionals’ physical health, but also for their mental health.
Calibrated automated thrombogram II: removing barriers for thrombin generation measurements
Authors: Giesen P. L. A. , Gulpen A. J. W. , van Oerle R. , ten Cate H. , Nagy M. , Spronk H. M. H.
Published: August 2021

Background

Thrombin generation (TG) assessed by Calibrated Automated Thrombogram (CAT-I) reflects the overall capacity of plasma to generate thrombin, thus evaluating the balance between the anti- and procoagulant processes. However, with this method the calibrator curve is usually not measured until completion which has a severe impact on the calculation of the TG parameters, especially under conditions where almost all substrate is consumed. In addition, direct thrombin inhibitor (DTI) cannot be present in the calibration sample due to inhibition of the calibrator. We have developed a modified TG assay (CAT-II) and performed head-to-head comparison with the CAT-I method using the same fluorometer. Furthermore, we have compared our CAT-II method to a new automated TG instrument (ST®-Genesia) using the same calibration method.

Methods

TG was assessed with CAT-I and CAT-II using the same fulorometer and with ST®-Genesia in control plasma and plasma containing different anticoagulants (dabigatran, rivaroxaban, apixaban) and plasmas to which common interfering substances, bilirubin, hemoglobin and lipids were added. In CAT-I, calibration was against the same plasma containing calibrator in the presence of fluorogenic substrate (Z-GGR-AMC). In contrast, CAT-II method and ST®-Genesia used a standard concentration of thrombin in buffer and 7-amino-4-methylcoumarin (AMC) in a separate plasma sample for calibration.

Results

TG obtained from CAT-I using anticoagulant-free plasmas was lower compared with TG from CAT-II but both methods demonstrated an intra-assay variation less than 5% on all measured parameters. When comparing the two different calibration methods in the presence of different anticoagulants, a high correlation was seen in the presence of rivaroxaban and apixaban (R2 > 0.97), but not with dabigatran, a direct thrombin inhibitor. CAT-II method showed dose-dependent inhibition of TG in the presence of dabigatran, while CAT-I was not able to detect it. Both methods were able to correct for the interfering substances.

Conclusions

Our results showed high similarity between the results of CAT-I and CAT-II method when it is applied in control plasmas and plasmas not inhibited with a direct thrombin inhibitor. Furthermore, both the CAT-II method and ST-Genesia using the same calibration method were able to detect the effect of all oral anticoagulants. Taken together, applying a new calibration method is a significant improvement for monitoring patients on direct thrombin inhibitors while not introducing any bias to results obtained on other types of samples.
Associations of immune cell homing gene signatures and infiltrates of lymphocyte subsets in human melanomas: discordance with CD163+ myeloid cell infiltrates
Authors: Kwak Minyoung , Erdag Gulsun , Leick Katie M. , Bekiranov Stefan , Engelhard Victor H. , Slingluff Craig L.
Published: August 2021

Background

Immune cells in the tumor microenvironment have prognostic value. In preclinical models, recruitment and infiltration of these cells depends on immune cell homing (ICH) genes such as chemokines, cell adhesion molecules, and integrins. We hypothesized ICH ligands CXCL9-11 and CCL2-5 would be associated with intratumoral T-cells, while CXCL13 would be more associated with B-cell infiltrates.

Methods

Samples of human melanoma were submitted for gene expression analysis and immune cells identified by immunohistochemistry. Associations between the two were evaluated with unsupervised hierarchical clustering using correlation matrices from Spearman rank tests. Univariate analysis performed Mann–Whitney tests.

Results

For 119 melanoma specimens, analysis of 78 ICH genes revealed association among genes with nonspecific increase of multiple immune cell subsets: CD45+, CD8+and CD4+T-cells, CD20+B-cells, CD138+plasma cells, and CD56+NK-cells. ICH genes most associated with these infiltrates included ITGB2, ITGAL, CCL19, CXCL13, plus receptor/ligand pairs CXCL9 and CXCL10 with CXCR3; CCL4 and CCL5 with CCR5. This top ICH gene expression signature was also associated with genes representing immune-activation and effector function. In contrast, CD163+M2-macrophages was weakly associated with a different ICH gene signature.

Conclusion

These data do not support our hypothesis that each immune cell subset is uniquely associated with specific ICH genes. Instead, a larger set of ICH genes identifies melanomas with concordant infiltration of B-cell and T-cell lineages, while CD163+M2-macrophage infiltration suggesting alternate mechanisms for their recruitment. Future studies should explore the extent ICH gene signature contributes to tertiary lymphoid structures or cross-talk between homing pathways.
Contraception needs and pregnancy termination in sub-Saharan Africa: a multilevel analysis of demographic and health survey data
Authors: Adde Kenneth Setorwu , Dickson Kwamena Sekyi , Ameyaw Edward Kwabena , Amo-Adjei Joshua
Published: August 2021

Background

Women in sub-Saharan Africa (SSA) have a higher risk of unintended pregnancies that are more likely to be terminated, most of which are unsafe with associated complications. Unmet need for contraception is highest in SSA and exceeds the global average. This study investigates the association between unmet/met need for contraception and pregnancy termination SSA.

Methods

We used pooled data from Demographic and Health Surveys conducted from January 2010 to December 2018 in 32 countries in SSA. Our study involved 265,505 women with diverse contraception needs and with complete data on all variables of interest. Multilevel logistic regression at 95% CI was used to investigate the association between individual and community level factors and pregnancy termination.

Results

We found an overall pregnancy termination rate of 16.27% ranging from 9.13% in Namibia to 38.68% in Gabon. Intriguingly, women with a met need for contraception were more likely to terminate a pregnancy [aOR = 1.11; 95% CI 1.07–1.96] than women with unmet needs. Women with secondary education were more likely to terminate a pregnancy as compared to those without education [aOR = 1.23; 95% CI 1.19–1.27]. With regards to age, we observed that every additional age increases the likelihood of terminating a pregnancy. At the contextual level, the women with female household heads were less likely to terminate a pregnancy [aOR = 0.95; 95% CI 0.92–0.97]. The least socio-economically disadvantaged women were less likely to terminate a pregnancy compared to the moderately and most socio-economically disadvantaged women.

Conclusions

Our study contributes towards the discussion on unmet/met need for contraception and pregnancy termination across SSA. Women with met need for contraception have higher odds of terminating a pregnancy. The underlying cause of this we argued could be poor adherence to the protocols of contraceptives or the reluctance of women to utilise contraceptives after experiencing a failure. Governments of SSA and non-governmental organisations need to take pragmatic steps to increase met needs for contraception and also utilise mass media to encourage women to adhere to the prescription of contraceptives in order to reduce the incidence of unplanned pregnancies and unsafe abortions.
Metabolic responses of plasma to extreme environments in overwintering Tibetan frogs Nanorana parkeri: a metabolome integrated analysis
Authors: Niu Yonggang , Zhang Xuejing , Zhang Haiying , Xu Tisen , Zhu Lifeng , Storey Kenneth B. , Chen Qiang
Published: August 2021

Many animals lower their metabolic rate in response to low temperatures and scarcity of food in the winter in phenomena called hibernation or overwintering. Living at high altitude on the Tibetan Plateau where winters are very cold, the frogNanorana parkeri, survives in one of the most hostile environments on Earth but, to date, relatively little is known about the biochemical and physiological adjustments for overwintering by this species. The present study profiled changes in plasma metabolites ofN. parkeribetween winter and summer using UHPLC-QE-MS non-target metabolomics in order to explore metabolic adaptations that support winter survival. The analysis showed that, in total, 11 metabolites accumulated and 95 were reduced in overwintering frogs compared with summer-active animals. Metabolites that increased included some that may have antioxidant functions (canthaxanthin, galactinol), act as a metabolic inhibitor (mono-ethylhexylphthalate), or accumulate as a product of anaerobic metabolism (lactate). Most other metabolites in plasma showed reduced levels in winter and were generally involved in energy metabolism including 11 amino acids (proline, isoleucine, leucine, valine, phenylalanine, tyrosine, arginine, tryptophan, methionine, threonine and histidine) and 4 carbohydrates (glucose, citrate, succinate, and malate). Pathway analysis indicated that aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, and nitrogen metabolism were potentially the most prominently altered pathways in overwintering frogs. Changes to these pathways are likely due to fasting and global metabolic depression in overwintering frogs. Concentrations of glucose and urea, commonly used as cryoprotectants by amphibians that winter on land, were significantly reduced during underwater hibernation inN. parkeri. In conclusion, winter survival of the high-altitude frog,N. parkeriwas accompanied by substantial changes in metabolomic profiles and this study provides valuable information towards understanding the special adaptive mechanisms ofN. parkerito winter stresses.
Development of a method for evaluating the mRNA transcription activity of influenza virus RNA-dependent RNA polymerase through real-time reverse transcription polymerase chain reaction
Authors: Horio Yuka , Shichiri Mototada , Isegawa Yuji
Published: August 2021

Background

The development of an influenza RNA-dependent RNA polymerase (RdRp) inhibitor is required; therefore, a method for evaluating the activity of influenza RdRp needs to be developed. The current method uses an ultracentrifuge to separate viral particles and quantifies RdRp activity with radioisotope-labeled nucleosides, such as 32P-GTP. This method requires special equipment and radioisotope management, so it cannot be implemented in all institutions. We have developed a method to evaluate the mRNA transcription activity of RdRp without using ultracentrifugation and radioisotopes.

Results

RdRp was extracted from viral particles that were purified from the culture supernatant using anionic polymer-coated magnetic beads that can concentrate influenza virus particles from the culture supernatant in approximately 30 min. A strand-specific real-time reverse transcription polymerase chain reaction (RT-PCR) method was developed based on reverse transcription using tagged primers. RT primers were designed to bind to a sequence near the 3' end of mRNA containing a poly A tail for specific recognition of the mRNA, with an 18-nucleotide tag attached to the 5' end of the sequence. The RT reaction was performed with this tagged RT primer, and the amount of mRNA was analyzed using real-time qPCR. Real-time qPCR using the tag sequence as the forward primer and a segment-specific reverse primer ensured the specificity for quantifying the mRNA of segments 1, 4, and 5. The temperature, reaction time, and Mg2+ concentration were determined to select the optimum conditions for in vitro RNA synthesis by RdRp, and the amount of synthesized mRNAs of segments 1, 4, and 5 was determined with a detection sensitivity of 10 copies/reaction. In addition, mRNA synthesis was inhibited by ribavirin triphosphate, an RdRp inhibitor, thus indicating the usefulness of this evaluation method for screening RdRp inhibitors.

Conclusion

This method makes it possible to analyze the RdRp activity even in a laboratory where ultracentrifugation and radioisotopes cannot be used. This novel method for measuring influenza virus polymerase activity will further promote research to identify compounds that inhibit viral mRNA transcription activity of RdRp.
Resistance induction based on the understanding of molecular interactions between plant viruses and host plants
Authors: Akhter Md. Shamim , Nakahara Kenji S. , Masuta Chikara
Published: August 2021

Background

Viral diseases cause significant damage to crop yield and quality. While fungi- and bacteria-induced diseases can be controlled by pesticides, no effective approaches are available to control viruses with chemicals as they use the cellular functions of their host for their infection cycle. The conventional method of viral disease control is to use the inherent resistance of plants through breeding. However, the genetic sources of viral resistance are often limited. Recently, genome editing technology enabled the publication of multiple attempts to artificially induce new resistance types by manipulating host factors necessary for viral infection.

Main body

In this review, we first outline the two major (R gene-mediated and RNA silencing) viral resistance mechanisms in plants. We also explain the phenomenon of mutations of host factors to function as recessive resistance genes, taking the eIF4E genes as examples. We then focus on a new type of virus resistance that has been repeatedly reported recently due to the widespread use of genome editing technology in plants, facilitating the specific knockdown of host factors. Here, we show that (1) an in-frame mutation of host factors necessary to confer viral resistance, sometimes resulting in resistance to different viruses and that (2) certain host factors exhibit antiviral resistance and viral-supporting (proviral) properties.

Conclusion

A detailed understanding of the host factor functions would enable the development of strategies for the induction of a new type of viral resistance, taking into account the provision of a broad resistance spectrum and the suppression of the appearance of resistance-breaking strains.
One-week recall period gives a more accurate estimate of exclusive breastfeeding practice than 24-h recall among infants younger than six months of age
Authors: Andarge Sewitemariam Desalegn , Fenta Esete Habtemariam , Gebreyesus Seifu Hagos , Belachew Robel Yirgu
Published: August 2021

Background

The World Health Organization recommends a 24-h recall period to estimate breastfeeding practice of mothers of infants aged younger than six-months. Though 24-h recall was preferred for its low recall bias and for practical reasons, it can overestimate exclusive breastfeeding practice (EBF). Validating this indicator will help account for the deviation from the true estimate. This prospective cohort study measured accuracy of the 24-h recall method and validates a week recall as an alternative approach for use in a small sample population.

Method

The study was conducted from March to April 2018 involving 408 mother-infant pairs living in Butajira Health and Demographic Surveillance Site (HDSS), Southern Ethiopia. Participants were prospectively followed for 14 consecutive days; where their breastfeeding practice in the past 24 h was measured daily. Exclusive breastfeeding prevalence estimate obtained using the 24-h recall method and recall periods spanning a varying number of days (short period recalls) was compared against the cumulative of the responses from a prospectively measured repeated 24-h recalls over the course of 14 days. McNemar statistics was used to assess statistical significance of the difference in the EBF prevalence estimates of the single 24-h recall and the reference standard. Sensitivity, specificity, positive predictive value and negative predictive values were calculated to determine the level of accuracy. Receiver Operating Characteristics curve was used to measure the difference in performance between the two methods.

Result

The highest prevalence (71.4%) of exclusive breastfeeding practice was estimated using the single 24-h recall method whereas the lowest breastfeeding practice (47.1%) was obtained from a cumulative of 14 repeated 24-h recalls. A week recall (a recall over 7 days’ period), resulted in the smallest discrepancy in estimate (7.1%) as compared to cumulative estimate of 14 repeated 24-h recalls. Comparing against our reference standard, a week recall had 96.7% sensitivity and 83.5% specificity in estimating exclusive breastfeeding practice.

Conclusions

Using single 24-h recall method overestimated exclusive breastfeeding prevalence. However, a week recall gave an estimate close to the estimate from the standard method. A week recall has a potential to balance the tradeoff between the accuracy of EBF estimates and the resource implication of using multiple prospective measurements that have a proven superior accuracy.
Influence of physician networks on prescribing a new ingredient combination in heart failure: a longitudinal claim data-based study
Authors: Arnold Christine , Koetsenruijter Jan , Forstner Johanna , Peters-Klimm Frank , Wensing Michel
Published: August 2021

Background

Since 2016, the combination of sacubitril/valsartan, which combines an angiotensin receptor and neprilysin inhibitor (ARNI), has been recommended in the guidelines for the treatment of heart failure. The adoption of new drugs may be influenced by collaboration and exchange between physicians. We aimed to determine whether characteristics of the professional networks of prescribing physicians were associated with the prescribing of ARNI in Germany.

Methods

We conducted a longitudinal analysis based on claims data in 2016–2018 in Germany. The characteristics of ambulatory care physicians’ networks were determined in the analysis of the patient-sharing networks of physicians in 2017. Binary logistic regression analysis with the outcome ‘prescribes ARNI in 2018’ (present or absent) was carried out, using network characteristics as predictors, adjusted for specialty and sociodemographic characteristics of physicians.

Results

The network analysis included 8370 physicians, who had 144,636 connections. Prescribers had more connections to other physicians compared to non-prescribers (median 31 vs. 23). Regression analysis showed that the numbers of linkages to prescribers of ARNI were positively associated with prescribing ARNI. For 6–10 connections, the average marginal effect (AME) was 0.04 (confidence interval [CI] 95% 0.01–0.06) and for > 10 links the AME 0.07 (CI 95% 0.05–0.10) compared to 0–5 connections to prescriber.

Conclusion

Physicians who shared patients with many other physicians were more likely to prescribe ARNI, independent of physicians’ specialty. This suggested that collaboration and exchange on the basis of patient-sharing with other physicians influenced their medication prescribing decisions.
Outcome of intracerebral cavernoma treated by Gamma Knife radiosurgery based on a double-blind assessment of treatment indication
Authors: Shen Chiung-Chyi , Sun Ming Hsi , Yang Meng-Yin , You Weir-Chiang , Sheu Meei-Ling , Chen Yen-Ju , Chen Ying Ju , Sheehan Jason , Pan Hung-Chuan
Published: August 2021

Background

The benefit and the risk profile of Gamma Knife radiosurgery (GKRS) for intracerebral cavernoma remains incompletely defined in part due to the natural history of low incidence of bleeding and spontaneous regression of this vascular malformation. In this study, we retrieved cases from a prospectively collected database to assess the outcome of intracerebral cavernoma treated with GKRS using a double blinded review process for treatment.

Methods

From 2003 to 2018, there were 94 cases of cavernoma treated by GKRS in the doubly blinded assessments by two experienced neurological and approved for GKRS treatment. All the patients received GKRS with margin dose of 11–12 (Gray) Gy and afterwards were assessed for neurological outcome, radiologic response, and quality of life.

Results

The median age of the patients was 48 (15–85) years with median follow up of 77 (26–180) months post SRS. The mean target volume was 1.93 ± 3.45 cc. In those who has pre-SRS epilepsy, 7 of 16 (43.7%) achieved seizure freedom (Engel I/II) and 9 of 16 (56.3%) achieved decreased seizures (Engel III) after SRS. Rebleeding occurred in 2 cases (2.1%) at 13 and 52 months post SRS. The radiologic assessment demonstrated 20 (21.3%) cases of decreased cavernoma volume, 69 (73.4%) were stable, and 5 (7.3%) increased size. Eighty-seven of 94 (92.5%) cases at the last follow up achieve improvement in their quality of life, but 7 cases (7.4%) showed a deterioration. In statistical analysis, the effective seizure control class (Engel I/II) was highly correlated with patient harboring a single lesion (p < 0.05) and deep seated location of the cavernoma (p < 0.01). New neurological deficits were highly correlated with decreased mental (p < 0.001) and physical (p < 0.05) components of quality of life testing, KPS (p < 0.001), deep seated location (p < 0.01), and increased nidus volume (p < 0.05). Quality of life deterioration either in physical component (p < 0.01), mental component (p < 0.01), and KPS (p < 0.05) was highly correlated with increased cavernoma volume.

Conclusion

Low margin dose GKRS for intracerebral cavernoma offers reasonable seizure control and improved quality of life while conferring a low risk of treatment complications including adverse radiation effect.