bluuebunny/crossref_metadata_2025 huggingface dataset:
Unanticipated Fractures of the Zygomatic-Maxillary Suture in LeFort III Internal Distraction: Salvage of Midfacial Advancement via Rigid External Distraction of an Orphaned LeFort II Segment
Authors: Coalson Elam , Roy Tulsi , Bruce Timothy , Reid Russell R.
Published: June 2021

Currently, the most common approach for treating midface hypoplasia in syndromic craniosynostoses patients is the LeFort III with distraction osteogenesis. Distraction osteogenesis can be performed through either internal or external distraction systems. Each modality offers unique advantages and disadvantages. A rare complication associated with internal distraction is fracture of the zygomatic-maxillary suture caused by distraction forces on this area. This complication has been reported in patients with Pfeiffer and Apert syndromes, related to convexity of temporal bones increasing force on the zygomatic-maxillary suture. In the current report, we present the first case in the literature of an internal distraction associated zygomatic-maxillary fracture in a patient with Crouzon syndrome. We also present a subunit osteotomy salvage approach. Through mobilization of a LeFort II segment and rigid external distraction to advance orphaned segments of the midface, a favorable aesthetic result was salvaged from this complication.
Introduction to a review series on molecular mechanisms of hematologic malignancies
Authors: Crispino John D.
Published: June 2021

To reach the goal of curing currently incurable hematologic malignancies, we need to go beyond focusing on single gene mutatons and gain deeper understanding of the consequences of genetic alterations on gene-regulatory pathways. Edited by John Crispino, these 5 cutting-edge reviews from leaders in the their fields not only summarize our current understanding of key pathways that contribute to myeloid malignancies, but also discuss new therapeutic avenues related to them. They provide a springboard for further groundbreaking basic and clinical advances in hematologic malignancies.
Approach to the diagnosis of aplastic anemia
Authors: DeZern Amy E. , Churpek Jane E.
Published: June 2021

Establishing a diagnosis of aplastic anemia (AA) can be challenging, but it is absolutely critical to appropriate management, especially differentiating between acquired and inherited forms of the disease. The hematology field requires updated diagnostic guidelines to ensure that appropriate clinical pathways are pursued for patients and their safety. There are increasing clinical options for patients with immunosuppressive therapy and transplant once the diagnosis is made. In a case-based format, this review emphasizes the newer data on molecular (somatic and germline) findings in AA and how they are (or are not) helpful during diagnosis. There are key details on somatic mutation profiles and stated evidence where available for prognostic and treatment indications. Germline details of newer syndromes are also outlined, which make this review modern and reflect areas of uncertainty for clinicians.
Defining the limits of caesarean scar niche repair: new anatomical landmarks
Authors: Rao Tanushree , Lambert Neera , Ghosh Bhaswati , Chang Timothy
Published: June 2021

Background

Caesarean scar niche is increasingly being seen due to the rise in the number of caesarean sections worldwide. Indications and the ideal route for niche repair are still being researched. If the residual myometrium is less than 3 mm thick and potential fertility is needed, laparoscopy is the ideal surgical method for caesarean scar niche repair. The aim of this video presentation is to demonstrate techniques of identifying new anatomical landmarks during laparoscopic uterine niche repair.

Results

As seen in the video, Caesarean scar niche repair can be done in a step-by-step manner, with lateral bands serving as anatomical landmarks.

Conclusions

Lateral bands are a consistent anatomical landmark which identify the level and width of the uterine niche and thus simplify the laparoscopic repair making this a reproducible technique.
Radiological survey on radon entry path in an underground mine and implementation of an optimized mitigation system
Authors: Shahrokhi Amin , Kovacs Tibor
Published: June 2021

Background

The European Union council has introduced the basic safety standards (EU-BSS) for protection against the dangers arising from exposure to ionizing radiation by laying down a new radon reference level at workplaces. In this regard, all European state members must establish a national reference level based on all pre-defined requirements. After implanting the directive 2013/59/Euratom by European state members, new challenges have been revealed to mitigate radon appropriately in underground workplaces due to the exciting limitations (e.g., ventilation system, dust dispersion, air injection, etc.). Therefore, a conceptual design of an environmental radiological survey was defined and implemented by examining the hypothesis to find practical solutions following EU-BSS. The main objectives of this study were to identify the potential radon entry paths, utilize an optimized ventilation system, and carry on long-term radon monitoring in an operational underground manganese mine.

Results

The mullock rocks (the geological structure of the mine walls) contained a small amount of Ra-226 (2–4 Bq kg−1). On the other hand, the mine ore (black shale, underlayer black shale, and carbonate ore) has shown the highest concentration of Ra-226 (12–16 Bq kg−1) and the highest radon exhalation (1.2–1.6 mBq s−1 m−2). The surface radon exhalation from the mine walls was in the range of 0.7 ± 0.1 and 1.5 ± 0.2 mBq m−2 s−1. It was found that shortly after mining activity was undertaken, radon concentration increased dramatically with an average of about 5900 ± 420 Bq m−3 near the freshly broken walls. The optimized mobile mitigation system reduced radon concentration to 250 ± 41 Bq m−3 on average.

Conclusion

Apart from the fact that aged walls were involved in the radon accumulation, considering the mine ventilation performance and the total active surface area, the exhaled radon from the aged walls could not be the primary potential source of high radon concentration when mining activity was undertaken. According to the obtained results, the ores, recently fragmented during the course of mining operations, were the primary path. Therefore, after successfully identifying the radon entry path, radon concentration could be reduced to meet the EU-BSS requirement by implementing the developed mitigation system.
The legacy of Eastern Mediterranean mountain uplifts: rapid disparity of phylogenetic niche conservatism and divergence in mountain vipers
Authors: Ahmadi Mohsen , Hemami Mahmoud-Reza , Kaboli Mohammad , Nazarizadeh Masoud , Malekian Mansoureh , Behrooz Roozbeh , Geniez Philippe , Alroy John , Zimmermann Niklaus E.
Published: June 2021

Background

The orogeny of the eastern Mediterranean region has substantially affected ecological speciation patterns, particularly of mountain-dwelling species. Mountain vipers of the genus Montivipera are among the paramount examples of Mediterranean neo-endemism, with restricted ranges in the mountains of Anatolia, the Levant, Caucasus, Alborz, and Zagros. Here we explore the phylogenetic and ecological diversification of Montivipera to reconstruct its ecological niche evolution and biogeographic history. Using 177 sequences of three mitochondrial genes, a dated molecular phylogeny of mountain vipers was reconstructed. Based on 320 occurrence points within the entire range of the genus and six climatic variables, ecological niches were modelled and used to infer ancestral niche occupancy. In addition, the biogeographic history and ancestral states of the species were reconstructed across climate gradients.

Results

Dated phylogenetic reconstruction revealed that the ancestor of mountain vipers split into two major clades at around 12.18 Mya followed by multiple vicariance events due to rapid orogeny. Montivipera colonised coastal regions from a mountain-dwelling ancestor. We detected a highly complex ecological niche evolution of mountain vipers to temperature seasonality, a variable that also showed a strong phylogenetic signal and high contribution in niche occupation.

Conclusion

Raising mountain belts in the Eastern Mediterranean region and subsequent remarkable changes in temperature seasonality have led to the formation of important centres of diversification and endemism in this biodiversity hotspot. High rates of niche conservatism, low genetic diversity, and segregation of ranges into the endemic distribution negatively influenced the adaptive capacity of mountain vipers. We suggest that these species should be considered as evolutionary significant units and priority species for conservation in Mediterranean mountain ecosystems.
Sativex® (nabiximols) cannabinoid oromucosal spray in patients with resistant multiple sclerosis spasticity: the Belgian experience
Authors: D’hooghe Marie , Willekens Barbara , Delvaux Valerie , D’haeseleer Miguel , Guillaume Daniel , Laureys Guy , Nagels Guy , Vanderdonckt Patrick , Van Pesch Vincent , Popescu Veronica
Published: June 2021

Background

This retrospective study evaluates patient-reported outcomes in patients with multiple sclerosis (MS) spasticity who were treated with a cannabinoid oromucosal spray (Sativex®, USAN name: nabiximols) after not sufficiently responding to previous anti-spasticity medications.

Methods

Of 276 patients from eight centers in Belgium who began treatment prior to 31 December 2017, effectiveness assessment data were available for 238 patients during the test period of 4 to 8/12 weeks, and for smaller patient cohorts with continued treatment for 6/12 months.

Results

Mean 0–10 spasticity Numerical Rating Scale (NRS) scores improved from 8.1 at baseline to 5.2 (week 4), 4.6 (week 8) and 4.1 (week 12). Mean EuroQoL Visual Analogue Scale (EQ VAS) scores increased from 39 at baseline to 52 (week 4), 57 (week 8) and 59 (week 12). Mean NRS and EQ VAS scores remained in the same 12 weeks’ range in patients with longer-term data. The average dose of cannabinoid oromucosal spray was 6 sprays/day. Most of the 93 out of 276 patients, with initial prescription (33.7%), who discontinued treatment by week 12 did so within the first 8 weeks, mainly due to lack of effectiveness. By week 12, 171 (74%) of the 230 effectiveness evaluable patients reported a clinically meaningful response, corresponding to ≥30% NRS improvement. The tolerability of cannabinoid oromucosal spray was consistent with its known safety profile.

Conclusions

More than 60% of the patients with MS who started add-on treatment with cannabinoid oromucosal spray reported a clinically relevant symptomatic effect and continued treatment after 12 weeks.
Anxiety among Lebanese adolescents: scale validation and correlates
Authors: Merhy Georges , Azzi Vanessa , Salameh Pascale , Obeid Sahar , Hallit Souheil
Published: June 2021

Background

The Lebanese population has undergone several conflicts and were the most afflicted by shelling and chaos during the civil war from 1975 to 1990, or even by displacement, bereavement, emigration, family separations, not to mention the economic crises that have hit the country since 2019 under which young adults are still succumbing. Our study aims to validate the Lebanese Anxiety Scale and assess correlates of anxiety among Lebanese adolescents.

Methods

A cross-sectional study was carried between January and May 2019, using a proportionate random sampling of schools from all five Lebanese governorates, among which 1810 adolescents aged 14 to 17 years.

Results

All LAS items remained in the model and formed one factor solution that explained 61.38% of the total variance (KMO = 0.873; pBartlett test < 0.001), with an excellent Cronbach’s alpha of 0.93. Higher neglect (B = 0.38), insomnia (B = 0.21) and child psychological abuse (B = 0.08) were significantly associated with more anxiety. Those results were considered adjusted overall sociodemographic variables since the latter had no statistically significant association with anxiety.

Conclusion

The study confirmed the association between anxiety and some variables such as psychological child abuse, neglect, and insomnia and emphasized the correlation between anxiety and these factors. Further, the LAS appears to be a short, valid and efficient tool for assessing anxiety among Lebanese adolescents. Further studies need to be carried to evaluate whether the LAS-10 gives a similar diagnosis to psychiatrists.
Transdiagnostic efficacy of a group exercise intervention for outpatients with heterogenous psychiatric disorders: a randomized controlled trial
Authors: Zeibig Johanna-Marie , Seiffer Britta , Sudeck Gorden , Rösel Inka , Hautzinger Martin , Wolf Sebastian
Published: June 2021

Background

Exercise efficaciously reduces disorder-specific symptoms of psychiatric disorders. The current study aimed to examine the efficacy of a group exercise intervention on global symptom severity and disorder-specific symptoms among a mixed outpatient sample.

Methods

Groups of inactive outpatients, waiting for psychotherapy, with depressive disorders, anxiety disorders, insomnia, and attention-deficit/hyperactivity disorders were randomized to a manualized 12-week exercise intervention, combining moderate to vigorous aerobic exercise with techniques for sustainable exercise behaviour change (n = 38, female = 71.1% (n = 27), Mage = 36.66), or a passive control group (n = 36, female = 75.0% (n = 27), Mage = 34.33). Primary outcomes were global symptom severity and disorder-specific symptoms, measured with the Symptom Checklist-90-Revised and Pittsburgh Sleep Quality Index pre- and post-treatment. Secondary outcome was the self-reported amount of exercise (Physical Activity, Exercise, and Sport Questionnaire), measured pre-treatment, intermediate-, and post-treatment. Intention-to-treat analyses were conducted using linear mixed models. Linear regressions were conducted to examine the effect of the change of exercise behaviour on the change of symptoms.

Results

The intervention significantly improved global symptom severity (d = 0.77, p = .007), depression (d = 0.68, p = .015), anxiety (d = 0.87, p = .002), sleep quality (d = 0.88, p = .001), and increased the amount of exercise (d = 0.82, p < .001), compared to the control group. Post-treatment differences between groups were significant for depression (d = 0.63, p = .031), sleep quality (d = 0.61, p = .035) and the amount of exercise (d = 1.45, p < .001). Across both groups, the reduction of global symptom severity was significantly predicted by an increase of exercise (b = .35, p = .012).

Conclusions

The exercise intervention showed transdiagnostic efficacy among a heterogeneous clinical sample in a realistic outpatient setting and led to sustained exercise behaviour change. Exercise may serve as an efficacious and feasible transdiagnostic treatment option improving the existing treatment gap within outpatient mental health care settings.

Trial registration

The study was registered on ClinicalTrials.gov (ID: NCT03542396, 25/04/2018).
Trends in mortality and life expectancy in Fiji over 20 years
Authors: Dearie Catherine , Linhart Christine , Rafai Eric , Nand Devina , Morrell Stephen , Taylor Richard
Published: June 2021

Background

Fiji, a Pacific Island nation of 884,887 (2017 census), has experienced a prolonged epidemiological transition. This study examines trends in mortality and life expectancy (LE) in Fiji by sex and ethnicity over 1996–2017, with comparisons to published estimates.

Methods

Trends in infant mortality rates (IMR), under-5 mortality (U5M), adult mortality (probability of dying), LE (at birth) and directly age-standardised death rates (DASRs) by sex and ethnicity, are calculated (with 95% confidence limits) using unit death records from the Fiji Ministry of Health and Medical Services. The LE gap between populations, or within populations over time, is examined using decomposition by age. Period trends are assessed for statistical significance using linear regression.

Results

Over 1996–98 to 2014–17: IMR and U5M for i-Taukei and Fijians of Indian descent declined; U5M decline for i-Taukei (24.6 to 20.1/1000 live births) was significant (p = 0.016). Mortality (15–59 years) for i-Taukei males was unchanged at 27% but declined for Indians 33 to 30% (p = 0.101). Mortality for i-Taukei females increased 22 to 24% (p = 0.011) but declined for Indians 20 to 18% (p = 0.240). DASRs 1996–2017 were lower for i-Taukei (9.3 to 8.2/1000 population) than Indian males (10.6 to 9.8/1000). DASRs declined for i-Taukei (both sexes,p < 0.05), and for Indians (both sexes,p > 0.05). Over 22 years, LE at birth increased by 1 year or less (p = 0.030 in male i-Taukei). In 2014–17, LE (years) for males was: i-Taukei 64.9, Indians 63.5; and females: i-Taukei 67.0 and Indians 68.2. Mortality changes in most 5-year age groups increased or decreased the LE gap less than 10 weeks over 22 years. Compared to international agency reports, 2014–17 empirical LE estimates (males 64.7, females 67.8) were lower, as was IMR.

Conclusions

Based on empirical data, LE in Fiji has minimally improved over 1996–2017, and is lower than some international agencies report. Adult mortality was higher in Indian than i-Taukei men, and higher in i-Taukei than Indian women. Exclusion of stillbirths resulted in IMRs lower than previously reported. Differing mortality trends in subgroups highlight the need to collect census and health data by ethnicity and sex, to monitor health outcomes and inform resource allocation.
Frequent POLE-driven hypermutation in ovarian endometrioid cancer revealed by mutational signatures in RNA sequencing
Authors: Davila Jaime I. , Chanana Pritha , Sarangi Vivekananda , Fogarty Zachary C. , Weroha S. John , Guo Ruifeng , Goode Ellen L. , Huang Yajue , Wang Chen
Published: June 2021

Background

DNA polymerase epsilon (POLE) is encoded by the POLE gene, and POLE-driven tumors are characterized by high mutational rates. POLE-driven tumors are relatively common in endometrial and colorectal cancer, and their presence is increasingly recognized in ovarian cancer (OC) of endometrioid type. POLE-driven cases possess an abundance of TCT > TAT and TCG > TTG somatic mutations characterized by mutational signature 10 from the Catalog of Somatic Mutations in Cancer (COSMIC). By quantifying the contribution of COSMIC mutational signature 10 in RNA sequencing (RNA-seq) we set out to identify POLE-driven tumors in a set of unselected Mayo Clinic OC.

Methods

Mutational profiles were calculated using expressed single-nucleotide variants (eSNV) in the Mayo Clinic OC tumors (n = 195), The Cancer Genome Atlas (TCGA) OC tumors (n = 419), and the Genotype-Tissue Expression (GTEx) normal ovarian tissues (n = 84). Non-negative Matrix Factorization (NMF) of the mutational profiles inferred the contribution per sample of four distinct mutational signatures, one of which corresponds to COSMIC mutational signature 10.

Results

In the Mayo Clinic OC cohort we identified six tumors with a predicted contribution from COSMIC mutational signature 10 of over five mutations per megabase. These six cases harbored known POLE hotspot mutations (P286R, S297F, V411L, and A456P) and were of endometrioid histotype (P = 5e−04). These six tumors had an early onset (average age of patients at onset, 48.33 years) when compared to non-POLE endometrioid OC cohort (average age at onset, 60.13 years; P = .008). Samples from TCGA and GTEx had a low COSMIC signature 10 contribution (median 0.16 mutations per megabase; maximum 1.78 mutations per megabase) and carried no POLE hotspot mutations.

Conclusions

From the largest cohort of RNA-seq from endometrioid OC to date (n = 53), we identified six hypermutated samples likely driven by POLE (frequency, 11%). Our result suggests the clinical need to screen for POLE driver mutations in endometrioid OC, which can guide enrollment in immunotherapy clinical trials.
Cutaneous T-cell-attracting chemokine as a novel biomarker for predicting prognosis of idiopathic pulmonary fibrosis: a prospective observational study
Authors: Niwamoto Takafumi , Handa Tomohiro , Murase Yuko , Nakatsuka Yoshinari , Tanizawa Kiminobu , Taguchi Yoshio , Tomioka Hiromi , Tomii Keisuke , Kita Hideo , Uyama Michihiro , Tsuchiya Michiko , Emura Masahito , Kawamura Tetsuji , Arai Naoki , Arita Machiko , Uno Kazuko , Yoshizawa Akihiko , Uozumi Ryuji , Yamaguchi Izumi , Matsuda Fumihiko , Chin Kazuo , Hirai Toyohiro
Published: June 2021

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease that leads to respiratory failure and death. Although there is a greater understanding of the etiology of this disease, accurately predicting the disease course in individual patients is still not possible. This study aimed to evaluate serum cytokines/chemokines as potential biomarkers that can predict outcomes in IPF patients.

Methods

A multi-institutional prospective two-stage discovery and validation design using two independent cohorts was adopted. For the discovery analysis, serum samples from 100 IPF patients and 32 healthy controls were examined using an unbiased, multiplex immunoassay of 48 cytokines/chemokines. The serum cytokine/chemokine values were compared between IPF patients and controls; the association between multiplex measurements and survival time was evaluated in IPF patients. In the validation analysis, the cytokines/chemokines identified in the discovery analysis were examined in serum samples from another 81 IPF patients to verify the ability of these cytokines/chemokines to predict survival. Immunohistochemical assessment of IPF-derived lung samples was also performed to determine where this novel biomarker is expressed.

Results

In the discovery cohort, 18 cytokines/chemokines were significantly elevated in sera from IPF patients compared with those from controls. Interleukin-1 receptor alpha (IL-1Rα), interleukin-8 (IL-8), macrophage inflammatory protein 1 alpha (MIP-1α), and cutaneous T-cell-attracting chemokine (CTACK) were associated with survival: IL-1Rα, hazard ratio (HR) = 1.04 per 10 units, 95% confidence interval (95% CI) 1.01–1.07; IL-8, HR = 1.04, 95% CI 1.01–1.08; MIP-1α, HR = 1.19, 95% CI 1.00–1.36; and CTACK, HR = 1.12 per 100 units, 95% CI 1.02–1.21. A replication analysis was performed only for CTACK because others were previously reported to be potential biomarkers of interstitial lung diseases. In the validation cohort, CTACK was associated with survival: HR = 1.14 per 100 units, 95% CI 1.01–1.28. Immunohistochemistry revealed the expression of CTACK and CC chemokine receptor 10 (a ligand of CTACK) in airway and type II alveolar epithelial cells of IPF patients but not in those of controls.

Conclusions

CTACK is a novel prognostic biomarker of IPF.

Trial registrationNone (because of no healthcare intervention)
Aging and high-fat diet feeding lead to peripheral insulin resistance and sex-dependent changes in brain of mouse model of tau pathology THY-Tau22
Authors: Kacířová Miroslava , Železná Blanka , Blažková Michaela , Holubová Martina , Popelová Andrea , Kuneš Jaroslav , Šedivá Blanka , Maletínská Lenka
Published: June 2021

Background

Obesity leads to low-grade inflammation in the adipose tissue and liver and neuroinflammation in the brain. Obesity-induced insulin resistance (IR) and neuroinflammation seem to intensify neurodegeneration including Alzheimer’s disease. In this study, the impact of high-fat (HF) diet-induced obesity on potential neuroinflammation and peripheral IR was tested separately in males and females of THY-Tau22 mice, a model of tau pathology expressing mutated human tau protein.

Methods

Three-, 7-, and 11-month-old THY-Tau22 and wild-type males and females were tested for mobility, anxiety-like behavior, and short-term spatial memory in open-field and Y-maze tests. Plasma insulin, free fatty acid, cholesterol, and leptin were evaluated with commercial assays. Liver was stained with hematoxylin and eosin for histology. Brain sections were 3′,3′-diaminobenzidine (DAB) and/or fluorescently detected for ionized calcium-binding adapter molecule 1 (Iba1), glial fibrillary acidic protein (GFAP), and tau phosphorylated at T231 (pTau (T231)), and analyzed. Insulin signaling cascade, pTau, extracellular signal-regulated kinase 1/2 (ERK1/2), and protein phosphatase 2A (PP2A) were quantified by western blotting of hippocampi of 11-month-old mice. Data are mean ± SEM and were subjected to Mann-Whitney t test within age and sex and mixed-effects analysis and Bonferroni’s post hoc test for age comparison.

Results

Increased age most potently decreased mobility and increased anxiety in all mice. THY-Tau22 males showed impaired short-term spatial memory. HF diet increased body, fat, and liver weights and peripheral IR. HF diet-fed THY-Tau22 males showed massive Iba1+ microgliosis and GFAP+ astrocytosis in the hippocampus and amygdala. Activated astrocytes colocalized with pTau (T231) in THY-Tau22, although no significant difference in hippocampal tau phosphorylation was observed between 11-month-old HF and standard diet-fed THY-Tau22 mice. Eleven-month-old THY-Tau22 females, but not males, on both diets showed decreased synaptic and postsynaptic plasticity.

Conclusions

Significant sex differences in neurodegenerative signs were found in THY-Tau22. Impaired short-term spatial memory was observed in 11-month-old THY-tau22 males but not females, which corresponded to increased neuroinflammation colocalized with pTau(T231) in the hippocampi and amygdalae of THY-Tau22 males. A robust decrease in synaptic and postsynaptic plasticity was observed in 11-month-old females but not males. HF diet caused peripheral but not central IR in mice of both sexes.
Timber identification of Autranella, Baillonella and Tieghemella in the taxonomically challenging Sapotaceae family
Authors: Deklerck V. , Price E. , Vanden Abeele S. , Lievens K. , Espinoza E. , Beeckman H.
Published: June 2021

Background

To enforce timber import laws and perform timber species identification, the identity of the botanical species must be well-defined. Since the Sapotaceae family is known as a taxonomically challenging family, we focus in this study on the four most valuable Sapotaceae timber species from tropical Africa: Autranella congolensis (De Wild.) A.Chev., Baillonella toxisperma Pierre, Tieghemella africana Pierre and Tieghemella heckelii (A.Chev.) Pierre ex Dubard. The wood anatomical characteristic fiber lumen fraction and Direct Analysis in Real Time—Time of Flight Mass Spectrometry (DART-TOFMS) were used to differentiate the four species and to make inferences on species delineation and taxonomic identity.

Results

We observed differences in the fiber lumen fraction measurements and discerned two groups: (1) A. congolensis and B. toxisperma, and (2) T. africana and T. heckelii. In addition, all Mann–Whitney U comparisons and differences in distributions (Kolmogorov–Smirnov) for the fiber lumen fraction measurements were significant between all species. When permutating the data between species within those two groups, significant differences were still found between the species within those groups. This could indicate that the fiber lumen fraction is not diagnostic to discern the species. DART-TOFMS analysis showed that A. congolensis and B. toxisperma have distinct chemotypes, while T. heckelii and T. africana have remarkably similar chemotypes.

Conclusions

Based on our observations of similar chemotype and weakly differentiated fiber lumen ratio, we support an alternative taxonomic hypothesis that considers Tieghemella monotypic, because of the strong resemblance between T. heckelii and T. africana. Larger sample sizes and further research is required to develop methodology for the identification of these species. A taxonomic study utilizing molecular genetics would be beneficial to assess the status of the genus and the species limits. This could have implications towards their potential inclusion on CITES appendices if there is ever need for them to be listed. If Tieghemella africana and T. heckelii remain two distinct species, they should both be listed. Screening agents should be aware that the morphological and chemical differences between T. africana and T. heckelii are minimal.
Role of hippocampal location and radiation dose in glioblastoma patients with hippocampal atrophy
Authors: Le Fèvre Clara , Cheng Xue , Loit Marie-Pierre , Keller Audrey , Cebula Hélène , Antoni Delphine , Thiery Alicia , Constans Jean-Marc , Proust François , Noel Georges
Published: June 2021

Background

The hippocampus is a critical organ for irradiation. Thus, we explored changes in hippocampal volume according to the dose delivered and the location relative to the glioblastoma.

Methods

All patients were treated for glioblastoma with surgery, concomitant radiotherapy and temozolomide, and adjuvant temozolomide. Hippocampi were retrospectively delineated on three MRIs, performed at baseline, at the time of relapse, and on the last MRI available at the end of follow-up. A total of 98, 96, and 82 hippocampi were measured in the 49 patients included in the study, respectively. The patients were stratified into three subgroups according to the dose delivered to 40% of the hippocampus. In the group 1 (n = 6), the hippocampal D40% was < 7.4 Gy, in the group 2 (n = 13), only the Hcontra D40% was < 7.4 Gy, and in the group 3 (n = 30), the D40% for both hippocampi was > 7.4 Gy.

Results

Regardless of the time of measurement, homolateral hippocampal volumes were significantly lower than those contralateral to the tumor. Regardless of the side, the volumes at the last MRI were significantly lower than those measured at baseline. There was a significant correlation among the decrease in hippocampal volume regardless of its side, and Dmax (p = 0.001), D98% (p = 0.028) and D40% (p = 0.0002). After adjustment for the time of MRI, these correlations remained significant. According to the D40% and volume at MRIlast, the hippocampi decreased by 4 mm3/Gy overall.

Conclusions

There was a significant relationship between the radiotherapy dose and decrease in hippocampal volume. However, at the lowest doses, the hippocampi seem to exhibit an adaptive increase in their volume, which could indicate a plasticity effect. Consequently, shielding at least one hippocampus by delivering the lowest possible dose is recommended so that cognitive function can be preserved.

Trial registration Retrospectively registered.
T-614 attenuates knee osteoarthritis via regulating Wnt/β-catenin signaling pathway
Authors: Cong Shan , Meng Yan , Wang Lingrui , Sun Jiao , shi·Nu er xia ti Ta bu , Luo Li
Published: June 2021

Background

The aim of this study was to investigate the effect of Iguratimod (T-614) on rat knee osteoarthritis (KOA) and further to explore its underlying mechanism.

Methods

In this study, papain-induced KOA model was constructed. Hematoxylin and eosin (H&E) staining was conducted to observe the pathological changes of cartilage tissue and Mankin scoring principle was used for quantitative scoring. Transmission electron microscopy (TEM) was applied to observe the ultrastructure of cartilage tissue. ELISA was used to measure the levels of matrix metalloproteinase 13 (MMP-13) and inflammatory factors (interleukin (IL)-6 and tumor necrosis factor a (TNF-a)) in serum. RT-qPCR and immunohistochemistry were conducted to detect mRNA expression and protein expression of key genes in Wnt/β-catenin pathway.

Results

H&E, Mankin scoring, and TEM data confirmed that compared with model group, T-614 significantly improved the degeneration of articular cartilage. Besides, we observed that low, middle, and high doses of T-614 could decrease the levels of MMP13, TNF-α, and IL-6 in serum to different degrees. Mechanically, T-614 downregulated the mRNA and protein expression of β-catenin and MMP13 in cartilage tissue via a dose-dependent manner, and on the contrary upregulated the mRNA and protein expression of glucogen synthase kinase-3 beta (GSK-3β).

Conclusion

Our results suggested that T-614 can reduce the level of its downstream target gene MMP-13 and downregulate the expression of inflammatory cytokines TNF-α and IL-6 by regulating the Wnt/β-catenin signaling pathway, thereby inhibiting joint inflammation and controlling KOA degeneration of articular cartilage.
LncRNA CASC19 accelerates chondrocytes apoptosis and proinflammatory cytokine production to exacerbate osteoarthritis development through regulating the miR-152-3p/DDX6 axis
Authors: Zhou Chang , He Tianda , Chen Liji
Published: June 2021

Background

Osteoarthritis (OA) is one kind of degenerative joint disease that happens in articular cartilage and other joint tissues. Long non-coding RNAs (lncRNAs) have been reported to serve as pivotal regulators in many diseases, including OA. However, the role and relevant regulatory mechanisms of CASC19 in OA remain unknown.

Methods

The expression levels of CASC19, miR-152-3p, and DDX6 were identified by reverse-transcription polymerase chain reaction (RT-qPCR). Cell viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. The relationship between miR-152-3p and CASC19 or DDX6 was predicted by bioinformatics tools and verified by the dual-luciferase reporter assay.

Results

CASC19 was verified to exhibit higher expression in OA tissues and cells. Moreover, inhibition of CASC19 weakened proinflammatory cytokine (IL-6, IL-8, and TNF-α) production and cell apoptosis but facilitated cell viability. Experiments of the ceRNA mechanism elucidated that miR-152-3p was a sponge for CASC19, and miR-152-3p targeted DDX6, suggesting that CASC19 sponged miR-152-3p to release DDX6. Finally, results from rescue assays proved that the impacts of CASC19 silencing on chondrocytes apoptosis and proinflammatory cytokine production could be reversed by DDX6 overexpression.

Conclusions

It was concluded that lncRNA CASC19 accelerated chondrocytes apoptosis and proinflammatory cytokine production to exacerbate osteoarthritis development through regulating the miR-152-3p/DDX6 axis. These findings may offer an effective biological target for OA treatment.
Impact of body mass index on early and mid-term outcomes after surgery for acute Stanford type A aortic dissection
Authors: Liu Yanxiang , Zhang Bowen , Liang Shenghua , Dun Yaojun , Wang Luchen , Gao Haoyu , Ren Jie , Guo Hongwei , Sun Xiaogang
Published: June 2021

Background

Obesity is dramatically increasing worldwide, and more obese patients may develop aortic dissection and present for surgical repair. The study aims to analyse the impact of body mass index (BMI) on surgical outcomes in patients with acute Stanford type A aortic dissection (ATAAD).

Methods

From January 2017 to June 2019, the clinical data of 268 ATAAD patients in a single centre were retrospectively reviewed. They were divided into three groups based on the BMI: normal weight (BMI 18.5 to < 25 kg/m2, n = 110), overweight (BMI 25 to < 30 kg/m2, n = 114) and obese (BMI ≥30 kg/m2, n = 44).

Results

There was no statistical difference among the three groups in terms of the composite adverse events including 30-day mortality, stroke, paraplegia, renal failure, hepatic failure, reintubation or tracheotomy and low cardiac output syndrome (20.9% vs 21.9% vs 18.2% for normal, overweight and obese, respectively; P = 0.882). No significant difference was found in the mid-term survival among the three groups. The proportion of prolonged ventilation was highest in the obese group followed by the overweight and normal groups (59.1% vs 45.6% vs 34.5%, respectively; P = 0.017). Multivariable logistic regression analysis suggested that BMI was not associated with the composite adverse events, while BMI ≥30 kg/m2 was an independent risk factor for prolonged ventilation (OR 2.261; 95% CI 1.056–4.838; P = 0.036).

Conclusions

BMI had no effect on the early major adverse outcomes and mid-term survival after surgery for ATAAD. Satisfactory surgical outcomes can be obtained in patients with ATAAD at all weights.
SARS-CoV-2 quantitative real time PCR and viral loads analysis among asymptomatic and symptomatic patients: an observational study on an outbreak in two nursing facilities in Campania Region (Southern Italy)
Authors: Cardillo Lorena , de Martinis Claudio , Viscardi Maurizio , Esposito Claudia , Sannino Emanuela , Lucibelli Gabriella , Limone Antonio , Pellino Stefania , Anastasio Rosa , Pellicanò Roberta , Baldi Loredana , Galiero Giorgio , Fusco Giovanna
Published: June 2021

Background

In December 2019 an outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 was first observed in Wuhan, China. The virus has spread rapidly throughout the world creating a pandemic scenario. Several risk factors have been identified, such as age, sex, concomitant diseases as well as viral load. A key point is the role of asymptomatic people in spreading SARS-CoV-2. An observational study in Southern Italy was conducted in order to elucidate the possible role of asymptomatic individuals related to their viral loads in the transmission of the virus within two nursing facilities.

Methods

Oro-nasopharyngeal swabs from 179 nursing health care workers and patients were collected. SARS-CoV-2 RT-qPCR was performed and viral loads were calculated by using standard curve. A statistical correlation between viral loads, the presence/absence of symptoms, age and sex variables was investigated.

Results

SARS-CoV-2 was confirmed in the 50.8 % (n = 91) of the cases. Median age of positive individuals resulted higher than negative ones. Over 65 year as well as female individuals showed higher susceptibility to SARS-CoV-2 infection, OR = 3.93 and 2.86, respectively. Among 91 tested positive, the 70.3 % was symptomatic while the 29.7 % was asymptomatic. Median viral loads of asymptomatic individuals were found statistically significant higher than symptomatic ones (p = 0.001), while no influence was observed in age and sex variables. The presence of comorbidities was 8.9 folds higher in patients who showed and developed symptoms compared to non-symptomatic ones. Moreover, higher viral loads were found in patients who remained asymptomatic than pre-symptomatic (p = 0.022).

Conclusions

A range from 9.2 to 69 % of confirmed SARS-CoV-2 cases remains asymptomatic, moreover, sporadic transmissions from asymptomatic people are reported, that makes their involvement an important issue to take into account in the spreading control of the virus. An asymptomatic clinical course was observed in the 29.7 % of positive individuals, moreover, median viral loads resulted to be statistically significant when compared to symptomatic ones. Surely, such a relevant frequency should not be ignored in relation to the spread of the disease in an environment which has not only important intrinsic (age, sex, concomitant diseases) but also extrinsic factors such as high population density and close contacts.
Enzymatic hydrolysis of the gelatinous layer in tension wood of Salix varieties as a measure of accessible cellulose for biofuels
Authors: Gao Jie , Jebrane Mohamed , Terziev Nasko , Daniel Geoffrey
Published: June 2021

Background

Salix (willow) species represent an important source of bioenergy and offer great potential for producing biofuels. Salix spp. like many hardwoods, produce tension wood (TW) characterized by special fibres (G-fibres) that produce a cellulose-rich lignin-free gelatinous (G) layer on the inner fibre cell wall. Presence of increased amounts of TW and G-fibres represents an increased source of cellulose. In the present study, the presence of TW in whole stems of different Salix varieties was characterized (i.e., physical measurements, histochemistry, image analysis, and microscopy) as a possible marker for the availability of freely available cellulose and potential for releasing d-glucose. Stem cross sections from different Salix varieties (Tora, Björn) were characterized for TW, and subjected to cellulase hydrolysis with the free d-glucose produced determined using a glucose oxidase/peroxidase (GOPOD) assay. Effect of cellulase on the cross sections and progressive hydrolysis of the G-layer was followed using light microscopy after staining and scanning electron microscopy (SEM).

Results

Tension wood fibres with G-layers were developed multilaterally in all stems studied. Salix TW from varieties Tora and Björn showed fibre G-layers were non-lignified with variable thickness. Results showed: (i) Differences in total % TW at different stem heights; (ii) that using a 3-day incubation period at 50 °C, the G-layers could be hydrolyzed with no apparent ultrastructural effects on lignified secondary cell wall layers and middle lamellae of other cell elements; and (iii) that by correlating the amount of d-glucose produced from cross sections at different stem heights together with total % TW and density, an estimate of the total free d-glucose in stems can be derived and compared between varieties. These values were used together with a literature value (45%) for estimating the contribution played by G-layer cellulose to the total cellulose content.

Conclusions

The stem section-enzyme method developed provides a viable approach to compare different Salix varieties ability to produce TW and thus freely available d-glucose for fermentation and biofuel production. The use of Salix stem cross sections rather than comminuted biomass allows direct correlation between tissue- and cell types with d-glucose release. Results allowed correlation between % TW in cross sections and entire Salix stems with d-glucose production from digested G-layers. Results further emphasize the importance of TW and G-fibre cellulose as an important marker for enhanced d-glucose release in Salix varieties.
Circulating bacterial signature is linked to metabolic disease and shifts with metabolic alleviation after bariatric surgery
Authors: Chakaroun Rima M. , Massier Lucas , Heintz-Buschart Anna , Said Nedal , Fallmann Joerg , Crane Alyce , Schütz Tatjana , Dietrich Arne , Blüher Matthias , Stumvoll Michael , Musat Niculina , Kovacs Peter
Published: June 2021

Background

The microbiome has emerged as an environmental factor contributing to obesity and type 2 diabetes (T2D). Increasing evidence suggests links between circulating bacterial components (i.e., bacterial DNA), cardiometabolic disease, and blunted response to metabolic interventions. In this aspect, thorough next-generation sequencing-based and contaminant-aware approaches are lacking. To address this, we tested whether bacterial DNA could be amplified in the blood of subjects with obesity and high metabolic risk under strict experimental and analytical control and whether a putative bacterial signature is related to metabolic improvement after bariatric surgery.

Methods

Subjects undergoing bariatric surgery were recruited into sex- and BMI-matched subgroups with (n = 24) or without T2D (n = 24). Bacterial DNA in the blood was quantified and prokaryotic 16S rRNA gene amplicons were sequenced. A contaminant-aware approach was applied to derive a compositional microbial signature from bacterial sequences in all subjects at baseline and at 3 and 12 months after surgery. We modeled associations between bacterial load and composition with host metabolic and anthropometric markers. We further tested whether compositional shifts were related to weight loss response and T2D remission. Lastly, bacteria were visualized in blood samples using catalyzed reporter deposition (CARD)-fluorescence in situ hybridization (FISH).

Results

The contaminant-aware blood bacterial signature was associated with metabolic health. Based on bacterial phyla and genera detected in the blood samples, a metabolic syndrome classification index score was derived and shown to robustly classify subjects along their actual clinical group. T2D was characterized by decreased bacterial richness and loss of genera associated with improved metabolic health. Weight loss and metabolic improvement following bariatric surgery were associated with an early and stable increase of these genera in parallel with improvements in key cardiometabolic risk parameters. CARD-FISH allowed the detection of living bacteria in blood samples in obesity.

Conclusions

We show that the circulating bacterial signature reflects metabolic disease and its improvement after bariatric surgery. Our work provides contaminant-aware evidence for the presence of living bacteria in the blood and suggests a putative crosstalk between components of the blood and metabolism in metabolic health regulation.
In situ rumen degradation characteristics and bacterial colonization of whole cottonseed, cottonseed hull and cottonseed meal with different gossypol content
Authors: Wang Wei-Kang , Wang Yan-Lu , Li Wen-Juan , Wu Qi-Chao , Yang Kai-Lun , Li Sheng-Li , Yang Hong-Jian
Published: June 2021

Regarding whole cottonseed (WCS), cottonseed meal (CSM), and cottonseed hull (CSH), in situ rumen incubation was applied to determine their nutrient and gossypol degradation characteristics and bacterial colonization profile in lactating Holstein cows. Nylon bags containing the cotton by-products were incubated for 0, 6, 12, 24, 36, 48 and 72 h in the rumen, respectively. The relationship between nutrient degradability and free gossypol (FG) content were examined, and the differences in the composition and inferred gene function of the colonized microbiota were studied. As a result, CSM presented highest effective degradability of dry matter, neutral detergent fibre and acid detergent fibre, but the highest effective degradability of crude protein was found in WCS. Free gossypol disappearance rate increased significantly in the first 6 h, and it reached approximately 94% at 72 h of incubation among all samples. The level of FG did not affect nutrient degradability of cotton by-products. Significant differences were noted in attached bacterial community structure among cotton by-products after 24 h rumen incubation. Among the most abundant taxa at genus level, a greater abundance of Cercis gigantea and Succiniclasticum was observed in WCS samples, whereas the CSH and CSM samples contained a greater proportion of Prevotella 1 and Rikenellaceae RC9 gut group. The redundancy analysis revealed that the level of neutral detergent fibre, ether extract, and FG in cotton by-products were significantly positive related with the composition of the attached bacteria. Collectively, our results revealed the dynamics of degradation characteristics, and the difference in the composition of bacterial colonization. These findings are of importance for the targeted improvement of cotton by-products nutrient use efficiency in ruminants and further understanding of the gossypol degradation mechanism in the rumen.