bluuebunny/crossref_metadata_2025 huggingface dataset:
Petrovite, Na10CaCu2(SO4)8, a new fumarolic sulfate from the Great Tolbachik fissure eruption, Kamchatka Peninsula, Russia
Authors: Filatov Stanislav K. , Shablinskii Andrey P. , Krivovichev Sergey V. , Vergasova Lidiya P. , Moskaleva Svetlana V.
Published: June 2020

Petrovite, Na10CaCu2(SO4)8, is a new sulfate mineral discovered on the Second scoria cone of the Great Tolbachik fissure eruption. The mineral occurs as globular aggregates of tabular crystals up to 0.2 mm in maximal dimension, generally with gaseous inclusions. The empirical formula calculated on the basis of O = 32 is Na6(Na1.80K0.20)Σ2Na(Ca0.82Na0.06Mg0.02)Σ0.90(Cu1.84Mg0.16)Σ2(Na0.52□0.48)Σ1S8.12O32. The crystal-chemical formula is CuNa6−2xCax(SO4)4, which, forx≈ 0.5, results in the idealised formula Na10CaCu2(SO4)8. The crystal structure of petrovite was determined using single-crystal X-ray diffraction data; the space group isP21/c,a= 12.6346(8),b= 9.0760(6),c= 12.7560(8) Å, β = 108.75(9)°,V= 1385.1(3) Å3,Z= 2 andR1= 0.051. There are one Cu and six Na sites, one of which is also occupied by the essential amount of Ca. The Cu atom forms five Cu–O bonds in the range 1.980–2.180 Å and two long bonds ≈ 2.9 Å resulting in the formation of the CuO7polyhedra, which share corners with SO4tetrahedra to form isolated [Cu2(SO4)8]12−clusters. The clusters are surrounded by Na sites, which provide their linkage into a three-dimensional framework. The Mohs’ hardness is 4. The mineral is biaxial (+), with α = 1.498(3), βcalc= 1.500, γ = 1.516(3) and 2V = 20(10) (λ = 589 nm). The seven strongest lines of the powder X-ray diffraction pattern [d, Å (I, %) (hkl)] are: 7.21(27)(110); 6.25(38)(102); 4.47(31)(212); 3.95(21)(30$\bar{2}$); 3.85(17)(121); 3.70(36)(202); and 3.65(34)(22$\bar{1}$). The mineral is named in honour of Prof Dr Tomas Georgievich Petrov (b. 1931) for his contributions to mineralogy and crystallography and, in particular, for the development of technology for the industrial fabrication of jewellery malachite.
Pitfals in recognition and management of trigeminal neuralgia
Authors: Antonaci F. , Arceri S. , Rakusa M. , Mitsikostas D. D. , Milanov I. , Todorov V. , Ramusino M. Cotta , Costa A. ,   On behalf of Headache and Pain Scientific Panels of the European Academy of Neurology (EAN)
Published: June 2020

Background

Trigeminal neuralgia (TN) is a severe, disabling form of painful cranial neuropathy. Even though TN has a typical clinical picture, diagnosis it is often missed or delayed in clinical practice. In order to investigate the occurrence of diagnostic and therapeutic errors in TN, we studied 102 patients suffering from TN recruited through a multicentric survey.

Methods

We performed a Pubmed database search on errors and pittfalls in TN diagnosis and management. Then, patients with TN were consecutively enrolled in the period from February 2017 to October 2019, by several European Headache Centers participating in the study, following a call of the Headache and Pain Scientific Panels of the European Academy of Neurology (EAN). Diagnosis of Classical Trigeminal Neuralgia (CTN) was made according to the International Headache Society (IHS) criteria (Tölle et al., Pain Pract 6:153-160, 2006). All the patients were evaluated using telephone/frontal interviews conducted by headache/pain specialists using an ad hoc questionnaire.

Results

A number of 102 patients were recruited, mostly females (F:M ratio 2.64:1). Eighty-six percent of the patients consulted a physician at the time they experienced the first pain attacks. Specialists consulted before TN diagnosis were: primary care physicians (PCP) (43.1%), dentists (in 30.4%), otorhinolaryngologists (3.9%), neurosurgeons (3.9%), neurologists or headache specialists (14.7%), others (8%). The final diagnosis was made mainly by a neurologist or headache specialist (85.3%), and the mean interval between the disease onset and the diagnosis made by a specialist was 10.8 ± 21.2 months. The “diagnostic delay” was 7.2 ± 12.5 months, and misdiagnoses at first consultation were found in 42.1% of cases. Instrumental and laboratory investigations were carried out in 93.1% of the patients before the final diagnosis of TN.

Conclusion

While TN has typical features and it is well defined by the available international diagnostic criteria, it is still frequently misdiagnosed and mistreated. There is a need to improve the neurological knowledge in order to promptly recognize the clinical picture of TN and properly adhere to the specific guidelines. This may result in a favorable outcome for patients, whose quality of life is usually severely impaired.
Influence of genetic diversity of seventeen Beauveria bassiana isolates from different hosts on virulence by comparative genomics
Authors: Zhang Zhengkun , Lu Yang , Xu Wenjing , Sui Li , Du Qian , Wang Yangzhou , Zhao Yu , Li Qiyun
Published: June 2020

Background

Beauveria bassiana (B. bassiana) is a famous entomopathogenic fungus that could parasitize on hundreds of insect species, which are being used as an environmentally friendly mycoinsecticide. Nevertheless, the possible effect of genetic diversity of these B. bassiana isolates from different hosts on virulence has not been explored before. In order to explore that issue, we compared the genome sequences among seventeen B. bassiana isolates from 17 different insects using whole genome re-sequencing, with B. bassiana strain ARSEF 2860 as the reference genome.

Results

There were a total of 10,098 missense mutated genes, 720 positively selected genes were identified in 17 strains of B. bassiana. Among these, two genes with high frequency mutations encode the toxin-producing non-ribosomal peptide synthase (NRPS) protein. Seven genes undergoing positive selection were enriched in the two-component signaling pathway that is known to regulate the fungal toxicity. In addition, the domain changes of three positively selected genes are also directly related to the virulence plasticity. Besides, the functional categorization of mutated genes showed that most of them involved in the biological functions of toxic proteins involved in.

Conclusions

Based on our data, our results indicate that several mutated genes and positively selected genes may underpin virulence of B. bassiana towards hosts during infection process, which provide an insight into the potential effects of natural variation on the virulence of B. bassiana, which will be useful in screening out potential virulence factors in B. bassiana.
A meta-review of literature reviews assessing the capacity of patients with severe mental disorders to make decisions about their healthcare
Authors: Calcedo-Barba A. , Fructuoso A. , Martinez-Raga J. , Paz S. , Sánchez de Carmona M. , Vicens E.
Published: June 2020

Background

Determining the mental capacity of psychiatric patients for making healthcare related decisions is crucial in clinical practice. This meta-review of review articles comprehensively examines the current evidence on the capacity of patients with a mental illness to make medical care decisions.

Methods

Systematic review of review articles following PRISMA recommendations. PubMed, Scopus, CINAHL and PsycInfo were electronically searched up to 31 January 2020. Free text searches and medical subject headings were combined to identify literature reviews and meta-analyses published in English, and summarising studies on the capacity of patients with serious mental illnesses to make healthcare and treatment related decisions, conducted in any clinical setting and with a quantitative synthesis of results. Publications were selected as per inclusion and exclusion criteria. The AMSTAR II tool was used to assess the quality of reviews.

Results

Eleven publications were reviewed. Variability on methods across studies makes it difficult to precisely estimate the prevalence of decision-making capacity in patients with mental disorders. Nonetheless, up to three-quarters of psychiatric patients, including individuals with serious illnesses such as schizophrenia or bipolar disorder may have capacity to make medical decisions in the context of their illness. Most evidence comes from studies conducted in the hospital setting; much less information exists on the healthcare decision making capacity of mental disorder patients while in the community. Stable psychiatric and non-psychiatric patients may have a similar capacity to make healthcare related decisions. Patients with a mental illness have capacity to judge risk-reward situations and to adequately decide about the important treatment outcomes. Different symptoms may impair different domains of the decisional capacity of psychotic patients. Decisional capacity impairments in psychotic patients are temporal, identifiable, and responsive to interventions directed towards simplifying information, encouraging training and shared decision making. The publications complied satisfactorily with the AMSTAR II critical domains.

Conclusions

Whilst impairments in decision-making capacity may exist, most patients with a severe mental disorder, such as schizophrenia or bipolar disorder are able to make rational decisions about their healthcare. Best practice strategies should incorporate interventions to help mentally ill patients grow into the voluntary and safe use of medications.
The evolution of the Puf superfamily of proteins across the tree of eukaryotes
Authors: Najdrová Vladimíra , Stairs Courtney W. , Vinopalová Martina , Voleman Luboš , Doležal Pavel
Published: June 2020

Background

Eukaryotic gene expression is controlled by a number of RNA-binding proteins (RBP), such as the proteins from the Puf (Pumilio and FBF) superfamily (PufSF). These proteins bind to RNA via multiple Puf repeat domains, each of which specifically recognizes a single RNA base. Recently, three diversified PufSF proteins have been described in model organisms, each of which is responsible for the maturation of ribosomal RNA or the translational regulation of mRNAs; however, less is known about the role of these proteins across eukaryotic diversity.

Results

Here, we investigated the distribution and function of PufSF RBPs in the tree of eukaryotes. We determined that the following PufSF proteins are universally conserved across eukaryotes and can be broadly classified into three groups: (i) Nop9 orthologues, which participate in the nucleolar processing of immature 18S rRNA; (ii) ‘classical’ Pufs, which control the translation of mRNA; and (iii) PUM3 orthologues, which are involved in the maturation of 7S rRNA. In nearly all eukaryotes, the rRNA maturation proteins, Nop9 and PUM3, are retained as a single copy, while mRNA effectors (‘classical’ Pufs) underwent multiple lineage-specific expansions. We propose that the variation in number of ‘classical’ Pufs relates to the size of the transcriptome and thus the potential mRNA targets. We further distinguished full set of PufSF proteins in divergent metamonad Giardia intestinalis and initiated their cellular and biochemical characterization.

Conclusions

Our data suggest that the last eukaryotic common ancestor (LECA) already contained all three types of PufSF proteins and that ‘classical’ Pufs then underwent lineage-specific expansions.
Multidrug-resistant tuberculosis surveillance and cascade of care in Madagascar: a five-year (2012–2017) retrospective study
Authors: Knoblauch Astrid M. , Grandjean Lapierre Simon , Randriamanana Daniella , Raherison Mamy Serge , Rakotoson Andrianantenaina , Raholijaona Bienvenue Solofomandimby , Ravaoarimanga Masiarivony , Ravololonandriana Pascaline Elisabeth , Rabodoarivelo Marie-Sylvianne , Ratsirahonana Orelys , Rakotomanana Fanjasoa , Razafindranaivo Turibio , Rasolofo Voahangy , Rakotosamimanana Niaina
Published: June 2020

Background

In Madagascar, the multidrug-resistant tuberculosis (MDR-TB) surveillance programme was launched in late 2012 wherein previously treated TB cases and symptomatic MDR-TB contacts (hereafter called presumptive MDR-TB cases) undergo drug susceptibility testing. This retrospective review had per aim to provide an update on the national MDR-TB epidemiology, assess and enhance programmatic performance and assess Madagascar’s MDR-TB cascade of care.

Methods

For 2012–2017, national TB control programme notification, clinical management data and reference laboratory data were gathered. The development and coverage of the surveillance programme, the MDR-TB epidemiology and programmatic performance indicators were assessed using descriptive, logistic and spatial statistical analyses. Data for 2017 was further used to map Madagascar’s TB and MDR-TB cascade of care.

Results

The geographical coverage and diagnostic and referral capacities of the MDR-TB surveillance programme were gradually expanded whereas regional variations persist with regard to coverage, referral rates and sample referral delays. Overall, the rate of MDR-TB among presumptive MDR-TB cases remained relatively stable, ranging between 3.9% in 2013 and 4.4% in 2017. Most MDR-TB patients were lost in the second gap of the cascade pertaining to MDR-TB cases reaching diagnostic centres but failing to be accurately diagnosed (59.0%). This poor success in diagnosis of MDR-TB is due to both the current use of low-sensitivity smear microscopy as a first-line diagnostic assay for TB and the limited access to any form of drug susceptibility testing. Presumptive MDR-TB patients’ sample referral took a mean delay of 28 days before testing. Seventy-five percent of diagnosed MDR-TB patients were appropriately initiated on treatment, and 33% reached long-term recurrence-free survival.

Conclusions

An expansion of the coverage and strengthening of MDR-TB diagnostic and management capacities are indicated across all regions of Madagascar. With current limitations, the surveillance programme data is likely to underestimate the true MDR-TB burden in the country and an updated national MDR-TB prevalence survey is warranted. In absence of multiple drivers of an MDR-TB epidemic, including high MDR-TB rates, high HIV infection rates and inter-country migration, Madagascar is in a favourable starting position for MDR-TB control and elimination.
Changes in retinal layer thickness with maturation in the dog: an in vivo spectral domain - optical coherence tomography imaging study
Authors: Occelli Laurence M. , Pasmanter Nate , Ayoub Elias E. , Petersen-Jones Simon M.
Published: June 2020

Background

Retinal diseases are common in dogs. Some hereditary retinal dystrophies in dogs are important not only because they lead to vision loss but also because they show strong similarities to the orthologous human conditions. Advances in in vivo non-invasive retinal imaging allow the capture of retinal cross-section images that parallel low power microscopic examination of histological sections. Spectral domain - optical coherence tomography (SD-OCT) allows the measurement of retinal layer thicknesses and gives the opportunity for repeat examination to investigate changes in thicknesses in health (such as changes with maturation and age) and disease (following the course of retinal degenerative conditions). The purpose of this study was to use SD-OCT to measure retinal layer thicknesses in the dog during retinal maturation and over the first year of life. SD-OCT was performed on normal beagle cross dogs from 4 weeks of age to 52 weeks of age. To assess changes in layer thickness with age, measurements were taken from fixed regions in each of the 4 quadrants and thearea centralis(the region important for most detailed vision). Additionally, changes in retinal layer thickness along vertical and horizontal planes passing through the optic nerve head were assessed.

Results

In the four quadrants an initial thinning of retinal layers occurred over the first 12 to 15 weeks of life after which there was little change in thickness. However, in thearea centralisthere was a thickening of the photoreceptor layer over this time period which was mostly due to a lengthening of the photoreceptor inner/outer segment layer. The retina thinned with greater distances from the optic nerve head in both vertical and horizontal planes with the dorsal retina being thicker than the ventral retina. Most of the change in thickness with distance from the optic nerve head was due to difference in thickness of the inner retinal layers. The outer retinal layers remained more constant in thickness, particularly in the horizontal plane and dorsal to the optic nerve head.

Conclusions

These measurements will provide normative data for future studies.
A case study of monofilament line entanglement in a common bottlenose dolphin (Tursiops truncatus): entanglement, disentanglement, and subsequent death
Authors: Marks Wendy , Burton Steve , Stratton Elizabeth , Zolman Eric , Biedenbach George , Page-Karjian Annie
Published: June 2020

Background

Free-ranging common bottlenose dolphins (Tursiops truncatus) can become entangled in fishing line and other marine debris. Infrequently, dolphins can be successfully disentangled, released back into the wild, and later examined postmortem to better understand the pathology and long-term effects of these entanglements.

Case presentation

An entangled common bottlenose dolphin (Tursiops truncatus) calf was observed in the Indian River Lagoon, Florida, USA, with monofilament fishing line wrapped tightly around its maxilla. A multi-agency team successfully disentangled the dolphin for immediate release back into its natural habitat. A year after disentanglement, photos and observations indicated that the now independent calf showed a decline in body condition, characterized by grossly visible ribs and a prominent post-nuchal depression. More than 2 years post-disentanglement, the freshly dead carcass of this juvenile dolphin was recovered with extensive predation wounds. Despite the forestomach being ~ 50% full of ingesta (fish), the dolphin was emaciated. During postmortem examination, we collected and evaluated photographs and measurements of the maxillary damage resulting from the entanglement.

Conclusion

The monofilament entanglement caused permanent, bilateral deformation of the maxillary dental arcade, including a 4.0–4.2 cm long, 0.5 cm deep linear groove where the entanglement eroded the lateral edges of the maxilla. There was no evidence of maxillary fracture and the dolphin survived for more than 2 years after disentanglement. External evidence of propeller scars and a fishing hook discovered embedded in the laryngeal mucosa at necropsy indicated repeated human interactions.
Association of the dietary patterns with the risk of non-alcoholic fatty liver disease among Iranian population: a case-control study
Authors: Dehghanseresht Narges , Jafarirad Sima , Alavinejad Seyed Pejman , Mansoori Anahita
Published: June 2020

Background

Diet-based recommendations can be developed for preventing and treating non-alcoholic fatty liver disease (NAFLD) after investigating the effects of whole diets on NAFLD. The aim of this study was to identify major dietary patterns and their association with the risk of NAFLD.

Methods

A total of 244 individuals (122 NAFLD patients and 122 controls) participated in this case-control study. The patients with NAFLD were diagnosed by a gastroenterologist. The participants’ dietary intake data were collected using a 147-item semi-quantitive food frequency questionnaire and major dietary patterns were identified by principal component analysis. Adherence to dietary patterns was divided into tertiles and its association with odds of NAFLD was investigated by multivariate logistic regression.

Results

The results showed four major dietary patterns, among which adherence to the “ordinary pattern” was positively associated with NAFLD risk. After adjusting for all confounding factors, individuals in the highest tertile of “ordinary pattern” exhibited a significantly elevated risk of NAFLD compared to the lowest tertile (OR = 3.74, 95%CI = 1.23–11.42, P trend< 0.001). As well as, Individuals in the second and third tertiles of the “traditional pattern” were associated with the risk of NAFLD compared to the lowest tertile (medium vs. lowest tertile OR = 2.37, 95%CI = 1.02–5.53; highest vs. lowest tertile OR = 3.58, 95% CI = 1.48–8.68, P trend< 0.001). The highest tertile of “vegetable and dairy pattern” compared to the lowest tertile was inversely associated with NAFLD risk (OR = 0.23, 95%CI = 0.09–0.58, P trend = 0.02). No significant association was found between “fast food type pattern” and the risk of NAFLD.

Conclusion

A significant association was observed between different dietary patterns and the risk of NAFLD. These results can potentially serve as a dietary strategy for preventing NAFLD in individuals who are at a high risk for progression of NAFLD.
Upregulation of miR-1825 inhibits the progression of glioblastoma by suppressing CDK14 though Wnt/β-catenin signaling pathway
Authors: Lu Fengqin , Li Chunhong , Sun Yuping , Jia Ting , Li Na , Li Haiyan
Published: June 2020

Background

Mounting evidences displayed that miRNAs play crucial roles in tumor initiation and development. However, the regulation and relevant mechanism of miR-1825 in glioblastoma (GBM) remain unclear.

Methods

qRT-PCR was used to detect miR-1825 and CDK14 mRNA expression. Western blot was applied for testing protein levels (VEGF, E-cadherin, N-cadherin, vimentin, β-catenin, c-myc, p-c-Jun). MTT and transwell assays were used for detecting GBM cell progression, including cell viability, migration, and invasion.

Results

The results showed that miR-1825 was decreased in GBM tissue specimens by qRT-PCR and it was confirmed as a prognostic marker of GBM by Kaplan-Meier survival analysis. Moreover, we also found that miR-1825 upregulation suppressed GBM cell viability, tumor growth, invasion, and migration. Furthermore, CDK14 was first identified as the direct target of miR-1825 by Luciferase reporter assay. CDK14 acted as an oncogene in GBM development by immunohistochemistry. In addition, Western blot analysis demonstrated that miR-1825 regulated Wnt/β-catenin signaling pathway in GBM development.

Conclusion

In conclusion, miR-1825 upregulation suppressed GBM progression by targeting CDK14 through Wnt/β-catenin pathway.
Kidney ventrally rotation technique in retroperitoneal robot-assisted partial nephrectomy for posterior hilar tumor: technical feasibility and preliminary results
Authors: Yin Xiaotao , Jiang Sinan , Shao Zhiqiang , Lu Yongliang , Guo Jiaxiang , Xiao Yi , Zhu Xiaoying , Yu Hualiang , Ma Han , Yang Yu , Gao Jiangping
Published: June 2020

Purpose

The retroperitoneal robotic assisted partial nephrectomy (RAPN) is suitable for tumors locating on the posterior side of the kidney. However, the posterior hilar tumor poses an additional surgical challenge due to the special location and poor tumor exposure. We developed a novel kidney ventrally rotation technique to overcome this difficulty during retroperitoneal RAPN and evaluated its efficacy in a retrospective case-control comparative study.

Methods

From March 2016 to April 2019, a total of 39 patients with posterior renal hilar tumor underwent retroperitoneal RAPN. The kidney ventrally rotation technique, which improved the tumor exposure by opening the peritoneum and rotating the kidney ventrally, was applied in 24 cases, and the conventional RAPN was performed in the other 15 cases (control group). Perioperative data was analyzed to evaluate the efficacy of the kidney ventrally rotation technique.

Results

In kidney rotation group, the 24 patients underwent RAPN successfully without converting to open surgery or radical nephrectomy. The warm ischemia time was 17.4 ± 6.6 min, which was significantly shorter than 24.5 ± 8.3 min in control group. The mean operation time (80 ± 24 min) and estimated blood loss (104 ± 65 ml) were not different from the control group. No sever complications occurred, and no positive surgical margin was found in all the malignant cases. After 14 months follow-up, no recurrence or metastasis occurred in all cases.

Conclusion

Kidney ventrally rotation technique is safe and feasible for improving the exposure of posterior renal hilar tumor during retroperitoneal RAPN. It could be regarded as an efficient option for the management of posterior hilar tumor.
The trajectory of high sensitivity C-reactive protein is associated with incident diabetes in Chinese adults
Authors: Xu Renying , Jiang Xiaomin , Fan Zhuping , Wan Yanping , Gao Xiang
Published: June 2020

Background

We performed a cohort study to evaluate the association between the CRP trajectory and incident diabetes in Chinese adults.

Methods

Included were 6439 adults (4111 men and 2249 women; aged 46.6 ± 11.9 years). The concentration of high sensitivity CRP (hs-CRP) was measured in 2013 (baseline), 2014, and 2015. The hs-CRP trajectory was identified based the above three measurements by latent mixture modeling. Incident diabetes cases were diagnosed by fasting blood glucose (≥126 mg/dl) or Hb A1c (≥6.5%) during subsequent 3 years (2016–2018).

Results

Hs-CRP concentration during 2013–2015 was classified into 3 levels: low (< 1.0 mg/L), moderate (1.0–3.0 mg/L), and high (≥3.0 mg/L) based on a statement by American Heart Association. We named four hs-CRP trajectories as following: “low-stable” (low in 2013 and maintained at low concentration in 2014 and 2015), “moderate-fluctuated” (moderate in 2013, then increased to high concentration in 2014, and decreased to low concentration in 2015), “high-decreased” (high in 2013 but decreased to moderate concentration in 2014 and 2015), and “moderate-increased (moderate in 2013 and increased to high concentration in 2014 and 2015)”. We identified 235 incident diabetes during subsequent 3 years. The adjusted HR for incident diabetes was 1.71 (95% CI: 1.02, 2.87) comparing the moderate-increased and the low-stable group, after adjusting for potential confounders. In the secondary analyses, two single-measured hs-CRP concentration (in 2013 or in 2015) and the average of hs-CRP were associated with high risk of diabetes (P-trend< 0.01 for all).

Conclusions

The hs-CRP trajectory pattern was associated with altered incident diabetes in Chinese adults.
Alcohol use disorders and the risk of progression of liver disease in people with hepatitis C virus infection – a systematic review
Authors: Llamosas-Falcón Laura , Shield Kevin D. , Gelovany Maya , Manthey Jakob , Rehm Jürgen
Published: June 2020

Liver cirrhosis and other chronic liver diseases are usually compartmentalized into separate categories based on etiology (e.g., due to alcohol, virus infection, etc.), but it is important to study the intersection of, and possible interactions between, risk factors. The aim of this study is to summarize evidence on the association between alcohol use disorders (AUDs) and decompensated liver cirrhosis and other complications in patients with chronic Hepatitis C virus (HCV) infection. A systematic search of epidemiological studies was conducted using Ovid Medline databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Relative Risk estimates were combined using random-effects meta-analyses. The proportion of cases with liver disease progression that could be avoided if no person with a chronic HCV infection had an AUD was estimated using an attributable fraction methodology. A total of 11 studies fulfilled the inclusion criteria, providing data from 286,641 people with chronic HCV infections, of whom 63,931 (22.3%) qualified as having an AUD. Using decompensated liver cirrhosis as the outcome for the main meta-analysis (n = 7 unique studies), an AUD diagnosis was associated with a 3.3-fold risk for progression of liver disease among people with a chronic HCV infection (95% Confidence Interval (CI): 1.8–4.8). In terms of population-attributable fractions, slightly less than 4 out of 10 decompensated liver cirrhosis cases were attributable to an AUD: 35.2% (95% CI: 16.2–47.1%). For a secondary analyses, all outcomes related to liver disease progression were pooled (i.e., liver deaths or cirrhosis in addition to decompensated liver cirrhosis), which yielded a similar overall effect (n = 13 estimates; OR = 3.7; 95% CI: 2.2–5.3) and a similar attributable fraction (39.3%; 95% CI: 21.9–50.4%). In conclusion, AUDs were frequent in people with chronic HCV infections and contributed to worsening the course of liver disease. Alcohol use and AUDs should be assessed in patients who have liver disease of any etiology, and interventions should be implemented to achieve abstinence or to reduce consumption to the greatest possible extent.
Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: an observational cohort study
Authors: Bolondi Giuliano , Russo Emanuele , Gamberini Emiliano , Circelli Alessandro , Meca Manlio Cosimo Claudio , Brogi Etrusca , Viola Lorenzo , Bissoni Luca , Poletti Venerino , Agnoletti Vanni
Published: June 2020

Background

Iron metabolism and immune response to SARS-CoV-2 have not been described yet in intensive care patients, although they are likely involved in Covid-19 pathogenesis.

Methods

We performed an observational study during the peak of pandemic in our intensive care unit, dosing D-dimer, C-reactive protein, troponin T, lactate dehydrogenase, ferritin, serum iron, transferrin, transferrin saturation, transferrin soluble receptor, lymphocyte count and NK, CD3, CD4, CD8 and B subgroups of 31 patients during the first 2 weeks of their ICU stay. Correlation with mortality and severity at the time of admission was tested with the Spearman coefficient and Mann–Whitney test. Trends over time were tested with the Kruskal–Wallis analysis.

Results

Lymphopenia is severe and constant, with a nadir on day 2 of ICU stay (median 0.555 109/L; interquartile range (IQR) 0.450 109/L); all lymphocytic subgroups are dramatically reduced in critically ill patients, while CD4/CD8 ratio remains normal. Neither ferritin nor lymphocyte count follows significant trends in ICU patients. Transferrin saturation is extremely reduced at ICU admission (median 9%; IQR 7%), then significantly increases at days 3 to 6 (median 33%, IQR 26.5%, p value 0.026). The same trend is observed with serum iron levels (median 25.5 μg/L, IQR 69 μg/L at admission; median 73 μg/L, IQR 56 μg/L on days 3 to 6) without reaching statistical significance. Hyperferritinemia is constant during intensive care stay: however, its dosage might be helpful in individuating patients developing haemophagocytic lymphohistiocytosis. D-dimer is elevated and progressively increases from admission (median 1319 μg/L; IQR 1285 μg/L) to days 3 to 6 (median 6820 μg/L; IQR 6619 μg/L), despite not reaching significant results. We describe trends of all the abovementioned parameters during ICU stay.

Conclusions

The description of iron metabolism and lymphocyte count in Covid-19 patients admitted to the intensive care unit provided with this paper might allow a wider understanding of SARS-CoV-2 pathophysiology.
High content drug screening for Fanconi anemia therapeutics
Authors: Montanuy Helena , Camps-Fajol Cristina , Carreras-Puigvert Jordi , Häggblad Maria , Lundgren Bo , Aza-Carmona Miriam , Helleday Thomas , Minguillón Jordi , Surrallés Jordi
Published: June 2020

Background

Fanconi anemia is a rare disease clinically characterized by malformations, bone marrow failure and an increased risk of solid tumors and hematologic malignancies. The only therapies available are hematopoietic stem cell transplantation for bone marrow failure or leukemia, and surgical resection for solid tumors. Therefore, there is still an urgent need for new therapeutic options. With this aim, we developed a novel high-content cell-based screening assay to identify drugs with therapeutic potential in FA.

Results

A TALEN-mediated FANCA-deficient U2OS cell line was stably transfected with YFP-FANCD2 fusion protein. These cells were unable to form fluorescent foci or to monoubiquitinate endogenous or exogenous FANCD2 upon DNA damage and were more sensitive to mitomycin C when compared to the parental wild type counterpart. FANCA correction by retroviral infection restored the cell line’s ability to form FANCD2 foci and ubiquitinate FANCD2. The feasibility of this cell-based system was interrogated in a high content screening of 3802 compounds, including a Prestwick library of 1200 FDA-approved drugs. The potential hits identified were then individually tested for their ability to rescue FANCD2 foci and monoubiquitination, and chromosomal stability in the absence of FANCA.

Conclusions

While, unfortunately, none of the compounds tested were able to restore cellular FANCA-deficiency, our study shows the potential capacity to screen large compound libraries in the context of Fanconi anemia therapeutics in an optimized and cost-effective platform.
A ruthenium(II)-curcumin compound modulates NRF2 expression balancing the cancer cell death/survival outcome according to p53 status
Authors: Garufi Alessia , Baldari Silvia , Pettinari Riccardo , Gilardini Montani Maria Saveria , D’Orazi Valerio , Pistritto Giuseppa , Crispini Alessandra , Giorno Eugenia , Toietta Gabriele , Marchetti Fabio , Cirone Mara , D’Orazi Gabriella
Published: June 2020

Background

Tumor progression and tumor response to anticancer therapies may be affected by activation of oncogenic pathways such as the antioxidant one induced by NRF2 (nuclear factor erythroid 2-related factor 2) transcription factor and the pathways modified by deregulation of oncosuppressor p53. Often, oncogenic pathways may crosstalk between them increasing tumor progression and resistance to anticancer therapies. Therefore, understanding that interplay is critical to improve cancer cell response to therapies. In this study we aimed at evaluating NRF2 and p53 in several cancer cell lines carrying different endogenous p53 status, using a novel curcumin compound since curcumin has been shown to target both NRF2 and p53 and have anti-tumor activity.

Methods

We performed biochemical and molecular studies by using pharmacologic of genetic inhibition of NRF2 to evaluate the effect of curcumin compound in cancer cell lines of different tumor types bearing wild-type (wt) p53, mutant (mut) p53 or p53 null status.

Results

We found that the curcumin compound induced a certain degree of cell death in all tested cancer cell lines, independently of the p53 status. At molecular level, the curcumin compound induced NRF2 activation, mutp53 degradation and/or wtp53 activation. Pharmacologic or genetic NRF2 inhibition further increased the curcumin-induced cell death in both mutp53- and wtp53-carrying cancer cell lines while it did not increase cell death in p53 null cells, suggesting a cytoprotective role for NRF2 and a critical role for functional p53 to achieve an efficient cancer cell response to therapy.

Conclusions

These findings underline the prosurvival role of curcumin-induced NRF2 expression in cancer cells even when cells underwent mutp53 downregulation and/or wtp53 activation. Thus, NRF2 inhibition increased cell demise particularly in cancer cells carrying p53 either wild-type or mutant suggesting that p53 is crucial for efficient cancer cell death. These results may represent a paradigm for better understanding the cancer cell response to therapies in order to design more efficient combined anticancer therapies targeting both NRF2 and p53.
The efficacy of different treatment approaches for pediatric OSAHS patients with mandibular retrognathia: study protocol for a multicenter randomized controlled trial
Authors: Li Yuanyuan , Wu Jiali , Guo Jinghan , Yu Liming , Wang Jing , Li Xiaoyan , Xu Shuhua , Zhu Min , Feng Jinqiu , Liu Yuehua
Published: June 2020

Background

Pediatric obstructive sleep apnea/hypopnea syndrome (OSAHS) is a multifactorial syndrome caused by many risk factors, such as craniofacial anomalies, adenotonsillar hypertrophy, obesity, and airway inflammation. Although new treatment patterns have recently been proposed, treatment methods for children remain particularly challenging and controversial. This randomized controlled trial was designed to investigate the efficacy of adenotonsillectomy and/or orthodontic treatment for children who have mild OSAHS with mandibular retrognathia.

Methods

A sample of 352 children with mild OSAHS and mandibular retrognathia, who are aged between 7 and 10 years, will be enrolled in the study. They will be randomized into four groups: the drug treatment group, the surgical treatment group, the orthodontic treatment group, or the surgery and postoperative orthodontic group. After randomization the children will receive treatments within 4 weeks. Outcome assessment will take place at the following points: (1) baseline, (2) 7 months after the treatment starting point, (3) 12 months after the treatment starting point, and (4) 24 months after the treatment starting point. The primary endpoint of the trial is the mean change in obstructive apnea/hypopnea index. Other endpoints will consist of the lowest oxygen saturation, apnea index, and hypopnea index assessed by polysomnography, subjective symptoms (assessed by the OSA-20 questionnaire), cephalometric measurements, and morphologic analysis of the upper airway.

Discussion

The results of this study will provide valuable evidence for the merits and long-term efficacy of different treatment approaches and contribute to facilitating the multidisciplinary treatment of pediatric OSAHS.

Trial registration

ClinicalTrials.gov: NCT03451318. Registered on 2 March 2018 (last update posted 19 April 2018).
Effectiveness and cost-effectiveness of a community-based mental health care programme (GBV) for people with severe mental illness in Germany: study protocol for a randomised controlled trial
Authors: Mueller-Stierlin Annabel Sandra , Meixner Friedrich , Kohlmann Anne , Schumacher Mara , Hänsel Anke , Pouwels Melanie , Bias Nicole , Hartl Sabrina , Reichstein Jessica , Prestin Elke , Greve Nils , Becker Thomas , Kilian Reinhold
Published: June 2020

Background

The community-based mental health care programme GBV is based on the British Community Mental Health Teams and the Dutch Flexible Assertive Community Treatment model. In addition, the programme offers crisis-intervention services. A special feature of this integrated care programme is the initial standardised assessment process regarding empowerment, unmet care needs, and psychosocial functioning, used to verify the need for such a comprehensive form of care. The project evaluates the assessment process and analyses the effectiveness and cost-effectiveness of GBV compared to treatment as usual.

Methods

This randomised, controlled study includes five assessments over 2 years. In twelve regions in Germany, 1000 patients with severely impaired psychosocial functioning and unmet care needs will be recruited. Study eligibility relies on an indication for GBV based on the results of the initial assessment. The primary outcome is improved self-reported empowerment. Further outcomes include improved treatment satisfaction and subjective quality of life, reductions in patients’ unmet needs and illness-related clinical and social impairment, and an improved cost-effectiveness ratio of the resources used (from the perspectives of both statutory health insurance and the national economy). In addition, the GBV’s effects on the burden and quality of life of informal caregivers of patients will be investigated.

Discussion

The study’s results are expected to provide information on whether the community-based mental health care programme GBV contributes to improving mental health care provision in Germany. In addition, the study will show whether the GBV successfully overcomes the weaknesses that former research has identified regarding a German integrated care programme. Such improvement is particularly expected with respect to the semi-structured assessment within GBV.

Trial registration

German Clinical Trial Register, DRKS00019086. Registered on 3 January 2020.
Multiple approaches for massively parallel sequencing of SARS-CoV-2 genomes directly from clinical samples
Authors: Xiao Minfeng , Liu Xiaoqing , Ji Jingkai , Li Min , Li Jiandong , Yang Lin , Sun Wanying , Ren Peidi , Yang Guifang , Zhao Jincun , Liang Tianzhu , Ren Huahui , Chen Tian , Zhong Huanzi , Song Wenchen , Wang Yanqun , Deng Ziqing , Zhao Yanping , Ou Zhihua , Wang Daxi , Cai Jielun , Cheng Xinyi , Feng Taiqing , Wu Honglong , Gong Yanping , Yang Huanming , Wang Jian , Xu Xun , Zhu Shida , Chen Fang , Zhang Yanyan , Chen Weijun , Li Yimin , Li Junhua
Published: June 2020

Background

COVID-19 (coronavirus disease 2019) has caused a major epidemic worldwide; however, much is yet to be known about the epidemiology and evolution of the virus partly due to the scarcity of full-length SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) genomes reported. One reason is that the challenges underneath sequencing SARS-CoV-2 directly from clinical samples have not been completely tackled, i.e., sequencing samples with low viral load often results in insufficient viral reads for analyses.

Methods

We applied a novel multiplex PCR amplicon (amplicon)-based and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of SARS-CoV-2 from serials dilutions of a cultured isolate, and eight clinical samples covering a range of sample types and viral loads. We also examined and compared the sensitivity, accuracy, and other characteristics of these approaches in a comprehensive manner.

Results

We demonstrated that both amplicon and capture methods efficiently enriched SARS-CoV-2 content from clinical samples, while the enrichment efficiency of amplicon outran that of capture in more challenging samples. We found that capture was not as accurate as meta and amplicon in identifying between-sample variations, whereas amplicon method was not as accurate as the other two in investigating within-sample variations, suggesting amplicon sequencing was not suitable for studying virus-host interactions and viral transmission that heavily rely on intra-host dynamics. We illustrated that meta uncovered rich genetic information in the clinical samples besides SARS-CoV-2, providing references for clinical diagnostics and therapeutics. Taken all factors above and cost-effectiveness into consideration, we proposed guidance for how to choose sequencing strategy for SARS-CoV-2 under different situations.

Conclusions

This is, to the best of our knowledge, the first work systematically investigating inter- and intra-individual variations of SARS-CoV-2 using amplicon- and capture-based whole-genome sequencing, as well as the first comparative study among multiple approaches. Our work offers practical solutions for genome sequencing and analyses of SARS-CoV-2 and other emerging viruses.
Fecal microbiota transplantation in gastrointestinal disorders: time for precision medicine
Authors: Benech Nicolas , Sokol Harry
Published: June 2020

Fecal microbiota transplantation (FMT) has demonstrated efficacy in treating inflammatory bowel diseases and irritable bowel syndrome in an increasing number of randomized controlled trials. Recently published data gives striking insights into the factors associated with FMT success paving the road for the use of precision medicine in gastrointestinal disorders.
Community memory screening as a strategy for recruiting older adults into Alzheimer’s disease research
Authors: Peavy Guerry M. , Jenkins Cecily W. , Little Emily A. , Gigliotti Christina , Calcetas Amanda , Edland Steven D. , Brewer James B. , Galasko Douglas , Salmon David P.
Published: June 2020

Background

Growing awareness of Alzheimer’s disease (AD) has prompted a demand for quick and effective ways to screen for memory loss and cognitive decline in large numbers of individuals in the community. Periodic Memory Screening Day events provide free, brief cognitive screening aimed at those 65 years and older, and can serve as an opportunity to gauge participants’ attitudes towards AD research and recruit them into ongoing research projects.

Methods

Over 6 single-day events in 2 years, more than 574 individuals were individually screened using the MoCA and a story recall task (immediate and delayed), given feedback about their performance, and introduced to AD research and opportunities to participate.

Results

Screening classified 297 individuals (52.0%) as having “No Decline,” 192 (33.6%) as “Possible decline,” and 82 (14.4%) as “Likely decline.” Those with “Likely decline” were older and less educated, had more memory concerns, were more likely to be men, and were less likely to have a positive family history of dementia than those with “No Decline.” Subsequent validation of screening procedures against a full clinical evaluation showed 72% classification accuracy with a skew towards over-calling Possible and Likely decline and thereby guiding questionable individuals to a more thorough evaluation. Of those screened, 378 (66%) agreed to additional research and consented to being listed in a research registry, and a majority (70–85%) of those consenting reported they were amenable to various AD research procedures including lumbar puncture, MRI, and autopsy. Overall, 19.1% of those screened met inclusion criteria for ongoing studies and were successfully recruited into AD research.

Conclusions

Conducting a few concentrated community memory screening events each year may help meet the public’s demand for brief assessment of memory concerns and can be a relatively effective and efficient recruitment strategy for AD research.
Endometriosis of the Bartholin gland: a case report and review of the literature
Authors: Heijink Tetske , Bogers Hein , Steensma Anneke
Published: June 2020

Background

In this case report we present a case of endometriosis in the Bartholin gland without surgery in the perineal area. So far, only five cases concerning endometriosis in the Bartholin gland, which may or may not be an isolated finding, have been reported in the literature.

Case presentation

A 31-year-old Indo-surinamese woman with primary infertility presented at our out-patient clinic with cyclical vulvar pain. On gynecological examination, a cyst of 1 × 2 cm was found in the right gland of Bartholin. A transvaginal ultrasound revealed normal gynecological anatomy and did not reveal any contributing information. Due to the recurring pain of the cyst, surgery was scheduled.

During surgery, the marsupialization of the cyst resulted in drainage of a chocolate-colored fluid. Pathological examination revealed stroma lined with non-typical columnar epithelium with hemosiderin pigments, which confirmed a diagnosis of endometriosis in the Bartholin gland.

Conclusion

Our findings revealed a case of endometriosis outside the pelvis, without any deep intraperitoneal involvement. So far, only five cases concerning endometriosis in the Bartholin gland, which may or may not be an isolated finding, have been reported in literature.
Stochastic Hopf–Hopf bifurcation of two-species discrete coupling logistic system with symbiotic interaction
Authors: Yang Maosong , Ma Shaojuan
Published: June 2020

In this paper, stochastic Hopf–Hopf bifurcation of the discrete coupling logistic system with symbiotic interaction is investigated. Firstly, orthogonal polynomial approximation of discrete random function in the Hilbert spaces is applied to reduce the discrete coupling logistic system with random parameter to the deterministic equivalent system. Then, it is concluded that Hopf–Hopf bifurcation exists in the equivalent deterministic system according to the principle of algebraic criteria. Numerical simulations show that the bifurcation critical value varies with the intensity of random parameter, and Hopf–Hopf bifurcation and period-doubling bifurcation behavior exist. In particular, Hopf–Hopf bifurcation can be drift with the change of random intensity, and frequency locking phenomenon occurs in the stochastic system.