bluuebunny/crossref_metadata_2025 huggingface dataset:
The genome of the zoonotic malaria parasite Plasmodium simium reveals adaptations to host switching
Authors: Mourier Tobias , de Alvarenga Denise Anete Madureira , Kaushik Abhinav , de Pina-Costa Anielle , Douvropoulou Olga , Guan Qingtian , Guzmán-Vega Francisco J. , Forrester Sarah , de Abreu Filipe Vieira Santos , Júnior Cesare Bianco , de Souza Junior Julio Cesar , Moreira Silvia Bahadian , Hirano Zelinda Maria Braga , Pissinatti Alcides , Ferreira-da-Cruz Maria de Fátima , de Oliveira Ricardo Lourenço , Arold Stefan T. , Jeffares Daniel C. , Brasil Patrícia , de Brito Cristiana Ferreira Alves , Culleton Richard , Daniel-Ribeiro Cláudio Tadeu , Pain Arnab
Published: October 2021

Background

Plasmodium simium, a malaria parasite of non-human primates (NHP), was recently shown to cause zoonotic infections in humans in Brazil. We sequenced the P. simium genome to investigate its evolutionary history and to identify any genetic adaptions that may underlie the ability of this parasite to switch between host species.

Results

Phylogenetic analyses based on whole genome sequences of P. simium from humans and NHPs reveals that P. simium is monophyletic within the broader diversity of South American Plasmodium vivax, suggesting P. simium first infected NHPs as a result of a host switch of P. vivax from humans. The P. simium isolates show the closest relationship to Mexican P. vivax isolates. Analysis of erythrocyte invasion genes reveals differences between P. vivax and P. simium, including large deletions in the Duffy-binding protein 1 (DBP1) and reticulocyte-binding protein 2a genes of P. simium. Analysis of P. simium isolated from NHPs and humans revealed a deletion of 38 amino acids in DBP1 present in all human-derived isolates, whereas NHP isolates were multi-allelic.

Conclusions

Analysis of the P. simium genome confirmed a close phylogenetic relationship between P. simium and P. vivax, and suggests a very recent American origin for P. simium. The presence of the DBP1 deletion in all human-derived isolates tested suggests that this deletion, in combination with other genetic changes in P. simium, may facilitate the invasion of human red blood cells and may explain, at least in part, the basis of the recent zoonotic infections.
Design and user experience testing of a polygenic score report: a qualitative study of prospective users
Authors: Brockman Deanna G. , Petronio Lia , Dron Jacqueline S. , Kwon Bum Chul , Vosburg Trish , Nip Lisa , Tang Andrew , O’Reilly Mary , Lennon Niall , Wong Bang , Ng Kenney , Huang Katherine H. , Fahed Akl C. , Khera Amit V.
Published: October 2021

Background

Polygenic scores—which quantify inherited risk by integrating information from many common sites of DNA variation—may enable a tailored approach to clinical medicine. However, alongside considerable enthusiasm, we and others have highlighted a lack of standardized approaches for score disclosure. Here, we review the landscape of polygenic score reporting and describe a generalizable approach for development of a polygenic score disclosure tool for coronary artery disease.

Methods

We assembled a working group of clinicians, geneticists, data visualization specialists, and software developers. The group reviewed existing polygenic score reports and then designed a two-page mock report for coronary artery disease. We then conducted a qualitative user-experience study with this report using an interview guide focused on comprehension, experience, and attitudes. Interviews were transcribed and analyzed for themes identification to inform report revision.

Results

Review of nine existing polygenic score reports from commercial and academic groups demonstrated significant heterogeneity, reinforcing the need for additional efforts to study and standardize score disclosure. Using a newly developed mock score report, we conducted interviews with ten adult individuals (50% females, 70% without prior genetic testing experience, age range 20–70 years) recruited via an online platform. We identified three themes from interviews: (1) visual elements, such as color and simple graphics, enable participants to interpret, relate to, and contextualize their polygenic score, (2) word-based descriptions of risk and polygenic scores presented as percentiles were the best recognized and understood, (3) participants had varying levels of interest in understanding complex genomic information and therefore would benefit from additional resources that can adapt to their individual needs in real time. In response to user feedback, colors used for communicating risk were modified to minimize unintended color associations and odds ratios were removed. All 10 participants expressed interest in receiving a polygenic score report based on their personal genomic information.

Conclusions

Our findings describe a generalizable approach to develop a polygenic score report understandable by potential patients. Although additional studies are needed across a wider spectrum of patient populations, these results are likely to inform ongoing efforts related to polygenic score disclosure within clinical practice.
The management of type 2 diabetes before, during and after Covid-19 infection: what is the evidence?
Authors: Czupryniak Leszek , Dicker Dror , Lehmann Roger , Prázný Martin , Schernthaner Guntram
Published: October 2021

Patients with Covid-19 place new challenges on the management of type 2 diabetes, including the questions of whether glucose-lowering therapy should be adjusted during infection and how to manage a return to normal care after resolution of Covid-19 symptoms. Due to the sudden onset of the pandemic, physicians have by necessity made such important clinical decisions in the absence of robust evidence or consistent guidelines. The risk to patients is compounded by the prevalence of cardiovascular disease in this population, which alongside diabetes is a major risk factor for severe disease and mortality in Covid-19. We convened as experts from the Central and Eastern European region to consider what advice we can provide in the setting of type 2 diabetes and Covid-19, considering the evidence before, during and after infection. We review recommendations that have been published to date, and consider the best available—but currently limited—evidence from large observational studies and the DARE-19 randomized control trial. Notably, we find a lack of guidance on restarting patients on optimal antidiabetic therapy after recovering from Covid-19, and suggest that this may provide an opportunity to optimize treatment and counter clinical inertia that predates the pandemic. Furthermore, we emphasize that optimization applies not only to glycaemic control, but other factors such as cardiorenal protection. While we look forward to the emergence of new evidence that we hope will address these gaps, in the interim we provide a perspective, based on our collective clinical experience, on how best to manage glucose-lowering therapy as patients with Covid-19 recover from their disease and return to normal care.
Pharmacology-based ranking of anti-cancer drugs to guide clinical development of cancer immunotherapy combinations
Authors: Lemaire Vincent , Shemesh Colby S. , Rotte Anand
Published: October 2021

The success of antibodies targeting Programmed cell death protein 1 (PD-1) and its ligand L1 (PD-L1) in cancer treatment and the need for improving response rates has led to an increased demand for the development of combination therapies with anti-PD-1/PD-L1 blockers as a backbone. As more and more drugs with translational potential are identified, the number of clinical trials evaluating combinations has increased considerably and the demand to prioritize combinations having potential for success over the ones that are unlikely to be successful is rising. This review aims to address the unmet need to prioritize cancer immunotherapy combinations through comprehensive search of potential drugs and ranking them based on their mechanism of action, clinical efficacy and safety. As lung cancer is one of the most frequently studied cancer types, combinations that showed potential for the treatment of lung cancer were prioritized. A literature search was performed to identify drugs with potential in combination with PD-1/PD-L1 blockers and the drugs were ranked based on their mechanism of action and known clinical efficacy. Nineteen drugs or drug classes were identified from an internal list of lead molecules and were scored for their clinical potential. Efficacy and safety data from pivotal studies was summarized for the selected drugs. Further, overlap of mechanisms of action and adverse events was visualized using a heat map illustration to help screen drugs for combinations. The quantitative scoring methodology provided in this review could serve as a template for preliminary ranking of novel combinations.
The phenomenon of degeneration of industrial Trichoderma reesei strains
Authors: Martzy R. , Mello-de-Sousa T. M. , Mach R. L. , Yaver D. , Mach-Aigner A. R.
Published: October 2021

Background

Even if the loss of production capacity of a microorganism is said to be a serious problem in various biotechnology industries, reports in literature are rather rare. Strains of the genera Trichoderma reesei are used for large-scale production of cellulases, which are needed in food and feed, textile, paper industries and biofuel production.

Results

Here, we describe the phenomenon of spontaneous degeneration of T. reesei strains during large-scale cultivation. The phenotype of the degenerated population is characterized most importantly by a loss of any cellulase formation. Interestingly, promoter regions of relevant genes had a more compact chromatin in the (cel −) strains compared to productive strains. For a systematic investigation of the phenomenon a protocol for artificially induced and lab-scaled strain degeneration was developed. This workflow allows to determine the degeneration rate and thus, to compare the occurrence of a degenerated population in differently productive strains on the one hand, and to monitor the success of any strategies to prevent or decrease the degeneration on the other hand. While highly productive strains have higher degeneration rates compared to moderate producers, the degeneration can hardly be triggered in moderate producers. The observed (cel −) phenotype is not caused by a mutation in the gene encoding the essential transactivator Xyr1. The development of a non-producing population is also not triggered by any compounds released by either producing or non-producing cells.

Conclusions

The extent of the occurrence of a degenerated strain population relates to the production capacity of the strain and goes along with chromatin condensation in relevant promoter regions.
Physical–chemical properties of cell wall interface significantly correlated to the complex recalcitrance of corn straw
Authors: Wang Yufen , Xu Xianyang , Xue Huiting , Zhang Dejian , Li Guanhua
Published: October 2021

Background

Tissue heterogeneity significantly influences the overall saccharification efficiency of plant biomass. However, the mechanisms of specific organ or tissue recalcitrance to enzymatic deconstruction are generally complicated and unclear. A multidimensional analysis of the anatomical fraction from 12 corn cultivars was conducted to understand the essence of recalcitrance.

Results

The results showed that leaf, leaf sheath, stem pith and stem rind of corn straw exhibited remarkable heterogeneity in chemical composition, physical structure and cell type, which resulted in the different saccharification ratio of cellulose. The high saccharification ratio ranging from 21.47 to 38.96% was in stem pith, whereas the low saccharification ratio ranging from 17.1 to 27.43% was in leaf sheath. High values of lignin, hemicelluloses, degree of polymerization and crystallinity index were critical for the increased recalcitrance, while high value of neutral detergent soluble and pore size generated weak recalcitrance. Interestingly, pore traits of cell wall, especial for microcosmic interface structure, seemed to be a crucial factor that correlated to cellulase adsorption and further affected saccharification.

Conclusions

Highly heterogeneity in cell wall traits influenced the overall saccharification efficiency of biomass. Furthermore, the holistic outlook of cell wall interface was indispensable to understand the recalcitrance and promote the biomass conversion.

Graphic abstract
Prevalence of intestinal parasites and molecular characterization of Giardia intestinalis, Blastocystis spp. and Entamoeba histolytica in the village of Fortín Mbororé (Puerto Iguazú, Misiones, Argentina)
Authors: Candela Ernesto , Goizueta Carolina , Periago M. Victoria , Muñoz-Antoli Carla
Published: October 2021

Background

Intestinal parasites (IPs) are widely distributed worldwide and are one of the major contributors to gastrointestinal disease. Their prevalence is associated with poor access to water, sanitation and hygiene (WASH). The objective of this study was to identify the prevalence of IPs, including soil-transmitted helminths (STH), and their relation to socioeconomic characteristics, as well as a first approach to molecularly characterize the types ofGiardia intestinalis,Blastocystisspp. andEntamoeba histolyticapresent in an indigenous community from Puerto Iguazú, Misiones, Argentina.

Methods

A cross-sectional study was conducted in the rural settlement of Fortin Mbororé between January and March 2018. Socioeconomic variables, household characteristics, and stool and blood samples were collected. Standard coprological techniques were used to analyze stool samples, and a complete hemogram was performed on the blood samples.Giardia intestinalismicroscopy-positive samples were genetically typed by the β-giardin (bg) gene. Molecular identification ofBlastocystisspp. subtypes andE. histolyticawere carried out by amplification and sequencing of a partial fragment of the small subunit ribosomal RNA gene (SSU rDNA).

Results

The overall prevalence of IPs was 92.7%, with 72.0% specifically for hookworm. IPs were significantly more prevalent in preschool- and school-age children (P < 0.05). No formal education (P = 0.035), the presence of unimproved floors (P = 0.001) and overcrowding (P = 0.005) were significantly associated with IP infection. Hookworm was associated with anemia (P = 0.019). Molecular characterization revealed the presence ofE. histolyticasub-assemblages AII (12.5%), AIII (87.5%) and BIV (100%); one case of sub-assemblage D forG. intestinalis; and the presence of subtypes ST1 (14.8%), ST2 (14.8%) and ST3 (70.4%) ofBlastocystisspp.

Conclusions

Protozoans detected in this study are transmitted mainly through water contaminated with fecal matter, evidencing the need to improve the quality of water and sanitation for the inhabitants of Fortín Mbororé. Molecular characterization showed that domestic animals can be implicated in the zoonotic transmission ofG. intestinalisandBlastocystisspp. to humans. A hyperendemic area for STH was found, with hookworm prevalence greater than 50%. Therefore, improvements in WASH as well as mass deworming programs need to be implemented in this area to control and decrease the prevalence of IPs in general and STH in particular.

Graphical Abstract
A comparative analysis of the platforms for decentralized autonomous organizations in the Ethereum blockchain
Authors: Faqir-Rhazoui Youssef , Arroyo Javier , Hassan Samer
Published: October 2021

Blockchain technology has enabled a new kind of distributed systems. Beyond its early applications in Finance, it has also allowed the emergence of novel new ways of governance and coordination. The most relevant of these are the so-called Decentralized Autonomous Organizations (DAOs). DAOs typically implement decision-making systems to make it possible for their online community to reach agreements. As a result of these agreements, the DAO operates automatically by executing the appropriate portion of code on the blockchain network (e.g., hire people, delivers payments, invests in financial products, etc). In the last few years, several platforms such as Aragon, DAOstack and DAOhaus, have emerged to facilitate the creation of DAOs. As a result, hundreds of these new organizations have appeared, with their communities interacting mediated by blockchain. However, the literature has yet to appropriately explore empirically this phenomena. In this paper, we aim to shed light on the current state of the DAO ecosystem. We review the three main platforms nowadays (Aragon, DAOstack, DAOhaus) which facilitate the creation and management of DAOs. Thus, we introduce their main differences, and compare them using quantitative metrics. For such comparison, we retrieve data from both the main Ethereum network (mainnet) and a parallel Ethereum network (xDai). We analyze data from 72,320 users and 2,353 DAO communities in order to study the three ecosystems across four dimensions: growth, activity, voting system and funds. Our results show that there are notable differences among the DAO platforms in terms of growth and activity, and also in terms of voting results. Still, we consider that our work is only a first step and that further research is needed to better understand these communities, and evaluate their level of accomplishment in reaching decentralized governance.
Neuromyelitis optica with brain stem involvement in a middle-aged Ethiopian woman: a case report and review of literature
Authors: Kassu Rodas Asrat , Mulatu Hailu Abera , Gizaw Sisay , Fisseha Henok , Musema Amir , Keder Ayube , Negash Semere , Tefera Fithanegest , Lissanwerk Adugna , Tamrat Lemlem
Published: October 2021

Introduction

Neuromyelitis optica is a demyelinating disease of the central nervous system that predominantly affects the optic nerves and spinal cord. In neuromyelitis optica, white blood cells and antibodies primarily attack the optic nerves and the spinal cord, but may also attack the brain. Brainstem manifestation has been described recently. So far, neuromyelitis optica is very rare in Ethiopia and there were only two case reports, but this is the first case report of neuromyelitis optica with brainstem involvement.

Case presentation

A 47-year-old Addis Ababa woman presented to Saint Paul’s Hospital Millennium Medical College with a history of visual loss of 7 years and bilateral lower limb weakness of 4 days duration. She had bilateral oculomotor nerve palsy. Her past medical history showed systemic hypertension for 18 years and dyslipidemia for 1 year. The objective evaluation of the patient revealed right optic nerve atrophy suggesting optic neuritis and flaccid paraplegia with sensory level at the fourth thoracic vertebra. Diagnostic work-up using electromyography and spinal magnetic resonance imaging revealed demyelinating anterior visual pathway dysfunction and signs of extensive cervicothoracic transverse myelitis from the third cervical to lower thoracic vertebrae, respectively. Then a diagnosis of neuromyelitis optica was established. After treatment with high-dose systemic steroid followed by azathioprine, the patient was stable for several months with significant improvement of vision and lower-extremity weakness with no relapse of symptoms.

Conclusion

The case described here is a rare inflammatory demyelinating disorder of the central nervous system occurring in East Africa. It reminds clinicians to suspect neuromyelitis optica in a patient who presented with unexplained recurrent optic neuritis to make a timely diagnosis and prevention of permanent neuronal damage. Neuromyelitis optica can also be associated with oculomotor nerve involvement.
Uterine cervix metastasis from primary colon adenocarcinoma: a case report and review of the literature
Authors: Sassi I. , Ghalleb M. , Chemlali M. , Mbarek M. , Charfi L. , Chargui R. , Rahal K.
Published: October 2021

Introduction

Metastases to the female genital tract from extragenital primary tumors are unusual. We report a rare case of uterine cervix metastasis from colon adenocarcinoma and discuss diagnostic and therapeutic issues.

Case report

We report a case of a 38-year-old North African Caucasian woman treated for a non-metastatic colon adenocarcinoma. She had a sigmoidectomy and incomplete adjuvant chemotherapy. Six months later, she consulted with vaginal bleeding caused by a cervical tumor, which was confirmed to be metastatic disease, and the patient underwent decompressive and hemostatic radiotherapy.

Conclusion

Uterine cervix metastasis from primary colon adenocarcinoma is rare. The resection remains the standard protocol for the local treatment of resectable metastatic disease. Otherwise, systemic therapy is the preferable option.
Adipose tissue-derived mesenchymal stem cells and chitosan/poly (vinyl alcohol) nanofibrous scaffolds for cartilage tissue engineering
Authors: Nour-Eldeen Ghada , Abdel-Rasheed Mazen , EL-Rafei Amira M. , Azmy Osama , El-Bassyouni Gehan T.
Published: October 2021

Osteoarthritis (OA) has been defined as a chronic inflammatory joint disease characterized by progressive articular cartilage degeneration. Recently growing interest in regenerative medicine, using cell therapy and tissue engineering, where cellular components in combination with engineered scaffolds and bioactive materials were used to induce functional tissue regeneration. In the present study, nanofibrous scaffold based on chitosan (CS)/poly (vinyl alcohol) (PVA) were used to develop biologically functionalized biomaterial to mimic the extracellular matrix, allowing the human adipose tissue derived mesenchymal stem cells (ADSCs) to proliferate and differentiate to chondrogenic cells. The morphology of the nanofibrous mat was examined using field emission scanning electron microscope (FE/SEM). The characteristic functional groups and the nature of the chemical bonds between atoms were evaluated using Fourier transform infrared spectroscopy (FTIR) spectrum. Characterization of the seeded cells was morphologically evaluated by scanning electron microscopy and by flow cytometry for the expression of the stem cell surface markers. The differentiation potential was verified after chondrogenic induction by analyzing the expression of chondrogenic marker genes using real-time (RT PCR). Current study suggest significant potential for the use of ADSCs with the nanofibrous scaffolds in improving the osteoarthritis pathology.
Retrotransposons in pluripotent stem cells
Authors: Wang Jingwen , Huang Junjiu , Shi Guang
Published: October 2021

Transposable elements constitute about half of the mammalian genome, and can be divided into two classes: the class I (retrotransposons) and the class II (DNA transposons). A few hundred types of retrotransposons, which are dynamic and stage specific, have been annotated. The copy numbers and genomic locations are significantly varied in species. Retrotransposons are active in germ cells, early embryos and pluripotent stem cells (PSCs) correlated with low levels of DNA methylation in epigenetic regulation. Some key pluripotency transcriptional factors (such as OCT4, SOX2, and NANOG) bind retrotransposons and regulate their activities in PSCs, suggesting a vital role of retrotransposons in pluripotency maintenance and self-renewal. In response to retrotransposons transposition, cells employ a number of silencing mechanisms, such as DNA methylation and histone modification. This review summarizes expression patterns, functions, and regulation of retrotransposons in PSCs and early embryonic development.
All routes lead to Rome: multifaceted origin of hepatocytes during liver regeneration
Authors: Gao Ce , Peng Jinrong
Published: October 2021

Liver is the largest internal organ that serves as the key site for various metabolic activities and maintenance of homeostasis. Liver diseases are great threats to human health. The capability of liver to regain its mass after partial hepatectomy has widely been applied in treating liver diseases either by removing the damaged part of a diseased liver in a patient or transplanting a part of healthy liver into a patient. Vast efforts have been made to study the biology of liver regeneration in different liver-damage models. Regarding the sources of hepatocytes during liver regeneration, convincing evidences have demonstrated that different liver-damage models mobilized different subtype hepatocytes in contributing to liver regeneration. Under extreme hepatocyte ablation, biliary epithelial cells can undergo dedifferentiation to liver progenitor cells (LPCs) and then LPCs differentiate to produce hepatocytes. Here we will focus on summarizing the progresses made in identifying cell types contributing to producing new hepatocytes during liver regeneration in mice and zebrafish.
Defining cell identity beyond the premise of differential gene expression
Authors: Kim Hani Jieun , Tam Patrick P. L. , Yang Pengyi
Published: October 2021

Identifying genes that define cell identity is a requisite step for characterising cell types and cell states and predicting cell fate choices. By far, the most widely used approach for this task is based on differential expression (DE) of genes, whereby the shift of mean expression are used as the primary statistics for identifying gene transcripts that are specific to cell types and states. While DE-based methods are useful for pinpointing genes that discriminate cell types, their reliance on measuring difference in mean expression may not reflect the biological attributes of cell identity genes. Here, we highlight the quest for non-DE methods and provide an overview of these methods and their applications to identify genes that define cell identity and functionality.
Using density of antecedent events and trajectory path analysis to investigate family-correlated patterns of onset of bipolar I disorder: a comparison of cohorts from Europe and USA
Authors: Scott Jan , Vorspan Florence , Loftus Josephine , Bellivier Frank , Etain Bruno
Published: October 2021

Background

Major contributors to the global burden of bipolar disorders (BD) are the early age at onset (AAO) and the co-occurrence of non-mood disorders before and after the onset of BD. Using data from two independent cohorts from Europe and the USA, we investigated whether the trajectories of BD-I onset and patterns of psychiatric comorbidities differed in (a) individuals with or without a family history (FH) of BD, or (b) probands and parents who both had BD-I.

Methods

First, we estimated cumulative probabilities and AAO of comorbid mental disorders in familial and non-familial cases of BD-I (Europe, n = 573), and sex-matched proband-parent pairs of BD-I cases (USA, n = 194). Then we used time to onset analyses to compare overall AAO of BD-I and AAO according to onset polarity. Next, we examined associations between AAO and polarity of onset of BD-I according to individual experiences of comorbidities. This included analysis of the density of antecedent events (defined as the number of antecedent comorbidities per year of exposure to mental illness per individual) and time trend analysis of trajectory paths plotted for the subgroups included in each cohort (using R2 goodness of fit analysis).

Results

Earlier AAO of BD-I was found in FH versus non-FH cases (log rank test = 7.63; p = 0.006) and in probands versus parents with BD-I (log rank test = 15.31; p = 0.001). In the European cohort, AAO of BD-I was significantly associated with factors such as: FH of BD (hazard ratio [HR]: 0.60), earlier AAO of first non-mood disorder (HR: 0.93) and greater number of comorbidities (HR: 0.74). In the USA cohort, probands with BD-I had an earlier AAO for depressive and manic episodes and AAO was also associated with e.g., number of comorbidities (HR: 0.65) and year of birth (HR: 2.44). Trajectory path analysis indicated significant differences in density of antecedents between subgroups within each cohort. However, the time trend R2 analysis was significantly different for the European cohort only.

Conclusions

Estimating density of antecedent events and comparing trajectory plots for different BD subgroups are informative adjuncts to established statistical approaches and may offer additional insights that enhance understanding of the evolution of BD-I.
Cognitive behavioural therapy for anxiety in children and young people on the autism spectrum: a systematic review and meta-analysis
Authors: Sharma Shivani , Hucker Abigail , Matthews Terry , Grohmann Dominique , Laws Keith R.
Published: October 2021

Background

Anxiety is common in youth on the autism spectrum and cognitive behavioural therapy (CBT) has been adapted to address associated symptoms. The aim of the current systematic review and meta-analysis was to examine the efficacy of CBT for reducing anxiety in autistic youth.

Method

Searches of PubMed and Scopus databases were undertaken from January 1990 until December 2020. Studies were included if they consisted of randomised controlled trials (RCTs) using CBT to reduce anxiety in autistic youth. Separate random effects meta-analyses assessed anxiety ratings according to informant (clinician; parent; child), both at end-of-trial and at follow-up.

Results

A total of 19 RCTs met our inclusion criteria (833 participants: CBT N = 487; controls N = 346). Random effects meta-analyses revealed a large effect size for clinician rated symptoms (g = 0.88, 95% CI 0.55, 1.12, k = 11), while those for both parent (g = 0.40, 95% CI 0.24, 0.56; k = 18) and child-reported anxiety (g = 0.25, 95% CI 0.06, 0.43; k = 13) were smaller, but significant. These benefits were not however maintained at follow-up. Moderator analyses showed that CBT was more efficacious for younger children (for clinician and parent ratings) and when delivered as individual therapy (for clinician ratings). Using the Cochrane Risk of Bias 2 tool, we found concerns about reporting bias across most trials.

Conclusions

The efficacy of CBT for anxiety in autistic youth was supported in the immediate intervention period. However, substantial inconsistency emerged in the magnitude of benefit depending upon who was rating symptoms (clinician, parent or child). Follow-up analyses failed to reveal sustained benefits, though few studies have included this data. It will be important for future trials to address robustness of treatment gains overtime and to further explore inconsistency in efficacy by informant. We also recommend pre-registration of methods by trialists to address concerns with reporting bias.
Biosynthesis of lactones from diols mediated by an artificial flavin
Authors: Zhang Xiaowang , Tan Zhuotao , Li Chaojian , Qi Siyu , Xu Mengjiao , Li Ming , Xiong Wenlong , Zhuang Wei , Liu Dong , Zhu Chenjie , Ying Hanjie
Published: October 2021

Background

Lactones are important compounds in the field of medicine, material and chemical industry. One of the promising accesses to these flexible scaffolds is NAD(P)+-dependent alcohol dehydrogenases-catalyzed oxidative lactonization of diols, which relies on the construction of an efficient NAD(P)+ regeneration system.

Results

In this study, a novel system combining horse liver alcohol dehydrogenase (HLADH) with the synthetic bridged flavin cofactor was established for biosynthesis of lactones. The reaction conditions of this system were optimized and a variety of lactones including chiral lactones were efficiently obtained from various diols. Compared to the previously reported NAD(P)+-regeneration systems, this system showed better regeneration efficiency and product yield. A two-phase system was further applied to solve the problem of product inhibition, and 80% yield was obtained at the condition of 300 mM substrate.

Conclusions

This study provides an efficient method to synthesis of lactones from diols under mild conditions. We believe this system will be a promising alternative to promote the synthesis of other valuable compounds.

Graphic abstract
Evaluation of factors related to overdose in patients with impaired consciousness who are transported by emergency medical services: an age-specific research
Authors: Nagashima Kazuki , Sumida Megumi , Imanaka Shoichi , Kuwabara Tatsuro , Kaneko Ichiro , Miyake Yasufumi , Yasuno Nobuhiro , Itagaki Fumio , Watanabe Machiko
Published: October 2021

Background

Drug overdose accounts for most of the admissions to the emergency department. Prescription drugs, most of which are psychotropic medications, are often misused for drug overdose. The purpose of this study was to investigate the association between overdose in patients transported with disorders of consciousness and psychotropic medications administered prior to transport, so as to enable quick differentiation of drug overdose patients from patients with disorders of consciousness.

Methods

We evaluated 222 patients transported to the Advanced Critical Care Center of Teikyo University Hospital due to disorders of consciousness. The patients were categorized into two groups: overdose group (n = 128) and control group with other disorders of consciousness (n = 94). Logistic regression models were used to assess the association between disorders of consciousness due to drug overdose and psychotropic drugs prescribed before emergency transportation based on sex and age.

Results

According to multivariate logistic regression analysis, only female sex (odds ratio [OR] 4.54, 95% confidence interval [CI] 2.43–8.05, P < 0.0001) was associated with overall overdose. Results from the univariate logistic regression analysis showed that in the group of patients aged 40–50 years, female sex (OR 4.36, 95% CI; 1.54–12.4, P = 0.006) and the use of psychotropic drugs (OR 5.05, 95% CI; 1.75–14.6, P = 0.003), benzodiazepines (OR 4.64, 95% CI; 1.61–13.4, P < 0.05), antidepressants (OR 11.4, 95% CI; 2.35–55.8, P = 0.003), and anticonvulsants (OR 4.46, 95% CI; 1.11–17.9, P = 0.035) were associated with overdose. According to multivariate logistic regression analysis, female sex (OR 4.44, 95% CI; 1.37–14.3, P = 0.013) and antidepressants (OR 7.95, 95% CI; 1.21–52.1, P = 0.031) were associated with overdose patients aged 40–50 years.

Conclusions

As a reference in distinguishing overdose in women in their 40s and 50s who present with impaired consciousness, attention may need to be paid to the type of psychotropic drug used, especially antidepressants.
Multidimensional linear cryptanalysis with key difference invariant bias for block ciphers
Authors: Cao Wenqin , Zhang Wentao
Published: October 2021

For block ciphers, Bogdanov et al. found that there are some linear approximations satisfying that their biases are deterministically invariant under key difference. This property is called key difference invariant bias. Based on this property, Bogdanov et al. proposed a related-key statistical distinguisher and turned it into key-recovery attacks on LBlock and TWINE-128. In this paper, we propose a new related-key model by combining multidimensional linear cryptanalysis with key difference invariant bias. The main theoretical advantage is that our new model does not depend on statistical independence of linear approximations. We demonstrate our cryptanalysis technique by performing key recovery attacks on LBlock and TWINE-128. By using the relations of the involved round keys to reduce the number of guessed subkey bits. Moreover, the partial-compression technique is used to reduce the time complexity. We can recover the master key of LBlock up to 25 rounds with about 260.4 distinct known plaintexts, 278.85 time complexity and 261 bytes of memory requirements. Our attack can recover the master key of TWINE-128 up to 28 rounds with about 261.5 distinct known plaintexts, 2126.15 time complexity and 261 bytes of memory requirements. The results are the currently best ones on cryptanalysis of LBlock and TWINE-128.
Urinary albumin-to-creatinine ratio in decompensated liver cirrhosis among elderly Egyptian patients: a single-center experience
Authors: Abdelghani Ahmed , Ibrahim Maha Hosam El-Din , Mohamed Osama Mohamady , Rizk Sobhi Eid , Ahmed Rabab Mahmoud
Published: October 2021

Background

Hepatitis C virus and nonalcoholic steatohepatitis (NASH) are the most common causes of liver cirrhosis in Egypt. Increasing aging population is a worldwide issue, and societies are facing various problems, including long-term care for populations with a high prevalence of chronic conditions; hence, comprehensive geriatric assessment is important for determining patients’ mental health, functional capacity, and social circumstances. Normally, a small amount of protein (normal urinary albumin-to-creatinine ratio [UACR] < 30 mg/g) excreted in daily urine and excess amounts warrant further examination. The present study aims to evaluate the relationship between UACR and the severity of liver cirrhosis among 47 elderly patients (more than 65 years old) and 47 adult patients (control group) admitted to the hospital as well as the relationship between UACR and geriatric cognitive functions, functional capacity, depression, and nutritional status.

Results

The present study showed that the cognitive, functional, and nutritional status of patients aged 65 years old or more were significantly affected by the severity of liver disease. The investigators also reported a significant relationship between UACR and Child–Pugh score in the elderly patient group. No significant relationship was found between UACR and the cognitive, functional, mood, or nutritional status of the elderly age group.

Conclusion

Overall, UACR was correlated to the severity of liver disease among elderly patients compared with adult patients with liver cirrhosis.
President's Page: Leading the way to a carbon-neutral world
Authors: Singleton Scott
Published: October 2021

Carbon capture and storage (CCS) and carbon capture, utilization, and storage (CCUS) are expanding at lightning speed as the world increasingly embraces the need for a carbon-neutral future. As it is described on the U.S. Department of Energy (DOE) website, “CCUS is a process that captures carbon dioxide emissions from sources like coal-fired power plants and either reuses or stores it so it will not enter the atmosphere. Carbon dioxide storage in geologic formations includes oil and gas reservoirs, unmineable coal seams and deep saline reservoirs — structures that have stored crude oil, natural gas, brine and carbon dioxide over millions of years” ( https://www.energy.gov/carbon-capture-utilization-storage ). The International Energy Agency (IEA) states that “CCUS is the only group of technologies that contributes both to reducing emissions in key sectors directly and to removing CO2 to balance emissions that are challenging to avoid – a critical part of “net-zero” goals. After years of slow progress, new investment incentives and strengthened climate goals are building new momentum behind CCUS” ( https://www.iea.org/reports/ccus-in-clean-energy-transitions ).
Seismic facies discrimination incorporating relative rock physics
Authors: Liu Di , Zou Changchun , Chang Yihang , Yang Ping , Wan Zhonghong , Liu Weiguang
Published: October 2021

Seismic facies discrimination is usually performed based on a rock-physics-driven quantitative interpretation approach. The accuracy of the study of rock physics largely impacts the reservoir and fluid recognition. However, the study is commonly conducted with absolute well logs without removing the trend effect. Such an approach may introduce inappropriate low-frequency information and bias further analysis of seismic data (crossplotting, facies probability density function generation, and projection angle determination). By contrast, relative rock physics with the trend decomposed reflects the rock-property variation of the overburden and underlying formation. The relative portions are more consistent with the seismic reflectivity, providing an alternative tool to facies interpretation through a seismic inversion scheme. A workflow for seismic facies discrimination has been investigated that incorporates relative rock physics, long short-term memory-based nonlinear seismic inversion, and Bayesian classification. This workflow is employed in a case study from Songliao Basin in northeast China, through which the results of relative and absolute approaches in key steps are analyzed and compared. The consistency of facies, determined through relative and absolute methods with petrophysical interpretation, is calculated. The relative analysis exhibits improved agreement with petrophysical interpretation in overall facies and reservoir sand discrimination of the blind wells. This indicates the potential to minimize the trend bias by integrating relative rock physics in quantitative interpretation.
Rock-physics machine learning toolkit for joint litho-fluid facies classification and compaction modeling
Authors: Beloborodov Roman , Gunning James , Pervukhina Marina , Waters Kester , Huntbatch Nick
Published: October 2021

Correct lithofacies interpretation sourced from wireline log data is an essential source of prior information for joint seismic inversion for facies and impedances, among other applications. However, this information is difficult to interpret or extract manually due to the multivariate and high dimensionality of wireline logs. Facies inference is also challenging for traditional clustering-based approaches because pervasive compaction trends affect a number of petrophysical measurements simultaneously. Another common pitfall in automated clustering approaches is the inability to account for underlying diagenetic processes that correlate with depth. Here, we address these challenges by introducing a rock-physics machine learning toolkit for joint litho-fluid facies classification. The litho-fluid types are inferred from the borehole data within the objective framework of a maximum-likelihood approach for latent facies variables and rock-physics model parameters, explicitly accounting for compaction and depth effects. The inference boils down to an expectation-maximization (EM) algorithm with strong spatial coupling. Each litho-fluid type is associated with an instance of a particular rock-physics model with a unique set of fitting parameters, constrained to a physically reasonable range. These fitting parameters in turn are inferred using bound-constrained optimization as part of the EM algorithm. Outputs produced by the toolkit can be used directly to specify the necessary prior information for seismic inversion, including per-facies rock-physics models and facies proportions. We present an example application of the tool to real borehole data from the North West Shelf of Australia to illustrate the method and discuss its characteristic features in depth.
Prevalence of mental illness among COVID-19 survivors in South Korea: nationwide cohort
Authors: Park Hye Yoon , Song In-Ae , Lee So Hee , Sim Min young , Oh Hong Sang , Song Kyoung-Ho , Yu Eun-Seung , Park Hye Youn , Oh Tak Kyu
Published: October 2021

Background

Mental illness among survivors of coronavirus disease 2019 (COVID-2019) during the post-illness period is an emerging and important health issue.

Aims

We aimed to investigate the prevalence of mental illness and the associated factors for its development among COVID-2019 survivors.

Method

From 1 January to 4 June 2020, data were extracted from the National Health Insurance Service COVID-19 database in South Korea. Patients with COVID-19 were defined as those whose test results indicated that they had contracted the infection, regardless of disease severity. COVID-19 survivors were defined as those who recovered from the infection. The primary end-point was the development of mental illness, which was evaluated between 1 January and 1 December 2020.

Results

A total 260 883 individuals were included in this study, and 2.36% (6148) were COVID-19 survivors. The COVID-19 survivors showed higher prevalence of mental illness than the control group (12.0% in the COVID-19 survivors v. 7.7% in the control group; odds ratio (OR) = 2.40, 95% CI 2.21–2.61, P < 0.001). Additionally, compared with the control group, the no specific treatment for COVID-19 group (OR = 2.23, 95% CI 2.03–2.45, P < 0.001) and specific treatment for COVID-19 group (OR = 3.27, 95% CI 2.77–3.87, P < 0.001) showed higher prevalence of mental illness among survivors.

Conclusions

In South Korea, COVID-19 survivors had a higher risk of developing mental illness compared with the rest of the populations. Moreover, this trend was more evident in COVID-19 survivors who experienced specific treatment in the hospital.
Randomised controlled trials of antidepressant and anti-anxiety medications for people with autism spectrum disorder: systematic review and meta-analysis
Authors: Deb Shoumitro , Roy Meera , Lee Rachel , Majid Madiha , Limbu Bharati , Santambrogio Jacopo , Roy Ashok , Bertelli Marco O.
Published: October 2021

Background

Although widely used, the current evidence for the efficacy of antidepressant and anti-anxiety medications for people with autism spectrum disorder (ASD) is limited and conflicting.

Aims

We carried out a systematic review and meta-analysis of randomised controlled trials that assessed the effectiveness of these medications in people with ASD.

Method

We searched the following databases: Cochrane Library, Medline, EMBASE, CINAHL, PsycINFO, ERIC, DARE and ClinicalTrials.gov. Additionally, we hand-searched 11 relevant journals. We used the Cochrane risk-of-bias tool and Jadad score to assess the quality of each included study. We carried out a meta-analysis using a random effects model.

Results

We included 15 randomised controlled trials (13 on antidepressants and two on anti-anxiety medications) for a total of 958 people with ASD. Data showed contradictory findings among the studies, with larger studies mostly showing a non-significant difference in outcomes between the treatment and the placebo groups. Meta-analysis of pooled Yale-Brown Obsessive Compulsive Scale and Clinical Global Impression Scale data from nine studies (60%) did not show any statistically significant inter-group difference on either of the outcome measures. The adverse effects reported were mild and, in most studies, their rates did not show any significant inter-group difference.

Conclusions

Given the methodological flaws in the most included studies and contradictory findings, it is difficult to draw any definitive conclusion about the effectiveness of either antidepressant or anti-anxiety medications to treat either ASD core symptoms or associated behaviours. Robust, large-scale, randomised controlled trials are needed to address this issue.