bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization of a tetra segmented ssDNA virus infecting Botrytis cinerea worldwide
Authors: Ruiz-Padilla Ana , Turina Massimo , Ayllón María A. 
Published: December 2023

Abstract
Background
Family Genomoviridae was recently established, and only a few mycoviruses have been described and characterized, and almost all of them (Sclerotinia sclerotiorum hypovirulence-associated DNA virus 1, Fusarium graminearum gemyptripvirus 1 and Botrytis cinerea gemydayirivirus 1) induced hypovirulence in their host. Botrytis cinerea ssDNA virus 1 (BcssDV1), a tetrasegmented single-stranded DNA virus infecting the fungus Botrytis cinerea, has been molecularly characterized in this work.

Methods
BcssDV1 was detected in Spanish and Italian B. cinerea field isolates obtained from grapevine. BcssDV1 variants genomes were molecularly characterized via NGS and Sanger sequencing. Nucleotide and amino acid sequences were used for diversity and phylogenetic analysis. Prediction of protein tertiary structures and putative associated functions were performed by AlphaFold2 and DALI.

Results
BcssDV1 is a tetrasegmented single-stranded DNA virus. The mycovirus was composed by four genomic segments of approximately 1.7 Kb each, which are DNA-A, DNA-B, and DNA-C and DNA-D, that coded, respectively, for the rolling-circle replication initiation protein (Rep), capsid protein (CP) and two hypothetical proteins. BcssDV1 was present in several Italian and Spanish regions with high incidence and low variability among the different viral variants. DNA-A and DNA-D were found to be the more conserved genomic segments among variants, while DNA-B and DNA-C segments were shown to be the most variable ones. Tertiary structures of the proteins encoded by each segment suggested specific functions associated with each of them.

Conclusions
This study presented the first complete sequencing and characterization of a tetrasegmented ssDNA mycovirus, its incidence in Spain and Italy, its presence in other countries and its high conservation among regions.
Detection of parechovirus A in respiratory, gastrointestinal, and neurological clinical samples of pediatric patients from Panama (2014–2015)
Authors: Gutierrez Lizette , Sáenz Viridiana , Franco Danilo , Moreno Brechla , Fuentes-Campos Ediner , Capitan-Barrios Zeuz , Rivera Luis Felipe , Carrera Jean-Paul , Castillo Juan , Castillo Marlene , Pascale Juan Miguel , López-Vergès Sandra , Sosa Néstor , Ábrego Leyda 
Published: December 2023

AbstractParechovirus A (PeV-A, Parechovirus, Picornaviridae) are human pathogens associated with mild to severe gastrointestinal and respiratory diseases in young children. While several studies have investigated the association of PeV-A with human disease, little is known about its epidemiology or detection in Latin America. Between the years 2014 and 2015, a total of 200 samples were collected from Panamanian pediatric patients aged < 16 years old exhibiting symptoms associated with respiratory (n = 64), gastrointestinal (n = 68), or neurological (n = 68) diseases. These samples were gathered from patients who had previously received negative diagnoses for the main respiratory viruses, rotavirus, and neurological viruses like herpes virus, enterovirus, and cytomegalovirus. The presence of PeV-A was analyzed by real time RT-PCR.Eight positive PeV-A infections (4.0%, 95% CI: 1.7 to 7.7) were detected: two in respiratory samples (3.0%, 95% CI: 0.3 to 10.8), five in gastrointestinal samples (7.3%, 95% CI: 2.4 to 16.3), and one in cerebrospinal fluid (1.5%, 95% CI: 1.4 to 7.9). The study provides evidence of PeV-A circulation in Panama and the data collectively, remarked on the importance of considering PeV-A in the Panamanian pediatric diagnostic landscape, especially when conventional testing for more common viruses yields negative results.
Statistical recommendations for count, binary, and ordinal data in rare disease cross-over trials
Authors: Geroldinger Martin , Verbeeck Johan , Hooker Andrew C. , Thiel Konstantin E. , Molenberghs Geert , Nyberg Joakim , Bauer Johann , Laimer Martin , Wally Verena , Bathke Arne C. , Zimmermann Georg 
Published: December 2023

Abstract
Background
Recommendations for statistical methods in rare disease trials are scarce, especially for cross-over designs. As a result various state-of-the-art methodologies were compared as neutrally as possible using an illustrative data set from epidermolysis bullosa research to build recommendations for count, binary, and ordinal outcome variables. For this purpose, parametric (model averaging), semiparametric (generalized estimating equations type [GEE-like]) and nonparametric (generalized pairwise comparisons [GPC] and a marginal model implemented in the R package nparLD) methods were chosen by an international consortium of statisticians.

Results
It was found that there is no uniformly best method for the aforementioned types of outcome variables, but in particular situations, there are methods that perform better than others. Especially if maximizing power is the primary goal, the prioritized unmatched GPC method was able to achieve particularly good results, besides being appropriate for prioritizing clinically relevant time points. Model averaging led to favorable results in some scenarios especially within the binary outcome setting and, like the GEE-like semiparametric method, also allows for considering period and carry-over effects properly. Inference based on the nonparametric marginal model was able to achieve high power, especially in the ordinal outcome scenario, despite small sample sizes due to separate testing of treatment periods, and is suitable when longitudinal and interaction effects have to be considered.

Conclusion
Overall, a balance has to be found between achieving high power, accounting for cross-over, period, or carry-over effects, and prioritizing clinically relevant time points.
The impact of family alexithymia on the severity of restrictive eating disorders in adolescent patients
Authors: Marazzi Francesca , Orlandi Marika , De Giorgis Valentina , Borgatti Renato , Mensi Martina Maria 
Published: December 2023

Abstract
Background
Alexithymia is the inability to identify and describe one’s own emotions. Adolescents who suffer from Restrictive Eating Disorders (REDs) show a higher prevalence of alexithymia than the general population.

Methods
The study explored the correlation between levels of alexithymia in mothers, fathers, and adolescents affected by REDs and patients’ ability to recognize their emotions. The study also aimed to evaluate if patients’ emotional distress can significantly impact the severity of their disorder and functioning measured by the Clinical Global Impression Scale - Severity (CGI-S) and the Children’s Global Assessment Scale (CGAS). We enrolled 67 families of adolescents affected by REDs. Parents and patients’ levels of alexithymia were assessed through the Toronto Alexithymia Scale (TAS-20). Spearman’s correlation shows a statistically significant correlation between mothers and patients’ levels of alexithymia.

Results
Our findings also suggest that fathers and mothers’ TAS scores correlate with each other. However, there is no statistically significant relationship between the influence of the TAS scores of fathers and sons/daughters.

Conclusions
In conclusion, mothers’ level of alexithymia could influence both fathers and patients’ difficulty in identifying and describing their own emotions. This relationship can be investigated further when considering externally oriented thinking. However, the severity of the disease and overall functioning do not appear to be affected by patients’ levels of alexithymia.
Bubonic plague: can the size of buboes be accurately and consistently measured with a digital calliper?
Authors: Bourner Josephine , Randriamparany Ravaka , Rasoanaivo Tsinjo Fehizoro , Denis Emmanuelle , Randremanana Rindra Vatosoa , Vaillant Michel , Salam Alex Paddy , Gonçalves Bronner P. , Olliaro Piero 
Published: December 2023

Abstract
Introduction
Conducting clinical research on treatments for emerging infectious diseases is often complicated by methodological challenges, such as the identification of appropriate outcome measures to assess treatment response and the lack of validated instruments available to measure patient outcomes. In bubonic plague, some studies have assessed bubo size as an indicator of treatment success, a measure widely assumed to be indicative of recovery. Evaluating this outcome however is challenging as there is no validated method for measuring bubo size. The aim of this study is to assess the accuracy and inter- and intra-rater agreement of artificial bubo measurements using a digital calliper to understand whether a calliper is an appropriate measurement instrument to assess this outcome.

Methods
Study technicians measured 14 artificial buboes made from silicone overlaid with artificial silicone skin sheets over the course of two training sessions. Each artificial bubo was measured by each study technician once per training session, following a Standard Operating Procedure. The objectives of this study are to (i) evaluate the accuracy of individual measurements against the true size of the artificial bubo when using a digital calliper, (ii) understand whether the characteristics of the artificial bubo influence measurement accuracy and (iii) evaluate inter- and intra-rater measurement agreement.

Results
In total, 14 artificial buboes ranging from 52.7 to 121.6 mm in size were measured by 57 raters, generating 698 measurements recorded across two training sessions. Raters generally over-estimated the size of the artificial bubo. The median percentage difference between the measured and actual bubo size was 13%. Measurement accuracy and intra-rater agreement decreased as the size of the bubo decreased. Three quarters of all measurements had a maximum of 25% difference from another measurement of the same artificial bubo. Inter-rater agreement did not vary with density, size or presence of oedema of the artificial bubo.

Conclusions
The results of this study demonstrate the challenges for both individual and multiple raters to repeatedly generate consistent and accurate measurements of the same artificial buboes with a digital calliper.
Genetic diversity of Toxoplasma gondii in South America: occurrence, immunity, and fate of infection
Authors: Brito Ramayana Morais de Medeiros , de Lima Bessa Gabriella , Bastilho Alexandre Lazoski , Dantas-Torres Filipe , de Andrade-Neto Valter Ferreira , Bueno Lilian Lacerda , Fujiwara Ricardo Toshio , Magalhães Luisa M. D. 
Published: December 2023

AbstractToxoplasma gondii is an intracellular parasite with a worldwide distribution. Toxoplasma gondii infections are of great concern for public health, and their impact is usually most severe in pregnant women and their foetuses, and in immunocompromised individuals. Displaying considerable genetic diversity, T. gondii strains differ widely according to geographical location, with archetypal strains predominantly found in the Northern Hemisphere and non-archetypal (atypical) strains, with highly diverse genotypes, found mainly in South America. In this review, we present an overview of the identification and distribution of non-archetypal strains of T. gondii. Special attention is paid to the strains that have been isolated in Brazil, their interaction with the host immunological response, and their impact on disease outcomes. The genetic differences among the strains are pivotal to the distinct immunological responses that they elicit. These differences arise from polymorphisms of key proteins released by the parasite, which represent important virulence factors. Infection with divergent non-archetypal strains can lead to unusual manifestations of the disease, even in immunocompetent individuals.
Graphical Abstract
A workflow for deriving chemical entities from crystallographic data and its application to the Crystallography Open Database
Authors: Vaitkus Antanas , Merkys Andrius , Sander Thomas , Quirós Miguel , Thiessen Paul A. , Bolton Evan E. , Gražulis Saulius 
Published: December 2023

AbstractKnowledge about the 3-dimensional structure, orientation and interaction of chemical compounds is important in many areas of science and technology. X-ray crystallography is one of the experimental techniques capable of providing a large amount of structural information for a given compound, and it is widely used for characterisation of organic and metal-organic molecules. The method provides precise 3D coordinates of atoms inside crystals, however, it does not directly deliver information about certain chemical characteristics such as bond orders, delocalization, charges, lone electron pairs or lone electrons. These aspects of a molecular model have to be derived from crystallographic data using refined information about interatomic distances and atom types as well as employing general chemical knowledge. This publication describes a curated automatic pipeline for the derivation of chemical attributes of molecules from crystallographic models. The method is applied to build a catalogue of chemical entities in an open-access crystallographic database, the Crystallography Open Database (COD). The catalogue of such chemical entities is provided openly as a derived database. The content of this catalogue and the problems arising in the fully automated pipeline are discussed, along with the possibilities to introduce manual data curation into the process.
Eldecalcitol prevents muscle loss and osteoporosis in disuse muscle atrophy via NF-κB signaling in mice
Authors: Zhang Haichao , Du Yanping , Tang Wenjing , Chen Minmin , Yu Weijia , Ke Zheng , Dong Shuangshuang , Cheng Qun 
Published: December 2023

AbstractWe investigated the effect of eldecalcitol on disuse muscle atrophy. C57BL/6J male mice aged 6 weeks were randomly assigned to control, tail suspension (TS), and TS-eldecalcitol–treated groups and were injected intraperitoneally twice a week with either vehicle (control and TS) or eldecalcitol at 3.5 or 5 ng for 3 weeks. Grip strength and muscle weights of the gastrocnemius (GAS), tibialis anterior (TA), and soleus (SOL) were determined. Oxidative stress was evaluated by malondialdehyde, superoxide dismutase, glutathione peroxidase, and catalase. Bone microarchitecture was analyzed using microcomputed tomography. The effect of eldecalcitol on C2C12 myoblasts was analyzed by measuring myofibrillar protein MHC and the atrophy markers Atrogin-1 and MuRF-1 using immunofluorescence. The influence of eldecalcitol on NF-κB signaling pathway and vitamin D receptor (VDR) was assessed through immunofluorescence, (co)-immunoprecipitation, and VDR knockdown studies. Eldecalcitol increased grip strength (P < 0.01) and restored muscle loss in GAS, TA, and SOL (P < 0.05 to P < 0.001) induced by TS. An improvement was noted in bone mineral density and bone architecture in the eldecalcitol group. The impaired oxidative defense system was restored by eldecalcitol (P < 0.05 to P < 0.01 vs. TS). Eldecalcitol (10 nM) significantly inhibited the expression of MuRF-1 (P < 0.001) and Atrogin-1 (P < 0.01), increased the diameter of myotubes (P < 0.05), inhibited the expression of P65 and P52 components of NF-κB and P65 nuclear location, thereby inhibiting NF-κB signaling. Eldecalcitol promoted VDR binding to P65 and P52. VDR signaling is required for eldecalcitol-mediated anti-atrophy effects. In conclusion, eldecalcitol exerted its beneficial effects on disuse-induced muscle atrophy via NF-κB inhibition.
Characterization of genotypes and antimicrobial resistance profiles of clinical isolates of Shigella from patients in the southern region of Iran
Authors: Shoja Saeed , Ghasemi Saba , Dastranj Mahsa , Shamseddin Jebreil , Ebrahimi Nasim , Alizade Hesam , Farahani Abbas 
Published: December 2023

Abstract
Background
Shigella spp., which are facultative anaerobic bacilli within the Enterobacteriaceae family, present a significant public health burden due to their role as prominent contributors to diarrheal diseases worldwide. A molecular analysis can facilitate the identification and assessment of outbreaks involving this bacterium. So, we aimed to investigate the antibiotic susceptibility pattern and clonal relatedness of clinical Shigella spp. isolates obtained from patients with diarrhea in Hormozgan province, South of Iran.

Methods
From 2019 to 2021, a cross-sectional investigation was conducted on 448 stool samples obtained from patients who were experiencing diarrhea, in the southern region of Iran. Shigella spp. isolates were identified based on biochemical and serological tests. All Shigella species were verified using species-specific polymerase chain reaction (PCR), followed by susceptibility testing to antimicrobial agents. Subsequently, genotyping of all Shigella species was conducted using ERIC-PCR.

Results
Out of a total of 448 stool samples, the presence of Shigella was detected in 62 cases, accounting for a prevalence rate of 13.84%. Among the identified isolates, the majority were attributed to S. flexneri, representing 53.23% of the cases. This was followed by S. sonnei at 24.19% and S. boydii at 22.58%. Notably, no instances of S. dysenteriae were found. The highest prevalence of Shigella isolates was observed in infants and children under the age of five. A significant proportion of the identified isolates demonstrated resistance to various antibiotics. Specifically, high resistance rates were noted for ampicillin (90.78%), piperacillin–tazobactam (87.1%), cefixime (83.87%), trimethoprim–sulfamethoxazole (83.87%), cefotaxime (82.26%), and ceftriaxone (80.65%). In addition, a substantial number (87.1%) of the isolates exhibited a multidrug-resistant (MDR) phenotype. Using the ERIC-PCR method, a total of 11 clusters and 6 distinct single types were identified among all the Shigella isolates.

Conclusion
A notable occurrence of antibiotic-resistant Shigella species has been noted, with multi-drug resistant (MDR) strains presenting an increasing challenge for treating shigellosis worldwide, and this includes Iran. Techniques such as ERIC-PCR are useful for assessing the genetic variation and connections between Shigella strains, which indirectly contributes to understanding antimicrobial resistance patterns. Further research is needed to explore the specific correlation between resistance genes and ERIC genotyping patterns in Shigella strains.
Operationalizing deployment time in police calls for service
Authors: Langton Samuel , Verlaan Tim , Ruiter Stijn 
Published: December 2023

AbstractAnalyses of emergency calls for service data in the United States suggest that around 50% of dispatched police deployment time is spent on crime-related incidents. The remainder of time is spent in a social service capacity: attending well-being checks and resolving disturbances, for instance. These findings have made a considerable contribution to the discourse around public perceptions of the police and the distribution of public funds towards (or away) from law enforcement. Yet, an outstanding issue remains. No investigation has been undertaken into whether findings are robust to the different ways in which ‘time spent’ is operationalized in these studies. Using dispatch data for Amsterdam during 2019, this study compares three operationalizations of ‘time spent’. Additionally, in order to provide some context on the potential mechanisms through which these different operationalizations might yield different results, we report on dispatch numbers per incident category and provide an initial exploration into ‘multi-dispatch’ incident types. We find that general proportional breakdowns are fairly robust to the time measure used. However, for some incident categories (e.g. Health) and incident types (e.g. Shootings), analyzed in isolation, the results are not robust to the different operationalizations. We propose that the mechanism explaining this lack of robustness can be traced to the high dispatch numbers for specific incident categories and types, particularly those with an imminent threat to life.Preregistration: This study has been preregistered under the title: Scale and composition of emergency reactive police demand in Amsterdam, Netherlands (https://osf.io/qgwv6/).
Apoptosis-resistant megakaryocytes produce large and hyperreactive platelets in response to radiation injury
Authors: Du Chang-Hong , Wu Yi-Ding , Yang Ke , Liao Wei-Nian , Ran Li , Liu Chao-Nan , Zhang Shu-Zhen , Yu Kuan , Chen Jun , Quan Yong , Chen Mo , Shen Ming-Qiang , Tang Hong , Chen Shi-Lei , Wang Song , Zhao Jing-Hong , Cheng Tian-Min , Wang Jun-Ping 
Published: December 2023

Abstract
Background
The essential roles of platelets in thrombosis have been well recognized. Unexpectedly, thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological, physical and chemical origins, which could be suffered by military personnel and civilians during chemical, biological, radioactive, and nuclear events. Especially, thrombosis is considered a major cause of mortality from radiation injury-induced thrombocytopenia, while the underlying pathogenic mechanism remains elusive.

Methods
A mouse model of radiation injury-induced thrombocytopenia was built by exposing mice to a sublethal dose of ionizing radiation (IR). The phenotypic and functional changes of platelets and megakaryocytes (MKs) were determined by a comprehensive set of in vitro and in vivo assays, including flow cytometry, flow chamber, histopathology, Western blotting, and chromatin immunoprecipitation, in combination with transcriptomic analysis. The molecular mechanism was investigated both in vitro and in vivo, and was consolidated using MK-specific knockout mice. The translational potential was evaluated using a human MK cell line and several pharmacological inhibitors.

Results
In contrast to primitive MKs, mature MKs (mMKs) are intrinsically programmed to be apoptosis-resistant through reprogramming the Bcl-xL-BAX/BAK axis. Interestingly, mMKs undergo minority mitochondrial outer membrane permeabilization (MOMP) post IR, resulting in the activation of the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway via the release of mitochondrial DNA. The subsequent interferon-β (IFN-β) response in mMKs upregulates a GTPase guanylate-binding protein 2 (GBP2) to produce large and hyperreactive platelets that favor thrombosis. Further, we unmask that autophagy restrains minority MOMP in mMKs post IR.

Conclusions
Our study identifies that megakaryocytic mitochondria-cGAS/STING-IFN-β-GBP2 axis serves as a fundamental checkpoint that instructs the size and function of platelets upon radiation injury and can be harnessed to treat platelet pathologies.