bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging characteristics and treatment strategies of traumatic diaphragmatic hernia with aortic dissection: a report of 3 cases
Authors: Wu Hao-Hao , Tu Shao-Song , Zhang Fang-Biao
Published: January 2023

Background

Traumatic aortic dissection with traumatic diaphragmatic hernia is a rare traumatic disease. The purpose of this article is to investigate the imaging characteristics and treatment strategies for traumatic diaphragmatic hernia with aortic dissection.

Case presentation

The imaging and clinical data of 3 patients with traumatic diaphragmatic hernia combined with aortic dissection were analyzed retrospectively. Of the three cases, two were males, and one was female; their mean age was 52.7 years (range, 47–62 years). Plain chest CT scans revealed diaphragmatic hernia in 2 patients, but no traumatic aortic dissection was found. Diaphragmatic hernia repair was performed in all patients. Aortic dilatation was found during intraoperative exploration, and aortic dissection was confirmed by postoperative enhanced CT. One patient underwent stent implantation and recovered smoothly (Case 1). The other patient refused stent implantation and died of thoracic hemorrhage (Case 2). The third patient underwent preoperative enhanced CT to identify traumatic diaphragmatic hernia with aortic dissection (Case 3). Aortic covered stent implantation was performed immediately, and diaphragmatic hernia repair was performed at a selected time. The patient’s postoperative recovery was good.

Conclusion

A preoperative plain chest CT scan indicated diaphragmatic hernia in major blunt thoracic trauma patients with a history of trauma and blurred periaortic spaces accompanied by hematocele and other imaging manifestations. Chest-enhanced CT should be performed to improve the diagnostic accuracy of aortic dissection.
A pangenome analysis pipeline provides insights into functional gene identification in rice
Authors: Wang Jian , Yang Wu , Zhang Shaohong , Hu Haifei , Yuan Yuxuan , Dong Jingfang , Chen Luo , Ma Yamei , Yang Tifeng , Zhou Lian , Chen Jiansong , Liu Bin , Li Chengdao , Edwards David , Zhao Junliang
Published: January 2023

Background

A pangenome aims to capture the complete genetic diversity within a species and reduce bias in genetic analysis inherent in using a single reference genome. However, the current linear format of most plant pangenomes limits the presentation of position information for novel sequences. Graph pangenomes have been developed to overcome this limitation. However, bioinformatics analysis tools for graph format genomes are lacking.

Results

To overcome this problem, we develop a novel strategy for pangenome construction and a downstream pangenome analysis pipeline (PSVCP) that captures genetic variants’ position information while maintaining a linearized layout. Using PSVCP, we construct a high-quality rice pangenome using 12 representative rice genomes and analyze an international rice panel with 413 diverse accessions using the pangenome as the reference. We show that PSVCP successfully identifies causal structural variations for rice grain weight and plant height. Our results provide insights into rice population structure and genomic diversity. We characterize a new locus (qPH8-1) associated with plant height on chromosome 8 undetected by the SNP-based genome-wide association study (GWAS).

Conclusions

Our results demonstrate that the pangenome constructed by our pipeline combined with a presence and absence variation-based GWAS can provide additional power for genomic and genetic analysis. The pangenome constructed in this study and the associated genome sequence and genetic variants data provide valuable genomic resources for rice genomics research and improvement in future.
Seasonal changes in the diversity, host preferences and infectivity of mosquitoes in two arbovirus-endemic regions of Costa Rica
Authors: Romero-Vega Luis M. , Piche-Ovares Marta , Soto-Garita Claudio , Barantes Murillo Daniel Felipe , Chaverri Luis Guillermo , Alfaro-Alarcón Alejandro , Corrales-Aguilar Eugenia , Troyo Adriana
Published: January 2023

Background

Mosquitoes are vectors of various arboviruses belonging to the genera Alphavirus and Flavivirus, and Costa Rica is endemic to several of them. The aim of this study was to describe and analyze the community structure of such vectors in Costa Rica.

Methods

Sampling was performed in two different coastal locations of Costa Rica with evidence of arboviral activity during rainy and dry seasons. Encephalitis vector surveillance traps, CDC female gravid traps and ovitraps were used. Detection of several arboviruses by Pan-Alpha and Pan-Flavi PCR was attempted. Blood meals were also identified. The Normalized Difference Vegetation Index (NDVI) was estimated for each area during the rainy and dry seasons. The Chao2 values for abundance and Shannon index for species diversity were also estimated.

Results

A total of 1802 adult mosquitoes belonging to 55 species were captured, among which Culex quinquefasciatus was the most caught species. The differences in NDVI were higher between seasons and between regions, yielding lower Chao-Sørensen similarity index values. Venezuelan equine encephalitis virus, West Nile virus and Madariaga virus were not detected at all, and dengue virus and Zika virus were detected in two separate Cx. quinquefasciatus specimens. The primary blood-meal sources were chickens (60%) and humans (27.5%). Both sampled areas were found to have different seasonal dynamics and population turnover, as reflected in the Chao2 species richness estimation values and Shannon diversity index.

Conclusion

Seasonal patterns in mosquito community dynamics in coastal areas of Costa Rica have strong differences despite a geographical proximity. The NDVI influences mosquito diversity at the regional scale more than at the local scale. However, year-long continuous sampling is required to better understand local dynamics.

Graphical Abstract
Long-term study reveals central European aerial insectivores as an unusual group of hosts that harbor mostly helminths that are unable to complete life-cycles in the nesting quarters of their hosts
Authors: Sitko Jiljí , Heneberg Petr
Published: January 2023

Background

Central European aerial insectivores are long-distance migrants that winter in sub-Saharan Africa. Most of them employ the fly-and-forage migrating strategy and differ in their food composition. The composition and structure of helminth component communities of these hosts are poorly understood, and information regarding seasonality and long-term changes is unavailable.

Methods

From 1963 to 2022, we analyzed the population trends of helminths in five aerial insectivore species. Namely, we examinedApus apus,Hirundo rustica,Delichon urbicum,Riparia riparia, andFicedula albicollis; all originated from the Czech Republic.

Results

We identified central European aerial insectivores as hosts that are parasitized mostly by helminths that cannot complete their life-cycles in the nesting quarters of their hosts. This phenomenon is unknown in other bird host species. In contrast, only a single dominant trematode species that completes its life-cycle locally colonized the central European aerial insectivores. All other dominant species of Trematoda, all Nematoda, and all Acanthocephala were dependent on intermediate hosts unavailable in the nesting quarters of the examined bird hosts. Surprisingly, these helminths transmitted from winter quarters or migratory routes were diverse, and many of them were abundant in terms of both prevalence and intensity of infection. The helminth component communities of aerial insectivores were dynamic systems. During the study period, three species became new and regularly encountered members of helminth fauna of examined hosts, and other species gradually increased or decreased their intensity of infection. In contrast to other groups of bird hosts, the dominant helminth species of aerial insectivores did not experience local extinctions or rapid population losses.

Conclusions

The analysis of helminths of five central European aerial insectivores revealed component communities that heavily rely on completing host–parasite cycles at migration routes or wintering grounds. The composition of the analyzed component communities changed dynamically during the 60-year-long study period, but there was no evidence of large-scale declines in abundance or prevalence.

Graphical Abstract
Leishmania tarentolae: a vaccine platform to target dendritic cells and a surrogate pathogen for next generation vaccine research in leishmaniases and viral infections
Authors: Bandi Claudio , Mendoza-Roldan Jairo Alfonso , Otranto Domenico , Alvaro Alessandro , Louzada-Flores Viviane Noll , Pajoro Massimo , Varotto-Boccazzi Ilaria , Brilli Matteo , Manenti Alessandro , Montomoli Emanuele , Zuccotti Gianvincenzo , Epis Sara
Published: January 2023

Parasites of the genus Leishmania are unusual unicellular microorganisms in that they are characterized by the capability to subvert in their favor the immune response of mammalian phagocytes, including dendritic cells. Thus, in overt leishmaniasis, dendritic cells and macrophages are converted into a niche for Leishmania spp. in which the parasite, rather than being inactivated and disassembled, survives and replicates. In addition, Leishmania parasites hitchhike onto phagocytic cells, exploiting them as a mode of transport to lymphoid tissues where other phagocytic cells are potentially amenable to parasite colonization. This propensity of Leishmania spp. to target dendritic cells has led some researchers to consider the possibility that the non-pathogenic, reptile-associated Leishmania tarentolae could be exploited as a vaccine platform and vehicle for the production of antigens from different viruses and for the delivery of the antigens to dendritic cells and lymph nodes. In addition, as L. tarentolae can also be regarded as a surrogate of pathogenic Leishmania parasites, this parasite of reptiles could possibly be developed into a vaccine against human and canine leishmaniases, exploiting its immunological cross-reactivity with other Leishmania species, or, after its engineering, for the expression of antigens from pathogenic species. In this article we review published studies on the use of L. tarentolae as a vaccine platform and vehicle, mainly in the areas of leishmaniases and viral infections. In addition, a short summary of available knowledge on the biology of L. tarentolae is presented, together with information on the use of this microorganism as a micro-factory to produce antigens suitable for the serodiagnosis of viral and parasitic infections.

Graphical Abstract
Wild deer (Pudu puda) from Chile harbor a novel ecotype of Anaplasma phagocytophilum
Authors: Santodomingo Adriana , Thomas Richard , Robbiano Sofía , Uribe Juan E. , Parragué-Migone Catalina , Cabello-Stom Javier , Vera-Otarola Frank , Valencia-Soto Carola , Moreira-Arce Darío , Hidalgo-Hermoso Ezequiel , Muñoz-Leal Sebastián
Published: January 2023

Background

Deer species play an important role in the enzootic cycles of several Anaplasma species. While in the Northern Hemisphere ticks of genus Ixodes are well recognized vectors of these intracellular bacteria, less is known regarding the biological cycles of Anaplasma spp. in South America.

Methods

Using PCR protocols and Sanger sequencing, we assessed the presence of Anaplasma spp. in blood and ticks collected on a native deer species (Pudupuda) from southern Chile.

Results

Based on phylogenetic analyses of the 16S rRNA, gltA and groEL genes and calculation of average sequence divergence for groEL, our results bring to light a novel genovariant of Anaplasmaphagocytophilum (named strain “Patagonia”). The strain represents a novel ecotype within the A. phagocytophilum species complex and was detected in both P.puda and their ticks. Using a larger matrix, denser taxon sampling and outgroup, our maximum-likelihood- and Bayesian-inferred phylogenies for groEL provide an accurate picture of the topology of A. phagocytophilum ecotypes and their evolutionary relationships.

Conclusions

This is the first report of an ecotype of A. phagocytophilum in South America. Our results provide novel insight into the genetic diversity and ecology of this complex of bacterial lineages. Further studies should elucidate the enzootic cycle of A. phagocytophilum strain “Patagonia” and assess its pathogenic potential for pudues, domestic animals and humans in the region.

Graphical Abstract
Reduced field-of-view DWI‑derived clinical–radiomics model for the prediction of stage in cervical cancer
Authors: Huang Qiuhan , Deng Baodi , Wang Yanchun , Shen Yaqi , Hu Xuemei , Feng Cui , Li Zhen
Published: January 2023

Background

Pretreatment prediction of stage in patients with cervical cancer (CC) is vital for tailoring treatment strategy. This study aimed to explore the feasibility of a model combining reduced field-of-view (rFOV) diffusion-weighted imaging (DWI)-derived radiomics with clinical features in staging CC.

Methods

Patients with pathologically proven CC were enrolled in this retrospective study. The rFOV DWI with b values of 0 and 800 s/mm2 was acquired and the clinical characteristics of each patient were collected. Radiomics features were extracted from the apparent diffusion coefficient maps and key features were selected subsequently. A clinical–radiomics model combining radiomics with clinical features was constructed. The receiver operating characteristic curve was introduced to evaluate the predictive efficacy of the model, followed by comparisons with the MR-based subjective stage assessment (radiological model).

Results

Ninety-four patients were analyzed and divided into training (n = 61) and testing (n = 33) cohorts. In the training cohort, the area under the curve (AUC) of clinical–radiomics model (AUC = 0.877) for staging CC was similar to that of radiomics model (AUC = 0.867), but significantly higher than that of clinical model (AUC = 0.673). In the testing cohort, the clinical–radiomics model yielded the highest predictive performance (AUC = 0.887) of staging CC, even without a statistically significant difference when compared with the clinical model (AUC = 0.793), radiomics model (AUC = 0.846), or radiological model (AUC = 0.823).

Conclusions

The rFOV DWI-derived clinical–radiomics model has the potential for staging CC, thereby facilitating clinical decision-making.
The study of coefficient estimates and Fekete–Szegö inequalities for the new classes of m-fold symmetric bi-univalent functions defined using an operator
Authors: Breaz Daniel , Cotîrlă Luminiţa-Ioana
Published: January 2023

The objective of this paper is to introduce new classes of m-fold symmetric bi-univalent functions. We discuss estimates on the Taylor–Maclaurin coefficients$|a_{m+1}|$|am+1|and$|a_{2m+1}|$|a2m+1|, and the Fekete–Szegő problem is also considered for the new classes of functions introduced. We denote these classes by$MF-S_{\Sigma ,m}^{p,q}(h)$MF−SΣ,mp,q(h),$MF-S_{\Sigma , m}^{p,q}(s)$MF−SΣ,mp,q(s), and$MF-S_{\Sigma , m}^{b,d}$MF−SΣ,mb,d. Quantum calculus aspects are also considered in this study to enhance its novelty and to obtain more interesting results.
TRMT6 promotes hepatocellular carcinoma progression through the PI3K/AKT signaling pathway
Authors: Ye Yanqing , Liu Maosheng , Wu Fengfei , Ou Shiyu , Wang Weidong , Fei Jieying , Xie Fang , Bai Lan
Published: January 2023

Background

Hepatocellular carcinoma is one of the most common and deadly cancers. The aim of this study was to elucidate the role of tRNA methyltransferase 6 (TRMT6) during HCC progression.

Methods

The role of TRMT6 in the progression and prognosis of HCC was confirmed by analysis of online databases and clinical human samples. The effects of up-regulation or down-regulation of TRMT6 on HCC cell proliferation and PI3K/AKT pathway-related protein expressions were verified. The molecular mechanism was investigated in vivo by constructing subcutaneous xenograft tumor model.

Results

TRMT6 was overexpressed in HCC tissues and associated with Tumour-Node-Metastasis (TNM) stage, primary tumor (T) and regional lymph node (N) classification. TRMT6 expressions in HCC cell lines were higher than that in normal liver cell. TRMT6 overexpression can promote HCC cell proliferation, increase the number of S phase cells. Interference with TRMT6 reduced the PI3K/AKT pathway-related protein expressions, and was reversed by the addition of IGF1. Interference with TRMT6 inhibited tumor growth in vivo and was related to PI3K/AKT pathway.

Conclusions

Overexpression of TRMT6 promote HCC cell proliferation in vivo and in vitro through PI3K/AKT/mTOR axis, which provides a potential choice for the treatment of HCC in clinical practice.
Distribution characteristics and influencing factors of Intangible Cultural Heritage in Beijing-Tianjin-Hebei
Authors: Pang Ling , Wu Lina
Published: January 2023

The Beijing-Tianjin-Hebei region, with the capital Beijing as the core, carries a profound geo-culture and gathers numerous intangible cultural heritages. Studying the spatial distribution characteristics and influencing factors of intangible cultural heritage can help to propose positive suggestions for protection and development from the perspective of sustainable development. Taking 329 national intangible cultural heritages in Beijing-Tianjin—Hebei as the research objects, and using ArcGIS spatial analysis technology, combined with methods such as kernel density analysis, standard deviation ellipse and geographical detector, to visualize the spatial distribution of intangible cultural heritages and explore the influencing factors of their distribution. The results show that: (1) the distribution of intangible cultural heritage in Beijing-Tianjin-Hebei is not balanced, mainly concentrated in the central and southern regions, and three high-density core circles are formed in Beijing, Tianjin, and Handan-Xingtai in Hebei Province, showing large differences in spatial distribution density; (2) Traditional techniques, traditional arts, dramatic balladry, sports, music, and medicine show the characteristics of aggregated distribution. folkways, dance, and drama show the characteristics of random distribution. Folk literature shows the characteristics of uniform distribution; (3) The Cultural Development Period is an important evolutionary turning point in the spatial and temporal distribution of intangible cultural heritage in Beijing-Tianjin-Hebei, as well as an accelerating period in the development of intangible cultural heritage, and completes the transformation from decentralized distribution to localized aggregation distribution. In The Period of Regional Cultural Integration, the peak value is reached; (4) Economic development and social culture have the greatest influence on the spatial distribution of intangible cultural heritage in Beijing-Tianjin-Hebei, while the influence of physical environment is relatively small.
Identification of a novel transcription factor under long-term drought resistance in highland barley: a DNA affinity purification sequencing-based transcriptomic analysis
Authors: Wang Yulin , Li Heng , Zhao Chuansen , Yang Chunbao , Xu Qijun , Yuan Hongjun , Yang Haizhen , Zeng Xingquan
Published: January 2023

Stress emanating from drought condition is one of the inevitable conditions that occurs in many environments and spread across borders and results in severe hindrance to the morphology, physiology, biochemistry and molecular attributes of plants. Highland barley drought tolerance has been demonstrated to be a polygenic related characteristic and genetic composition that can assist in dissecting the gene network(s) controlling the drought tolerance needs to be adequately understood. DNA affinity purification sequencing (DAP-seq) has been shown to contribute to ways of making pure some of the protein with rare sequence-specific DNA binding and can help understand the molecular dynamics in barley under varying exposure time to drought. The present study aimed at identifying novel transcription factors (TFs) in highland barley that are key in drought resistance through DAP-seq-based transcriptomic analysis. The experimental design included two hulless barley accessions; drought-resistant Sheera 10 (X) and drought-sensitive 5171–7 (W), that were both subjected to short-term (4 h) and long-term (48 h) exposure to drought (T1 and T5, respectively), with the control group (CK) involving not subjecting the two accessions to any treatment. Through transcriptome analysis, one candidate transcription factor (GATA family; (bHLH, MYB-related, GARP-G2-like, bZIP, HB-HD-ZIP, C2H2, SET, mTERF, AP2/ERF-ERF, ARID, NAC, GARP-ARR-B, C2C2-GATA, FAR1, Trihelix, NF-YB, B3 and AUX/IAA) was found. The motif obtained was found to be consistent with GATA transcription factor. The DAP-seq highlighted the differential expression target gene which were verified by RT-qPCR. The associated genes were found to be a cluster of structural gene IP_HOR_1, IP_HOR_2 and In_HOR locus. Through RT-qPCR, it was also proved that the gene expressions were indeed upregulated. The TF HOVUSG2784400 was confirmed to be responsible to drought stress under long-term exposure, which regulates the differential expression of the genes, thereby improving the drought resistance of barley.

Graphical Abstract
Innate immune recognition against SARS-CoV-2
Authors: Yamada Taisho , Takaoka Akinori
Published: January 2023

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative virus of pandemic acute respiratory disease called coronavirus disease 2019 (COVID-19). Most of the infected individuals have asymptomatic or mild symptoms, but some patients show severe and critical systemic inflammation including tissue damage and multi-organ failures. Immune responses to the pathogen determine clinical course. In general, the activation of innate immune responses is mediated by host pattern-recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) as well as host damage-associated molecular patterns (DAMPs), which results in the activation of the downstream gene induction programs of types I and III interferons (IFNs) and proinflammatory cytokines for inducing antiviral activity. However, the excessive activation of these responses may lead to deleterious inflammation. Here, we review the recent advances in our understanding of innate immune responses to SARS-CoV-2 infection, particularly in terms of innate recognition and the subsequent inflammation underlying COVID-19 immunopathology.
Accelerating corneal wound healing using exosome-mediated targeting of NF-κB c-Rel
Authors: Zhao Wenbo , He Xiaozhen , Liu Ruiling , Ruan Qingguo
Published: January 2023

The integrity of the corneal epithelium is essential for the maintenance of the physiological function of the cornea. Studies have found that inflammation greatly delays corneal wound healing. NF-κB c-Rel is preferentially expressed by immune cells and promotes the expression of inflammatory cytokines. In the current study, we sought to investigate whether c-Rel could be used as a potential therapeutic target for treating a corneal injury. Our studies reveal that expressions of c-Rel and its inflammatory targets are significantly increased in the cornea of mice with corneal injury. In addition, we find that c-Rel-deficient mice exhibit accelerated corneal wound healing and reduced expression of inflammatory cytokines. Further studies show that topical treatment on the corneal surface using nano-polymers or exosomes loaded with c-Rel-specific siRNA (siRel) can effectively accelerate regular and diabetic corneal wound healing. More importantly, we find that exosomes, as carriers of siRel, showed better efficacy than nano-polymers in treating corneal injury. We further demonstrate that exosomes secreted by mesenchymal stem cells can efficiently transfer siRNA into macrophages and dendritic cells but not T cells. Taken together, these results indicate that blocking c-Rel may represent an attracting strategy for the treatment of both regular and diabetic corneal injury.
Eco-friendly management of Spodoptera litura (Lepidoptera: Noctuidae) in tomato under polyhouse and field conditions using Heterorhabditis bacteriophora Poinar, their associated bacteria (Photorhabdus luminescens), and Bacillus thuringiensis var. kurstaki
Authors: Thakur Neelam , Tomar Preety , Kaur Jaspreet , Kaur Simranjeet , Sharma Anuja , Jhamta Samiksha , Yadav Ajar Nath , Dhaliwal Harcharan Singh , Thakur Rajesh , Thakur Seema
Published: January 2023

Background

Insect pests cause substantial agriculture losses annually, and their regulation through chemical pesticides instigates a prolonged detrimental impact on the environment and human health. The upsurge in difficulties such as pesticide residue, soil degradation and pest resistance acted as the pacesetter for research on biological control with a prime focus on entomopathogens. To aid in knowing the biocontrol potential of these creatures, the present work deals with the applications of entomopathogenic nematode Heterorhabditis bacteriophora EUPT-SD, and entomopathogenic bacteria (EPBs) Photorhabdus luminescens and Bacillus thuringiensis var. kurstaki against the 4th larval instar of Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae) in the laboratory experiment, polyhouse as well as field condition.

Results

The results demonstrated that EPB, P. luminescens, caused the highest 100% larval mortality at the highest concentration of 5 × 102 CFU/ml after 96 h of infection, followed by B. thuringiensis var. kurstaki which resulted in 98% at a concentration of 5 × 102 CFU/ml and 92% mortality at the treatment with H. bacteriophora EUPT-SD (140IJs/ml) under laboratory bioassay study. In the polyhouse and field evaluation tests, again the P. luminescens was recorded as the most effective, followed by B. thuringiensis and H. bacteriophora, respectively. It was found that the treated plots experienced lesser damage when compared to non-treated plots.

Conclusion

Applications of these pathogens are nature friendly and are a proficient alternative to synthetic chemical insecticides. It is suggested from the present investigation that the use of P. luminescens was the best biocontrol agent to overcome the local pest problems of this region because it is safe for animals, humans, non-target insect pests, plants, as well as for the environment.
Optimising the process of knowledge mobilisation in Communities of Practice: recommendations from a (multi-method) qualitative study
Authors: Swaithes Laura , Paskins Zoe , Quicke Jonathan G. , Stevenson Kay , Fell Kathy , Dziedzic Krysia
Published: January 2023

Background

Communities of Practice (CoPs) offer a strategy for mobilising knowledge and integrating evidence-based interventions into musculoskeletal practice, yet little is known about their practical application in this context. This study aimed to (i) explore the process of knowledge mobilisation in the context of a CoP to implement evidence-based interventions in musculoskeletal care and (ii) co-develop recommendations to optimise the process of knowledge mobilisation in CoPs.

Methods

A qualitative study comprising observation of a CoP and related planning meetings (n = 5), and interviews with CoP stakeholders (including clinicians, lay members, managers, commissioners, academics) (n = 15) was undertaken. Data were analysed using thematic analysis and interpreted considering the Integrated Promoting Action on Research Implementation in Health Services theory. Public contributors were collaboratively involved at key stages of the study.

Results

Four themes were identified: identifying and interpreting knowledge, practical implementation of a CoP, culture and relationship building, and responding to the external context. Resource and infrastructure enabled the set-up, delivery and running of the CoP. Support for lay members is recommended to ensure effective participation and equity of power. CoP aims and purpose can develop iteratively, and this may enhance the ability to respond to contextual changes. Several recommendations for the practical application of CoPs are suggested to create the best environment for knowledge exchange and creation, support an equitable platform for participation, and help members to navigate and make sense of the CoP in a flexible way.

Conclusion

This study identified how a CoP with diverse membership can promote partnership working at the intersection between knowledge and practice. Several important considerations for preparing for and operationalising the approach in implementation have been identified. Evaluation of the costs, effectiveness and impact of CoPs is needed to better understand the value added by the approach. More broadly, research is needed to explore the practical application of online CoPs and the role of international CoPs in optimising the uptake of innovations and best practice.
Therapeutic monitoring of plasma clozapine andN-desmethylclozapine (norclozapine): practical considerations
Authors: Flanagan Robert J. , Gee Siobhan , Belsey Sarah , Couchman Lewis , Lally John
Published: January 2023

Clozapine dose assessment in treatment-refractory schizophrenia is complicated. There is a narrow margin between an effective and a potentially toxic dose and wide inter-individual variation in clozapine metabolic capacity. Moreover, factors such as changes in smoking habit, infection/inflammation, co-prescription of certain drugs, notably fluvoxamine, and age alter the dose requirement within individuals. Therapeutic drug monitoring (TDM) of plasma clozapine andN-desmethylclozapine (norclozapine) can help assess adherence, guide dosage and guard against toxicity. This article gives an overview of clozapine pharmacokinetics and factors affecting clozapine dose requirements. It then outlines the procedures and processes of clozapine TDM, from taking the blood sample for laboratory assay or point-of-contact (finger-prick) testing (POCT) to interpreting and acting on the results.
Dissociation, trauma and the experience of visual hallucinations in post-traumatic stress disorder and schizophrenia
Authors: Quidé Yann
Published: January 2023

Dissociative behaviours and hallucinations are often reported in trauma-exposed people with schizophrenia spectrum disorders and post-traumatic stress disorder (PTSD). Auditory hallucinations are the most commonly reported type of hallucination, but often co-occur with experiences in other sensory modalities. The phenomenology and the neurobiological systems involved in visual experiences are not well characterised. Are these experiences similar in nature, content or severity among people with schizophrenia and/or PTSD? What are the neurobiological bases of these visual experiences and what is the role of dissociative behaviours in the formation of these experiences? A study by Wearne and colleagues in BJPsych Open aimed to characterise these phenomenological systems in groups of people with PTSD, schizophrenia or both (schizophrenia + PTSD).
Product Quality Research for Developing and Assessing Regulatory Submissions for Generic Cyclosporine Ophthalmic Emulsions
Authors: Belenos Avery , Wood Erin Leigh , Hu Meng , Kozak Darby , Xu Xiaoming , Fisher Adam C.
Published: January 2023

Approval of the first generic 0.05% cyclosporine ophthalmic emulsion (COE) in the U.S. represents a milestone achievement of the science and research program in the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research (CDER). COE is a locally acting complex drug product indicated to increase tear production in patients whose production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca. The path to approval required overcoming numerous scientific challenges to determining therapeutic equivalence to the reference listed drug. Researchers in CDER’s Office of Pharmaceutical Quality and Office of Generic Drugs developed a quality by design approach to understand the effects of process and formulation variables on the product’s critical quality attributes, including globule size distribution (GSD), turbidity, viscosity, zeta potential, surface tension, and osmolality. CDER researchers explored multiple techniques to perform physicochemical characterization and analyze the GSD including laser diffraction, nanoparticle tracking analysis, cryogenic transmission electron microscopy, dynamic light scattering, asymmetric field flow fractionation, and two-dimensional diffusion ordered spectroscopy nuclear magnetic resonance. Biphasic models to study drug transfer kinetics demonstrated that COEs with qualitative and quantitative sameness and comparable GSDs, analyzed using earth mover’s distance, can be therapeutic equivalents. This body of research facilitated the review and approval of the first U.S. generic COE. In addition, the methods and fundamental understanding developed from this research may support the development and assessment of other complex generics. The approval of a generic COE should improve the availability of this complex drug product to U.S. patients.

Graphical Abstract
Recommended Best Practices in Freeze Dryer Equipment Performance Qualification: 2022
Authors: Ganguly Arnab , Hardwick Lisa , Tchessalov Serguei , Nail Steven L. , Dixon Dan , Kanka Frank , Guidinas Anthony , Thompson T. N. , Reiter Cindy , Yusoff Zakaria , Tharp Ted , Azzarella Joseph , Sharma Prerona , Kazarin Petr , Alexeenko Alina , Pikal Michael J.
Published: January 2023

Best practices for performing freeze dryer equipment qualification are recommended, focusing on identifying methods to quantify shelf thermal uniformity (also known as “shelf surface uniformity”), equipment capability, and performance metrics of the freeze dryer essential to the pharmaceutical Quality by Design paradigm. Specific guidelines for performing shelf temperature mapping, freeze dryer equipment limit testing (the capability curve), and condenser performance metrics have been provided. Concerning shelf temperature mapping and equipment capability measurements, the importance of paying attention to the test setup and the use of appropriate testing tools are stressed. In all the guidelines provided, much attention has been paid to identifying the balance between obtaining useful process knowledge, logistical challenges associated with testing in the production environment vs that at laboratory scale, and the frequency of the testing necessary to obtain such useful information. Furthermore, merits and demerits of thermal conditions maintained on the cooled surfaces of the freeze dryer condenser have been discussed identifying the specific influence of the condenser surface temperature on the process conditions using experimental data to support the guidelines. Finally, guidelines for systematic leak rate testing criteria for a freeze dryer are presented. These specific procedural recommendations are based on calculations, measurements, and experience to provide useful process and equipment knowledge.

Graphical Abstract
Second harmonic in FELs: Generation, amplification and suppression
Authors: Zhukovsky K. V.
Published: January 2023

Theoretical analysis of the second harmonic generation in undulators shows physical reasons for their radiation in free electron lasers (FELs). The harmonic powers, the second in particular, are calculated with several different analytical approaches and compared with each other and with well documented experimental data for LEUTL and LCLS FELs. Various contributions to the harmonic powers are distinguished, their influence is explored. The possibility to suppress the second harmonic radiation by the second harmonic of the undulator magnetic field is shown in the example of LCLS FEL. The amplification and radiation of the second FEL harmonic in a FEL, using harmonic lasing self-seed (HLSS), is shown in the example of SwissFEL with separate harmonic buncher and amplifier.
Progesterone Receptor Gene Polymorphisms and Breast Cancer Risk
Authors: Vang Alecia , Salem Kelley , Fowler Amy M
Published: January 2023

The objective of this systematic review was to investigate the association between polymorphisms in the progesterone receptor gene (PGR) and breast cancer risk. A search of PubMed, Scopus, and Web of Science databases was performed in November 2021. Study characteristics, minor allele frequencies, genotype frequencies, and odds ratios were extracted. Forty studies met the eligibility criteria and included 75 032 cases and 89 425 controls. Of the 84 PGR polymorphisms reported, 7 variants were associated with breast cancer risk in at least 1 study. These polymorphisms included an Alu insertion (intron 7) and rs1042838 (Val660Leu), also known as PROGINS. Other variants found to be associated with breast cancer risk included rs3740753 (Ser344Thr), rs10895068 (+331G/A), rs590688 (intron 2), rs1824128 (intron 3), and rs10895054 (intron 6). Increased risk of breast cancer was associated with rs1042838 (Val660Leu) in 2 studies, rs1824128 (intron 3) in 1 study, and rs10895054 (intron 6) in 1 study. The variant rs3740753 (Ser344Thr) was associated with decreased risk of breast cancer in 1 study. Mixed results were reported for rs590688 (intron 2), rs10895068 (+331G/A), and the Alu insertion. In a pooled analysis, the Alu insertion, rs1042838 (Val660Leu), rs3740753 (Ser344Thr), and rs10895068 (+331G/A) were not associated with breast cancer risk. Factors reported to contribute to differences in breast cancer risk associated with PGR polymorphisms included age, ethnicity, obesity, and postmenopausal hormone therapy use. PGR polymorphisms may have a small contribution to breast cancer risk in certain populations, but this is not conclusive with studies finding no association in larger, mixed populations.
Vertebral Bone Quality Score Independently Predicts Proximal Junctional Kyphosis and/or Failure After Adult Spinal Deformity Surgery
Authors: Kuo Cathleen C. , Soliman Mohamed A. R. , Aguirre Alexander O. , Ruggiero Nicco , Kruk Marissa , Khan Asham , Ghannam Moleca M. , Almeida Neil D. , Jowdy Patrick K. , Smolar David E. , Pollina John , Mullin Jeffrey P.
Published: January 2023

BACKGROUND:

Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) can be catastrophic complications associated with adult spinal deformity (ASD) surgery. These complications are markedly influenced by osteoporosis, leading to additional vertebral fracture and pedicle screw loosening. The MRI-based vertebral bone quality score (VBQ) is a newly developed tool that can be used to assess bone quality.

OBJECTIVE:

To investigate the utility of the VBQ score in predicting PJK and/or PJF (PJF/PJK) after ASD correction.

METHODS:

We conducted a retrospective chart review to identify patients age ≥50 years who had received ASD surgery of 5 or more thoracolumbar levels. Demographic, spinopelvic parameters, and procedure-related variables were collected. Each patient's VBQ score was calculated using preoperative T1-weighted MRI. Univariate analysis and multivariate logistic regression were performed to determine potential risk factors of PJK/PJF. Receiver operating characteristic analysis and area-under-the-curve values were generated for prediction of PJK/PJF.

RESULTS:

A total of 116 patients were included (mean age, 64.1 ± 6.8 years). Among them, 34 patients (29.3%) developed PJK/PJF. Mean VBQ scores were 3.13 ± 0.46 for patients with PJK/PJF and 2.46 ± 0.49 for patients without, which was significantly different between the 2 groups (P < .001). On multivariate analysis, VBQ score was the only significant predictor of PJK/PJF (odds ratio = 1.745, 95% CI = 1.558-1.953, P < .001), with a predictive accuracy of 94.3%.

CONCLUSION:

In patients undergoing ASD correction, higher VBQ was independently associated with PJK/PJF occurrence. Measurement of VBQ score on preoperative MRI may be a useful adjunct to ASD surgery planning.
Nailed Through Superior Sagittal Sinus: A Case Report and Surgical Considerations
Authors: Kow Chien Yew , Hakim Jeffrey S. , Aspoas A Robert , Brew Stefan , McGuinness Ben , Correia Jason
Published: January 2023

BACKGROUND AND IMPORTANCE:

We report a case of nail gun–related penetrating brain injury, puncturing through the anterior third of superior sagittal sinus, which remained patent and was associated with an arteriovenous (AV) shunt revealed on catheter angiogram.

CLINICAL PRESENTATION:

A previously well 35-year-old male patient presented with a self-inflicted pneumatic nail gun injury. Neurological examination was unremarkable. Computed tomography (CT) of the brain demonstrated the nail had penetrated through the skull, traversed the anterior third of the superior sagittal sinus (SSS), right frontal lobe parenchyma, frontal horn of right lateral ventricle, caudate, and right cerebral peduncle. CT angiogram showed no associated vascular injury, with CT venogram showing a short segment of filling defect within SSS adjacent to nail penetration. However, digital subtraction angiography revealed an associated arteriovenous shunt 8 mm anterior to the dural penetration site, which filled the SSS in arterial phase. Removal of the nail was performed using a double concentric craniotomy around the nail entry site. Before removal of the nail, the SSS anterior to the nail penetration site was tied off and divided along with coagulation and division of the falx, while the SSS posterior to the nail penetration site was also tied off to isolate the penetrated SSS segment. The patient recovered well with repeat digital subtraction angiography demonstrating no residual AV shunting.

CONCLUSION:

This case report aims to highlight the importance of performing a catheter angiogram and describe our stepwise considerations and approach in treating a penetrating injury involving the superior sagittal sinus with concurrent AV fistula.
Balloon-Assisted Corpus Callosotomy. Reducing the Impact of Transcallosal Approaches
Authors: Paolini Sergio , Severino Rocco , Ciavarro Marco , Missori Paolo , Cardarelli Giovanni , Mancarella Cristina
Published: January 2023

BACKGROUND:

The interhemispheric transcallosal approach is widely used to remove intraventricular lesions. Corpus callosotomy gives immediate access to the ventricular chambers but is invasive in nature. Loss of callosal fibers, although normally tolerate, may cause disturbances ranging from a classical disconnection syndrome up to minor neuropsychological changes.

OBJECTIVE:

To open an operative window in the corpus callosum through separation rather than disconnection of the white matter fibers.

METHODS:

In 7 patients undergoing the interhemispheric transcallosal approach for intraventricular lesions, lying around or below the foramen of Monro, a stoma was created within the corpus callosum by using a 4F Fogarty catheter. The series included 3 colloid of the third ventricle, 2 thalamic cavernomas, 1 subependymoma, and 1 ependymoma of the foramen of Monro. We illustrate the technique and the clinico-radiological outcome, focusing on the size of callosotomy as seen on postoperative MRI.

RESULTS:

The balloon-assisted corpus callosotomy provided a circular, smooth-walled access to the ventricular chambers, which allowed uncomplicated removal of the lesions. On postoperative MRI, the size of the callosotomy shrinked compared with surgery (2.8-6.4 mm at follow-up vs 6-9 mm as measured intraoperatively). No signs of disconnection syndrome or new permanent deficits were observed in this series.

CONCLUSION:

The balloon-assisted technique produces a small callosotomy, without clinical consequences, showing a self-closing trend on postoperative MRI. This technique is a rewarding tool to reduce the impact of callosotomy while keeping the advantages of microsurgical interhemispheric approaches.
Supraclinoid Internal Carotid Artery Dolichoectasia Causing Compression of the Prechiasmatic Optic Nerve
Authors: Gamboa Nicholas T. , Makarenko Serge , Couldwell William T.
Published: January 2023

BACKGROUND AND IMPORTANCE:

Intracranial arterial dolichoectasia (or dilatative arteriopathy) is characterized by abnormal elongation, tortuosity, or increase in diameter of at least one of the main cerebral vessels. Dolichoectasia can be found incidentally or can present with cranial neuropathies (including vision loss) or stroke. Here, we describe the presentation and open surgical treatment of a patient with dolichoectasia of the intracranial internal carotid artery (ICA) causing monocular vision loss.

CLINICAL PRESENTATION:

A 73-year-old man presented with several months of progressive monocular vision loss and was found to have dolichoectasia of the supraclinoid ICA and subsequently underwent microsurgical decompression of the overlying affected optic nerve. The patient's postoperative convalescence was uncomplicated, and he had improvement in his right-sided monocular vision loss after surgery.

CONCLUSION:

We present the case of a patient with dolichoectasia of the supraclinoid ICA causing compression of the optic nerve with resultant monocular vision loss. Timely microvascular decompression proves to be an effective technique for vision preservation in the setting of this rare pathologic entity.
The “Crista Ovale”: A Reliable Anatomical Landmark in Transorbital Endoscopic Approaches to the Middle Cranial Fossa
Authors: Yanez-Siller Juan C. , Noiphithak Raywat , Martinez-Perez Rafael , Dallan Iacopo , Moe Kris S. , Revuelta Barbero Juan M. , Howe Edmund , Prevedello Daniel M. , Carrau Ricardo L.
Published: January 2023

BACKGROUND:

Transorbital endoscopic approaches (TOEAs) have emerged as adjunct and alternatives for accessing the middle cranial fossa (MCF). Nuances of the skull base anatomy from a ventral transorbital endoscopic viewpoint remain to be fully described.

OBJECTIVE:

To assess the anatomy of the “crista ovale” (COv), described transcranially as the midsubtemporal ridge (MSR), from a ventral transorbital perspective and evaluate its role as a landmark in TOEA to the MCF.

METHODS:

Lateral TOEAs to the MCF were performed in 20 adult cadaveric heads (40 sides). The presence of the COv/MSR was evaluated under endoscopic visualization. Anatomic relationships between COv/MSR and surrounding structures were assessed. The presence of COv/MSR was also examined in 30 cadaveric head computed tomography (CT) scans (60 sides).

RESULTS:

The COv/MSR was identified in 98% (39/40) of sides at the MCF, as 1 of 4 major configurations. The COv/MSR was found anterolateral to the foramen ovale and foramen spinosum (mean distance: 9.2 ± SD 2.4 mm and 12.3 ± SD 2.6 mm, respectively) directly anterior or anteromedial to the petrous apex (mean distance: 26.2 ± SD 2.6 mm) and at a mean 47.6 ± SD 4.7 mm from the approach's surgical portal. It was recognized in 95% (57/60) of CT scans.

CONCLUSION

The COv/MSR can be readily identified during TOEA to the MCF and on CT. It serves as a reliable landmark to localize the foramen ovale, foramen spinosum, and petrous apex. Further studies may confirm its surgical significance in transorbital endoscopic procedures.