bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic insights into zoonotic transmission and antimicrobial resistance in Campylobacter jejuni from farm to fork: a one health perspective
Authors: dessouky Yara El , Elsayed Salma W. , Abdelsalam Nehal Adel , Saif Nehal A. , Álvarez-Ordóñez Avelino , Elhadidy Mohamed
Published: December 2022

Background

Campylobacteriosis represents a global public health threat with various socio-economic impacts. Among different Campylobacter species, Campylobacter jejuni (C. jejuni) is considered to be the foremost Campylobacter species responsible for most of gastrointestinal-related infections. Although these species are reported to primarily inhabit birds, its high genetic and phenotypic diversity allowed their adaptation to other animal reservoirs and to the environment that may impact on human infection.

Main body

A stringent and consistent surveillance program based on high resolution subtyping is crucial. Recently, different epidemiological investigations have implemented high-throughput sequencing technologies and analytical pipelines for higher resolution subtyping, accurate source attribution, and detection of antimicrobial resistance determinants among these species. In this review, we aim to present a comprehensive overview on the epidemiology, clinical presentation, antibiotic resistance, and transmission dynamics of Campylobacter, with specific focus on C. jejuni. This review also summarizes recent attempts of applying whole-genome sequencing (WGS) coupled with bioinformatic algorithms to identify and provide deeper insights into evolutionary and epidemiological dynamics of C. jejuni precisely along the farm-to-fork continuum.

Conclusion

WGS is a valuable addition to traditional surveillance methods for Campylobacter. It enables accurate typing of this pathogen and allows tracking of its transmission sources. It is also advantageous for in silico characterization of antibiotic resistance and virulence determinants, and hence implementation of control measures for containment of infection.
Mycoplasma gallisepticum escapes the host immune response via gga-miR-365-3p/SOCS5/STATs axis
Authors: Wang Yingjie , Han Yun , Wang Lulu , Zou Mengyun , Sun Yingfei , Sun Huanling , Guo Qiao , Peng Xiuli
Published: December 2022

A disruption in the expression of gga-miR-365-3p was confirmed in theMycoplasma gallisepticum(MG)-infected Chicken primary alveolar type II epithelial (CP-II) cells based on previous sequencing results, but the role it plays in the infection was unclear. In the present study, we demonstrate that MG evaded cellular host immunity via a gga-miR-365-3p/SOCS5-JAK/STATs negative feedback loop. Specifically, we found that at the initial stage of MG infection in cells, gga-miR-365-3p was rapidly increased and activated the JAK/STAT signaling pathway by inhibiting SOCS5, which induced the secretion of inflammatory factors and triggered immune response against MG infection. Over time, though, the infection progressed, MG gradually destroyed the immune defences of CP-II cells. In late stages of infection, MG escaped host immunity by reducing intracellular gga-miR-365-3p and inhibiting the JAK/STAT pathway to suppress the secretion of inflammatory factors and promote MG adhesion or invasion. These results revealed the game between MG and host cell interactions, providing a new perspective to gain insight into the pathogenic mechanisms of MG or other pathogens. Meanwhile, they also contributed to novel thoughts on the prevention and control of MG and other pathogenic infections, shedding light on the immune modulating response triggered by pathogen invasion and their molecular targeting.

Graphic Abstract
Astrocyte derived TSP2 contributes to synaptic alteration and visual dysfunction in retinal ischemia/reperfusion injury
Authors: Hu Tu , Meng Shuhan , Zhang Qianyue , Song Shuang , Tan Cheng , Huang Jufang , Chen Dan
Published: December 2022

Background

Despite current intervention measures/therapies are able to ameliorate neuronal death following retinal injuries/diseases, the recovery of visual function remains unsatisfactory. Previous studies revealed that the retinal synapse and neurite changed during the early stage after retinopathy, which was considered to be detrimental to visual signal transmission. However, the specific profiles and the mechanisms underlying retinal neurite and synaptic alteration after retinal pathologies remain poorly understood.

Methods

Here, we revealed the spatiotemporal pattern of neurite and synaptic alteration following retinal pathologies using a rat model of acute RI/R induced by high intraocular pressure (HIOP) with Western blotting, Immunofluorescence, and electron microscopy. We further explored the potential role of activated astrocytes and their derived thrombospondin 2 (TSP2) in RI/R induced retinal neurite and synaptic alteration and visual dysfunction through viral transduction and drug injection.

Results

We found a defasciculation of RGC axons, a compensatory increase of presynaptic proteins (synaptophysin and synapsin 1) and synaptic vesicles between bipolar cells and ganglion cells in the inner plexiform layer (IPL), and the degenerated visual function preceded the neuronal death in rat retinae. These events were accompanied by the activation of astrocytes. Furthermore, we showed that suppressing the activation of astrocytes (intravitreal injection of fluorocitric acid, FC), TSP2 knockdown (TSP2 shRNA-AAV transduction), and competitively inhibiting the binding of TSP2 and α2δ1 (intraperitoneal injection of gabapentin, GBP) effectively alleviated the retinal synaptic and neurite alteration and the visual dysfunction following RI/R injury.

Conclusions

(1) At the early stage following RI/R injury, the rat retinae develop a degeneration of ganglion cell axons and the resulting compensatory synaptic remodeling between bipolar cells and ganglion cells in IPL. These changes occur earlier than the massive loss of neurons in the ganglion cell layer (GCL). (2) Activated astrocytes may secret TSP2, which bind to α2δ1, to mediate the degeneration of rat retinal ganglion cell axons, compensatory synaptic remodeling in IPL, and visual dysfunction following RI/R injury.
Analysis of influencing factors on excellent teachers' professional growth based on DB-Kmeans method
Authors: Gao Xu , Ding Xiaoming , Han Tingting , Kang Yueyuan
Published: December 2022

The Kmeans clustering algorithm is widely used for the advantages of simplicity and efficient operation. However, the lack of clustering centers in the algorithm usually causes incorrect category of some discrete points. Therefore, in order to obtain more accurate clustering results when studying the factors affecting the professional growth of outstanding teachers, this paper proposes an improved algorithm of Kmeans combined with DBSCAN. Observing the clustering results of the influencing factors and calculating the evaluation standard values of the clustering results, it is found that the optimized DB-Kmeans algorithm has obvious improvements in the accuracy of the clustering results, and the clustering effect of the algorithm on edge points is more advantageous than the original algorithms according to the scatter diagram.
Software architecture for pervasive critical health monitoring system using fog computing
Authors: Ilyas Abeera , Alatawi Mohammed Naif , Hamid Yasir , Mahfooz Saeed , Zada Islam , Gohar Neelam , Shah Mohd Asif
Published: December 2022

Because of the existence of Covid-19 and its variants, health monitoring systems have become mandatory, particularly for critical patients such as neonates. However, the massive volume of real-time data generated by monitoring devices necessitates the use of efficient methods and approaches to respond promptly. A fog-based architecture for IoT healthcare systems tends to provide better services, but it also produces some issues that must be addressed. We present a bidirectional approach to improving real-time data transmission for health monitors by minimizing network latency and usage in this paper. To that end, a simplified approach for large-scale IoT health monitoring systems is devised, which provides a solution for IoT device selection of optimal fog nodes to reduce both communication and processing delays. Additionally, an improved dynamic approach for load balancing and task assignment is also suggested. Embedding the best practices from the IoT, Fog, and Cloud planes, our aim in this work is to offer software architecture for IoT-based healthcare systems to fulfill non-functional needs. 4 + 1 views are used to illustrate the proposed architecture.
The in situ efficacy of whole room disinfection devices: a literature review with practical recommendations for implementation
Authors: van der Starre Caroline M. , Cremers-Pijpers Suzan A. J. , van Rossum Carsten , Bowles Edmée C. , Tostmann Alma
Published: December 2022

Background

Terminal cleaning and disinfection of hospital patient rooms must be performed after discharge of a patient with a multidrug resistant micro-organism to eliminate pathogens from the environment. Terminal disinfection is often performed manually, which is prone to human errors and therefore poses an increased infection risk for the next patients. Automated whole room disinfection (WRD) replaces or adds on to the manual process of disinfection and can contribute to the quality of terminal disinfection. While the in vitro efficacy of WRD devices has been extensively investigated and reviewed, little is known about the in situ efficacy in a real-life hospital setting. In this review, we summarize available literature on the in situ efficacy of WRD devices in a hospital setting and compare findings to the in vitro efficacy of WRD devices. Moreover, we offer practical recommendations for the implementation of WRD devices.

Methods

The in situ efficacy was summarized for four commonly used types of WRD devices: aerosolized hydrogen peroxide, H2O2 vapour, ultraviolet C and pulsed xenon ultraviolet. The in situ efficacy was based on environmental and clinical outcome measures. A systematic literature search was performed in PubMed in September 2021 to identify available literature. For each disinfection system, we summarized the available devices, practical information, in vitro efficacy and in situ efficacy.

Results

In total, 54 articles were included. Articles reporting environmental outcomes of WRD devices had large variation in methodology, reported outcome measures, preparation of the patient room prior to environmental sampling, the location of sampling within the room and the moment of sampling. For the clinical outcome measures, all included articles reported the infection rate. Overall, these studies consistently showed that automated disinfection using any of the four types of WRD is effective in reducing environmental and clinical outcomes.

Conclusion

Despite the large variation in the included studies, the four automated WRD systems are effective in reducing the amount of pathogens present in a hospital environment, which was also in line with conclusions from in vitro studies. Therefore, the assessment of what WRD device would be most suitable in a specific healthcare setting mostly depends on practical considerations.
Familial load of psychiatric disorders and overall functioning in patients newly diagnosed with bipolar disorder and their unaffected first-degree relatives
Authors: Sletved Kimie Stefanie Ormstrup , Maiggaard Katrine , Thorup Anne Amalie Elgaard , Kessing Lars Vedel , Vinberg Maj
Published: December 2022

Background

Overall functioning is already impaired in patients newly diagnosed with bipolar disorder (BD) and, to a lesser degree, also in their unaffected first-degree relatives (UR). Further, aggregation of psychiatric disorders among the patients’ first-degree relatives seems to be associated with higher illness burden and poorer prognosis. However, whether this aggregation of psychiatric disorders among first-degree relatives, the familial load (FL), impacts overall functioning in patients newly diagnosed with BD and their UR remains unresolved.

Methods

In total, 388 patients newly diagnosed with BD, 144 of their UR and 201 healthy control individuals were included. Overall functioning was assessed using three different assessment methods: The interviewer based “Functioning Assessment Short Test” (FAST), the questionnaire “Work and Social Adjustment Scale” (WSAS) and six outcome measures covering the participants’ socio-economic status (SES); educational achievement, employment, work ability, relationship, cohabitation and marital status. Familial load of psychiatric disorder was assessed using the “Family History Research Diagnostic Criteria” interview. Associations between FL and overall functioning in patients and UR were investigated categorically using logistic and continuously in linear regression models.

Results

Contrasting with the hypotheses, the FL of psychiatric disorders was not associated with impaired overall functioning, neither in patients newly diagnosed with BD nor in their UR.

Conclusion

The findings indicate that impaired functioning in the early phase of BD is not associated with aggregation of psychiatric disorders among first-degree relatives. The observed functional impairment in patients newly diagnosed with BD seems driven by the personal impact of the disorder rather than the impact of having first-degree relatives with psychiatric disorders. Keywords: bipolar disorder, first-degree relatives, familial load of psychiatric disorders, functioning, socio-economic status.
Adaption and validation of the Perceived Control of Internal States Scale (PCOISS) in Chinese adults: a cross-sectional study
Authors: Chen Yantao , Yao Zhuxi , Wang Naiyi , Wu Jianhui , Xin Yuanyuan
Published: December 2022

Background

Perceived control of internal states is important for disease prevention, stress buffering and life adaptability. However, there is no psychometric scale to measure control beliefs over internal states in China. This study aimed to adapt and validate the Perceived Control of Internal States Scale (PCOISS) in a large sample of Chinese adults.

Methods

Data was collected through a big project, in which a cross-sectional online survey was conducted nationwide in China using a powerful Chinese online survey platform named WenJuanXing (https://www.wjx.cn/). We translated the PCOISS into Chinese (C-PCOISS) with the forward–backward translation procedure. For the first time of the survey, a sample of 2709 participants (Sample 1) was valid for final analysis. Sample 1 was split into two datasets for principal component analysis (PCA) (nA = 1355) and confirmatory factor analyses (CFA) (nB = 1354) to determine potential factor structure. The scale’s validity (i.e., discriminant validity, convergent validity, criterion validity) and internal consistency reliability were evaluated. Among the 1354 respondents (nB), 761 (nC = 761) participated in the follow-up second wave of the survey to assess a cross-sectional test–retest reliability.

Results

The C-PCOISS retained 14 items. PCA yielded a three-factor model which was supported with the best fit indices in CFA. The C-PCOISS had satisfactory internal consistency with Cronbach’s alpha coefficients of 0.86, 0.78 and 0.72 for three subscales, respectively. The scale also showed adequate test–retest reliability (Pearson correlations coefficient of 0.64, 0.62 and 0.54 with p < 0.001 for three subscales, respectively). Three factors of the C-PCOISS were positively associated with positive affect, and negatively associated with negative affect, depression, compulsion-anxiety and perceived stress.

Conclusions

The C-PCOISS is reliable and valid for measuring control beliefs over internal states in Chinese adults.
The impact of outcome expectancy on therapy outcome in adolescents with borderline personality disorder
Authors: Bäumer Anna-Valeska , Fürer Lukas , Birkenberger Carolin , Wyssen Andrea , Steppan Martin , Zimmermann Ronan , Gaab Jens , Kaess Michael , Schmeck Klaus
Published: December 2022

Background

Outcome expectancy has been found to be a significant predictor of psychotherapy outcome. However, given that severity, chronicity and comorbidity are moderators of outcome expectancy, it is important to provide evidence of whether the same holds true in clinical conditions marked by these attributes, such as in borderline personality disorder (BPD). The aim of the present study was to investigate the role of patients’ outcome expectancy in adolescents undergoing early intervention for BPD using pre-post difference of psychosocial functioning as outcome.

Methods

Forty-four adolescent BPD patients were treated with Dialectical Behavior Therapy for Adolescents (DBT-A) or Adolescent Identity Treatment (AIT). We investigated the effect of outcome expectancy on outcome with type of treatment as moderator. Based on the relevant literature, we assess the correlation between outcome expectancy and pretreatment symptomatology, namely BPD severity, personality functioning, childhood trauma and depression.

Results

The results showed a significant effect of expectancy on outcome (stand. β = 0.30,p = 0.020) above autoregression. ANOVA analysis revealed no difference between the two treatments. Further, results indicate that pretreatment symptomatology, i.e., depression, childhood trauma and personality functioning dimensions self-direction and intimacy, are associated with early treatment expectancy.

Conclusion

Outcome expectancy as a common factor plays a key role in successful psychotherapy with adolescent BPD patients. Elevated pretreatment depression, childhood trauma and impairment in personality functioning dimensions self-direction and intimacy are risk factors associated with lower expectancy. Low outcome expectancy should be addressed in early psychotherapy to improve the therapeutical process.
Effects of bacterial inoculants on the microbial community, mycotoxin contamination, and aerobic stability of corn silage infected in the field by toxigenic fungi
Authors: Wang Wenbo , Cai Xinyu , Shao Tao , Yangzong Zhaxi , Wang Wenkang , Ma Pengfei , Li Junfeng , Zhao Jie , Gallo Antonio , Yuan Xianjun
Published: December 2022

This study aimed to evaluate the effects of inoculants on the microbial community and mycotoxins contamination of corn silage during aerobic exposure. Whole-crop corn infected with or without mycotoxigenic fungi were ensiled with Lentilactobacillus buchneri (LB, 1.0 × 106 cfu/g fresh weight (FW)), Lactiplantibacillus plantarum (LP, 1.0 × 106 cfu/g FW), or LBLP at 1.0 × 106 cfu/g FW each. The concentration of acetic acid (AcA) (P < 0.05) in LB and LBLP silages was higher than in control (C) and LP of non-fungal infection (NFI) silages. The fungal infection resulted in a larger increase of zearalenone (ZEN, P = 0.01), fumonisin B1 (FUB1, P = 0.02), and fumonisin B2 (FUB2, P = 0.02). The relative abundance (RA) of Issatchenkia in NFI was higher (P < 0.001) than FI silages, whereas the RA of Kazachstania (P < 0.001), Zygosaccharomyces (P = 0.047), and Candida (P = 0.025) in NFI were lower than these of FI silages. The aerobic stability was improved by the application of LB and LBLP as compared with the C of NFI silages. The LB and LBLP had the potential to improve aerobic stability and alleviate mycotoxins contamination of non-fungal infected corn silages.

Graphical Abstract
Point mutation of V252 in neomycin C epimerase enlarges substrate-binding pocket and improves neomycin B accumulation in Streptomyces fradiae
Authors: Li Xiangfei , Yu Fei , Wang Fang , Wang Sang , Han Rumeng , Cheng Yihan , Zhao Ming , Sun Junfeng , Xue Zhenglian
Published: December 2022

Neomycin, an aminoglycoside antibiotic with broad-spectrum antibacterial resistance, is widely used in pharmaceutical and agricultural fields. However, separation and purification of neomycin B as an active substance from Streptomyces fradiae are complicated. Although NeoN can catalyze conversion of neomycin C to neomycin B, the underlying catalytic mechanism is still unclear. In this study, the genomic information of high-yielding mutant S. fradiae SF-2 was elucidated using whole-genome sequencing. Subsequently, the mechanism of NeoN in catalyzing conversion of neomycin C to neomycin B was resolved based on NeoN–SAM–neomycin C ternary complex. Mutant NeoNV252A showed improved NeoN activity, and the recombinant strain SF-2-NeoNV252A accumulated 16,766.6 U/mL neomycin B, with a decrease in neomycin C ratio from 16.1% to 6.28%, when compared with the parental strain SF-2. In summary, this study analyzed the catalytic mechanism of NeoN, providing significant reference for rational design of NeoN to improve neomycin B production and weaken the proportion of neomycin C.

Graphical Abstract
A novel intelligent radiomic analysis of perfusion SPECT/CT images to optimize pulmonary embolism diagnosis in COVID-19 patients
Authors: Baeza Sonia , Gil Debora , Garcia-Olivé Ignasi , Salcedo-Pujantell Maite , Deportós Jordi , Sanchez Carles , Torres Guillermo , Moragas Gloria , Rosell Antoni
Published: December 2022

Background

COVID-19 infection, especially in cases with pneumonia, is associated with a high rate of pulmonary embolism (PE). In patients with contraindications for CT pulmonary angiography (CTPA) or non-diagnostic CTPA, perfusion single-photon emission computed tomography/computed tomography (Q-SPECT/CT) is a diagnostic alternative. The goal of this study is to develop a radiomic diagnostic system to detect PE based only on the analysis of Q-SPECT/CT scans.

Methods

This radiomic diagnostic system is based on a local analysis of Q-SPECT/CT volumes that includes both CT and Q-SPECT values for each volume point. We present a combined approach that uses radiomic features extracted from each scan as input into a fully connected classification neural network that optimizes a weighted cross-entropy loss trained to discriminate between three different types of image patterns (pixel sample level): healthy lungs (control group), PE and pneumonia. Four types of models using different configuration of parameters were tested.

Results

The proposed radiomic diagnostic system was trained on 20 patients (4,927 sets of samples of three types of image patterns) and validated in a group of 39 patients (4,410 sets of samples of three types of image patterns). In the training group, COVID-19 infection corresponded to 45% of the cases and 51.28% in the test group. In the test group, the best model for determining different types of image patterns with PE presented a sensitivity, specificity, positive predictive value and negative predictive value of 75.1%, 98.2%, 88.9% and 95.4%, respectively. The best model for detecting pneumonia presented a sensitivity, specificity, positive predictive value and negative predictive value of 94.1%, 93.6%, 85.2% and 97.6%, respectively. The area under the curve (AUC) was 0.92 for PE and 0.91 for pneumonia. When the results obtained at the pixel sample level are aggregated into regions of interest, the sensitivity of the PE increases to 85%, and all metrics improve for pneumonia.

Conclusion

This radiomic diagnostic system was able to identify the different lung imaging patterns and is a first step toward a comprehensive intelligent radiomic system to optimize the diagnosis of PE by Q-SPECT/CT.

Highlights

Artificial intelligence applied to Q-SPECT/CT is a diagnostic option in patients with contraindications to CTPA or a non-diagnostic test in times of COVID-19.
Targeting treatment of bladder cancer using PTK7 aptamer-gemcitabine conjugate
Authors: Xiang Wei , Peng Yongbo , Zeng Hongliang , Yu Chunping , Zhang Qun , Liu Biao , Liu Jiahao , Hu Xing , Wei Wensu , Deng Minhua , Wang Ning , Liu Xuewen , Xie Jianfei , Hou Weibin , Tang Jin , Long Zhi , Wang Long , Liu Jianye
Published: December 2022

Background

Gemcitabine (GEM) is one of the first-line chemotherapies for bladder cancer (BC), but the GEMs cannot recognize cancer cells and have a low long-term response rate and high recurrence rate with side effects during the treatment of BC. Targeted transport of GEMs to mediate cytotoxicity to tumor and avoid the systemic side effects remains a challenge in the treatment of BC.

Methods

Based on a firstly confirmed biomarker in BC-protein tyrosine kinase 7 (PTK7), which is overexpressed on the cell membrane surface in BC cells, a novel targeting system protein tyrosine kinase 7 aptamer-Gemcitabine conjugate (PTK7-GEMs) was designed and synthesized using a specific PTK7 aptamer and GEM through auto-synthesis method to deliver GEM against BC. In addition, the antitumor effects and safety evaluation of PTK7-GEMs was assessed with a series of in vitro and in vivo assays.

Results

PTK7-GEMs can specifically bind and enter to BC cells dependent on the expression levels of PTK7 and via the macropinocytosis pathway, which induced cytotoxicity after GEM cleavage from PTK7-GEMs respond to the intracellular phosphatase. Moreover, PTK7-GEMs showed stronger anti-tumor efficacy and excellent biosafety in three types of tumor xenograft mice models.

Conclusion

These results demonstrated that PTK7-GEMs is a successful targeted aptamer-drug conjugates strategy (APDCs) to treat BC, which will provide new directions for the precision treatment of BC in the field of biomarker-oriented tumor targeted therapy.
Growth, maturity, reproduction, and life expectancy in ex-situ pacific walruses (Odobenus rosmarus divergens)
Authors: Robeck Todd , Katsumata Etsuko , Arai Kazutoshi , Montano Gisele , Schmitt Todd , DiRocco Stacy , Steinman Karen J.
Published: December 2022

Background

Pacific walruses are found in Arctic regions of the Chukchi and Bering Sea where rapid changes in environmental conditions resulting in loss of sea ice are occurring. Therefore, accurate life history data are crucial for species management plans and longitudinal data collected over the lives of individual walruses housed in zoos and aquaria provide otherwise difficult to obtain biological information.

Results

While similar at birth, Gompertz regression curves indicated that males grew faster than females (p < 0.0001) in weight (99 kg vs 57.6 kg/y) and length (26.9 cm vs 26.3 cm/y) with physical differences being detected by age 3 for weight and age 7 for length. Males reached adult weight at 13.5 ± 3.3 y and females by age 12.3 ± 2.3 y. The mean age at first ovulation and at first conception occurred at 8.8 y and 9.6 y. Greater than 75% of all conceptions and calving occurred between February and March and from May to June, respectively. Mean gestation lasted 423 d and false pregnancies lasted at least 169 d with a decrease (p < 0.05) in serum progesterone concentration between false pregnancy and pregnancy occurring within 6 months after ovulation. Based on these results, we estimated embryonic diapause to last from 120 to 139 days, and fetal growth last ~ 284 days. All males older than 8 y had an increase in serum testosterone and body weight that was highest in February and lowest in July. Overall, no differences were observed between male and female survival, with a mean (± SEM) life expectancy of 19.5 ± 1.5 y, respectively. Currently, the oldest male and female captive walruses are 40 and 43 y, respectively.

Conclusions

Data provided herein include details of life history characteristics of zoo and aquaria housed walruses that are useful for wild population recovery models. In particular, results on survivorship and the identification of the most vulnerable period for calf survival can help with model development and suggests that for recovery to occur birthing locations for this species must be protected.
A Blueprint for Involvement: Reflections of lived experience co-researchers and academic researchers on working collaboratively
Authors:   The Blueprint Writing Collective, Fraser Claire , Carrington Bekah , Crooks Jodie , Diffey James , Evans Nicola , Kirk Sue , Lane Rhiannon , McGowan Rose , Naughton Georgia , Pryjmachuk Steven , Saund Keeya , Temple Rachel
Published: December 2022

Patient and public involvement in health research is important to ensure that research remains relevant to the patient groups it intends to benefit. The UK NIHR funded Blueprint study aimed to develop a ‘model’ of effective service design for children and young people with common mental health problems. To ensure Blueprint’s findings were rooted in lived experience and informed by different perspectives, six young adults with lived experience of mental health issues were recruited, trained and employed as co-researchers to work alongside academic researchers
. Blueprint collaborated with a third sector partner (McPin) to recruit, employ and mentor the co-researchers and deliver a bespoke training and mentoring package to support their development. Since Blueprint’s scheduled work plan was significantly impacted by the Covid-19 pandemic, planned co-researcher activities had to be adapted to accommodate distance learning and remote fieldwork and analysis. Blueprint’s co-researchers, academic researchers and a representative of McPin collaboratively used a process of reflexivity and thematic analysis to capture Blueprint’s involvement journey. We identified numerous benefits but also challenges to involvement, some of which were exacerbated by the pandemic. Navigating and overcoming these challenges also allowed us to collectively identify key guidelines for involvement for the wider research community which focus on enabling access to involvement, supporting co-researchers and optimising involvement for the benefit of co-researchers and research teams. This paper presents an overview of the Blueprint involvement journey from co-researcher, academic researcher and McPin perspectives, sharing our learning from the recruitment, training, fieldwork and analysis phases in order to inform the knowledge base on lived experience involvement and provide guidance to other researchers who seek to emulate this approach.
Meeting report: Advancing accelerated regulatory review with Real-Time Oncology Review (RTOR), Project Orbis, and the Product Quality Assessment Aid
Authors: Algorri Marquerita , Acharya Ajay , Bernstein James , Cauchon Nina S. , Chen Xiao Hong , Huynh-Ba Kim , Krantz Carol , Li Tao , Li Yiwei , McLamore Sherita , Roberts Scott W. , Schwinke David , Shah Rakhi , Schirmer Andrea , Strickland Helen , Tang Kin , Watson Timothy
Published: December 2022

The American Association of Pharmaceutical Scientists (AAPS) Chemistry, Manufacturing, and Controls (CMC) Community hosted two virtual panel discussions focusing on several novel regulatory review pathways for innovative oncology products: Real-Time Oncology Review (RTOR), Project Orbis, and the Product Quality Assessment Aid (PQAAid). The panel sessions were held on August 27, 2021, for the discussion of RTOR, and January 21, 2022, for the discussion of Project Orbis and the PQAAid. Both panel sessions included representatives from the US Food and Drug Administration (FDA) and subject matter experts from the pharmaceutical and biotechnology industries, with the aim of facilitating knowledge sharing on CMC-specific advantages, challenges, eligibility criteria for participation, and operational modifications instituted through the utilization of these acceleration initiatives. Key topics included managing cross-regional regulatory CMC requirements, adapting to expedited development timelines, coordinating interactions between health authorities and industry, and potential opportunities for future improvement and expansion of these programs. As RTOR, Project Orbis, and PQAAid are relatively new initiatives, the experiences shared by the panel experts are valuable for providing deeper insight into these new regulatory pathways and processes.
2D and 3D cultured human umbilical cord-derived mesenchymal stem cell-conditioned medium has a dual effect in type 1 diabetes model in rats: immunomodulation and beta-cell regeneration
Authors: Isildar Basak , Ozkan Serbay , Ercin Merve , Gezginci-Oktayoglu Selda , Oncul Mahmut , Koyuturk Meral
Published: December 2022

Background

Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disease characterized by the irreversible destruction of insulin-producing β-cells in pancreatic islets. Helper and cytotoxic T-cells and cytokine production, which is impaired by this process, take a synergetic role in β-cell destruction, and hyperglycemia develops due to insulin deficiency in the body. Mesenchymal stem cells (MSCs) appear like an excellent therapeutic tool for autoimmune diseases with pluripotent, regenerative, and immunosuppressive properties. Paracrine factors released from MSCs play a role in immunomodulation by increasing angiogenesis and proliferation and suppressing apoptosis. In this context, the study aims to investigate the therapeutic effects of MSC’s secretomes by conditioned medium (CM) obtained from human umbilical cord-derived MSCs cultured in 2-dimensional (2D) and 3-dimensional (3D) environments in the T1D model.

Methods

First, MSCs were isolated from the human umbilical cord, and the cells were characterized. Then, two different CMs were prepared by culturing MSCs in 2D and 3D environments. The CM contents were analyzed in terms of total protein, IL-4, IL-10, IL-17, and IFN-λ. In vivo studies were performed in Sprague-Dawley-type rats with an autoimmune T1D model, and twelve doses of CM were administered intraperitoneally for 4 weeks within the framework of a particular treatment model. In order to evaluate immunomodulation, the Treg population was determined in lymphocytes isolated from the spleen after sacrification, and IL-4, IL-10, IL-17, and IFN-λ cytokines were analyzed in serum. Finally, β-cell regeneration was evaluated immunohistochemically by labeling Pdx1, Nkx6.1, and insulin markers, which are critical for the formation of β-cells.

Results

Total protein and IL-4 levels were higher in 3D-CM compared to 2D-CM. In vivo results showed that CMs induce the Treg population and regulate cytokine release. When the immunohistochemical results were evaluated together, it was determined that CM application significantly increased the rate of β-cells in the islets. This increase was at the highest level in the 3D-CM applied group.

Conclusion

The dual therapeutic effect of MSC-CM on immunomodulation and homeostasis/regeneration of β-cells in the T1D model has been demonstrated. Furthermore, this effect could be improved by using 3D scaffolds for culturing MSCs while preparing CM.
Anatomical, scanning electron microscopy, histological and histochemical studies of the orbital glands of the Egyptian agama Trapelus mutabilis
Authors: Mahmoud Fatma Abdel-Regal , Gaber Samia Abdalla , Mahmoud Amany Salah Saad , Gadel-Rab Ali Gamal
Published: December 2022

Background

The orbital gland of the group agama (Agamidae) is not well-studied. Here is a first description of anatomical and histological studies on the orbital gland of the Egyptian agama Trapelus mutabilis.

Results

The Harderian gland (HG) of the Egyptian agama is well-developed, with a tongue shape, appearing whitish in color, and reaching approximately 1.47 mm in length. The gland can be divided into head and tail regions and lies at the medial corner of the orbit ventral to the ventralis oblique muscle and dorsal to the medialis rectus muscle. Secretory product of the HG is released into the conjunctival fornix, which is deep into the nictitating membrane. The HG is a compound tubuloacinar type, consisting of columnar and pyramidal glandular cells with rounded nuclei and lumina that are variable in size and containing pigments in the connective tissue capsule that envelops the tail portion of this gland. The glandular cells of the HG react positively to periodic acid-Schiff (PAS) and alcian blue staining at pH 2.5. In contrast, lacrimal gland (LG) of Egyptian agama is a reduced mucous gland that appears whitish in color, opens on the surface by numerous orifices at the base of nictitating membrane, and reaches approximately 0.1 mm in length. The lacrimal gland is composed of a simple tubulo-acini of columnar cells with narrow lumen and basal oval-shaped nuclei and exhibits a weak response to PAS but a strong response to alcian blue at pH 2.5.

Conclusions

Morphology of LG and HG isn't impacted by features of the orbit, such as the existence or absence of nictitating membrane and/or fixed or movable eyelid. The small size of the LG of the Egyptian agama does not affect the performance of its main function in lubricating the surface of the cornea. The pigmentation envelope of the HG of the Egyptian agama allows heat to be absorbed in order to increase its secretion activity, thereby increasing the protection of the eyes against mechanical damage. Finally, both orbital glands may play a secondary function in digestion via indirect connection with the oral cavity.
Biocontrol potential of endosymbiotic bacteria of entomopathogenic nematodes against the tomato leaf miner, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae)
Authors: Yüksel Ebubekir
Published: December 2022

Background

The tomato leaf miner, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) is a major pest of tomato plants threatening global tomato production. The control of the pest is becoming increasingly difficult due to the rapid development of resistance to insecticides. Entomopathogenic nematodes (EPNs) of families Steinernematidae and Heterorhabditidae are successful biocontrol agents for many insect pests. Recently, their bacteria, Xenorhabdus spp. and Photorhabdus spp. have attracted great attention due to their major role in the pathogenicity of EPNs. In the present study, the pathogenicity of eleven EPNs isolates belonging to Steinernema feltiae and Heterorhabditis bacteriophora species was screened against the 1st/2nd and 3rd/4th instar larvae of T. absoluta. The cell-free supernatants and cell suspensions of the symbiotic bacteria from the most efficient isolates were further evaluated for their biocontrol potential in the oral and contact treatments on the larvae of T. absoluta.

Results

KBC-4 and MCB-8 isolates of S. feltiae showed superior virulence relative to other EPNs species/isolates and induced 90% larval mortality against the 3rd/4th instar of T. absoluta larvae, whereas there were no clear differences in the efficacy of EPNs species/isolates against the 1st/2nd instar of T. absoluta. The 1st/2nd instar of T. absoluta larvae was more susceptible to cell-free supernatants and cell suspension of selected EPNs. The highest mortality (80%) was obtained from X. bovienii MCB-8 strain in the contact treatment of supernatants. In contact treatment of cell suspension, higher mortalities were obtained compared to oral treatments. Mortality rates ranged between 30 and 57.5% in the contact treatments of cell suspensions while the highest mortality did not exceed 20% in oral treatments. The antifeedant activity was observed in oral treatments of cell suspension and most of the larvae avoided feeding on treated leaves.

Conclusion

The results indicated that symbiotic bacteria of EPNs had a great potential against T. absoluta larvae and contact treatment of cell-free supernatants against early instars of T. absoluta can be an ideal application. However, further studies are needed to investigate the field effectiveness of symbiotic bacteria.
Level and relationships of academic skills and family functions with academic performance during Covid 19 pandemic
Authors: Alammar Muath A. , Ram Dushad , Almansour Ibrahim Abdulrahman , Aljammaz Abdulrhman Saad
Published: December 2022

Background

The research indicates that academic skills and family function may influence academic achievement. The Covid 19 epidemic has impacted regular academic and family function. However, there is a dearth of studies evaluating the relevance of academic skills and family function on college students' academic achievement. This research was done to determine the levels and relationships between academic achievement and study skills and family functions. Two hundred seventy-nine college students were assessed with Sociodemographic and academic proforma, Study Skills Assessment Questionnaire (SSAQ), and The McMaster Family Functioning Scale (MFFS).

Results

Results revealed that the mean score of SSAQ and MFFS were 179.92 and 17.88, respectively. Multiple regression analysis showed that the score of reading skills and the MFFS score statistically significantly predicted the score of the exam.

Conclusions

On the basis of this study's results, it is possible to conclude that reading skills and family functioning may influence academic success.
A dual tracer [11C]PBR28 and [18F]FDG microPET evaluation of neuroinflammation and brain energy metabolism in murine endotoxemia
Authors: Palandira Santhoshi P. , Carrion Joseph , Turecki Lauren , Falvey Aidan , Zeng Qiong , Liu Hui , Tsaava Tea , Herschberg Dov , Brines Michael , Chavan Sangeeta S. , Chang Eric H. , Vo An , Ma Yilong , Metz Christine N. , Al-Abed Yousef , Tracey Kevin J. , Pavlov Valentin A.
Published: December 2022

Background

Brain metabolic alterations and neuroinflammation have been reported in several peripheral inflammatory conditions and present significant potential for targeting with new diagnostic approaches and treatments. However, non-invasive evaluation of these alterations remains a challenge.

Methods

Here, we studied the utility of a micro positron emission tomography (microPET) dual tracer ([11C]PBR28 – for microglial activation and [18F]FDG for energy metabolism) approach to assess brain dysfunction, including neuroinflammation in murine endotoxemia. MicroPET imaging data were subjected to advanced conjunction and individual analyses, followed by post-hoc analysis.

Results

There were significant increases in [11C]PBR28 and [18F]FDG uptake in the hippocampus of C57BL/6 J mice 6 h following LPS (2 mg/kg) intraperitoneal (i.p.) administration compared with saline administration. These results confirmed previous postmortem observations. In addition, patterns of significant simultaneous activation were demonstrated in the hippocampus, the thalamus, and the hypothalamus in parallel with other tracer-specific and region-specific alterations. These changes were observed in the presence of robust systemic inflammatory responses manifested by significantly increased serum cytokine levels.

Conclusions

Together, these findings demonstrate the applicability of [11C]PBR28 - [18F]FDG dual tracer microPET imaging for assessing neuroinflammation and brain metabolic alterations in conditions “classically” characterized by peripheral inflammatory and metabolic pathogenesis.
Spatiotemporal dynamics of the microbial diversity on salt-preserved goatskins assessed by culturing and 16S rRNA gene amplicon sequencing
Authors: Li Xiaoguang , Sen Keya , Zhang Yuqin , Tian Yongqiang , Shi Bi
Published: December 2022

Wet-salted skin, as a special artificial high-salt environment, is rich in protein, fat, collagen and other nutrient substrates, and is a rich resource of halotolerant and halophilic microorganisms. However, knowledge gaps regarding the microbial community structure and inter taxa associations of wet-salted skin are large. In this study, the spatiotemporal dynamics and community structure of microorganisms present on wet-salted goatskins were investigated using 16S rRNA gene amplicon sequencing and culturable technique. Alpha diversity analysis based on Sobs, Chao, Ace and Shannon indices revealed that microbial diversity on the wet-salted goatskins exhibited a trend of ‘down → up → down → flat’ with time. During preservation, genera belonging to the bacteria domain such as Acinetobacter, Weissella and Streptococcus were slowly dying out, whereas those belonging to halophilic archaea such as Natrialba and Haloterrigena were gradually flourishing. Moreover, to resist high-salt stress, microorganisms on the wet-salted goatskin gradually migrated from the outside to the inside, eventually leading to the microbial diversity inside the skin being the same as or even higher than that on the skin surface. Venn diagram analysis revealed that the strains of some genera, including Psychrobacter, Salimicrobium, Salinicola, Ornithinibacillus, Halomonas, Bacillus and Chromohalobacter, were distributed throughout the interior and exterior of the wet-salted goatskin and existed during various periods. Accordingly, 45 protease-producing halophilic or halotolerant microorganisms were isolated and screened from the wet-salted goatskin using the gradient dilution plate method. Importantly, 16S rRNA genes of some bacteria exhibited less than 99.5% similarity to valid published species, indicating that they likely are novel species and have a good potential for application.

Graphical Abstract
Explicit finite-difference modeling for the acoustic scalar wave equation in tilted transverse isotropic media with optimal operators
Authors: Nikonenko Yury , Charara Marwan
Published: December 2022

We have developed an explicit finite-difference modeling scheme for the scalar acoustic wave equation in tilted transverse isotropic (TTI) media, which is computationally efficient in terms of speed and memory and can be used for reverse time migration. Our method uses local spatial operators optimized in the least-squares sense by matching the discrete operator in the wavenumber domain. The calculated operator is applied locally to the wavefield in the space-time domain when the medium is TTI and turns into a conventional finite-difference operator when the medium is isotropic. Our wavefield modeling is stable with no limits such as [Formula: see text] on anisotropic parameters and does not generate S-wave artifacts. The accuracy and the efficiency of our modeling scheme are demonstrated for homogeneous, two half-space TTI, and the BP 2007 TTI models.
Model parameter design for modeling surface topography in VTI elastic finite-difference near-surface simulations
Authors: Zhou Xuhui , Huo Shoudong , Wang Hao , Dong Shuli , Liang Yao , Cao Jian
Published: December 2022

The near-surface anisotropy is one of the factors leading to an inaccurate velocity estimation in the shallow area, which has a strong impact on the static correction of land data and seismic imaging of the subsurface in depth. To investigate the anisotropy influence, the consideration of medium anisotropy in near-surface seismic modeling becomes necessary. In the oil and gas industry, finite-difference (FD) methods are commonly used for seismic wave modeling, thanks to their simplicity, accuracy, and high efficiency. However, for near-surface modeling, the implementation of free-surface boundary conditions and nonflat topography representation are the two main obstacles preventing the effectiveness of FD methods. To address these two issues in the vertical transversely isotropic anisotropic scenarios, we have developed a simple and efficient method for the discrete model design which can be easily applied to the conventional Cartesian-grid FD modeling. Our method involves: (1) the parameter-averaging method for implicitly implementing the stress-free condition by a modification of model anisotropy parameters near the (non) flat free-surface boundary and (2) an independent wavefield superposition with modeling results of different parameter configurations to accurately represent the rugged topography and significantly reduce the staircase diffractions caused by a staircase approximation of continuous surface in the Cartesian-grid discretization. For validation of this method, we conduct several numerical tests in 2D and 3D spaces. The accuracy is demonstrated by a comparison of the spectral-element solutions of SPECFEM in modeling the seismic wave propagation in the presence of an irregular free surface. From the aspect of computational efficiency, it is more promising in practical applications due to the use of wavefield superposition strategy in this method which does not require finer spatial sampling to eliminate the staircase diffractions.