bluuebunny/crossref_metadata_2025 huggingface dataset:
Closure of Macular Holes With Topical Therapy
Authors: Small Kent W. , Avetisjan Jessica , Shaya Fadi S.
Published: December 2022

Purpose: To report the results of a nonsurgical approach to repair macular holes (MHs). Methods: A retrospective chart review of consecutive patients with MHs from 2018 to 2021 was performed. Topical therapy consisted of a steroidal agent, a nonsteroidal agent, and a carbonic anhydrase inhibitor. Data collected included the size, stage, and duration of the MH; topical agents used and the duration; lens status; and complications. Macular edema was graded on a scale ranging from 0 (no edema) to 4 (large amount of edema) and recorded. Before and after MH closure, the best-corrected visual acuity (BCVA) was measured and converted to logMAR notation. Spectral-domain optical coherence tomography was performed. Results: Seven (54%) of the 13 eyes initially treated topically experienced successful MH closure. Small holes (<230 µm) with a better initial BCVA (0.474 logMAR vs 0.796 logMAR) were more likely to respond favorably to topical therapy (mean 121 µm vs 499 µm). In addition, holes with less surrounding edema responded better. All holes not responding to topical therapy were subsequently closed with pars plana vitrectomy, membrane peeling, and fluid–gas exchange. Conclusions: Topical therapy is a reasonable first-line treatment for MHs, with a better than 50% success rate. This is especially true for small early-onset holes with minimal or no edema. Surgery still had a high success rate after a 1- to 3-month delay while the MH was treated with eyedrops.
Case Study on the World of Art, Counterfeits and Aspirations
Authors: Sunil Julie
Published: December 2022

The world of art has both fake and original works competing for the attention of art collectors. Chances of accepting a forged work of art as authentic is very high because of the advanced techniques available to forgers who do as much research as those appointed to certify it. Counterfeits flourish because of economic and psychological reasons. Scarcity, status symbols and social cues become vital factors in driving up the prices. India has not given enough attention to regulations in art market and this has led to wide spread scams and monetary loss to the government and society. What can be done to correct the market for art and how can application of Bayesian theorem and artificial intelligence assist the ordinary buyers and experts to make better judgments before accepting a piece of work as original?
Severe community-acquired pneumonia
Authors: Niederman Michael S. , Torres Antoni
Published: December 2022

Severe community-acquired pneumonia is the most life-threatening form of community-acquired pneumonia, characterised by intensive care unit admission and high morbidity and mortality. In this review article, we cover in depth six aspects of severe community-acquired pneumonia that are still controversial: use of PCR molecular techniques for microbial diagnosis; the role of biomarkers for initial management; duration of treatment, macrolides or quinolones in the initial empirical antibiotic therapy; the use of prediction scores for drug-resistant pathogens to modify initial empiric therapy; the use of noninvasive mechanical ventilation and high-flow nasal oxygen; and the use of corticosteroids as adjunctive therapy in severe community-acquired pneumonia.
Response of arboreal Collembola communities to the conversion of lowland rainforest into rubber and oil palm plantations
Authors: Mawan Amanda , Hartke Tamara R. , Deharveng Louis , Zhang Feng , Buchori Damayanti , Scheu Stefan , Drescher Jochen
Published: December 2022

Background

In the last decades, Southeast Asia has experienced massive conversion of rainforest into rubber and oil palm monoculture plantations. The effects of this land-use change on canopy arthropods are still largely unknown. Arboreal Collembola are among the most abundant canopy arthropods in tropical forests, potentially forming a major component of the canopy food web by contributing to the decomposition of arboreal litter and being an important prey for canopy arthropod predators. We investigated abundance, richness, and community composition of, as well as the influence of a series of environmental factors on, canopy Collembola communities in four land-use systems in Jambi Province, Sumatra, Indonesia: (1) lowland rainforest, (2) jungle rubber (rubber agroforest), and monoculture plantations of (3) rubber and (4) oil palm.

Results

Using canopy fogging in 32 research plots in both the dry and rainy seasons in 2013, we collected 77,104 specimens belonging to 68 (morpho) species. Generally, Collembola communities were dominated by few species including two species of the genusSalina(Paronellidae; 34% of total individuals) and two species of Lepidocyrtinae (Entomobryidae; 20%). The abundance of Collembola in lowland rainforest (53.4 ± 30.7 ind. m−2) was more than five times higher than in rubber plantations, and more than ten times higher than in oil palm plantations; abundances in jungle rubber were intermediate. Collembola species richness was highest in rainforest (18.06 ± 3.60 species) and jungle rubber (16.88 ± 2.33 species), more than twice that in rubber or oil palm. Collembola community composition was similar in rainforest and jungle rubber, but different from monoculture plantations which had similar Collembola community composition to each other. The environmental factors governing community composition differed between the land-use systems and varied between seasons.

Conclusions

Overall, this is the first in-depth report on the structure of arboreal Collembola communities in lowland rainforest and agricultural replacement systems in Southeast Asia. The results highlight the potentially major consequences of land-use change for the functioning of arboreal arthropod food webs.
Transcranial direct current stimulation combined with amantadine in repetitive mild traumatic brain injury in rats
Authors: Han Soo Jeong , Park Gahee , Suh Jee Hyun
Published: December 2022

Background

Balance and memory deficits are common in patients with repetitive mild traumatic brain injury (mTBI).

Objective

To investigate the combined effects of amantadine and transcranial direct current stimulation (tDCS) on balance and memory in repetitive mTBI rat models.

Methods

In this prospective animal study, 40 repetitive mTBI rats were randomly assigned to four groups: tDCS, amantadine, combination of amantadine and anodal tDCS, and control. The tDCS group received four sessions of anodal tDCS for four consecutive days. The amantadine group received four intraperitoneal injections of amantadine for four consecutive days. The combination group received four intraperitoneal injections of amantadine and anodal tDCS for four consecutive days. Motor-evoked potential (MEP), rotarod test, and novel object test results were evaluated before mTBI, before treatment, and after treatment.

Results

All groups showed significant improvements in the rotarod and novel object tests, particularly the combination group. The combination group showed a significant improvements in duration (p < 0.01) and maximal speed in the rotarod test (p < 0.01), as well as an improvement in novel object ratio (p = 0.05) and MEP amplitude (p = 0.05) after treatment. The combination group exhibited a significant increase in novel object ratio compared to the tDCS group (p = 0.04). The GFAP integral intensity of the left motor cortex and hippocampus was the lowest in the combination group.

Conclusion

Combination treatment with amantadine and tDCS had positive effects on balance and memory recovery after repetitive mTBI in rats. Therefore, we expect that the combination of amantadine and tDCS may be a treatment option for patients with repetitive mTBIs.
The willingness and influencing factors to choose smart senior care among old adults in China
Authors: Huang Qiyuan , Li Ying , Wu Xiang , Ge Song , Qu Zhe , Wang Aming , Tang Xianping
Published: December 2022

Background

Population aging has become an escalating issue in China resulting in increasing healthcare demand. Smart senior care has the potential to help older adults live independently and relieve the pressure of healthcare including home-based care. This study aimed to explore Chinese older adults’ preferred access models and service content of smart senior care and factors affecting their willingness to choose smart senior care.

Methods

This was a cross-sectional study. A total of 760 community-dwelling older adults from Xuzhou, China were included in this study. Their demographics, family support, health status, smart senior care use, and willingness to choose smart senior care were collected. The Chi-square test was used for single factor analysis of each variable. The statistically significant variables were included in the logistics regression model to analyze factors influencing older adults’ willingness to choose smart senior care. The chi-square goodness of fit test was used to analyze the preferred content and access models of smart senior care; the Bonferroni method was used to correct the results.

Results

The finding indicated that participants’ age, number of children, frequency of children visiting parents, adequate senior care, self-reported health, chronic diseases, smartphone use, and attitude toward smart senior care were significantly associated with their willingness to choose the smart senior care (p < 0.05). For smart senior care access models, participants preferred the remote monitoring model, telephone call model, and the community site model over the health smart home model and the smart application platform model. There was no statistical difference among these three preferred access models (p’ > 0.005). Regarding service content, participants desired medical care service the most (p’ < 0.005).

Conclusions

Chinese older adults’ willingness to choose smart senior care is affected by personal, family, health, and other factors. To develop China’s senior care, we should consider their demand and preference for smart senior care. It is important to enrich the content of smart senior care, especially on medical care services, and maintain the dynamic balance between supply and demand using a diverse supply approach.
Concordance between single-nucleotide polymorphism–based genomic instability assays and a next-generation sequencing–based homologous recombination deficiency test
Authors: Cristescu Razvan , Liu Xiao Qiao , Arreaza Gladys , Chen Cai , Albright Andrew , Qiu Ping , Marton Matthew J.
Published: December 2022

Background:

We evaluated the performance of single-nucleotide polymorphism (SNP) genotyping arrays OncoScan (Thermo Fisher Scientific, San Diego, CA) and Infinium CytoSNP-850K (CytoSNP; Illumina, Waltham, MA) for assessing homologous recombination deficiency (HRD) genomic instability.

Methods:

DNA (pretreatment samples) across 20 tumor types was evaluated with OncoScan, CytoSNP, and the clinically validated HRD test. Copy number variation (CNV) and loss of heterozygosity (LOH) analyses were performed with ASCATv2.5.1. Aggregate HRD genomic metrics included LOH, telomeric-allelic imbalance number (TAI), and large-scale state transition (LST). Associations between BRCA mutation (BRCAm) status and the clinically validated HRD test metric (dichotomized at a clinical cut-off) were evaluated using area under the receiver operating characteristic (AUROC); Spearman ρ was calculated for continuous metrics. CNV segmentation and HRD genomic metrics were calculated (n = 120, n = 106, and n = 126 for OncoScan, CytoSNP and clinically validated HRD test, respectively).

Results:

When assessed by SNP arrays, the genomic metric demonstrated good association with BRCAm (AUROC of HRD: OncoScan, 0.87; CytoSNP, 0.75) and the clinically validated test (cut-off, 42; AUROC of HRD: OncoScan, 0.92; CytoSNP, 0.91). The genomic metrics demonstrated good correlation with the clinically validated aggregate HRD test metric (ρ: OncoScan, 0.82; CytoSNP, 0.81) and for each component (ρ: OncoScan, 0.68 [LOH], 0.76 [TAI], and 0.78 [LST]; CytoSNP, 0.59 [LOH], 0.77 [TAI], and 0.82 [LST]). HRD assessed by SNP genotyping arrays and the clinically validated test showed good correlation.

Conclusion:

OncoScan and CytoSNP may potentially identify most HRD-positive tumors with appropriate clinically relevant cut-offs.
Autophagy inhibition and reactive oxygen species elimination by acetyl-CoA acetyltransferase 1 through fused in sarcoma protein to promote prostate cancer
Authors: Guan Jingqian , Jiang Xizi , Guo Yaoxing , Zhao Wenhui , Li Ji , Li Yizhuo , Cheng Ming , Fu Lin , Zhao Yue , Li Qingchang
Published: December 2022

Background

Prostate cancer is a major health issue affecting the male population worldwide, and its etiology remains relatively unknown. As presented on the Gene Expression Profiling Interactive Analysis database, acetyl-CoA acetyltransferase 1 (ACAT1) acts as a prostate cancer-promoting factor. ACAT1 expression in prostate cancer tissues is considerably higher than that in normal tissues, leading to a poor prognosis in patients with prostate cancer. Here, we aimed to study the role of the ACAT1-fused in sarcoma (FUS) complex in prostate cancer and identify new targets for the diagnosis and treatment of the disease.

Methods

We conducted immunohistochemical analysis of 57 clinical samples and in vitro and in vivo experiments using a mouse model and plasmid constructs to determine the expression of ACAT1 in prostate cancer.

Results

The relationship between the expression of ACAT1 and the Gleason score was significant. The expression of ACAT1 was higher in tissues with a Gleason score of > 7 than in tissues with a Gleason score of ≤7 (P = 0.0011). In addition, we revealed that ACAT1 can interact with the FUS protein.

Conclusions

In prostate cancer, ACAT1 promotes the expression of P62 and Nrf2 through FUS and affects reactive oxygen species scavenging. These effects are due to the inhibition of autophagy by ACAT1. That is, ACAT1 promotes prostate cancer by inhibiting autophagy and eliminating active oxygen species. The expression of ACAT1 is related to prostate cancer. Studying the underlying mechanism may provide a new perspective on the treatment of prostate cancer.
Perioperative outcomes of robotic versus laparoscopic distal gastrectomy for gastric cancer: a meta-analysis of propensity score-matched studies and randomized controlled trials
Authors: Sun Tao , Wang Yinghua , Liu Yan , Wang Zhanyu
Published: December 2022

Background

Da Vinci robotic surgery system, a novel type of surgery, was widespread in surgical field. However, the perioperative outcomes of robotic distal gastrectomy (RDG) are still controversy, despite several observational studies and randomized controlled trials (RCT) had been reported. Therefore, we performed a meta-analysis of propensity score-matched (PSM) and RCT studies to evaluated the perioperative feasibility and safety of RDG.

Methods

Studies were systematically searched in PubMed, Web of Science, Cochrane Library, and Embase database, and screened according to the defined limitations. The quality of PSM studies and RCT studies were respectively assessed by ROBINS-I and Cochrane risk-of-bias tool. Extracted data were analyzed by Review Manager 5.4.

Results

7 PSM studies and 1 RCT with a total of 2763 patients were included in this analysis. The longer operative time (MD = 31.42, 95% CI [22.88, 39.96], p < 0.00001), less blood loss (MD = − 25.89, 95% CI [− 36.18, − 15.6], p < 0.00001), more retrieved lymph nodes (MD = 3.46, 95% CI [2.94, 3.98], p < 0.00001), shorter time to first flatus (MD = − 0.08, 95% CI [− 0.13, − 0.02], p = 0.006) and liquid intake (MD = − 0.13, 95% CI [− 0.22, − 0.05], p = 0.002) were observed in RDG group compared with LDG group. There are no statistically significant in time to start soft diet, postoperative hospital stays, overall complications, complications Grade I–II, complications Grade ≥ III, anastomotic leakage, bleeding, intra-abdominal bleeding, intraluminal bleeding, ileus, abdominal infection, delayed gastric emptying and wound complications.

Conclusions

RDG showed less blood loss and more retrieved lymph nodes, revealed less time to first flatus and liquid intake after operation. But the operative time was longer in RDG group than in LDG. The incidence rate of postoperative complications was comparable between RDG and LDG.
Removal capability, implant-abutment connection damage and thermal effect using ultrasonic and drilling techniques for the extraction of fractured abutment screws: an in vitro study
Authors: Bufalá Pérez María , Zubizarreta-Macho Álvaro , Borrajo Sánchez Javier , Hernández Rodríguez Jorge , Alonso Pérez-Barquero Jorge , Riad Deglow Elena , Hernández Montero Sofía
Published: December 2022

The aim of this work was to analyze and compare the removal capability, conical internal hex implant-abutment connection damage and thermal effect using ultrasonic and drilling techniques for the extraction of fractured abutment screws. Twenty abutment screws were randomly fractured into twenty dental implants and randomly extracted using the following removal techniques: Group A: drilling technique without irrigation (n = 10) (DT) and Group B: ultrasonic technique without irrigation (n = 10) (UT). The dental implants were submitted to a preoperative and postoperative micro-computed tomography (micro-CT) scan to obtain a Standard Tessellation Language (STL) digital file that determined the wear comparison by morphometry. Moreover, the thermographic effects generated by the DT and UT removal techniques were registered using a thermographic digital camera. Comparative analysis was performed by comparing the volumetric differences (mm3) between preoperative and postoperative micro-CT scans and thermographic results (°C) using the Student t test. The DT extracted 8/10 and the US 9/10 abutment screws. The pairwise comparison revealed statistically significant differences between the volumetric differences of postoperative and preoperative micro-CT scans of the DT (− 0.09 ± − 0.02mm3) and UT (− 0.93 ± − 0.32mm3) study groups (p = 0.0042); in addition, the pairwise comparison revealed statistically significant differences between the thermographic values of the DT (38.12 ± − 10.82 °C) and UT (78.52 ± 5.43 °C) study groups (p < 0.001). The drilling technique without irrigation provides a less removal capability, less conical internal hex implant-abutment connection damage and less thermal effect than ultrasonic technique for the extraction of fractured abutment screws; however, the ultrasonic technique resulted more effective for the extraction of fractured abutment screws.
What we think about professional and unprofessional behaviors: differences between the perception of clinical faculty members and medical students
Authors: Tabatabaei Zahra Sadat , Mirzazadeh Azim , Amini Homayoun , Mafinejad Mahboobeh Khabaz
Published: December 2022

Introduction

Differences in the viewpoints of clinical faculty members and medical students about prioritizing professional norms accepted by the professional community and lack of alignment of these views can lead to distortion of understanding, problems in learning and assessment of professionalism, and failure in students’ professional identity formation. This study aimed to identify the differences in viewpoints of clinical faculty members and medical students about prioritizing the importance and prevalence of professional and unprofessional behaviors among undergraduate medical students.

Methods

A multi-stage qualitative study was conducted at Tehran University of Medical Sciences during 2020–2021. At first, a systematic search was conducted to identify professional and unprofessional behaviors using the directional content analysis method. A panel of experts was formed to check the codes obtained from reviewing the literature and to evaluate its compliance with the context. Then, the modified nominal group technique sessions were held with clinical faculty members and medical students to strengthen the codes extracted from the studies and systematically integrate their views to achieve a comprehensive list of professional and unprofessional behaviors in accordance with the context. Finally, a consensus was made among them about prioritizing the importance and prevalence of these behaviors in undergraduate medical students.

Results

A total of 490 codes of professional behaviors and 595 unprofessional behavior codes were identified in the literature review. In the following sessions of the modified nominal group, 13 clinical faculty members listed 105 codes of professional and unprofessional behaviors, and 51 medical students also listed 313 codes. The results of the modified nominal group technique showed that the faculty members reported the importance of unprofessional behaviors higher than professional ones. At the same time, students rated the importance of professional behaviors higher than unprofessional ones. Both faculty members and students rate the prevalence of professional behaviors as high and the prevalence of unprofessional behaviors as low.

Conclusion

The results showed a difference of views between clinical faculty members and medical students about prioritizing professional and unprofessional behaviors. It is essential to align their viewpoints to understand, learn and value professionalism to develop a professional identity.
Female factors modulate Sex Peptide’s association with sperm in Drosophila melanogaster
Authors: Misra Snigdha , Buehner Norene A. , Singh Akanksha , Wolfner Mariana F.
Published: December 2022

Background

Male-derived seminal fluid proteins (SFPs) that enter female fruitflies during mating induce a myriad of physiological and behavioral changes, optimizing fertility of the mating pair. Some post-mating changes in female Drosophila melanogaster persist for ~10–14 days. Their long-term persistence is because the seminal protein that induces these particular changes, the Sex Peptide (SP), is retained long term in females by binding to sperm, with gradual release of its active domain from sperm. Several other “long-term response SFPs” (LTR-SFPs) “prime” the binding of SP to sperm. Whether female factors play a role in this process is unknown, though it is important to study both sexes for a comprehensive physiological understanding of SFP/sperm interactions and for consideration in models of sexual conflict.

Results

We report here that sperm in male ejaculates bind SP more weakly than sperm that have entered females. Moreover, we show that the amount of SP, and other SFPs, bound to sperm increases with time and transit of individual seminal proteins within the female reproductive tract (FRT). Thus, female contributions are needed for maximal and appropriate binding of SP, and other SFPs, to sperm. Towards understanding the source of female molecular contributions, we ablated spermathecal secretory cells (SSCs) and/or parovaria (female accessory glands), which contribute secretory proteins to the FRT. We found no dramatic change in the initial levels of SP bound to sperm stored in mated females with ablated or defective SSCs and/or parovaria, indicating that female molecules that facilitate the binding of SP to sperm are not uniquely derived from SSCs and parovaria. However, we observed higher levels of SP (and sperm) retention long term in females whose SSCs and parovaria had been ablated, indicating secretions from these female tissues are necessary for the gradual release of Sex Peptide’s active region from stored sperm.

Conclusion

This study reveals that the SP-sperm binding pathway is not entirely male-derived and that female contributions are needed to regulate the levels of SP associated with sperm stored in their storage sites.
Clinical staging and the differential risks for clinical and functional outcomes in young people presenting for youth mental health care
Authors: Capon William , Hickie Ian B. , Varidel Mathew , Prodan Ante , Crouse Jacob J. , Carpenter Joanne S. , Cross Shane P. , Nichles Alissa , Zmicerevska Natalia , Guastella Adam J. , Scott Elizabeth M. , Scott Jan , Shah Jai , Iorfino Frank
Published: December 2022

Background

Clinical staging proposes that youth-onset mental disorders develop progressively, and that active treatment of earlier stages should prevent progression to more severe disorders. This retrospective cohort study examined the longitudinal relationships between clinical stages and multiple clinical and functional outcomes within the first 12 months of care.

Methods

Demographic and clinical information of 2901 young people who accessed mental health care at age 12–25 years was collected at predetermined timepoints (baseline, 3 months, 6 months, 12 months). Initial clinical stage was used to define three fixed groups for analyses (stage 1a: ‘non-specific anxious or depressive symptoms’, 1b: ‘attenuated mood or psychotic syndromes’, 2+: ‘full-threshold mood or psychotic syndromes’). Logistic regression models, which controlled for age and follow-up time, were used to compare clinical and functional outcomes (role and social function, suicidal ideation, alcohol and substance misuse, physical health comorbidity, circadian disturbances) between staging groups within the initial 12 months of care.

Results

Of the entire cohort, 2093 young people aged 12–25 years were followed up at least once over the first 12 months of care, with 60.4% female and a baseline mean age of 18.16 years. Longitudinally, young people at stage 2+ were more likely to develop circadian disturbances (odds ratio [OR]=2.58; CI 1.60–4.17), compared with individuals at stage 1b. Additionally, stage 1b individuals were more likely to become disengaged from education/employment (OR=2.11, CI 1.36–3.28), develop suicidal ideations (OR=1.92; CI 1.30–2.84) and circadian disturbances (OR=1.94, CI 1.31–2.86), compared to stage 1a. By contrast, we found no relationship between clinical stage and the emergence of alcohol or substance misuse and physical comorbidity.

Conclusions

The differential rates of emergence of poor clinical and functional outcomes between early versus late clinical stages support the clinical staging model's assumptions about illness trajectories for mood and psychotic syndromes. The greater risk of progression to poor outcomes in those who present with more severe syndromes may be used to guide specific intervention packages.
Construction and experimental validation of an acetylation-related gene signature to evaluate the recurrence and immunotherapeutic response in early-stage lung adenocarcinoma
Authors: Wang Haiqiang , Lu Xiyan , Chen Jiakuan
Published: December 2022

Background

Acetylation is a reversible epigenetic process, playing an important role in the initiation and progression of malignant tumors. However, the prognosis value of acetylation-related genes in the early-stage lung adenocarcinoma (LUAD) remains obscure.

Materials and methods

The acetylation-related genes were collected and clustered based on transcriptome sequencing of the patients with early-stage LUAD from the Cancer Genome Atlas. The genomic divergence analysis, protein–protein interaction network construction, Lasso regression, and univariate Cox regression were used to identify the significant biomarkers for the recurrence of the early-stage LUAD. The multivariate Cox regression was used to establish the predictive model. Gene Expression Omnibus was systemically retrieved and four independent datasets were used for external validation. 23 early-stage LUAD samples were collected from the local hospital to detect the expression difference of the genes in the model. Transfection assays were performed to verify the regulatory ability of the screened gene to the proliferation of LUAD cell lines. The single-cell RNA sequencing of the early-stage LUAD patients and two lung cancer cohorts receiving immunotherapy were utilized to explore the predictive ability of the established model to immunotherapeutic sensitivity.

Results

The clustering based on acetylation-related genes was significantly associated with the recurrence (P < 0.01) and immune infiltration statuses. Through a series of bioinformatical and machine learning methods, RBBP7 and YEATS2 were ultimately identified. Accordingly, a novel gene signature containing RBBP7 and YEATS2 was developed to evaluate the recurrence-free survival of early-stage LUAD, which was then validated in five independent cohorts (pooled hazard ratio = 1.88, 95% confidence interval = 1.49–2.37) and 23 local clinical samples (P < 0.01). The knock-down of YEATS2 obviously suppressed proliferation of H1975 and HCC-827 cells. Single-cell RNA sequencing analyses indicated that RBBP7 and YEATS2 were both associated with the tumor immune response, and the prognosis signature could predict the immunotherapeutic response in two cohorts receiving immunotherapy (P < 0.05; P < 0.01).

Conclusions

Totally, an acetylation-related gene signature is constructed, helping to evaluate the recurrence and immunotherapeutic effectiveness of early-stage LUAD patients.
A novel structurally identified epitope delivered by macrophage membrane-coated PLGA nanoparticles elicits protection against Pseudomonas aeruginosa
Authors: Gao Chen , Chen Yin , Cheng Xin , Zhang Yi , Zhang Yueyue , Wang Ying , Cui Zhiyuan , Liao Yaling , Luo Ping , Wu Weihui , Wang Cheng , Zeng Hao , Zou Quanming , Gu Jiang
Published: December 2022

The increasing prevalence of antibiotic resistance by Pseudomonas aeruginosa (PA) raises an urgent need for an effective vaccine. The outer membrane proteins of PA, especially those that are upregulated during infection, are ideal vaccine targets. However, the strong hydrophobicity of these proteins hinders their application for this purpose. In this study, we selected eight outer membrane proteins from PA with the most significantly upregulated expression. Their extracellular loops were analyzed and screened by using sera from patients who had recovered from PA infection. As a result, a novel immunogenic epitope (Ep167-193) from PilY1 (PA4554) was found. Moreover, we constructed a macrophage membrane-coated PLGA (poly lactic-co-glycolic acid) nanoparticle vaccine carrying PilY1 Ep167-193 (PNPs@M-Ep167-193) that elicits a Th2 immune response and confers adequate protection in mice. Our data furnished the promising vaccine candidate PNPs@M-Ep167-193 while providing additional evidence for structure-based epitope identification and vaccine design.

Graphical Abstract
Chaihu-Guizhi-Ganjiang Decoction is more efficacious in treating irritable bowel syndrome than Dicetel according to metabolomics analysis
Authors: Li Mingming , Zhu Jiawei , Liu Xuan , Dong Zhiying , Tang Jigui , Zhang Cian , Jiao Jianpeng , Chen Jiani , Yin Fenghao , Qiu Shi , Zhang Feng , Gao Shouhong , Wang Zhipeng , Tao Xia , Yue Xiaoqiang , Sun Lianna , Chen Wansheng
Published: December 2022

Background

Chaihu-Guizhi-Ganjiang Decoction (CGGD) is a traditional Chinese medicine (TCM) prescription used to treat viral influenza. There is evidence that CGGD can be used to treat irritable bowel syndrome (IBS) but the potential mechanism of action and metabolites produced upon CGGD treatment remains elusive.

Methods

Patients with IBS were treated with pinaverium bromide (Dicetel™) and then CGGD after a washout period of 1 week. Both treatments lasted for 30 days. The efficacy and changes of metabolites in plasma after the two treatments were compared. Plasma samples were acquired before and after each treatment, and untargeted metabolics analysis was performed.

Results

Efficacy was measured according to the Rome IV criteria and TCM theory. Our results indicated that CGGD showed significantly better efficacy than Dicetel in the treatment of IBS utilizing each criterion. CGGD exerted greater effects on plasma metabolism than Dicetel. Dicetel treatment led to increased tryptophan metabolism (increased levels of 5-Hydroxyindoleacetaldehyde) and increased protein metabolism (increased levels of L-arginine). CGGD treatment significantly (p < 0.05) increased carnitine metabolism, with elevated levels of L-carnitine and acylcarnitine in plasma. Such changes in these metabolites could exert effects against IBS by improving gastrointestinal motility and suppressing pain, depression, and inflammation.

Conclusions

CGGD appeared to be more efficacious than Dicetel for treating patients with IBS. The findings provide a sound support for the underlying biomolecular mechanism of CGGD in the prevention and treatment of IBS.
Defining post-acute COVID-19 syndrome (PACS) by an epigenetic biosignature in peripheral blood mononuclear cells
Authors: Nikesjö Frida , Sayyab Shumaila , Karlsson Lovisa , Apostolou Eirini , Rosén Anders , Hedman Kristofer , Lerm Maria
Published: December 2022

Post-acute COVID-19 syndrome (PACS) has been defined as symptoms persisting after clearance of a COVID-19 infection. We have previously demonstrated that alterations in DNA methylation (DNAm) status persist in individuals who recovered from a COVID-19 infection, but it is currently unknown if PACS is associated with epigenetic changes. We compared DNAm patterns in patients with PACS with those in controls and in healthy COVID-19 convalescents and found a unique DNAm signature in PACS patients. This signature unravelled modified pathways that regulate angiotensin II and muscarinic receptor signalling and protein–protein interaction networks that have bearings on vesicle formation and mitochondrial function.
A biostatistical approach for augmenting rare bianthraquinone antibiotic production by Streptomyces sp. RA-WS2 using Taguchi design
Authors: Manhas Ravi Singh , Kumar Amit , Chaubey Asha
Published: December 2022

Consistent production of bioactives from microbial sources remains a big challenge for fermentation based bio-processes. Setomimycin, a rare 9,9'-bianthrylanthracene antibiotic reported to be active against Gram positive bacteria i.e. Staphyloccocus aureus, Bacillus subtilis, Bacillus cereus, and Mycobacterium smegmatis, including mycobacteria is one of the least exploited antibiotic. Present work aims to enhance and maximize setomimycin production using One Factor at a Time (OFAT) approach, followed by Taguchi L9 orthogonal array (OA) design in 30L fermenter. Four most influential parameters, namely carbon source, nitrogen source, air and agitation were selected for optimization studies. The optimized production medium supplemented with 150 g/L glycerol and 7.5 g/L soyabean meal with an agitation rate of 100 RPM and air flow rate of 20 LPM (Liters Per Minute) resulted in 675 mg/L setomimycin production within 96–108 h of fermentation as compared to the initial production i.e. 40 mg/L. Thus, an overall enhancement of 16.8 folds was achieved in setomimycin production after optimization in 30L fermenter.

Graphical Abstract
Occupational physicians dealing with mental health: between employee and company interests: a qualitative study
Authors: Pößnecker Tim , Baxendale Maximilian , Braun Simone , Schwarz Elena , Hölzer Michael , Angerer Peter , Gündel Harald , Balint Elisabeth , Rothermund Eva
Published: December 2022

Background

Occupational health physicians are increasingly confronted with mental health issues at their workplace. Facing them, most of them feel insecure and not sufficiently trained. Employee’s mental well-being depends at the same time on individual and significantly on organizational variables. This complicates the physician’s position, since they have to serve many interests. The focus of the present study is to investigate what difficulties occupational health physicians face and how organizational culture and management influence their work.

Methods

Interviews were conducted with N = 25 physicians as part of a training for basic mental health care. Interviews were interpreted using qualitative content analysis.

Results

Working with mentally ill employees was difficult for the physicians interviewed. Many felt insecure managing and preventing mental health issues. A need for further education was observed. Environmental factors (organizational culture, management) have a strong impact on the work of an occupational health physician and highlight its systemic dimension. Even though many of our participants report a meanwhile more open attitude towards mental disorders at their workplace, on the level of direct contact to the management prevail descriptions of little acceptance and a high priority of economic outcomes.

Conclusions

More education on topics of mental health is needed for occupational health physicians. Future trainings should consider the intertwined nature of their work and enable them in dealing consciously with other actors in the company. For enhancing employee’s mental well-being occupational health physicians could be granted a strengthened position in companies or be supported through more exchange with colleagues in other companies.
SNCA genetic lowering reveals differential cognitive function of alpha-synuclein dependent on sex
Authors: Brown Jennifer L. , Hart Damyan W. , Boyle Gabriel E. , Brown Taylor G. , LaCroix Michael , Baraibar Andrés M. , Pelzel Ross , Kim Minwoo , Sherman Mathew A. , Boes Samuel , Sung Michelle , Cole Tracy , Lee Michael K. , Araque Alfonso , Lesné Sylvain E.
Published: December 2022

Antisense oligonucleotide (ASO) therapy for neurological disease has been successful in clinical settings and its potential has generated hope for Alzheimer’s disease (AD). We previously described that ablating SNCA encoding for α-synuclein (αSyn) in a mouse model of AD was beneficial. Here, we sought to demonstrate whether transient reduction of αSyn expression using ASOSNCA could be therapeutic in a mouse model of AD. The efficacy of the ASOSNCA was measured via immunocytochemistry, RT-qPCR and western blotting. To assess spatial learning and memory, ASOSNCA or PBS-injected APP and non-transgenic (NTG) mice, and separate groups of SNCA-null mice, were tested on the Barnes circular maze. Hippocampal slice electrophysiology and transcriptomic profiling were used to explore synaptic function and differential gene expression between groups. Reduction of SNCA transcripts alleviated cognitive deficits in male transgenic animals, but surprisingly, not in females. To determine the functional cause of this differential effect, we assessed memory function in SNCA-null mice. Learning and memory were intact in male mice but impaired in female animals, revealing that the role of αSyn on cognitive function is sex-specific. Transcriptional analyses identified a differentially expressed gene network centered around EGR1, a central modulator of learning and memory, in the hippocampi of SNCA-null mice. Thus, these novel results demonstrate that the function of αSyn on memory differs between male and female brains.
Genomic, transcriptomic and RNA editing analysis of human MM1 and VV2 sporadic Creutzfeldt-Jakob disease
Authors: Tarozzi Martina , Baiardi Simone , Sala Claudia , Bartoletti-Stella Anna , Parchi Piero , Capellari Sabina , Castellani Gastone
Published: December 2022

Creutzfeldt-Jakob disease (CJD) is characterized by a broad phenotypic spectrum regarding symptoms, progression, and molecular features. Current sporadic CJD (sCJD) classification recognizes six main clinical-pathological phenotypes. This work investigates the molecular basis of the phenotypic heterogeneity of prion diseases through a multi-omics analysis of the two most common sCJD subtypes: MM1 and VV2. We performed DNA target sequencing on 118 genes on a cohort of 48 CJD patients and full exome RNA sequencing on post-mortem frontal cortex tissue on a subset of this cohort. DNA target sequencing identified multiple potential genetic contributors to the disease onset and phenotype, both in terms of coding, damaging-predicted variants, and enriched groups of SNPs in the whole cohort and the two subtypes. The results highlight a different functional impairment, with VV2 associated with higher impairment of the pathways related to dopamine secretion, regulation of calcium release and GABA signaling, showing some similarities with Parkinson’s disease both on a genomic and a transcriptomic level. MM1 showed a gene expression profile with several traits shared with different neurodegenerative, without an apparent distinctive characteristic or similarities with a specific disease. In addition, integrating genomic and transcriptomic data led to the discovery of several sites of ADAR-mediated RNA editing events, confirming and expanding previous findings in animal models. On the transcriptomic level, this work represents the first application of RNA sequencing on CJD human brain samples. Here, a good clusterization of the transcriptomic profiles of the two subtypes was achieved, together with the finding of several differently impaired pathways between the two subtypes. The results add to the understanding of the molecular features associated with sporadic CJD and its most common subtypes, revealing strain-specific genetic signatures and functional similarities between VV2 and Parkinson’s disease and providing preliminary evidence of RNA editing modifications in human sCJD.
Feasibility and acceptability of novel functional electronic stimulated rehabilitation application for treatment in patients with cerebrovascular disorders: the FRAT study protocol
Authors: Mano Tomoo , Asada Kiyoshi , Suzuki Shota , Kasama Shu , Kinugawa Kaoru , Sugie Kazuma , Kasahara Masato , Kido Akira
Published: December 2022

Background

The prognosis of patients with cerebrovascular disorders is poor owing to their high residual rate of hemiplegia. Delayed withdrawal from synkinesis is a major cause of prolonged hemiplegia; however, effective rehabilitation has not been established. This single-arm, open-label study aims to evaluate the influence of a low-frequency treatment device on canceling synkinesis in patients with incomplete paralysis and cerebrovascular disorders.

Methods

Eligible participants will include patients aged 20 years or older with incomplete paralysis, defined as upper limb Brunnstrom stage (BRS) of 2–4, who are within 1 month of onset of a cerebrovascular disorder. Qualified patients will be assigned to the novel rehabilitation treatment with IVES+ for 4 weeks. The primary endpoint of the study is the change from baseline in the upper-limb Fugl-Meyer Assessment (FMA) 2 weeks after the start of treatment. The secondary endpoints are changes in the amount of Functional Independence Measure, changes in the amount of upper-limb BRS, and changes in the amount of Barthel Index (BI) compared to the pre-intervention value at weeks 2 and 4; changes in the upper-limb FMA scores at 1, 3, and 4 weeks; changes in grip strength compared to the pre-intervention values at 1, 2, 3, and 4 weeks; and changes in upper-limb strength (manual muscle test) compared to the pre-intervention values at 1, 2, 3, and 4 weeks.

Discussion

This study will explore the usefulness of IVES+ for recovery from motor paralysis in patients with cerebrovascular disorders.

Trial registration

Japanese Clinical Registry, jRCTs052180226. Date of registration: February 1, 2022
The use of technology in higher education teaching by academics during the COVID-19 emergency remote teaching period: a systematic review
Authors: Sum McQueen , Oancea Alis
Published: December 2022

This paper presents a systematic review of scholarly efforts that uniquely emerged at the onset of the COVID-19 pandemic and focused primarily on higher education teachers’ perspectives on technology use and on associated changes in the relationship between teachers and students amidst the transition to emergency remote teaching worldwide. Our narrative synthesis of 32 studies, the majority of which come from lower-and middle-income countries/regions, suggests that numerous factors interact to shape academics’ technology use in emergency remote teaching across higher education contexts. We report strong findings of teachers’ resilience and resourcefulness in their self-exploration of various technologies and teaching strategies in response to the continued severity of the pandemic. Ultimately, this review suggests directions for further research on engaging educational leaders and faculty in reimagining teaching as not only a core academic function of higher education, but also, and importantly, a humanising experience shaped by an ethics of care.
Intra-operative ultrasound (IOUS) value in cases of AVM and cavernoma excision: single-center experience
Authors: El-Tantawy Ibrahim M. S. , Kassem Mohammed A. , El-Badry Ashraf A. , AbdElwahab Khaled M.
Published: December 2022

Objective

The aim of the study is to use ultrasound to get maximal lesion resection without doing harm to the brain tissue in the absence of neuronavigation system in neurovascular cases as AVM and cavernoma.

Methods

The study is held in Mansoura University Hospitals, Department of Neurosurgery. Two different cases (AVM and cavernoma) were operated, and IOUS was used to assess its value during the surgery. Postoperatively the patients are followed up clinically and radiologically.

Results

In 2 different parenchymal lesions: AVM and cavernoma, IOUS was valuable in accurate localization of the lesions and the related vascularity specially in AVM case. It also helped to evaluate the extent of resection and confirm total excision. It also helped to determine the site of cortical incision and so to minimize brain tissue manipulation to prevent development of postoperative neurological deficit.

Conclusion

IOUS can be very helpful in cases of parenchymal neurovascular lesions such as AVM and cavernoma.
Endovascular treatment of haemorrhagic pancreatic serous cystadenoma
Authors: Le Tat Thomas , Carlier Robert , El Hajjam Mostafa , Sarrot Guillaume-Marie , Obadia Ilan , Tordjman Mickael , Zhou Jeffery
Published: December 2022

Background

Pancreatic microcystic serous cystadenoma are rare benign pancreatic tumors. No treatment is needed in most cases as this lesion is often discovered incidentally. Surgery is not required except in symptomatic cases.

Case presentation

We report herein a rare case of pancreatic serous cystadenoma complicated with a hemorrhage in a 95 years old patient treated with arterial embolization since surgery was not possible. The patient recovered without any adverse events or bleed recurrence in the 6 months following the procedure.

Conclusion

Hemorrhage secondary to a pancreatic serous cystadenoma was successfully treated with arterial embolization, which may represent an alternative therapeutic option to surgery.
Pareto optimality based PID controller design for vehicle active suspension system using grasshopper optimization algorithm
Authors: Gampa Srinivasa Rao , Mangipudi Siva Kumar , Jasthi Kiran , B. Mahesh Babu , Goli Preetham , Das D. , Balas Valentina E.
Published: December 2022

In this paper, a Pareto multiobjective and grasshopper optimization algorithm (GOA) based optimum proportional–integral–derivative (P–I–D) controller design is proposed for improving the vehicle active suspension system dynamics under road disturbance conditions. The Pareto objectives considered are minimization of sprung mass suspension deflection, tyre deflection, sprung mass acceleration minimization and eigenvalue-based objective function. State space model for quarter vehicle active suspension system with P–I–D controller is developed for analyzing the stability and dynamic performance of the system. The sinusoidal-based bump road disturbances are used for testing the robustness of the proposed control technique. Simulation results have been presented to show the advantage of the proposed Pareto multiobjective and GOA-based P–I–D controller over the weighted multiobjective and genetic algorithm-based P–I–D controller in terms of stability and dynamics of the active suspension system.