bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Normothermic Machine Perfusion on the Immune Profile of Donor Liver
Authors: Lee Andy Chao Hsuan , Edobor Arianna , Lysandrou Maria , Mirle Vikranth , Sadek Amir , Johnston Laura , Piech Ryan , Rose Rebecca , Hart John , Amundsen Beth , Jendrisak Martin , Millis James Michael , Donington Jessica , Madariaga Maria Lucia , Barth Rolf N. , di Sabato Diego , Shanmugarajah Kumaran , Fung John
Published: June 2022

Background

Normothermic machine perfusion (NMP) allows viability assessment and potential resuscitation of donor livers prior to transplantation. The immunological effect of NMP on liver allografts is undetermined, with potential implications on allograft function, rejection outcomes and overall survival. In this study we define the changes in immune profile of human livers during NMP.

Methods

Six human livers were placed on a NMP device. Tissue and perfusate samples were obtained during cold storage prior to perfusion and at 1, 3, and 6 hours of perfusion. Flow cytometry, immunohistochemistry, and bead-based immunoassays were used to measure leukocyte composition and cytokines in the perfusate and within the liver tissue. Mean values between baseline and time points were compared by Student’s t-test.

Results

Within circulating perfusate, significantly increased frequencies of CD4 T cells, B cells and eosinophils were detectable by 1 hour of NMP and continued to increase at 6 hours of perfusion. On the other hand, NK cell frequency significantly decreased by 1 hour of NMP and remained decreased for the duration of perfusion. Within the liver tissue there was significantly increased B cell frequency but decreased neutrophils detectable at 6 hours of NMP. A transient decrease in intermediate monocyte frequency was detectable in liver tissue during the middle of the perfusion run. Overall, no significant differences were detectable in tissue resident T regulatory cells during NMP. Significantly increased levels of pro-inflammatory and anti-inflammatory cytokines were seen following initiation of NMP that continued to rise throughout duration of perfusion.

Conclusions

Time-dependent dynamic changes are seen in individual leukocyte cell-types within both perfusate and tissue compartments of donor livers during NMP. This suggests a potential role of NMP in altering the immunogenicity of donor livers prior to transplant. These data also provide insights for future work to recondition the intrinsic immune profile of donor livers during NMP prior to transplantation.
Tislelizumab Plus Chemotherapy Sequential Neoadjuvant Therapy for Non-cCR Patients After Neoadjuvant Chemoradiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma (ETNT): An Exploratory Study
Authors: He Wenwu , Wang Chenghao , Wu Lei , Wan Gang , Li Baisen , Han Yongtao , Li Haojun , Leng Xuefeng , Du Kunyi , Chen Haijun , Wang Qifeng , Peng Lin
Published: June 2022

Background

Esophageal squamous cell carcinoma (ESCC) remains a challenging malignant tumor with poor prognosis and limited treatment methods worldwide, and most patients are at a locally advanced stage at diagnosis. High recurrence and metastasis rates remain the main factors leading to the failure of the current standard treatment of neoadjuvant chemoradiotherapy plus surgery for resectable locally advanced ESCC. Improving the pathological complete response (pCR) rate may significantly benefit the survival of patients with resectable locally advanced ESCC after neoadjuvant therapy.

Methods

Tislelizumab plus sequential neoadjuvant chemotherapy was administered to non-clinical complete response (cCR) patients after neoadjuvant chemoradiotherapy for locally advanced ESCC. The patients then received surgery and adjuvant therapy according to the postoperative pathological results. Eighty patients with locally advanced ESCC were recruited for the study. The primary outcomes of the pCR rate and the incidence of adverse events will be analyzed completely within 24 months, and the secondary endpoints will include cCR rate, major pathological response rate, objective response rate, R0 resection rate, event-free survival, and overall survival.

Discussion

This study explored the safety and efficacy of tislelizumab plus chemotherapy sequential neoadjuvant therapy for non-cCR patients and provided a total neoadjuvant therapy model that can benefit patients with locally advanced ESCC.

Clinical Trial Registration

ClinicalTrials. gov NCT05189730. Registered: November 26, 2021, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BBD5&selectaction=Edit&uid=U0004UG3&ts=47&cx=e0cm59.
Decoy Receptor 3 Suppresses T-Cell Priming and Promotes Apoptosis of Effector T-Cells in Acute Cell-Mediated Rejection: The Role of Reverse Signaling
Authors: Weng Shuo-Chun , Wen Mei-Chin , Hsieh Shie-Liang , Chen Nien-Jung , Tarng Der-Cherng
Published: June 2022

Background

Decoy receptor 3 (DcR3) belongs to the tumor necrosis factor (TNF) receptor superfamily and neutralizes TNF ligands, including FasL and TRAIL, to prevent T activation during T-cell priming. However, the cellular mechanisms underlying acute cell-mediated rejection (ACMR) remain unknown.

Methods

We generated DcR3 transgenic (Tg) mice and mice with high DcR3 expression (HDE) to study both in vivo and in vitro. FasR RNA knockdown in immortalized CD4+CD8+ T-cells was used to survey the role of DcR3 on FasR/Fas-associated protein with death domain (FADD)/caspase 8 pathway and its cross-link to TNF receptor-associated factor 1 (TNFR1)-associated death domain protein (TRADD) in suppressing TNFR1. TNF/TRADD knockout mice were used to show the importance of TNF adaptor protein.

Results

DcR3.Fc suppressed C57BL/6 female T-cell activation and transformation into CD4+CD69+, CD4+CD44+, and CD4+CD25+Foxp3+ when compared with isotype IgG1 and its co-treatment with FasL/TRAIL after exposing to bone marrow-derived dendritic cells (BMDCs) that carried alloantigen with male H-Y and minor antigenic determinant. Interleukin-17 and interferon-γ productions by BMDC-activated T-cells were lowered after co-treating with DcR3.Fc. DcR3.Fc induced effector T-cells (Teffs) and was susceptible to FasR-mediated apoptosis through the FADD/TRADD/caspase 8 pathway. After exposing to DcR3.Fc, TRADD was silenced, likely turning down the inflammatory response. The systemic effects of DcR3 Tg mice and HDE phenotype induced by the promoter of cytomegalovirus not only attenuated ACMR severity but also ameliorated the high serum creatinine and blood urea nitrogen levels even with high T-cell exposure frequencies. Besides this, DcR3 has minor biological effects on both MHC-matched and MHC-mismatched models.

Conclusions

High DcR3 doses protect renal tubular epithelial cells from acute T-cell attack during the T-cell priming stage via interfering with TNF ligand-mediated reverse signaling and possibly promoting Teff apoptosis through FasR upregulation. Our findings supported that the decoy receptor is involved in T-cell modulation in kidney transplant rejection.
Bothrops jararaca Snake Venom Inflammation Induced in Human Whole Blood: Role of the Complement System
Authors: Leonel Thyago Bispo , Gabrili Joel José Megale , Squaiella-Baptistão Carla Cristina , Woodruff Trent M. , Lambris John D. , Tambourgi Denise V.
Published: June 2022

The clinical manifestations of envenomation by Bothrops species are complex and characterized by prominent local effects that can progress to tissue loss, physical disability, or amputation. Systemic signs can also occur, such as hemorrhage, coagulopathy, shock, and acute kidney failure. The rapid development of local clinical manifestations is accompanied by the presence of mediators of the inflammatory process originating from tissues damaged by the bothropic venom. Considering the important role that the complement system plays in the inflammatory response, in this study, we analyzed the action of Bothrops jararaca snake venom on the complement system and cell surface receptors involved in innate immunity using an ex vivo human whole blood model. B. jararaca venom was able to induce activation of the complement system in the human whole blood model and promoted a significant increase in the production of anaphylatoxins C3a/C3a-desArg, C4a/C4a-desArg, C5a/C5a-desArg and sTCC. In leukocytes, the venom of B. jararaca reduced the expression of CD11b, CD14 and C5aR1. Inhibition of the C3 component by Cp40, an inhibitor of C3, resulted in a reduction of C3a/C3a-desArg, C5a/C5a-desArg and sTCC to basal levels in samples stimulated with the venom. Exposure to B. jararaca venom induced the production of inflammatory cytokines and chemokines such as TNF-α, IL-8/CXCL8, MCP-1/CCL2 and MIG/CXCL9 in the human whole blood model. Treatment with Cp40 promoted a significant reduction in the production of TNF-α, IL-8/CXCL8 and MCP-1/CCL2. C5aR1 inhibition with PMX205 also promoted a reduction of TNF-α and IL-8/CXCL8 to basal levels in the samples stimulated with venom. In conclusion, the data presented here suggest that the activation of the complement system promoted by the venom of the snake B. jararaca in the human whole blood model significantly contributes to the inflammatory process. The control of several inflammatory parameters using Cp40, an inhibitor of the C3 component, and PMX205, a C5aR1 antagonist, indicates that complement inhibition may represent a potential therapeutic tool in B. jararaca envenoming.
Case Report: Rubella Virus-Induced Cutaneous Granulomas in Two Pediatric Patients With DNA Double Strand Breakage Repair Disorders – Outcome After Hematopoietic Stem Cell Transplantation
Authors: Baumann Ulrich , Schulte Johannes H. , Groß Jonathan P. , Beier Rita , Ludwig Marius , Wahn Volker , Hofmann Jörg , Maecker-Kolhoff Britta , Sauer Martin , Kaiser-Labusch Petra , Karimian Negin , Blume-Peytavi Ulrike , Ghoreschi Franziska , Ott Hagen , Perelygina Ludmila , Klemann Christian , Blankenstein Oliver , von Bernuth Horst , Krüger Renate
Published: June 2022

We report two patients with DNA repair disorders (Artemis deficiency, Ataxia telangiectasia) with destructive skin granulomas, presumably triggered by live-attenuated rubella vaccinations. Both patients showed reduced naïve T cells. Rapid resolution of skin lesions was observed following hematopoietic stem cell transplantation. However, the patient with AT died due to complications of severe hepatic veno-occlusive disease 6 month after HSCT. Dried blood spots obtained after birth were available from this patient and showed absent T-cell receptor excision circles (TRECs). Therefore, newborn screening may help to prevent patients with moderate T-cell deficiency from receiving live-attenuated rubella vaccine potentially causing granulomas.
Utility and Drawbacks of Chimeric Antigen Receptor T Cell (CAR-T) Therapy in Lung Cancer
Authors: Kandra Prameela , Nandigama Rajender , Eul Bastian , Huber Magdalena , Kobold Sebastian , Seeger Werner , Grimminger Friedrich , Savai Rajkumar
Published: June 2022

The present treatments for lung cancer include surgical resection, radiation, chemotherapy, targeted therapy, and immunotherapy. Despite advances in therapies, the prognosis of lung cancer has not been substantially improved in recent years. Chimeric antigen receptor (CAR)-T cell immunotherapy has attracted growing interest in the treatment of various malignancies. Despite CAR-T cell therapy emerging as a novel potential therapeutic option with promising results in refractory and relapsed leukemia, many challenges limit its therapeutic efficacy in solid tumors including lung cancer. In this landscape, studies have identified several obstacles to the effective use of CAR-T cell therapy including antigen heterogeneity, the immunosuppressive tumor microenvironment, and tumor penetration by CAR-T cells. Here, we review CAR-T cell design; present the results of CAR-T cell therapies in preclinical and clinical studies in lung cancer; describe existing challenges and toxicities; and discuss strategies to improve therapeutic efficacy of CAR-T cells.
Non-Coding RNAs as Novel Regulators of Neuroinflammation in Alzheimer’s Disease
Authors: Liu Yuqing , Cheng Xin , Li Hongli , Hui Shan , Zhang Zheyu , Xiao Yang , Peng Weijun
Published: June 2022

Alzheimer’s disease (AD) is one of the most common causes of dementia. Although significant breakthroughs have been made in understanding the progression and pathogenesis of AD, it remains a worldwide problem and a significant public health burden. Thus, more efficient diagnostic and therapeutic strategies are urgently required. The latest research studies have revealed that neuroinflammation is crucial in the pathogenesis of AD. Non-coding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs), microRNAs (miRNAs), circular RNAs (circRNAs), PIWI-interacting RNAs (piRNAs), and transfer RNA-derived small RNAs (tsRNAs), have been strongly associated with AD-induced neuroinflammation. Furthermore, several ongoing pre-clinical studies are currently investigating ncRNA as disease biomarkers and therapeutic interventions to provide new perspectives for AD diagnosis and treatment. In this review, the role of different types of ncRNAs in neuroinflammation during AD are summarized in order to improve our understanding of AD etiology and aid in the translation of basic research into clinical practice.
Ocean and Marine Stewardship in Africa: The Marine Stewardship Council Certification in Namibia and The Gambia
Authors: Nyiawung Richard Achankeng , Erasmus Victoria Ndinelago
Published: June 2022

Ocean and marine stewardship activities across different geographical areas contribute to global sustainability efforts, management, and conservation of ocean resources. The Marine Stewardship Council (MSC), through its sustainability standards and market-based mechanisms, rewards best practices for wild-caught seafood. To date, very few fisheries in Africa have participated in the MSC’s full assessment and obtained its certification. This paper explores the MSC certification scheme in the African continent by examining two case studies: the Namibian hake (Merluccius capensis and M. paradoxus) trawl and longline fishery and The Gambian sole bottom set gillnet fishery (Cynoglossus senegalenis and Synaptura cadenati). Drawing on document analysis, institutional ethnography, and extensive collaborative research with actors in these fisheries, we utilize three stewardship dimensions, i.e., Care-Knowledge-Agency, to qualitatively analyze how the MSC program provides an opportunity of actors to design ocean stewardship tools and promote fisheries sustainability in Africa. The Namibian fishery demonstrates a large-scale fishery with the adequate agency, technical knowledge, and interest in self-design improvements and stewardship, compared to The Gambian fishery, a small-scale fishery motivated to achieve certification but depends largely on external support to coordinate improvements and stewardship activities. The key motivation for Namibia and The Gambia actors to participate in the MSC’s assessment is the interest in increasing their international market access while ensuring ecosystem-based management and sustainability of the fisheries. Successful engagement with MSC requires establishing good governance structures, involvement of local actors, technical knowledge, and sufficient financial resources. The paper demonstrates the need for practitioners, government/market-actors, and academia to encourage sustainable seafood management in Africa by promoting various national and regional sustainability campaigns, environmental awareness programs and ocean stewardship initiatives.
Acceleration of Ovarian Maturation in the Female Mud Crab With RNA Interference of the Vitellogenesis-Inhibiting Hormone (VIH)
Authors: Duangprom Supawadee , Saetan Jirawat , Phanaksri Teva , Songkoomkrong Sineenart , Surinlert Piyaporn , Tamtin Montakan , Sobhon Prasert , Kornthong Napamanee
Published: June 2022

In the present study, double strand RNA technology (dsRNA) was used to inhibit transcripts of vitellogenesis-inhibiting hormone (VIH) that mainly synthesized and secreted from the central nervous system in Scylla olivacea females. The results presented in this study clearly demonstrate the potential dsRNA-VIH was highly effective to inhibit VIH in the eyestalks of females injected with dsRNA-VIH on the 3rd, 7th and 14th day, respectively. The dsRNA-VIH injections were performed at 14-day intervals, a single dsRNA dose of 0.6 µg/gram body weight was enough to suppress VIH expression until 14th day after injection. The dsRNA-VIH injection significantly increased gonad-somatic index (GSI) and hemolymph vitellin level at day 14 and 28 when compared with control groups. The histological observation found that the number of oocyte step 4 in dsRNA-VIH group was significantly higher than that of the control group. Also, dsRNA-VIH has stimulatory function on other reproduction-related genes such as the Scyol-PGES and Scyol-ESULT that both genes gradually increased their expressions in brain and ventral nerve cord. In conclusion, the silence of VIH gene could reduce the production of VIH from eyestalk and brain that affected other downstream genes related to ovarian maturation in the mud crab.
Change of the Long-Term Nitrogen and Phosphorus in the Changjiang (Yangtze) River Estuary
Authors: Liu Jing , Yao Qingzhen , Mi Tiezhu , Wei Qinsheng , Chen Hongtao , Yu Zhigang
Published: June 2022

The concentration and structure of nutrients play a key role in sustaining marine ecosystems. In recent decades, the change in nutrient input from land has led to significant changes in nutrient concentration and structure in the marginal sea and has had an important impact on the coastal ecosystem. Based on historical data from 1984 to 2016, the long-term variations in nutrients and their potential influencing factors, were analyzed in the Changjiang River Estuary. The concentration of dissolved inorganic nitrogen (DIN) increased gradually from 1984 to 2003, but after 2003 the concentration began to decrease. Compared with DIN, the change in dissolved inorganic phosphate (DIP) had a delayed effect and has exhibited a slow downward trend since 2005. The decreases in DIN and DIP are mainly due to the improvement of wastewater treatment efforts and chemical fertilizer use efficiency in recent years. The retention of nutrients by the Three Gorges Reservoir (TGR) has been another important factor since its completion in 2003, especially because the large amount of particulate phosphorus retained by the TGR has led to a significant decrease in the total phosphorus flux into the sea, which is the main reason for the decrease in DIP. The vatiations of DIP and DIN have been instrumental in causing the observed changes of phytoplankton community in the Changjiang River Estuary.
Drainage Efficiency and Geometric Nuances of Tidal Channel Network Mediate Spartina alterniflora Landward Invasion in Marsh-Channel System
Authors: Zheng Shaoyan , Shao Dongdong , Gao Weilun , Nardin William , Ning Zhonghua , Liu Zezheng , Cui Baoshan , Sun Tao
Published: June 2022

As an aggressive invasive salt marsh plant, Spartina alterniflora has been found to invade along tidal channel networks and threaten native salt marsh ecosystems. Previous studies have established patterning correlations between S. alterniflora invasion and tidal channel functions (drainage efficiency). However, a systematic analysis of S. alterniflora invasion in relation to functional and geometric features of tidal channel networks is still lacking. In this study, we extracted tidal channel networks from remote sensing images of the Yellow River Delta, China, and performed numerical experiments to examine S. alterniflora invasion patterns with tidal channel networks with varying drainage efficiency and geometric nuances. An existing vegetation dynamics model was adapted to incorporate hydrochorous seed dispersal and salinity buffer zone as the primary mechanisms of tidal channels to facilitate vegetation colonization and was further coupled with Delft3D. We analyzed the correlation of the simulated S. alterniflora area with a comprehensive set of tidal channel functional and geometric metrics across different spatial scales. Our results confirmed that watersheds with higher drainage efficiency (larger tidal channel density (TCD) and geometric efficiency (GE), smaller overmarsh path length (OPL)) attained larger S. alterniflora area. Given a similar drainage efficiency, tidal channel networks with greater geometric mean bifurcation ratio enhanced S. alterniflora invasion. On a local scale, channel order dictated local drainage efficiency (spatially-varying TCDo) and further influenced S. alterniflora area. The observed patterns were further verified in principle by two real cases in the Yellow River Delta. Finally, in viewing the efficacy of all metrics tested and further considering their computational costs, we proposed a holistic metric framework consisting of global metrics including TCD and geometric mean bifurcation ratio and local metric including spatially-varying TCDo, to assess how tidal channel network mediates S. alterniflora invasion in particular and salt marsh vegetation expansion in general in marsh-channel systems.
3D-Printing Assisted SF-SA Based MgP Hybrid Hydrogel Scaffold for Bone Tissue Engineering
Authors: Mao Qiuyi , Zhu Bowen , Zhuang Hai , Bu Shoushan
Published: June 2022

A new prototype of hybrid silk fibroin and sodium alginate (SF-SA) based osteogenic hydrogel scaffold with a concentration of 2.5% magnesium phosphate (MgP) based gel was prepared with the assistance of an extrusion-based three-dimensional (3D) printing machine in this study. To determine the optimum ratio of MgP-based gel in the hydrogel, a series of physical and biochemical experiments were performed to determine the proper concentration of MgP in two-dimensional hydrogel films, as well as the cell compatibility with these materials in sequence. The SF-SA hydrogel with 2.5wt% magnesium phosphate (SF-SA/MgP) stood out and then was used to fabricate 3D hydrogel scaffolds according to the consequences of the experiments, with SF-SA hydrogel as a control. Then the morphology and osteogenic activity of the scaffolds were further characterized by field emission scanning electron microscope (SEM), calcium mineralization staining, and reverse transcription-polymerase chain reaction (rt-PCR). The SF-SA/MgP hydrogel scaffold promoted the adhesion of rat mesenchymal stem cells with higher degrees of efficiency under dynamic culture conditions. After co-culturing in an osteogenic differentiation medium, cells seeded on SF-SA/MgP hydrogel scaffold were shown to have better performance on osteogenesis in the early stage than the control group. This work illustrates that the 3D structures of hybrid SF-SA/MgP hydrogel are promising headstones for osteogenic tissue engineering.
One-Year Outcomes of Modified Technique for Scleral Fixation of a Three-Piece Intraocular Lens Without Conjunctival Opening
Authors: Ye Hongfei , Zhang Shiguang , Mi Wei , Fei Ping , Zhao Peiquan
Published: June 2022

Purpose

This study aimed to present the 1-year follow-up of a modified technique for scleral fixation of three-piece intraocular lens (IOLs) without conjunctival incision.

Materials and Methods

A retrospective chart review of a consecutive series of 10 eyes of nine patients who underwent scleral IOL fixation using the modified technique was performed. Data were collected 1 year after surgery for all patients.

Results

The range of follow-up time was between 1 year and 31 months. At the last follow-up point, the IOL was well-positioned and the visual acuity was good (as limited by primary diseases). Short-term complications included pupillary IOL capture (n = 1) and decreased intraocular pressure (n = 1), and no long-term complications were observed.

Conclusion

Outcome data support this technique as a viable option for the management of secondary IOL fixation with flexible usage of more designs of IOLs.
Impact of Lung Function Decline on Mortality in Lung Transplant Recipients: Long-Term Results From the L-CsA-i Study for the Prevention of Bronchiolitis Obliterans Syndrome
Authors: Kneidinger Nikolaus , Ghiani Alessandro , Milger Katrin , Monforte Víctor , Knoop Christiane , Jaksch Peter , Parmar Jasvir , Ussetti Piedad , Solé Amparo , Müller-Quernheim Joachim , Voelp Andreas , Behr Juergen , Neurohr Claus
Published: June 2022

Background

Chronic lung allograft dysfunction (CLAD) is defined by a progressive loss of FEV1 and is associated with premature mortality. The aim of this study was to investigate the direct association between FEV1 decline and risk of mortality in patients after lung transplantation (LTx).

Methods

10-year follow up data from lung transplant recipients participating in randomized placebo-controlled clinical trial investigating the role of liposomal Cyclosporine A for inhalation (L-CsA-i) in the prevention of bronchiolitis obliterans syndrome (NCT01334892) was used. The association between the course of FEV1 over time and the risk of mortality was assessed using joint modeling and Cox regression analysis.

Results

A total of 130 patients were included. Predictors of FEV1 decline were a higher absolute FEV1 at baseline and male sex. The joint model analysis indicated a significant association of change of FEV1 and risk of mortality (p < 0.001), with a predicted 3.4% increase in mortality risk for each 1% decline in FEV1. Significant predictors of a progressive phenotype were single LTx and treatment with placebo (as opposed to L-CsA-i). At the end of follow-up, 82 patients (63.1%) were still alive. Cox regression analyses for mortality identified only single LTx as a predictor of higher risk.

Conclusion

Based on our observation of a close association between FEV1 and mortality over a period of 10 years we suggest FEV1 as a valid predictor of mortality and a suitable surrogate endpoint in the investigation of early interventions.
Revisiting the Biological Behavior of Salmonella enterica in Hydric Resources: A Meta-Analysis Study Addressing the Critical Role of Environmental Water on Food Safety and Public Health
Authors: Rocha Alan Douglas de Lima , Ferrari Rafaela Gomes , Pereira Walter Esfrain , Lima Laiorayne Araújo de , Givisiez Patrícia Emília Naves , Moreno-Switt Andrea Isabel , Toro Magaly , Delgado-Suárez Enrique Jesús , Meng Jianghong , Oliveira Celso José Bruno de
Published: June 2022

The increasing number of studies reporting the presence of Salmonella in environmental water sources suggests that it is beyond incidental findings originated from sparse fecal contamination events. However, there is no consensus on the occurrence of Salmonella as its relative serovar representation across non-recycled water sources. We conducted a meta-analysis of proportions by fitting a random-effects model using the restricted maximum-likelihood estimator to obtain the weighted average proportion and between-study variance associated with the occurrence of Salmonella in water sources. Moreover, meta-regression and non-parametric supervised machine learning method were performed to predict the effect of moderators on the frequency of Salmonella in non-recycled water sources. Three sequential steps (identification of information sources, screening and eligibility) were performed to obtain a preliminary selection from identified abstracts and article titles. Questions related to the frequency of Salmonella in aquatic environments, as well as putative differences in the relative frequencies of the reported Salmonella serovars and the role of potential variable moderators (sample source, country, and sample volume) were formulated according to the population, intervention, comparison, and outcome method (PICO). The results were reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyzes statement (PRISMA). A total of 26 eligible papers reporting 148 different Salmonella serovars were retrieved. According to our model, the Salmonella frequency in non-recycled water sources was 0.19 [CI: 0.14; 0.25]. The source of water was identified as the most import variable affecting the frequency of Salmonella, estimated as 0.31 and 0.17% for surface and groundwater, respectively. There was a higher frequency of Salmonella in countries with lower human development index (HDI). Small volume samples of surface water resulted in lower detectable Salmonella frequencies both in high and low HDI regions. Relative frequencies of the 148 serovars were significantly affected only by HDI and volume. Considering that serovars representation can also be affected by water sample volume, efforts toward the standardization of water samplings for monitoring purposes should be considered. Further approaches such as metagenomics could provide more comprehensive insights about the microbial ecology of fresh water and its importance for the quality and safety of agricultural products.
Genomic Characterization of Cronobacter spp. and Salmonella spp. Strains Isolated From Powdered Infant Formula in Chile
Authors: Parra-Flores Julio , Holý Ondřej , Acuña Sergio , Lepuschitz Sarah , Pietzka Ariane , Contreras-Fernández Alejandra , Chavarría-Sepulveda Pamela , Cruz-Córdova Ariadnna , Xicohtencatl-Cortes Juan , Mancilla-Rojano Jetsi , Castillo Alejandro , Ruppitsch Werner , Forsythe Stephen
Published: June 2022

This study characterized five Cronobacter spp. and six Salmonella spp. strains that had been isolated from 155 samples of powdered infant formula (PIF) sold in Chile and manufactured in Chile and Mexico in 2018–2020. Two strains of Cronobacter sakazakii sequence type (ST) ST1 and ST31 (serotypes O:1 and O:2) and one strain of Cronobacter malonaticus ST60 (O:1) were identified. All Salmonella strains were identified as Salmonella Typhimurium ST19 (serotype O:4) by average nucleotide identity, ribosomal multilocus sequence typing (rMLST), and core genome MLST (cgMLST). The C. sakazakii and C. malonaticus isolates were resistant to cephalothin, whereas the Salmonella isolates were resistant to oxacillin and ampicillin. Nineteen antibiotic resistance genes were detected in the C. sakazakii and C. malonaticus isolates; the most prevalent were mcr-9.1, blaCSA, and blaCMA. In Salmonella, 30 genes encoding for aminoglycoside and cephalosporin resistance were identified, including aac(6′)-Iaa, β-lactamases ampH, ampC1, and marA. In the Cronobacter isolates, 32 virulence-associated genes were detected by WGS and clustered as flagellar proteins, outer membrane proteins, chemotaxis, hemolysins, invasion, plasminogen activator, colonization, transcriptional regulator, survival in macrophages, use of sialic acid, and toxin-antitoxin genes. In the Salmonella strains, 120 virulence associated genes were detected, adherence, magnesium uptake, resistance to antimicrobial peptides, secretion system, stress protein, toxin, resistance to complement killing, and eight pathogenicity islands. The C. sakazakii and C. malonaticus strains harbored I-E and I-F CRISPR-Cas systems and carried Col(pHHAD28) and IncFIB(pCTU1) plasmids, respectively. The Salmonella strains harbored type I-E CRISPR-Cas systems and carried IncFII(S) plasmids. The presence of C. sakazakii and Salmonella in PIF is a health risk for infants aged less than 6 months. For this reason, sanitary practices should be reinforced for its production and retail surveillance.
Modulation of the Response to Mycobacterium leprae and Pathogenesis of Leprosy
Authors: Cabral Natasha , de Figueiredo Vilma , Gandini Mariana , de Souza Cíntia Fernandes , Medeiros Rychelle Affonso , Lery Letícia Miranda Santos , Lara Flávio Alves , de Macedo Cristiana Santos , Pessolani Maria Cristina Vidal , Pereira Geraldo Moura Batista
Published: June 2022

The initial infection by the obligate intracellular bacillus Mycobacterium leprae evolves to leprosy in a small subset of the infected individuals. Transmission is believed to occur mainly by exposure to bacilli present in aerosols expelled by infected individuals with high bacillary load. Mycobacterium leprae-specific DNA has been detected in the blood of asymptomatic household contacts of leprosy patients years before active disease onset, suggesting that, following infection, the bacterium reaches the lymphatic drainage and the blood of at least some individuals. The lower temperature and availability of protected microenvironments may provide the initial conditions for the survival of the bacillus in the airways and skin. A subset of skin-resident macrophages and the Schwann cells of peripheral nerves, two M. leprae permissive cells, may protect M. leprae from effector cells in the initial phase of the infection. The interaction of M. leprae with these cells induces metabolic changes, including the formation of lipid droplets, that are associated with macrophage M2 phenotype and the production of mediators that facilitate the differentiation of specific T cells for M. leprae-expressed antigens to a memory regulatory phenotype. Here, we discuss the possible initials steps of M. leprae infection that may lead to active disease onset, mainly focusing on events prior to the manifestation of the established clinical forms of leprosy. We hypothesize that the progressive differentiation of T cells to the Tregs phenotype inhibits effector function against the bacillus, allowing an increase in the bacillary load and evolution of the infection to active disease. Epigenetic and metabolic mechanisms described in other chronic inflammatory diseases are evaluated for potential application to the understanding of leprosy pathogenesis. A potential role for post-exposure prophylaxis of leprosy in reducing M. leprae-induced anti-inflammatory mediators and, in consequence, Treg/T effector ratios is proposed.
The Impact of Glycoengineering on the Endoplasmic Reticulum Quality Control System in Yeasts
Authors: Piirainen Mari A. , Frey Alexander D.
Published: June 2022

Yeasts are widely used and established production hosts for biopharmaceuticals. Despite of tremendous advances on creating human-type N-glycosylation, N-glycosylated biopharmaceuticals manufactured with yeasts are missing on the market. The N-linked glycans fulfill several purposes. They are essential for the properties of the final protein product for example modulating half-lives or interactions with cellular components. Still, while the protein is being formed in the endoplasmic reticulum, specific glycan intermediates play crucial roles in the folding of or disposal of proteins which failed to fold. Despite of this intricate interplay between glycan intermediates and the cellular machinery, many of the glycoengineering approaches are based on modifications of the N-glycan processing steps in the endoplasmic reticulum (ER). These N-glycans deviate from the canonical structures required for interactions with the lectins of the ER quality control system. In this review we provide a concise overview on the N-glycan biosynthesis, glycan-dependent protein folding and quality control systems and the wide array glycoengineering approaches. Furthermore, we discuss how the current glycoengineering approaches partially or fully by-pass glycan-dependent protein folding mechanisms or create structures that mimic the glycan epitope required for ER associated protein degradation.
Different Profiles of Spatial Navigation Deficits In Alzheimer’s Disease Biomarker-Positive Versus Biomarker-Negative Older Adults With Amnestic Mild Cognitive Impairment
Authors: Laczó Martina , Martinkovic Lukas , Lerch Ondrej , Wiener Jan M. , Kalinova Jana , Matuskova Veronika , Nedelska Zuzana , Vyhnalek Martin , Hort Jakub , Laczó Jan
Published: June 2022

Background

Spatial navigation impairment is a promising cognitive marker of Alzheimer’s disease (AD) that can reflect the underlying pathology.

Objectives

We assessed spatial navigation performance in AD biomarker positive older adults with amnestic mild cognitive impairment (AD aMCI) vs. those AD biomarker negative (non-AD aMCI), and examined associations between navigation performance, MRI measures of brain atrophy, and cerebrospinal fluid (CSF) biomarkers.

Methods

A total of 122 participants with AD aMCI (n = 33), non-AD aMCI (n = 31), mild AD dementia (n = 28), and 30 cognitively normal older adults (CN) underwent cognitive assessment, brain MRI (n = 100 had high-quality images for volumetric analysis) and three virtual navigation tasks focused on route learning (body-centered navigation), wayfinding (world-centered navigation) and perspective taking/wayfinding. Cognitively impaired participants underwent CSF biomarker assessment [amyloid-β1–42, total tau, and phosphorylated tau181 (p-tau181)] and amyloid PET imaging (n = 47 and n = 45, respectively), with a subset having both (n = 19).

Results

In route learning, AD aMCI performed worse than non-AD aMCI (p < 0.001), who performed similarly to CN. In wayfinding, aMCI participants performed worse than CN (both p ≤ 0.009) and AD aMCI performed worse than non-AD aMCI in the second task session (p = 0.032). In perspective taking/wayfinding, aMCI participants performed worse than CN (both p ≤ 0.001). AD aMCI and non-AD aMCI did not differ in conventional cognitive tests. Route learning was associated with parietal thickness and amyloid-β1–42, wayfinding was associated with posterior medial temporal lobe (MTL) volume and p-tau181 and perspective taking/wayfinding was correlated with MRI measures of several brain regions and all CSF biomarkers.

Conclusion

AD biomarker positive and negative older adults with aMCI had different profiles of spatial navigation deficits that were associated with posterior MTL and parietal atrophy and reflected AD pathology.
Cerebellar Continuous Theta Burst Stimulation for Aphasia Rehabilitation: Study Protocol for a Randomized Controlled Trial
Authors: Zheng Kai , Chen Mingyun , Shen Ying , Xu Xinlei , Gao Fanglan , Huang Guilan , Ji Yingying , Su Bin , Song Da , Fang Hui , Liu Peng , Ren Caili
Published: June 2022

Background

Language recovery is limited in moderate to severe post-stroke aphasia patients. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising tool in improving language dysfunctions caused by post-stroke aphasia, but the treatment outcome is as yet mixed. Considerable evidence has demonstrated the essential involvement of the cerebellum in a variety of language functions, suggesting that it may be a potential stimulation target of TMS for the treatment of post-stroke aphasia. Theta burst stimulation (TBS) is a specific pattern of rTMS with shorter stimulation times and better therapeutic effects. The effect of continuous TBS (cTBS) on the cerebellum in patients with aphasia with chronic stroke needs further exploration.

Methods

In this randomized, sham-controlled clinical trial, patients (n = 40) with chronic post-stroke aphasia received 10 sessions of real cTBS (n = 20) or sham cTBS (n = 20) over the right cerebellar Crus I+ a 30-min speech-language therapy. The Western Aphasia Battery (WAB) serves as the primary measure of the treatment outcome. The secondary outcome measures include the Boston Diagnostic Aphasia Examination, Boston Naming Test and speech acoustic parameters. Resting-state fMRI data were also obtained to examine treatment-induced changes in functional connectivity of the cerebro-cerebellar network. These outcome measures are assessed before, immediately after, and 12 weeks after cerebellar cTBS intervention.

Discussion

This protocol holds promise that cerebellar cTBS is a potential strategy to improve language functions in chronic post-stroke aphasia. The resting-state fMRI may explore the neural mechanism underlying the aphasia rehabilitation with cerebellar cTBS.
Anterior Circulation Fusiform Aneurysms Have a Lower Occlusion Rate After Pipeline Embolization Device Treatment Than Posterior Circulation Fusiform Aneurysms: A Multicenter Cohort Study
Authors: Xu Chao , Wu Pei , Zou Liang , Xu Shancai , Luo Bin , Yang Xinjian , Shi Huaizhang
Published: June 2022

Objective:

Intracranial fusiform aneurysms are uncommon and can occur in vessels of the anterior circulation (AC) or posterior circulation (PC). While flow diversion is one treatment option, research into Pipeline Embolization Device (PED) treatment is lacking. This study explored the efficacy and safety of PED treatment for intracranial fusiform aneurysms, and compared therapeutic effects between AC and PC aneurysms.

Methods

In the post-market multi-center cohort study of embolization of intracranial aneurysms with PED in China (PLUS) registry study, we retrospectively analyzed 71 fusiform aneurysms in 67 patients among 1,171 patients treated with a PED from November 2014 to October 2019. The general characteristics, perioperative status, aneurysm occlusion rate at the last follow-up angiography, and changes in modified Rankin Scale scores were analyzed. Aneurysms were divided into AC and PC groups, and univariate and multivariate analyses were conducted.

Results

The study included 26 AC (25 patients) and 45 PC (42 patients) aneurysms. A total of 75 PEDs were used, an average of 1.1 PEDs were used, and the median follow-up was 6.7 months. Fifty aneurysms (71.4%) were occluded and twenty (28.5%) were incompletely occluded. There were significantly more occluded aneurysms in the PC group than in the AC group (12 vs. 38; P = 0.001). Risk factors for incomplete occlusion were AC aneurysms (P = 0.001) and a perforating artery originating from the aneurysm (P = 0.006). The mean modified Rankin Scale score was significantly lower at the last follow up than preoperatively (0.58 vs. 0.21; P = 0.0001).

Conclusion

Non-overlapping PED is a safe and effective treatment for both AC and PC fusiform aneurysms. The occlusion rate of AC fusiform aneurysms is lower than that of PC.
Altered Brain Activity in Strabismic Amblyopic Children as Determined by Regional Homogeneity: A Resting-State Functional Magnetic Resonance Imaging Study
Authors: Tan Si-Wen , Cai Guo-Qian , Li Qiu-Yu , Guo Yu , Pan Yi-Cong , Zhang Li-Juan , Ge Qian-Min , Shu Hui-Ye , Zeng Xian-Jun , Shao Yi
Published: June 2022

Objective

Earlier research has determined that amblyopia or strabismus may cause remarkable brain anatomical and functional variations. Nonetheless, thus far, the spontaneous changes in brain activity in children with strabismus amblyopia (SA) remain unclear. The purpose of this study was to determine the association between abnormal brain activity in children with SA and its behavioral manifestations.

Patients and Methods

?A total of 24 children with SA (10 male and 14 female children) as well as 24 healthy controls (HCs), including 10 male and 14 female children were closely matched in sex and age, and examined using resting-state functional magnetic resonance imaging (fMRI). The regional homogeneity (ReHo) technique was applied to evaluate spontaneous cerebral activity variations in children with SA and HCs. Moreover, associations between altered ReHo values in distinct cerebral areas and the degree of strabismus were assessed using Pearson correlation analysis.

Results

Remarkably increased ReHo values were observed in the right lingual, right superior frontal medial, bilateral superior parietal, and right inferior parietal gyri of children with SA compared with HCs. In contrast, mean ReHo values in children with SA were lower in the right cerebellum, left superior frontal gyrus, and left putamen nucleus. Furthermore, esotropia showed a positive correlation with ReHo values of the left putamen.

Conclusion

The anomalous spontaneous activity changes in several brain areas that are caused by SA may indicate neuropathologic mechanisms of visual deficits and oculomotor disorders in children with SA.
Differences in the Association Between Modifiable Lifestyle Factors and Gastric Precancerous Lesions Among Mongolians and Han Chinese
Authors: Wang Weiwei , Qiao Liying , Dong Weiqi , Ren Jing , Chang Xiaotian , Zhan Siyan , Du Peng , Xi Yunfeng , Wang Shengfeng
Published: June 2022

Background

There has been a paucity of evidence examining whether preventable behavioral risk factors led to ethnic differences of gastric precancerous lesions (GPL). We aimed to investigate the ethnic disparity of associations between GPL and lifestyle factors in Mongolian and Han Chinese populations.

Methods

The study included participants aged 36-75 years enrolled in the Cancer Screening Program during 2016-2017 in Hohhot and Tongliao City, Inner Mongolia. GPL was defined as the gross cascading events (i.e., gastric ulcer, atrophic gastritis, intestinal metaplasia, and dysplasia) that preceded gastric cancer.

Results

A total of 61638 participants were included, of whom 6863(11·1%) were Mongolians. Alcohol consumption was positively associated with GPL risk in both ethnic groups, but the magnitude was greater in Mongolians (odds ratio (OR) 6·91, 95%CI 5·82-8·28) than in Han Chinese (OR 5·64, 95%CI 5·27-6·04), corresponding to a higher population attributable fraction (PAF) for Mongolians (53·18% vs 43·71%). Besides, the strength of the positive association between physical inactivity and GPL risk was greater among Mongolians (OR 2·02, 95%CI 1·70-2·41; OR 1·09, 95%CI 1·02-1·17 among Han Chinese) with a higher PAF. Smoking was strongly associated with GPL risk in both ethnic groups as well, but the association was more prominent among Han Chinese (OR 5·24 (1·70-2·41) for <10 cigarettes/d, 8·19 (7·48-8·97) for 11-20 cigarettes/d, 7·07 (6·40-7·81) for ≥21 cigarettes/d; the corresponding ORs were 2·96 (2·19-4·00), 6·22 (5·04-7·68), and 7·03 (5·45-9·08) among Mongolians). Lastly, our findings revealed that a significant correlation between insufficient fruits and vegetable consumption and GPL risk was only found among Mongolians (OR 1·27, 95%CI 1·04-1·56).

Conclusions

Our result suggested that high-risk lifestyle factors should be reduced, particularly in Mongolians. Further studies are needed to elucidate the underlying mechanisms and to reduce health disparities in underserved ethnic groups.
Development of Approaches and Metrics to Measure the Impact and Improve the Clinical Outcomes of Patients With Frailty in the Era of COVID-19. The COMETA Italian Protocol
Authors: Silvestris Nicola , Belleudi Valeria , Addis Antonio , Pimpinelli Fulvia , Morrone Aldo , Sciacchitano Salvatore , Mancini Rita , Garrisi Vito Michele , Costantini Massimo , Ciliberto Gennaro , Frisardi Vincenza , Piaggio Giulia
Published: June 2022

The outbreak of the coronavirus 2 disease 2019 (COVID-19) puts an enormous burden on healthcare systems worldwide. This may worsen outcomes in patients with severe chronic diseases such as cancer, autoimmune diseases, and immune deficiencies. In this critical situation, only a few available data exist, which do not allow us to provide practical guides for the treatment of oncological or immunocompromised patients. Therefore, a further step forward is needed, addressing the specific needs and demands of frail patients in the pandemic era. Here we aim to present a protocol of a study approved by an ethical committee named “CO.M.E.TA”. CO.M.E.TA protocol is a network project involving six Italian institutions and its goals are: i) to measure and compare the impact of the pandemic on the access of cancer and immunocompromised patients to therapies in three Italian regions; ii) to assess how reorganizational measures put in place in these different institutions have impacted specific metrics of performance; iii) to establish a COVID-19 Biobank of biological samples from SARS-CoV-2 infected patients to be used to study immunological alterations in patients with immune frailty.