bluuebunny/crossref_metadata_2025 huggingface dataset:
Is prophylactic lateral lymph node dissection needed for lower rectal cancer? A single-center retrospective study
Authors: Kondo Hiroka , Yamaguchi Shigeki , Hirano Yasumitsu , Aikawa Masayasu , Sato Hiroshi , Okamoto Kojun , Sakuramoto Shinichi , Koyama Isamu
Published: May 2021

Background

The effectiveness of prophylactic lateral lymph node dissection (LLND) in treating patients with lower rectal cancer remains controversial and has not been clearly established. Therefore, we aimed to retrospectively analyze the survival impact of prophylactic LLND in patients with lower rectal cancer.

Methods

Data of 301 patients with lower rectal cancer (tumor’s lower edge on the anal side of the peritoneal reflexion) with clinical T3 disease and negative preoperative lateral lymph node metastasis, who underwent radical resection (R0) at our hospital between April 2007 and March 2017, were included in this study. Patients who received preoperative chemotherapy or radiotherapy were excluded. The relapse-free survival (RFS) and overall survival (OS) rates were compared between the dissection (prophylactic LLND, n = 37) and non-dissection (no prophylactic LLND, n = 264) groups.

Results

Significantly fewer men and younger patients were noted in the dissection group than in the non-dissection group. Post-surgery 3- and 5-year RFS rates were 69.6% and 66.8% in the dissection group and 75.1% and 72.5% in the non-dissection group, respectively (5-year post-surgery RFS, p = 0.58). In the dissection and non-dissection groups, the 5-year OS rates were 86.5% and 79.7%, respectively (p = 0.29), and the 5-year cancer-specific survival rates were 88.9% and 86.0%, respectively (p = 0.29), with no significant differences. Lateral lymph node recurrence was observed in one (2.7%) and 10 patients (3.8%) in the dissection and non-dissection groups, respectively, and there was no significant difference between the groups.

Conclusions

In this study, the effectiveness of prophylactic LLND was limited in patients with > T3 lower rectal cancer with no evidence of preoperative lymph node metastasis. Prophylactic LLND may not be necessary if there is no preoperative lymph node metastasis, even if the invasion depth is T3 or higher.
Exploring the anti-HIV-1 reverse transcriptase, anti-inflammatory, anti-cancer activities and cytotoxicity of two fermented commercial herbal concoctions sold in Limpopo Province of South Africa
Authors: Ntlhamu Matimba I. , Ndhlala Ashwell R. , Masoko Peter
Published: May 2021

Background and objectives

The use of herbal concoctions is very popular in South Africa, including Limpopo Province. The herbal concoctions are claimed to be capable of treating numerous illnesses such as ulcers, cancer, HIV/AIDS, diabetes, certain STDs, blood cleansing to mention but a few. The focus of this study was to evaluate the anti-HIV 1 reverse transcriptase, anti-inflammatory and anti-cancerous activities as well as cytotoxic effects of 2 fermented herbal concoctions used for the treatment of the related ailments in Limpopo province of South Africa.

Method

Two fermented herbal concoctions obtained from a herbalist in Polokwane were extracted with 80% acetone. The anti-HIV activity of the herbal concoctions was determined using the anti-HIV reverse transcriptase assay. The anti-cancer and cytotoxic effects of the herbal concoctions were evaluated using cancerous Human Colon (HT-29) cells and the normal human Hepatoma cells (C3A) respectively.

Results

Notable anti-HIV reverse transcriptase activity was observed from the 80% acetone fraction of herbal concoction 1 (IC50 38.031 μg/mL) which exhibited better activity than the positive control Lamivudine (IC50 40.90 μg/mL). There was variation in the anti-inflammation activity as determined by the sPL2, 15-LOX and COX enzyme assays. The only concerning matter was the high COX-1 activity in some of the extracts, which is not desirable due to the mucosal protection action of COX-1 enzyme. The herbal concoctions did not exhibit cytotoxic effects on normal human cells, however, toxicity against cancerous cells was observed.

Conclusion

The herbal concoctions displayed some considerable pharmacological effects against various ailments as claimed by the herbalist. More work to ascertain the toxicity of both concoctions against cancerous cells need to be followed as this could lead to the discovery of anticancer drugs.
Teaching the social determinants of health through medical legal partnerships: a systematic review
Authors: Welch Kristian , Robinson Benjamin , Martin Michaela Lieberman , Salerno Amy , Harris Drew
Published: May 2021

Background

Undergraduate and graduate medical education often includes the social determinants of health, but questions remain regarding how best to ensure that trainees become empowered to take action on the social determinants of health in their future practice. The authors conducted a systematic review to better define the impact that educational programs centered on medical legal partnerships have on trainees’ knowledge, attitudes and future practice.

The authors sourced data from PubMed, Web of Science, Index to Legal Periodicals, LegalTrac, Google Scholar, Academic Search Complete, Business Source Complete, SocINDEX, SSRN, and Proquest Social Sciences. Selected studies included those centered on Medical Legal Partnerships in undergraduate or graduate medical education and that measured outcomes of the participating trainees. Two abstractors independently extracted information about the study population, setting, design, intervention and outcomes.

Results

Six out of 483 studies met the inclusion criteria. One study highlighted four different MLPs, thus nine total MLP programs were included. Trainees included medical students as well as interns and residents from pediatrics, family medicine and internal medicine. Interventions ranged from didactic sessions, to advocacy projects, to hands-on community-based learning, to poverty simulation trainings. Benefits to trainees were wide in scope but all programs showed improvements in participants’ understanding, comfort, confidence, and/or abilities in identifying and intervening on the social determinants of health in their patients.

Conclusion

As medical schools and residency programs are increasingly considering how to effectively teach trainees to understand and address the social determinants of health, the findings in this systematic review suggest that inclusion of Medical Legal Partnerships into training programs is an effective approach.
Fertility desires of people living with HIV: does the implementation of a sexual and reproductive health and HIV integration model change healthcare providers’ attitudes and clients’ desires?
Authors: Milford Cecilia , Beksinska Mags , Greener Ross , Pienaar Jacqueline , Rambally Greener Letitia , Mabude Zonke , Smit Jennifer
Published: May 2021

Background

There is a need for information and healthcare support for the fertility desires and contraceptive needs of people living with HIV (PLHIV) in order to provide safer conception support for sero-discordant couples wanting to safely conceive. A model to integrate sexual and reproductive health and HIV services was developed and implemented in a district hospital and six clinics in the eThekwini District, South Africa.

Methods

To evaluate the model’s success, a cross-sectional survey was conducted before and after implementation of the model. As part of this evaluation, fertility desires of PLHIV (both male and female), and providers’ perspectives thereof were explored. Changes in desires and attitudes after integration of services were investigated.

Results

Forty-six healthcare providers and 269 clients (48 male, 221 female) were surveyed at baseline, and 44 providers and 300 clients (70 male, 230 female) at endline. Various factors including relationship status, parity and antiretroviral treatment (ART) access influenced PLHIVs’ desires for children. Concerns for their own and their child’s health negatively impacted on PLHIV’s fertility desires. These concerns declined after integration of services. Similarly, providers’ concerns about PLHIV having children decreased after the implementation of the model.

Conclusions

Integrated services are important to facilitate provision of information on contraceptive options as well as safer conception information for PLHIV who want to have children.
Ichthyosis: case report in a Colombian man with genetic alterations in ABCA12 and HRNR genes
Authors: Arias-Pérez Ruben D. , Gallego-Quintero Salomón , Taborda Natalia A. , Restrepo Jorge E. , Zambrano-Cruz Renato , Tamayo-Agudelo William , Bermúdez Patricia , Duque Constanza , Arroyave Ismael , Tejada-Moreno Johanna A. , Villegas-Lanau Andrés , Mejía-García Alejandro , Zapata Wildeman , Hernandez Juan C. , Cuartas-Montoya Gina
Published: May 2021

Background

Ichthyosis is a heterogeneous group of diseases caused by genetic disorders related to skin formation. They are characterized by generalized dry skin, scaling, hyperkeratosis and frequently associated with erythroderma. Among its different types, harlequin ichthyosis (HI) stands out due to its severity. HI is caused by mutations in theABCA12gene, which encodes essential proteins in epidermal lipid transport, and it helps maintain the homeostasis of the stratum corneum of the epidermis. However, due to the wide spectrum of genetic alterations that can cause ichthyosis, holistic medical care, and genetic studies are required to improve the diagnosis and outcomes of these diseases.

Case presentation

Here, we presented the case of a 19 years old male patient who was a premature infant and exhibited clinical features consistent with HI, including bright yellow hyperkeratotic plates with erythematous fissures that covered his entire body like a collodion baby. Currently, he exhibited erythroderma, photosensitivity, ectropion, auricular pavilion alterations, and musculoskeletal disorders, such as equinovarus feet, fingers, hands, and hypoplastic feet with contractures in flexion and marked difficulty in fine motor skills. In addition, he presented dyschromatopsia, Achilles reflex hyporeflexia, slight speech, dental alteration and deficient cognitive performance. After the genetic sequencing, variants were found inABCA12andHRNRwhich are related to several skin diseases, including ichthyosis.

Conclusions

Although in clinical practice, ichthyosis is a common entity, a severe type of ichthyosis is presented, highlighting the importance of appropriate genetic diagnosis, given the broad spectrum of genetic alterations with similar phenotypic and clinical characteristics. These pathologies must be known to guarantee initial support measures to prevent complications and offer multidisciplinary management to those patients.
3-Methyladenine but not antioxidants to overcome BACH2-mediated bortezomib resistance in mantle cell lymphoma
Authors: Feng Min , Wang Jia , Sun Ming , Li Guilan , Li BingXiang , Zhang Han
Published: May 2021

Background

Bortezomib (BTZ) is an inhibitor of the proteasome that has been used to treat patients with mantle cell lymphoma (MCL), but the resistance to BTZ in clinical cases remains a major drawback. BACH2 is a lymphoid-specific transcription repressor recognized as a tumor suppressor in MCL. Reduced BACH2 levels contribute to BTZ resistance; however, the molecular events underlying BACH2-mediated BTZ resistance are largely unclear.

Methods

We silenced BACH2 in MCL cells using a lentiviral shRNA-mediated knockdown system. Bioinformatic, real-time RT-PCR, immunoblotting and a series of functional assays were performed to describe the molecular mechanisms underlying BTZ resistance in MCL. The therapeutic effects of chemicals were evaluated on numerous cellular and molecular processes in resistant MCL cell lines and xenografts.

Results

In resistant cells, BTZ-triggered mild oxidative stress induced a strong activation of PI3K-AKT signaling, which further blocked nuclear translocation of BACH2. Defective nuclear translocation of BACH2 or silencing BACH2 removed its transcriptional repression on HMOX1, leading to upregulation of heme oxygenase-1 (HO-1). Increased HO-1 further maintained reactive oxygen species (ROS) within a minimal tumor-promoting level and enhanced cytoprotective autophagy. Interestingly, although mild increase in ROS exhibited a pro-tumorigenic effect on resistant cells, simply blocking ROS by antioxidants did not lead to cell death but aggravated BTZ resistance via stabilizing BACH1, the other member of BACH family. Instead, 3-methyladenine (3-MA), a dual inhibitor to suppress PI3K signaling and autophagosome formation, sensitized resistant MCL cells to BTZ, both in vitro and in vivo.

Conclusion

Our results dissected the interconnected molecular network in resistant MCL cells in which 3-MA represents an effective therapeutic strategy to overcome BTZ resistance. Notably, BACH1 and BACH2, albeit from the same family, are likely to play opposite roles in pathogenesis and progression of MCL.
Low-dose X-ray enhanced tumor accumulation of theranostic nanoparticles for high-performance bimodal imaging-guided photothermal therapy
Authors: Wei Qiaolin , He Jian , Wang Shuaifei , Hua Shiyuan , Qi Yuchen , Li Fangyuan , Ling Daishun , Zhou Min
Published: May 2021

Background

Theranostic nanoparticles (NPs) have achieved rapid development owing to their capacity for personalized multimodal diagnostic imaging and antitumor therapy. However, the efficient delivery and bulk accumulation of NPs in tumors are still the decisive factors in improving therapeutic effect. It is urgent to seek other methods to alters tumor microenvironment (like vascular permeability and density) for enhancing the efficiency of nanoparticles delivery and accumulation at the tumor site.

Methods

Herein, we developed a Raman-tagged hollow gold nanoparticle (termed as HAuNP@DTTC) with surface-enhanced Raman scattering (SERS) property, which could be accumulated efficiently in tumor site with the pre-irradiation of low-dose (3 Gy) X-ray and then exerted highly antitumor effect in breast cancer model.

Results

The tumor growth inhibition (TGI) of HAuNP@DTTC-induced photothermal therapy (PTT) was increased from 60% for PTT only to 97%, and the lethal distant metastasis of 4T1 breast cancer (such as lung and liver) were effectively inhibited under the X-ray-assisted PTT treatment. Moreover, with the strong absorbance induced by localized surface plasmon resonance in near-infrared (NIR) region, the signals of Raman/photoacoustic (PA) imaging in tumor was also significantly enhanced after the administration of HAuNP@DTTC, indicating it could be used as the Raman/PA imaging and photothermal agent simultaneously under 808 nm laser irradiation.

Conclusions

Our studied of the as-prepared HAuNP@DTTC integrated the Raman/PA imaging and PTT functions into the single platform, and showed the good prospects for clinical applications especially with the low-dose X-ray irradiation as an adjuvant, which will be a productive strategy for enhancing drug delivery and accumulation in tumor theranostics.

Graphic Abstract
ZNF445: a homozygous truncating variant in a patient with Temple syndrome and multilocus imprinting disturbance
Authors: Kagami Masayo , Hara-Isono Kaori , Matsubara Keiko , Nakabayashi Kazuhiko , Narumi Satoshi , Fukami Maki , Ohkubo Yumiko , Saitsu Hirotomo , Takada Shuji , Ogata Tsutomu
Published: May 2021

Background

ZNF445, as well as ZFP57, is involved in the postfertilization methylation maintenance of multiple imprinting-associated differentially methylated regions (iDMRs). Thus, ZNF445 pathogenic variants are predicted to cause multilocus imprinting disturbances (MLIDs), as do ZFP57 pathogenic variants. In particular, the MEG3/DLK1:IG-DMR would be affected, because the postzygotic methylation imprint of the MEG3/DLK1:IG-DMR is maintained primarily by ZNF445, whereas that of most iDMRs is preserved by both ZFP57 and ZNF445 or primarily by ZFP57.

Results

We searched for a ZNF445 variant(s) in six patients with various imprinting disorders (IDs) caused by epimutations and MLIDs revealed by pyrosequencing for nine iDMRs, without a selection for the original IDs. Re-analysis of the previously obtained whole exome sequencing data identified a homozygous ZNF445 variant (NM_181489.6:c.2803C>T:p.(Gln935*)) producing a truncated protein missing two of 14 zinc finger domains in a patient with Temple syndrome and MLID. In this patient, array-based genomewide methylation analysis revealed severe hypomethylation of most CpGs at the MEG3:TSS-DMR, moderate hypomethylation of roughly two-thirds of CpGs at the H19/IGF2:IG-DMR, and mild-to-moderate hypomethylation of a few CpGs at the DIRAS3:TSS-DMR, MEST:alt-TSS-DMR, IGF2:Ex9-DMR, IGF2:alt-TSS, and GNAS-AS1:TSS-DMR. Furthermore, bisulfite sequencing analysis for the MEG3/DLK1:IG-DMR delineated a markedly hypomethylated segment (CG-A). The heterozygous parents were clinically normal and had virtually no aberrant methylation pattern.

Conclusions

We identified a ZNF445 pathogenic variant for the first time. Since ZNF445 binds to the MEG3/DLK1:IG-DMR and other iDMRs affected in this patient, the development of Temple syndrome and MLID would primarily be explained by the ZNF445 variant. Furthermore, CG-A may be the target site for ZNF445 within the MEG3/DLK1:IG-DMR.
Soil microbial community variation with time and soil depth in Eurasian Steppe (Inner Mongolia, China)
Authors: Zhao Hongbin , Zheng Wenling , Zhang Shengwei , Gao Wenlong , Fan Yueyue
Published: May 2021

Purpose

Soil microorganisms play an indispensable role in the material and energy cycle of grassland ecosystems. The abundance of these organisms vary according to environmental factors, such as time of year and soil depth. There have been few studies on the transformation of soil microbial communities in degraded typical steppe according to these temporal and spatial changes. In this study, we analyze the community structure and diversity of soil bacteria and fungi, and the impact of these changing temporal and spatial factors upon the community structure.

Methods

From May to September 2018, we collected 90 soil samples from different depths (10, 20, and 30 cm) from the typical degraded steppe area of Xilingol. We carried out studies on soil physical and chemical properties and soil microbial diversity using high-throughput sequencing technology.

Results

We found that depth significantly affected abundance and diversity of bacteria and fungi. Bacteria and fungi diversity at 10 cm was higher than that at 20 cm and 30 cm. The abundance of Acidobacteria, Proteobacteria, Actinomycetes, Ascomycetes, and Basidiomycetes varies significantly with depth. In addition, soil pH increased significantly with increasing depth, while soil organic matter (SOM), available nitrogen (AN), volume water content of soil (VWC), and soil temperature (ST) decreased significantly with increasing depth. Finally, the depth, total organic carbon (TOC), and AN had a significant impact on the bacterial and fungal communities’ abundance (p< 0.05).

Conclusions

Spatial heterogeneity (in soil depth) is more significant than the time of year (month) in predicting changes in microbial community composition and soil properties. SOM, VWC, and the abundance of Proteobacteria and Actinomycetes positively correlate with soil depth, while pH and the abundance of Acidobacteria, Ascomycetes, and Basidiomycetes negatively correlate with soil depth. We speculate that SOM and VWC account for the variations in the abundance of Acidobacteria and Proteobacteria, while pH causes variations in the abundance of Actinomycetes, Ascomycetes and Basidiomycota.
Felty syndrome: a case report
Authors: Gupta Anupam , Abrahimi Aryan , Patel Aesha
Published: May 2021

Background

Felty syndrome is a rare manifestation of chronic rheumatoid arthritis in which patients develop extraarticular features of hepatosplenomegaly and neutropenia. The typical presentation of Felty syndrome is in Caucasians, females, and patients with long-standing rheumatoid arthritis of 10 or more years. This case report presents a patient with an early-onset and atypical demographic for Felty syndrome.

Case presentation

Our patient is a 28-year-old African American woman with past medical history of rheumatoid arthritis diagnosed in 2017, asthma, pneumonia, anemia, and mild intellectual disability who was admitted to inpatient care with fever, chills, and right ear pain for 7 days. The patient’s mother, also her caregiver, brought the patient to the hospital after symptoms of fever and ear pain failed to improve. Our patient was diagnosed with sepsis secondary to pneumonia and urinary tract infection. She had been admitted twice in the past year, both times with a diagnosis of pneumonia. During this visit in September 2019, it was discovered that the patient had leukopenia and neutropenia. Bone marrow biopsy revealed increased immature mononuclear cells with left shift and rare mature neutrophils. During the hospital course, the patient was provisionally diagnosed with Felty syndrome and treated with adalimumab and hydroxychloroquine for her rheumatoid arthritis. Her sepsis secondary to pneumonia and urinary tract infection was treated with ceftriaxone and doxycycline, which was later switched to cefepime because of positive blood and urine cultures for Pseudomonas aeruginosa. She was discharged with stable vital signs and is continuing to control her rheumatoid arthritis with adalimumab.

Conclusion

This case report details the clinical course of sepsis secondary to pneumonia and urinary tract infection in the setting of Felty syndrome. Our patient does not fit the conventional profile for presentation given her race, age, and the length of time following diagnosis of rheumatoid arthritis.
Mesenchymal stem cell-derived microvesicles improve intestinal barrier function by restoring mitochondrial dynamic balance in sepsis rats
Authors: Zheng Danyang , Zhou Henan , Wang Hongchen , Zhu Yu , Wu Yue , Li Qinghui , Li Tao , Liu Liangming
Published: May 2021

Background

Sepsis is a major cause of death in ICU, and intestinal barrier dysfunction is its important complication, while the treatment is limited. Recently, mesenchymal stem cell-derived microvesicles (MMVs) attract much attention as a strategy of cell-free treatment; whether MMVs are therapeutic in sepsis induced-intestinal barrier dysfunction is obscure.

Methods

In this study, cecal ligation and puncture-induced sepsis rats and lipopolysaccharide-stimulated intestinal epithelial cells to investigate the effect of MMVs on intestinal barrier dysfunction. MMVs were harvested from mesenchymal stem cells and were injected into sepsis rats, and the intestinal barrier function was measured. Afterward, MMVs were incubated with intestinal epithelial cells, and the effect of MMVs on mitochondrial dynamic balance was measured. Then the expression of mfn1, mfn2, OPA1, and PGC-1α in MMVs were measured by western blot. By upregulation and downregulation of mfn2 and PGC-1α, the role of MMVs in mitochondrial dynamic balance was investigated. Finally, the role of MMV-carried mitochondria in mitochondrial dynamic balance was investigated.

Results

MMVs restored the intestinal barrier function by improving mitochondrial dynamic balance and metabolism of mitochondria. Further study revealed that MMVs delivered mfn2 and PGC-1α to intestinal epithelial cells, and promoted mitochondrial fusion and biogenesis, thereby improving mitochondrial dynamic balance. Furthermore, MMVs delivered functional mitochondria to intestinal epithelial cells and enhanced energy metabolism directly.

Conclusion

MMVs can deliver mfn2, PGC-1α, and functional mitochondria to intestinal epithelial cells, synergistically improve mitochondrial dynamic balance of target cells after sepsis, and restore the mitochondrial function and intestinal barrier function. The study illustrated that MMVs might be a promising strategy for the treatment of sepsis.
Upregulation of Apol8 by Epothilone D facilitates the neuronal relay of transplanted NSCs in spinal cord injury
Authors: Xue Weiwei , Zhang Haipeng , Fan Yongheng , Xiao Zhifeng , Zhao Yannan , Liu Weiyuan , Xu Bai , Yin Yanyun , Chen Bing , Li Jiayin , Cui Yi , Shi Ya , Dai Jianwu
Published: May 2021

Background

Microtubule-stabilizing agents have been demonstrated to modulate axonal sprouting during neuronal disease. One such agent, Epothilone D, has been used to treat spinal cord injury (SCI) by promoting axonal sprouting at the lesion site after SCI. However, the role of Epothilone D in the differentiation of neural stem cells (NSCs) in SCI repair is unknown. In the present study, we mainly explored the effects and mechanisms of Epothilone D on the neuronal differentiation of NSCs and revealed a potential new SCI treatment.

Methods

In vitro differentiation assays, western blotting, and quantitative real-time polymerase chain reaction were used to detect the effects of Epothilone D on NSC differentiation. Retrograde tracing using a pseudotyped rabies virus was then used to detect neuronal circuit construction. RNA sequencing (RNA-Seq) was valuable for exploring the target gene involved in the neuronal differentiation stimulated by Epothilone D. In addition, lentivirus-induced overexpression and RNA interference technology were applied to demonstrate the function of the target gene. Last, an Apol8-NSC-linear ordered collagen scaffold (LOCS) graft was prepared to treat a mouse model of SCI, and functional and electrophysiological evaluations were performed.

Results

We first revealed that Epothilone D promoted the neuronal differentiation of cultured NSCs and facilitated neuronal relay formation in the injured site after SCI. Furthermore, the RNA-Seq results demonstrated that Apol8 was upregulated during Epothilone D-induced neuronal relay formation. Lentivirus-mediated Apol8 overexpression in NSCs (Apol8-NSCs) promoted NSC differentiation toward neurons, and an Apol8 interference assay showed that Apol8 had a role in promoting neuronal differentiation under the induction of Epothilone D. Last, Apol8-NSC transplantation with LOCS promoted the neuronal differentiation of transplanted NSCs in the lesion site as well as synapse formation, thus improving the motor function of mice with complete spinal cord transection.

Conclusions

Epothilone D can promote the neuronal differentiation of NSCs by upregulating Apol8, which may provide a promising therapeutic target for SCI repair.
Network analysis of the left anterior descending coronary arteries in swim-trained rats by an in situ video microscopic technique
Authors: Török Marianna , Merkely Petra , Monori-Kiss Anna , Horváth Eszter Mária , Sziva Réka Eszter , Péterffy Borbála , Jósvai Attila , Sayour Alex Ali , Oláh Attila , Radovits Tamás , Merkely Béla , Ács Nándor , Nádasy György László , Várbíró Szabolcs
Published: May 2021

Background

We aimed to identify sex differences in the network properties and to recognize the geometric alteration effects of long-term swim training in a rat model of exercise-induced left ventricular (LV) hypertrophy.

Methods

Thirty-eight Wistar rats were divided into four groups: male sedentary, female sedentary, male exercised and female exercised. After training sessions, LV morphology and function were checked by echocardiography. The geometry of the left coronary artery system was analysed on pressure-perfused, microsurgically prepared resistance artery networks using in situ video microscopy. All segments over > 80 μm in diameter were studied using divided 50-μm-long cylindrical ring units of the networks. Oxidative-nitrative (O-N) stress markers, adenosine A2A and estrogen receptor (ER) were investigated by immunohistochemistry.

Results

The LV mass index, ejection fraction and fractional shortening significantly increased in exercised animals. We found substantial sex differences in the coronary network in the control groups and in the swim-trained animals. Ring frequency spectra were significantly different between male and female animals in both the sedentary and trained groups. The thickness of the wall was higher in males as a result of training. There were elevations in the populations of 200- and 400-μm vessel units in males; the thinner ones developed farther and the thicker ones closer to the orifice. In females, a new population of 200- to 250-μm vessels appeared unusually close to the orifice.

Conclusions

Physical activity and LV hypertrophy were accompanied by a remodelling of coronary resistance artery network geometry that was different in both sexes.
Biosynthesis of silver nanoparticles using Haloferax sp. NRS1: image analysis, characterization, in vitro thrombolysis and cytotoxicity
Authors: Tag Hend M. , Saddiq Amna A. , Alkinani Monagi , Hagagy Nashwa
Published: May 2021

Haloferax sp strain NRS1 (MT967913) was isolated from a solar saltern on the southern coast of the Red Sea, Jeddah, Saudi Arabia. The present study was designed for estimate the potential capacity of the Haloferax sp strain NRS1 to synthesize (silver nanoparticles) AgNPs. Biological activities such as thrombolysis and cytotoxicity of biosynthesized AgNPs were evaluated. The characterization of silver nanoparticles biosynthesized by Haloferax sp (Hfx-AgNPs) was analyzed using UV–vis spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). The dark brown color of the Hfx-AgNPs colloidal showed maximum absorbance at 458 nm. TEM image analysis revealed that the shape of the Hfx-AgNPs was spherical and a size range was 5.77- 73.14 nm. The XRD spectra showed a crystallographic plane of silver nanoparticles, with a crystalline size of 29.28 nm. The prominent FTIR peaks obtained at 3281, 1644 and 1250 cm− 1 identified the Functional groups involved in the reduction of silver ion reduction to AgNPs. Zeta potential results revealed a negative surface charge and stability of Hfx-AgNPs. Colloidal solution of Hfx-AgNPs with concentrations ranging from 3.125 to 100 μg/mL was used to determine its hemolytic activity. Less than 12.5 μg/mL of tested agent showed no hemolysis with high significant decrease compared with positive control, which confirms that Hfx-AgNPs are considered non-hemolytic (non-toxic) agents according to the ISO/TR 7405-1984(f) protocol. Thrombolysis activity of Hfx-AgNPs was observed in a concentration-dependent manner. Further, Hfx-AgNPs may be considered a promising lead compound for the pharmacological industry.
Review of Nomad’s land: Pastoralism and French environmental policy in the nineteenth-century Mediterranean world by Andrea E. Duffy
Authors: Guerin Adam
Published: May 2021

Book details

Andrea E. Duffy, Nomad’s Land: Pastoralism and French Environmental Policy in the Nineteenth-Century Mediterranean World (Lincoln, NE: University of Nebraska Press, 2019). 191 pages + notes, index and bibliography ISBN: 9780803290976
Semaphorin3A increases M1-like microglia and retinal ganglion cell apoptosis after optic nerve injury
Authors: Yun-Jia Liu , Xi Chen , Jie-Qiong Zhang , Jing-Yi Zhu , Sen Lin , Jian Ye
Published: May 2021

Background

The mechanisms leading to retinal ganglion cell (RGC) death after optic nerve injury have not been fully elucidated. Current evidence indicates that microglial activation and M1- and M2-like dynamics may be an important factor in RGC apoptosis after optic nerve crush (ONC). Semaphorin3A (Sema3A) is a classic axonal guidance protein,which has been found to have a role in neuroinflammation processes. In this study, we investigated the contribution of microglial-derived Sema3A to progressive RGC apoptosis through regulating paradigm of M1- and M2-like microglia after ONC.

Method

A mouse ONC model and a primary microglial-RGC co-culture system were used in the present study. The expression of M1- and M2-like microglial activation markers were assessed by real-time polymerase chain reaction (RT-qPCR). Histological and Western blot (WB) analyses were used to investigate the polarization patterns of microglia transitions and the levels of Sema3A. RGC apoptosis was investigated by TUNEL staining and caspase-3 detection.

Results

Levels of Sema3A in the mouse retina increased after ONC. Treatment of mice with the stimulating factor 1 receptor antagonist PLX3397 resulted in a decrease of retinal microglia. The levels of CD16/32 (M1) were up-regulated at days 3 and 7 post-ONC. However, CD206 (M2) declined on day 7 after ONC. Exposure to anti-Sema3A antibodies (anti-Sema3A) resulted in a decrease in the number of M1-like microglia, an increase in the number of M2-like microglia, and the amelioration of RGC apoptosis.

Conclusions

An increase in microglia-derived Sema3A in the retina after ONC partially leads to a continuous increase of M1-like microglia and plays an important role in RGC apoptosis. Inhibition of Sema3A activity may be a novel approach to the prevention of RGC apoptosis after optic nerve injury.
Correction to: Impact of systematic screening for AmpC-hyperproducing Enterobacterales intestinal carriage in intensive care unit patients
Authors: Manquat Elsa , Le Dorze Matthieu , Pean De Ponflly Gauthier , Benmansour Hanaa , Amarsy Rishma , Cambau Emmanuelle , Soyer Benjamin , Chousterman Benjamin Glenn , Jacquier Hervé
Published: May 2021

An amendment to this paper has been published and can be accessed via the original article.
Exotic pets in Ireland: 1. Prevalence of ownership and access to veterinary services
Authors: Goins Matt , Hanlon Alison J.
Published: May 2021

Background

There has been increasing concern expressed about the welfare of exotic pets worldwide. For the purposes of this article, an exotic pet is considered to be a non-domesticated species, where there are knowledge gaps on good practice (minimum standards of care), veterinary diagnostics and treatments. The categories of exotic pets included in this study were: small mammals (< 20 kg), large mammals (> 20 kg), birds, reptiles, amphibians, fish and invertebrates. Dogs, cats, rabbits, hamsters, gerbils, guinea pigs, mice, rats, and ferrets were excluded from the study. An online survey of pet owning staff at University College Dublin was conducted between July and August 2020 to provide the first empirical data for Ireland. In this pilot study (the first in this thematic series) we aim to characterise exotic pet ownership, the challenges and benefits of keeping exotic pets, and access to veterinary services from the pet owner’s perspective.

Results

Using an online survey this pilot study gathered evidence from 83 domestic and 32 exotic pet owners within the staff (n = ~ 3600 FTE) at University College Dublin, the largest third level institution in Ireland. The prevalence of exotic pet ownership was determined to be 34.4 % of households with more than 10 % of pet owning households owning only exotic pets. Fish (n = 15), reptiles (n = 13) and birds (n = 8) were the most common types of exotic pets. Thirty-four per cent of exotic pet owners never sought veterinary services, the most common reasons were due to lack of local veterinary specialists (n = 10) and good owner knowledge (n = 8). However identifying appropriate guidance on the animals’ needs was a common challenge for exotic pet owners (n = 13). A reasonable monthly cost of caring for an exotic ranged from €20–180, depending on the species.

Conclusions

This pilot study contains important implications for veterinary education to support the veterinary community with providing services to the exotic pet owning community. Policy issues with exotic pet ownership also need to be considered and further research into the proposed strategies to support the health and welfare of exotic pets should be carried out such as the introduction of white lists and guidelines on responsible pet ownership.
Opportunistic routing based on partial CSI in MIMO random ad-hoc networks
Authors: Richter Yiftach , Bergel Itsik
Published: May 2021

In this paper we consider opportunistic routing in multiple-input–multiple-output (MIMO) random wireless ad-hoc networks (WANETs). Our analysis uses a proper model of the physical layer together with an abstraction of the higher communication layers. We assume that the nodes are distributed according to a Poisson point process and consider a routing scheme that opportunistically selects the next relay and the number of spatially multiplexed data streams. The routing decisions are based on geographic locations, the channel gains of the neighbor nodes, and the statistical characterization of all other nodes. Unlike the single antenna case, the optimal routing scheme cannot be explicitly expressed. Hence, we propose a smart-routing scheme for MIMO that adapts the number of data streams per user to the channel conditions. The numerical results demonstrate that this scheme outperforms all previously published schemes for this scenario. The findings highlight the importance of channel state information for efficient routing, and the need for an adaptive selection of the number of data streams at each transmitter.
Dzherelo (Immunoxel) as adjunctive therapy to standard antituberculosis treatment in patients with pulmonary tuberculosis: a systematic review and meta-analysis of clinical trials
Authors: Kitenge Marcel , Phiri Bessie , Pheeha Sara M. , Ogunrombi Modupe , Nyasulu Peter S.
Published: May 2021

Background

Dzherelo (Immunoxel) is one of the few approved immunomodulators that has been shown to produce positive treatment outcomes in patients with tuberculosis (TB). The aim of this review was to assess the effectiveness of Immunoxel used as adjunct therapy with conventional anti-TB therapy for the treatment of pulmonary TB.

Methods

Comprehensive search was conducted in different major databases: PubMed (MEDLINE), EMBASE (OVID), Cochrane Central Register of Controlled Trials (CENTRAL), Scopus (Elsevier). We also searched Google Scholar along with trial registries and hand-searched the reference list of identified original research as well as review articles. Conference proceedings of relevant TB and lung disease annual conferences were also screened. Two independent authors extracted outcome data using a standardised extraction form. Relative risk (RR), mean difference (MD) and standardised mean difference (SMD) with a 95% confidence interval (CI) were used as measures of effect. We assessed certainty of evidence using GRADE.

Results

Six clinical trials, which met the criteria for the review, were identified, and these provided data for the review. Overall results from the six trials that compared antituberculosis treatment (ATT) alone versus ATT and Immunoxel, and ATT and placebo versus ATT and Immunoxel showed an increased number of patients becoming sputum-negative in the Immunoxel group (RR 3.19; 95% CI 2.44 to 4.17; 488 participants). There was also reduction in body temperature among patients receiving Immunoxel compared to ATT alone (MD −0.20, 95% CI −0.22 to −0.18, 345 participants). However, there were no differences in body weight changes across all the studies (MD 5.65; 95% CI −0.80 to 12.11; 382 participants).

Conclusion

Current evidence indicates that the use of Immunoxel as an adjunctive treatment in patients with pulmonary tuberculosis has the potential to enhance the efficacy of antituberculosis treatment. However, well-designed, conducted and adequately powered clinical trials are needed to establish the effectiveness of this adjunctive treatment.

Systematic review registration

PROSPERO registration number: CRD42019127823
Text mining to support abstract screening for knowledge syntheses: a semi-automated workflow
Authors: Pham Ba’ , Jovanovic Jelena , Bagheri Ebrahim , Antony Jesmin , Ashoor Huda , Nguyen Tam T. , Rios Patricia , Robson Reid , Thomas Sonia M. , Watt Jennifer , Straus Sharon E. , Tricco Andrea C.
Published: May 2021

Background

Current text mining tools supporting abstract screening in systematic reviews are not widely used, in part because they lack sensitivity and precision. We set out to develop an accessible, semi-automated “workflow” to conduct abstract screening for systematic reviews and other knowledge synthesis methods.

Methods

We adopt widely recommended text-mining and machine-learning methods to (1) process title-abstracts into numerical training data; and (2) train a classification model to predict eligible abstracts. The predicted abstracts are screened by human reviewers for (“true”) eligibility, and the newly eligible abstracts are used to identify similar abstracts, using near-neighbor methods, which are also screened. These abstracts, as well as their eligibility results, are used to update the classification model, and the above steps are iterated until no new eligible abstracts are identified. The workflow was implemented in R and evaluated using a systematic review of insulin formulations for type-1 diabetes (14,314 abstracts) and a scoping review of knowledge-synthesis methods (17,200 abstracts). Workflow performance was evaluated against the recommended practice of screening abstracts by 2 reviewers, independently. Standard measures were examined: sensitivity (inclusion of all truly eligible abstracts), specificity (exclusion of all truly ineligible abstracts), precision (inclusion of all truly eligible abstracts among all abstracts screened as eligible), F1-score (harmonic average of sensitivity and precision), and accuracy (correctly predicted eligible or ineligible abstracts). Workload reduction was measured as the hours the workflow saved, given only a subset of abstracts needed human screening.

Results

With respect to the systematic and scoping reviews respectively, the workflow attained 88%/89% sensitivity, 99%/99% specificity, 71%/72% precision, an F1-score of 79%/79%, 98%/97% accuracy, 63%/55% workload reduction, with 12%/11% fewer abstracts for full-text retrieval and screening, and 0%/1.5% missed studies in the completed reviews.

Conclusion

The workflow was a sensitive, precise, and efficient alternative to the recommended practice of screening abstracts with 2 reviewers. All eligible studies were identified in the first case, while 6 studies (1.5%) were missed in the second that would likely not impact the review’s conclusions. We have described the workflow in language accessible to reviewers with limited exposure to natural language processing and machine learning, and have made the code available to reviewers.
Characterization of the public transit air microbiome and resistome reveals geographical specificity
Authors: Leung M. H. Y. , Tong X. , Bøifot K. O. , Bezdan D. , Butler D. J. , Danko D. C. , Gohli J. , Green D. C. , Hernandez M. T. , Kelly F. J. , Levy S. , Mason-Buck G. , Nieto-Caballero M. , Syndercombe-Court D. , Udekwu K. , Young B. G. , Mason C. E. , Dybwad M. , Lee P. K. H.
Published: May 2021

Background

The public transit is a built environment with high occupant density across the globe, and identifying factors shaping public transit air microbiomes will help design strategies to minimize the transmission of pathogens. However, the majority of microbiome works dedicated to the public transit air are limited to amplicon sequencing, and our knowledge regarding the functional potentials and the repertoire of resistance genes (i.e. resistome) is limited. Furthermore, current air microbiome investigations on public transit systems are focused on single cities, and a multi-city assessment of the public transit air microbiome will allow a greater understanding of whether and how broad environmental, building, and anthropogenic factors shape the public transit air microbiome in an international scale. Therefore, in this study, the public transit air microbiomes and resistomes of six cities across three continents (Denver, Hong Kong, London, New York City, Oslo, Stockholm) were characterized.

Results

City was the sole factor associated with public transit air microbiome differences, with diverse taxa identified as drivers for geography-associated functional potentials, concomitant with geographical differences in species- and strain-level inferred growth profiles. Related bacterial strains differed among cities in genes encoding resistance, transposase, and other functions. Sourcetracking estimated that human skin, soil, and wastewater were major presumptive resistome sources of public transit air, and adjacent public transit surfaces may also be considered presumptive sources. Large proportions of detected resistance genes were co-located with mobile genetic elements including plasmids. Biosynthetic gene clusters and city-unique coding sequences were found in the metagenome-assembled genomes.

Conclusions

Overall, geographical specificity transcends multiple aspects of the public transit air microbiome, and future efforts on a global scale are warranted to increase our understanding of factors shaping the microbiome of this unique built environment.
A synthetic probiotic engineered for colorectal cancer therapy modulates gut microbiota
Authors: Chung Yusook , Ryu Yongku , An Byung Chull , Yoon Yeo-Sang , Choi Oksik , Kim Tai Yeub , Yoon Jaekyung , Ahn Jun Young , Park Ho Jin , Kwon Soon-Kyeong , Kim Jihyun F. , Chung Myung Jun
Published: May 2021

Background

Successful chemoprevention or chemotherapy is achieved through targeted delivery of prophylactic agents during initial phases of carcinogenesis or therapeutic agents to malignant tumors. Bacteria can be used as anticancer agents, but efforts to utilize attenuated pathogenic bacteria suffer from the risk of toxicity or infection. Lactic acid bacteria are safe to eat and often confer health benefits, making them ideal candidates for live vehicles engineered to deliver anticancer drugs.

Results

In this study, we developed an effective bacterial drug delivery system for colorectal cancer (CRC) therapy using the lactic acid bacterium Pediococcus pentosaceus. It is equipped with dual gene cassettes driven by a strong inducible promoter that encode the therapeutic protein P8 fused to a secretion signal peptide and a complementation system. In an inducible CRC cell-derived xenograft mouse model, our synthetic probiotic significantly reduced tumor volume and inhibited tumor growth relative to the control. Mice with colitis-associated CRC induced by azoxymethane and dextran sodium sulfate exhibited polyp regression and recovered taxonomic diversity when the engineered bacterium was orally administered. Further, the synthetic probiotic modulated gut microbiota and alleviated the chemically induced dysbiosis. Correlation analysis demonstrated that specific bacterial taxa potentially associated with eubiosis or dysbiosis, such as Akkermansia or Turicibacter, have positive or negative relationships with other microbial members.

Conclusions

Taken together, our work illustrates that an effective and stable synthetic probiotic composed of P. pentosaceus and the P8 therapeutic protein can reduce CRC and contribute to rebiosis, and the validity and feasibility of cell-based designer biopharmaceuticals for both treating CRC and ameliorating impaired microbiota.