Abstract Background The OLIF procedure is aimed at mitigating some of the challenges seen with traditional ALIF and transpsoas LLIF and allows for interbody fusion at L1-S1. Purpose To describe the ...OLIF technique and assess the complication and fusion rates. Study Design A retrospective cohort study. Patient Sample 137 patients who underwent the oblique lateral interbody fusion (OLIF) procedure. Outcome measures Adverse events within 6 months of surgery: Infection, symptomatic pseudarthrosis, hardware failure, vascular injury, perioperative blood transfusion, ureteral injury, bowel injury, renal injury, prolonged postoperative ileus (greater than 3 days), incisional hernia, pseudohernia, reoperation, neurological deficits (weakness, numbness, paresthesia), hip flexion pain, retrograde ejaculation, sympathectomy affecting lower extremities, deep vein thrombosis, pulmonary embolism, myocardial infarction, pneumonia, and cerebrovascular accident. Fusion and subsidence rates based on CT done at 6 months postoperatively. Methods Retrospective chart review of 150 consecutive patients was performed to examine the complications associated with OLIF at L1-L5 (OLIF25), OLIF at L5-S1 (OLIF51) and OLIF at L1-5 combined with OLIF at L5-S1 (OLIF25 + OLIF51). Only patients who had a minimum of 6 months follow-up, including CT scan at 6 months after surgery, were included. Independent radiology review of CT data was performed to assess fusion and subsidence rates at 6 months. Results A total of 137 patients underwent fusion at 340 levels. An overall complication rate of 11.7% was seen. The most common complications were subsidence (4.4%), postoperative ileus (2.9%) and vascular injury (2.9%). Ileus and vascular injury were only seen in cases including OLIF51. No patient suffered neurological injury. No cases of ureteral injury, sympathectomy affecting the lower extremities or visceral injury were seen. Successful fusion was seen at 97.9% of surgical levels. Conclusion OLIF is a safe procedure at L1-5 as well as L5-S1. The complication profile appears acceptable when compared to LLIF and ALIF. The oblique trajectory mitigates psoas muscle and lumbosacral plexus-related complications seen with the lateral transpsoas approach. Furthermore, there is a high fusion rate based on CT data at 6 months.
Containment of the COVID-19 pandemic requires reducing viral transmission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by membrane fusion between the viral and ...host cell membranes, which is mediated by the viral spike protein. We have designed lipopeptide fusion inhibitors that block this critical first step of infection and, on the basis of in vitro efficacy and in vivo biodistribution, selected a dimeric form for evaluation in an animal model. Daily intranasal administration to ferrets completely prevented SARS-CoV-2 direct-contact transmission during 24-hour cohousing with infected animals, under stringent conditions that resulted in infection of 100% of untreated animals. These lipopeptides are highly stable and thus may readily translate into safe and effective intranasal prophylaxis to reduce transmission of SARS-CoV-2.
Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We ...identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy.
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•Highly recurrent fusions were found in prostate, bladder, breast, and lung cancers•Expression increased in oncogene fusions but decreased in tumor suppressor genes•Thyroid carcinoma showed significantly higher rates of kinase fusions•Tumors with fusion events tend to have lower mutational burden
Gao et al. analyze a 9,624 sample TCGA cohort with 33 cancer types to detect gene fusion events. They provide a landscape of fusion events detected, relate fusions to gene expression, focus on kinase fusion structures, examine mutually exclusive mutation and fusion patterns, and highlight fusion druggability.
Sexual reproduction is almost universal in eukaryotic life and involves the fusion of male and female haploid gametes into a diploid cell. The sperm-restricted single-pass transmembrane protein ...HAP2-GCS1 has been postulated to function in membrane merger. Its presence in the major eukaryotic taxa—animals, plants, and protists (including important human pathogens like Plasmodium)—suggests that many eukaryotic organisms share a common gamete fusion mechanism. Here, we report combined bioinformatic, biochemical, mutational, and X-ray crystallographic studies on the unicellular alga Chlamydomonas reinhardtii HAP2 that reveal homology to class II viral membrane fusion proteins. We further show that targeting the segment corresponding to the fusion loop by mutagenesis or by antibodies blocks gamete fusion. These results demonstrate that HAP2 is the gamete fusogen and suggest a mechanism of action akin to viral fusion, indicating a way to block Plasmodium transmission and highlighting the impact of virus-cell genetic exchanges on the evolution of eukaryotic life.
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•The primordial gamete fusogen HAP2 exhibits homology to class II viral fusion proteins•HAP2 inserts into the target gamete membrane via a hydrophobic fusion loop•HAP2 links virus entry into target cells and the origins of sexual reproduction•HAP2 is a sex-specific target for blocking fertilization in multiple kingdoms
Gamete fusion across eukaryotic branches uses an ancient factor homologous to viral fusion proteins.
This book includes papers from the section “Multisensor Information Fusion”, from Sensors between 2018 to 2019. It focuses on the latest research results of current multi-sensor fusion technologies ...and represents the latest research trends, including traditional information fusion technologies, estimation and filtering, and the latest research, artificial intelligence involving deep learning.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, at the end of 2019, and there are currently no specific antiviral treatments or vaccines available. SARS-CoV-2 ...has been shown to use the same cell entry receptor as SARS-CoV, angiotensin-converting enzyme 2 (ACE2). In this report, we generate a recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. A fusion protein containing an ACE2 mutant with low catalytic activity is also used in this study. The fusion proteins are then characterized. Both fusion proteins have a high binding affinity for the receptor-binding domains of SARS-CoV and SARS-CoV-2 and exhibit desirable pharmacological properties in mice. Moreover, the fusion proteins neutralize virus pseudotyped with SARS-CoV or SARS-CoV-2 spike proteins in vitro. As these fusion proteins exhibit cross-reactivity against coronaviruses, they have potential applications in the diagnosis, prophylaxis, and treatment of SARS-CoV-2.
Arginine-rich cell-penetrating peptides do not enter cells by directly passing through a lipid membrane; they instead passively enter vesicles and live cells by inducing membrane multilamellarity and ...fusion. The molecular picture of this penetration mode, which differs qualitatively from the previously proposed direct mechanism, is provided by molecular dynamics simulations. The kinetics of vesicle agglomeration and fusion by an iconic cellpenetrating peptide—nonaarginine—are documented via real-time fluorescence techniques, while the induction of multilamellar phases in vesicles and live cells is demonstrated by a combination of electron and fluorescence microscopies. This concert of experiments and simulations reveals that the identified passive cell penetration mechanism bears analogy to vesicle fusion induced by calcium ions, indicating that the two processes may share a common mechanistic origin.
Epidemiological study using national administrative data.
To provide a complete analysis of national trends in spinal fusion from 1998 to 2008 and compare with trends in laminectomy, hip replacement, ...knee arthroplasty, percutaneous transluminal coronary angioplasty, and coronary artery bypass graft.
Previous studies have reported a rapid increase in volume of spinal fusions in the United States prior to 2001, but limited reports exist beyond this point, analyzing all spinal fusion procedures collectively.
Data were obtained from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample for the years 1998 to 2008. Discharges were identified using International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes for the following procedures: spinal fusion, laminectomy, hip replacement, knee arthroplasty, percutaneous transluminal coronary angioplasty, and coronary artery bypass graft. Population-based utilization rates were calculated from the US census data.
Between 1998 and 2008, the annual number of spinal fusion discharges increased 2.4-fold (137%) from 174,223 to 413,171 (P < 0.001). In contrast, during the same time period, laminectomy, hip replacement, knee arthroplasty, and percutaneous coronary angioplasty yielded relative increases of only 11.3%, 49.1%, 126.8%, and 38.8% in discharges, while coronary artery bypass graft experienced a decrease of 40.1%. Between 1998 and 2008, mean age for spinal fusion increased from 48.8 to 54.2 years (P < 0.001), in-hospital mortality rate decreased from 0.29% to 0.25% (P < 0.01), and mean total hospital charges associated with spinal fusion increased 3.3-fold (P < 0.001). The national bill for spinal fusion increased 7.9-fold (P < 0.001).
Frequency, utilization, and hospital charges of spinal fusion have increased at a higher rate than other notable inpatient procedures, as seen in this study from 1998 to 2008. In addition, patient demographics and hospital characteristics changed significantly; in particular, whereas the average age for spinal fusion increased, the in-hospital mortality rate decreased.
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