bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction and description of a constitutive plipastatin mono-producing Bacillus subtilis
Authors: Vahidinasab Maliheh , Lilge Lars , Reinfurt Aline , Pfannstiel Jens , Henkel Marius , Heravi Kambiz Morabbi , Hausmann Rudolf
Published: November 2020

Background: Plipastatin is a potent Bacillus antimicrobial lipopeptide with the prospect to replace conventional antifungal chemicals for controlling plant pathogens. However, the application of this lipopeptide has so far been investigated in a few cases, principally because of the yield in low concentration and unknown regulation of biosynthesis pathways. B. subtilis synthesizes plipastatin by a non-ribosomal peptide synthetase encoded by the ppsABCDE operon. In this study, B. subtilis 3NA (a non-sporulation strain) was engineered to gain more insights about plipastatin mono-production.Results: The 4-phosphopantetheinyl transferase Sfp posttranslationally converts non-ribosomal peptide synthetases from inactive apoforms into their active holoforms. In case of 3NA strain, sfp gene is inactive. Accordingly, the first step was an integration of a repaired sfp version in 3NA to construct strain BMV9. Subsequently, plipastatin production was doubled after integration of a fully expressed degQ version from B. subtilis DSM10T strain (strain BMV10), ensuring stimulation of DegU-P regulatory pathway that positively controls the ppsABSDE operon. Moreover, markerless substitution of the comparably weak native plipastatin promoter (Ppps) against the strong constitutive promoter Pveg led to approximately fivefold enhancement of plipastatin production in BMV11 compared to BMV9. Intriguingly, combination of both repaired degQ expression and promoter exchange (Ppps::Pveg) did not increase the plipastatin yield. Afterwards, deletion of surfactin (srfAA-AD) operon by the retaining the regulatory comS which is located within srfAB and is involved in natural competence development, resulted in the loss of plipastatin production in BMV9 and significantly decreased the plipastatin production of BMV11. We also observed that supplementation of ornithine as a precursor for plipastatin formation caused higher production of plipastatin in mono-producer strains, albeit with a modified pattern of plipastatin composition.Conclusions: This study provides evidence that degQ stimulates the native plipastatin production. Moreover, a full plipastatin production requires surfactin synthetase or some of its components. Furthermore, as another conclusion of this study, results point towards ornithine provision being an indispensable constituent for a plipastatin mono-producer B. subtilis strain. Therefore, targeting the ornithine metabolic flux might be a promising strategy to further investigate and enhance plipastatin production by B. subtilis plipastatin mono-producer strains.
Treatment of Volar Defects of the Finger using Dorsal Digital–metacarpal Flap Versus Free Medial Plantar Artery Flap: A Comparative Study
Authors: Liu Quanzhe , Guo Wenlai , Qu Wenrui , Ou Xiaolan , Li Rui , Tian Heng
Published: November 2020

Background: The treatment of defects on the volar surface of the finger has been scarcely reported, and its utility for digital resurfacing remains unclear. This study compared the outcomes of free medial plantar artery flap (MPAF) and dorsal digital–metacarpal flap (DDMF) in finger reconstruction.Methods: This retrospective cohort study included 24 patients with soft-tissue defects on the volar surface of the finger from March 2014 to March 2017. The patients were divided into two groups: the MPAF group and the DDMF group. The operation time, complications, such as flap necrosis, graft loss, infection, paresthesia, and donor-site morbidity, as well as two-point discrimination (2-PD) were carefully recorded. The Michigan Hand Outcomes Questionnaire was used for conduct follow-up assessment.Results: After more than 12 months of follow-up, the MPAF group had a longer operative time compared with DDMF group, but there was no significant difference in postoperative complications and the results (2-PD and Modified VSS score) were significant. In terms of overall function, MPAF was superior to DDMF (p < 0.005).Conclusion: MPAF and DDMF are reliable for reconstruction of the volar surface of the finger; however, MPAF offers better functional outcomes and is associated with a lower incidence of postoperative complications.
Fall Inducing Movable Platform (FIMP) for Overground Trips and Slips
Authors: Er Jie Kai , Donnelly Cyril John William , Wee Seng Kwee , Ang Wei Tech
Published: November 2020

Background: The study of falls and fall prevention/intervention devices requires the recording of true fallsincidence. However, true falls are rare, random, and difficult to collect in real world settings. A system capableof producing falls in an ecologically valid manner will be very helpful in collecting the data necessary toadvance our understanding of the neuro and musculoskeletal mechanisms underpinning real-world falls events.Methods: A fall inducing movable platform (FIMP) was designed to arrest or accelerate a subject's ankle toinduce a trip or slip. The ankle was arrested posteriorly with an electromagnetic brake and acceleratedanteriorly with a motor. A power spring was connected in series between the ankle and the brake/motor toallow freedom of movement (system transparency) when a fall is not being induced. A gait phase detectionalgorithm was also created to enable precise activation of the fall inducing mechanisms. Statistical ParametricMapping (SPM1D) and one-way repeated measure ANOVA were used to evaluate the ability of the FIMP toinduce a trip or slip.Results: During FIMP induced trips, the brake activates at the terminal swing or mid swing gait phase toinduce the lowering or skipping strategies, respectively. For the lowering strategy, the characteristic leg loweringand subsequent contralateral leg swing was seen in all subjects. Likewise, for the skipping strategy, all subjectsskipped forward on the perturbed leg.Slip was induced by FIMP by using a motor to impart unwanted forward acceleration to the ankle with thehelp of friction-reducing ground sliding sheets. Joint stiffening was observed during the slips, and subjectsuniversally adopted the surfing strategy after the initial slip.Conclusion: The results indicate that FIMP can induce ecologically valid falls under controlled laboratoryconditions. The use of SPM1D in conjunction with FIMP allows for the time varying statistical quanticationof trip and slip reactive kinematics events. With future research, fall recovery anomalies in subjects can nowalso be systematically evaluated through the assessment of other neuromuscular variables such as joint forces,muscle activation and muscle forces.
Isolation, heterologous expression, and purification of a novel antifungal protein from Bacillus subtilis strain Z-14
Authors: Zhang Xuechao , Guo Xiaojun , Wu Cuihong , Li Chengcui , Zhang Dongdong , Zhu Baocheng
Published: November 2020

Background: Wheat sheath blight, a soil borne fungal disease caused by Rhizoctonia cerealis, is considered as one of the most serious threats to wheat worldwide. Bacillus subtilis Z-14 was isolated from soil sampled from a wheat rhizosphere and was confirmed to have strong antifungal activity against R. cerealis. Results: An antifungal protein, termed F2, was isolated from the culture supernatant of Z-14 strain using precipitation with ammonium sulfate, anion exchange chromatography, and reverse phase chromatography. Purified F2 had a molecular mass of approximately 8 kDa, as assessed using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Edman degradation was used to determine the amino acid sequence of the N-terminus, which was NH2‑ASGGTVGIYGANMRS. This sequence is identical to a hypothetical protein RBAM_004680 (YP_001420098.1) synthesized by B. amyloliquefaciens FZB42. The recombinant F2 protein (rF2) was heterologously expressed in the yeast host Pichia pastoris, purified using a Ni‑affinity column, and demonstrated significant antifungal activity against R. cerealis. The purified rF2 demonstrated broad spectrum antifungal activity against different varieties of fungi such as Fusarium oxysporum, Verticillium dahliae, Bipolaris papendorfii, and Fusarium proliferatum. rF2 was thermostable, retaining 91.5% of its activity when incubated for 30 min at 100 °C. Meanwhile, rF2 maintained its activity under treatment by proteinase K and trypsin and over a wide pH range from 5 to 10.Conclusions: A novel antifungal protein, F2, was purified from biocontrol Bacillus subtilis Z-14 strain fermentation supernatant and heterologously expressed in Pichia pastoris to verify its antifungal activity against R. cerealis and the validity of the gene encoding F2. Considering its significant antifungal activity and stable characteristics, protein F2 presents an alternative compound to resist fungal infections caused by R. cerealis.
Barriers in Implementing the Dying Patient Law: The Israeli Experience - A Qualitative Study
Authors: Zigdon Avi , Nissanholtz-Gannot Rachel
Published: November 2020

Background: Coping with end-of-life issues is a major challenge for governments and health systems. Despite progress in legislation, many barriers exist to its full implementation. This study is aimed at identifying these end-of-life barriers in relation to Israel.Methods: Qualitative in-depth interviews using professionals and decision makers in the health-care and related systems (n=37) were carried out, along with two focus groups based on brainstorming techniques consisting of nurses (n=10) and social workers (n=10). Data was managed and analyzed using Naralyzer software.Results: Qualitative analysis showed identification of six primary barriers: 1) law, procedures, and forms; 2) clinical aspects; 3) human aspects; 4) knowledge and skills of medical teams; 5) communication; and 6) resource allocation. These were further divided into 44 sub area barriers.Conclusions: This study highlights the role of the family doctor in end-of-life by training physicians in decision-making workshops and increasing their knowledge in the field of palliative medicine. Effectively channeling resources, knowledge, and support for medical teams, by accounting for the structure and response of the units for home treatment will improve patient's access to information on and support for end-of-life laws, as well as reduce legislative barriers in other countries that face the same issues.
Relationship between medial meniscus extrusion and cartilage measurements in the knee by fully automatic three-dimensional MRI analysis
Authors: Aoki Hayato , Ozeki Nobutake , Katano Hisako , Hyodo Akinobu , Miura Yugo , Matsuda Junpei , Takanashi Kimiko , Suzuki Kenji , Masumoto Jun , Okanouchi Noriya , Fujiwara Takeo , Sekiya Ichiro
Published: November 2020

Background: We developed a fully automatic three-dimensional knee MRI analysis software that can quantify meniscus extrusion and cartilage measurements, including the projected cartilage area ratio (PCAR), which represents the ratio of the subject’s actual cartilage area to their ideal cartilage area. We also collected 3D MRI knee data from 561 volunteers (aged 30–79 years) from the “Kanagawa Knee Study.” Our purposes were to verify the accuracy of the software for automatic cartilage and meniscus segmentation using knee MRI and to examine the relationship between medial meniscus extrusion measurements and cartilage measurements from Kanagawa Knee Study data. Methods: We constructed a neural network for the software by randomly choosing 10 healthy volunteers and 103 patients with knee pain. We validated the algorithm by randomly selecting 108 of these 113 subjects for training, and determined Dice similarity coefficients from five other subjects. We constructed a neural network using all data (113 subjects) for training. Cartilage thickness, cartilage volume, and PCAR in the medial femoral, lateral femoral, medial tibial, and lateral tibial regions were quantified by using the trained software on Kanagawa Knee Study data and their relationship with subject height was investigated. We also quantified the medial meniscus coverage ratio (MMCR), defined as the ratio of the overlapping area between the medial meniscus area and the medial tibial cartilage area to the medial tibial cartilage area. Finally, we examined the relationship between MMCR and PCAR at middle central medial tibial (mcMT) subregion located in the center of nine subregions in the medial tibial cartilage. Results: Dice similarity coefficients for cartilage and meniscus were both approximately 0.9. The femoral and tibial cartilage thickness and volume at each region correlated with height, but PCAR did not correlate with height in most settings. PCAR at the mcMT was significantly correlated with MMCR. Conclusions: Our software showed high segmentation accuracy for the knee cartilage and meniscus. PCAR was more useful than cartilage thickness or volume since it was less affected by height. A relationship was observed between the medial tibial cartilage measurements and the medial meniscus extrusion measurement in our cross-sectional study.
Regional differences between superficial and deep lumbar multifidus in patients with chronic lumbar spine pathology
Authors: Padwal Jennifer , Berry David B , Hubbard James C. , Zlomislic Vinko , Allen R. Todd , Garfin Steven R. , Ward Samuel R. , Shahidi Bahar
Published: November 2020

Background: Due to its unique arrangement, the deep and superficial fibers of the multifidus may have differential roles for maintaining spine stabilization and lumbar posture; the superficial multifidus is responsible for lumbar extension and the deep multifidus for intersegmental stability. In patients with chronic lumbar spine pathology, muscle activation patterns have been shown to be attenuated or delayed in the deep, but not superficial, multifidus. This has been interpreted as pain differentially influencing the deep region. However, it is unclear if degenerative changes affecting the composition and function of the multifidus differs between the superficial and deep regions, an alternative explanation for these electrophysiological changes. Therefore, the goal of this study was to investigate macrostructural and microstructural differences between the superficial and deep regions of the multifidus muscle in patients with lumbar spine pathology.Methods: In 16 patients undergoing lumbar spinal surgery for degenerative conditions, multifidus biopsies were acquired at two distinct locations: 1) the most superficial portion of muscle adjacent to the spinous process and 2) approximately 1 cm lateral to the spinous process and deeper at the spinolaminar border of the affected vertebral level. Structural features related to muscle function were histologically compared between these superficial and deep regions, including tissue composition, fat fraction, fiber cross sectional area, fiber type, regeneration, degeneration, vascularity and inflammation. Results: No significant differences in fat signal fraction, muscle area, fiber cross sectional area, muscle regeneration, muscle degeneration, or vascularization were found between the superficial and deep regions of the multifidus. Total collagen content between the two regions was the same. However, the superficial region of the multifidus was found to have less loose and more dense collagen than the deep region. Conclusions: The results of our study did not support that the deep region of the multifidus is more degenerated in patients with lumbar spine pathology, as gross degenerative changes in muscle microstructure and macrostructure were the same in the superficial and deep regions of the multifidus. In these patients, the multifidus is not protected in order to maintain mobility and structural stability of the spine.
Pulmonary Benign Metastasizing Leiomyomas: a Case Series of 23 Patients at a Single Facility
Authors: Fan Rong , Feng Fengzhi , Yang Hua , Xu Kaifeng , Li Shanqing , You Yan , Wan Xirun , Zhu Lan
Published: November 2020

Background: Pulmonary benign metastasizing leiomyoma (PBML) is a rare disease characterized by leiomyoma of benign histopathology existing in the lungs. Because of its rarity, limited literature with a single case or small number of cases has been regarding to the clinical course, pathology or management of PBML. Methods: A retrospective study was performed of all PBML cases diagnosed and managed at Peking Union Medical College Hospital (PUMCH) from 2001 to 2019. The clinical characteristics, pathology, treatment and outcomes of each case were studied. Results: There were 25 PBML patients identified in the 19-year period in PUMCH, and 23 patients’ data was analyzed. The median age at diagnosis was 46 years. There were 7 patients (30.4%) diagnosed with postmenopausal status. 2 patients (8.7%) had no uterine leiomyoma, and 3 patients (13.0%) had no gynecologic surgery history. Immunohistochemistry of most lesions demonstrated positive for desmin, SMA and Estrogen/Progesterone Receptors; and negative for S-100 were shown in 7 cases. After curative or diagnostic surgeries for the PBML, several treatments from observation to medical or surgical castration were performed. 9 premenopausal patients preserved their ovaries at first. At a median follow-up of 8 years, 3 patients finally had oophorectomy.Conclusions: PBML is a rare disease and should be treated by individualization according to the patients’ age, symptoms and extent of lesion. Curative surgery for patients with limited lesions can achieve the complete response. For patients that are young and asymptomatic, close observation is recommended as the first choice. All patients should undergo long-term surveillance.
Development and implementation of a patient assistance fund: A descriptive study
Authors: Soffe Burke W. , Miranda Justine E. , Fang Jenny , Epperson Daniel G. , Lara Roberto A. , Williamson Hazel L. , Lipsky Martin S.
Published: November 2020

Background: The purpose of this descriptive study is to outline the Roseman University of Health Sciences (RUHS) College of Dental Medicines’ Patient Assistance Fund development, organization and outcomes. The description and reported results provide insight to others considering similar health professions programs.Methods: The Patient Assistance Fund (PAF) affords dental students an opportunity to petition for and obtain financial assistance for their most disadvantaged patients. In this study, two sources of data were collected and used with a quantitative analysis for data collected as part of the PAFs operation and a qualitative analysis to evaluate the patient experiences.Results: A total of 16 student advocates, consisting of 6 males and 10 females from the D3 and D4 classes made 26 presentations to the PAF board committee. The combined amount requested from the PAF was $47,428.00 (“Cost of Treatment Plan”) representing an average request per patient of $1,824.15 (range $324.00 to $4070.00). The approved procedures and treatment plans totaled $21,278.36 (“Cost of Approved Procedures”) with an average of $818.40 (range $204.00 to $2434.00) per patient. Patients and students expressed a high degree of satisfaction with the program.Conclusions: This study provides an overview of the structure, funding sources, expenditures and patient services supported by a dental student managed patient assistance fund. The experiences at RUHS College of Dental Medicine (CODM) suggest that other healthcare professions schools can develop similar type programs that yield benefit both to students and to patients in need. Trial Registration: Not applicable
Genome-wide identification and characterization of NBS-encoding genes in Raphanus sativus L. and their roles related to Fusarium oxysporum resistance
Authors: Ma Yinbo , Chhapekar Sushil Satish , Lu Lu , Oh Sangheon , Singh Sonam , Kim Chang Soo , Kim Seungho , Choi Gyung Ja , Lim Yong Pyo , Choi Su Ryun
Published: November 2020

Background: The nucleotide-binding site–leucine-rich repeat (NBS-LRR) genes are important for plant development and disease resistance. Although genome-wide studies of NBS-encoding genes have been performed in several species, the evolution, structure, expression, and function of these genes remain unknown in radish (Raphanus sativus L.). A recently released draft R. sativus L. reference genome has facilitated the genome-wide identification and characterization of NBS-encoding genes in radish.Results: A total of 225 NBS-encoding genes were identified in the radish genome based on the essential NB-ARC domain through HMM search and Pfam database, with 202 mapped onto nine chromosomes and the remaining 23 localized on different scaffolds. According to a gene structure analysis, we identified 99 NBS-LRR-type genes and 126 partial NBS-encoding genes. Additionally, 80 and 19 genes respectively encoded an N-terminal Toll/interleukin-like domain and a coiled-coil domain. Furthermore, 72% of the 202 NBS-encoding genes were grouped in 48 clusters distributed in 24 crucifer blocks on chromosomes. The U block on chromosomes R02, R04, and R08 had the most NBS-encoding genes (48), followed by the R (24), D (23), E (23), and F (17) blocks. These clusters were mostly homogeneous, containing NBS-encoding genes derived from a recent common ancestor. Tandem (15 events) and segmental (20 events) duplications were revealed in the NBS family. Comparative evolutionary analyses of orthologous genes among Arabidopsis thaliana, Brassica rapa, and Brassica oleracea reflected the importance of the NBS-LRR gene family during evolution. Moreover, examinations of cis-elements identified 70 major elements involved in responses to methyl jasmonate, abscisic acid, auxin, and salicylic acid. According to RNA-seq expression analyses, 75 NBS-encoding genes contributed to the resistance of radish to Fusarium wilt. A quantitative real-time PCR analysis revealed that RsTNL03 (Rs093020) and RsTNL09 (Rs042580) expression positively regulates radish resistance to Fusarium oxysporum, in contrast to the negative regulatory role for RsTNL06 (Rs053740).Conclusions: The NBS-encoding gene structures, tandem and segmental duplications, synteny, and expression profiles in radish were elucidated for the first time and compared with those of other Brassicaceae family members (A. thaliana, B. oleracea, and B. rapa) to clarify the evolution of the NBS gene family. These results may be useful for functionally characterizing NBS-encoding genes in radish.
Genetic characterization of G12P[6] and G12P[8] rotavirus strains collected in six African countries between 2010 and 2014 
Authors: Rakau Kebareng G. , Nyaga Martin M. , Gededzha Maemu P. , Mwenda Jason M. , Mphahlele M. Jeffrey , Seheri L. Mapaseka , Steele Duncan
Published: November 2020

Background: G12 rotaviruses were first observed in sub-Saharan Africa in 2004 and since then have continued to emerge and spread across the continent and are reported as a significant human rotavirus genotype in several African countries, both prior to and after rotavirus vaccine introduction. This study investigated the genetic variability of 15 G12 rotavirus strains associated with either P[6] or P[8] identified between 2010 and 2014 from Ethiopia, Kenya, Rwanda, Tanzania, Togo and Zambia. Methods: The investigation was carried out by comparing partial VP7 and partial VP4 sequences of the African G12P[6] and G12P[8] strains with the available GenBank sequences and exploring the recognized neutralization epitopes of these strains. Results: The findings suggested that the VP7 and VP4 genes of the G12 strains circulating in African countries are closely related at the nucleotide and amino acid level, irrespective of country of origin and year of detection, although there was a unique clustering of the Ethiopian strains. Neutralization epitope screening revealed that rotavirus VP4 P[8] genes associated with G12 had amino acids similar to those reported globally including the vaccines RotaTeq and Rotarix. Conclusions: At present it appears to be unlikely that widespread vaccine use has driven the molecular evolution and sustainability of G12 strains in Africa. Continuous monitoring of rotavirus genotypes is recommended to assess the long-term impact of rotavirus vaccination on the dynamic nature of rotavirus evolution on the continent.
Self-perceived preparedness of dental school graduates and the impact of COVID-19 pandemic on their confidence
Authors: Alraheam Islam Abd , Alashqar Mays A. , Hattar Susan , AlHadidi Abeer , Alhaddad Alaa , Sawair FA
Published: November 2020

Background. To study self-perceived preparedness of dental school graduates and the impact of COVID-19 on their preparedness. Method. An online survey was designed and sent electronically to students who were graduating in 2020, dentists who graduated in 2019 and were doing their prelicensure training, and dentists who graduated before 2019. Four- point Likert scale was used to assess participants’ perception.Results. There were 209 participants responded to the online questionnaire. The mean total preparedness score (TPS) for the 209 participants was 97.6 (SD ±9.7) with a range of 69 to 120. The mean TPS of the different classes of participants was 99.5 for the class graduated before 2019, 98.1 for the 2020 class, and 95.1 for the 2019 class. Participants felt they are confident and extremely confident doing the majority of the required competencies. Weakness was mainly reported in surgical extraction for 2020 graduates due to the 8 weeks loss of their training. COVID-19 had considerable impact on 59.7% of the participants and marginal to no impact on 40.3%. The highest prevalence of those who thought it had some to severe impact on their confidence were those who graduated in year 2019 (73.4%).Conclusions. The graduates of University of Jordan felt confident in performing the majority of general dentistry procedures. COVID-19 pandemic negatively impacted the confidence of all the classes of participants even those graduated before 2019.
A clinical practice guideline appraisal for appropriate use of echocardiography in adult infective endocarditis—when and by which mode to perform an Echo?
Authors: Xie Peihan , Zhuang Xiaodong , Liu Menghui , Zhang Shaozhao , Liu Jia , Liu Donghong , Liao Xinxue
Published: November 2020

BackgroundEchocardiography (Echo) is the primary imaging modality of infective endocarditis (IE). However, the recommendations on timing and mode selection for transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) are not fully in agreement among different guidelines, which can be confusing for clinical decision makers. In this case, we aim to appraise the quality of recommendations by appraising the quality of guidelines. MethodsA search of guidelines containing recommendations for the appropriate use of Echo in IE adult patients published in English between 2007 and 2020 has been conducted. APPRAISAL OF GUIDELINES FOR RESEARCH & EVALUATION II (AGREE II) instrument is applied independently by two reviewers to assess the integrated quality of identified guidelines. The recommendations of concern are extracted from related chapters.ResultsA total of 9 guidelines meet the criteria with AGREE II score ranging from 36% to 79%, and the domain of “stakeholder involvement” receives the lowest score. The most contentious issue is, whether a follow-up TEE is mandatory in uncomplicated native valve IE with initial positive TTE. And conflicting recommendations on it are presented with low evidence level for hardly any related evidence based on.ConclusionsIn general, the recommendations proposed in the 9 identified guidelines on the appropriate use of Echo are satisfying. And the guideline quality score could be taken into account by the clinicians when evaluating the recommendations for making clinical decision. More researches are needed in the future, which should be with high evidence level on the most controversial issues of whether a subsequent TEE is mandatory in uncomplicated native valve IE with an initial positive TTE.
Rapid Response Team activation after major hip surgery: patient characteristics and outcomes
Authors: Pritchard Angus , Jones Daryl , Bellomo Rinaldo , Hardidge Andrew , Harley Ian , Tan Chong Oon , Nazareth Justin , Guha Ranj , Ellard Louise , Hu Raymond , Churilov Leonid , Weinberg Laurence
Published: November 2020

Background: Rapid response teams (RRTs) are a critical care resource that review deteriorating patients within the hospital. We aimed to describe demographic, preoperative, surgical, anesthetic, and postoperative characteristics of patients who required RRT activation after major hip surgery. We also sought to assess whether these characteristics where associated with mortality during the index hospital admission.Methods: We reviewed an RRT database of adult patients undergoing orthopedic surgery at a university teaching hospital. We then retrospectively reviewed the medical records to extract a priori–defined patient, preoperative, surgical, anesthetic, and postoperative data of major hip surgery admissions between September 2014 and December 2017. Patients who survived the index hospital stay were compared to those who died.Results: Overall, 187 patients had postoperative RRT activations. Median (interquartile range) age was 84.0 (78-90) years; 125 (67%) were female, and most patients had at least one significant comorbidity, median Charlson Comorbidity Index (CCI) 5.0 (4.0-7.0). The majority of patients were frail (68%), American Society of Anesthesiologists physical status Class 3 or greater (91%), and underwent nonelective surgery (88%). Median (interquartile range) time from surgery to RRT activation was 29.4 (11.3–75.0) hours, and 25 (13%) patients had unplanned admissions to intensive care or high dependency units. Compared to patients who survived RRT activation, those who died displayed higher mean CCI (6.5 [1.8] vs. 5.5 [2.1], p = 0.02), were more frail (80.1% vs. 56.5%, OR = 3.2, 95% CI: 1.2,8.1; p = 0.03), and received less intraoperative opioids (intravenous morphine equi-analgesia: median = 5.8 (0.1–8.20 vs. 11.7 (3.7–19.0) mg, p = 0.03). They were also more likely to have received an urgent medical review prior to RRT activation (62% vs. 40%, OR = 2.4, 95% CI: 1.1, 5.6); p = 0.05.Conclusions: Death after RRT activation occurred in 1 in 7 patients undergoing major hip surgery. Common patient characteristics included advanced age (> 82 years), frailty, high CCI, and emergency surgery. Further studies investigating perioperative surveillance teams in the identification of the high-risk patients before surgery and deteriorating patients after major hip surgery are warranted.
Dexamethasone blunts post-spinal hypotension in geriatric patients undergoing orthopedic surgery: a double blind, placebo-controlled study
Authors: Ashoor Tarek , Hussien Noha S. , Anis Sherif G. , Esmat Ibrahim M.
Published: November 2020

Background: Post-spinal anesthesia (PSA) hypotension in elderly patients is challenging. Correction of PSA hypotension by fluids either colloids or crystalloids or by vasoconstrictors pose the risk of volume overload or compromising cardiac conditions. Dexamethasone is used to treat conditions manifested by decrease of peripheral vascular resistance. The research team was the first to test the hypothesis of its role in preventing or decreasing the incidence of PSA hypotension.Methods: 110 patients, aged 60 years or more were recruited to receive a single preoperative dose of dexamethasone 8 mg IVI in 100 ml normal saline (D group) (55 patients) 2 hours preoperatively, and 55 patients were given placebo (C group) in a randomized, double-blind trial. Variations in blood pressure and heart rate in addition to the needs of ephedrine and/or atropine following spinal anesthesia (SA) were recorded. SA was achieved using subarachnoid injection of 3 ml hyperbaric bupivacaine 0.5%.Results: Demographic data and the quality of sensory and motor block were comparable between groups. At 5th, 10th minutes post SA; systolic, diastolic and, mean arterial pressures were statistically significant higher in D group. At 20th minutes post SA; pressure readings and heart rate changes didn’t show any statistically significance between groups. The need for ephedrine and side effects were statistically significant lower in D group than C group.Conclusion. Post spinal anesthesia hypotension, nausea, vomiting and shivering in elderly patients were less common after receiving a single preoperative dose of dexamethasone 8 mg IVI than control.Registration number: Clinical Trials. gov Identifier: NCT 03664037Registered 17 September 2018 - Retrospectively registered, http://www.Clinical Trial.gov
Long noncoding RNA MEG3 blocks telomerase activity in human liver cancer stem cells epigenetically
Authors: Jiang Xiaoxue , Wang Liyan , Xie Sijie , Chen Yingjie , Song Shuting , Lu Yanan , Lu Dongdong
Published: November 2020

Background: MEG3 is down-regulated expression in several tumors and inhibits human tumorigenesis. But so far, the mechanism of MEG3 in tumorigenesis is still unclear. Methods: Gene infection, cellular and molecular technologies and tumorigenesis test in vitro and in vivo were performed,respectively.Results: our results indicate that MEG3 enhances the P53 expression by triggering the loading of P300 and RNA polymerase II onto its promoter regions dependent on HP1α. Moreover, MEG3 increases the methylation modification of histone H3 at the 27th lysine via P53. Furthermore, MEG3 inhibits the expression of TERT by increasing the H3K27me3 in TERT promoter regions. Thereby, MEG3 inhibits the activity of telomerase by reducing the binding of TERT to TERC. Furthermore, MEG3 also increases the expression of TERRA ,therefore, the interaction between TERC and TERT was competitively attenuated by increasing the interaction between TERRA and TERT, which inhibits the activity of telomerase in hLCSCs. Strikingly, MEG3 reduces the length of telomere by blocking the formation of complex maintaining telomere length(POT1-Exo1-TRF2-SNM1B) and decreasing the binding of the complex to telomere by increasing the interplay between P53 and HULC. Ultimately, MEG3 inhibits the growth of hLCSCs by reducing the activity of telomerase and attenuating telomeric repeat binding factor 2(TRF2). Conclusions: Our results demonstrates MEG3 inhibits the occurrence of human liver cancer by blocking telomere and these findings provide an important insight into the prevention and treatment of human liver cancer.
Accumulation of the delivered dose based on cone-beam CT and deformable image registration for non-small cell lung cancer treated with hypofractionated radiotherapy
Authors: Wang Bin , Wang DaQuan , Lin MaoSheng , Lu ShiPei , Zhang Jun , Chen Li , Li QiWen , Cheng ZhangKai , Liu FangJie , Guo JinYu , Liu Hui , Qiu Bo
Published: November 2020

Background: This study aimed to quantify the dosimetric differences between the planned and delivered dose to tumor and normal organs in locally advanced non-small cell lung cancer (LANSCLC) treated with hypofractionated radiotherapy (HRT), and to explore the necessity and identify optimal candidates for adaptive radiotherapy (ART). Methods: Twenty-seven patients with stage III NSCLC were enrolled. Planned radiation dose was 51Gy in 17 fractions with cone-beam CT (CBCT) acquired at each fraction. Virtual CT was generated by deformable image registration (DIR) of the planning CT to CBCT for dose calculation and accumulation. Dosimetric parameters were compared between original and accumulated plans using Wilcoxon signed rank test. Correlations between dosimetric differences and clinical variables were analyzed using Mann-Whitney U test or Chi-square test.Results: Patients had varied gross tumor volume (GTV) reduction by HRT (median reduction rate 11.1% , range -2.9%-44.0%). The V 51 of planning target volume for GTV (PTV-GTV) was similar between original and accumulated plans (mean, 88.2% vs. 87.6%, p=0.452). Only 11.1% of patients had above 5% relative decrease in V 51 of PTV-GTV in accumulated plans. Compared to the original plan, limited increase (median relative increase <5%) was observed in doses of total lung (mean dose, V 20 and V 30 ), esophagus (mean dose, maximum dose) and heart (mean dose, V 30 and V 40 ) in accumulated plans. Less than 30% of patients had above 5% relative increase of lung or heart doses. Patients with quick tumor regression or baseline obstructive pneumonitis showed more notable increase in doses to normal structures. Patients with baseline obstructive atelectasis showed notable decrease (10.3%) in dose coverage of PTV-GTV. Conclusions: LANSCLC patients treated with HRT had sufficient tumor dose coverage and acceptable normal tissue dose deviation. ART should be applied in patients with quick tumor regression and baseline obstructive pneumonitis/atelectasis to spare more normal structures.
Expression and Prognostic Analyses of the Insulin-like Growth Factor 2 mRNA Binding Protein Family in Human Pancreatic Cancer
Authors: Cui Xiao-Han , Hu Shu-Yi , Qin Xihu , Zhu Chun-Fu
Published: November 2020

Background: Despite advances in early diagnosis and treatment, cancer remains the leading cause of mortality worldwide. The insulin-like growth factor 2 mRNA binding protein(IGF2BP) family has been reported to be involved in a variety of human malignant tumours. However, little is known about their expression and prognostic value in human pancreatic cancer. Therefore, we performed a detailed cancer versus normal differential analysis. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were uesd to analyse the mRNA expression levels of the IGF2BP family in various cancers, including pancreatic cancer. Then, the LinkedOmics and GEPIA databases were used to assess the relation between the expression levels of IGF2BPs and overall survival (OS). Then, univariate and multivariate Cox regression analyses were performed , and subgroups based on grade and stage were analysed. The signalling pathways associated with IGF2BP2 and IGF2BP3 were then investigated via gene set enrichment nalysis(GSEA). Results: IGF2BP2 and IGF2BP3 were associated with each subset of OS based on grade and stage. Further clinical correlation analysis of IGF2BP2 and IGF2BP3 confirmed that IGF2BP2 and IGF2BP3 are fundamental factors in promoting pancreatic cancer progression. Conclusion: IGF2BP2 and IGF2BP3 are key factors in promoting the progression of pancreatic cancer and are closely related to overall survival.
Sexual dimorphism in age-related changes in the expression of genes involved into regulation of calcium metabolism in aorta and myocardium of rats
Authors: Kozhevnikova Lubov , Sukhanova Irina , Semenova NP , Efimova Alena , Kryzhanovskii Sergey
Published: November 2020

Age is the main risk factor for cardiovascular disease development. Understanding of mechanism underlying the vascular and myocardial ageing is necessary both for prevention and for treatment of age-associated diseases. The research aimed to evaluate age-related changes in the transcriptional activity of genes involved in the regulation of Ca2 + signalling – IP3R, RyR, and modulators of their activity CaM and Epac in blood vessels and myocardium of rats of both sexes.Gene expression was evaluated according to the mRNA content of the test protein relative to the β-actin mRNA content. It is proven that rats of both sexes develop unidirectional changes in the expression of genes encoding IP3Rs and RyR2, and different ones in the expression of protein genes modulating their activity – CaM and Epac depending on the sex of animals. In the vessels of old rats (24 months) of both sexes the relative level of mRNA for IP3R type 2 and 3 was reduced and not changed for IP3R1, and significantly increased for RyR2 receptors compared to these indicators in young rats (4 months). In the aorta of old females the relative mRNA content for CaM and Epac1 was reduced and not changed for Epac2. On the contrary, the expression of Epac1 and Epac2 was increased by 67% and 50% respectively compared to similar indicators in young rats (4 months) and rests unchanged for CaM which indicates gender differences in the violation of subtle mechanisms for modulating the activity of RyR2 and IP3Rs in blood vessels. Old rats showed significant changes in myocardium. In older males, the expression of RyR2,IP3R1,2, 3 increases in the left ventricle, RyR2 and IP3R1 – in the left atrium, and RyR2 and IP3R3 – in the right atrium. Unlike males, the mRNA content for RyR2, IP3R1, 2, 3 was significantly lower in the left ventricle of females than in young animals. High levels of IP3R1 and IP3R3 expression were detected in the right atrium of senior females, and IP3R3 expression was detected in the left atrium. The expression of IP3R2 was unchanged in all parts of the female heart. In the myocardium of old rats of both sexes the expression of CaM and Epac2 proteins increased significantly. The revealed age differences in the transcriptional activity of genes involved in the regulation of intracellular Ca2 + signalling at the level of IP3Rs-and RyR2-mediated mechanisms suggest that with the increasing life expectancy males are significantly more likely to develop myocardial hypertrophy and heart rhythm disorders than females.
Modified Kocher-Langenbeck approach for the treatment of posterior wall or column acetabular fractures: The one-incision two-window method
Authors: Yang Tien-Yu , Huang Kuo-Chin
Published: November 2020

Abstract
The Kocher-Langenbeck (K-L) approach is the standard method for the treatment of posterior wall or column acetabular fractures. This approach allows direct access to the posterior structures of the acetabulum, but is limited cranially and caudally by the neurovascular bundle. The present study was conducted to assess the quality of reduction and the incidence of complications in patients who underwent the modified “one-incision two-window” K-L approach.
Methods : This is a Retrospective case series with recruited thirteen consecutive patients from 2015 to 2017 who sustained an acute, displaced posterior wall or column acetabular fracture. All patients were treated with modified “one-incision two-window” K-L approach.
Results: The mean operation time, mean intraoperative blood loss, and mean incision wound length were estimated to be 103.8 min (60-120 min), 373.1 mL (100-700 mL), and 9.7 cm (8.0-13.0 cm), respectively. The radiographic quality of reduction was graded as anatomical reduction (maximum residual displacement [MRD] ≤ 2 mm) in all cases, according to Matta’s criteria. Concerning the incidence of complications, there were no iatrogenic neurovascular injury, no surgical site infections, and no osteonecrosis of the femoral head or heterotopic ossification in this cohort. One patient with transverse with posterior wall fracture (group 1) experienced deep vein thrombosis in the lesion leg. Another two patients with solitary posterior wall fracture (group 2) developed posttraumatic osteoarthritis, with one diagnosed as Tonnis grade I lesion and the other as Tonnis grade III lesion. With respect to the clinical treatment outcome, the mean visual analogue scale (VAS), mean modified Harris Hip Score (mHHS) and subjective satisfaction rate were 1.7 (1.0-2.0), 90.6 (81-100), and 84.6% (80%-90%), respectively. Although there was no significant difference in the satisfaction rate (82.9% vs. 87.0%, P = 0.941) at 12 months after surgery, group 1 patients had more increased VAS score (2.0 vs. 1.2, P = 0.016) and more decreased mHHS (87.7 vs. 94.6, P = 0.014) than group 2 patients.
Conclusions: Our pilot study confirmed that the “one-incision two-window” K-L approach is a simple, safe, reliable, and effective way to manage acute, displaced posterior wall or column acetabular fractures.
Infant sex modifies associations between placental malaria and risk of malaria in infancy
Authors: Kakuru Abel , Roh Michelle E. , Kajubi Richard , Ochieng Teddy , Ategeka John , Ochokoru Harriet , Nakalembe Miriam , Clark Tamara D. , Ruel Theodore , Staedke Sarah G. , Chandramohan Daniel , Havlir Diane V. , Kamya Moses R , Dorsey Grant , Jagannathan Prasanna
Published: November 2020

BackgroundPlacental malaria (PM) has been associated with a higher risk of malaria during infancy. However, it is unclear whether this association is causal, and is modified by infant sex, and whether intermittent preventive treatment in pregnancy (IPTp) can reduce infant malaria by preventing PM. MethodsData from a birth cohort of 656 infants born to HIV-uninfected mothers randomized to IPTp with dihydroartemisinin-piperaquine (DP) or sulfadoxine-pyrimethamine (SP) was analyzed. PM was categorized as no PM, active PM (presence of parasites), mild-moderate past PM (>0-20% high powered fields [HPFs] with pigment), or severe past PM (>20% HPFs with pigment). The association between PM and incidence of malaria in infants stratified by infant sex was examined. Causal mediation analysis was used to test whether IPTp can impact infant malaria incidence via preventing PM. ResultsThere were 1088 malaria episodes diagnosed among infants during 596.6 person years of follow-up. Compared to infants born to mothers with no PM, the incidence of malaria was higher among infants born to mothers with active PM (adjusted incidence rate ratio [aIRR] 1.30, 95% CI 1.00-1.71, p=0.05) and those born to mothers with severe past PM (aIRR 1.28, 95% CI 0.89-1.83, p=0.18), but the differences were not statistically significant. However, when stratifying by infant sex, compared to no PM, severe past PM was associated a higher malaria incidence in male (aIRR 2.17, 95% CI 1.45-3.25, p<0.001), but not female infants (aIRR 0.74, 95% CI 0.46-1.20, p=0.22). There were no significant associations between active PM or mild-moderate past PM and malaria incidence in male or female infants. Male infants born to mothers given IPTp with DP had significantly less malaria in infancy than males born to mothers given SP, and 89.7% of this effect was mediated through prevention of PM.ConclusionPM may have more severe consequences for male infants, and interventions which reduce PM could mitigate these sex-specific adverse outcomes. More research is needed to better understand this sex-bias between PM and infant malaria risk.Trial registrationTrial registration: ClinicalTrials.gov, NCT02793622. Registered 8 June 2016, https://clinicaltrials.gov/ct2/show/NCT02793622
Lower Mutant-allele tumor heterogeneity is a biomarker in FGFR3-mutant bladder cancer for better prognosis
Authors: Han Yuying , Liu Xu , Ye Haihong , Tian Ye , Ji Zhengguo
Published: November 2020

Background: Bladder cancer displays a broad mutational spectrum and intratumor heterogeneity (ITH), which results in difference in molecular phenotypes and resistance to therapies. However, there are currently no clinically available measures to predict patient prognosis using ITH. We aimed to establish clinically relevant biomarker by using ITH for informing predictive of outcomes.Methods: We used the Bioconductor R package Maftools to efficiently and comprehensively analyze somatic variants of muscle-invasive bladder cancer (MIBC) from The Cancer Genome Atlas (TCGA). We then used a mutant-allele tumor heterogeneity (MATH) algorithm to measure ITH and explored its correlation with clinical parameters as well as mutational subtypes.Results: We observed a broad range of somatic mutations in MIBC from TCGA. MATH value was higher for the high-grade group than for the low-grade group (p < 0.05). There was a strong correlation between higher MATH value and presence of TP53 mutations (p = 0.008), as well as between lower MATH value and presence of FGFR3 mutations (p = 0.006). Patients with FGFR3 mutation and low MATH value exhibit longer overall survival time than that of all BLCA patients (p = 0.044), which was replicated in another bladder cancer database composed of 109 BLCA patients.Conclusion: Measures of tumor heterogeneity may be useful biomarkers for identifying patients with bladder cancer. Low MATH value was an independent risk factor that predicted better prognosis for patients with FGFR3 mutation compared to all BLCA patients.