bluuebunny/crossref_metadata_2025 huggingface dataset:
WITHDRAWN: Long-term Complications After Stent Assist Coiling Dependent on Clopidogrel Response
Authors: Shoda Kenji , Enomoto Yukiko , Egashira Yusuke , Kinoshita Takamasa , Mizutani Daisuke , Iwama Toru
Published: January 2021

BACKGROUND: Dual antiplatelet therapy (DAPT) is necessary for stent assisted coiling. However, long term use of DAPT has a potential risk of hemorrhagic events. We aimed to examine the relationship between clopidogrel reactivity and complications.METHODS: Patients who underwent stent assisted coiling for unruptured aneurysms and received periprocedural DAPT in our institution between August 2011 to March 2020 were included. Platelet reactivity for clopidogrel was measured by VerifyNow assay system, and we defined the cut off value of P2Y12 Reaction Units (PRU) at 208, and classified patients as hypo-responders (PRU≧208) or responders (PRU＜208). The rates of hemorrhagic and thrombotic events within 30 days (acute phase) and 30 days after the procedure (delayed phase) were compared between the two groups. Furthermore, changes in hemoglobin levels were measured before and after the procedure and at chronic stages (1 to 6 months thereafter).RESULTS: From 62 patients included in this study, 36 patients were hypo-responders and 26 patients were responders. Hemorrhagic events occurred 7.7% only in responders in the acute phase (p = 0.17), and 2.78% in hypo-responders and 23.1% in responders in the delayed phase (p = 0.02). Changes in hemoglobin levels before and after the procedure were 1.21 g/dl in hypo-responders and 1.92 g/dl in responders (p = 0.02) while before the procedure and chronic stages they were 0.39g/dl in hypo-responders and 1.41 g/dl in responders (p < 0.01). Thrombotic events were not significantly different between the two groups.CONCLUSION: Long term use of DAPT after stent assisted coiling is related to hemorrhagic events in the delayed phase. Preventing for hemorrhagic events, the duration of DAPT should be carefully considered in clopidogrel responders.
Rare manifestations and malignancies in tuberous sclerosis complex: Findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA)
Authors: Sauter Matthias , Belousova Elena , Benedik Mirjana P , Carter Tom , Cottin Vincent , Curatolo Paolo , Dahlin Maria , D´Amato Lisa , d'Augères Guillaume B. , de Vries Petrus J , Ferreira Jose C , Feucht Martha , Fladrowski Carla , Hertzberg Christoph , Jozwiak Sergiusz , Lawson John A , Macaya Alfons , Marques Ruben , Nabbout Rima , O’Callaghan Finbar , Qin Jiong , Sander Valentin , Shah Seema , Takahashi Yukitoshi , Touraine Renaud , Youroukos Sotiris , Zonnenberg Bernard , Jansen Anna , Kingswood John C
Published: January 2021

Background
Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disorder caused by pathogenic mutations in either the TSC1 or TSC2 gene. Common manifestations of TSC have been grouped into major and minor clinical diagnostic criteria and assessed in clinical routine workup. However, case studies point towards the existence of rare disease manifestations and to the potential association of TSC with malignant tumors. In this study we sought to characterize rare manifestations and malignancies using a large cohort of patients.
Methods
TuberOus SClerosis registry to increAse disease awareness (TOSCA) is a multicenter, international disease registry collecting clinical manifestations and characteristics of patients with TSC, both retrospectively and prospectively. We report rates and characteristics of rare manifestations and malignancies in patients with TSC who had enrolled in the TOSCA registry. We also examined these manifestations by age, sex, and genotype (TSC1 or TSC2).
Results
Overall, 2211 patients with TSC were enrolled in the study. Rare manifestations were reported in 382 (17.3%) study participants and malignancies in 65 (2.9%). Of these rare manifestations, the most frequent were bone sclerotic foci (39.5%), scoliosis (23%), thyroid adenoma (5.5%), adrenal angiomyolipoma (4.5%), hemihypertrophy and pancreatic neuroendocrine tumors (pNET; both 3.1%). These rare manifestations were more commonly observed in adults than children (66.23% vs. 22.7%), in females versus males (58.4% vs. 41.6%; except for scoliosis: 48.9% vs. 51.1%), and in those with TSC2 versus TSC1 (67.0% vs. 21.1%; except for thyroid adenoma: 42.9% vs. 57.1%). In the 65 individuals with reported malignancies, the most common were renal cell carcinoma (47.7%), followed by breast (10.8%) and thyroid cancer (9.2%). Although malignancies were more common in adult patients, 26.1% were reported in children and 63.1% in individuals < 40 years. TSC1 mutations were over-represented in individuals with malignancies compared to the overall TOSCA cohort (32.1% vs. 18.5%).
Conclusion
Rare manifestations collectively were observed in a significant proportion of individuals with TSC. We recommend further examination of rare manifestations in TSC. Collectively, malignancies were infrequent findings in our cohort. However, compared to the general population, malignant tumors occurred earlier in age and some tumor types were more common.
Diagnosis, treatment of Type Ⅰ autoimmune pancreatitis and management of relapse and side effects after steroid treatment in China
Authors: Tang Neng , Dou Xiao-lin , He Qun , Gong Xue-jun , Zhou Jun , Liu Guo-dong , You Xing , Ning Cai-hong , Ou Zheng-lin , Ke Mu-jing , Yi Xiao-ping , Ji Lian-dong
Published: January 2021

Background: Type Ⅰ autoimmune pancreatitis (AIP) have a dramatic response to steroid therapy, but the relapse rates (RRs) is very high, and the side effects of steroid therapy are inevitable. However, the management of relapse and side effects of steroid therapy have been poorly investigated and no series have been reported previously, so this article focuses on the management of relapse and side effects. Methods: A single-centre, retrospective, cohort study of the type Ⅰ AIP patients admitted to Xiangya Hospital Central South University from September 2008 to September 2019. Collection and retrospectively analyzed the clinicopathologic data and outcomes of type Ⅰ AIP patients. Results: 82 patients with type Ⅰ AIP were included. The ratio of male with female was 2.73: 1 with median age of onset of 52 years old. 73.2% were histologically confirmed, 62.2% were showed other organ involvement (OOI). 78.0% treated by medications: 40 cases (62.5%) prednisolone, 24 cases (37.5%) prednisolone plus cyclophosphamide. The effective rate of prednisolone and prednisolone plus cyclophosphamide was no significant difference (37/40 vs 22/24, P = 0.904). The RRs of prednisolone and prednisolone plus cyclophosphamide after remission have no significant difference (14/40 vs 7/24, P = 0.630). Increasing the dosage of prednisolone, the effective rate of the prednisolone treatment and prednisolone plus cyclophosphamide treatment relapsed patients were 78.57% and 71.43%, respectively. The side effects were diabetes mellitus (DM) in 12.5%; central obesity in 15.6%; hyperlipidemia in 18.8%; gastric ulcer in 6.3%; osteoporosis in 9.4%; bone fracture in 1.6%. For those side effects patients performed low dose prednisolone and expectant treatment have a ideal results. Conclusions: There was no significant difference between prednisolone and prednisolone plus cyclophosphamide in the treatment of type Ⅰ AIP. Increasing the dose of prednisolone can effectively treat relapsed patients. Low dose steroid and expectant treatment should be performed when side effects arised.
Thrombocytopenia in Pregnancy: Identification and Management at a reference Centre in Pakistan
Authors: Borhany Munira , Abid Madiha , Zafar Sidra , Zaidi Uzma , siddiqui Saima , Shamsi Tahir
Published: January 2021

The authors have requested that this preprint be removed from Research Square.
Potential role of liver enzymes for predicting elevated blood glucose levels
Authors: Wu Mengna , Nian Shiyan , feng lei , Bai Xuejing , Ye Dan , Zhang Chunting , Yan Zefeng , Ma Qixin , Shao Cong , Bi Qianye , Luo Beibei
Published: January 2021

Background

This study was to explore the potential effect of different liver enzymes on elevated blood glucose with the use of a more detailed blood glucose grouping.
Methods

This cross-sectional study enrolled 144,135 participants who had biochemical examinations from 2014–2018. Participants were classified by sex and different blood glucose levels (< 5.0 mmol/L, 5.0-5.5 mmol/L, 5.6–6.2 mmol/L, 6.3–6.9 mmol/L, and ≥ 7.0 mmol/L). The associations between liver function indicators and occurrence of type 2 diabetes (T2DM) were analyzed through multivariate linear regression and multiple logistic regression.
Results

There was a significant difference among the biochemical indices between different blood glucose groups in males and females. Liver enzymes such as alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and γ-glutamyl transpeptidase (GGT) were independent risk factors for raised blood glucose, and there were gender differences in the predictive performance of each liver enzyme to elevated blood glucose levels. In men, GGT was the most appropriate to predict progressive elevation of blood glucose or T2DM risk, and ALT and ALP may only be applicable to the prediction of impaired fasting glucose (IFG). By contrast, ALT and ALP were the most appropriate enzymes for the prediction of the risk of elevated blood glucose or T2DM in women, and AST and GGT may only be appropriate for the prediction of IFG.
Conclusions

Liver enzymes were independent risk factors for elevated blood glucose. There were gender differences in the role of each liver enzyme for elevated blood glucose. GGT was more suitable as a predictor for dynastic elevated blood glucose in men, whereas for women, ALT and ALP were more suitable.
Increased Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 to Antibody Neutralization
Authors: Ho David , Wang Pengfei , Liu Lihong , Iketani Sho , Luo Yang , Guo Yicheng , Wang Maple , Yu Jian , Zhang Baoshan , Kwong Peter , Graham Barney , Mascola John , Chang Jennifer , Yin Michael , Sobieszczyk Magdalena , Kyratsous Christos , Shapiro Lawrence , Sheng Zizhang , Nair Manoj , Huang Yaoxing
Published: January 2021

The Covid-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. Prospects of ending this pandemic rest on the development of effective interventions. Two monoclonal antibody (mAb) therapeutics have received emergency use authorization, and more are in the pipeline. Furthermore, multiple vaccine constructs have shown promise, including two with ~95% protective efficacy against Covid-19. However, these interventions were directed toward the initial SARS-CoV-2 that emerged in 2019. Considerable viral evolution has occurred since, including variants with a D614G mutation that have become dominant. Viruses with this mutation alone do not appear to be antigenically distinct, however. Recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK and B.1.351 in South Africa is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a number of mAbs to the receptor-binding domain (RBD). It is modestly more resistant to convalescent plasma (~3 fold) and vaccinee sera (~2 fold). Findings on B.1.351 are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple potent mAbs to the receptor-binding motif on RBD, largely due to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (~11-33 fold) and vaccinee sera (~6.5-8.6 fold). B.1.351 and emergent variants with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.
HDAC6/FOXP3/HNF4α Axis Promotes Bile Acids Induced Gastric Intestinal Metaplasia
Authors: Wang Na , Wu Siran , Zhang Luyao , Chen Min , Zeng Jiaoxia , Lu Guofang , Zhou Fenli , Wu Qiong , Liu Junye , Shi Yongquan
Published: January 2021

Background: Gastric intestinal metaplasia (IM) is an important precancerous lesion. Our previous study has shown that ectopic expression of HDAC6 promotes the activation of intestinal markers in bile acids (BA) induced gastric IM cells; however, the mechanism underlying how HDAC6-mediated epigenetic modifications regulate intestinal markers is not clear.Methods: RNA-sequencing (RNA-seq) was used to detect the molecular changes in GES-1 cells after HDAC6 overexpression. The potential binding sites of FOXP3 with the promoter region of HNF4α were verified by ChIP and luciferase reporter gene assays. The ChIP assay was also used to detect the histone deacetylation. The levels of mucin in gastric or intestinal mucosa were detected by AB-PAS staining. Transgenic mice were used to explore the pro-metaplastic function of DCA and HNF4α in vivo.Results: Deoxycholic acid (DCA) upregulated HDAC6 in gastric cells, which further inhibited the transcription of FOXP3. Then, FOXP3 transcriptionally inhibited HNF4α, which further inhibits the expression of downstream intestinal markers. These molecules have been shown to be clinically relevant, as FOXP3 levels were negatively correlated with HDAC6 and HNF4α in IM tissues. Transgenic mice experiments confirmed that HNF4α overexpression combined with DCA induced gastric mucosa to secrete intestinal mucus and caused an abnormal mucosal structure. Conclusions: Our findings suggest that HDAC6 reduces FOXP3 through epigenetic modification, thus forming HDAC6/FOXP3/HNF4α axis to promote gastric IM. Inhibition of HDAC6 may be a potential approach to prevent gastric IM in patients with bile reflux.
Outcomes in Thoracolumbar and Lumbar Traumatic Fractures: Does Restoration of Unfused Segmental Mobility Correlated to Implant Removal Time？：a retrospective study
Authors: Wu Jian , Zhu Jun , Wang Zhong , Jin Huaijian , Wang Yingbo , Liu Baiyi , Yin Xiang , Du Longbin , Wang Yu , Liu Mingyong , Liu Peng
Published: January 2021

Background

Posterior fixation without fusion can treat thoracolumbar and lumbar traumatic fractures effectively. However, whether patients benefit from implant removal, as well as the correlation between the range of motion (ROM) of the involved segments and the removal time, has not been determined.
Methods

Fifty consecutive cases with thoracolumbar traumatic fractures that had undergone implant removal at different times were enrolled. We found 17 patients (Group A), 21 patients (Group B), and 12 patients (Group C) underwent implant removal following the index surgery within 12 months, between 12 to 24 months, and over 24 months, respectively. Clinical and radiological outcomes, including visual analog scale (VAS) for back pain, patient satisfaction, the Oswestry disability index (ODI) and EuroQol five dimensions questionnaire (EQ-5D) for quality of life and segmental ROM were analyzed.
Results

The average follow-up time was 9.1 ± 5.7 months after implant removal. There were no significant differences in VAS and patient satisfaction among the three groups at the same observation time points. Patients of group A gained the lowest ODI and highest EQ-5D scores after removal and at final follow-up than those in group B and C. The best ROM was obtained in Group A followed by Group B and C (11.5 ± 6.2°, 5.5 ± 1.6° and 2.4 ± 0.6°, respectively).
Conclusions

Immobilization of the involved segments over 24 months may lead to ankylosis. Regained segmental ROM is correlated negatively with implant removal time. Patients have implant removal within 12 months can gain a better quality of life.
Synovial fluid IL-1β appears useful for the diagnosis of chronic periprosthetic joint infection
Authors: Wang Hai , Qin LeiLei , Wang Jiawei , Huang Wei
Published: January 2021

Purpose The purpose of this study was to investigate the role of synovial fluid interleukin (IL)-1β in diagnosing chronic periprosthetic joint infection (PJI) and to identify the optimal threshold of synovial fluid IL-1β for differentiating chronic PJI from aseptic failure after knee and hip arthroplasties.Methods Between January 2019 and December 2019, we prospectively included patients scheduled to have a revision surgery for chronic PJI or aseptic failure after total joint arthroplasty. Then synovial IL-1β was additionally measured along with routine preoperative diagnostic serum and synovial biomarkers. The receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker to determine diagnostic efficacy.Results Of the 93 patients included, their demographic data were not found to be statistically significant. The median synovial IL-1β levels were significantly higher in the chronic PJI group than in the aseptic group (894.73 pg/mL vs. 34.49 pg/mL, P<0.01). The AUC for synovial fluid IL-1β was 0.991, which was higher than serum ESR (0.627) and CRP (0.712). The optimal threshold value for detecting chronic PJI of synovial IL-1β was 312.7 pg/mL, with a sensitivity of 97.3% and a specificity of 94.64%. And the combined measurement of synovial fluid IL-1β and synovial fluid PMN% can led to a specificity of 1, and a negative predictive value (NPV) of 1.Conclusions The present study demonstrated that synovial fluid IL-1β is a valuable biomarker for detection of chronic PJI. The combination of synovial fluid IL-1β and PMN% led to an improvement in specificity compared with evaluation of each single index.
Bacterial profile, antimicrobial susceptibility pattern and associated factors of community and hospital acquired urinary tract infection at Dessie referral hospital, Dessie, Northeast Ethiopia
Authors: Adugna Berhanu , Sharew Bekele , Jemal Mohabaw
Published: January 2021

Back ground:

Urinary tract infection are one of the most common bacterial infections in the community and in the hospital. Nowadays, little is known about the status of community and hospital acquired urinary tract infection, antimicrobial susceptibility pattern and associated factors among urinary tract infection patients in Ethiopia, particularly in our study area.
Methods

A hospital based cross sectional study was carried out in Dessie referral hospital. A total of 422 urine samples were enrolled using systematic random sampling technique. All isolates were identified by standard microbiological techniques and their antibiotic susceptibility was done by Kirby Bauer disc diffusion method. Data was entered using Epi data version 3.1 and analyzed by SPSS software version 20. P- Value < 0.05 at 95% CI was considered as statistically significant.
Result

Of 422 urine samples processed 100 (23.7%) yielded bacterial isolates. About50(30.7%) and 50(19.3%) samples from hospitalized and community showed significant bacteriuria respectively. E. coli 44/103(42.7%), predominated across the two groups followed by S. aureus 25/103(24.3%), CONs,14/103(13.5%), Klebsiella spps 7/103(6.78), proteus spps 3/103(2.91), and Entrococcus spps 3/103 (2.91%). Pseudomonas spps 3/103 (2.91), Citrobacter spps 2/103(1.94%) and Acinetobacter Spp 1/103(0.999), which were isolated from only the hospitalized samples. Meropenem susceptibly was 100% in both study groups and Ampicillin resistance was documented as 83.3–100% and 76.9–100% in hospitalized and community acquired respectively. Among risk factors previous use of antibiotics, female gender, Age, Diabetics, catheterization were associated with the infection.
Conclusion

The present study revealed that slightly high prevalence of urinary tract infection. High antimicrobial resistance was observed to most antimicrobial drugs tested. Meropenem and Nitrofurantoin were the most active drugs for urinary tract infection. Empirical selection of antimicrobial agents should be based on antibiotic sensitivity pattern of uropathogens that prevalent in that area. Female sex, age, previous use of antibiotics, catheterization and diabetics were at risk of urinary tract infection.
Free congruence: an exploration of expanded similarity measures for time series data
Authors: Jacaruso Lucas Cassiel
Published: January 2021

Time series similarity measures are highly relevant in a wide range of emerging applications including training machine learning models, classification, and predictive modeling. Standard similarity measures for time series most often involve point-to-point distance measures including Euclidean distance and Dynamic Time Warping. Such similarity measures fundamentally require the fluctuation of values in the time series being compared to follow a corresponding order or cadence for similarity to be established. Other existing approaches use local statistical tests to detect structural changes in time series. This paper is spurred by the exploration of a broader definition of similarity, namely one that takes into account the sheer numerical resemblance between sets of statistical properties for time series segments irrespectively of value labeling. Further, the presence of common pattern components between time series segments was examined even if they occur in a permuted order, which would not necessarily satisfy the criteria of more conventional point-to-point distance measures. The newly defined similarity measures were tested on time series data representing over 20 years of cooperation intent expressed in global media sentiment. Tests determined whether the newly defined similarity measures would accurately identify stronger resemblance, on average, for pairings of similar time series segments (exhibiting overall decline) than pairings of differing segments (exhibiting overall decline and overall rise). The ability to identify patterns other than the obvious overall rise or decline that can accurately relate samples is regarded as a first step towards assessing the value of the newly explored similarity measures for classification or prediction. Results were compared with those of Dynamic Time Warping on the same data for context. Surprisingly, the test for numerical resemblance between sets of statistical properties established stronger resemblance for pairings of decline years with greater statistical significance than Dynamic Time Warping on the particular data and sample size used.
Initial experience of preoperative short-course radiotherapy followed by oxaliplatin-based consolidation chemotherapy for locally advanced rectal cancer
Authors: Song Seung Ho , Park Jun Seok , Kang Min Kyu , Choi Gyu-Seog , Park Soo Yeun , Kim Hye Jin , Kim Jong Gwang , Kang Byung Woog , Baek Jin Ho , Baek Dong Won , Kim Jae-Chul , Park Shin-Hyung , Cho Seung Hyun , Seo An Na
Published: January 2021

Purpose: We analyzed the safety and feasibility of preoperative short-course radiotherapy (SCRT) followed by consolidation chemotherapy for patients with locally advanced rectal cancer (LARC).Methods: From April 2018 to May 2019, 19 patients with LACR were treated with SCRT followed by three cycles of consolidation chemotherapy with leucovorin, fluorouracil, and oxaliplatin (FOLFOX6) before surgery. Adjuvant chemotherapy relied on oxaliplatin. Tumor response, patient compliance, and toxicities were analyzed.Results: The median age was 60 years (range 44–71), and 16 of the patients were male. The median tumor height was 5 cm (range 0–9) from anal verge. All patients received a total dose of 25 Gy in five fractions. The number of cycles of FOLFOX6 before surgery was three in 17, four in one, five in one. Five patients required dose reductions in consolidation chemotherapy. The median interval between initiation of SCRT and surgery was 10.6 weeks (range 8.6–16.4). A pathologic complete response was seen in two patients (11%). Grade III toxicities to the preoperative treatment were seen in five patients (26%): diarrhea in two, a decreased white blood cell count in one, and anemia in two. Postoperative complications arising within 30 days developed in five patients (26%). During the median follow-up period of 20.4 months, there was no tumor recurrence. Conclusion: Preoperative SCRT followed by oxaliplatin-based consolidation chemotherapy showed acceptable toxicity and feasibility in patients with LARC. Prospective randomized trials are warranted to verify the efficacy and safety of this treatment strategy compared with conventional long-course concurrent chemoradiotherapy.
Following the outbreak: preliminary findings on the landscape effect on Dasineura oleae and its parasitoids in Central Italy
Authors: Picchi Malayka Samantha , Tondini Elena , Albertarelli Nicola , Monteforti Gaia , Petacchi Ruggero
Published: January 2021

Dasineura oleae (Angelini, 1831) (Diptera: Cecidomyiidae), the olive leaf gall midge, is a pest of olive crops that has never been problematic in Italy since 2016, when a massive infestation of this pest was reported in a small region of Central Italy. We selected infested olive orchards through farmers’ reports aiming at quantifying the pest infestation level and the parasitism rate in each site. Also, we aimed at exploring the landscape effect in both pest and parasitoids, using proportion of olive crops and semi-natural habitats, as well as the Shannon index as a measurement of the landscape diversity, estimated at four different scales (250m, 500m, 750m and 1000m buffers around the sampling points). Results showed different landscape effect depending on the organism and on the scale. We underlined a small-scale effect on the parasitism rate and a large-scale effect on the olive leaf midge mediated by the Shannon Index. Moreover, some preliminary results showed that the parasitism rate was high in sites where plants associated with D. oleae parasitoids were present in the adjacent semi-natural habitat. Further study should deepen and validate our findings on the effect of landscape and of the vegetation on natural enemies of D.oleae. These results should stimulate new approaches in the studying of the olive gall leaf midge as well as new suppression strategies.
Role of open cerclage wires used in patients with comminuted fractures of femoral shaft treated with intramedullary nails
Authors: Wang Tzu-Hao , Chuang Hao-Chun , Kuan Fa-Chuan , Hong Chih-Kai , Yeh Ming-Long , Su Wei-Ren , Hsu Kai-Lan
Published: January 2021

IntroductionThe role of open cerclage wiring in comminuted femoral shaft fracture treatment with intramedullary nails remains unclear. Here, we analyzed the effect of open cerclage wiring and the risk factors for nonunion after interlocking nailing in comminuted femoral shaft fracture treatment. We hypothesize that open cerclage wiring is applicable to patients with severe comminuted femoral shaft fractures without affecting bone healing.Patients and MethodsThis retrospective cohort study used data of consecutive patients who underwent interlocking nail fixation of a comminuted femoral shaft fracture between January 1, 2009, and December 31, 2016. First, eligible patients were divided into wire and no wire groups according to the surgical technique used and their union rate was recorded. The patients were then divided into union and nonunion groups and their perioperative data were analyzed.ResultsIn total, 71 comminuted femoral shaft fractures treated with interlocking nail fixation were included: 38 fractures (53.5%) augmented with the open wiring technique and 33 reduced with closed or mini–open wound without wiring. The wire group demonstrated significant improvements in fracture reduction compared with the no wire group, whereas no significant difference was observed in the union rate between the wire and no wire groups (p = 0.180). Moreover, 46 (65%) of 71 fractures united smoothly, and no significant difference was observed in any perioperative data between union and nonunion groups.DiscussionAugmented open cerclage wiring is indicated for comminuted femoral shaft fractures treated with intramedullary nails, even when the fragments are large or far displaced. Thus, open cerclage wiring can be used for fracture treatment, without decreasing the union rate.
Effect of groundwater forced seepage on heat transfer characteristics of borehole heat exchangers
Authors: Ma Jiuchen , Jiang Qian , Zhang Qiuli , Xie Yacheng , Wang Yahui , Yi Feiyu
Published: January 2021

A borehole heat exchangers (BHEs) combined with pumping-injection well is established in areas where the groundwater is shallow and the seepage velocity is weak. The pumping and injection wells are set on both sides of the BHEs. According to the three-dimensional unsteady heat transfer model in aquifer, the convection-dispersion analytical solution of excess temperature is derived that considers groundwater forced seepage and thermal dispersion effects and axial effect of the BHEs. Then, the dimensional analysis method and similarity criteria we used to build a controllable forced seepage sandbox. The software FEFLOW 7.1 is adopted and the simulation results are validated by the theoretical analysis and the indoor experiment test. On this basis, the numerical simulation calculation is used to explore the influence of different pumping-injection flow volume on the Darcy flow velocity of the aquifer where the BHEs are located, the average heat transfer efficiency and the heat transfer rates with borehole depth. The results show that when the pumping flow volume increases from 200 m3∙d-1 to 1200 m3∙d-1, the Darcy velocity correspondingly increases to about 10 times. The average heat efficiency coefficient of the BHEs is increased by 11.5% in cooling stage, and by 7.5% in heating stage. When the pumping-injection flow volume is 400~600 m3∙d-1, the increment of heat transfer rates of the BHEs reaches 12.8~17.9 W∙m-1 and 3.6~4.2 W∙m-1 per unit of borehole depth during the cooling stage and heating stage respectively, and then decreases as the flow volume increases gradually.
Continuous Erector Spinae Plane Block versus Intercostal Nerve Block in Patients Undergoing Video-assisted Thoracoscopic Surgery: A Pilot Randomized Controlled Trial
Authors: Horth Dillon , Sanh William , Moisiuk Peter , O’Hare Turlough , Shargall Yaron , Finley Christian , Hanna Waël , Agzarian John , Forero Mauricio , Davis Kim , Vanniyasingam Thuva , Thabane Lehana , Shanthanna Harsha
Published: January 2021

Background: The optimal analgesia method in video-assisted thoracoscopic surgery (VATS) remains controversial. Intercostal nerve blockade (ICNB) is limited by its duration of action. The erector spinae plane (ESP) block has the potential to provide satisfactory analgesia for VATS; however, the effectiveness of continuous ESP versus surgeon-performed ICNB has not been investigated. The objectives of this study were to establish feasibility of patient recruitment and follow-up before undertaking a fully powered randomized controlled trial (RCT); and, secondarily, to compare opioid usage, pain control, and sensory blockade.Methods: This feasibility RCT was undertaken at St Joseph’s Hospital, Hamilton, Ontario, Canada, and included 24 patients (>18 years) having elective VATS with at least one overnight stay. Exclusion criteria were patient refusal; body mass index >40 kg/m2; contraindications to neuraxial analgesia techniques as per the American Society of Regional Anesthesia and Pain guidelines; known allergy to local anesthetics; language or comprehension barriers; procedures with a higher chance of open surgery; and regular opioid use for ≥3 months preoperatively. Patients underwent either continuous ESP (n=12) or surgeon-performed ICNB (n=12). All patients received routine intraoperative anesthesia care and multimodal analgesia. Feasibility criteria were recruitment rate of two patients/week and full follow-up in all patients in-hospital. We compared opioid consumption, postoperative pain scores (0–10 numerical rating scale), adverse events, patient satisfaction, and distribution of sensory blockade as clinical outcomes (secondary).Results: Feasibility of primary outcomes was successfully demonstrated. Five patients had an epidural in anticipation of open surgery. Mean opioid consumption as equivalent morphine units, was less in the ESP group over the first 24 h (mean difference, 1.63 [95% CI –1.20 to 4.45]) and 48 h (mean difference, 2.34 [95% CI –1.93 to 6.61]). There were no differences in adverse effects.Conclusions: A fully powered RCT is feasible with modifications. Our results also suggest that continuous ESP is safe and can decrease opioid needs. However, it is important to consider procedures to improve compliance to protocol and adherence to assigned interventions.Trial registration: Clinicaltrials.gov identifier: NCT03176667. Registered June 5, 2017, https://clinicaltrials.gov/ct2/show/NCT03176667
Erwin Scheuchel, Wolfgang Willner: Quelle & Meyer Bestimmungskarten, Fauna
Authors: Steinecke Hilke
Published: January 2021

#
Improved neural network Monte Carlo simulation
Authors: Chen I-Kai , Klimek Matthew , Perelstein Maxim
Published: January 2021

The algorithm for Monte Carlo simulation of parton-level events based
on an Artificial Neural Network (ANN) proposed in Ref.~ is used to
perform a simulation of H\to 4\ellH→4ℓ
decay. Improvements in the training algorithm have been implemented to
avoid numerical instabilities. The integrated decay width evaluated by
the ANN is within 0.7% of the true value and unweighting efficiency of
26% is reached. While the ANN is not automatically bijective between
input and output spaces, which can lead to issues with simulation
quality, we argue that the training procedure naturally prefers
bijective maps, and demonstrate that the trained ANN is bijective to a
very good approximation.
Guidelines for the association of rural settlements (based on the materials of the Republic of Bashkortostan)
Authors: Атаева А.Г.
Published: January 2021

В статье предлагаются методические рекомендации по объединению (укрупнению) сельских поселений, включающие в себя предложения не только по процессу преобразования и формированию органов местного самоуправления, но по подготовительным работам перед преобразованием. На основе оценки значений ключевых критериев возможности объединения предлагаются варианты укрупнения сельских поселений Республики Башкортостан.

In the article, the author offers methodological recommendations for the unification (enlargement) of rural settlements. Based on the assessment of the values of the key criteria for the possibility of unification, options for enlarging rural settlements of the Republic of Bashkortostan are proposed.
Principles of state budget management
Authors: Доброскок О.В.
Published: January 2021

Принципы бюджетного менеджмента являются основой организации государственной системы управления финансовыми ресурсами на макроуровне, реализующей стратегические цели и текущие задачи бюджетной политики государства. Перечень принципов бюджетного менеджмента должен быть достаточным, научно обоснованным и иметь практическое применение в государственном менеджменте различного уровня. В статье рассмотрены принципы построения бюджетной системы Российской Федерации, принципы финансового менеджмента, принципы управления государственными и муниципальными финансами, общие принципы управленческих систем. В результате исследования проведен анализ принципов бюджетного менеджмента, предложен расширенный перечень принципов, в том числе учитывающий положения Конституции Российской Федерации, дано теоретическое обоснование предложенных принципов.

The principles of budget management lay down the foundations of the organization of the financial resources management state system at the macro level, which implements strategic goals and present-day problems of the state budget policy. The list of the budget management principles should be sufficient, scientifically substantiated and have practical application in public management at various levels. The article examines the principles of building the budget system of the Russian Federation, the principles of financial management, public and municipal finance management, as well as general principles of management systems. In the course of the study, the analysis of the budget management principles was carried out. As a result, an extended list of principles, in which the provisions of the Constitution of the Russian Federation are taken into consideration, was proposed. A theoretical justification of the proposed principles was given.
A rational approach to opioid dose reduction in the treatment of bone pain. Clinical discussion
Authors: Rozengard S. A. , Ryazankina A. A. , Latipova D. Kh. , Malygin A. Yu. , Kasparov B. S.
Published: January 2021

Narcotic drugs have become more available for use, but it is obvious that monotherapy of pain syndrome with narcotic drugs is not always effective. Patients sometimes change prescribed opiates to NSAIDs on their own, because it is more effective despite the high risk of complications. In this case patient has a grade 2 pain syndrome associated with bone metastases despite taking the maximum daily dose of tramadol complicated by nausea. Treatment was successfully changed with medium doses of tramadol and dexketoprophen. We consider the combination of narcotic drugs and NSAIDs as opiate-sparing and suggest that dexketoprophen is effective for treatment of pain associated with bone metastases because of the effect on neuropathiс and central components of pain syndrome. We have analyzed the main mechanisms and options for systemic pharmacotherapy of pain syndrome in bone metastases. Some NSAIDs are known to have central analgesic effects. For example, the analgesic effect of ketorolac after an injury of sciatic nerve is explained by its ability to inhibit the synthesis of algogenic peptides in the posterior horns of the spinal cord and the decrease in astrocyte activation. However, it is the dexketoprofen/tramadol combination that is recognized as the most effective in the world.
FOLFOXIRI versus FOLFOX or FOLFIRI with targeted therapy in patients with mutant BRAF metastatic colorectal cancer: A systematic review and meta-analysis
Authors: Fedyanin M. Yu. , Polyanskaya E. M. , Elsnukaeva H. H.-M. , Tryakin A. A. , Pokataev I. A. , Bulanov A. A. , Tjulandin S. A.
Published: January 2021

Introduction. Based on the subgroup analysis of the TRIBE study FOLFOXIRI with bevacizumab is the recommended option for patients (pts) with mBRAF metastatic colorectal cancer (mCRC) in the 1st line. However, subgroup analysis of other studies showed conflicting results. Therefore, we performed systemic review and meta-analysis to compare efficacy FOLFOXIRI and doublets with targeted therapy in pts with mBRAF mCRC in terms of progression free survival (PFS), objective response rate (ORR) and overall survival (OS).

Methods. We performed a search of all prospective randomizes studies in PubMed, ASCO and ESMO congresses for all years before May, 2020, compared FOLFOXIRI plus bevacizumab or anti-EGFR antibodies and FOLFOX or FOLFIRI with targeted agents at the 1st line with information of the BRAF status. Primary outcome was hazard ratio (HR) for PFS and 95% confidence interval (CI); secondary – HR for OS and odds ratio (OD) for ORR. Fixed effects were used for analysis. Meta-analysis was conducted by Review Manager Ver. 5.3.

Results. We identified 6 trials (CHARTA, STEAM, TRIBE, TRIBE2, VISNU, METHEP2), which included 158 pts with mBRAF (FOLFOXIRI – 82 (52%) and doublets – 76 (48%). According to results of the meta-analysis there was a tendency for higher ORR in pts with FOLFOXIRI (OR 2.07, 95% CI 0.61–7.06; p = 0.24; I2 = 27%, p for heterogeneity 0.26; 3 trials). However we didn’t find any significant improvement in PFS (HR 0.89, 95% CI 0.64–1.23; p = 0.48; I2 = 0%, p for heterogeneity 0.63; 5 trials) or OS (HR 0.9, 95% CI 0.37–1.19; p = 0.048; I2 = 71%, p for heterogeneity 0.06; 2 trials) in the group of triplet.

Conclusions. FOLFOXIRI with targeted therapy did not show significant improvement in the PFS and OS in pts with mBRAF compared with FOLFOX or FOLFIRI with targeted antibodies. A prospective randomized trial is needed to determine the optimal chemotherapy regimen at the 1st line for pts with mBRAF mCRC.
Fibrolamellar liver cancer: the modern concept
Authors: Antonova E. Yu. , Breder V. V. , Moroz E. A. , Laktionov K. K. , Dzhanyan I. A. , Volkov A. Yu.
Published: January 2021

Fibrolamellar hepatocellular carcinoma (FLC) is a relatively rare primary liver tumor of unknown etiology (chronic infections with hepatitis B or C viruses, chronic alcohol poisoning, cirrhosis of the liver), which occurs mainly in the young population. FLK is more often diagnosed already at common stages due to the absence of pronounced clinical manifestations in patients for a long time. In pathomorphological diagnostics, FLC is a cluster of large polygonal eosinophilic cells with a clearly defined vesicular nucleus, surrounded by abundant growths of lamellar fibrosis. In most cases, collagen fibers are arranged in parallel strands; in metastatic tumors, collagen fibers can be arranged haphazardly (the so-called “tangled fibers”).For many years, attempts have been made to identify reliable markers for the detection and differential diagnosis of FLC and to determine the cause of tumors in young patients, and the molecular mechanisms of FLC carcinogenesis have been studied. In 2014 during the full transcriptome analysis of FLC samples, the chimeric transcript DNAJB1PRKACA was discovered, which is formed as a result of deletion of a section of chromosome 19 with a size of 400 thousand nucleotide pairs and leads to the fusion of two genes, which Is found in most FLC samples. Surgery is the only curative treatment of this tumor type and radical method of treating the disease. Given that lymph node involvement is an important prognostic factor, complete periportal lymphadenectomy should be performed as part of radical surgery for patients with FLK. The role and possibilities of locoregional and drug-based treatment methods are not fully clear, and the search for effective treatment regimens and potential targets specific to this form of HCR is urgent. Studies show conflicting results for different chemotherapy regimens and the use of targeted therapy. The literature describes isolated clinical cases of successful use of immunotherapy in patients with PD-L1-expressing tumors. The most important condition for successful treatment is an in-depth study of the molecular mechanisms of FLC carcinogenesis. This review presents current data on epidemiology, classification, clinico-morphological, molecular and genetic aspects, as well as some diagnostic features and FLC treatment modalities.
The dynamics of the incidence of breast cancer in the Moscow region (2011–2018)
Authors: Kogoniya L. M. , Astashov V. I. , Minakov S. N.
Published: January 2021

Introduction. Breast cancer is a serious medical and social challenge and the statistics around the world look daunting.

Relevance. The incidence of breast cancer is increasing in most countries and this may be due to a number of reasons. First of all, it should be noted the improvement of diagnostic methods, in particular, mass mammographic screening, which allows detecting neoplasms at early stages, before the onset of clinical symptoms. As for mortality rates, in recent years, world statistics show a downward trend in rates.

Goal. To analyze the incidence and mortality rates of breast cancer (BC) in the Moscow Region (MO) for the period from 2011 to 2018. The study of indicators in one of the regions of Russia – MO – is of great importance for determining and predicting the true needs of the population in specialized medical care.

The purpose of the study was to analyze the incidence of breast cancer (breast cancer) in the Moscow Region (MO) for a period of time from 2011 to 2018.

Materials and methods. Some data of the territorial cancer registry of the Ministry of Defense of the Russian Federation on the diagnosis and treatment of patients with breast cancer were used, which will make it possible to determine the needs of this cohort of patients in specialized care.

Results. From 2011 to 2018, 26755 new cases of breast cancer were diagnosed in the Moscow Region. The analysis of the comparative stratification in breast cancer in the medical district made it possible to obtain statistically significant differences indicating an increase in the incidence in the period from 2015–2018 in comparison with the period of 2011–2014. The presented data also indicate a trend towards a decrease in the one-year mortality rate over 8 years: from 6.33% in 2011 to 5.32% in 2018. For the period from 2011 to 2018 (8 years) there is an increase in the number of patients with breast cancer who have been in the medical center under dispensary supervision for 5 years or more.

Conclusions. Analysis of the data obtained on the indicators of morbidity and mortality from malignant neoplasms is of great importance for determining the needs of the population in specialized medical care.
Trastuzumab emtansine of the treatment of HER2-positive breast cancer with brain metatases
Authors: Vladimirova L. Yu. , Popova I. L. , Abramova N. A. , Teplyakova M. A. , Tikhanovskaya N. M. , Novoselova K. A. , Lyanova A. A. , Ryadinskaya L. A. , Ezhova M. O. , Myagkova V. S. , Strakhova L. K.
Published: January 2021

Patients with brain metastases of HER2-positive breast cancer (BC) is a special group of patients who are difficult to treat and have a short life expectancy. The possibilities of whole brain radiotherapy, stereotactic radiosurgery and surgery in such patients are rather limited. Trastuzumab emtansine (T-DM1) showed potential activity in this subset of patients. T-DM1 is an antibody-chemical conjugate (ADC) that delivers directly to HER2-positive cancer cells, thereby limiting damage to healthy tissue. At this point, the efficacy of trastuzumab emtansine has been demonstrated in several randomized trials as a second and subsequent lines of therapy for advanced breast cancer with a favorable toxicity profile of the drug. This article describes a clinical case of a patient with luminal B HER-2 positive breast cancer who, underwent stereotactic radiosurgery and was treated with trastuzumab emtansine as a the second line of treatment for disease progression with metastatic brain lesions after trastuzumab/pertuzumab-containing therapy. Partial regression of metastases with long-term duration of the effect was achieved treatment with trastuzumab emtazine has been being continued for 24 months. Tolerability of therapy was good: thrombocytopenia 2 degree was the main among side effects. The effect has been persisted for 2 years and the patient continues the treatment. Discussion of the results of real clinical practice with well-known studies was carried out.
Experience of targeted therapy for ALK positive non-small cell lung cancer – a clinical case
Authors: Sultanbaev A. V. , Musin Sh. I. , Menshikov K. V. , Nasretdinov A. F. , Ibragimov B. A. , Nigmatullin A. G. , Ayupov R. T. , Izmailov A. A. , Sultanbaeva N. I.
Published: January 2021

Lung cancer holds a leading position in the cancer mortality pattern worldwide. The emergence of knowledge about driver mutations heralded a new era in the targeted therapy for lung carcinomas. ALK translocation is identified in 5–7% of non-small cell lung cancer cases. ALK-positive lung adenocarcinomas are associated with specific clinical features, including no or light smoking history and younger age. Alectinib is a novel ALK inhibitor that has been granted a breakthrough therapy status by the FDA to accelerate approval as a second-line therapy after progression during crizotinib therapy.

Here, the case of a patient with metastatic ALK-positive lung adenocarcinoma treated with alectinib has been discussed. Molecular genetic testing for driver mutations makes it possible to personalize approaches to anticancer drug therapy. At the same time, the custom-compounded targeted therapy is more often accompanied by significant objective responses and moderate symptoms of toxicity, which is relevant for patients in critical condition. The experience in using alectinib demonstrates the possibility of its long-term administration with high efficiency and a controlled safety profile.