bluuebunny/crossref_metadata_2025 huggingface dataset:
Using An Optimized Generative Model To Infer The Progression of Complications In Type 2 Diabetes Patients
Authors: Wang Xiaoxia , Xiong Yun , Plasek Joseph M. , Bates David , Tang Chunlei
Published: February 2022

Background: People with type 2 diabetes would progress slowly and have few symptoms before diagnosed, if any, and don’t discover their condition until complications develop. Furthermore, with the development of the diabetes, patients often develop comorbidities. However, heterogeneity of progression coupled with deficiencies in electronic health records related to incomplete data, discrete events, and irregular event intervals make identification of pre-diabetes and critical points of diabetes progression challenging. Methods: We utilized longitudinal electronic health records of 9,298 patients with type 2 diabetes or prediabetes from 2005 to 2016 from a large regional healthcare delivery network in China. We optimized a generative Markov-Bayesian-based model to generate 5000 synthetic illness trajectories. The synthetic data were manually reviewed by endocrinologists. Results: We build an optimized generative progression model for type 2 diabetes using anchor information to reduce the number of parameters learning in the third layer of the model from O(N×W) to O(N-C), where N is the number of clinical findings, W is the number of complications, C is the number of anchors. Based on this model, we infer the relationships between progression stages, the onset of complication categories, and the associated diagnoses during the whole progression of type 2 diabetes using electronic health records. Conclusions: The full type 2 diabetes patient trajectories generated by the chronic disease progression model can counter a lack of real-world evidence of desired longitudinal timeframe while facilitating population health management.
An Extended Sepic DC-DC Converter for Micro-Grid Based Photovoltaic (Pv) Applications.
Authors: ISAH HUZAIFA , Yunusa Abdu , Hajara Mukhtar Ali
Published: February 2022

Background

The demands for clean energy is growing rapidly and the fossil fuel we use in our everyday live is ushered in CO2 and other greenhouse effects, resulting in natural disasters and other climate threats. To continue on this route, the world is challenged to prepare for the unknown disasters. Hence, the search for a clean, alternative energy resource, which could bring resilience back to our cities is in incredibly rapid velocity. Solar energy is a clean and alternative energy that can be use but PV panels tend to generate low energy in nature which is why a lot of panels have to be employed in order to go off-grid. A simple DC-DC converter can be used to boost the energy generated by PV panels. Provided herein is an extended DC-DC single ended primary inductor converter (SEPIC) for micro-grid based photovoltaic (PV) applications. The new topology was designed with an addition of some components to the conventional SEPIC.
Results

The extended SEPIC topology utilizes a single power switch with high voltage gain, low duty-cycle, reduced voltage stress across the power switch, low density and cheap. The new topology was designed with an addition of some components to the conventional SEPIC. A 125 V DC output was generated from a 12 V DC input through MATLAB/SIMULINK. The new SEPIC converter revealed the best value voltage gain as 10.42, duty-cycle value of 0.8 and voltage stress of 62.5 V compared to the conventional SEPIC or SEPIC integrated with other converters.
Conclusions

the results of voltage gain, duty-cycle and voltage stress obtained validate the credibility of the new converter and show the potentiality of the converter for the adoption in power step-up applications.
Effect of Formic Acid Treatment on Colostrum Quality, and on Absorption and Function of Immunoglobulins: A Randomized Controlled Trial in Holstein Dairy Calves
Authors: Smith Billy I. , Cady Sarah V. , Aceto Helen W.
Published: February 2022

Background

Good quality colostrum is characterized by high immunoglobulin levels and low pathogen load. Techniques to decrease pathogens can damage immunoglobulins, potentially reducing both absorption and function. Objectives were to determine the effect of formic acid treatment on colostral bacterial and immunoglobulin (IgG) levels before feeding, and serum immunoglobulin levels and neutralizing capabilities after feeding. Fifteen female Holstein calf pairs born < 12 h apart from different dams were randomly assigned to receive four liters of either untreated pooled (both dams) colostrum (MC) or colostrum acidified to pH 4.0-4.5 (AC). Colostrum characteristics evaluated; pH, bacterial load, IgG, and neutralization of Infectious Bovine Rhinotracheitis (IBRV), Bovine Viral Diarrhea (BVDV) Types 1 and 2. Blood collected on days 1, 3 and monthly for 6 months was analyzed for IgG, and both viral plus leptospiral neutralization.
Results

Compared to MC (mean 6.7, SD 0.4; median 6.8, range 6.0-7.3), AC pH was significantly reduced (mean 4.3, SD 0.2; median 4.3, range 4.0-4.5; P < 0.001). Total coliform count (cfu/mL) was also reduced (MC mean 149, SD 444; median 1, range 0-1,700; AC mean 8, SD 31; median 0, range 0-120; P = 0.02). Colostrum IgG levels were not significantly different between MC (mean 93.3, SD 39.7; median 92.80, range 36.7-164.4 g/L) and AC (mean 101.9, SD 36.7; median 108.3, range 33.8-164.4 g/L; P = 0.54). In calves, serum IgG peaked on day 3 (MC mean 26.1, SD 34.9; median 169.2, range 8.3-151.0 g/L; AC mean 30.24, SD 48.7; median 188.8, range 3.1-204.4 g/L; P = 0.77), and apparent efficiency of IgG absorption was not different between groups (MC mean 24.3, SD 11.4, median 25.3, range 8.6–51.3%; AC mean 22.6, SD 21.7, median 21.6, range 4.1-58.9%; P = 0.65). Thereafter, IgG levels declined but did not differ between groups. MC and AC serum neutralizing titers for IBRV, BVDV Types 1 and 2, or Leptospira canicola, hardjo, and pomona were not different.
Conclusions

Colostrum acidification significantly decreased bacterial load fed to newborn calves without affecting IgG concentration or virus neutralization. Nor did acid treatment impact serum IgG levels in calves or activity against common pathogens.
Temporo-spatial Variations in Resistance Determinants and Clonality of Acinetobacter Baumannii and Pseudomonas Aeruginosa Strains From Romanian Hospitals and Wastewaters
Authors: Gheorghe Irina , Barbu Ilda Czobor , Popa Laura Ioana , Parcalabioru Gratiela Gradisteanu , Popa Marcela , Marutescu Luminita , Nita-Lazar Mihai , Banciu Alina , Stoica Catalina , Gheorghe Stefania , Lucaciu Irina , Sandulescu Oana , Paraschiv Simona , Surleac Marius , Talapan Daniela , Muntean Andrei Alexandru , Preda Madalina , Muntean Madalina-Maria , Dragomirescu Cristiana Cerasella , Popa Mircea Ioan , Otelea Dan , Chifiriuc Mariana Carmen
Published: February 2022

Background: Romania is one of the European countries reporting very high antimicrobial resistance (AMR) rates and consumption of antimicrobials. We aimed to characterize the AMR profiles and clonality of 304 multi-drug resistant (MDR), carbapenemase (CP) and extended spectrum beta-lactamase (ESBL) producing Acinetobacter baumannii (Ab) and Pseudomonas aeruginosa (Pa) strains isolated during two consecutive years (2018 and 2019) from hospital settings, hospital collecting sewage tanks and the receiving wastewater treatment plants (WWTPs) located in the main geographical regions of Romania. Methods: The strains were isolated on chromogenic media and identified by MALDI-TOF-MS. Antibiotic susceptibility testing and confirmation of ESBL- and CP- producing phenotype were performed. The genetic analyses consisted of PCR for ESBL and CP genes, horizontal gene transfer experiments, whole-genome sequencing (WGS), assembling, annotation and characterization. Results: Both clinical and aquatic isolates exhibited high MDR rates, especially the Ab strains isolated from nosocomial infections and hospital effluents. The phenotypic resistance profiles and MDR rates have largely varied by sampling point and by geographic location. The highest MDR rates in aquatic isolates were recorded in Galați WWTP followed by Bucharest. The Ab strains harbored mostly blaOXA-23, blaOXA-24, blaSHV, blaTEM and blaGES, while Pa strains blaIMP, blaVIM, blaNDM, blaVEB, blaGES and blaTEM, with high variations depending on the geographical zone and the sampling point. The WGS analysis revealed the presence of antibiotic resistance genes (ARGs) to other antibiotic classes, such as aminoglycosides, tetracyclines, sulphonamides, fosfomycin, phenicols, trimethoprim-sulfamethoxazole as well as class 1 integrons. The molecular Ab and Pa analyses highlighted: i) the presence of epidemic clones such as ST2 for Ab and ST233 and ST357 for Pa; ii) the relatedness between clinical and hospital wastewater strains and iii) the possible dissemination of clinical Ab strains belonging to ST2 (also proved in the conjugation assays to transfer blaOXA-23 or blaOXA-72 genes), ST79 and ST492 and of clinical Pa strains belonging to ST357, ST640 and ST621 in the wastewaters. Conclusion: The prevalent clones were strongly associated with the presence of class 1 integrons, suggesting that those isolates could be a significant reservoir of ARGs and are able to persist into the environment.
Modified Geriatric Nutritional Risk Index in Patients with Pancreatic Cancer
Authors: Sakamoto Teruhisa , Sunaguchi Teppei , Goto Keisuke , Morimoto Masaki , Murakami Yuki , Miyatani Kozo , Hanaki Takehiko , Shishido Yuji , Kihara Kyoichi , Matsunaga Tomoyuki , Yamamoto Manabu , Tokuyasu Naruo , Fujiwara Yoshiyuki
Published: February 2022

Background: The geriatric nutritional risk index (GNRI) was recently reported not as a nutritional assessment tool but as a useful index for predicting prognosis in various diseases including malignancies. The modified nutritional geriatric risk index (mGNRI), incorporating C-reactive protein instead of albumin, was developed as a novel index and provides a more appropriate prognostic index than the original GNRI. This study aimed to establish the prognostic significance of the mGNRI compared with the GNRI in patients with pancreatic cancer.Methods: This retrospective study included 137 patients who had undergone pancreatectomy for pancreatic cancer. The enrolled patients were grouped as high mGNRI (≥ 85.3) or low mGNRI (< 85.3), and high GNRI (≥ 92) or low GNRI (< 92) for prognostic analysis based on cutoff values.Results: The 5-year overall survival and recurrence-free survival of patients in the high mGNRI group were significantly longer than those in the low mGNRI group. Similarly, the 5-year overall survival and recurrence-free survival of patients in the high GNRI group were significantly longer than those in the low GNRI group. The concordance index of the mGNRI to predict the 5-year overall survival was greater than that of the GNRI. Multivariate analysis revealed that the mGNRI was an independent prognostic factor for patients with pancreatic cancer (P = 0.004).Conclusions: The mGNRI might be a useful prognostic factor for patients with pancreatic cancer and might predict prognostic outcomes more accurately than the GNRI.
One-Year Retention of Gait Speed Improvement in Stroke Survivors After Treatment With a Wearable Home-Use Gait Device
Authors: Darcy Brianne , Rashford Lauren , Tsai Nancey T. , Huizenga David , Reed Kyle B. , Bamberg Stacy J.M.
Published: February 2022

Background: A majority of stroke survivors experience gait impairments, some of which persist into the chronic phase of stroke. Treatment with the iStrideTM gait device has been shown to improve symmetry, gait speed, and functional balance for chronic stroke survivors. In this study, we examine the long-term gait speed changes up to twelve months after treatment with the iStrideTM gait device.Methods: Eighteen individuals (mean 56.7 years, range 44-77 years) at least one-year post-stroke (mean 59.7 months, range 13-308 months) participated in this single group, before-after study with multiple follow-ups. Participants completed 12 treatment sessions (three times per week over four weeks) with the gait device. During each session, participants ambulated over ground on the gait device for a goal of 30 minutes. Gait speed was measured using the Ten-Meter Walk Test at a comfortable pace at baseline and at five follow-up sessions after the treatment period: one week, one month, three months, six months, and twelve months. All study aspects were performed in the home environment of each participant and under the guidance of a licensed physical therapist. Gait speed changes were analyzed using repeated-measures ANOVA from baseline to each follow-up time frame, comparison to the minimal clinically important difference threshold, evaluation of functional ambulation category changes, and subjective questionnaires.Results: Participants retained more than a 0.21 m/s gait speed improvement at all post-treatment time frames, p<0.01. Additionally, 94% of participants improved their gait speed beyond the minimally clinical important difference during one or more post-treatment measurements. 88% of participants subjectively reported a gait speed improvement.Conclusion: The findings of this study indicate that this four-week treatment protocol using the iStrideTM gait device in the home environment may result in meaningful, long-term gait speed improvement for chronic stroke survivors with hemiparetic gait impairments.Trial Registration: NCT03649217. Registered August 28, 2018 – Retrospectively registered for 11 participants who were consented before August 28, 2018; seven participants were consented after August 28, 2018.
Clinical Significance of Notch Receptors In Triple Negative Breast Cancer
Authors: Shah Heer , Mistry Mittal , Patel Nupur , Vora Hemangini
Published: February 2022

Background: The Notch signaling pathway is an evolutionary conserved cell signaling pathway that plays an indispensable role in essential developmental processes. Aberrant activation of Notch pathway is known to initiate wide array of diseases and cancers. The role of Notch receptors and the effect of their expression in Triple Negative Breast Cancer is unknown. Methods and Results: In this study, we evaluated the association between Notch receptors and clinicopathological parameters including disease-free survival and overall survival of one hundred TNBC patients by immunohistochemistry. We observed membrane, cytoplasmic and nuclear localization of Notch receptors in tumor cells of TNBC patients. It was observed that positive expression of nuclear Notch1 receptor (18%) was found be significantly correlated with high BR score (p=0.009) and necrosis (p=0.003) while cytoplasmic expression of Notch2 receptor (26%) was significantly correlated with local or distant metastasis (p=0.04), worse DFS (p=0.05) and poor OS (p=0.02) in TNBC patients. Further, it was determined that cytoplasmic (65%) and cytonuclear (3%) expression of Notch3 was significantly associated with poorly differentiated tumors (p=0.008) and necrosis (p=0.04) respectively. However, cytoplasmic Notch3 and Notch4 expression were negatively correlated with poor prognostic factors. Conclusion: Our data indicated that Notch receptors play a key role in promoting TNBC and mainly, Notch2 receptor may contribute to poor prognosis of the disease. Hence, it is implicated that Notch2 receptor may serve as a potential biomarker and therapeutic target for TNBC.
Chalcone Derivative B8HA as A Novel Histone Deacetylase and Tubulin Dual Inhibitors, Inhibits Triple-Negative Breast Cancer Cells Proliferation
Authors: li kangkang , zheng qiuling , qi shulei , xie yi , chen xuehong
Published: February 2022

Designing and synthesizing dual- and multi-target drugs have raised considerable interests due to their advantages in improving potencies as antitumor agents. In previous studies, our group designed and synthesized a series of novel chalcone based tubulin and histone deacetylase (HDAC) dual-targeting inhibitors. Among them, compound B8HA exhibited promising potency for the treatment of triple-negative breast cancer. In this work, we highlighted its biological evaluations in MDA-MB-231 and 4T1 cells, including anti-proliferative effects, cell cycle arresting effects, anti-metastatic and anti-angiogenesis effects. In vivo results further demonstrated that B8HA significantly inhibited the 4T1 breast tumor growth and destroyed tumor blood vessel as compared to its counterparts. The results indicated that compound B8HA could be a potent inhibitor of both HDAC and tubulin, leading to excellent in vitro and in vivo antiproliferative activities, and is a promising therapeutic agent for triple-negative breast cancer.
Urine Myoglobin is Associated with Different Severities and Depths for Burn Patients
Authors: Li Tao , Zhao Qiaomei , Wang Jitu , Liu Tianci , Zhang Man
Published: February 2022

Backgrounds It is important to make reasonable clinical decision based on precise burn depth for burn specialists. However, the identification of burn depth based upon clinical assessment was not accurate. It still needs more biomarkers to rapidly distinguish different depths for burn specialists. The potential value of urine myoglobin (UM) is still unknown in burn patients. Patients and methods The urine of 30 burn patients and 10 Healthy volunteers (Discover set) were collected from January 2017 to December 2020. Urine proteomics of all samples was identified by Label-free mass spectrometry and functional analysis for differential expression proteins (DEPs) was also analyzed. The Receiver Operating Characteristic curve to evaluate the value of UM from another 67 burn patients (Validation set). Results A total of 8253 peptides and 1465 proteins were identified in four groups. For severe burn patients, 402 DEPs (279 up-regulated and 123 down-regulated) were identified and functional analysis demonstrated that neutrophil-mediated immunity, response to stimulus, and complement and coagulation cascades pathway were the most enrichment function. UM had significant differences in burn patients with different severities and depths (Discover and Validation set; P<0.05). UM as a novel biomarker could rapidly distinguish different depths for burn patients (Discover set, AUC=0.8203, 95%CI: 0.6448~0.9957; Validation set, AUC=0.7393, 95%CI: 0.618~0.8606). Conclusion The urine DEPs were mainly identified in the severe group. UM might as a novel biomarker help burn specialists to rapidly determine different depths for burn patients.
Acetylation of ATP5f1c mediates cardiomyocyte senescence via metabolic dysfunction in radiation induced heart damage
Authors: Zeng Zhimin , Xu Peng , He Yanqing , Yi Yali , Liu Zhicheng , Cai Jing , Huang Long , Liu Anwen
Published: February 2022

Objective: Ionizing radiation (IR) causes heart senescence, which eventually manifests as radiation-induced heart damage (RIHD). Energy metabolism of cardiomyocytes is involved in senescence. This study attempts to explore radiation-induced senescence mechanisms through TMT-labeled proteomics.Methods: Echocardiography, senescence-associated secretory phenotype (SASP), telomere length and P21 expression were conducted to detect IR induced senescence. Total protein acetylation of irradiated heart apex and H9C2 cells was discovered by Western blotting compared with the control. To further investigate lysine acetylation alterations in irradiated heart proteins, proteomics of lysine acetylation was performed. Acetylated level of Atp5f1c was verified by Co-IP. The plasmids of the acetylated-mimicking Atp5f1c mutant (K55Q), deacetylated-mimicking Atp5f1c mutant (K55R) and WT were constructed and used for to transfect H9C2 cells to prove that acetylated Atp5f1c participated in energy metabolism and senescence. Deacetylation inhibitors, plasmid transfection and Co-IP were used to determine the mechanism of upstream regulation of Atp5f1c K55-Ac.Results: LVEF was decreased, SASP was elevated, telomere length was shortened and P21was overexpressed after IR. In addition, the total protein acetylation level significantly increased, and 69 proteins, including 90 sites, showed a lysine acetylation response to irradiation. The majority of the hyperacetylated proteins were related to energy metabolism. The ATP synthase γ subunit was hyperacetylated at the 55th lysine site and led to decreased ATP enzyme activity and synthesis decreased. Atp5f1c K55-Ac induced H9C2 metabolic dysfunction and senescence. Sirt4 and Sitr5, deacetylase inhibitors, mediated Atp5f1c K55-Ac deacetylation. Conclusion: IR induced cardiomyocyte senescence and energy metabolism disorder. Atp5f1c K55-ac, which is modulated by Sirt4 or Sirt5, might be a potential molecular target underlying RIHD.
Modelling can reduce contamination from mosquito population control
Authors: Djerdj Tamara , Hackenberger Domagoj K. , Klanjšček Tin , Hackenberger Branimir K.
Published: February 2022

Environmental contamination due to pest control in general, and mosquito control in particular, is an important issue expected to increase with climate change. We use a validated model for population dynamics of mosquitoes and historical environmental data to explore performance of larvicidal, adulticidal, and combined treatments. Results show that depending on treatment timing, larvicidal treatments can induce very good results, or have negative outcomes that increase overall mosquito population. Combined larvicidal and adulticidal treatments, however, exhibit much lesser dependence on timing, and therefore give the greatest chance of positive outcomes if environmental conditions are not known. Based on the results, we argue for adaptive mosquito management, in which weather data and forecasts are used to drive a model that identifies best intervals for insecticide use. Such an approach can have considerably better results than static, calendar-driven management and, therefore, considerably reduce environmental contamination. Adaptive management could consider larvicidal treatment because it gives good results if the timing is correct. Static management should, however, combine larvicidal and adulticidal treatments for the greatest chance of success.
Multi-omics Reveal the Enabling Factors of Aplastic Anaemia
Authors: Zhao Xiaoyu , Wang Chaomeng , Liu Chenchen , Jiang Nan , Ding Shaoxue , Chen Yingying , Yang Liping , Liu Chunyan , Fu Rong
Published: February 2022

Background: Aplastic anemia is a kind of anemia caused by bone marrow failure due to autoimmune abnormalities. Numerous studies have shown that autoimmunity is regulated by intestinal microflora, and that most intestinal microflora regulates immunity through short chain fatty acids. At the same time, almost all patients with aplastic anemia will have bone marrow adipose tissue, and the process of bone marrow adipose tissue is regulated by medium and long chain fatty acids. Our previous studies have found that the intestinal flora of aplastic anemia patients is different from that of normal people. Therefore, this study aims to conduct a comprehensive detection of the intestinal flora and fatty acid metabolism in patients with aplastic anemia and to study their correlation.Methods: Fatty acid compositions in the peripheral plasma and bone marrow supernatants of 12 newly diagnosed aplastic anaemia patients and 10 normal controls were comprehensively analysed by CG-MS. Gene sequencing of faecal samples from both groups was also performed with macrogene sequencing technology.Results: Based on the metagenomic sequencing technology, we analyzed the difference of intestinal flora between group AA and group NC. We found that the main difference between the two groups existed in the bacterial community, and the abundance of most microbial species showed a downward trend. Based on the CG-MS lipid detection technique, we found that there were differences in lipid metabolism between the AA group and the NC group, whether short chain fatty acids or medium and long chain fatty acids. 8. The most attractive findings are interrelationships between the Citrobacter spp 、stearic acid (c18:0), isobutyric acid, and lysine degradation and betaine biosynthesis pathway and the interrelationship between catenibacterium_mitsuokai species at Catenibacterium, cis-7,10,13,16-docosatetraenoic acid (c22:4), ubiquinone and other terpenoid quinones pathway.We also found the intercorrelation between the abundance of Enhydrobacter genus and Enhydrobacter_aerosaccus species, cis-13,16-docosadienoic acid in peripheral plasma, cis-7,10,13,16-docosatetraenoic acid in bone marrow supernatant, tyrosine and tryptophan biosynthesis pathways.Conclusions: Our results show that Citrobacter infection may be a driving factor for aplastic anaemia, identifying a potential role for stearic acid in the immunopathogenesis of aplastic anaemia. Our study also demonstrates the potential role of 22-carbon long-chain polyunsaturated fatty acids, which may not only be involved in the metabolism of fibroblasts in bone marrow but also influence the formation of the bone marrow microenvironment, in aplastic anaemia.
Short measures of youth psychopathology: Psychometric properties of the Brief Problem Monitor (BPM) and Behavior and Feelings Survey (BFS) in a Norwegian clinical sample
Authors: Rognstad Kristian , Helland Siri Saugstad , Neumer Simon-Peter , Baardstu Silje , Kjøbli John
Published: February 2022

Background: Tracking clinical outcomes during therapy can be useful for improving both clinical practice and research. For repeated data collection, short, reliable, and valid measures of central aspects of psychopathology are necessary. The current paper investigates the psychometric properties of two short surveys for measuring central dimensions of psychopathology in youth. Methods: We investigated factor structure and validity of the Norwegian translations of the Behavior and Feelings Survey (BFS) and the Brief Problem Monitor (BPM). The BFS has previously shown a two-factor structure and indications of validity as a measure of internalizing and externalizing problems in youth. Likewise, the BPM has support for a three-factor structure of internalizing, externalizing and attention problems. In our sample of 503 youths and caregivers in a Norwegian outpatient clinic, we conducted confirmatory factor analyses to test the assumed measurement models and further considered concurrent validity of the measures. Results: The results suggest that the assumed measurement models for both questionnaires only partly fit our data but that subscales of the BFS and BPM still indicate convergent validity. Conclusions: Alternative measurement models, and the usefulness and limitations of these short form questionnaires for internalizing and externalizing problems, are discussed.
ct-DNA is useful to diagnose mutations at codon 641 of exon 16 of EZH2, which is a biomarker for relapse in patients with Diffuse Large B-cell Lymphoma treated with the R-CHOP scheme.
Authors: Díaz-Chavez Jose , Gutiérrez-Hernández Olga , Taja-Chayeb Lucia , Gutiérrez-Chavarría Sindy , Aviles-Salas Alejandro , Candelaria Myrna
Published: February 2022

Background: The epigenetic regulator EZH2 is a subunit of the polycomb repressive complex 2 (PRC2), methylates H3K27, resulting in transcriptional silencing. The mutation at Y646 amino acid in the EZH2 gene is mutated in up to 40 % of B-cell lymphomas. We compared the presence of exon 16 EZH2 mutations in tumor samples and ctDNA in a prospective trial. The mutations were determined by sanger sequencing, and by ddPCR. We also evaluated the impact of these mutations on response, relapse, and survival. Results: One hundred and thirty-eight cases were included. Ninety-eight were germinal center, and twenty had EZH2 mutations. Mean follow-up (IQR 25-75) was 23 (7- 42) months. The tumor samples were considered the standard of reference. Considering the results of the mutation in ctDNA by Sanger sequencing, the sensibility (Se) and specificity (Sp) were 52 % and 99 %, respectively. After adding the droplet digital PCR (ddPCR) analysis, the Se and Sp increased to 95 and 100 %, respectively. After bivariate analysis, only the presence of double-hit lymphoma (p=0.04), or EZH2 mutations were associated with relapse. The median PFS (95 % Interval confidence) was 27.7 (95 % IC: 14-40) vs 44.1 (95 % IC: 40-47.6) months for the mutated vs wt patients. Conclusions: The ctDNA is usefull to analyse EZH2 mutations, which have an impact in PFS.
Pretreatment neutrophil to lymphocyte ratio as prognostic factor in metastatic breast cancer treated with cyclin dependent kinase 4/6 inhibitors
Authors: Rottier Pauline , SILVA Angélique DA , JOHNSON Alison , LEVY Christelle , ALLOUACHE Djelila , HRAB Ioana , SEGURA Carine , MOREL Adeline , VILLEMIN Maud , BOSCHER Clémence , BERTHO Marion , BOISMOREAU Louis , CHERIFI François , LEQUESNE Justine , EMILE George
Published: February 2022

Background: Cyclin dependent kinase inhibitors (CdK4/6i) changed the course of hormone receptor positive (HR+) HER2negative (HER2-) metastatic breast cancer (mBC). To date, no factors have been shown to predict response to CdK4/6i. Neutrophil-to-lymphocyte ratio (NLR), an indicator of the host systemic inflammatory response, is an independent prognostic factor for survival in cancers. We conducted this study to evaluate the addition of NLR for survival assessment in mBC patients treated with first line CdK4/6i. Methods: All mBC patients treated with first line CdK4/6i between November 2015 and December 2019 were retrospectively included. We analyzed 12-month progression free survival (PFS), overall survival (OS) and response rate according to NLR in univariable and multivariable analysis.Results: A total of 126 patients treated with palbociclib (n=101), ribociclib (n=18) or abemaciclib (n=7) were included, with a median follow-up of 16 months [range: 2.9-37]. Median age was 65 years [29-86], 88% patients had good performance status (0-1). Most patients were included at the metastatic relapse stage (71%) and 20% had visceral metastases without bone lesions. High NLR (≥ 2.53) was significantly associated with worse PFS (Hazard Ratio (HR)=0.52, CI95% =[0.29-0.94]). Fourteen patients died (11.1%). Complete responses were more frequent in the low NLR group (<2.53) (14.5% vs. 3.1%, p=0.029). Conclusion: High NLR is associated with worse PFS in HR+ HER2- mBC patients treated with first line CdK4/6i. NLR is a reliable and inexpensive prognostic marker, easily accessible in routine clinical practice, which could optimize the therapeutic strategy. These results need to be confirmed in larger prospective studies.
Impact of the COVID19-related economic crisis and mitigation effects of social protection on HIV/AIDS and Tuberculosis: an integrated economic, mathematical and epidemiological modelling study
Authors: Rubio Felipe , Amad Alan , Moya Erick , de Oliveira Robson , Aransiola Temidayo , Anderle Rodrigo , Sironi Alberto , Ordoñez José , Sanchez Mauro , de Oliveira Juliane , de Souza Luis Eugenio , Dourado Inês , Macinko James , Rasella Davide
Published: February 2022

The COVID-19 pandemic will have impactful long-term effects on the global rise of poverty and social inequalities, potentially compromising the achievement of SDGs for poverty-related diseases. We aimed to evaluate the impact of poverty increases, and the mitigation effects of social protection policies, on HIV/AIDS and Tuberculosis (TB) in Brazil, one of the largest and most unequal LMICs. We integrated economic, mathematical, and epidemiological models to forecast the trends of HIV/AIDS and TB according to different future scenarios, showing that the implementation of social protection policies could mitigate long-lasting rises in poverty, avoiding -in the most pessimistic economic projections- an increase of 41% in the incidence and 50% in the mortality from HIV/AIDS, and of 32% in the incidence and 53% in the mortality from TB. Overall, more than 250 thousand cases and 43 thousand deaths from HIV/AIDS and TB could be averted up to 2030.
Evaluated the Role of N6-Methyladenosine-associated lncRNAs in Prognosis and Immune Microenvironment of Colorectal Cancer
Authors: Yuan Congfei , Liu Caidong , Zhao Shuli , Zhang Xishan , Jia Haifeng , Chen Baiyu , Zhang Maojin , Zheng Yuan , Wei Xiaowei , Zhou Jin , Bo Yanzhi
Published: February 2022

Background: The role of N6-methyladenosine medicated long non-coding RNAs (lncRNAs) is elusive in colorectal cancer (CRC). Materials and Methods: We identified m6A-associated lncRNAs by using the data gathered from The Cancer Genome Atlas (TCGA) and stratified CRC patients into different subgroups. Cox-regression analysis were performed to construct a m6A-associated lncRNA signature. And the role of this signature in prognosis and immune microenvironment was dissected subsequently. Finally, a gene set enrichment analysis (GSEA) were executed to predict the possible bio-mechanisms on the basis of the signature.Results: Three m6A-associated clusters were constructed from 866 differentially expressed lncRNAs. Cluster 2 had poor prognosis and low immune cell infiltration. A m6A-associated lncRNA signature consisting of 14 lncRNAs was constructed, and recognized as an independent prognostic indicator in CRC by using survival analysis and receiver operating characteristic (ROC) curves. The clinical features and immune cell infiltration status were significantly different in the patients stratified by risk score. Furthermore, GSEA showed that P53 pathway and Natural killer cell mediated cytotoxicity were more enriched in the low risk group.Conclusion: Our data revealed that m6A-associated lncRNAs could be potential prognostic and immunogenicity indicators in CRC.
Imagined Head Rotations Facilitate Spatial Memory
Authors: Wyssen Gerda , Mast Fred W. , Ertl Matthias
Published: February 2022

Neuroimaging studies have shown great similarities between the cortical networks involved in motor execution and motor imagery. However, none of those studies report data on head or full body motions and only few provide evidence of behavioral consequences of this similarity. Here, we report results from a novel kinesthetic spatial memory task, in which participants encoded a target position by an active, passive or imagined head rotation. During the experiment, participants were seated on a motion platform with a VR headset, which allowed passive motion and head tracking. To compare all three encoding conditions, precision and head velocity in the executions of head movements were analyzed with Bayesian hierarchical generalized linear regression models. We found comparable performance in precision in the active and imagery conditions whereas performance in the passive condition was significantly reduced. Head motion profiles were similar after active and imagined encoding. The results suggest that imagined head rotations provide useful sensorimotor information despite the absence of sensory and motor information during encoding. This can be explained by corollary discharge which is necessary for appropriate motor behavior and is likely also generated when the motor behavior is imagined but not executed.
COVID-19 in Tunisia (North Africa): Seroprevalence of SARS-CoV-2 in the general population of the capital city Tunis
Authors: Cherif Ines , Kharroubi Ghassen , Chaabane Sana , Yazidi Rihab , Dellagi Mongi , Snoussi Mohamed Ali , Salem Sadok , Marzouki Soumaya , Rebai Wafa Kammoun , Rourou Samia , Dellagi Koussay , Barbouche Mohamed Ridha , Benabdessalem Chaouki , Ahmed Melika Ben , Bettaieb Jihene
Published: February 2022

Background:Monitoring the coronavirus disease-19 (COVID-19) pandemic is primarily based on Reverse transcription polymerase chain reaction (RT PCR) detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As this test is mainly applied on persons with symptomatic disease, it may overlook individuals with pauci- or a-symptomatic infection. Seroprevalence studies are thus essential to get an accurate estimate of the actual SARS-CoV-2 diffusion within the populations. We report on the findings of the first serosurvey conducted in the capital city of Tunisia prior to the implementation of mass vaccination and analyzed factors associated with seropositivity. Methods:A cross sectional survey was conducted among households living in two areas of the governorate of Tunis, the capital city of the country. The survey was realized between March and April 2021, spanning the end of the second wave and the beginning of the third wave of COVID-19 and prior to the implementation of mass vaccination in Tunisia. SARS-CoV-2 specific immunoglobulin G (IgG) antibodies to the spike (S-RBD) or the nucleocapsid (N) proteins were detected using an in-house ELISA test. Results were adjusted for test performance. Multivariate logistic regression analysis was performed to determine factors independently associated with SARS-COV-2 seropositivity.Results:The survey included 1676 individuals from 431 households. The mean age and sex ratio were 43.3±20.9 years and 0.6 respectively. The weighted and test-performance adjusted prevalence of IgG antibodies to the N and the S-RBD proteins were 26.6% [22.9-30.8] and 25.1% [22.2-28.4] respectively. The weighted seroprevalence of anti-N and/or anti-S-RBD IgG antibodies was equal to 38.0% [34.6-41.5]. In multivariate analysis, age under 10, no tobacco use, previous diagnosis of COVID-19, a history of COVID-19 related symptoms and contact with a COVID-19 case within the household, were independently associated with higher SARS-CoV-2 seroprevalence. Conclusions:After the end of the second epidemic wave, more than one third of people living in Tunis got antibodies to SARS-CoV-2. Further studies are needed to monitor changes in these figures as Tunisian population is confronted to the subsequent epidemic waves and to guide the vaccine strategy.
Differential Microbial Signature Associated With Benign Prostatic Hyperplasia and Prostate Cancer
Authors: Sarkar Purandar , Malik Samaresh , Banerjee Anwesha , Datta Chhanda , Pal Dilip Kumar , Ghosh Amlan , Saha Abhik
Published: February 2022

Apart from other risk factors, chronic inflammation is also associated with the onset of Prostate Cancer (PCa), wherein pathogen infection and tissue microbiome dysbiosis are known to play a major role for both inflammatory response and cancer development. However, except for a few studies, the link between microbes and PCa remained poorly understood. To explore the potential microbiome signature associated with PCa in Indian patients, we investigated differential compositions of commensal bacteria among patients with benign prostatic hyperplasia (BPH) and PCa using 16S rRNA amplicon sequencing followed by qPCR analyses using two distinct primer sets. Using two independent cohorts, we show that Prevotella copri, Cupriavidus campinensis and Propionibacterium acnes represent three most abundant bacteria in diseased prostate lesions. LEfSe analyses identified that while Cupriavidus taiwanensis and Methylobacterium organophilum are distinctly elevated in PCa samples, Kocuria palustris and Cellvibrio mixtus are significantly enriched in BPH samples. Furthermore, we identify that a number of human tumor viruses including Epstein-Barr virus (EBV), hepatitis B virus (HBV) along with two high risk human papillomaviruses - HPV-16 and HPV-18 are significantly associated with the PCa development and strongly correlated with PCa bacterial signature. The study may thus offer to develop a framework for exploiting this microbial signature for early diagnosis and prognosis of PCa development.
A Proposal of Two-step Autoregressive Model
Authors: Nguyen Loc
Published: February 2022

Autoregressive (AR) model and conditional autoregressive (CAR) model are specific regressive models in which independent variables and dependent variable imply the same object. They are powerful statistical tools to predict values based on correlation of time domain and space domain, which are useful in epidemiology analysis. In this research, I combine them by the simple way in which AR and CAR is estimated in two separate steps so as to cover time domain and space domain in spatial-temporal data analysis. Moreover, I integrate logistic model into CAR model, which aims to improve competence of autoregressive models.
Towards a Full Verification of How Light Spreads at Large Distances
Authors: Costescu Corneliu I. , Costescu Ruxandra M. , Costescu Doina M.
Published: February 2022

We recognize that the spreading of light at large distances (the whole space) is the only property which can decide by yes or no if light really behaves physically like waves, while the fit of the waves for describing the diffraction fringes is insufficient for this purpose. Indeed, the fringe space is too limited and hence, brings the possibility of misinterpretation. Hence, the experiment for the verification if light is spreading like waves at large distances is necessary in principle, and is crucial. However, very surprisingly and tragically, this experiment was totally missing in history. This experiment uses the simplest diffraction case, in which a beam of light falls perpendicularly with its axis on the line and the plane of a straight edge. Practically, this experiment verifies if there is a dependence of the diffracted light at large distances in the geometrical shadow on the changes in beam thickness traversal to a single straight edge, while the distribution of light along the straight edge remains the same. If this dependence exists, as the wave theory for light fundamentally predicts, then the wave approach to light is physically true. If there is no dependence then light cannot behave physically like waves. This experiment can clearly be developed and performed without any calculation from the wave approach, just by a careful measurement practice. However, for a broader view, we describe in detail wave results for spreading of light at large distance, which illustrate the experiment – what are the spatial points where the measurement must be done to see if the above dependence exists, and which is the big picture for the wave approach. We attempted this experiment for many years, but could not finish it because of the lack of resources to measure at 100 – 500 m. The present article will empower big labs to perform this experiment. However, we show alternatively that the answer to how light spreads also comes from comparing the well known data for the diffraction on macroscopic holes with relatively recent data for the diffraction on nanoscopic holes. This comparison clearly shows that light does not spread physically like waves, which makes necessary a new, non-wave but periodic structure for light. Such an alternative answer regarding the spreading of light also makes absolutely necessary to perform the above missing experiment, as a direct way that convinces anybody how light is spreading.
Literature Review on Social and Organizational Acceptance of Digital Transformation
Authors: Skrynnyk Olena
Published: February 2022

Enterprise digitization continues to drive the transformation of business processes and the content of human work. Despite the diachronic nature of these changes, social and organizational acceptance is not clearly determined. Therefore, the importance of researching the social attitudes in organizations towards digitalization arises. The relevance of the decision of this scientific problem consists in the increased digitalization and automation of all areas of the company. The main purpose of the research is to investigate the dominant research perspectives on the acceptance of digital changes in organizations. In order to provide the comprehensive review, the methods of bibliometric and network analysis were applied. For this purpose, publications on corresponding terms were searched, filtered, structured and analyzed with appropriate tools. Methodological tools of the research methods were supported by digital tool VosViewer. This article provides the results of the investigation of scientific publications on the topic of social and organizational acceptance of digital transformation in the economy and in the enterprises. The findings of the analysis, such as current subject fields, the contributing organizations, and related research focuses, point to a profound basis for further research, as well as the future potential of this issue. The results of the research can be useful for obtaining the overview and generalization of trends. The knowledge gained can be applied by scientists and practitioners.
INVESTIGATION ON SOME CONVENTIONAL HULLS FORMS OF THE PREDICTIVE ACCURACY OF A PARAMETRIC SOFTWARE FOR PRELIMINARY PREDICTIONS OF RESISTANCE AND POWER
Authors:   University of Vlora “Ismail Qemali” – Albania, Xhaferaj Blenard
Published: February 2022

Preliminary prediction of resistance and power is a fundamental aspect of the ship design process since they directly influence the developments of the design process, fuel consumption and costs, and environmental impact from the early design stage. Parametric predictions of resistance and power, based mainly on statistical regression models that are also ideal for computer programming, are often performed during initial design stages, providing rapid predictions and optimisations for minimum resistance. The paper aims to present the results of the comparative analysis on some conventional hulls of the predictive accuracy of a computer program developed by the author for parametric predictions of resistance and power of ships. The program (entitled Ship Power V 1.0) is developed in the Visual Basic 6.0 environment based on two well-known regression models Holtrop and Van Oortmerssen. The program can perform detailed predictions of resistance and power, resistance coefficients, propeller thrust, hull efficiency, wake, and trust fractions, with no restriction on the number of velocities. In this study, only the analysis of the accuracy of resistance and power prediction is considered. Results of the comparative analysis of the computational procedures of Ship Power V 1.0 versus experimental data, and against results of another well-known commercial software, performed on three models of the Ridgely-Nevitt trawler series and KCS hull have shown a good level of accuracy and reliability as other well-known commercial software.
La investigación en la educación universitaria en pandemia
Authors: Alvites Huamaní Cleofé Genoveva
Published: February 2022

La pandemia que azota a nivel mundial y la que ha incidido en que la educación diera un giro abismal en todos los niveles, sobre todo a nivel universitario, al tener que reestructurar sus procesos de enseñanza y sus practicas investigativas ha hecho que se de una mira distinta a esta, en las que con mayor énfasis se han involucrado a los estudiantes, como capital humano de las universidades junto con los docentes (Dilas-Jiménez et al., 2020), quienes están haciendo que se reconozca y se valore el lado académico e investigativo con todo el aporte que están realizando para esta finalidad, tal como lo menciona Valencia-Rodríguez, (2013) al referirse que la gestión del conocimiento es la valoración del Know-how orientada a compartir el conocimiento, y sumado a ello es un activo de propiedad privada, que tiene un valor y con ello una capacidad de generar ingresos a los que la poseen,  tanto material como académico e investigativo, (INS, 2010).
Hacia la epistemología de la tecnología educativa
Authors: Sánchez Ambriz Mercedes Leticia
Published: February 2022

Iniciamos el año 2022, nuevamente con el aumento de contagios y nuevas variaciones de COVID, lo que nos lleva a seguir por el camino de los ambientes educativos híbridos o virtuales, que iniciamos hace casi dos años de manera emergente y a decir por Hodges et al., (2020), no fue bien diseñada la estrategia ni implementada, y se le consideró como una instrucción alternativa y temporal. A lo largo de este período de pandemia y postpandemia, han surgido diversos estudios sobre el impacto en la educación, que trajo consigo este cambio abrupto de la educación presencial a la virtualidad, así como experiencias prácticas que demuestran el esfuerzo para dar continuidad a las clases, al respecto Zimmerman (2020) señala, que lo sucedido fue un gran experimento de aprendizaje en línea y una oportunidad de probar nuevas formas de enseñanza.