bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Autophagy in Progression of Liver Fibrosis in Chronic Hepatitis B Patients on Antiviral Treatment
Authors: Sadidoost Atefeh , Lankarani Kamran B.
Published: January 2022

Introduction: Despite antiviral treatment, there are patients with chronic hepatitis B (CHB) who progress to cirrhosis. Enhancement of autophagy has been implicated in the proliferation of hepatitis B in hepatocytes. This study was designed to evaluate the role of autophagy in the progression of liver fibrosis in patients on antiviral therapies and negative viral load. Methods: Patients on anti-hepatitis B nucleotide treatments for at least two years and had not been cirrhotic at baseline but who later developed cirrhosis were identified. For the control group, patients who were on the nucleotide regimens and did not have cirrhosis at baseline or follow-up were randomly selected from our registry. Serum Beclin-1 and LC3 measured by enzyme-linked immunosorbent tests were compared between two groups. Results: Beclin-1 level was higher in those with cirrhosis, but no statistical difference was seen for the level of LC3. Conclusion: Autophagy may have a role in progression to cirrhosis in patients with CHB. Future prospective studies are required to find the effect of blockage of autophagy on liver disease progression in this group.
Conformational Changes in Light-Harvesting Complex II Trimer Depending on Its Binding Location
Authors: Kim Eunchul , Kubota-Kawai Hisako , Kawai Fumihiro , Minagawa Jun
Published: January 2022

In green plants, the light-harvesting complex II (LHCII) trimer functions as a major antenna complex to the photosystem II (PSII) complex and a quencher to protect it from photooxidative damage. Theoretical studies on the structure of the LHCII trimer have demonstrated that excitation energy transfer between chlorophylls (Chls) can be modulated by its exquisite conformational fluctuation. However, the conformational changes in the LHCII trimer depending on its binding location have not yet been investigated, even though protein-protein interactions tend to lead conformational changes. In this study, we investigated the conformational changes in LHCII by analyzing an identical LHCII trimer comprising three different photosystem supercomplexes—PSII–LHCII supercomplexes (C2S2 type and C2S2M2L2 type) and PSI–LHCI–LHCII supercomplex—from the green alga Chlamydomonas reinhardtii. Consequently, the distinct differences in Chl configurations as well as polypeptide conformations of the LHCII trimers were detected based on where LHCII binds. Our analysis of the configurational factors between Chls suggests that these configurational changes lead to higher light-harvesting compatibilities in the PSII–LHCII supercomplex (C2S2M2L2 type) and PSI–LHCI–LHCII supercomplex. This study suggests a fine-tuned mechanism of energy transfer dynamics in LHCII trimers by regulation of protein-protein interactions.
circAGFG1 Facilitates the Progression of Non-Triple-Negative Breast Cancer Through miR-143-5p/USP14 Axis
Authors: Yang Rui , Chen Hang , Chen Junxia
Published: January 2022

Circular RNAs (circRNAs) emerged as a new class of regulators in various human diseases, including breast cancer (BC). Our previous study identified that circAGFG1 could promote triple-negative breast cancer (TNBC) progression. However, the clinical values and functions of circAGFG1 in non-TNBC remain elusive. Here, we applied qRT-PCR in 30 pairs of non-TNBC tissues and para-cancerous tissues and in situ hybridization (ISH) in 346 paraffin-embedded non-TNBC tissues to evaluate the expression pattern and clinical significance of circAGFG1 in non-TNBC. Gain- and loss-of-function studies were carried out to determine the biological function of circAGFG1 in non-TNBC in vitro and in vivo. Mechanistically, RNA pull-down, RNA immunoprecipitation, dual luciferase reporter, fluorescent in situ hybridization assays were employed to validate the interaction between circAGFG1 and miR-143-5p as well as miR-143-5p and USP14. We found that circAGFG1 was markedly increased in non-TNBC tissues as well. Moreover, patient suffering from non-TNBC with a higher expression level of circAGFG1 presents a worse clinical outcome. Multivariate analysis uncovered that high level of circAGFG1 might serve as a standalone risk factor for non-TNBC patients. Functional studies substantiated that enforced expression of circAGFG1 increased the malignance of non-TNBC cells, whereas silencing of circAGFG1 produced the opposite. Mechanistic investigations proved that circAGFG1 sponged miR-143-5p to regulate the level of oncogene USP14, leading to the progression of non-TNBC. Taken together, our data revealed that circAGFG1 could also accelerate the progression of non-TNBC via miR-143-5p/USP14 axis and might provide an alternative target for the diagnosis and treatment of non-TNBC.
Using Water Quality Parameters To Predict Trihalomethane Ion Based On An Artificial Neural Network Model
Authors: Baboli Zeynab , Birgani Yaser Tahmasebi , Maleki Heidar , Angali Kambiz Ahmadi , Babaei Ali Akbar
Published: January 2022

Background: Trihalomethanes (THMs) are the first disinfectant by-products in the drinking water distribution network and classified as potential carcinogens. The presence of THMs in chlorinated water depends on the pH, water temperature, contact time between water and chlorine, type and dose of disinfection, bromide ion concentration, and type and concentration of natural organic materials (NOMs). In the present study, the formation of THMs was evaluated by water quality parameters and modeled by an artificial neural network (ANN) approach through five water distribution networks (WDNs) and Karoun river in Khuzestan province.Results: This study was conducted from October 2014 to September 2015. Results showed that THMs concentration ranged in five WDNs, including Shoushtar, Ahvaz 2, Ahvaz 3, Mahshahr, Khorramshahr, and Karoun river through N.D.-9.39 µg/L, 7.12-28.60, 38.16- 67.00, 17.15-90.46, 15.14-29.99 and N.D.-156, respectively.Conclusions: The concentration of THMs exceeded Iran and EPA standards in many cases in Mahshahr and Khorramshahr WDNs. Evaluation of R2, MSE, and RMSE showed the appropriate correlation between measured and modeled THMs, indicating good ANN potential for estimating THM formation in water sources.
Comparative Advantage of Tractor Utilization in Southeastern Oromia, Ethiopia.
Authors: Dawid Ibsa , Gebiso Tamrat , Boka Ephrem
Published: January 2022

This study analyzes the effect of tractorization on cropping intensity, crop yields, and adoption of major agricultural inputs, on human labor employment, determine the utilization and per-unit cost of tractor power according to the farm size, compare the different costs and profits for Draught animal power and Tractor operated farms according to the farm size. Data was collected from the stratified sample of 345 farmers from three purposively selected districts, Hexosa, Asasa, and Sinana, where the agricultural mechanization operations are becoming increasingly practiced. The Tobit model showed that wheat farmland size, tractor use, and labor for the adoption of the chemical fertilizers, land allocated for Wheatland and tractor use for the adoption of improved seed, and Age and total cultivated land for the adoption of agrochemicals affected positively and significantly. Tractorization has a positive and statistically significant effect on the adoption of chemical fertilizers and improved seed rate, except for the adoption of agrochemical applications. The average wheat production in all farms of tractor-operated farms was higher (34.67 qt ha-1) than other operated farms. There has been a reduction of total human labor employment to the extent of about 76 % on the tractor farms as compared to both the draught animal and mixed operated farms. The net income was higher on tractor-operated farms than both mixed and draught animal-operated farms. Therefore, the tractor-operated farms were economically more efficient than the draught animal power and mixed-operated farms especially in the case of farms of small and large farm sizes.
Independent Evaluation of Peg Travel and Reach Movement Time Using A Newly Developed Nine-Hole Pegboard
Authors: Tochio Kensuke , Kimura Daisuke , Kinoshita Hiroshi , Ryuhei Okuno , Fukui Takeshi
Published: January 2022

Background: Hand dexterity in patients is often assessed with the nine-hole peg test (NHPT). In this test, the time to complete the test is the only outcome variable. However, the evaluation time alone does not provide detailed information about test execution. By introducing a newly developed PC-connected nine-hole pegboard, we divided the peg test exercise into four parts, calculated the difficulty level, and clarified the characteristics of the NHPT. In addition, we provided baseline data of detailed NHPT performance in healthy young women.Methods: A pegboard with a container equipped with an accelerometer and nine holes with small photo reflectors at the bottom was developed for the present study. Pegboard features and peg dimensions were the same as those of a commercially available NHPT. Dominant and nondominant hands and container-to-peg hole distances (index of difficulty; ID) were analyzed as dependent variables for the four phases of the task in 16 healthy young women.Results: Handedness was examined using the Edinburgh Handedness Inventory, and all participants were strongly right-handed. It was possible to accurately measure the total performance time, peg movement time and reaching time for each task. The total performance time was shorter for the dominant (right) hand (15595.4 ± 1039.5 msec) than for the nondominant (left) hand (17494.4 ± 1478.7 msec) (P<0.001). Peg movement time showed an increase in performance time 900 ± 67.7 to 979.3 ± 112.2 as the task difficulty increased from an ID of 7.6 bits to 8.4 bits (P=0.035).Conclusions: The newly developed pegboard makes it possible to accurately and separately measure movement times with individual pegs and the time to reach pegs, without the need for stopwatch assessments. A detailed evaluation will clarify problems in upper limb function, suggest a training protocol, and identify problems needing intervention to develop future approaches to the rehabilitation of hand dexterity.Trial registrationNot applicable
Diversity-aware Unmanned Vehicle Team Arrangement in Mobile Crowdsourcing
Authors: Li Yu , Feng Haonan , Peng Zhankui , Zhou Li , Wan Jian
Published: January 2022

With the continuous development of mobile edge computing and the improvement of unmanned vehicle technology, unmanned vehicle could handle ever-increasing demands. As a significant application of unmanned vehicle, spatial crowdsourcing will provide an important application scenario, which is about to organize a lot of unmanned vehicle to conduct the spatial tasks by physically moving to its locations, called task assignment. Previous works usually focus on assigning a spatial task to one single vehicle or a group of vehicles. Few of them consider that vehicle team diversity is essential to collaborative work. Collaborative work is benefits from organizing teams with various backgrounds vehicles. In this paper, we consider a spatial crowdsourcing scenario. Each vehicle has a set of skills and a property. The property denotes vehicle’s special attribute, (e.g., size, speed or weight). We introduce a concept of entropy to measure vehicle team diversity. Each spatial task (e.g., delivering the take-out, and carrying freight) is under the time and budget constraint, and required a set of skills. We need to assure that the assigned vehicle team is diverse. To address this issue, we first propose a practical problem, called team diversity spatial crowdsourcing (TD-SC) problem which finds an optimal team-and-task assignment strategy. Moreover, We design a framework which includes a greedy with diversity (GD) algorithm and a divide-and-conquer (D&C) algorithm to get team-and-task assignments. Finally, we demonstrate efficiency and effectiveness of the proposed methods through extensive experiments.
Long Memory Recursive Prediction Error Method for Identification of Continuous-time Fractional Models
Authors: victor stephane , Duhé Jean-François , Melchior Pierre , Abdelmoumen Youssef , Roubertie François
Published: January 2022

This paper deals with recursive continuoustime system identification using fractional differentiation models. Long-memory recursive prediction error method is proposed for recursive estimation of all parameters of fractional order models. When differentiation orders are assumed known, least-squares and prediction error methods, being direct extensions of the classic methods used for integer order models, are compared to our new method, thus proving the efficiency of our algorithms. Then, when the differentiation orders are unknown, two-stage algorithms are necessary for both parameter and differentiation order estimation. The performances of the new proposed recursive algorithm is studied through Monte-Carlo simulations. Finally, the proposed algorithm is validated on a biological example where heat transfer in lungs is modeled by using thermal two-port network formalism with fractional models.
Multistability Route in a PWL Multi-scroll System through Fractional-Order Derivatives
Authors: Monroy José Luis Echenausía , Wang Ning , Huerta-Cuellar G.
Published: January 2022

Recently, it was discovered that the use of fractional derivatives induces the occurrence of multistable states in PWL systems with multiple scrolls. In this paper, we show the path of the system from monostable to multistable behavior by reducing the integration order. Using bifurcation diagrams, which describe the evolution of the attractor under the modification of the bifurcation parameter, and basins of attraction, we show that the system has a path to multistability, revealing the mechanism for the emergence of the behavior. The resulting dynamics shows the coexistence of up to n + 2 attractors, where n is the number of scrolls generated by the integer-order system. Moreover, the existence and uniqueness of the dynamics is proved by Poincar´e sections showing that the behaviors exist and coexist and are not a section of the same solution.
Weight Spectrum and Executive Function in Adolescents: The Moderating Role of Depression
Authors: Lin Qingmin , Jiang Yanrui , Sun Xiaoning , Zhang Yunting , Shan Wenjie , Zhao Jin , Wang Xuelai , Zhu Qi , Sun Wanqi , Lu Hui , Jiang Fan
Published: January 2022

Background: Overweight/obesity may impair executive function (EF). However, adolescent EF impairments across the weight spectrum were not well studied, with the moderating effect of negative emotions in the weight-EF association being limitedly investigated. We aimed to determine whether overall and abdominal weight spectrum associated with EF impairments and to identity whether negative emotions moderate the weight-EF link in adolescents.
Methods: We applied a subsample of the SCHEDULE-A project. Adolescents (11-18 years) were recruited using a multi-stage cluster random sampling approach. Overall and abdominal weight were measured by body mass index z-score and waist-to-height ratio, respectively. We used the Behavior Rating Inventory of Executive Function (BRIEF) to evaluate adolescent EF in nature setting, and utilized the Depression Anxiety and Stress Scales (DASS-21) to assess three types of negative emotional states (i.e., depression, anxiety, and stress).
Results: Of the 1 935 adolescents, 963 (49.8%) were male. We observed that abdominal, not overall, overweight was associated with the Global Executive Composite (GEC) impairment (OR = 1.59, 95% CI: 1.07-2.35), particularly for inhibit, emotion control, shift, working memory, and monitor domains. Furthermore, depression moderated the abdominal overweight-GEC association (P = 0.032 for interaction term), especially for emotional control, working memory, and initiate dimensions. Moreover, we also found abdominal thinness was associated with the Metacognition Index problem (OR = 1.33, 95% CI: 1.04-1.72), particularly for plan and monitor areas.
Conclusions: Both abdominal overweight and thinness were associated with adolescent EF, and depression would be a modifiable target to improve EF in adolescents with abdominal overweight.
Synovial Tissue Lymphoid Aggregates Are Associated With Response To Rituximab Therapy In Rheumatoid Arthritis Patients
Authors: Turk Matthew A , Low Candice , Orr Carl , Conway Richard , Murray Kieran , Young Francis , Molloy Eamonn , Mongey Anne Barbara , Fearon Ursula , Veale Douglas J.
Published: January 2022

Background: To evaluate the clinical and laboratory factors associated with long-term responses to rituximab therapy in patients with RA. Methods: One hundred fourteen RA patients received intravenous Rituximab between 2003-2016. Prior to treatment, arthroscopy and synovial biopsy was performed on a subgroup of this cohort who had active knee arthritis. Demographic, clinical, and outcome data were collected prospectively and immunohistology was performed on synovial tissue biopsies.Results: In the overall cohort, 89% of patients were seropositive for either RF (rheumatoid factor) or ACPA (anti-citrullinated protein antibodies). At baseline, median disease duration was 13.5 years. Seventy-four percent of patients had received a csDMARD and two thirds had received a bDMARD before rituximab. Rituximab monotherapy was used in 34 patients, while 80 patients received rituximab-csDMARD combination therapy. Twenty-six of the 68 patients in remission (38%) received rituximab monotherapy and 42/68 (62%) received combination therapy with a csDMARD. Twenty-four of 39 (62%) biologic naïve patients achieved remission on treatment with rituximab. Forty-four patients underwent an arthroscopy and synovial biopsy prior to treatment. Synovial tissue lymphoid aggregates (LA) were observed in 21 subjects, of which 17 (81%) showed complete or partial remission in response to treatment with rituximab. The presence of LA was significantly associated with rituximab-induced remission in these patients (p=0.007, OR=7.286 [1.737-30.555]). Conclusion: In this real world series, patients with RA demonstrate long-term, high response rates to rituximab therapy and synovial biopsy B-cell rich lymphoid aggregates are associated with a higher rate of good response.
MYC overexpression predicts poor prognosis and correlates with immune infiltration in chronic lymphocytic leukemia
Authors: Guo Dongmei , Li Ping , Wang Zan , Li Banban , Bi Gaofeng , Li Chunpu
Published: January 2022

Background: Chronic lymphocytic leukemia (CLL) is a highly genetically heterogeneous disease that represents 30% of adult leukemia. We aimed to identify survival-associated key genes in CLL and investigate potential immunotherapy targets.Methods: The survival information and microarray mRNA expression profiles of CLL patients were downloaded from the Gene Expression Omnibus (GEO) and the International Cancer Genome Consortium (ICGC) database. Hub genes were uncovered in CLL. The bioinformatics technology was applied to identify key genes and performe functional analysis. Finally, we explored the role of this key gene and the situation of immune infiltration in the bone marrow.Results: We uncovered 223 differentially expressed genes (DEGs) as hub genes associated with CLL. MYC was identified as the key gene in CLL. High MYC expression was associated with poor prognosis. The biological pathways such as "Hypoxia", "Myc Targets V2", "P53 pathway" etc, were remarkably linked with MYC high expression phenotype. The expression level of MYC was positively correlated with infiltration levels of Eosinophils and follicular helper T cells, while negatively correlated with infiltration levels of regulatory T cells.Conclusion: Overexpression of MYC predicts poor prognosis and correlates with immune infiltration. MYC could serve as a potential immunotherapeutic target for CLL.
Prognostic Nomograms Based on Microvascular Invasion Grade for Early-stage Hepatocellular Carcinoma Patients After Curative Hepatectomy
Authors: Ke Jingpeng , Ye Honghao , Lin Fangzhou , Shi Yingjun , Zhong Aoxue , Chen Hengkai
Published: January 2022

Background: This is the first study to develop and evaluate a predictive model based on the microvascular invasion (MVI) classification for early recurrence and survival after curative hepatectomy in patients with early-stage hepatocellular carcinoma (HCC).Methods: The database of patients with early-stage HCC who underwent curative hepatectomy in the First Affiliated Hospital of Fujian Medical University and the First Affiliated Hospital of Xiamen University were retrospectively reviewed. Kaplan-Meier curves and Cox proportional hazards regression models were used to analyze disease-free survival (DFS) and overall survival (OS). Nomogram models were constructed on the datasets from the First Affiliated Hospital of Fujian Medical University and the datasets were validated using bootstrap resampling with 30% samples as internal validation. Data of patients from First Affiliated Hospital of Xiamen University were used for external validation.Results: A total of 703 patients with early-stage HCC were included in our study. An eight-factor nomogram for predicting recurrence or metastasis and a six-factor for predicting survival were created. The concordance indexes (C-index) were 0.775 (95% confidence interval [CI], 0.720-0.830) for the DFS nomogram and 0.812 for the OS nomogram (95% CI, 0.732-0.892), respectively, in the training cohort, and 0.865 (95% CI, 0.806-0.924) and 0.839 (95% CI, 0.675-1.00), respectively, in the internal validation cohort, and 0.857 (95% CI, 0.763-0.951) and 0.842 (95% CI, 0.708-0.970), respectively, in the external validation cohort. The calibration curves showed optimal agreement between the predicted and observed DFS and OS rates. The predictive accuracy was significantly better than that of the classic HCC staging systems.Conclusions: This study developed and validated nomograms for predicting recurrence, especially early recurrence, and overall survival in early-stage HCC patients after curative resection with high predictive accuracy.
Male Mortality from Conditions Sensitive to Primary Care Under The Perspective of The National Men's Health Policy
Authors: de Paula Cácia Régia , Pelazza Bruno Bordin , de Lima Flavio Henrique Alves , Maia Ludmila Grego , de Araújo Reila Campos Guimarães , Tacsi Yolanda Rufina Condorimay , Ferri Lucila Pesuti , Meireles Gláucia Oliveira Abreu Batista , Ferreira Pedro Lopes , Sousa Ana Luiza Lima , Matos Marcos André , Barbosa Maria Alves
Published: January 2022

Background: To evaluate the trend of male mortality and its relationship with conditions sensitive to primary care (CSPCs), considering the coverage of the Family Health Strategy (FHS) and the implementation of the National Policy for Comprehensive Health Care of the Male (PNAISH).Methods: Ecological study of the time series of male deaths in the age group of 20 to 59 years, according to CSPC from 2009 to 2018 with data extraction from the Mortality Information System. The relationship between death rate due to CSPCs and FHS coverage was quantified by Spearman’s correlation. The trend in the number of deaths was adjusted by univariate quasi-Poisson regression models. Mortality trends were considered stationary (p > 0.05), declining (p < 0.05 and negative regression coefficient), or ascending (p < 0.05 and positive regression coefficient). Values of p < 0.05 were considered statistically significant.Results: CSPCs were responsible for 1,092,070 (19.2%) deaths in the 127 municipalities under study, a with year-on-year variation of -4.89% to 3.06% and showed no significant relationship with mean FHS coverage (r < 0.09; p < 0.160). PNAISH was implemented in 100% of the municipalities, and the FHS coverage showed a significant upward trend [95% CI; 1.03-1.09], with an annual average of 6%. The trend of deaths in the study groups due to CSPCs was generally stable (Exp (β) = 1.01; p > 0.593). Notably, deaths in specific groups increased over time: bacterial pneumonia, asthma, hypertension, epilepsy, kidney and urinary tract infections, and skin and subcutaneous tissue infections. The heart failure group showed a decreasing mortality rate (Exp (β) = 0.92; p = 0.008).Conclusions: The expansion of FHS coverage and the fact that PNAISH was implemented in all municipalities in the state of Goiás did not influence the rate of deaths due to CSPCs in general. The analysis of death trends due to CSPCs in general indicates stability in the investigated period. The present study, the first of its kind in country, allows an evaluation of actions related to PNAISH, confirming the need for urgent investments. It can serve as feedback to researchers and policy-makers on interventions in humans.
Polymorphisms of Potential Drug Resistant Molecular Markers in Plasmodium Vivax From China–Myanmar Border During 2008 to 2017
Authors: Wang Zhen-sheng , Wei Chun-yan , Pan Yun-chun , Wang Zhi-hua , Ji Xin , Chen Qianqian , Zhang Lian-hui , Wang Zenglei , Wang Heng
Published: January 2022

Background: Plasmodium vivax remains the predominant species at the China–Myanmar border, imposing a major challenge to the recent gains in regional malaria elimination. To closely supervise the emerging of drug resistance in this area, we surveyed the variations in genes potentially correlated with drug resistance in P. vivax parasite and the possible drug selection with time.Methods: A total of 235 P. vivax samples were collected from patients suffering uncomplicated malaria at Yingjiang, Tengchong, and Longling counties, and Nabang port in China, Yunnan province, and Laiza township in Myanmar, during 2008 to 2017. Five potential drug resistance genes were amplified utilizing nested-PCR and analyzed, including pvdhfr, pvdhps, pvmdr1, pvcrt-o, and pvk12. Results: The pvdhfr F57I/L, S58R, T61M and S117T/N presented in 40.64%, 56.68%, 40.11%, and 56.04% of the sequenced P. vivax isolates, and these mutations significantly decreased with years. The haplotype formed by these quadruple mutations predominated at Yingjiang, Tengchong, Longling and Nabang. While a mutation H99S/R (56.59%) dominated at Laiza and increased with time. In pvdhps, the A383G prevailed in 69.16% of the samples, which remained the most prevalent haplotype. However, a significant decrease of its occurrence was also noticed over the time. The S382A/C and A553G existed in 8.37% and 30.84% of the isolates, respectively. In pvmdr1, the mutation Y976F occurred at a low frequency in 5/232 (2.16%), while T958M was fixed and F1076L was approaching fixed (72.41%). The K10 insertion was detected at an occurrence of 33.17% in pvcrt-o, whereas there was no significant difference among the sites or over the time. No mutation was identified in pvk12.Conclusions: Mutations related with resistance to antifolate drugs are prevalent in this area as expected, while their frequencies decrease significantly with time, suggestive of increased susceptibility of P. vivax parasite to antifolate drugs. Resistance to CQ is possibly emerging. However, since the molecular mechanisms underneath CQ resistance is yet to be better understood, close supervision of clinical drug efficiency and continuous function investigation is urgently needed to alarm drug resistance.
Evaluation of the effects of vaccination regimes on the transmission dynamics of COVID-19 pandemic
Authors: Nakamoto Ichiro , Zhang Jilin , Zhuang Weiqing , Guo Yan
Published: January 2022

The COVID-19 pandemic has yet to be eliminated globally despite the advancement of immunization programs. Evaluation of the effects of the vaccination regimes of COVID-19 is critical for understanding the potential capacity of countermeasures and informing subsequent prioritization strategies of responses. Research and observational data provide broad support regarding the importance of effective vaccines, in contrast, debates remain on the timing and priority of booster vaccination under the assumption of resource constraint. This study aims to evaluate the effect of vaccination regimes on the trajectory of the COVID-19 pandemic from the medium-term perspective. We employ a mathematical model to infer critical epidemiological characteristics associated with COVID-19, thereafter perform simulation on the transmission dynamics of the epidemic up to 3 years. The outcomes imply that in the absence of severe variants of the pathogen, administration of booster vaccination curtails the peak size of total cases and share of severe infections at later waves. Nevertheless, it can be better off by prioritizing the primary doses to unvaccinated individuals when vaccine shortage is challenged. The effects of priority categories are consistent across a broad range of profiles. Increasing the rollout capacity (i.e., administration rate) of doses can render the reproduction number lower than one and hence contain the transmission of pandemic ultimately controlling for other factors. The timing of rollout of primary doses is pivotal in reducing the magnitude of transmission saturation. It is of importance to prioritize the administration of primary vaccination series to vulnerable individuals efficiently and thereafter increment of administration capacity when the supply of vaccine increases over time to scale down the size of an epidemic.
HER2-positive Apocrine Carcinoma of the Breast: A population-based Analysis of Treatment and Outcome
Authors: Skenderi Faruk , Alahmad Mohamad Alhoda Mohamad , Tahirovic Emin , Alahmad Yaman M. , Gatalica Zoran , Vranic Semir
Published: January 2022

Aims
Apocrine carcinoma of the breast (APO) expresses HER2 in 30-50% of cases. This study explored the clinicopathological features and outcome of HER2+ APO (HER2+/APO) and matched HER2-positive invasive carcinomas of no special type (HER2+/NST).
Methods
We used the SEER database to explore the HER2+/APO and HER2+/NST cohorts. Univariate and multivariate analyses were used to assess the breast cancer-specific (BCSS) and overall survival (OS). Based on ER and PR [=HR] and HER2 status, we divided the cohorts to match the intrinsic molecular subtypes for comparisons [Apocrine Luminal B (HER2+/HR+/APO) vs. NST Luminal B (HER2+/HR+/NST) and Apocrine HER2-Enriched (HER2+/HR-/APO) vs. NST HER2-Enriched (HER2+/HR-/NST)].
Results
We retrieved 259 cases of HER2+/APO with an active follow-up among the 446,806 breast malignancies (frequency ~0.06%). Most HER2+/APO were HR negative (65%). HER2+/APO carcinomas were more prevalent in the 80+ age group (24.7% vs. 15.7%, p<0.001). HER2+/HR-/APO had a significantly lower histological grade than the HER2+/HR-/NST (p<0.001). Breast cancer-related deaths were more prevalent in HER2+/NST (7.8% vs. 3.9%, p=0.019). This was particularly evident between HR- subgroups (10.4% in HER2+/HR-/NST vs. 4.2% in HER2+/HR-/APO, p=0.008) and was reaffirmed in BCSS in univariate analysis (p=0.03). Other than race and ER/PR status, HER2+/APO subgroups did not differ in clinicopathological parameters.
Conclusions
Our study confirms the rarity of the APO and reveals that ER/PR status in HER2+ APO does not affect these patients' prognosis. HER2+/APO tumors tend to have a less aggressive phenotype and a more favorable outcome despite a markedly lower ER/PR positivity.
Prognostic Factors of Gliosarcoma in the Real World: A Retrospective Cohort Study
Authors: Xu Hongzhi , Yu Ziye , Zhou Zhirui , Xu Ming , Song Kun , Shen Jingjing , Zhu Wenhao , Wei Liqun
Published: January 2022

Introduction:
Gliosarcoma is a histopathological variant of glioblastoma, which is characterized by a biphasic growth pattern consisting of glial and sarcoma components. Owing to its scarcity, data regarding the impact of available treatments on the clinical outcomes of gliosarcoma are inadequate. The purpose of this retrospective cohort study was to analyze the prognostic factors of gliosarcoma.
Methods
By screening the clinical database of neurosurgical cases at a single center, patients with gliosarcoma diagnosed histologically from 2015 to 2021 were identified. Clinical, pathological and molecular data were gathered founded on medical records and follow-up interviews. Prognostic factors were derived using Cox proportional hazards model with backward stepwise regression analysis.
Results
Forty-five GSM patients were included. Median overall survival was 20.6 months (95%CI 5.8 – 35.3), and median relapse free survival was 15.2 months (95%CI 6.1 – 24.3). In multivariable analysis, total resection (p = 0.029, HR = 0.198, 95%CI 0.046 – 0.849) indicated an improved prognosis. And low expression of Ki-67 (p = 0.067, HR = 2.813, 95%CI 0.930 – 8.506) would be likely to show statistical significance. However, there might be no statistically significant survival benefit from radiotherapy (n = 33, 75%, log-rank p = 0.92), adjuvant temozolomide (n = 33, 73.3%, log-rank p = 0.78) or concurrent temozolomide (n = 36, 80%, log-rank p = 0.79).
Conclusion
This retrospective study with a limited cohort size has demonstrated the treatment of gross total resection and low expression of Ki-67 are beneficial for patients with GSM, while radiotherapy or temozolomide is not.
Recursive Integral Terminal Sliding Mode Control of MEMS Gyroscopes via Composite Neural Learning and Disturbance Observer
Authors: Zhang Rui , Xu Bin , Wang Hai
Published: January 2022

The recursive integral terminal sliding mode control based on disturbance observer and composite neural learning is studied in this paper to control the dynamics of MEMS gyroscopes in the presence of system uncertainties and external disturbances. To achieve more accurate approximation accuracy of system uncertainties, the composite neural learning is employed, where the updating law of the weight vector is designed by the tracking error and the prediction error constructed by serial-parallel estimation model. To further improve the system robustness, the recursive integral terminal sliding mode controller is utilized, where faster convergence can be obtained by forcing the system state to start from the sliding mode manifold at the initial time. To deal with external disturbances with unknown upper bounds, the disturbance observer is designed. Furthermore, simulations results are demonstrated to verify that faster convergence and higher tracking accuracy can be achieved under the proposed method.
Environmental and Morphological Detrimental Effects of Microplastics on Marine Organisms to Human Health
Authors: Bhuyan Md. Simul , Rashed-Un-Nabi Md. , Alam Md. Wahidul , Islam Md. Nazrul , Cáceres-Farias Lenin , Bat Levent , Musthafa M. Saiyad , Senapathi Venkatramanan , Chung Sang Yong , Núñez Alonzo Alfaro
Published: January 2022

The ubiquitous presence of microplastics (MPs) in all oceans has become a significant threat to nature as global plastic production continues to increase. Now, and over the next 20 to 30 years, it is the time to address the consequences of the rise of the plastic industry global production of millions of items, ranging from a single pen to automobiles. Inappropriate management, lack of awareness of the harmful effects, reckless universal use, and indiscriminate disposal of plastics have turned the earth into a "plastic planet”. The aim of the present study review is to identify the scenarios for the structure, and functions of MPs and the resulting impacts on marine organisms. The different origins of MPs in the oceans and their negative impacts on marine organisms are critically discussed in this review. Due to their small size, these plastic particles are easily ingested by a wide range of marine organisms (e.g., fish, Mollusca, Arthropoda, Annelida, Echinodermata, Nematoda, phytoplankton, zooplankton, algae, birds, Mammalia, marine reptiles, and corals), posing a threat to their health. The ability of MPs to absorb a variety of hazardous hydrophobic chemicals from the environment allows transfers these toxins to enter directly into the food chain, ultimately becoming a threat to human health. As a result, numerous policies and laws have been created to address the major problems of marine pollution. However, these regulations need to be improved and implemented worldwide. To avert future threats, it is crucial to stop the production of toxic chemicals associated to the production of plastics and replaces them with environmentally suitable alternatives.
Small molecules from Bacopa monneiri as potent inhibitors against Neurodegenerative Disorders
Authors: Sangeet Satyam , Khan Arshad
Published: January 2022

Alzheimer’s is characterized by the formation of senile plaques and fibril tangles. Several methodologies have been employed to treat the disease. Albeit engineered medications that are accessible for the treatment of Alzheimer’s, due to their numerous side-effects, it becomes imperative to formulate and synthesize novel drug candidates. Plants could be utilized as an alternative for these manufactured medications because of their low incidental effects in contrast with the engineered drugs. Bacopa monneiri (BM) is a therapeutic plant that is accounted for to be utilized to treat NDs. Therefore, in the current study, an in-silico approach was carried out to evaluate the pharmacological effect of BM. Molecular Docking was carried out to screen the active phytochemicals of BM which can act as potential drug candidates against amyloid-β plaques. A total of 8 biologically active phytochemicals from BM were docked against the p75NTR receptor. Based on molecular docking study it was observed that the phytocompounds Bacopasaponin D and Bacopasaponin G of BM significantly fit the active site of p75NTR. Further Molecular Dynamics simulation study was performed to examine the stability of the binding of these phytochemicals with the selected targets. Our findings suggested that the phytocompounds Bacopasaponin D and Bacopasaponin G significantly bind with p75NTR and thusmight have the potential to inhibit the natural binding activity of amyloid-b plaques and act as a potential anti-neurodegenerative drug.
Stroke and internal carotid dissection as the first manifestation of giant cell arteritis: a case report
Authors: Hashami Leila , Ketabforoush Arsh Haj Mohamad Ebrahim , Nirouei Matineh
Published: January 2022

Introduction: Giant Cell Arteritis (GCA) is a systemic vasculitis that involves medium-sized and larger arteries.GCA rarely can affect the brain-arteries, resulting in ischemic strokes and transient ischemic attacks, whereby the most affected region is vertebrobasilar. Also, it's very unusual that cocurate with large artery dissections. We describe a patient with anterior brain territory stroke and right internal carotid dissection as the first manifestation of GCA.Case report: A 51-year-old man was presented with sudden onset of right-side blurred vision, frozen movements, and ptosis in the right eye and left side paresis. There was a history of right-sided frontotemporal headache, diabetes mellitus, and dyslipidemia. The Laboratory tests show erythrocyte sedimentation rate (ESR)=90, C-reactive protein (CRP)=15mg/L. CT scan and brain MRI indicated an acute ischemic infarction in the right frontal region. CT-Angiography has shown internal carotid artery dissection. Due to the presentation and lab tests, we started Methylprednisolone 1 gr for treating GCA, and temporal artery biopsy was positive for GCA in pathology findings. After ten days, inflammatory markers were reduced (ESR:40). Besides improving headaches, there was no significant change in eye deficits and reduction of left limb's force.Conclusion: Due to the noisy symptoms in patients with Stroke and carotid dissection, the diagnosis of GCA may be neglected as an underlying cause. The association of high CRP levels and the rate of ESR with Stroke, although nonspecific, should draw some attention to vasculitis, topped by GCA.
Difficulties in monitoring of premature infants in outpatient facilities (third stage of nursing)
Authors: Koltuntseva I. V. , Sakhno L. V. , Bairova S. V. , Mishkina T. V. , Revnova M. O.
Published: January 2022

Premature birth remains an urgent problem of modern healthcare around the world. At the same time, the improvement of neonatal care for premature babies has led to a significant decrease in infant mortality and an increase in the survival rate of children with very low and extremely low body weight. Nursing and monitoring such children requires a special approach. A premature baby has one or more reasons for the early development of chronic pathology and needs a long-term, differentiated, continuous monitoring, provided a clear continuity of all stages of nursing.

The article presents the results of observation of premature babies in 20 polyclinics of Saint Petersburg in the first year of life at the time of the study. The authors analyzed medical histories (form 112/y) of 88 children born prematurely (from 22 to 36 weeks of gestation). It has been determined that most often the dispensary observation groups include children with pathology of the central nervous system, organs of vision, and surgical pathology. Insufficient coverage with vaccine prophylaxis (from 33 to 78% for various vaccine-preventable infections) was revealed not only with additional drugs for the risk group, but also with the main vaccinations of the National Calendar. Monitoring premature babies, their rehabilitation and habilitation are the responsibility of the third (outpatient) level of nursing. However, the lack of uniform approaches to dispensary observation, rehabilitation treatment of premature babies, the lack of clear routing create difficulties in the management of such children in a polyclinic. The authors proposed options for solving this important problem in order to increase the efficiency of the primary pediatric care for premature babies at the place of residence of the child.
Difficulties in diagnosis of chronic granulomatous disease in a 10-year-old child
Authors: Gubkina M. F. , Sterlikova S. S. , Yukhimenko N. V. , Petrakova I. Yu. , Khokhlova Yu. Yu.
Published: January 2022

Objective: to familiarize doctors with one of the rare variants of primary immunodeficiency – chronic granulomatous disease. The authors present a case of late diagnosis of chronic granulomatous disease in a 10-year-old child. The doctors missed the development of complications after BCG vaccination in the form of axillary lymphadenitis on the left (BCGitis), which led to the development of disseminated BCG infection, regarded as an infectious tuberculous process. The onset of chronic granulomatous disease occurred at the age of 10 months (paraproctitis complicated by an anal fistula). The assumption of the presence of immunodeficiency arose in connection with the recurrent course of pneumonia at the age of 4-5 years, but was regarded as a manifestation of a tuberculous infectious process. At the age of 8, during the protracted course of nonspecific polysegmental pneumonia, primary immunodeficiency without specific clinical form was diagnosed on the basis of the results of a comprehensive immunological examination. At the age of 10, chronic granulomatous disease was verified using a study of spontaneous and stimulated chemiluminescence of neutrophils and the results of a genetic study.
Effectiveness, User Engagement and Experience, and Safety of a Mobile App (Lumi Nova) Delivering Exposure-Based Cognitive Behavioral Therapy Strategies to Manage Anxiety in Children via Immersive Gaming Technology: Preliminary Evaluation Study (Preprint)
Authors: Lockwood Joanna , Williams Laura , Martin Jennifer L , Rathee Manjul , Hill Claire
Published: January 2022

BACKGROUND

Childhood anxiety disorders are a prevalent mental health problem that can be treated effectively with cognitive behavioral therapy, in which exposure is a key component; however, access to treatment is poor. Mobile-based apps on smartphones or tablets may facilitate the delivery of evidence-based therapy for child anxiety, thereby overcoming the access and engagement barriers of traditional treatment. Apps that deliver therapeutic content via immersive gaming technology could offer an effective, highly engaging, and flexible treatment proposition.

OBJECTIVE

In this paper, we aim to describe a preliminary multi-method evaluation of Lumi Nova, a mobile app intervention targeting mild to moderate anxiety problems in children aged 7-12 years using exposure therapy delivered via an immersive game. The primary objective is to evaluate the effectiveness, user engagement and experience, and safety of the beta version of Lumi Nova.

METHODS

Lumi Nova was co-designed with children, parents, teachers, clinicians, game industry experts, and academic partnerships. In total, 120 community-based children with mild to moderate anxiety and their guardians were enrolled to participate in an 8-week pilot study. The outcome measures captured the app’s effectiveness (anxiety symptoms, child-identified goal-based outcomes, and functional impairment), user engagement (game play data and ease-of-use ratings), and safety (mood ratings and adverse events). The outcome measures before and after the intervention were available for 30 children (age: mean 9.8, SD 1.7 years; girls: 18/30, 60%; White: 24/30, 80%). Additional game play data were automatically generated for 67 children (age: mean 9.6, SD 1.53 years; girls: 35/67, 52%; White: 42/67, 63%). Postintervention open-response data from 53% (16/30) of guardians relating to the primary objectives were also examined.

RESULTS

Playing Lumi Nova was effective in reducing anxiety symptom severity over the 8-week period of game play (t29=2.79; P=.009; Cohen d=0.35) and making progress toward treatment goals (z=2.43; P=.02), but there were no improvements in relation to functional impairment. Children found it easy to play the game and engaged safely with therapeutic content. However, the positive effects were small, and there were limitations to the game play data.

CONCLUSIONS

This preliminary study provides initial evidence that an immersive mobile game app may safely benefit children experiencing mild to moderate anxiety. It also demonstrates the value of the rigorous evaluation of digital interventions during the development process to rapidly improve readiness for full market launch.
Risk Factors Associated With Dengue in District Khyber, Khyber Pakhtunkhwa, Pakistan, From September 2 to November 24, 2019: Case-Control Study (Preprint)
Authors: Ajam Saba , Khan Muhammad Qasim , Ashraf Nosheen , Malik Muhammad Wasif , Baig Zeeshan Iqbal , Ranjha Muazzam Abbas , Chaudhary Ambreen , Khan Mumtaz Ali , Ansari Jamil A , Ikram Aamer
Published: January 2022

BACKGROUND

Dengue is a vector-borne disease endemic to Pakistan as well as to Khyber Pakhtunkhwa. A total of 300 confirmed cases of dengue were reported in District Khyber in 2019, where a prompt response was initiated by the Disease Surveillance and Response Unit. Subsequently, a study was planned to identify the risk factors associated with dengue and to propose recommendations for containment of the disease.

OBJECTIVE

This study aimed to assess the risk factors associated with dengue in District Khyber and to provide recommendations for improving the existing system and preventing dengue.

METHODS

A case-control study was conducted in District Khyber from September 2 to November 24, 2019. Cases were enrolled from health care facilities based on predefined criteria, which included the presence of clinical signs and symptoms as well as laboratory confirmation of dengue NS1 antigen. Controls were enrolled from the community at a case-control ratio of 1:2. Data were collected using a pretested questionnaire in face-to-face interviews.

RESULTS

A total of 300 cases were enrolled; 87% (263) of cases were men. This study found that 45% (269/601; odds ratio [OR] 15, 95% CI 9.9-24.07; P<.001) of enrolled participants did not use bed nets and 39% (236/601; OR 1.7, 95% CI 1.1-2.4; P<.001) did not use mosquito repellents. A total of 39% (233/601; OR 16.6, 95% CI 11.11-24.93; P<.001) of enrolled participants who tested positive for dengue were neighbors, 35% (213/601; OR 1.47, 95% CI 1.04-2.0; P<.001) lived in a joint family, and 40% (241/601; OR 3.32, 95% CI 2.3-4.7; P<.001) slept outdoors; these factors were significantly associated with dengue.

CONCLUSIONS

Dengue is a preventable disease and can be controlled by the proper use of bed nets and mosquito repellents, modification of sleeping habits, and improvement in family structure. Dengue management training for health care personnel and community awareness are recommended.