bluuebunny/crossref_metadata_2025 huggingface dataset:
IRIS: Integrated Retinal Functionality in Image Sensors
Authors: Yin Zihan , Kaiser Md , Camara Lamine , Camarena Mark , Parsa Maryam , Jacob Ajey , Schwartz Gregory , Jaiswal Akhilesh
Published: December 2022

Neuromorphic image sensors draw inspiration from the biological retina to implement visual computations in electronic hardware. Gain control in phototransduction and temporal differentiation at the first retinal synapse inspired the first generation of neuromorphic sensors, but processing in downstream retinal circuits, much of which has been discovered in the past decade, has not been implemented in image sensor technology. We present a technology-circuit co-design solution that implements two motion computations occurring at the output of the retina that could have wide applications for vision based decision making in dynamic environments. Our simulations on Globalfoundries 22nm technology node show that, by taking advantage of the recent advances in semiconductor chip stacking technology, the proposed retina-inspired circuits can be fabricated on image sensing platforms in existing semiconductor foundries. Integrated Retinal Functionality in Image Sensors (IRIS) technology could drive advances in machine vision applications that demand robust, high-speed, energy-efficient and low-bandwidth real-time decision making.
Individual need and health system factors associated with cervical cancer screening uptake among women of child-bearing age in Mangochi district, Malawi: a facility-based cross-sectional study
Authors: Mpachika-Mfipa Felistas , Kululanga² Lucy Ida , Mfipa Dumisani , Kazembe Abigail
Published: December 2022

Background
Cervical cancer screening (CCS) uptake remains low in poor countries. Limited studies have assessed individual need and health system factors which facilitate/impede use of healthcare services, including CCS uptake. Thus, we examined associations between these factors and CCS uptake among women of child-bearing age (WCBA) in Mangochi, Malawi.
Methods
A cross-sectional study, sampling 482 women (18–49 years) using a multi-stage sampling method was conducted in five health facilities (HFs). Data were collected from June-July, 2019. Chi-squared or Fisher’s exact tests were used to compare the distribution of CCS uptake according to different independent groups.
Results
The proportion of WCBA who did CCS was significantly higher among HIV + women than those who were HIV- and with unknown HIV status, respectively [27.3% (33/121) vs 8.5% (30/353) vs 0% (0/8), χ2 = 29.18, df = 2, p < 0.001]. Significantly higher among those who had ever heard of cervical cancer (CC) than those who had not [23.0% (60/261) vs 1.4% (3/221), χ2 = 49.28, df = 1, p < 0.001]. Significantly higher among those who heard of CC from HFs than those who heard through radios, friends/family and other sources, respectively [31.2% (44/141) vs 16.7% (7/42) vs 9.3% (5/54) vs 16.7% (4/24), χ2 = 12.62, df = 3, p = 0.006]. Significantly higher among those with positive beliefs towards CCS than those with negative beliefs [19.2% (53/276) vs 4.9% (10/206), χ2 = 21.37, df = 1 p < 0.001]. Significantly higher among those recommended for CCS by health workers (HWs) than those not recommended [19.6% (53/270) vs 4.7% (10/212), χ2 = 23.24, df = 1, p < 0.001]. Significantly higher among those willing to be screened by male HWs than those unwilling [14.4% (60/418) vs 4.7% (3/64), χ2 = 4.57, df = 1, p = 0.033]. Fisher’s exact test showed that CCS uptake among WCBA varied significantly by level of knowledge of CC signs/symptoms, with 66.7% (12/18) and 19.8% (48/243) among those with high-level and low-level knowledge screened, respectively (p < 0.001).
Conclusions
HIV status, ever heard of CC, sources of information, knowledge of CC signs/symptoms, beliefs, recommendations by HWs for CCS, willingness to be screened by male HWs were associated with CCS uptake. These should be prioritized to improve CCS uptake among WCBA.
Design and Analysis of a Syngas Catalytic Combustor for Micro Electrical Mechanical Systems (MEMS)
Authors: Bazooyar Bahamin , Zhu Mingming , Manovic Vasilije , Nabavi Seyed Ali
Published: December 2022

In this work, a catalytic combustor for micro electrical mechanical system using renewable syngas was designed and analysed using Direct Numerical Simulation (DNS) in conjunction with finite rate chemistry. The effect of catalyst (rhodium, palladium, and rhodium), shape and packing of the catalyst and operating conditions (e.g., inlet temperature and velocity, fuel/air ratio, H2 content in the fuel mixture) on combustion efficiency and pressure drop were studied. Findings demonstrate that the catalyst in the shape of intalox saddle resulted in the bed effectiveness factor (An ideal reactor effectiveness factor is 1 which 0.5 is equivalent to 100% combustion efficiency and 0.5 is from 0% pressure drop at the combustor outlet) 0.93, while the packing geometry of the catalyst has negligible impact on the operation of the reactor. Analysis under different operating conditions reveals that the designed reactor can operate effectively with syngas of varying compositions. The combustion mainly takes place on the surface of the catalyst without gas phase reaction. The analyses of Damköhler number demonstrated that the timescale of chemical reactions is at the same order of magnitude for concentration of hydroxyl radicals (OH) over the entire length of the reactor, suggesting a uniform combustion.
Excavate the role of E2F family in the prognosis, drug sensitivity analyses, and Immune cell infiltration of KIRC (Kidney Clear Cell Carcinoma)
Authors: He Xing Jun , Li Junhui , Tian Feng , Yin Gui Cao , Tian Hao Yu , Sha Wei , Qi Le Zhong , Li Yi Fan , Wang Xiao Xiang , Pan Xiang
Published: December 2022

KIRC is a common malignant tumor with few early symptoms, usually been found and diagnosed when it becomes large with hematuria, kidney injury and abdominal mass. E2F family include 8 genes (E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, E2F7 and E2F8) and express high in virtually all cancers. Their role in cell proliferation has been extensively studied. Regrettably, there are very few reports about the interrelationship between KIRC and E2Fs. In order to research their relation, by taking great advantage of some reliable datasets and bioinformaticsx tools, we excavated the expression level of E2Fs, the prognostic value of E2Fs in KIRC, co-expression network, drug sensitivity analysis, kinase target and immune cell infiltration of E2Fs in KIRC patient. Our work may provide new insights into the selection of immunotherapeutic targets and prognostic biomarkers for KIRC. It also provides more data to help clinicians select appropriate therapeutic agents and more accurately predict the long-term prognosis of patients with renal cancer. Method: GEPIA, UALCAN, cBioPortal, GeneMANIA, DAVID 6.8, Metascape, TRRUST, TIMER, and LinkedOmics were used in this study.
An efficient constraint programming approach to signal recovery in compressed sensing
Authors: Nouasria Hamid , Et-tolba Mohamed
Published: December 2022

Compressed sensing (CS) allows for the useful information conveyed by a signal to be completely acquired in a few measurements from which the original signal can be accurately reconstructed. This is made possible because of the sparsity property of the original signal, and the existing powerful optimization theory that gave birth to numerous recovery algorithms. With the aim of CS performance improvement, in this paper, we propose the constraint programming (CP) solvers as an alternative to the classical recovery algorithms in the CS process. We show that contrarily to the conventional recovery algorithms, the proposed approach is sensitive to the sensing matrix variance, and provides better performance. Besides, we demonstrate that even non-sparse signals can be recovered with CP-based signal recovery.
Potentials of Cellulose and Silica-based Materials for Enzyme Immobilization
Authors: Wonorahardjo Surjani , Suharti Suharti , Yuniawati Nurakhma , Fatimasari Emada , Setyaningtyas Anis , Haula Hamizah , Susanti Evi , Molo Antonius DRP , Maharani Chariztya A , Sari Dian Puspita
Published: December 2022

This research aims to develop biomaterials for a place for enzyme immobilization in a designed porous matrix. Hydrolyzed bacterial cellulose was entrapped in the silica rice husk surface during gelling to modify the surface properties. Immobilized enzymes were investigated for their life duration and reusability. In this research, cellulase, trypsin, and lipase enzymes were used as probe enzymes to be immobilized in the silica-cellulose matrix, and their activity was tested using spectroscopic techniques. The systems exhibited good reusability up to 6 cycles with the also interesting outcome from the dynamics in the interface, which were varied by temperature, pH, and stirring speed. Silica-cellulose was also compared to silica alone in this experiment. When physical interaction with surfaces was assumed, enzyme activity decreased to 10, 20, and 40% due to confinement but underwent complex dynamics due to speedy adsorption-desorption equilibrium.
Evolution and divergence of the genetic lineage of Rabies Virus Desmodus rotundus/Artibeus lituratus in São Paulo State
Authors: de Souza Débora Nunes , Oliveira Rafael Novaes , Bettoni Fabiana , Asprino Paula Fontes , Macedo Carla Isabel , Achkar Samira Maria , Fahl Willian de Oliveira , Brandão Paulo Eduardo , Castilho Juliana Galera
Published: December 2022

Since 1998, with the occurrence of the last case of rabies in dogs or cats in São Paulo State related to the dog-specific rabies virus (RABV) lineage, 55 cases of rabies in these animals have been reported until 2021, and the vast majority (51) have been genetically characterized as belonging to the Desmodus rotundus/Artibeus lituratus lineage of RABV, However, it has not been demonstrated so far if there is the possibility to infer which of these bats acted as a source of infection in these cases through the genetic sequencing of isolated RABV. In order to characterize the Desmodus rotundus/Artibeus lituratus lineage aiming at the possibility of differentiating its isolates in RABV associated with each of these reservoirs, this research performed the DNA sequencing technique by amplification on the Illumina Miseq platform in 70 RABV isolates from the State of São Paulo, sent to the virology laboratory of the Pasteur Institute of São Paulo between 2006–2015, being 33 related to the hematophagous bat D. rotundus and 37 to the fruit bat A. lituratus. A genomic approach using phylogenetic and nucleotide identity analyses demonstrated that the isolates investigated in this study can be considered as belonging to the same genetic lineage of RABV and that in São Paulo State the D. rotundus/A. lituratus lineage is subdivided into at least four phylogenetic sub lineages, two associated with D. rotundus and two with A. lituratus, and that these results can be practically applied to the epidemiological surveillance of rabies in this state.
Exploring the Quality of Nexus among the College-going Adolescents with their Parents in Bangladesh: A Public Health Perspective
Authors: Chowdhury Farhana Ishrat , Hossain Syed Billal , BakiBillah Abul Hasan , Khan Ayub , Shahjahan Md. , Chowdhury ABM Alauddin
Published: December 2022

This study aims to investigate the relationship between parental bonding and parent-child relationships among college-going adolescents. A scale suggested by Robert C. Pianta (1992) was used in this quantitative, cross-sectional study with a descriptive design. Among 1000 students of Chattogram Biggan College and Chattogram Commerce College in Chattogram, Bangladesh, 101 individuals were selected. The demographic profile of the participants; 46% of the respondents were male and 54% were female, all of them were aged between 17 to 19. Regarding feelings about spending time with parents, it was discovered that 62.4% of the total 101 participants are delighted with their mother, while 49% are very happy with their father. While 5.9% and 3% of participants are unhappy and very unhappy with their mothers, just 3.5% of the total participants are unhappy with their fathers. While a significant proportion (almost 40%) have a strong bond with their mother. On the other hand, over three-quarters of respondents have disagreements with their fathers' proximity and dependence, according to the research. While a sizable proportion (about 30%) have a strong bond with their father. Whereas over 40% of respondents calculated overall intimacy with their father was low, and nearly 30% with their mother, the remaining respondents were either medium or highly intimate with their parents. Overall relationship intimacy with mothers and fathers was also found to be linked to various relationship characteristics such as conflict (P<0.000), closeness (P<0.000), and dependence (P<0.000) according to the findings. Things that participants liked (P-value=0.047) and disliked (P-value=0.040) most about their mother, feelings when spending time with their mother (P-value=0.066), and things that dislike most about their father (P-value=0.058) had a marginally significant connection with gender.
GATA4 regulates mitochondrial biogenesis and functions during cardiac development and rescues cardiac and mitochondrial functions impaired by TKIs
Authors: Liu Qing , Wu Haodi , Duren Zhana , Jiang Chao , Bortle Kevin Van , Zhao Mingtao , Guo Hongchao , Zhu Chenchen , Luo Qing-Jun , Zhao Bingqing , Liu Jun , Marciano David , Gruber Joshua , Lipchik Andrew , Narasimha Anil , Watson Nathaniel , Tsai Ming-Shian , Furihata Takaaki , Tian Lei , Wei Eric , Li Yingxin , Steinmetz Lars , Wong Wing H. , Kay Mark , Wu Joseph , Snyder Michael
Published: December 2022

Tyrosine kinase inhibitors (TKIs) have been widely used for cancer chemotherapy, but they also cause cardiotoxicities in cancer patients. In this study, we used human stem cells as anin-vitrosystem to interrogate the mechanisms underlying drug-induced toxicity in differentiated cardiomyocytes, including anticancer tyrosine kinase inhibitor (TKI) drugs, including imatinib, sunitinib, and vandetanib. Sublethal TKI exposure produces multiple effects, including disarranged sarcomere structure, interrupted Ca2+-handling, and impaired mitochondrial function, evident of TKI-induced toxicity in differentiated cardiomyocytes. GATA4-mediated regulatory networks, including key mitochondrial target genes, emerge as significant molecular signatures in integrated analyses of transcriptome and chromatin accessibility dynamics. We find that, on a molecular level, GATA4 acts as a regulatory factor in mitochondrial biogenesis and OXPHOS by directly regulating specific metabolism-related genes, such asPPARGC1A. Functional genomic experiments targeting GATA4 reveals that GATA4 upregulation by CRISPR-activation is able to restore mitochondrial morphology and OXPHOS upon TKI exposure. In addition, we also identified that GATA4 is involved in regulation of mitochondrial biogenesis during early cardiac differentiation; inhibition of GATA4 during differentiation reduces mitochondrial DNA content, ATP production, and OXPHOS in differentiated cardiomyocytes, demonstrating a developmental role of GATA4 in metabolic management during early cardiac differentiation. Altogether, our study identifies a novel link between GATA4 and mitochondria in cardiomyocytes, and identifies GATA4 as a promising therapeutic target for reducing TKI-induced cardiotoxicity for human health.
Monkeypox-induced proctitis: a case report of an emerging complication
Authors: Rathore Azeem , Kahn Cameron , Reich Daniel , Qadir Nadim , Verdecia Jorge , House Jeffrey G.
Published: December 2022

At the outset of the 2022 human monkeypox virus outbreak, the World Health Organization described the self-limited disease as a rash illness associated with nonspecific symptoms such as fever, myalgias, and lymphadenopathy. Historically, the infection caused by this zoonotic virus has presented with rashes primarily on the face, palms, and soles of feet. However, emerging case report literature from the 2022 recent outbreak highlighted more atypical presentations ranging from ocular manifestations to myocarditis. We present a case of a 32-year-old African American male with a past medical history of poorly controlled acquired immunodeficiency syndrome and external hemorrhoids that presented for worsening rectal pain. The patient was afflicted with diffuse skin lesions even present on his hemorrhoids. Initial imaging significant circumferential rectal thickening consistent with proctitis. Subsequent polymerase chain reaction testing confirmed active monkeypox infection and a 14-day course of twice daily tecovirimat 600 mg was initiated to treat disseminated monkeypox infection. After improved pain control and starting antiviral treatment, the patient was discharged two days later. As more cases of monkeypox-associated proctitis emerge, clinicians should keep this disease in their differential due to the growing atypical presentations that have diverged from previous patterns to avoid the risk of misdiagnosing another sexually transmitted infection. Additionally, appropriate medical management is still not definitive and requires further development of evidence-based protocols to treat such patients.
Dealing with Wolves and Livestock Protection Measures in the Alps: Perspectives about Farmers and Shepherds Knowledge and Perceptions
Authors: Maria Benciolini , Julia Stauder
Published: December 2022

The current study aims at understanding the reasons behind herd protection measures rejection or approval among shepherds and livestock farmers in selected regions of the Alps. Through semi-structured interviews, the study examines the sources of knowledge and perceptions of target groups toward wolves and livestock protection. Furthermore, the study explores the problems related to the implementation of herd protection measures and to the exercise of the shepherd’s profession. The results clearly show multiple challenges related to livestock protection and farming that go beyond the sole problem of wolf presence. Key results highlight the general distrust of farmers towards official authorities or NGOs and the importance of peer-to-peer information for experience-based knowledge creation. Additionally, the potential social pressure within groups, and the need to support farmers and shepherds willing to adapt protection measures on a larger scale must be considered in future management actions.
Mechanism Based Designing, Synthesis and Evaluation of Nitrogen and Non-nitrogen Derivatives of Biphosphonates as Anti-inflammatory Agents
Authors: Nagar Akhil , Bardiya Ruchita , Shirkhedkar Atul , Patil Kalpesh R , Soni Viren , Modi Arjun , Shah Khushbu , Patel Roshani
Published: December 2022

The inflammatory mechanisms are complex due to the involvement of multiple pathways. The messengers like PIP2 and IP3 are phosphonate containing biomolecules which are desirable for the delivery of biological responses. In the present study, we designed a novel series of nitrogen and non-nitrogen containing bisphosphonates fused with more lipophilic chalcone moiety. We assume to maintain the hydrophilic ratio of BPs with hydrophobic chalcone substitution. The synthesized compounds 1–11, demonstrated potential anti-inflammatory activity against carrageenan-induced rat paw edema model and in-vitro COX-2 assay. The modifications over the synthesized derivatives were supported by in silico studies and SAR of bisphosphonates. In vitro study was carried out at concentration of 1µM while in vivo study was performed using the carrageenan-induced rat paw edema model. From the study it was concluded that the binding pattern of synthesized derivatives was remarkably similar to the co-crystallized ligand, and also the anti-inflammatory effect of compound was based on the interactions between bisphosphonates and amino acids. The distance between the P-C-P linkage of bisphosphonates to nitrogen and free carbon attached to nitrogen were found to be important for the maximum interaction and biological response considering the co-crystalized ligand in another enzyme. An assessment of cyclooxygenase inhibitory activity (in vitro) of compounds (1, 9, and 11) revealed a structure activity relationship while in vivo inhibitory action of compound 9, 11, 1, 10, and 3 is indicative of its inhibitory action on the prostaglandin synthesis which may be mediated through the inhibition of COX-2 enzyme.
Convergent Encryption Enabled Secure Data Deduplication Algorithm for Cloud Environment
Authors: Ahmad Shahnawaz , Mehfuz Shabana , Shakeel Iman
Published: December 2022

The exponential growth of data management nowadays is quite a tedious and critical issue. It is also evident that methods employed for collecting data for cloud storage exert additional load on different cloud servers operated by many enterprises. Various approaches are used these days to reduce the burden on computer servers. One such approach is de-duplication, which has gained much attention due to its efficient, extensive storage system. In this approach, redundant data is removed, which improves storage utilization and reduces the cost of secure storage. International Data Corporation (IDC) reported 33 Zettabytes in 2018 to 175 ZB by 2025, putting cumbersome loads on present servers. Due to this enormous amount of data, it is challenging for the local and small servers, usually used in various enterprises, to handle it. It has also been observed that most data are generally duplicated in terms of space; therefore, data transmission places extra effort on small servers. This study provides a more comprehensive analysis of the literature on safe data duplication. Furthermore, it classifies the various secure data storage techniques applied at different levels of encrypted data collecting storage. Furthermore, this article looks into the classification of the de-duplication procedures as per literature and other Unified Modeling Language (UML) activity diagrams, exhibiting both their classification and detection difficulties. Moreover, current duplication techniques suffer from a couple of security challenges. Therefore, a convergent encryption algorithm has been proposed and implemented along with the de-duplication techniques, and the different UML diagrams and comparative analysis have illustrated the proposal's viability.
Dyslipidemia and metabolic syndrome among apparently healthy adolescents in Nigerian Secondary Schools: A Preliminary Investigation
Authors: Holdbrooke Susan , Afolabi Bamgboye Morakinyo
Published: December 2022

Introduction:
Metabolic syndrome (MetS), a group of risk factors that occur together, increases the possibility of heart disease, stroke, and type 2 diabetes. In MetS, blood pressure and blood sugar are elevated, excess body fat accumulate around the waist and there is dyslipidemia (abnormally high blood cholesterol levels). Most of the disorders related with MS have no symptoms.
Objective
To determine the prevalence of dyslipidemia and other risk factors for metabolic syndrome among apparently health adolescents in Secondary Schools in Lagos, Nigeria.
Materials and Methods
An institution-based, cross-sectional, descriptive study was conducted from October 2019 to March 2020. Multi-stage sampling approach was used to recruit 624 adolescent students in secondary schools in Lagos State of Nigeria. Data were collected using a structured questionnaire and fasting venous blood samples were collected for serum glucose and lipid profile analysis. Systolic and diastolic blood pressures were appropriately measured. Data were analyzed using NCSS version 22 (Kaysville, Utah, USA). Relevant statistical analyses were performed and p-value < 0.05 was considered as statistically significant.
Results
Overall, the median values (mg/dl) of triglyceride (TG), total cholesterol (T-Chol), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were 180.8, 199.4, 289.6 and 55.9 respectively. Isolated lipid profile abnormality of hypertriglyceridemia, hypercholesterolemia, high level of low-density lipoprotein (LDL-C) and low level of high-density lipoprotein (HDL-C) were observed in 70.5%, 49.7%, 85.9%, and 24.7% study participants. The overall prevalence of metabolic (MetS) was 5.9%) more frequent among males 7.5%, mid-adolescents (8.2%) and among overweight subjects (20.0%).
Conclusion
Fasting blood sugar and lipid profiles as well as blood pressure and anthropometric indices of adolescents in secondary schools were evaluated for dyslipidemia and metabolic syndrome. A high proportion of them presented with hypertriglyceridemia and metabolic syndrome, especially males, those in mid adolescents and those overweight. A nation-wide, multi-center and multi-disciplinary study of metabolic syndrome should be conducted, through implementation of routine screening, for early recognition of and appropriate intervention measures on, identified risk factors, and for the treatments and prevention of metabolic syndrome in adolescents.
Analysis of associated factors with success of bariatric surgery: rs1800497 ANKK1, rs1799732 DRD2 genetic polymorphisms, eating behavior, hedonic hunger, and depressive symptoms
Authors: Daza-Hernandez Edgar Steven , Perez-Luque Elva , Cordero Claudia Martínez , Figueroa-Vega Nicte , Muñoz-Montes Norberto
Published: December 2022

Introduction:
Obesity is considered a risk factor for other chronic illnesses, such as type 2 diabetes mellitus, hypertension, dyslipidemia, cardiovascular diseases, and other disorders. A therapeutic approach is bariatric surgery (BS), which is considered the most effective intervention for severe obesity and ameliorates these comorbidities. Some polymorphisms are considered markers for addictive disorders and hedonic hunger and are associated with BMI. The objective was to analyze factors associated with the success of BS, including rs1800497 ANKK1 and rs1799732 DRD2 polymorphisms, eating behavior, hedonic hunger, and depressive symptoms.
Methods
We included 101 patients who underwent BS from 2010 to 2021 from the surgery service of a public hospital. We registered anthropometry and applied 3 questionnaires to evaluate eating behavior (TFEQ-R18), hedonic hunger (PFS), and depressive symptoms (PHQ-9). We typed the ANKK1 rs1800497 and rs1799732 DRD2 polymorphisms and evaluated biochemistry characteristics.
Results
The median weight loss was 34.7 kg with a BMI of 33.8 kg/m2. Weight loss was negatively associated with triglycerides (p = 0.011) and positively associated with the TFEQ-R18 (p = 0.006). Regarding polymorphisms, rs1800497 ANKK1 was associated with TFEQ-R18 (OR = 1.13 (1.02–1.25), p = 0.009), but rs1799732 DRD2 was not associated with either studied variable. We also found a negative correlation of actual BMI with scholarship (r=-0.29, p = 0.02).
Conclusion
We observed an improvement in metabolic and anthropometric parameters post-BS. Interestingly, the ANKK1 Taq1A polymorphism was associated with eating behavior, and scholarship with BMI could consider predictors of BS outcomes.
Safety outcomes in patients with rheumatoid arthritis treated with abatacept: results from a multinational surveillance study across seven European registries
Authors: Dominique Alyssa , Hetland Merete Lund , Finckh Axel , Gottenberg Jacques-Eric , Iannone Florenzo , Caporali Roberto , Kou Tzuyung Douglas , Nordstrom Dan , Hernandez Maria Victoria , Sánchez-Piedra Carlos , Sánchez-Alonso Fernando , Pavelka Karel , Bond T. Christopher , Simon Teresa A.
Published: December 2022

Background
Patients with rheumatoid arthritis (RA) have an increased risk of infection and malignancy compared with the general population. Infection risk is increased further with the use of disease-modifying antirheumatic drugs (DMARDs), whereas evidence on whether the use of biologic DMARDs increases cancer risk remains equivocal. This single-arm, post-marketing study estimated the incidence of prespecified infection and malignancy outcomes in patients with RA treated with intravenous or subcutaneous abatacept.
Methods
Data were included from seven European RA quality registries: ATTRA (Anti-TNF Therapy in Rheumatoid Arthritis [Czech Republic]), DANBIO (Danish Rheumatologic Database), ROB-FIN (National Registry of Biological Treatment in Finland), ORA (Orencia and Rheumatoid Arthritis [France]), GISEA (Italian Group for the Study of Early Arthritis), BIOBADASER (Spanish Register of Adverse Events of Biological Therapies in Rheumatic Diseases), and the SCQM (Swiss Clinical Quality Management) system. Each registry is unique with respect to design, data collection, definition of study cohort, reporting, and validation of outcomes. In general, registries defined the index date as the first day of abatacept treatment and reported data for infections requiring hospitalization and overall malignancies; data for other infection and malignancy outcomes were not available for every cohort. Abatacept exposure was measured in patient-years (p-y). Incidence rates (IRs) were calculated as number of events per 1000 p-y of follow-up with 95% confidence intervals.
Results
Over 5000 patients with RA treated with abatacept were included. Most patients (78–85%) were female and the mean age range was 52–58 years. Baseline characteristics were largely consistent across registries. Among patients treated with abatacept, IRs for infections requiring hospitalization across the registries ranged from 4 to 100 events per 1000 p-y, while IRs for overall malignancy ranged from 3 to 19 per 1000 p-y.
Conclusions
Despite heterogeneity between registries in terms of design, data collection, and ascertainment of safety outcomes, as well as the possibility of under-reporting of adverse events in observational studies, the safety profile of abatacept reported here was largely consistent with previous findings in patients with RA treated with abatacept, with no new or increased risks of infection or malignancy.
Trial registration:
not applicable
A fast and high-order IMEX method for non-linear time-space-fractional reaction-diffusion equations
Authors: Kazmi Kamran
Published: December 2022

An efficient and high-order numerical method is presented for solving a time-space-fractional reaction-diffusion equation. Matrix transfer technique based on fourth order compact finite differences are first used to discretize the space-fractional Laplacian operator which results in a system with a linear stiff term. Then an implicit-explicit (IMEX) trapezoidal product-integration rule is implemented for time integration which treats the stiff linear term implicitly and non-linear non-stiff term explicitly. The stability and convergence of the method are analyzed. Due to the discontinuity of the solution derivative at t = 0, the numerical method is only 1+α order accurate in time where α is the order of the time-fractional derivative. Richardson extrapolation is introduced to obtain a modified version of the method which is second order accurate in time. A fast algorithm based on discrete sine transform is also implemented to reduce the cost of computing the discretized space-fractional Laplacian operator.
A prospective, multicenter, cohort study to evaluate the long-term quality of life and psychological factors among patients with breast cancer, 5-year follow-up: a study protocol
Authors: Lahiji Mahsa Raji , Sajadian Akram , Hashemi Elahe , Montazeri Ali , Anbiaee Robab , Omranipour Ramesh , Nafissi Nahid , Heydari Leila , Rasouli Mohsen , Kazemnejad Anoshirvan , Alaeddini Farshid
Published: December 2022

Background: Breast cancer is the most commonly occurring cancer among women worldwide. Quality of life and psychological status of patients with breast cancer could be affected after diagnosis, especially during treatment. The main objective of this study is investigation of long-term influence of breast cancer on quality of life’s dimensions and mental health status.
Methods: This is a multicenter, ongoing longitudinal prospective cohort study which administered in national institute for medical research development in May 2018 in Iran. 1250 patients with breast cancer who were completed their treatments, will be recruited from 5 referral medical centers located in Tehran, to be followed for 5 years. Questionnaires for evaluating the primary and secondary outcomes will be complete by trained investigators during face-to-face interviews with each participant in three phases: immediately after treatment, 1 year and 5 years later. Data will be collected on socio-demographic, quality of life, body image, hope, psychological problems such as anxiety, depression and mood, also sexual function and physical activity. Data will be analyzed in each phase and at the end of the project by SPSS version 22.
Discussion: It is the first nationwide, prospective, cohort study with large sample size, long-term follow-up and broad research aims which will evaluate quality of life-related factors in Iranian breast cancer population to justify the existing gap in literature.
Trial registration number: National Institute for Medical Research Development (NIMAD) (IR.NIMAD.REC.1397.322) July 1th, 2018.
Genome-wide association study identifies genes and networks that influence innate immune response in an age-specific manner in Drosophila melanogaster
Authors: Campbell Shonda , Gudino Isabella , Rhee Mary , Leips Jeff
Published: December 2022

Background
The innate immune response is an evolutionarily conserved process that is essential for survival in multicellular organisms. As individuals age, immune functions decline, a phenomenon known as immunosenescence, reducing one’s ability to fight infections. While immunosenescence is a universal feature of aging, the rate at which immune functions decline with age varies greatly among individuals and this variation has a genetic component. However, we have limited knowledge of the actual genes that contribute to this variation.
Methods
Here, we used 183 genetically distinct genotypes of the Drosophila Genetic Reference panel (DGRP) to assess their ability to clear an infection at one and five weeks of age. We then carried out a genome-wide association study (GWAS) to identify candidate genes that contribute to differences in immune responses among genotypes at each age.
Results
We found that, on average, the ability to clear infection declined by 70% with age. However, the effect of age on clearance ability varied significantly among genotypes. We identified a total of 242 single nucleotide polymorphisms (SNPs) and 107 candidate genes associated with variation in clearance ability. Polymorphisms in 48 genes were associated with clearance in 1 week old flies and fifty-nine genes were associated with clearance ability at 5 weeks of age. Only one gene, a G-coupled protein receptor, CG31760, was a candidate at both ages. Of the 107 candidate genes, 25 were mapped to genetic networks.
Conclusion
Our results identify candidate genes that could be targets for age-appropriate therapeutic treatments to maintain or restore immune function in the elderly.
Integration of bioinformatics and machine learning strategies identifies APM-related gene signatures to predict clinical outcomes and therapeutic responses for breast cancer patients
Authors: Shen Hong-yu , Xu Jia-lin , Zhu Zhen , Liang Ming-xing , Xu Di , Chen Wen-quan , Fang Zheng , Tang Jin-hai
Published: December 2022

Background: Tumor antigenicity and efficiency of antigen presentation jointly influence tumor immunogenicity, which largely determines the effectiveness of immune checkpoint blockade (ICB). However, the role of altered antigen processing and presentation machinery (APM) in breast cancer (BRCA) has not been fully elucidated.
Methods: A series of bioinformatic analyses and machine learning strategies were performed to construct APM-related gene signatures to guide personalized treatment for BRCA patients. A single-sample gene set enrichment analysis (ssGSEA) algorithm and weighted gene co-expression network analysis (WGCNA) were combined to screen for BRCA-specific APM-related genes. The non-negative matrix factorization (NMF) algorithm was used to divide the cohort into different clusters and the fgsea algorithm was applied to investigate the altered signaling pathways. Random survival forest (RSF) and the least absolute shrinkage and selection operator (Lasso) Cox regression analysis were combined to construct an APM-related risk score (APMrs) signature to predict overall survival. Furthermore, a nomogram and decision tree were generated to improve predictive accuracy and risk stratification for individual patients. Based on Tumor Immune Dysfunction and Exclusion (TIDE) method, random forest (RF) and Lasso logistic regression model were combined to establish an APM-related immunotherapeutic response score (APMis). Finally, immune infiltration, immunomodulators, mutational patterns, and potentially applicable drugs were comprehensively analyzed in different APM-related risk groups. Results: In this study, APMrs and APMis showed favorable performances in risk stratification and therapeutic prediction for BRCA patients. APMrs exhibited more powerful prognostic capacity and accurate survival prediction compared to conventional clinicopathological features. APMrs was closely associated with distinct mutational patterns, immune cell infiltration and immunomodulators expression. Furthermore, the two APM-related gene signatures were independently validated in external cohorts with prognosis or immunotherapeutic responses. Potential applicable drugs and targets were further mined in the APMrs-high group.
Conclusion: The APM-related gene signatures established in our study could improve the personalized assessment of survival risk and guide ICB decision-making for BRCA patients.
HNRNPA2B1 mediated MircoRNA-92a upregulation and section acts a promising non-invasive diagnostic biomarker in colorectal cancer
Authors: Li Yiling , Li Kexin , Lou Xiaoying , Wu Yue , Seery Samuel , Xu Danfei , Pei Yuqing , Qian Benheng , Wu Yuxin , Liang Shuang , Wu Kui , Cui Wei
Published: December 2022

Background MicroRNA-92a (miR-92a) may serve as a novel promising biomarker in multiple cancers including colorectal cancer (CRC). However, the diagnostic accuracy and the underlying molecular mechanism of miR-92a in CRC is poorly understood. Method Diagnostic studies were retrieved from PubMed, Embase, the Cochrane Library, and Web of Science, up until May 2022. Besides, an independent validation participants group (n = 144) was recruited for stool miR-92a test to prove the diagnosis efficiency in CRC. Then, totally studies were enrolled for meta-analysis using pooled sensitivity, specificity, and diagnostic odds ratios (DOR), summary receiver operating characteristic (SROC) curve and area under the curve (AUC) analysis. Next, GEO datasets, TCGA dataset and previous study data were used to explore the relationship between HRNPA2B1 and miR-92a. Finally, cell experiments demonstrated the regulatory effect of HRNPA2B1 on miR-92a in vitro. Results We first carried out meta-analysis and found that serum/plasma miR-92a yield better diagnostic efficacy when compared to stool samples and CRC tissues. And this finding was validated by our independent study through stool sample. Multiple bioinformatics assay indicated that miR-92a expression was positively correlated with heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) expression and closely related with the clinical characteristics of CRC. Experimental evidence shown that knockdown of HNRNPA2B1 could significantly decreased miR-92a expression and secretion in CRC cell lines. HNRNPA2B1 mediated miR-92a via with N6-methyladenosine (m6A) RNA modification validated by both bioinformatic analysis and vitro experiments. Conclusions These findings indicate that HNRNPA2B1-m6A RNA modification derived mircoRNA-92a upregulation and section from the local CRC acts a candidate non-invasive serum biomarker in colorectal cancer. Our study provides a novel insight into miR-92a mechanisms in relation to both expression and secretion for CRC diagnosis.
Mixed localized wave solutions of the (2+1)-dimensional Fokas-Lenells equation
Authors: Song Huijie , Zhao Qiulan , Li Xinyue
Published: December 2022

In this paper, we investigate the mixed localized wave solutions of the (2+1)-dimensional Fokas-Lenells equation. These localized wave solutions contain solitons, degenerate solitons, lumps and lump chains. Our focus is the mixed solutions including solitons and degenerate solitons, lumps and lump chains. The effective method we use to obtain the above solutions is generalized (n, M)-fold Darboux transformation. The characteristics and properties of these solutions are discussed analytically and graphically. Actually, these solutions can change the strength of the interactions by adjusting parameters, and preserve their own properties throughout the interaction process.
Carotid Atherosclerosis and its Correlation with ApoB/ApoA-I and Non-HDL-c/HDL-c Ratios among Adults with Type 2 Diabetes: A Cross-Sectional Study in Southwestern Uganda
Authors: Saasita Patrick Kambale , Kaddumukasa Mark , Najjuma Josephine Nambi , Mbalinda Scovia Nalugo , Kaddumukasa Martin , Lekuya Hervé Monka , Nakibuuka Jane , Burant Christopher J. , Moore Shirley , Blixen Carol , Katabira Elly T. , Sajatovic Martha , Malunde Frederick , Acan Moses , Muyingo Anthony
Published: December 2022

Background: Type 2 diabetes mellitus (T2DM) poses an increased risk for cardiovascular disease (CVD) through atherosclerosis. The apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) (ApoB/ApoA-I) ratio is a powerful predictor of atherosclerotic CVD and is associated with carotid atherosclerosis (CA) in T2DM; however, this association had never been studied in our setting. This study set out to determine the prevalence of CA and its correlation with ApoB/ApoA-I and non-high-density lipoprotein cholesterol (non-HDL-c)/high-density lipoprotein cholesterol (non-HDL-c/HDL-c) ratios among patients with T2DM in Southwestern Uganda.
Methods: A cross-sectional study conducted at Mbarara Regional Referral Hospital included 212 ambulatory patients with T2DM aged ≥40 years. Socio-demographic, clinical, and behavioral characteristics were determined. Fasting blood samples were collected for measuring serum glucose, Apo B, Apo A-I, and the routine lipid profile. The apoB/apoA-I ratio and the non-HDL-c/HDL-c ratio were calculated. Carotid intima-media thickness (CIMT) was measured bilaterally at three points by high-resolution B-mode ultrasound. A mean value of six measurements from the right and left carotid arteries was used as a measure of CIMT. Carotid atherosclerosis was defined as a mean CIMT≥1.0 mm. A stepwise multivariate regression analysis and Pearson’s correlation were used to assess the association and correlation of CIMT with clinical factors, apoB/apoA-I, and non-HDL/HDL-c ratios.
Results: The prevalence of CA was 35.9%. Age ≥55 years (OR 3.1; 95% CI:1.4 – 7.1; p<007) and age ≥ 65 years (OR 10.2; 95% CI: 3.5–29.5; p-< 0.001), coinfection with HIV (OR 3.8; 95% CI: 1.1–12.5; p-value = 0.030), high waist circumference (OR 2.7; 95% CI: 1.2 – 6.5; p-value = 0.022) and non-HDL-c/HDL-c ratio ≥ 4 (OR 3.0; 95% CI 1.0–8.5; p = 0.045) were associated with CA. The apoB/apoA-I ratio was elevated among T2DM patients with CA, but was not significantly associated with CA (OR 1.0; 95% CI: 0.4 – 2.5, p= 0.25). The optimal non-HDL-c/HDL-c ratio cutoff value for detecting CA was 3.39 (a sensitivity of 60.53% and a specificity of 54.41%).
Conclusion: There is a high prevalence of CA among patients with T2DM. The non-HDL-c/HDL-c ratio was significantly associated with high CIMT but not the apoB/apoA-I ratio.
Detectability analysis of very low frequency earthquakes: Methods and application in Nankai using F-net and DONET broadband seismometers
Authors: Takemura Shunsuke , Baba Satoru , Yabe Suguru , Yamashita Yusuke , Shiomi Katsuhiko , Matsuzawa Takanori
Published: December 2022

For a more quantitative discussion of slow earthquake activity, we evaluated the detectable limits of very low frequency earthquakes (VLFEs), which are seismic slow earthquakes observed in very low frequency (< 0.05 Hz) bands, in the Nankai subduction zone. We performed numerical simulations using a local three-dimensional model and used the observed noise level of permanent broadband seismometers. First, we investigated the effects of the source-time functions on the maximum amplitudes of the VLFE signals at a certain station. The maximum amplitudes of the VLFE signals were controlled by the VLFE moment rate. The detectable limit of VLFEs at each source location can be defined as the lowest moment rate of detectable VLFEs, which radiate signals larger than the noise levels of any component at ≥ 3 stations. For inland seismometers only, the detectable limits of VLFEs at deep (30–40 km) and shallow (≤ 10 km) depths were 1012.5–1012.8 and 1013.2 Nm/s, respectively. Due to the geometrical spreading of VLFE signals and large noise levels in horizontal components, offshore seismometers improved the detectability of shallow VLFEs in regions where seismometers were densely deployed. Based on our detectability and published catalogs, shallow slow earthquakes are less active south-southwest off the Kii Peninsula, where geodetic studies expect mechanical coupling.
A simple score for predicting cancer cachexia status in patients with Stage I–III colorectal cancer: Cancer Cachexia Score
Authors: Takano Yasuhiro , Kodera Keita , Tsukihara Shu , Takahashi Sumika , Yasunobu Kobayashi , Kanno Hironori , Ishiyama Satoshi , Saito Ryota , Hanyu Nobuyoshi , Eto Ken
Published: December 2022

Purpose: Cancer cachexia, a complex multifactorial syndrome associated with sarcopenia, negatively affects quality of life and survival in patients with several cancers. We aimed to develop a new score for cachexia assessment and evaluate its effectiveness in classification of patients undergoing radical resection for colorectal cancer.
Methods: This study included 396 patients who underwent radical resection for Stage I–III colorectal cancer. To develop the Cancer Cachexia Score (CCS), we analyzed predictive factors of cachexia status related to the development of sarcopenia and incorporated significant factors into the score. We then evaluated the relationship between CCS and overall survival after radical resection for colorectal cancer.
Results: As body mass index (P < 0.001), prognostic nutritional index (P = 0.005), and tumor volume (P < 0.001) were significantly associated with the development of sarcopenia, these factors were included in CCS. Using CCS, 221 (56 %), 98 (25 %), and 77 (19 %) patients were diagnosed with mild, moderate, and severe cancer cachexia, respectively. In multivariate analysis, severe CCS (P < 0.001), N stage 1–2 (P < 0.001), and occurrence of postoperative complications (P = 0.007) were independent predictors of disease-free survival. Age ≥ 65 years (P = 0.009), severe CCS (P < 0.001), and N stage 1–2 (P < 0.001) were independent predictors of overall survival.
Conclusions: CCS may be a strong predictor of poor survival in patients with colorectal cancer, suggesting the usefulness of CCS in classifying patients according to their cachexia status and predicting postoperative prognosis.