bluuebunny/crossref_metadata_2025 huggingface dataset:
The results of an experimental study of the mud cake growth
Authors: Golikov N. A.
Published: October 2022

To determine the formation parameters of mud cake, experiments were carried out on the installation developed by the author in IPGG SB RAS. The experiment was carried out on a sample of West Sibirea’s sandstone. In the process of the experiment, the thickness of the mud cake was measured and the permeability of the «sample-cake» system. According to the results of the experiments, a comparison of the thickness and permeability of the mud cake with theoretical dependence was carried out.
Optimization of the PLT complex for the problems of the inflow profile estimate in low-rate gas wells on the example of the Berezovskaya suite
Authors: Fedosova A. V. , Mitrofanov D. A.
Published: October 2022

Currently, more and more attention is being paid to hard-to-recover reserves characterized by low flow rates. And one of the problematic issues in the process of studying them is the correct determination of the inflow profile by conducting production logging tool (PLT). In this regard, there is a need to increase the information content of the PLT in the conditions of gas reservoirs with a low flow rate, where the Berezovskaya suite is an actual research area. In this paper, a new PLT scheme is proposed, based on the actual PLT scheme, which will allow more reliable determination of operating intervals in low-rate gas-saturated reservoirs.
Change in the magnetic moment of an equivalent dipole and the distance to it according to oservatories (1950-2020)
Authors: Gniteeva O. S. , Kovalev A. A. , Semakov N. N.
Published: October 2022

The average annual values of the characteristics of the magnetic field obtained at observatories from different regions make it possible to calculate the values of the local magnetic constant in the corresponding years. Changes in this parameter can be associated with both a change in the magnetic moment of an equivalent dipole and a change in the distance to it. The paper assessed the magnitude of these changes over the past 60 years and the possible combined influence of both of these factors.
Determination of the Required Air Exchange on a Metro Line with a Double-Track Tunnel
Authors: Alferova E. L.
Published: October 2022

The paper investigates the air distribution in the subway tunnel ventilation network with a double-track tunnel, depending on the length of the line under study. The study of static air distribution was carried out in the analytical complex of designing ventilation, air treatment and air conditioning systems of mining enterprises based on the contour flow method. It is shown that when the number of runs on the line is more than two, the provision of air exchange is carried out by the same fans in any mode of operation of tunnel ventilation. At the same time, the maximum parameters of the fans in the normal operation of tunnel ventilation are: 73.8 m/s capacity and 684 Pa pressure, and in emergency mode: 66 m/s capacity and 843 Pa pressure.
Justification of the layout of the automated complex for the construction of degassing wells from the surface
Authors: Danilov B. B. , Cheshchin D. O. , Plokhikh V. V.
Published: October 2022

The article discusses the technology of well construction for degassing coal seams. The most used drilling rigs at domestic enterprises are presented. According to their capabilities, well drilling methods and corresponding rock cutting tools are analyzed. The most used method of casing a degassing well is described, its main disadvantages are identified. It is shown that the creation of the proposed automated complex with a new class of adaptive impact machines can eliminate these shortcomings. Its schematic diagram is presented and the main technological and scientific tasks for creating such a complex are determined.
Some results of laboratory researches of the vibration effect on the cohesive fine-dispersed geomaterials strength characteristics
Authors: Kulikova E. G.
Published: October 2022

The effect of strength characteristics, and specifically the cohesion and the angle of internal friction, on the conditions for the displacement and compaction of dispersed materials is described. The employment of the physical modeling method in the researches of these parameters changes under vibration is justified. The laboratory stand, a measuring complex and a technique for experiments performed in two stages are presented. At the first stage, the dispersed material was loaded statically, and the efficiency of moisture and clay content on its strength characteristics was determined. At the second stage, the vibrational acceleration effected, additional to the static one, on the change in the effective cohesion and the effective angle of internal friction of dispersed materials of various compositions and moisture was considered. Recommendations on using of the vibration impact on fine-dispersed materials regimes, directed at the efficiency increase and reducing the energy intensity of the forced processes of their movement and compaction, have been established.
Numerical calculation of rock deformation during mining operations
Authors: Mirenkov V. E.
Published: October 2022

The paper analyzes the classical definition of the stress field of an intact rock mass and proposes a new one. The definition of the daytime surface is generalized in the case of a work-out that goes to the border. The process of transition to the additional task of calculating elastic stresses and displacements near mutually influencing workings, independent of the own weight of the removed rocks, is described. A two-dimensional version of an array of rocks is considered. The presence of a recess, workings presupposes the removal of rocks in an appropriate volume, which only causes displacements and stresses. Models from elastic to elastic-plastic do not take into account the own weight of rocks and other irreversible processes, but consider weightless areas of counting. If the area of the rock deformation account near the mine contains an infinitely distant point, then, according to the general theory of equations of mathematical physics, the stresses and displacements found tend to zero when moving away from the cavity, a well-known fact in practice. The results obtained are significant when the transition from open to underground mining of minerals takes into account the sequence of workings, without which there is no mining. It is proved that the calculation of deformation in the vicinity of any weakening is carried out only through an additional task, formulating symmetric boundary conditions on the contour due to the refusal to take into account the weight of rocks.
Data interpretation method in HF stress measurement for the total stress tensor determination in rock mass
Authors: Panov A. V. , Miroshnichenko N. A. , Skulkin A. A.
Published: October 2022

The data interpretation method is validated for the hydraulic fracturing stress measurements for determining simultaneously all components of external stress tensor in rock mass in the vicinity of underground geotechnical structures. The analysis of the alternative patterns of 6 measurement boreholes reveals allowable drilling directions of boreholes to ensure the formulated problem resolvability. The analysis includes the solution of direct problems on finding “the normal stresses in the areas orthogonal to the axes of the boreholes at the known external stresses” and the solution of an inverse problem on finding the external stresses. In the proposed method, the input information may be the data obtained in the in-situ HF stress measurement. The numerical experiments with the synthetic input data determine allowable variations in orientation of measurement holes in directional drilling such that the measuring fault of external stresses is no thigher than 10%.
A physical model and a stand for the research of a single-acting hydroimpact device
Authors: Gorodilov L. V. , Kudryavcev V. G. , Pershin A. I.
Published: October 2022

The paper presents a physical model of a single-acting hydroimpact device. Its design can be used to create a hydraulic punch for drilling wells in soft soils. A stand with a clamping device has been developed to simulate the friction force acting on the punch housing when it moves in the soil. Methods of recording dynamic characteristics of working cycles of the hydraulic device are worked out. Tests were carried out with changes in the force acting on the housing from the clamping device. Oscillograms of the characteristics of working cycles (displacements of the housing and striker, pressures in the working chambers and the accumulator) are given.
Oil in Novosibirsk region: first discoveries and long-term prospects
Authors: Zapivalov N. P.
Published: October 2022

The article discusses the problems of petroleum mining and oil-field development in the northern part of Novosibirsk region, and the history of oil discoveries. The author proposes to set up a testing ground for oil recovery techniques in this area characterized by geological diversity.
Stress state analysis of rock mass in mining close-spaced coal seams with smooth roof subsidence
Authors: Seryakov V. M.
Published: October 2022

The author analyzes stress state of rock mass in mining bedded deposits with roof rock deformation in the course of the smooth subsidence of the roof in the mined-out area. The analysis focuses on modeling roof and floor interaction in roadways, which governs the distribution and values of stresses in the zones of the abutment pressure and stress relief. The features of stress redistribution in enclosing rock mass during successive mining of closely spaced coal seams are studied. The recommendations on selection of the parameters of technology for joint mining of closely spaced coal seams with regard to mutual effect of mining-induced geomechanical processes are given.
Application of Waves with Circular Polarization in Solving Inverse Problems of Magnetotelluric Sounding
Authors: Plotkin V. V.
Published: October 2022

With the help of numerical experiments results of application of waves with circular polarization in solution of inverse problems of magnetotelluric sounding are considered.
Geoelectric structure of the section on the Anmangynda ice (Magadan region) according to the data of the TEM method
Authors: Potapov V. V. , Makarieva O. M. , Olenchenko V. V.
Published: October 2022

In March of 2021, measurements were carried out by the TEM method on the Anmangynda aufeis in the Magadan region. The purpose of the research was to use the TEM method to determine the places of discharge of groundwater, which presumably feeds the aufeis, and to determine the geoelectric structure of the environment under the aufeis and its immediate surroundings to depths of 500 meters. Within the research area, profile soundings were performed by the TEM method, along 8 profiles of different lengths that intersect the aufeis itself and the bed of the Anmangynda River upstream and downstream. The measurements were carried out by a generator loop measuring 71 * 71 meters, a measuring loop measuring 20 * 20 meters with a distance of 100 meters from the center of the generator loop. When conducting research on the Anmangynda aufeis, 98 pickets were measured along 9 profiles. Within the research area, the electrical resistivity of rocks is determined primarily by their lithological features, degree of fracturing and material composition. This significantly complicates the geocryological interpretation of the sections and makes it almost impossible to isolate taliks in conditions of low-resistance clay shales. The places of groundwater outlets to the surface above the aufeis glade spatially coincide with the access to the surface of the steeply falling zones of the lowered UES, interpreted as faults along which the discharge of groundwater is likely to occur.
Increase in rock drill penetration depth
Authors: Alekseev S. E. , Kubanychbek B.
Published: October 2022

The application range of remote drilling machines is described. The common shortage of these machines is the dependence of the blow energy transfer to the bottomhole on the bottomhole depth. Aimed to reduce the influence of this factor, it is proposed to use the mixed-type method of drilling with a downhole rock drill to be placed directly at the bottomhole. The key element of this method is a small-size DTH rock drill. The layout of the rock drill and its prototype testing results are presented.
Higiene Sanitasi Pengolahaan dan Keberadaan Bakteri E. coli pada Es Teh di Warung Makan Kelurahan Mamboro Palu Utara
Authors: Politon Fellysca V. M. , Novarianti Novarianti
Published: October 2022

Pendahuluan: Minuman es teh dapat terkontaminasi oleh beberapa jenis mikroba apabila pengolahannya tidak memenuhi standar kesehatan. Misalnya air tidak dimasak hingga mendidih. Mikroba yang terdapat pada minuman ini adalah jenis bakteri Escherichia coli. Tujuan: Tujuan penelitian untuk mengetahui higiene sanitasi pengolahan dengan keberadaan bakteri E. coli pada minuman Es Teh yang dijual Di Warung Makan Kelurahan Mamboro Palu Utara. Metode: Metode penelitian ini adalah deskriptif  dengan pendekatan observasional pengolahan es teh dan pemeriksaan keberadaan bakteri E. coli pada es teh. Populasi dan sampel adalah 9 kantong plastik es teh masing-masing 1 kantong  dari 9 warung makan  di Kelurahan Mamboro Palu Utara. Hasil: Hasil penelitian, Higiene pengolahan makanan Tidak memenuhi syarat dengan nilai yang diperoleh 55% - <75%. sanitasi pengolahan dari hasil observasi mendapatkan 3 rumah makan dengan skor ≥ 75 % kategori memenuhi syarat dan 6 rumah makan nilai presentasi yang di dapat 55% - <75% kategori tidak memenuhi syarat). Pengujian 9 sampel ditemukan mengandung bakteri E. coli. Kesimpulan: Higiene pengolahan makanan tidak memenuhi syarat, Sanitasi pengolahan sebagian besar memenuhi syarat. Pada es teh yang dijual di Kelurahan Mamboro Palu utara 100% bernilai positif mengandung bakteri E. coli (Tidak Memenuhi Syarat).
The human DEAD-box helicase DDX3X as a regulator of mRNA translation
Authors: Ryan Cathal S. , Schröder Martina
Published: October 2022

The human DEAD-box protein DDX3X is an RNA remodelling enzyme that has been implicated in various aspects of RNA metabolism. In addition, like many DEAD-box proteins, it has non-conventional functions that are independent of its enzymatic activity, e.g., DDX3X acts as an adaptor molecule in innate immune signalling pathways. DDX3X has been linked to several human diseases. For example, somatic mutations in DDX3X were identified in various human cancers, andde novogermline mutations cause a neurodevelopmental condition now termed ‘DDX3X syndrome’. DDX3X is also an important host factor in many different viral infections, where it can have pro-or anti-viral effects depending on the specific virus. The regulation of translation initiation for specific mRNA transcripts is likely a central cellular function of DDX3X, yet many questions regarding its exact targets and mechanisms of action remain unanswered. In this review, we explore the current knowledge about DDX3X’s physiological RNA targets and summarise its interactions with the translation machinery. A role for DDX3X in translational reprogramming during cellular stress is emerging, where it may be involved in the regulation of stress granule formation and in mediating non-canonical translation initiation. Finally, we also discuss the role of DDX3X-mediated translation regulation during viral infections. Dysregulation of DDX3X’s function in mRNA translation likely contributes to its involvement in disease pathophysiology. Thus, a better understanding of its exact mechanisms for regulating translation of specific mRNA targets is important, so that we can potentially develop therapeutic strategies for overcoming the negative effects of its dysregulation.
Identification of tumor antigens and immunogenic cell death-related subtypes for the improvement of immunotherapy of breast cancer
Authors: Cao Xi , Zhou Xingtong , Chen Chang , Wang Zhe , Sun Qiang
Published: October 2022

The current immunotherapy strategy for breast cancer is limited. Tumor neoantigens have been proven to be a promising biomarker and potential target of immunotherapy in a variety of tumors. However, their effectiveness for breast cancer remains unclear. Immunogenic cell death (ICD) is a regulated form of cell death that can reshape the tumor immune microenvironment and activate adaptive immune responses. To this end, we screened potential antigens that could be used both for the development of immunotherapy and differentiating the patient-specific immune responses based on ICD-related risk signatures, in order to formulate an accurate scheme for breast cancer immunotherapy. We retrieved the gene expression profiles of the breast invasive cancer cohort and their corresponding clinical control data from The Cancer Genome Atlas. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to evaluate tumor antigen expression, the cBioPortal program was used to identify genetic variations, and the TIMER website was used to estimate the immune infiltration signatures. The risk score predictive model based on the ICD-related genes was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm, and the cohort was divided into low- and high-risk score groups. Two tumor antigens, namely, CCNE1 and PLK1, were associated with poor prognosis and infiltration of antigen-presenting cells. Furthermore, the ICD-related risk signature could significantly predict survival outcomes. The risk groups based on the ICD-related signature predictive model showed diverse immune infiltration and molecular and clinical features. The high-risk group was associated with low immune cell infiltration, immune score, expression of immune checkpoints, and human leukocyte antigen genes but high levels of CCNE1 and PLK1 and poor survival outcome. In conclusion, CCNE1 and PLK1 were identified as potential antigens in breast cancer. The ICD-related prognostic model distinguished immune response heterogeneity and predicted prognosis. Patients with high ICD-related risk scores were suitable to receive combination treatments based on CCNE1 or PLK1 and immune checkpoint inhibitors. In the future, these results will help us develop more accurate treatment schemes for patients with breast cancer.
A simple interactive robot to promote computational thinking
Authors: Funk Matthias , Cascalho José , Santos Ana Isabel , Pedro Francisco , Medeiros Paulo , Amaral Bárbara , Domingos Manuel , Ramos Alberto , Mendes Armando
Published: October 2022

This paper described the functionalities of a simple robot adopted in the classroom to promote computational thinking (CT) in the context of the project PeCOT—computational thinking with tangible objects. This robot, similar to some commercial educational robots, was developed to be used in primary education classroom contexts (second, third, and fourth grades) by children between 8 and 10 years old. PeCOT is a pedagogical intervention project and research project that will run over the next 2 years. The aim of this paper is to present the robot, how it works, and some activities that can be implemented in the educational context to promote CT skills, including learning in different subject areas, such as mathematics or natural science. Thus, we begin by presenting a general description of the robot. Next, we identify activities and formalize the programming steps for each of the activities. Finally, we discuss the potential that the robot and the proposed activities may have to promote the development of CT skills.
Balloon pulmonary angioplasty can be an effective and safe therapeutic option in non-surgical elderly patients
Authors: Velázquez Martín Maite , Maneiro Melón Nicolás , Albarrán González-Trevilla Agustín , Sarnago Cebada Fernando , Huertas Nieto Sergio , Cruz-Utrilla Alejandro , Hinojosa Williams , López-Gude María Jesús , Alonso Charterina Sergio , Revilla Ostolaza Yolanda , Aguilar Colindres Ricardo José , Arribas Ynsaurriaga Fernando , Escribano Subias Pilar
Published: October 2022

Background

Advanced age, frailty, and age-related comorbidities are the major causes of pulmonary endarterectomy disqualification in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) is an attractive and less invasive therapy for elderly patients. However, information about the safety, procedure tolerance, and effectiveness of BPA in elderly patients is limited.

Objective and methods

We aimed to analyze the safety, tolerance, and efficacy of BPA in CTEPH patients aged ≥70 years. This observational, descriptive, and retrospective series included consecutive patients aged ≥70 years, who underwent completed or interrupted BPA programs at a pulmonary hypertension reference center between May 2013 and May 2022.

Results

We enrolled 155 patients in our institution's BPA program. Among these, 33 patients were aged ≥70 years (mean age, 76.4 years; women, 75.8%) and had finished or interrupted BPA programs. In this cohort, we performed 116 BPA procedures (average, 3.6 ± 1.8 sessions/patient). Among the 33 patients, 19 (57.6%) completed treatment for all lobes, while the BPA program was interrupted in the remaining 14 (42.4%). Among all 33 patients, BPA was associated with a significant reduction in mean pulmonary arterial pressure (39.2 ± 9.3 vs. 32.8 ± 8.8 mmHg; p < 0.001) and pulmonary vascular resistance (6.7 ± 3.1 vs. 4.4 ± 2.0 WU; p < 0.001), along with an improvement in the cardiac index (2.5 ± 0.6 vs. 2.8 ± 0.7 L/min/m2; p = 0.04) with significant reductions in the N-terminal prohormone of brain natriuretic peptide level (pre-BPA, 353 pg/mL [207–1,960 pg/mL] vs. post-BPA, 167 pg/mL [73–629 pg/mL]; p = 0.03). The patients' functional class improved, and pulmonary hypertension-targeting drug requirements were significantly reduced. The pulmonary injury appeared in 3.4% of the 116 procedures, of which 50% were of grade 2. No patient of ≥70 years had grade 5 pulmonary injury. One periprocedural mortality was recorded (3%), and the median follow-up period was 2.8 years. The survival rate of the entire cohort at 1 and 3 years was 90.5 and 82.8%, respectively.

Conclusion

BPA is an effective and safe approach in patients aged ≥70 years. It significantly improves patients' functional class, hemodynamic, and biomarkers, and reduces their pulmonary hypertension-targeting medical therapy requirements. These successes were achieved even though a significant percentage of patients did not complete the therapy. The rates of procedural complications and periprocedural mortality were low. Survival at 1 and 3 years was good in comparison to that of younger patients undergoing BPA.
Using machine learning to find genes associated with sudden death
Authors: Zhou Kena , Cai Congbo , He Yi , Chen Zhihua
Published: October 2022

Objective

To search for significant biomarkers associated with sudden death (SD).

Methods

Differential genes were screened by comparing the whole blood samples from 15 cases of accidental death (AD) and 88 cases of SD. The protein-protein interaction (PPI) network selects core genes that interact most frequently. Machine learning is applied to find characteristic genes related to SD. The CIBERSORT method was used to explore the immune-microenvironment changes.

Results

A total of 10 core genes (MYL1, TNNC2, TNNT3, TCAP, TNNC1, TPM2, MYL2, TNNI1, ACTA1, CKM) were obtained and they were mainly related to myocarditis, hypertrophic myocarditis and dilated cardiomyopathy (DCM). Characteristic genes of MYL2 and TNNT3 associated with SD were established by machine learning. There was no significant change in the immune-microenvironment before and after SD.

Conclusion

Detecting characteristic genes is helpful to identify patients at high risk of SD and speculate the cause of death.
A systematic review and Bayesian network meta-analysis comparing left bundle branch pacing, his bundle branch pacing, and right ventricular pacing for atrioventricular block
Authors: Zhang Yue , Jia Yuan , Liu Jia , Du Rongpin
Published: October 2022

Background

Although right ventricular pacing (RVP) is recommended by most of the guidelines for atrioventricular block, it can cause electrical and mechanical desynchrony, impair left ventricular function, and increase the risk of atrial fibrillation. Recently, the His–Purkinje system pacing, including His bundle pacing (HBP) and left bundle branch pacing (LBBP), has emerged as a physiological pacing modality. However, few studies have compared their efficacy and safety in atrioventricular block (AVB).

Methods and results:

The PubMed, Web of Science, Cochrane Library, and ScienceDirect databases were searched for observational studies and randomized trials of patients with atrioventricular block requiring permanent pacing, from database inception until 10 January 2022. The primary outcomes were complications and heart failure hospitalization. The secondary outcomes included changes in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD), pacing parameters, procedure duration, and success rate. After extracting the data at baseline and the longest follow-up duration available, a pairwise meta-analysis and a Bayesian random-effects network meta-analysis were performed. Odds ratios (ORs) with 95% confidence intervals (CIs) or 95% credible intervals (CrIs) were calculated for dichotomous outcomes, whereas mean differences (MDs) with 95% CIs or 95% CrIs were calculated for continuous outcomes. Seven studies and 1,069 patients were included. Overall, 43.4% underwent LBBP, 33.5% HBP, and 23.1% RVP. Compared with RVP, LBBP and HBP were associated with a shorter paced QRS duration and a more preserved LVEF. HBP significantly increased the pacing threshold and reduced the R-wave amplitude. There was no difference in the risk of complications or the implant success rate. The pacing threshold remained stable during follow-up for the three pacing modalities. The pacing impedance was significantly reduced in HBP, while a numerical but non-significant pacing impedance decrease was observed in both LBBP and RVP. LBBP was associated with an increased R-wave amplitude during follow-up.

Conclusion

In this systematic review and network meta-analysis, HBP and LBBP were superior to RVP in paced QRS duration and preservation of LVEF for patients with atrioventricular block. LBBP was associated with a lower pacing threshold and a greater R-wave amplitude than HBP. However, the stability of the pacing output of LBBP may be a concern. Further investigation of the long-term efficacy in left ventricular function and the risk of heart failure hospitalization is needed.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=315046], identifier [CRD42022315046].
Left ventricular remodeling following aortic root and ascending aneurysm repair
Authors: Houben Ignas B. , Chu Angel K. Y. , Yang Bo , Kim Karen M. , Fukuhara Shinichi , van Herwaarden Joost A. , Moll Frans L. , Nordsletten David A. , Figueroa C. Alberto , Burris Nicholas S. , Patel Himanshu J.
Published: October 2022

Objective

Adverse left ventricular remodeling due to a mismatch between stiffness of native aortic tissue and current polyester grafts may be under-recognized. This study was conducted to evaluate the impact of proximal aortic replacement on adverse remodeling of the left ventricle.

Materials and methods

All aortic root and ascending aortic aneurysm patients were identified (n = 2,001, 2006–2019). The study cohort consisted of a subset of patients (n = 98) with two or more electrocardiogram (ECG)-gated CT angiograms, but without concomitant aortic valve disease or bicuspid aortic valve, connective tissue disease, acute aortic syndrome or prior history of aortic repair or mitral valve surgery. LV myocardial mass was measured from CT data and indexed to body surface area (LVMI). The study cohort was divided into a surgery group (n = 47) and a control group; optimal medical therapy group (OMT, n = 51).

Results

The mean age was 60 ± 11 years (80% male). Beta-blocker use was significantly more frequent in the surgery group (89 vs. 57%, p < 0.001), whereas, all other antihypertensive drugs were more frequent in the OMT group. The average follow-up was 9.1 ± 4.0 months for the surgery group and 13.7 ± 6.3 months for the OMT group. Average LVMI at baseline was similar in both groups (p = 0.934). LVMI increased significantly in the surgery group compared to the OMT group (3.7 ± 4.1 vs. 0.6 ± 4.4 g/m2, p = 0.001). Surgery, baseline LVMI, age, and sex were found to be independent predictors of LVMI increased on multivariable analysis.

Conclusion

Proximal aortic repair with stiff polyester grafts was associated with increased LV mass in the first-year post-operative and may promote long-term adverse cardiac remodeling. Further studies should be considered to evaluate the competing effects of aortic aneurysm related mortality against risks of long-term graft induced aortic stiffening and the potential implications on current size thresholds for intervention.
Development of a novel diagnostic assay for insulin receptor autoantibodies based on a patient with autoimmune hypoglycaemia
Authors: Geng Leiluo , Wong Cheuk-Lik , Liao Boya , Lin Ying , Han Hao , Lam Karen S. L. , Xu Aimin , Lee Chi-Ho , Tam Vicki H. K.
Published: October 2022

Differential diagnosis of hypoglycaemia can at times be challenging for patients who appear to be well. Here we identify the case of a 66-year-old Chinese man presenting with recurrent episodes of fasting hypoglycaemia and confusion without any other manifestations. He had no personal or family history of diabetes, nor was he on any hypoglycaemic drugs. The fasting insulin levels were elevated while the C-peptide and pro-insulin levels were slightly low or normal. Antibodies against insulin were negative and levels of insulin-like growth factors were normal. A series of imaging diagnosis excluded the presence of insulinoma or ectopic insulin-secreting neuroendocrine tumor. Ultimately, insulin receptor autoantibodies (IRAb) were detected by both immunoprecipitation assay and enzyme-linked immunosorbent assay (ELISA) developed in house. In a cell study, the immunoglobulins isolated from this patient exerted insulin-like effects on stimulation of post-insulin receptor signaling and glucose uptake as well as inhibited 125I-insulin binding with insulin receptors. Collectively, this patient was diagnosed with IRAb-induced autoimmune hypoglycaemia. Although this patient had no obvious immune disorders, several autoantibodies were identified in his plasma samples, suggesting the patient might have mild aberrant autoimmunity and therefore generated IRAb. IRAb-related disease is uncommon and possibly underdiagnosed or missed due to the lack of simple detection methods for IRAb. Our in-house user-friendly ELISA kit provides a valuable tool for diagnosis of this disease.
Cryopreservation process alters the expression of genes involved in pathways associated with the fertility of bull spermatozoa
Authors: Ebenezer Samuel King John Peter , Sinha Manish Kumar , Kumaresan Arumugam , Nag Pradeep , Das Gupta Mohua , Arul Prakash Mani , Talluri Thirumala Rao , Datta Tirtha Kumar
Published: October 2022

In bovines, cryopreserved semen is used for artificial insemination; however, the fertility of cryopreserved semen is far lower than that of fresh semen. Although cryopreservation alters sperm phenotypic characteristics, its effect on sperm molecular health is not thoroughly understood. The present study applied next-generation sequencing to investigate the effect of cryopreservation on the sperm transcriptomic composition of bull spermatozoa. While freshly ejaculated bull spermatozoa showed 14,280 transcripts, cryopreserved spermatozoa showed only 12,375 transcripts. Comparative analysis revealed that 241 genes were upregulated, 662 genes were downregulated, and 215 genes showed neutral expression in cryopreserved spermatozoa compared to fresh spermatozoa. Gene ontology analysis indicated that the dysregulated transcripts were involved in nucleic acid binding, transcription-specific activity, and protein kinase binding involving protein autophosphorylation, ventricular septum morphogenesis, and organ development. Moreover, the dysregulated genes in cryopreserved spermatozoa were involved in pathways associated with glycogen metabolism, MAPK signalling, embryonic organ morphogenesis, ectodermal placode formation, and regulation of protein auto-phosphorylation. These findings suggest that the cryopreservation process induced alterations in the abundance of sperm transcripts related to potential fertility-associated functions and pathways, which might partly explain the reduced fertility observed with cryopreserved bull spermatozoa.
Immunotherapy response and microenvironment provide biomarkers of immunotherapy options for patients with lung adenocarcinoma
Authors: Zhan Xue , Feng Shihan , Zhou Xutao , Liao Wei , Zhao Bin , Yang Qian , Tan Qi , Shen Jian
Published: October 2022

Background: Immunotherapy has been a promising approach option for lung cancer.

Method: All the open-accessed data was obtained from the Cancer Genome Atlas (TCGA) database. All the analysis was conducted using the R software analysis.

Results: Firstly, the genes differentially expressed in lung cancer immunotherapy responders and non-responders were identified. Then, the lung adenocarcinoma immunotherapy-related genes were determined by LASSO logistic regression and SVM-RFE, respectively. A total of 18 immunotherapy response-related genes were included in our investigation. Subsequently, we constructed the logistics score model. Patients with high logistics score had a better clinical effect on immunotherapy, with 63.2% of patients responding to immunotherapy, while only 12.1% of patients in the low logistics score group responded to immunotherapy. Moreover, we found that pathways related to immunotherapy were mainly enriched in metabolic pathways such as fatty acid metabolism, bile acid metabolism, oxidative phosphorylation, and carcinogenic pathways such as KRAS signaling. Logistics score was positively correlated with NK cells activated, Mast cells resting, Monocytes, Macrophages M2, dendritic cells resting, dendritic cells activated and eosinophils, while was negatively related to Tregs, macrophages M0, macrophages M1, and mast cells activated. In addition, ERVH48-1 was screened for single-cell exploration. The expression of ERVH48-1 increased in patients with distant metastasis, and ERVH48-1 was associated with pathways such as pancreas beta cells, spermatogenesis, G2M checkpoints and KRAS signaling. The result of quantitative real-time PCR showed that ERVH48-1 was upregulated in lung cancer cells.

Conclusion: Our study developed an effective signature to predict the immunotherapy response of lung cancer patients.
Tetrabromobisphenol A effects on differentiating mouse embryonic stem cells reveals unexpected impact on immune system
Authors: Tribondeau Alicia , Sachs Laurent M. , Buisine Nicolas
Published: October 2022

Tetrabromobisphenol A (TBBPA) is a potent flame retardant used in numerous appliances and a major pollutant in households and ecosystems. In vertebrates, it was shown to affect neurodevelopment, the hypothalamic-pituitary-gonadal axis and thyroid signaling, but its toxicity and modes of actions are still a matter of debate. The molecular phenotype resulting from exposure to TBBPA is only poorly described, especially at the level of transcriptome reprogramming, which further limits our understanding of its molecular toxicity. In this work, we combined functional genomics and system biology to provide a system-wide description of the transcriptomic alterations induced by TBBPA acting on differentiating mESCs, and provide potential new toxicity markers. We found that TBBPA-induced transcriptome reprogramming affect a large collection of genes loosely connected within the network of biological pathways, indicating widespread interferences on biological processes. We also found two hotspots of action: at the level of neuronal differentiation markers, and surprisingly, at the level of immune system functions, which has been largely overlooked until now. This effect is particularly strong, as terminal differentiation markers of both myeloid and lymphoid lineages are strongly reduced: the membrane T cell receptor (Cd79a, Cd79b), interleukin seven receptor (Il7r), macrophages cytokine receptor (Csf1r), monocyte chemokine receptor (Ccr2). Also, the high affinity IgE receptor (Fcer1g), a key mediator of allergic reactions, is strongly induced. Thus, the molecular imbalance induce by TBBPA may be stronger than initially realized.
A GABA-receptor agonist reduces pneumonitis severity, viral load, and death rate in SARS-CoV-2-infected mice
Authors: Tian Jide , Dillion Barbara J. , Henley Jill , Comai Lucio , Kaufman Daniel L.
Published: October 2022

Gamma-aminobutyric acid (GABA) and GABA-receptors (GABA-Rs) form a major neurotransmitter system in the brain. GABA-Rs are also expressed by 1) cells of the innate and adaptive immune system and act to inhibit their inflammatory activities, and 2) lung epithelial cells and GABA-R agonists/potentiators have been observed to limit acute lung injuries. These biological properties suggest that GABA-R agonists may have potential for treating COVID-19. We previously reported that GABA-R agonist treatments protected mice from severe disease induced by infection with a lethal mouse coronavirus (MHV-1). Because MHV-1 targets different cellular receptors and is biologically distinct from SARS-CoV-2, we sought to test GABA therapy in K18-hACE2 mice which develop severe pneumonitis with high lethality following SARS-CoV-2 infection. We observed that GABA treatment initiated immediately after SARS-CoV-2 infection, or 2 days later near the peak of lung viral load, reduced pneumonitis severity and death rates in K18-hACE2 mice. GABA-treated mice had reduced lung viral loads and displayed shifts in their serum cytokine/chemokine levels that are associated with better outcomes in COVID-19 patients. Thus, GABA-R activation had multiple effects that are also desirable for the treatment of COVID-19. The protective effects of GABA against two very different beta coronaviruses (SARS-CoV-2 and MHV-1) suggest that it may provide a generalizable off-the-shelf therapy to help treat diseases induced by new SARS-CoV-2 variants and novel coronaviruses that evade immune responses and antiviral medications. GABA is inexpensive, safe for human use, and stable at room temperature, making it an attractive candidate for testing in clinical trials. We also discuss the potential of GABA-R agonists for limiting COVID-19-associated neuroinflammation.
Comprehensive analysis of cuproptosis-related genes in immune infiltration and diagnosis in ulcerative colitis
Authors: Huang Jinke , Zhang Jiaqi , Wang Fengyun , Zhang Beihua , Tang Xudong
Published: October 2022

Objectives

Cuproptosis is a recently discovered form of programmed cell death; however, its role in ulcerative colitis (UC) remains a void.

Methods

Three gene expression profiles were acquired from the GEO database. Subsequently, the single sample gene set enrichment analysis (ssGSEA) was performed to identify the immune infiltration characteristics of UC. Correlation analysis between cuproptosis and immune infiltration was further conducted, and the cuproptosis-related genes were applied to construct a UC diagnostic model. Subsequently, analysis results of microarray data were experimentally validated by DSS-induced colitis in mice. Finally, therapeutic agents for the cuproptosis-related genes were screened owing to the gaping field of therapeutic agents on cuproptosis.

Results

Three gene expression profiles with 343 samples (290 UC and 53 healthy samples) were included. Immune infiltration revealed that UC patients had a higher level of DCs, B cells, CD8+ T cells, iDCs, Macrophages, neutrophils, pDCs, T helper cells, Tfh, Th1 cells, Th2 cells, TIL and Treg than normal subjects. Moreover, almost all cuproptosis-related genes were significantly negatively associated with immune infiltration in UC patients. The risk prediction model based on cuproptosis-related genes showed an excellent discrimination for UC. Animal experiments revealed significant alterations in genes essential for cuproptosis between DSS-induced colitis mice and healthy controls, providing experimental validation for the analysis results of microarray data. Further analysis revealed that latamoxef, vitinoin, clomipramine, chlorzoxazone, glibenclamide, pyruvic acid, clindamycin, medrysone, caspan, and flavin adenine dinucleotide might be the target agents for cuproptosis-related genes.

Conclusions

In conclusion, cuproptosis was significantly associated with immune infiltration in UC, and the cuproptosis-related genes showed an excellent discrimination for UC.
Checkpoint inhibitors as immunotherapy for fungal infections: Promises, challenges, and unanswered questions
Authors: Wurster Sebastian , Watowich Stephanie S. , Kontoyiannis Dimitrios P.
Published: October 2022

Opportunistic fungal infections have high mortality in patients with severe immune dysfunction. Growing evidence suggests that the immune environment of invasive fungal infections and cancers share common features of immune cell exhaustion through activation of immune checkpoint pathways. This observation gave rise to several preclinical studies and clinical case reports describing blockade of the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte Antigen 4 immune checkpoint pathways as an adjunct immune enhancement strategy to treat opportunistic fungal infections. The first part of this review summarizes the emerging evidence for contributions of checkpoint pathways to the immunopathology of fungal sepsis, opportunistic mold infections, and dimorphic fungal infections. We then review the potential merits of immune checkpoint inhibitors (ICIs) as an antifungal immunotherapy, including the incomplete knowledge of the mechanisms involved in both immuno-protective effects and toxicities. In the second part of this review, we discuss the limitations of the current evidence and the many unknowns about ICIs as an antifungal immune enhancement strategy. Based on these gaps of knowledge and lessons learned from cancer immunology studies, we outline a research agenda to determine a “sweet spot” for ICIs in medical mycology. We specifically discuss the importance of more nuanced animal models, the need to study ICI-based combination therapy, potential ICI resistance, the role of the immune microenvironment, and the impact of ICIs given as part of oncological therapies on the natural immunity to various pathogenic fungi.
Modified aluminosilicates display antibacterial activity against nontuberculous mycobacteria and adsorb mycolactone and Mycobacterium ulcerans in vitro
Authors: Dermody Roslyn , Ali Farizah , Popovich John , Chen Shaojiang , Seo Dong-Kyun , Haydel Shelley E.
Published: October 2022

Mycobacterium ulcerans (MU) infection of skin and soft tissue leads to chronic skin ulceration known as Buruli ulcer. MU releases a lipid-like toxin, mycolactone, that diffuses into the tissue, effecting disease through localized tissue necrosis and immunosuppression. Cutaneous Buruli ulcer wounds slowly advance from a painless pre-ulcerative stage to an ulcerative lesion, leading to disparities in the timing of medical intervention and treatment outcomes. Novel Buruli ulcer wound management solutions could complement and supplement systemically administered antimicrobials and reduce time to healing. Capitalizing on nanopore structure, adsorption, and exchange capacities, aluminosilicate nanozeolites (nZeos) and geopolymers (GPs) were developed and investigated in the context of therapeutics for mycobacterial disease ulcerative wound care. nZeos were ion exchanged with copper or silver to assess the antimicrobial activity against MU and Mycobacterium marinum, a rapid growing, genetic ancestor of MU that also causes skin and soft tissue infections. Silver- and copper-exchanged nZeos were bactericidal against MU, while only silver-exchanged nZeos killed M. marinum. To mediate adsorption at a biological scale, GPs with different pore sizes and altered surface modifications were generated and assessed for the ability to adsorb MU and mycolactone. Macroporous GPs with and without stearic acid modification equivalently adsorbed MU cells, while mesoporous GPs with stearic acid adsorbed mycolactone toxin significantly better than mesoporous GPs or GPs modified with phenyltriethoxysilane (PTES). In cytotoxicity assays, Cu-nZeos lacked toxicity against Detroit 551, U-937, and WM-115 cells. GPs demonstrated limited cytotoxicity in Detroit 551 and WM-115, but produced time-dependent toxicity in U-937 cells. With their large surface area and adsorptive capacities, aluminosilicates nZeos and GPs may be modified and developed to support conventional BU wound care. Topical application of nZeos and GPs could kill MU within the cutaneous wound environment and physically remove MU and mycolactone with wound dressing changes, thereby improving wound healing and overall patient outcomes.
Phytoplankton photophysiology varies depending on nitrogen and light availability at the subsurface chlorophyll maximum in the northern Chukchi Sea
Authors: Ko Eunho , Gorbunov Maxim Y. , Jung Jinyoung , Lee Youngju , Cho Kyoung-Ho , Yang Eun Jin , Park Jisoo
Published: October 2022

Vertical distributions of phytoplankton in the Arctic Ocean are characterized by a very narrow subsurface chlorophyll maximum (SCM) layer formed every summer after the sea ice retreats. Despite the prevalence of this narrow SCM layer, phytoplankton photosynthetic response to climate change remains to be elucidated. Here, we examined the photophysiological properties of phytoplankton in the SCM layer in the northern Chukchi Sea during the summers of 2015–2018. There was a significant difference in the SCM depth between the northwestern and northeastern Chukchi Sea determined by the distribution of Pacific Summer Water (PSW) around the SCM layer (34 ± 14 m vs. 49 ± 10 m, respectively). The maximum quantum yield of photochemistry in photosystem II (Fv/Fm) in the SCM phytoplankton was high (Fv/Fm ≥ 0.54) and similar in both regions until 2016; however, since then, Fv/Fm in the northeastern Chukchi Sea has decreased by approximately 10%. This decrease was accompanied by a marked decrease in the fraction of microplankton, which are known to be susceptible to nutrient limitation. This result suggests a reduction in nitrogen availability in the SCM layer in the northeastern Chukchi Sea. Meanwhile, the maximum electron transfer rate (ETRmax) did not have a significant relationship with the nitrogen availability and phytoplankton community size structure in the SCM layer; however the improved light conditions (with an approximately two-fold increase in the relative ratio of surface PAR reaching the SCM layer) increased ETRmax by up to 30% in the SCM phytoplankton in the northwestern Chukchi Sea. Therefore, these results provide a better understanding of how changes in nitrogen and light availability could affect phytoplankton photosynthesis and primary production in the Arctic Ocean.