bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytogenetic and molecular analysis of distal 4q duplication with distinctive phenotype using single-nucleotide polymorphism array
Authors: Zhuang Jianlong , Zhang Na , Fu Wanyu , Yao Jianfeng , Li Yanqing , Zeng Shuhong , Wang Yuanbai , Xie Yingjun , Jiang Yuying
Published: September 2021

Aims

There is little knowledge about partial trisomy 4q and the genotype–phenotype correlation. In this study, we presented the detail of two Chinese families with partial distal 4q duplication in an attempt to clarify the correlation between the genotype and the phenotype.

Methods

Two pedigrees with distal 4q duplication were enrolled in this study. Karyotype analysis and single-nucleotide polymorphism (SNP) array detection were performed for prenatal diagnosis. Fluorescence in situ hybridization analysis. (FISH) was conducted to verify the copy number variants.

Results

Two families with partial trisomy 4q were identified. The fetus in pedigree 1 exhibited multiple ultrasound anomalies including intrauterine growth restriction and an atrioventricular septal defect who had a duplication of 4q28.3-qter associate with 6p25.2-p25.3 deletion, which resulted from balanced translocation carried by his father t(4;6)(q28.3;p25.2). The fetus in pedigree 2 had a distal 4q28.3-qter duplication combined with monosomy of Xp21.3-p22.3, and the karyotype was described as 46,X,der(X)t(X;4)(p21.3;q28.3)mat, which originally inherited from the pregnant woman who exhibited a mild clinical phenotype limited to short stature.

Conclusions

In our study, we for the first time identified the partial trisomy 4q associate with 6p or Xp deletion. In addition, our finding further strengthens that mild clinical phenotype in 4q duplication case may be due to the spreading of X inactivation to the autosomal in derivation of chromosome X.
Targeting INMT and interrupting its methylation pathway for the treatment of castration resistant prostate cancer
Authors: Zhong Shangwei , Jeong Ji-Hak , Huang Changhao , Chen Xueyan , Dickinson Shohreh Iravani , Dhillon Jasreman , Yang Li , Luo Jun-Li
Published: September 2021

Background

Castration-resistant prostate cancer (CRPC) is associated with a very poor prognosis, and the treatment of which remains a serious clinical challenge.

Methods

RNA-seq, qPCR, western blot and immunohistochemistry were employed to identify and confirm the high expression of indolethylamine N-methyltransferase (INMT) in CRPC and the clinical relevance. Chip assay was used to identify Histone-Lysine N-Methyltransferase (SMYD3) as a major epigenetic regulator of INMT. LC-MS/MS were used to identify new substrates of INMT methylation in CRPC tissues. Gene knockdown/overexpression, MTT and mouse cancer models were used to examine the role of INMT as well as the anticancer efficacy of INMT inhibitor N,N-dimethyltryptamine (DMT), the SMYD3 inhibitor BCl-12, the selenium compounds methaneseleninic acid (MSA) and Se-(Methyl)selenocysteine hydrochloride (MSC), and the newly identified endogenous INMT substrate Bis(7)-tacrine.

Results

We found that the expression of INMT was highly increased in CRPC and was correlated with poor prognosis of clinical prostate cancer (PCa). INMT promoted PCa castration resistance via detoxification of anticancer metabolites. Knockdown of INMT or treatment with INMT inhibitor N,N-dimethyltryptamine (DMT) significantly suppressed CRPC development. Histone-Lysine N-Methyltransferase SMYD3 was a major epigenetic regulator of INMT expression, treatment with SMYD3 inhibitor BCl-121 suppressed INMT expression and inhibits CRPC development. Importantly, INMT knockdown significantly increased the anticancer effect of the exogenous selenium compounds methaneseleninic acid (MSA) and Se-(Methyl)selenocysteine hydrochloride (MSC) as well as the endogenous metabolite Bis(7)-tacrine.

Conclusions

Our study suggests that INMT drives PCa castration resistance through detoxification of anticancer metabolites, targeting INMT or its regulator SMYD3 or/and its methylation metabolites represents an effective therapeutic avenue for CRPC treatment.
Design, synthesis, and biological evaluation of symmetrical azine derivatives as novel tyrosinase inhibitors
Authors: Karimian Somaye , Kazemi Fatemeh , Attarroshan Mahshid , Gholampour Maryam , Hemmati Shiva , Sakhteman Amirhossein , Behzadipour Yasaman , Kabiri Maryam , Iraji Aida , Khoshneviszadeh Mehdi
Published: September 2021

A series of symmetrical azine derivatives containing different substituted benzyl moieties were designed, synthesized, and evaluated for their inhibitory activity against tyrosinase. The results showed that compounds 3e, 3f, 3h, 3i, 3j, and 3k possess effective tyrosinase inhibition with IC50 values ranging from 7.30 μM to 62.60 μM. Particularly, compounds 3f displayed around three-fold improvement in the potency (IC50 = 7.30 ± 1.15 μM) compared to that of kojic acid (IC50 = 20.24 ± 2.28 μM) as the positive control. Kinetic study of compound 3f confirmed uncompetitive inhibitory activity towards tyrosinase indicating that it can bind to enzyme–substrate complex. Next, molecular docking analysis was performed to study the interactions and binding mode of the most potent compound 3f in the tyrosinase active site. Besides, the cytotoxicity of 3f, as well as its potency to reduce the melanin content were also measured on invasive melanoma B16F10 cell line. Also, 3f exhibited above 82% cell viability in the A375 cell line at 10 µM. Consequently, compounds 3f could be introduced as a potent tyrosinase inhibitor that might be a promising candidate in the cosmetics, medicine, and food industry.
In vivo quantitative assessment of therapeutic response to bortezomib therapy in disseminated animal models of multiple myeloma with [18F]FDG and [64Cu]Cu-LLP2A PET
Authors: Ghai Anchal , Fettig Nikki , Fontana Francesca , DiPersio John , Rettig Mike , Neal Julie O. , Achilefu Samuel , Shoghi Kooresh I. , Shokeen Monica
Published: September 2021

Background

Multiple myeloma (MM) is a disease of cancerous plasma cells in the bone marrow. Imaging-based timely determination of therapeutic response is critical for improving outcomes in MM patients. Very late antigen-4 (VLA4, CD49d/CD29) is overexpressed in MM cells. Here, we evaluated [18F]FDG and VLA4 targeted [64Cu]Cu-LLP2A for quantitative PET imaging in disseminated MM models of variable VLA4 expression, following bortezomib therapy.

Methods

In vitro and ex vivo VLA4 expression was evaluated by flow cytometry. Human MM cells, MM.1S-CG and U266-CG (C: luciferase and G: green fluorescent protein), were injected intravenously in NOD-SCID gamma mice. Tumor progression was monitored by bioluminescence imaging (BLI). Treatment group received bortezomib (1 mg/kg, twice/week) intraperitoneally. All cohorts (treated, untreated and no tumor) were longitudinally imaged with [18F]FDG (7.4–8.0 MBq) and [64Cu]Cu-LLP2A (2–3 MBq; Molar Activity: 44.14 ± 1.40 MBq/nmol) PET, respectively.

Results

Flow cytometry confirmed high expression of CD49d in U266 cells (> 99%) and moderate expression in MM.1S cells (~ 52%). BLI showed decrease in total body flux in treated mice. In MM.1S-CG untreated versus treated mice, [64Cu]Cu-LLP2A localized with a significantly higher SUVmean in spine (0.58 versus 0.31, p < 0.01) and femur (0.72 versus 0.39, p < 0.05) at week 4 post-tumor inoculation. There was a four-fold higher uptake of [64Cu]Cu-LLP2A (SUVmean) in untreated U266-CG mice compared to treated mice at 3 weeks post-treatment. Compared to [64Cu]Cu-LLP2A, [18F]FDG PET detected treatment-related changes at later time points.

Conclusion

[64Cu]Cu-LLP2A is a promising tracer for timely in vivo assessment of therapeutic response in disseminated models of MM.
Food system resilience: ontology development and impossible trinities
Authors: van Wassenaer Lan , Oosterkamp Elsje , van Asseldonk Marcel , Ryan Mark
Published: September 2021

Background

Given the polysemy of the concept resilience, is it possible to have a unified conceptualisation of food system resilience? This paper provides a multidisciplinary evaluation of the literature to identify common themes that prevail in food system resilience debates and the challenges to reach a unified conceptualisation. The aim is to provide insights into some of the main issues and tensions that we identified during our research which will then allow academics and policymakers to identify the most significant themes and topics for discussion in the debate. While we only focus on one application of resilience, namely, food system resilience during extreme events, we believe that our approach and findings could be integrated and applied to other areas of resilience, as well.

Results

Our ontological exploration shows that ‘resilience’ is a rich concept that has an important bearing on many themes and topics in the domain of food systems. This makes it highly relevant to develop and apply the concept of ‘food system resilience’. The application of the concept in research and practice, however, faces many challenges that are rooted in ontological and epistemological differences among different disciplines and practices. While posing serious challenges in interdisciplinary collaboration and communication, these challenges also foster new research opportunities as knowledge gaps are discovered. We propose that there is a need to critically investigate the social, environmental, and economic trade-offs implied in policy strategies towards resilience at various levels of food systems and among different actors or groups of actors.

Conclusion

Interdisciplinary communication between different fields can be difficult and divisive. The ambition to unify the theory may be counterproductive in addressing practical problems that often require multidisciplinary collaboration. The challenge is to identify context-specific challenges and policy options using the ‘resilience lens’ and translating the concept into measurable indicators. Our research identifies some of these challenges and aims to provide a way to improve dialogue between different actors, through discussions about tensions and issues within their research. The ontological differences and debates are unlikely to be resolved anytime soon, nor should it be a priority to resolve these differences. A pragmatic case-specific approach can be adopted to address the problem while considering ontological differences. Our research will provide food system resilience researchers with some guidance about challenges in their research, as well as those working on developing ontologies.
Effect of thinning intensity on the stem CO2 efflux of Larix principis-rupprechtii Mayr
Authors: Zhao Kuangji , Fahey Timothy J. , Wang Xiangzhen , Wang Jie , He Fang , Fan Chuan , Jia Zhongkui , Li Xianwei
Published: September 2021

Background

Stem CO2 efflux (ES) plays a critical role in the carbon budget of forest ecosystems. Thinning is a core practice for sustainable management of plantations. It is therefore necessary and urgent to study the effect and mechanism of thinning intensity (TI) on ES.

Methods

In this study, five TIs were applied in Larix principis-rupprechtii Mayr 21-, 25-, and 41-year-old stands in North China in 2010. Portable infrared gas analyzer (Li-8100 A) was used to measure ES and its association with environmental factors at monthly intervals from May to October in 2013 to 2015. In addition, nutrients, wood structure and nonstructural carbon (NSC) data were measured in August 2016.

Results

The results show that ES increased with increasing TI. The maximum ES values occurred at a TI of 35 % (3.29, 4.57 and 2.98 µmol∙m-2∙s-1) and were 1.54-, 1.94- and 2.89-fold greater than the minimum ES value in the CK stands (2.14, 2.35 and 1.03 µmol∙m-2∙s-1) in July for the 21-, 25- and 41-year-old forests, respectively. The ES of the trees in low-density stands was more sensitive to temperature than that of the trees in high-density stands. Soluble sugars (SS) and temperature are the main factors affecting ES. When the stand density is low enough as 41-year-old L. principis-rupprechtii forests with TI 35 %, bark thickness (BT) and humidity should be considered in addition to air temperature (Ta), wood temperature (Tw), sapwood width (SW), nitrogen concentration (N) and SS in the evaluation of ES. If a change in stand density is ignored, the CO2 released from individual 21-, 25- and 41-year-old trees could be underestimated by 168.89 %, 101.94 % and 200.49 %, respectively. CO2 release was estimated based on the stem equation in combination with the factors influencing ES for reference.

Conclusions

We suggest that it is not sufficient to conventional models which quantify ES only by temperature and that incorporating the associated drivers (e.g. density, SS, SW and N) based on stand density into conventional models can improve the accuracy of ES estimates.
Closing the know-do gap for child health: UNICEF’s experiences from embedding implementation research in child health and nutrition programming
Authors: Jackson Debra , Shahabuddin A. S. M. , Sharkey Alyssa B. , Källander Karin , Muñiz Maria , Mwamba Remy , Nyankesha Elevanie , Scherpbier Robert W. , Hasman Andreas , Balarajan Yarlini , Albright Kerry , Idele Priscilla , Peterson Stefan Swartling
Published: September 2021

UNICEF operates in 190 countries and territories, where it advocates for the protection of children’s rights and helps meet children’s basic needs to reach their full potential. Embedded implementation research (IR) is an approach to health systems strengthening in which (a) generation and use of research is led by decision-makers and implementers; (b) local context, priorities, and system complexity are taken into account; and (c) research is an integrated and systematic part of decision-making and implementation. By addressing research questions of direct relevance to programs, embedded IR increases the likelihood of evidence-informed policies and programs, with the ultimate goal of improving child health and nutrition.

This paper presents UNICEF’s embedded IR approach, describes its application to challenges and lessons learned, and considers implications for future work.

From 2015, UNICEF has collaborated with global development partners (e.g. WHO, USAID), governments and research institutions to conduct embedded IR studies in over 25 high burden countries. These studies focused on a variety of programs, including immunization, prevention of mother-to-child transmission of HIV, birth registration, nutrition, and newborn and child health services in emergency settings. The studies also used a variety of methods, including quantitative, qualitative and mixed-methods.

UNICEF has found that this systematically embedding research in programs to identify implementation barriers can address concerns of implementers in country programs and support action to improve implementation. In addition, it can be used to test innovations, in particular applicability of approaches for introduction and scaling of programs across different contexts (e.g., geographic, political, physical environment, social, economic, etc.). UNICEF aims to generate evidence as to what implementation strategies will lead to more effective programs and better outcomes for children, accounting for local context and complexity, and as prioritized by local service providers. The adaptation of implementation research theory and practice within a large, multi-sectoral program has shown positive results in UNICEF-supported programs for children and taking them to scale.
Imaging indigenous sacred sites: A tale of clay, silt, and sand
Authors: Nobes David C.
Published: September 2021

When studying indigenous sites, especially sacred sites such as burials, the needs and wishes of the indigenous people are paramount; the site integrity must be respected, and the site must be left intact and undisturbed. Noninvasive, nondestructive geophysical imaging is well suited to such investigations, but suspicion within indigenous communities because of past transgressions is a barrier to widespread use; skepticism is not uncommon, but we have always managed to convince skeptics. We have developed an overview of results from 10 Māori (the indigenous peoples of New Zealand) sites in the South Island of New Zealand: one historic burial site, six modern burial sites that also had historical use, one historic battle site, one prehistoric site that may have been a burial site, and one prehistoric site used for food storage that was tapu (sacred). Our approach was to let them ask us to delineate areas of importance, for example, old burial sites. There are, naturally, processes and protocols, cultural and technical, that we followed. The sites comprised a range of lithologies and soil types: one site where clay soil overlays limestone, five sites where loess (airborne silt) overlays basalt, one set of inland silty soil sites, one site on peat soils overlying sandy gravels, and two sites in coastal sands. The geophysical responses of the sites cluster into three groups: Horizontal loop electromagnetic (HLEM) and magnetic field methods worked well for the clay soil site, and once the effects of the conductive clay response were removed by filtering, ground-penetrating radar (GPR) worked well. HLEM and magnetic results were good to equivocal on the silty and peaty sites, whereas GPR excelled at delineating anomalous features, particularly burials, which yielded clear characteristic diffraction responses. Finally, results for coastal sand sites were disappointing. Such sites appear to be too dynamic to yield useful results.
Extended-space full-waveform inversion in the time domain with the augmented Lagrangian method
Authors: Gholami Ali , Aghamiry Hossein S. , Operto Stéphane
Published: September 2021

The search space of full-waveform inversion (FWI) can be extended via a relaxation of the wave equation to increase the linear regime of the inversion. This wave-equation relaxation is implemented by solving jointly (in a least-squares sense) the wave equation weighted by a penalty parameter and the observation equation such that the reconstructed wavefields closely match the data, hence preventing cycle skipping at receivers. Then, the subsurface parameters are updated by minimizing the temporal and spatial source extension generated by the wave-equation relaxation to push back the data-assimilated wavefields toward the physics. This extended formulation of FWI has been efficiently implemented in the frequency domain with the augmented Lagrangian method in which the overdetermined systems of the data-assimilated wavefields can be solved separately for each frequency with linear-algebra methods and the sensitivity of the optimization to the penalty parameter is mitigated through the action of the Lagrange multipliers. Applying this method in the time domain is, however, hampered by two main issues: the computation of data-assimilated wavefields with explicit time-stepping schemes and the storage of the Lagrange multipliers capturing the history of the source residuals in the state space. These two issues are solved by recognizing that the source residuals on the right side of the extended wave equation, when formulated in a form suitable for explicit time stepping, are related to the extended data residuals through an adjoint equation. This relationship first allows us to relate the extended data residuals to the reduced data residuals through a normal equation in the data space. Once the extended data residuals have been estimated by solving (exactly or approximately) this normal equation, the data-assimilated wavefields are computed with explicit time-stepping schemes by cascading an adjoint and a forward simulation. Second, the relationship between the source and the data residuals allows us to project the Lagrange multipliers tied to the wave-equation constraint in the data space at the expense of additional adjoint simulations. This leads to a formulation of the extended FWI that is very similar to that of the classic reduced-space FWI. The computational cost of the extended FWI is two times that of the classic reduced-space FWI, and the storage requirement is the same. Applications to different synthetic benchmarks involving large contrasts confirm the resilience of the method to cycle skipping even when the quadratic problem for the extended data residuals is solved approximately with one inner iteration of a steepest-descent method.
Dynamic Changes of Circulating Tumor DNA Predict Clinical Outcome in Patients With Advanced Non–Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors
Authors: Weber Sabrina , van der Leest Paul , Donker Hylke C. , Schlange Thomas , Timens Wim , Tamminga Menno , Hasenleithner Samantha O. , Graf Ricarda , Moser Tina , Spiegl Benjamin , Yaspo Marie-Laure , Terstappen Leon W. M. M. , Sidorenkov Grigory , Hiltermann T. Jeroen. N. , Speicher Michael R. , Schuuring Ed , Heitzer Ellen , Groen Harry J. M.
Published: September 2021

PURPOSE

Immune checkpoint inhibitors (ICIs) are increasingly being used in non–small-cell lung cancer (NSCLC), yet biomarkers predicting their benefit are lacking. We evaluated if on-treatment changes of circulating tumor DNA (ctDNA) from ICI start (t0) to after two cycles (t1) assessed with a commercial panel could identify patients with NSCLC who would benefit from ICI.

PATIENTS AND METHODS

The molecular ctDNA response was evaluated as a predictor of radiographic tumor response and long-term survival benefit of ICI. To maximize the yield of ctDNA detection, de novo mutation calling was performed. Furthermore, the impact of clonal hematopoiesis (CH)–related variants as a source of biologic noise was investigated.

RESULTS

After correction for CH-related variants, which were detected in 75 patients (44.9%), ctDNA was detected in 152 of 167 (91.0%) patients. We observed only a fair agreement of the molecular and radiographic response, which was even more impaired by the inclusion of CH-related variants. After exclusion of those, a ≥ 50% molecular response improved progression-free survival (10 v 2 months; hazard ratio [HR], 0.55; 95% CI, 0.39 to 0.77; P = .0011) and overall survival (18.4 v 5.9 months; HR, 0.44; 95% CI, 0.31 to 0.62; P < .0001) compared with patients not achieving this end point. After adjusting for clinical variables, ctDNA response and STK11/ KEAP1 mutations (HR, 2.08; 95% CI, 1.4 to 3.0; P < .001) remained independent predictors for overall survival, irrespective of programmed death ligand-1 expression. A landmark survival analysis at 2 months (n = 129) provided similar results.

CONCLUSION

On-treatment changes of ctDNA in plasma reveal predictive information for long-term clinical benefit in ICI-treated patients with NSCLC. A broader NSCLC patient coverage through de novo mutation calling and the use of a variant call set excluding CH-related variants improved the classification of molecular responders, but had no significant impact on survival.
Molecular Tumor Board Review and Improved Overall Survival in Non–Small-Cell Lung Cancer
Authors: Huang Bin , Chen Quan , Allison Derek , El Khouli Riham , Peh Keng Hee , Mobley James , Anderson Abigail , Durbin Eric B. , Goodin Donald , Villano John L. , Miller Rachel W. , Arnold Susanne M. , Kolesar Jill M.
Published: September 2021

PURPOSE

With the introduction of precision medicine, treatment options for non–small-cell lung cancer have improved dramatically; however, underutilization, especially in disadvantaged patients, like those living in rural Appalachian regions, is associated with poorer survival. Molecular tumor boards (MTBs) represent a strategy to increase precision medicine use. UK HealthCare at the University of Kentucky (UK) implemented a statewide MTB in January 2017. We wanted to test the impact of UK MTB review on overall survival in Appalachian and other regions in Kentucky.

METHODS

We performed a case-control study of Kentucky patients newly diagnosed with non–small-cell lung cancer between 2017 and 2019. Cases were reviewed by the UK MTB and were compared with controls without UK MTB review. Controls were identified from the Kentucky Cancer Registry and propensity-matched to cases. The primary end point was the association between MTB review and overall patient survival.

RESULTS

Overall, 956 patients were included, with 343 (39%) residing in an Appalachian region. Seventy-seven (8.1%) were reviewed by the MTB and classified as cases. Cox regression analysis showed that poorer survival outcome was associated with lack of MTB review (hazard ratio [HR] = 8.61; 95% CI, 3.83 to 19.31; P < .0001) and living in an Appalachian region (hazard ratio = 1.43; 95% CI, 1.17 to 1.75; P = .004). Among individuals with MTB review, survival outcomes were similar regardless of whether they lived in Appalachia or other parts of Kentucky.

CONCLUSION

MTB review is an independent positive predictor of overall survival regardless of residence location. MTBs may help overcome some health disparities for disadvantaged populations.
A novel kind of equations linking the quantum dynamics and the classical wave motions based on the catastrophe theory
Authors: Wu Jiu Hui , Zhang Lin , Zhou Ke jiang
Published: September 2021

Considering that the catastrophe theory could describe quantitatively any phase transition process, we adopt the folding and cusp catastrophe types as the potential functions in the Schrödinger equation to attempt to link the quantum dynamics and the classical wave motions. Thus, through the dimensionless analysis a novel kind of partial differential equations is derived out. When the scaling parameter of the novel equation is equal to the Planck's constant, this equation becomes a detailed time-independent Schrödinger equation, from which Bohr correspondence principle can be found. On the other hand, when the scaling parameter tends to zero, this equation could degenerate to the classical Helmholtz equation. Therefore, this novel kind of equations could describe quantitatively the variation process of the wave functions from the macroscopic level to the quantum size.
Coupling-modulation–mediated generation of stable entanglement of superconducting qubits via dissipation
Authors: Ma Sheng-li , Zhang Jing , Li Xin-ke , Ren Ya-long , Xie Ji-kun , Cao Ming-tao , Li Fu-li
Published: September 2021

We propose an experimentally feasible scheme for the dissipative generation of stable entanglement of superconducting qubits via coupling modulation without applying any drives on qubits and resonator. Firstly, we study the circuit of one superconducting transmission line resonator coupled to two separated qubits via two superconducting quantum interference devices (SUQIDs). By modulating the inductance of the SQUIDs via external fluxes, we can tailor an appropriate qubit-resonator coupling with both red- and blue-sideband interactions. Combined with the photon loss of the resonator, the two qubits can be autonomously steered into a long-lived entangled state with high fidelity. Moreover, we extend the model to one resonator coupled to two separated qubit chains, each of which contains N linearly coupled superconducting qubits. We show that the lossy resonator can drive the whole system into a unique dark state, i.e., a series of N entangled pairs of qubits across the chains can be stabilized at the stationary state. So, the present work enables the preparation of a stable long-range entangled state between the two qubits in the end sites of the chains, which plays an important role for implementing scalable quantum computation and quantum communication.
Engineering chromosome rearrangements in cancer
Authors: Alonso Salvador , Dow Lukas E.
Published: September 2021

The identification of large chromosomal rearrangements in cancers has multiplied exponentially over the last decade. These complex and often rare genomic events have traditionally been challenging to study, in part owing to lack of tools that efficiently engineer disease-associated inversions, deletions and translocations in model systems. The emergence and refinement of genome editing technologies, such as CRISPR, have significantly expanded our ability to generate and interrogate chromosomal aberrations to better understand the networks that govern cancer growth. Here we review how existing technologies are employed to faithfully model cancer-associated chromosome rearrangements in the laboratory, with the ultimate goal of developing more accurate pre-clinical models of and therapeutic strategies for cancers driven by these genomic events.
LRRC23 is a conserved component of the radial spoke that is necessary for sperm motility and male fertility in mice
Authors: Zhang Xin , Sun Jiang , Lu Yonggang , Zhang Jintao , Shimada Keisuke , Noda Taichi , Zhao Shuqin , Koyano Takayuki , Matsuyama Makoto , Zhou Shushu , Wu Jiayan , Ikawa Masahito , Liu Mingxi
Published: September 2021

Cilia and flagella are ancient structures that achieve controlled motor functions through the coordinated interaction based on microtubules and some attached projections. Radial spokes (RSs) facilitate the beating motion of these organelles by mediating signal transduction between dyneins and a central pair (CP) of singlet microtubules. RS complex isolation from Chlamydomonas axonemes enabled the detection of 23 radial spoke proteins (RSP1–RSP23), although the roles of some radial spoke proteins remain unknown. Recently, RSP15 has been reported to be bound to the stalk of RS2, but its homolog in mammals has not been identified. Herein, we show that Lrrc23 is an evolutionarily conserved testis-enriched gene encoding an RSP15 homolog in mice. We found that LRRC23 localizes to the RS complex within murine sperm flagella and interacts with RSPH3A and RSPH3B. The knockout of Lrrc23 resulted in male infertility due to RS disorganization and impaired motility in murine spermatozoa, whereas the ciliary beating was not significantly affected. These data indicate that LRRC23 is a key regulator that underpins the integrity of the RS complex within the flagella of mammalian spermatozoa, whereas it is dispensable in cilia.

This article has an associated First Person interview with the first author of the paper.
Coronary flow quantification estimated by dynamic 320-detector CT angiography: validation by 13N ammonia PET myocardial flow reserve
Authors: Matsuo Yuka , Nagao Michinobu , Yamamoto Atsushi , Ando Kiyoe , Nakao Risako , Fukushima Kenji , Momose Mitsuru , Sakai Akiko , Sato Kayoko , Sakai Shuji
Published: September 2021

Objectives:

Resting coronary flow index (rCFI) estimated by 320-detector low-dose dynamic coronary CT angiography (CCTA) is a direct flow quantification using intracoronary attenuation. We propose modified-rCFI from new protocol combining dynamic scan and standard CCTA using dose-modulation, and validate its consistency with quantitative values and ischemia depicted by 13N-ammonia PET (NH3-PET).

Methods:

46 patients who underwent dynamic CCTA and NH3-PET for coronary artery disease were evaluated using original rCFI in 21 patients and modified-rCFI in 25 patients. Two types of rCFI were calculated for three major coronary arteries. Myocardial blood flow (MBF) at rest and stress, myocardial flow reserve (MFR), and the presence or absence of ischemia for three major territories were depicted by NH3-PET. Coronary territories were categorized as territories with MFR <2.0, ≥2.0, or with and without ischemia. Receiver operating characteristic analysis was performed to determine the optimal cut-off of rCFI to distinguish territories with MFR <2.0 or the presence of ischemia.

Results:

rCFI and modified-rCFI had significant positive correlations with stress MBF and MFR. The optical cut-offs of rCFI and modified-rCFI of 0.39 and 0.61 could detect territories with MFR <2.0, with AUCs of 0.75 and 0.73, sensitivities of 48 and 34%, and specificities of 97 and 98%. Optimal cut-offs of rCFI and modified-rCFI distinguished ischemic segments from non-ischemic segments, with AUCs of 0.75 and 0.91, sensitivities of 53 and 50%, and specificities of 93 and 95%.

Conclusion:

Two types of rCFI correlated with quantitative values from NH3-PET, and were consistent with a high specificity in detecting functional ischemia.

Advances in knowledge:

rCFI can contribute as additional functional test over standard CCTA in clinical work-up.
PI-RADS and Likert scales for structured reporting in multiparametric MR imaging of the prostate
Authors: Desai Shivang , Costa Daniel N
Published: September 2021

Multiparametric MRI (mpMRI) plays a critical role in the detection, staging and risk stratification of prostate cancer (PCa). There are two widely accepted structured reporting systems used for interpretation of mpMRI of the prostate - PI-RADS v2.1 and Likert. Both these systems demonstrate good diagnostic performance with high cancer detection rates however have key conceptual differences. In this commentary, the authors highlight the individual strengths and areas of potential improvement as well as emphasize the need for continued clinical validation for these interpreting and reporting systems.
Neogene-Quaternary tectonic regime and macroseismic observations in the Tyrnavos-Elassona broader epicentral area of the March 2021, intense earthquake sequence
Authors: Galanakis Dimitrios , Sboras Sotiris , Konstantopoulou Garyfalia , Xenakis Markos
Published: September 2021

On March 3, 2021, a strong (Mw6.3) earthquake occurred near the towns of Tyrnavos and Elassona. One day later (March 4), a second strong (Mw6.0) earthquake occurred just a few kilometres toward the WNW. The aftershock spatial distribution and the focal mechanisms revealed NW-SE-striking normal faulting. The focal mechanisms also revealed a NE-SW oriented extensional stress field, different from the orientation we knew so far (ca. N-S). The magnitude and location of the two strongest shocks, and the spatiotemporal evolution of the sequence, strongly suggest that two adjacent fault segments were ruptured respectively. The sequence was followed by several coseismic ground deformational phenomena, such as landslides/rockfalls, liquefaction and ruptures. The landslides and rockfalls were mostly associated with the ground shaking. The ruptures were observed west of the Titarissios River, near to the Quaternary faults found by bore-hole lignite investigation. In the same direction, a fault scarp separating the alpidic basement from the alluvial deposits of the Titarissios valley implies the occurrence of a well-developed fault system. Some of the ground ruptures were accompanied by extensive liquefaction phenomena. Others cross-cut reinforced concrete irrigation channels without changing their direction. We suggest that this fault system was partially reactivated, as a secondary surface rupture, during the sequence as a steeper splay of a deeper low-to-moderate angle normal fault.
Hydrogen production via aqueous-phase reforming for high-temperature proton exchange membrane fuel cells - a review
Authors: Lakhtaria Paranjeet , Ribeirinha Paulo , Huhtinen Werneri , Viik Saara , Sousa José , Mendes Adélio
Published: September 2021

Aqueous-phase reforming (APR) can convert methanol and other oxygenated hydrocarbons to hydrogen and carbon dioxide at lower temperatures when compared with the corresponding gas phase process. APR favours the water-gas shift (WGS) reaction and inhibits alkane formation; moreover, it is a simpler and more energy efficient process compared to gas-phase steam reforming. For example, Pt-based catalysts supported on alumina are typically selected for methanol APR, due to their high activity at temperatures of circa 200°C. However, non-noble catalysts such as nickel (Ni) supported on metal-oxides or zeolites are being investigated with promising results in terms of catalytic activity and stability. The development of APR kinetic models and reactor designs is also being addressed to make APR a more attractive process for producing in situ hydrogen.
АКВАКУЛЬТУРА В КИРОВСКОЙ ОБЛАСТИ. ПРОБЛЕМЫ И ПЕРСПЕКТИВЫ
Authors: Dursenev Maxim S. , Chirkin Sergei A.
Published: September 2021

Согласно «Стратегии развития рыбохозяйственного комплекса Российской Федерации на период до 2030 года», в регионах, не имеющих выходов к морям, товарное рыбоводство в ближайшие годы должно стать приоритетным в развитии их рыбохозяйственных комплексов. К числу этих регионов относится и Кировская область, имеющая почти вековой опыт развития аквакультуры.
Цель. Анализ текущего состояния, проблем и перспектив устойчивого развития товарной аквакультуры в Кировской области.
Материалы и методы. Материалом для статьи послужили отчетные данные государственных органов о развитии рыбного хозяйства Кировской области за последние двадцать лет, а также данные периодических изданий с применением к ним статистических и монографических методов анализа.
Результаты. Показано, что современное состояние отрасли товарного рыбоводства в Кировской области можно охарактеризовать как кризисное. При этом, у нее большой потенциал, который до сих пор остается неиспользованным. Выявлены проблемы, которые сдерживают развитие аквакультуры в регионе. Отмечено социальное значение аквакультуры для развития сельских территорий Кировской области. С целью развития аквакультуры обоснована необходимость разработки новых методов и нетрадиционных решений, обеспечивающих поступательный рост объемов производства товарной рыбной продукции высокого качества.
Заключение. Высокотехнологичная аквакультура способствует социально-экономическому развитию Кировской области и улучшению качества жизни ее населения. Эта задача будет реализована в том случае, если частная заинтересованность в развитии данной отрасли получит подкрепление в виде благоприятных условий со стороны государства.
ВОЗРАСТНЫЕ ИЗМЕНЕНИЯ УРОВНЯ ЭКСПРЕССИИ МАРКЕРОВ ПЛОТНЫХ КОНТАКТОВ У ЖЕНЩИН ПОСЛЕ МИОМЭКТОМИИ
Authors: Shapovalova Alexandra I. , Polyakova Viktoria O. , Kleimenova Tatyana S.
Published: September 2021

Обоснование. Миома матки представляет собой доброкачественные опухоли, образующиеся из гладкомышечных клеток. Клаудины (CLDN) являются основными белками плотных контактов, демонстрируя различную экспрессию в тканях, причем профиль экспрессии CLDN является репрезентативным. CLDN играют важнейшую роль в неопластических процессах, так как принимают участие в формировании единого сигнального пути между внеклеточным матриксом и внутриклеточным цитоскелетом.
Цель. Изучить уровень экспрессии маркеров, отвечающих за функциональную активность плотных контактов клеток CLDN1, CLDN7 и CLDN10 в биоптатах интактного миометрия у женщин разных возрастных групп.
Материалы и методы. Обследовано 90 пациенток в возрасте от 23 до 47 лет, которые были рандоминизированы на 6 групп. В первые три группы вошли 45 практически здоровых пациенток, в четвертую, пятую и шестую группы – женщины с миомой матки. И контрольные группы и пациентки с миомой матки были разделены на ранний, средний и поздний репродуктивный возраст.
Исследование проводилось с разрешения этического комитета в отделении оперативной гинекологии с операционным блоком ФГБНУ «НИИ АГиР им. Д.О. Отта». (Директор – д.м.н., профессор Коган И.Ю.). Каждый участник подписывал форму информированного согласия на обследование.
Проведён комплекс диагностических методик: анамнестические данные, клинико-гинекологическое обследование, эхография, эндоскопия, гистологическое исследование соскобов и макропрепаратов, удаленных во время операций. Далее материал исследовался при помощи иммунофлуоресцентного анализа.
Статистическая обработка проводилась в программе «Excel 2010. Microsoft Office» и в аналитической программе «Statistica 10.0».
Результаты. В результате иммунофлуоренсцентного анализа было выявлено, что уровень экспрессии маркеров плотных межклеточных контактов Claudin 1, Claudin 7 и Claudin 10 снижается в эпителии мембран клеток у женщин, страдающих миомой матки.
Заключение. Таким образом, изменение функциональной активности плотных контактов приводит к нарушению связей между соседними клетками. Уровень экспрессии клаудинов может быть использован в качестве маркера и мишени для таргетной терапии.
IMPROVEMENT OF MECHANISMS FOR STATE MANAGEMENT OF CONTINUOUS IMPROVEMENT OF QUALITY OF PROVISION OF MEDICAL SERVICES IN UKRAINE
Authors: Karpenko Olena , Stavytska Svitlana , Artemenko Inna , Sidanich Iryna , Prozhoha Iryna
Published: September 2021

Objective. To substantiate theoretical and methodological principles, develop scientific and practical recommendations for state management of medical services in Ukraine.
Materials and methods. There were used such research methods as synthesis, analysis, scientific abstraction when specifying the categorical-conceptual framework of research; system structural analysis when developing the conceptual principles of state regulation of the provision of medical services of appropriate quality and accessibility; discriminant analysis when assessing the cost of public health services in Ukraine.
Results. An approach to the formation of a system to improve the efficiency and quality of medical services in Ukraine has been developed. The system of continuous improvement of the quality of medical services has been developed, which combines financial and economic calculations for provided medical services with screening examination of the technology of medical and diagnostic process according to the models of medical services and allows to build a hierarchical management system for financing and quality of medical services.
Conclusions. The has been proposed the method of payment for medical services according to the models of simple and complex medical services, which is the most promising for use in conditions of limited financial resources and involves compliance with the following rules.
Endodontic treatment regimens and their application in practice - survey and comparative study
Authors: Kula Łucja , Kalinowska Julita , Koczor-Rozmus Aleksandra
Published: September 2021

Introduction: Endodontics is a rapidly developing field of dentistry. Dentists have an increasing selection of techniques, tools, and materials to ensure therapeutic success.Aim: The aim of the study was to analyze the endodontic treatment regimens and their application in the daily practice of dentists. Material and Methods: A dentist survey was conducted through a Google Doc. The link to the form was placed on online dental groups, sent by e-mail to the offices and the questionnaire was also delivered to the dental offices in a printed form.Results: The majority of respondents always perform endodontic treatment procedures on pregnant women, take three X-rays and use a rubber dam during the treatment. Almost all respondents have the opportunity to take an X-ray in the workplace, and the working length is usually measured by the electronic method. The most commonly used methods of root canal preparation are the traditional and crown-down methods, and the most commonly used root canal filling method - the thermal method. Most of the respondents declared the following rinsing protocol: NaOCl and CA or EDTA.  Apex locator, ultrasounds, and microscopes are used in most dental offices, and more than half of the dentists responded that they perform procedures like broken tools removal or obliterated canals enlargement.Conclusions: Polish endodontics has developed over the years. Modern solutions are used more and more often. The canals are filled with the thermal method, and the popularity of performing complex endodontic procedures has increased. However, it is necessary to conduct further studies comparing the effectiveness of the canal preparation methods and the standardization of the root canal irrigation protocol.
Subjctive assessment of the quality of life of patients with rheumatological diseases
Authors: Tomaszewska Katarzyna , Majchrowicz Bożena , Szewczyk Magdalena
Published: September 2021

Background: Nowadays, rheumatic diseases are increasingly recognized as chronic diseases that lead to disability, reduced quality of life and dependence on others. They are caused by pain, stiffness and reduced mobility in the joints. Early treatment and rehabilitation can improve quality of life, prolong functional abilities and independence.Objectives: Assessment of functioning and quality of life in patients with rheumatologic diseases.Material and methods: The study group consisted of 200 patients diagnosed with rheumatological disease. The research method was the diagnostic survey method. As a technique, the survey technique was used, and the tool for collecting data from patients was a questionnaire, consisting of two parts: a questionnaire and a standardized quality of life questionnaire SF-36.Results: By far the greatest in the study group of patients were limitations in the performance of roles due to physical health (score at the average level of 96.8%) and also limitations due to emotional problems (score at the average level of 72.0%) classified as high. The severity of the study patients' limitations in physical functioning (50.6%), severity of pain (56.0%), assessment of general health (53.0%) and vitality (53.5%) were rated at medium level. The study patients' limitations in social functioning (34.8%) and mental health (46.2%) were relatively low.Conclusions: The quality of life of patients with rheumatologic diseases is rated at an average level, the physical dimension was rated worse by older people and better by people with higher education.
Juvenile Idiopathic Arthritis
Authors: Strońska Aleksandra , Grzeszczak Konrad , Rogulska Karolina
Published: September 2021

Młodzieńcze idiopatyczne zapalenie stawów (JIA) jest najczęstszą przewlekłą zapalną chorobą reumatyczną wieku dziecięcego. Jest to niejednorodna grupa chorób charakteryzująca się zapaleniem stawów, cechami pozastawowymi, w tym zapaleniem błony naczyniowej oka oraz, w niektórych przypadkach, markerami laboratoryjnymi. Przebieg choroby, postępowanie terapeutyczne i rokowanie różnią się w zależności od pierwotnej kategorii MIZS. Ostatnie postępy w leczeniu, zwłaszcza w stosowaniu środków biologicznych, znacznie zmniejszyły częstość występowania MIZS. Obecne podejścia do leczenia kładą nacisk na agresywne wczesne leczenie, aby opóźnić postęp choroby i poprawić wyniki. Jednak choroba może pozostać aktywna aż do wieku dorosłego i nadal potrzebne jest ciągłe uważne monitorowanie.
The impact of the COVID-19 pandemic on mental health
Authors: Budzyńska Julia , Leśniewska Magdalena , Kozioł Ilona , Milanowska Joanna
Published: September 2021

BACKGROUND: The outbreak of a coronavirus pandemic in 2019 posed a serious threat to the global population. Coronavirus Disease 2019 (COVID-19) has not only been a public health emergency, but has also affected mental health worldwide. Patients were exposed to a number of significant stressors during COVID-19 infection by which it appears that it may have had a major impact on mental health. Little is known about changes in levels of psychological affect, stress, anxiety and depression during this pandemic.AIM OF THE STUDY: The purpose of this study was to analyze the most recent available literature on the association of pandemic COVID-19 with psychiatric disorders occurring both as a result of past infection and in response to stress associated with the new situation of a global epidemic of Sars-CoV-2 virus.RESULTS: The psychological effects of the epidemic are clearly noticeable. The study identified groups particularly vulnerable to developing symptoms of anxiety, depression and post-traumatic stress disorder. Risk factors were also identified in people working in health care as having direct contact with the effects of infection with the new virus.SUMMARY AND CONCLUSIONS: Key elements of preventing psychological impact are the creation of a mental health organization. Another important task for governments is to create the conditions for economic security, as financial problems or job losses can also be the cause of mental crises.