bluuebunny/crossref_metadata_2025 huggingface dataset:
Intratumoral IFN-γ or topical TLR7 agonist promotes infiltration of melanoma metastases by T lymphocytes expanded in the blood after cancer vaccine
Authors: Tran Christine A , Lynch Kevin T , Meneveau Max O , Katyal Priya , Olson Walter C , Slingluff, Craig L
Published: February 2023

Background

Immune-mediated melanoma regression relies on melanoma-reactive T cells infiltrating tumor. Cancer vaccines increase circulating melanoma-reactive T cells, but little is known about vaccine-induced circulating lymphocytes (viCLs) homing to tumor or whether interventions are needed to enhance infiltration. We hypothesized that viCLs infiltrate melanoma metastases, and intratumoral interferon (IFN)-γ or Toll-like receptor 7 (TLR7) agonism enhances infiltration.

Methods

Patients on two clinical trials (Mel51 (NCT00977145), Mel53 (NCT01264731)) received vaccines containing 12 class I major histocompatibility complex-restricted melanoma peptides (12MP). In Mel51, tumor was injected with IFN-γ on day 22, and biopsied on days 1, 22, and 24. In Mel53, dermal metastases were treated with topical imiquimod, a TLR7 agonist, for 12 weeks, and biopsied on days 1, 22, and 43. For patients with circulating T-cell responses to 12MP by IFN-γ ELISpot assays, DNA was extracted from peripheral blood mononuclear cells (PBMCs) pre-vaccination and at peak T-cell response, and from tumor biopsies, which underwent T-cell receptor sequencing. This enabled identification of clonotypes induced in PBMCs post-vaccination (viCLs) and present in tumor post-vaccination, but not pre-vaccination.

Results

Six patients with T-cell responses post-vaccination (Mel51 n = 4, Mel53 n = 2) were evaluated for viCLs and vaccine-induced tumor infiltrating lymphocytes (viTILs). All six patients had viCLs, five of whom were evaluable for viTILs in tumor post-vaccination alone. Mel51 patients had viTILs identified in day 22 tumors, post-vaccination and before IFN-γ (median = 2, range = 0–24). This increased in day 24 tumors after IFN-γ (median = 30, range = 4–74). Mel53 patients had viTILs identified in day 22 tumors, post-vaccination plus imiquimod (median = 33, range = 2–64). Three of five evaluable patients across both trials had viTILs with vaccination alone. All five had enhancement of viTILs with tumor-directed therapy. viTILs represented 0.0–2.9% of total T cells after vaccination alone, which increased to 0.6–8.7% after tumor-directed therapy.

Conclusion

Cancer vaccines induce expansion of new viCLs, which infiltrate melanoma metastases in some patients. Our findings identify opportunities to combine vaccines with tumor-directed therapies to enhance T-cell infiltration and T cell-mediated tumor control. These combinations hold promise in improving the therapeutic efficacy of antigen-specific therapies for solid malignancies.
COVID-19 vaccination in patients with cancer receiving immune checkpoint inhibitors: a systematic review and meta-analysis
Authors: Ruiz Juan Ignacio , Lopez-Olivo Maria Angeles , Geng Yimin , Suarez-Almazor Maria E
Published: February 2023

Background

Immune checkpoint inhibitors (ICI) can cause off-target inflammatory and immune-related adverse events (irAE). Conceivably, COVID-19 vaccination could trigger an inflammatory and immune response that could induce or aggravate irAE.

Methods

The objective of this systematic review is to appraise the efficacy and safety of COVID-19 vaccination in patients with cancer treated with ICI. The literature search was performed in PubMed and Embase in English from December 2019 to February 2022. The review included clinical trials, observational cohort studies, case series, and case reports reporting on the clinical efficacy and safety of COVID-19 vaccines on patients with cancer treated with ICI. Outcomes of interest included seroconversion, SARS-CoV-2 infection rate, severe COVID-19, COVID-19 mortality rate. Incidence of ICI irAEs was also ascertained as well as vaccine adverse events. A meta-analysis was conducted to estimate the pooled effect sizes of the outcomes when possible, using random effects models.

Results

Overall, 19 studies were included for the analysis (n=10 865 with 2477 receiving ICI). We analyzed 15 cohort studies, 1 cross-sectional study, and 3 case reports. There were no statistically significant differences in seroconversion rates after the second dose of the vaccine when comparing patients with cancer receiving ICI with patients without cancer (risk ratio, RR 0.97, 95% CI 0.92 to 1.03) or with patients with cancer without active treatment (RR 1.00, 95% CI 0.96 to 1.04). There was a higher probability of seroconversion in patients with cancer treated with ICI compared with patients with cancer treated with chemotherapy (RR 1.09, 95% CI 1.00 to 1.18). In a single study in patients receiving ICI, no differences were observed in risk of irAE between those receiving inactivated vaccine and those unvaccinated (pneumonitis RR 0.88, 95% CI 0.33 to 2.3; rash RR 1.03, 95% CI 0.66 to 1.62; arthralgia RR 0.94, 95% CI 0.51 to 1.75). There were no studies for other types of vaccines comparing vaccinated vs not vaccinated in patients treated with ICI. The most common vaccine-related adverse events were local pain or fatigue. Overall, the quality of evidence was rated as very low.

Conclusion

COVID-19 vaccination appears to be effective and safe in patients with cancer receiving ICI.
Perceptions of uncertainty in forest planning: contrasting forest professionals’ perspectives with the latest research
Authors: de Pellegrin Llorente Irene , Eyvindson Kyle , Mazziotta Adriano , Lämås Tomas , Eggers Jeannette , Öhman Karin
Published: February 2023

Many of the intrinsic facets of forest planning are surrounded by uncertainty. Decision-makers strive to improve their understanding of the sources of uncertainty and their impact on the decision-making process. However, uncertainty is rarely integrated into real-world forestry applications or into decision support tools used in forest planning problems. To identify the needs, interests, and challenges of managing uncertainty in forest planning, we interviewed forestry professionals. All the interviewees indicated the positive potential of a tool that could address some facets of uncertainty. Additionally, we conducted a review of the most recent literature on this topic to understand current hot topics and future trends that could help address real-world challenges. This study highlights the next steps to incorporate uncertainty into the decision support systems for forest planning. However, to strengthen the bond between the practical needs of forestry professionals and the theoretical approaches proposed by recent literature, more effort should be placed on defining terminology and formulating a theoretical framework for uncertainty analysis. This will provide the forestry community with a common language and typology, help increase its general understanding, and improve communication between forestry researchers, forestry professionals, and other stakeholders.
DNN-based speech watermarking resistant to desynchronization attacks
Authors: Pavlović Kosta , Kovačević Slavko , Djurović Igor , Wojciechowski Adam
Published: February 2023

Desynchronization attacks proved to be the greatest challenge to audio watermarking systems as they introduce misalignment between the signal carrier and the watermark. This paper proposes a DNN-based speech watermarking system with two adversarial networks jointly trained on a set of desynchronization attacks to embed a randomly generated watermark. The detector neural network is expanded with spatial pyramid pooling layers to be able to handle signals affected by these attacks. A detailed training procedure of the aforementioned DNN system with gradual attack introduction is proposed in order to achieve robustness. Experiments performed on a speech dataset show that the system achieves satisfactory results according to all the benchmarks it was tested against. The system preserves signal quality after watermark embedding. Most importantly, the system achieved resistance to all considered desynchronization attacks. The majority of the attacks cause less than [Formula: see text]% of incorrectly detected watermarked bits on average, which outperforms comparative techniques in this regard.
An SFEM Abaqus UEL for Nonlinear Analysis of Solids
Authors: Kshirsagar Sandeep , Nguyen-Xuan H. , Liu G. R. , Natarajan Sundararajan
Published: February 2023

In this paper, three different smoothed finite element method (SFEM), viz., node-based smoothed finite element method (NS-FEM), face-based smoothed finite element method (FS-FEM) and [Formula: see text]-finite element method ([Formula: see text]-FEM) are adopted for 3D solids undergoing large deformation. The common feature of all these techniques is the introduction of smoothed strain which is written as a weighted average of the compatible strain field over smoothing domains. The choice of smoothing domain is what differentiates them. The spatial discretization can be based on the simplest and automatically genera-table four-node tetrahedral elements and aforementioned techniques have shown to yield accurate results even on a coarser discretization. To take the advantages of the SFEM, it is beneficial to the FEM community to have it implemented in the widely used Abaqus[Formula: see text] software. Such an implementation is challenging because the neighboring SFEM elements are interconnected in the smoothed strain matrices in the elemental level. In this work, the above-mentioned SFEM models are implemented in the commercial software Abaqus using the softwares’ user element (UEL) feature. The challenges during the definition and the assembly of the smoothing domains are effectively addressed in this work. The developed UEL and the associated files can be downloaded from https://github.com/nsundar/3DSFEM. The implementation is validated against benchmark examples and the robustness is demonstrated with complicated real-life problems, viz., tire patch contact with road and simulation of human thumb.
The influence of central metal in phthalocyanine for photodynamic therapy of glioblastoma
Authors: Oral Ayça Tunçel , Yüzer A. Celil , Özel Derya , Ince Mine , Yurt Fatma
Published: February 2023

Glioblastoma multiforme (GBM) is an aggressive and fatal brain tumor that tends to occur in older adults and has several subtypes. The fact that the mechanisms of initiation and progression of glioblastoma are not yet known is an obstacle to the treatment of the disease. For this reason, studies have been carried out in recent years to develop new therapeutic approaches. Photodynamic therapy (PDT) is a procedure that has been approved and is considered safe in most clinical trials. With the help of a photosensitizer (PS), tumor growth regression is promoted, aiming to prolong the survival of patients with glioma progression. It is extremely important to conduct studies focused on the development, application, and biodistribution of possible candidates for these photosensitizing drugs. Phthalocyanines (Pcs) are good photosensitizers for this purpose. Here, we describe an approach to the application of photodynamic therapy with metal-phthalocyanines [zinc-phthalocyanine (ZnPc) and cobalt-phthalocyanine (CoPc)] and their carboxylic acid derivatives in U87-MG cell lines. For the phototoxicity study, percent viability values were calculated using the MTT test. The results showed that cell death was effectively induced in U87-MG cells. In our study, the phthalocyanines applied in the in vitro treatment of glioblastoma cell lines with PDT have shown high toxicity and the treatment has been successful. Our findings highlight the potential of ZnPc-COOH and CoPc-COOH with their carboxylic acid derivatives as biological material for biomedical applications in the treatment of glioblastoma cells.
Finite Element Evaluation of Failure in Additively Manufactured Continuous Fiber-Reinforced Composites
Authors: Gljušćić Matej , Franulović Marina , Žerovnik Andrej
Published: February 2023

In an attempt to increase resource efficiency and reduce carbon emissions, the development of lightweight designs in structural applications is essential. In addition, the lightweight structures often follow complex topologically optimized designs which are more suitable for the application of additive, in contrast to conventional manufacturing techniques. Within the additive manufacturing (AM) process, constituents may be combined to design and produce durable and lightweight materials with predefined mechanical, electrical, and thermal properties, while also accounting for their sustainability and recyclability. Regretfully, due to the lack of research in material behavior, the AM technology implementation in engineering applications is still limited in comparison to traditional manufacturing methods. While the potential of additively manufactured continuous fiber composites has already been recognized in the scientific community, constitutive modeling and damage resistance are seldom reported. Since fiber-reinforced composite structures are rarely designed as unidirectional (UD), this study is focused on numerical analysis of failure for multi-directionally reinforced composite laminates loaded in a uniaxial direction. Specimens are modeled and evaluated using a progressive damage model, proposing guidelines for safer design and application.
Enhanced dielectric responses of Ba0.6Sr0.4TiO3 thin films onto BaxSr1−xTiO3-buffered stainless steel substrates
Authors: Dong Hanting , Ke Liang , Hui Xiangjun , Mao Jiangfeng , Du Haiqing , Yuan Wenqi
Published: February 2023

Misfit strain, lattice parameter, polarization, permittivity, and tunability of Ba[Formula: see text]Sr[Formula: see text]TiO3 thin films onto Ba[Formula: see text]Sr1−xTiO3-buffered stainless steel (SS) substrates are computed via a modified phenomenological model. When the Ba/Sr ratio of Ba[Formula: see text]Sr1−xTiO3 buffer layer grows, the permittivity and tunability first increase and then decrease with the maximum at [Formula: see text] = 0.75. The highest tunability of such films prepared by the sol-gel technique can reach 32.5% at the electric field of 320 kV/cm when [Formula: see text] = 0.8. The strains are qualitatively analyzed through combining XRD, Raman, and theoretical calculation. The computed data are generally supported by experimental lattice parameters, permittivities, and tunabilities, which show that polycrystalline BST thin films with smaller compressive strain obtain higher dielectric response, and that inserting buffer layer could regulate the strains and dielectric properties of BST thin films.
Automata Column
Authors: Viswanathan Mahesh
Published: February 2023

In this issue's Automata Theory Column, we have an article by Andreas Pavlogiannis on the CFL/Dyck reachability problem on graphs:

Given a graph
G
with edges labeled by symbols from an alphabet Σ, source and target nodes
s
and
t
, respectively, and a context-free language
L
over Σ, determine if there is a path from
s
to
t
that is labeled by a word in
L.
Verification Column
Authors: Lazić Ranko
Published: February 2023

In this article, the author takes us in a masterful and engaging manner from the basics of stochastic games to the cutting-edge work on them in the verification community. I expect it will quickly become a widely used reference.
Towards an Improved Electrocatalytic Material for Detection of Polyphenols Based on Transition Metal Phosphides Anchored on Reduced Graphene Oxide
Authors: Amorim Isilda , Yu Zhipeng , Bento Fátima , Liu Lifeng
Published: February 2023

The design of advanced materials with catalytic activity for detection of a target molecule is key to construct a sensitive electrochemical sensor. Transition metal phosphides (TMPs) have recently attracted substantial interest and are widely investigated as electrode material in the field of energy conversion/storage. TMPs have also been exploited for electrochemical sensing showing promising results for molecular detection. In this work, we report the preparation of a composite consisting of bimetallic cobalt−nickel phosphide (CoNiP) nanoparticles supported on reduced graphene oxide (rGO) and study the impact of phosphorization and presence of rGO on the electrochemical response using hydroquinone (HQ) as a model phenolic compound. The results show that the catalytic performance of CoNiP@rGO is a consequence of the synergetic interaction between different atoms of CoNiP and rGO, where P increases the proton concentration at the electrode interface favoring a catalytic mechanism where metal centers are oxidized. In the presence of rGO this effect is suppressed due to the formation of high valence states of CoNiP. The remarkable electrocatalytic performance may originate from the modulation of the electronic structure together with the large electroactive surface area and low electron-transfer resistance, enabling CoNiP@rGO to be a promising candidate for electrochemical sensor construction.
Shen Qi Wan‐Containing Serum Alleviates Renal Interstitial Fibrosis via Restraining Notch1‐Mediated Epithelial‐Mesenchymal Transition
Authors: Chen Hongshu , Zhou Xiaojie , Yang Yuanxiao , Feng Yaorong
Published: February 2023

Objective. Shen Qi Wan (SQW) is the most classic prescription for the clinical therapy of chronic kidney disease in China. Nevertheless, the function of SQW in renal interstitial fibrosis (RIF) has not been clearly clarified. Our purpose was to explore the protective function of SQW on RIF. Methods. After intervention with SQW‐containing serum alone at increasing concentrations (2.5, 5, and 10%) or in combination with siNotch1, the transforming growth factor‐beta (TGF‐β)‐induced HK‐2 cell viability, extracellular matrix (ECM)‐, epithelial‐mesenchymal transition (EMT), and Notch1 pathway‐associated protein expressions were assessed by cell counting kit‐8, qRT‐PCR, western blot, and immunofluorescence assays. Results.SQW‐containing serum intensified the viability of TGF‐β‐mediated HK‐2 cells. Besides, it augmented the collagen II and E‐cadherin levels, and weakened the fibronectin, α‐SMA, vimentin, N‐cadherin, and collagen I levels in HK‐2 cells triggered by TGF‐β. Moreover, it is found that TGF‐β led to the upregulation of Notch1, Jag1, HEY1, HES1, and TGF‐β in HK‐2 cells, which was partially offset by SQW‐containing serum. Furthermore, cotreatment of SQW‐containing serum and Notch1 knockdown further apparently alleviated the Notch1, vimentin, N‐cadherin, collagen I, and fibronectin levels in HK‐2 cells induced by TGF‐β. Conclusion. Collectively, these findings elucidated that SQW‐containing serum attenuated RIF via restraining EMT through the repression of the Notch1 pathway.
Numerical Simulation Study on Stability Control Technology of Large-Area Wall Caving Area (LAWCA) in Large-Inclined Face
Authors: Liu Xun , Tu Shihao , Tu Hongsheng , Tang Long , Ma Jieyang , Li Yan , Li Wenlong , Miao Kaijun , Tian Hao
Published: February 2023

The caving characteristics of the goaf significantly impact the mining stability of the working face. The coal-forming environment of the steeply dipping coal seam is complex. After mining, the caving rock mass rolls to the lower part of the working face due to gravity, and the caving compaction characteristics of the working face are different from those of the flat and gently inclined working face, taking Huainan Xinji No. 2 Mine 211112 high-angle composite roof working face large-area gang roof fall area as the engineering background. To safely pass through a large roof fall area, a FLAC3D numerical simulation method considering the goaf’s compaction effect and the excavation’s additional damage is proposed. The Weibull distribution function is introduced to modify the elastic modulus parameters of the rock mass after excavation, which more accurately reflects the damage process of the rock mass after hole. Based on the goaf compaction theory, the elastic model is developed for the second time, and the accurate simulation of the caving rock mass is realized. On this basis, the proposed numerical simulation method is used to simulate the large-area roof caving of the large-angle working face, a scheme to control the stability of the working face by using the paste filling technology is proposed, and the material parameters of the filling body are determined. The research results show that when the water-cement ratio of the backfill is 3 : 1, the simulation and field trial results are good, and the safe and efficient mining of the large-angle composite roof working face is realized, which verifies the feasibility and correctness of the coupled simulation method. At the same time, the research results can provide a reference for controlling the roof fall area of the working face with a large inclination angle.
Seasonal Variation in Fatty Acid and Amino Acid Composition of the Patagonian Marine Polychaete Abarenicola pusilla and Its By-Products
Authors: Farías Ana , Valenzuela Guillermo , Hernández Jorge , Uriarte Iker , Viana María Teresa
Published: February 2023

This study aims to provide a quantitative analysis of the amino acids (AAs) and fatty acids (FAs) found in by-products of the Patagonian marine polychaete Abarenicola pusilla. Samples of polychaetes were taken in different seasons and processed to generate three by-products: eviscerated whole body, press cake, and press liquid. The results showed a clear seasonal difference, with essential nutrients decreasing significantly in winter. For example, from eviscerated whole body specimens, essential fatty acids, eicosapentaenoic acid (EPA), and arachidonic acid (ARA) maintained a relationship of 1 in summer, 1.24 in winter, and 1.5 in spring and autumn. In comparison, docosahexaenoic acid (DHA) was undetected in some extracts in winter. However, the fatty acid content in press liquid resulted in high variation, with the lowest content during the autumn. In contrast, the press liquid and press cake responded similarly. DHA decreased from spring to winter (from 0.1 to 0.08), whereas EPA resulted in high variation along the seasons (from 0.57 to 0.03) from summer to autumn. The highest protein values were observed in the spring and summer. In contrast, lipid values remained under 10% constant throughout all seasons, unless in the eviscerated carcass, where 5 to 3% higher lipids were found, indicating that A. pusilla uses protein more efficiently than lipids as an energy source. The most abundant EAAs were lysine (LYS) and leucine (LEU), while glycine (GLY), glutamic acid (GLU), and alanine (ALA) were the most abundant NEAAs. Finally, A. pusilla harvest conditions and the type of extract recommended to produce a valuable ingredient for marine aquafeeds are discussed.
The Profertility and Aphrodisiac Activities of Tribulus terrestris L.: Evidence from Meta-Analyses
Authors: Ara Anam , Vishvkarma Rahul , Mehta Poonam , Rajender Singh
Published: February 2023

Tribulus terrestris L. (TT) is a traditional medicinal plant, which belongs to the Zygophyllaceae family. TT extracts have been widely used for diuretic, analeptic, aphrodisiac, and profertility properties. To quantitatively evaluate the profertility and aphrodisiac effects of Tribulus terrestris L., we undertook the present meta-analyses on published data. A thorough literature screening was performed to identify articles evaluating the effect of TT on spermatogenesis, male fertility, reproductive, and aphrodisiac parameters. We shortlisted 30 relevant studies conducted on humans and rodents. Meta-analyses were conducted to evaluate the quantitative impact of TT on various fertility parameters. In case of humans, the pooled analysis on 133 subjects showed significant improvements in sperm concentration (

SDM
=
0.624

, 95%

CI
=
0.13

to 1.117,

p
=
0.013

) and sperm motility (

SDM
=
0.742

, 95%

CI
=
0.331

to 1.152,

p
=
0.001

). TT resulted in nonsignificant increases in testosterone and LH and a nonsignificant decrease in FSH. Similar to the above, TT improved sperm count, sperm motility, and sperm viability in rodents with normal or compromised fertility. The effect on hormone levels was less credible with frequent variations across studies and animal models. The aphrodisiac activity was studied in castrated animal models or normal rodents, both of which showed significant improvements in mounting frequency and intromission frequency and significant declines in mounting latency and intromission latency. These meta-analyses suggested that TT possesses profertility and aphrodisiac activities.
Strategies for Solving the Issue of Malachite Green Residues in Aquatic Products: A Review
Authors: He Jiang , Mo Ping , Luo Yu-Shuang , Yang Pin-Hong
Published: February 2023

Malachite green (MG) residue in aquatic products is a widely concerning issue, and the possible source of MG contamination includes its illegal usage and environmental pollution. A variety of strategies for solving such a problem have been proposed, and the research about them is summarized in this review. The MG contamination in aquaculture environments can be eliminated by adsorption, degraded by advanced oxidation processes (AOPs), or biodegraded by microbes or enzymes. The illegal usage of MG can be prevented by screening novel anti-Saprolegnia sp. agents from current available agricultural antibiotics, plant extracts, or antagonistic microbes. Nevertheless, deficiencies also existed in these proposed solving strategies. Therefore, further research opportunities in such areas were provided. This includes developing effective combinatorial methods (adsorption + AOPs or biodegradation) for eliminating MG from the aquaculture environment; systematically considering the impact of practical conditions on the efficiency of MG elimination; screening more efficient anti-Saprolegnia sp. agents; and systematically evaluating both the in vivo activities and safety of these agents.
A Case of Leukocytoclastic Vasculitis and Associated Conjunctivitis Following MMR Vaccine Administration
Authors: Nazir Hana I. , Hess Aubrey A. , Soni Abha , Potter Kathryn A.
Published: February 2023

Introduction. Leukocytoclastic vasculitis (LCV) is a small-vessel vasculitis characterized by immune complex deposition in the walls of dermal capillaries and venules. With the COVID-19 pandemic, more adults are receiving the MMR vaccine, as it may enhance innate immune responses against COVID-19 infection. Here, we report a case of LCV and associated conjunctivitis arising in a patient secondary to immunization with the MMR vaccine. Methods and Results. A 78-year-old man on lenalidomide therapy for multiple myeloma presented to an outpatient dermatology clinic with a two-day history of a painful rash consisting of scattered pink dermal papules on bilateral dorsal and palmar hands, as well as bilateral conjunctival erythema. Histopathological findings—which revealed an inflammatory infiltrate with papillary dermal edema, as well as nuclear dust within small blood vessel walls with extravasation of red blood cells—were most consistent with LCV. It then became known that the patient had received an MMR vaccine two weeks prior to the onset of the rash. The rash was resolved with the use of topical clobetasol ointment, and the patient’s eyes were cleared as well. Conclusions. This is an interesting presentation of MMR vaccine-related LCV occurring only on the upper extremities with associated conjunctivitis. Had the patient’s oncologist not known about the recent vaccination, it is likely that the treatment of his multiple myeloma would have been postponed or altered, as lenalidomide can also cause LCV.
Assessment of Ozone Nanobubble Technology to Reduce Freshwater Algae
Authors: Ng Pok Him , Huang Qianjun , Huang Liqing , Cheng Tzu Hsuan , Man Ka Yan , Cheng Ka Po , Rita Pinheiro Marques Ana , Zhang Ju , St-Hilaire Sophie
Published: February 2023

Algal blooms can lead to low dissolved oxygen and fluctuating pH, and the toxins produced by some species can be toxic to aquatic animals. In this study, we assessed the potential of ozone nanobubble technology for reducing a diatom species, Nitzschia sp., commonly found in freshwater ponds in Hong Kong. This study suggests that ozone at a low dose of 0.025 ± 0.003 ppm was sufficient to reduce algae by 66.4% within 5 minutes of treatment. An even higher killing effect (68.2%) was observed when ozone was delivered using nanobubbles for 9 minutes. A 24-hour delayed effect was also detected, with a further reduction of approximately 10% of the algae for both ozone treatments (macro and nanobubble delivery methods). In addition to controlling algae, applying ozone at a level that is not detrimental to fish may also benefit the dissolved oxygen levels in pond systems.
Oncogenic IDH1 Mutation Imparts Therapeutically Targetable Metabolic Dysfunction in Multiple Tumor Types
Authors: Robinson Troy M. , Levine Ross L.
Published: February 2023

In this issue of Cancer Discovery, Thomas and colleagues leverage mass spectrometry metabolomics, stable isotope labeling, and functional studies to explore metabolic vulnerabilities in cancers harboring mutations in isocitrate dehydrogenase (IDH). The authors present compelling data to support the claim that dysregulated lipid synthesis underpins a synthetic lethal target in cancers with IDH1, but not IDH2, mutations.

See related article by Thomas et al., p. 496 (9).
Co-Occurrence of Nephronophthisis Type 1 and Alström Syndrome: A Case Report
Authors: Rossoni Lisa , Lugani Francesca , Orsi Silvia Maria , Verrina Enrico Eugenio , Ghiggeri Gian Marco , Angeletti Andrea , Caridi Gianluca , La Porta Edoardo
Published: February 2023

We describe the unique case of a patient in whom two ciliopathies with autosomal recessive transmission were clinically and molecularly diagnosed: nephronophthisis type 1 (NPHP1) and Alström syndrome (AS). NPHP1 is one of the main genetic causes of terminal kidney failure in childhood. AS is an ultra-rare multi-systemic disease, characterized by progressive kidney disease, hepatic failure, dystrophy of the rods and cones to blindness, slowly progressive neuro-sensory deafness, dilated cardiomyopathy, obesity, insulin resistance/type 2 diabetes mellitus. The coexistence in the same patient of two rare syndromes with overlapping clinical manifestations but genetically different is an eventuality to be considered. This case report would describe the onset and progression of the multi-organ manifestations of both syndromes to highlight that ciliopathies present a strong phenotype overlap but also specific peculiarities. Therefore, to make a correct diagnosis that is essential to achieve the best clinical management could be challenging.
Diagnosis and Management of Idiopathic Hypothalamic Dysfunction: A Case Series and Systematic Review
Authors: Xu Zhuoran , Wang Yawen , Duan Lian , Yao Yong , Feng Feng , Wang Linjie , Deng Kan , You Hui , Yang Hongbo , Lu Lin , Zhu Huijuan
Published: February 2023

Introduction: Idiopathic hypothalamic dysfunction (IHD) is a rare syndrome with heterogeneous clinical symptoms. This study aimed to systematically review the clinical features and potential treatment of IHD based on our case series and literature. Methods: We analysed six recently diagnosed cases of IHD in Peking Union Medical College Hospital and conducted a systematic review of IHD case studies published before August 25, 2021, using the PubMed/Medline database. All 12 articles that met the definition of IHD and provided individual clinical data were reviewed. Results: Of the 19 cases reviewed (13 from the literature and 6 from our centre), the median age at onset was 6 years. Obesity/weight gain (n = 14, 73.7%) and electrolyte abnormalities (n = 14, 73.7%) were the most common hypothalamic physiological dysfunction, followed by autonomic dysregulation (n = 13, 68.4%) and adipsia (n = 13, 68.4%). The most common initial symptom of young patients was obesity/weight gain, whereas the initial symptoms of the three adult patients were hypothalamic amenorrhoea, delayed sexual development, and polydipsia. 11 (57.9%) patients had obesity, and three of our patients were diagnosed with metabolic syndrome in late adolescence or early adulthood. Three of our cases diagnosed with growth hormone deficiency received growth hormone therapy, which exerted positive effects on growth promotion and weight stabilization. Conclusion: Although obesity/weight gain was the most common symptom of IHD, uncommon initial symptoms such as electrolyte abnormalities and sexual disorders also require attention, especially in patients with late childhood- or adult-onset IHD. Consistent monitoring of metabolic profiles is recommended. Positive effects of growth hormone replacement therapy on growth and weight were observed, but more extensive cohort studies are required to confirm its efficacy and safety.
A nova lei geral de licitações e os tribunais de contas brasileiros: notas sobre as inovações e os aperfeiçoamentos no controle das contratações públicas
Authors: Nascimento Leandro Maciel
Published: February 2023

O trabalho aborda pontos relativos ao controle realizado pelos tribunais de contas em face do advento da nova lei brasileira de licitações. Está dividido em duas partes, além da introdução e das considerações finais. Na primeira parte, apresenta-se um panorama do controle externo, de modo a justificar a origem, o fundamento, a legitimidade e os modelos no direito comparado. Na segunda parte, são expostas alterações de pontos específicos, que impactam diretamente o trabalho dos tribunais de contas. Nessa seção do texto, enfatiza-se o artigo 113 da lei n. 8.666/1993 e sua quase total revogação pela lei n. 14.133/2021. Busca-se, como objetivo geral, apresentar visão panorâmica do relevante papel que os tribunais de contas brasileiros exercem quando realizam sua competência de fiscalização e de controle das contratações públicas, de modo a contribuir com a busca da melhor contratação e com o aperfeiçoamento da gestão pública.
Do monte Hélicon ao Jaraguá: O caso particular do Brasilienses aurifodinae
Authors: Mariano Alexandra de Brito
Published: February 2023

O Brasilienses aurifodinae de José Basílio da Gama inscreve-se numa microtradição de poesia didáctica jesuítica que vai evidenciar-se em textos setecentistas sobre mineração escritos quer na Europa, quer no Novo Mundo. Ao destacar particularidades da mineração aurífera nas Minas Gerais e, simultaneamente, ao recordar tradições literárias e mitológicas da antiguidade clássica, o poeta reflete uma marcada intencionalidade. Pretendemos, entre outras questões, avaliar alguns aspetos que revelam essa intencionalidade e que tornam este poema basiliano distinto no conjunto da produção neolatina inaciana.
O terramoto como metáfora: O Grande Terramoto de Lisboa e o prenúncio do sismo jesuítico na Época da Luzes
Authors: Franco José Eduardo
Published: February 2023

A crise provocada pelo terramoto de 1755 revelou a capacidade de liderança do futuro Marquês de Pombal, afirmando-o como a figura decisiva do Reinado de D. José I (1750-1777) no processo de reconstrução de Lisboa e das reformas políticas, tomando como a Companhia de Jesus como adversário a abater e que acabará por expulsar em 1759. O nosso artigo retoma estes dois grandes acontecimentos mediáticos do Século das Luzes em Portugal e procura analisar a sua inter-relação, significados e consequências que conduziram à reconfiguração de diversos campos da paisagem física, social e cultural portuguesa.
Manuscrito truncado e inédito de Pombal sobre o terramoto [c. 1755]
Authors: Melo Sebastião José de Carvalho e
Published: February 2023

Fonte: Coleção Pombalina. Reservados da Biblioteca Nacional de Portugal. BNP, PBA. 696, ff. 11r-13v.
Antologia pombalina
Authors: Garção Correia , Quita Domingos dos Reis , Gama José Basílio da , Silva Antônio Dinis da Cruz e , Costa Cláudio Manuel da , Peixoto Inácio José de Alvarenga , Alvarenga Manuel Inácio da Silva , Breyner Teresa de Melo , Almeida Nicolau Tolentino de , Lencastre Catarina de , Bocage Manuel Maria Barbosa du , Magalhães Alberto , Dias Simões , Junqueiro Guerra , Assis Machado de , Branquinho José
Published: February 2023

Antologia de poemas (1759-1905).
Poema de Leonardo Gandolfi
Authors: Gandolfi Leonardo
Published: February 2023

Inédito de Leonardo Gandolfi.
Linha a linha
Authors: Nuernberger Renan
Published: February 2023

Resenha de "p:l:a:n:g:e  p:l:a:n:g:e", de Claudia Abeling.
Dysregulated Smooth Muscle Cell BMPR2–ARRB2 Axis Causes Pulmonary Hypertension
Authors: Wang Lingli , Moonen Jan-Renier , Cao Aiqin , Isobe Sarasa , Li Caiyun G. , Tojais Nancy F. , Taylor Shalina , Marciano David P. , Chen Pin-I. , Gu Mingxia , Li Dan , Harper Rebecca L. , El-Bizri Nesrine , Kim Yu-Mee , Stankunas Kryn , Rabinovitch Marlene
Published: February 2023

Objective:

Mutations in
BMPR2
(bone morphogenetic protein receptor 2) are associated with familial and sporadic pulmonary arterial hypertension (PAH). The functional and molecular link between loss of BMPR2 in pulmonary artery smooth muscle cells (PASMC) and PAH pathogenesis warrants further investigation, as most investigations focus on BMPR2 in pulmonary artery endothelial cells. Our goal was to determine whether and how decreased BMPR2 is related to the abnormal phenotype of PASMC in PAH.

Methods:

SMC-specific

Bmpr2
−/−

mice (

BKO
SMC

) were created and compared to controls in room air, after 3 weeks of hypoxia as a second hit, and following 4 weeks of normoxic recovery. Echocardiography, right ventricular systolic pressure, and right ventricular hypertrophy were assessed as indices of pulmonary hypertension. Proliferation, contractility, gene and protein expression of PASMC from

BKO
SMC

mice, human PASMC with
BMPR2
reduced by small interference RNA, and PASMC from PAH patients with a
BMPR2
mutation were compared to controls, to investigate the phenotype and underlying mechanism.

Results:

BKO
SMC

mice showed reduced hypoxia-induced vasoconstriction and persistent pulmonary hypertension following recovery from hypoxia, associated with sustained muscularization of distal pulmonary arteries. PASMC from mutant compared to control mice displayed reduced contractility at baseline and in response to angiotensin II, increased proliferation and apoptosis resistance. Human PASMC with reduced BMPR2 by small interference RNA, and PASMC from PAH patients with a
BMPR2
mutation showed a similar phenotype related to upregulation of pERK1/2 (phosphorylated extracellular signal related kinase 1/2)-pP38-pSMAD2/3 mediating elevation in ARRB2 (β-arrestin2), pAKT (phosphorylated protein kinase B) inactivation of GSK3-beta, CTNNB1 (β-catenin) nuclear translocation and reduction in RHOA (Ras homolog family member A) and RAC1 (Ras-related C3 botulinum toxin substrate 1). Decreasing ARRB2 in PASMC with reduced BMPR2 restored normal signaling, reversed impaired contractility and attenuated heightened proliferation and in mice with inducible loss of BMPR2 in SMC, decreasing ARRB2 prevented persistent pulmonary hypertension.

Conclusions:

Agents that neutralize the elevated ARRB2 resulting from loss of BMPR2 in PASMC could prevent or reverse the aberrant hypocontractile and hyperproliferative phenotype of these cells in PAH.
IAN: Iterated Adaptive Neighborhoods for Manifold Learning and Dimensionality Estimation
Authors: Dyballa Luciano , Zucker Steven W.
Published: February 2023

Invoking the manifold assumption in machine learning requires knowledge of the manifold's geometry and dimension, and theory dictates how many samples are required. However, in most applications, the data are limited, sampling may not be uniform, and the manifold's properties are unknown; this implies that neighborhoods must adapt to the local structure. We introduce an algorithm for inferring adaptive neighborhoods for data given by a similarity kernel. Starting with a locally conservative neighborhood (Gabriel) graph, we sparsify it iteratively according to a weighted counterpart. In each step, a linear program yields minimal neighborhoods globally, and a volumetric statistic reveals neighbor outliers likely to violate manifold geometry. We apply our adaptive neighborhoods to nonlinear dimensionality reduction, geodesic computation, and dimension estimation. A comparison against standard algorithms using, for example, k-nearest neighbors, demonstrates the usefulness of our approach.
Existential Well-being, Mental Health, and COVID-19: Reconsidering the Impact of Lockdown Stressors in Moscow
Authors: Klimochkina Anastasia Y. , Nekhorosheva Elena V. , Kasatkina Daria A.
Published: February 2023

Background. Initial psychological papers on COVID-19, mental health and wellbeing mostly focus on the aftermath lockdown-related stress and stress related to the disease itself. Still, we presume that personal well-being can be resistant to stressors depending on the way the person is settled in their life. Objective. We seek to reconsider the contribution of lockdown-related stressors to existential well-being, to assess existential well-being during the outbreak and to compare the contribution of living conditions and COVID-19-related factors on well-being. Design. An online survey was conducted during the peak of the outbreak in Moscow (April-May 2020) (N=880). The data was obtained using the “Test of Existential Motivations” questionnaire and a series of questions addressing (1) living conditions — mental and physical health, employment, and social distancing; (2) COVID-19-related stressors — non-chronic illness, financial losses, and unavailability of goods or services; (3) sociodemographic indicators — age, gender, and income. Data analysis included hierarchical multiple regression, one-sample ttest, and analysis of variance. Results. Surprisingly, the existential well-being of Moscow citizens during the period was moderate. Each of the three groups of factors predicted a similar proportion of the variance of well-being (3-3,9%). The strongest predictors of well-being were long-term mental health status and financial stability. The effect of COVID-19-related stressors was most pronounced when they co-occur. Conclusion. The negative association between lockdown-related stressors and poor well-being is not universal. It is necessary to study the effect of COVID19-related stressors in combination with individual living conditions and regionspecific factors and to focus on the prevention of the occurrence of stressors.
The Relationship between Subjective Well-being and Social Support among Jordanian University Students
Authors: Mahasneh Ahmad M.
Published: February 2023

Background. Although the interest in subjective well-being has flourished during recent decades, there is a general lack of research into this subject throughout the Arab world, and in the Jordanian academic environment in particular. Objective. The present study aimed to identify any significant gender differences in the level of subjective well-being, and to examine the relationship between subjective well-being and social support among a sample of Hashemite University students. Design. The study sample comprised 679 male and female undergraduate students from the Hashemite University chosen by purposive method. The College Student Subjective Well-being Questionnaire and Multidimensional Scale of Perceived Social Support were used to collect the data. Results. The results showed no significant differences in the level of subjective wellbeing due to the gender variable, but indicated significant differences between genders in satisfaction with academics and school connectedness. The results also showed a positive relationship between subjective well-being and social support. Conclusion. The current study contributes to enriching the theoretical literature related to gender differences in the level of subjective well-being of Jordanian university students and to examining the relationship between subjective well-being and social support.
Hartmann’s Boundaries Questionnaire: Measuring Psychometric Properties and the Structure in a Russian-speaking Sample
Authors: Kamardina Anna S.
Published: February 2023

Background. Psychological boundaries are defined as one’s ability to distinguish various components of psychological life: conscious and subconscious, self and others. The Boundaries in the Mind concept by E. Hartmann belongs to the psychodynamic tradition and is implemented in the Boundaries Questionnaire, which assesses the thinness of one’s psychological boundaries. Its shortest version (18 items) has been adapted in Russian but is a one-scale tool. The BQ-46 version, developed by D. Rawlings, consists of six subscales which allow for structural analysis. Objective. The objective of this study was to develop a Russian version of the questionnaire based on the BQ-46 and analyze its structure in a Russian-speaking sample. Design. The BQ-46 was translated into Russian and back. Data collection was arranged online. Three hundred eighty-seven (387) participants filled in the Russian version of the questionnaire. Two hundred ninety-six (296) of them also filled out four additional questionnaires for convergent validity assessment, and one hundred and one (101) subjects completed a BQ-46 retest. Results. The Russian version of the questionnaire (referred to as BQ-33) consists of 33 items and is a five-scale measurement tool. Its subscales are generally in line with the original BQ-46 version by D. Rawlings. The BQ-33 demonstrated acceptable-to-good reliability and good test-retest stability (r = 0.86). The convergent validity of the BQ-33 was supported by associations with the respective psychological concepts. My findings supported the idea of boundaries getting thicker with age, along with some tendency for gender differences for particular subscales. Conclusion. The study results supported the validity and reliability of the BQ33 in a Russian-speaking sample. This tool can be used to measure psychological boundaries and assess their structure.
Multitasking as a Personal Choice of the Mode of Activity in Russian Children and Adolescents: Its Relationship to Experimental Multitasking and its Effectiveness
Authors: Soldatova Galina U. , Rasskazova Elena I.
Published: February 2023

Background. A person’s ability to solve several tasks simultaneously, or within a limited amount of time, — i.e., multitasking — is becoming more and more highly valued in society, despite experimental data in cognitive science about the low effectiveness of such activity. But, in the modern world, the term multitasking has become increasingly used in another sense — that is, a personal choice to perform several tasks simultaneously even if a person could do them consecutively. Objective. The aim of this study was to reveal the relationship between a personal preference for multitasking, its subjective effectiveness in children and adolescents, and their tendency for and efficacy of multitasking under experimental conditions. Design. One hundred and fifty-seven (157) schoolchildren of different ages participated in the study, which called for responding to four windows on a screen, including texts (SMS) and video images, and reporting on their subjective multitasking and its efficacy. Results. The majority of children and adolescents said (the older they were, the more likely) that sometimes, or often, they combine several tasks, and argued that their performance was effective. Conclusion. The subjective perspective on multitasking and its effectiveness was more likely to be related to multitasking by carrying out several tasks simultaneously, than switching between tasks, and was not related to actual effectiveness when undertaking a variety of activities within a limited time period. In the case of distractions (for instance, incoming messages while undertaking tasks), they might be related to a decrease in effectiveness.