bluuebunny/crossref_metadata_2025 huggingface dataset:
In-vivo studies on Transitmycin, a potent Mycobacterium tuberculosis inhibitor
Authors: Mondal Rajesh , Dusthackeer V. N. Azger , Kannan Palaniyandi , Singh Amit Kumar , Thiruvengadam Kannan , Manikkam Radhakrishnan , A. S. Shainaba , Balasubramanian Mahizhaveni , Elango Padmasini , Ebenezer Rajadas Sam , Bharadwaj Dinesh , Arumugam Gandarvakottai Senthilkumar , Ganesan Suresh , Kumar A. K. Hemanth , Singh Manjula , Patil Shripad , U. C. A. Jaleel , Doble Mukesh , R. Balagurunathan , Tripathy Srikanth Prasad , Kumar Vanaja
Published: March 2023

This study involves the in-vitro and in-vivo anti-TB potency and in-vivo safety of Transitmycin (TR) (PubChem CID:90659753)- identified to be a novel secondary metabolite derived from Streptomyces sp (R2). TR was tested in-vitro against drug resistant TB clinical isolates (n = 49). 94% of DR-TB strains (n = 49) were inhibited by TR at 10μg ml-1. In-vivo safety and efficacy studies showed that 0.005mg kg-1 of TR is toxic to mice, rats and guinea pigs, while 0.001mg kg-1 is safe, infection load did not reduce. TR is a potent DNA intercalator and also targets RecA and methionine aminopeptidases of Mycobacterium. Analogue 47 of TR was designed using in-silico based molecule detoxification approaches and SAR analysis. The multiple targeting nature of the TR brightens the chances of the analogues of TR to be a potent TB therapeutic molecule even though the parental compound is toxic. Analog 47 of TR is proposed to have non-DNA intercalating property and lesser in-vivo toxicity with high functional potency. This study attempts to develop a novel anti-TB molecule from microbial sources. Though the parental compound is toxic, its analogs are designed to be safe through in-silico approaches. However, further laboratory validations on this claim need to be carried out before labelling it as a promising anti-TB molecule.
Ready for handwriting? A reference data study on handwriting readiness assessments
Authors: Haberfehlner Helga , de Vries Liesbeth , Cup Edith H. C. , de Groot Imelda J. M. , Nijhuis-van der Sanden Maria W. G. , van Hartingsveldt Margo J.
Published: March 2023

Introduction

Early evaluation of writing readiness is essential to predict and prevent handwriting difficulties and its negative influences on school occupations. An occupation-based measurement for kindergarten children has been previously developed: Writing Readiness Inventory Tool In Context (WRITIC). In addition, to assess fine motor coordination two tests are frequently used in children with handwriting difficulties: the modified Timed Test of In-Hand Manipulation (Timed TIHM) and the Nine-Hole Peg Test (9-HPT). However, no Dutch reference data are available.

Aim

To provide reference data for (1) WRITIC, (2) Timed-TIHM and (3) 9-HPT for handwriting readiness assessment in kindergarten children.

Methods

Three hundred and seventy-four children from Dutch kindergartens in the age of 5 to 6.5 years (5.6±0.4 years, 190 boys/184 girls) participated in the study. Children were recruited at Dutch kindergartens. Full classes of the last year were tested, children were excluded if there was a medical diagnosis such as a visual, auditory, motor or intellectual impairment that hinder handwriting performance. Descriptive statistics and percentiles scores were calculated. The score of the WRITIC (possible score 0–48 points) and the performance time on the Timed-TIHM and 9-HPT are classified as percentile scores lower than the 15th percentile to distinguish low performance from adequate performance. The percentile scores can be used to identify children that are possibly at risk developing handwriting difficulties in first grade.

Results

WRITIC scores ranged from 23 to 48 (41±4.4), Timed-TIHM ranged from 17.9 to 64.5 seconds (31.4± 7.4 seconds) and 9-HPT ranged from 18.2 to 48.3 seconds (28.4± 5.4). A WRITIC score between 0–36, a performance time of more than 39.6 seconds on the Timed-TIHM and more than 33.8 seconds on the 9-HPT were classified as low performance.

Conclusion

The reference data of the WRITIC allow to assess which children are possibly at risk developing handwriting difficulties.
Detection of azole-resistant Aspergillus fumigatus in the environment from air, plant debris, compost, and soil
Authors: Gómez Londoño Luisa F. , Brewer Marin T.
Published: March 2023

Aspergillus fumigatus is a ubiquitous fungus, a saprophyte of plants, and an opportunistic pathogen of humans. Azole fungicides are used in agriculture to control plant pathogens, and azoles are also used as a first line of treatment for aspergillosis. The continued exposure of A. fumigatus to azoles in the environment has likely led to azole resistance in the clinic where infections result in high levels of mortality. Pan-azole resistance in environmental isolates is most often associated with tandem-repeat (TR) mutations containing 34 or 46 nucleotides in the cyp51A gene. Because the rapid detection of resistance is important for public health, PCR-based techniques have been developed to detect TR mutations in clinical samples. We are interested in identifying agricultural environments conducive to resistance development, but environmental surveillance of resistance has focused on labor-intensive isolation of the fungus followed by screening for resistance. Our goal was to develop assays for the rapid detection of pan-azole-resistant A. fumigatus directly from air, plants, compost, and soil samples. To accomplish this, we optimized DNA extractions for air filters, soil, compost, and plant debris and standardized two nested-PCR assays targeting the TR mutations. Sensitivity and specificity of the assays were tested using A. fumigatus DNA from wild type and TR-based resistant isolates and with soil and air filters spiked with conidia of the same isolates. The nested-PCR assays were sensitive to 5 fg and specific to A. fumigatus without cross-reaction with DNA from other soil microorganisms. Environmental samples from agricultural settings in Georgia, USA were sampled and tested. The TR46 allele was recovered from 30% of samples, including air, soil and plant debris samples from compost, hibiscus and hemp. These assays allow rapid surveillance of resistant isolates directly from environmental samples improving our identification of hotspots of azole-resistant A. fumigatus.
Drosophila melanogaster resilin improves the mechanical properties of transgenic silk
Authors: Zhao Shuo , Ye Xiaogang , Dai Xiangping , Wang Xinqiu , Yu Shihua , Zhong Boxiong
Published: March 2023

Resilin is a natural protein with high extensibility and resilience that plays a key role in the biological processes of insects, such as flight, bouncing, and vocalization. This study used piggyBac-mediated transgenic technology to stably insert the Drosophila melanogaster resilin gene into the silkworm genome to investigate whether exogenous protein structures improve the mechanical properties of silkworm silk. Molecular detection showed that recombinant resilin was expressed and secreted into silk. Secondary structure and mechanical property analysis showed that the β-sheet content in silk from transgenic silkworms was higher than in wild-type silk. The fracture strength of silk fused with resilin protein was 7.2% higher than wild-type silk. The resilience of recombinant silk after one-time stretching and cyclic stretching was 20.5% and 18.7% higher than wild-type silk, respectively. In summary, Drosophila resilin can enhance the mechanical properties of silk, and this study is the first to improve the mechanical properties of silk using proteins other than spider silk, which broadens the possibilities for the design and application of biomimetic silk materials.
Effects of theophylline on ADCY5 activation—From cellular studies to improved therapeutic options for ADCY5-related dyskinesia patients
Authors: Tänzler Dirk , Kipping Marc , Lederer Marcell , Günther Wiebke F. , Arlt Christian , Hüttelmaier Stefan , Merkenschlager Andreas , Sinz Andrea
Published: March 2023

We show the effects of the three purine derivatives, caffeine, theophylline, and istradefylline, on cAMP production by adenylyl cyclase 5 (ADCY5)-overexpressing cell lines. A comparison of cAMP levels was performed for ADCY5 wild-type and R418W mutant cells. ADCY5-catalyzed cAMP production was reduced with all three purine derivatives, while the most pronounced effects on cAMP reduction were observed for ADCY5 R418W mutant cells. The gain-of-function ADCY5 R418W mutant is characterized by an increased catalytic activity resulting in elevated cAMP levels that cause kinetic disorders or dyskinesia in patients. Based on our findings in ADCY5 cells, a slow-release formulation of theophylline was administered to a preschool-aged patient with ADCY5-related dyskinesia. A striking improvement of symptoms was observed, outperforming the effects of caffeine that had previously been administered to the same patient. We suggest considering theophylline as an alternative therapeutic option to treat ADCY5-related dyskinesia in patients.
A century of climate warming results in growing season extension: Delayed autumn leaf phenology in north central North America
Authors: Calinger Kellen , Curtis Peter
Published: March 2023

Shifts in the timing of key leaf phenological events including budburst, foliage coloration, and leaf fall have been observed worldwide and are consistent with climate warming. Quantifying changes in growing season length (GSL) because of shifts in both spring and autumn leaf phenology is crucial for modeling annual net ecosystem carbon uptake. However, a lack of long-term autumn phenology datasets has prevented assessment of these growing season level changes. We investigated shifts in growing season length, budburst, foliage coloration, and leaf fall over the past century in seven native hardwood species using a historic leaf phenology dataset collected in Wauseon, OH from 1883–1912 paired with contemporary observations. Using long-term meteorological data, we investigated temperature and precipitation trends over 130 years. Finally, we correlated spring and fall phenophases with monthly temperature and precipitation variables from the twelve months preceding that phenophase using historical meteorological data. We found significant extension of growing season length over the past century in five of the seven study species (ANOVA,p< 0.05) which resulted primarily from delayed foliage coloration rather than from earlier budburst in contrast to the few other studies assessing total GSL change. Our results suggest that most of the leaf phenological studies that investigate only budburst are disregarding crucial information about the end of the growing season that is essential for accurately predicting the effects of climate change in mixed-species temperate deciduous forests.
Practitioners’ perspectives on acupuncture treatment for postpartum depression: A qualitative study
Authors: Liu Fan , Zhan Tian-yu , Xu Yu-qin , Lu Xiao-fei , Zhou Yu-mei , Huang Xing-xian , Zhuo Yuan-yuan , Yang Zhuo-xin
Published: March 2023

Background

Acupuncture may become a treatment for postpartum depression (PPD). Currently, little is known about the use of acupuncture in the treatment of PPD from the point of view of practitioners. The aim of this study was to explore practitioners’ perspectives on the treatment of PPD with acupuncture and provide suggestions for future improvement.

Methods

This study employed a qualitative descriptive method. Semistructured, open-ended interviews were conducted with 14 acupuncture practitioners from 7 hospitals via face-to-face or telephone interviews. The data were collected using interview outline from March to May 2022 and analysed using qualitative content analysis.

Results

In general, the use of acupuncture for treating PPD was positively regarded by practitioners. They claimed that acupuncture is both safe and helpful for breastfeeding women who are experiencing emotional discomfort and that it can alleviate a variety of somatic symptoms. The following three themes were extracted: (a) patient acceptance and compliance; (b) acupuncture as a treatment for PPD; and (c) the advantages and drawbacks of acupuncture treatment.

Conclusion

Practitioners’ optimistic outlooks demonstrated that acupuncture is a promising treatment option for PPD. However, the time cost was the most significant barrier to compliance. Future development will focus mostly on improving acupuncture equipment and the style of service.
Associations of age, sex, and socioeconomic status with adherence to guideline recommendations on protein intake and micronutrient supplementation in patients with sleeve gastrectomy or Roux-en-Y gastric bypass
Authors: Wiese Mats L. , Wilke Franziska , Gärtner Simone , Valentini Luzia , Keßler Wolfram , Aghdasssi Ali. A. , Lerch Markus M. , Steveling Antje
Published: March 2023

Introduction

Patients with bariatric surgery often show poor long-term compliance to recommendations for prevention of nutrient deficiency but it is unclear which factors contribute. We investigated the associations of age, sex, and socioeconomic status (SES) with adherence to guideline recommendations on protein intake and micronutrient supplementation.

Methods

In a monocentric cross-sectional study we prospectively recruited patients with sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) and a minimum postoperative period of 6 months. Clinical and demographic data were obtained from the patients’ medical files and by questionnaire. Patients reported on supplement usage, recorded their dietary intake for seven days and underwent physical examinations including blood testing.

Results

We included 35 patients (SG: n = 25, RYGB: n = 10) with a mean (+SD) postoperative period of 20.2 (±10.4) months. Distributions of age, sex and SES were comparable between the SG and RYGB groups. Non-adherence to recommended protein intake was associated with age ≥ 50 years (p = 0.041) but not sex or SES. Protein intake inversely correlated with markers of obesity. There were no significant associations of age or sex with micronutrient supplementation. Only for vitamins A (p = 0.049) and B1 (p = 0.047) higher SES was associated with greater compliance. The only manifest deficiency associated with non-adherence to micronutrient supplementation was that for folic acid (p = 0.044).

Conclusion

In patients after bariatric surgery, those of older age and of lower SES might have a greater risk of unfavorable outcome and may require greater attention to micronutrient and protein supplementation.
Association between participation in the Northern Finland Birth Cohort 1966 study and use of psychiatric care services
Authors: Kerkelä Martta , Gissler Mika , Nordström Tanja , Veijola Juha
Published: March 2023

Aims

In most population-based epidemiological follow-up studies the aim is not to intervene in the life of the participants. Although the idea is not to intervene, being a member of the longitudinal follow-up study and studies conducted during follow-up may affect the target population. A population-based study including mental health enquiries might reduce the unmet need for psychiatric treatment by motivating people to seek treatment for their psychiatric ill-health. We examined the use of psychiatric care services in the population born in the year 1966 in Northern Finland, of whom 96.3% are participants in the prospective Northern Finland Birth Cohort 1966 (NFBC1966).

Methods

As a study cohort we used people born in 1966 in Northern Finland (n = 11 447). The comparison cohort included all the people born in the years 1965 and 1967 in the same geographical area (n = 23 339). The follow-up period was from age 10 to 50 years. The outcome measure was the use of psychiatric care services, which was analysed using Cox Proportional Hazard regression and Zero-Truncated Negative Binomial Regression.

Results

People born in 1966 in Northern Finland did not differ from those born in 1965 and 1967 in terms of the outcome measure.

Conclusions

We found no association between participation in an epidemiological follow-up study and the use of psychiatric care services. The NFBC1966 may be regarded as a representative at the population level in terms of psychiatric outcomes despite the personal follow-up of the birth cohort. The associations of participation in epidemiological follow-up studies have previously been under-examined, and the results need to be replicated.
Structure of a HIV-1 IN-Allosteric inhibitor complex at 2.93 Å resolution: Routes to inhibitor optimization
Authors: Eilers Grant , Gupta Kushol , Allen Audrey , Montermoso Saira , Murali Hemma , Sharp Robert , Hwang Young , Bushman Frederic D. , Van Duyne Gregory
Published: March 2023

HIV integrase (IN) inserts viral DNA into the host genome and is the target of the strand transfer inhibitors (STIs), a class of small molecules currently in clinical use. Another potent class of antivirals is the allosteric inhibitors of integrase, or ALLINIs. ALLINIs promote IN aggregation by stabilizing an interaction between the catalytic core domain (CCD) and carboxy-terminal domain (CTD) that undermines viral particle formation in late replication. Ongoing challenges with inhibitor potency, toxicity, and viral resistance motivate research to understand their mechanism. Here, we report a 2.93 Å X-ray crystal structure of the minimal ternary complex between CCD, CTD, and the ALLINI BI-224436. This structure reveals an asymmetric ternary complex with a prominent network of π-mediated interactions that suggest specific avenues for future ALLINI development and optimization.
HPV upregulates MARCHF8 ubiquitin ligase and inhibits apoptosis by degrading the death receptors in head and neck cancer
Authors: Khalil Mohamed I. , Yang Canchai , Vu Lexi , Chadha Smriti , Nabors Harrison , Welbon Craig , James Claire D. , Morgan Iain M. , Spanos William C. , Pyeon Dohun
Published: March 2023

The membrane-associated RING-CH-type finger ubiquitin ligase MARCHF8 is a human homolog of the viral ubiquitin ligases Kaposi’s sarcoma herpesvirus K3 and K5 that promote host immune evasion. Previous studies have shown that MARCHF8 ubiquitinates several immune receptors, such as the major histocompatibility complex II and CD86. While human papillomavirus (HPV) does not encode any ubiquitin ligase, the viral oncoproteins E6 and E7 are known to regulate host ubiquitin ligases. Here, we report that MARCHF8 expression is upregulated in HPV-positive head and neck cancer (HNC) patients but not in HPV-negative HNC patients compared to normal individuals. The MARCHF8 promoter is highly activated by HPV oncoprotein E6-induced MYC/MAX transcriptional activation. The knockdown of MARCHF8 expression in human HPV-positive HNC cells restores cell surface expression of the tumor necrosis factor receptor superfamily (TNFRSF) death receptors, FAS, TRAIL-R1, and TRAIL-R2, and enhances apoptosis. MARCHF8 protein directly interacts with and ubiquitinates the TNFRSF death receptors. Further, MARCHF8 knockout in mouse oral cancer cells expressing HPV16 E6 and E7 augments cancer cell apoptosis and suppresses tumor growth in vivo. Our findings suggest that HPV inhibits host cell apoptosis by upregulating MARCHF8 and degrading TNFRSF death receptors in HPV-positive HNC cells.
Proposição de capacitação em Resiliência Organizacional
Authors: Schneider Eduardo Augusto , Wachs Priscila , Gayer Bruna Dones
Published: March 2023

Com o propósito de garantir a segurança e o bom desempenho das organizações, a Engenharia de Resiliência vem emergindo como alternativa para a Gestão da Segurança em cenários sociotécnicos complexos. Através de algumas ferramentas, como o jogo TORC (Training for Operational Resilience Capabilities), é possível desenvolver a capacidade de resiliência dos colaboradores e levar isso para as equipes e para a organização como um todo. Esse trabalho objetiva a proposição de uma capacitação do tipo TORC para uma empresa que trabalha no modelo de assinaturas por recorrência mensal. Utilizou-se o método de entrevistas do tipo CDM (Critical Decision Method) para criação dos cenários e game-changers a serem utilizados no jogo TORC. Como resultado dessa aplicação, descobriu-se que a combinação das entrevistas do CDM com o método dos game-changers do TORC foi viável e propiciou a criação de cenários próprios ao contexto da organização e aumentando a chance de capacitação dos colaboradores. Além de fazer a avaliação do jogo como ferramenta de capacitação, a aplicação do jogo resultou em novas sugestões para outras aplicações e apresentou percepções positivas dos jogadores a respeito do potencial de utilização dessa metodologia para a capacitação de indivíduos, equipes e organizações. Além do desenvolvimento da resiliência da organização, por meio do desenvolvimento da resiliência dos indivíduos e equipe, sugestões de ações para a organização do trabalho emergiram, como: sistema de medição de desempenho formal para fornecedores e para logística.
Logística reversa de medicamentos na cidade de Goiânia
Authors: Costa Valéria Caroliny Ataides da , Galo Nadya Regina
Published: March 2023

O crescimento do mercado farmacêutico e, consequentemente, o aumento de medicamentos em desuso, vencidos e de embalagens descartadas têm se tornado fatores de preocupação ambiental, sendo, dessa forma, de suma importância que as normas relacionadas a esse tipo de resíduo sejam seguidas. Assim, o presente trabalho foi desenvolvido com o objetivo de realizar um diagnostico quanto ao progresso na implementação do Decreto nº10.388, que trata da logística reversa de resíduos sólidos medicamentosos. Para isso, foi realizado uma pesquisa documental em sites e documentos públicos, bem como uma pesquisa de campo em algumas farmácias localizadas no município de Goiânia. Como resultado foi verificado que, quanto as fases de implementação, existem evidências de conclusão da fase 1 enquanto a fase 2 se encontra em execução. Com relação ao quantitativo de pontos de coleta implementados na cidade de Goiânia, foram identificados 73 locais, que se mostram insuficientes para a conclusão da fase 2. Com relação a campanhas de divulgação, verificou-se uma deficiência que pode dificultar o sucesso da implementação do decreto nos prazos estipulados.
Pathology gradual assessment of colorectal anastomosis
Authors: Klymenko A. V. , Klymenko V. M. , Kononenko I. Ye.
Published: March 2023

Aim: to analyze the state of the colorectal anastomosis after laparoscopic and open resection of the sigmoid and rectum in patients with colorectal cancer and to develop a unified grading of pathological changes in the anastomosis during its laparoscopic and videorectoscopic assessment.
Materials and methods. Results of the treatment of 79 patients who underwent resection of the rectum and sigmoid colon due to adenocarcinoma were analyzed. Patients were divided into two groups. The first group consisted of 34 (43.04 %) patients, whose treatment method was laparoscopic resection of the sigmoid and rectum (main group). The second group consisted of 45 (56.96 %) patients who underwent laparotomic resection. A stapler colorectal anastomosis was formed in both groups. The patients had II–III stages of the oncological disease without prior chemotherapy or radiotherapy in the anamnesis. During the operation visual assessment of the applied anastomosis was performed taking into account both external and internal characteristics. For external examination visual assessment of the anastomosed ends from the side of the serous membrane and a pneumohydrotest were used, for internal – an ordinary 10 mm laparoscope was inserted into the anus with CO2 insufflation at the level of 6 mm Hg and a visual assessment was carried out from the side of the mucosa. According to the received data, an original gradation of pathological changes in the colorectal anastomosis and recommendations for the prevention of its failure were developed.
Results. The developed technique for assessing and gradation of pathological changes in colorectal anastomosis made it possible to identify and eliminate suturing defects in 19 (24.05 %) patients, to eliminate stitching defects, control bleeding, identify ischemic zones of the anastomotic ends and improve total results of the treatment. One patient had anastomotic failure on the third day after operation. This case required reoperation with removal of the anastomosis and formation of the terminal colostomy. There were no lethal cases in both groups. Usage of additional methods for assessing the anastomosis is time-consuming and important in detecting pathological changes in the colorectal anastomosis.
Conclusions. The gradation of pathologic changes in the colorectal anastomosis should be comprehensive with an assessment of not only its external characteristics but also internal ones using videorectoscopy and allows to reduce the risks of colorectal anastomosis failure. The average number of points in the combination of laparoscopic and videorectoscopic evaluation is higher than in the laparoscopic one alone, but there is no statistical significance (U = 884.5; P = 0.071). This makes it possible to use the proposed grading system both in laparoscopy and in open surgery with the same results. There is no statistically significant difference in the number of detected anastomotic complications between open and laparoscopic resection of the sigmoid colon or the rectum (P = 0.137).
Microscopic, submicroscopic characterization of pro- and anti-inflammatory cell phenotypes of the lungs in conditions of experimental allergic inflammation
Authors: Popko S. S.
Published: March 2023

The aim is to study the microscopic and submicroscopic characteristics of pro- and anti-inflammatory cell phenotypes of the lungs under conditions of experimental allergic inflammation.
Material and methods. We used histological and electron microscopic methods to study the lungs of 48 male guinea pigs in experimental ovalbumin-induced allergic inflammation, simulated by subcutaneous sensitization and subsequent intranasal inhalation with ovalbumin. Submicroscopic changes of respiratory endocrine cells, goblet cells, exocrine bronchiolar cells, mast cells, macrophages, eosinophils, endothelial cells of guinea pigs lungs were determined.
Results. The most significant reactive submicroscopic changes were established on the 23rd and 30th days of observation in the form of an increase in the functional activity of exocrine bronchiolar and goblet cells, as evidenced by the presence of a light nucleus with a predominance of euchromatin, nucleoplasm of low electron-optical density, nucleoli, developed granular endoplasmic reticulum and an increase in the number of goblet cells secretory mucous granules by electron microscopic examination. The revealed ultramicroscopic features of respiratory endocrine cells (an increase in a number of “empty” core dense vesicles), eosinophilic granulocytes (piecemeal degranulation), an increase in the number of mast cells granules, numerous pseudopodia in macrophages are the confirmation of the active participation of these cell phenotypes in the initiation of inflammation during the early period of the allergic inflammatory process in lungs.
Conclusions. A significant reaction of the innate nonspecific and adaptive immunity occurs in airways during the experimental ovalbumin-induced allergic inflammation, consisting primarily of the functional activation of eosinophilic granulocytes, mast cells, and macrophages, as well as an increase in the secretory activity of exocrine bronchiolar cells and goblet cells, which is confirmed by the changes investigated by electron microscopic examination and are accompanied by reactive changes in the vessels of microcirculatory bed.
Nontrivial solution for Klein-Gordon equation coupled with Born-Infeld theory with critical growth
Authors: He Chuan-Min , Li Lin , Chen Shang-Jie
Published: March 2023

In this article, we study the following system:

−
Δ
u
+
V

(

x

)

u
−

(

2
ω
+
ϕ

)

ϕ
u
=
λ
f

(

u

)

+
∣
u

∣

4

u
,

in

R

3

,

Δ
ϕ
+
β

Δ

4

ϕ
=
4
π

(

ω
+
ϕ

)

u

2

,

in

R

3

,

\left\{\begin{array}{ll}-\Delta u+V\left(x)u-\left(2\omega +\phi )\phi u=\lambda f\left(u)+| u{| }^{4}u,& \hspace{0.1em}\text{in}\hspace{0.1em}\hspace{1em}{{\mathbb{R}}}^{3},\\ \Delta \phi +\beta {\Delta }_{4}\phi =4\pi \left(\omega +\phi ){u}^{2},& \hspace{0.1em}\text{in}\hspace{0.1em}\hspace{1em}{{\mathbb{R}}}^{3},\\ \end{array}\right.

where

f

(

u

)

f\left(u)

is without any growth and Ambrosetti-Rabinowitz condition. We use a cut-off function and Moser iteration to obtain the existence of nontrivial solution. Finally, as a by-product of our approaches, we obtain the same result for the Klein-Gordon-Maxwell system.
Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation
Authors: Hua Yinggang , Liu Yanling , Li Long , Liu Guoyan
Published: March 2023

The P2RY1 receptor is known to cause cancer by activating the ERK signal pathway, and its DNA methylation status and corresponding regulatory mechanism remain unknown. This study used the DNA methylation chip to profile the genome-wide DNA methylation level in gastric cancer tissues. The proliferation and apoptosis of the SGC7901 gastric cancer cell line were determined after treatment with a selective P2RY1 receptor agonist, MRS2365. The promoter region of P2RY1 was found to be highly methylated with four hypermethylated sites (|Δβ value| > 0.2) in diffuse gastric cancer and was validated by bioinformatics analysis in the TCGA database. Also, immunohistochemical staining data obtained from the HPA database demonstrated the downregulated expression of proteins encoded by P2RY1 in stomach cancer tissue. The analysis of MRS2365-treated cells by annexin V/propidium iodide staining and caspase-3 activity assays indicated the induction of apoptosis in SGC7901 cells. The P2RY1 receptor activation in human SGC7901 gastric cancer cells via the MRS2365 agonist induced apoptosis and reduced cell growth. High DNA methylation in the promoter region of P2RY1 might have contributed to the reduced expression of P2RY1’s mRNA, which was likely responsible for the “aggressive” nature of the diffuse gastric cancer.
Association between the VEGFR-2 -604T/C polymorphism (rs2071559) and type 2 diabetic retinopathy
Authors: Yuan Yazhen , Shao Chenjun , Guan Yongqing , Lu Hongwei , Wang Dandan , Zhang Shuangmei
Published: March 2023

This retrospective case–control study examined the association between the rs2071559 (-604T/C) single nucleotide polymorphism (SNP) in the vascular endothelial growth factor receptor (VEGFR)-2 gene and the risk of diabetic retinopathy (DR) in Northern Han Chinese. This study included patients diagnosed with diabetes mellitus (DM) in Shijiazhuang between 07/2014 and 07/2016. The healthy controls were unrelated individuals who received routine physical examinations. The diabetic patients were grouped as DM (diabetes but no fundus examination abnormalities), proliferative DR (PDR), and non-proliferative DR (NPDR). Finally, 438 patients were included: 114 controls and 123, 105, and 96 patients in the DM, NPDR, and PDR groups, respectively. In the multivariable analyses and all genetic models, the VEGFR-2 rs2071559 SNP was not associated with DR (among all diabetic patients) or with PDR (among the patients with DR) after adjustment for age, sex, duration of DM, blood glucose, systolic blood pressure, diastolic blood pressure, and body mass index (all P > 0.05). In conclusion, the VEGFR-2- 604T/C rs2071559 SNP is not associated with DR or PDR in the Han Chinese population of Shijiazhuang (China).
Triple-negative mouse breast cancer initiating cells show high expression of beta1 integrin and increased malignant features
Authors: Fu Jing , Peng Shengkun
Published: March 2023

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that exhibits aggressive tumor phenotypes, including rapid metastasis and tumor recurrence. Integrins belong to the family of transmembrane glycoproteins involved in regulating cell adhesion, proliferation, and differentiation through cell–cell and cell–extracellular matrix interactions. Aberrant β1 integrin signaling has been implicated in cancer invasion and metastasis processes. The present work aimed to investigate the role of β1 integrin in TNBC cancer progression using a mouse 4T1 cell line as a model system. We have sorted a subset of tumor-initiating cells (TICs) from the 4T1 cell line based on CD133 positivity by flow cytometry. RT-PCR and protein analysis studies showed the transcriptional upregulation of β1 integrin and its downstream target focal adhesion kinase in 4T1-TICs compared to parental 4T1 cells. In addition, the expression of β1 receptors in TICs is significantly higher than in parental population cells. Furthermore, in vitro cellular assays revealed that CD133+ TICs have higher clonogenic ability, invasion, and sphere formation potential. These findings suggest that β1 integrin has a potential role in TNBC invasion and metastasis. Hence, β1 integrin could be a possible factor for future targeted cancer therapies.
An imagery-based intervention for managing anxiety in esports
Authors: Munroe-Chandler Krista J. , Loughead Todd M. , Zuluev Erkin G. , Ely Frank O.
Published: March 2023

The popularity and commercial success of videogames in the current era has given rise to a new type of competition: electronic sports (or esports). Researchers have proposed that esports players would benefit greatly from the applied sport psychology work typically conducted with traditional athletes and more specifically from evidence-based interventions. Imagery interventions have proven beneficial for the traditional athlete at managing anxiety in competitive settings, and in fact League of Legends players have noted the importance of mental skills, including imagery, to achieving optimal performance. The aim of the current paper is to provide practitioners with an imagery intervention specifically designed for managing anxiety in League of Legends players. Three 30-min workshops are described wherein the practitioner follows the three phases of Psychological Skills Training; education, acquisition and practice.
Field enhancement of epsilon-near-zero modes in realistic ultrathin absorbing films
Authors: Anopchenko Aleksei , Gurung Sudip , Bej Subhajit , Lee Ho Wai Howard
Published: March 2023

Using electrodynamical description of the average power absorbed by a conducting film, we present an expression for the electric-field intensity enhancement (FIE) due to epsilon-near-zero (ENZ) polariton modes. We show that FIE reaches a limit in ultrathin ENZ films inverse of second power of ENZ losses. This is illustrated in an exemplary series of aluminum-doped zinc oxide nanolayers grown by atomic layer deposition. Only in a case of unrealistic lossless ENZ films, FIE follows the inverse second power of film thickness predicted by S. Campione, et al. [Phys. Rev. B, vol. 91, no. 12, art. 121408, 2015]. We also predict that FIE could reach values of 100,000 in ultrathin polar semiconductor films. This work is important for establishing the limits of plasmonic field enhancement and the development of near zero refractive index photonics, nonlinear optics, thermal, and quantum optics in the ENZ regime.
Beyond Negative Freedom and the Working Class Subject: Another Kind of Madness
Authors: Cruz Cynthia
Published: March 2023

Presented with the (non) choice of either assimilating into bourgeois society and, thus, annihilating themselves, or being annihilated by society, the working class subject may choose, neither, engaging, instead, in an act of negative freedom. By engaging in an act of negative freedom, the working class subject destroys all possibility of rehabilitation, thus, determining their fate. The act alone provides a means by which to mark the outer limits of what they are willing to tolerate. Through the act, the subject is altered, their world is changed. Furthermore, before engaging in the act, they do not know what will happen to them. They are, in other words, stepping into the abyss of unknowing. In this article, I will explore the concept of negative freedom in relation to the working class subject: how engaging in such an act marks their fate, separating them from bourgeois society while, also, setting them free. At the same time, due to its inherent withdrawal from civil society, negative freedom veers dangerously near nihilism, thus, reducing their act to one without meaning.
The Nexus between Federal Revenue and Spending in Canada: A Time-Frequency Perspective
Authors: Wang Yu , Wei William X.
Published: March 2023

The theoretical literature on the revenue-spending nexus suggests four possible relationships. They are tax-and-spend, negative tax-and-spend, spend-and-tax, and fiscal synchronization. Despite their homogenous research design, the empirical studies of Canada have provided mixed and inconclusive results. This study re-examines the topic from a time-frequency perspective. Specifically, it applies continuous wavelet analysis to the period 1867–2017 to delineate a complete picture of the revenue-spending nexus in Canada. Although results show the existence of all relationships suggested by theory at different time-frequency combinations, the spend-and-tax pattern is the most striking one and dominates the nexus in the long run. Theoretical, methodological, and policy-wise implications of this study are discussed at the end.
Abortion: Perspectives from an APA Past-President
Authors: Stotland Nada L.
Published: March 2023

The United States Supreme Court's decision in Dobbs v. Jackson Women's Health Organization, eliminating the national right to abortion, poses challenges to psychiatrists and patients. Abortion laws now vary widely from state to state and are constantly changing and being challenged. The laws affect both patients and health care professionals; some prohibit not only the performance of abortion but efforts to inform and assist patients seeking abortion. Patients may become pregnant during and/or because of episodes of clinical depression, mania, or psychosis, and recognize that their current circumstances will not allow them to become adequate parents. Some laws allowing abortion to protect a woman's life or health explicitly exclude mental health risks; many prohibit transfer of a patient to a permissive venue. Psychiatrists working with patients contemplating abortion can convey the scientific evidence that abortion does not cause mental illness and help them identify and work through their own beliefs, values, and likely responses to the decision. Psychiatrists will also have to decide whether medical ethics or state laws will govern their own professional behavior.
Mentalization Psychotherapy for Patients Presenting with a Psychotic Personality Structure: A Contemporary Approach
Authors: Constantinides Prometheas , Dauphin Julie
Published: March 2023

Overt psychotic symptoms, currently understood as resulting from both neurobiological and developmental etiological factors, are also associated with deficits in mentalization in a subgroup of patients presenting with psychotic personality structure. Neurodevelopmental and traumatic impairments seen in this subtype of psychotic disorders create a pressure or need for what has been called a transformational mentalizing process. This specific form of mental elaboration focuses explicitly on finding words and images that help patients to grasp their emotional and mental states. It thus differs from mainstream mentalization treatment, which puts a greater emphasis on reflective functioning. A psychodynamically informed mentalization-based individual and group psychotherapy for this subgroup of patients was developed, aiming at augmenting the patient's psychological resources through explicit transformational mentalization, rather than primarily targeting symptom reduction. This program stimulates curiosity about one's mental states, progressively aiming to give shape to and explore affectively charged mental states, and is integrated with other treatment modalities. This article presents a psychological model of psychotic personality structure and its psychotherapeutic implications, as well as clinical illustrations. Preliminary findings from a pilot study provide encouraging support for the model, including emerging reflective capacities and symptom reduction, as well as overall improvement of social and occupational functioning.
Resuscitation dynamics reveal persister partitioning after antibiotic treatment
Authors: Fang Xin , Allison Kyle R
Published: March 2023

Bacteria can survive antibiotics by forming dormant, drug‐tolerant persisters. Persisters can resuscitate from dormancy after treatment and prolong infections. Resuscitation is thought to occur stochastically, but its transient, single‐cell nature makes it difficult to investigate. We tracked the resuscitation of individual persisters by microscopy after ampicillin treatment and, by characterizing their dynamics, discovered that Escherichia coli and Salmonella enterica persisters resuscitate exponentially rather than stochastically. We demonstrated that the key parameters controlling resuscitation map to the ampicillin concentration during treatment and efflux during resuscitation. Consistently, we observed many persister progeny have structural defects and transcriptional responses indicative of cellular damage, for both β‐lactam and quinolone antibiotics. During resuscitation, damaged persisters partition unevenly, generating both healthy daughter cells and defective ones. This persister partitioning phenomenon was observed in S. enterica, Klebsiella pneumoniae, Pseudomonas aeruginosa, and an E. coli urinary tract infection (UTI) isolate. It was also observed in the standard persister assay and after in situ treatment of a clinical UTI sample. This study reveals novel properties of resuscitation and indicates that persister partitioning may be a survival strategy in bacteria that lack genetic resistance.
Otizm farkındalık ölçeğinin geliştirilmesi: Geçerlik ve güvenirlik çalışması
Authors: YAZICI Mahmut Serkan , KARSANTIK İsmail
Published: March 2023

Otizm spektrum bozukluğu (OSB) tanılı birey sayısı tüm dünyada olduğu gibi, Türkiye’de de yıllar içinde artmıştır. Diğer bir değişle, toplum içerisinde birçok alanda OSB tanılı bireylerle etkileşime giren kişi sayısı da artmıştır. Bu nedenle toplum yaşantısını daha nitelikli kılmak adına otizm farkındalığının toplum içerisinde arttırılması bir ihtiyaçtır. Bu amaçla yapılacak farkındalık çalışmaları için durum tespiti yapmak ve yapılan çalışmaların etkisini belirlemek önemlidir. Bu kapsamda çalışmanın amacı otizm farkındalığını belirlemeye yönelik geçerli ve güvenilir bir ölçek geliştirmektedir. Alanyazın incelemesinin ardından 55 maddeden oluşan madde havuzuna uzman görüşleri sonrası öneriler uygulanmıştır. Otizm farkındalık ölçeğinin geliştirilmesi amacıyla açımlayıcı faktör analizi (AFA) aşaması için 367 ve doğrulayıcı faktör analizi (DFA) aşaması için 410 katılımcıdan elde edilen veriler kullanılmıştır. Basit tesadüfi örnekleme yönteminin kullanıldığı çalışmada ölçeğin AFA sonrası elde edilen yedi faktör (otizmde sınırlı ilgiler ve yineleyici davranışlar, otizmde sosyal etkileşim ve iletişim, otizmin sebepleri, otizmde arkadaş ilişkileri, otizmde müdahale surecindeki temel unsurlar, otizmde fiziksel özellikler, otizmin erken uyarı işaretleri) DFA uygulaması ile doğrulanmıştır. Otizm farkındalık ölçeğinin güvenirlik katsayısı Cronbach Alpha katsayısı ile belirlenmiş olup ölçeğin yedi alt boyutu ve toplamının güvenirlik katsayılarının güvenilir referans aralığında olduğu görülmektedir. Otizm farkındalık ölçeğinin geliştirilmesine yönelik bulgular incelendiğinde ölçeğin otizm farkındalık düzeylerinin ölçülmesinde geçerli ve güvenilir bir ölçek olduğu görülmektedir.
Cancer Associated Retinopathy in Non-Hodgkin’s Lymphoma
Authors: Chisti Mohammad Muhsin , Muslimani Alaa , Daw Hamed , Jaiyesimi Ishmael , Klamerus Justin F.
Published: March 2023

Cancer-associated retinopathy (CAR) is an uncommon paraneoplastic retinopathy usually associated with small cell lung carcinoma. To our knowledge, there is no previous report in the English literature of CAR syndrome occurring in lymphoma patients. We describe a rare case of CAR syndrome in a 62-year-old male with non-Hodgkin’s lymphoma (NHL) treated with four doses of intravenous immunoglobulin.
Neutron dose evaluation in conventional and FLASH proton therapy
Authors: Souza Felipe M .L. , Neto Ruy S. R. , Rocha Arthur M. , Cardoso S. C.
Published: March 2023

Cancer is the second leading cause of death for children and one of the treatment options for this disease is radiotherapy. Children treated with radiotherapy using photon beams are more likely to develop secondary neoplasms. Proton therapy can reduce the probability of neoplasm formation by up to 50%. Recent studies propose the use of ultra high dose rates as a treatment option. From the threshold of 40 Gy/s it is possible to reach the FLASH effect. This technique protects healthy tissue while maintaining tumor control. The effect was validated in vivo using a proton beam and, therefore, it will be available as a new treatment option. On the other hand, the proposal for FLASH treatment with a proton beam would not use the Bragg peak located in the target volume, which is the differential of proton radiotherapy. In addition, the increase in the intensity of the beam and the energy of the particles, lead to the generation of a greater amount of neutrons. The objective of this work is to evaluate the dose due to the neutrons generated in the interaction with the accelerator components in FLASH proton therapy in relation to conventional proton therapy. The dose evaluation was performed through Monte Carlo simulations, using a water phantom, with the code TOPAS MC. The results found show that the dose of neutrons in the FLASH technique would be about 100 times greater than the dose in the conventional technique. Still, it would be below 1% of the prescribed dose.
The importance of quality management system to certify radioprotection professionals in the medical field
Authors: Luz C. P. V. C. , Delgado J. U. , Sá L. V. , Conceição Dayana D. A.
Published: March 2023

Certifying professionals in radioprotection (RP), according to the requirements and qualifications established in current Brazilian legislation, ensures that procedures and practices in radiology, radiotherapy and nuclear medicine be performed based on the fundamental principles of radioprotection. However, in none of the regulations and resolutions of the country involving the use of ionizing radiation, the qualification in RP for interventional physicians, radiologists, radiotherapists, nuclear physicians, dentists, nurses and auxiliaries, specialists in medical physics, radiopharmaceuticals, technologists and technicians are clearly defined.  It is necessary to adoption a certification scheme through the ABNT NBR ISO/IEC 17024:2013 standard, which will benefit the professionals themselves as well as the patients increasing the safety in RP in the country. This is to the fact that there is no harmony in the regulation of these professionals with the responsible bodies, nor uniformity in practices through international recommendations. This paper proposes the implementation of a quality management system to certify these professionals according to the principles of radiation protection through a survey of needs regarding to the certification of people and the evaluation of systems implemented in other countries.