bluuebunny/crossref_metadata_2025 huggingface dataset:
The regulatory mechanism of cyclic GMP-AMP synthase on inflammatory senescence of nucleus pulposus cell
Authors: Sun Rui , Wang Feng , Zhong Cong , Shi Hang , Peng Xin , Gao Jia-Wei , Wu Xiao-Tao
Published: July 2024

Background

Cellular senescence features irreversible growth arrest and secretion of multiple proinflammatory cytokines. Cyclic GMP-AMP synthase (cGAS) detects DNA damage and activates the DNA-sensing pathway, resulting in the upregulation of inflammatory genes and induction of cellular senescence. This study aimed to investigate the effect of cGAS in regulating senescence of nucleus pulposus (NP) cells under inflammatory microenvironment.

Methods

The expression of cGAS was evaluated by immunohistochemical staining in rat intervertebral disc (IVD) degeneration model induced by annulus stabbing. NP cells were harvested from rat lumbar IVD and cultured with 10ng/ml IL-1β for 48 h to induce premature senescence. cGAS was silenced by cGAS specific siRNA in NP cells and cultured with IL-1β. Cellular senescence was evaluated by senescence-associated beta-galactosidase (SA-β-gal) staining and flow cytometry. The expression of senescence-associated secretory phenotype including IL-6, IL-8, and TNF-a was evaluated by ELISA and western blotting.

Results

cGAS was detected in rat NP cells in cytoplasm and the expression was significantly increased in degenerated IVD. Culturing in 10ng/ml IL-1β for 48 h induced cellular senescence in NP cells with attenuation of G1-S phase transition. In senescent NP cells the expression of cGAS, p53, p16, NF-kB, IL-6, IL-8, TNF-α was significantly increased while aggrecan and collagen type II was reduced than in normal NP cells. In NP cells with silenced cGAS, the expression of p53, p16, NF-kB, IL-6, IL-8, and TNF-α was reduced in inflammatory culturing with IL-1β.

Conclusion

cGAS was increased by NP cells in degenerated IVD promoting cellular senescence and senescent inflammatory phenotypes. Targeting cGAS may alleviate IVD degeneration by reducing NP cell senescence.
Parental ADHD knowledge and medical visit status of school-aged children in Shanghai
Authors: Ma Xirui , Lin Yuanyuan , Yan Wenjie , Jin Zhijuan , Zhang Yiwen
Published: July 2024

Introduction

The diagnosis and care of children and adolescents with neurodevelopmental disorders presents a public health crisis in China. Attention deficit hyperactivity disorder (ADHD) is one of the most frequent conditions. Many Chinese children and adolescents with ADHD are underdiagnosed and undertreated. This study aimed to evaluate the awareness and attitude parents have about ADHD, and investigated potential factors influencing ADHD medical visit status among school-aged children in Shanghai.

Methods

A random cluster sampling method was used, and four primary schools in Shanghai were selected. One class was randomly selected from each grade, including students and their parents. Parents completed the Swanson, Nolan, and Pelham Version IV Questionnaire (SNAP-IV) parent form and questionnaire concerning ADHD awareness, knowledge, attitude and status of ADHD medical visit. Descriptive analysis was conducted on the overall results and logistic regression analysis was performed to explore the influencing factors of ADHD medical visit.

Results

We received 617 valid questionnaires. There were 313 boys (50.7%) and 304 girls (49.2%), with a median age of 8 years old (p25 = 7, p75 = 9). 42.4% parents believed they had some knowledge about ADHD, and 73.5% of them thought ADHD was a neurologically based disorder or neurological condition by nature. Parental ADHD information came from the following sources: Internet/TV (n = 458, 74.2%), families/friends (n = 267, 43.2%), print publication (n = 208, 33.7%), psychiatrists/pediatricians (n = 192, 31.1%), schools/teachers (n = 186, 30.1%) and other ADHD patients (n = 48, 7.7%). When children had ADHD-like behaviors, most parents (61.5%) educated children to behave themselves, 59.1% parents tried to get help from psychiatrists/pediatricians, 55.5% of them would ask psychologist for help. In terms of the ADHD prevalence, the SNAP-IV positive screen rate was 4.3% (n = 27). Only 33.3% (9/27) of parents went to the hospital for consultation and treatment. Multivariate logistic regression model showed that parental knowledge about ADHD (OR = 13.67, 95%CI: 1.72, 144.39, P = 0.01) was significantly correlated with the medical visit. Parents with sufficient knowledge of ADHD tend to visit hospital for help when they thought their children had ADHD related symptoms.

Conclusions

The majority of parents accepted ADHD as a neurodevelopmental disorder by nature, but some parents still had certain misunderstandings about ADHD. The main source of information for parents to obtain information about ADHD was through the TV/Internet. Parents’ perceptions and knowledge were key to whether children received appropriate treatment for their ADHD. However, medical visits to address ADHD among school-aged children were still lower than expected. Government and healthcare institutes should work to improve ADHD public awareness and to help patients and their families gain access to mental health resources.
CXCL5 impedes CD8+ T cell immunity by upregulating PD-L1 expression in lung cancer via PXN/AKT signaling phosphorylation and neutrophil chemotaxis
Authors: Sun Dantong , Tan Lipin , Chen Yongbing , Yuan Qiang , Jiang Kanqiu , Liu Yangyang , Xue Yuhang , Zhang Jinzhi , Cao Xianbao , Xu Minzhao , Luo Yang , Xu Zhonghua , Xu Zhonghen , Xu Weihua , Shen Mingjing
Published: July 2024

Background

Lung cancer remains one of the most prevalent cancer types worldwide, with a high mortality rate. Upregulation of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) may represent a key mechanism for evading immune surveillance. Immune checkpoint blockade (ICB) antibodies against PD-1 or PD-L1 are therefore widely used to treat patients with lung cancer. However, the mechanisms by which lung cancer and neutrophils in the microenvironment sustain PD-L1 expression and impart stronger inhibition of CD8+ T cell function remain unclear.

Methods

We investigated the role and underlying mechanism by which PD-L1+ lung cancer and PD-L1+ neutrophils impede the function of CD8+ T cells through magnetic bead cell sorting, quantitative real-time polymerase chain reaction (RT-PCR), western blotting, enzyme-linked immunosorbent assays, confocal immunofluorescence, gene silencing, flow cytometry, etc. In vivo efficacy and safety studies were conducted using (Non-obeseDiabetes/severe combined immune deficiency) SCID/NOD mice. Additionally, we collected clinical and prognostic data from 208 patients who underwent curative lung cancer resection between 2017 and 2018.

Results

We demonstrated that C-X-C motif chemokine ligand 5 (CXCL5) is markedly overexpressed in lung cancer cells and is positively correlated with a poor prognosis in patients with lung cancer. Mechanistically, CXCL5 activates the phosphorylation of the Paxillin/AKT signaling cascade, leading to upregulation of PD-L1 expression and the formation of a positive feedback loop. Moreover, CXCL5 attracts neutrophils, compromising CD8+ T cell-dependent antitumor immunity. These PD-L1+ neutrophils aggravate CD8+ T cell exhaustion following lung cancer domestication. Combined treatment with anti-CXCL5 and anti-PD-L1 antibodies significantly inhibits tumor growth in vivo.

Conclusions

Our findings collectively demonstrate that CXCL5 promotes immune escape through PD-L1 upregulation in lung cancer and neutrophils chemotaxis through autocrine and paracrine mechanisms. CXCL5 may serve as a potential therapeutic target in synergy with ICBs in lung cancer immunotherapy.
External validation of Standardized KELIM and platinum-resistant recurrence scores in patients with advanced epithelial ovarian cancer
Authors: Oufkir Nina , Rouzier Roman , Paoletti Xavier , Bonneau Claire
Published: July 2024

Background

Neoadjuvant chemotherapy followed by interval debulking surgery is currently a common treatment option for advanced epithelial ovarian cancer (EOC). The Standardized CA-125 ELIMination rate constant K (Std KELIM) and the Platinum Resistant Recurrence (PtRR) Score have been proposed as markers of tumor chemosensitivity. The aim of our study was to validate these tools for predicting platinum sensitivity in a real-world population of patients with advanced EOC treated with neoadjuvant chemotherapy.

Experimental design

All patients with advanced EOC treated with neoadjuvant chemotherapy at the Institut Curie between 2000 and 2015 were included. The Std KELIM was calculated with the CA-125 concentrations during the first 100 days of chemotherapy. The predictive value of Std KELIM and PtRR scores for the risk of subsequent PtRR was assessed using receiver operating characteristic (ROC) curve analysis, logistic regression and calibration curve. Kaplan–Meier survival analysis was performed for the treatment-free interval from platinum (TFIp) therapy and overall survival (OS).

Results

Std KELIM data were available for 149 patients. The AUC was 0.67 for PtRR. A low Std KELIM was significantly associated with PtRR (OR = 0.19 (95% CI [0.06, 0.53], p = 0.002)) according to the univariate analysis. The calibration curve of the PtRR showed a slight but significant underestimation (p = 0.02) of the probability of platinum resistance. Favorable Std KELIM (≥ 1) alone and combined with the completeness of surgery were associated with significantly better survival in terms of TFIp and OS.

Conclusions

Std KELIM is an early prognostic marker of chemosensitivity in a real-life setting complementary to surgical status. It could help the clinician in the early management of patients by identifying those with a worse prognosis.
Gastrointestinal manifestations in patients with gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a systematic review with analysis of individual patient data
Authors: Skat-Rørdam PA , Kaya Y , Qvist N , Hansen TvO , Jensen TD , Karstensen JG , Jelsig AM
Published: July 2024

Background and aim

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal dominant syndrome characterized by fundic gland polyps (FGP) as well as an increased risk of gastric cancer. The syndrome has been recognized as a clinical entity for less than a decade. A clinical suspicion may be complex and can vary from incidental findings of FGPs at gastroscopy to obstructive symptoms with dyspepsia and vomiting. The diagnosis is established by genetic detection of a pathogenic variant in the promotor 1B region of the APC gene. As of yet there are no established clinical criteria for the diagnosis. To increase knowledge of the condition and to discuss possible genetic testing and surveillance strategies, we performed a systematic review of all reported patients with GAPPS.

Methods

This review was organized according to PRISMA guidelines. The search, which was conducted on September 7th, 2023, was applied to MEDLINE and restricted to only humans and papers in the English language. Only the studies on patients/families with GAPPS verified by identification of a pathogenic variant in the APC promoter 1B were included.

Results

Twelve publications with a total of 113 patients were identified. In all instances the diagnosis was genetically verified with reports of four different variants within the APC promotor 1B region. Eighty-eight patients (90.1%) had gastric polyps, of these seven patients had low-grade dysplasia and five patients had both low- and high-grade dysplasia. Thirty-seven patients (45.7%) underwent gastrectomy. There were no reports of duodenal polyps (0%). Gastric cancer was found in 31 patients (30.1%) with a median age of 48 years (range 19–75). Twenty-six patients died (23.2%) of which 19 had developed gastric cancer (73.1%). One patient was diagnosed with metastatic colorectal cancer (2.2%) and died at 73 years of age. Nineteen patients had colorectal manifestations with < 20 polyps (41.3%).

Conclusion

Patients with a pathogenic variant in the APC promoter 1B region have an increased risk of gastric polyposis and early-onset gastric cancer. However, there is considerable variation in clinical expression and penetrance, which makes decisions on surveillance and the timing of prophylactic gastrectomy challenging.
Effects of starting one lung ventilation and applying individualized PEEP right after patients are placed in lateral decubitus position on intraoperative oxygenation for patients undergoing thoracoscopic pulmonary lobectomy: study protocol for a randomized controlled trial
Authors: Wang Qing-Yuan , Zhou Yang , Wang Meng-Rui , Jiao You-You
Published: July 2024

Background

For patients receiving one lung ventilation in thoracic surgery, numerous studies have proved the superiority of lung protective ventilation of low tidal volume combined with recruitment maneuvers (RM) and individualized PEEP. However, RM may lead to overinflation which aggravates lung injury and intrapulmonary shunt. According to CT results, atelectasis usually forms in gravity dependent lung regions, regardless of body position. So, during anesthesia induction in supine position, atelectasis usually forms in the dorsal parts of lungs, however, when patients are turned into lateral decubitus position, collapsed lung tissue in the dorsal parts would reexpand, while atelectasis would slowly reappear in the lower flank of the lung. We hypothesize that applying sufficient PEEP without RM before the formation of atelectasis in the lower flank of the lung may beas effective to prevent atelectasis and thus improve oxygenation as applying PEEP with RM.

Methods

A total of 84 patients scheduled for elective pulmonary lobe resection necessitating one lung ventilation will be recruited and randomized totwo parallel groups. For all patients, one lung ventilation is initiated the right after patients are turned into lateral decubitus position. For patients in the study group, individualized PEEP titration is started the moment one lung ventilation is started, while patients in the control group will receive a recruitment maneuver followed by individualized PEEP titration after initiation of one lung ventilation. The primary endpoint will be oxygenation index measured at T4. Secondary endpoints will include intrapulmonary shunt, respiratory mechanics, PPCs, and hemodynamic indicators.

Discussion

Numerous previous studies compared the effects of individualized PEEP applied alone with that applied in combination with RM on oxygenation index, PPCs, intrapulmonary shunt and respiratory mechanics after atelectasis was formed in patients receiving one lung ventilation during thoracoscopic surgery. In this study, we will apply individualized PEEP before the formation of atelectasis while not performing RM in patients allocated to the study group, and then we’re going to observe its effects on the aspects mentioned above. The results of this trial will provide a ventilation strategy that may be conductive to improving intraoperative oxygenation and avoiding the detrimental effects of RM for patients receiving one lung ventilation.

Trial registration

www.Chictr.org.cn ChiCTR2400080682. Registered on February 5, 2024.
The relationship between loneliness and blood glucose: a cross-sectional survey among Japanese
Authors: Tran Quyen An , Nakamura Sho , Watanabe Kaname , Chei Choy-Lye , Narimatsu Hiroto
Published: July 2024

Recently, researchers have uncovered a correlation between loneliness and both the development and management of diabetes. Nevertheless, previous studies employing an unvalidated loneliness questionnaire impair result accuracy. Furthermore, this aspect has not been researched in the Japanese population. Therefore, this cross-sectional study analyzed data from the Kanagawa prospective “ME-BYO” Cohort Study (ME-BYO cohort) to investigate the correlation between loneliness, as measured by 20 items on the UCLA Loneliness Scale, and blood glucose levels. A total of 666 participants were included in the analysis, with a mean age of 54.1 years and a mean BMI of 23 kg/m2. Half of the participants had obtained an education level beyond high school. The mean household income and physical activity level were reported as 6.83 million Japanese yen and 12.3 METs-h/day, respectively. Model 1 of the linear regression analysis determined that there was no significant association between the loneliness scale and HbA1c (p = 0.512). After adjusting for age, gender, BMI (model 2), sitting time, physical activity level (model 3), housemates, household income, and final education (model 4), and controlling for social support, quality of life, and depression (model 5), the results showed no significant association, with a p-value of 0.823, 0.791, 0.792, and 0.816, respectively. Thus, the study found no link between loneliness and HbA1c in the high SES population. This finding contradicts previous results and may be attributed to the impact of population characteristics, SES status, or genetic backgrounds.
Hormone therapy is associated with lower Alzheimer’s disease tau biomarkers in post-menopausal females -evidence from two independent cohorts
Authors: Wang Yi-Ting , Therriault Joseph , Tissot Cécile , Servaes Stijn , Rahmouni Nesrine , Macedo Arthur Cassa , Fernandez-Arias Jaime , Mathotaarachchi Sulantha S. , Stevenson Jenna , Lussier Firoza Z. , Benedet Andréa L. , Pascoal Tharick A. , Ashton Nicholas J. , Zetterberg Henrik , Blennow Kaj , Gauthier Serge , Rosa-Neto Pedro
Published: July 2024

Background

Females represent approximately 70% of the Alzheimer’s disease (AD) cases and the literature has proposed a connection between the decreased estrogen levels during menopause and an increased AD risk. Previous investigations have predominantly focused on assessing how hormone therapy (HT) affects the likelihood of AD development and cognitive deterioration. However, as the research framework has shifted toward a biomarker-defined AD and alterations in specific biomarkers could take place years before cognitive decline becomes discernible, it is crucial to examine how HT influences AD biomarkers. The main goal of this study was to evaluate the impact of HT on AD biomarker-informed pathophysiology in both cognitively unimpaired (CU) and cognitively impaired (CI) post-menopausal females across the aging and AD spectrum.

Methods

This cross-sectional study included post-menopausal females without HT history (HT-) and with HT (HT+) at the time of PET imaging assessment from two cohorts: the Translational Biomarkers in Aging and Dementia (TRIAD) cohort, and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Participants underwent magnetic resonance imaging (MRI), positron emission tomography (PET) and biofluid collection. Voxel-based t-tests were performed to assess the differences in amyloid-β (Aβ) and tau neurofibrillary tangles (NFTs) loads between HT- and HT + females. Linear regression models with interaction terms were also conducted to examine the interactive effects of HT and Aβ-PET on regional tau-PET.

Results

HT + females demonstrated significantly lower tau-PET standardized uptake value ratio (SUVR) in Braak I-II ROIs (P < 0.05, Hedges’ g = 0.73), Braak III-IV ROIs (P < 0.0001, Hedges’ g = 0.74) and Braak V-VI ROIs (P < 0.0001, Hedges’ g = 0.69) compared to HT- females. HT + females also showed significantly lower CSF p-tau181 (P < 0.001) and plasma p-tau181 (P < 0.0001) concentrations. Additionally, results from multivariate linear regression models indicated that HT interacts with cortical Aβ and is associated with lower regional NFT load.

Conclusions

Overall, findings from this observational study suggest that HT is associated with lower tau neuroimaging and fluid biomarkers in postmenopausal females. Due to the close link between tau and cognition, this study highlights the need for large randomized controlled trials designed to systemically study the influences of HT on AD biomarkers and disease progression.
3D imaging as a method of measuring serotiny
Authors: van Mantgem Carolyn F.
Published: July 2024

Background

Serotiny, or pyriscence, refers to delayed seed dissemination within plants and plays an important role in the population dynamics of species following fire. Accurately understanding the variation in serotiny is crucial to predicting ecosystem responses to changing fire regimes. Three-dimensional (3D) cone surface area is one critical trait that can be used to characterize responses in serotinous species following fire, yet approaches to accurately measure cone surface area are limited. Cone surface area in regards to this paper is the total area of all surfaces of the cone. Past studies have relied on visual estimation to determine the openness of cones or to identify when cones become open. Subjective assessments of cone opening may be insufficient to adequately characterize cone responses to fire. In this study, I demonstrate the effectiveness of 3D modeling using a readily available phone camera and applications (Polycam, Blender) to quantify differences in 3D surface area of cones before and after heating treatments by comparing two serotinous conifer species, Monterey cypress (Hesperocyparis macrocarpa) and bishop pine (Pinus muricata).

Results

Bishop pine had an average cone surface area increase of 175.7% while Monterey cypress had an average cone surface area increase of 43.5%. Paired t-tests showed that cone surface area significantly increased following heating for both species.

Conclusions

Bishop pine showed a much greater cone surface area change relative to Monterey cypress. 3D imaging with the phone application, Polycam, proved to be a successful method of quantifying cone opening, creating a mesh that could be measured with the post-image processing software, Blender. A mesh can be defined as a digital 3D representation of an object made up of connected vertices that create edges and faces. Using a readily available phone camera, one can create an accurate 3D model to measure changes in the surface area of cones before and after fire. Simple methods for quantifying serotiny, such as demonstrated here, allow for improved understanding and predictions of how species respond to fire and other environmental triggers but require further investigation including, but not limited to, comparisons between serotinous species, facultative serotinous species, and non-serotinous species.
Quantitative outcomes of a type 2 single arm hybrid effectiveness implementation pilot study for hypertension-HIV integration in Botswana
Authors: Moshomo Thato , Gaolathe Tendani , Ramotsababa Mareko , Molefe-Baikai Onkabetse Julia , Mogaetsho Edwin , Dintwa Evelyn , Gala Pooja , Ponatshego Ponego , Bogart Laura M. , Youssouf Nabila , Seipone Khumo , Van Pelt Amelia E. , Bennett Kara , Jaffar Shabbar , Ilias Maliha , Tonwe Veronica , Hurwitz Kathleen Wirth , Kebotsamang Kago , Steger-May Karen , Hirschhorn Lisa R. , Mosepele Mosepele
Published: July 2024

Background

Successful HIV treatment programs have turned HIV into a chronic condition, but noncommunicable diseases such as hypertension jeopardize this progress. Hypertension control rates among people with HIV (PWH) are low owing to gaps in patient awareness, diagnosis, effective treatment, and management of both conditions at separate clinic visits. Integrated management, such as in our study, InterCARE, can enhance HIV-hypertension integration and blood pressure (BP) control.

Methods

Our pilot study was conducted in two Botswana HIV clinics between October 2021 and November 2022. Based on our formative work, we adopted three main strategies; Health worker training on HTN/cardiovascular disease (CVD) management, adaptation of HIV Electronic Health Record (EHR) for HTN/CVD care, and use of treatment partners to support PWH with hypertension for implementation. We employed the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework to assess implementation effectiveness and outcomes for BP control at baseline, 6 and 12 months. HIV viral load (VL) suppression was also measured to assess impact of integration on HIV care.

Results

We enrolled 290 participants; 35 (12.1%) were lost to follow-up, leaving 255 (87.9%) at 12-months. Median age was 54 years (IQR 46–62), and 77.2% were females. Our interventions significantly improved BP control to < 140/90 mmHg (or < 130/80 mmHg if diagnosis of diabetes or chronic kidney disease), from 137/290 participants, 47.2% at baseline to 206/290 participants, 71.0%, at 12 months (p < 0.001). Among targeted providers, 94.7% received training, with an associated significant increase in counseling on exercise, diet, and medication (all p < 0.001) but EHR use for BP medication prescribing and cardiovascular risk factor evaluation showed no adoption. In the intention-to-treat analysis, HIV VL suppression at 12 months decreased (85.5% vs 93.8%, p = 0.002) due to loss to follow-up but the per protocol analysis showed no difference in VL suppression between baseline and 12 months (97.3% vs 93.3%, p = 0.060).

Conclusion

The InterCARE pilot study demonstrated that low-cost practical support measures involving the integration of HIV and hypertension/CVD management could lead to improvements in BP control. These results support the need for a large implementation and effectiveness trial.

Trial registration

ClinicalTrials.gov NCT05414526. Registered 18th May 2022.
Design of CRLH-TL BPF with controllable attenuation poles
Authors: Hirayama Atsuya , Ishikawa Hinata , Ohno Takanobu
Published: July 2024

Compact and pole-controllable resonators and bandpass filter (BPF) using a composite right/left-handed transmission line (CRLH-TL) are designed in this study. The distributed constant line in the CRLH-TL has applied a tap-coupling technique, and one tap-coupled stub is loaded with the left-handed (LH) circuit. Attenuation poles are generated when the input susceptance of the stub diverges. In the tap-coupled CRLH-TL resonator, the attenuation pole is controlled at either the desired lower or higher region frequency than a resonant frequency by adjusting the circuit parameters. Also, the BPF constructed by the CRLH-TL resonators is designed based on a filter design theory, where the attenuation poles are located at lower and higher region frequencies than a negative-first-order frequency. The BPF with microstrip structure is fabricated using MEGTRON6 R-5775 ($$\varepsilon _\text {r}$$

ε
r

: 3.7, h: 0.63 mm, t: 18 μm), chip capacitors, and wire inductors. The simulated results show that the desired characteristics are approximately satisfied, i.e., we can design the CRLH-TL BPF which is controllable for the attenuation poles at both lower and higher region frequencies than a resonant frequency. The measured results are good agreement with the simulation. The negative-first-order frequency is generated at 2.00 GHz with 133 MHz bandwidth, i.e., the fractional bandwidth is 6.65 %. The resonator lengths in the BPF are shortened by 81.5 % and 75.0 % in comparison with a conventional half-wavelength ($$\lambda /2$$

λ
/
2

) openstub, and the size of the fabricated BPF is 0.18 $$\lambda _\text {g} \times$$

λ
g

×

0.17 $$\lambda _\text {g}$$

λ
g

. Therefore, a compact BPF with two controllable attenuation poles is realized by the tap-coupled CRLH-TL.
Study on bending fatigue performance of recycled aggregate backfill subgrade
Authors: Zehui Chen , Xiaowei Feng , Xinjun Fang , Shijun Wu
Published: July 2024

Recycled aggregate (RA), as a backfill subgrade material, has strong reproducibility and environmental protection, which cannot only effectively reduce resource consumption and environmental pollution but also achieve recycling of resources. Therefore, a study on the bending fatigue performance of RA backfill subgrade is proposed. Based on linear elastic state, softening state, and damage accumulation state, the variation law of bending fatigue damage variables is analyzed, and the stiffness of RA under cyclic load is calculated. According to the correlation between fatigue damage corresponding to two different load links and the constitutive relationship of RA, the identification results of bending fatigue damage state based on RA backfilling subgrade is obtained. The advantages of the fatigue damage model of RA are analyzed, and the fatigue life equation is established based on the damage evolution equation. Strain, stiffness modulus, asphalt saturation, and asphalt mixture adjustment coefficient are selected as model parameters to establish the fatigue damage model of RA. The flexural bearing capacity of the double-reinforced rectangular section is calculated, and the flexural fatigue performance of RA backfill subgrade is analyzed. The test results show that the high stress level in this method leads to a sharp decline in the fatigue life of the specimen, and the influence of fatigue damage gradually appears, which is helpful to improve the durability and safety of the subgrade structure. The range of change shows a small range, which is close to the reduction coefficient result, indicating that this method has high reliability in analyzing the bending fatigue performance of RA backfill subgrade.
Molecular Characterization of Metastatic Oncocytoma With Exceptional Response to Treatment: A Case Report
Authors: Webster Bradley R. , Ricketts Christopher J. , Vocke Cathy D. , Gamble Dionna , Crooks Daniel R. , Yang Ye , Friedman Lindsay , Toubaji Antoun , Msaouel Pavlos , Hernandez Jonathan M. , Linehan W. Marston , Ball Mark W.
Published: July 2024

Comprehensive molecular characterization and effective therapy in a rare case of metastatic renal oncocytoma
Enhancing Laryngoscopy Mastery: The Impact of Autonomous Practice with Feedback-Providing Simulators
Authors: Patel Shiv H. , Rudolf Frances , Schwartz Kristy , Gabriel Rodney A. , Hastings Randolph H. , Daniel Michelle , Suresh Preetham J.
Published: July 2024

Mastery learning with fixed end points and variable training time leads to more consistent expertise but is difficult to implement. Here we piloted mastery learning of laryngoscopy with independent practice. 35 learners participated in independent mastery learning on a manikin that provides automated performance feedback. A pre- and postpractice assessment of intubation skills was completed. After an average of 21 minutes of open practice, the percentage of subjects that met mastery criteria improved from 24% to 89% (P < .05). Independent intubation practice with manikin feedback facilitated mastery learning, enhanced procedural education, and may impact clinical care.
A deep learning-based toolkit for 3D nuclei segmentation and quantitative analysis in cellular and tissue context
Authors: Vijayan Athul , Mody Tejasvinee Atul , Yu Qin , Wolny Adrian , Cerrone Lorenzo , Strauss Soeren , Tsiantis Miltos , Smith Richard S. , Hamprecht Fred A. , Kreshuk Anna , Schneitz Kay
Published: July 2024

We present a new set of computational tools that enable accurate and widely applicable 3D segmentation of nuclei in various 3D digital organs. We have developed an approach for ground truth generation and iterative training of 3D nuclear segmentation models, which we applied to popular CellPose, PlantSeg and StarDist algorithms. We provide two high-quality models trained on plant nuclei that enable 3D segmentation of nuclei in datasets obtained from fixed or live samples, acquired from different plant and animal tissues, and stained with various nuclear stains or fluorescent protein-based nuclear reporters. We also share a diverse high-quality training dataset of about 10,000 nuclei. Furthermore, we advanced the MorphoGraphX analysis and visualization software by, among other things, providing a method for linking 3D segmented nuclei to their surrounding cells in 3D digital organs. We found that the nuclear-to-cell volume ratio varies between different ovule tissues and during the development of a tissue. Finally, we extended the PlantSeg 3D segmentation pipeline with a proofreading tool that uses 3D segmented nuclei as seeds to correct cell segmentation errors in difficult-to-segment tissues.
Deletion of the Ebf1, a mouse deafness gene, causes a dramatic increase in hair cells and support cells of the organ of Corti
Authors: Powers Kathryn G. , Wilkerson Brent A. , Beach Kylie E. , Seo Sophie S. , Rodriguez Jose S. , Baxter Ashton N. , Hunter Sarah E. , Bermingham-McDonogh Olivia
Published: July 2024

Following up on our previous observation that early B cell factor (EBF) sites are enriched in open chromatin of the developing sensory epithelium of the mouse cochlea, we investigated the effect of deletion of Ebf1 on inner ear development. We used a Cre driver to delete Ebf1 at the otocyst stage before development of the cochlea. We examined the cochlea at postnatal day (P) 1 and found that the sensory epithelium had doubled in size but the length of the cochlear duct was unaffected. We also found that deletion of Ebf1 led to ectopic sensory patches in the Kölliker's organ. Innervation of the developing organ of Corti was disrupted with no obvious spiral bundles. The ectopic patches were also innervated. All the extra hair cells (HCs) within the sensory epithelium and Kölliker's organ contained mechanoelectrical transduction channels, as indicated by rapid uptake of FM1-43. The excessive numbers of HCs were still present in the adult Ebf1 conditional knockout (cKO) animal. The animals had significantly elevated auditory brainstem response thresholds, suggesting that this gene is essential for hearing development.
Focal adhesion kinase signaling – tumor vulnerabilities and clinical opportunities
Authors: Schlaepfer David D. , Ojalill Marjaana , Stupack Dwayne G.
Published: July 2024

Focal adhesion kinase (FAK; encoded by PTK2) was discovered over 30 years ago as a cytoplasmic protein tyrosine kinase that is localized to cell adhesion sites, where it is activated by integrin receptor binding to extracellular matrix proteins. FAK is ubiquitously expressed and functions as a signaling scaffold for a variety of proteins at adhesions and in the cell cytoplasm, and with transcription factors in the nucleus. FAK expression and intrinsic activity are essential for mouse development, with molecular connections to cell motility, cell survival and gene expression. Notably, elevated FAK tyrosine phosphorylation is common in tumors, including pancreatic and ovarian cancers, where it is associated with decreased survival. Small molecule and orally available FAK inhibitors show on-target inhibition in tumor and stromal cells with effects on chemotherapy resistance, stromal fibrosis and tumor microenvironment immune function. Herein, we discuss recent insights regarding mechanisms of FAK activation and signaling, its roles as a cytoplasmic and nuclear scaffold, and the tumor-intrinsic and -extrinsic effects of FAK inhibitors. We also discuss results from ongoing and advanced clinical trials targeting FAK in low- and high-grade serous ovarian cancers, where FAK acts as a master regulator of drug resistance. Although FAK is not known to be mutationally activated, preventing FAK activity has revealed multiple tumor vulnerabilities that support expanding clinical combinatorial targeting possibilities.
The genome sequence of the jumping weevil, Orchestes rusci (Herbst, 1795)
Authors: Moran Stephen ,   Natural History Museum Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: July 2024

We present a genome assembly from an individual female Orchestes rusci (the jumping weevil; Arthropoda; Insecta; Coleoptera; Curculionidae). The genome sequence spans 624.00 megabases. Most of the assembly is scaffolded into 12 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 21.73 kilobases in length.
The Shadow of the Parental Relationship: a Phenomenological View on Problems of Adaptation of First-Graders
Authors: Myshkovskaya A. , Viktoruk Elena
Published: July 2024

The article describes the experience of psychological and pedagogical diagnosis of the causes of difficulties in teaching a first-grader using the example of a particular case (parent-child triad). Based on phenomenological analysis, a conclusion is made about the primary role of parents in correcting the phenomenon of school maladjustment based on the identification of such parenting phenomena as authoritarian hypersocialization, dictate, rejection, conflict type of interaction, lack of quality communication, the study of which allows us to develop a strategy for improving family dynamics. A scheme of the consultation process based on a phenomenological approach is proposed, consisting of 10 sequentially implemented steps.
Study of the use of various humic preparations on crops and the quality of grain feed barley
Authors: Medvedev Nikita , Safin Radik
Published: July 2024

The results of studies on the effectiveness of seed treatment and plant spraying with various humic preparations on spring grain feed barley are presented. The objectives of the research included assessing the effect of various humic preparations on productivity, disease resistance and grain quality of spring barley under various methods of their application (seed treatment, plant spraying, seed treatment + plant spraying). The objects of research were spring two-row barley of the Raushan variety. Humic preparations Bigus and Gumat +7 were used. The research was carried out in 2022-2023 on gray forest, medium loamy soil. In 2022, moisture conditions during the growing season were favorable; in 2023, periodic severe drought events were observed. The use of humic preparations led to a decrease in the development of both leaf diseases (dark brown spot) and root rot. The drug Bigus Extra had a more pronounced effect on reducing the damage to plants by root rot. The use of humic preparations had a positive effect on the length of the stem and ear of barley. The maximum values of the stem length were when using seed treatment and spraying crops with Bigus Extra, and the greatest length of the ear was when using Gumi+7. The use of humic preparations increases the yield of spring barley from 11 to 27.8%. When using only seed treatment or only spraying of crops, Bigus Extra had an advantage in yield, and when using a combination – seed treatment + plant treatment Humat +7. The highest yield of spring barley (27.8% more than in the control) was obtained using a scheme in which seeds and plants were treated with Humate +7. The use of seed treatment followed by spraying of plants led to an increase in the protein content of barley grain. The use of humic preparations in which they are used for pre-sowing seed treatment and subsequently for spraying crops (twice) was optimal for spring barley.
Influence of mineral fertilizers in various combinations on the yield and grain quality of spring soft wheat in the conditions of the Pedkama Republic of Tatarstan
Authors: Serzhanova Al'bina , Garaev Razil , Serzhanov Igor , Shaykhutdinov Farit
Published: July 2024

The results of two-year experiments to study the effect on the yield and grain quality of spring soft wheat of a full dose of mineral fertilizers in various combinations for pre-sowing cultivation, as well as foliar top dressing at a dose of N30 in the tillering and milk ripeness phase are reported. Fertilizers increased grain yield to varying degrees and had different effects on the technological qualities of grain. According to the grain yield of spring wheat of the Ulyanovsk 105 variety, on average for 2 years, the best options were: N90P90K30 (an increase of 3,6 t /ha) and N30P90K30 + N30 with top dressing in the tillering phase (an increase of 3,71 t/ha). According to the Tulaykovskaya Nadezhda variety, the best is the introduction of a complete mineral fertilizer (N30P90K30) with one and two top dressing (an increase in yield of 0,53 and 0,57 t/ha). Mineral fertilizers had a positive effect on grain quality in both varieties of spring wheat. The grain quality of the Ulyanovsk 105 variety is significantly improved under the influence of fertilizers. The vitreous content of the grain in the control was 52% in 2022 and 64% in 2023. In all variants with fertilizer, it is in the range of 60,0-79,0% in 2022 and 68,5-75,9% in 2023. In the Tulaykovskaya Nadezhda variety, the vitreous content of grain in 2022 increased from 45% in the control to 49 ...60% in other variants, and in 2023, respectively, from 57 to 60 ... 71%. The content of the mass fraction of gluten in the grain of the control variant in 2022 was 17,1%, protein 10,5%. The use of fertilizers contributed to an increase in the amount of gluten to 28,8%, protein to 11,6...13,8%. A similar situation was observed in 2023. The highest content of protein and gluten in the grain of the harvest of 2022 and 2023. it was observed in the variant with one and two nitrogen fertilizers (13,5...13,8% and 14,5...14,9%), 26,0...28,8 % and 33,0...33,6%, respectively.
Agronomic and economic efficiency of the complex application of mineral fertilizers and Mizorin biologics on alfalfa crops of the Aislu variety in the soil and climatic conditions of the Republic of Tatarstan
Authors: Suleymanov Salavat , Sochneva Svetlana , Hamidullin Nail' , Safiollin Faik , Karimov Almaz
Published: July 2024

Field experiments on alfalfa crops of the Aisylu variety were conducted in 2020-2022 on the basis of the Agrobiotechnopark of the Kazan State Agrarian University (Narmonka village of the Laishevsky municipal district of the Republic of Tatarstan). The soils of the experimental site are gray forest with the following agrochemical indicators: the content of humus according to Tyurin is 3.0%, mobile phosphorus is very high (> 250 mg/kg) and exchangeable potassium is increased (145 mg/kg according to Kirsanov). The reaction of the soil medium was close to neutral (pH 6.6). The aim of the research was to develop methods to increase the yield and quality of the green mass of alfalfa on the basis of the use of various types of mineral fertilizers and the biological preparation Mizorin. The scheme of the experiment included the following options: control (without fertilizers and biologics); root dressing in spring and after the first mowing with ammonium nitrate of 100 kg/ha; root dressing in spring and after the first mowing with nitrogen strip of 100 kg/ha; root dressing in spring and after the first mowing with ammonium nitrate of 100 kg/ha in combination with leaf dressing with the biopreparation Mizorin 2 l/ha; root dressing in spring and after the first mowing with a 100 kg/ha nitrogen strip in combination with a leaf dressing with the biopreparation Mizorin 2 l/ha. Early spring feeding of alfalfa and after the first mowing with ammonium nitrate at the rate of 100 kg / ha provided additional 4.7 t/ha of green mass. In the variant of azofoska top dressing, the yield increase increases to 29.8 t/ha of the green mass of the research object. The maximum yield of the studied crop was obtained in variants of combining root and leaf fertilization, the increase in green mass increased to 64.4 and 92%, respectively.
The effectiveness of using chicken manure during the cultivation of winter wheat grain
Authors: Haliullina Zul'fiya , Ganiev Almaz , Gayfullin Ilnur
Published: July 2024

In this paper, the possibility and effectiveness of using chicken manure as an organic fertilizer "Soil improver (UP-1)" is studied. "Soil improver (UP-1)" was obtained by adding the plant growth regulator "Mephosphone" to chicken manure. The drug "Mephosphone" is intended for the cultivation of grain crops, as well as the production of organic products. Experimentally, the prospects of using the drug "Mephosphone" to accelerate the processing of organic waste have been revealed. As a result of the research, field data were obtained on the cultivation of winter wheat of the Kazanskaya 560 Elite variety in the fields of JSC Agrofirma Ak Bars - Pestretsy. The introduction of chicken manure - "Soil improver (UP-1)", treated with the drug "Mephosphone" was carried out according to the described method. The local variety of winter wheat "Kazanskaya 560" Elite with a seeding rate of 280 kg/ha was used as an experimental crop. The predecessor was perennial herbs. Before the experiment and after harvesting, soil was selected for analysis from both experimental fields with an area of 300 hectares from 6 random plots at a layer depth of 0-20 cm. As a result of field tests, an increase in the yield of grain of the Kazanskaya 560 Elite variety was recorded when applying chicken manure. In the experimental plots, the yield was 33.5 and 36.0 c/ha. The grown grain with the use of chicken manure treated with the preparation "Mephosphone" meets the basic quality requirements and is practically not inferior to the grain of the control group, which allows it to be freely used for processing into flour of proper quality. Analysis of the indicators of experimental soil samples shows that they do not exceed the requirements of scientific and technical documentation. Thus, the resulting soil is safe for humans and agricultural production. The proposed technology for processing poultry waste will improve the environmental situation around modern poultry farms, reduce the use of unprocessed chicken manure as fertilizers, replacing it with higher-quality and environmentally friendly organic fertilizers formed as a result of anaerobic disposal of manure.
Campylobacter: understanding its role as the primary bacterial cause of food-borne illnesses – current state of knowledge
Authors: Nowak Martyna , Rak Kacper , Kłosowska Wiktoria , Błaszczyszyn Katarzyna , Gaweł-Dąbrowska Dagmara , Paluch Emil
Published: July 2024

Introduction
Campylobacteriosis, caused primarily by Campylobacter jejuni and Campylobacter coli, is a significant public health concern worldwide. Since 2007 it has been the most frequently reported zoonotic disease in humans across the European Union. Campylobacteriosis is also the leading cause of bacterial diarrhea.
 
Aim of the study
This review aims to provide a comprehensive overview of the epidemiology, clinical manifestations, transmission dynamics, diagnostic approaches, and prevention strategies associated with Campylobacter infections.
 
Brief description of the state of knowledge
The transmission of Campylobacter spp. typically occurs via the fecal-oral route, with contaminated food, especially poultry, and water serving as common sources of infection. Notably, Campylobacter infections exhibit distinct seasonal patterns and demographic trends, with children and young adults being particularly susceptible. Clinical manifestations range from mild gastrointestinal symptoms to more severe complications, such as reactive arthritis, and Guillain-Barré syndrome. Diagnosis usually relies on microbiological testing. Some of these methods require specialized cultivation techniques, with challenges posed by the phenotypic diversity of Campylobacter species.
 
Summary
Effective surveillance and prevention strategies are essential for mitigating the burden of campylobacteriosis and its associated sequelae on both individual and population health.  Current research focuses on improving preventive measures, underscoring the importance of advancing public health strategies, and further studies into the epidemiology, pathogenesis, and treatment options. These efforts are crucial for effectively addressing Campylobacteriosis and reducing its effects on human health and agriculture.