bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete genome sequence of PETase type IIa-harboring
Marinobacter nanhaiticus
D15-8W, isolated from a South China Sea sediment
Authors: Suzuki Yukako , Fukazawa Ayako , Sugawara Koki , Galipon Josephine , Arakawa Kazuharu
Published: November 2023

Marinobacter nanhaiticus
D15-8W is known for its ability to metabolize polycyclic aromatic hydrocarbons. Here, we report the complete circular genome sequence of this strain to be 5,336,660 bp (G + C content, 58.6%; 4,869 protein-coding sequences) with one plasmid (69,655 bp).
On Observed Effects in Experiments on the Fissile Nuclei Rotaton (ROT Effects)
Authors: Danilyan G. V.
Published: November 2023

In experiments on polarized neutron beams, the effects indicating the rotation of a fissile nucleus have been observed. The main factor for this conclusion is the asymmetry of the coincidence count between the particle detectors accompanying the fission and the fragment detectors when reversing the direction of polarization of the neutron beam causing the fission of the studied nuclei. According to the opinions of the discovery authors, the measured asymmetry can be caused by the shift of the angular distribution in the direction or against the direction of the nucleus deformation rotation axis. In most publications, this shift is explained by the rotation of the angular distribution of particles in the direction of rotation of the nuclear fission axis. This article provides a simple and obvious explanation.
New perspectives in cancer immunotherapy: targeting IL-6 cytokine family
Authors: Soler Maria Florencia , Abaurrea Andrea , Azcoaga Peio , Araujo Angela M , Caffarel Maria M
Published: November 2023

Chronic inflammation has been recognized as a canonical cancer hallmark. It is orchestrated by cytokines, which are master regulators of the tumor microenvironment (TME) as they represent the main communication bridge between cancer cells, the tumor stroma, and the immune system. Interleukin (IL)-6 represents a keystone cytokine in the link between inflammation and cancer. Many cytokines from the IL-6 family, which includes IL-6, oncostatin M, leukemia inhibitory factor, IL-11, IL-27, IL-31, ciliary neurotrophic factor, cardiotrophin 1, and cardiotrophin-like cytokine factor 1, have been shown to elicit tumor-promoting roles by modulating the TME, making them attractive therapeutic targets for cancer treatment.

The development of immune checkpoint blockade (ICB) immunotherapies has radically changed the outcome of some cancers including melanoma, lung, and renal, although not without hurdles. However, ICB shows limited efficacy in other solid tumors. Recent reports support that chronic inflammation and IL-6 cytokine signaling are involved in resistance to immunotherapy. This review summarizes the available preclinical and clinical data regarding the implication of IL-6-related cytokines in regulating the immune TME and the response to ICB. Moreover, the potential clinical benefit of combining ICB with therapies targeting IL-6 cytokine members for cancer treatment is discussed.
Sensitivity to triple Higgs couplings via di-Higgs production in the 2HDM at the (HL-)LHC
Authors: Arco F. , Heinemeyer S. , Mühlleitner M. , Radchenko K.
Published: November 2023

An important task of the LHC is the investigation of the Higgs-boson sector. Of particular interest is the reconstruction of the Higgs potential, i.e. the measurement of the Higgs self-couplings. Based on previous analyses, within the 2-Higgs-Doublet Model (2HDM) type I, we analyze several two-dimensional benchmark planes that are over large parts in agreement with all theoretical and experimental constraints. For these planes we evaluate di-Higgs production cross sections at the (HL-)LHC with a center-of-mass energy of $$14 \,\, \textrm{TeV}$$

14

TeV

at next-to-leading order in the heavy top-quark limit with the code . We investigate in particular the process $$gg \rightarrow hh$$

g
g
→
h
h

, with h being the Higgs boson discovered at the LHC with a mass of about $$125 \,\, \textrm{GeV}$$

125

GeV

. The top box diagram of the loop-mediated gluon fusion process into Higgs pairs interferes with the s-channel exchange of the two $${\mathcal{C}\mathcal{P}}$$

C
P

-even 2HDM Higgs bosons h and H. The latter two involve the triple Higgs couplings (THCs) $$\lambda _{hhh}$$

λ

hhh

and $$\lambda _{hhH}$$

λ

hhH

, respectively, possibly making them accessible at the HL-LHC. Depending on the size of the involved top-Yukawa and THCs as well as on the mass of H, the contribution of the s-channel H diagram can be dominating or be highly suppressed. We find regions of the allowed parameter space in which the di-Higgs production cross section can differ by many standard deviations from its SM prediction, indicating possible access to deviations in $$\lambda _{hhh}$$

λ

hhh

from the SM value $$\lambda _{\textrm{SM}}$$

λ
SM

and/or contributions involving $$\lambda _{hhH}$$

λ

hhH

. The sensitivity to the beyond-the-SM (BSM) THC $$\lambda _{hhH}$$

λ

hhH

is further analyzed employing the $$m_{hh}$$

m

hh

distributions. We demonstrate how a possible measurement of $$\lambda _{hhH}$$

λ

hhH

depends on the various experimental uncertainties. Depending on the underlying parameter space, the HL-LHC may have the option not only to detect BSM THCs, but also to provide a first rough measurement of their sizes.
Simple stochastic model with safe speed using Exchange approach to recognizing synchronized flow as speed-synchronized phase
Authors: Fukuichi Masayuki
Published: November 2023

In order to unravel the physical and mathematical mystery of synchronized-flow mechanism and to reveal the fundamental mechanism and origin of synchronized flow produced by nonlinear stochastic processes, we have produced simple stochastic traffic flow models (the gradual-NaSch, Phoenix and mPhoenix models) with nonlinear safe speeds. In the mNaSch model and our gradual-NaSch model, the [Formula: see text]th vehicle’s speed is the same as or different from the [Formula: see text]th vehicle’s speed because they are discrete values. In the mNaSch and gradual-NaSch models, the same discrete values of the [Formula: see text]th and [Formula: see text]th states make it easy to identify synchronized flow with speed-synchronized phase of the [Formula: see text]th and [Formula: see text]th states. On the other hand, when we deal with synchronized flow in continuous traffic flow models, we face a problem. Continuous values cause the difficulty in identification of synchronization. In order to definitely clarify whether or not synchronized flow occurs in continuous models, we have established a novel idea of Exchange approach to recognizing synchronized flow as speed-synchronized phase. Our idea is generated from the analogical image that the whole system of synchronized metronomes does not change even if the [Formula: see text]th and [Formula: see text]th synchronized metronomes are exchanged. The Exchange approach (exchanging the [Formula: see text]th vehicle’s state for any [Formula: see text]th vehicle’s state in the whole system of traffic flow), which causes distortion such as a collision if non-synchronized vehicle’s states are exchanged and makes it possible to definitely clarify whether or not synchronized flow occurs in continuous models, is applied to our simple stochastic continuous model (the mPhoenix model). On the basis of the Exchange approach, we can recognize that the mPhoenix model surely reproduces synchronized flow. In addition, we have proposed mathematical approach to deriving nonlinear safe speeds which guarantee collision free driving and reproduce synchronized flow.
Two kinds of gravitational forces in transport: An analysis using the gravity model
Authors: Lee Changgi , Woo Hyungsoo , Yang Jae-Suk
Published: November 2023

The gravity model is a widely recognized tool for estimating the movement of people and goods. In this study, we introduce two gravitational variables, population size and regional GDP per capita (RGDPPC), to explain the characteristics of population movement between and within cities in South Korea. A log-linearized gravity model is employed to run regression analyses at three spatial levels: the national level (encompassing the entirety of South Korea), the metropolitan level (focusing on the Seoul and Busan Metropolitan Transportation Areas) and the city level (specifically in Seoul and Busan). The study incorporates data on various modes of transportation from 246 of the 250 municipalities in South Korea. Predictive performance of the model is better when utilizing national-level data. However, as spatial area decreases and population density increases, the models explanatory power decreases significantly when relying solely on data related to either population size or RGDPPC. The findings suggest that incorporation of both population size and RGDPPC into the gravity model best captures the dynamics of traffic flow within economically integrated regions. This relationship is analogous to gravitational fields generated by two distinct types of mass. Including both population size and RGDPPC, the gravity model can be leveraged effectively to estimate traffic patterns, particularly within regions characterized by high economic integration.
MODELING THE ASYMMETRIC EFFECTS OF EXCHANGE RATE, FINANCIAL DEVELOPMENT, AND OIL PRICES ON ECONOMIC GROWTH
Authors: APPIAH MICHAEL , GYAMFI BRIGHT AKWASI , USMAN OJONUGWA , BEKUN FESTUS VICTOR
Published: November 2023

Recent studies on the relationship between exchange rates, oil prices, and economic growth in developing countries like Ghana have used linear methods, but do not account for potential asymmetries. This research investigates the intricate asymmetric effects of exchange rates, financial development, and oil prices on Ghana’s growth from 1990–2017 using a nonlinear model. The findings indicate that global oil price has asymmetric effects on short- and long-term growth, with positive price changes having different impacts than negative changes. However, there is no evidence for asymmetric long-term effects of exchange rates and financial development on growth, only short-term asymmetries. The cumulative effects of exchange rates and financial development outweigh oil prices. Recommendations include modernizing fuel efficiency, investing in renewable energy and public transit to address oil price shocks, and increasing market transparency and collaboration between major consumer and producer countries. The nonlinear model provides an evidence-based analysis of the intricate asymmetric relationships between these factors and developing country growth.
Voltage Controlled Ring Oscillator with Phase Compensation Technique for Jitter Reduction in 180 nm CMOS Technology
Authors: Mishra Abhishek , Singh Anil , Agarwal Alpana
Published: November 2023

This paper presents a novel jitter reduction technique for a voltage-controlled ring oscillator (VCRO). This technique is helpful in employing VCRO-based circuits like Analog to Digital Converter (ADC), Phase Locked Loop (PLL) and time-based circuits whose performance is severely degraded by high jitter. In the proposed technique, the jitter is extracted using Excess Phase Discrimination (EPD) block and is transformed into Pulse Width Modulated (PWM) signal, which is then fed into the Phase Compensator (PC) block. This block reduces the jitter by about half its value after enabling the Single Ended Injection Locking (SEIL). The proposed work is designed in SCL 180 nm CMOS technology at 1.8 V supply. On enabling the proposed circuit, the Root Mean Square (RMS) jitter reduces from 5.94 to 2.58 ps (about 56%) for VCRO running at 58 MHz and consumes a total power of 375.84 [Formula: see text]W. The overall performance of the proposed circuit does not vary much in the post-layout simulations, hence demonstrating the effectiveness of the proposed technique.
INCIDENCE OF KNEE SURGERIES OVER 5 YEARS AMONG PATIENTS WITH KNEE OSTEOARTHRITIS TREATED WITH A NON-INVASIVE, HOME-BASED, BIOMECHANICAL INTERVENTION
Authors: Hasanoglu Asude N. , Hsu Audree , Yerra Sandeep , Aklile Natnael , Huang Daniel , Manatt Robby , Regala Danilo , Rand Stephanie , Bartels Matthew N.
Published: November 2023

Background: The annual demand for total knee arthroplasty (TKA) will increase by 182%, from more than 700,000 in 2014 to 1.2M in the year 2030, placing an immense financial and social burden on healthcare systems to control medical costs and quality of care. This study aimed to examine the long-term effect of a home-based, non-surgical biomechanical intervention on surgery incidence amongst patients with moderate-severe knee osteoarthritis (OA).

Methods: This is a retrospective registry review done at the Department of Rehabilitation Medicine of Albert Einstein College of Medicine, Montefiore Medical Center. Between September 2015 and December 2018, 95 patients (81% females, mean age 62.6± 8.3 years) diagnosed with primary knee OA were referred to receive a new non-invasive biomechanical foot-worn device after exhausting other non-surgical care. Patients were personally fitted with a non-invasive, biomechanical device, that alters the foot’s pressure points to reduce loads, minimize symptoms, and promote neuromuscular control training using adjustable, convex pods under the sole. Patients used the device for short periods during regular home/work activities. The primary outcome was the occurrence of knee surgery during an average follow-up time of 5.6 years. TKA incidence was compared to that of a reference group of patients with knee OA who were referred to receive traditional physical therapy (PT).

Results: Of the patients who were treated with the biomechanical intervention, 12/95 patients (12.6%) had a TKA, compared to 23/67 patients (34.3%) who received traditional PT and had a TKA.

Conclusion: The use of the biomechanical intervention was associated with avoiding TKA in more than 87% of patients at five years. Increased use of biomechanical intervention to treat knee OA may help reduce some of the burden on healthcare and society associated with end-stage knee OA by delaying or avoiding surgery.
Trimethoprim inhibits renal H+-K+-ATPase in states of K+ depletion
Authors: Ayasse Niklas , Berg Peder , Svendsen Samuel L. , Rousing Amalie Quist , Sørensen Mads Vaarby , Fedosova Natalya U. , Leipziger Jens
Published: November 2023

The antibiotic trimethoprim (TMP) often mediates K+ retention and metabolic acidosis. We suggest a revision of the underlying mechanism that causes metabolic acidosis. Our results indicate that TMP-induced metabolic acidosis is secondary to epithelial Na+ channel-dependent K+ retention. Under control dietary conditions, TMP does not per se inhibit collecting duct H+ secretion. These findings add further argument against a physiologically relevant voltage-dependent mechanism of collecting duct H+ excretion.
Eight weeks of heavy strength training increases hemoglobin mass and V̇o2peak in well-trained to elite female and male rowers
Authors: Lundby Carsten , Mazza Oscar , Nielsen Joachim , Haubro Mads , Kvorning Thue , Ørtenblad Niels , Gejl Kasper Degn
Published: November 2023

This study in female and male rowers demonstrates that hemoglobin mass (Hbmass), V̇o2peak, and muscle strength increases with 8 wk of heavy strength training and that this response is not different between conventional (3 × 10 repetitions) and high-volume strength training (10 × 10 repetitions). Moreover, female rowers exhibited less hemoglobin per kilogram of lean body mass compared with their male counterparts, which likely contributes to sex differences in V̇o2peak and rowing performance.
Weight Loss App Descriptors in App Stores: A Qualitative Analysis of the Spanish Market
Authors: Martin-Vicario Lara , Bustos Díaz Javier , Nicolas-Sans Ruben
Published: November 2023

Mobile applications for weight loss have arisen the interest of private companies and developers, who have put great efforts on the development of this kind of apps. This topic has attracted the interest of the scientific community, both in terms of usability and design. Two main issues have, however, arisen: firstly, research focus has been on the apps themselves, but little attention has been paid to how they are presented in the application stores, and secondly, current literature focuses solely on applications in English. The study objective is to observe how the most popular weight loss applications for the Spanish market are presented in the stores. Using thematic analysis, this study is aimed at discovering the themes featured in the store descriptions and to observe what functionalities are highlighted in these descriptions. The initial sample was based on 247 weight loss applications, which after revision was reduced to 7 applications. Our results show that they focused on efficacy, speed, and, to a much lesser degree, safety in weight loss. Among the main results, we found that app descriptors analyzed did not employ a scientific language and demonstrate technical expertise, or user testimonials. On the other hand, the claims made by the apps about weight loss were mainly based on effectiveness. This sometimes included the concept of quick results and, to a lesser extent, health and safety. Lastly, we observed that there is room for improvement in the linguistic and cultural adaptation of the texts of these application descriptions. Regarding the study limitations, the reduced number of the sample is because our study focuses on applications with features that follow international weight loss guidelines, which most of them did not follow.
Storage Stability Assessment of Indigenous Guava Fruits (Psidium guajava L.) cv. “Gola” in Response to γ-Irradiation
Authors: Yousaf Ali Asad , Sarfraz Kashif , Ahmed Asif , Hassan Imran , Ali Haider , Mehmood Talat
Published: November 2023

Postharvest losses in fruits and vegetables pose a key challenge to the global horticulture industry. Improved storage stability of horticultural commodities through irradiation is a technological intervention which has greater compliance over more than 60 foods and food products. The present study was intended to explore the effect of γ-irradiation doses on the postharvest quality of fresh guava fruits stored under ambient (temperature

20
±
2

°C, RH 85%) conditions. Various storage specific quality attributes including physiological weight loss, respiration rate (CO2), ethylene estimation, ripening index, fruit firmness, ascorbic acid, nutraceutical potential, and enzyme kinetics were evaluated during postharvest storage at four days of interval. The results indicated that the fruits irradiated at doses (0.8 kGy and 1.0 kGy) exhibited significant reduction in physiological parameters in contrast with untreated fruit samples. Firmness, total phenolic compounds, flavonoids, and radical scavenging activity were successfully retained in irradiated fruit samples up to twenty days of storage. The respiration and ethylene production rates were suppressed in irradiated guava fruits compared to control. Moreover, it has also been discovered that the fruits exposed to 1.0 kGy had considerably decreased the polyphenol oxidase (PPO) activity compared to nonirradiated fruits, thus resulting in lowering the enzymatic browning. Aside from that, irradiation guava fruits had considerably enhanced antioxidant enzyme activity (

P
≤
0.05

) in terms of catalase, peroxidase, and superoxide dismutase. In conclusion, the study revealed that

γ

-rays irradiation doses up to 1.0 kGy might be considered effective to improve the postharvest storage of native guava fruits variety with intact nutritional attributes.
Prognostic Factors and Outcome of Patients with Adult Acute Lymphoblastic Leukemia Treated with the Hyper-CVAD Regimen: A Retrospective Study
Authors: Malakoutikhah Zahra , Ashrafi Farzaneh , Derakhshandeh Ali
Published: November 2023

Aim. The Hyper-CVAD regimen has shown promising results for adult patients with acute lymphoblastic leukemia (ALL), as designed by the MD Anderson Cancer Center (MDACC). This treatment has resulted in a complete remission rate of 92% and a 5-year overall survival of 38%. However, given the diversity of patient demographics and institutional methods, outcomes may differ between various institutions. This study will compare the outcome of adult ALL patients treated with the Hyper-CVAD regimen in Iran with those obtained in the original series presented at the MDACC. Patients and Method. In this retrospective study, we evaluated the 2-year leukemia-free survival (LFS) and the 2-year overall survival (OS) of 70 ALL patients treated between 2014 and 2019 in the Seyed Al-Shohada Hospital in Isfahan, Iran. Results. In total, 59 ALL patients (84.28%) achieved complete remission (CR). The CR rate had statistical differences by bone marrow transplantation (BMT) and WBC count. The 2-year LFS and OS were 40% and 42%, respectively. There were significant differences in LFS and OS by BMT, myeloid marker, and WBC count. Conclusion. The outcome of the traditional Hyper-CVAD regimen in treating adult ALL was not satisfying. More efficient therapies should be applied for the treatment of adult ALL.
Battery Cell Balancing of V2G-Equipped Microgrid in the Presence of Energy Storage Aggregator
Authors: Peter Geno , Alexander Stonier Albert , Vanaja Dishore Shunmugham , Justin Fitrahsya , Kuppusamy Ramya , Teekaraman Yuvaraja
Published: November 2023

High electricity consumption in Sarawak’s cities is a concern, driven by residential, industrial, and commercial users. Greater demand for electrical energy requires more electrical resources, affecting grid stability. To prevent blackouts and enhance grid resilience, electric vehicles can serve as distributed energy storage in microgrids. The biggest problem facing energy storage is that not all batteries within energy storage are the same. Every battery cell in the battery pack has a different rate of self-discharge, capacity, internal resistance, and aging, even though they have the same chemical and physical characteristics. These variations lead to power imbalances in energy storage. Therefore, to address this issue, a unique voltage equalization method using a modular flyback converter is presented. Its core objective is to correct voltage imbalances among batteries. The proposed method is modelled using MATLAB, and the performance of the system has been evaluated. Furthermore, the developed model is implemented in a microgrid and tested for two different cases (with and without energy storage for electric cars). From the simulation outcomes, it has been verified that the developed cell balancing technique performs well in equalizing the voltage of cells than the conventional methods.
Evaluation of the Effect of Nanographene Oxide on Microleakage of Conventional and Resin-Modified Glass Ionomer
Authors: Sharafeddin Farahnaz , Ghodrati Parisa
Published: November 2023

Objectives. One of the important features of the restorative materials is the ability to seal and prevent the microleakage. Glass ionomer cement (GIC) still exhibits some microleakage despite establishing a chemical bond to the tooth. The aim of this study was to evaluate the effect of nanographene oxide (nGO) on the microleakage of conventional (CGIC) and resin-modified glass ionomer cement (RMGIC). Methods. Thirty intact extracted molars were used. Class V cavities were prepared on their buccal and lingual surfaces. The samples randomly divided into two main groups of CGIC and RMGIC; each of them was randomly subdivided into three subgroups, including the group without nGO (control), the group with 1% nGO, and the group with 2% nGO. After restoring the cavities, they were subjected to thermocycling (1,000 cycles at 5/55°C). Two percent basic fuchsin solution was used to perform the microleakage test, and then the sectioned samples were examined by a stereomicroscope 40x. Kruskal–Wallis test, Dunn’s test, and Mann–Whitney U test were used to analyze the data (

P
<
0.05

). Results. Group CGIC + 1% nGO at the gingival margin and group RMGIC + 1% nGO at both gingival and occlusal margins had significantly less microleakage than their control groups (

P
=
0.008

,

P
=
0.002

,

P
=
0.023

, respectively). Also, in these two groups, there were no significant differences between the microleakage of the occlusal and gingival margins (

P
=
0.132

,

P
=
0.511

, respectively), while in all other groups, the gingival microleakage was significantly higher than that of occlusal microleakage. Conclusions. The addition of 1% nGO significantly reduced the gingival microleakage of CGIC and the occlusal and the gingival microleakage of RMGIC, while the addition of 2% nGO did not cause a significant reduction in microleakage.
Thermo-Physiological Comfort Property of Military Combat Boot Material for Hot and Cold Climatic Conditions
Authors: Bekele Weldeyesus Wendowesen
Published: November 2023

Military combat boots require materials that balance thermo-physiological comfort in hot and cold climates. The aim of this research was to analyze the thermo-physiological comfort properties of military combat boot materials in extreme hot and cold conditions to maintain optimal functionality. One-way ANOVA and Tukey’s pairwise comparison statistical tests were conducted, resulting in a

p

value less than 0.05, indicating statistically significant differences between the materials’ air permeability, water vapor permeability, and thermal resistance. For hot climates, plain nylon canvas four-thread upper and warp-knitted lining fabrics had thermo-physiological indexes of 8.15 and 119.5, respectively. The high airflow and moisture wicking of these materials kept feet cool and dry. For cold climates, chrome-tanned waterproof upper leather and sheepskin lining leather had thermo-physiological indexes of 33.33 and 24.18, respectively. Their waterproofing and insulation maintained warmth and dryness. The thermal properties of the sample uppers were determined to evaluate breathability and insulating ability for hot and cold climatic conditions. The selection of proper materials for military combat boots in different climates is the main approach to reducing foot heat, foot pain, and foot injuries under any condition, providing comfort for wearers, and protecting feet against harsh conditions.
Table S2 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Authors: Frigault Melanie M. , Mithal Arushi , Wong Harvey , Stelte-Ludwig Beatrix , Mandava Vinay , Huang Xin , Birkett Joseph , Johnson Amy J. , Izumi Raquel , Hamdy Ahmed
Published: November 2023

Supplementary Table 2 contains the statistical analysis for pSer2 downregulation in SU-DHL-4 and SU-DHL-10 cell lines across CDK9 inhibitor treatments.
Figure S1 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Authors: Frigault Melanie M. , Mithal Arushi , Wong Harvey , Stelte-Ludwig Beatrix , Mandava Vinay , Huang Xin , Birkett Joseph , Johnson Amy J. , Izumi Raquel , Hamdy Ahmed
Published: November 2023

Supplementary Figure 1 shows the principal component analysis of RNA sequencing of either SU-DHL-4 and SU-DHL-10 cell lines as well as that from RNA sequencing of patient blood samples.
FIGURE 5 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Authors: Frigault Melanie M. , Mithal Arushi , Wong Harvey , Stelte-Ludwig Beatrix , Mandava Vinay , Huang Xin , Birkett Joseph , Johnson Amy J. , Izumi Raquel , Hamdy Ahmed
Published: November 2023

Comparison of DEGs identified in MYC+ DLBCL cell lines to blood samples from enitociclib-treated patienst with MYC+ NHL. A, Comparison of significant DEGs (Padj ≤ 0.05, fold change ≥2) after at 4 hours pretreatment with 250 nmol/L enitociclib. Heat map showing gene intensity per sample relative to the average level across all samples. Individual genes are shown on the Y axis while samples are shown along the X axis. Red and blue cells correspond to higher and lower RNA-seq levels, respectively after 4 hours of treatment. B, Transcription factors MYC, JUNB, ZFP36 mRNA have statistically significant fold change downregulation with enitociclib treatment in DLBCL cell lines SU-DHL-4 and SU-DHL-10 where other 4 hours treatments do not. PHF23 and TP53RK were the most significantly DEGs with enitociclib treatment at both concentrations. * denotes Padj ≤ 0.05 and fold change ≥2.
FIGURE 1 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Authors: Frigault Melanie M. , Mithal Arushi , Wong Harvey , Stelte-Ludwig Beatrix , Mandava Vinay , Huang Xin , Birkett Joseph , Johnson Amy J. , Izumi Raquel , Hamdy Ahmed
Published: November 2023

Enitociclib delivers robust inhibition of RNA polymerase II Ser2 phosphorylation for up to 48 hours in cell lines. A, The gene expression of MYC, and MCL1 as determined by RNA-seq expressed as transcripts per million (TPM) from parental untreated SU-DHL-4 and SU-DHL-10 DLBCL cells. B, SU-DHL-4 and SU-DHL-10 DLBCL cells were seeded 18 hours prior to treatment with one of three CDK9 inhibitors: enitociclib (0.25 or 1 µmol/L), atuveciclib (1 µmol/L), or KB-0742 (1 µmol/L). Following the 4-hour treatment, the cells were washed, and the incubation continued for up to 48 hours. Samples were collected 4 hours before treatment (−4), immediately after treatment (0), and at 1, 2, 4, 8, 12, 16, 24, and 48 hours after washout for RNA-seq, qPCR, and Western blotting analysis. C, Western blots of phosphorylated Ser2 RNA polymerase II (p-Ser2-RNApolII), total RNApolII and HSP90 (D) quantification of p-Ser2-RNApolII protein levels (p-Ser2) in SU-DHL-4 and SU-DHL-10 DLBCL cells normalized to HSP90 as a ratio to DMSO matched timepoint.
Malnutrition in Institutionalized and Non-Institutionalized Neurologically Impaired Children in Bulgaria
Authors: Pancheva Rouzha , Toneva Albena , Nikolova Silviya , Huysentruyt Koen , Dimitrov Lyubomir , Yoncheva Nikoleta , Nedelcheva Alexandra , Zhelyazkova Desislava
Published: November 2023

Introduction: The nutritional status of children with neurological impairment affects their health and quality of life. Bulgaria has many abandoned disabled children in residential homes. Lack of parental care puts them at risk for poor growth, suboptimal nutrition, and physical and mental development. Our study aims to identify factors associated with poor nutrition in Bulgarian children with neurological impairment living in different environments. Methods: From January to December 2017, a cross-sectional study was conducted in northeastern Bulgaria. We recruited 109 residential and nonresidential children. The study included demographics, medical history, anthropometric measurements, biochemical tests, nutritional assessment, and gastrointestinal signs and symptoms. Data were analyzed with Jamovi 2.2.5 at a 0.05 significance level. Logistic regression was used to predict wasting in both environmental settings. Results: About 70% of the neurologically impaired children living in residential settings have malnutrition based on weight-for-age Z-score, compared to 25% of the non-residential children. Prematurity, low gross motor function (as measured by the gross motor function classification system), pureed food consumption, birth before 37 weeks, and living in residential care homes are linked to poor nutrition. Conclusion: Neurologically impaired children have a poor nutritional state, especially those living in residential homes. The study underscores the pressing need for the allocation of additional nutrition resources to effectively address the nutritional and developmental needs of children with neurological disabilities in Bulgaria.
Association between Troponin Elevation and Decreased Myocardial Blood Flow Reserve in Patients without Obstructive Coronary Artery Disease
Authors: Yang Ning , Zhang Rongzhen , Zhao Chaoqun , Sun Bochen , Wang Biyu , Song Yuwei , Qi Shuhan , Liu Jianan , Sun Yujia , Liu Hui , An Huanhuan , Zhang Xingyue , Xiang Fei , Yang Qinghui , Han Wei
Published: November 2023

Introduction: To study the prognostic factors of patients with chest pain and without obstructive coronary artery disease is of great significance for the management of such patients. We assessed whether a high-sensitivity troponin I (hs-TnI) is associated with prognosis in patients with chest pain and without obstructive coronary artery disease. Methods: From 2011 to 2017, 489 consecutively hospitalized patients with chest pain and without significant coronary artery stenosis (<50%) were tested for hs-TnI and underwent stress myocardial contrast echocardiography (MCE). Myocardial blood flow reserve (MBFR) was measured by stress MCE. Patients were followed (median, 41 months) for composite endpoints, including cardiovascular death and non-fatal myocardial infarction. Cox proportional hazards models were performed to determine associations between hs-TnI and the composite endpoints. Results: Among 489 patients with chest pain and without significant coronary artery stenosis, 257 patients (52.6%) had elevated hs-TnI. Compared to patients with normal hs-TnI, patients with elevated hs-TnI were older (p = 0.013) and had a higher prevalence of atrial fibrillation (p = 0.003), higher left ventricular mass index (p = 0.002) and E/e’ septal (p < 0.001), and a lower MBFR (p < 0.001). After adjustment, there was still a significant association between hs-TnI and MBFR (odds ratio = 1.145; 95% confidence interval [CI], 1.079–1.214; p < 0.001). Compared with patients with normal hs-TnI, patients with elevated hs-TnI had a greater cumulative event rate (log-rank p = 0.002). Males (hazard ratio [HR], 4.770; 95% CI, 1.175–19.363; p = 0.029) and reduced MBFR (HR, 2.496; 95% CI, 1.446–4.311; p = 0.001) were risk factors associated with composite endpoints in patients with elevated hs-TnI. Conclusions: In patients with chest pain and without obstructive coronary artery disease, elevated hs-TnI is associated with decreased myocardial perfusion by contrast echocardiography as well as a higher incidence of cardiovascular events.
The Improvement in Function of Poststroke Spasticity by Vibrational and Heated Stone-Needle Therapy and Meridian Dredging Exercise: A Randomized, Controlled, Preliminary Trial
Authors: Sun Hui-Jun , Zhang Jie , Lu Jian-ping , Wu Mei-ting
Published: November 2023

Background: Poststroke spasticity (PSS) is a common complication of stroke. Current PSS treatments have been linked to high costs, lack of long-term effectiveness, and undesirable side effects. Vibrational and heated stone-needle therapy (VHS) has not been utilized to treat PSS, and its safety and effectiveness have yet to be proven by high-quality clinical research. Objective: The aim of this study was to determine the effectiveness of VHS combined with meridian dredging exercise (MDE) in patients with PSS. Methods: One hundred participants with stroke were included and randomly assigned to a treatment group (VHS plus MDEs) and a control group (MDEs alone). Patients in both groups were treated for 4 weeks. The primary outcome measures were the Modified Ashworth Scale (MAS) and Fugl-Meyer Assessment (FMA), while the secondary outcome measures were the Activity of Daily Living (ADL) Scale and Stroke-Specific Quality of Life Scale (SS-QOL). The evaluations were at baseline (T0) at 4 weeks of treatment (T1) and at 12 weeks of follow-up without treatment (T2). Results: At T1 and T2, there were significant differences in MAS between the two groups (p = 0.001). From the perspective of distribution, the VHS plus MDE group had significant changes, and the group-time interactions of upper and lower extremities in FMA, ADL, and SS-QOL were statistically significant (p < 0.001), indicating that patients’ symptoms improved after treatment. But the overall effect size is small, especially the effect size of improvement in SS-QOL at T1. Conclusion: VHS in combination with MDE can consistently alleviate PSS, enhance limb function, and improve the quality of life of patients with PSS. But we need to optimize the device further and observe the improvement of patients for a more extended period.
Associations of Arterial Thickness, Stiffness, and Blood Pressure With Brain Morphology in Early Adolescence: A Prospective Population-Based Study
Authors: Defina Serena , Silva Carolina C.V. , Cecil Charlotte A.M. , Tiemeier Henning , Felix Janine F. , Mutzel Ryan L. , Jaddoe Vincent W.V.
Published: November 2023

BACKGROUND:

Arterial wall thickness and stiffness, and high blood pressure have been repeatedly associated with poorer brain health. However, previous studies largely focused on mid- or late-life stages. It is unknown whether any arterial health–related brain changes may be observable already in adolescence.

METHODS:

We examined whether (1) carotid intima-media thickness, (2) carotid distensibility, and (3) systolic blood pressure and diastolic blood pressure, measured at the age of 10 years, were associated with brain volumes and white matter microstructure (ie, fractional anisotropy and mean diffusivity) at the age of 14 years. In addition to cross-sectional analyses, we explored associations with longitudinal change in each brain outcome from 10 to 14 years. Analyses were based on 5341 children from the Generation R Study.

RESULTS:

Higher diastolic blood pressure was associated with lower total brain volume (β, −0.04 [95% CI, −0.07 to −0.01]) and gray matter volume (β, −0.04 [95% CI, −0.07 to −0.01]) at the age of 14 years, with stronger associations in higher diastolic blood pressure ranges. Similar associations emerged between systolic blood pressure and brain volumes, but these were no longer significant after adjusting for birth weight. No associations were observed between blood pressure and white matter microstructure or between carotid intima-media thickness or distensibility and brain morphology.

CONCLUSIONS:

Arterial blood pressure, but not intima-media thickness and distensibility, is associated with structural neuroimaging markers in early adolescence. Volumetric measures may be more sensitive to these early arterial health differences compared with microstructural properties of the white matter, but further studies are needed to confirm these results and assess potential causal mechanisms.
Antithrombotic and Statin Prescription After Intracerebral Hemorrhage in the Get With The Guidelines-Stroke Registry
Authors: Murthy Santosh B. , Zhang Cenai , Shah Shreyansh , Schwamm Lee H. , Fonarow Gregg C. , Smith Eric E. , Bhatt Deepak L. , Ziai Wendy C. , Kamel Hooman , Sheth Kevin N.
Published: November 2023

BACKGROUND:

Survivors of intracerebral hemorrhage (ICH) face an increased risk of ischemic cardiovascular events. Current ICH guidelines do not provide definitive recommendations regarding the use of antithrombotic and statin therapies. We, therefore, sought to study practice patterns and factors associated with the use of such medications after ICH.

METHODS:

This was a cross-sectional study of patients with ICH in the Get With The Guidelines-Stroke registry, between 2011 and 2021. Patients transferred to another hospital, those who died during hospitalization, and those with missing information on discharge medications were excluded. The study exposure was the proportion of patients who were prescribed antithrombotic or statin medications. We first ascertained the proportion of patients prescribed antithrombotic and lipid-lowering medications at discharge overall and across strata defined by pre-ICH use and history of previous ischemic vascular disease or atrial fibrillation. We then studied factors associated with the discharge prescription of these medications after ICH, using multiple logistic regressions.

RESULTS:

In the final cohort, 50 416 (10.4%) of 486 586 patients with ICH were prescribed antiplatelet medications, 173 322 (35.1%) of 493 491 patients with ICH were prescribed statins, and 27 085 (5.4%) of 486 585 patients with ICH were prescribed anticoagulation therapy at discharge. The proportion of patients with antiplatelet therapy was 16.6% with pre-ICH use and 15.6% in those with previous ischemic vascular disease. Statins were prescribed to 41.1% and 43.7% of patients on previous lipid-lowering therapy and ischemic vascular disease, respectively. Anticoagulation therapy was restarted in 11.1% of patients. In logistic regression analysis, factors associated with higher use of antithrombotic or statin therapies after ICH were younger age, male sex, pre-ICH medication use, previous ischemic vascular disease, atrial fibrillation, lower admission National Institutes of Health Stroke Scale, longer length of stay, and favorable discharge outcome.

CONCLUSIONS:

Few patients with ICH are prescribed antithrombotic or statin therapies at hospital discharge. Given the emerging association between ICH and future major cardiovascular events, trials examining the net benefit of antiplatelet and lipid-lowering therapy after ICH are warranted.
Analysis of Farm Work in a Vertical Farm
Authors: Yoo Na-Yeon , Kim Seon-Ok , Park Sin-Ae
Published: November 2023

Background and objective: Farm work involves a range of postures depending on the type of work, and repeated farm work performed in an uncomfortable posture can cause serious functional disorders affecting the lower back, shoulders, joints, and muscles. For the physically disabled to participate in farm work, it is essential to analyze farm work based on their individual levels of physical ability. This study analyzed farm work in vertical smart farms to develop care farming services for the purpose of vocational rehabilitation of the physically handicapped.Methods: Farm work was analyzed through a field survey in a vertical farm located in P-si, Gyeonggi-do. Based on the analysis, major farm work was classified into duties and tasks.Results: Through a filed survey, farm work in a vertical farm was categorized into six duties, and all tasks were mainly performed within the same workplace. The six duties were analyzed as sowing, raising seedlings, transplanting, planting, harvesting (including sorting and packaging), and post-harvest cleaning, which were further classified into 28 tasks as sub-areas.Conclusion: The result of this farm work analysis in a vertical farm will provide useful basic data for the development of care farming services for the vocational rehabilitation of the physically handicapped.
Port State Control of Civilian Search and Rescue Vessels before the European Court of Justice: The Sea Watch Cases
Authors: Schatz Valentin , Wissmann Sara
Published: November 2023

On 1 August 2022, the Grand Chamber of the European Court of Justice (ECJ) rendered its preliminary ruling in the joined cases C-14/21 and C-15/21, which concerned the detention of two German-flagged civilian rescue vessels operated by the German non-governmental organisation Sea Watch. The detention was executed by Italian port authorities following port State inspections carried out pursuant to Directive 2009/16 on Port State Control (PSC Directive). The ECJ’s judgment is the first to comprehensively address and clarify the legal framework governing the European Union’s system of port State control. The Court provided several clarifications concerning the interpretation of the PSC Directive as well as relevant rules of the international law of the sea. Overall, these clarifications may be considered positive for the rule of law in the context of port State inspections of civilian search and rescue vessels.
Patterns of Teaching And Learning of First-Year Chemistry in Scottish Universities
Authors: Hoare D. E. , Yeaman E. J.
Published: November 2023

Student attitudes to the teaching and learning of first-year chemistry in Scottish Universities were assessed by means of a questionnaire answered by nearly 1,000 students at seven of the eight universities.

Students were critical of lecturing techniques and would like to have changes in the form of examinations. They liked the use of structural models and duplicated notes and wanted more tutorial classes (favouring smaller groups).

There seemed a tendency for the weaker English student to come to Scotland, perhaps because of the assumed lower levels of knowledge required.

Students who had taken the alternative chemistry SCE course were more critical of university practical classes; and Scottish students, on average, spent more time on reading and less on preparation for tutorials than others. Well motivated students and introverts had better study habits than poorly motivated or extraverts.

Students were in general content with their instruction and worked reasonably hard.
Scotland and Infant Education in the Nineteenth Century
Authors: Roberts A. F. B.
Published: November 2023

This article argues that a false impression of infant education in Scotland has resulted from the prominence of Owen and Stow in the field. Statistical evidence from census returns and from SED reports is used to show that children under five and even children aged five were virtually outside the educational system. The contrast is noted between this and the contemporary situation in England, with its thriving .infant schools for children aged two to seven. Various reasons for the difference are suggested, the most acceptable apparently being 'cultural climate'. The significance of a weak early stage, it is concluded, is its relationship to the formalism of later stages in Scottish education.
Guidance in a Scottish Comprehensive School
Authors: McDonald Rosemary
Published: November 2023

This article is based on research into a guidance system which had been established in a typical Scottish Comprehensive School. The research provides an analysis of the function and the role of guidance within the organisational structure of the school; it also analyses the attitude of the school staff to this recent educational development.

The research found that, while the guidance concept was generally accepted by the staff, there were some reservations about its actual operation within the school; there was no general acceptance of guidance as a system within the school structure. It also appeared that the staff regarded the guidance personnel as an integral part of the school organisation and not as separate counselling or guidance figures. These views were all substantiated by the facts of the research.

The article concludes that the major development of the guidance concept has been as an administrative adjunct of the school organisation. It postulates some problems likely to be encountered in the future development of the guidance concept proposed by the S.E.D. and suggests some ideas worthy of further consideration in the implementation of guidance systems in Scottish schools.
The Development of Geographical and Spatial Concepts and the Concepts of Country and Nationality among 9 Year Old Scottish Children
Authors: Towers James D.
Published: November 2023

25 nine year old children from the Outer Islands of Orkney were compared with a matched group of 25 children from Kirkwall in order to find out whether any differences existed in the development of geographical and spatial concepts. Kirkwall children were further compared with a matched group from Alford, a village outside Aberdeen, to determine whether similar differences existed between Isles children and children living on the mainland of Scotland. In addition the three groups were compared to see whether any differences existed in the development of the concepts of country and of nationality. Results indicate that (a) North Isles children are superior to Kirkwall children in their understanding of the orientation and spatial relationships of the Islands of Orkney; (b) that North Isles children are superior to Kirkwall children in their verbal understanding of the inter-relationships involving Kirkwall-Orkney and Scotland, though this superiority is not reflected in a corresponding spatial test; (c) that children from Alford have a more highly developed understanding of the relationships involving Aberdeen, Scotland and Britain than do Kirkwall children of the relationships involving Kirkwall, Orkney and Scotland; (d) that, although no difference was found between North Isles and Kirkwall children in their development of the concepts of country and nationality, the Alford children have a better understanding of the concept 'town' and of Scotland/Britain as their country, than do Kirkwall children.