bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unexpected identification of obesity-associated mutations in LEP and MC4R genes in patients with anorexia nervosa
Authors: Rajcsanyi Luisa Sophie , Zheng Yiran , Herpertz-Dahlmann Beate , Seitz Jochen , de Zwaan Martina , Herzog Wolfgang , Ehrlich Stefan , Zipfel Stephan , Giel Katrin , Egberts Karin , Burghardt Roland , Föcker Manuel , Antel Jochen , Fischer-Posovszky Pamela , Hebebrand Johannes , Hinney Anke 
Published: January 2024

Abstract

Mutations leading to a reduced or loss of function in genes of the leptin-melanocortin system confer a risk for monogenic forms of obesity. Yet, gain of function variants in the melanocortin-4-receptor (MC4R) gene predispose to a lower BMI. In individuals with reduced body weight, we thus expected mutations leading to an enhanced function in the respective genes, like leptin (LEP) and MC4R. Therefore, we have Sanger sequenced the coding regions of LEP and MC4R in 462 female patients with AN, and 445 healthy-lean controls. In total, we have observed four and eight variants in LEP and MC4R, respectively. Previous studies showed different functional in vitro effects for the detected frameshift and non-synonymous variants: (1) LEP: reduced/loss of function (p.Val94Met), (2) MC4R: gain of function (p.Val103Ile, p.Ile251Leu), reduced or loss of function (p.Thr112Met, p.Ser127Leu, p.Leu211fsX) and without functional in vitro data (p.Val50Leut). In LEP, the variant p.Val94Met was detected in one patient with AN. For MC4R variants, one patient with AN carried the frameshift variant p.Leu211fsX. One patient with AN was heterozygous for two variants at the MC4R (p.Val103Ile and p.Ser127Leu). All other functionally relevant variants were detected in similar frequencies in patients with AN and lean individuals.
Sexual symptoms in relation to curative pelvic radiotherapy in patients with primary cervical cancer and uterine tumors
Authors: Knutsen Annika Elisabet , Mikiver Rasmus , Redelius Kristina , Uppugunduri Srinivas 
Published: January 2024

Abstract
Purpose
Pelvic radiotherapy (RT) causes tissue injury which could lead to vaginal problems including dryness, shortening, and tightening of the vagina, causing discomfort, and affect sexual activity. In this longitudinal, prospective study, the association between pelvic RT and sexual function were studied in primary cervical cancer and in primary uterine tumor patients.
Methods
This prospective longitudinal cohort study comprised patients with primary cervical cancer and primary uterine tumors with pelvic radiotherapy (RT). Sevety-nine cervical cancer and 43 uterine tumor patients were included from May 2014 to February 2019. Patients completed questionnaires for global health status and sexual functioning before RT start and at 3 and 12 months after RT.
Results
In primary cervical cancer patients, the sexual activity was significantly higher in patients with pelvic RT alone compared to patients with pelvic RT + vaginal brachytherapy/boost at 3 months (P = 0.007, 34.6% vs. 73.3%) and12 months after RT (P = 0.054, 45.7% vs. 76.9%). No significant relationship was found in primary uterine tumor patients. At 12 months after RT, 52.5% of the cervix and 42.3% of the primary uterine tumor patients were sexually active. Of the cervical cancer patients, 81.8% reported symptoms as dry vagina 12 months after RT. Local estrogens did not improve the sexual activity in cervical cancer or uterine tumor patients after RT.
Conclusion
In cervical cancer patients, the sexual activity was significantly higher with pelvic RT alone compared to pelvic RT + vaginal brachytherapy/boost. Better medical interventions are needed to reduce the sexual symptoms.
Determination of Oxidative Stress Responses Induced by Copper Oxide (Cuo) Nanoparticle in Gammarus Pulex
Authors: Aydin Ayse Nur , SERDAR Osman , Çimen Işıl Canan Çiçek 
Published: January 2024

Abstract
As Copper Oxide (CuO) has a wide range of uses in industry, it is thought to have a wide polluting effect on the environment and aquatic environment. Gammarus pulex was chosen as the model organism in this study, which was carried out with the aim of realizing the effect of CuO mixed into the water environment. In order to carry out the study, CuO was exposed to 0 (control), 10, 20, 40 ppm concentrations for 24, 96 and 120 (elimination) hours. Samples were taken from the experimental environment at the end of 24, 96 and 120 hours. The study was carried out in 3 replicates. The assessment of oxidative stress and antioxidant biomarkers was conducted using ELISA kits obtained from CAYMAN Chemical Company. The parameters analyzed included the activity of SOD and CAT, as well as the levels of TBARS and GSH. The biochemical studies were evaluated using the one-way ANOVA (Duncan 0.05) feature of the SPSS 24.0 package program. With the study data, increases in SOD activities and fluctuations in CAT activity were determined. Decreases in GSH levels and increases in TBARS levels occurred.
Anthropogenic impacts drive habitat suitability in South Asian bats
Authors: Srinivas Aditya , Senapathi Deepa , González-Suárez Manuela 
Published: January 2024

Abstract

Despite their diversity and importance as ecological indicators and ecosystem service providers, the macroecology of bats in South Asia is poorly understood, and until recently studies on the ecological niches of these species have been rare. This study analyses the ecogeographic predictors of habitat suitability in South Asian bats by conducting ensemble ecological niche modelling using four algorithms (random forests, artificial neural networks, multivariate adaptive regression splines, and maximum entropy) to define suitability envelopes for 30 selected bat species, based on topographic, land-use and -cover, and additional anthropogenic impact factors. Anthropogenic impact variables were associated with the highest importance, and Median Night-time Light was the biggest driver of habitat suitability for most of the study species. Projected suitable areas ranged between 6.54% and 22.98% of the study area. Regions such as the Thar desert of northwestern India were consistently identified to have low suitability. The Western Ghats region, the Himalayas, and Sri Lanka were identified as suitability hotspots for more than half the study species and comprised a majority of anthropogenic or human-impacted habitats. This study offers insight into the impacts of anthropogenic pressure on the macroecology of bats in a megadiverse region and stresses the importance of analysing ecogeographic effects on ecological niches and habitat suitability, which can be vital to inform conservation planning and policymaking in the future.
Ultraviolet B irradiation increases the expression of cornulin and retepin in human skin xenotransplants
Authors: Makino Teruhiko , Mizawa Megumi , Takemoto Keita , Shimizu Tadamichi 
Published: January 2024

Abstract

Cornulin (CRNN) and repetin (RPTN) belong to the fused-type S100 protein family. Although these proteins have been reported to be expressed in the granular layer of the epidermis and are suggested to be associated with barrier formation in the epidermis, the exact function of these proteins remains unclear. The present study examined the effects of UVB irradiation on the CRNN and RPTN expression in human skin xenotransplantation. The expression of CRNN increased in the granular layer of UVB-irradiated skin two days after UVB irradiation in comparison to sham-irradiated skin. Interestingly, CRNN signals were observed not only in the cytoplasm but also in the peripheral region of the granular keratinocytes. In contrast, RPTN was rarely expressed in sham-irradiated skin; however, RPTN signals were markedly increased in the granular layer of UVB-irradiated skin. The number of RPTN-positive keratinocytes on day 2 after UVB irradiation was significantly higher than that in the sham-irradiated skin. Accordingly, the present study demonstrated that CRNN and RPTN are novel proteins whose expression can be increased by UVB irradiation. In addition, we speculate that the role of CRNN and RPTN in barrier formation of the epidermis may differ according to the expression pattern of these proteins in UVB-irradiated skin.
Synchronization networks reflect the contents of visual working memory
Authors: Haque Hamed , Wang Sheng H. , Siebenhühner Felix , Robertson Edwin , Palva J. Matias , Palva Satu 
Published: January 2024

Abstract

Visual working memory (VWM) comprises of distinct short-term storage of sensory information coupled with executive processes. It has remained untested whether long-range synchronization of neuronal oscillations in the human brain would reflect sensory contents of VWM. We used a VWM task in which memorized contents were precisely controlled to test the sensitivity of synchronization to VWM contents using concurrent magneto- and electroencephalography (M/EEG) combined with source-connectivity analysis. We show here that alpha-band phase-synchronization and theta-band desynchronization track VWM contents and correlates with performance. The alpha-band network was found in visual areas corresponding to the memorized features coupled to the fronto-parietal network (FPN) such that key connections of the FPN network were shared across contents. Machine-learning analysis established that only alpha-band networks contained content-information and allowed decoding of VWM contents. Our results establish that alpha-band phase synchronization reflects remembered VWM contents and provides a novel perspective for the organization of VWM.
Enabling the uptake of circular water solutions
Authors: Frijns Jos , Smith Heather M. , Makropoulos Christos 
Published: January 2024

Abstract

This study advances the discourse on the transition from a linear to a circular water paradigm, within which water is reused and resources such as nutrients and energy can be recovered. The research provides an empirical evidence from demonstrative cases, identifying the technological, economic, socio-cultural, and regulatory factors that facilitate or impede the broader adoption of circular solutions in the water sector. It proposes an integrated system approach, which encompasses a comprehensive set of enabling instruments, including (a) the demonstration of the sustainability of circular water technologies at a system level, thereby providing a robust proof of concept; (b) a shift from a conventional financial cost-benefit approach to a business model predicated on circular value chains, underscoring the economic feasibility of these solutions; (c) the enhancement of social acceptance through active stakeholder engagement, thereby fostering a supportive community for these transformative changes; and (d) the adaptation of the regulatory framework to incentivise circular water solutions, such as the establishment of dedicated end-of-waste criteria to facilitate market access for recovered resources. The study concludes that a concerted effort is required to reconceptualise our water systems as circular systems, and to legitimise the role of circular water within our society and economy.
Exploration of Key Genes Combining with Immune Infiltration Level and
Tumor Mutational Burden in Hepatocellular Carcinoma
Authors: Chen Jing , Zhang Lu , Lu Cui-Hua , Xu Chen-Zhou 
Published: January 2024

Background:
Hepatocellular carcinoma (HCC) is a lethal malignancy due to its heterogeneity and
aggressive behavior. Recently, somatic mutations and tumor cell interactions with the surrounding tumor
immune microenvironment (TIME) have been reported to participate in HCC carcinogenesis and predict
HCC progression. In this study, we aimed to investigate the association between tumor mutational burden
(TMB) and TIME in HCC. Additionally, we sought to identify differentially expressed genes (DEGs) associated
with HCC prognosis and progression.

Methods:
The expression, clinical, and mutational data were downloaded from the cancer genome atlas
(TCGA) database. The immune infiltration levels and TMB levels of the HCC samples were estimated and
the samples were divided into immune cluster (ICR)-1 and 2 based on immune infiltration score and high and
low TMB groups based on TMB score. Thereafter, differential gene expression analysis was conducted to
identify the DEGs in the ICR1/2 and high/low TMB groups, and the intersecting DEGs were selected. Thereafter,
Cox regression analysis was performed on 89 significant DEGs, among which 19 were associated with
prognosis. These 19 DEGs were then used to construct a prognostic model based on their expression levels
and regression coefficients. Thereafter, we analyzed the DEGs in mutant and wildtype TP53 HCC samples
and identified high BCL10 and TRAF3 expression in the mutant TP53 samples. BCL10 and TRAF3 expression
was detected by real-time quantitative reverse transcription PCR and immunohistochemistry, and their
clinical correlation, biological function, and immune infiltration levels were analyzed by chi-square analyses,
Gene Set Enrichment Analysis (GSEA), and “ssGSEA”, respectively.

Results:
The results of our study revealed that immune infiltration level was correlated with TMB and that
they synergistically predicted poor prognosis of HCC patients. DEGs enriched in immune-related pathways
could serve as indicators of immunotherapy response in HCC. Among these DEGs, BCL10 and TRAF3 were
highly expressed in HCC tissues, especially in the mutant TP53 group, and they co-operatively exhibited
immunological function, thereby affecting HCC progression and prognosis.

Conclusion:
In this study, we identified BCL10 and TRAF3 as potential prognostic indicators in HCC patients.
Additionally, we found that BCL10 and TRAF3 influence TMB and TIME in HCC patients and can be
used for the development of immune-based therapies for improving the long-term survival of HCC patients.
Simultaneous Determination of Levo-tetrahydropalmatine and Naltrexone
in Rat Plasma by LC-MS/MS and its Application in a Pharmacokinetic
Study
Authors: Feng Kun , Sy Sherwin K. B. , Yu Mingming , Lv Zhihua , Yan Meixing 
Published: January 2024

Background:
Levo-tetrahydropalmatine and low-dose naltrexone are used in association
with reducing cocaine-related cravings, but there are no analytical methods for the quantitative
simultaneous analysis of this drug combination.

Objective:
A highly selective and sensitive LC-MS/MS assay was developed and validated to
simultaneously quantify l-THP and naltrexone. The analytical method for l-THP offers improved
sensitivity compared to previously published methods.

Methods:
The product ion transitions of l-THP and naltrexone were 357.0→193.0 and
342.2→324.1, respectively. Chromatographic separations were performed using a BEH-C18
column by an isocratic elution mode with acetonitrile and 0.1% formic acid in water containing 3
mM ammonium acetate. L-THP and naltrexone were extracted from rat plasma using a liquidliquid
extraction method.

Results:
For l-THP and naltrexone, the assay displayed good linear response over a concentration
range of 0.5-1000 ng/mL and 0.25-500 ng/mL, respectively. The intra-day accuracy of the
method for l-THP and naltrexone was 93.8-101% with a precision (%CV) of 2.43-8.15% and
93.4-108% with a precision of 3.47-8.22%. The inter-day accuracy for l-THP and naltrexone was
91.2-102% with a CV of 2.46–8.06% and 91.5–97.8% with a CV of 3.29–8.92%, respectively.

Conclusion:
The assay has been used for pharmacokinetic studies of l-THP and naltrexone in the rat.
Targeting Protein Phosphatases for the Treatment of Chronic Liver
Disease
Authors: Li Yi-Ming , He Hong-Wei , Zhang Na 
Published: January 2024

Abstract:
There exists a huge number of patients suffering from chronic liver disease worldwide.
As a disease with high incidence and mortality worldwide, strengthening the research on the pathogenesis
of chronic liver disease and the development of novel drugs is an important issue related
to the health of all human beings. Phosphorylation modification of proteins plays a crucial role in
cellular signal transduction, and phosphatases are involved in the development of liver diseases.
Therefore, this article summarized the important role of protein phosphatases in chronic liver disease
with the aim of facilitating the development of drugs targeting protein phosphatases for the
treatment of chronic liver disease.
Cytokines and Regulating Epithelial Cell Division
Authors: Abdullah Marzoog Basheer 
Published: January 2024

Abstract::
Physiologically, cytokines play an extremely important role in maintaining cellular and
subcellular homeostasis, as they interact almost with every cell in the organism. Therefore, cytokines
play a significantly critical role in the field of pathogenic pharmacological therapy of different
types of pathologies. Cytokine is a large family containing many subfamilies and can be
evaluated into groups according to their action on epithelial cell proliferation; stimulatory include
transforming growth factor-α (TGF-α), Interlukine-22 (IL-22), IL-13, IL-6, IL-1RA and IL-17 and
inhibitory include IL-1α, interferon type I (IFN type I), and TGF-β. The balance between stimulatory
and inhibitory cytokines is essential for maintaining normal epithelial cell turnover and tissue
homeostasis. Dysregulation of cytokine production can contribute to various pathological conditions,
including inflammatory disorders, tissue damage, and cancer. Several cytokines have shown
the ability to affect programmed cell death (apoptosis) and the capability to suppress non-purpose
cell proliferation. Clinically, understanding the role of cytokines' role in epithelial tissue is crucial
for evaluating a novel therapeutic target that can be of use as a new tactic in the management of
carcinomas and tissue healing capacity. The review provides a comprehensive and up-to-date synthesis
of current knowledge regarding the multifaceted effects of cytokines on epithelial cell proliferation,
with a particular emphasis on the intestinal epithelium. Also, the paper will highlight the
diverse signaling pathways activated by cytokines and their downstream consequences on epithelial
cell division. It will also explore the potential therapeutic implications of targeting cytokine-
epithelial cell interactions in the context of various diseases.
A Review on the Recent Advancements and Artificial Intelligence in
Tablet Technology
Authors: Sahu Amit , Rathee Sunny , Saraf Shivani , Jain Sanjay K. 
Published: January 2024

Background::
Tablet formulation could be revolutionized by the integration of modern
technology and established pharmaceutical sciences. The pharmaceutical sector can develop tablet
formulations that are not only more efficient and stable but also patient-friendly by utilizing artificial
intelligence (AI), machine learning (ML), and materials science.

Objectives::
The primary objective of this review is to explore the advancements in tablet technology,
focusing on the integration of modern technologies like artificial intelligence (AI), machine
learning (ML), and materials science to enhance the efficiency, cost-effectiveness, and quality of
tablet formulation processes.

Methods::
This review delves into the utilization of AI and ML techniques within pharmaceutical
research and development. The review also discusses various ML methodologies employed, including
artificial neural networks, an ensemble of regression trees, support vector machines, and
multivariate data analysis techniques.

Results::
Recent studies showcased in this review demonstrate the feasibility and effectiveness of
ML approaches in pharmaceutical research. The application of AI and ML in pharmaceutical research
has shown promising results, offering a potential avenue for significant improvements in
the product development process.

Conclusion::
The integration of nanotechnology, AI, ML, and materials science with traditional
pharmaceutical sciences presents a remarkable opportunity for enhancing tablet formulation processes.
This review collectively underscores the transformative role that AI and ML can play in advancing
pharmaceutical research and development, ultimately leading to more efficient, reliable
and patient-centric tablet formulations.
Synapsin 1 Ameliorates Cognitive Impairment and Neuroinflammation in
Rats with Alzheimer’s Disease: An Experimental and Bioinformatics
Study
Authors: Ma Wei , Lu Kui , Liang Hua-Min , Zhang Jin-Yuan 
Published: January 2024

Background:::
Alzheimer’s disease (AD) is a persistent neuropathological injury that
manifests via neuronal/synaptic death, age spot development, tau hyperphosphorylation, neuroinflammation,
and apoptosis. Synapsin 1 (SYN1), a neuronal phosphoprotein, is believed to be responsible
for the pathology of AD.

Objective::
This study aimed to elucidate the exact role of SYN1 in ameliorating AD and its potential
regulatory mechanisms.

Methods::
The AD dataset GSE48350 was downloaded from the GEO database, and SYN1 was focused
on differential expression analysis and Gene Ontology (GO) and Kyoto Encyclopedia of
Genes and Genomes (KEGG) enrichment analyses. After establishing an AD rat model, they were
treated with RNAi lentivirus to trigger SYN1 overexpression. The amelioration of SYN1 in AD-associated
behavior was validated using multiple experiments (water maze test and object recognition
test). SYN1’s repairing effect on the important factors in AD was confirmed by detecting the
concentration of inflammatory factors (interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α),
neurotransmitters (acetylcholine (ACh), dopamine (DA), and 5-hydroxytryptophan (5-HT)) and
markers of oxidative stress (glutathione (GSH), malondialdehyde (MDA), reactive oxygen species
(ROS)). Molecular biology experiments (qRT-PCR and western blot) were performed to examine
AD-related signaling pathways after SYN1 overexpression.

Results::
Differential expression analysis yielded a total of 545 differentially expressed genes, of
which four were upregulated and 541 were downregulated. The enriched pathways were basically
focused on synaptic functions, and the analysis of the protein– protein interaction network focused
on the key genes in SYN1. SYN1 significantly improved the spatial learning and memory abilities
of AD rats. This enhancement was reflected in the reduced escape latency of the rats in the water
maze, the significantly extended dwell time in the third quadrant, and the increased number of
crossings. Furthermore, the results of the object recognition test revealed reduced time for rats to
explore familiar and new objects. After SYN1 overexpression, the cAMP signaling pathway was
activated, the phosphorylation levels of the CREB and PKA proteins were elevated, and the secretion
of neurotransmitters such as ACh, DA, and 5-HT was promoted. Furthermore, oxidative
stress was suppressed, as supported by decreased levels of MDA and ROS. Regarding inflammatory
factors, the levels of IL-6, IL-1β, and TNF-α were significantly reduced in AD rats with SYN1
overexpression.

Conclusion::
SYN1 overexpression improves cognitive function and promotes the release of various
neurotransmitters in AD rats by inhibiting oxidative stress and inflammatory responses
through cAMP signaling pathway activation. These findings may provide a theoretical basis for
the targeted diagnosis and treatment of AD.