bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone deacetylase inhibitors VPA and WT161 ameliorate the pathological features and cognitive impairments of the APP/PS1 Alzheimer’s disease mouse model by regulating the expression of APP secretases
Authors: Zhang Miaomiao , Wang Wanyao , Ye Qun , Fu Yun , Li Xuemin , Yang Ke , Gao Fan , Zhou An , Wei Yonghui , Tian Shuang , Li Shen , Wei Fengjiang , Shi Wentao , Li Wei-Dong 
Published: January 2024

Abstract
Background
Alzheimer’s disease (AD) is a degenerative neurological disorder. Recent studies have indicated that histone deacetylases (HDACs) are among the most prominent epigenetic therapy targets and that HDAC inhibitors have therapeutic effects on AD. Here, we identified sodium valproate (VPA), a pan-HDAC inhibitor, and WT161, a novel HDAC6 selective inhibitor, as potential therapeutic agents for AD. Underlying molecular mechanisms were investigated.

Methods
A cellular model, N2a-APPswe, was established via lentiviral infection, and the APPswe/PSEN1dE9 transgenic mouse model was employed in the study. LC–MS/MS was applied to quantify the concentration of WT161 in the mouse brain. Western blotting, immunohistochemical staining, thioflavin-S staining and ELISA were applied to detect protein expression in cells, tissues, or serum. RNA interference was utilized to knockdown the expression of specific genes in cells. The cognitive function of mice was assessed via the nest-building test, novel object recognition test and Morris water maze test.

Results
Previous studies have focused mainly on the impact of HDAC inhibitors on histone deacetylase activity. Our study discovered that VPA and WT161 can downregulate the expression of multiple HDACs, such as HDAC1 and HDAC6, in both AD cell and mouse models. Moreover, they also affect the expression of APP and APP secretases (BACE1, PSEN1, ADAM10). RNA interference and subsequent vitamin C induction further confirmed that the expression of APP and APP secretases is indeed regulated by HDAC1 and HDAC6, with the JNK pathway being the intermediate link in this regulatory process. Through the above pathways, VPA and WT161 effectively reduced Aβ deposition in both AD cell and mouse models and significantly improved cognitive function in AD mice.

Conclusions
In general, we have discovered that the HDAC6-JNK-APP secretases cascade is an important pathway for VPA and WT161 to exert their therapeutic effects on AD. Investigations into the safety and efficacy of VPA and WT161 were also conducted, providing essential preclinical evidence for assessing these two epigenetic drugs for the treatment of AD.
Carcinosarcoma of the parotid gland: a case report and review of the literature
Authors: Jain Swachi , Abdelwahed Mohammed , Chavarria Daniel Hector , Pereira Lucio , Stone Gary , Johnson Alan , Li Jian Yi 
Published: January 2024

Abstract
Background
Carcinosarcoma of the parotid gland is an extremely rare malignancy comprising of 0.04–0.16% of all salivary gland tumors. This is the first case of an adenoid cystic carcinoma with chondrosarcoma to the best of our knowledge. They consist of distinct carcinomatous and sarcomatous components and may arise de novo or from a preexisting pleomorphic adenoma.

Case presentation
Herein we present a case of an 80-year-old white female who presented with progressively increasing left facial swelling over 6 weeks. Magnetic Resonance Imagining revealed a mass (3.4 cm) in the parotid gland with a predominant cystic/necrotic component. The cytology was atypical (Milan3) and a total parotidectomy and selective lymph node dissection was done. The resection showed extensive necrosis with high grade sarcomatous (chondrosarcoma) areas. The epithelial component was adenoid cystic carcinoma with perineural invasion. The patient is currently undergoing radiotherapy of the tumor bed and skull base due to propensity of perineural invasion of the adenoid cystic component. The most common carcinomas in carcinosarcomas of salivary glands are adenocarcinoma and squamous cell carcinoma.

Conclusion
Carcinosarcoma is a high-grade aggressive lesion with a poor prognosis and should be treated aggressively. More studies are needed to understand the origin of these tumors.
MIIP downregulation drives colorectal cancer progression through inducing peri-cancerous adipose tissue browning
Authors: Wang Qinhao , Su Yuanyuan , Sun Ruiqi , Xiong Xin , Guo Kai , Wei Mengying , Yang Guodong , Ru Yi , Zhang Zhengxiang , Li Jing , Zhang Jing , Qiao Qing , Li Xia 
Published: January 2024

Abstract
Background
The enrichment of peri-cancerous adipose tissue is a distinctive feature of colorectal cancer (CRC), accelerating disease progression and worsening prognosis. The communication between tumor cells and adjacent adipocytes plays a crucial role in CRC advancement. However, the precise regulatory mechanisms are largely unknown. This study aims to explore the mechanism of migration and invasion inhibitory protein (MIIP) downregulation in the remodeling of tumor cell-adipocyte communication and its role in promoting CRC.

Results
MIIP expression was found to be decreased in CRC tissues and closely associated with adjacent adipocyte browning. In an in vitro co-culture model, adipocytes treated with MIIP-downregulated tumor supernatant exhibited aggravated browning and lipolysis. This finding was further confirmed in subcutaneously allografted mice co-injected with adipocytes and MIIP-downregulated murine CRC cells. Mechanistically, MIIP interacted with the critical lipid mobilization factor AZGP1 and regulated AZGP1’s glycosylation status by interfering with its association with STT3A. MIIP downregulation promoted N-glycosylation and over-secretion of AZGP1 in tumor cells. Subsequently, AZGP1 induced adipocyte browning and lipolysis through the cAMP-PKA pathway, releasing free fatty acids (FFAs) into the microenvironment. These FFAs served as the primary energy source, promoting CRC cell proliferation, invasion, and apoptosis resistance, accompanied by metabolic reprogramming. In a tumor-bearing mouse model, inhibition of β-adrenergic receptor or FFA uptake, combined with oxaliplatin, significantly improved therapeutic efficacy in CRC with abnormal MIIP expression.

Conclusions
Our data demonstrate that MIIP plays a regulatory role in the communication between CRC and neighboring adipose tissue by regulating AZGP1 N-glycosylation and secretion. MIIP reduction leads to AZGP1 oversecretion, resulting in adipose browning-induced CRC rapid progression and poor prognosis. Inhibition of β-adrenergic receptor or FFA uptake, combined with oxaliplatin, may represent a promising therapeutic strategy for CRC with aberrant MIIP expression.
Gated recurrent unit predictor model-based adaptive differential pulse code modulation speech decoder
Authors: Sheferaw Gebremichael Kibret , Mwangi Waweru , Kimwele Michael , Mamuye Adane 
Published: January 2024

AbstractSpeech coding is a method to reduce the amount of data needs to represent speech signals by exploiting the statistical properties of the speech signal. Recently, in the speech coding process, a neural network prediction model has gained attention as the reconstruction process of a nonlinear and nonstationary speech signal. This study proposes a novel approach to improve speech coding performance by using a gated recurrent unit (GRU)-based adaptive differential pulse code modulation (ADPCM) system. This GRU predictor model is trained using a data set of speech samples from the DARPA TIMIT Acoustic-Phonetic Continuous Speech Corpus actual sample and the ADPCM fixed-predictor output speech sample. Our contribution lies in the development of an algorithm for training the GRU predictive model that can improve its performance in speech coding prediction and a new offline trained predictive model for speech decoder. The results indicate that the proposed system significantly improves the accuracy of speech prediction, demonstrating its potential for speech prediction applications. Overall, this work presents a unique application of the GRU predictive model with ADPCM decoding in speech signal compression, providing a promising approach for future research in this field.
LASSO regression shows histidine and sphingosine 1 phosphate are linked to both sepsis mortality and endothelial damage
Authors: Johansson Pär I. , Henriksen Hanne H. , Karvelsson Sigurður T. , Rolfsson Óttar , Schønemann-Lund Martin , Bestle Morten H. , McGarrity Sarah 
Published: January 2024

AbstractSepsis is a major cause of death worldwide, with a mortality rate that has remained stubbornly high. The current gold standard of risk stratifying sepsis patients provides limited mechanistic insight for therapeutic targeting. An improved ability to predict sepsis mortality and to understand the risk factors would allow better treatment targeting. Sepsis causes metabolic dysregulation in patients; therefore, metabolomics offers a promising tool to study sepsis. It is also known that that in sepsis endothelial cells affecting their function regarding blood clotting and vascular permeability. We integrated metabolomics data from patients admitted to an intensive care unit for sepsis, with commonly collected clinical features of their cases and two measures of endothelial function relevant to blood vessel function, platelet endothelial cell adhesion molecule and soluble thrombomodulin concentrations in plasma. We used least absolute shrinkage and selection operator penalized regression, and pathway enrichment analysis to identify features most able to predict 30-day survival. The features important to sepsis survival include carnitines, and amino acids. Endothelial proteins in plasma also predict 30-day mortality and the levels of these proteins also correlate with a somewhat overlapping set of metabolites. Overall metabolic dysregulation, particularly in endothelial cells, may be a contributory factor to sepsis response. By exploring sepsis metabolomics data in conjunction with clinical features and endothelial proteins we have gained a better understanding of sepsis risk factors.
Fibroblasts inhibit osteogenesis by regulating nuclear-cytoplasmic shuttling of YAP in mesenchymal stem cells and secreting DKK1
Authors: Huang Fei , Wei Guozhen , Wang Hai , Zhang Ying , Lan Wenbin , Xie Yun , Wu Gui 
Published: January 2024

Abstract
Background
Fibrous scars frequently form at the sites of bone nonunion when attempts to repair bone fractures have failed. However, the detailed mechanism by which fibroblasts, which are the main components of fibrous scars, impede osteogenesis remains largely unknown.

Results
In this study, we found that fibroblasts compete with osteogenesis in both human bone nonunion tissues and BMP2-induced ectopic osteogenesis in a mouse model. Fibroblasts could inhibit the osteoblastic differentiation of mesenchymal stem cells (MSCs) via direct and indirect cell competition. During this process, fibroblasts modulated the nuclear-cytoplasmic shuttling of YAP in MSCs. Knocking down YAP could inhibit osteoblast differentiation of MSCs, while overexpression of nuclear-localized YAP-5SA could reverse the inhibition of osteoblast differentiation of MSCs caused by fibroblasts. Furthermore, fibroblasts secreted DKK1, which further inhibited the formation of calcium nodules during the late stage of osteogenesis but did not affect the early stage of osteogenesis. Thus, fibroblasts could inhibit osteogenesis by regulating YAP localization in MSCs and secreting DKK1.

Conclusions
Our research revealed that fibroblasts could modulate the nuclear-cytoplasmic shuttling of YAP in MSCs, thereby inhibiting their osteoblast differentiation. Fibroblasts could also secrete DKK1, which inhibited calcium nodule formation at the late stage of osteogenesis.
Adjuvant Therapy for Patients with a Tumor-Positive Resection Margin After Neoadjuvant Chemoradiotherapy and Esophagectomy
Authors: van der Zijden C. J. , van der Sluis P. C. , Mostert B. , Nuyttens J. J. M. E. , Spaander V. M. C. W. , Valkema R. , Ruurda J. P. , Wijnhoven B. P. L. , Lagarde S. M. 
Published: January 2024

Abstract
Background
Approximately 4–9% of patients have a tumor-positive resection margin after neoadjuvant chemoradiotherapy (nCRT) and esophagectomy. Although it is associated with decreased survival, Western guidelines do not recommend adjuvant treatment.

Objective
The aim of this study was to assess the proportion of patients who received adjuvant therapy, and to evaluate overall survival (OS) after esophagectomy in patients with a tumor-positive resection margin.

Methods
Patients diagnosed with resectable (cT2-4a/cTxN0-3/NxM0) esophageal cancer between 2015 and 2022, and treated with nCRT followed by irradical esophagectomy, were selected from the Netherlands Cancer Registry. The primary outcome was the proportion of patients with a tumor-positive resection margin who started adjuvant treatment ≤16 weeks after esophagectomy, including chemotherapy/radiotherapy, immunotherapy, or targeted therapy. OS was calculated from the date of surgery until the date of death or last day of follow-up.

Results
Overall, 376 patients were included in our study, of whom 357 were treated with nCRT. Of these 357 patients, 98.3% had a microscopically irradical resection and 1.7% had a macroscopically irradical resection. Approximately 72.3% of tumors showed a partial response (Mandard 2–3) and 11.8% showed little/no pathological response (Mandard 4–5) to nCRT. One of 357 patients underwent adjuvant chemoradiotherapy and 39 patients (61%) underwent adjuvant immunotherapy (nivolumab). The median and 5-year OS rate of all patients was 16.4 months (95% confidence interval 13.1–19.8) and 21%, respectively.

Conclusion
Real-world population-level data showed that no patients with a tumor-positive resection margin underwent adjuvant therapy following nCRT and esophagectomy prior to 2021. Interestingly, 61% of patients were treated with adjuvant nivolumab in 2021–2022. OS after irradical esophagectomy is poor and long-term data will explore the added value of nivolumab.
Physical activity in type II diabetes
Authors: Kępczyk Martyna , Kościołek Aleksandra , Kłak Igor , Czekaj Oliwia , Demianenko Yehor , Kościołek Dawid , Misiak Jakub , Urbaś Michał , Ojdana Miłosz , Surowiecka Kaja 
Published: January 2024

INTRODUCTION AND AIM OF WORK
A factor significantly influencing the risk of lifestyle diseases, including diabetes, is physical activity. The last decades have been characterized by reduced physical activity in developed countries. This is associated with deteriorating population health and the risk of developing type 2 diabetes. Appropriately tailored physical effort is essential for the proper functioning of the body.

MATERIALS AND METHODS

The aim of the study is to compare the physical activity levels among individuals with diabetes. To achieve this goal, a survey was created and subsequently distributed via social media (Telegram platform) in August 2023.

RESULTS
A total of 101 surveys were collected, with the average age of respondents being 34 years old. Among the respondents, 25 individuals (24.75%) had diabetes, while the rest did not have the condition. Out of the participants, 46 respondents indicated a family history of diabetes. Diabetes was statistically significantly associated with a family history of diabetes (p=0.037). Furthermore, the diabetes group exhibited a higher frequency of overweight and obesity (p=0.027). The respondents' body weight was positively correlated with both the frequency of food intake (r=0.31, p=0.011) and negatively correlated with the frequency of exercise (r= -0.22, p=0.046).

CONCLUSIONS
The gathered results confirm the familial nature of diabetes occurrence. They also highlight the significant role of exercise in maintaining body weight, as well as the importance of diet.
Chronic stress and its relationship with increased food consumption and the risk of obesity
Authors: Kępczyk Martyna , Kwaśniewska Oliwia , Misiak Jakub , Urbaś Michał , Ojdana Miłosz , Demianenko Yehor , Czekaj Oliwia , Kościołek Aleksandra , Kościołek Dawid , Surowiecka Kaja 
Published: January 2024

INTRODUCTION AND AIM OF WORK
Stress often accompanies daily functioning. This mechanism is activated by the body in response to external factors to effectively cope with challenges. With prolonged exposure, stress significantly impairs physiological functions, including impacting body weight.
MATERIALS AND METHODS
The aim of the study is to understand the impact of chronic stress on changes in dietary habits and body weight. For this purpose, a custom survey was created to investigate the correlation between stress and other factors. It was distributed using social media (Telegram) in the first half of August 2023 among the population of Ukraine.
RESULTS
The survey was completed by 110 individuals, with the majority being males, accounting for 67 participants (61%). The participants had an average age of 28 years with a standard deviation of 7.12. Among the responses, the most common frequency of experiencing stress was once every two weeks, with 41 answers (37.27% of participants). A majority of the respondents declared having a normal body weight (55.45%).
In our study, we demonstrated a correlation between stress and unhealthy eating habits (rho-Spearman p=0.0002, r=0.34), as well as a lower frequency of stress among individuals taking antidepressant medication (p=0.012). However, we did not establish a connection with abnormal body weight (p>0.05), physical activity (p>0.05), or healthy eating (p>0.05).
CONCLUSIONS
The obtained results suggest that stress may trigger a response in the form of overeating. The reduction in the frequency of stress is also influenced by the use of medications. The findings may indicate a strong association between diet and the experience of stress.
Infant periodic breathing and apneic threshold
Authors: Yamashiro Stanley M. , Iyer Narayan P. 
Published: January 2024

AbstractA mathematical model was proposed to predict the role played by apneic threshold in periodic breathing in preterm infants. Prior models have mainly applied linear control theory which predicted instability but could not explain sustained periodic breathing. Apneic threshold to CO2 which has been postulated to play a major role in infant periodic breathing is a nonlinear effect and cannot be described by linear theory. Another previously unexplored nonlinear factor affecting instability is brain vascular volume change with CO2 which affects time delay to chemoreceptors. The current model explored the influences of apneic threshold, central and peripheral chemoreceptor gains, cardiac output, lung volume, and circulatory time delay on periodic breathing. Apneic threshold was found to play a major role in ventilatory responses to spontaneous sighs. Sighs led to apneic pauses followed by periods of periodic breathing with peripheral chemoreceptor CO2 gain, cardiac output, and lung volume were at reported normal levels. Apneic threshold when exceeded was observed to cause an asymmetry in the periodic breathing cycling and an increased periodic breathing frequency. Sighs in infants occur frequently enough to lead to repeated stimulation within the epoch duration of periodic breathing for a single sigh. Multiple sighs may then play a major role in promoting continuous periodic breathing in infants. Peripheral chemoreceptor gain estimated using endogenous CO2 led to validated predicted periodic breathing cycle duration as a function of age. Brain vascular volume increase with CO2 contributes to periodic breathing in very young (1–2 day old) preterm infants.
Roles of electrostatics and intermolecular electronic motions in the structural and spectroscopic features of hydrogen- and halogen-bonded systems
Authors: Torii Hajime 
Published: January 2024

Abstract
It is widely recognized that electrostatics plays a central role in the intermolecular interactions in condensed phases, as evidenced by the “electrostatics + Lennard-Jones” form of the potential functions that are commonly used in classical molecular dynamics simulations. Then, do we understand all about electrostatics in condensed phases? In this review, recent theoretical advances in relation to this topic will be discussed: (1) vibrational spectroscopic probing of the electrostatics in condensed phases, and (2) some phenomena affected by deviation from the scheme of isotropic fixed atomic partial charges, i.e., anisotropy and intermolecular transfer of electron distributions. A theoretical basis for better understanding on them and some theoretical models for practical calculations will be shown with some typical example cases of hydrogen- and halogen-bonded systems.
Recommendations on training objectives and staff qualification for the manual preparation of capsules in pharmacy
Authors: Marçon Frédéric , Lagarce Frédéric , Roland Isabelle , Brossard Denis , Merienne Camille , Chennell Philip , d’Huart Elise , Briot Thomas , Carrez Laurent , Podilsky Gregory , Rohrbach Pascal , Lannoy Damien , Storme Thomas , Guerrault-Moro Marie Noelle , Soulairol Ian , Crauste-Manciet Sylvie 
Published: January 2024

Abstract
Training and certification of personnel in capsule preparation are essential procedures, overseen by the pharmacist who delegates these tasks. These procedures aim not only to ensure the efficacy and safety of operations but also to establish a clear chain of responsibility. They align with established best practices. Certification grants formal authorization to qualified individuals to perform specific tasks. For new hires, a comprehensive training program is designed to facilitate their integration and empower them from the onset. We propose training objectives structured around a competency-based approach, highlighting objective evaluation criteria applicable in real-world practical settings. These training objectives address critical aspects such as the handling of hazardous substances, weighing and mixing of powders, and capsule filling. They also emphasize the importance of documentation and traceability. Specialized preparations and tools are offered to facilitate the assessment of learning outcomes.
Heat Loss Optimization of a Building with Different Window to Wall Area Ratios
Authors: Koyun Tansel , Koc Ersin , Akcay Ismail Hakki , Kent Emin Fuad 
Published: January 2024

Abstract
The types of glass and exterior walls and the window-to-wall ratio (WWR) on building façades play a major role in heat losses that occur in every type of building, residential or commercial. The opaque and transparent surfaces of buildings have an important role in terms of both energy losses and energy gains. Windows are the parts of the building envelope where heat losses mostly occur. As the WWR increases on the façades of a building, heat losses increase, but heat gains from solar energy also increase, which assists in free heating of the building. In this study, a detached residential building located in Antalya, Turkey, a province with hot–humid climatic conditions, has been examined. A series of simulations were carried out to detect the effects of WWRs and different glass, frame, and exterior wall types on heat losses of the building. The heat loss values obtained from these simulations were processed by using a special mechanical installation calculation software. Simulations were performed for apartment rooms with levels of WWR ranging from 30 to 60 % of the wall areas facing the façade. In order to minimize heat loss, double-pane glass (or double-glazed glass) was used instead of single-pane glass. The aim of this study was to find the optimum value in terms of applicability and economy. The optimum value was calculated by minimization according to both the linear graphical method and the dual simplex optimization method. The values found in both methods were compared and interpreted. It is believed that the optimized glass, frame, joinery, and exterior wall parameters, which are influential to the energy performance of the building, will make a positive contribution to the architectural design phase in addition to improving the energy efficiency of existing buildings.