bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiometabolic sex differences in adults born small for gestational age
Authors: Rodríguez-López Mérida , Sepúlveda-Martínez Álvaro , Bernardino Gabriel , Crovetto Francesca , Pajuelo Carolina , Sitges Marta , Bijnens Bart , Gratacós Eduard , Crispi Fàtima
Published: October 2023

Aim

This study aimed to assess the cardiometabolic sex similarities and differences in adults born small for gestational age.

Methods

This study was an ambispective cohort study from a birth registry in Barcelona, Spain, including 523 adult participants (20–40 years-old) subdivided as born small for gestational age (SGA, if birth weight <10th centile) or adequate fetal growth for gestational age (AGA). Cardiometabolic health was assessed by echocardiography, electrocardiogram, blood pressure measurement, vascular ultrasound, anthropometric measurements, and serum glycemia and lipid profile. Stratified analyses by sex were performed by estimation of adjusted absolute difference (AAD) using inverse probability weighting.

Results

Compared with AGA, the stratified analyses by sex showed a more pronounced reduction in ejection fraction [AAD: female −1.73 (95% CI −3.2 to −0.28) vs. male −1.33 (−3.19 to 0.52)] and increment in heart rate [female 3.04 (0.29–5.8) vs. male 2.25 (−0.82 to 5.31)] in SGA females compared with SGA males. In contrast, a more pronounced reduction in PR interval [female −1.36 (−6.15 to 3.42) vs. male −6.61 (−11.67 to −1.54)] and an increase in systolic blood pressure [female 0.06 (−2.7 to 2.81) vs. male 2.71 (−0.48 to 5.9)] and central-to-peripheral fat ratio [female 0.05 (−0.03 to 0.12) vs. male 0.40 (0.17–0.62)] were mainly observed in SGA male compared with SGA female.

Conclusions

Sex differences were observed in the effect of SGA on cardiometabolic endpoints with female being more prone to cardiac dysfunction and male to electrocardiographic, vascular, and metabolic changes. Future research including sex-stratification data is warranted.
A stream processing abstraction framework
Authors: Bartolini Ilaria , Patella Marco
Published: October 2023

Real-time analysis of large multimedia streams is nowadays made efficient by the existence of several Big Data streaming platforms, like Apache Flink and Samza. However, the use of such platforms is difficult due to the fact that facilities they offer are often too raw to be effectively exploited by analysts. We describe the evolution of RAM3S, a software infrastructure for the integration of Big Data stream processing platforms, to SPAF, an abstraction framework able to provide programmers with a simple but powerful API to ease the development of stream processing applications. By using SPAF, the programmer can easily implement real-time complex analyses of massive streams on top of a distributed computing infrastructure, able to manage the volume and velocity of Big Data streams, thus effectively transforming data into value.
Assessment of noticing of classroom disruptions: a multi-methods approach
Authors: Biermann Antje , Brünken Roland , Lewalter Doris , Grub Ann-Sophie
Published: October 2023

Teachers’ noticing as a basic precondition for effective teaching is characterized by focusing on relevant events in the classroom and ignoring the irrelevant. In recent years, many researchers have used eye-tracking methodology in classroom observations to gather information about the continuous attentional processes of teachers. Despite the general validity of the eye–mind assumption, methodological triangulation is necessary to draw conclusions about the where and why of the focus of attention. Although in previous studies, different data sources like gaze and verbal data have been used, the analyses were mostly conducted separately, instead of directly combining the data. In our study, we collected verbal data (retrospective think-aloud; RTA) and a reaction-based concurrent measure (keystroke) to assess the noticing process of novice and experienced teachers (N = 52) while they watched staged videos of classroom situations. For a direct triangulation, we combined these data with eye-tracking data. The aim of the study was to combine both measures with eye-tracking parameters that indicate attentional processes (fixation count, mean fixation duration, and revisits), and with expertise. We found that participants who were aware of the critical incidents in the videos (they gave a keystroke or mentioned the incident in the RTA), showed—as expected—a higher number of fixations and more revisits to the appropriate area, but a comparable mean fixation duration. However, expertise differences regarding accuracy in both measures could not be shown. We discuss methodological issues regarding the implementation of RTA and keystroke as measurements for the noticing process because—despite only partially significant results—both methods are promising as they allow complementation and possible correction of eye-movement-only data.
Heavy metal contamination in rice, pulses, and vegetables from CKDu-endemic areas in Cuttack district, India: a health risk assessment
Authors: Mohanty Shraddha , Nayak Rabindra Kumar , Jena Bandita , Padhan Kshitipati , Mohapatra Kiran Kumar , Sahoo Sanjib Kumar , Dash Prava Kiran , Das Jyotirmayee , Behera Sujit Kumar , Sahu Anukiran , Nayak Jitendra Kumar , Padhan Sudipta , Datta Diptanu
Published: October 2023

Introduction:Chronic kidney disease of unknown aetiology (CKDu) is an emerging public health concern in India. The present study was carried out to investigate the concentrations of potentially toxic heavy metals (Cd, Pb, Ni, Cr, Hg, and As) in locally grown food crops (rice, pulses, and vegetables) in CKDu prevalent areas of Cuttack district, India.

Methods:Exposure risks from food crops were analysed, including estimated daily intake, hazard quotient, hazard index, and carcinogenic risk.

Result:The overall heavy metal concentrations in the crop samples were in the following order: Pb>Ni>Cd>Cr>As>Hg. The mean concentration of heavy metals in different crops were as follows, ranked from highest to lowest: spinach, rice, okra, mustard, potato, carrot, tomato, green gram, black gram. A statistical multivariate analysis revealed that the primary sources of Cd, Pb, Ni, Cr, Hg, and As in crop samples were both natural and human activities. For lead, target hazard quotient (THQ) values in rice were greater than 1, indicating significant noncarcinogenic health risks to both adults and children.

Discussion:While the majority of the crop samples had Pb levels below the permissible level (10−5), the target carcinogenic risk of Cd was higher than the USEPA threshold value (10−4), showing a cancer risk to adults and children. This study concluded that long-term intake of locally grown food crops may produce a significant health risk to the local inhabitants, and that of regular heavy metal monitoring is strongly recommended in this region.
Digital research on the resilience control of water ecological space under the concept of urban-water coupling
Authors: Yang Hua , Ning Qimeng , Zhou Hui , Lai Nan , Song Qidi , Ji Qianfu , Zeng Zhiwei
Published: October 2023

Introduction: The construction of digital governance of national land space depends greatly on the development of a digital model for robust control of water and ecological space. However, how changes to the urban-water coupling relationships affect the resilience control of water ecological space is rarely reported.

Methods: The evolution characteristics of urban and water space in the study area from 2000 to 2020 and the correlation between them are analyzed based on the grid analysis using InVEST and Moran’I methods. Based on the theory of human-environment interaction territorial system to provide a theoretical framework to explain the urban and water space. We used digital to construct an resilience control framework in the Dongting Lake area based on the correlation between the urban and water space.

Results: The results show that: 1) From 2000 to 2020, the geographical evolution of towns and cities in the research area displayed obvious spatial variation in intensity, indicating a process of expansion and change. The regional and temporal fluctuations of the water conservation function are significant. The mountainous areas in the east, south, and northwest are where the high values of the water conservation function are primarily found. These regions have more vegetation, which increases the water conservation function. 2) According to the results of local binary spatial autocorrelation analysis, it can be seen that from 2000 to 2020, the high-high agglomeration of town space and water-related is mainly distributed in Linxiang City, Yueyang County, Miluo City, Li County, and Yiyang City, and the low-low agglomeration is mainly distributed in Dongting Lake, Datong Lake, and along the Yangtze River. 3) Based on how urban spatial evolution affects water ecological space, we construct a theoretical framework of urban-water coupling and establish a digital model of water ecological space resilience control in the Dongting Lake area from four perspectives: threshold, visualization, dynamics, and intelligence.
Three doses of COVID-19 mRNA vaccine induce class-switched antibody responses in inflammatory arthritis patients on immunomodulatory therapies
Authors: Lee Jenny M. , Figueroa Alexis , Sachithanandham Jaiprasath , Li Maggie , Connolly Caoilfhionn M. , Shapiro Janna R. , Chen Yiqun , Jones Michelle , Dhara Venkata Gayatri , Towns Marilyn , Lee John S. , Peralta Stephanie R. , Milstone Aaron M. , Betenbaugh Michael , Debes Amanda K. , Blankson Joel , Sitaras Ioannis , Yoon Steve , Thompson Elizabeth A. , Bingham Clifton O. , Klein Sabra L. , Pekosz Andrew , Bailey Justin R.
Published: October 2023

Patients with inflammatory arthritis (IA) are at increased risk of severe COVID-19 due to medication-induced immunosuppression that impairs host defenses. The aim of this study was to assess antibody and B cell responses to COVID-19 mRNA vaccination in IA patients receiving immunomodulatory therapies. Adults with IA were enrolled through the Johns Hopkins Arthritis Center and compared with healthy controls (HC). Paired plasma and peripheral blood mononuclear cell (PBMC) samples were collected prior to and 30 days or 6 months following the first two doses of mRNA vaccines (D2; HC=77 and IA=31 patients), or 30 days following a third dose of mRNA vaccines (D3; HC=11 and IA=96 patients). Neutralizing antibody titers, total binding antibody titers, and B cell responses to vaccine and Omicron variants were analyzed. Anti-Spike (S) IgG and S-specific B cells developed appropriately in most IA patients following D3, with reduced responses to Omicron variants, and negligible effects of medication type or drug withholding. Neutralizing antibody responses were lower compared to healthy controls after both D2 and D3, with a small number of individuals demonstrating persistently undetectable neutralizing antibody levels. Most IA patients respond as well to mRNA COVID-19 vaccines as immunocompetent individuals by the third dose, with no evidence of improved responses following medication withholding. These data suggest that IA-associated immune impairment may not hinder immunity to COVID-19 mRNA vaccines in most individuals.
The multifaceted role of macrophages in homeostatic and injured skeletal muscle
Authors: Wang Xingyu , Zhou Lan
Published: October 2023

Skeletal muscle is essential for body physical activity, energy metabolism, and temperature maintenance. It has excellent capabilities to maintain homeostasis and to regenerate after injury, which indispensably relies on muscle stem cells, satellite cells (MuSCs). The quiescence, activation, and differentiation of MuSCs are tightly regulated in homeostatic and regenerating muscles. Among the important regulators are intramuscular macrophages, which are functionally heterogeneous with different subtypes present in a spatiotemporal manner to regulate the balance of different MuSC statuses. During chronic injury and aging, intramuscular macrophages often undergo aberrant activation, which in turn disrupts muscle homeostasis and regenerative repair. Growing evidence suggests that the aberrant activation is mainly triggered by altered muscle microenvironment. The trained immunity that affects myeloid progenitors during hematopoiesis may also contribute. Aged immune system may contribute, in part, to the aging-related sarcopenia and compromised skeletal muscle injury repair. As macrophages are actively involved in the progression of many muscle diseases, manipulating their functional activation has become a promising therapeutic approach, which requires comprehensive knowledge of the cellular and molecular mechanisms underlying the diverse activation. To this end, we discuss here the current knowledge of multifaceted role of macrophages in skeletal muscle homeostasis, injury, and repair.
Impacting T-cell fitness in multiple myeloma: potential roles for selinexor and XPO1 inhibitors
Authors: Binder Adam F. , Walker Christopher J. , Mark Tomer M. , Baljevic Muhamed
Published: October 2023

Competent T-cells with sufficient levels of fitness combat cancer formation and progression. In multiple myeloma (MM), T-cell exhaustion is caused by several factors including tumor burden, constant immune activation due to chronic disease, age, nutritional status, and certain MM treatments such as alkylating agents and proteasome inhibitors. Many currently used therapies, including bispecific T-cell engagers, anti-CD38 antibodies, proteasome inhibitors, and CART-cells, directly or indirectly depend on the anti-cancer activity of T-cells. Reduced T-cell fitness not only diminishes immune defenses, increasing patient susceptibility to opportunistic infections, but can impact effectiveness MM therapy effectiveness, bringing into focus sequencing strategies that could modulate T-cell fitness and potentially optimize overall benefit and clinical outcomes. Certain targeted agents used to treat MM, such as selective inhibitors of nuclear export (SINE) compounds, have the potential to mitigate T-cell exhaustion. Herein referred to as XPO1 inhibitors, SINE compounds inhibit the nuclear export protein exportin 1 (XPO1), which leads to nuclear retention and activation of tumor suppressor proteins and downregulation of oncoprotein expression. The XPO1 inhibitors selinexor and eltanexor reduced T-cell exhaustion in cell lines and animal models, suggesting their potential role in revitalizating these key effector cells. Additional clinical studies are needed to understand how T-cell fitness is impacted by diseases and therapeutic factors in MM, to potentially facilitate the optimal use of available treatments that depend on, and impact, T-cell function. This review summarizes the importance of T-cell fitness and the potential to optimize treatment using T-cell engaging therapies with a focus on XPO1 inhibitors.
An evaluation of the General Bathymetric Chart of the Ocean in shoreline-crossing geomorphometric investigations of volcanic islands
Authors: Klein Elisa , Hadré Emma , Krastel Sebastian , Urlaub Morelia
Published: October 2023

Digital elevation models (DEMs) are crucial in natural hazard assessments, as they often present the only comprehensive information. While satellites deliver remote sensing information of the land surface of up to 2m resolution, only 25% of the seafloor is mapped with a minimum resolution of 400m. The acquisition of high-resolution bathymetry requires hydroacoustic surveys by research vessels or autonomous vehicles, which is time-consuming and expensive. Predicted bathymetry from satellite altimetry, on the other hand, is widely available but has a significantly lower spatial resolution and high uncertainties in elevation, especially in shallow waters. The research on volcanic islands as a source of both volcanic as well as marine hazards such as tsunamis, is greatly limited by the lack of high-resolution bathymetry. Here we compare 24 geomorphometric parameters of 47 volcanic islands derived from a) the comprehensive bathymetric data of the General Bathymetric Chart of the Ocean (GEBCO) and b) high-resolution (< 250m), ship-based bathymetry. Out of 24 parameters tested, 20 show < ± 2.5% median deviation, and quartiles < ± 10%. Parameters describing the size of a volcanic island are the most robust and slope parameters show the greatest deviations. With this benchmark, we will be able to increase geomorphometric investigations to volcanic islands where little or no high-resolution bathymetry data is available.
Changjiang and Kuroshio contributions to oxygen depletion on the Zhejiang Coast
Authors: Wu Haokun , Yang Wen , Zhang Wenxia , Zhao Xin
Published: October 2023

In recent decades, intensified anthropogenic activities have resulted in increasing occurrence of hypoxia in the East China Sea. Kuroshio, as a natural factor, also threatens the oxygen content over the continental shelf. There have been many studies investigating the different contributions of Changjiang and Kuroshio to oxygen depletion over the continental shelf. This study revisited this issue and further investigated the mechanisms controlling the different role of Changjiang and Kuroshio in oxygen depletion and focused mainly on the Zhejiang Coast. A coupled high-resolution physical-biogeochemical model was used to investigate the connections between the variations in nutrients, chlorophyll, stratification, and oxygen and the delivery of Changjiang diluted water and Kuroshio subsurface water over the shelf, especially on the Zhejiang Coast in the summer of 2017. The distinct features of hypoxia off the Changjiang estuary (severe but transient) and that along the Zhejiang Coast (mild but prolonged) are caused by the different dynamic environments and nutrients sources. North of 30˚N, intense oxygen depletion and bottom hypoxia are typically under the constraint of Changjiang diluted water. While the impacts of upwelled materials associated with the Kuroshio subsurface water enhance southward with the simultaneously weakened impacts from the Changjiang diluted water. Besides confirming the support of upwelling on surface phytoplankton bloom along the Zhejiang Coast, this study detected subsurface chlorophyll maximum immediately underneath the main pycnocline offshore of the Zhejiang Coast during upwelling. This indicated that the upwelled oceanic nutrients were transported further offshore along isopycnals and also fertilized phytoplankton growth at the subsurface. The exacerbation of either anthropogenic or natural factors could potentially intensify oxygen depletion along the Zhejiang Coast.
Pharmacokinetic–pharmacodynamic cutoff values for benzylpenicillin in horses to support the establishment of clinical breakpoints for benzylpenicillin antimicrobial susceptibility testing in horses
Authors: Lallemand Elodie A. , Bousquet-Mélou Alain , Chapuis Laura , Davis Jennifer , Ferran Aude A. , Kukanich Butch , Kuroda Taisuke , Lacroix Marlène Z. , Minamijima Yohei , Olsén Lena , Pelligand Ludovic , Portugal Felipe Ramon , Roques Béatrice B. , Santschi Elizabeth M. , Wilson Katherine E. , Toutain Pierre-Louis
Published: October 2023

Introduction

The aim of this international project was to establish a species-specific Clinical Breakpoint for interpretation of Antimicrobial Susceptibility Testing of benzylpenicillin (BP) in horses.

Methods

A population pharmacokinetic model of BP disposition was developed to compute PK/PD cutoff values of BP for different formulations that are commonly used in equine medicine around the world (France, Sweden, USA and Japan). Investigated substances were potassium BP, sodium BP, procaine BP, a combination of procaine BP and benzathine BP and penethamate, a prodrug of BP. Data were collected from 40 horses that provided 63 rich profiles of BP corresponding to a total of 1022 individual BP plasma concentrations.

Results

A 3-compartment disposition model was selected. For each of these formulations, the PK/PD cutoff was estimated for different dosage regimens using Monte Carlo simulations. ThefAUC/MIC orfT>MIC were calculated with a free BP fraction set at 0.4. ForfAUC/MIC, a target value of 72 h (for a 72h treatment) was considered. ForfT>MIC, efficacy was assumed when free plasma concentrations were above the explored MIC (0.0625-2 mg/L) for 30 or 40 % of the dosing interval. For continuous infusion, afT>MIC of 90 % was considered. It was shown that a PK/PD cutoff of 0.25 mg/L can be achieved in 90 % of horses with routine regimen (typically 22,000 IU/kg or 12.4 mg/kg per day) with IM procaine BP once a day (France, Japan, Sweden but not USA1) and with IM sodium BP at 14.07 mg/kg, twice a day or IV sodium BP infusion of 12.4 mg/kg per day. In contrast, penethamate and the combination of procaine BP and benzathine BP were unable to achieve this PK/PD cutoff not even an MIC of 0.125 mg/L.

Discussion

The PK/PD cutoff of 0.25 mg/L is one dilution lower than the clinical breakpoint released by the CLSI (0.5 mg/ L). From our simulations, the CLSI clinical breakpoint can be achieved with IM procaine BP twice a day at 22,000 IU i.e. 12.4 mg/kg.
Application of spectral CT in diagnosis, classification and prognostic monitoring of gastrointestinal cancers: progress, limitations and prospects
Authors: Hong Yuqin , Zhong Lijuan , Lv Xue , Liu Qiao , Fu Langzhou , Zhou Daiquan , Yu Na
Published: October 2023

Gastrointestinal (GI) cancer is the leading cause of cancer-related deaths worldwide. Computed tomography (CT) is an important auxiliary tool for the diagnosis, evaluation, and prognosis prediction of gastrointestinal tumors. Spectral CT is another major CT revolution after spiral CT and multidetector CT. Compared to traditional CT which only provides single-parameter anatomical diagnostic mode imaging, spectral CT can achieve multi-parameter imaging and provide a wealth of image information to optimize disease diagnosis. In recent years, with the rapid development and application of spectral CT, more and more studies on the application of spectral CT in the characterization of GI tumors have been published. For this review, we obtained a substantial volume of literature, focusing on spectral CT imaging of gastrointestinal cancers, including esophageal, stomach, colorectal, liver, and pancreatic cancers. We found that spectral CT can not only accurately stage gastrointestinal tumors before operation but also distinguish benign and malignant GI tumors with improved image quality, and effectively evaluate the therapeutic response and prognosis of the lesions. In addition, this paper also discusses the limitations and prospects of using spectral CT in GI cancer diagnosis and treatment.
Association between the risk and severity of Parkinson’s disease and plasma homocysteine, vitamin B12 and folate levels: a systematic review and meta-analysis
Authors: Quan Yuxin , Xu Jisen , Xu Qing , Guo Zhiqing , Ou Ruwei , Shang Huifang , Wei Qianqian
Published: October 2023

Background

Parkinson’s disease (PD) is recognized as the second most prevalent progressive neurodegenerative disease among the elderly. However, the relationship between PD and plasma homocysteine (Hcy), vitamin B12, and folate has yielded inconsistent results in previous studies. Hence, in order to address this ambiguity, we conducted a meta-analysis to summarize the existing evidence.

Methods

Suitable studies published prior to May 2023 were identified by searching PubMed, EMBASE, Medline, Ovid, and Web of Science. The methodological quality of eligible studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Meta-analysis and publication bias were then performed using R version 4.3.1.

Results

The results of our meta-analysis, consisting of case–control and cross-sectional studies, showed that PD patients had lower folate and vitamin B12 levels (SMD [95%CI]: −0.30[−0.39, −0.22], p < 0.001 for Vitamin B12; SMD [95%CI]: −0.20 [−0.28, −0.13], p < 0.001 for folate), but a significant higher Hcy level (SMD [95%CI]: 0.86 [0.59, 1.14], p < 0.001) than healthy people. Meanwhile, PD was significantly related to hyperhomocysteinemia (SMD [95%]: 2.02 [1.26, 2.78], p < 0.001) rather than plasma Hcy below 15 μmol/L (SMD [95%]: −0.31 [−0.62, 0.00], p = 0.05). Subgroup analysis revealed associations between the Hcy level of PD patients and region (p = 0.03), age (p = 0.03), levodopa therapy (p = 0.03), Hoehn and Yahr stage (p < 0.001), and cognitive impairment (p < 0.001). However, gender (p = 0.38) and sample size (p = 0.49) were not associated.

Conclusion

Hcy, vitamin B12, and folic acid potentially predict the onset and development of PD. Additionally, multiple factors were linked to Hcy levels in PD patients. Further studies are needed to comprehend their roles in PD.
Crucial role of autophagy in propofol-treated neurological diseases: a comprehensive review
Authors: Yu Sicong , Liao Jian , Lin Xuezheng , Luo Yu , Lu Guangtao
Published: October 2023

Neurological disorders are the leading cause of disability and death globally. Currently, there is a significant concern about the therapeutic strategies that can offer reliable and cost-effective treatment for neurological diseases. Propofol is a widely used general intravenous anesthetic in the clinic. Emerging studies demonstrate that propofol exerts neuroprotective effects on neurological diseases and disorders, while its underlying pathogenic mechanism is not well understood. Autophagy, an important process of cell turnover in eukaryotes, has been suggested to involve in the neuroprotective properties developed by propofol. In this narrative review, we summarized the current evidence on the roles of autophagy in propofol-associated neurological diseases. This study highlighted the effect of propofol on the nervous system and the crucial roles of autophagy. According to the 21 included studies, we found that propofol was a double-edged sword for neurological disorders. Several eligible studies reported that propofol caused neuronal cell damage by regulating autophagy, leading to cognitive dysfunction and other neurological diseases, especially high concentration and dose of propofol. However, some of them have shown that in the model of existing nervous system diseases (e.g., cerebral ischemia-reperfusion injury, electroconvulsive therapy injury, cobalt chloride-induced injury, TNF-α-induced injury, and sleep deprivation-induced injury), propofol might play a neuroprotective role by regulating autophagy, thus improving the degree of nerve damage. Autophagy plays a pivotal role in the neurological system by regulating oxidative stress, inflammatory response, calcium release, and other mechanisms, which may be associated with the interaction of a variety of related proteins and signal cascades. With extensive in-depth research in the future, the autophagic mechanism mediated by propofol will be fully understood, which may facilitate the feasibility of propofol in the prevention and treatment of neurological disorders.
The auditory function in migraine model rats induced by postauricular nitroglycerin injection
Authors: Qi Rongxiang , Zhang Jilei , Diao Tongxiang , Yu Lisheng
Published: October 2023

Objective

The mechanism by which migraines produce inner ear-related symptoms is not well understood. Previous studies have found that the latency of auditory brainstem response (ABR) in animal models of migraine has changed, but the threshold has not changed significantly. Therefore, it is necessary to establish a better animal model with both migraine and hearing loss to explore the relationship between migraine and auditory function deeply.

Methods

In this study, the rat model of migraine was induced by postauricular injection of nitroglycerin (NTG), and the effect on the auditory function of the inner ear was explored by comparing with intraperitoneal injection of nitroglycerin. The rats were given the drug repeatedly on alternate days, a total of 5 dosing, with the body weight monitored during the drug administration. The tactile threshold of the rats' forepaw was measured using von-Frey filaments and auditory function was assessed by ABR.

Results

The results showed that the baseline tactile threshold of rats gradually decreased during the modeling process, and hyperalgesia appeared. Postauricular injection of NTG did not affect the weight gain of rats, while intraperitoneal injection of NTG showed slow or even negative weight gain. The ABR threshold of Click, 4 and 8 kHz of postauricular NTG injection rats increased, the latency was prolonged, and the ABR threshold in the right ear was higher than that in the left ear.

Conclusions

We demonstrated that postauricular injection of nitroglycerin may be safer and more effective than intraperitoneal injection of nitroglycerin in the process of creating rat migraine model without affecting the weight gain. Postauricular injection of nitroglycerin has more damage to the auditory function of rats. Therefore, the migraine model rat induced by postauricular injection of nitroglycerin may be a new model of cochlear migraine.
Anti-Kelch-like protein 11 antibody encephalitis: a case report and literature review
Authors: Song Yanling , Hu Quanzhong , Zhang Qing
Published: October 2023

Anti-Kelch-like protein 11 (KLHL11) antibody encephalitis is a rare clinical condition characterized by autoimmune-mediated encephalomyelitis associated with the presence of KLHL11 antibodies. Diagnosis requires the detection of serum and cerebrospinal fluid anti-KLHL11 antibodies, while immunotherapy serves as the principal treatment approach. This paper presents a case report highlighting the emergence of anti-KLHL11 antibody encephalitis. A 66-year-old male patient presented with seizures, impaired cognitive function, disturbance of consciousness, apathy, hypologia, dysphoria, and ataxia. Serum and cerebrospinal fluid (CSF) were identified as positive for anti-KLHL11 antibodies, leading to a diagnosis of autoimmune encephalitis associated with KLHL11 antibodies. After treatment with glucocorticoid, the patient did not experience further convulsions and recovered consciousness, with improved cognitive function. Tumor screening suggested the presence of an underlying malignancy. The clinical manifestations of anti-KLHL11 antibody encephalitis vary widely, and timely identification and treatment can improve prognosis.
Frequency dependent whole-brain coactivation patterns analysis in Alzheimer’s disease
Authors: Zhang Si-Ping , Mao Bi , Zhou Tianlin , Su Chun-Wang , Li Chenxi , Jiang Junjie , An Simeng , Yao Nan , Li Youjun , Huang Zi-Gang ,   Alzheimer’s Disease Neuroimaging Initiative
Published: October 2023

Background

The brain in resting state has complex dynamic properties and shows frequency dependent characteristics. The frequency-dependent whole-brain dynamic changes of resting state across the scans have been ignored in Alzheimer’s disease (AD).

Objective

Coactivation pattern (CAP) analysis can identify different brain states. This paper aimed to investigate the dynamic characteristics of frequency dependent whole-brain CAPs in AD.

Methods

We utilized a multiband CAP approach to model the state space and study brain dynamics in both AD and NC. The correlation between the dynamic characteristics and the subjects’ clinical index was further analyzed.

Results

The results showed similar CAP patterns at different frequency bands, but the occurrence of patterns was different. In addition, CAPs associated with the default mode network (DMN) and the ventral/dorsal visual network (dorsal/ventral VN) were altered significantly between the AD and NC groups. This study also found the correlation between the altered dynamic characteristics of frequency dependent CAPs and the patients’ clinical Mini-Mental State Examination assessment scale scores.

Conclusion

This study revealed that while similar CAP spatial patterns appear in different frequency bands, their dynamic characteristics in subbands vary. In addition, delineating subbands was more helpful in distinguishing AD from NC in terms of CAP.
Evaluation of subjective visual vertical and horizontal in patients with acoustic neuroma based on virtual reality
Authors: Zhang Lin , Ouyang Shunlin , Chen Ling , Huang Hemei , Ou Yongkang , Tang Xiaowu
Published: October 2023

Objective

To investigate potential differences in absolute deviation values of subjective visual vertical and horizontal between unilateral acoustic neuroma patients and healthy young adults under varying degrees of static head tilt, as well as the impact of proprioception on these values, with the aim of determining the effect of acoustic neuroma on gravity sensory pathway function in patients.

Methods

We recruited 22 patients diagnosed with unilateral acoustic neuroma and 25 healthy young adults and employed virtual reality technology to assess the absolute deviation values of subjective visual vertical (SVV) and subjective visual horizontal (SVH) under eight different static tilted head positions (Head centered (0° tilt), PdP, Head tilt 15°, 30°, 45° to the left and right), then compare and analyze intergroup differences.

Results

In the Head-centered position, both SVV and SVH absolute deviated values were significantly higher in the AN group compared to healthy young adults. The AN group exhibited significantly higher absolute deviation values of SVV compared to the healthy group when tilting their head 30° left and right. Additionally, when tilting their heads to the right at 15° and 45° the AN group showed significant increases in SVH absolute deviated values compared to healthy adults. The SVV and SVH absolute deviation values of LAN and SAN groups did not reach statistical significance. The results of the SVV test for PDP position did not show any significant differences among all groups. However, the SVH test revealed that the absolute deviation values of the LAN group was significantly higher than that of healthy individuals.

Conclusion

Our study shows that the gravity sensing function of patients with unilateral acoustic neuroma is affected to different degrees, however, the degree of gravity sensing function damage of patients has little relationship with tumor size. When acoustic neuroma is larger than 2 cm, the effect of proprioception on patients’ SVH outcome is noteworthy. So, we should pay attention to the postoperative follow-up of patients with acoustic neuroma and the evaluation of vestibular rehabilitation effect. Meanwhile, for patients opting for conservative treatment, it is imperative to monitor the dynamic changes in vestibular function and seize timely opportunities for intervention.
Adolescent traumatic brain injury leads to incremental neural impairment in middle-aged mice: role of persistent oxidative stress and neuroinflammation
Authors: Chen Ziyuan , Wang Pengfei , Cheng Hao , Wang Ning , Wu Mingzhe , Wang Ziwei , Wang Zhi , Dong Wenwen , Guan Dawei , Wang Linlin , Zhao Rui
Published: October 2023

Background

Traumatic brain injury (TBI) increases the risk of mental disorders and neurodegenerative diseases in the chronic phase. However, there is limited neuropathological or molecular data on the long-term neural dysfunction and its potential mechanism following adolescent TBI.

Methods

A total of 160 male mice aged 8 weeks were used to mimic moderate TBI by controlled cortical impact. At 1, 3, 6 and 12 months post-injury (mpi), different neurological functions were evaluated by elevated plus maze, forced swimming test, sucrose preference test and Morris water maze. The levels of oxidative stress, antioxidant response, reactive astrocytes and microglia, and expression of inflammatory cytokines were subsequently assessed in the ipsilateral hippocampus, followed by neuronal apoptosis detection. Additionally, the morphological complexity of hippocampal astrocytes was evaluated by Sholl analysis.

Results

The adolescent mice exhibited persistent and incremental deficits in memory and anxiety-like behavior after TBI, which were sharply exacerbated at 12 mpi. Depression-like behaviors were observed in TBI mice at 6 mpi and 12 mpi. Compared with the age-matched control mice, apoptotic neurons were observed in the ipsilateral hippocampus during the chronic phase of TBI, which were accompanied by enhanced oxidative stress, and expression of inflammatory cytokines (IL-1β and TNF-α). Moreover, the reactive astrogliosis and microgliosis in the ipsilateral hippocampus were observed in the late phase of TBI, especially at 12 mpi.

Conclusion

Adolescent TBI leads to incremental cognitive dysfunction, and depression- and anxiety-like behaviors in middle-aged mice. The chronic persistent neuroinflammation and oxidative stress account for the neuronal loss and neural dysfunction in the ipsilateral hippocampus. Our results provide evidence for the pathogenesis of chronic neural damage following TBI and shed new light on the treatment of TBI-induced late-phase neurological dysfunction.
The causal association between obesity and gastric cancer and shared molecular signatures: a large-scale Mendelian randomization and multi-omics analysis
Authors: Xing Abao , Tong Henry H. Y. , Liu Songyan , Zhai Xiaobing , Yu Li , Li Kefeng
Published: October 2023

Purpose

While observational studies have identified obesity as a potential risk factor for gastric cancer, the causality remains uncertain. This study aimed to evaluate the causal relationship between obesity and gastric cancer and identify the shared molecular signatures linking obesity to gastric cancer.

Methods

A two-sample Mendelian randomization (MR) analysis was conducted using the GWAS data of body fat percentage (exposure, n = 331,117) and gastric cancer (outcome, n = 202,308). Bioinformatics and meta-analysis of multi-omics data were performed to identify key molecules mediating the causality. The meta-analysis of the plasma/serum proteome included 1,662 obese and 3,153 gastric cancer patients. Obesity and gastric cancer-associated genes were identified using seven common gene ontology databases. The transcriptomic data were obtained from TCGA and GEO databases. The Bioinformatic findings were clinically validated in plasma from 220 obese and 400 gastric cancer patients across two hospitals. Finally, structural-based virtual screening (SBVS) was performed to explore the potential FDA-approved drugs targeting the identified mediating molecules.

Results

The MR analysis revealed a significant causal association between obesity and gastric cancer (IVW, OR = 1.37, 95% CI:1.12-1.69, P = 0.0028), without pleiotropy or heterogeneity. Bioinformatic and meta-analysis of multi-omics data revealed shared TNF, PI3K-AKT, and cytokine signaling dysregulation, with significant upregulation of AKT1, IL-6, and TNF. The clinical study confirmed widespread upregulation of systemic inflammatory markers in the plasma of both diseases. SBVS identified six novel potent AKT1 inhibitors, including the dietary supplement adenosine, representing a potentially preventive drug with low toxicity.

Conclusion

Obesity causally increases gastric cancer, likely mediated by persistent AKT1/IL-6/TNF upregulation. As a potential AKT1 inhibitor, adenosine may mitigate the obesity-to-gastric cancer transition. These findings could inform preventive drug development to reduce gastric cancer risk in obesity.
Identification and characterization of interferon-γ signaling-based personalized heterogeneity and therapeutic strategies in patients with pancreatic cancer
Authors: Chen Xu , Yuan Qihang , Guan Hewen , Shi Xueying , Sun Jiaao , Wu Zhiqiang , Ren Jie , Xia Shilin , Shang Dong
Published: October 2023

Background

Interferon-γ (IFN-γ) is a key cytokine with diverse biological functions, including antiviral defense, antitumor activity, immune regulation, and modulation of cellular processes. Nonetheless, its role in pancreatic cancer (PC) therapy remains debated. Therefore, it is worthwhile to explore the role of Interferon-γ related genes (IFN-γGs) in the progression of PC development.

Methodology

Transcriptomic data from 930 PC were sourced from TCGA, GEO, ICGC, and ArrayExpress, and 93 IFN-γGs were obtained from the MSigDB. We researched the characteristics of IFN-γGs in pan-cancer. Subsequently, the cohort of 930 PC was stratified into two distinct subgroups using the NMF algorithm. We then examined disparities in the activation of cancer-associated pathways within these subpopulations through GSVA analysis. We scrutinized immune infiltration in both subsets and probed classical molecular target drug sensitivity variations. Finally, we devised and validated a novel IFN-γ related prediction model using LASSO and Cox regression analyses. Furthermore, we conducted RT-qPCR and immunohistochemistry assays to validate the expression of seven target genes included in the prediction model.

Results

We demonstrated the CNV, SNV, methylation, expression levels, and prognostic characteristics of IFN-γGs in pan-cancers. Notably, Cluster 2 demonstrated superior prognostic outcomes and heightened immune cell infiltration compared to Clusters 1. We also assessed the IC50 values of classical molecular targeted drugs to establish links between IFN-γGs expression levels and drug responsiveness. Additionally, by applying our prediction model, we segregated PC patients into high-risk and low-risk groups, identifying potential benefits of cisplatin, docetaxel, pazopanib, midostaurin, epothilone.B, thapsigargin, bryostatin.1, and AICAR for high-risk PC patients, and metformin, roscovitine, salubrinal, and cyclopamine for those in the low-risk group. The expression levels of these model genes were further verified through HPA website data and qRT-PCR assays in PC cell lines and tissues.

Conclusion

This study unveils IFN-γGs related molecular subsets in pancreatic cancer for the first time, shedding light on the pivotal role of IFN-γGs in the progression of PC. Furthermore, we establish an IFN-γGs related prognostic model for predicting the survival of PC, offering a theoretical foundation for exploring the precise mechanisms of IFN-γGs in PC.
Knowledge mapping and current trends of Warburg effect in the field of cancer
Authors: Zhao Quan , Wang Lina , Lv Zongwei , Wang Xia , Xu Zhenqun , Wang Kefeng
Published: October 2023

Background

Since abnormal aerobic glycolysis was first identified in cancer cells, many studies have focused on its mechanisms. The purpose of this study was to analyze the global research status of the Warburg effect in cancer using bibliometrics.

Methods

Articles published from 01 January 2013 to 31 December 2022 (n=2,067) were retrieved from the Web of Science core collection database and analyzed using VOSviewer and CiteSpace software.

Results

Over the past decade, there was an overall increase in the number of annual publications. China was the most productive country with 790 articles, while the United States received the most citations, with 25,657 citations in total. Oncotarget was the most productive and most cited journal, with 99 articles and 4,191 citations, respectively. International cooperation was common, with the USA cooperating most with other countries. Lactate metabolism, citrate production, and non-coding RNAs related to the Warburg effect have received increasing attention in cancer research. These areas may become future research trends.

Conclusion

The study findings help summarize the research status and hotspots of the Warburg effect cancer, and will inform subsequent research.
Identification of tumor-agnostic biomarkers for predicting prostate cancer progression and biochemical recurrence
Authors: Lautert-Dutra William , Melo Camila M. , Chaves Luiz P. , Souza Francisco C. , Crozier Cheryl , Sundby Adam E. , Woroszchuk Elizabeth , Saggioro Fabiano P. , Avante Filipe S. , dos Reis Rodolfo B. , Squire Jeremy A. , Bayani Jane
Published: October 2023

The diverse clinical outcomes of prostate cancer have led to the development of gene signature assays predicting disease progression. Improved prostate cancer progression biomarkers are needed as current RNA biomarker tests have varying success for intermediate prostate cancer. Interest grows in universal gene signatures for invasive carcinoma progression. Early breast and prostate cancers share characteristics, including hormone dependence and BRCA1/2 mutations. Given the similarities in the pathobiology of breast and prostate cancer, we utilized the NanoString BC360 panel, comprising the validated PAM50 classifier and pathway-specific signatures associated with general tumor progression as well as breast cancer-specific classifiers. This retrospective cohort of primary prostate cancers (n=53) was stratified according to biochemical recurrence (BCR) status and the CAPRA-S to identify genes related to high-risk disease. Two public cohort (TCGA-PRAD and GSE54460) were used to validate the results. Expression profiling of our cohort uncovered associations between PIP and INHBA with BCR and high CAPRA-S score, as well as associations between VCAN, SFRP2, and THBS4 and BCR. Despite low levels of the ESR1 gene compared to AR, we found strong expression of the ER signaling signature, suggesting that BCR may be driven by ER-mediated pathways. Kaplan-Meier and univariate Cox proportional hazards regression analysis indicated the expression of ESR1, PGR, VCAN, and SFRP2 could predict the occurrence of relapse events. This is in keeping with the pathways represented by these genes which contribute to angiogenesis and the epithelial-mesenchymal transition. It is likely that VCAN works by activating the stroma and remodeling the tumor microenvironment. Additionally, SFRP2 overexpression has been associated with increased tumor size and reduced survival rates in breast cancer and among prostate cancer patients who experienced BCR. ESR1 influences disease progression by activating stroma, stimulating stem/progenitor prostate cancer, and inducing TGF-β. Estrogen signaling may therefore serve as a surrogate to AR signaling during progression and in hormone-refractory disease, particularly in prostate cancer patients with stromal-rich tumors. Collectively, the use of agnostic biomarkers developed for breast cancer stratification has facilitated a precise clinical classification of patients undergoing radical prostatectomy and highlighted the therapeutic potential of targeting estrogen signaling in prostate cancer.
Decoding TROP2 in breast cancer: significance, clinical implications, and therapeutic advancements
Authors: Yao Liqin , Chen Junfeng , Ma Wenxue
Published: October 2023

Breast cancer is a heterogeneous disease characterized by distinct molecular subtypes, varied prognoses, and differential treatment responses. Understanding the molecular landscape and identifying therapeutic targets, such as trophoblast cell-surface antigen 2 (TROP2), is vital. TROP2 is notably overexpressed in breast cancer, playing a significant role in tumor growth, invasion, metastasis, and treatment resistance. While significant progress has been made in targeting TROP2 in breast cancer, several challenges and knowledge gaps remain. These challenges include the heterogeneity of TROP2 expression within breast cancer subtypes, resistance to its targeted therapies, potential off-target effects, limited therapeutic agents, and identifying optimal combination treatments. Integrating findings from clinical trials into clinical practice further complicates the landscape. This review article delves deep into TROP2 in breast cancer, highlighting its expression patterns, clinical implications, and therapeutic advancements. By understanding the role of TROP2, we can pave the way for personalized treatments, and transform the landscape of breast cancer care.