bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulatory agilities impacting review timelines for Pfizer/BioNTech’s BNT162b2 mRNA COVID-19 vaccine: a retrospective study
Authors: Patel Prisha , Macdonald Judith C. , Boobalan Jayanthi , Marsden Matthew , Rizzi Ruben , Zenon Marianne , Ren Jinma , Chu Haitao , Cappelleri Joseph C. , Roychoudhury Satrajit , O’Brien Julie , Izaki-Lee Konoha , Boyce Donna
Published: November 2023

The appropriate use of regulatory agilities has the potential to accelerate regulatory review, utilize resources more efficiently and deliver medicines and vaccines more rapidly, all without compromising quality, safety and efficacy. This was clearly demonstrated during the COVID-19 pandemic where regulators and industry rapidly adapted to ensure continued supply of existing critical medicines and review and approve new innovative medicines. In this retrospective study, we analyze the impact of regulatory agilities on the review and approval of Pfizer/BioNTech’s BNT162b2 mRNA COVID-19 Vaccine globally using regulatory approval data from 73 country/regional approvals. We report on the critical role of reliance and provide evidence that demonstrates reliance approaches and certain regulatory agilities reduced review times for the COVID-19 vaccine. These findings support the case for more widespread implementation of regulatory agilities and demonstrate the important role of such approaches to improve public health outcomes.
Causal associations between gut microbiota and primary biliary cholangitis: a bidirectional two-sample Mendelian randomization study
Authors: Zhang Jiahao , Wu Gefeng , Tang Yuhong , Liu Huanxiang , Ge Xinyu , Peng Rui , Cao Jun , Tu Daoyuan , Su Bingbing , Jin Shengjie , Jiang Guoqing , Zhang Chi , Bai Dousheng
Published: November 2023

Background

Previous studies have suggested an association between gut microbiota and primary biliary cholangitis (PBC). Nonetheless, the causal relationship between gut microbiota and PBC risk remains unclear.

Methods

A bidirectional two-sample Mendelian Randomization (MR) study was employed using summary statistical data for gut microbiota and PBC from the MiBioGen consortium and Genome-Wide Association Studies (GWAS) database to investigate causal relationships between 211 gut microbiota and PBC risk. Inverse variance weighted (IVW) method was the primary analytical approach to assess causality, and the pleiotropy and heterogeneity tests were employed to verify the robustness of the findings. Additionally, we performed reverse MR analyses to investigate the possibility of the reverse causal association.

Results

The IVW method identified five gut microbiota that demonstrated associations with the risk of PBC. Order Selenomonadales [odds ratio (OR) 2.13, 95% confidence interval (CI) 1.10–4.14, p = 0.03], Order Bifidobacteriales (OR 1.58, 95% CI 1.07–2.33, p = 0.02), and Genus Lachnospiraceae_UCG_004 (OR 1.64, 95%CI 1.06–2.55, p = 0.03) were correlated with a higher risk of PBC, while Family Peptostreptococcaceae (OR 0.65, 95%CI 0.43–0.98, p = 0.04) and Family Ruminococcaceae (OR 0.33, 95%CI 0.15–0.72, p = 0.01) had a protective effect on PBC. The reverse MR analysis demonstrated no statistically significant relationship between PBC and these five specific gut microbial taxa.

Conclusion

This study revealed that there was a causal relationship between specific gut microbiota taxa and PBC, which may provide novel perspectives and a theoretical basis for the clinical prevention, diagnosis, and treatment of PBC.
Analysis of the mRNA export protein ZC3H11A in HCMV infection and pan-cancer
Authors: Li Jiawen , Song Min , Liu Zhen , Nan Fulong , Wang Bin , Qian Dongmeng , Hu Ming
Published: November 2023

Background

We have previously reported that human cytomegalovirus (HCMV) infection could promote the progression of glioma. Here we discovered a stress-induced nuclear protein ZC3H11A (ZC3) through high-throughput sequencing after HCMV infection, which has been reported recently by our research group in regulating mRNA export under stress conditions. And also, a thorough analysis of ZC3 in pan-cancer and the omics data of ZC3 are yet to be conducted.

Methods

The transcriptomes of glioma cells after HCMV infection were assessed by RNA sequencing. ZC3 mRNA and protein level following HCMV infection were validated and measured by qRT-PCR and Western-blot. The RNA sequencing and protein expression information of ZC3 across pan-cancer were analyzed and visualized by R packages. The localization of ZC3 protein was assessed by IHC images from HPA. The ZC3 proteomics and transcriptomics data in different cancers were extracted through the CPTAC data portal, and comparisons were conducted with a Python script. The genetic alteration, survival prognosis, immune infiltration analysis of ZC3 in pan-cancer were analyzed by cBioPortal, TCGA, and TIMER2 databases. The protein interaction networks were revealed by STRING, GEPIA2 and TCGA.

Results

Genes in mRNA processing pathways were upregulated after HCMV infection and ZC3 expression in mRNA and protein level was validated. We also discovered that the status of ZC3 were generally at high levels in cancers, although varied among different cancer types. ZC3 protein in tumor cells localized to the nuclear whereas in normal cells it was mainly found in cytoplasmic/membranous. However, from ZC3 proteomics and transcriptomics data in some cancer types, the increase in ZC3 protein was not accompanied by a significant elevation in mRNA level. Additionally, our analysis indicated that elevated ZC3 expression was primarily linked to a negative prognosis in majority cancers but still varied depending on the cancer types. Our annotation analysis suggested that ZC3-related proteins are mainly involved in mRNA processing clusters.

Conclusion

We demonstrated that ZC3 significantly impacted by HCMV infection in gliomas. Furthermore, we identified a set of genes exhibiting analogous expression patterns to ZC3H11A in TCGA pan-cancer cohorts, implying a potential functional role for ZC3H11A in mRNA processing. Our study provided valuable insights into the role of a new mRNA export protein ZC3 in HCMV infection and pan-cancer progression. These results lay the foundation for our next research on the regulatory mechanism of ZC3 in virus-infected tumors.
Harnessing sulfate-reducing bacteria with plants growing to revitalize metal-tainted coal mine soils in Midwest China: metal sequestration performance, ecological networking interaction, and functional enzymatic prediction
Authors: Yang Zhendong , Wu Qihong , Liu Zhenghua , Qi Xiang , Zhang Zhenyu , He Miao , Peng Cong , Zeng Li , Wang Jing , Li Fan , Yang Zhaoyue , Yin Huaqun
Published: November 2023

Heavy metal contamination from coal mining calls for advanced bioremediation, i.e., using sulfate-reducing bacteria (SRB) technology. Yet, the interaction of SRB with native soil microbiota during metal sequestration, especially in the presence of plants, remains ambiguous. In this study, we assessed the metal sequestration capabilities, ecological network interactions, and enzymatic functions in soils treated with a predominant SRB consortium, mainly Desulfovibrio (14 OTUs, 42.15%) and Desulfobulbus (7 OTUs, 42.27%), alongside Acacia dealbata (AD) and Pisum sativum (PS) plants. The SRB consortium notably enhanced the immobilization of metals such as Zn, Cu, As, and Pb in soil, with the conversion of metals to residual forms rising from 23.47 to 75.98%. Plant inclusion introduced variability, potentially due to changes in root exudates under metal stress. While AD flourished, PS demonstrated significant enhancement in conjunction with SRB, despite initial challenges. Comprehensive microbial analyses revealed the pivotal role of SRB in influencing microbial networking, underpinning critical ecological links. This interplay between plants and SRB not only enhanced microbial diversity but also enriched soil nutrients. Further, enzymatic assessments, highlighting enzymes like NADH:ubiquinone reductase and non-specific serine/threonine protein kinase, reinforced contribution of SRB to energy metabolism and environmental resilience of the entire soil microbial community. Overall, this research underscores the potential of SRB-driven bioremediation in revitalizing soils affected by coal mining.
Retinal ganglion cell-inner plexiform layer, white matter hyperintensities, and their interaction with cognition in older adults
Authors: Wang Ruilin , Wu Xinmao , Zhang Zengyi , Cao Le , Kwapong William Robert , Wang Hang , Tao Wendan , Ye Chen , Liu Junfeng , Wu Bo
Published: November 2023

Purpose

We explored the interaction of optical coherence tomography (OCT) parameters and white matter hyperintensities with cognitive measures in our older adult cohort.

Methods

This observational study enrolled participants who underwent a comprehensive neuropsychological battery, structural 3-T brain magnetic resonance imaging (MRI), visual acuity examination, and OCT imaging. Cerebral small vessel disease (CSVD) markers were read on MR images; lacune, cerebral microbleeds (CMB), white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS), were defined according to the STRIVE standards. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses (μm) were measured on the OCT tool.

Results

Older adults with cognitive impairment (CI) showed lower RNFL (p = 0.001), GCIPL (p = 0.009) thicknesses, and lower hippocampal volume (p = 0.004) when compared to non-cognitively impaired (NCI). RNFL (p = 0.006) and GCIPL thicknesses (p = 0.032) correlated with MoCA scores. GCIPL thickness (p = 0.037), total WMH (p = 0.003), PWMH (p = 0.041), and DWMH (p = 0.001) correlated with hippocampal volume in our older adults after adjusting for covariates. With hippocampal volume as the outcome, a significant interaction (p < 0.05) between GCIPL and PWMH and total WMH was observed in our older adults.

Conclusion

Both GCIPL thinning and higher WMH burden (especially PWMH) are associated with hippocampal volume and older adults with both pathologies are more susceptible to subclinical cognitive decline.
Gamma oscillations in visual statistical learning correlate with individual behavioral differences
Authors: Sáringer Szabolcs , Fehér Ágnes , Sáry Gyula , Kaposvári Péter
Published: November 2023

Statistical learning is assumed to be a fundamentally general sensory process across modalities, age, other cognitive functions, and even species. Despite this general role, behavioral testing on regularity acquisition shows great variance among individuals. The current study aimed to find neural correlates of visual statistical learning showing a correlation with behavioral results. Based on a pilot study, we conducted an EEG study where participants were exposed to associated stimulus pairs; the acquisition was tested through a familiarity test. We identified an oscillation in the gamma range (40–70 Hz, 0.5–0.75 s post-stimulus), which showed a positive correlation with the behavioral results. This change in activity was located in a left frontoparietal cluster. Based on its latency and location, this difference was identified as a late gamma activity, a correlate of model-based learning. Such learning is a summary of several top-down mechanisms that modulate the recollection of statistical relationships such as the capacity of working memory or attention. These results suggest that, during acquisition, individual behavioral variance is influenced by dominant learning processes which affect the recall of previously gained information.
Endovascular treatment of middle cerebral artery aneurysms: current status and future prospects
Authors: Zhou Zibo , Lan Wenjing , Yu Jinlu
Published: November 2023

Middle cerebral artery (MCA) aneurysms are complex and widely distributed throughout the course of the MCA. Various types of aneurysms can occur in the MCA. Ruptured as well as unruptured MCA aneurysms may require treatment to avoid bleeding or rebleeding. Currently, clipping is regarded as the first-line choice for the treatment of MCA aneurysms. However, endovascular treatment (EVT) is emerging as an alternative treatment in selected cases. EVT techniques vary. Therefore, it is necessary to review EVT for MCA aneurysms. In this review, the following issues were discussed: MCA anatomy and anomalies, classifications of MCA aneurysms, the natural history of MCA aneurysms, EVT status and principle, deployments of traditional coiling techniques and flow diverters (FDs), and deployments and prospects of intrasaccular flow disruptors and stent-like devices. According to the review and our experience, traditional coiling EVT is still the preferred therapy for most MCA aneurysms. FD deployment can be used in selective MCA aneurysms. Parent artery occlusion (PAO) can be used to treat distal MCA aneurysms. In addition, new devices can be used to treat MCA aneurysms, such as intrasaccular flow disruptors and stent-like devices. In general, EVT is gaining popularity as an alternative treatment option; however, there is still a lack of evidence regarding EVT, and longer-term data are not currently available for most EVT devices.
Association between bronchopulmonary dysplasia and death or neurodevelopmental impairment at 3 years in preterm infants without severe brain injury
Authors: Li Wenli , Wang Yong , Song Juan , Zhang Chen , Xu Yiran , Xu Falin , Wang Xiaoyang , Zhu Changlian
Published: November 2023

Objective

We investigated the association between bronchopulmonary dysplasia (BPD) and 3 years death or neurodevelopmental impairment (NDI) in very preterm infants without severe brain injury.

Method

Our prospective cohort study recruited preterm infants who were born prior to 32 weeks of gestational age and survived in the neonatal intensive care unit until 36 weeks of corrected age. Upon reaching 3 years of age, each infant was assessed for death or NDI such as cerebral palsy, cognitive deficit, hearing loss, and blindness. Correlations between BPD and death or NDI were determined using multiple logistic regression analyses adjusted for confounding factors.

Result

A total of 1,417 infants without severe brain injury who survived until 36 weeks of corrected age were initially enrolled in the study. Over the study period, 201 infants were lost to follow-up and 5 infants were excluded. Our final dataset, therefore, included 1,211 infants, of which 17 died after 36 weeks of corrected age and 1,194 were followed up to 3 years of age. Among these infants, 337 (27.8%) developed BPD. Interestingly, by 3 years of age, BPD was demonstrated to be independently associated with death or NDI, with an adjusted odds ratio of 1.935 (95% confidence interval: 1.292–2.899, p = 0.001), in preterm infants without severe neonatal brain injury.

Conclusion

Our findings indicate that BPD is strongly associated with death or NDI in preterm infants without severe neonatal brain injury at 3 years of age. Further research is needed to understand the mechanisms linking the development of BPD with death or NDI and whether appropriate treatment of BPD may ameliorate or prevent the development of neurological complications.
Results of longitudinal Nutri-D study: factors influencing winter and summer vitamin D status in a Caucasian population
Authors: Hribar Maša , Pravst Igor , Pogačnik Tina , Žmitek Katja
Published: November 2023

Introduction

Inadequate vitamin D status is a worldwide public health issue. In humans, vitamin D status is affected by diet, and even more by exposure to ultraviolet B (UVB) light and consequential endogenous synthesis. Various personal and environmental factors influence endogenous synthesis. Factors affecting vitamin D status were investigated in a prospective longitudinal cohort study with a summer and winter observation period.

Methods

The final sample included 292 adults, of those 111 (38%) males and 181 (62%) females, with a mean age of 38.2 (±11.8) years from Slovenia who were not supplementing vitamin D. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured in both periods; vitamin D intake, self-reported body mass index (BMI), and protective behaviors against sun were also recorded. Other measured parameters included measurements of constitutive skin color using the objective individual typology angle (ITA), and difference in the melanin index (ΔMI) for assessment of objective sun exposure.

Results

In winter a high prevalence (63.4%) of insufficient vitamin D status (< 50 nmoL/L) was observed with higher odds ratios (OR) for insufficiency in those with a higher BMI and light ITA. During summer, insufficiency prevalence was low (5.5%), but half of the participants (50.0%) had suboptimal 25(OH)D concentration (< 75 nmol/L). In summer OR for suboptimal status were higher in those with obesity, lower ΔMI, light ITA, low vitamin D intake, and protective clothing behaviors.

Conclusion

Using a series of measures, we showed that vitamin D status is hugely affected by several personal factors such as BMI, ITA, vitamin D intake, ΔMI, and protective behavior against the sun. This conclusion questions the usefulness of generalized population-level recommendations since personal factors are a major predictor of vitamin D status.
Clinical manifestations of pain in patients suffering from COVID-19 infected with Delta variant of SARS-Cov-2
Authors: Mohammadian Erdi Ali , Zakavi Minoo , Amani Mohammad , Fooladi Shahnaz , Abedi Ali
Published: November 2023

Background

Although respiratory presentations of COVID-19 predominate, the extra pulmonary involvement such as muscle pain, joint pain, headache, back pain, abdominal pain, and sore throat are usually included in the clinical picture of the disease and it can be considered as an early symptom in COVID-19 patients. The objective of the present study was to determine the frequency, localization, and intensity of pain in COVID-19 patients hospitalized in Imam Khomeini hospital of Ardabil, Iran.

Methods and materials

A prospective study was conducted on 388 COVID-19 patients who were admitted to Ardabil, Iran's Imam Khomeini Central Hospital between March and June 2020. Demographic characteristics of patients and general clinical manifestations of pain at the first admission to the hospital, localization, severity, and continuity of pain were evaluated by using a questionnaire and the Visual Analog Scale (VAS).

Findings

For the 388 (51.3% female, age 47.25 + 15.55 and 48.7% male, age 50.12 + 15.26 years old) Delta COVID-19 patients, the median duration from illness onset to hospitalization was 5 days. Patients' complaints included 89.7% fatigue, 85.56% cough, 67.8% fever, 64.17% loss of taste, 63.91% loss of smell, 37.9% diarrhea, and 11.85% skin lesions, respectively. Pain including muscle, joint, bone and low back pain was the chief complaint in both sexes. Pain complaints had started on average 5 days before admission. The distribution of pain was 313 (80.41%) muscle pain, 264 (70.61%) joint pain, 299 (77.1%) headache, 208 (53.6%) low back pain, 312 (80.41%) sore throat, and 157 (40.46%) abdominal pain. Out of 388 patients, 292 (75.25%) had diffuse pain.

Conclusions

Acute pain including myalgia, sore throat, arthralgia, headache, and low back pain were the most common symptoms of COVID-19 patients. Viral diseases such as COVID-19 may trigger the immune system to release cytokines that lead to muscle pain. Patients presenting to healthcare centers with complaints of pain should be evaluated for suspected COVID-19 infection.
Maternal pre-pregnancy obesity affects the uncinate fasciculus white matter tract in preterm infants
Authors: Lee Joo Young , Lee Hyun Ju , Jang Yong Hun , Kim Hyuna , Im Kiho , Yang Seung , Hoh Jeong-Kyu , Ahn Ja-Hye
Published: November 2023

Background

A growing body of evidence suggests an association between a higher maternal pre-pregnancy body mass index (BMI) and adverse long-term neurodevelopmental outcomes for their offspring. Despite recent attention to the effects of maternal obesity on fetal and neonatal brain development, changes in the brain microstructure of preterm infants born to mothers with pre-pregnancy obesity are still not well understood. This study aimed to detect the changes in the brain microstructure of obese mothers in pre-pregnancy and their offspring born as preterm infants using diffusion tensor imaging (DTI).

Methods

A total of 32 preterm infants (born to 16 mothers with normal BMI and 16 mothers with a high BMI) at <32 weeks of gestation without brain injury underwent brain magnetic resonance imaging at term-equivalent age (TEA). The BMI of all pregnant women was measured within approximately 12 weeks before pregnancy or the first 2 weeks of gestation. We analyzed the brain volume using a morphologically adaptive neonatal tissue segmentation toolbox and calculated the major white matter (WM) tracts using probabilistic maps of the Johns Hopkins University neonatal atlas. We investigated the differences in brain volume and WM microstructure between preterm infants of mothers with normal and high BMI. The DTI parameters were compared among groups using analysis of covariance adjusted for postmenstrual age at scan and multiple comparisons.

Results

Preterm infants born to mothers with a high BMI showed significantly increased cortical gray matter volume (p = 0.001) and decreased WM volume (p = 0.003) after controlling for postmenstrual age and multiple comparisons. We found a significantly lower axial diffusivity in the uncinate fasciculus (UNC) in mothers with high BMI than that in mothers with normal BMI (1.690 ± 0.066 vs. 1.762 ± 0.101, respectively; p = 0.005).

Conclusion

Our study is the first to demonstrate that maternal obesity impacts perinatal brain development patterns in preterm infants at TEA, even in the absence of apparent brain injury. These findings provide evidence for the detrimental effects of maternal obesity on brain developmental trajectories in offspring and suggest potential neurodevelopmental outcomes based on an altered UNC WM microstructure, which is known to be critical for language and social–emotional functions.
Peripheral muscle fractional tissue oxygen extraction in stable term and preterm neonates during the first 24 h after birth
Authors: Wolfsberger Christina H. , Höller Nina , Baik-Schneditz Nariae , Schwaberger Bernhard , Suppan Ena , Mileder Lukas , Avian Alexander , Urlesberger Berndt , Pichler Gerhard
Published: November 2023

Background

Peripheral muscle fractional tissue oxygen extraction (pFTOE) represents the relative extraction of oxygen from the arterial to venous compartment, providing information about dynamic changes of oxygen delivery and oxygen consumption. The aim of the present study was to establish reference values of pFTOE during the first 24 h after birth in stable term and late preterm neonates.

Methods

The present study is a post-hoc analysis of secondary outcome parameters of prospective observational studies. Only stable neonates without infection, asphyxia and any medical support were eligible for our analysis to obtain normal values. For measurements of peripheral muscle tissue oxygenation index (pTOI) during the first 24 h after birth in term and preterm neonates, the NIRO200/NIRO200NX was used. Arterial oxygen saturation (SpO2) was obtained by pulse oximetry. pFTOE was calculated out of pTOI and SpO2: pFTOE = (SpO2-pTOI)/SpO2. Measurements of neonates were stratified into four groups according to their respective measurement time point (6 h periods) after birth. Term and preterm neonates were analyzed separately. Mean values of measurements during the first time period (0–6 h after birth) were compared to measurements of the following time periods (second = 7–12 h, third = 13–18 h, fourth = 19–24 h after birth).

Results

Two-hundred-fourty neonates (55 term and 185 late preterm neonates) had at least one peripheral muscle NIRS measurements within the first 24 h after birth. Mean gestational age and birth weight were 39.4 ± 1.1 weeks and 3360 (2860–3680)g in term neonates and 34.0 ± 1.4 weeks and 2060 (1750–2350)g in preterm neonates, respectively. In term neonates pFTOE was 0.264 (0.229–0.300), 0.228 (0.192–0.264), 0.237 (0.200–0.274) and 0.220 (0.186–0.254) in the first, second, third and fourth time period. In preterm neonates pFTOE was 0.229 (0.213–0.246), 0.225 (0.209–0.240), 0.226 (0.210–0.242) and 0.238 (0.222–0.255) in the first, second, third and fourth time period. pFTOE did not show any significant changes between the time periods, neither in term nor in preterm neonates.

Conclusion

We provide reference values of pFTOE for stable term and late preterm neonates within the first 24 h after birth, which were stable when comparing four 6-h periods. These normal values are of great need for interpreting pFTOE in scientific context as well as for potential future clinical applications.
Initial therapeutic target attainment of perampanel in pediatric patients with epilepsy
Authors: Yu Lingyan , Chen Meng , Liu Jieqiong , Yu Zhenwei , Feng Jianhua , Dai Haibin
Published: November 2023

Perampanel is a promising option for the treatment of pediatric epilepsy, but its plasma concentration varies among patients. This retrospective study aimed to investigate the initial target attainment of perampanel plasma concentration in pediatric patients with epilepsy in China. Inpatients admitted from January 2020 to December 2021 in a tertiary hospital were retrospectively included according to pre-set criteria. Demographic characteristics of patients and dosing strategies and therapeutic drug monitoring results were collected. A total of 137 pediatric patients (84 females and 53 males, aged from 0.6 to 16.4 years) were include for analysis. The perampanel concentrations varied greatly from 60 to 1,560 mg/L among patients, but 89.8% had suitable perampanel concentrations (100–1,000 ng/mL). The concomitant use of enzyme-inductive antiepileptic drugs (AEDs) was the only identified risk factor associated with target nonattainment (OR = 5.92, 95% confidence interval 1.68–20.9). Initial perampanel target attainment in pediatric patients is satisfactory. Routine therapeutic drug monitoring to achieved the suggested concentration range for these patients may be unnecessary, except for those receiving combined enzyme inductive AEDs.
Antidepressant effect of bright light therapy on patients with Alzheimer’s disease and their caregivers
Authors: Mei Xi , Zou Chenjun , Si Zizhen , Xu Ting , Hu Jun , Wu Xiangping , Zheng Chengying
Published: November 2023

Background: As a non-pharmacologic treatment, bright light therapy (BLT) is often used to improve affective disorders and memory function. In this study, we aimed to determine the effect of BLT on depression and electrophysiological features of the brain in patients with Alzheimer’s disease (AD) and their caregivers using a light-emitting diode device of 14000 lux.

Methods: A 4-week case-control trial was conducted. Neuropsychiatric and electroencephalogram (EEG) examination were evaluated at baseline and after 4 weeks. EEG power in delta (1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), and beta (12–30 Hz) bands was calculated for our main analysis. Demographic and clinical variables were analyzed using Student’s t test and the chi-square test. Pearson’s correlation was used to determine the correlation between electrophysiological features, blood biochemical indicators, and cognitive assessment scale scores.

Results: In this study, 22 in-patients with AD and 23 caregivers were recruited. After BLT, the Hamilton depression scale score decreased in the fourth week. Compared with the age-matched controls of their caregivers, a higher spectral power at the lower delta and theta frequencies was observed in the AD group. After BLT, the EEG power of the delta and theta frequencies in the AD group decreased. No change was observed in blood amyloid concentrations before and after BLT.

Conclusion: In conclusion, a 4-week course of BLT significantly suppressed depression in patients with AD and their caregivers. Moreover, changes in EEG power were also significant in both groups.
The association between aspirin use and immune-related adverse events in specific cancer patients receiving ICIs therapy: analysis of the FAERS database
Authors: Yang Huaju , Liu Zheran , Li Ruidan , Huang Rendong , Peng Xingchen
Published: November 2023

Background: The promise of immune checkpoint inhibitors (ICIs) therapy in cancer treatment is tempered by the occurrence of immune-related adverse events (irAEs). Many patients undergoing ICIs also take aspirin, but the association between aspirin and irAEs is not well understood.

Methods: This study analyzed adverse reaction data associated with the use of ICIs in the US Food and Drug Administration (FDA) Adverse Event Reporting System FDA Adverse Event Reporting System database, from the approval date of each drug until 1 October 2022. Multivariate logistic regression was employed to assess the association of aspirin use with irAEs in patients receiving ICIs.

Results: The results indicated that aspirin use was associated with an increased risk of irAEs in a pan-cancer analysis, with a more pronounced association in specific cancer types such as lung cancer, mesothelioma, and pancreatic cancer. However, in lymphoma, aspirin use was associated with a reduced risk of irAEs. Furthermore, aspirin use was associated with an increased risk of certain irAEs, such as anemia, colitis, myocarditis, myositis, pancreatitis, pericarditis, and pneumonia, while it was associated with a reduced risk of rash, Stevens-Johnson syndrome, and thyroiditis.

Conclusion: This study has unveiled an association between aspirin use and irAEs in cancer patients receiving ICIs therapy, emphasizing the need for individualized consideration of patients’ medication history when devising cancer treatment plans to enhance efficacy and reduce risks.
Cellular crosstalk of macrophages and therapeutic implications in non-small cell lung cancer revealed by integrative inference of single-cell transcriptomics
Authors: Wu Lei , Xia Wenying , Hua Yiting , Fan Kun , Lu Yanfei , Wang Min , Jin Yuexinzi , Zhang Wei , Pan Shiyang
Published: November 2023

Introduction: Non-small cell lung cancer (NSCLC) exhibits heterogeneity with diverse immune cell infiltration patterns that can influence tumor cell behavior and immunotherapy. A comprehensive characterization of the tumor microenvironment can guide precision medicine.

Methods: Here, we generated a single-cell atlas of 398170 cells from 52 NSCLC patients, and investigated the imprinted genes and cellular crosstalk for macrophages. Subsequently, we evaluated the effect of tumor cells on macrophages and verified the expression of marker genes using co-culture experiments, flow cytometry and RT-qPCR assays.

Results: Remarkable macrophage adaptability to NSCLC environment was observed, which contributed to generating tumor-associated macrophages (TAMs). We identified 5 distinct functional TAM subtypes, of which the majority were SELENOP-positive macrophages, with high levels of SLC40A1 and CCL13. The TAMs were also involved in mediating CD8+ T cell activity and form intercellular interaction with cancer cells, as indicated by receptor-ligand binding. Indirect coculture of tumor cells SPC-A1 and THP-1 monocytes, produced M2-like TAMs that highly expressed several markers of SELENOP-positive macrophages. The abundance of this type TAMs seemed to be associated with poorer overall survival rates [hazard ratio (HR) = 1.34, 95% confidence interval (CI) = 0.98-1.83, p = 0.068] based on deconvolution of TCGA-LUAD dataset.

Discussion: In summary, we provided a high-resolution molecular resource of TAMs, and displayed the acquired properties in the tumor microenvironment. Dynamic crosstalk between TAMs and tumor cells via multiple ligand-receptor pairs were revealed, emphasizing its role in sustaining the pro-tumoral microenvironment and its implications for cancer therapy.
Mechanosensitive channels in lung disease
Authors: Zheng Mengning , Borkar Niyati A. , Yao Yang , Ye Xianwei , Vogel Elizabeth R. , Pabelick Christina M. , Prakash Y. S.
Published: November 2023

Mechanosensitive channels (MS channels) are membrane proteins capable of responding to mechanical stress over a wide dynamic range of external mechanical stimuli. In recent years, it has been found that MS channels play an important role as “sentinels” in the process of cell sensing and response to extracellular and intracellular force signals. There is growing appreciation for mechanical activation of ion channels and their subsequent initiation of downstream signaling pathways. Members of the transient receptor potential (TRP) superfamily and Piezo channels are broadly expressed in human tissues and contribute to multiple cellular functions. Both TRP and Piezo channels are thought to play key roles in physiological homeostasis and pathophysiology of disease states including in the lung. Here, we review the current state of knowledge on the expression, regulation, and function of TRP and Piezo channels in the context of the adult lung across the age spectrum, and in lung diseases such as asthma, COPD and pulmonary fibrosis where mechanical forces likely play varied roles in the structural and functional changes characteristic of these diseases. Understanding of TRP and Piezo in the lung can provide insights into new targets for treatment of pulmonary disease.
Deciphering the mechanisms, hormonal signaling, and potential applications of endophytic microbes to mediate stress tolerance in medicinal plants
Authors: Pandey Praveen , Tripathi Arpita , Dwivedi Shweta , Lal Kanhaiya , Jhang Tripta
Published: November 2023

The global healthcare market in the post-pandemic era emphasizes a constant pursuit of therapeutic, adaptogenic, and immune booster drugs. Medicinal plants are the only natural resource to meet this by supplying an array of bioactive secondary metabolites in an economic, greener and sustainable manner. Driven by the thrust in demand for natural immunity imparting nutraceutical and life-saving plant-derived drugs, the acreage for commercial cultivation of medicinal plants has dramatically increased in recent years. Limited resources of land and water, low productivity, poor soil fertility coupled with climate change, and biotic (bacteria, fungi, insects, viruses, nematodes) and abiotic (temperature, drought, salinity, waterlogging, and metal toxicity) stress necessitate medicinal plant productivity enhancement through sustainable strategies. Plants evolved intricate physiological (membrane integrity, organelle structural changes, osmotic adjustments, cell and tissue survival, reclamation, increased root-shoot ratio, antibiosis, hypersensitivity, etc.), biochemical (phytohormones synthesis, proline, protein levels, antioxidant enzymes accumulation, ion exclusion, generation of heat-shock proteins, synthesis of allelochemicals. etc.), and cellular (sensing of stress signals, signaling pathways, modulating expression of stress-responsive genes and proteins, etc.) mechanisms to combat stresses. Endophytes, colonizing in different plant tissues, synthesize novel bioactive compounds that medicinal plants can harness to mitigate environmental cues, thus making the agroecosystems self-sufficient toward green and sustainable approaches. Medicinal plants with a host set of metabolites and endophytes with another set of secondary metabolites interact in a highly complex manner involving adaptive mechanisms, including appropriate cellular responses triggered by stimuli received from the sensors situated on the cytoplasm and transmitting signals to the transcriptional machinery in the nucleus to withstand a stressful environment effectively. Signaling pathways serve as a crucial nexus for sensing stress and establishing plants’ proper molecular and cellular responses. However, the underlying mechanisms and critical signaling pathways triggered by endophytic microbes are meager. This review comprehends the diversity of endophytes in medicinal plants and endophyte-mediated plant-microbe interactions for biotic and abiotic stress tolerance in medicinal plants by understanding complex adaptive physiological mechanisms and signaling cascades involving defined molecular and cellular responses. Leveraging this knowledge, researchers can design specific microbial formulations that optimize plant health, increase nutrient uptake, boost crop yields, and support a resilient, sustainable agricultural system.
Artificial intelligence-driven systems engineering for next-generation plant-derived biopharmaceuticals
Authors: Parthiban Subramanian , Vijeesh Thandarvalli , Gayathri Thashanamoorthi , Shanmugaraj Balamurugan , Sharma Ashutosh , Sathishkumar Ramalingam
Published: November 2023

Recombinant biopharmaceuticals including antigens, antibodies, hormones, cytokines, single-chain variable fragments, and peptides have been used as vaccines, diagnostics and therapeutics. Plant molecular pharming is a robust platform that uses plants as an expression system to produce simple and complex recombinant biopharmaceuticals on a large scale. Plant system has several advantages over other host systems such as humanized expression, glycosylation, scalability, reduced risk of human or animal pathogenic contaminants, rapid and cost-effective production. Despite many advantages, the expression of recombinant proteins in plant system is hindered by some factors such as non-human post-translational modifications, protein misfolding, conformation changes and instability. Artificial intelligence (AI) plays a vital role in various fields of biotechnology and in the aspect of plant molecular pharming, a significant increase in yield and stability can be achieved with the intervention of AI-based multi-approach to overcome the hindrance factors. Current limitations of plant-based recombinant biopharmaceutical production can be circumvented with the aid of synthetic biology tools and AI algorithms in plant-based glycan engineering for protein folding, stability, viability, catalytic activity and organelle targeting. The AI models, including but not limited to, neural network, support vector machines, linear regression, Gaussian process and regressor ensemble, work by predicting the training and experimental data sets to design and validate the protein structures thereby optimizing properties such as thermostability, catalytic activity, antibody affinity, and protein folding. This review focuses on, integrating systems engineering approaches and AI-based machine learning and deep learning algorithms in protein engineering and host engineering to augment protein production in plant systems to meet the ever-expanding therapeutics market.
Validation of the factor structure of the Experiences Questionnaire using Exploratory Graph Analysis
Authors: Rader Lena , Drueke Barbara , Forster Saskia Doreen , Gauggel Siegfried , Mainz Verena
Published: November 2023

Introduction

Decentering describes the ability to shift the focus away from one’s subjective experience onto the experience itself. The Experiences Questionnaire (EQ) is a self-report measure that was developed to systematically assess changes in Decentering ability. Although several studies show the validity of the questionnaire, there are discrepancies between the factorial structure of the Decentering scale of the EQ (EQ-D) found in the initial study (one factor) and other studies (two factors). Therefore, the current study aimed to assess the dimensionality of the EQ-D using Exploratory Graph Analysis (EGA).

Methods

In total, 1,100 participants were recruited online (790 female, 307 male, 3 non-binary; age 18 to 65 years). Participants completed the EQ and the Rosenberg Self-esteem scale (RSES).

Results

The bootstrapped EGA results revealed a two-dimensional structure of the EQ-D (Factor 1: Distanced Perspective, DP; Factor 2: Accepting Self-perception, AS) with high structural and item stability (all items > 0.70). The two dimensions of the EQ-D showed a high internal consistency (DP: ω = 0.74; AS: ω = 0.86) and discriminant validity with the rumination items of the EQ. Furthermore, a high convergent validity of the EQ was established, as the AS factor exhibited a significantly stronger correlation with self-esteem than the DP factor (z = 7.98, p < 0.001), which aligns with theoretical considerations suggesting that the AS factor encompasses aspects of self-compassion alongside decentering. We also found measurement invariance of the DP and AS factor across age, gender and country but not for education.

Discussion

These results support the EQ’s validity, demonstrated in a larger sample with a new methodology, aligning with existing two-factor decentering models literature.
Familial aspects of fear of cancer recurrence: current insights and knowledge gaps
Authors: Faraji Aida , Dehghani Mohsen , Khatibi Ali
Published: November 2023

Fear of cancer recurrence is fear or worry about cancer recurrence or progress. Fear of recurrence can impact patients’ quality of life and wellbeing. Cancer survivors’ families support them practically and emotionally, making them a vital supplement for official healthcare. Given the well-established important role of the family in dealing with cancer, we compiled the studies that examined the relationship between family-related factors and fear of cancer recurrence (FCR) among cancer survivors (CSs). One of the foremost studies in this field is the FCR model presented by Mellon and colleagues, which included concurrent family stressors and family-caregiver FCR as factors linked to survivor FCR. Our goal was to prepare the ground for a family-based model of FCR that is more comprehensive than the one proposed by Mellon et al. sixteen years ago. The studies included those with samples of adult cancer survivors from different regions of the world. Most of the studies we reviewed are cross-sectional studies. We categorized family-related factors associated with survivor FCR into partner-related factors, including subgroups of disclosure to partner, cognitions of partner, and partner’s sources of support; parenthood-related factors, including having children and parenting stress; family-related factors, including living situation, family history of cancer, family’s perception of the illness, and family characteristics; and social interactions including social support, disclosure, social constraints, and attitudes of others. This review sheds light on how significant others of cancer survivors can affect and be affected by cancer-related concerns of survivors and emphasizes the necessity of further investigation of family-related factors associated with FCR.
Korean adolescents’ coping strategies on self-harm, ADHD, insomnia during COVID-19: text mining of social media big data
Authors: Do Ryemi , Kim Soyeon , Lim You Bin , Kim Su-Jin , Kwon Hyerim , Kim Jong-Min , Lee Sooyeon , Kim Bung-Nyun
Published: November 2023

Introduction

Since the Coronavirus disease 2019 (COVID-19), public safety measures, including social distancing and school closures, have been implemented, precipitating psychological difficulties and heightened online activities for adolescents. However, studies examining the impact of the pandemic on adolescent mental health and their coping strategies in Asian countries are limited. Further, most studies have used survey measures to capture mental health challenges so far. Accordingly, this study aimed to examine the psychological challenges South Korean adolescents experienced and their coping strategies during the pandemic using the Natural Language Processing (NLP) and Text mining (TM) technique on adolescents’ social media texts/posts.

Methods

The data were gathered from social media texts/posts such as online communities, Twitter, and personal blogs from January 1, 2019, to October 31, 2021. The 12,520,250 texts containing keywords related to adolescents’ common psychological difficulties reported during the pandemic, including self-harm, Attention-Deficit/Hyperactivity Disorders (ADHD), and insomnia, were analyzed by TM, NLP using information extraction, co-occurrence and sentiment analysis. The monthly frequency of the keywords and their associated words was also analyzed to understand the time trend.

Results

Adolescents used the word “self-harm” in their social media texts more frequently during the second wave of COVID-19 (August to September 2020). “Friends” was the most associated word with “self-harm.” While the frequency of texts with “Insomnia” stayed constant throughout the pandemic, the word “ADHD” was increasingly mentioned in social media. ADHD and insomnia were most frequently associated with ADHD medications and sleeping pills, respectively. Friends were generally associated with positive words, while parents were associated with negative words.

Conclusion

During COVID-19, Korean adolescents often expressed their psychological challenges on social media platforms. However, their coping strategies seemed less efficient to help with their difficulties, warranting strategies to support them in the prolonged pandemic era. For example, Korean adolescents shared psychological challenges such as self-harm with friends rather than their parents. They considered using medicine (e.g., sleeping pills and ADHD medication) as coping strategies for sleep and attention problems.
Statin for mood and inflammation among adult patients with major depressive disorder: an updated meta-analysis
Authors: Xiao Xue , Deng Hu , Li Peng , Sun Jifei , Tian Jing
Published: November 2023

Introduction

Several small sample-sized clinical trials have demonstrated a beneficial effect of statin on depressive mood among major depressive disorder (MDD) patients. However, observational studies have showed the increased risk of anxiety/depression with statin treatment. Therefore, we aimed to evaluate the effects of statin on depressive mood and inflammation status among MDD patients.

Methods

We performed an updated meta-analysis RCTs identified in systematic searches of PubMed, Cochrane library, Embase, ClinicalTrials.gov, CNKI, Wan fang, VIP, and SinoMed database (up to August 2023). The primary endpoint was the Hamilton depression rating scale (HDRS). The secondary endpoints were rate of response to treatment, remission rate, levels of C-reactive protein (CRP), cognition and blood lipid. We evaluated the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

Results

The search identified seven RCTs involving 448 patients with a median follow-up of 10.4 weeks (range, 6–12 weeks). Compared with selective serotonin reuptake inhibitors (SSRIs) alone, treatment with statin plus SSRIs was associated with a significantly decreased HDRS [mean difference (MD) = −2.79; 95% confidence interval (CI): −3.83 to −1.76] and C-reactive protein (MD = −0.42 mg/L; 95% CI: −0.53 to −0.12 mg/L), and decreased levels of lipid profiles (P < 0.05). Moreover, statin plus SSRIs was associated with a comparable rate of treatment response [relative risk (RR) = 1.26; 95% CI: 0.98 to 1.62], remission rate (RR = 1.33; 95% CI: 0.89 to 1.99). Meta-regression indicated that the follow-up period was a source of heterogeneity regarding the HDRS (r = 0.302, P = 0.041). The quality of evidence was rated as moderate for HDRS and response rate according to the GRADE.

Conclusion

Statin could safely and effectively improve the symptoms of depression and inflammation status among MDD patients.

Systematic review registration

https://inplasy.com/inplasy-2022-3-0016/, identifier INPLASY2022230016.