bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Mendelian randomization to assess host gene–gut microbiota correlations in patients with esophageal cancer
Authors: Zhang Zhenhu , Zhang Guodong , Huang Zhulan , Shi Yamin , Wang Dong
Published: December 2023

Background

Increasing evidence suggests that esophageal cancer (ESCA) may be correlated with gut flora. However, their causal connection remains unclear. This study aimed to evaluate potential causal linkages and gene–gut microbiome associations between the gut microbiota and ESCA using Mendelian randomization (MR).

Methods

We analyzed the data using genome-wide association studies. The exposure factor and outcome variable were the gut microbiota and ESCA, respectively. The MR-Egger method, weighted median, inverse-variance weighted method, heterogeneity test, sensitivity analysis, and multiplicity analysis were used for the MR analysis. And it was validated using an external dataset. Further meta-analysis was performed to validate the robustness of this relationship. Finally, we annotated single nucleotide polymorphisms in the gut microbiota that were causally associated with ESCA to explore possible host gene-gut microbiota correlations in patients with ESCA.

Results

We identified four species with potential associations with ESCA. Three of these species had a negative causal relationship with ESCA (odds ratio (OR): 0.961; 95% confidence interval (CI): 0.923–0.971; p = 0.047 for Romboutsia; OR: 0.972; 95% CI: 0.921–0.961; p = 0.018 for Lachnospira; OR: 0.948; 95% CI: 0.912–0.970; p = 0.032 for Eubacterium). A positive causal relationship was observed between one bacterial group and ESCA (OR: 1.105; 95% CI: 1.010–1.072; p = 0.018 for Veillonella). External datasets show the same trend. This is further supported by meta-analysis. None of the data showed pleiotropy, and leave-one-out analysis indicated the reliability of these findings. The gut microbiomes of patients with ESCA may correlate with the 19 identified genes.

Conclusion

Our data indicate a potential causal link between these four gut bacteria and ESCA and identify a correlation between host genes and gut microbiota in ESCA, offering novel therapeutic options.
Advances in machine learning-based bacteria analysis for forensic identification: identity, ethnicity, and site of occurrence
Authors: Xu Geyao , Teng Xianzhuo , Gao Xing-Hua , Zhang Li , Yan Hongwei , Qi Rui-Qun
Published: December 2023

When faced with an unidentified body, identifying the victim can be challenging, particularly if physical characteristics are obscured or masked. In recent years, microbiological analysis in forensic science has emerged as a cutting-edge technology. It not only exhibits individual specificity, distinguishing different human biotraces from various sites of occurrence (e.g., gastrointestinal, oral, skin, respiratory, and genitourinary tracts), each hosting distinct bacterial species, but also offers insights into the accident’s location and the surrounding environment. The integration of machine learning with microbiomics provides a substantial improvement in classifying bacterial species compares to traditional sequencing techniques. This review discusses the use of machine learning algorithms such as RF, SVM, ANN, DNN, regression, and BN for the detection and identification of various bacteria, including Bacillus anthracis, Acetobacter aceti, Staphylococcus aureus, and Streptococcus, among others. Deep leaning techniques, such as Convolutional Neural Networks (CNN) models and derivatives, are also employed to predict the victim’s age, gender, lifestyle, and racial characteristics. It is anticipated that big data analytics and artificial intelligence will play a pivotal role in advancing forensic microbiology in the future.
Ethorobotic rats for rodent behavioral research: design considerations
Authors: Siddall Robert
Published: December 2023

The development of robots as tools for biological research, sometimes termed “biorobotics”, has grown rapidly in recent years, fueled by the proliferation of miniaturized computation and advanced manufacturing techniques. Much of this work is focused on the use of robots as biomechanical models for natural systems. But, increasingly, biomimetic robots are being employed to interact directly with animals, as component parts of ethology studies in the field and behavioral neuroscience studies in the laboratory. While it has been possible to mechanize and automate animal behavior experiments for decades, only recently has there been the prospect of creating at-scale robotic animals containing the sensing, autonomy and actuation necessary for complex, life-like interaction. This not only opens up new avenues of enquiry, but also provides important ways to improve animal welfare, both by reducing or replacing the use of animal subjects, and by minimizing animal distress (if robots are used judiciously). This article will discuss the current state of the art in robotic lab rats, providing perspective on where research could be directed to enable the safe and effective use of biorobotic animals.
Comparison of state-of-the-art deep learning architectures for detection of freezing of gait in Parkinson’s disease
Authors: Klaver Emilie Charlotte , Heijink Irene B. , Silvestri Gianluigi , van Vugt Jeroen P. P. , Janssen Sabine , Nonnekes Jorik , van Wezel Richard J. A. , Tjepkema-Cloostermans Marleen C.
Published: December 2023

Introduction

Freezing of gait (FOG) is one of the most debilitating motor symptoms experienced by patients with Parkinson’s disease (PD). FOG detection is possible using acceleration data from wearable sensors, and a convolutional neural network (CNN) is often used to determine the presence of FOG epochs. We compared the performance of a standard CNN for the detection of FOG with two more complex networks, which are well suited for time series data, the MiniRocket and the InceptionTime.

Methods

We combined acceleration data of people with PD across four studies. The final data set was split into a training (80%) and hold-out test (20%) set. A fifth study was included as an unseen test set. The data were windowed (2 s) and five-fold cross-validation was applied. The CNN, MiniRocket, and InceptionTime models were evaluated using a receiver operating characteristic (ROC) curve and its area under the curve (AUC). Multiple sensor configurations were evaluated for the best model. The geometric mean was subsequently calculated to select the optimal threshold. The selected model and threshold were evaluated on the hold-out and unseen test set.

Results

A total of 70 participants (23.7 h, 9% FOG) were included in this study for training and testing, and in addition, 10 participants provided an unseen test set (2.4 h, 11% FOG). The CNN performed best (AUC = 0.86) in comparison to the InceptionTime (AUC = 0.82) and MiniRocket (AUC = 0.76) models. For the CNN, we found a similar performance for a seven-sensor configuration (lumbar, upper and lower legs and feet; AUC = 0.86), six-sensor configuration (upper and lower legs and feet; AUC = 0.87), and two-sensor configuration (lower legs; AUC = 0.86). The optimal threshold of 0.45 resulted in a sensitivity of 77% and a specificity of 58% for the hold-out set (AUC = 0.72), and a sensitivity of 85% and a specificity of 68% for the unseen test set (AUC = 0.90).

Conclusion

We confirmed that deep learning can be used to detect FOG in a large, heterogeneous dataset. The CNN model outperformed more complex networks. This model could be employed in future personalized interventions, with the ultimate goal of using automated FOG detection to trigger real-time cues to alleviate FOG in daily life.
Triggers for freezing of gait in individuals with Parkinson’s disease: a systematic review
Authors: Conde Carolina I. , Lang Charlotte , Baumann Christian R. , Easthope Chris A. , Taylor William R. , Ravi Deepak K.
Published: December 2023

Background

Freezing of Gait (FOG) is a motor symptom frequently observed in advanced Parkinson’s disease. However, due to its paroxysmal nature and diverse presentation, assessing FOG in a clinical setting can be challenging. Before FOG can be fully investigated, it is critical that a reliable experimental setting is established in which FOG can be evoked in a standardized manner, but the efficacy of various gait tasks and triggers for eliciting FOG remains unclear.

Objectives

This study aimed to conduct a systematic review of the existing literature and evaluate the available evidence for the relationship between specific motor tasks, triggers, and FOG episodes in individuals with Parkinson’s disease (PwPD).

Methods

We conducted a literature search on four online databases (PubMed, Web of Science, EMBASE, and Cochrane Library) using the keywords “Parkinson’s disease,” “Freezing of Gait”, “triggers” and “tasks”. A total of 128 articles met the inclusion criteria and were included in our analysis.

Results

The review found that a wide range of gait tasks were employed in studies assessing FOG among PD patients. However, three tasks (turning, dual tasking, and straight walking) emerged as the most frequently used. Turning (28%) appears to be the most effective trigger for eliciting FOG in PwPD, followed by walking through a doorway (14%) and dual tasking (10%).

Conclusion

This review thereby supports the utilisation of turning, especially a 360-degree turn, as a reliable trigger for FOG in PwPD. This finding could be beneficial to clinicians conducting clinical evaluations and researchers aiming to assess FOG in a laboratory environment.
Polypharmacy in patients with multiple sclerosis and the impact on levels of care and therapy units
Authors: Brüggemann Finn , Gross Stefan , Süße Marie , Hok Pavel , Strauss Sebastian , Ziemssen Tjalf , Frahm Niklas , Zettl Uwe K. , Grothe Matthias
Published: December 2023

Background

The aim of this study was to examine the societal costs of polypharmacy in patients with multiple sclerosis (MS). We therefore focused on the association between the number of medications on the level of care (LOC), the German classification of the need for care, and the number of therapy sessions (TTU).

Methods

In addition to demographic information and medication, 101 MS patients performed the Multiple Sclerosis Health Resource Utilization Survey (MS-HRS). Medications were subdivided into a total number of medications (TD), MS-related medication [MSD, i.e., disease-modifying drugs (DMDs) and symptomatic treatment (SD)], and medication for comorbidities (CDs). Multivariate linear regression models were performed to estimate if the amount of each medication type affects LOC or TTU.

Results

Polypharmacy appeared in 54 patients at the time of the survey. The relative risk (RR) of LOC 1 increased significantly by 2.46 (p = 0.001) per TD and by 2.55 (p = 0.004) per MSD, but not per CD (RR 1.44; p = 0.092). The effect of RR on MSD was driven by SD (RR 2.2; p = 0.013) but not DMD (RR 2.6; p = 0.4). RR of MSD remained significant for LOC 2 (1.77; p = 0.009) and LOC 3/4 (1.91; p = 0.015), with a strong trend in RR of SD, but not DMD. TTU increased significantly per MSD (p = 0.012), but not per TD (p = 0.081) and CD (p = 0.724).

Conclusion

The number of MSDs is related to the likelihood of a higher level of care and the number of therapy sessions and is therefore a good indication of the extent of the societal costs.
Evaluation of visual performance and eye movements in patients with blue light-filtering intraocular lenses versus ultraviolet light-filtering intraocular lenses
Authors: Liu Yan , Ren Xiaotong , Wan Yu , Yang Luling , Zhang Rong , Li Xuemin
Published: December 2023

Background

Eye movement plays an important role in visual perception and provides essential visual information for everyday tasks. Our previous study indicated that the visual performance and eye movement pattern were impaired in age-related cataract patients and could be improved after cataract surgery, but the impact of different intraocular lens (IOL) types was obscure. Previous studies found that blue light might affect the eye movement pattern and cognitive function. In this study, we explored the visual performance and eye movement pattern in post-cataract surgery patients implanted with blue light-filtering IOLs or ultraviolet (UV) light-filtering IOLs to further understand the impact of different types of IOLs on and daily visual performance and eye movement pattern and to help ophthalmologists and patients make the personalized option of IOL types in future.

Methods

Patients after both-eye cataract surgeries were included in this study. Eye movement behaviors were automatically recorded by an eye tracker while performing three performance-based everyday tasks (non-social object search, face recognition, and reading). Visual performance and eye movement parameters were compared between participants with blue light-filtering IOLs and UV light-filtering IOLs. The correlation between visual performance and eye movement parameters was explored to determine which eye movement parameters had a significant influence on visual performance outcomes.

Results

A total of 30 patients (16 with blue light-filtering IOLs and 14 with UV light-filtering IOLs) were included. In this study, we found that the eye movement pattern was slightly different with these two IOLs: during non-social object visual search task, time to first fixation and fixation counts before first fixation were notably increased in yellow-tinted blue light-filtering IOL patients. During reading task, a higher total fixation count was also found in blue light-filtering IOL patients. However, the visual performance of these two IOLs was close, except for a quicker search of the target object with clear UV light-filtering IOLs.

Conclusion

Both blue light-filtering and UV light-filtering IOLs were able to successfully restore visual function and yield satisfactory outcomes after cataract surgery. Although subtle, yellow-tinted IOLs did have a slight but significant impact on visual performance and the eye movement pattern of elderly patients when handling everyday tasks.
Comparison of dynamic visual acuity after implantation of toric bifocal or trifocal intraocular lens in age-related cataract patients: a randomized controlled trial
Authors: Li Yuanting , Li Xiaodan , Jiang Xiaodan , Wang Yuexin , Wu Tingyi , Xia Huaqin , Li Xuemin
Published: December 2023

Purpose

To investigate the dynamic visual acuity (DVA) after implantation of toric bifocal or trifocal intraocular lens in age-related cataract patients.

Methods

This was a prospective randomized controlled trial. Of one hundred and twenty-four patients enrolled and randomized to receive unilateral phacoemulsification and toric trifocal (939 M/MP, Carl Zeiss Meditec AG, Jena, Germany) or toric bifocal (909 M, Carl Zeiss Meditec AG, Jena, Germany) intraocular lenses (IOL) implantation, ninety-nine patients completed the follow-up and were included in final analysis. Postoperatively, uncorrected and corrected distance (UDVA and CDVA), intermediate (UIVA and DCIVA) and near (UNVA and DCNVA) static visual acuity, manifest refraction and uncorrected and corrected distance DVA (UDDVA and CDDVA) at 20, 40 and 80 degrees per second (dps) were evaluated at one week, one month and three months.

Results

Three months postoperatively, the UDVA were 0.13 ± 0.11 and 0.14 ± 0.13 in the toric trifocal and bifocal IOL group, respectively. Significant better UIVA (trifocal, 0.17 ± 0.13 vs. bifocal, 0.23 ± 0.13, p = 0.037) and DCIVA (trifocal, 0.16 ± 0.11 vs. bifocal, 0.20 ± 0.12, p = 0.048) were observed in patients implanting toric trifocal than bifocal IOL at three months postoperatively. Patients implanted with toric bifocal IOL obtained better CDDVA at 80 dps (0.5607 ± 0.2032) than the trifocal group (0.6573 ± 0.2450, p = 0.039) at three months. Postoperative UDDVA and CDDVA at 20, 40 and 80 dps were significantly associated with age (p < 0.05, respectively) and postoperative static visual acuity (p < 0.05, respectively).

Conclusion

Toric trifocal IOL provides better static intermediate visual acuity, and toric bifocal IOL implantation provides better distance dynamic visual acuity at high speed.
Exploring the potential role of genus Sophora in the management of osteoporosis: a phytochemical and biological review
Authors: Aly Shaza H. , Elbadry Abdullah M. M. , El-Shazly Mohamed , Hwang Tsong-Long
Published: December 2023

Bone metabolism is characterized by an interplay between the deposition of bone matrix and mineralization and the resorption process. Osteoporosis is a form of systemic metabolic bone condition that causes bone density to decline and its microarchitecture to deteriorate, increasing the risk of fracture owing to fragility. The underlying cause of this clinical disease lies in the imbalance in bone remodeling, in which bone resorption by osteoclasts predominates over bone creation by osteoblasts. Natural remedies have long been used to cure and prevent osteoporosis. Genus Sophora of the Fabaceae family comprises about 69 species that showed many pharmacological effects, including bone health preservation. The activity of Sophora sp. in maintaining bone health was attributed to its antioxidant, regenerative, and anti-inflammatory qualities. In this review, we focused on the therapeutic properties of the extracts and isolated compounds from the genus Sophora in maintaining bone health, with special emphasis on the management of osteoporosis.
Decrease in the number of new cancer diagnoses during the first year of the COVID-19 pandemic – cohort study of 3.5 million individuals in western Poland
Authors: Trojanowski Maciej , Radomyski Piotr , Kycler Witold , Michalek Irmina Maria
Published: December 2023

Introduction

The COVID-19 pandemic has considerably affected healthcare systems worldwide and is expected to influence cancer incidence, mortality, stage at diagnosis, and survival. This study aimed to assess COVID-19-related changes in cancer incidence observed in 2020 in the Greater Poland region.

Materials and methods

Data from the Greater Poland Cancer Registry on cancer patients diagnosed between 2010 and 2020 were analysed. To quantify the change in the number of incident cancer cases during the COVID-19 pandemic, we calculated the standardized incidence ratio (SIR) and the incidence rate difference (IRD) to assume the pandemic-attributable gap in cancer incidence.

Results

In 2020, in Greater Poland, the expected number of new cancer cases was 18 154 (9 226 among males and 8 927 among females), while the observed number was 14 770 (7 336 among males and 7 434 among females). The registered number of cancer cases decreased in 2020 by 20% (SIR 0·80, 95% CI 0·78 to 0·81) and 17% (SIR 0·83, 95% CI 0·81 to 0·85) in males and females, respectively. Among men, the most significant difference was reported for myeloma (SIR 0·59, 95% CI 0·45 to 0·77), among women for bone cancer (SIR 0·47, 95% CI 0·20 to 0·93). In females the observed incidence was higher than expected for cancer of an unspecified site (SIR 1·19, 95% CI 1·01 to 1·38). In our study, the decrease in new cancer cases was greater in males than in females.

Discussion

The observed incidence was affected in most cancer sites, with the most significant deviation from the expected number in the case of myeloma. An increase in the observed incidence was reported only in women diagnosed with cancer of an unspecified site, which might reflect shortages in access to oncological diagnostics.
Psychosocial distress and associated factors among adult cancer patients at oncology: a case of Ethiopia
Authors: Baye Astewle Andargie , Bogale Sitotaw Kerie , Delie Abebu Tegenaw , Melak Fekadie Mengistu , Wondyifraw Haileyesus Gedamu , Tigabu Mengistu Ewunetu , Kebede Mulu
Published: December 2023

Background

Psychosocial distress is a chronic burden for cancer survivors, which impacts both their quality of life and their oncologic prognosis. Although the national cancer prevention and control program in Ethiopia has made efforts in cancer prevention, control, and management by implementing the national cancer control plan 2016–2020, there was no enough evidence about psychosocial distress among adult cancer patients. So, it is critical to understand the magnitude of psychosocial distress and the factors that contribute to it.

Objective

The purpose of this study was to assess the prevalence of psychosocial distress and associated factors among adult cancer patients at oncology units in the Amhara regional state, Ethiopia. 2022.

Methods

A multicenter institution-based cross-sectional study was conducted among a sample of 605 adult cancer patients from 30 April to 22 June 2022. A systematic random sampling technique was employed to select the study units. In addition, data were collected through interviewers administered questionnaires by using the validated and pretested tools. Distress was assessed using the Questionnaire on Stress in Cancer Patients Revised 10. Both bivariable and multivariable logistic regression was used to describe the association between dependent and independent variables. Independent variable with p < 0.25 in the bivariable logistic regression analyses were entered into multivariable logistic regression model. Variables with p < 0.05 in the multivariable logistic regression analyses were considered as statistically significant associated factors of psychosocial distress.

Result

A total of 593 adult cancer patients took part in this study with mean age of 46.86 ± 14.5 years. The overall prevalence of psychosocial distress was 63.74%. Variables such as being female [AOR = 1.98, 95% confidence interval (CI): 1.24–3.17], patients who lives in rural areas (AOR = 2.3, 95% CI: 1.49–3.54), community-based health insurance utilization (AOR = 0.34, 95% CI: 0.23–0.51), patients on chemotherapy treatment (AOR = 2.72, 95% CI: 1.38–5.39), patients with comorbidity (AOR = 3.2, 95% CI: 1.67–6.10), and symptom burdens such as severe fatigue (AOR = 1.65, 95% CI:1.09–2.39) and severe nausea (AOR = 2.07, 95% CI: 1.43–3.00) were statistically associated with psychosocial distress.

Conclusion and recommendation

In general, the findings of this study showed a relatively high magnitude in which around two-thirds of patients experienced psychosocial distress. It is better to establish and enforce the integration and coordination of psychosocial oncology service programs at national level with parallel guidelines and policies.
Drug-induced QT prolongation and torsade de pointes: a real-world pharmacovigilance study using the FDA Adverse Event Reporting System database
Authors: Li Dongxuan , Chai Shuang , Wang Hongli , Dong Jie , Qin Chunmeng , Du Dan , Wang Yalan , Du Qian , Liu Songqing
Published: December 2023

Introduction: Drug-induced QT prolongation and (or) Torsade de Pointes (TdP) is a well-known serious adverse reaction (ADR) for some drugs, but the widely recognized comprehensive landscape of culprit-drug of QT prolongation and TdP is currently lacking.

Aim: To identify the top drugs reported in association with QT prolongation and TdP and provide information for clinical practice.

Method: We reviewed the reports related to QT prolongation and TdP in the FDA Adverse Event Reporting System (FAERS) database from January 1, 2004 to December 31, 2022, and summarized a potential causative drug list accordingly. Based on this drug list, the most frequently reported causative drugs and drug classes of QT prolongation and TdP were counted, and the disproportionality analysis for all the drugs was conducted to in detect ADR signal. Furthermore, according to the positive–negative distribution of ADR signal, we integrated the risk characteristic of QT prolongation and TdP in different drugs and drug class.

Results: A total of 42,713 reports in FAERS database were considered to be associated with QT prolongation and TdP from 2004 to 2022, in which 1,088 drugs were reported as potential culprit-drugs, and the largest number of drugs belonged to antineoplastics. On the whole, furosemide was the most frequently reported drugs followed by acetylsalicylic acid, quetiapine, citalopram, metoprolol. In terms of drug classes, psycholeptics was the most frequently reported drug classes followed by psychoanaleptics, analgesics, beta blocking agents, drugs for acid related disorders. In disproportionality analysis, 612 drugs showed at least one positive ADR signals, while citalopram, ondansetron, escitalopram, loperamide, and promethazine were the drug with the maximum number of positive ADR signals. However, the positive-negative distribution of ADR signals between different drug classes showed great differences, representing the overall risk difference of different drug classes.

Conclusion: Our study provided a real-world overview of QT prolongation and TdP to drugs, and the presentation of the potential culprit-drug list, the proportion of reports, the detection results of ADR signals, and the distribution characteristics of ADR signals may help understand the safety profile of drugs and optimize clinical practice.
Evaluation of NTP42, a novel thromboxane receptor antagonist, in a first-in-human phase I clinical trial
Authors: Reid Helen M. , Maginn Mark , Perkins C. Michael , Mulvaney Eamon P. , Boyce Malcolm , Yamamoto Takahiro , Kinsella B. Therese
Published: December 2023

Background: The thromboxane receptor (TP) antagonist NTP42 is in clinical development for treatment of cardiopulmonary diseases, such as pulmonary arterial hypertension. In this randomized, placebo-controlled Phase I clinical trial, NTP42, administered as the oral formulation NTP42:KVA4, was evaluated for safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) in healthy males.

Methods: The first-in-human trial had three Parts: A, single ascending dose (SAD) study with seven groups given 0.25–243 mg NTP42:KVA4 or placebo; B, food effect study where one SAD group (9 mg) was also given NTP42:KVA4 or placebo after a high-fat breakfast; C, multiple ascending dose study with three groups given 15–135 mg NTP42:KVA4 or placebo once-daily for 7 days.

Results: Seventy-nine volunteers participated. No serious adverse events occurred, where any drug- or placebo-related adverse events were mild to moderate, with no correlation to NTP42:KVA4 dose. NTP42 was rapidly absorbed, yielding dose proportional increases in exposure after single and repeat dosing. PK confirmed that, with a clearance (T1/2) of 18.7 h, NTP42:KVA4 is suited to once-daily dosing, can be taken with or without food, and does not accumulate on repeat dosing. At doses ≥1 mg, NTP42 led to complete and sustained inhibition of thromboxane-, but not ADP-, induced platelet aggregation ex vivo, with direct correlation between NTP42 exposure and duration of PD effects.

Conclusion: Orally administered NTP42:KVA4 was well tolerated, with favorable PK/PD profiles and evidence of specific TP target engagement. These findings support continued clinical development of NTP42:KVA4 for cardiopulmonary or other relevant diseases with unmet needs.

Clinical Trial Registration:clinicaltrials.gov, identifier NCT04919863.
Skin-protective biological activities of bio-fermented Aframomum angustifolium extract by a consortium of microorganisms
Authors: Albouy Marion , Aubailly Simon , Jeanneton Olivier , Marteau Clarisse , Sobilo Lauren , Boulgana Rachid , Bru Gerard , Bellanger Marine , Leblanc Emmanuelle , Dos Santos Morgan , Pays Karl , Choisy Patrick , Bossard Elodie , Nizard Carine , Thepot Amelie , Gourguillon Lorene , Bulteau Anne-Laure
Published: December 2023

Background:Aframomum sp. is a genus of plants in the Zingiberaceae family. It includes several species, some of which are used in cosmetics for their various properties, making them useful in skincare products, particularly for anti-aging, moisturizing, and brightening the skin. However, to date, there is no experimental evidence on its natural extracts obtained or modified using microorganisms (bio-fermentation) as an anti-aging agent.

Objective: The present study aimed to evaluate the antiaging effect of a Bio-fermented Aframomum angustifolium (BAA) extract on 3D bioprinted skin equivalent.

Methods: The consortium of microorganisms contained Komagataeibacter, Gluconobacter, Acetobacter, Saccharomyces, Torulaspora, Brettanomyces, Hanseniaspora, Leuconostoc, Lactobacillus, Schizosaccharomyces. It was developed on a media containing water, sugar, and infused black tea leaves. The seeds of Aframomum angustifolium previously grounded were mixed with the culture medium, and the ferments in growth; this fermentation step lasted 10 days. Then, the medium was collected and filtered (0.22 µm) to obtain the BAA extract. To enhance our comprehension of the impact of BAA extract on skin aging, we developed skin equivalents using bio-printing methods with the presence or absence of keratinocyte stem cells (KSC). These skin equivalents were derived from keratinocytes obtained from both a middle-aged donor, with and without KSC. Moreover, we examined the effects of treating the KSC-depleted skin equivalents with Bio-fermented Aframomum angustifolium (BAA) extract for 5 days. Skin equivalents containing KSC-depleted keratinocytes exhibited histological characteristics typical of aged skin and were compared to skin equivalents derived from young donors.

Results: The BAA extract contained specific organic acids such as lactic, gluconic, succinic acid and polyphenols. KSC-depleted skin equivalents that were treated with BAA extract exhibited higher specular reflection, indicating better hydration of the stratum corneum, higher mitotic activity in the epidermis basal layer, improved dermal-epidermal connectivity, and increased rigidity of the dermal-epidermal junction compared to non-treated KSC-depleted equivalents. BAA extract treatments also resulted in changes at the dermis level, with an increase in total collagen and a decrease in global laxity, suggesting that this extract could help maintain youthful-looking skin.

Conclusion: In summary, our findings indicated that BAA extract treatments have pleiotropic beneficial effects on skin equivalents and that the bio-fermentation provides new biological activities to this plant.
A real-world pharmacovigilance study of mepolizumab in the FDA adverse event reporting system (FAERS) database
Authors: Zou Fan , Zhu Chengyu , Lou Siyu , Cui Zhiwei , Wang Dan , Ou Yingyong , Wang Li , Chen Junyou , Lan Yuanbo
Published: December 2023

Mepolizumab is primarily used in the treatment of asthma, eosinophilic granulomatosis with polyangiitis, eosinophilia syndrome, and chronic rhinitis with nasal polyps. The information about its adverse drug reactions is mainly derived from clinical trials, and there is a shortage of real-world studies with extensive sample sizes. In this study, the U.S. FDA’s Adverse Event Reporting System (FAERS) database was analyzed to evaluate the side effects of mepolizumab. A total of 18,040 reports of mepolizumab-associated adverse events were identified from the FDA Adverse Event Reporting System database. Multiple disproportionality analysis algorithms were used to determine the significance of these AEs. The study identified 198 instances of mepolizumab-induced AEs, including some important AEs not mentioned in the product labeling. The time to onset of adverse reactions was also analyzed, with a median time of 109 days. Most AEs occurred within the first month of mepolizumab use, but some may still occur after 1 year of treatment. Gender-specific analysis showed different high-risk AEs for females (digestive and neurological side effects) and males (serious adverse effects leading to hospitalization and death). The findings mentioned provide valuable insights on optimizing the use of mepolizumab, enhancing its effectiveness, and minimizing potential side effects. This information will greatly contribute to the practical implementation of the drug in clinical settings.
Deciphering the biological processes in root hairs required for N-self-fertilizing cereals
Authors: Pree Simon , Malekian Babak , Sandén Hans , Nicolaisen Mogens , Weckwerth Wolfram , Vestergård Mette , Retzer Katarzyna
Published: December 2023

The need for increasing for crop productivity leads to a higher usage of synthetic fertilizers, which has tremendous effects on the environment. Nitrogen (N) is a crucial plant macronutrient, but the production of synthetic N fertilizer and its leakage into aquatic systems represent sources of environmental damage. To reduce the usage of synthetic fertilizers, current studies addressed innovative approaches to develop “N-self-fertilizing” crops that can utilize atmospheric nitrogen through enhanced interaction with the root microbiome. In this review we discuss recently obtained knowledge about the role of root hairs and their functions in root exudate secretion for plant-microbiome interactions. Recent studies have shown the beneficial impact of root hairs and exudate secretion on the recruitment of N2 fixing bacteria. Root hair plays a crucial role in shaping the rhizosphere, and first insights into the biological processes that underpin root hair formation and function in relation to microbiome interaction were gained. We summarize to which extent this knowledge can be applied to develop cereals with an enhanced ability to benefit from N2 fixing bacteria. Finally, we describe non-destructive methods and their limitations to study root hair growth directly in the field under natural growth conditions.
DriveLEDs: software for synchronous control and video acquisition of fluorescent signals
Authors: Zakharov Andrey , Ponomareva Daria , Petukhova Elena , Bregestovski Piotr
Published: December 2023

Current research uses various fluorescent biosensors to measure ion concentrations, neuronal activity, or cellular components in biological preparations. Several free solutions are available to researchers for recording or analysing fluorescent signals. However, when using different software packages, there are great difficulties in converting data between them. Problems also arise with linking and coordination of individual hardware devices into a single measurement system. Our paper presents useful software that allows to avoid most of these problems. It enables the recording, online visualization and preliminary analysis of fluorescent signals in brain cells and other experimental models. We describe and test software optimized for ratiometric measurements. The program selects device operating modes that allow reliable changes in illumination wavelength, camera image capture, and online graphical visualization of fluorescent signal amplitudes or ratiometric data. The performance of the software was successfully tested on mouse brain using two experimental models; i) simultaneous monitoring of intracellular chloride and hydrogen in transgenic mice expressing genetically encoded biosensor; ii) recording changes in reactive oxygen species during synaptic stimulation of neurons in mouse hippocampal slices. This software allows to overcome the incompatibility of the devices used and reduce the cost of experimental measurements. The software is completely original, easy to use and may be of interest to many scientists involved in the analysis of light-controlled signals in a variety of experimental models, including drug screening, epilepsy models, and other applications. The software is open-source product and can be obtained via GitHub: https://github.com/AndreyZakharovExp/DriveLEDs.
A compact portable photoacoustic sensor for sub-ppm level SO2 detection with a DUV-LED and a non-resonant photoacoustic cell
Authors: Jing Yujing , Feng Chaofan , Cui Ruyue , Xue Jiyu , Dong Lei , Wu Hongpeng
Published: December 2023

A photoacoustic module based on a novel 273 nm deep-ultraviolet light-emitting diode (DUV-LED) was developed for sulfur dioxide (SO2) detection. The DUV-LED with an emission angle of 60° emitted a power of 10 mW. A high-sensitivity non-resonant photoacoustic cell with a gas chamber volume of only 0.39 mL was introduced to reduce the thermal noise generated by the contact of scattered DUV light with the photoacoustic cell. Assembly of the DUV-LED with the non-resonant photoacoustic cell resulted in a robust and portable photoacoustic module without any moving parts. The minimum detection limit of 725 ppb was achieved with 1s integration time at room temperature and atmospheric pressure. Furthermore, the photoacoustic module performance was evaluated in terms of DUV modulation frequency, linearity and the long-term stability.
Transgenic rodents as dynamic models for the study of respiratory rhythm generation and modulation: a scoping review and a bibliometric analysis
Authors: Olmos-Pastoresa Carol Alejandra , Vázquez-Mendoza Enrique , López-Meraz María Leonor , Pérez-Estudillo César Antonio , Beltran-Parrazal Luis , Morgado-Valle Consuelo
Published: December 2023

The pre-Bötzinger complex, situated in the ventrolateral medulla, serves as the central generator for the inspiratory phase of the respiratory rhythm. Evidence strongly supports its pivotal role in generating, and, in conjunction with the post-inspiratory complex and the lateral parafacial nucleus, in shaping the respiratory rhythm. While there remains an ongoing debate concerning the mechanisms underlying these nuclei’s ability to generate and modulate breathing, transgenic rodent models have significantly contributed to our understanding of these processes. However, there is a significant knowledge gap regarding the spectrum of transgenic rodent lines developed for studying respiratory rhythm, and the methodologies employed in these models. In this study, we conducted a scoping review to identify commonly used transgenic rodent lines and techniques for studying respiratory rhythm generation and modulation. Following PRISMA guidelines, we identified relevant papers in PubMed and EBSCO on 29 March 2023, and transgenic lines in Mouse Genome Informatics and the International Mouse Phenotyping Consortium. With strict inclusion and exclusion criteria, we identified 80 publications spanning 1997–2022 using 107 rodent lines. Our findings revealed 30 lines focusing on rhythm generation, 61 on modulation, and 16 on both. The primary in vivo method was whole-body plethysmography. The main in vitro method was hypoglossal/phrenic nerve recordings using the en bloc preparation. Additionally, we identified 119 transgenic lines with the potential for investigating the intricate mechanisms underlying respiratory rhythm. Through this review, we provide insights needed to design more effective experiments with transgenic animals to unravel the mechanisms governing respiratory rhythm. The identified transgenic rodent lines and methodological approaches compile current knowledge and guide future research towards filling knowledge gaps in respiratory rhythm generation and modulation.
Estimation of physiological exercise thresholds based on dynamical correlation properties of heart rate variability
Authors: Kanniainen Matias , Pukkila Teemu , Kuisma Joonas , Molkkari Matti , Lajunen Kimmo , Räsänen Esa
Published: December 2023

Aerobic and anaerobic thresholds of the three-zone exercise model are often used to evaluate the exercise intensity and optimize the training load. Conventionally, these thresholds are derived from the respiratory gas exchange or blood lactate concentration measurements. Here, we introduce and validate a computational method based on the RR interval (RRI) dynamics of the heart rate (HR) measurement, which enables a simple, yet reasonably accurate estimation of both metabolic thresholds. The method utilizes a newly developed dynamical detrended fluctuation analysis (DDFA) to assess the real-time changes in the dynamical correlations of the RR intervals during exercise. The training intensity is shown to be in direct correspondence with the time- and scale-dependent changes in the DDFA scaling exponent. These changes are further used in the definition of an individual measure to estimate the aerobic and anaerobic threshold. The results for 15 volunteers who participated in a cyclo-ergometer test are compared to the benchmark lactate thresholds, as well as to the ventilatory threshods and alternative HR-based estimates based on the maximal HR and the conventional detrended fluctuation analysis (DFA). Our method provides the best overall agreement with the lactate thresholds and provides a promising, cost-effective alternative to conventional protocols, which could be easily integrated in wearable devices. However, detailed statistical analysis reveals the particular strengths and weaknessess of each method with respect to the agreement and consistency with the thresholds—thus underlining the need for further studies with more data.
Phenotypic and genetic characterization of an Avena sativa L. germplasm collection of diverse origin: implications for food-oat breeding in Chile
Authors: Mathias-Ramwell Mónica , Pavez Valentina , Meneses Marco , Fernández Feledino , Valdés Adriana , Lobos Iris , Silva Mariela , Saldaña Rodolfo , Hinrichsen Patricio
Published: December 2023

Oats are known for their nutritional value and also for their beneficial properties on human health, such as the reduction of cholesterol levels and risk of coronary heart disease; they are an important export product for Chile. During the last decade (2010-2022) over 90% of the oat cultivated area in Chile has been covered with Avena sativa L. cv. Supernova INIA. This lack of genetic diversity in a context of climate change could limit the long-term possibility of growing oats in Chile. The present study is a phenotypic and genetic analysis of 132 oat cultivars and pure lines of diverse origin that can be considered as potential breeding material. The germplasm was evaluated for 28 traits and analyzed with 14 SSR markers. The effects of genotypes on phenotype were significant over all traits (P ≤ 0.05). Most traits exhibited moderate to high broad-sense heritability with exceptions such as yield (H2 = 0.27) and hulls staining (H2 = 0.32). Significant undesirable correlations between traits were generally of small biological importance, which is auspicious for achieving breeding objectives. Some of the heritability data and correlations provided here have not been previously reported. The overall phenotypic diversity was high (H’ = 0.68 ± 0.18). The germplasm was grouped into three phenotypic clusters, differing in their qualities for breeding. Twenty-six genotypes outperforming Supernova INIA were identified for breeding of conventional food-oats. The genetic diversity of the germplasm was moderate on average (He = 0.58 ± 0.03), varying between 0.32 (AM22) and 0.77 (AME178). Two genetic subpopulations supported by the Structure algorithm exhibited a genetic distance of 0.24, showing low divergence of the germplasm. The diversity and phenotypic values found in this collection of oat genotypes are promising with respect to obtaining genetic gain in the short term in breeding programs. However, the similar genetic diversity, higher phenotypic diversity, and better phenotypic performance of the germplasm created in Chile compared to foreign germplasm suggest that germplasm harboring new genetic diversity will be key to favor yield and quality in new oat cultivars in the long term.
Using head-mounted eye trackers to explore children’s color preferences and perceptions of toys with different color gradients
Authors: Chen Zihe , Yan Tingmin , Cai YuXin , Cui Tianjian , Chen Shangbin
Published: December 2023

This study investigated how color gradients affect the attraction and visual comfort of children aged 4 to 7 years. We analyzed 108 eye-tracking datasets, including the color attraction index (COI), visual comfort index (PUI), and saccade rate (SR). The findings revealed that children are more attracted to colors as saturation decreases and brightness increases within a specific range. Beyond this range, reduced saturation diminishes color appeal. Moderate brightness and contrast enhance visual comfort during play, while extremely low contrast hinders concentration. Warm colors (red, orange, and yellow) slightly dominate preferences; however, the roles of hue, saturation, and brightness in children’s color preferences remain inconclusive. These insights have practical implications for age-appropriate toy design and marketing. Future research should explore age-specific color preferences for more targeted design strategies.
Remission with or without comorbid substance use disorders in early psychosis: long-term outcome in integrated care (ACCESS III study)
Authors: Rühl Friederike , Lambert Martin , Rohenkohl Anja , Kraft Vivien , Daubmann Anne , Schneider Brooke C. , Luedecke Daniel , Karow Anne , Gallinat Jürgen , Leicht Gregor , Schöttle Daniel
Published: December 2023

Introduction

Schizophrenia-Spectrum-Disorders are associated with poor long-term outcome as well as disability and often severely affect the lives of patients and their families often from symptom onset. Up to 70% of first episode psychosis (FEP) patients suffer from comorbid substance use disorders (SUD). We aimed at studying the course of illness in FEP patients within evidence-based care, with and without comorbid SUD, to examine how decreased, remitted or persistent substance use impacted rates of a combined symptomatic and functional long-term recovery compared with patients without SUD.

Methods

ACCESS III is an integrated care model for FEP or patients in the early phase of non-affective and affective psychotic disorders. Treatment trajectories of patients, who had been in ACCESS care for 1 year, with and without SUD were compared with regard to the course of illness and quality of life using Mixed Model Repeated Measures (MMRM) and recovery rates were compared using binary logistic regression. Change in substance use was coded as either persistent, decreased/remitted or no use.

Results

ACCESS III was a prospective 1-year study (N = 120) in patients aged 12–29 years. Of these, 74 (61.6%) had a comorbid SUD at admission. There were no group differences regarding the course of illness between patients with or without comorbid SUD or between patients with a substance abuse or substance dependence. The only outcome parameter that was affected by SUD was quality of life, with larger improvement found in the group without substance use (p = 0.05) compared to persistent and remitted users. Using LOCF, 44 patients (48.9%) fulfilled recovery criteria at the endpoint; recovery did not differ based on substance use status.

Discussion

SUD and especially substance dependence are common in psychotic disorders even in FEP patients. Evidence-based integrated care led to long-term improvement in patients with comorbid SUD and rate of recovery did not differ for patients with substance use.
Revisiting the debriefing debate: does psychological debriefing reduce PTSD symptomology following work-related trauma? A meta-analysis
Authors: Stileman Harry M. , Jones Christopher A.
Published: December 2023

Psychological debriefing is an early post-trauma intervention which aims to prevent the development of PTSD and accelerate normal recovery through discussing, validating, and normalising group members responses to trauma. While originally designed in the 1980s for groups of emergency service personnel, the scope of psychological debriefing extended to individual primary victims of trauma. A Cochrane review in 2002 concluded that psychological debriefing was ineffective, yet some authors have argued that many of the studies that informed the Cochrane review did not adhere to key elements of psychological debriefing. This meta-analysis sought to re-examine the effectiveness of psychological debriefing in preventing or reducing PTSD symptoms following work-related trauma. Appropriate studies were selected from three databases (MEDLINE, Embase and PsycINFO). Inclusion criteria was intentionally broad so that features of psychological debriefing that may determine its effectiveness could be explored through a series of subgroup analyses. The overall synthesis did not find consistent evidence that psychological debriefing helps to prevent or reduce PTSD symptoms following work-related trauma. Shortcomings in the methodology and reporting of many of the studies meant that several important subgroup analyses could not be conducted. Further well-designed studies in this field are warranted to ensure that employees exposed to potentially traumatic events receive the effective support they need and deserve.