bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the toxic effects of aspartame as an artificial sweetener in food: effect on redox and inflammatory biomarkers in rat
Authors: Bhoumik Sukanya , Kumar Raushan , Srivastava Parisha , Singh Akanksha , Siddiqui Zainab , Rizvi Syed Ibrahim
Published: August 2023

Aspartame (L-aspartyl-L-phenylalanine methyl ester) is a widely used synthetic sweetener. The safety of aspartame consumption remains controversial due to its widespread and sometimes indiscriminate use above the FDA-recommended level. The study focused on investigating the toxic effects of aspartame administration at high doses on redox and inflammatory biomarkers in male Wistar rats. Rats were divided into two groups: Group I was given normal saline (0.9%) orally and Group II was administered with aspartame (100 mg/kg body weight) for 30 days. Administration of aspartame significantly (p<0.05) increased the levels of Malondialdehyde (MDA), protein carbonyl (PCO), and Advanced Oxidation Protein Products (AOPP) content which are prominent markers of oxidative stress. The assessment of antioxidant defenses in both the groups denoted a significant (p<0.05) decrease in levels of Ferric Reducing Ability of Plasma (FRAP), Superoxide Dismutase (SOD), and Catalase in the aspartame-treated group in comparison to the control. The proinflammatory markers Tumour Necrosis Factor -α (TNF-α), Interleukin-6 (IL-6) and C - reactive protein (CRP) were also significantly (p<0.05) increased in the treated group. These results suggest that aspartame intake of 100 mg/kg body weight contributes to oxidative stress in erythrocytes which in turn may play a role in predisposing an individual to obesity, cardiovascular disease, and cancer. Aspartame should be strictly limited to the FDA-recommended levels since its indiscriminate use causes severe toxic effects.
Bacteriological quality of meat and hygiene practice among meat handlers in Kathmandu, Nepal
Authors: Saud Bhuvan , Amatya Neetu , Yadav Rajkishor Kumar , Paudel Govinda , Adhikari Saroj , Shrestha Vikram , Lakhey Ashish
Published: August 2023

We investigated bacterial growth from raw meats and items used during meat handling, and hygiene practices followed by meat handlers at butcher shops in Kathmandu. A cross-sectional study was conducted; a total of 200 swab samples were collected from 121 butcher shops. A mean bacterial count was performed, and bacterial identification and antibiotic susceptibility test were performed. A face-to-face interview was conducted to evaluate the hygiene practices. Out of 200 samples, 90.5% showed bacterial growth. All Buffalo meat samples and more than 90.0% of Goat and Pork meat samples showed bacterial growth, and only 60.0% of knife swabs showed bacterial growth. Staphylococcus aureus was the predominant isolate followed by Escherichia coli, Salmonella spp., Citrobacter spp., Klebsiella spp., and Proteus spp. Mean bacterial count in Buffalo meat (6.43 log cfu/cm2 ) was the highest followed by Pork meat (5.26 log cfu/cm2 ) and Goat meat (5.04 log cfu/cm2 ). A total of 456 bacteria were isolated, of which 24.3% were multi-drug resistant. Out of 136 S. aureus isolated, 10.2% were Methicillin Resistant S. aureus. A statistically significant difference was noted in carcass handling during hand injury, before and after knives and chopping block cleaning, use of fly and rodent controllers, and clean water supply. Hygiene practices depicted a significant relation with the mean bacterial count, whilst no significant relation with hand hygiene practice after the use of restrooms and use of gloves. Bacterial growth in meat and butcher items is at an alarming rate in spite of having good hygiene practices and nearly a quarter of isolates are multi-drug resistant.
Correlation between Aspergillus flavus fungal biomass and aflatoxin contamination in harvested maize: insights from Kenya and Tanzania
Authors: Temba Benigni Alfred , Bakari Gaymary George , Mgonja Frida Richard , Mushi James Richard
Published: August 2023

Controlling the occurrence of aflatoxins in foods must be accompanied by managing the fungi responsible for their production. The abundance and diversity of aflatoxin-producing Aspergillus flavus are responsible for the accumulation of these toxins in crops, posing a persistent threat to public health and the economy in tropical developing countries. A study was conducted to investigate the occurrence and level of A. flavus and relate them to aflatoxin levels in maize in Kenya and Tanzania. A total of 786 maize samples were collected during harvesting in selected areas of the two countries for analysis. The fungal abundance in the samples was measured as the amount of fungal DNA relative to maize DNA. This was accomplished by quantifying the fungal DNA using qPCR, targeting the internal transcribed spacer (ITS) gene, while the maize DNA was quantified through the alpha-tubulin gene, the two genes known to be conserved. Aflatoxins were quantified using ultra-high performance liquid chromatography, coupled with ultra-high sensitivity, ultra-fast triple quadrupole tandem-mass spectrophotometer. A. flavus was detected in 88.5% of the 786 tested samples, and the average fungal load for these samples (expressed as the log host/pathogen ratio) was 5.53. Aflatoxin occurrence was positive in 31.9% of the samples, with an average level of 2.3 ± 0.643 ppb. The study established a positive relationship between the occurrence and level of aflatoxin B1 and the presence and biomass of A. flavus, which was statistically proven. These findings emphasize the need to place substantial attention on preharvest control of A. flavus in cereal fields as an effort to control the accumulation of aflatoxin B1 in foods.
Challenges of implementing family-based dignity intervention
Authors: Rezaei Masoud , Seyedfatemi Naima , Ghezeljeh Tahereh Najafi
Published: August 2023

The Article Abstract is not available.
Family caregivers' perspectives on barriers to caring for patients with schizophrenia: A descriptive qualitative study
Authors: Asgari Masoumeh , Adib Masoomeh , Nayeri Nahid Dehghan , Rezayat Fatemeh
Published: August 2023

Background & Aim: Schizophrenia significantly burdens family members when a member of their family is afflicted with this condition. Family caregivers play a pivotal role in providing care and support to individuals experiencing schizophrenia within the community. Therefore, an in-depth study of family caregivers' experiences is crucial for developing effective care quality improvement programs. This study aimed at exploring family caregivers' experiences of the barriers to caregiving to patients with schizophrenia.
Methods & Materials: This study was conducted in 2021–2022 through in-depth semi-structured. The duration of the interviews varied in length from 45 to 90 minutes. Interviews were conducted with sixteen family caregivers of patients with schizophrenia. The conventional content analysis proposed by Graneheim and Lundman was used for data analysis.
Results: The findings can be classified into three primary categories. The category "Inefficiency of Support Resources" encompasses the subcategories of "Inadequate Support by Family Members," "Inadequate Support by the Healthcare System," and "Financial Predicament." The category "Limited Public Knowledge about Psychiatric Disorders" includes the subcategories of "Social Stigmatization" and "Being Social Rejection." Lastly, the category "destructive nature of schizophrenia" encompasses the subcategories of "Gradual Loss of Abilities" and "Gradual Patient Passivity."
Conclusion: Family caregivers encounter various barriers in providing patient care. Thus, they require support from the treatment team and family members, as well as financial and the development of rehabilitation programs. Additionally, involving caregivers in the patient's treatment plan and planning programs to reduce the stigma associated with caregivers is crucial.
Medication adherence and its influencing factors in community-dwelling older adults with chronic illnesses in a rural area
Authors: Ahmed Eman Hafez , Abdel-Aziz Hassanat Ramadan , Ahmed Soad
Published: August 2023

Background & Aim: Older adults with chronic diseases are usually required to manage multiple medications and complex medication regimens. Medication adherence is crucial in older adults which is increasingly being recognized due to its potential to impact healthcare utilization and treatment efficacy. The current study aimed to assess medication adherence and its influencing factors in community-dwelling older adults with chronic illnesses in rural areas. ‎
Methods & Materials: A cross-sectional study design was used to achieve the study aim. The study sample was composed of 310 older patients from a rural area in Sharkia Governorate, Egypt. Medication adherence was assessed by the Arabic version of the General Medication Adherence Scale. Association between medication adherence and older patients' characteristics was identified through the Chi-square test, Pearson's correlation coefficient, and Logistic regression.
Results: Among 310 older patients, 84.8% of them were non-adherent to their medications. Significant relationships were found between medication adherence and age, gender, educational level, marital status, and monthly income. Aging less than 70 years, female gender, sufficient income, fewer illnesses, and medication number were significant predictors for medication adherence.
Conclusion: The current study findings revealed that most rural older adults with chronic illnesses were non-adherent to their medications, with many influencing factors such as age, gender, educational level, monthly income, and illnesses and medication number. So, the study recommends the importance of developing strategies to improve medication adherence in community-dwelling older adults in rural areas.
Quantitative Analysis of the Coordinated Movement of Cells in a Freely Moving Cell Population
Authors: Umetsu Daiki , Yamaji Satoshi , Wakita Daiki , Kano Takeshi
Published: August 2023

Coordinated movement of self-propelled agents has been well studied in collectives or swarms that display directional movement. Self-propelled agents also develop stable spatial patterns in which the agents do not necessarily exhibit directional collective movement. However, quantitative measures that are required to analyze the local and temporal coordinated movements during pattern formation processes have not been well established. Here, we study the coordinated movement of individual pairs of two different types of cells in a freely moving cell population. We introduced three criteria to evaluate coordinated movement in live imaging data obtained from the abdomen of the fruit fly, Drosophila melanogaster, at the pupal stage. All three criteria were able to reasonably identify coordinated movement. Our analysis indicates that the combined usage of these criteria can improve the evaluation of whether a pair of cells exhibits coordinated movement or not by excluding false positives. Quantitative approaches to identifying coordinated movement in a population of freely moving agents constitute a key foundational methodology to study pattern formations by self-propelled agents.
Exploration of a Simple Navigation Method for Swarm Robots Pioneered by Heterogeneity
Authors: Sueoka Yuichiro , Okada Mitsuki , Tsunoda Yusuke , Sugimoto Yasuhiro , Osuka Koichi
Published: August 2023

In recent years, research has been conducted on swarm robot systems in which multiple autonomous mobile robots cooperate to perform tasks. Swarm robot systems are expected to perform high functionality as a group by cooperating with each other, in spite of the limited capabilities of the individual robots. This paper explores a method of simplifying swarm robot controllers as much as possible for swarm robot navigation. If we can achieve autonomous navigation of swarm robots to a target area with minimal resource consumption, they only need to implement the task execution function in that area. This leads to lower costs for swarm robot design and more efficient system architecture design. To address the above aims, this study focuses on heterogeneity. Specifically, we introduce a navigator robot that indirectly guides swarm robots named the worker robots. Heterogeneity in this paper refers to the worker robots and the navigator robots. We design the interaction between the navigator robot and the worker robots to provide a system that guides the worker robots to the destination.
Cooperative Passing Based on Chaos Theory for Multiple Robot Swarms
Authors: Yamagishi Kohei , Suzuki Tsuyoshi
Published: August 2023

Swarm robotics can cooperatively perform large, multiple tasks by controlling a swarm composed of many robots. Currently, approaches for operating multiple robot swarms are being studied for further evolution of this system. This study addresses a multiple movement task in which robot swarms move collectively in the same environment. In this task, the movement paths of robot swarms must pass each other in a cooperative manner when they intersect. The robots in this system behave under autonomous distributed control, thus must consider a passing behavior suitable for their own situation. This study proposes a turning behavior based on the chaos theory to ensure that a robot swarm avoids other approaching robot swarms. Each robot swarm applying the proposed method passes other swarms while autonomously deciding its turning direction and continuing its own collective movement task. In addition, the decision making based on the chaos theory predicts future values according to the current value. Therefore, it is expected to be useful for task scheduling. The performance of multiple robots passing each other is evaluated with the proposed method using numerical simulations. This performance shows that the robot swarms can avoid each other without collision using the closest inter-robot distance as the evaluation metric. Finally, robot swarms with varying shapes and scales complete their own movements in an environment where these movement paths intersect at a single point.
Bi-Connectivity Control for Multi-Robot Network Considering Line-of-Sight Communication
Authors: Murayama Toru , Iwasaki Aoi
Published: August 2023

This study proposes a bi-connectivity control algorithm for a multi-robot system consisting of a robot that communicates through line-of-sight communication. Optical observation and communication require a line of sight to a subject, and a robot in a multi-robot system sometimes impedes the line of sight between other robots. The motion of individual robots may violate the connectivity of the communication network. A distributed control strategy for bi-connectivity was constructed by modifying a previous method that does not consider line-of-sight restrictions. The results of the numerical simulation and experiments with actual robots are reported to emphasize the validity of the proposed control method.
Biomolecular Motor-Based Swarm Robot: An Innovation in Molecular Delivery
Authors: Akter Mousumi , Kakugo Akira
Published: August 2023

Biomolecular motor-based micro-sized robots have recently created an innovation in the field of science and technology as molecular transporters. Groups of these tiny robots can work substantially better than individual ones in terms of the transported distance and number or size of cargo. Site-specific molecular delivery, the main feature of these robots, has helped to improve the workability of robots in a more controllable manner.
Development of Action-Intention Indicator for Sidewalk Vehicles
Authors: Ohkubo Tomoyuki , Yamamoto Riku , Kobayashi Kazuyuki
Published: August 2023

Many small ground vehicles that travel on sidewalks, such as electric wheelchairs, are equipped with a differential-wheeled mechanism to turn precisely on the spot and accurately control their trajectory. Conventional ground vehicles operating on public roads have action indicator devices such as blinkers and brake lights, which are effective in preventing collisions during operations. However, similar blinkers may not be suitable for sidewalk navigation because the differential-wheeled mechanism allows a neutral turn without considering the surroundings. In this study, we developed a new action-intention indicator for future differential-wheeled mobile robots that employs RGB light-emitting diode strip lights to express various colors and complex blinking patterns. Sensitivity evaluation experiments were conducted with approximately 50 subjects to determine the optimal colors and blinking patterns for a differential-wheeled mobile robot. Additionally, reaction-time acquisition experiments were conducted to confirm the effectiveness of the proposed intention-display device for mobile robots. Finally, we evaluated whether the determined blinking patterns exhibited appropriate power consumption.
Coronary Ischemia Study For Patients Admitted To Damascus Hospital Under The Age Of Forty years
Authors: AJI Samer Emad
Published: August 2023

Introduction: Coronary artery disease is a common heart condition that involves the formation of atherosclerotic plaques in the lumen of blood vessels. This study describes the evaluation, diagnosis, and management of coronary artery disease and highlights the role of the health care team in the evaluation and treatment of patients with this condition.
Materials And Methodology: A cross-sectional study targeting 200 patients under the age of 40 attending a Damascus hospital with coronary ischemia.
Results: We extracted, by interpreting the results of the descriptive statistics and applying the Chi-Square tests and ANOVA, many interesting results regarding the assessment of coronary heart injury in patients admitted from the age groups younger than 40, and we found a concentration of infection in the ages. At older ages, as it develops in adults younger than 40 years old.
Recommendations: One of the most important recommendations of our study is to ascertain the reasons for the absence of this relationship in the age groups younger than 40 years, and to search for other non-traditional risk factors that may be useful in determining the causality behind the increasing incidence of coronary heart diseases in unusually young age groups.
Protective efficacy of a Zika purified inactivated virus vaccine candidate during pregnancy in marmosets
Authors: Kim In-Jeong , Gonzalez Olga , Tighe Mike , Lanthier Paula , Clark Madeline , Travis Kelsey , Lanzer Kathleen , Bernacki Derek , Szaba Frank , Barrera Rafael De La , Dussupt Vincent , Mendez-Rivera Letzibeth , Krebs Shelly , Ross Corinna , Md Stephanie , Brasky Kathleen , Layne-Colon Donna , Tardif Suzette , Thomas Stephen , Modjarrad Kayvon , Blackman Marcia , Patterson Jean , Low-Beer Timothy
Published: August 2023

Zika virus (ZIKV) infection during pregnancy poses significant threats to maternal and fetal health, leading to intrauterine fetal demise and severe developmental malformations that constitute congenital Zika syndrome (CZS). As such, the development of a safe and effective ZIKV vaccine is a critical public health priority. However, the safety and efficacy of such a vaccine during pregnancy remain uncertain. Historically, the conduct of clinical trials in pregnant women has been challenging. Therefore, clinically relevant animal pregnancy models are in high demand for testing vaccine efficacy. We previously reported that a marmoset pregnancy model of ZIKV infection consistently demonstrated vertical transmission from mother to fetus during pregnancy. Using this marmoset model, we also showed that vertical transmission could be prevented by pre-pregnancy vaccination with Zika purified inactivated virus (ZPIV) vaccine. Here, we further examined the efficacy of ZPIV vaccination during pregnancy. Vaccination during pregnancy elicited virus neutralizing antibody responses that were comparable to those elicited by pre-pregnancy vaccination. Vaccination also prevented vertical transmission of ZIKV during pregnancy, without causing adverse effects. These results provide key insights into the safety and protective efficacy of ZPIV vaccination during pregnancy, an important advance in preparedness for future ZIKV outbreaks.
Interdependent random network: a model of protein-protein interaction
Authors: M Paul Asir
Published: August 2023

Proteins are complex biomolecules that are responsible for gene encoding. These encoding happen through nucleotide transcription. The sequence of amino acids defines the various types of proteins. Proteins differ by the nucleotide sequence of their genes. Gene expression usually results in proteins folding into a specific 3D structure that determines their activity. We propose a novel model for protein folding based on complex networks that enable us to understand umpteen facets of the experimental process that causes conformational states. We chose an ensemble of nonlinear oscillators embedded in a complex network. A complex network following a random topology has been proficient of producing the largest plausibile conformation states. Also, statistical measures of the complex network capture the essence of the substates. We perform analysis on the basis of the average energy of the molecule, here an ensemble of oscillators. The model encompasses the averaged solvent-molecule interaction that assists the osmotic exchange of ions. Two models of nonlinear oscillators are studied under the chosen framework. Note that the fluctuations from equilibrium correspond to the oscillations of bond angles. We chose a relaxation oscillator and a damped harmonic oscillator to study the nuances of protein folding. Numerical studies are based on the averaged energy of the network. We also tune the density of linkers in the network to elucidate the feature of the shape factor. We remark that this model could mimic the protein data structure obtained by the solution nuclear magnetic resonance method.
A case study of Daily and Seasonal Changes in Total Electron Content in mid-latitudes Regions in the Period of 2019-2021
Authors: Taji Banafsheh , Memarian Mohammad Hossein , Rastegar Seyed Mohammad
Published: August 2023

The behavior of the total electron content (TEC) on a global scale has been the subject of research for several years. However, certain features of this behavior, including the effectiveness of energetic particles and their anomalies at different latitudes, are poorly understood. This paper reports a comparative analysis of the seasonal and daily changes in the total electron content (TEC) as observed from 2019 to 2021 during the 11-year solar cycle in eight stations in the mid-latitudes between 33.1 and 40.1 degrees. The points include eight stations across four countries with the following coordinates: Tehran (Iran) (35.6 N; 51.5 E), Hamedan (Iran) (34.6 N; 48.5 E), Tabriz (Iran) (38.1 N; 46.5 E), Yerevan (Armenia) (40.1 N; 44.5 E), Diyarbakir (Turkey) (37.6 N; 40.5 E), Ankara (Turkey) (39.6 N; 33.0 E), Cyprus (Cyprus) (35.1 N; 33.5 E), and Baghdad (Iraq) (33.1 N; 44.5 E). Also, by taking the quiet solar activity conditions into account, TEC’s variations are investigated hourly, daily, and seasonally. For this research, absolute total electron content (ATEC) observations from Global Positioning System (GPS) have been analyzed. The results showed that the highest TEC values occurred during 08:00–12:00 UT (12:00–16:00 LT), and the lowest values occurred during 23:00–02:00 UT (3:00–6:00 LT). From a seasonal point of view, in 2019 and 2020, the maximum value of TEC is observed during the March equinox and the September equinox, respectively, and the lowest maximum value of TEC is observed during the December solstice, but in 2021, the maximum value of TEC is observed during the June solstice and the lowest maximum value of TEC is observed during the December solstice.
Comparative study before and after the use of Episil ® oral liquid in patients with hematological malignancies
Authors: Fukutani Taeko , Yoshioka Yukio , Imori Shinpei , Yanagihara Hirokazu , Sumi Kensaku , Myoken Yoshinari , Fujita Yoshinori , Yanamoto Souichi
Published: August 2023

Background. Episil® is a non-absorbable liquid medical material used to cover and protect oral lesions, particularly those caused by mucositis associated with chemotherapy and radiation therapy. While there are some scattered reports on its use in head and neck cancer, there have been few studies in other malignancies.
Methods. In this study, 38 patients with hematologic malignancies treated for oral mucositis (OM) with Episil® at the Hiroshima Red Cross & Atomic-bomb Survivors Hospital were included; the degree of OM before and after use was examined. Of these 23 patients were interviewed about the effects of OM on pain, conversation, and eating, using our original evaluation protocol, and the results were compared.
Results. The severity of mucositis decreased after the use of Episil® in eight patients (21%), particularly in those with mucositis at multiple sites. Patient evaluations showed significant pain relief and improvements in speech and feeding functions. Patients with Grade 3 mucositis had higher ratings for improvement in pain relief, speech, and eating functions than those with Grade 2.
Conclusions. Episil® performed well in patients with hematologic malignancies and was particularly effective in multiple mucositis. In addition to pain relief, Episil has been suggested to improve speech and feeding functions effectively.
Prevalence and risk factors for diabetic foot complications among people living with diabetes in Harare, Zimbabwe
Authors: Kuguyo Oppah , Mukona Doreen Macherera , Chikwasha Vasco , Gwanzura Lovemore , Chirenda Joconiah , Matimba Alice
Published: August 2023

Background
Diabetic foot (DF) is one of the most common diabetes-related complications, however, the prevalence and associated risk factors of DF are not well characterized among people living with diabetes (PLWD) in Zimbabwe. This study aims to determine the prevalence of diabetic foot and associated risk factors in PLWD in Zimbabwe.
Methods
This was a cross-sectional study, employing a mixed-methods approach was used to obtain data. A total of 352 PLWD were recruited from 16 primary care clinics across Harare. Face-to-face interviews and patient record reviews were used to collect sociodemographic and clinical data. Screening for DF included sole pressure, peripheral neuropathy, ankle-brachial index, deep tendon reflexes, ulceration, and amputation were performed. Self-administered questionnaires were used to assess knowledge, attitudes, and practices (KAPs). Scoring for KAPs was done using Bloom’s cutoff, and regression analyses were used to associate variables with DF risk.
Results
This group was made up of 82 men and 279 women. The combined mean age was 57.9 ± 14 years, and the age was comparable by gender (p > 0.05). More than a quarter (n = 21) of men and 15% (n = 41) ofwomen had Type 1 diabetes. The distribution of diabetes type significantly differed by gender (p < 0.001). DF was observed in 53% of PLWD. Abnormal ankle-brachial index (53%) and peripheral neuropathy (53%), foot ulceration (17%) and amputations (3%) were observed. Peripheral neuropathy increased the risk of ulceration (OR = 1.7; 95% CI = 1.1–2.6; p = 0.019), while insulin adherence was protective against amputation (OR = 0.1; 95% CI = 0.1–0.9; p = 0.049). Most (87%) of the group demonstrated good DF knowledge and the importance of adhering to medication to prevent DF. However, 96% did not know that smoking was a risk of DF. Nearly two-thirds (63%) of the group demonstrated poor attitudes and practices. Poor attitudes and practices were not predictors of diabetic foot ulceration risk (p > 0.05).
Conclusion
Our findings report a high prevalence of DF (53%) in PLWD in Zimbabwe. However, DF is not routinely assessed in Zimbabwe. Adherence to insulin was found to protect against DF, underscoring the need for policy revisions to include screening and increasing insulin adherence to prevent DF as integral primary care for PLWD.
Tumor cell p38 inhibition to overcome immunotherapy resistance
Authors: Luke Jason , Dadey Rebekah , Augustin Ryan , Newman Sarah , Singh Krishna , Doerfler Rose , Behr Sarah , Lee Patrice , Isett Brian , Deitrick Christopher , Li Aofei , Joy Marion , Reeder Carly , Smith Katelyn , Urban Julie , Sellitto Lorenzo , Jelinek Mark , Christner Susan , Beumer Jan , Villaruz Liza , Kulkarni Aditi , Davar Diwakar , Poklepovic Andrew , Najjar Yana , Zandberg Dan , Soloff Adam , Bruno Tullia , Vujanović Lazar , Skinner Heath , Ferris Robert , Bao Riyue
Published: August 2023

Patients with tumors that do not respond to immune-checkpoint inhibition often harbor a non-T cell-inflamed tumor microenvironment, characterized by the absence of IFN-γ-associated CD8+ T cell and dendritic cell activation. Understanding the molecular mechanisms underlying immune exclusion in non-responding patients may enable the development of novel combination therapies. p38 MAPK is a known regulator of dendritic and myeloid cells however a tumor-intrinsic immunomodulatory role has not been previously described. Here we identify tumor cell p38 signaling as a therapeutic target to potentiate anti-tumor immunity and overcome resistance to immune-checkpoint inhibitors (ICI). Molecular analysis of tumor tissues from patients with human papillomavirus-negative head and neck squamous carcinoma reveals a p38-centered network enriched in non-T cell-inflamed tumors. Pan-cancer single-cell RNA analysis suggests that p38 activation may be an immune-exclusion mechanism across multiple tumor types. P38 knockdown in cancer cell lines increases T cell migration, and p38 inhibition plus ICI in preclinical models shows greater efficacy compared to monotherapies. In a clinical trial of patients refractory to PD1/L1 therapy, pexmetinib, a p38 inhibitor, plus nivolumab demonstrated deep and durable clinical responses. Targeting of p38 with anti-PD1 has the potential to induce the T cell-inflamed phenotype and overcome immunotherapy resistance.
Analysis of Risk Factors of Infection in Diabetic Foot Patients
Authors: Hsu Limei , Li Le , Poon Lee Yam
Published: August 2023

Objectives This cross-sectional study assessed the risk factors for infection in 150 diabetic foot patients admitted to the Xiamen University Hospital between October 2020 and October 2022.Methods Patients were categorized as infected (n = 80) or uninfected (n = 70) cohorts. The diabetic foot was evaluated using the American Diabetic Foot Grading system, whereas ulcers were categorized using Wagner's method. Analyzed were patient-specific information, clinical data, and risk factors including neuropathy, arterial disease and foot deformities.Results Our findings revealed no statistically significant differences between infected and uninfected cohorts concerning age, BMI, gender, duration of diabetes, or ankle-brachial index values (p > 0.05). However, infected group had a higher proportion of smokers and reduced socioeconomic status (p < 0.05). Wagner grades indicated a greater severity in the infected group, with grade 3, grade 4, and grade 5 differing significantly (p < 0.05). Comparative analysis of ulcer characteristics revealed no statistically significant differences in ulcer surface area and depth, but the infected group had a higher prevalence of osteomyelitis and a greater number of ulcers (p > 0.05). Blood vessel complications, retinopathy, the presence of three or more ulcers, osteomyelitis, and diabetic nephropathy were substantially more prevalent in the infected group, as determined by univariate analysis (p < 0.05). Subsequent multivariate logistic analysis revealed that patients with blood vessel complications, retinopathy, osteomyelitis, diabetic nephropathy, and three or more ulcers were at increased risk for infection (p < 0.05). In addition, lifestyle factors, such as smoking, sedentary behavior, inadequate foot hygiene, obesity, and poor glycemic control, were also associated with higher infection rates. A multivariate analysis of foot wound factors revealed that deeper, longer, and recurrent lesions increased the likelihood of infection. Escherichia coli was the most frequently isolated bacterium from the infected group's bacterial culture, followed by Pseudomonas aeruginosa and Staphylococcus aureus.Conclusion The study enhanced our comprehension of the multifactorial risk factors associated with infections in diabetic foot patients, highlighting the need for thorough clinical evaluation, lifestyle modification, and vigilant infection control.
Atomic-scale visualization of the interlayer Rydberg exciton complex in moiré heterostructures
Authors: Wang Zhongjie , Zhao Meng , Liu Lu , Wang Chunzheng , Liu Cheng-Yen , Yang Fang , Wu Hua , Gao Chun-Lei
Published: August 2023

Exciton complex, namely bound aggregate of multiple charged particles, represents an archetypical exemplification of correlated few-body physics. The system of long-lived excitonic states, facilitated by the negative band gap, optical pumping, electrostatic gating or magnetic field, sustains composite bosons or fermions with fascinating physics such as moiré-dominated correlated phenomena and exciton superfluidity. Although a broad spectrum of intriguing excitonic phases has been revealed via global measurements, the atomic-scale accessibility towards the intra-exciton few-body information and inter-exciton nanoscale order has yet to be established. Here, without the aforementioned approaches to maintain excitons, we instead realize the ground-state interlayer exciton complexes through the intrinsic charge transfer in monolayer YbCl3/highly oriented pyrolytic graphite (HOPG) heterostructure. Combining scanning tunneling microscope (STM) and first-principle calculations, a comprehensive understanding of the electronic structure of rare-earth insulator YbCl3 is established, and excitonic in-gap states with Rydberg-like orbitals are directly visualized. It is found that the out-of-plane excitonic charge clouds exhibit oscillating nodal structure of Rydberg type, while their in-plane arrangements are particularly determined by moiré periodicity. Exploiting the tunneling probe to reflect the shape of charge clouds, we reveal the principal quantum number hierarchy of Rydberg series, which points to an excitonic energy-level configuration with unusually large binding energy on the magnitude of electron volts. The direct imaging of ground-state exciton complexes at the lattice scale demonstrates the feasibility of mapping out the charge clouds of excitons microscopically and paves a brand-new way to directly investigate the nanoscale order of exotic correlated phases in the moiré system.
Adipose stromal cells bioproducts as cell-free therapies: manufacturing and therapeutic dose determine in vitro functionality
Authors: Skovronova Renata , Scaccia Eleonora , Calcat-i-Cervera Sandra , Bussolati Benedetta , O’Brien Timothy , Bieback Karen
Published: August 2023

Background
Extracellular vesicles (EV) are considered a cell-free alternative to mesenchymal stromal cell (MSC) therapy. Numerous reports describe the efficacy of EV in conferring immunomodulation and promoting angiogenesis, yet others report these activities to be conveyed in EV-free bioproducts. We hypothesized that this discrepancy may depend either on the method of isolation or rather the relative impact of the individual bioactive components within the MSC secretome.
Methods
To answer this question, we performed an inter-laboratory study evaluating EV generated from adipose stromal cells (ASC) by either sequential ultracentrifugation (UC) or size-exclusion chromatography (SEC). The effect of both EV preparations on immunomodulation and angiogenesis in vitro was compared to that of the whole secretome and of the EV-free protein fraction after SEC isolation.
Results
In the current study, neither the EV preparations, the secretome or the protein fraction were efficacious in inhibiting mitogen-driven T cell proliferation – highlighting the need for direct cell-to-cell contact. However, EV generated by SEC stimulated macrophage phagocytic activity to a similar extent as the secretome. In turn, tube formation and wound healing were strongly promoted by the ASC secretome and protein fraction, but not by EV. Within the secretome/protein fraction, VEGF was identified as a potential driver of angiogenesis, and was absent in both EV preparations.
Conclusions
Our data indicate that the effects of MSCs on immunomodulation and angiogenesis are EV-independent and rely on direct cell-to-cell contact or on the secretion of soluble factors, respectively. Specific MSC-EV effects need to be dissected for their use as cell-free therapeutics.
Administration of ivermectin to cattle induced mortality, reduced fecundity and survivorship of Anopheles arabiensis in Ethiopia: an implication for expansion of vector toolbox
Authors: Damene Ephrem , Massebo Fekadu
Published: August 2023

Background Although many countries have shown interest in eliminating malaria, approaches that complement existing vector control interventions are needed because existing methods have been scaled up and malaria is still present. Therefore, the effect of ivermectin administration to cattle was evaluated for its effect on mortality, survivorship and mortality of laboratory reared Anopheles arabiensis.
Methods Three calves were randomly selected and injected with ivermectin at a therapeutic dose of 0.2 mg/kg, while the other two calves received no treatment and served as controls. Five tents were constructed for the trial. Calves were housed in tents (one per tent) and then 30 hungry female An. arabiensis were introduced into each tent. Only fully engorged females were collected from each tent and placed in different mosquito cages to monitor their mortality, survival and fecundity. Data analysis was done using SPSS version 16.
Results During the follow-up period (until day 21), ivermectin induced significantly higher mortality when compared to controls. It resulted in an average 24-hour mortality rate of 81.6% against An. arabiensis on the first day following treatment. 100% An. arabiensis that fed on ivermectin-treated calves on the first day after treatment died within four days. Egg production rate of An. arabiensis that fed on ivermectin-treated calves was significantly lower compared to controls (F = 768.7, P < 0.001).
Conclusion In conclusion, ivermectin induced mortality, reduced fecundity and survivorship of laboratory maintained An. arabiensis. Further study is recommended using a wild mosquito population. Moreover, mass ivermectin administration to domestic animals could be recommended to supplement the existing indoor based interventions.
Functional restoration of REM sleep fragmentation, hippocampal oscillatory activity and altered cholinergic signaling at presymptomatic stages of AD
Authors: Berg Monica van den , Heymans Loran , Toen Danielle , Adhikari Mohit A. , Audekerke Johan van , Verschuuren Marlies , Pintelon Isabel , De Vos Winnok H. , Linden Annemie van der , Verhoye Marleen , Keliris Georgios A.
Published: August 2023

BackgroundAlzheimer’s disease (AD) is a severe neurodegenerative disorder that is hallmarked by the progressive accumulation of amyloid beta (Aβ) and tau proteins in the brain, leading to dementia. Sleep alterations occur at early stages of AD, before cognitive symptoms become apparent, which could play an important role in the pathophysiology and detection of AD. The current study aimed to evaluate how circadian rhythm, sleep macro-architecture and hippocampal oscillations are altered at pre-plaque and early-plaque stages of AD in TgF344-AD rats.MethodsWe performed 24-hour hippocampal electrophysiological measurements in TgF344-AD rats and wildtype littermates at pre- and early-plaque stages of AD, combined with histological analysis to evaluate histopathological alterations.ResultsWe observed a differential impact of AD on rapid eye movement (REM) and non-REM (NREM) sleep. Circadian rhythmicity was intact and TgF344-AD rats did not show signs of NREM sleep fragmentation. We observed a significantly increased probability for shorter REM bouts, suggestive of REM sleep fragmentation, in TgF344-AD rats at the pre-plaque stage, which recovered at the early-plaque stage. In addition, we observed a significantly decreased theta-gamma coupling, a measure for task-related information ordering, at the pre-plaque stage, which was partially restored at the early-plaque stage. Moreover, theta-gamma coupling in the slow gamma range was significantly increased during the pre-plaque stage in TgF344-AD rats but returned to WT levels at the early-plaque stage. Interestingly, the partial compensation of hippocampal activity and REM sleep behavior coincided with an increased number of cholinergic synapses in the hippocampus during the early-plaque stage in TgF344-AD rats, suggestive of basal forebrain cholinergic compensation mechanisms.ConclusionThe results from this study reveal early changes in sleep architecture and hippocampal function prior to Aß plaque deposition in AD. In addition, the current findings highlight the important role of the cholinergic system to compensate for AD-related network alterations. Network disturbances and sleep alterations are known to drive disease progression. Modulation of cholinergic signaling in early, presymptomatic AD might be a promising therapeutic strategy to alter disease progression by restoring network function and sleep architecture.
Comparative analysis of chloroplast and mitochondrial genomes of sweet potato provides evidence of gene transfer
Authors: li Guoliang , zhang hong , lin zhaomiao , li huawei , xu guochun , xu yongqing , ji rongchang , luo wenbin , qiu yongxiang , qiu sixin , tang hao
Published: August 2023

The increasing number of plant mitochondrial genomes (mtDNA) sequenced reveals the extent of transfer from both chloroplast (cpDNA) and nuclear genomes (nDNA). This study created a library and assembled the chloroplast and mitochondrial genomes of the leafy sweet potato Fucaishu18 better to understand the extent of mitochondrial and chloroplast gene transfer. The full-length chloroplast genome of Fucaishu18 (OM808940) is 161387 bp, with 132 genes annotated, including 87 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. The mitochondrial genome (OM808941) was 269578 bp in length and contained 70 functional genes, including 41 protein-coding genes, 6 rRNA genes, and 24 tRNA genes. 68 SSR loci were found in the leafy sweet potato organelle genome, including 54 in the chloroplast genome and 14 in the mitochondria genome. In the sweet potato mitochondrial genome, most genes have RNA editing sites, and the conversion ratio from hydrophilic amino acids to hydrophobic amino acids is the highest, reaching 47.12%. Horizontal transfer occurs in the sweet potato organelle genome and nuclear genome. 40 mitochondrial genome segments share high homology with 14 chloroplast genome segments, 33 of which may be derived from chloroplast genome horizontal transfer. 171 mitochondrial genome sequences come from the horizontal transfer of nuclear genome.The phylogenetic analysis of organelle genes revealed that the leafy sweet potato was closely related to the tetraploid wild species Ipomoea tabascana and the wild diploid species Ipomoea trifida.
Robust Alternating Multilayered Cellulose Nanofiber Composite Membranes Fabricated by High-Efficiency Ca 2+ -Precomplexed Vacuum-Assisted Self- Assembly towards Electromagnetic Interference Shielding
Authors: Zeng Lingjun , Xue Bai , Wu Changmei , Qi Wenjing , Ai Peng , Xie Lan , Zheng Qiang
Published: August 2023

One-dimensional cellulose nanofiber (CNF) is prone to constructing connected nanofiber networks in vacuum-assisted self-assembly due to intense hydrogen bonds, which exhibits great superiority in fabricating electromagnetic interference (EMI) shielding composite membranes. However, time-consuming vacuum-assisted assembly process creates vast bottlenecks for spreading EMI shielding CNF composites. Herein, a Ca2+-precomplexed vacuum-assisted self-assembly strategy is first proposed to high-efficiently assemble robust CNF&Carbon nanotube/Polyethylene oxide (CNF&CNT/PEO) composite membranes with alternating multilayer architectures. The introduction of Ca2+ pre-complexation can not only largely improve the fabrication efficiency but also immensely enhance the mechanical properties of alternating multilayered CNF&CNT/PEO membranes. The self-assembly time of CNF-5&CNT/PEO-4 is greatly decreased to 756 min at 0.45 mmol/L Ca2+, in comparison with the common vacuum-assisted filtration (i.e., without Ca2+) of 1192 min, owing to the hydrogen bonds between CNF and water broken down by Ca2+ complexation. With the Ca2+ concentration increasing from 0 to 0.23 further to 0.45 mmol/L, the tensile strength of CNF-3&CNT/PEO-2 is gradually reinforced from 40.2 to 43.2 and to 47.6 MPa, as a consequence of the excellent Ca2+ crosslinking and hierarchical “Zigzag” crack paths. The favorable electrical conductivity and unique alternating multilayered structures endow CNF-5&CNT/PEO-4 membrane with the maximal EMI shielding effectiveness (SE) of 43.3 dB. The Ca2+-precomplexed strategy sheds new light on high-efficient self-assembly of multilayered CNF composite membranes with pretty EMI shielding performances, which has prospective application in advanced electronics and microelectronic packaging.
Transcriptional and epigenetic changes during tomato yellow leaf curl virus infection in tomato
Authors: Romero-Rodriguez Beatriz , Petek Marko , Jiao Chen , Križnik Maja , Zagorščak Maja , Fei Zhangjun , Bejarano Eduardo R. , Gruden Kristina , Castillo Araceli G.
Published: August 2023

Background: Geminiviruses are DNA plant viruses that cause highly damaging diseases affecting crops worldwide. During the infection, geminiviruses hijack cellular processes, suppress plant defenses, and cause a massive reprogramming of the infected cells leading to major changes in the whole plant homeostasis. The advances in sequencing technologies allow the simultaneous analysis of multiple aspects of viral infection at a large scale, generating new insights into the molecular mechanisms underlying plant-virus interactions. However, an integrative study of the changes in the host transcriptome, small RNA profile and methylome during a geminivirus infection has not been performed yet. Using a time-scale approach, we aim to decipher the gene regulation in tomato in response to the infection with the geminivirus, tomato yellow curl virus (TYLCV).Results: We showed that tomato undergoes substantial transcriptional and post-transcriptional changes upon TYLCV infection and identified the main altered regulatory pathways. Interestingly, although the principal plant defense-related processes, gene silencing and the immune response were induced, this cannot prevent the establishment of the infection. Moreover, we identified extra- and intracellular immune receptors as targets for the deregulated microRNAs (miRNAs) and established a network for those that also produced phased secondary small interfering RNAs (phasiRNAs). On the other hand, there were no significant genome-wide changes in tomato methylome at 14 days post infection, the time point at which the symptoms were general, and the amount of viral DNA had reached its maximum level, but we were able to identify differentially methylated regions that could be involved in the transcriptional regulation of some of the differentially expressed genes.Conclusion: We have conducted a comprehensive and reliable study on the changes at transcriptional, post-transcriptional and epigenetic levels in tomato throughout TYLCV infection. The generated genomic information is substantial for understanding the genetic, molecular and physiological changes caused by TYLCV infection in tomato.
Unique Measure for Time-Dependent Random PDEs
Authors: Varner Gregory
Published: August 2023

This paper proves the uniqueness of measure for time-inhomogeneous random dynamical systems that exhibit particular controllability and coupling conditions. This is done by extending a result for uniqueness of measure for time-homogeneous Markov processes to the time-inhomogeneous case, showing that the Markov process is exponentially mixing in the dual-Lipschitz norm. It is then shown that the 2D Navier-Stokes equations on the sphere with a time-dependent deterministic force and a "kick"-type random perturbation satisfy the conditions and thus have a unique limiting measure.
MSC Classification: 35Q30 , 60H15 , 60J05 , 93C20 , 35R01 , 60J99