bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular vesicles remodel tumor environment for cancer immunotherapy
Authors: Yue Ming , Hu Shengyun , Sun Haifeng , Tuo Baojing , Jia Bin , Chen Chen , Wang Wenkang , Liu Jinbo , Liu Yang , Sun Zhenqiang , Hu Junhong
Published: December 2023

Tumor immunotherapy has transformed neoplastic disease management, yet low response rates and immune complications persist as major challenges. Extracellular vesicles including exosomes have emerged as therapeutic agents actively involved in a diverse range of pathological conditions. Mounting evidence suggests that alterations in the quantity and composition of extracellular vesicles (EVs) contribute to the remodeling of the immune-suppressive tumor microenvironment (TME), thereby influencing the efficacy of immunotherapy. This revelation has sparked clinical interest in utilizing EVs for immune sensitization. In this perspective article, we present a comprehensive overview of the origins, generation, and interplay among various components of EVs within the TME. Furthermore, we discuss the pivotal role of EVs in reshaping the TME during tumorigenesis and their specific cargo, such as PD-1 and non-coding RNA, which influence the phenotypes of critical immune cells within the TME. Additionally, we summarize the applications of EVs in different anti-tumor therapies, the latest advancements in engineering EVs for cancer immunotherapy, and the challenges encountered in clinical translation. In light of these findings, we advocate for a broader understanding of the impact of EVs on the TME, as this will unveil overlooked therapeutic vulnerabilities and potentially enhance the efficacy of existing cancer immunotherapies.
Associations with experience of non-fatal opioid overdose in British Columbia, Canada: a repeated cross sectional survey study
Authors: Ferguson Max , Choisil Paul , Lamb Jessica , Burmeister Charlene , Newman Cheri , Lock Kurt , Tobias Samuel , Liu Lisa , Buxton Jane A.
Published: December 2023

Introduction

Lives lost in North America due to the unregulated drug poisoning emergency are preventable and those who survive an opioid overdose may suffer long-term disability. Rates of opioid overdose more than doubled following the onset of the COVID-19 pandemic in British Columbia, Canada.

Materials and methods

Our analytical sample was comprised of 1447 participants from the 2018, 2019, and 2021 Harm Reduction Client Survey who responded yes or no to having experienced an opioid overdose in the past 6 months. Participants were recruited from harm reduction sites from across British Columbia. We used logistic regression to explore associations of experiencing an opioid overdose.

Results

Overall, 21.8% of participants reported experiencing an opioid overdose in the last six months (18.2% in 2019 and 26.6% in 2021). The following factors were positively associated with increased adjusted odds of experiencing a non-fatal opioid overdose: cis men relative to cis women (AOR 1.49, 95% CI 1.10–2.02), unstably housed compared to people with stable housing (AOR 1.87, 95% CI 1.40–2.50), and participants from 2021 compared to those from 2019 (AOR 3.06, 95% CI 1.57–5.97). The effects of both previous experience of a stimulant overdose and having witnessed an opioid overdose depended on the year of study, with both effects decreasing over subsequent years.

Conclusions

Overdoses have increased over time; in 2021 more than one in four participants experienced an overdose. There is an urgent need for policy and program development to meaningfully address the unregulated drug poisoning emergency through acceptable life-saving interventions and services to prevent overdoses and support overdose survivors.
Interactions between local medical systems and the biomedical system: a conceptual and methodological review in light of hybridization subprocesses
Authors: Abreu Marina Barros , Ferraz Thais Samila de Oliveira , Albuquerque Ulysses Paulino , Ferreira Júnior Washington Soares
Published: December 2023

Local medical systems (LMSs) are complex and dynamic, encompassing local perceptions of diseases, prevention and treatment strategies, and evaluations of therapeutic responses. These systems are not isolated and interact with other medical systems, such as the biomedical system. The interaction between these systems creates a "contact zone", which some authors refer to as intermedicality, involving both competitive and complementary interactions. However, there is limited discussion in the literature regarding the complexity of these interactions. Some studies seek to understand this interaction through the lens of hybridization, a concept introduced to ethnobiology by Ana Ladio and Ulysses Albuquerque. The authors conceptualize hybridization as "discrete structures and practices coming together to form a new practice not necessarily implying homogenization." They discuss hybridization in the context of medicinal plants used in urban settings and propose seven hybridization subprocesses to gain a deeper understanding of this phenomenon. In this study, we update these hybridization subprocesses, expanding the concepts to comprehend the specific interaction of resources from LMS and biomedical systems known and used by different human groups. In this context, we propose a new subprocess and have made adjustments to the existing subprocesses to encompass the diversity of possible interactions between medicinal plants and pharmaceuticals, providing evidence from the literature demonstrating interactions that can be classified within the proposed subprocesses. Furthermore, we discuss, from a theoretical standpoint, how these subprocesses may have implications for the resilience of medical systems. Moreover, we propose a flowchart that can be utilized to identify these hybridization subprocesses in intermedicality contexts in future studies. These classifications are crucial because they enable us to comprehend the complexity of interactions between medicinal plants and pharmaceuticals, as well as the impacts that these different interactions can have on the resilience of LMSs.
Cross-cultural adaptation and validation for central sensitization inventory: based on Chinese patients undergoing total knee arthroplasty for knee osteoarthritis
Authors: Xu Chao , Yao Shuxin , Wei Wei , Zhang Haiyue , Ma Jianbing , Shang Lei
Published: December 2023

Background

This study was conducted to develop a simplified Chinese version of the central sensitization inventory (CSI-CV) and to evaluate its reliability and validity.

Methods

The CSI-CV was developed through a process involving the translation and back translation of the original CSI. Subsequently, experts reviewed and revised the content of the items to ensure their appropriateness. A total of 325 patients with knee osteoarthritis (KOA), who were scheduled to undergo total knee arthroplasty (TKA), completed the CSI-CV at a prominent orthopedic center in Xi'an, China. Afterward, a random selection of 100 participants was chosen for retesting after one week. The reliability and validity of the inventory were evaluated through exploratory factor analysis, correlation coefficient calculation and other methods.

Results

The CSI-CV consists of 25 items in five dimensions (emotional distress, headache and jaw symptoms, physical symptoms, urological symptoms, and fatigue and sleep problems). The cumulative variance contribution rate was 75.3%, the Cronbach's α coefficient was 0.83, the Guttman split-half reliability coefficient was 0.88 and the intraclass correlation coefficient was 0.965. The CSI-CV scores correlated moderately with the total scores of the brief pain inventory (r = 0.506), Western Ontario and McMaster Universities Osteoarthritis Index (r = 0.466) and EuroQoL Group's five-dimension questionnaire (r = 0.576).

Conclusions

The findings demonstrate that the CSI was successfully trans-culturally adapted into a simplified Chinese version (CSI-CV) that was reliable and valid for Chinese-speaking patients who awaiting TKA for KOA.
Are floating toes associated with lifestyle in children? A cross‐sectional study
Authors: Nagamoto Hideaki , Okunuki Takumi , Takahashi Shimpei , Wakamiya Kazuki , Liu Zijian , Maemichi Toshihiro , Katsutani Hirofumi , Yamada Yoshiyasu , Takahashi Hiroyuki , Tanaka Hirofumi , Aizawa Toshimi , Kumai Tsukasa
Published: December 2023

Background

Floating toes are a condition and deformity in which some of the toes are afloat. Many functional impairments in floating toes have been previously studied lately and several factors related to floating toes have also been reported. However, no reports have considered the relationship between lifestyle and floating toes among children. The purpose of this study was to reveal the prevalence of floating toes among school children and reveal its relationship with lifestyle.

Methods

In total, 138 young male baseball players were recruited. Lifestyle was evaluated by using a questionnaire and chosen whether the main lifestyle was Japanese or Western, if the bedding was futons or beds, and if the toilet was Japanese style (a squat toilet) or Western style. Floating toes were defined as toes that were not in contact with the mat. Ankle dorsiflexion in the knee‐flexed and knee‐extended positions was measured in a weight‐bearing position. The relationship between the floating toes and lifestyles, and the comparison of ankle dorsiflexion range of motion between the lifestyles were statistically analyzed.

Results

Players living in a Western style showed a significantly higher prevalence of floating toes on both feet compared with the players living in a Japanese style (throwing side; 39% vs. 19%, p = 0.04, and non‐throwing side; 43% vs. 19%, p = 0.01). Players living in a Western style with beds showed a significantly smaller range of motion on both sides of ankle dorsiflexion in the knee‐flexed position compared with those who were not (throwing side; 37.2 ± 5.7° vs. 39.0 ± 6.6°, p = 0.04, and non‐throwing side; 36.8 ± 5.8° vs. 38.6 ± 6.1°, p = 0.04).

Conclusion

Children mainly living in a Western lifestyle showed a significantly higher prevalence of floating toes on both feet compared to those mainly living in a Japanese lifestyle. The prevalence of floating toes may be related to lifestyles among children.

Trial registration

The study was approved by the institutional review board of the Waseda University Graduate School of Sport Sciences (IRB number 2021–185).
The association between systemic immune-inflammation index and in vitro fertilization outcomes in women with polycystic ovary syndrome: a cohort study
Authors: Li Xin , Luan Ting , Wei Yi , Zhang Juan , Zhang JuanJuan , Zhao Chun , Ling Xiufeng
Published: December 2023

Background

As a novel prognostic and inflammatory marker, the systemic immune-inflammation index (SII) has come to the foreground in recent years. SII may be used as an indicator reflecting the progressive inflammatory process in patients with polycystic ovary syndrome (PCOS). This study aimed to evaluate the correlation between SII and assisted reproductive outcomes in PCOS patients.

Results

A total of 966 women undergoing in vitro fertilization (IVF) procedure with PCOS were included in the study. The SII was calculated as platelet count (/L) × neutrophil count (/L)/lymphocyte count (/L). Participants were divided into four groups according to SII quartiles calculated at baseline, and the differences of clinical and laboratory outcomes between these four groups were compared. Moreover, a univariate linear regression model was used to evaluate the associations between SII and the outcomes. Patients in the highest SII quartile (Q4) had lower antral follicle count (AFC), estradiol (E2), and progesterone (P) levels on the day of human chorionic gonadotropin (HCG) start compared with the lower three SII quartiles (Q1-Q3). Moreover, our analysis demonstrated that women in the lower SII quartiles had a higher rate of available embryos and blastocyst formation compared with those in the highest SII quartile. Logarithm of SII correlated negatively with available embryo rate, but not with number of available embryos. Additionally, the results of our multivariate logistic regression analyses indicated that the highest SII quartile was negatively associated with biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), live birth rate (LBR), and implantation rate (IR). A non-linear relationship between the SII and number of available embryos, with a negative relationship seen to the right of the inflection point was also found.

Conclusions

The interplay among thrombocytosis, inflammation, and immunity could influence assisted reproductive outcomes in PCOS patients. In this regard, SII may serve as a valuable marker for exploring potential correlations.
Interleukin-36 is overexpressed in human sepsis and IL-36 receptor deletion aggravates lung injury and mortality through epithelial cells and fibroblasts in experimental murine sepsis
Authors: Wang Huachen , Wang Meixiang , Chen Junlan , Hou Hongda , Guo Zheng , Yang Hong , Tang Hua , Chen Bing
Published: December 2023

Background

Sepsis is defined as a life-threatening syndrome caused by an unbalanced host response to infection. The role of interleukin (IL)-36 cytokines binding to the IL-36 receptor (IL-36R) in host response during sepsis remains unknown.

Methods

Serum IL-36 level was measured in 47 septic patients sampled on the day of intensive care unit (ICU) and emergency department admission, 21 non-septic ICU patient controls, and 21 healthy volunteers. In addition, the effects of IL-36R deletion on host inflammatory response in cecal ligation and puncture (CLP)-induced polymicrobial sepsis was determined.

Results

On the day of ICU and emergency department admission, the patients with sepsis showed a significant increase in serum IL-36 levels compared with ICU patient controls and healthy volunteers, and the serum IL-36 levels were related to the severity of sepsis. Non-survivors of septic patients displayed significantly lower serum IL-36 levels compared with survivors. A high serum IL-36 level in ICU and emergency department admission was associated with 28-day mortality, and IL-36 was found to be an independent predictor of 28-day mortality in septic patients by logistic regression analysis. Furthermore, IL-36R deletion increased lethality in CLP-induced polymicrobial sepsis. Septic mice with IL-36R deletion had higher bacterial load and demonstrated more severe multiple organ injury (including lung, liver, and kidney) as indicated by clinical chemistry and histopathology. Mechanistically, IL-36R ligands released upon lung damage activated IL-36R+lung fibroblasts thereby inducing expression of the antimicrobial protein lipocalin 2. Moreover, they induced the apoptosis of lung epithelial cells.

Conclusions

Septic patients had elevated serum IL-36 levels, which may correlate with disease severity and mortality. In experimental sepsis, we demonstrated a previously unrecognized role of IL-36R deletion in increasing lethality.
Dry suction versus wet suction technique of endoscopic ultrasound-guided fine-needle biopsy for diagnosis of solid pancreatic lesions: study protocol of a multicenter randomized controlled non-inferiority trial
Authors: Xu Shenglin , Wang Junfen , Guo Jianian , Xie Fang , Qiao Weiguang , Meng Yiteng , Peng Peng , Hu Haiyan , Huang Ying , Liu Side , Qin Mengbin , Yao Jun , Li Yue
Published: December 2023

Background

Studies have shown that the wet suction technique in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) generates better histological diagnostic accuracy and specimen quality than the dry suction technique. However, conclusions of wet suction on the diagnostic accuracy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) are still controversial. Besides, the optimal number of passes for EUS-FNB has not been determined. We aimed to design a large multicenter randomized trial to compare the diagnostic accuracy of dry suction versus wet suction technique in solid pancreatic lesions (SPLs) using 22G Franseen needles and determine the optimal number of passes required for EUS-FNB.

Methods

This is a multi-center open-label, randomized controlled non-inferiority trial with two parallel groups. Two hundred patients with SPLs will undergo EUS-FNB using 22G Franseen needles in 4 tertiary hospitals in China and will be randomly assigned to the dry suction group and wet suction group in a ratio of 1:1. The primary endpoint is diagnostic accuracy. Secondary endpoints include the optimal number of needle passes, sensitivity, specificity, specimen quality, cytological diagnoses, time of the procedure, and incidence of complications.

Discussion

This study has been designed to determine (i) whether EUS-FNB using 22G Franseen needle with dry suction is non-inferior to wet suction in terms of diagnostic accuracy and (ii) the optimal number of passes during EUS-FNB of SPLs using 22G Franseen needle.

Trial registration

ClinicalTrials.gov NCT05549856. Registered on September 22, 2022.
Glycosides from the leaves of Fraxinus Hubeiensis
Authors: Liu Xin-Yi , Tang Hong-Xia , Sheng Wen-Bing , Luo Qu-Jing , Mao Lin-Xi , Yang Yu-Pei , Guo Xiao-Zhou , Wu Qing-Lai , Jian Yu-Qing , Wang Wei , Zhou Xu-Dong
Published: December 2023

Fraxinus hubeiensis is a plant endemic to China and widely used as folk medicine to treat various diseases. However, its chemical constituents have never been reported sufficiently. Thus, the primary objective of this study was to investigate the phytochemical constituents and biological activities of F. hubeiensis leaves. Hence, combined column chromatographic and spectroscopic techniques were used to identify and characterize the secondary metabolites such as a pair of 3-keto-glycoside epimers (1) and (2), along with five known compounds (3 ~ 7). The results of α-glucosidase inhibitory activity exhibited that 1 and 2 had moderate activity with IC50 values of 359.50 and 468.43 µM, respectively, compared to a positive control acarbose with the IC50 value of 164.08 µM. However, Compounds 1–6 were shown to be inactive against the tested microbes.
Smart green spectrophotometric assay of the ternary mixture of drotaverine, caffeine and paracetamol in their pharmaceutical dosage form
Authors: Ghonim Rana , Tolba Manar M. , Ibrahim Fawzia , El-Awady Mohamed I.
Published: December 2023

Three green and facile spectrophotometric methods were developed for the assay of Petro® components; drotaverine HCl (DRT), caffeine (CAFF), and paracetamol (PAR). The three methods depend on measuring the absorbance of the studied drugs through their ethanolic solution. The first derivative spectrophotometry (FDS) at (Δλ = 10) were good parameters for DRT and CAFF resolution; DRT and CAFF could be well calibrated using FDS at 320 and 285 nm, respectively. PAR could be estimated at 308 nm utilizing the second derivative spectrophotometry (SDS). Method II relies on the double divisor ratio derivative spectroscopy (DDRDS). The first derivative was applied on each drug where they would be assayed at 309, 288, and 255 nm for DRT, CAFF, and PAR, respectively. Method III depends on the mean centering (MCR) technique. DRT, CAFF, and PAR could be determined at 309, 214, and 248 nm, respectively. The concentrations were rectilinear in the ranges of 2–20 µg/mL for DRT, 1.5–15 µg/mL for CAFF, and 2–40 µg/mL for PAR in double devisor and mean centering but PAR from 5 to 40 µg/mL in derivative method. Method validation was performed according to ICH guidelines assured by the agreement with the comparison method. In addition, greenness assessment of the proposed methods was investigated. The application of the proposed method was extended to analyse tablet dosage form and performing invitro dissolution testing.
Lentinan has a beneficial effect on cognitive deficits induced by chronic Toxoplasma gondii infection in mice
Authors: Liu Shuxi , Yan Ziyi , Peng Yuan , Liu Yunqiu , Li Yiling , Xu Daxiang , Gong Yuying , Cui Zeyu , Wu Yongshui , Zhang Yumei , Wang Dahui , Pan Wei , Yang Xiaoying
Published: December 2023

Background

Toxoplasma gondii (T. gondii) is increasingly considered a risk factor for neurodegenerative diseases. However, there is only limited information on the development of drugs for T. gondii infection. Lentinan from Lentinula edodes is a bioactive ingredient with the potential to enhance anti-infective immunity. The present study aimed to investigate the neuroprotective effect of lentinan on T. gondii-associated cognitive deficits in mice.

Methods

A chronic T. gondii infection mouse model was established by administering 10 cysts of T. gondii by gavage. Lentinan was intraperitoneally administered 2 weeks before infection. Behavioral tests, RNA sequencing, immunofluorescence, transmission electron microscopy and Golgi-Cox staining were performed to assess the effect of lentinan on cognitive deficits and neuropathology in vivo. In vitro, the direct and indirect effects of lentinan on the proliferation of T. gondii tachyzoites were evaluated in the absence and presence of BV-2 cells, respectively.

Results

Lentinan prevented T. gondii-induced cognitive deficits and altered the transcriptome profile of genes related to neuroinflammation, microglial activation, synaptic function, neural development and cognitive behavior in the hippocampus of infected mice. Moreover, lentinan reduced the infection-induced accumulation of microglia and downregulated the mRNA expression of proinflammatory cytokines. In addition, the neurite and synaptic ultrastructural damage in the hippocampal CA1 region due to infection was ameliorated by lentinan administration. Lentinan decreased the cyst burden in the brains of infected mice, which was correlated with behavioral performance. In line with this finding, lentinan could significantly inhibit the proliferation of T. gondii tachyzoites in the microglial cell line BV2, although lentinan had no direct inhibitory effect on parasite growth.

Conclusions

Lentinan prevents cognitive deficits via the improvement of neurite impairment and synaptic loss induced by T. gondii infection, which may be associated with decreased cyst burden in the brain. Overall, our findings indicate that lentinan can ameliorate T. gondii-related neurodegenerative diseases.

Graphical Abstract
Laparoscopic retroperitoneal heminephrectomy for renal cell carcinoma in horseshoe kidney: a case report and review of the literature
Authors: Ngo Xuan Thai , El-Achkar Adnan , Dobbs Ryan W. , Tiong Ho Yee , Chau Quy Thuan , Tran Trong Tri , Van Dinh Le Quy , Zein Marwan , Le Nho Tinh , Truong Ho Trong Tan , Tran Tan Sang , Thai Minh Sam , Nguyen Tuan Thanh
Published: December 2023

Introduction

In this case report, we demonstrate our technique of a retroperitoneal laparoscopic heminephrectomy for a T1b right hilar tumor in a horseshoe kidney.

Case presentation

A 77-year-old Vietnamese woman presented to the hospital because of right flank pain. On presentation, her serum creatinine was 0.86 mg/dL and glomerular filtration rate was 65.2 mL/minute/1.73 m2. According to her renal scintigraphy, glomerular filtration rates of the right and left moieties were 24.2 and 35.5 mL/minute, respectively. Computed tomography imaging demonstrated a 5.5 × 5.0 cm solid hilar mass with a cT1bN0M0 tumor stage was in the right moiety. After discussion, the patient elected a minimally invasive surgery to treat her malignancy. The patient was placed in a flank position. We used Gaur’s balloon technique to create the retroperitoneal working space, and four trocar ports were planned for operation. Three arteries were dissected, including two arteries feeding the right moiety, one artery feeding the isthmus, and one vein, which was clipped and divided by Hem-o-lok. The isthmusectomy was performed with an Endostapler. Consequently, the ureter was clipped and divided. Finally, the whole right segment of the horseshoe kidney was mobilized and taken out via the flank incision.

Results

The total operative time was 250 min with an estimated blood loss of 200 mL. The patient's serum creatinine after surgery was 1.08 mg/dL, and glomerular filtration rate was 49.47 mL/minute/1.73 m2. The patient was discharged on postoperative day #4 without complication. Final pathologic examination of the tumor specimen revealed a Fuhrman grade II clear cell renal cell carcinoma, capsular invasion, with negative surgical margins. After a three-month follow-up, the serum creatinine was 0.95 mg/dL, and glomerular filtration rate was 57.7 mL/minute/1.73 m2. Local recurrence or metastasis was not detected by follow-up computed tomography imaging.

Conclusions

Retroperitoneal laparoscopic heminephrectomy is a safe and feasible technique for patients with renal cell carcinoma in a horseshoe kidney and may be particularly useful in low income settings without access to robotic technology.
Evaluation of energy consumption of LPWAN technologies
Authors: Rajab Husam , Al-Amaireh Husam , Bouguera Taoufik , Cinkler Tibor
Published: December 2023

The majority of IoT implementations demand sensor nodes to run reliably for an extended time. Furthermore, the radio settings can endure a high data rate transmission while optimizing the energy-efficiency. The LoRa/LoRaWAN is one of the primary low-power wide area network (LPWAN) technologies that has highly enticed much concentration. The energy limits is a significant issue in wireless sensor networks since battery lifetime that supplies sensor nodes have a restricted amount of energy and neither expendable nor rechargeable in most cases. A common hypothesis is that the energy consumed by sensors in sleep mode is negligible. With this hypothesis, the usual approach is to consider subsets of nodes that reach all the iterative targets. These subsets also called coverage sets, are then put in the active mode, considering the others are in the low-power or sleep mode. In this paper, we address this question by proposing an energy consumption model based on LoRa and LoRaWAN, which optimizes the energy consumption of the sensor node for different tasks for a period of time. Our energy consumption model assumes the following, the processing unit is in on-state along the working sequence which enhances the MCU unit by constructing it in low-power modes through most of the activity cycle, a constant time duration, and the radio module sends a packet of data at a specified transmission power level. The proposed analytical approach permits considering the consumed power of every sensor node element where the numerical results show that the scenario in which the sensor node transfers data to the gateway then receives an acknowledgment RX2 without receiving RX1 consumes the most energy; furthermore, it can be used to analyze different LoRaWAN modes to determine the most desirable sensor node design to reach its energy autonomy where the numerical results detail the impact of scenario, spreading factor, and bandwidth on power consumption.
Genetic association studies in critically ill patients: protocol for a systematic review
Authors: Cox Eline G. M. , Zhang Wenbo , van der Voort Peter H. J. , Lunter Gerton , Keus Frederik , Snieder Harold
Published: December 2023

Introduction

Patients in the intensive care unit (ICU) are highly heterogeneous in characteristics, their clinical course, and outcomes. Genetic variability may partly explain the variability and similarity in disease courses observed among critically ill patients and may identify clusters of subgroups. The aim of this study is to conduct a systematic review of all genetic association studies of critically ill patients with their outcomes.

Methods and analysis

This systematic review will be conducted and reported according to the HuGE Review Handbook V1.0. We will search PubMed, Embase, and the Cochrane Library for relevant studies. All types of genetic association studies that included acutely admitted medical and surgical adult ICU patients will be considered for this review. All studies will be selected according to predefined selection criteria, evaluated and assessed for risk of bias independently by two reviewers. Risk of bias will be assessed according to the HuGE Review Handbook V1.0 with some modifications reflecting recent insights. We will provide an overview of all included studies by reporting the characteristics of the study designs, the patients included in the studies, the genetic variables, and the outcomes evaluated.

Ethics and dissemination

We will use data from peer-reviewed published articles, and hence, there is no requirement for ethics approval. The results of this systematic review will be disseminated through publication in a peer-reviewed scientific journal.

Systematic review registration

PROSPERO CRD42021209744.
Recent progress on drugs discovery study for treatment of COVID-19: repurposing existing drugs and current natural bioactive molecules
Authors: Oktavianawati Ika , Santoso Mardi , Bakar Mohd Fadzelly Abu , Kim Yong-Ung , Fatmawati Sri
Published: December 2023

COVID-19 has been a major global health concern for the past three years, and currently we are still experiencing coronavirus patients in the following years. The virus, known as SARS-CoV-2, shares a similar genomic identity with previous viruses such as SARS-CoV and MERS-CoV. To combat the pandemic, modern drugs discovery techniques such as in silico experiments for docking and virtual screening have been employed to design new drugs against COVID-19. However, the release of new drugs for human use requires two safety assessment steps consisting of preclinical and clinical trials. To bypass these steps, scientists are exploring the potential of repurposing existing drugs for COVID-19 treatment. This approach involves evaluating antiviral activity of drugs previously used for treating respiratory diseases against other enveloped viruses such as HPV, HSV, and HIV. The aim of this study is to review repurposing of existing drugs, traditional medicines, and active secondary metabolites from plant-based natural products that target specific protein enzymes related to SARS-CoV-2. The review also analyzes the chemical structure and activity relationship between selected active molecules, particularly flavonol groups, as ligands and proteins or active sites of SARS-CoV-2.
Research progress of metabolomics in cervical cancer
Authors: Jia Yuhan , Zou Kun , Zou Lijuan
Published: December 2023

Introduction

Cervical cancer threatens women's health seriously. In recent years, the incidence of cervical cancer is on the rise, and the age of onset tends to be younger. Prevention, early diagnosis and specific treatment have become the main means to change the prognosis of cervical cancer patients. Metabolomics research can directly reflect the changes of biochemical processes and microenvironment in the body, which can provide a comprehensive understanding of the changes of metabolites in the process of disease occurrence and development, and provide new ways for the prevention and diagnosis of diseases.

Objectives

The aim of this study is to review the metabolic changes in cervical cancer and the application of metabolomics in the diagnosis and treatment.

Methods

PubMed, Web of Science, Embase and Scopus electronic databases were systematically searched for relevant studies published up to 2022.

Results

With the emergence of metabolomics, metabolic regulation and cancer research are further becoming a focus of attention. By directly reflecting the changes in the microenvironment of the body, metabolomics research can provide a comprehensive understanding of the patterns of metabolites in the occurrence and development of diseases, thus providing new ideas for disease prevention and diagnosis.

Conclusion

With the continuous, in-depth research on metabolomics research technology, it will bring more benefits in the screening, diagnosis and treatment of cervical cancer with its advantages of holistic and dynamic nature.
Role of Topical Antibiotic Ointment in the Lateral Graft following Underlay Myringoplasty: A Prospective Randomised Study
Authors: Lou Zhengcai , Lou Zihan , Lv Tian , Chen Zhengnong
Published: December 2023

Objective

The objective of this study was to compare the graft outcome and postoperative infection of with and without the use of antibiotic ointment following myringoplasty for the treatment of chronic perforations.

Study Design

Randomized controlled trial.

Material and Methods

135 chronic perforations were prospectively randomized to use of antibiotic ointment group (UAO, n = 68) or no use of antibiotic ointment group (NAO, n = 67) following myringoplasty. The graft outcomes and postoperative infection were compared among two groups at 6 months.

Results

At postoperative 6 months, the graft infection rate was 4.4% in the UAO group and 10.4% in the NAO group, the difference was not significant ( P = 0.312). The graft success rates were 92.6% in the UAO group and 91.0% in the NAO group, the difference was not significant ( P = 0.979). In the UAO group, 3 patients with purulence ear discharge resulted in a residual perforation although they received ofloxacin ear drops and intravenous antibiotic therapy treatment. In the NAO group, 6 patients with purulence ear discharge resulted in a residual perforation, only one, with mild purulence discharge was successfully treated and closed. In addition, no significant between-group differences were observed pre- ( P = 0.746) or post- ( P = 0.521) operative air bone gap (ABG) values or mean ABG gain ( P = 0.745). However, granular myringitis with minimal moistness but without infection has been noted in 3 (4.4%) patients in the UAO group and in 5 (7.5%) in the NAO group, the difference was not significant ( P = 0.699).

Conclusions

Use and non-use of antibiotic ointments for lateral packing of graft are both comparable methods following myringoplasty for postoperative infection and graft outcomes.
Computational techniques for virtual reconstruction of fragmented archaeological textiles
Authors: Gigilashvili Davit , Lukesova Hana , Gulbrandsen Casper Fabian , Harijan Akash , Hardeberg Jon Yngve
Published: December 2023

Archaeological artifacts play important role in understanding the past developments of the humanity. However, the artifacts are often highly fragmented and degraded, with many details and parts missing due to centuries’ long degradation. Archaeologists and conservators attempt to reconstruct the original state of the objects either physically or virtually. This process includes characterizing and matching fragments’ features to identify which ones belong together. However, this process currently requires an extensive and tedious manual labor. Recent development in computational techniques gave rise to computer-assisted ways of virtual reconstruction, where the computer suggests solutions to the puzzle of scattered fragments and supplements or fully replaces manual labor. However, the capabilities of computational techniques remain limited in many aspects. This review summarizes the state-of-the-art computational techniques for puzzle and virtual reconstruction problems in cultural heritage applications, in general – with a particular interest in archaeological textiles. We overview existing computational methods, their applications and limitations. Afterward, based on the current knowledge gaps, we discuss where the field should go next.
Functional intervention following cardiac surgery to prevent postoperative delirium in older patients (FEEL WELL study)
Authors: Dogan Tuğce Dinç , Guttenthaler Vera , Zimmermann Alexa , Kunsorg Andrea , Dinç Merve Özlem , Knuelle Niko , Schewe Jens-Christian , Wittmann Maria
Published: December 2023

Background

Postoperative delirium is a common complication in patients after cardiac surgery, especially in older patients, and can manifest as a disturbance of attention and consciousness. It can lead to increased postoperative morbidity, prolonged need for care, and mortality. The presented study investigates whether the occurrence of postoperative delirium after cardiac surgery can be prevented by a multisensory stimulation. It was conducted as a prospective, randomized, controlled, non-pharmacological intervention study in the years 2021 and 2022 at the University Hospital Bonn in Germany. A total of 186 patients over 65 years with elective cardiac surgery were enrolled. Patients were randomized either to the intervention or control group. In both groups, postoperative delirium was assessed with the 3-min diagnostic interview for confusion assessment method on the first 5 days after surgery and pain was assessed using the Numeric Rating Scale. Multisensory stimulation was performed 20 min a day for the first three postoperative days in the intervention group.

Results

The incidence of postoperative delirium was 22.6% in the intervention group and 49.5% in the control group (p < 0.001). Duration of postoperative delirium was significantly shorter in the intervention group (p < 0.001). Stay in the intensive care unit was significantly longer in the control group (p = 0.006). In the regression model non-intervention, high pain scores, advanced age, and prolonged mechanical ventilation were associated with postoperative delirium (p = 0.007; p = 0.032; p = 0.006; p = 0.006, respectively).

Conclusions

Results of the study imply that a multisensory stimulation done on the first 3 days after planned cardiac surgery can reduce the incidence and duration of postoperative delirium in older patients. Influence of the treatment on the incidence of delirium in other patient groups, the length of stay in the intensive care unit, and patients´ postoperative pain should be confirmed in further clinical studies.

Trial registration: DRKS, DRKS00026909. Registered 28 October 2021, Retrospectively registered, https://drks.de/search/de/trial/DRKS00026909.
Assessing the potential of ionosonde for forecasting post-sunset equatorial spread F: an observational experiment in Southeast Asia
Authors: Abadi Prayitno , Ali Ahmad Umar , Otsuka Yuichi , Jamjareegulgarn Punyawi , Almahi Alif , Perwitasari Septi , Supriadi Slamet , Harjupa Wendi , Septiawan Reza Rendian
Published: December 2023

The occurrence of equatorial spread F (ESF) has the potential to detrimentally impact space-based technological systems. This study investigates the utility of ionosondes in forecasting the incidence of post-sunset ESF in the zonal direction, utilizing observational data obtained from four ionosondes located near the magnetic Equator in Southeast Asia. Data were collected during the equinox seasons (March–April and September–October) between 2003 and 2020. To establish a relationship between the probability of post-sunset ESF occurrence and the evening vertical plasma drift (v), a logistic regression model was employed. Post-sunset ESF occurrence is defined as the presence of ESF during the time window between 19:00 and 21:00 LT, while v is derived from the average time derivative of virtual heights during the interval from 18:30 to 19:00 LT. Results indicate that the probability of post-sunset ESF occurrence approaches zero, signifying that ESF is unlikely to develop when v is negative. Conversely, when v exceeds 30 m/s, the probability of post-sunset ESF occurrence surpasses 0.87, indicating that ESF occurs almost invariably. The likelihood of post-sunset ESF occurrence reaches 1 when v equals or exceeds 40 m/s. Utilizing this model, the study determined that a single ionosonde positioned at the Equator can effectively forecast the incidence of post-sunset ESF up to a longitudinal distance of 30° from its location. The accuracy of ionosondes in predicting post-sunset ESF occurrence above their respective locations is approximately 0.80, with a 10% decrease in accuracy when forecasting ESF occurrence at longitudinal distances of 30°. In conclusion, this study enhances our understanding of the link between the evening vertical plasma drift and the manifestation of post-sunset ESF by leveraging ionosonde data. Furthermore, it provides valuable insights into the recommended coverage range of ionosondes for predicting post-sunset ESF occurrence in the zonal direction, which can be employed to fortify regional space weather services.

Graphical Abstract
Extrusion of the anterior segment of the medial meniscus extrusion initiates knee osteoarthritis: evaluation using magnetic resonance imaging
Authors: Ichiba Atsushi , Ito Eichi , Kino Keiichiro
Published: December 2023

Purpose

Meniscus extrusion contributes to the progression of knee osteoarthritis (OA). It is not clear which site of the medial meniscus (MM) extrusion (MME) is greatest. Moreover, the relationship between sites of MME and progression of OA has not yet been elucidated. The purpose of this study was to determine which sites of MME that showed the greatest extrusion and to investigate the relationship between the presence of MM tears and MME, the relationship between the progression of OA and MME.

Methods

A cohort of 111 patients were studied retrospectively. The OA grade was classified using the Kellgren‐Lawrence (K‐L) grade. MME was measured at 13 positions from the anterior to the posterior segment using magnetic resonance imaging (MRI) with slices perpendicular to the MM (radial MRI). The relationship between the K‐L grade and the site of the MME was investigated. The patients were grouped as follows: The patients over 40‐years‐old were grouped as follows: patients with the K‐L grade ≤1 and without a MM tear (Group En (early, no meniscus tear)); patients with the K‐L grade ≤1 with a MM tear (Group Ep (early, positive meniscus tear)); patients with the K‐L grade ≥2 and without a MM tear (Group An (advanced, no meniscal tear)); patients over‐40 years‐old with the K‐L grade ≥2 and with a MM tear (Group Ap (advanced, positive meniscus tear)). And patients between 15 and 39‐years‐old with no abnormal findings on MRI were defined as control group (Group C).

Results

In the Groups En and Ep, MME was greatest in the anterior segment, and was greater in Group Ep than in Group En. In Groups Ap and Group C, extrusion was greatest in the middle segment.

Conclusion

The results suggest that MME predominantly occurred in the anterior segment with increasing age, after that, MM extruded at the middle segment with progression of OA and MM tear.

Level of evidence IV
Surgical technique: posterior cruciate ligament (PCL) reconstruction using double posteromedial arthroscopic portals
Authors: Lucidi Gian Andrea , Seil Romain , Agostinone Piero , Toanen Cécile , Grassi Alberto , Zaffagnini Stefano
Published: December 2023

The posterior cruciate ligament (PCL) reconstruction is a technically demanding surgical procedure that requires optimal identification of both the femoral and the tibial anatomical footprints. To aid the tibial tunnel placement and many authors recommend creating a posteromedial (PM) portal. The further addition of a second PM portal, which could be used as a “working portal”, may further allow a more straightforward reconstruction by improving the identification of the anatomical footprint, the clearing of the stump, and the graft passage.
Evaluating medical students’ knowledge of patient-reported outcomes and the impact of curriculum intervention in consecutive cohorts
Authors: Florentino Samuel A. , Karan Suzanne B. , Ramirez Gabriel , Baumhauer Judith F.
Published: December 2023

Background

Patient-reported outcomes (PROs) collection and utilization improves patient-provider communication, symptom reporting, and patient satisfaction. Despite their significance, the science and utility of PROs are not part of required curriculum in medical education. The authors describe the results of a survey distributed to medical students evaluating their experience, knowledge, and perceptions of PROs, report on outcomes of the impact of formal PRO education on medical student knowledge, and describe strategies to foster the spread of PRO education into other programs.

Methods

The authors developed and distributed a 20-question web-based survey distributed to medical students at two U.S. medical schools to evaluate students’ experience, knowledge, and perceptions of PROs. To compare medical students’ knowledge in their pre-clinical years (M1-M2) to those in their clinical years (M3-M4), the authors calculated odds ratios and determined significance determined using chi-squared tests. To determine the utility of formal education on medical students’ knowledge of PROs, the authors invited 4th year medical students at a single institution to participate in a survey before and two weeks after receiving formal PRO education as part of the medical school curriculum, spanning three years.

Results

137 (15%) medical students responded to the initial survey. Respondents’ knowledge of PROs was low and did not differ when comparing pre-clinical to clinical years in school. Less than 10% had received education on PROs and only 16% felt prepared to use PROs in patient care. Respondents demonstrated positive attitudes towards PROs, with 84% expressing interest in learning about PROs. In the second phase education cohort of 231 (77% response rate) 4th -year medical students over three years, formal education improved correct response rates to PRO questions. After education, 90% (121/134) agreed PROs are an important component of high-quality care.

Conclusions

This study identifies a gap in knowledge about PROs among medical students irrespective of year in training. It also shows that structured education may help fill the PRO knowledge gap, potentially providing future clinicians with the skills to implement PROs into clinical practice, aligning with the broader shift towards patient-centric evidence-based healthcare practices.
Learning together: facing the challenges of sustainability transitions by engaging uncertainty tolerance and post-normal science
Authors: Lazarus Michelle D. , Funtowicz Silvio
Published: December 2023

Current efforts towards sustainability tend to focus on maintaining existing systems and structures, by relying on reductionist approaches to problem solving. Increasingly, there is a call for more effective action in reaching sustainability, not through reductionism (e.g. solutions which reinforce the status quo), but through transformative societal changes and cultural shifts. Despite these calls, widespread resistance to such changes remains. This work discusses one of the underlying causes, namely maladaptive responses to uncertainty.

Uncertainty impacts nearly every aspect of sustainability transformations within a society. There are uncertainties related to the defining characteristics of sustainability, the complexity of sustainability, and to the changing roles and identities of individuals within a society as they transition to sustainability. Furthermore, the process which is increasingly called upon to address these diverse sources of uncertainty, known as post-normal science, introduces novel sources of uncertainty.

Up to this point, many societies’ responses to this array of sustainability transitions uncertainty is to respond maladaptively, representing uncertainty intolerance (e.g. denial, dismissal, disengagement), as opposed to adaptive responses (e.g. curiosity, acknowledgement and action). Herein, we describe the sources of uncertainty related to sustainable transitions, the role that post-normal science can play in addressing these uncertainties, and describe strategies to support societies’ collective capacity for developing uncertainty tolerance to better engage with the processes required for a sustainable future.