bluuebunny/crossref_metadata_2025 huggingface dataset:
Activity of volatiles induced by microbes and natural plants stifled the growth of Pythium aphanidermatum - the damping off in Tomato
Authors: Thangaraj Praveen , Subbiah Krishnamoorthy Akkanna , Sevugapperumal Nakkeeran , Uthandi Sivakumar , Damodarasamy Amirtham , Shanmugam Haripriya
Published: August 2023

Background

Volatilomes from natural plants and microbes imparts diverse antifungal properties to suppress the growth of plant pathogens and therefore can be a suitable alternative of chemical fungicides. The present experiment was to study effect of volatiles produced by natural plants and microbes on the fungal growth of Pythium aphanidermatum, which is a tomato seedling pathogen.

Results

Isolate of P. aphanidermatum, causing damping off in tomato were isolated and incubated at 25 ± 2 °C. The isolate was tested for the anti-oomycetes activities of volatiles in vitro. The volatiles produced by the leaves of Mentha spicata and Cymbopogon citratus showed the maximum inhibitory effect of 45.56 and 24.70 percent, respectively on the mycelial growth of P. aphanidermatum, whereas, the pathogen was not inhibited on exposure to the volatiles of macro-basidiomycetes fungi. The volatiles of T. asperellum showed the maximum inhibitory effect of 69.26 percent against P. aphanidermatum. The study also included the identification of Volatile Organic Compounds (VOCs) involved in the suppression of pathogens by Headspace Gas Chromatography Mass Spectrometry (HS GCMS). The results revealed the production of carvone by the leaves of M. spicata; citronellol and geraniol by C. citratus; isopentyl alcohol and limonene by T. asperellum with increased peak area percentage and these compounds possessed antifungal properties. The vaporous action of isopentyl alcohol completely suppressed the mycelial growth of P. aphanidermatum, which is highly correlated to the T. asperellum extract on pathogenic growth. While the compounds, carvone, and citronellol showed the maximum inhibitory effect of 89.02 and 85.49 percent, respectively when used at 500 ppm and also altered the sporulation behavior of P. aphanidermatum.

Conclusion

Results showed that volatiles of M. spicata and T. asperellum have anti-oomycetes action on pathogenic growth leading to a distortion of sporulation of P. aphanidermatum. High antifungal properties make VOCs suitable for incorporation as a new integrated plant disease management programs.
Optimal dose of neostigmine antagonizing cisatracurium-induced shallow neuromuscular block in elderly patients: a randomized control study
Authors: Cao Mengya , Huang Huifan , Tong Jianbin , Ou Yangwen , Liao Yan
Published: August 2023

Background

Residual neuromuscular block after using neuromuscular blocking agents is a common and potentially harmful complication of general anesthesia. Neostigmine is a widely used antagonist, but its optimal dose for elderly patients is unclear.

Objectives

To compare the optimal dosage and safety of neostigmine for reversing shallow residual block in elderly patients after cisatracurium-induced neuromuscular block.

Methods

A randomized controlled trial was conducted in 196 elderly patients undergoing non-cardiac surgery under general anesthesia with cisatracurium. Patients were assigned to receive either no neostigmine (control group) or neostigmine at 20 µg/kg, 40 µg/kg or 50 µg/kg when train-of-four (TOF) ratio reached 0.2 at the end of surgery. The primary outcome was the time to reach TOF ratio of 0.9 after administration. Secondary outcomes included TOF ratio at 10 min after administration, postoperative nausea and vomiting, postoperative cognitive impairment and post-anesthesia care unit (PACU) stay time.

Results

The time to reach TOF ratio of 0.9 in the 20 µg/kg, 40 µg/kg and 50 µg/kg groups was significantly shorter than the control group (H = 104.257, P < 0.01), and the time of 40 µg/kg group and 50 µg/kg group was significantly shorter than the 20 µg/kg group (P < 0.001). There was no significant difference between 40 µg/kg and 50 µg/kg groups (P = 0.249). The TOF ratio at 10 min after administration showed similar results. There were no significant differences among groups in postoperative nausea and vomiting, postoperative cognitive impairment or post-operation hospital stay.

Conclusions

Timely use of neostigmine after general anesthesia in elderly patients can significantly shorten time of TOF value reaching 0.9, among which 40 µg/kg dosage may be a more optimized choice.

Trial registration

this study was registered on chictr.org.cn (ChiCTR2100054685, 24/12/2021).
Perceptions of service providers, service recipients and female community health volunteers on a rural obstetric ultrasound program in rural Nepal: a qualitative study
Authors: Kim Christine , Wagle Kusum , Shrestha Bhagawati , Bhatta Surya , Maharjan Sajana , Dhakal Liladhar , Rizal Rajiv , Kristensen Sibylle
Published: August 2023

Background

In rural Nepal, where women face financial and geographic barriers in accessing ultrasound scans, the government initiated a Rural Obstetric Ultrasound Program (ROUSG) to train skilled birth attendants (SBAs) in rural birthing centers and expand access to routine ultrasound scans for local pregnant women. This study explores the perceived benefits and limitations of the training and implementation of this program.

Methods

A qualitative study was conducted in 15 primary care facilities in Bhojpur and Dhading, two rural districts of Nepal. The research team conducted in-depth interviews with 15 trained SBAs and focus group discussions with 48 service recipients and 30 FCHVs to gain insight into their perceptions. All interviews and focus group discussions were recorded, reviewed, and manually coded into MS Excel.

Results

Overall, our findings indicated that the ROUSG program was very well received among all our study participants, though critical gaps were identified, mostly during the training of the SBAs. These included insufficient guidance or practice opportunities during training and the challenges of implementing the mobile obstetric ultrasound service. Most importantly, though, our results suggest that the implementation of the ROUSG program increased access to prenatal care, earlier identification and referrals for abnormal scans, as well as reduced pregnancy-related stress. There was also a notable anecdotal increase in antenatal care utilization and institutional deliveries, as well as high satisfaction in both service providers and recipients.

Conclusion

Our findings highlighted that while the training component could use some strengthening with increased opportunities for supervised practice sessions and periodic refresher training after the initial 21-days, the program itself had the potential to fill crucial gaps in maternal and newborn care in rural Nepal, by expanding access not only to ROUSG services but also to other MNH services such as ANC and institutional deliveries. Our findings also support the use of ultrasound in areas with limited resources as a solution to identify potential complications at earlier stages of pregnancy and improve timely referrals, indicating the potential for reducing maternal and neonatal morbidities. This initial study supports further research into the role ROUSG can play in expanding critical MNH services in underserved areas and improving broader health outcomes through earlier identification of potential obstetric complications.
Age- and sex-related trends in body composition among Beijing adults aged 20–60 years: a cross-sectional study
Authors: Huayi Zhou , Gang Xie , Laiyuan Luo , Hui He
Published: August 2023

Background

Obesity is the most serious global epidemic and body composition is the main indicator to evaluate obesity. This study aimed to investigate the changing trends of body composition by age and gender in Beijing adults aged 20–60 years and explore the distribution of obesity rates in different age groups of both sexes under different evaluation criteria.

Methods

A total of 24,948 adults aged 20–60 years in Beijing, including 10,225 males and 14,192 females, were included, divided into four age groups (20–29, 30–39, 40–49, and ≥ 50 years) with each decade of age as an age group. Body composition indicators (BMI, fat mass, BF%, muscle mass, visceral fat area, and WHR) were measured in all subjects.

Results

BMI and total fat mass peaked in males aged 40–49 years (BMI = 25.75 kg/m2, total fat mass = 17.70 kg). Female BMI, fat mass and BF% all increased significantly with age (p < 0.01). Total muscle peaked in males aged 30–39 years and decreased significantly thereafter (p < 0.0001). Visceral fat area and WHR increased significantly with age in both sexes (p < 0.0001). Age was significantly positively correlated with BMI, BF%, fat mass, WHR, and visceral fat area in both sexes (p < 0.0001), and age was negatively correlated with muscle mass in males (standard β =  − 0.14, p < 0.0001) while positive in female (standard β = 0.05, p < 0.0001). Under the BMI criterion, the obesity rate peaked at 27.33% in males at the age of 20–29 years. Under the BF% criterion, the obesity rate peaked at 17.41% in males at the age of 30–39 years, and increased in females with age. The central obesity rate of both sexes increased with age under the criteria of WHR and visceral fat area.

Conclusion

The results of this study reveal that age- and sex-related patterns of body composition and obesity change among Beijing adults aged 20–60 years may differ across age groups and that such patterns of change should be considered when developing public health strategies.
Dyslipidemia, diabetes and periodontal disease, a cross-sectional study in Rafsanjan, a region in southeast Iran
Authors: Ayoobi Fatemeh , Salari Sedigh Somaye , Khalili Parvin , Sharifi Zeinab , Hakimi Hamid , Sardari Farimah , Jamali Zahra
Published: August 2023

The objectives

The association between dyslipidemia, diabetes and alterations in periodontal health are inconsistent. The aim of this study was to determine the association between dyslipidemia, diabetes and periodontal disease in the Oral Health Branch of Rafsanjan Cohort Study (OHBRCS).

Methods

Rafsanjan Cohort Study (RCS) was launched in 2015 in Rafsanjan City a region in the southeast of Iran. A total of 8682 participants aged 35–70 years of both gender were recruited into the OHBRCS as a part of RCS. Bleeding on probing (BOP), probing pocket depth (PPD) and Clinical attachment loss (CAL) were used to assess periodontal health status. When CAL progression was ≥ 1 mm and PPD was > 3 mm, it was defined as periodontitis.

Results

The final sample consisted of 6751 individuals with mean age of 47.67 ± 8.79 years. Among this population, 73.32% (n = 4949), 13.75% (n = 928), 59.67% (n = 4028) and 11.76% (n = 794) had BOP, PPD > 3 mm, CAL ≥ 1 mm and periodontitis respectively. The odds of CAL ≥ 1 mm increased 14% in subjects with high LDL cholesterol (OR: 1.14; 95% CI: 1.01–1.30), 17% in subjects with diabetes (OR: 1.17; 95% CI: 1.01–1.36) and 23% in subjects with both dyslipidemia and diabetes (OR: 1.23; 95% CI: 1.05–1.44). Also, the odds of PPD > 3 mm in the group with high total cholesterol (TC) was 16% higher compared to those with normal TC (OR: 1.16; 95% CI: 1.01–1.34).

Conclusions

There was an increased odds in periodontal disease in association with high TC, high LDL cholesterol, diabetes and having both dyslipidemia and diabetes. This suggests that high TC, high LDL cholesterol, diabetes and having both dyslipidemia and diabetes might be potential indicators for the presence of periodontal disease.
Machine learning algorithms to predict intraoperative hemorrhage in surgical patients: a modeling study of real-world data in Shanghai, China
Authors: Shi Ying , Zhang Guangming , Ma Chiye , Xu Jiading , Xu Kejia , Zhang Wenyi , Wu Jianren , Xu Liling
Published: August 2023

Background

Prediction tools for various intraoperative bleeding events remain scarce. We aim to develop machine learning-based models and identify the most important predictors by real-world data from electronic medical records (EMRs).

Methods

An established database of surgical inpatients in Shanghai was utilized for analysis. A total of 51,173 inpatients were assessed for eligibility. 48,543 inpatients were obtained in the dataset and patients were divided into haemorrhage (N = 9728) and without-haemorrhage (N = 38,815) groups according to their bleeding during the procedure. Candidate predictors were selected from 27 variables, including sex (N = 48,543), age (N = 48,543), BMI (N = 48,543), renal disease (N = 26), heart disease (N = 1309), hypertension (N = 9579), diabetes (N = 4165), coagulopathy (N = 47), and other features. The models were constructed by 7 machine learning algorithms, i.e., light gradient boosting (LGB), extreme gradient boosting (XGB), cathepsin B (CatB), Ada-boosting of decision tree (AdaB), logistic regression (LR), long short-term memory (LSTM), and multilayer perception (MLP). An area under the receiver operating characteristic curve (AUC) was used to evaluate the model performance.

Results

The mean age of the inpatients was 53 ± 17 years, and 57.5% were male. LGB showed the best predictive performance for intraoperative bleeding combining multiple indicators (AUC = 0.933, sensitivity = 0.87, specificity = 0.85, accuracy = 0.87) compared with XGB, CatB, AdaB, LR, MLP and LSTM. The three most important predictors identified by LGB were operative time, D-dimer (DD), and age.

Conclusions

We proposed LGB as the best Gradient Boosting Decision Tree (GBDT) algorithm for the evaluation of intraoperative bleeding. It is considered a simple and useful tool for predicting intraoperative bleeding in clinical settings. Operative time, DD, and age should receive attention.
Intensive community care services for children and young people in psychiatric crisis: an expert opinion
Authors: Keiller Eleanor , Masood Saba , Wong Ben Hoi-ching , Avent Cerian , Bediako Kofi , Bird Rebecca Margaret , Boege Isabel , Casanovas Marta , Dobler Veronika Beatrice , James Maya , Kiernan Jane , Martinez-Herves Maria , Ngo Thinh Vinh Thanh , Pascual-Sanchez Ana , Pilecka Izabela , Plener Paul L , Prillinger Karin , Lim Isabelle Sabbah , Saour Tania , Singh Nidhita , Skouta Eirini , Steffen Mariana , Tolmac Jovanka , Velani Hemma , Woolhouse Ruth , Zundel Toby , Ougrin Dennis
Published: August 2023

Background

Children and young people’s (CYP) mental health is worsening, and an increasing number are seeking psychiatric and mental health care. Whilst many CYPs with low-to-medium levels of psychiatric distress can be treated in outpatient services, CYPs in crisis often require inpatient hospital treatment. Although necessary in many cases, inpatient care can be distressing for CYPs and their families. Amongst other things, inpatient stays often isolate CYPs from their support networks and disrupt their education. In response to such limitations, and in order to effectively support CYPs with complex mental health needs, intensive community-based treatment models, which are known in this paper as intensive community care services (ICCS), have been developed. Although ICCS have been developed in a number of settings, there is, at present, little to no consensus of what ICCS entails.

Methods

A group of child and adolescent mental health clinicians, researchers and academics convened in London in January 2023. They met to discuss and agree upon the minimum requirements of ICCS. The discussion was semi-structured and used the Dartmouth Assertive Community Treatment Fidelity Scale as a framework. Following the meeting, the agreed features of ICCS, as described in this paper, were written up.

Results

ICCS was defined as a service which provides treatment primarily outside of hospital in community settings such as the school or home. Alongside this, ICCS should provide at least some out-of-hours support, and a minimum of 90% of CYPs should be supported at least twice per week. The maximum caseload should be approximately 5 clients per full time equivalent (FTE), and the minimum number of staff for an ICCS team should be 4 FTE. The group also confirmed the importance of supporting CYPs engagement with their communities and the need to remain flexible in treatment provision. Finally, the importance of robust evaluation utilising tools including the Children’s Global Assessment Scale were agreed.

Conclusions

This paper presents the agreed minimum requirements of intensive community-based psychiatric care. Using the parameters laid out herein, clinicians, academics, and related colleagues working in ICCS should seek to further develop the evidence base for this treatment model.
Single institution retrospective study evaluating the frequency of implant removal and associated risk factors following open fracture fixation in 80 cases (2010–2020)
Authors: Sandness Brea M. , Perry Karen L. , Bruce Mieghan
Published: August 2023

Background

Open fractures occur commonly in small animals and are characterised by contamination of the fracture site. While never quantified, it is believed that open fractures stabilised with internal implants are at a higher risk for requiring explantation. This retrospective study determines the frequency and risk factors for explantation following use of internal fixation. Medical records of client-owned dogs and cats with an open fracture, between 2010 and 2020 stabilised using internal implants, were included. Data retrieved included signalment, cause and characterisation of the fracture, comorbidities, preexisting infections, and all details related to anesthesia and surgery. Pre-, Peri- and post-operative antibiotic use were detailed. All cases were followed to clinical union. Postoperative complications, including requirement for implant removal were recorded and classified as major or minor. Associations between potential risk factors and need for explantation were assessed.

Results

Of 80 cases, 72 (90%) were dogs and eight (10%) cats. Major complications were encountered in 23 (28.75%) cases and minor complications in 16 (20%) cases. Explantation was performed in 17 cases (21.25%). Out of 72 dogs, 13 required explantation (18%) whereas four of the eight cats needed implants removed (50%). Only diagnosis of postoperative infection was associated with an increased risk of explantation (RR 2.77; 95% CI 1.25; 6.15; p = 0.045).

Conclusion

Approximately 1 in 5 open fractures stabilised using internal fixation can be anticipated to require explantation, with cats potentially being at a higher risk than dogs. Cases diagnosed with postoperative infection are at a higher risk for requiring implant removal.
Causal associations of remnant cholesterol with cardiometabolic diseases and risk factors: a mendelian randomization analysis
Authors: Guan Baoyi , Wang Anlu , Xu Hao
Published: August 2023

Background

Emerging evidence suggests that remnant cholesterol (RC) is strongly associated with an increased incidence of cardiometabolic diseases (CMD). However, the causality have not been confirmed. We aimed to evaluate the causal associations of RC with CMD and the relative risk factors using two-sample Mendelian randomization (MR) methods.

Methods

Summary-level statistics of RC, CMD, and cardiometabolic risk factors were obtained from the published data from individuals with a predominantly European ancestry mainly from the UK Biobank and the FinnGen biobank. Univariable and multivariable MR analyses were used to evaluate the causal relationships between RC and CMD. A bidirectional MR analysis was performed to estimate the causality between RC and cardiometabolic risk factors. The main MR method was conducted using the inverse-variance weighted method.

Results

Univariable MR analyses showed that genetically predicted RC was causally associated with higher risk of ischemic heart disease, myocardial infarction, atrial fibrillation and flutter, peripheral artery disease, and non-rheumatic valve diseases (all P < 0.05). Multivariable MR analyses provided compelling evidence of the harmful effects of RC on the risk of ischemic heart disease (P < 0.05). Bidirectional MR analysis demonstrated that RC was bidirectionally causally linked to total cholesterol, triglycerides, low-density lipoprotein cholesterol, hypercholesterolemia (all P < 0.05). However, no genetic association was found between RC and metabolic disorders or the other cardiometabolic risk factors.

Conclusions

This MR study demonstrates that genetically driven RC increases the risk of several CMD and cardiometabolic risk factors, suggesting that targeted RC-lowering therapies may be effective for the primary prevention of CMD.
Socioeconomic and environmental determinants of asthma prevalence: a cross-sectional study at the U.S. County level using geographically weighted random forests
Authors: Lotfata Aynaz , Moosazadeh Mohammad , Helbich Marco , Hoseini Benyamin
Published: August 2023

Background

Some studies have established associations between the prevalence of new-onset asthma and asthma exacerbation and socioeconomic and environmental determinants. However, research remains limited concerning the shape of these associations, the importance of the risk factors, and how these factors vary geographically.

Objective

We aimed (1) to examine ecological associations between asthma prevalence and multiple socio-physical determinants in the United States; and (2) to assess geographic variations in their relative importance.

Methods

Our study design is cross sectional based on county-level data for 2020 across the United States. We obtained self-reported asthma prevalence data of adults aged 18 years or older for each county. We applied conventional and geographically weighted random forest (GWRF) to investigate the associations between asthma prevalence and socioeconomic (e.g., poverty) and environmental determinants (e.g., air pollution and green space). To enhance the interpretability of the GWRF, we (1) assessed the shape of the associations through partial dependence plots, (2) ranked the determinants according to their global importance scores, and (3) mapped the local variable importance spatially.

Results

Of the 3059 counties, the average asthma prevalence was 9.9 (standard deviation ± 0.99). The GWRF outperformed the conventional random forest. We found an indication, for example, that temperature was inversely associated with asthma prevalence, while poverty showed positive associations. The partial dependence plots showed that these associations had a non-linear shape. Ranking the socio-physical environmental factors concerning their global importance showed that smoking prevalence and depression prevalence were most relevant, while green space and limited language were of minor relevance. The local variable importance measures showed striking geographical differences.

Conclusion

Our findings strengthen the evidence that socio-physical environments play a role in explaining asthma prevalence, but their relevance seems to vary geographically. The results are vital for implementing future asthma prevention programs that should be tailor-made for specific areas.
Target delivery of a PD-1-TREM2 scFv by CAR-T cells enhances anti-tumor efficacy in colorectal cancer
Authors: Chen Jian , Zhu Tianchuan , Jiang Guanmin , Zeng Qi , Li Zhijian , Huang Xi
Published: August 2023

Background

Chimeric antigen receptor (CAR) -T cell therapy is an efficient therapeutic strategy for specific hematologic malignancies. However, positive outcomes of this novel therapy in treating solid tumors are curtailed by the immunosuppressive tumor microenvironment (TME), wherein signaling of the checkpoint programmed death-1 (PD-1)/PD-L1 directly inhibits T-cell responses. Although checkpoint-targeted immunotherapy succeeds in increasing the number of T cells produced to control tumor growth, the desired effect is mitigated by the action of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) in the TME. Previous studies have confirmed that targeting triggering-receptor-expressed on myeloid cells 2 (TREM2) on TAMs and MDSCs enhances the outcomes of anti-PD-1 immunotherapy.

Methods

We constructed carcinoembryonic antigen (CEA)-specific CAR-T cells for colorectal cancer (CRC)-specific antigens with an autocrine PD-1-TREM2 single-chain variable fragment (scFv) to target the PD-1/PD-L1 pathway, MDSCs and TAMs.

Results

We found that the PD-1-TREM2-targeting scFv inhibited the activation of the PD-1/PD-L1 pathway. In addition, these secreted scFvs blocked the binding of ligands to TREM2 receptors present on MDSCs and TAMs, reduced the proportion of MDSCs and TAMs, and enhanced T-cell effector function, thereby mitigating immune resistance in the TME. PD-1-TREM2 scFv-secreting CAR-T cells resulted in highly effective elimination of tumors compared to that achieved with PD-1 scFv-secreting CAR-T therapy in a subcutaneous CRC mouse model. Moreover, the PD-1-TREM2 scFv secreted by CAR-T cells remained localized within tumors and exhibited an extended half-life.

Conclusions

Together, these results indicate that PD-1-TREM2 scFv-secreting CAR-T cells have strong potential as an effective therapy for CRC.
Identification of cholesterol metabolism-related subtypes in nonfunctioning pituitary neuroendocrine tumors and analysis of immune infiltration
Authors: Feng Tianshun , Hou Pengwei , Mu Shuwen , Fang Yi , Li Xinxiong , Li Ziqi , Wang Di , Chen Li , Lu Lingling , Lin Kunzhe , Wang Shousen
Published: August 2023

Objective

This study aimed to investigate the role of cholesterol metabolism-related genes in nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs) invading the cavernous sinus and analyze the differences in immune cell infiltration between invasive and noninvasive NF-PitNETs.

Methods

First, a retrospective analysis of single-center clinical data was performed. Second, the immune cell infiltration between invasive and noninvasive NF-PitNETs in the GSE169498 dataset was further analyzed, and statistically different cholesterol metabolism-related gene expression matrices were obtained from the dataset. The hub cholesterol metabolism-related genes in NF-PitNETs were screened by constructing machine learning models. In accordance with the hub gene, 73 cases of NF-PitNETs were clustered into two subtypes, and the functional differences and immune cell infiltration between the two subtypes were further analyzed.

Results

The clinical data of 146 NF-PitNETs were evaluated, and the results showed that the cholesterol (P = 0.034) between invasive and noninvasive NF-PitNETs significantly differed. After binary logistic analysis, cholesterol was found to be an independent risk factor for cavernous sinus invasion (CSI) in NF-PitNETs. Bioinformatics analysis found three immune cells between invasive and noninvasive NF-PitNETs were statistically significant in the GSE169498 dataset, and 34 cholesterol metabolism-related genes with differences between the two groups were obtained 12 hub genes were selected by crossing the two machine learning algorithm results. Subsequently, cholesterol metabolism-related subgroups, A and B, were obtained by unsupervised hierarchical clustering analysis. The results showed that 12 immune cells infiltrated differentially between the two subgroups. The chi-square test revealed that the two subgroups had statistically significance in the invasive and noninvasive samples (P = 0.001). KEGG enrichment analysis showed that the differentially expressed genes were mainly enriched in the neural ligand–receptor pathway. GSVA analysis showed that the mTORC signaling pathway was upregulated and played an important role in the two-cluster comparison.

Conclusion

By clinical data and bioinformatics analysis, cholesterol metabolism-related genes may promote the infiltration abundance of immune cells in NF-PitNETs and the invasion of cavernous sinuses by NF-PitNETs through the mTOR signaling pathway. This study provides a new perspective to explore the pathogenesis of cavernous sinus invasion by NF-PitNETs and determine potential therapeutic targets for this disease.
Cracking the intestinal lymphatic system window utilizing oral delivery vehicles for precise therapy
Authors: Miao Yang-Bao , Xu Tianxing , Gong Ying , Chen Anmei , Zou Liang , Jiang Tao , Shi Yi
Published: August 2023

Oral administration is preferred over other drug delivery methods due to its safety, high patient compliance, ease of ingestion without discomfort, and tolerance of a wide range of medications. However, oral drug delivery is limited by the poor oral bioavailability of many drugs, caused by extreme conditions and absorption challenges in the gastrointestinal tract. This review thoroughly discusses the targeted drug vehicles to the intestinal lymphatic system (ILS). It explores the structure and physiological barriers of the ILS, highlighting its significance in dietary lipid and medication absorption and transport. The review presents various approaches to targeting the ILS using spatially precise vehicles, aiming to enhance bioavailability, achieve targeted delivery, and reduce first-pass metabolism with serve in clinic. Furthermore, the review outlines several methods for leveraging these vehicles to open the ILS window, paving the way for potential clinical applications in cancer treatment and oral vaccine delivery. By focusing on targeted drug vehicles to the ILS, this article emphasizes the critical role of these strategies in improving therapeutic efficacy and patient outcomes. Overall, this article emphasizes the critical role of targeted drug vehicles to the ILS and the potential impact of these strategies on improving therapeutic efficacy and patient outcomes.
IL-17 A correlates with disease progression in papillary thyroid carcinoma
Authors: Banerjee Sohini , Nahar Uma , Dahiya Divya , Gupta Rijuneeta , Mukherjee Soham , Sachdeva Naresh , Sood Ashwani , Dey Pranab , Radotra Bishan , Bhansali Anil
Published: August 2023

Background

Cancer progression can be promoted by chronic inflammation. Local immune response may be associated with favourable or unfavourable prognosis of Papillary Thyroid Carcinoma (PTC). Regulatory T (Treg) cells and T helper 17 (Th17) cells exert opposing function and their balance may have a vital role in promotion of tumor growth. Treg cells in tumor microenvironment (TME) may promote tumor progression and reduced survival of patients. Whereas, Th17 cells can promote or inhibit tumor progression depending on phenotypic characteristics of tumor. In this study, we aimed to analyse the kind of immune response developed and its prognostic impact in future therapeutics.

Methods

Cytometric Bead Array (CBA) analysis of pro and anti-inflammatory cytokines (IFN-gamma, IL-2, IL-6, IL-17 A, TNF-alpha and IL-4, IL-10) was done in 15 PTC irrespective of Lymphocytic Thyroiditis (LT) and 16 Hashimoto’s Thyroiditis (HT) cases. Immunohistochemical expression of FoxP3 and IL-17 A was studied in 27 cases of PTC with LT. Whereas, quantitative gene expression of both was analysed in 10 cases.

Results

All the pro-inflammatory cytokines showed mild elevation in PTC with LT. On IHC, IL-17 A expression was observed in 74% PTC with LT. Whereas, FoxP3 was present in only 40% cases. Also, IL-17 A expression was significantly associated with age group (> 45 years), tumor size ≤ 1 cm and disease progression.

Conclusions

Increased expression of cytokines suggested correlation between inflammatory factors and progression of thyroid tumors. Along with this, the balance between IL-17 A and FoxP3 may play an important role in PTC development, prognosis and future management.
Efficacy and safety of single- and double-dose intravenous tranexamic acid in hip and knee arthroplasty: a systematic review and meta-analysis
Authors: Yang Yong-Ze , Cheng Qing-Hao , Zhang An-Ren , Yang Xin , Zhang Zhuang-Zhuang , Guo Hong-Zhang
Published: August 2023

Objective

With the increasing prevalence of osteoarthritis of the hip and knee, total joint replacement, the end-stage treatment, provides pain relief and restoration of function, but is often associated with massive blood loss. Tranexamic acid (TXA) has been reported to reduce perioperative blood loss in hip or knee arthroplasty. However, the optimal dose of TXA administration remains controversial. Therefore, we performed a meta-analysis combining data from 5 trials comparing the efficacy and safety of one fixed dose of 1 g intravenously administered TXA with two doses of 1 g each administered intravenously for hip or knee arthroplasty.

Methods

PubMed, Medline, Embase, Web of Science, and The Cochrane Library were searched from January 2000 to February 2023. Our meta-analysis included randomized controlled trials and cohort studies comparing the efficacy and safety of different doses of intravenous TXA (IV-TXA) for THA or TKA. The observation endpoints included total blood loss, postoperative hemoglobin drop, blood transfusion rate, length of hospital stay, incidence of deep venous thrombosis (DVT), and incidence of pulmonary embolism (PE). Meta-analysis was performed according to Cochrane's guidelines and PRISMA statement. The Danish RevMan5.3 software was used for data merging.

Results

Five cohort studies involving 5542 patients met the inclusion criteria. Our meta-analysis showed that the two groups were significantly higher in total blood loss (mean difference (MD) = − 65.60, 95% confidence interval (CI) [− 131.46, 0.26], P = 0.05); blood transfusion rate (risk difference (RD) = 0.00, 95% CI [− 0.01, 0.02], P = 0.55); postoperative hemoglobin (MD = 0.02, 95% CI [− 0.09, 0.13], P = 0.31); postoperative hospital stay days (MD = − 0.13), 95% CI [− 0.35, 0.09], P = 0.25); DVT (RD = 0.00, 95% CI [− 0.00, 0.01], P = 0.67); PE (RD = 0.00, 95% CI [− 0.01, 0.00], P = 0.79). There was some inherent heterogeneity due to variance in sample size across each major study.

Conclusion

1 dose of 1 g and 2 doses of 1 g IV-TXA each time have similar effects on reducing blood loss, blood transfusion rate, postoperative hemoglobin level, and postoperative hospital stay after TKA or THA, without increasing the risk of postoperative complications risk. For patients at high risk of thromboembolic events, one dose of 1 g TXA throughout surgery may be preferred. However, higher-quality RCT is needed to explore the optimal protocol dose to recommend the widespread use of TXA in total joint arthroplasty.

Trial registration We conducted literature selection, eligibility criteria evaluation, data extraction and analysis on the research program registered in Prospero (CRD42023405387) on March 16, 2023.
TMEM106B aggregation in neurodegenerative diseases: linking genetics to function
Authors: Jiao Hai-Shan , Yuan Peng , Yu Jin-Tai
Published: August 2023

Background

Mutations of the gene TMEM106B are risk factors for diverse neurodegenerative diseases. Previous understanding of the underlying mechanism focused on the impairment of lysosome biogenesis caused by TMEM106B loss-of-function. However, mutations in TMEM106B increase its expression level, thus the molecular process linking these mutations to the apparent disruption in TMEM106B function remains mysterious.

Main body

Recent new studies reported that TMEM106B proteins form intracellular amyloid filaments which universally exist in various neurodegenerative diseases, sometimes being the dominant form of protein aggregation. In light of these new findings, in this review we systematically examined previous efforts in understanding the function of TMEM106B in physiological and pathological conditions. We propose that TMEM106B aggregations could recruit normal TMEM106B proteins and interfere with their function.

Conclusions

TMEM106B mutations could lead to lysosome dysfunction by promoting the aggregation of TMEM106B and reducing these aggregations may restore lysosomal function, providing a potential therapeutic target for various neurodegenerative diseases.
Maternal adverse childhood experiences and behavioral problems in preschool offspring: the mediation role of parenting styles
Authors: Luo Shengyu , Chen Dezhong , Li Chunrong , Lin Li , Chen Weiqing , Ren Yan , Zhang Yuchi , Xing Fenglin , Guo Vivian Yawei
Published: August 2023

Background

Maternal history of adverse childhood experiences (ACEs) has been found to be associated with children’s health outcomes. However, the underlying mechanisms were unclear. This study aimed to examine the association between maternal ACEs and behavioral problems in their preschool offspring and to explore the potential mediating role of maternal parenting styles in the association.

Methods

A cross-sectional study was conducted involving 4243 mother-child dyads in Chengdu, China. Mothers completed the Adverse Childhood Experiences-International Questionnaire (ACE-IQ) to assess their history of ACEs (i.e., physical abuse, emotional abuse, physical neglect, emotional neglect, witnessing domestic violence, household substance abuse, household mental illness, incarcerated household member, parental separation or divorce, parental death, bullying, and community violence), the short Egna Minnen Beträffande Uppfostran Parent Form (S-EMBU-P) to evaluate their parenting styles (i.e., emotional warmth, rejection, and overprotection), and the 48-item Conners’ Parent Rating Scale (CPRS-48) to measure behavioral problems in their children. Logistic regression models were established to examine the association between cumulative number of maternal ACEs and children’s behavioral problems. The mediating role of parenting styles in this association was explored by generalized structural equation models (GSEM).

Results

Of the participating mothers, 85.8% (n = 3641) reported having experienced at least one type of ACE. Children of mothers with ≥2 ACEs showed a significantly increased risk of behavioral problems across all dimensions, including conduct problems, learning problems, psychosomatic problems, impulsive-hyperactive, anxiety, and hyperactivity index, in both crude and adjusted models (all p-values < 0.05). Dose-response patterns were also observed between the cumulative number of maternal ACEs and children’s behavioral problems. In addition, maternal parenting styles of rejection emerged as a significant mediator, accounting for approximately 8.4–15.0% of the associations.

Conclusions

Our findings indicated an intergenerational association of maternal ACEs with behavioral problems in preschool offspring, which was mediated by maternal parenting styles of rejection. Early screening and targeted intervention strategies are critical to mitigate the downstream consequences of maternal ACEs on young children’s outcomes. Providing support and resources to improve parenting skills may prove beneficial.
Fertility preservation after gonadotoxic treatments for cancer and autoimmune diseases
Authors: Saito Saki , Yamada Mitsutoshi , Yano Rika , Takahashi Kazuko , Ebara Akiko , Sakanaka Hiroe , Matsumoto Miho , Ishimaru Tomoko , Utsuno Hiroki , Matsuzawa Yuichi , Ooka Reina , Fukuoka Mio , Akashi Kazuhiro , Kamijo Shintaro , Hamatani Toshio , Tanaka Mamoru
Published: August 2023

Background

The indications for fertility preservation (FP) have expanded. A few patients who underwent gonadotoxic treatment did not have the opportunity to receive FP, leading to concerns that these patients may develop premature ovarian insufficiency. However, the usefulness of FP in women with reduced ovarian reserve has also been questioned. Progestin-primed ovarian stimulation can improve the controlled ovarian stimulation (COS) protocol, but there is limited data on the efficacy of FP with progestin-primed ovarian stimulation.

Methods

We conducted a prospective study of 43 women with cancer or autoimmune diseases before and after gonadotoxic treatment at the reproductive unit of Keio University Hospital, counselled between 1 January 2018 and 31 December 2021. After counselling, informed consent was obtained for FP from 43 patients, with those who underwent gonadotoxic treatment of the primary disease being prioritised. Gonadotropin-releasing hormone analogue or progestin was used to suppress luteinising hormone in COS before or after gonadotoxic treatment. The number of cryopreserved mature oocytes was the primary outcome.

Results

Forty-three patients and 67 assisted reproductive technology cycles were included in the analysis. The median age at entry was 32 [inter quartile range (IQR), 29–37] years. All patients in the post-gonadotoxic treatment group had their oocytes frozen. Gonadotoxic treatment resulted in fewer oocytes [median 3 (IQR 1–4); pre-gonadotoxic treatment group: five patients, 13 cycles] vs. median 9 (IQR 5–14; pre-gonadotoxic treatment group: 38 patients, 54 cycles; P < 0.001). Although anti-Müllerian hormone levels were lower in the post-gonadotoxic treatment group (n = 5, 13 cycles, median 0.29 (IQR 0.15–1.04) pg/mL) than in the pre-gonadotoxic treatment group (n = 38, 54 cycles, median 1.89 (IQR 1.15–4.08) pg/mL) (P = 0.004), oocyte maturation rates were higher in the post-gonadotoxic treatment group [median 100 (IQR 77.5–100) %] than in the pre-gonadotoxic group [median 90.3 (IQR 75.0–100) %; P = 0.039]. Five patients in the pre-gonadotoxic treatment group had their cryopreserved embryos thawed, of which three had live births.

Conclusions

Oocytes obtained for FP from women with cancer or autoimmune disease for FP are of satisfactory quality, regardless of whether they are obtained post-gonadotoxic treatment or COS protocols.
A heparin-binding protein of Plasmodium berghei is associated with merozoite invasion of erythrocytes
Authors: Gao Junying , Jiang Ning , Zhang Yiwei , Chen Ran , Feng Ying , Sang Xiaoyu , Chen Qijun
Published: August 2023

Background

Malaria caused by Plasmodium species is a prominent public health concern worldwide, and the infection of a malarial parasite is transmitted to humans through the saliva of female Anopheles mosquitoes. Plasmodium invasion is a rapid and complex process. A critical step in the blood-stage infection of malarial parasites is the adhesion of merozoites to red blood cells (RBCs), which involves interactions between parasite ligands and receptors. The present study aimed to investigate a previously uncharacterized protein, PbMAP1 (encoded by PBANKA_1425900), which facilitates Plasmodium berghei ANKA (PbANKA) merozoite attachment and invasion via the heparan sulfate receptor.

Methods

PbMAP1 protein expression was investigated at the asexual blood stage, and its specific binding activity to both heparan sulfate and RBCs was analyzed using western blotting, immunofluorescence, and flow cytometry. Furthermore, a PbMAP1-knockout parasitic strain was established using the double-crossover method to investigate its pathogenicity in mice.

Results

The PbMAP1 protein, primarily localized to the P. berghei membrane at the merozoite stage, is involved in binding to heparan sulfate-like receptor on RBC surface of during merozoite invasion. Furthermore, mice immunized with the PbMAP1 protein or passively immunized with sera from PbMAP1-immunized mice exhibited increased immunity against lethal challenge. The PbMAP1-knockout parasite exhibited reduced pathogenicity.

Conclusions

PbMAP1 is involved in the binding of P. berghei to heparan sulfate-like receptors on RBC surface during merozoite invasion.
Healthcare policy changes in an era of health workforce shortage
Authors: Angel Yoel , Fire Gil
Published: August 2023

In their recent IJHPR article, Wimpfheimer and colleagues outline the implications for the field of anesthesia of two major healthcare policy changes in Israel: The Yatziv Reform in licensing foreign medical graduates and the efforts to reduce residents' on-call shift duration. We argue that these reforms are necessary to strengthen the healthcare workforce and improve the quality of care in the long term, even though they may limit the availability of healthcare personnel for several years, particularly in the field of anesthesia. In this commentary, we examine the background to these policy changes, their likely impact on the medical workforce in Israel in general, and propose steps to reconcile these reforms with the global and national shortage of physicians. We urge policymakers to allocate the required resources and begin preparing for an era of continuous mismatch between physician supply and demand, which will necessitate creative solutions, increased reliance on technology, and the introduction of paramedical professionals to help offload tasks and better utilize the scarce physician workforce.
Performance prediction and enhancement of 5G networks based on linear regression machine learning
Authors: Malekzadeh Mina
Published: August 2023

The feature-rich nature of 5G introduces complexities that make its performance highly conditional and dependent on a broad range of key factors, each with unique values and characteristics that further complicate 5G deployments. To address the complexities, this work develops a new modular model based on machine learning on both architecture and service factors (5GPA) that actively contribute to variations in 5G network performance. The objectives are to address the complications during the design and planning phases according to the requirements before 5G deployment, simplify the whole feature-selection process for different deployments, and optimize 5G network performance. The model is implemented and the results are utilized to determine the correlation between the 5GPA factors and the overall performance. Additionally, a simulated 5G dataset is generated and utilized to make predictions on 5G performance based on unseen factors and values of interest. The reliability of the model is validated by comparing the predicted and actual results in the context of quality of service requirements. The results represent a high level of accuracy, with an average of 95%, and low error rates in terms of mean absolute error, mean squared error, and root mean squared error, averaging 7.60e−03, 1.18e−04, and 8.77e−03, respectively.