bluuebunny/crossref_metadata_2025 huggingface dataset:
Leonurine pretreatment protects the heart from myocardial ischemia-reperfusion injury
Authors: Lu Huiping , Gong Jingru , Zhang Tongtong , Jiang Zhe , Dong Wenmin , Dai Jing , Ma Fenfen
Published: October 2023

Myocardial ischemia-reperfusion (I/R), an important complication of reperfusion therapy for myocardial infarction, is characterized by hyperactive oxidative stress and inflammatory response. Leonurine (4-guanidino-n-butyl syringate, SCM-198), an alkaloid extracted from Herbaleonuri, was previously found to be highly cardioprotective both in vitro and in vivo. Our current study aimed to investigate the effect of SCM-198 preconditioning on myocardial I/R injury in vitro and in vivo, respectively, as well as to decipher the mechanism involved. Rats were pretreated with SCM-198 before subjected to 45 min of myocardial ischemia, which was followed by 24 h of reperfusion. Primary neonatal rat cardiac ventricular myocytes (NRCMs) were exposed to hypoxia (95% N2 + 5% CO2) for 12 h, and then to 12 h reoxygenation so as to mimic I/R. The enzymatic measurements demonstrated that SCM-198 reduced the release of infarction-related enzymes, and the hemodynamic and echocardiography measurements showed that SCM-198 restored cardiac functions, which suggested that SCM-198 could significantly reduce infarct size, maintaining cardiomyocyte morphology, and that SCM-198 pretreatment could significantly reduce cardiomyocytes apoptosis. Moreover, we demonstrated that SCM-198 could exert a cardioprotective effect by reducing reactive oxygen species (ROS) level and Akt phosphorylation while reducing the phosphorylation of p38 and JNK. In addition, the upregulation of p-Akt, Bcl-2/Bax induced by SCM-198 treatment were blocked by PI3K inhibitor LY294002, and the total protein level of Akt was not affected by SCM-198 pretreatment. Our experimental results indicated that SCM-198 could have a cardioprotective effect on I/R injury, which confirmed the utility of SCM-198 preconditioning as a strategy to prevent I/R injury.
Clinical decision-making and treatment of myelodysplastic syndromes
Authors: Hellström-Lindberg Eva S. , Kröger Nicolaus
Published: October 2023

The myelodysplastic syndromes (MDSs) constitute a profoundly heterogeneous myeloid malignancy with a common origin in the hemopoietic stem cell compartment. Consequently, patient management and treatment are as heterogeneous. Decision-making includes identifying risk, symptoms, and options for an individual and conducting a risk-benefit analysis. The only potential cure is allogeneic stem cell transplantation, and albeit the fraction of patients with MDS who undergo transplant increase over time because of better management and increased donor availability, a majority are not eligible for this intervention. Current challenges encompass to decrease the relapse risk, the main cause of hematopoietic stem cell transplantation failure. Hypomethylating agents (HMAs) constitute firstline treatment for higher-risk MDSs. Combinations with other drugs as firstline treatment has, to date, not proven more efficacious than monotherapy, although combinations approved for acute myeloid leukemia, including venetoclax, are under evaluation and often used as rescue treatment. The treatment goal for lower-risk MDS is to improve cytopenia, mainly anemia, quality of life, and, possibly, overall survival. Erythropoiesis-stimulating agents (ESAs) constitute firstline treatment for anemia and have better and more durable responses if initiated before the onset of a permanent transfusion need. Treatment in case of ESA failure or ineligibility should be tailored to the main disease mechanism: immunosuppression for hypoplastic MDS without high-risk genetics, lenalidomide for low-risk del(5q) MDS, and luspatercept for MDS with ring sideroblasts. Approved therapeutic options are still scarcer for MDS than for most other hematologic malignancies. Better tools to match disease biology with treatment, that is, applied precision medicines are needed to improve patient outcome.
Inhibition of SQSTM1 S403 phosphorylation facilitates the aggresome formation of ubiquitinated proteins during proteasome dysfunction
Authors: Zhang Chenliang , Duan YiChun , Huang Chen , Li Liping
Published: October 2023

Background

Ubiquitin–proteasome-system-mediated clearance of misfolded proteins is essential for cells to maintain proteostasis and reduce the proteotoxicity caused by these aberrant proteins. When proteasome activity is inadequate, ubiquitinated proteins are sorted into perinuclear aggresomes, which is a significant defense mechanism employed by cells to combat insufficient proteasome activity, hence mitigating the proteotoxic crisis. It has been demonstrated that phosphorylation of SQSTM1 is crucial in regulating misfolded protein aggregation and autophagic degradation. Although SQSTM1 S403 phosphorylation is essential for the autophagic degradation of ubiquitinated proteins, its significance in proteasome inhibition-induced aggresome formation is yet unknown. Herein, we investigated the influence of SQSTM1 S403 phosphorylation on the aggresome production of ubiquitinated proteins during proteasome suppression.

Methods

We examined the phosphorylation levels of SQSTM1 S403 or T269/S272 in cells after treated with proteasome inhibitors or/and autophagy inhibitors, by western blot and immunofluorescence. We detected the accumulation and aggresome formation of ubiquitinated misfolded proteins in cells treated with proteasome inhibition by western blot and immunofluorescence. Furthermore, we used SQSTM1 phosphorylation-associated kinase inhibitors and mutant constructs to confirm the regulation of different SQSTM1 phosphorylation in aggresome formation. We examined the cell viability using CCK-8 assay.

Results

Herein, we ascertained that phosphorylation of SQSTM1 S403 did not enhance the autophagic degradation of ubiquitinated proteins during proteasome inhibition. Proteasome inhibition suppresses the phosphorylation of SQSTM1 S403, which facilitated the aggresome production of polyubiquitinated proteins. Interestingly, we found proteasome inhibition-induced SQSTM1 T269/S272 phosphorylation inhibits the S403 phosphorylation. Suppressing S403 phosphorylation rescues the defective aggresome formation and protects cells from cell death caused by unphosphorylated SQSTM1 (T269/S272).

Conclusions

This study shows that inhibition of SQSTM1 S403 phosphorylation facilitates the aggresome formation of ubiquitinated proteins during proteasome dysfunction. SQSTM1 T269/S272 phosphorylation inhibits the S403 phosphorylation, boosting the aggresome formation of ubiquitinated protein and shielding cells from proteotoxic crisis.
Validation of ANG-1 and P-SEL as biomarkers of post-COVID-19 conditions using data from the Biobanque québécoise de la COVID-19 (BQC-19)
Authors: Yamga Eric , Soulé Antoine , Piché Alain , Emad Amin , Durand Madeleine , Rousseau Simon
Published: October 2023

The quest for understanding and managing the long-term effects of COVID-19, often referred to as Long COVID or post-COVID-19 condition (PCC), remains an active research area. Recent findings highlighted angiopoietin-1 (ANG-1) and p-selectin (P-SEL) as potential diagnostic markers, but validation is essential, given the inconsistency in COVID-19 biomarker studies. Leveraging the biobanque québécoise de la COVID-19 (BQC19) biobank, we analyzed the data of 249 participants. Both ANG-1 and P-SEL levels were significantly higher in patients with PCC participants compared with control subjects at 3 months using the Mann-Whitney U test. We managed to reproduce and validate the findings, emphasizing the importance of collaborative biobanking efforts in enhancing the reproducibility and credibility of Long COVID research outcomes.
Untangling an insect’s virome from its endogenous viral elements
Authors: Rozo-Lopez Paula , Brewer William , Käfer Simon , Martin McKayla M. , Parker Benjamin J.
Published: October 2023

Background

Insects are an important reservoir of viral biodiversity, but the vast majority of viruses associated with insects have not been discovered. Recent studies have employed high-throughput RNA sequencing, which has led to rapid advances in our understanding of insect viral diversity. However, insect genomes frequently contain transcribed endogenous viral elements (EVEs) with significant homology to exogenous viruses, complicating the use of RNAseq for viral discovery.

Methods

In this study, we used a multi-pronged sequencing approach to study the virome of an important agricultural pest and prolific vector of plant pathogens, the potato aphid Macrosiphum euphorbiae. We first used rRNA-depleted RNAseq to characterize the microbes found in individual insects. We then used PCR screening to measure the frequency of two heritable viruses in a local aphid population. Lastly, we generated a quality draft genome assembly for M. euphorbiae using Illumina-corrected Nanopore sequencing to identify transcriptionally active EVEs in the host genome.

Results

We found reads from two insect-specific viruses (a Flavivirus and an Ambidensovirus) in our RNAseq data, as well as a parasitoid virus (Bracovirus), a plant pathogenic virus (Tombusvirus), and two phages (Acinetobacter and APSE). However, our genome assembly showed that part of the ‘virome’ of this insect can be attributed to EVEs in the host genome.

Conclusion

Our work shows that EVEs have led to the misidentification of aphid viruses from RNAseq data, and we argue that this is a widespread challenge for the study of viral diversity in insects.
Investigation of milk microbiota of healthy and mastitic Sahiwal cattle
Authors: Salman Mian Muhammad , Nawaz Muhammad , Yaqub Tahir , Mushtaq Muhammad Hassan
Published: October 2023

Background

Sahiwal cattle is an indigenous cattle breed of Pakistan and mastitis is one of the major problems faced by Sahiwal cattle which hinders its production potential. The study was designed to investigate the milk microbiota of healthy and mastitic Sahiwal cattle as part of a multistep project to develop probiotics for the mitigation and control of mastitis. Milk samples of Sahiwal cattle (healthy clinical mastitis and subclinical mastitis) reared under similar husbandry and management practices were processed for 16S rRNA gene base metagenomics analysis.

Results

Results revealed that Proteobacteria were dominant in the healthy group and subclinical mastitis group (56.48% and 48.77%, respectively) as compared to the clinical mastitis group (2.68%). In contrast, Firmicutes were abundant in the clinical mastitis group (64%) as compared to the healthy and subclinical mastitis groups (15.87% and 38.98%, respectively). Dominant species assigned in the healthy group were Ignavibacterium album, Novosphingobium capsulatum, Akkermansia muciniphila and Lactobacillus fermentum.The clinical mastitis group was dominated by Streptococcus dysgalactiae and Corynebacterium bovis, while subclinical mastitis group included Lactobacillus fermentum and uncultured acidobacteriales and Akkermansia muciniphila as dominant species. Alpha diversity indices showed higher microbial diversity in the healthy group compared to the clinical and sub-clinical mastitis groups.

Conclusion

It is concluded that the milk microbiota of healthy sahiwal cattle has higher diversity and dominant taxa in the different groups may be used as signature microbes for mastitis susceptibility. Akkermansia muciniphila is one of candidate specie that was identified and may be used for development of probiotics.
Sex- and reproductive status-specific relationships between body composition and non-alcoholic fatty liver disease
Authors: Cao Yu-tian , Zhang Wen-hui , Lou Yan , Yan Qian-hua , Zhang Yu-juan , Qi Fang , Xiang Liu-lan , Lv Tian-su , Fang Zhu-yuan , Yu Jiang-yi , Zhou Xi-qiao
Published: October 2023

Background

Sex and reproductive status differences exist in both non-alcoholic fatty liver disease (NAFLD) and body composition. Our purpose was to investigate the relationship between body composition and the severity of liver steatosis and fibrosis in NAFLD in different sex and reproductive status populations.

Methods

This cross-sectional study included 880 patients (355 men, 417 pre-menopausal women, 108 post-menopausal women). Liver steatosis and fibrosis and body composition data were measured using FibroScan and a bioelectrical impedance body composition analyzer (BIA), respectively, and the following parameters were obtained: liver stiffness measurement (LSM), controlled attenuation parameter (CAP), waist circumference (WC), body mass index (BMI), percent body fat (PBF), visceral fat area (VFA), appendicular skeletal muscle mass (ASM), appendicular skeletal muscle mass index (ASMI), fat mass (FM), fat free mass (FFM), and FFM to FM ratio (FFM/FM). Multiple ordinal logistic regression (MOLR) was used to analyze the independent correlation between body composition indicators and liver steatosis grade and fibrosis stage in different sex and menopausal status populations.

Results

Men had higher WC, ASM, ASMI, FFM, and FFM/FM than pre- or post-menopausal women, while pre-menopausal women had higher PBF, VFA, and FM than the other two groups (p < 0.001). Besides, men had greater CAP and LSM values (p < 0.001). For MOLR, after adjusting for confounding factors, WC (OR, 1.07; 95% CI, 1.02–1.12; P = 0.011) and FFM/FM (OR, 0.52; 95% CI, 0.31–0.89; P = 0.017) in men and visceral obesity (OR, 4.16; 95% CI, 1.09–15.90; P = 0.037) in post-menopausal women were independently associated with liver steatosis grade. WC and visceral obesity were independently associated with liver fibrosis stage in men (OR, 1.05; 95% CI, 1.01–1.09, P = 0.013; OR, 3.92; 95% CI, 1.97–7.81; P < 0.001, respectively).

Conclusions

Increased WC and low FFM/FM in men and visceral obesity in post-menopausal women were independent correlates of more severe liver steatosis. In addition, increased WC and visceral obesity were independent correlates of worse liver fibrosis in men. These data support the sex- and reproductive status-specific management of NAFLD.
Cholecystitis in older patients following hip fracture: a case series and literature review
Authors: Yuan Yuan , Tian Wei , Jin Zhenzhen , Wang Ling , Zhu Shiwen
Published: October 2023

Objective

This study’s aim is to describe the characteristics of perioperative acute cholecystitis in older patients with hip fracture.

Methods

From January 1, 2018, to April 30, 2023, 7,746 medical records were retrospectively collected for patients aged ≥ 65 years who were hospitalised for hip fracture in Beijing Jishuitan Hospital, Capital Medical University. We reviewed 10 cases with confirmed diagnoses of acute cholecystitis.

Results

Of these 10 cases, five femoral neck fractures and five intertrochanteric fractures received orthopaedic surgery. The ratio of males to females was 2:8, the median age was 83.1 years (71–91 years), and there was a median BMI of 25.35 (15.56–35.16). 50% of cases had a poor functional capacity before fracture of below four metabolic equivalents. The median onset time of acute cholecystitis was five days (2–14 days) after fracture, including five cases before orthopaedic surgery and five cases after orthopaedic surgery. All patients had anorexia and fever during the course of the disease. In seven cases of calculous cholecystitis, two underwent percutaneous transhepatic biliary drainage, and one underwent percutaneous cholecystostomy. Two cases of calculous cholecystitis had poor prognosis; one died 49 days after fracture operation, and the reason for death was multiple organ failure caused by severe infection. The other one developed acute cerebellar infarction after gallbladder surgery through treatment in an intensive care unit and neurology department. The case was discharged with dysphasia, and the duration from fracture to discharge was 92 days.

Conclusion

This is the first study on the characteristics of acute cholecystitis in older patients with hip fracture in China. The incidence of acute cholecystitis in our study was 0.13%, with a high risk of in-hospital mortality and elevated hospitalisation costs. Our 10 cases with hip fractures accompanied by acute cholecystitis have common characteristics of poor-to-moderate functional capacity before fracture, increased blood glucose levels and enhanced protein metabolism after fracture. The death and the severe case have similar characteristics of low BMI, multiple underlying diseases, high plasma osmotic pressure and calculous cholecystitis, which occurred after orthopaedic surgery. These issues require attention and prompt, active intervention. Related issues require further research.
Segmental bioimpedance in pregnant end stage renal failure patient for dry weight titration and volume management (case report)
Authors: Haroon Sabrina , Tan Jia Neng , Lau Titus , Chan Shiao-Yng , Davenport Andrew
Published: October 2023

Background

Volume assessment, dry weight titration, and blood pressure control in pregnant kidney failure patients are often challenging, with physiological fluid accumulation in the trunk and lower limbs and an increased risk of preeclampsia. We used segmental bioimpedance in the volume management of our kidney failure patient on haemodialysis.

Case presentation

We report a case of a female patient on maintenance haemodiafiltration with no residual kidney function for whom we used segmental bioimpedance to guide dry weight adjustment. At different gestational periods, we targeted a different extracellular to total body water ratio according to body segments. This allowed us to support her high-risk pregnancy, identify her as probably developing preeclampsia and trigger a plan for closer monitoring and delivery during the third trimester when she had rapid weight gain.

Conclusion

Segmental bioimpedance is a practical, simple, and non-invasive test that can be performed at the dialysis unit and is useful as an adjunct decision-making tool in the management of pregnant dialysis patients.
Risk factors analysis of surgical site infections in postoperative colorectal cancer: a nine-year retrospective study
Authors: Han Cong , Chen Wei , Ye Xiao-Li , Cheng Fei , Wang Xin-You , Liu Ai-Bin , Mu Zai-Hu , Jin Xiao-Jun , Weng Yan-Hong
Published: October 2023

Background

Colorectal cancer (CRC) patients undergoing surgery are at a high risk of developing surgical site infections (SSIs), which contribute to increased morbidity, prolonged hospitalization, and escalated healthcare costs. Understanding the incidence, risk factors, and impact of SSIs is crucial for effective preventive strategies and improved patient outcomes.

Methods

This retrospective study analyzed data from 431 CRC patients who underwent surgery at Huangshan Shoukang Hospital between 2014 and 2022. The clinical characteristics and demographic information were collected. The incidence and impact of SSIs were evaluated, and independent risk factors associated with SSIs were identified using multivariable logistic regresison. A nomogram plot was constructed to predict the likelihood of SSIs occurrence.

Results

The overall incidence rate of SSIs was 7.65% (33/431). Patients with SSIs had significantly longer hospital stays and higher healthcare costs. Risk factors for SSIs included elevated Body Mass Index (BMI) levels (odds ratio, 1.12; 95% CI, 1.02—1.23; P = 0.017), the presence of diabetes (odds ratio, 3.88; 95% CI, 1.42 – 9.48; P = 0.01), as well as specific surgical factors such as open surgical procedures (odds ratio, 2.39; 95% CI [1.09; 5.02]; P = 0.031), longer surgical duration (odds ratio, 1.36; 95% CI [1.01; 1.84]; P = 0.046), and the presence of a colostomy/ileostomy (odds ratio, 3.17; 95% CI [1.53; 6.62]; P = 0.002). Utilizing multivariable regression analysis, which encompassed factors such as open surgical procedures, the presence of diabetes and colostomy/ileostom, the nomogram plot functions as a visual aid in estimating the individual risk of SSIs for patients.

Conclusions

Risk factors for SSIs included higher BMI levels, the presence of diabetes, open surgical procedures, longer surgical duration, and the presence of colostomy/ileostomy. The nomogram plot serves as a valuable tool for risk assessment and clinical decision-making.
Effect of ABO blood group on postoperative overall survival and recurrence-free survival rate in patients with hepatocellular carcinoma after hepatectomy: a multi-center retrospective cohort study
Authors: Bahardoust Mansour , Dehkharghani Maryam Zolfaghari , Ebrahimi Pouya , Najafirashed Maryam , Mousavi Safa , Haghmoradi Meisam , Khaleghian Mohsen , Tizmaghz Adnan
Published: October 2023

Background

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The survival rate after hepatectomy as the first line of treatment for HCC depends on various factors. This study evaluated the association of the ABO blood group and Rh with overall survival (OS) and Recurrence-free survival (RFS) rate after hepatectomy.

Methods

This multicenter retrospective cohort study reviewed the medical files of 639 HCC patients who underwent hepatectomy from 2010 to 2022 in three medical centers affiliated with the Iran University of Medical Sciences. Patient data, including demographic, clinical, tumor characteristics, and post-surgery outcomes, were collected by referring to the patient’s medical profiles. The Cox proportional hazard investigated the relationship between ABO blood group type and OS and RFS rate after hepatectomy.

Results

The five-year OS and RFS rates were 25.4% and 18.7%, respectively. The five-year OS (Lok rank:40.89, P:0.001) and RFS rate in patients with blood type A were significantly lower than in non-A patients. (Lok rank:10.8, P:0.001) The multivariate Cox analysis showed that blood type A, age < 45 years, tumor size > 5 cm, Poor tumor differentiation, presence of metastasis, The number of involved lymph nodes ≤ 2, and serum Alpha-Fetoprotein)AFP( level ≥ 400 were significantly related to the decreased survival rate of HCC patients after hepatectomy (P < 0.05) There was no significant association between Rh with OS and RFS (P > 0.05).

Conclusion

Blood group type A, compared to non-A, can be associated with decreased OS and RFS rates in patients with HCC after hepatectomy.
suPARnostic: an advanced predictive tool for detecting recurrence in renal cell carcinoma
Authors: Azawi Nessn , Mosholt Karina Sif Sondergaard , Fryd Nathalie Demuth , Lund Lars , Brignone Juan Ignacio , Hvid Nanna , Wulf-Johansson Helle , Pedersen Ole Birger Vesterager , Saekmose Susanne Gjørup , Dabestani Saeed
Published: October 2023

Background

Plasma soluble urokinase-type Plasminogen Activator Receptor (suPAR) predicts disease aggressiveness in renal cell carcinoma (ccRCC), but its prognostic accuracy has not been investigated. To investigate the prognostic accuracy of preoperative plasma suPAR in patients who received curative treatment for initially localized ccRCC.

Methods

We retrospectively analyzed plasma samples stored in the Danish National Biobank between 2010 and 2015 from 235 patients with ccRCC at any stage. Relationships with outcome analyzed using univariate and multiple logistic Cox regression analysis.

Results

There were 235 patients with ccRCC. The median follow-up period was 7.7 years. In univariate analysis suPAR ≥ 6 ng/mL was significantly associated with overall survival (OS) and recurrence-free survival (RFS). Patients with elevated suPAR were more likely to recur, with a Hazard Ratio (HR) of 2.3 for RFS. In multiple logistic regression, suPAR ≥ 6 ng/mL remained a negative predictor of OS and RFS. Limitations include retrospective study design, wide confidence intervals, and tumor subtype heterogeneity bias.

Conclusions

ccRCC patients with high plasma suPAR concentrations are at an elevated risk of disease recurrence and see lower OS. suPAR is a promising surveillance tool to more precisely follow up with ccRCC patients and detect future recurrences.

Patient Summary

In this study, we showed that new type of liquid marker in blood plasma, called suPAR, is associated to a higher risk of kidney cancer recurrence when elevated above 6ng/mL. We also showed suPAR to independently be able to predict patients overall and recurrence free survival in patient with any stage of kidney cancer.
Distinct effects of Fgf7 and Fgf10 on the terminal differentiation of murine bladder urothelium revealed using an organoid culture system
Authors: Suda Kazuto , Matsumoto Yuka , Ochi Takanori , Koga Hiroyuki , Hattori Nobutaka , Yamataka Atsuyuki , Nakamura Tetsuya
Published: October 2023

Background

Dysregulation of the terminal differentiation of bladder urothelium is associated with the pathogenesis of urinary tract disorders. Fibroblast growth factor (Fgf)7 and Fgf10 stimulate urothelial proliferation; however, their roles in cellular differentiation remain unclear. In this study, we used an organoid system to investigate the roles of these Fgfs in regulating bladder urothelium differentiation and identify their distribution patterns in the mouse bladder.

Methods

Adult bladder epithelia (AdBE) isolated from adult mouse bladder tissues (AdBTs) were used to culture adult bladder organoids (AdBOs) in the presence of Fgf7 and Fgf10. The differentiation status of the cells in AdBTs, AdBEs, AdBOs, and neonatal bladder tissues (NeoBTs) was analyzed via quantitative real-time-PCR for the presence of undifferentiated cell markers (Krt5, Trp63, and Krt14) and differentiated cell markers (Krt20, Upk1a, Upk2, and Upk3a). Organoid cell proliferation was assessed by counting cell numbers using the trypan blue method. The effects of Fgf7 and Fgf10 on organoid differentiation were assessed using different doses of Fgfs, and the involvement of peroxisome proliferator-activated receptor γ (PPARγ) signaling in these processes was tested by introducing a PPARγ agonist (Rosiglitazone) and antagonist (T0070907) to the culture. The expression patterns of Fgf7 and Fgf10 were examined via in situ hybridization of AdBTs.

Results

AdBOs showed higher expression of undifferentiated cell markers and lower expression of differentiated cell markers than AdBTs, NeoBTs, and AdBEs, indicating the relatively immature state of AdBOs. Differentiation of AdBOs was enhanced by Rosiglitazone and Fgf7, suggesting an interplay of intracellular signals between Fgf7 and PPARγ. Co-addition of T0070907 suppressed Fgf7-mediated differentiation, demonstrating that PPARγ is activated downstream of Fgf7 to promote cellular differentiation into umbrella cells. Furthermore, we found that Fgf7 is predominantly expressed in the umbrella cells of the urothelium, whereas Fgf10 is predominantly expressed in the urothelium and stroma of AdBTs.

Conclusions

We demonstrated that unlike Fgf10, Fgf7 induces cellular differentiation via PPARγ activity and has a unique tissue distribution pattern in the adult bladder. Further studies on the Fgf7-PPARγ signaling axis would provide insights into the differentiation mechanisms toward functional umbrella cells and the pathogenesis of several urinary tract diseases.
Association between childhood obesity and infertility in later life: a systematic review of cohort studies
Authors: Pourghazi Farzad , Eslami Maysa , Mohammadi Sammy , Ghoreshi Reza , Ejtahed Hanieh-Sadat , Qorbani Mostafa
Published: October 2023

Background

The global prevalence of childhood obesity has exhibited a troubling surge in recent years. Due to the raised questions regarding its potential correlation with infertility in adulthood, this systematic review has been undertaken to explore the relationships between childhood obesity, and infertility later in life.

Methods

A comprehensive search was performed in three international databases (PubMed, Web of Science, and Scopus). All cohort (retrospective or prospective), case-cohort, and nested case-control studies until April 2022 which assessed the association of obesity in children and adolescents with male and female infertility indicators in later life were included. The quality of the included studies was assessed by Newcastle-Ottawa quality assessment checklists.

Result

Out of the initial 32,501 documents, eleven eligible studies with a total sample size of 498,980 participants were included. Five studies focused on the number of offspring and indicated that obesity, especially in adolescence had an association with later life lower number of children, nulliparity, and childlessness in both men and women. Concerning conceiving problems, two studies showed that obesity before age 12 increased the risk of female fertility problems in the future. Two studies reported that obesity in early life raised the risk of impaired female reproductive system such as menstrual or ovulatory problems. As well as females, a study discovered that obesity in men during their 20s was linked to an elevated risk of low sperm motility and poor sperm morphology. Another study has reported men with higher pre-pubertal BMI had lower sex hormone-binding globulin; however, the same association was not seen between childhood BMI and semen quality.

Conclusion

The evidence suggests a positive association between childhood obesity with infertility indicators in later life. Childhood weight reduction strategies are suggested to be implemented in societies in order to reduce infertility rates in later life.
Early childhood caries: parents’ knowledge, attitude and practice towards its prevention in refugee camps in Erbil, Iraq
Authors: Mohammed Al-Dahan Hamsa , Ali Ismael Sherzad
Published: October 2023

Background

Early childhood caries is a significant oral health issue in socially deprived communities, including refugees, where prevention plays a crucial role in minimizing the challenges and costs associated with treating early childhood caries. To improve oral health outcomes, it is important to understand parents’ knowledge, attitudes, and practices. This study aims to assess the oral health knowledge, practices, and attitudes of refugee parents.

Methods

This cross-sectional study included 503 parents/caregivers residing in Erbil’s refugee camps in Iraq, with healthy preschool children aged one to six years. Structured questionnaire was utilized in conducting individual interviews with parents to evaluate their knowledge, attitudes, and practices. The questionnaire collected demographic information and data on access to oral health services.

Results

A total of 503 out of 505 households actively participated in the study, resulting in a high response rate of 99.6%. Demographic analysis revealed that the majority of respondents were female parents, constituting 92.05% of the sample. Within the participant pool, the primary age groups were 26–35 years (55.3%) and 18–25 years (26.2%). Educational background analysis revealed that a significant proportion of parents had attained a secondary school education (29.6%) or primary school education (27.4%). Statistical analysis further established a noteworthy association between educational background and knowledge level. The investigation of participants’ knowledge uncovered notable gaps and misconceptions pertaining to early childhood caries, with an overall mean score of 5.1. Assessing the overall attitude of parents, a mean score of 3.87 (SD = 1.29) suggested a generally unfavorable attitude towards oral hygiene practices and prevention of early childhood caries. In terms of actual practices, parents demonstrated a mean practice score of 5.7.

Conclusions

This study emphasizes knowledge gaps and misconceptions among parents in refugee camps regarding early childhood caries in preschool children. Findings revealed low knowledge scores, limited understanding of hidden sugars, delayed oral hygiene practices, and limited knowledge about fluoride.
Association of oral health awareness and practice of proper oral hygiene measures among Saudi population: a systematic review
Authors: AlJasser Reham , Alsinaidi Aljoharah , Bawazir Noor , AlSaleh Lama , AlOmair Aseel , AlMthen Haifa
Published: October 2023

Background

Several studies have proven that increasing oral hygiene knowledge correlates with good oral health status compared to those who lack this knowledge. Therefore, the aims of the study to evaluate the overall oral health awareness among the Saudi population based on knowledge and practice of proper oral hygiene measures.

Methods

A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews guidelines. Cross-sectional, cohort, and case-control studies were included in the study and framed into a PICO question. Initially, a search was conducted on PubMed/Medline, Google Scholar, and Cochrane databases. Four independent reviewers screened the identified titles, abstracts, and full texts. Cohen’s Kappa score was used to evaluate the level of agreement between the reviewers.

Results

Forty cross-sectional studies and one prospective cohort study were included. Several studies showed that most students across all departments of universities knew the protective effects of fluoride on teeth. Two studies assessing the attitude and practice of oral hygiene found that most students knew that poor oral health leads to gum disease, and 59.1% were aware of maintaining oral hygiene using a toothbrush and paste. Most participants knew the importance of oral and dental care before pregnancy and how to reduce dental problems during pregnancy. Pregnant women clean their teeth daily and consider brushing and using toothpaste essential for pregnant women. Studies on oral hygiene practices of patients with diabetes reported that flossing habits were rated less important and most of their respondents never flossed their teeth.

Conclusion

Strong correlation between oral health knowledge and practices was observed, with the higher the knowledge level, the better the practice. Therefore, new technologies and strategies must be tested for an effective oral health system.

Trial Registration

A protocol was specified and registered with the International Prospective Register of Systematic Reviews (PROSPERO) on August 2020 (registration number CRD 42,020,200,373).
Chief resident behaviors that lead to effective morning reports, a multisite qualitative study
Authors: Yang Yihan , Schulze Arian , Bekui Amenuve M. , Elisseou Sadie , Sun Stephanie W. , Hay Seonaid , Moriarty John P. , Holt Stephen R.
Published: October 2023

Background

Morning report is a fundamental component of internal medicine training and often represents the most significant teaching responsibility of Chief Residents. We sought to define Chief Resident behaviors essential to leading a successful morning report.

Methods

In 2016, we conducted a multi-site qualitative study using key informant interviews of morning report stakeholders. 49 residents, Chief Residents, and faculty from 4 Internal Medicine programs participated. Interviews were analyzed and coded by 3 authors using inductive reasoning and thematic analysis. A preliminary code structure was developed and expanded in an iterative process concurrent with data collection until thematic sufficiency was reached and a final structure was established. This final structure was used to recode all transcripts.

Results

We identified four themes of Chief Resident behaviors that lead to a successful morning report: report preparation, delivery skills, pedagogical approaches, and faculty participation. Preparation domains include thoughtful case selection, learning objective development, content editing, and report organization. Delivery domains include effective presentation skills, appropriate utilization of technology, and time management. Pedagogical approach domains include learner facilitation techniques that encourage clinical reasoning while nurturing a safe learning environment, as well as innovative teaching strategies. Moderating the involvement of faculty was identified as the final key to morning report effectiveness. Specific behavior examples are provided.

Conclusion

Consideration of content preparation, delivery, pedagogical approaches, and moderation of faculty participation are key components to Chief Resident-led morning reports. Results from this study could be used to enhance faculty development for Chief Residents.
Positive Francisella tularensis meningitis outcome despite delayed identification: a case report
Authors: Mäki-Koivisto Vesa , Korkala Marianne , Simola Lotta , Suutari-Kontio Sonja , Koivunen Sini , Puhto Teija , Junttila Ilkka S.
Published: October 2023

Francisella tularensis is a Gram-negative bacteria, that may cause a zoonotic disease, tularemia. Here, we describe a patient case, where a previously healthy young woman in Northern Finland contacted health care because of fever and headache. Due to the symptoms and lack of further diagnostic tools in primary health care, she was transferred to University Hospital (UH) where ampicillin and ceftriaxone was given empirically. A cerebrospinal fluid sample (CSF) was drawn showing small Gram-negative rods that grew on chocolate agar after 2 days of incubation. Matrix-assisted laser-desorption-ionization time of-flight (Maldi-tof) did not provide identification, but the bacteria was interpreted as sensitive to ciprofloxacin and the treatment was changed to ciprofloxacin. During the time the patient was infected, there were several positive tularemia samples found in the area. Therefore, an in house tularemia nucleic acid method (PCR) was used on the bacterial culture. Additionally, 16S rDNA sequencing was performed and these methods identified the bacteria as F. tularensis. Fortunately, the patient recovered completely with ciprofloxacin and was discharged without any complications. Our case underlines the need to understand the limits of specific diagnostic methods, such as Maldi-tof, used in clinical laboratory settings. It also highlights the need of both clinicians and laboratory staff to be aware of the many clinical presentations of tularemia when working in an endemic area.
Dual antibody-aided mesoporous nanoreactor for H2O2 self-supplying chemodynamic therapy and checkpoint blockade immunotherapy in triple-negative breast cancer
Authors: Chen Ying-Tzu , Luo Ying-Xiang , Chan Shih-Hsuan , Chiu Wen-Yi , Yang Hung-Wei
Published: October 2023

Triple-negative breast cancer (TNBC) represents a formidable challenge due to the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, rendering it unresponsive to conventional hormonal and targeted therapies. This study introduces the development of mesoporous nanoreactors (NRs), specifically mPDA@CuO2 NRs, as acid-triggered agents capable of self-supplying H2O2 for chemodynamic therapy (CDT). To enhance therapeutic efficacy, these NRs were further modified with immune checkpoint antagonists, specifically anti-PD-L1 and anti-CD24 antibodies, resulting in the formation of dual antibody-aided mesoporous nanoreactors (dAbPD−L1/CD24-mPDA@CuO2 NRs). These NRs were designed to combine CDT and checkpoint blockade immunotherapy (CBIT) for precise targeting of 4T1 TNBC cells. Remarkably, dAbPD−L1/CD24-mPDA@CuO2 NRs exhibited tumor-targeted CDT triggered by H2O2 and successfully activated immune cells including T cells and macrophages. This integrated approach led to a remarkable inhibition of tumor growth by leveraging the collaborative effects of the therapies. The findings of this study introduce a novel and promising strategy for the integrative and collaborative treatment of refractory cancers, providing valuable insights into addressing the challenges posed by aggressive breast cancer, particularly TNBC.
Antibacterial micro/nanomotors: advancing biofilm research to support medical applications
Authors: Jiang Zeyu , Fu Lejun , Wei Chuang , Fu Qinrui , Pan Shuhan
Published: October 2023

Multi-drug resistant (MDR) bacterial infections are gradually increasing in the global scope, causing a serious burden to patients and society. The formation of bacterial biofilms, which is one of the key reasons for antibiotic resistance, blocks antibiotic penetration by forming a physical barrier. Nano/micro motors (MNMs) are micro-/nanoscale devices capable of performing complex tasks in the bacterial microenvironment by transforming various energy sources (including chemical fuels or external physical fields) into mechanical motion or actuation. This autonomous movement provides significant advantages in breaking through biological barriers and accelerating drug diffusion. In recent years, MNMs with high penetrating power have been used as carriers of antibiotics to overcome bacterial biofilms, enabling efficient drug delivery and improving the therapeutic effectiveness of MDR bacterial infections. Additionally, non-antibiotic antibacterial strategies based on nanomaterials, such as photothermal therapy and photodynamic therapy, are continuously being developed due to their non-invasive nature, high effectiveness, and non-induction of resistance. Therefore, multifunctional MNMs have broad prospects in the treatment of MDR bacterial infections. This review discusses the performance of MNMs in the breakthrough and elimination of bacterial biofilms, as well as their application in the field of anti-infection. Finally, the challenges and future development directions of antibacterial MNMs are introduced.
CRISPR/Cas9 technology: applications in oocytes and early embryos
Authors: Zhang Yi-ran , Yin Tai-lang , Zhou Li-quan
Published: October 2023

CRISPR/Cas9, a highly versatile genome-editing tool, has garnered significant attention in recent years. Despite the unique characteristics of oocytes and early embryos compared to other cell types, this technology has been increasing used in mammalian reproduction. In this comprehensive review, we elucidate the fundamental principles of CRISPR/Cas9-related methodologies and explore their wide-ranging applications in deciphering molecular intricacies during oocyte and early embryo development as well as in addressing associated diseases. However, it is imperative to acknowledge the limitations inherent to these technologies, including the potential for off-target effects, as well as the ethical concerns surrounding the manipulation of human embryos. Thus, a judicious and thoughtful approach is warranted. Regardless of these challenges, CRISPR/Cas9 technology undeniably represents a formidable tool for genome and epigenome manipulation within oocytes and early embryos. Continuous refinements in this field are poised to fortify its future prospects and applications.
One episode of low intensity aerobic exercise prior to systemic AAV9 administration augments transgene delivery to the heart and skeletal muscle
Authors: Pacak Christina A. , Suzuki-Hatano Silveli , Khadir Fatemeh , Daugherty Audrey L. , Sriramvenugopal Mughil , Gosiker Bennett J. , Kang Peter B. , Cade William Todd
Published: October 2023

Introduction

The promising potential of adeno-associated virus (AAV) gene delivery strategies to treat genetic disorders continues to grow with an additional three AAV-based therapies recently approved by the Food and Drug Administration and dozens of others currently under evaluation in clinical trials. With these developments, it has become increasingly apparent that the high doses currently needed for efficacy carry risks of toxicity and entail enormous manufacturing costs, especially for clinical grade products. Strategies to increase the therapeutic efficacy of AAV-mediated gene delivery and reduce the minimal effective dose would have a substantial impact on this field. We hypothesized that an exercise-induced redistribution of tissue perfusion in the body to favor specific target organs via acute aerobic exercise prior to systemic intravenous (IV) AAV administration could increase efficacy.

Background

Aerobic exercise triggers an array of downstream physiological effects including increased perfusion of heart and skeletal muscle, which we expected could enhance AAV transduction. Prior preclinical studies have shown promising results for a gene therapy approach to treat Barth syndrome (BTHS), a rare monogenic cardioskeletal myopathy, and clinical studies have shown the benefit of low intensity exercise in these patients, making this a suitable disease in which to test the ability of aerobic exercise to enhance AAV transduction.

Methods

Wild-type (WT) and BTHS mice were either systemically administered AAV9 or completed one episode of low intensity treadmill exercise immediately prior to systemic administration of AAV9.

Results

We demonstrate that a single episode of acute low intensity aerobic exercise immediately prior to IV AAV9 administration improves marker transgene delivery in WT mice as compared to mice injected without the exercise pre-treatment. In BTHS mice, prior exercise improved transgene delivery and additionally increased improvement in mitochondrial gene transcription levels and mitochondrial function in the heart and gastrocnemius muscles as compared to mice treated without exercise.

Conclusions

Our findings suggest that one episode of acute low intensity aerobic exercise improves AAV9 transduction of heart and skeletal muscle. This low-risk, cost effective intervention could be implemented in clinical trials of individuals with inherited cardioskeletal disease as a potential means of improving patient safety for human gene therapy.
Psychosocial determinants of sexual health in newly married couples: a protocol for a mixed-methods study
Authors: Toghiani Zahra , Kazemi Ashraf , Taebi Mahbobeh
Published: October 2023

Background

Regarding psychosocial factors affecting sexual health and in most cultures, healthy and pleasurable sexual relations are valued in the family context, the present study aims to identify the psychosocial determinants of sexual health in newly married couples.

Methods

The present mixed-methods study will be conducted in three phases. The first phase will be carried out qualitatively based on which psychosocial determinants of the sexual health of newly married couples will be extracted. In the second phase, questionnaire items of psychosocial determinants of sexual health in newly married couples will be compiled, and face validity (quantitative and qualitative), content validity (quantitative and qualitative), and reliability of the questionnaire will be evaluated. In the third phase, which will be the quantitative phase of the study, the construct validity of the questionnaire will be assessed by analyzing the main items. Moreover, at this stage, the relationship between the extracted psychosocial determinants and the sexual health of newly married couples will be investigated.

Discussion

By explaining the psychosocial determinants of sexual health in newly married couples, it is possible to identify key variables for designing interventions that improve the sexual health of this group, based on their cultural sensitivities.