bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between maternity waiting home stay and obstetric outcomes in Yetebon, Ethiopia: a mixed-methods observational cohort study
Authors: Erickson Anne K. , Abdalla Safa , Serenska Alice , Demeke Bete , Darmstadt Gary L.
Published: July 2021

Background

A strategy for reducing adverse pregnancy outcomes is the expanded implementation of maternity waiting homes (MWHs). We assessed factors influencing MWH use, as well as the association between MWH stay and obstetric outcomes in a hospital in rural Ethiopia.

Methods

Data from medical records of the Glenn C. Olson Memorial Primary Hospital obstetric ward were cross matched with records from the affiliated MWH between 1 and 2011 to 31 March 2014. Poisson regression with robust variance was conducted to estimate the relative risk (RR) of childbirth complications associated with MWH use vs. non-use. Five key informant interviews of a convenience sample of three MWH staff and two users were conducted and a thematic analysis performed of social, cultural, and economic factors underlying MWH use.

Results

During the study period, 489 women gave birth at the hospital, 93 of whom were MWH users. Common reasons for using the MWH were post-term status, previous caesarean section/myomectomy, malposition/malpresentation, and low-lying placenta, placenta previa, or antepartum hemorrhage, and hypertension or preeclampsia. MWH users were more likely than non-users to have had a previous caesarean Sec. (15.1 % vs. 5.3 %, p < 0.001) and to be post-term (21.5 % vs. 3.8 %, p < 0.001). MWH users were also more likely to undergo a caesarean Sec. (51.0 % vs. 35.4 %, p < 0.05) and less likely (p < 0.05) to have a spontaneous vaginal delivery (49.0 % vs. 63.6 %), obstructed labor (6.5 % vs. 14.4 %) or stillbirth (1.1 % vs. 8.6 %). MWH use (N = 93) was associated with a 77 % (adjusted RR = 0.23, 95 % Confidence Interval (CI) 0.12–0.46, p < 0.001) lower risk of childbirth complications, a 94 % (adjusted RR = 0.06, 95 % CI 0.01–0.43, p = 0.005) lower risk of fetal and newborn complications, and a 73 % (adjusted RR = 0.27, 95 % CI 0.13–0.56, p < 0.001) lower risk of maternal complications compared to MWH non-users (N = 396). Birth weight [median 3.5 kg (interquartile range 3.0-3.8) vs. 3.2 kg (2.8–3.5), p < 0.001] and 5-min Apgar scores (adjusted difference = 0.25, 95 % CI 0.06–0.44, p < 0.001) were also higher in offspring of MWH users. Opportunity costs due to missed work and need to arrange for care of children at home, long travel times, and lack of entertainment were suggested as key barriers to MWH utilization.

Conclusions

This observational, non-randomized study suggests that MWH usage was associated with significantly improved childbirth outcomes. Increasing facility quality, expanding services, and providing educational opportunities should be considered to increase MWH use.
Serum epidermal growth factor-like domain 7 serves as a novel diagnostic marker for early hepatocellular carcinoma
Authors: Yang Meng-Yuan , Wu Fan , Fang Feng , Yang Hao , Zhang Jing-Fan , Chen Guo-Dong , Yang Lian-Yue
Published: July 2021

Background

Epidermal growth factor-like domain 7 (Egfl7), a recently identified secreted protein, was significantly increased in patients with HCC by our previous studies. However, its efficacy in the diagnosis of early HCC remains unknown. In this study, we therefore evaluate the efficacy of serum Egfl7 for early HCC diagnosis and compare it with alpha-fetoprotein (AFP).

Methods

Serum Egfl7 levels in testing cohort (1081 participants) and validation cohort (476 participants) were measured by a sandwich enzyme-linked immunoassay (ELISA). The cut-off value of Egfl7 was determined by Youden’s index and the efficacies of Egfl7 and AFP in diagnosing early HCC were estimated by receiver operating characteristic (ROC).

Results

Serum Egfl7 was significantly elevated in patients with early HCC than all non-HCC controls in whatever Testing Cohort or Validation Cohort. In the Testing Cohort, ROC curves showed the optimum cut-off value of Egfl7 was 2610 ng/mL and Egfl7 showed a significantly higher sensitivity than AFP in discriminating early HCC from healthy individuals (77.4% vs. 65.3%, P = 0.0013) but the area under ROC (AUROC) and accuracy of Egfl7 and AFP were similar (0.860 vs. 0.868, P = 0.704; 80.2% vs. 83.8%, P = 0.184). In distinguishing patients with early HCC from patients with chronic liver disease (CLD), the AUROC, sensitivity, specificity and accuracy of Egfl7 were 0.800, 75.2, 71.7 and 73.5%, which were all significantly higher than AFP (0.675, 61.8, 62.0 and 61.9% in order). Egfl7 also showed a significant higher sensitivity and accuracy than AFP (76.6% vs. 64.0%, P = 0.0031; 79.9% vs. 66.1%, P < 0.0001) in differentiating early HCC patients from non-HCC individuals. Additionally, 70.8% of early HCC patients with negative AFP could be diagnosed by Egfl7 and the combined use of Egfl7 and AFP increased the sensitivity to 91.0%. These results were confirmed by a validation cohort.

Conclusion

Egfl7 is a valuable serum marker in the diagnosis of early HCC and could complement the efficacy of AFP, especially in distinguishing early HCC from CLD and identifying patients with AFP-negative early HCC.
RETRACTED ARTICLE: Vitamin A deficiency and sleep disturbances related to autism symptoms in children with autism spectrum disorder: a cross-sectional study
Authors: Wen Jing , Yang Ting , Zhu Jiang , Guo Min , Lai Xi , Tang Ting , Chen Li , Chen Jie , Xue Ming , Li Tingyu
Published: July 2021

Background

Vitamin A deficiency (VAD) and sleep disturbances have been reported in children with autism spectrum disorder (ASD). The influence of vitamin A (VA) levels on sleep regulation and sleep disturbances in ASD has garnered concern. The present study aimed to characterize the association of VA levels with sleep disturbances in children with ASD.

Methods

This cross-sectional study compared children with ASD (n = 856) to typically developing children (TDC; n = 316). We used the Children’s Sleep Habits Questionnaire to assess sleep disturbances, Childhood Autism Rating Scale to evaluate the severity of autism symptoms, and Autism Behavior Checklist and Social Responsiveness Scale to assess autism behaviors. Serum VA levels were estimated using high-performance liquid chromatography. Multivariable linear regression and two-way analysis of variance were performed to investigate if VAD was related to sleep disturbances in children with ASD.

Results

Children with ASD had lower serum VA levels and a higher prevalence of sleep disturbances than TDC did. The incidence of VAD in ASD children with sleep disturbances was higher, and the symptoms more severe than those without sleep disturbances and TDC. Interestingly, the interaction between VAD and sleep disturbances was associated with the severity of autism symptoms.

Conclusion

VAD and sleep disturbances are associated with the core symptoms of ASD in children. Regular monitoring of sleep and VA levels may be beneficial for children with ASD.

Trial registration

Chinese Clinical Trial Registry, registration number: ChiCTR-ROC-14005442, registration date: December 9th 2014.
The effect of depression status change on daily cigarette smoking amount according to sex: an eleven-year follow up study of the Korea Welfare Panel Study
Authors: Kang Soo Hyun , Jeong Wonjeong , Jang Sung-In , Park Eun-Cheol
Published: July 2021

Background

In the past decade, the Korean smoking rate has only decreased by 3%, despite several smoking control policies. There is a need for such policies to take smokers’ psychological characteristics into account. Depression is a well-known contributor to failed smoking cessation. This study aimed to examine the effect of smokers’ depression status changes on their daily cigarette smoking amount (DCA).

Methods

This study used a sample drawn from the Korea Welfare Panel Study (KoWePS) waves 3 (2008) to 13 (2018). The DCA refers to the number of the cigarettes smoked per day at the time of the survey. Depression was measured using an 11-item version of the Center for Epidemiologic Studies Depression Scale (CESD-11). A generalized estimating equation (GEE) model was employed to analyse the effect of change of depression status on DCA.

Results

The 2008 baseline included a total of 1821 participants: 1645 males and 176 females. The Yes→No male depression status group had lower DCA (β = − 0.631, p-value = 0.0248) than the No→No group. The Yes→No male depression status group that began smoking before age 19 had lower DCA (β = − 0.881, p-value: 0.0089) than the No→No group that started smoking before 19.

Conclusions

We found that a change from depressed to non-depressed and non-depressed to depressed status is associated with decreasing and increasing DCA among men, respectively. Also, for smokers who began smoking before 19 years of age, the subgroup that went from depressed to non-depressed had much a lower DCA than general smokers. Thus, when treating people participating in smoking cessation programs, counsellors should check for depression symptoms and encourage individuals to pursue depression treatment simultaneously.
Rupture and hemorrhage of a seminoma mixed with yolk sac tumors in 46XY partial gonadal dysgenesis: a case report and literature review
Authors: Lin Rui , Liu Nanbin , Wang Xiuyan , Zhu Xuyou , Huang Daojing , Shi Baomin
Published: July 2021

Background

46XY partial gonadal dysgenesis (PGD) is a rare subtype of disorder of sex development (DSD). 46YY PGD is a congenital disease with atypical chromosomal, gonadal, or anatomical sex development. The patient in this case report had male and female genitalia simultaneously. We created a flowchart of the differential diagnosis for clinicians.

Case presentation

A 41-year-old male was admitted to the hospital complaining of lower quadrant abdominal pain for 1 day. Physical examination revealed that his penis size was normal, but a urethral orifice was located in the perineum area between the scrotum and anus. One small testicle was in the left scrotum, but no testicle was present on the right. The patient’s abdomen was bulging, and he had lower abdominal pain. According to the emergency CT scan, a lesion (74*65 mm) was found in the right pelvis between the bladder and rectum. The lesion showed an unclear boundary and hematocele appearance. The lesion was removed by emergency surgery, and the pathology report indicated a mixed germ cell tumor with a seminoma and yolk sac tumors.

Conclusion

This article is a case report of germ cell tumors in 46XY PGD patients. The literature review summarizes the clinical diagnosis, and a flowchart is provided for physicians in future practice. The importance of this report is that it will help acquaint physicians with this rare disease and make the right initial clinical decision quickly through the use of this flowchart. However, the variants of special subtypes of 46XY DSD are myriad, and all the diagnoses could not be covered in one flowchart.
Unusual presentation of a first branchial arch fistula with maxillofacial infection: a case report
Authors: Han Yu , Yang Run-qin , Hong Liu , Zhong Cui-ping , Zha Ding-jun
Published: July 2021

Background

First branchial cleft anomaly (FBCA) is a rare congenital defect that arises due to incomplete closure of the ventral portion of the first and second branchial arches. There are variable complex clinical manifestations for patients with FBCA, which are prone to misdiagnosis and inadequate treatment. FBCAs usually involve the facial nerve with a consequent increased risk of facial nerve damage. Here, we present an unusual case of FBCA presenting with two preauricular pits in association with an abnormal maxillofacial cyst.

Case presentation

A 10-month-old girl presented to our department due to recurrent maxillofacial infections accompanied by swelling or abscess of the left cheek and purulent discharge from the preauricular pit for 4 months. A 3D-computed tomography (CT) fistulogram and magnetic resonance imaging (MRI) revealed two conjunctive tract lesions: one tract arose from the skin surface anteroinferior to the external auditory canal (EAC), through the deep lobe of the left parotid, and anteriorly extended to the left masseter; the other extended from the superficial lobe of the left parotid to the intertragic notch. After the maxillofacial infection was controlled by intravenous antibiotic administration, surgery was performed. Intraoperative tools, such as facial nerve monitors, microscopes, and methylene blue dyes, were used to facilitate the complete dissection and protection of the facial nerve. On follow-up over one year, the patient recovered well without facial palsy or recurrence.

Conclusion

FBCA with maxillofacial cysts is rare and prone to misdiagnosis. Physicians should pay attention to this anatomic variant of FBCA with the fistula track located deep inside the facial nerve and projected medially to the masseter.
Balance and motion coordination parameters can be improved in patients with type 2 diabetes with physical balance training: non-randomized controlled trial
Authors: Stolarczyk Artur , Jarzemski Igor , Maciąg Bartosz M. , Radzimowski Kuba , Świercz Maciej , Stolarczyk Magda
Published: July 2021

Background

Type 2 diabetes (T2D) is a cause of multiple complications, including retinopathy and peripheral neuropathy. These complications are well understood and believed to contribute to gait instability. Poor balance control and increased falling risk have also been reported in people with diabetic peripheral neuropathy (DPN).

Patients with DPN have increased risk of falling due to decreased proprioceptive feedback. Effective balance training should improve postural control in patients with DPN. For this purpose further evaluation was conducted and balance training was designed.

Methods

The goal of our study was to determine values of proprioception, balance, muscle coordination and strength in patients with T2D and analyze whether biofeedback balance training with use of the Biodex Balance System could improve these parameters. To assess the fall risk the general stability index (GSI), the index of frontal-posterior (FPI) and medial–lateral (MLI) stability were evaluated. 37 patients with diagnosed type 2 diabetes mellitus were recruited to this study. Their results were compared with control group consisting of 41 healthy participants who were homogenic to the study group in terms of age and body mass index (BMI).

Results

There were statistically significant differences between patients with diabetes compared to healthy subjects in GSI (2.79 vs 1.1), FPI (1.66 vs 0.7), MLI (0.88 vs 0.52) and risk of falling (5.18 vs 2.72) p < 0.05. There were also statistically significant changes before and after training in all stability indices (GSI: 2.79 vs 1.26, FPI: 1.66 vs 0.77, MLI: 0.88 vs 0.54 accordingly) p < 0.05 and risk of falling (5.18 vs 3.87) p < 0.05 in the study group who had undergone training with biofeedback.

Conclusions

This study found that there is a decreased balance and motor coordination and an increased risk of falling in patients with type 2 diabetes. These parameters improved in patients who have undergone training programme with biofeedback. Furthermore, an age-dependent deprivation of static balance was observed along with an increased risk of falling as a result of increasing BMI.
Increasing adiposity and the presence of cardiometabolic morbidity is associated with increased Covid-19-related mortality: results from the UK Biobank
Authors: Patel Kiran H. K. , Li Xinyang , Quint Jennifer K. , Ware James S. , Peters Nicholas S. , Ng Fu Siong
Published: July 2021

Background

Although obesity, defined by body mass index (BMI), has been associated with a higher risk of hospitalisation and more severe course of illness in Covid-19 positive patients amongst the British population, it is unclear if this translates into increased mortality. Furthermore, given that BMI is an insensitive indicator of adiposity, the effect of adipose volume on Covid-19 outcomes is also unknown.

Methods

We used the UK Biobank repository, which contains clinical and anthropometric data and is linked to Public Health England Covid-19 healthcare records, to address our research question. We performed age- and sex- adjusted logistic regression and Chi-squared test to compute the odds for Covid-19-related mortality as a consequence of increasing BMI, and other more sensitive indices of adiposity such as waist:hip ratio (WHR) and percent body fat, as well as concomitant cardiometabolic illness.

Results

13,502 participants were tested for Covid-19 (mean age 70 ± 8 years, 48.9% male). 1582 tested positive (mean age 68 ± 9 years, 52.8% male), of which 305 died (mean age 75 ± 6 years, 65.5% male). Increasing adiposity was associated with higher odds for Covid-19-related mortality. For every unit increase in BMI, WHR and body fat, the odds of death amongst Covid19-positive participants increased by 1.04 (95% CI 1.01–1.07), 10.71 (95% CI 1.57–73.06) and 1.03 (95% CI 1.01–1.05), respectively (allp < 0.05). Referenced to Covid-19 positive participants with a normal weight (BMI 18.5–25 kg/m2), Covid-19 positive participants with BMI > 35 kg/m2had significantly higher odds of Covid-19-related death (OR 1.70, 95% CI 1.06–2.74,p < 0.05). Covid-19-positive participants with metabolic (diabetes, hypertension, dyslipidaemia) or cardiovascular morbidity (atrial fibrillation, angina) also had higher odds of death.

Conclusions

Anthropometric indices that are more sensitive to adipose volume and its distribution than BMI, as well as concurrent cardiometabolic illness, are associated with higher odds of Covid-19-related mortality amongst the UK Biobank cohort that tested positive for the infection. These results suggest adipose volume may contribute to adverse Covid-19-related outcomes associated with obesity.
Administration of oxytocin antagonist at the same time as using a Foley catheter with cotton swab before embryo transfer for cervical stenosis
Authors: Chae Heesuk
Published: July 2021

Background

Embryo transfer without difficulty in a patient with cervical stenosis can be a great challenge for in vitro fertilization (IVF). We report a successful pregnancy following a frozen thawed embryo transfer after administration of an oxytocin antagonist at the same time as using a Foley catheter with cotton swab in a patient with refractory cervical stenosis.

Case presentation

A 40-year-old woman undergoing IVF. The patient’s previous embryo transfers were difficult. For every transfer, uterine manipulation was needed, force was required, and dilatation was necessary. A Foley catheter with a cotton swab was inserted into the cervical canal, atosiban was administered at the same time, and the Foley catheter was removed immediately before embryo transfer. A smooth transfer was performed without bleeding, force, uterine manipulation, or cervical dilator. The patient became pregnant and delivered by cesarean section at term.

Conclusion

This method is effective in performing atraumatic embryo transfer in patients with cervical stenosis.
What resources do elderly people choose for managing their symptoms? Clarification of rural older people’s choices of help-seeking behaviors in Japan
Authors: Ohta Ryuichi , Sato Mikiya , Ryu Yoshinori , Kitayuguchi Jun , Maeno Tetsuhiro , Sano Chiaki
Published: July 2021

Background

Appropriate help-seeking behavior (HSB) that involves lay and professional care may moderate the usage of medical resources and promote good health, especially among the rural elderly. However, there is little evidence regarding the rural elderly’s HSB choices for mild symptoms. Therefore, this study attempts to bridge this gap.

Methods

The participants were patients living in rural areas and over the age of 65, who attended Japanese clinics and general hospitals. In Phase 1, monthly diaries and one-on-one interviews about their mild symptoms and HSB were used to establish HSB items and assess its content validity. Content analysis helped determine the items. In Phase 2, participants were asked to complete the list to measure HSB. The answers to the list and HSB mentioned in the diaries were compared to evaluate concurrent validity. Retests were conducted to examine the content’s reliability and test-retest reliability.

Results

Phase 1 included 267 participants (average age = 75.1 years, standard deviation [SD] = 4.3; 50.1% male). The diary collection rate was 97.6%. Of the participants, 70.4% used lay care and 25.4% used professional care. Content analysis identified eight types of lay care and four types of professional care. Phase 2 included 315 participants (average age = 77.7 years, SD = 8.27; 46.0% male). In terms of validity, the results of the list and the diaries were correlated (Spearman r 0.704; p < 0.001). The most common behavior with mild symptoms was consulting with primary care physicians, followed by self-care and using home medicine. The test-retest reliability for mild symptoms found kappa values of 0.836 for lay care and 0.808 for professional care.

Conclusions

The choices of HSB for mild symptoms clarified identified in this study have high validity and reliability. Therefore, it can be used to assess the relationships between HSB and health conditions and the effectiveness of health promotion on rural older people’s HSB.
Socioeconomic differences in healthcare expenditure and utilization in The Netherlands
Authors: Loef Bette , Meulman Iris , Herber Gerrie-Cor M. , Kommer Geert Jan , Koopmanschap Marc A. , Kunst Anton E. , Polder Johan J. , Wong Albert , Uiters Ellen
Published: July 2021

Background

Worldwide, socioeconomic differences in health and use of healthcare resources have been reported, even in countries providing universal healthcare coverage. However, it is unclear how large these socioeconomic differences are for different types of care and to what extent health status plays a role. Therefore, our aim was to examine to what extent healthcare expenditure and utilization differ according to educational level and income, and whether these differences can be explained by health inequalities.

Methods

Data from 18,936 participants aged 25–79 years of the Dutch Health Interview Survey were linked at the individual level to nationwide claims data that included healthcare expenditure covered in 2017. For healthcare utilization, participants reported use of different types of healthcare in the past 12 months. The association of education/income with healthcare expenditure/utilization was studied separately for different types of healthcare such as GP and hospital care. Subsequently, analyses were adjusted for general health, physical limitations, and mental health.

Results

For most types of healthcare, participants with lower educational and income levels had higher healthcare expenditure and used more healthcare compared to participants with the highest educational and income levels. Total healthcare expenditure was approximately between 50 and 150 % higher (depending on age group) among people in the lowest educational and income levels. These differences generally disappeared or decreased after including health covariates in the analyses. After adjustment for health, socioeconomic differences in total healthcare expenditure were reduced by 74–91 %.

Conclusions

In this study among Dutch adults, lower socioeconomic status was associated with increased healthcare expenditure and utilization. These socioeconomic differences largely disappeared after taking into account health status, which implies that, within the universal Dutch healthcare system, resources are being spent where they are most needed. Improving health among lower socioeconomic groups may contribute to decreasing health inequalities and healthcare spending.
Analysis and application of a suite of recombinant endo-β(1,3)-d-glucanases for studying fungal cell walls
Authors: Carvalho Vanessa S. D. , Gómez-Delgado Laura , Curto M. Ángeles , Moreno M. Belén , Pérez Pilar , Ribas Juan Carlos , Cortés Juan Carlos G.
Published: July 2021

Background

The fungal cell wall is an essential and robust external structure that protects the cell from the environment. It is mainly composed of polysaccharides with different functions, some of which are necessary for cell integrity. Thus, the process of fractionation and analysis of cell wall polysaccharides is useful for studying the function and relevance of each polysaccharide, as well as for developing a variety of practical and commercial applications. This method can be used to study the mechanisms that regulate cell morphogenesis and integrity, giving rise to information that could be applied in the design of new antifungal drugs. Nonetheless, for this method to be reliable, the availability of trustworthy commercial recombinant cell wall degrading enzymes with non-contaminating activities is vital.

Results

Here we examined the efficiency and reproducibility of 12 recombinant endo-β(1,3)-d-glucanases for specifically degrading the cell wall β(1,3)-d-glucan by using a fast and reliable protocol of fractionation and analysis of the fission yeast cell wall. This protocol combines enzymatic and chemical degradation to fractionate the cell wall into the four main polymers: galactomannoproteins, α-glucan, β(1,3)-d-glucan and β(1,6)-d-glucan. We found that the GH16 endo-β(1,3)-d-glucanase PfLam16A from Pyrococcus furiosus was able to completely and reproducibly degrade β(1,3)-d-glucan without causing the release of other polymers. The cell wall degradation caused by PfLam16A was similar to that of Quantazyme, a recombinant endo-β(1,3)-d-glucanase no longer commercially available. Moreover, other recombinant β(1,3)-d-glucanases caused either incomplete or excessive degradation, suggesting deficient access to the substrate or release of other polysaccharides.

Conclusions

The discovery of a reliable and efficient recombinant endo-β(1,3)-d-glucanase, capable of replacing the previously mentioned enzyme, will be useful for carrying out studies requiring the digestion of the fungal cell wall β(1,3)-d-glucan. This new commercial endo-β(1,3)-d-glucanase will allow the study of the cell wall composition under different conditions, along the cell cycle, in response to environmental changes or in cell wall mutants. Furthermore, this enzyme will also be greatly valuable for other practical and commercial applications such as genome research, chromosomes extraction, cell transformation, protoplast formation, cell fusion, cell disruption, industrial processes and studies of new antifungals that specifically target cell wall synthesis.
Upregulation of ARNTL2 is associated with poor survival and immune infiltration in clear cell renal cell carcinoma
Authors: Wang Song , Ma Xueyou , Ying Yufan , Sun Jiazhu , Yang Zitong , Li Jiangfeng , Jin Ke , Wang Xiao , Xie Bo , Zheng Xiangyi , Liu Ben , Xie Liping
Published: July 2021

Background

Aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2) is a member of the PAS superfamily. Previous studies explored the carcinogenic roles of transcription factor ARNTL2 in human malignancies. However, its roles in ccRCC have not been elucidated. This study sought to explore the roles of ARNTL2 in ccRCC and determine its correlations with tumor immunity.

Methods

The expression of ARNTL2 was analyzed using the GEO, TCGA and GTEx database, and verified in ccRCC tissue samples and cell lines by qRT-PCR and western blot analysis. Kaplan–Meier survival curve analysis, Cox regression analysis (including univariate and multivariate analysis) was utilized to evaluate the prognostic values of ARNTL2. Potential biological mechanisms of ARNTL2 were explored using GSEA method. Colony formation and wound healing assays were conducted to explore the oncogenic role of ARNTL2 in ccRCC. ssGSEA and xCell algorithm were used to explore the correlation between ARNTL2 expression and tumor immune microenvironment (TIME).

Results

ARNTL2 was significantly upregulated in ccRCC tissues and cell lines compared to normal kidney tissues and cell line. Enhanced expression of ARNTL2 was strongly linked to advanced clinical stage and unfavorable overall survival in ccRCC. ARNTL2 was determined as an independent prognostic marker through cox regression analysis. A prognostic nomogram was constructed to predict 1-, 3- and 5-year overall survival of ccRCC patients by integrating ARNTL2 expression with other clinicopathologic variables. GSEA analysis showed that focal adhesion, T cell receptor, cell cycle, and JAK-STAT signaling pathway were significantly enriched in high ARNTL2 samples. Silencing of ARNTL2 suppressed the colony formation ability and wound healing efficacy of ccRCC cell lines. xCell analysis showed that high expression level of ARNTL2 exhibited an immune infiltration status similar to CD8 + inflamed ccRCC subtype, which was characterized by high infiltration level of CD8 + T cell and high expression level of the immune escape biomarkers such as PD-L1, PD-L2, PD1 and CTLA4.

Conclusion

ARNTL2 is an independent adverse predictor of ccRCC patient survival. High expression level of ARNTL2 is associated with immune infiltration, and may be a novel therapeutic target in ccRCC.
LRRK2 is a candidate prognostic biomarker for clear cell renal cell carcinoma
Authors: Yang Chunxiu , Pang Jingjing , Xu Jian , Pan He , Li Yueying , Zhang Huainian , Liu Huan , Xiao Shu-Yuan
Published: July 2021

Background

Clear cell renal cell carcinoma (ccRCC), derived from renal tubular epithelial cells, is the most common malignant tumor of the kidney. The study of key genes related to the pathogenesis of ccRCC has become important for gene target therapy.

Methods

Bioinformatics analysis of The Cancer Genome Atlas (TCGA), the NCBI Gene Expression Omnibus (GEO) database, USUC Xena database, cBioPortal for Cancer Genomics, and MethSurv were performed to examine the aberrant genetic pattern and prognostic significance of leucine-rich repeat kinase 2 (LRRK2) expression and its relationship to clinical parameters. Immunohistochemistry and Western blot were performed to verify LRRK2 expression. The regulation of ccRCC tumor cell lines proliferation by LRRK2 was examined by CCK8 assay.

Results

Bioinformatics analysis showed that LRRK2 expression was up-regulated and largely correlated with DNA methylation in ccRCC. The up-regulation of LRRK2 was confirmed in ccRCC tissue immunohistochemically and by protein analysis. The level of expression was related to gender, pathological grade, stage, and metastatic status of ccRCC patients. Meanwhile, Kaplan–Meier analysis showed that high expression of LRRK2 correlates to a better prognosis; knockdown of LRRK2 expression attenuated the proliferation ability of ccRCC tumor cell lines; protein–protein interaction network analysis showed that LRRK2 interacts with HIF1A and EGFR.

Conclusion

We found that LRRK2 may play an important role in the tumorigenesis and progression of ccRCC. Our findings provided a potential predictor and therapeutic target in ccRCC.
Multi-omics analysis reveals prognostic value of tumor mutation burden in hepatocellular carcinoma
Authors: Xu Qianhui , Xu Hao , Deng Rongshan , Wang Zijie , Li Nanjun , Qi Zhixuan , Zhao Jiaxin , Huang Wen
Published: July 2021

Background

Hepatocellular carcinoma (HCC) was the sixth common malignancies characteristic with highly aggressive in the world. It was well established that tumor mutation burden (TMB) act as indicator of immunotherapeutic responsiveness in various tumors. However, the role of TMB in tumor immune microenvironment (TIME) is still obscure.

Method

The mutation data was analyzed by employing “maftools” package. Weighted gene co-expression network analysis (WGCNA) was implemented to determine candidate module and significant genes correlated with TMB value. Differential analysis was performed between different level of TMB subgroups employing R package “limma”. Gene ontology (GO) enrichment analysis was implemented with “clusterProfiler”, “enrichplot” and “ggplot2” packages. Then risk score signature was developed by systematical bioinformatics analyses. K-M survival curves and receiver operating characteristic (ROC) plot were further analyzed for prognostic validity. To depict comprehensive context of TIME, XCELL, TIMER, QUANTISEQ, MCPcounter, EPIC, CIBERSORT, and CIBERSORT-ABS algorithm were employed. Additionally, the potential role of risk score on immune checkpoint blockade (ICB) immunotherapy was further explored. The quantitative real-time polymerase chain reaction was performed to detect expression of HTRA3.

Results

TMB value was positively correlated with older age, male gender and early T status. A total of 75 intersection genes between TMB-related genes and differentially expressed genes (DEGs) were screened and enriched in extracellular matrix-relevant pathways. Risk score based on three hub genes significantly affected overall survival (OS) time, infiltration of immune cells, and ICB-related hub targets. The prognostic performance of risks score was validated in the external testing group. Risk-clinical nomogram was constructed for clinical application. HTRA3 was demonstrated to be a prognostic factor in HCC in further exploration. Finally, mutation of TP53 was correlated with risk score and do not interfere with risk score-based prognostic prediction.

Conclusion

Collectively, a comprehensive analysis of TMB might provide novel insights into mutation-driven mechanism of tumorigenesis further contribute to tailored immunotherapy and prognosis prediction of HCC.
Targeting DNAJC19 overcomes tumor growth and lung metastasis in NSCLC by regulating PI3K/AKT signaling
Authors: Zhou Ji , Peng Yang , Gao Ying-chun , Chen Tai-yu , Li Peng-cheng , Xu Ke , Liu Tao , Ren Tao
Published: July 2021

Background

Some driver oncogenes are still unknown in non-small-cell lung cancer (NSCLC). DNAJC19, a major component of the translocation machinery of mitochondrial membranes, is a disease-associated protein. Herein, we report the role of DNAJC19 in NSCLC cell growth and metastasis.

Methods

Immunohistochemistry (IHC) was performed to investigate DNAJC19 expression in NSCLC clinical samples. For knockdown or overexpression assays in A549 or NCI-H1299 lung cancer cells, lentiviral vectors were used. After assessment of cell functions, DNAJC19-knockdown A549 cells were further applied to establish mouse xenograft and metastasis tumor models. Assessments based on the RNA-seq data, western blotting, PCR and IHC were performed for the mechanistic study.

Results

Expression of DNAJC19 was higher in tumors than in noncancerous adjacent tissues. Survival analysis indicated that low DNAJC19 levels were correlated with an increased progression-free survival rate. ShRNA-mediated knockdown of DNAJC19 markedly inhibited cell growth, viability, migration and invasion. Moreover, RNA-seq analysis revealed that the PI3K/AKT signaling pathway was involved in molecular events when A549 cells were treated with shDNAJC19. In addition, DNAJC19 knockdown decreased PI3Kp85a, AKT and p-AKT expression in A549 cells, and cellular functions were greatly rescued in DNAJC19-knockdown A549 cells by ectopic overexpression of AKT. Furthermore, tumor xenograft growth and lung metastasis were markedly repressed in the shDNAJC19 group compared to the control group. As expected, the expression levels of DNAJC19, PI3K and AKT in xenograft mouse samples were also lower in the shDNAJC19 group than in the shCtrl group.

Conclusions

DNAJC19 greatly promotes NSCLC cell growth and lung metastasis by regulating PI3K/AKT signaling, providing a novel therapeutic target for treating NSCLC patients.
SHP2 inhibition enhances the anticancer effect of Osimertinib in EGFR T790M mutant lung adenocarcinoma by blocking CXCL8 loop mediated stemness
Authors: Xia Leiming , Yang Fan , Wu Xiao , Li Suzhi , Kan Chen , Zheng Hong , Wang Siying
Published: July 2021

Background

Additional epidermal growth factor receptor (EGFR) mutations confer the drug resistance to generations of EGFR targeted tyrosine kinase inhibitor (EGFR-TKI), posing a major challenge to developing effective treatment of lung adenocarcinoma (LUAD). The strategy of combining EGFR-TKI with other synergistic or sensitizing therapeutic agents are considered a promising approach in the era of precision medicine. Moreover, the role and mechanism of SHP2, which is involved in cell proliferation, cytokine production, stemness maintenance and drug resistance, has not been carefully explored in lung adenocarcinoma (LUAD).

Methods

To evaluate the impact of SHP2 on the efficacy of EGFR T790M mutant LUAD cells to Osimertinib, SHP2 inhibition was tested in Osimertinib treated LUAD cells. Cell proliferation and stemness were tested in SHP2 modified LUAD cells. RNA sequencing was performed to explore the mechanism of SHP2 promoted stemness.

Results

This study demonstrated that high SHP2 expression level correlates with poor outcome of LUAD patients, and SHP2 expression is enriched in Osimertinib resistant LUAD cells. SHP2 inhibition suppressed the cell proliferation and damaged the stemness of EGFR T790M mutant LUAD. SHP2 facilitates the secretion of CXCL8 cytokine from the EGFR T790M mutant LUAD cells, through a CXCL8-CXCR1/2 positive feedback loop that promotes stemness and tumorigenesis. Our results further show that SHP2 mediates CXCL8-CXCR1/2 feedback loop through ERK-AKT-NFκB and GSK3β-β-Catenin signaling in EGFR T790M mutant LUAD cells.

Conclusions

Our data revealed that SHP2 inhibition enhances the anti-cancer effect of Osimertinib in EGFR T790M mutant LUAD by blocking CXCL8-CXCR1/2 loop mediated stemness, which may help provide an alternative therapeutic option to enhance the clinical efficacy of osimertinib in EGFR T790M mutant LUAD patients.
Analysis of EGFR, KRAS, and PIK3CA gene mutation rates and clinical distribution in patients with different types of lung cancer
Authors: Li Shuo , Li Xinju
Published: July 2021

Background

To analyze and evaluate EGFR, KRAS, and PIK3CA gene mutation rates and clinical distribution in patients with different types of lung cancer

Method

A total of 221 lung cancer patients treated in our hospital between January 2016 and June 2019 were enrolled. Tissue and whole blood samples were collected and analyzed to determine the mutation status of EGFR, KRAS, and PIK3CA genes. The gene exon mutation rates were determined. Relevant clinical data, such as age, gender, tumor sample type, treatment method, pathologic type, and lung cancer stage were recorded and statistically analyzed.

Results

The EGFR gene mutation rates in exons E18-E21 were 2.3%, 17.6%, 3.6%, and 20.4%, respectively. E18, E19, and E20 mutations were commonly detected in adenosquamous carcinoma, and E21 mutations were commonly detected in adenocarcinoma. Mutations in exons E18-E21 were frequently detected in patients with lung cancer stages IA, IB, IIA, or IIB, respectively. The KRAS gene mutation rate in lung cancer patients in exon E2 was higher in whole blood and tissue samples than other exon mutations, while the KRAS gene mutation rate in exons E2 and E3 was significantly higher in patients with lung cancer stages IIB and IA, respectively. PIK3CA gene mutations in exons E9 and E20 occurred in patients < 60 years of age. Exon E9-positive mutations were more common in men or patients with squamous cell carcinoma, while exon E20-positive mutations were more common in females.

Conclusion

The EGFR, KRAS, and PIK3CA gene exon mutation rates differ and were shown to be correlated with different clinical indicators, which have significance in clinical treatment.
Y-27632, a ROCK inhibitor, improved laser-induced shock wave (LISW)-induced cochlear synaptopathy in mice
Authors: Koizumi Yutaka , Mizutari Kunio , Kawauchi Satoko , Sato Shunichi , Shiotani Akihiro , Kakehata Seiji
Published: July 2021

Recently, a pathological condition called cochlear synaptopathy has been clarified, and as a disorder of the auditory nerve synapses that occurs prior to failure of hair cells, it has been recognized as a major cause of sensorineural hearing loss. However, cochlear synaptopathy is untreatable. Inhibition of rho-associated coiled-coil containing protein kinase (ROCK), a serine-threonine protein kinase, has been reported to have neuroprotective and regenerative effects on synaptic pathways in the nervous system, including those in the inner ear. We previously demonstrated the regenerative effect of the ROCK inhibitor, Y-27632, on an excitotoxic cochlear nerve damage model in vitro. In this study, we aimed to validate the effect of ROCK inhibition on mice with cochlear synaptopathy induced by laser-induced shock wave (LISW) in vivo. After the elevation of ROCK1/2 expression in the damaged cochlea was confirmed, we administered Y-27632 locally via the middle ear. The amplitude of wave I in the auditory brainstem response and the number of synapses in the Y-27632-treated cochlea increased significantly. These results clearly demonstrate that ROCK inhibition has a promising clinical application in the treatment of cochlear synaptopathy, which is the major pathology of sensorineural hearing loss.
Gut microbiota-mediated immunomodulation in tumor
Authors: Liu Xinyi , Chen Yanjie , Zhang Si , Dong Ling
Published: July 2021

Tumor immunity consists of various types of cells, which serve an important role in antitumor therapy. The gastrointestinal tract is colonized by trillions of microorganisms, which form the gut microbiota. In addition to pathogen defense and maintaining the intestinal ecosystem, gut microbiota also plays a pivotal role in various physiological processes. Recently, the association between these symbionts and cancer, ranging from oncogenesis and cancer progression to resistance or sensitivity to antitumor therapies, has attracted much attention. Metagenome analysis revealed a significant difference between the gut microbial composition of cancer patients and healthy individuals. Moreover, modulation of microbiome could improve therapeutic response to immune checkpoint inhibitors (ICIs). These findings suggest that microbiome is involved in cancer pathogenesis and progression through regulation of tumor immunosurveillance, although the exact mechanisms remain largely unknown. This review focuses on the interaction between the microbiome and tumor immunity, with in-depth discussion regarding the therapeutic potential of modulating gut microbiota in ICIs. Further investigations are warranted before gut microbiota can be introduced into clinical practice.
The impact of Health Transformation Plan on natural vaginal delivery and cesarean section frequency in Iran: an interrupted time series analysis
Authors: Lotfi Farhad , Lohivash Saeed , Kavosi Zahra , Owjimehr Sakine , Bayati Mohsen
Published: July 2021

Objective

This study was conducted to evaluate the effect of the Iran’s Health Transformation Plan on the frequency of natural vaginal deliveries (NVDs), cesarean sections (CSs), and total deliveries in the Fars province of Iran.

Results

Average number of total deliveries before and after the reform were 3946 and 3810, respectively (p  =  0.164). The ratio of CS to total deliveries in the first study month was 54%. This rate reached 47% in the last month (p  <  0.01). However, it had much fluctuation trend. The ITSA results showed that in the short-run, the NVD rate increased (β  =  492.79, p  <  0.01), the rate of CS decreased (β  =  − 407.09, p  <  0.01), and total deliveries increased (β  =  85.75, p  <  0.724). However, in the long-run, the NVD (β  =  5.74, p  <  0.423), CS (β  =  10.21, p  <  0.189), and total deliveries (β  =  15.96, p  <  0.256) had no significant changes after the reform. Encouraging the NVD package was influential in the short-run but not in the longrun in Iran. Pricing and supply-side policies could not reduce the rate of non-clinical CS on their own. Therefore, paying attention to demand-side policies and changes in consumer behaviors, such as educating the women at the age of pregnancy about the advantages and disadvantages of CS and NVD and correcting misconceptions, could be helpful.
The new criteria for a COVID19 patient for the clinical practice to determine the need for an early therapeutic regimen and to decrease mortality
Authors: Bukhari Mulazim Hussain , Zain Shahzadi , Syed Mobeen
Published: July 2021

A new predictive criterion is being proposed for the determination of cytokine storm (CS) in COVID-19 (COVID-CS). It is comprised of results of laboratory that associate the pro-inflammatory status, systemic cell death, multi-organ tissue damage, and pre-renal electrolyte imbalance. The data identifies the patients’ stay in hospitals and their mortality with the relevance of hyper-inflammation and tissue damage during the CS. The criteria can be readily used in clinical practice to determine the need for an early therapeutic regimen, block the hyper-immune response and possibly decrease mortality. It helps to understand the nature of the virus by following a specific criterion to predict the disease. The SARS-CoV-2 tells us in few days what nature has decided for the patient i.e., recovery, death or permanent disability.

doi: https://doi.org/10.12669/pjms.37.5.3630

How to cite this:Bukhari MH, Zain S, Syed M. The new criteria for a COVID19 patient for the clinical practice to determine the need for an early therapeutic regimen and to decrease mortality. Pak J Med Sci. 2021;37(5):1536-1539.  doi: https://doi.org/10.12669/pjms.37.5.3630

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The challenge of Burnout in Public Medical Teachers in Pakistan: A mixed methods study
Authors: Hashmi Ali Madeeh
Published: July 2021

Background and Objectives: Burnout is common in healthcare workers and affects multiple domains of functioning. The objective of this study was to assess burnout in medical teachers in a large public medical university in Lahore, Pakistan and explore the factors behind it.

Methods: Using an explanatory sequential mixed methods design, we first sent out the abbreviated Maslach Burnout Inventory (aMBI) to all teaching faculty of basic and clinical science at King Edward Medical University (KEMU) Lahore. Descriptive analysis was performed on the 203 respondents who returned the survey. Of those who scored higher on the aMBI, 10 respondents (8 clinical science faculty and two basic science faculty) were selected for detailed semi-structured interviews exploring possible reasons for burnout. Thematic analysis of interview transcripts was performed using Interpretive Phenomenological Analysis. Triangulation and member checking was used for validation.

Results: About 38.9% of respondents scored high on the Emotional Exhaustion subscale and 31.5% scored high on the Depersonalization subscale. There were statistically significant differences on the mean Emotional Exhaustion scores (p <0.001) between Basic and Clinical Sciences Departments with respondents from the Clinical Departments having higher scores (7.84 ± 4.32). Four main themes and multiple sub-themes emerged around burnout after qualitative analysis of the data. These included 1. Work-related factors 2. Family and social factors including challenges related specifically to women 3. Feelings and emotions and 4. Personal Qualities.

Conclusion: A significant proportion of medical faculty experiences burnout related to their professional and personal responsibilities. The reasons are varied. Policy planners and University/College administrators must acknowledge the negative effects of burnout on medical teachers and take steps to ameliorate it in the interests of improving medical education and training.

doi: https://doi.org/10.12669/pjms.37.5.4429

How to cite this:Hashmi AM. The challenge of Burnout in Public Medical Teachers in Pakistan: A mixed methods study. Pak J Med Sci. 2021;37(5):1268-1275. doi: https://doi.org/10.12669/pjms.37.5.4429

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.